MRC 04-07 Review

MRC (UK) Leading Relevant, Cost-
The Gambia Effective Research

04 - 07
Review
Contents
04 Foreword from Unit Director
08 Science Research Overview
12 Science Support Services
18 Unit Communications
22 Bacterial Diseases Programme

48 Malaria Programme
66 Viral Diseases Programme
104 Nutrition
124 Genetics
138 Translational Research
144 Clinical Services
150 Statistics & Data Management

151 Clinical Trials Support
152 Staff Training & Development
OUR VISION
To be a global leader in scientific research, contributing to the development, testing and safe adoption of interventions aimed at
reducing the burden of morbidity and mortality from infectious disease in the developing world.
OUR MISSION
To develop a cost-effective centre of excellence for scientific research, focusing resources and energy on core competencies
and areas of comparative competitive advantage
To consistently attract/develop a team of international calibre scientific researchers and partners able to propose, implement
and publish excellent quality science relevant to the Unit’s vision
To develop and strengthen our relationships in The Gambia and the sub-region towards capacity building and partnership in
the implementation of internationally competitive research on issues of immediate local priority
To ensure that the Unit’s scale and breadth is matched by its capacity to manage processes, people and resources effectively
towards its vision and objectives.
We aim to develop, assess and implement new interventions that will reduce infectious disease, morbidity and mortality in the
developing world.
To achieve this:
Disciplines will be resourced to facilitate, innovate, and develop tools across the disease areas
Funds are allocated to projects on the basis of
a. scientific excellence and international impact
b. alignment to Unit strategy
c. competitive advantages
d. making the best use of opportunities, local resources and strengths of local and international partners/collaborators
e. appropriateness in terms of scale and resources requested in relationship to expected outputs and risks (costs vs
benefits)
potential to facilitate innovative approaches and cross-fertilisation.
Foreword from the
Unit Director
Professor Tumani Corrah CBE, MRG, Unit

Director & Chairman, Executive Management
Board
Since the last Annual Report was published in 2004, the Unit has continued on
its quest for renewal, relevance and cost effectiveness. The period under review
has been productive and eventful; new staff have brought a wealth of international
MRC (UK)
expertise and our five-year plan (submitted in 2005) is nearing the end of its
second year of implementation. All this is very good news indeed, and comes
The Gambia -
as a welcome relief following the rejection of our previous quinquennial plan,
submitted in 2002. I am pleased to say that we are now getting it right, justifying
our existence as the UK’s largest overseas investment in tropical infectious disease
Leading Relevant,
research.
Cost-Effective
2007 marked 60 years of the Medical Research Council in The Gambia. The
anniversary was commemorated with public engagement activities at our main site
in Fajara and at our Field Site in Farafenni which celebrated 25 years of existence.
Research
In 2007, we were also visited by the out-going Chief Executive of the MRC,
Professor Colin Blakemore, who commissioned our new multi-million pound
laboratory complex and clinical services department. The site development, the
first major investment by MRC UK in The Gambia unit in over half a century,
marked a significant vote of confidence in our future as a centre of research
excellence in sub-Saharan Africa.
4 MRC UK The Gambia - 04-07 Review

An illustrious history
In 1947 the remit of the Medical Research Council in the then British colony of
The Gambia was to identify and investigate determinants of health important in
the context of tropical Africa. The original focus was on dietetic and nutritional
research and one of the earliest successes was the realization that mortality rates,
particularly in small children, fluctuated according to the season.
The significance of malaria was early recognized and cross sectional studies in
communities provided evidence that malaria lessened in prevalence and clinical
importance as individuals got older, which implied the acquisition of effective
immunity. Significantly, at a point in the 1950s, interest in malaria research began
to decline, due to the belief that anti-malarials and insecticides would eradicate the
disease. However, in an almost visionary manner, the MRC provided resources for
malaria research, including the successful passive immunity studies of that period,
led by Professor Sir Ian McGregor, who sadly passed away in 2007.
Under the leadership of Professor Brian Greenwood (1980-1995), field research

activity increased significantly. Farafenni was chosen as a suitable site for
community studies on the prevention of malaria and Basse as a focus for studies
on schistosomiasis and later on acute respiratory infections. The establishment of
field stations facilitated an expansion of the Unit’s research activities into the health
problems of rural areas. Initial studies in Farafenni showed that the treatment of
presumptive episodes of malaria by village health workers was not effective while
the administration of chemoprophylaxis to young children by village health workers
resulted in a dramatic reduction in overall mortality in children aged 1 to four years
by about 50%.
Subsequent trials with insecticide impregnated bednets carried out by Bob

Snow, Pedro Alonso and their colleagues achieved similar results and led to the
establishment of a national insecticide treated bednet programme coordinated by
Kabir Cham and Umberto D’Alessandro. Later work showed that despite similar
levels of exposure, reinfection after treatment was more rapid in children than
adults, demonstrating convincingly for the first time the development of natural
immunity to this infection.
By the mid 1980s, a new programme of HIV research was started under the
leadership of Hilton Whittle and Andrew Wilkins. Early epidemiological studies
suggested that many of the HIV-2 infected commercial sex workers attending the
clinic in Fajara had strong links with Caio, a village in Guinea Bissau. In 1988 a new
field site was established in Caio in collaboration with Dr Peter Aaby of the Statens
Serum Institute in Denmark and the Bissau Ministry of Health to undertake a long
term study of the epidemiology of HIV 2 infection. The reputation of MRC The
Gambia as a centre of excellence for HIV research was further enhanced by Sarah
Rowland-Jones and her colleagues in Oxford and The Gambia, who discovered
that some heavily exposed commercial sex workers are resistant to infection.
Many vaccine trials have taken place in The Gambia over the years, and they
are carried out only after the epidemiology of the infection in question has been
carefully defined in the country. For example, studies indicated that perinatal
transmission of Hepatitis B is not an important mode of transmission in The
Gambia so that vaccination in infancy through the Gambia Government’s
Expanded Programme of Immunisation (EPI) was an appropriate way of controlling
this infection. Unfortunately, the end point of this study – the prevention of liver
cancer – is still some years away.
The Gambia’s Extended Programme on Immunisation (EPI) is recognized as one

of the best in Africa. It includes Haemophilus influenzae type B and Hepatitis B –
vaccines that are not routinely included in many EPI programmes on the continent.
Both of these vaccines were trialled in The Gambia, demonstrating the fruits of
the outstanding partnership that exists between the MRC, the Government and
people of The Gambia.
MRC UK The Gambia - 04-07 Review 5

Leading research today changing disease patterns; attractive
enough to lure the best staff;
Our science, directed by Professor Sarah Rowland-Jones, consists of three main competitive enough to retain the
programmes: Bacterial Diseases, Viral Diseases and Malaria, with well developed confidence of international donors.
capacity in immunology, epidemiology, genetics and clinical trials. Nutrition
research continues in Keneba, under the direction of Professor Andrew Prentice MRC in The Gambia is the envy
(London School of Hygiene & Tropical Medicine, UK). of other research facilities in the
region, with superior infrastructure,
Today, we focus on what we do best: there is probably no other country in Sub- world class scientists and an
Saharan Africa where there exists such a successful combination of bench, bush unrivalled relationship with the
and bedside research. Our support services, ably led by Mr Mark Radford, continue host Government, local population
to deliver quality services crucial to the production of internationally competitive and collaborators. Our scientists,
science. support teams and ever growing
number of students are proud to
Our upgraded laboratory facilities strive to comply with Good Clinical Practice/ be Leading research for better health
Good Laboratory Practice (GCP/GCLP) regulations, under the management of the and we hope to continue for many
Clinical Trials Support Manager, appointed in 2007. Following the commissioning years to come, going from strength
of the new clinical services complex in 2007, the former MRC ward at Fajara is to strength.
being converted into a clinical trials unit with added facilities and staffing for phase
1 vaccine and drug trials. Our field sites in Basse, Farafenni, Keneba and Walikunda
continue to host international trials, with MRC supported research projects in
Sukuta Health Centre and Sibanor. Caio in Guinea Bissau took on the full status of
an MRC field site in 2006.
Building capacity
A stream of initiatives focused on building local capacity at MRC (UK) The Gambia
Professor Tumani Corrah
has been introduced over the past few years, with the aim of creating a critical
CBE, MRG, Unit Director & Chairman,
mass of Gambian and West African staff capable of carrying this unit forward and
Executive Management Board
safeguarding its future. Our biomedical sciences professional development pathway
aims to nurture the unit’s laboratory technologists from school leavers to graduates
to post doctoral scientists, capable of becoming independent researchers. Indeed,
training opportunities are available for all cadres of staff to facilitate the production
and support of world class science.
As a Gambian, committed to the continuation of research excellence in this

country and Africa at large, I wish to leave a legacy of having seen through a
number of studentships and other mission critical training opportunities. I am
delighted to say that the number of scholarship opportunities has multiplied in
recent times and continues to grow, and I am particularly grateful to the Training
team for their efforts in seeking out and securing a variety of studentships and
other opportunities.
An enduring partnership
In 2007, we celebrated the success of our sixty year partnership with the
Government and people of The Gambia, without whom none of our
achievements would have been possible. The size and stability of this country
have facilitated our research no end; I find it hard to imagine anywhere in sub-
Saharan Africa where after a thirty year longitudinal study, 75% of the study
participants could still be traced. I would like to take the opportunity to thank The
Government and people of The Gambia for this partnership; I hope that we will
continue to work together in the quest to reduce the burden of disease and death
from tropical infectious diseases in this country and the developing world for many
years to come.
Looking forward
History has taught us that there is no room for complacency. The competitive
nature of international scientific research has sharpened our focus through success
and failure - and although we won the battle for UK Government funding in 2005,
we have also witnessed losses due to potential collaborators taking their research
elsewhere on the continent. We must remain flexible enough to cope with

MRC UK THE GAMBIA
EXECUTIVE MANAGEMENT BOARD
Professor Tumani Corrah

Unit Director & Chairman
Executive Management
Board
Professor Sarah Rowland- Mr Mark Radford

Jones Director of Operations
Director of Research & Administration
& Head of the Viral
Diseases Programme

A Personal Message
from the Director
of Research
Prof Sarah Rowland-Jones

Director of Research, Head of Viral Diseases
Programme
The MRC Gambia Unit is rightly proud of its important contributions to

understanding, treating and preventing the major infectious diseases of the
developing world, as well as the leading figures in international health research that
The aim of
have worked here over the past six decades. Nevertheless, the Gambia Unit faced
a number of challenges following the failure of the its Quinquennial Plan submitted
the unit is to
in 2002. Central amongst these was the need to rebuild morale among the
Unit’s scientists, recruit a credible team of researchers capable of restructuring the
scientific programmes and putting together a five-year research plan for the Unit
understand more
that would meet the MRC’s rigorous requirements for scientific excellence. As
part of this process, I was recruited to the Unit in 2004 on secondment from the
about the major
University of Oxford. For the three years prior to my arrival in the Gambia, I was
Director of the Oxford Centre for Tropical Medicine, which provides logistic and
scientific support for the overseas centres funded by the Wellcome Trust that are
infectious diseases
linked with Oxford University. I arrived with a background of training to consultant
level in adult infectious diseases and a research career in cellular immunology,
of the developing
largely based in the MRC Human Immunology Unit in Oxford (Director Prof.
Andrew McMichael). My research has focused on the T-cell immune response
to HIV infection with a particular emphasis on the immune responses of people
world, particularly
with an unusually good outcome of their encounter with HIV, such as individuals
who have resisted infection despite considerable exposure to the virus or those
those that cause
who have survived for an unusually long time with HIV infection. I carried out
some of these studies in exposed but uninfected sex workers in collaboration with
Professor Hilton Whittle in the Gambia in 1993 to 1994, so I was no stranger to
problems in The
the MRC Unit and its tradition of excellent research. My background, therefore,
had given me an increasing interest in applying basic science to the health
Gambia.
problems of the developing world and I was keen to take up the challenge of the
new position in the Gambia Unit.

Science Research
Overview
Scientific Challenges
In response to the suggestions of the MRC Review Board, the Unit Leadership
had already rationalised the Unit scientific programmes into three main themes,
namely Malaria, Bacterial Diseases (including TB) and Viral Diseases (incorporating
HIV and infant immunology). In addition “cross cutting disciplines” were identified,
with activities across the programmes: these included genetics, immunology,
translational research and epidemiology. In 2004 we began the search for
scientists with an international reputation and leadership skills to head the Malaria
and Bacterial Diseases Programmes. For one of these posts we did not have to
look too far! The selection panel was delighted formally to appoint Professor
Richard Adegbola, already the interim head of the Bacterial Diseases programme
and internationally respected for his work on respiratory pathogens. Another
excellent scientist, Dr. David Conway, well-known for his studies on the molecular
pathogenesis of malaria, was recruited on secondment from the London School
of Hygiene and Tropical Medicine to head the Malaria Programme. Together we
recruited a number of talented and enthusiastic scientists to vacant international
posts in the Unit. We were particularly pleased to be able to appoint no fewer
than six West African scientists to the first twelve of our international posts,
entirely based on their impressive performances in open competition. The new
team had a very short time to assemble a credible scientific plan to put forward
to the MRC Review Board: indeed new scientists in the malaria programme were
arriving with only weeks to spare before the Quinquennial plan was submitted!
We were asked to submit an outline proposal in January, only four months after
my arrival in the Gambia, and the full proposal was submitted in early June 2005.
Scientific Priorities
In putting together the Unit Quinquennial Plan, we wanted to ensure that our
work focused on important health needs in the Gambia and in the West African
sub-region. At the same time we elected to focus on projects that could uniquely
be done in the setting of the MRC Unit in the Gambia or in which the Unit had a
clear competitive advantage. The Unit was able to draw on considerable strengths
built up over many years in putting together these proposals. For example in
Bacterial Diseases, the recent successful outcome of the Pneumococcal Vaccine
Trial (PVT) in children in the Basse area gave rise to important questions about
implementing the commercially available vaccine (which lacks two of the key
serotypes of the 9-valent vaccine tested in the PVT, which are responsible for 25%
of invasive disease in the Gambia) whilst monitoring closely to see what changes
might occur in the background population of organisms carried by people in the
region. In TB research, the team was able to build on the unique resource of the
TB Case Contact Cohort (TBCC) to ask important questions about protective
immunity to tuberculosis in those contacts who remain free of disease and about
the transmission of different TB strains present in the Gambia. One key theme of
the TB proposals came from the observation that almost one in three cases of TB
disease in the Gambia is caused by the organism Mycobacterium Africanum.
The Viral Diseases Programme benefited from several long-standing studies

involving well-designed and well-characterised clinical cohorts, such as the
community cohort of HIV-2 infected subjects in Caio in Guinea Bissau and the
Infant Immunology cohort in Sukuta, close to the MRC main base, which provides
an ideal setting to look how best to protect infants against infectious diseases
using combinations of vaccines.

The Malaria Programme already had a strong base in clinical studies looking at
the best treatment for both mild malaria in the community and severe malaria
in children in hospital but their new programme built on this in an exciting way,
focusing on understanding aspects of the biology of the malaria parasite along with
the host immune response in children who are severely ill with malaria.
A central theme of work in all the programmes has been the development
of vaccine science: trying to understand the relationship between the infected
person and the infecting organism in the laboratory and clinic and building on this
knowledge to test and assess new vaccines in the field.
To summarise, the Quinquennial proposal aimed to build on areas that were
already strong and productive within the Unit and to develop new lines of
research that played to these strengths of the Unit and its collaborators.
New funding
We were delighted to receive many positive reviews of our proposal, which
ultimately received a score from the MRC’s Infection and Immunity review board
of 5 out of 6 (Alpha A under the previous scoring system). Although tight budget
constraints were imposed by the MRC, we began our new funding cycle in
April 2006. In addition, Unit researchers have been able to attract considerable
amount of funding from bodies other than the MRC. Examples of this include
funding from the National Institutes of Health in the USA, the Bill and Melinda
Gates Foundation (the Unit is collaborating on three projects funded under the
Gates Grant Challenges in Global Health Scheme), the European and Developing
Countries Clinical Trials Partnership (EDCTP) and the Centre for HIV AIDS
Vaccine Immunology (CHAVI).
New laboratory and staffing structures

Another challenge to the Unit’s scientific productivity was its relative lack
of energetic PhD students and post-doctoral fellows, who are usually the
powerhouse of a research institution. We have been able to meet this challenge
by recruiting an increased number of talented and enthusiastic PhD students from
all over the world: our current students hail from places as far afield as Cameroon,
Kenya, Zimbabwe, Pakistan, Nigeria and Ghana, as well as more traditional places
for the Unit such as the Gambia, UK, USA and Canada. The training department
at MRC Head office awarded three full-time PhD studentships a year to the
Gambia unit, open to UK and African candidates, and we have been able to fund
other PhD students through EDCTP and other charitable funding. We have been
delighted to be able to attract outstanding candidates to these positions – although
we still wish we had more studentships available! MRC also relaxed its ruling on
appointing band 4 (early post-doctoral) scientists to its overseas units, allowing
us to promote two very talented Gambian researchers to international positions
and to recruit a number of post-doctoral fellows, both clinical and basic scientists.
Several excellent West African scientists have been awarded EDCTP career
development fellowships at Senior and Intermediate level for their studies in the
Unit.
We have endeavoured to increase our collaborative efforts, both within

the Unit and with external collaborators in a way that enhances our joint
productivity. Central to these endeavours has been building and strengthening
our collaborations with other institutions and scientists in Africa. We have been
glad to see the return of former Unit collaborators and to welcome back former
senior Unit staff, Professors Brian Greenwood and Kim Mulholland, as external
consultants: their wisdom and insight is much appreciated.
Although it is still early days in our current quinquennial programme, scientists in

the Unit have generated exciting data and are publishing important papers, as can
be seen in the pages of this report. It is particularly good to see papers from the
Unit appearing in high-profile journals such as Nature Genetics, Nature Immunology,
PLoS Medicine and the Journal of Clinical Investigation, and we hope to see many
more in the coming years.

Coupled with the opening of our new laboratory facilities and the arrival of major
new equipment (a DNA sequencer and a multi-parameter flow cytometer), I
believe these changes are increasingly reflected in a vibrant research culture in the
Unit. I would like to take this opportunity to thank everyone involved in making
the MRC Laboratories in the Gambia such an exciting place in which to conduct
good science!
Bacterial
Viral Diseases Diseases Malaria Nutrition
Immunology &
Genetics
Clinical Trials &
Epidemiology
Public Health/Translational
Research
The unit’s science portfolio

Science
Support Services
Mark Radford,
Director of Operations and Administration
The MRC Gambia support, infrastructural and administrative services provide

the backbone to our work, and an enabling and accountable environment
underpinning the diversity of high quality scientific endeavour at the Unit. Recent
infrastructural
years have seen the achievement of a number of significant milestones:
and administrative
Infrastructure for Science
services provide
The most visible change has been the Unit’s “site development programme”,
begun in 2004 and commissioned by Professor Colin Blakemore in May 2007. The
the backbone to
largest infrastructural development in the Unit’s 60 year history, this has been an
ambitious project aimed at improving and modernizing facilities for our science.
our work
At Fajara this has included the building of a brand new cellular immunology
laboratory and of a molecular facility, as well as a whole new clinical site. This
in turn has given us the opportunity to re-plan and refurbish a wide variety of
buildings vacated in the process, and to add, amongst other things, a dedicated
research ward for phase 1 clinical trials.
In terms of the Unit’s field sites in The Gambia and Guinea Bissau a variety of
laboratories, offices and other buildings have been refurbished, modernized and
re-equipped in line with the Unit’s strategic requirements.
Power Supply and Utilities

In the Unit’s geographic context, self-sufficiency in terms of electricity generation,
water generation and safe waste disposal are all essential to pursuing our scientific
and clinical activities. Ageing infrastructure and a steadily growing internal
demand have required a major overhaul in this area also. During 2006 both
power generation and distribution infrastructures at Fajara were completely

replaced, and water generation/storage capacity at all sites was improved. Waste
management was also strengthened with the construction of new incinerators and
a tightening of internal policies. During the final quarter of 2006 the Unit invited
an experienced electrical/mechanical consultant to review our electrical facilities
(both generation and distribution) at the Unit’s field sites. His recommendations
form the basis of an action strategy for further improvement of electrical supply at
the field sites during 2007-08.
IT and Internet
Our IT department looks after the needs of approximately 500 users across the
MRC locations, and supports a wide range of software from standard business
applications to statistical and specialist programmes designed for specific items of
equipment. Unit IT both within and between locations is linked through a network
managed internally by our own IT team.
IT security, governance and internet connectivity have all been major items on the
agenda, and objectives have been successfully met in all these areas. In particular,
internet speed and reliability have been greatly enhanced by the implementation of
a long awaited VSAT installation at both Fajara and Keneba during 2006. This has
not only improved bandwidth availability at the Unit dramatically, but also reduced
our previous reliance on a sometimes unreliable external internet backbone in The
Gambia.
Systems up-time in the last 3 years has averaged at:

• server /email (99.68%)
• network (99.82%)
• Internet (98.91%)
Telephony
In 2007, the IT department oversaw the implementation of a new telephone
system at the unit, replacing the old Matracom switchboard, installed some 14
years ago. The new switchboard improves reliability and is fully supported by
the manufacturer (through a service contract with the Unit). It has a capability
for remote diagnosis and problem repair, and our own in-house staff have been
trained to deal with most routine repairs, thus reducing downtime (and cost)
significantly should a problem occur. The new switchboard allows us to have 60
lines coming into the Unit (for traffic in/out) and over 600 extensions. This means
it can adequately meet our forecast need for increased extensions, and give us
plenty of excess capacity for further expansion in the future. Full call management
analysis makes it possible for department heads to receive reports about usage
and costs within their sections at whatever level of detail they require. The new
switchboard is fully compatible with voice over IP technology, and would allow us
to test and eventually implement this technology once it is possible to do so.
Biomedical Engineering
A lack of professional servicing options in the sub-region for our clinical and
research equipment has meant, in the past, the Unit being heavily reliant on
service suppliers sending engineers from Europe and elsewhere when things go
wrong. This is clearly very costly and can involve substantial delays and disruption
to the work of our scientists. For this reason, during 2005-06 the development
of an internal Biomedical Engineering department was prioritised and successfully
completed.
As well as coordinating procurement planning, installation and retirement/

replacement of research and clinical technology, this department now runs an
effective pre-planned and responsive maintenance service as well as organizing
user training when new technologies are acquired. The main result for the Unit
has been a major reduction in down-time, more reliable technology and improved
value for money.

Procurement & Logistics
Due to our geographic location and relatively low local availability of goods, most
of this procurement needs to be done internationally. To ensure availability of
supplies and equipment at the Unit, resource accountability and value for money,
MRC The Gambia has established a professional procurement, logistics and
warehousing department, working to internationally recognized good practice
standards.
The Gambia Unit sources, procures and freights over 200 metric tons of
consumables and equipment for its projects from international suppliers each
year, as well as making a major contribution to the Gambian economy through
a substantial local purchase programme. Presently it is also supporting the
Government of The Gambia in establishing transparent, efficient and value for
money procurement of goods on behalf of Global Fund sponsored activities in the
country.
An internal e-procurement system is being tested and set up for all Unit budget
holders, along with a logistics e-tracking system that allows users to track status
from time of ordering to arrival of goods at the Unit. This will improve both
accountability and information flow as well as simplifying procedures for our users.
This will be followed during 2007-08 with an improved electronic stock control
and stock ordering system.
Transport Services
MRC The Gambia runs a fleet of 92 vehicles and over 300 motorbikes, giving it
extensive capacity for field work. These are serviced and maintained in the Unit’s
own workshops at Fajara and up-country.
Following the set up of a sustainable vehicle replacement policy in 2004, the

average age of the present Land-Rover fleet is 3.5 years. The MRC Garage is
working towards becoming an accredited Land Rover workshop.
Human Resources
The Unit’s greatest asset lies in its staff. Around 750 people from over 20
countries are part of the MRC The Gambia team, providing a unique breadth of
experience, skills and perspectives to our work environment.
The HR Department takes prime responsibility for recruitment, contractual and

performance matters, and for areas such as staff travel, work and residential
permits and accommodation for displaced staff. It also liaises closely with the
Training & Staff Development section on developing career pathways and
opportunities for professional growth across a variety of occupational areas.
Guided by HR, the Unit is committed to best practice and is implementing a locally
adapted version of the Investors in People principles. Recent achievements by
the Department include the introduction (in collaboration with the MRC Workers
Union) of a user friendly staff code for locally employed personnel, and the
introduction of individual and team performance awards alongside (but de-linked
from) the annual staff appraisal exercise. Staff inductions and information packs
have also been given a lot of attention, to ensure that new staff and their families
are properly informed, introduced and welcomed on arrival to the Gambia or the
Unit.
HR’s current priorities include a strengthening of our pan-African recruitment

capability, improvements in manpower planning and structures and a review of the
Unit’s housing policies.

Finance & Administration
The Unit manages both core and donor funds through its Finance office in Fajara.
Staffed by trained accountancy staff and working to internationally recognized
guidelines, accountability is further strengthened through regular reviews by the
Unit’s own internal auditor and by the Research Councils UK audit team, as well as
sporadically by external donors.
A dedicated external grants administrator at the Unit provides one focal point for
support, advice and management of all contractual, administrative and budgetary
matters pertaining to donor funded projects.
Health Safety & Security

MRC The Gambia is committed to providing its staff with a pleasant, safe and
secure working environment. To this end considerable attention has been devoted
to the strengthening of the Unit’s health, safety and security functions over recent
years. The Unit presently operates its facilities to audited UK H&S standards.
It is a testament to the strength and to the standards achieved by our many and
diverse support service teams, that their key contribution to providing an enabling
environment for our science is not just recognized internally at the Unit. On an
increasing basis, we are being asked by the Gambia Government, by institutions
across Africa and by the international donor community to provide advisory
support, capacity building assistance and full training programmes. Areas to date
include Finance & Administration, Procurement, Biomedical Engineering, Health &
Safety, Environment and Laboratory Management. We welcome this as a growing
trend, which not only allows us to spread good practice and our own lessons
learned to other institutions. It is also an enriching experience for our own staff,
which helps to broaden our own perspectives and to develop new ideas.
A robust, effective and accountable support and management infrastructure is

an essential component of a thriving institution, creating an environment which
makes internationally competitive scientific innovation and achievement possible in
a developing world environment. I am personally proud of the great strides made
over the period by all of the different teams that come under the support service
and operations banner. I am also personally committed to working with them on
the process of continuing improvement and confident of their vision and ability to
meet head on the challenges and changes which the future will inevitably bring.
Mark Radford
Director of Operations and Administration

The Hilton Whittle Laboratory, commissioned in May 2007

17
MRC UK The Gambia - 04-07 Review
MRC (UK) THE GAMBIA
Unit Director
Executive Management Board
&
Leadership Group EMB Chair
Managers/Assistants/Administrators
Depts. /Teams
Director of Research
External Grants/Office Director of Operations
& Head of Viral Diseases Personal Assistant
Manager & Administration
Programme
Internal Auditor
Head of Health,
Field Site Procurement & Head of Bacterial Viral Diseases Heads of Scientific Statistics & Data
HR Manager Facilities Manager IT Manager Finance Manager Safety & Security Head of Malaria
Administrators Logistics Manager Diseases Programme Staff Disciplines Administrator Management
& Evninromnent
Building & Networks, Servers Health & Safety
HR Team Procurement Finance ARIs HIV 1-2 Genetics & DNA Laboratory
Electrical Teams & IT Services Teams
Management
Transport/Fleet Security
Housing Estates Telephony TB Measles
& Mechanical Team
Biomedical Environment Hepatitis/
Travel
Engineering Team Liver Cancer
Chlamydia/
Trachoma
Staff Development Executive Assistant
Clinical Trials
Clinical Services & Communications
& Training Team Support Team
Team
Unit
Communications
MRC The Gambia remains committed to promoting the value of the unit’s work
and demonstrating its relevance to improving the health of Gambians and the
people of the developing world.
Our outreach and public communication activities are designed to ensure that
MRC The Gambia’s research is promoted, its significance and relevance is
understood, and is seen as beneficial to the nation’s development.
Visibility
MRC is known throughout the country as a provider of excellent healthcare
services. Much less is understood about the unit’s research into tropical infectious
diseases. The aim of our public engagement strategy is to foster understanding and
acceptance of our work, to promote the benefits of health research and to gain
public respect and trust.
Open Days
MRC has opened its gates to the public three times in the last two years. In 2006,
a two day open day programme was held at our main site in Fajara; guests on the
first day included Gambia Government representatives, members of the diplomatic
community, religious leaders, elders and political figures. The second day of the
2006 programme was devoted to 300 senior secondary science students from all
over The Gambia. In March 2007, a successful open day programme dedicated
to ‘Strengthening Community Partnerships’ was held in Farafenni; students and
community leaders were invited to participate in this programme – the first of its
kind at one of our field sites. To commemorate sixty years of the MRC in The
Gambia, an open day for science students was organised in May 2007, officially
opened by the Chief Executive of the MRC, Professor Colin Blakemore.
A smaller programme was held at Sukuta Health Centre in December 2007, on

the theme ‘Vaccinations Save Lives’ to thank and inform the host community and

the mothers whose infants have participated in MRC studies at the site over the
years.
The open day programmes include poster presentations, demonstrations from

various departments and computer animations. These programmes are now in
great demand within the MRC and a further two open days are planned for 2008
in our Field Sites in Basse and Caio (Guinea Bissau).
Schools Outreach
November 2007 saw the commencement of a schools outreach programme;
MRC staff visited a local primary school and talked to a group of sixty children
about the unit’s work, with the aim of creating enthusiasm about science in general
and opportunities at the MRC in particular. Add the sentence, ‘In addition, the unit
regularly receives small groups of school students who are given a guided tour of
the laboratories and meet with various senior members of scientific staff.
Open Forums
A series of open seminars has been held since July 2004, providing a forum for
the general public to meet MRC scientists and ask questions about the unit and
our activities. These events are held at major hotels in the vicinity, are open to
the general public and on average attract more than 200 guests. Past topics have
included the ethics of medical research, tobacco, malaria and global health. In
2007, a special forum was organised highlighting the unit’s achievements over the
past 60 years.
Entertainment that informs

In 2007, the sites at Fajara, Farafenni and Sukuta worked with local volunteer
groups who composed plays and songs about the MRC’s work in the local
languages. Skits were performed at the Farafenni Open Day, the official opening
of the new MRC Clinical Services Department at Fajara and at the Sukuta Health
Centre Open Day. Themes included malaria and the purpose of taking blood
samples for diagnostic purposes.
‘Griots’* of the MRC

Field workers are often the first (and sometimes only) point of contact with the
MRC in the community. They are our de facto ‘ambassadors’, gatekeepers of the
MRC’s name and reputation at the grassroots level. Without field workers,

the unit would not be able to produce relevant, internationally competitive
research. They are responsible for sensitizing and mobilizing communities;
collecting samples; collating good data and feeding back the research results to
the community. Field workers are largely responsible for building and promoting
TRUST in the community, by demonstrating that our work is relevant, ethical and
is contributing to better health for all Gambians and to the development of the
nation. Excellence in field work is vital to the success of MRC’s research. Field
workers who establish a good rapport with the community contribute immensely
to the success of current and future studies.
Communication workshops for MRC’s fieldworkers commenced in November

2007 to debate the unit’s key messages and exchange ideas about how we may
relate with the communities of The Gambia more effectively. Workshops are also
planned for clinical services staff and the unit’s drivers, to commence in 2008.
Radio sensitisation
The reach of radio is far greater than television in The Gambia. A series of radio
programmes in the local languages about pneumonia were aired in late 2007, the
result of a collaboration between Alhagie Darboe, Fieldwork Supervisor with the
Bacterial Diseases Programme and Abdoulie Cham of the Communications Team.
(*griot (Mandinka) – story teller, praise singer)
MRC’s face in the community

In November 2006, a Community Relations Officer was appointed to act as a
bridge between the MRC and the communities of The Gambia. The role is
pivotal in implementing a range of activities such as schools liaison, participation
in local events, understanding the health needs of communities and building on
relationships with the local print and electronic media.
Partnership built on trust

MRC has enjoyed unparalled goodwill from the people and Government of The
Gambia over the past 60 years. Factors include our contribution to supplementing
government’s efforts in the provision of health care and MRC’s position as one of
the largest employers in the country. The rigour of the scientific and ethical review
process, involving Government and lay persons has also assisted in safeguarding the
unit’s credibility in the country.
Gambia Government/MRC Ethics Committee

The Committee is chaired by a lay person and judges all projects undertaken
in The Gambia that have been reviewed and approved by the MRC Scientific
Co-ordinating Committee. The main considerations of the Ethics Committee’s
members ( Gambia Government, lay persons and senior MRC staff), in their role
as advocates for the subjects of research projects, are the safety and well being of
the participants, issues of personal intrusion, and the real or potential benefit that
the trial or project offers to the people of The Gambia.
Gambia Government/MRC Joint Committee

Twice a year, MRC scientists and their counterparts in Government meet to
provide a summary of on-going activities, discuss future plans and explore potential
areas of collaboration.
University of The Gambia School of Medicine

MRC staff regularly deliver lectures to the students of the recently established
School of Medicine. Students of the School of Medicine are also given the
opportunity to spend their elective periods with the MRC’s Clinical Services
Department at Fajara.

Royal Victoria Teaching Hospital (RVTH), Banjul
MRC provides support to RVTH in several areas including the provision of staff,
disease surveillance, management of severe malaria in children and a malnutrition
ward. Once a week, MRC/RVTH conduct joint ward rounds at RVTH.
Collaboration throughout The Gambia

MRC works at the regional level with Divisional Health Teams, encouraging
dialogue between MRC project leaders and village and community leaders about
proposed studies or results of such studies.
MRC also works closely with a large number of organisations in the country
including Sight Savers International, Gambia Family Planning Association, Nova
Scotia Gambia Association, World Health Organisation , Hands on Care, WEC
International, Action Aid, Santa Yalla Support Society (Support group for people
living with HIV/AIDS) and CIAM (Centre for Innovation against Malaria).
School students looking at malaria

parasites under the microscope at MRC
Fajara
Sarah Burl and Alice Halliday answering

the question ‘What is Blood’ at Fajara
Open Day 2006
Professor Tumani Corrah fielding

questions from students at Farafenni
Open Day March 2007
Rohey John Jallow (centre) explaining

the Demographic Surveillance System
at Farafenni Open Day, March 2007

Bacterial Diseases
Programme
Prof Richard Adegbola

Head of Bacterial Diseases Programme
Following the re-organisation of the Gambia Government’s National

unit’s science portfolio in January TB Control Programme. Recently,
2004, Acute Respiratory Infection our bacteriology laboratory was
(ARI) and Tuberculosis (TB) studies accorded the status of a WHO
have been fully integrated into a sub-regional pneumococcal
new Bacterial Diseases Programme reference centre.
(BDP). The programme is engaged
in a wide variety of projects
in clinical, epidemiological and
laboratory science, which range
from preparatory to small and
large-scale clinical intervention trials
and effectiveness studies.
BDP also provides laboratory

diagnostic services for the MRC
hospital and reference culture, and
drug susceptibility services for the

Acute Respiratory Infections (ARI)
Pneumonia remains the most as Haemophilus influenzae type

important cause of illness and death b and pneumococcal conjugate
in children throughout the world. vaccines; and case management
In The Gambia, as in much of with appropriate antibiotics.
sub-Saharan Africa, the importance Despite important advances
of ARI is similar to that of malaria in these approaches, there are
as a cause of illness and death in major information gaps which are
children, yet pneumonia has not hampering effective ARI control.
received the same level of attention ARI studies have been undertaken
from the international community. for many years at the MRC and
Pneumonia accounts for 2 million our vision is informed by gaps in
of 10 million deaths annually in the vaccines and case management.
under 5 year old age group. There
is an urgent need to find out how
deaths from pneumonia can be
most effectively reduced to achieve
the United Nations Millennium
Development Goal of reducing
under-5 deaths by two-thirds by
2015.
There are three possible

approaches to the control of
ARI: non-specific prevention
such as improved nutrition and
housing; effective vaccines such

Vaccinating against pneumonia
Routine vaccination against the the effects of routine immunisation
In a cohort of infants that
commonest bacteria causing on pneumococcal carriage in 21
were enrolled at birth, our
pneumonia will be a significant Gambian villages.
main objectives are:
step in The Gambia. However,
it will be important to look The prevalence of S. pneumoniae i. to determine prevalence
carefully to see if there is any sign carriage in 2872 villagers was 72% of pneumococcal
that other bacteria are filling the (Figure 1). Carriage was highest in carriage rates of vaccine
vacuum left by those removed by infants (97%). It was 93% in babies and non-vaccine
vaccination. under 1 month old and decreased serotypes by age group
with increasing age (p<0.001). and village;
Several studies have shown Prevalence of carriage was linked ii. to identify risk factors for
that Streptococcus pneumoniae to closeness to another village. carriage of pneumococci;
(pneumococcus) is the most In children under 5 years of age, iii. to determine rates
important cause of pneumonia. The 63% of isolates were of a 7-valent of nasopharyngeal
pneumococcus is also commonly vaccine or vaccine related serotype, acquisition of
found in the throat of many compared to 43% overall (Figure pneumococci, density
healthy children in developing 2). 14.3% isolates tested were and persistence of
countries. Routine use of a initially penicillin resistant: none serotype colonization,
7-valent pneumococcal conjugate had high-level resistance, 4 had
vaccine in an infant immunisation intermediate resistance. Resistance
programme in the USA has led to other antibiotics was 39% (co-
to a significant reduction in the trimoxazole), 32.3% (tetracycline),
incidence of pneumococcal disease 6.3% (chloramphenicol),
among children in that country 0.3% (cefotaxime) and 0%
and a substantial positive impact (erythromycin) and was highest in
of vaccination due to the indirect isolates of vaccine serotype.
effect of vaccination has been
recorded in un-vaccinated children Pneumococcal carriage in
and adults. Gambian villagers is very high. A
pneumococcal conjugate vaccine
The long-term consequences containing restricted serotypes
of introducing a vaccine, which should reduce the pool of antibiotic
provides protection against only resistant pneumococci. The large
a limited number of pneumocccal reservoir of pneumococci of
serotypes are uncertain. We are non-vaccine serotypes will require
undertaking a series of carriage close monitoring upon vaccine
studies that will allow us to evaluate introduction.
Forward look
Enrolment of infants at birth has provided baseline data that were
been completed and the specimens used for sample size calculations
are undergoing laboratory analysis and randomisation of villages for
to determine rates of acquisition our vaccine study, which is now in
of new serotypes of pneumococci. progress.
Our first cross-sectional survey

Figure 1
Prevalence of Streptococcus
pneumoniae carriage by age
group (n=2872), expressed as a
proportion.
Figure 2
Proportion of Streptococcus
pneumoniae isolates of 7 -valent
serotype, 7-valent and related
serotypes, 9-valent serotype or
9-valent and related serotypes by
age group (n=2428).
Studies of pneumococcal carriage in Gambian

villages
Key investigators at MRC The Gambia:

Richard Adegbola, Philip Hill, Martin Antonio, Uzochukwu Egere, George Lahai,
David Nsekpong, Mark Saaka, Kawsu Sankareh
Collaborators:
Brian Greenwood, Yin Bun Cheung (London School of Hygiene & Tropical
Medicine, UK).
Funding:
Medical Research Council, Wyeth

Pneumonia Clinical Studies
Pneumonia in Children
Does zinc improve recovery?

Giving children zinc supplements will improve recovery. We expect deficiency and zinc supplementation
could help them recover better to include 600 young children in on these children’s immune system
from severe pneumonia. We are this study over a period of 4 years. in collaboration with the Nutrition
testing whether this is the case in Starting at the end of 2006 we Programme.
The Gambia began studying the effect of zinc
Zinc is an important trace element

in the diet that helps the body grow Zinc supplementation for treating severe
and protect itself from infection.
Studies have shown that where pneumonia
children’s diets are lacking in zinc,
giving zinc supplements can reduce
the chances of getting serious
infections like pneumonia and
diarrhoea. It has also been shown Key investigators at MRC The Gambia:
that giving zinc during illness with Stephen Howie, Akram Zaman, Richard Adegbola, Gerard Morris, Philip Hill,
diarrhoea hastens recovery. It is Martin Antonio, Osaretin Chima, Readon Ideh, Uduak Okomo, Martin Ota, Pa
not known, however, whether zinc Tamba Ngom,,Marie Janneh, Pamela Collier-Njie, Mary Tapgun, Tumani Corrah
given to children who have severe
pneumonia can hasten recovery. A Collaborators:
small number of studies from Asia Kim Mulholland, Brian Greenwood, Peter Smith, Yin Bun Cheung (London
have given mixed results and no School of Hygiene & Tropical Medicine, UK); Majid Ezzati (Harvard School of
studies have been done in Africa. Public Health, USA)
Therefore in November 2005 we
started a randomised placebo- Funding:
controlled trial of zinc supplements Medical Research Council
as an add-on treatment for children
with severe pneumonia to see if this
Forward look
Aetiology of Severe surveillance will be needed if the for severe pneumonia examining
Pneumonia gains from new vaccines are not to the contribution of indoor air
be lost. We are starting a detailed pollution (IAP), bed-sharing, and
A better understanding of the study in 2007 using conventional poor weaning practices. IAP
organisms causing pneumonia is and molecular techniques, both measurement will be done using
urgently needed. Previous efforts on-site in The Gambia and off-site the most appropriate modern
have been limited by insensitive and with key collaborators, to better methods in collaboration with Dr
impractical laboratory techniques. define the causes of pneumonia in Majid Ezzati of the Harvard School
New molecular approaches offer Gambian children. of Public Health.All of these risk
the potential for significant headway factors are potentially amenable to
in this area, the ultimate aim being Risk Factors for Severe intervention.
simple, accurate and practical testing Pneumonia
for use in the developing world.
As conjugate pneumococcal and Measures such as exclusive breast
Haemophilus influenzae type b feeding and appropriate antibiotics
vaccines are widely introduced, the are important in preventing severe
aetiology of pneumonia may change pneumonia. Further key preventive
through serotype replacement and measures need to be identified.
the emergence of new bacterial Starting in 2007 we will undertake
pathogens. Better diagnostics for a case-control study of risk-factors

Simpler antibiotic treatment for pneumonia
Standard treatment for less severe double blind controlled trial among
pneumonia is 5-day treatment 1109 children to assess the efficacy
with amoxycillin given 3-times of high-dose amoxicillin compared
daily. Unfortunately this often to the five-day regime. Children
fails because it is not taken aged 2-59 months presenting
properly. A higher dose given just with CAP at Basse Health Centre,
twice each day for 3 days may Bansang Hospital, and MRC Fajara’s
improve recovery because it is Outpatients’ Department were
just as effective and easier to take individually randomized to one of
properly. these two treatments. The rate of
failure to treatment and subsequent
The Gambian Acute Lower carriage of non-susceptible
Respiratory Tract Infection pneumococci to co-trimoxazole will
control programme is threatened be compared between high-dose
by a high prevalence of co- amoxicillin and standard therapy
trimoxazole resistant bacteria groups. If high-dose amoxicillin
which is associated with non-severe is found to be more efficacious
community acquired pneumonia than the standard therapy, it will
(CAP). WHO recommends the help the ARI control programme
alternative therapy for this to be a to confidently recommend this
course of five-day oral amoxicillin regimen for treatment of non-
45 mg/kg-per-day given thrice daily. severe CAP in children.
However, this regime has been
associated with poor compliance
and high failure rates. Three-day
oral amoxicillin 90 mg/kg-per-
day given twice daily (high-dose
amoxicillin) is expected to increase
compliance, reduce failure rates and
save societal costs.
We have completed a randomized
Efficacy of short course high-dose amoxicillin

in the treatment of non-severe community
acquired-pneumonia in children

Akram Zaman, Richard Adegbola, Felicity Cutts, Godwin Enwere, Emmanuel
Biney, Claire Oluwalana, Adeola Vaughn
Collaborators:
Robin Bailey, Shabbar Jaffar (London School of Hygiene & Tropical Medicine,
UK); B M Jobarteh (Gambia Government Hospital, Bansang); Martin Weber
(WHO, Switzerland)
Funding:
Medical Research Council

Vaccine protection
The Gambian Pneumococcal of nasopharyngeal carriage of
Vaccine Trial showed that a pneumococci in children over 30 The objectives of this study are:
new (conjugate) vaccine is very months of age immunized with • To determine the level of
successful in preventing disease polysaccharide conjugate vaccine immunological memory
from pneumococcus, which kills (PCV) in infancy. Antibody levels following 7-valent
1 million children every year to the different vaccine serotypes pneumococcal conjugate
worldwide. However, it is not will be measured and the response vaccine challenge of 31/2
know how long children remain to challenge with polysaccharide to 5 years old children
protected after vaccination and vaccine evaluated among children who had received PCV in
whether an additional booster who had 3 doses of PCV in infancy. infancy
dose will be needed. This question In addition prevalence of carriage • To determine vaccine
is currently being addressed in a with pneumococci of vaccine and efficacy against
new study. non vaccine type will be studied in nasopharyngeal carriage of
children aged 3-5 years. vaccine serotypes at age
There are concerns about the 3-4 years and compare this
unequivocal recommendation Enrolment of subjects started in with findings at age 1 and 2
of the wide spread use of October 2005 and was completed years in children who had
pneumococcal conjugate vaccines in February 2006. received PCV in infancy
in developing countries. It is not All children received pneumococcal • To determine the extent
known how long protection will conjugate vaccine as appropriate. of serotype replacement in
last following infant immunisation Polysaccharide vaccination and nasopharyngeal carriage at
and whether or not booster safety evaluation were completed age 3-4 years and compare
immunization will be needed. The in November 2006. Laboratory this with findings at age
Gambia Pneumococcal Vaccine assays for isolation and serotyping 1 and 2 years in children
Trial provides the opportunity of pneumococci and evaluation of who had received PCV in
for studying the persistence serotype-specific pneumococcal infancy.
of immunological memory antibodies are now underway.
on the serotype distribution
Pneumococcal vaccine trial (PVT) follow up study

Godwin Enwere , Adebayo Akinsola, Richard Adegbola, Felicity Cutts, Akram
Zaman, Mark Saaka, David Nsekpong
Collaborators:
Brian Greenwood, Yin Bun Cheung (London School of Hygiene & Tropical
Medicine, UK); Janko Jimbara (Gambia Government Divisional Health Team,
Basse, Upper River Division)
Funding:

How many doses?
For vaccines to really make a vaccine given early in life with a
difference in the developing world booster dose of polysaccharide.
they must be cost effective. We We will compare this with
are measuring how well the a standard 3-dose regimen.
pneumococcal vaccine performs Additionally, we plan to evaluate
when Gambian children are given persistence of antibody at age
fewer doses. 15 months, evidence of memory
response following conjugate
Pneumococcal conjugate vaccines vaccines using assays of antibody
have proven to be highly effective in avidity and affinity and naso-
preventing invasive pneumococcal pharyngeal carriage of vaccine and
disease and pneumonia in America non-vaccine serotypes at ages
in a 3-4 dose schedule. The recent 6 weeks, 18 weeks, 10 and 15
successful pneumococcal conjugate months.
vaccine trial in The Gambia was
a 3-dose schedule given at ages Enrolment of subjects started in
2, 3 and 4 months. The unit cost October 2005 and was completed
of this current vaccine will almost in February 2006.
certainly prohibit its availability All children received the
and widespread use in a standard pneumococcal conjugate vaccine
3-dose regimen in resource-poor as appropriate. Polysaccharide
countries. There is need for a revaccination and safety evaluation
evaluation of the number of doses were completed in November
and schedules required with a view 2006. Laboratory assays for
to adopting fewer doses, simpler isolation and serotyping of
schedules and implementing cost pneumococci and evaluation of
effective vaccine regimens that offer serotype-specific pneumococcal
early protection. antibodies were undertaken from
March 2006 to July 2007. Data
The objective of our study is to cleaning and analysis are being
evaluate the safety and antibody undertaken from July 2007 to
responses to 1 or 2 doses of a December 2007.
7-valent conjugate pneumococcal
Alternative vaccination schedules with

pneumococcal conjugate vaccine among
Gambian infants

Richard Adegbola, Adebayo Akinsola, Godwin Enwere, Brown Okoko, Felicity
Cutts, Akram Zaman, Mark Saaka., David Nsekpong
Collaborators:
David Goldblatt (Institute of Child Health, University College, London); Yin Bun
Cheung (London School of Hygiene & Tropical Medicine, UK); Janko Jimbara,
Gambia Government Divisional Health Team, Basse, Upper River Division)
Funding:
World Health Organization, Medical Research Council

Meningococcal vaccine
A new vaccine against epidemics in sub-Saharan
meningococcal epidemics has Africa. They want to accelerate
moved into phase two of clinical meningococcal conjugate vaccine
trials. It is hoped the new vaccine development and introduction at
will give children and communities affordable costs for widespread use
living in the ‘meningitis belt’ better in Africa.
protection than the existing
vaccine. A new MenA conjugate vaccine,
manufactured by the Serum
Recurrent and severe epidemics Institute of India was found to
of meningococcal disease strikes be safe and immunogenic with
the Sub-Saharan area extending durable immunity when tested in
from Senegal to Ethiopia known a Phase I study in Indian adults.
as the ‘meningitis belt’. Annual A pivotal Phase II, observer-
incidences can reach 1,000/100,000 blind, randomized, controlled
compared to 1/100,000 in study started in October 2006
developed countries. Over the last to assess safety, immunogenicity,
century, Group A has remained induction of immune memory and
unique in its ability to cause large antibody persistence of PsA-TT
epidemics. The polysaccharide in 600 African toddlers aged 2
vaccines currently available provide to 23 months in Mali and The
only short-lasting protection, Gambia. Immunogenicity at 4
especially in young children, and do weeks assessed in terms of serum
not reduce carriage of the disease. bactericidal antibody activity and
A vaccine, inducing long-lasting anti–polysaccharide group A
protection and herd immunity, are (anti-PsA ) IgG responses showed
urgently needed. unambiguous and encouraging
results. Similarly, 900 2-29 year old
The Meningitis Vaccine Project subjects have been enrolled in MRC
(MVP) was founded in 2001 as a Basse, Mali and Senegal to assess
partnership between WHO and safety and immunogenicity of this
the Programme for Appropriate study vaccine where subjects will be
Technology in Health. MVP’s goal followed up for 1 year.
is to eliminate meningococcal
Phase II trial of a Neisseria meningitidis group A

conjugate vaccine

Brown Okoko, Richard Adegbola, OT Idoko Adebayo Akinsola, Kalifa Bojang,
Usman Bittaye,
Collaborators:
Marie-Pierre Preziosi (WHO/Meningitis Vaccine Project); Elisa Marchetti, Marc
LaForce (Meningitis Vaccine Project); Prasad Kulkami, Vasudeo Ginde, Varsha
Parulekar (Serum Institute, India); Kebba Gibba (Gambia Government Extended
Programme on Immunisation); Janko Jimbara (Divisional Health Team, Basse,
Upper River Division); Brian Greenwood (London School of Hygiene &
Tropical Medicine, UK – project advisor)
Funding:
Program for Appropriate Technology in Health, (PATH), Serum Institute of
India (SSIL)

Outwitting pneumococcus
New insights into how our
immune systems respond to
pneumococci, which cause
pneumonia and meningitis, could
lead to the development of
smarter vaccines.
Recent data suggest that T

cells could play a central role
in providing protection against
pneumococcus. The T cell
responses are likely to be induced
by pneumococcal protein antigens.
These antigens are conserved
across all pneumococcal serotypes
and could potentially be candidates
for novel vaccines that provide
protection against a broader
spectrum of pneumococcal
serotypes.
We aim to identify the

immunodominant protein antigens,
and characterize the magnitude
and quality of T cell responses in
Gambian adults and children who
must have been naturally exposed
to pneumococcus. Figure 3. The number of IFN-γ spot-forming units per million PBMCs following
overnight stimulation with various pneumococcal protein antigens and controls.
Various assays were used to The wild-type (WT), pneumolysin-deficient (Ply-),CbpA-deficient (CbpA-) mutant
evaluate immunological responses strains as well as recombinant pneumolysin protein (rPly) induced significant
in peripheral blood mononuclear IFN-γ response compared to negative controls, with rPly being the most
cells obtained from healthy adult immunodominant.
blood donors following stimulation
with various protein antigens,
including culture supernatants
derived from a standard
encapsulated type 2 (D39), an
isogenic CbpA-deficient and a
pneumolysin deficient mutant strain.
Wild-type, CbpA-deficient as well
as pneumolysin-deficient strains of
pneumococcus induced significant
immune responses. The heat-
inactivated form of pneumolysin is
the immunodominant, and most
of the responses were induced
from mainly CD4+ T lymphocytes
(Figures 3 and 4).
Figure 4. Pneumococcal proteins antigens induce proliferative responses

predominantly from CD4+ T lymphocytes

Forward Look
Further characterisation and pneumococcal protein antigens
comparison of the phenotype and in children in The Gambia. This
magnitude of immune responses will help in revealing the pattern
between urban and rural dwellers is of immuno-recognisation of the
planned. pneumococcal proteins and also
indicate the relationship between
As infants are the target population the magnitude of immunological
for pneumococcal vaccination we response to the nasopharyngeal
intend to conduct a prospective carriage. Such should be pertinent
observational study. It will evaluate in the rational development of a
the acquisition and evolution protein-based vaccine.
of natural immunity to these
Pneumococcal Immunology

Martin Ota, Richard Adegbola, Sarah Crozier, Marianne Mureithi, Jayne
Sutherland
Collaborators:
Robert Heyderman, Adam Finn (University of Bristol, UK)
Funding:
Joan Franklin Adams Trust, Medical Research Council

Family differences
A new screening technique is invasive disease and with global
helping to identify important isolates at the genetic level. The objective of this project
differences within families of is to use MLST as a discovery
bacteria causing serious diseases. So far, we have characterised platform:
139 and 64 S. pneumoniae and • To assess the genetic
The ability to distinguish accurately Salmonella Enteritidis isolates diversity of invasive bacterial
between different strains within respectively from cases of invasive pathogens isolated from
a bacterial species is key to disease. We used the e-BURST patients compared to
disease treatment, epidemiological algorithm to identify mutually healthy carriers in the
surveillance and to vaccine exclusive groups of related community
development. Until recently genotypes in the population. For • To improve the
the methods that were used to S. pneumoniae, we identified epidemiological information
characterise bacterial isolates were highly clonal lineages of serotype on invasive disease
unsatisfactory as they indexed 1 (ST618) belonging to the ST217 caused by N. meningitidis,
genetic variation that was difficult clonal complex (figure 1). Our data S. pneumoniae, S. aureus
to compare between laboratories. and others indicate that the ST217 and Salmonella spp in The
A relatively new approach, complex is expanding and spreading Gambia.
multilocus sequence typing (MLST), along the Sahel region (African
unambiguously characterises isolates meningitis belt). ST618 belongs to
of bacterial pathogens. To do this the same clonal complex (ST 217,
it uses the nucleotide sequences of ST303 and ST612) of serotype 1
internal fragments of seven house- isolate that caused an outbreak
keeping genes which are scattered of meningitis in Northern Ghana
roughly equally around the circular indicating a dominant West African
bacterial chromosome. We are clone. In The Gambia, we found
currently undertaking a detailed ST618 in 10/11 serotypes 1 and a
MLST study on bacterial isolates to novel single locus variant.
determine which bacterial clones Future rational pneumococcal
are more likely to cause invasive conjugate vaccine design that targets
disease in The Gambia. We will the ST217 hypervirulent clonal
then compare the strains causing complex including their subtypes
more invasive disease with those should be considered.
less likely to be associated with
Invasiveness of bacteria pathogens in

Gambian children

Martin Antonio, Ishrat Hakeem, Usman Ikumapayi, Philip Hill, Richard Adegbola
Collaborators:
Brian Spratt (Imperial College, University of London, UK); Brian Greenwood,
Yin Bun Cheung (London School of Hygiene & Tropical Medicine, UK);
Felicity Cutts (London School of Hygiene & Tropical Medicine, UK/WHO,
Switzerland);
Funding:

Future Look
Ascertaining by MLST the severe pneumonia in Gambian
invasiveness of selected children using real-time
bacterial pathogens in The quantitative bacterial load PCR,
Gambia including Streptococcus multiplex PCR and 16s rRNA
pneumoniae, Salmonella cloning/sequencing
Enteritidis, Staphylococcus Development of cps DNA
aureus, Neisseria meningitidis microarray for identification
and Haemophilus influenzae of multiple serotypes of
Molecular serotyping S. pneumoniae in clinical
Streptococcus pneumoniae specimens.
Determining the aetiology of
Talking about healthcare access

Talking to villagers is helping across different segments of the
us understand the barriers that population with respect to equity.
stand in the way of healthcare. This study aims to use recent
These insights are a valuable tool advances in the understanding of
in developing more appropriate access to healthcare in developing
healthcare delivery systems. countries (including insights from
work in The Gambia), including the
The 1978 Alma Ata declaration role of social networks, to conduct
stated in addition to other factors, a case-control study within the
that there is a need to increase Farafenni Demographic Surveillance
access to health care, especially for System.
populations in rural areas and those
living in under resourced countries. The recruitment and interviews
Despite initiatives to improve for this study were completed in
access, child mortality in many mid-2006. One hundred and forty
regions, including The Gambia, caregivers of children who died
continues to be unacceptably high. were interviewed and the caregivers
Many health initiatives appear to of 700 controls. Verbal autopsies
benefit the worse off the least and were obtained in relation to all the
new tools are required to identify children who died and have been
the effects of new health initiatives reviewed by two senior clinicians.
Case control study of mortality in under 5

year old children and access to healthcare

Philip Hill, Merrin Rutherford, Stephen Howie, Warren Stevens, Momodou
Jasseh, Samuel Dunyo.
Collaborators:
John Dockerty (University of Otago, New Zealand); Melissa Leach (University
of Sussex, UK); Kim Mulholland (London School of Hygiene and Tropical
Medicine, UK)
Funding:

Merrin Rutherford with villagers
involved in the Access study
Forward look
The study will provide insights that that can help shape larger studies
will contribute to the development in the 33 IN-DEPTH Demographic
of new tools that can be used to Surveillance Systems (DSS) that we
drive policy with respect to health collaborate with.
initiatives in similar settings. It will
also provide important information

Tuberculosis (TB)
TB in The Gambia is increasing, development of new TB vaccination
with an incidence rate of programmes in our setting. MRC The Gambia’s TB research
approximately 170/100,000 per An increasing number of began in 1995. It is currently
year in the Western Division of publications from our TB studies are focused on:
the country. making important contributions to
the understanding of the process Immuno-epidemiology
Our TB case-contact model involved in progression to disease biomarkers conferring
continues to be central to our from infection with M. tuberculosis protection against
research. The TB immunology in a highly endemic setting. progression to disease from
laboratory has full capacity to New TB vaccines need to be tested Mycobacterium tuberculosis
perform ex vivo ELISPOT assays, in endemic countries. We recently infection
flow cytometry analysis and concluded the first trials in Africa TB diagnosis and vaccine
gene expression studies. The TB of a new generation TB vaccine studies.
Diagnostic laboratory has been with our colleagues from the
upgraded to contain automated University of Oxford. A follow up
Bactec 9000 MB and MIGIT culture trial designed to evaluate the impact
facility; GenProbe for definitive of the simultaneous vaccination
identification of TB organisms and of a new TB vaccine MVA85A
DNA based detection capacity on the immunogenicity of the EPI
aimed at improving diagnosis and vaccines in healthy infants who have
molecular fingerprinting of M. previously been vaccinated with
tuberculosis. Recently we used BCG is underway.
molecular characterisation of It is expected that our expertise
mycobacterial isolates obtained in high-tech TB vaccine trials will
from sputum to show that one attract other vaccine developers
third of our TB cases were infected to the unit and promote direct
with M. africanum. This finding comparisons between new vaccines.
has important implications for the
TB case contact studies

Working in close proximity to a those with M. tuberculosis. Clinical and their contacts infected
major TB clinic in the community, characteristics and response to with M. tuberculosis
together with our own outpatients’ therapy were indistinguishable complex.
department, provides significant between M. africanum and M. iv. To develop efficacy
competitive advantage in tuberculosis. markers for the evaluation
conducting research to understand of interventions against M.
the relationship of infecting We aim to define more precisely tuberculosis infection and
M.tuberculosis to the human host, the phenotypes of infection and disease.
developing new diagnostic tools disease with M. tuberculosis
v. To identify phenotypic
and evaluating new interventions. complex, identify factors related to
differences between
ESAT-6 is the best known virulence protection, and develop efficacy
M. africanum and M.
factor of M. tuberculosis complex, markers for the evaluation of new
tuberculosis.
and loss of the RD1 sequence, interventions. The specific objectives
containing the ESAT-6 gene, of this research are: vi. To identify genotypic
explains the attenuation of M. correlates of the phenotypic
i. To assess new diagnostic
bovis BCG. While the ESAT-6 differences.
tests for M. tuberculosis
sequence in M. africanum is identical infection and disease in TB vii. To assess the reservoir of
to the one in M. tuberculosis, cases and their household latent M. africanum infection
further studies on whole genome contacts. among humans and possibly
sequencing and gene expression ex animals.
ii. To identify host and
vivo are conducted to try to identify viii. To assess phenotypic and
pathogen biomarkers of
the genomic correlates of the functional immune responses
protection and progression
attenuated ESAT-6 response. to M. tuberculosis, including
through detailed high-tech
laboratory studies in samples the role of CD4, CD8, and
We have identified an association regulatory T cells.
from TB cases and contacts.
between M. africanum and HIV
iii. To investigate the clinical and ix. To evaluate the role of
and hypothesize that CD4 counts
immunological phenotypic innate immunity and M.
are lower among HIV infected
differences between cases tuberculosis receptors in the
patients with M. africanum than

pathogenesis of tuberculosis. Over the last 2 years the outputs test response.
x. To explore mechanisms of the TBCC work in The Gambia Discovery that patients
behind defective have included the following: and their contacts who are
immunological memory A relational database system infected with M. africanum,
following M. tuberculosis to support the work generate lower IFNg
infection: proapoptotic A large-scale evaluation of responses to the TB peptide
factors, activation markers the ELISPOT assay for M. ESAT-6 in the ex vivo
and homing receptors. tuberculosis infection in 735 ELISPOT test. This leads
xi. To establish an in vitro case-contacts to a 1/3 loss of sensitivity
model of M. tuberculosis among household contacts
Demonstration of a dose-
infection. when compared with
response relationship
M. tuberculosis contacts,
between infecting M.
Sputum smear positive TB cases although tuberculin skin test
tuberculosis and the host
and their household contacts are rates are similar (see figure
Evaluation of a fusion protein 5)
recruited. Contacts are classified
of ESAT-6/CFP-10 as a
according to 3 sleeping proximity Discovery that M. africanum
diagnostic test in 488 case
categories which reflect a gradient is associated with HIV
contacts
of recent exposure, examined infection and a lower rate
for evidence of TB, have an The first longitudinal of primary progression
anthropometric assessment and assessment of the ELISPOT to disease in household
DEXA scanning, a PPD skin test assay contacts
and are bled. Those who have Assessment of latency Bio-bank of cells and plasma
a positive PPD (purified protein antigens for the diagnosis for future nested case
derivative) skin test are requested of latent M. tuberculosis control studies
to have a chest x-ray to exclude infection
Bio-bank of DNA for
TB disease. Consecutively recruited Identification of FoxP3 gene ongoing studies of the
contacts are actively followed for expression differences in genetics of disease and
the development of disease over case contacts with evidence infection
2 years. Repeat blood sampling is of recent M. tuberculosis
conducted according to the needs Work package leader
infection, suggesting T cell
of particular studies. for a Bill and Melinda
regulation may cause down-
Gates Foundation Grand
regulation of the PPD skin
Challenge.
Figure 5. Tuberculin skin test and ESAT-6/ CFP-10 ELISPOT results in contacts of
cases infected with M. africanum vs. M. tuberculosis by gradient of proximity to the
case. Tuberculin skin test (TST) results are not significantly different between M.
africanum and M. tuberculosis-exposed contacts, whereas differences in ESAT-6/
CFP-10 ELISPOT (E/C) results are significant.

TB case contact studies

Philip Hill, Ifedayo Adetifa, Richard Adegbola, Bouke de Jong, Roger Brookes,
Martin Ota, Jayne Sutherland, Martin Antonio, Tumani Corrah. Assan Jaye
David Jeffries, Sarah Burl
Collaborators:
Stefan Kaufmann (Max Plank Institute for Infection Biology, Germany); Tom
Ottenhoff, Michel Klein (Leiden University Medical Centre, Germany); Mike
Barer (University of Leicester, UK); Keith McAdam (Infectious Diseases Institute,
Makerere University, Uganda); Adrian Hill (University of Oxford, UK); Peter
Small (Institute for Systems Biology, Seattle, USA); Gary Schoolnik (Stanford
University, USA); Kris Huygen (Institut Pasteur, Belgium); Peter Aaby (Bandim
Health Project, Bissau, Guinea Bissau); Mike Quail (Wellcome Trust Sanger
Centre, UK); Andreas Schoenfeld (International Trypanosomiasis Project, The
Gambia)
Funding:
Medical Research Council (UK), National Institutes of Health (USA), Bill and
Melinda Gates Foundation
Forward look
We seek to improve the precision will be conducted to identify host
around the diagnosis of M. tuber- factors related to progression to TB
culosis infection and TB disease by disease in infected case contacts. A
the identification and assessment randomised trial is assessing the abil-
of new immunogenic antigens and ity of isoniazid to induce reversion
through technological advances in of a positive ELISPOT result.
conducting assays. We will expand
our options by working with our
collaborators, who are combing
whole genome micro-arrays with
tailored Multiplex ligation-depend-
ent probe amplification assays. We
will explore organism factors re-
lated to progression to TB disease
with a focus on M. africanum. A
series of nested case control studies
and high-tech laboratory studies

TB vaccine trials
A new vaccine against tuberculosis BCG scar positive individuals
The objectives of this research which is more effective than the were recruited and screened for
are: BCG in endemic areas is being vaccination with MVA-85A. The
To evaluate the safety tested in Gambian adults and vaccine was only given once. Of
and immunogenicity of children. over 100 recruits, 11 met the entry
new TB vaccines, specifi- criteria and 10 were immunised.
cally MVA85A in the first The vaccine currently available for All volunteers completed the trial.
instance, in Gambian adults tuberculosis is M. bovis BCG. It There were no serious adverse
To conduct detailed immu- is largely ineffective at protecting events. The vaccination proved to
nological studies of new TB against adult pulmonary disease in be highly immunogenic, with all
vaccines, including acquisi- endemic areas, which warrants an individuals responding in the ex vivo
tion of memory. urgent need for new vaccines and ELISPOT assay.
To establish the dose, safety vaccination strategies that improve
and immunogenicity of upon it. MVA85A was found to MVA85A vaccine safety,
MVA85A in babies be safe and immunogenic in adults immunogenicity and interaction
To evaluate whether both in the UK and The Gambia. study in Gambian infants
MVA85A interferes with The ideal time to introduce such
EPI vaccines and vice versa. a vaccine will be in early infancy, This project aims at establishing the
which coincides with the time dose, safety and immunogenicity of
other Expanded Programme on MVA85A, as well as its interference
Immunisation vaccines are also with immune responses to EPI
given. vaccines and vice versa when
administered simultaneously in 4
For the phase I safety and month old healthy Gambian infants.
immunogenicity trial of MVA85A Data obtained will be essential for
in adults, there was a strict entry the planning of further studies on
criteria. Over 150 BCG scar the efficacy of MVA85A against TB.
negative volunteers were recruited,
out of whom 12 met the inclusion An open randomized MVA85A
criteria and 11 were vaccinated. vaccine trial that will involve a total
All volunteers completed the trial of about 500 infants has started
(6 months post vaccination) and enrolling infants at the trial site,
all 9 follow-up bleeds were taken. Sukuta Health Centre; the study
There were no serious adverse should be completed by September
events. The vaccination has proven 2008.
to be highly immunogenic with all
individuals responding in the ex vivo
ELISPOT assay (see figure 6).
Figure 6. Stimulation of PBMCs with antigen 85A induces IFN-γ from a large
number of PBMCs following MVA85A vaccine in both BCG scar positive and
negative Gambian adults.

Martin Ota, Richard Adegbola, Aderonke Odutola, Sarah Crozier, Simon
Donkor, Kathy Flanagan, Jenny Mueller, Patrick Owiafe, Sarah Rowland-Jones,
Jayne Sutherland, Philip Hill, Roger Brookes, Akram Zaman
Collaborators:
Helen McShane, Adrian Hill (Oxford University, UK); Sally Savage (Sukuta
Health Centre, The Gambia); Kebba Gibba (Gambia Government Extended
Programme on Immunisation)
Funding:
European Union (AFTBVAC), Medical Research Council
Community TB action
The local community has been video in local languages that can be
assisting in the identification and used as an intervention to improve Despite the introduction of
treatment of TB. Traditional knowledge and change behaviour. Directly Observed Therapy in
healers now collaborate with the Our work with traditional healers, West Africa, treatment success
National TB Programme and an which showed that they can be rates range from 32-80%. The
information video is helping to positively engaged for referral and objectives of our TB public
change people’s behaviour towards treatment, has led to policy change health studies are:
the disease. to involve them in the work of the • To identify factors
National TB Programme. amenable to intervention
Working closely with the National that cause delay in diagnosis
TB Control Programme, MRC We have identified risk factors or failure in treatment,
conducts public health research that for defaulting from treatment that and to design and conduct
is of relevance both locally and to are amenable to intervention. In intervention studies to
the global control of TB. collaboration with the Farafenni address them
demographic surveillance team, we • To develop a tool that will
Recent TB public health projects also identified that most people enable those running TB
in The Gambia have demonstrated with cough in The Gambia seek programmes in resource
knowledge and gender issues in appropriate help early and that poor settings to identify
the health seeking behaviour of TB there are significant health system system failures and
cases. We have used participatory delays. prioritise interventions.
research methods to develop a TB
TB public health studies

Philip Hill, Warren Stevens, David Jeffries, Momodou Jasseh, Samuel Dunyo
Collaborators:
Adama Jallow, (National Leprosy and TB Control Programme, The Gambia)
Funding:
Medical Research Council, Global Fund

Forward look
We plan to work through the and allowing prioritisation to those
problem of delays and non- areas contributing to the highest
compliance as a whole. We will burden of disease and the greatest
identify where subjects end up in cost to the system. In 2007 a series
the public health progression, from of related studies were planned,
symptoms to treatment completion, looking specifically at TB clustering
for a rural, an urban and a mixed through use of spatial epidemiology
urban/rural setting. Bayesian belief tools. If we are able to confirm that
networks, which have been used in clustering occurs we will explore
clinical diagnosis allow new evidence the reasons, ranging from studies of
(e.g. subject-specific factors or behaviour to geographic differences
numbers of subjects) to be entered in strain distribution.
at any stage in a model, after which
all the probabilities are re-calculated.
This allows a sensitivity analysis
based on a ‘what-if’ approach, thus
predicting the effects of different
possibly multi-stage interventions,

PhD Studentships - Bacterial Diseases Programme
Marianne Mureithi.
‘Investigation of Naturally Acquired Immunity to Streptococcus pneumoniae – Development of Field Tools for Population
Studies’
Brenda Kwanbana.
‘The effect of vaccination with a pneumococcal conjugate vaccine on upper respiratory tract (URT) microbiota in The
Gambia’
Ifedayo Adetifa.
‘Epidemiologic Studies of Interferon gamma release assays in tuberculosis and their potential as efficacy markers for
intervention trials’
Stephen Howie.
‘Causes, remediable risk factors and interventions for severe pneumonia in children under 5 years of age’
Bacterial Diseases Programme: Publications
2004
01. Eastwood SV, Hill PC. A gender-focused qualitative study of barriers to accessing tuberculosis treatment in The
Gambia, West Africa. Int J Tub Lung Dis 2004 ; 8:70-75.
02. Hill P.C, Brookes RH, Fox A, Fielding K, Jeffries DJ, Jackson-Sillah D, Lugos M, Owiafe PK, Donkor SA, Hammond
AS, Otu JK, Corrah T, Adegbola RA, McAdam KPWJ. Large-Scale Evaluation of Enzyme-Linked Immunospot Assay
and Skin Test for Diagnosis of Mycobacterium tuberculosis Infection against a Gradient of Exposure in The Gam-
bia. Clin Infect Dis 2004 ; 38:966-73.
03. Demissie A, Abebe M, Aseffa A, Rook G, Fletcher H, Zumla A, Weldingh K, Brock I, Andersen P, Doherty TM;
VACSEL Study Group. Healthy individuals that control a latent infection with Mycobacterium tuberculosis express
high levels of Th1 cytokines and the IL-4 antagonist IL-4delta2. J Immunol. 2004 ; 172:6938-43.
04. Fletcher H, Owiafe P, Jeffries D, Hill P, Rook G, Zumla A, Doherty M Brookes RH, VACSEL Study Group.
Increased expression of mRNA encoding interleukin (IL-4) and its splice variant IL-4d2 in cells from contacts of
Mycobacterium tuberculosis, in the absence of in vitro stimulation. Immunology 2004; 112:669-73.
05. Jeffries DJ, Donkor S, Brookes RH, Fox A, and Hill PC. Design and implementation of relational databases relevant
to the diverse needs of a tuberculosis case contact study in The Gambia. Int J Tub Lung Dis 2004 ; 8:1095-99.
06. Harper M, Hill PC, Bah AH, Manneh K, McAdam KP, Lienhardt C. Traditional healers participate in tuberculosis
control in The Gambia. Int J Tub Lung Dis 2004; 10:1266-68.
07. Bornman L, Campbell SJ, Fielding K, Bah B, Sillah J, Gustafson P, Manneh K, Lisse I, Allen A, Sirugo G, Sylla A, Aaby
P, McAdam KP, Bah-Sow O, Bennett S, Lienhardt C, Hill AV. Vitamin D receptor polymorphisms and susceptibil-
ity to tuberculosis in West Africa: a case-control and family study. J Infect Dis. 2004 Nov 1;190(9):1631-41. Epub
2004 Sep 28.
08. Stockton JC, Howson JM, Awomoyi AA, McAdam KP, Blackwell JM, Newport MJ. Polymorphism in NOD2,
Crohn’s disease, and susceptibility to pulmonary tuberculosis. FEMS Immunol Med Microbiol. 2004 Jun
1;41(2):157-60.
09. Cooke GS, Campbell SJ, Fielding K, Sillah J, Manneh K, Sirugo G, Bennett S, McAdam KP, Lienhardt C, Hill AV.
Interleukin-8 polymorphism is not associated with pulmonary tuberculosis in the gambia. J Infect Dis. 2004 Apr
15;189(8):1545-6; author reply 1546. No abstract available.
10. Awomoyi AA, Nejentsev S, Richardson A, Hull J, Koch O, Podinovskaia M, Todd JA, McAdam KP, Blackwell JM,
Kwiatkowski D, Newport MJ. No association between interferon-gamma receptor-1 gene polymorphism and

Publications
pulmonary tuberculosis in a Gambian population sample. Thorax. 2004 Apr;59(4):291-4.
11. Vekemans J, Ota MO, Sillah J, Fielding K, Alderson MR, Skeiky YA, Dalemans W, McAdam KP, Lienhardt C, March-
ant A. Immune responses to mycobacterial antigens in the Gambian population: implications for vaccines and
immunodiagnostic test design. Infect Immun. 2004 Jan;72(1):381-8.
12. McNulty SL, Mole BM, Dailidiene D, Segal I, Ally R, Mistry R, Secka O, Adegbola RA, Thomas JE, Lenarcic EM, Peek
RM Jr, Berg DE, Forsyth MH. Novel 180- and 480-base-pair insertions in African and African-American strains of
Helicobacter pylori. J Clin Microbiol. 2004 Dec;42(12):5658-63.
13. Obaro SK, Deubzer HE, Newman VO, Adegbola RA, Greenwood BM, Henderson DC. Serotype-specific pneu-
mococcal antibodies in breast milk of Gambian women immunized with a pneumococcal polysaccharide vaccine
during pregnancy. Pediatr Infect Dis J. 2004 Nov;23(11):1023-9.
14. Deubzer HE, Obaro SK, Newman VO, Adegbola RA, Greenwood BM, Henderson DC. Colostrum obtained from
women vaccinated with pneumococcal vaccine during pregnancy inhibits epithelial adhesion of Streptococcus
pneumoniae. J Infect Dis. 2004 Nov 15;190(10):1758-61. Epub 2004 Oct 7.
15. Newport MJ, Allen A, Awomoyi AA, Dunstan SJ, McKinney E, Marchant A, Sirugo G. The toll-like receptor 4
Asp299Gly variant: no influence on LPS responsiveness or susceptibility to pulmonary tuberculosis in The Gambia.
Tuberculosis (Edinb). 2004;84(6):347-52.
Tuberculosis
16. Hill PC, Fox A, Jeffries DJ, Jackson-Sillah D, Lugos MD, Owiafe PK, Donkor SA, Hammond AS, Corrah T, Adegbola
RA, McAdam KPWJ, Brookes RH. Quantitative T cell assay reflects infectious load of Mycobacterium tuberculosis
in an endemic case contact model. Clin Infect Dis 2005; 40:273-8.
17. Doherty TM, Demissie A, Menzies D, Andersen P, Rook G, Zumla A, VACSEL Study Group. Effect of sampling
handling on analysis of cytokine responses to Mycobacterium tuberculosis in clinical samples using ELISA, ELISPOT
and quantitative PCR. J Immunol Methods 2005 ; 298:129-141.
18. Hill PC, Jackson-Sillah D, Fox A, Franken KL, Lugos MD, Jeffries DJ, Donkor SA, Hammond AS, Adegbola RA,
Ottenhoff THM, Klein M, Brookes RH. ESAT-6/CFP-10 fusion protein and peptides for optimal detection of My-
cobacterium tuberculosis infection by ex vivo ELISPOT in The Gambia. J Clin Microbiol 2005 ; 43:2070-74.
19. De Jong B, Hill PC, Brookes R, Otu J, Peterson K, Small P, Adegbola R. Mycobadcterium africanum: a new oppor-
tunistic pathogen in HIV infection? AIDS 2005; 19:1714-15.
20. Hill PC, Stevens W, Hill S, Bah J, Jallow A, Lienhardt C. Risk factors for defaulting from TB treatment-a prospective
cohort study of 301 patients from The Gambia. Int J Tub Lung Dis 2005; 12: 1349-54.
21. Onipede AO, DeJong B, Adegbola RA. Mycobacterium africanum- A Review. African J Clin Exp Microbiol
2005;6:167-175.
22. Lienhardt C, Fielding K, Sillah J, Bah B, Gustafson P, Warndorff D, Palayew M, Lisse I, Donkor S, Diallo S, Manneh
K, Adegbola R, Aaby P, Bah-Sow O, Bennett S, McAdam K. Investigation of the risk factors for tuberculosis: a case-
control study in three countries in West Africa. International Journal of Epidemiology 2005; 34 (4):914-923
23. Martin M, Brookes L, Cham A, Thomas DR, Hill PC. Tuberculosis education in an endemic setting: Application of
participatory methods to video development in The Gambia. Int J Tub Lung Dis 2005;9:550-55.
24. Greenaway C, Lienhardt C, Adegbola R, Brusasca P, McAdam K, Menzies D. Humoral response to Mycobacterium
tuberculosis antigens in patients with tuberculosis in the Gambia. International Journal of Tuberculosis and Lung
Disease 2005; 9(10):1112-1119.

Publications
25. Howie S, Voss L, Baker M, Calder L, Grimwood K, Byrnes C. , Tuberculosis in New Zealand 1992-2001: a resur-
gence. Archives of Disease in Childhood; 2005, 90(11): 1157-61
26. Demissie A, Leyten EMS, Markos A, Wassie L, Aseffa A, Fletcher H, Owiafe P, Hill PC, Brookes R, Rook G, Zumla
A, Arend S, Klein M, Ottenhoff THM, Andersen P, Doherty M, and the VACSEL Study Group. Recognition of
stage-specific mycobacterial antigens differentiates between acute or latent infection with M. tuberculosis. Clin Vac-
cine Immunol 2006 ; 13:179-86.
27. Jeffries DJ, Hill PC, Fox A, Lugos M, Jackson-Sillah DJ, Adegbola RA, Brookes RH. Identifying ELISPOT assay and
PPD skin test cut-offs for diagnosis of Mycobacterium tuberculosis infection in The Gambia. Int J Tub Lung Dis
2006; 10:192-98.
28. Aiken AM, Hill PC, Fox A, McAdam KP, Jackson-Sillah DJ, Lugos M, Donkor SA, Adegbola RA, Brookes RH. Re-
peat ELISPOT results reflect treatment efficacy in Gambian tuberculosis cases. BMC Infect Dis 2006 ; 6:epub.
29. Hill PC, Brookes RH, Adetifa IMO, Fox A, Jackson-Sillah D, Lugos, M, Donkor S, Marshall RJ, Howie SR, Jeffries DJ,
Adegbola RA, McAdam KP. Comparison of Enzyme-linked immunospot assay and tuberculin skin test in healthy
children exposed to Mycobacterium tuberculosis. Pediatrics 2006; 17:1542-48.
30. De Jong BC, Hill PC, Brookes RH, Gagneux S, Jeffries DJ, Otu JK, Donkor SA, Fox A, McAdam KP, Small PM,
Adegbola RA. Mycobacterium africanum elicits an attenuated T-cell response to ESAT-6 in tuberculosis patients
and their household contacts. J Infect Dis 2006 ;193 :1279-86.
31. Hill PC, Jackson-Sillah DJ, Donkor SA, Otu J, Adegbola RA, Lienhardt C. Risk factors for tuberculosis : a clinic based
case-control study in The Gambia. BMC Public Health 2006; 6: epub.
32. Ibanga HI, Brookes RH, Hill PC, Owiafe PK, Fletcher HA, Lienhardt C, Hill AVS, Adegbola RA, McShane H. Early
clinical trials with a new tuberculosis vaccine, MVA85A, in tuberculosis endemic countries : issues in study design.
Lancet Infect Dis 2006; 6:522-28.
33. Kasse Y, Jasseh M, Corrah T, Antonio M, Jallow A Adegbola RA, Hill PC. Health seeking behaviour, health system
experience and tuberculosis case finding in Gambians with cough. BioMed Central Public Health 2006; 6:143
34. Demissie A, Wassie L, Abebe M, Aseffa A, Rook G, Zumla A, Andersen P, Doherty TM, VACSEL Study Group.
The 6-kilodalton early secreted antigenic target-responsive, asymptomatic contacts of tuberculosis patients express
elevated levels of interleukin-4 and reduced levels of gamma interferon. Infect Immun 2006;74:2817-22
35. Hill PC, Jeffries DJ, Brookes RH, Fox A, Jackson-Sillah D, Lugos MD, Donkor SA, de Jong BC, Corrah T, Adegbola
RA, McAdam KP. Using ELISPOT to expose false positive skin test conversion in tuberculosis contacts. PLoS ONE
2007;2:e 183
36. Adetifa IM, Lugos MD, De Jong B, Antonnio M, Adegbola RA, Hill PC. Rising ELISPOT count prior to the onset of
symptoms of full-blown tuberculosis disease. Int J Tub Lung Dis 2007; 11(3):350-352.
37. Hill PC, Brookes RH, Fox A, Jackson-Sillah D, Lugos MD, Jeffries DJ, Donkor SA, Adegbola RA, McAdam KPWJ.
Surprisingly high specificity of the PPD skin test for Mycobacterium tuberculosis infection from recent exposure in
The Gambia. PLoS ONE 2006; 1:e68
38. De Jong BC, Hill PC, Jeffries D, Onipede A, Small PM, Adegbola RA, Corrah TC. Presentation and treatment
outcome of tuberculosis patients infected with M. africanum versus M. tuberculosis. Int J Tub Lung Dis 2007;
11(4):450-456.
39. Jackson-Sillah DJ, Hill PC, Fox A, Brookes RH, Donkor SA, Lugos MD, Howie SR, Fielding K, Lienhardt C, Cor-
rah T, Adegbola RA, McAdam KP. Screening for tuberculosis among 2381 household contacts of smear positive
tuberculosis cases in The Gambia. Trans R Soc Trop Med Hyg 2007;101:595-602.
40. Burl S, Hill PC, Jeffries DJ, Holland MJ, Fox A, Lugos MD, Adegbola RA, Rook GA, Zumla A, McAdam KP, Brookes

Publications
RH. FOXP3 gene expression in a tuberculosis case contact study. Clinical and Experimental Immunology 2007;
Apr 2006; Epub ahead of print.
41. Hill PC, Brookes RH, Fox A, Jackson-Sillah D, Jeffries DJ, Lugos MD, Donkor SA, Adetifa IM, de Jong BC, Aiken
AM, Adegbola RA, McAdam KP. Longitudinal assessment of an ELISPOT test for Mycobacterium tuberculosis
infection. PLoS Medicine 2007; 4(6):e192.
42. Olesen R, Wejse C, Velez DR, Bisseye C, Sodemann M, Aaby P, Rabna P, Worwui A, Chapman H, Diatta M,
Adegbola RA, Hill PC, Ostergaard L, Williams SM, Sirugo G. DC-SIGN (CD209), Pentraxin 3 and Vitamin D Re-
ceptor gene variants associate with pulmonary tuberculosis risk in West Africans. Genes and Immunity 2007; Jul 5;
[Epub ahead of print].
43. Cehovin A, Cliff JM, Hill PC, Brookes RH, Dockrell HM. Extended culture enhances sensitivity of Interferon- assay
for latent Mycobacterium tuberculosis infection. Clin Vacc Immunol 2007; 14:796-98.
44. Hammond AS, McConkey SJ, Hill PC, Crozier S, Klein MR, Adegbola RA, Rowland-Jones S, Brookes RH, Whittle
H, Jaye A. Mycobacterial T-cell responses in HIV-infected patients with advanced immunosuppression. Journal of
Infectious Diseases 2007; (in press).
45. Adetifa IMO, Lugos MD, Hammond A, Jeffries D, Donkor S, Adegbola RA, Hill PC. Comparison of two Interferon
Gamma Release Assays in the diagnosis of Mycobacterium tuberculosis infection and disease in The Gambia BMC
Infectious Diseases 2007; (in press).
46. Ota MOC, Brookes R, Hill PC, Owiafe PK, Ibanga HB, Donkor S, Awine T, McShane H, Adegbola RA. The effect
of tuberculin skin test and BCG vaccination on the expansion of PPD-specific IFN- producing cells ex vivo. Vac-
cine 2007; (in press).
Acute respiratory Infections

47. Adegbola RA, Secka O, Lahai G, Lloyd-Evans N, Njie A, Usen S, Oluwana C, Obaro S, Weber M, Corrah T,
Mulholland K, McAdam K, Greenwood B, Milligan PJM. Elimination of Haemophilus influenzae type b (Hib) disease
from The Gambia after the introduction of routine immunisation with a Hib conjugate vaccine. Lancet 2005;
366:144-150
48. Mulholland EK, Adegbola RA. Bacterial infections- a major cause of death among children in Africa. N Eng J Med
2005; 352:75-77.
49. Cutts FT, Zaman SMA, Enwere G, Jaffar S, Levine OS, Okoko JB, Oluwalana C, Vaughan A, Obaro SK, Leach A,
McAdam KP, Biney E, Saaka M, Onwuchekwa U, Yallop F, Pierce NF, Greenwood BM, Adegbola RA. Efficacy of
nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gam-
bia: randomised, double-blind, placebo-controlled trial. Lancet 2005;365:1139-1146.
50. Weber MW, Gopalakrishna G, Awomoyi A, Cunningham A, Adegbola RA, Falade AG, Ogunlesi OO, Whittle HC,
Mulholland EK. The role of Chlamydia pneumoniae in acute respiratory tract infections in young children in The
Gambia, West Africa. Ann Trop Paediatri 2006; 26:87-94.
51. Adegbola RA, Hill PC, Secka O, Ikumapayi UN, Lahai G, Greenwood BM, Corrah T. Serotype and antimicrobial
susceptibility patterns of isolates of Streptococcus pneumoniae causing invasive disease in The Gambia 1996-2003.
Trop Med Int Health 2006; 11(7):1-8.
52. Hill PC, Akisanya A, Sankareh K, Cheung YB, Saaka M, Lahai G, Greenwood BM Adegbola RA. Nasopharyngeal
carriage of Streptococcus pneumoniae in Gambian villagers. Clin Infect Dis 2006; 43: 673-679
53. Enwere G, Biney E, Cheung Y, Zaman SM, Okoko B, Oluwalana C, Vaughan A, Greenwood B, Adegbola R, Cutts
FT. Epidemiologic and Clinical Characteristics of Community-Acquired Invasive Bacterial Infections in Children

Publications
Aged 2-29 Months in The Gambia. Pediatr Infect Dis J 2006; 25(8):700-705.
54. Levine OS, O’Brien KL, Knoll M, Adegbola RA, Black S, Cherian T, Dagan R, Goldblatt D, Grange A, Brian Green-
wood B, Hennessy T, Klugman KP, Madhi SA, Mulholland K, Nohynek H, Santosham M, Saha SK, Scott JA, Sow S,
Whitney CG, Cutts F. Time to begin pneumococcal vaccination in developing countries. Lancet 2006; 367:1880-
1882.
55. Howie S, Howie R. Valuing children. Lancet 2006; 368(9530): 117-18
56. Howie SRC, Adegbola RA. Pneumonia and child mortality. Lancet 2006; 368:1646
57. Cutts FT, Enwere G, Zaman SM, Yallop FG. Operational Challenges in Large Clinical Trials: Examples and Lessons
Learned from the Gambia Pneumococcal Vaccine Trial. PLoS Clin Trials. 2006 14;1(3):e16 (Epub)
Mulholland EK. The role of Chlamydia pneumoniae in acute respiratory tract infections in young children in The
Gambia, West Africa. Annals of Tropical Paediatrics 2006; 26:87-94.
59. Obaro SK, Ota MO. Sense and the science of childhood immunization: Can we achieve more with less? Vaccine
2006;24:6460-7. Epub 2006 Jul 7.
60. Howie S, Zaman A, Omoruyi O, Prentice A, Adegbola R. Severe pneumonia research and the problem of case
definition: the example of zinc trials. American J of Clinic Nutrition 2007; 85:242-3
61. Hill P, Onyeama C, Ikumapayi U, Secka O, Ameyaw S, Simmonds N, Donkor S, Howie S, Tapgun M, Corrah T,
Adegbola R. Bacteraemia in patients admitted to an urban hospital in West Africa. BMC Infectious Diseases; 2007,
7:2.
62. Howie S, Hill S, Sanneh M, Njie M, Hill P, Mulholland K, Adegbola R. Beyond good intentions: lessons on equip-
ment donation from an African hospital. Bulletin World Health Organization (in press): accepted 25 June 200
63. Howie S. Conduct of clinical trials in developing countries. Lancet; 2007, 370(9587):562
64. Howie S, Antonio M, Akisanya A, Sambou S, Hakeem I, Secka O, Adegbola R. Re-emergence of Haemophilus
influenzae type b (Hib) disease in The Gambia following successful elimination with conjugate Hib vaccine. Vaccine;
2007, 25(34):6305-9.
65. Ikumapayi UN, Antonio M, Sonne-Hansen J, Biney E, Enwere G, Okoko B, Oluwalana C, Vaughan A, Zaman SMA,
Greenwood BM, Cutts FT, Adegbola RA.. Molecular epidemiology of community-acquired, invasive, non-typhoidal
Salmonella among children aged 2-29 months in rural Gambia and discovery of a new serovar, Salmonella enterica
Dingiri. Journal of Medical Microbiology 2007; 56(11):1479-84
66. Enwere GC, Cheung YB, Zaman S, Akano A, Oluwalana C, Okoko B, Vaughan A, Adegbola R, Greenwood B,
Cutts F. The epidemiology and clinical features of pneumonia according to radiographic findings in Gambian chil-
dren. Tropical Medicine & International Health 2007; (in press).
67. Hill PC, Cheung YB, Akisanya A, Sankareh K, Lahai G, Greenwood BM, Adegbola RA. Nasopharyngeal carriage of
Streptococcus pneumoniae in Gambian infants – a longitudinal study. Clinical Infectious Diseases Journal 2007; in
press.
68. Klugman KP, Cutts F, Adegbola RA, Black S, Madhi SA, O’Brien KL, Santosham M, Shinefield H, Sterne JAC. Meta-
analysis of the efficacy of conjugate vaccines against invasive pneumococcal disease. Siber G, Klugman KP, Makela
H editors. Pneumococcal vaccine ASM 2007; in press

Publications
Other related microbial infections and all others

69. Howie S, Adegbola R, Corrah T. Migration of health professionals Lancet 2005; 199-200 .
70. Howie S, Guy M, Fleming L, Bailey W, Noyes H, Faye JA, Pepin J, Greenwood B, Whittle H Mplyneux D, Corrah
T. Gambian infant with fever and an unexpected blood film PLoS Med 2006; 3 (9): e355 (Epub)
71. Burton MJ, Bowman RJC, Faal H, Aryee EAN, Ikumapayi UN, Alexander NDE, Adegbola RA, West SK, Mabey
DCW, Foster A, Johnson GJ, Bailey RL. The long-term outcome of trichiasis surgery in The Gambia. Bri J Ophthal-
mol 2005;89:575-579.
72. Burton MJ, Kinteh F, Jallow O, Sillah A, Bah M, Faye M, Aryee EAN, Ikumapayi UN,Alexander NDE, Adegbola RA,
Faal H, Mabey DCW, Foster A, Johnson GJ, Bailey RL. A randomised controlled trial of azithromycin following
surgery for trachomatous trichiasis in The Gambia. Bri J Ophthalmol 2005;89:1282-1288.
73. Burton MJ, Bowman RJC, Faal H, Aryee EAN, Ikumapayi UN, Alexander NDE, Adegbola RA, Mabey DCW, Foster
A, Johnson GJ, Bailey RB. The long-term natural history of trachomatous trichiasis in The Gambia. Invest Ophthal-
mol Vis Sci 2006; 47: 847-852.
74. Herring AJ, Ballard RC, Pope V, Adegbola RA, Changalucha J, Fitzgerald DW, Hook III EW, Kubanova A, Manan-
watte S, Pape JW, Sturm AW, West B, Yin YP, Peeling RW. A Multi-centre Evaluation of Nine Rapid, Point of
Care Syphilis Tests Using Archived sera. Sexually Transmitted Infections 2006; e pub.
75. Oh S, Stegman B, Pendleton CD, Ota MO, Pan CH, Griffin DE, Burke DS, Berzofsky JA. Protective immunity pro-
vided by HLA-A2 epitopes for fusion and hemagglutinin proteins of measles virus. Virology 2006; 352:390-9. Epub
2006 Jun 14.
76. Darboe MK, Thurnham DI, Morgan G, Adegbola RA, Secka O, Solon JA, Jackson SJ, Northrop-Clewes C, Ful-
ford TJ, Doherty CP, Prentice AM. Effectiveness of an early supplementation scheme of high-dose vitamin A
versus standard WHO protocol in Gambian mothers and infants: a randomised controlled trial. Lancet 2007;
369:2088-2096.
77. Burton MJ, Adegbola RA, Kinteh F, Ikumapayi UN, Foster A, Mabey DCW, Bailey RL. Bacterial infection and tra-
choma in The Gambia: a case-control study. Investigative Ophthalmology and Visual Science 2007;48:4440-4444.
78. Ota MO, Ndhlovu Z, Oh S, Piyasirisilp S, Berzofsky JA, Moss WJ, Griffin DE. Hemagglutinin Protein Is a Primary
Target of the Measles Virus-Specific HLA-A2-Restricted CD8+ T Cell Response during Measles and after Vaccina-
tion. J Infect Dis. 2007;195:1799-807. Epub 2007 May 9.
79. Moss WJ and Ota MO. “Measles.” Nelson KE, Williams GM, Graham NMH, Eds. Infectious Disease Epidemiology,
2nd Ed., Aspen Publishers.
80. Ota MOC, Brookes R, Hill PC, Owiafe PK, Ibanga HB, Donkor S, Awine T, McShane H, Adegbola RA. The effect
of tuberculin skin test and BCG vaccination on the expansion of PPD-specific IFN- producing cells ex vivo. Vac-
cine 2007 Oct 31; [Epub ahead of print].
81. Cheung YB, Zaman SMA, Ruopuro ML, Enwere G, Adegbola RA, Greenwood B, Cutts FT. C-reactive protein
and procalcitonin in the evaluation of pneumococcal vaccine efficacy in Gambian children. Tropical Medicine &
International Health 2008; (in press)
82. Hill PC, Jackson-Sillah DJ, Fox A, Brookes RH, de Jong BC, Jeffries DJ, Donkor SA, Lugos MD, Adetifa IM, Aiken
AM, Howie SR, Corrah T, McAdam KP, Adegbola RA. Incidence of secondary disease and predictive value of initial
ELISPOT and Mantoux tests in Gambian tuberculosis contacts. PLoS ONE 2008; (in press).
83. Garton NJ, Waddell SJ, Sherratt AL, Smith RJ, Free RC, Senner C, Hinds J, Rajakumar K, Adegbola RA, Besra GS,
Butcher PD, Barer MR. Cytological and transcript analyses reveal fat and lazy persister-like bacilli in tuberculous
sputum. PLoS Medicine 2008; (in press).

Malaria
Programme
This report emphasizes the research

that is targeted towards our core
objectives:
To make a leading contribution to the

Dr David Conway
international understanding of: Head of Malaria Programme
Molecular parasitology,
immunology, and pathogenesis of
severe malaria The current research on malaria was initiated from 2005 onwards as new senior
Targets and mechanisms of research staff joined the unit, leading into the 2006-11 core funded programme.
naturally acquired immunity and Studies that had previously started were successfully completed or continued and
immune regulation some staff who moved on became valued collaborators. The outline below of
recent research activity and achievements also reflects vital input of colleagues
To design and perform with who remained in the unit over this time.
excellence:
We first list projects that involve studies of molecular, cellular and genetic
Efficacy trials of novel preventative mechanisms of disease or immunity, then epidemiological, clinical and
and therapeutic interventions interventional studies.
Effectiveness trials and methods
We also note the training and career development of a new generation of
for delivery of effective
research scientists and clinicians who will make it possible to break new ground in
interventions
understanding and control of malaria. We are particularly pleased for those who
Novel diagnostic and molecular have gained support for postgraduate training at MSc or PhD level or who have
methods that strengthen secured competitive postdoctoral fellowships. These are outlined in the project
intervention trials reports.

Molecular, cellular and genetic mechanisms of disease and
immunity
Invading red cells

The parasite that causes malaria erythrocyte receptors to mediate Isolates for which there is sufficient
can invade blood cells in different alternative pathways of erythrocyte parasite RNA are being assayed for
ways. We are investigating if this invasion. We are conducting a genome wide expression profiles
makes a difference to the type of case control study of severe and using P. falciparum Affymetrix gene
malaria a person suffers. mild malaria cases to study the chips. Analysis is in progress to test
erythrocyte invasion phenotype whether there are clusters of genes
Receptor-ligand interactions profiles from fresh field isolates, the that are associated with disease or
involved in the invasion of associations of these phenotypes with invasion phenotype.
erythrocytes by the malaria parasite with clinical outcome and gene
Plamodium falciparum are central expression profiles.
to its replication and virulence. By
changing the levels of expression Expression profiles of four Rh genes
of some of these ligands, such as and three eba genes are being
the erythrocyte binding antigenic analysed, as well as six merozoite
proteins (eba) and reticulocyte surface associated protein genes
binding protein homologues (RH), (in the msp3 and msp7 gene
cultured adapted parasite lines clusters) and four genes belonging
have been shown to use different to the CLAG/RhopH1 gene family.

Clustering of variable gene expression
profiles among P.falciparum. The
shading shows the degree of variation
in the relative expression of rh and eba
genes that encode alternative invasion
ligands (dark indicates low expression,
light indicates high expression)
Erythrocyte invasion phenotypes and parasite

gene expression in severe and mild malaria cases
Key investigators at MRC Gambia:

Natalia Gomez Escobar, Michael Walther, Alfred Anambua Ngwa, Joseph
Okebe, Augustine Ebonyi
Collaborators:
Celine Carret, Al Ivens (Sanger Institute, UK)
Funding:

Natural immunity
Occasionally, people who are using age-specific prevalences of titres). The frequency of regulatory
continually exposed to malaria antibodies to the malarial antigen T cells was significantly higher in
gradually become immune to the MSP-119. 30 adults were selected the adults from the higher endemic
disease. By looking at how the from each area according to their population of Brefet.
immune system of these people antibody status (donors from
reacts to the malaria parasite we Brefet were selected for their high
hope to better understand the antibody titres to malaria antigens;
disease. donors from Bakau were selected
for their low or absent antibody
To study the association between
Th1/regulatory cell balance and
malaria disease severity, a case-
control study is underway. It uses
cases presenting with severe malaria
and controls with mild malaria at
the paediatric ward of the Royal
Victoria Teaching Hospital, the
outpatient clinic at MRC Fajara,
the Jammeh Foundation for
Peace Hospital (Serrekunda) and
Brikama Health Centre. All subjects
are resident in the Kombo area
(excluding Banjul city and the
coastal strip from Bakau to Bijilo
where malaria transmission is low
or absent). The severe cases are
matched for age (+/- 1 year) to
controls with mild malaria that
present at the outpatient facilities.
We hypothesise that blood from

severe malaria cases contains
more Th1, or fewer regulatory
T cells, than blood from mild
malaria controls. Blood for analysis The number of CD4+CD127low FOXP3+ T cells at the end of the rainy season
of lymphocytes is collected in an area of moderate (Brefet) and low (Bakau) malaria transmission
at admission as well as four
weeks afterwards, when the
immune-homeostasis has been Role of regulatory T cells in immunity to severe
re-established. Currently, we
determine the phenotype, absolute malaria and their distribution in populations of
numbers, and relative proportions
of cells expressing a phenotype
differing endemicity
of regulatory T cells ex vivo using
flowcytometric analysis. We also
attempt to identify the phenotype Key investigators at MRC The Gambia:
of IL-10 and IFN-γ producing cells Michael Walther, Olivia Finney, Natalia Gomez-Escobar, Joseph Okebe,
after short-term re-stimulation Augustine Ebonyi, David Conway
with malarial and control antigens.
A comprehensive analysis of these Collaborators:
data will be performed at the end Eleanor Riley (London School of Hygiene and Tropical Medicine, UK)
of this transmission season.
Funding:
To test for population differences in Medical Research Council
the frequencies of regulatory T cells
that may be induced by malaria,
two communities were studied. The
entomological inoculation rate (EIR,
number of infective bites per year)
was estimated as 0.62 for Brefet (a
rural village in Foni) and 0.014 for
Bakau (an urban town at the coast)

The genes of resistance
Understanding why some people Infinium multiplexed bead array,
are resistant to malaria could help which is optimally configured for
in the search for better treatments experiments of this magnitude.
or a vaccine for the disease. We The genotyping of the controls
are analyzing the genes of people has been carried out as part of
who have experienced severe the Wellcome Trust Case Control
malaria. Consortium [http://www.wtccc.org.
uk/] and genotyping of the cases
DNA and clinical data from 2000 is supported by a Challenges in
cases of severe malaria were Global Health project grant to the
recruited for genetic studies by Dr MalariaGen consortium.
Muminatou Jallow and colleagues
at Royal Victoria Teaching Hospital
over the period 1997-2006, and
appropriate population controls for
a large case-control analysis were
recruited in 2006, yielding 2000
newborn DNA samples (from cord
blood) and 2000 maternal DNA
samples (from mouth brushes).
The samples are being analysed in
the largest study of malaria genetics
to date. Stage 1 is a broad screen
of the whole genome, involving
typing ~ 500,000 SNPs in 1,000
Gambian cases of severe malaria
plus 1,500 ethnically-matched
cord blood controls. These SNPs
have been selected using statistical Muminatou Jallow and team recruited and processed samples for the largest case-
genetic algorithms as the most control study of severe malaria (2000 cases and 4000 population controls)
efficient subset of known SNPs
to capture the overall diversity of
the genome, using data from the A genome-wide screen for malaria
International HapMap Project. Stage
2 will narrow down the analysis resistance genes
to a smaller number of SNPs that
show the strongest evidence of
association in stage 1, which will
be typed in a different set of 1000
Gambian cases of severe malaria,
Muminatou Jallow, David Conway, Giorgio Sirugo, Kalifa Bojang
plus 1000 ethnically-matched
cord blood controls. A high-
Collaborators:
throughput genotyping assay will
Dominic Kwiatkowski, Miguel San Joaquin (Oxford University, UK), Kirk
be developed using the Illumina
Rockett, Anna Richardson
Funding:
Medical Research Council, Wellcome Trust, Foundation of the National
Institutes of Health/Gates Grand Challenges in Global Health programme

Duration of antibody responses
Naturally acquired antibody
responses provide partial
protection from clinical malaria.
Blood stage vaccines under
development aim to prime such
responses.
To investigate the determinants of

antibody response longevity, serum
IgG to several blood stage vaccine
candidate antigens was examined
in two cohorts of children aged up
to 6 years during the dry seasons
of 2003 and 2004 in The Gambia.
The first cohort showed that
most antibodies were lost within
less than four months of the first
sampling, if a persistent infection
was not present. In the second
year cohort samples were taken
from individuals every 2 weeks over
a three month period. Antibody
responses in this cohort were also
influenced by persistent malaria
infection, so analysis focused
particularly on children who did
not have parasites detected after
the first time point. Antibodies to
most antigens declined more slowly
in the oldest age group of children
where children were over five, and
more rapidly in the youngest group
of children which were under three.
However, antibodies to merozoite
surface protein 2 (MSP2) were
shorter-lived and were not more
persistent in older children. The Decline of antibody levels (as % of starting levels that remained) to blood stage
age-specific and antigen-specific malaria antigens through the driest part of the year (February to May) season in
differences were not explained children that were antibody positive but who do not have chronic infections
by different IgG subclass response
profiles. This indicates the probable
importance of differential longevity Duration of naturally acquired antibody
of plasma cell populations rather responses to blood stage Plasmodium falciparum
than antibody molecules.
is age dependent and antigen specific
It is likely that young children mostly
have short-lived plasma cells and
thus experience rapid decline in Key investigators at MRC The Gambia:
antibody levels, while older children Onome Akpogheneta, Nancy Duah, Samuel Dunyo, Margaret Pinder, David
have longer lasting antibody Conway
responses that depend on long-
lived plasma cells. Collaborators:
Kevin Tetteh (London School of Hygiene and Tropical Medicine, UK), David
Lanar (Walter Reed Army Institute of Research, Maryland, USA)
Funding:

Epidemiological, clinical and interventional studies
Prevention of malaria in children

Scientists have found that it is to receive IPT from the trekking end of the malaria transmission
possible to lower the number of team or a village health worker. season in December. The primary
incidences of malaria in children The ITP treatment, with a single end points are the incidence of
by giving them intermittent doses dose of sulfadoxine/pyrimethamine clinical attacks of malaria detected
of antimalarial medication as a plus three doses of amodiaquine, by passive case detection, and
preventative measure. was given to all study subjects at cost-effectiveness of the delivery
monthly intervals from September methods. Important secondary
Antimalarial chemoprophylaxis can to November. In addition, 1040 endpoints will be the coverage and
reduce morbidity and mortality children were randomly selected the equity of coverage of IPT in
from malaria in children. Yet this for cross-sectional survey at the preventing malaria morbidity.
approach to malaria control has
never been widely implemented
because of concerns over its
possible effects on natural immunity
and the development of resistance.
Intermittent preventive treatment
(IPT) may be able to achieve
some of the beneficial effects of
chemoprophylaxis without its
drawbacks.
Recently, it was shown that IPT

given to Senegalese children under
five years of age on three occasions
during the malaria transmission
season reduced the incidence of
clinical malaria by approximately
90%. Despite this success it is
uncertain how such an intervention
Mamkumba Sanneh (Malaria Programme Administrator) coordinates the
can be most effectively and
operational support of clinical trials
sustainably delivered.
Twenty-six reproductive and child
health trekking clinics in Upper Comparison of two strategies for the delivery of
River Division of The Gambia,
south of the River Gambia were intermittent preventative treatment of children
recruited in August 2006. Each
clinic has an average catchment
(IPTc) against malaria in an area of seasonal
population of 400-500 children transmission
under five years of age. The
children were randomly allocated
Kalifa Bojang, Francis Akor
Collaborators:
Lesong Conteh, Paul Milligan, Brian Greenwood (London School of Hygiene
and Tropical Medicine, UK); Saikouna Sanyang (Gambia Government
Department of State for Health District Health Team, Upper River Division);
Ayo Palmer (Centre for Innovation against Malaria, Banjul)
Funding:
Medical Research Council and Gates Malaria Partnership

Treating children with severe malaria
Quinine is still the most widely
used treatment for severe malaria.
However artesunate is considered
to be an excellent drug for the
treatment that may be more
effective.
There have been no large trials of

parenteral artesunate completed
in African children. A randomised
trial conducted in Southeast Asia
has shown that mortality in the
artesunate group was reduced
by about 35% compared to
the quinine group. Most of the
patients in this study were adults
and because of differences in the
disease process between adults
and children, there is uncertainty Severe malaria studies investigators in Fajara
whether the very encouraging
results of this trial can be translated
to Africa, where malaria mainly A multi-centre open label randomised
affects children. Furthermore, comparison of injectable Artesunate and quinine
quinine is cheap, and it is unlikely
that a more expensive anti-malarial in patients with severe falciparum malaria in
agent will replace it without
convincing scientific evidence
Africa
to show reduction in mortality
associated with severe malaria.
Kalifa Bojang, Rasaq Olaosebikan
To answer the question as to
whether parenteral artesunate can
Collaborators:
reduce mortality in severe malaria
Arjen Dondorp, Nick Day, Nick White (Wellcome Trust Unit, Bangkok); Malick
in African children, a large trial to
Njie (Royal Victoria Teaching Hospital, Banjul)
compare the two drugs in around
5,300 patients in several sites in
Funding:
Africa was started in 2005. The
Medical Research Council, Wellcome Trust
trial is powered to detect a 25%
reduction in mortality overall. It is a
simple, open label, comparison of
parenteral quinine versus parenteral
artesunate. The outcome of this
study may determine the future
treatment of severe malaria in
African children. So far over 160
severe malaria patients have been
recruited at the Royal Victoria
Teaching Hospital in Banjul.

New methods for detecting malaria
infection
Slide microscopy has been the parasite DNA in saliva and urine
‘gold standard’ diagnostic method of malaria patients was quantifiable
for malaria for over a hundred by qPCR with density estimates
years, but it presents many being generally higher in saliva than
problems. We are looking at the in the corresponding urine sample
possibility of developing alternative and, on average, respectively ~
methods. 1000 and 5000-fold less than in
the corresponding blood sample.
Quantitative real-time PCR Parasite density estimated by
protocols have been developed qPCR of saliva samples had a
that are more sensitive, specific significant correlation (Rho=0.58)
and faster at the processing of
batches of samples. They may also
be cheaper in overall real costs.
We are evaluating and developing
methods for use in The Gambia,
with the aim of implementing
assays for P. falciparum parasitaemia
measurement for Good Clinical
Laboratory Practice use in clinical
trials.
Recently, it has also been shown

that malaria parasite DNA could be
detected in urine and saliva samples
obtained from patients 24 hours
after slide diagnosis. However, it
is not known if parasite densities
measured in blood, urine and saliva
correlate. We obtained blood,
urine and saliva samples from 386
patients who were ten years of
age and above that were attending
the MRC out-patient clinic with
symptoms of malaria. Parasite DNA
was extracted from blood, saliva
and urine samples of each patient.
Parasite detection and density
estimation was by amplification
of P. falciparum 18s rDNA using
previously described primers.
Saliva-PCR detected 58% of
all microscopy-positive cases,
improving to 82% in samples with
parasite density ≥ 1000/µL while
PCR of urine samples performed
rather poorly, detecting only
24% of positive samples with no
significant increase in sensitivity
at 1000 parasites/µL or higher
parasite density endpoints. The
diagnostic performance of saliva-
PCR, assessed by receiver operating
characteristic (ROC) plots using
microscopic detection as the gold
standard, had an area under the
ROC curve (AUCROC) of 0.79,
for all microscopy-positive samples Receiver Operating Characteristics (ROC) plot showing the diagnostic
increasing to 0.90 at 1000 parasites/ performance of nested PCR of blood, saliva and urine in (A) all microscopy-
µL cut-off. . The concentration of positive cases and (B) patients with parasite density ≥1000 per microlitre

with microscopy parasite counts
while urine-based estimates did not
correlate with microscopy.
The detection of parasite DNA in

saliva samples by PCR appears to
have potential use in the detection
of malaria infection. With the
increasing application of predefined
parasite density cut-off in the case
definition of clinical malaria for
vaccine trials, saliva-PCR could
be used as a marker of clinically-
relevant parasitaemia.
Davis Nwakanma (centre) and colleagues in the laboratory at Fajara
New methodologies for malaria parasite detec-

tion in clinical trials

The Gambia: Davis Nwakanma, David Conway
Collaborators:
Malaria Vaccine Initiative programme officers
Funding:
Malaria Vaccine Initiative, European and Developing Countries Clinical Trial
Partnership, Medical Research Council

Comparing different malaria treatments
Lapdap is a cheap and effective Lapdap and 31% on Coartem did
antimalarial. However, its safety not complete the treatment course.
in anaemic patients has been 5% of children received only the
questioned so we assessed the supervised dose and these children
safety and effectiveness of Lapdap were at increased risk of treatment
for treatment of malaria in failure.
children in The Gambia.
Coartem was found to be more
1238 children aged 6 months effective than Lapdap, but there
to 10 years with uncomplicated was no evidence that Lapdap
malaria were randomized to caused anaemia in G6PD deficient
receive Lapdap or Coartem and children. Combining artesunate
then followed for 28 days. The with Lapdap may be expected to
first dose was supervised, with reduce the anaemia associated with
subsequent doses to be given parasitaemia by achieving more
unsupervised at home. G6PD rapid parasite clearance.
genotype was determined to assess
the interaction between treatment
and G6PD status and their effects
on anaemia.
The main endpoints were clinical

treatment failure by day 28,
incidence of severe anaemia and
haemoglobin concentration on day
3. There were 44 serious adverse
events - 33 in the Lapdap group
and 11 in the Coartem group -
including 13 severe malaria cases
(11 Lapdap, 2 Coartem) and 23
severe anaemia (17 Lapdap, 6
Coartem). Overall, 18% of children
treated with Lapdap and 6.1%
with Coartem required rescue Local drama group performing a skit about malaria at the programme’s retreat in
medication within 4 weeks, risk Walikunda
difference 12% (95%CI 8.9%-16%).
Haemoglobin concentration
on day 3 was lower among
Randomised trial of safety and effectiveness of
children treated with Lapdap than chlorproguanil-dapsone (Lapdap) compared to
Coartem, and was lower among
G6PD-deficient than G6PD- lumefantrine-artemether (Coartemether) for
normal children, but there was no uncomplicated malaria in children in the Gambia
evidence of an interaction between
treatment drug and G6PD status
in their effects on haemoglobin Key investigators at MRC The Gambia:
concentration. 9% of children on Samuel Dunyo, Giorgio Sirugo, Sanie Sesay, Cyrille Bisseye, Fanta Njie,
Majidah Adiamoh, Davis Nwakanma, Mathurin Diatta, Fatoumatta Sisay-Joof,
Ramatoulie Janha, Robert Walton, Paul Snell, David Conway, Paul Milligan
Collaborators:
Beth Temple, Yin Bun Cheung (London School of Hygiene and Tropical
Medicine, UK); Omar Sey (AFPRC Hospital, Farafenni).
Funding:

Evolving mosquitos
Studying the genetics of the S-form in areas east of The
mosquitoes which carry the Gambia). Analysis of the samples
malaria parasite is important. A collected during the 2006 rainy
survey has first identified which of season is ongoing.
the malaria transmitting mosquito
species is more common, where
and when, so that intervention
efforts can be more precisely
targeted.
The three important malaria

vector species in The Gambia,
A. gambiae sensu stricto (ss),
A. arabiensis and A. melas are
morphologically indistinct members
of the A. gambiae sensu lato
species complex. Their ecology
and contribution to transmission
of the disease varies greatly, and
differs throughout the year. The
most anthropophilic species, A.
gambiae ss is dominant in the
rainy season (the major malaria
transmission season). A. arabiensis
is more adapted to drier conditions,
whereas A. melas can breed
throughout the year in saline water
on the edge of the tidal part of the
river. It has recently become clear
that the most important vector
species, Anopheles gambiae ss,
is undergoing incipient speciation
(with major molecular forms ‘M’
and ‘S’), and that ecologically
important adaptive inversions
Musa Jawara
appear to be genetically restricted
within these forms.
During the beginning of the 2005 Molecular ecology and genetics of malaria vectors
dry season (October–November) in The Gambia and Senegal
and in the 2006 rainy season
(August-September) we conducted
two cross sectional entomological
surveys covering an east to west
transect from the coastal region of
The Gambia to eastern Senegal. Key investigators at MRC:
Results from the October- Davis Nwakanma, Musa Jawara, Majidah Adiamoh, David Conway
November 2005 collections show
that the A. gambiae S molecular Collaborators:
form was found in eastern Senegal Beniamino Caputo, Alessandra della Torre (University of Rome);
and at low frequency in most Ebraima Dia, Lassana Konate (Institut Pasteur and University Cheikh Anta
of The Gambia. The S-form Diop, Dakar); Steve Lindsay, Clare Green (University of Durham)
individuals from eastern Senegal
have a high frequency of 2Rj Funding:
chromosomal inversion (~30%) FNIH/Gates Grand Challenges in Global Health programme
that is rare elsewhere. The M-form
predominates in The Gambia, but
has unexpectedly high frequencies
of 2Rb chromosomal inversion, in
some cases associated with 2Rd
inversion (karyotypes typical of

Keeping mosquitos away
Killing mosquito larvae and substantially reduce exposure to
keeping the insects out of House screening against mosquitoes malaria vectors. The haemoglobin
Gambian homes using screens are has the potential benefit of status of children sleeping in the
being tested for their potential protecting everyone sleeping houses at the end of each of two
effect against malaria. inside, avoiding issues of inequity transmission seasons is being
within a household, but has not compared with those in unscreened
After two years of studying the yet been tested for effectiveness houses. The acceptability of
ecology of mosquitoes and their in Africa. A randomised-controlled the interventions is also being
breeding sites and mapping trial is being conducted over 2 assessed through focus groups and
their spatial distribution, a large years in 500 homes in Farafenni questionnaires. Experimental hut
scale programme of larviciding town and surrounding villages to studies are being used to determine
using Bti (Bacillus thuringiensis assess whether (i) net screening of whether any additional benefit can
israelensis) started in 2006 (June windows and doors or (ii) installing be achieved by impregnating torn
to November). Larviciding was net ceilings to local houses can screens with insecticide.
conducted in two (Zones 1 and
3) of the four study zones east of
Farafenni while the other zones (2
and 4) served as controls.
The results show that where

larvicides were sprayed, the number
of sites positive with mosquito
larvae dropped consistently, with
no late instar larvae found in any
sprayed site. The average number
of larvae/dip in treated zones was
reduced to zero while it remained
at 0.5 and 0.3 larvae/dip in the two
non-treated zones. Reduction in
adult mosquito density in houses
was observed in one of the treated
zones but no marked reduction
could be observed in the other
treated zone. Larviciding will start
again in the 2007 transmission A trial of prevention of mosquito vector entry by screening eaves, windows and
season in zones 2 and 4 while doors of houses in Farafenni (STOPMAL project)
zones 1 and 3 will not be sprayed
and will serve as control (a cross-
over design). Malaria endpoints are Entomological interventions: Larval control
being measured in sentinel cohorts
to test for an impact on malaria project (LCP) and screening houses to prevent
incidence and prevalence. malaria (STOPMAL)

Samuel Dunyo, David Ameh, Musa Jawara
Collaborators:
Matt Kirby, Silas Majambere, Clare Green, Rob Hutchinson, Margaret Pinder,
Steve Lindsay (University of Durham, UK); Paul Milligan (London School of
Hygiene and Tropical Medicine, UK)
Funding:
National Institutes of Health, Medical Research Council

Monitoring malaria incidence
Increased support for malaria
prevention in The Gambia,
particularly insecticide treated
net coverage and intermittent
preventative treatment of
pregnant women, has been
provided since 2003 by the Global
Fund and by UNICEF and WHO.
Retrospective analysis was

performed on numbers and
proportions of malaria inpatients,
deaths, and malaria positive blood
slides at MRC Fajara over an eight-
year period (April 1999 to March
2007), and at other health facilities
(Brikama, Sibanor, Keneba, and Proportions of slides that were malaria positive at the Outpatients Department of
Farafenni) over a six-year period MRC Fajara over the 8 year period 1999-2006. The small bars around the points
(April 2001 to March 2007). An show the 95% confidence intervals of the estimates (117,917 slides in total were
unprecedented large decline in the examined).
highly seasonal number of inpatient
admissions and deaths attributed
to malaria, and malaria positive A recent decline in the incidence of malaria at
slides, has occurred in each of
three successive years since 2003. health facilities in The Gambia
The mean age of malaria cases has
increased since 2004 at the site
where data on age of children were
available (MRC Fajara).
To test for recent transmission, Key investigators at MRC Gambia:

antibodies to malaria antigens were Serign Ceesay, Climent Casals-Pascual, Nancy Duah, Anthony Fulford, Sanie
measured in a cohort of children Sesay, Ismaela Abubakar, Samuel Dunyo, Tumani Corrah, Kalifa Bojang, Hilton
born in 2003-4 and followed until Whittle, David Conway.
3 years of age. Most of the children
had made no detectable malaria Collaborators:
antibody response by three years Jamie Erskine (WEC Clinic, Sibanor); Samuel Anya, Ayo Palmer (CIAM), Malang
of age. This reduced incidence of Fofana (National Malaria Control Programme, The Gambia), Brian Greenwood
malaria was most pronounced in (London School of Hygiene & Tropical Medicine, UK)
the Western Region, and followed
increased implementation of malaria Funding:
prevention. Lower exposure to Medical Research Council
infection may be reducing the
level of acquired immunity in the
population, leading to an age shift in
cases of clinical malaria.
Close epidemiological surveillance
is now required to know the
extent of reduction in malaria
cases throughout the country and
in neighbouring countries, and
to detect any adverse changes
that could result from unstable
endemicity.

Malaria Programme: Postgraduate studentship & postdoctoral fellowship
awards
Dr Sanie Sesay
studying for MSc Epidemiology (LSHTM) by distance learning
Dr Augustine Ebonyi
Dr Muminatou Jallow
Dr Joseph Okebe
studying for MSc in Public Health (LSHTM) by distance learning
Nancy Duah
studying for PhD (LSHTM) on ‘Determinants and effects of different antibody isotype responses to malaria’
Olivia Finney
studying for PhD (LSHTM) on ‘The role of regulatory T cells in natural immunity to P. falciparum’
Ian Cheeseman
studying for PhD (LSHTM) on ‘Analysis of gene deletion and copy number polymorphisms in clinical and in vitro cultured
isolates of Plasmodium falciparum’.
Dr Abraham Oduro
studying for PhD (LSHTM) on ‘Measuring changes in the epidemiology of malaria in The Gambia’
Dr Davis Nwakanma
EDCTP Senior Research Fellow supported for ‘Development and evaluation of molecular methods of malaria parasite detection
in clinical trials’
Majidah Adiamoh
studying for MSc in Biomedical Sciences (Queens University Belfast) by distance learning
Malaria Programme: Publications

(only included if the MRC Gambia is an author’s primary address and it is clear that the publication is not mainly on research done
elsewhere – other publications of members of staff relating to non-MRC work are not included here)
2004
01. Burton M, Nyong’o O, Burton K, John W, Inkoom E, Pinder M, Corrah T, Johnson G, Bailey R. (2004) Retinopathy
in Gambian children admitted to hospital with malaria. Trop Doct.34:214-8.
02. Moorthy VS, Imoukhuede EB, Milligan P, Bojang K, Keating S, Kaye P, Pinder M, Gilbert SC, Walraven G,
Greenwood BM, Hill AS. (2004) A randomised, double-blind, controlled vaccine efficacy trial of DNA/MVA ME-
TRAP against malaria infection in Gambian adults. PLoS Med. 1:e33.
03. Moorthy VS, Imoukhuede EB, Keating S, Pinder M, Webster D, Skinner MA, Gilbert SC, Walraven G, Hill AV.
(2004) Phase 1 evaluation of 3 highly immunogenic prime-boost regimens, including a 12-month reboosting
vaccination, for malaria vaccination in Gambian men. J Infect Dis.189:2213-9.
04. Reece WH, Pinder M, Gothard PK, Milligan P, Bojang K, Doherty T, Plebanski M, Akinwunmi P, Everaere S,
Watkins KR, Voss G, Tornieporth N, Alloueche A, Greenwood BM, Kester KE, McAdam KP, Cohen J, Hill AV.
(2004) A CD4(+) T-cell immune response to a conserved epitope in the circumsporozoite protein correlates with
protection from natural Plasmodium falciparum infection and disease. Nat Med. 10:406-10.
05. Pinder M, Reece WH, Plebanski M, Akinwunmi P, Flanagan KL, Lee EA, Doherty T, Milligan P, Jaye A, Tornieporth

Publications
N, Ballou R, McAdam KP, Cohen J, Hill AV. (2004) Cellular immunity induced by the recombinant Plasmodium
falciparum malaria vaccine, RTS,S/AS02, in semi-immune adults in The Gambia. Clin Exp Immunol.135:286-93.
06. Drakeley CJ, Jawara M, Targett GA, Walraven G, Obisike U, Coleman R, Pinder M, Sutherland CJ. (2004) Addition
of artesunate to chloroquine for treatment of Plasmodium falciparum malaria in Gambian children causes a
significant but short-lived reduction in infectiousness for mosquitoes. Trop Med Int Health. 9:53-61.
2005
07. Sutherland CJ, Ord R, Dunyo S, Jawara M, Drakeley CJ, Alexander N, Coleman R, Pinder M, Walraven G,
Targett GA. (2005) Reduction of malaria transmission to Anopheles mosquitoes with a six-dose regimen of co-
artemether. PLoS Med 2:e92.
08. Tetteh KK, Cavanagh DR, Corran P, Musonda R, McBride JS, Conway DJ. (2005) Extensive antigenic polymorphism
within the repeat sequence of the Plasmodium falciparum merozoite surface protein 1 block 2 is incorporated in a
minimal polyvalent immunogen. Infect Immun. 73:5928-35.
09. Bojang KA, Olodude F, Pinder M, Ofori-Anyinam O, Vigneron L, Fitzpatrick S, Njie F, Kassanga A, Leach A, Milman
J, Rabinovich R, McAdam KP, Kester KE, Heppner DG, Cohen JD, Tornieporth N, Milligan PJ. (2005) Safety and
immunogenicty of RTS,S/AS02A candidate malaria vaccine in Gambian children. Vaccine. 23:4148-57.
10. Meerman L, Ord R, Bousema JT, van Niekerk M, Osman E, Hallett R, Pinder M, Walraven G, Sutherland CJ. (2005)
Carriage of chloroquine-resistant parasites and delay of effective treatment increase the risk of severe malaria in
Gambian children. J Infect Dis. 192:1651-7.
11. Ackerman H, Usen S, Jallow M, Sisay-Joof F, Pinder M, Kwiatkowski DP. (2005) A comparison of case-control and
family-based association methods: the example of sickle-cell and malaria. Ann Hum Genet. 69:559-65.
12. Wilson JN, Rockett K, Jallow M, Pinder M, Sisay-Joof F, Newport M, Newton J, Kwiatkowski D. (2005) Analysis of
IL10 haplotypic associations with severe malaria. Genes Immun. 6:462-6.
13. Koch O, Rockett K, Jallow M, Pinder M, Sisay-Joof F, Kwiatkowski D. (2005) Investigation of malaria susceptibility
determinants in the IFNG/IL26/IL22 genomic region. Genes Immun. 6:312-8.
14. Greenwood BM, Bojang K, Whitty CJ, Targett GA. (2005) Malaria. Lancet. 365:1487-98.
2006
15. Dunyo S, Milligan P, Edwards T, Sutherland C, Targett G, Pinder M. (2006) Gametocytaemia after Drug Treatment
of Asymptomatic Plasmodium falciparum. PLoS Clin Trials 1:e20
16. Dunyo S, Ord R, Hallett R, Jawara M, Walraven G, Mesa E, Coleman R, Sowe M, Alexander N, Targett GA, Pinder
M, Sutherland CJ. (2006) Randomised Trial of Chloroquine/Sulphadoxine-Pyrimethamine in Gambian Children
with Malaria: Impact against Multidrug-Resistant P. falciparum. PLoS Clin Trials 1:e14
17. Hallett RL, Dunyo S, Ord R, Jawara M, Pinder M, Randall A, Alloueche A, Walraven G, Targett GA, Alexander N,
Sutherland CJ. (2006) Chloroquine/Sulphadoxine-Pyrimethamine for Gambian Children with Malaria: Transmission
to Mosquitoes of Multidrug-Resistant Plasmodium falciparum. PLoS Clin Trials 1:e15
18. Mbaye A, Richardson K, Balajo B, Dunyo S, Shulman C, Milligan P, Greenwood B, Walraven G. (2006) A
randomized, placebo-controlled trial of intermittent preventive treatment with sulphadoxine-pyrimethamine in
Gambian multigravidae. Trop Med Int Health 11:992-1002.

Publications
19. Mbaye A, Richardson K, Balajo B, Dunyo S, Shulman C, Milligan P, Greenwood B, Walraven G. (2006) Lack of
inhibition of the anti-malarial action of sulfadoxine-pyrimethamine by folic acid supplementation when used for
intermittent preventive treatment in Gambian primigravidae. Am J Trop Med Hyg 74:960-4.
20. Imoukhuede EB, Berthoud T, Milligan P, Bojang K, Ismaili J, Keating S, Nwakanma D, Keita S, Njie F, Sowe M,
Todryk S, Laidlaw SM, Skinner MA, Lang T, Gilbert S, Greenwood BM, Hill AV. (2006) Safety and immunogenicity
of the malaria candidate vaccines FP9 CS and MVA CS in adult Gambian men. Vaccine 24:6526-33.
21. Newton PN, McGready R, Fernandez F, Green MD, Sunjio M, Bruneton C, Phanouvong S, Millet P, Whitty
CJ, Talisuna AO, Proux S, Christophel EM, Malenga G, Singhasivanon P, Bojang K, Kaur H, Palmer K, Day NP,
Greenwood BM, Nosten F, White NJ. (2006) Manslaughter by fake artesunate in Asia--will Africa be next? PLoS
Med. 3:e197.
22. Simpson JA, Hughes D, Manyando C, Bojang K, Aarons L, Winstanley P, Edwards G, Watkins WA, Ward S. (2006)
Population pharmacokinetic and pharmacodynamic modelling of the antimalarial chemotherapy chlorproguanil/
dapsone. Br J Clin Pharmacol. 61:289-300.
23. Jukes MC, Pinder M, Grigorenko EL, Smith HB, Walraven G, Bariau EM, Sternberg RJ, Drake LJ, Milligan P, Cheung
YB, Greenwood BM, Bundy DA. (2006) Long-Term Impact of Malaria Chemoprophylaxis on Cognitive Abilities
and Educational Attainment: Follow-Up of a Controlled Trial. PLoS Clin Trials. 1:e19
24. Walther M. Advances in vaccine development against the pre-erythrocytic stage of Plasmodium falciparum malaria.
(2006) Expert Rev Vaccines. 5:81-93.
25. Bojang KA. (2006) RTS,S/AS02A for malaria. Expert Rev Vaccines. 5:611-5.
26. Pinder M, Sutherland CJ, Sisay-Joof F, Ismaili J, McCall MB, Ord R, Hallett R, Holder AA, Milligan P. (2006)
Immunoglobulin G antibodies to merozoite surface antigens are associated with recovery from chloroquine-
resistant Plasmodium falciparum in Gambian children. Infect Immun. 74:2887-93.
27. Olola CH, Missinou MA, Issifou S, Anane-Sarpong E, Abubakar I, Gandi JN, Chagomerana M, Pinder M, Agbenyega
T, Kremsner PG, Newton CR, Wypij D, Taylor TE; SMAC Network. (2006) Medical informatics in medical
research - the Severe Malaria in African Children (SMAC) Network’s experience. Methods Inf Med. 45:483-91.
28. Lee EA, Flanagan KL, Minigo G, Reece WH, Bailey R, Pinder M, Hill AV, Plebanski M. (2006) Dimorphic
Plasmodium falciparum merozoite surface protein-1 epitopes turn off memory T cells and interfere with T cell
priming. Eur J Immunol. 36:1168-78.
29. Taylor T, Olola C, Valim C, Agbenyega T, Kremsner P, Krishna S, Kwiatkowski D, Newton C, Missinou M, Pinder
M, Wypij D. (2006) Standardized data collection for multi-center clinical studies of severe malaria in African
children: establishing the SMAC network. Trans R Soc Trop Med Hyg. 100:615-22.
30. Panter-Brick C, Clarke SE, Lomas H, Pinder M, Lindsay SW. (2006) Culturally compelling strategies for behaviour
change: a social ecology model and case study in malaria prevention. Soc Sci Med. 62:2810-25.
2007
31. Polley SD, Tetteh KK, Lloyd JM, Akpogheneta OJ, Greenwood BM, Bojang KA, Conway DJ. (2007) Plasmodium
falciparum merozoite surface protein 3 is a target of allele-specific immunity and alleles are maintained by natural
selection. J Infect Dis. 195:279-87.
32. Weedall GD, Preston BM, Thomas AW, Sutherland CJ, Conway DJ. (2007) Differential evidence of natural
selection on two leading sporozoite stage malaria vaccine candidate antigens. Int J Parasitol. 37:77-85.
33. Conway DJ. (2007) Molecular epidemiology of malaria. Clin Microbiol Rev. 20:188-204.

Publications
34. Conteh L, Stevens W, Wiseman V. (2007) The role of communication between clients and health care providers:
implications for adherence to malaria treatment in rural Gambia. Trop Med Int Health. 12:382-91.
35. Walther B, Walther M. (2007) What does it take to control malaria? Ann Trop Med & Parasitol. 101: 657-672.
36. Gray, J.C., Corran, P.H., Mangia, E., Gaunt, M.W., Li, Q., Tetteh, K.K.A., Polley, S.D., Conway, D.J., Holder, A.A., Anders,
R.A., Bacarese-Hamilton, T., Riley, E.M. & Crisanti, A. (2007) Profiling the antibody immune response against blood
stage malaria vaccine candidates. Clin Chem, 53: 1244-1253.
37. The Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven
common diseases and 3,000 shared controls. Nature, 447: 661-678 doi:10.1038/nature05911
38. Nwakanma, D., Kheir, A., Sowa, M., Dunyo, S., Jawara, M., Milligan, P., Walliker, D., Babiker, H.A. (2007) High
gametocyte complexity and mosquito infectivity of Plasmodium falciparum in The Gambia. Int J Parasitol in press.
39. Hanchard, N., Elsein, A., Trafford, C., Rockett, K., Pinder, M., Jallow, M., Harding, R., Kwiatkowski, D., McKenzie, C.
(2007) Classical beta-globin sickle haplotypes exhibit a high degree of long-range haplotype similarity in African and
Afro-Caribbean populations. BMC Genetics 8:52
40. Bogh, C., Lindsay, S.W., Clarke, S.E., Dean, A., Jawara, M., Pinder, M., Thomas, C.J. (2007) High spatial resolution
mapping of malaria transmission risk in The Gambia, West Africa, using LANDSAT TM satellite imagery. Am J Trop
Med Hyg 76: 875-881.
41. Wiseman, V., Scott, A., McElroy, B., Conteh, L., Stevens, W. (2007) Determinants of bed net use in The Gambia:
implications for malaria control. Am J Trop Med Hyg 76:830-836.
42. Conteh, L., Stevens, W., Wiseman, V. (2007) The role of communication between clients and health care providers:
implications for adherence to malaria treatment in rural Gambia. Trop Med Int Health 12: 382-391.
43. Imoukhuede, E.B., Andrews, L., Milligan, P., Berthoud, T., Bojang, K., Nwakanma, D., Ismaili, J., Buckee, C., Njie, F., Keita,
S., Sowe, M., Lang, T., Gilbert, S.C., Greenwood, B.M., Hill, A.V.S. (2007) Low level malaria infections detected by a
sensitive polymerase chain reaction assay and use of this technique in the evaluation of malaria vaccines in an endemic
area. Am J Trop Med Hyg 76: 486-493.
44. Coulibaly, M.B., Pombi, M., Caputo, B., Nwakanma, D., Jawara, M., Konate, L.,, Dia, D., Fofana, A., Kern, M., Simard, F.,
Conway, D.J., Petrarca, V., della Torre, A. Traoré, S. & Besansky, N.J. PCR-based karyotyping of Anopheles gambiae
inversion 2Rj identifies the BAMAKO chromosomal form. Malaria Journal 6:133. doi:10.1186/1475-2875-6-133
45. Akpogheneta OJ, Duah NO, Tetteh KK, Dunyo S, Lanar DE, Pinder M, Conway DJ. Duration of naturally acquired
antibody responses to blood stage Plasmodium falciparum is age dependent and antigen specific. Infect Immun. in
press.
46. Kirby MJ, Green C, Milligan PM, Sismanidis C, Jasseh M, Conway DJ, Lindsay SW. Risk factors for house-entry by
malaria vectors in a rural town and satellite villages in The Gambia. Malaria J. in press.
47. Ndugwa RP, Ramroth H, Mueller O, Jasseh M, Sie A, Kouyate B, Greenwood B, Becher H. Comparison of all-cause
and malaria-specific mortality from two West African countries with different malaria transmission patterns. Malaria J.
in press.
48. Ord R, Alexander N, Dunyo S, Hallett R, Jawara M, Targett G, Drakeley CJ, Sutherland CJ. (2007) Seasonal carriage of
pfcrt and pfmdr1 alleles in Gambian Plasmodium falciparum imply reduced fitness of chloroquine-resistant parasites. J
Infect Dis. 196:1613-9.

Viral Diseases
Programme
Prof Sarah Rowland-Jones

Director of Research, Head of Viral Diseases
Programme
The Viral Diseases Programme Ireland, Marianne van der Sande

(VDP) has been through a number from Amsterdam, Steve Kaye from
of changes in the past few years, London, David Miles from Malawi,
particularly in its scientific team. Akram Zaman from the UK and
Senior scientists appointed since Jerome Feldmann from France.
2004 include Sarah Rowland-Jones Continued senior support has come
(Head of VDP), Katie Flanagan from Assan Jaye (immunologist).
(infant immunology) and Matt
Cotten (virologist). Coming In addition several excellent PhD
into international posts in 2007 students have been working in the
were Thushan Da Silva (clinical programme, two of whom (Melody
training fellow) and Maimuna Duvall and Beatrice Ondondo)
Mendy (hepatitis virologist). Senior have successfully defended their
staff who left during this period theses in recent times, whilst a third
continue to collaborate with the (Victor Nuvor) will submit shortly.
programme: Sam McConkey from

However, some things never characterised patient cohorts, some
The major theme of the Viral change and the VDP continues of which have been followed for
Diseases Programme remains to benefit from the wisdom and 15 to 20 years. These include the
the study of host-pathogen insights of Hilton Whittle (Emeritus Fajara Genito-Urinary Medicine
interactions that are clinically Scientist), who celebrated his 70th Clinic cohort, the Caio (Guinea
relevant to The Gambia. birthday in 2006. Bissau) cohort and the Gambia
Studies fall into the following Hepatitis Intervention Studies
broad categories: Chlamydia and trachoma research cohort.
was incorporated into the Viral
Retrovirology: HIV-1, Diseases Programme’s research
HIV-2 and HTLV-1 portfolio, following the re-
infection organisation of the Unit in 2003.
Infant immunology: Trachoma, caused by Chlamydia
infections and trachomatis, is the most important
vaccinations of early life infectious cause of blindness. It
Hepatitis B infection, affects 150 million people in 48
hepatocellular carcinoma countries, 6 million of whom are
and their prevention blind (Thylefors, Negrel et al. 1995;
Mabey, Solomon et al. 2003). The
Chlamydia and trachoma
Chlamydia programme is led by
research
Professors David Mabey and Robin
Bailey in the London School of
Hygiene and Tropical Medicine
(UK), together with Dr Martin
Holland, who leads the work on the
ground in The Gambia.
The Viral Diseases Programme

benefits from several well-

Retrovirology: HIV-1 and HIV-2 infection
HIV Immunology
The primary goal of the HIV immunology work in MRC is to understand the underlying immunological mechanisms contributing
to long-term non-progression in HIV-2 infection. Epidemiological studies in The Gambia and Guinea-Bissau have shown that the
majority of HIV-2 infected people remain healthy, whilst a minority progress in a manner indistinguishable from HIV-1 infection.
A better understanding of the protective mechanisms underlying non-progression in HIV-2 infection would help in the rational
design of HIV vaccines and immunotherapy.
Many of our studies involve comparing cell mediated (cytotoxic, T helper and NK innate) immune responses between HIV-1 and
HIV-2 infections. We have been building on these comparative immunological studies, utilising both the MRC Clinical and Caio
Community cohorts in The Gambia and Guinea Bissau respectively, to investigate further the characteristics and quality of cellular
responses in HIV-2 infection.
Potent immune responses to HIV-2 infection

The way the immune system cytometry have extended these targeting of various Gag peptides
responds to HIV-2 infection may findings to show much more in HIV-1 and HIV-2 infected
help us understand protective polyfunctional CD4+ and CD8+ individuals, but certain Gag peptides
immunity to HIV. T-cell responses in HIV-2 compared were frequently targeted by both
to HIV-1 infection. HIV-1 and HIV-2 infected people
Individuals infected with HIV-2 (Fig 2). These could represent
have a higher number of virus In a parallel study, a comprehensive cross-reactive responses that may
fighting cells in the blood than those 20-mer peptide mapping by protect against divergent strains of
infected with HIV-1. Our studies Matrix Elispot was done to HIV, and hence such peptides may
have found that in cases of HIV-2 identify the frequently targeted, be important in HIV vaccine design.
these cells are more potent in immunodominant and cross reactive
fighting infection than they do in the responses in HIV-2 infection.
cases in HIV-1. Results indicated differential
HIV infects CD4 T cells and yet

preservation of functional CD4
T cells is key to efficient immune
control of viral replication. We
sought to compare the quality of
CD4 T cell responses in the two
retroviral infections, HIV-1 and
HIV-2. Our data showed that in
individuals with a CD4 count within
normal limits (>28%), there was a
significantly greater proportion of
HIV-2 specific CD4+ T cells that
produced IFNγ (p=0.0160) and IL-2
(p=0.0075) compared with HIV-1
infected individuals (Fig. 1). At CD4
counts <28%, differences between
HIV-1 and HIV-2 infection were no
longer seen. We also detected a
population of HIV-2 specific CD4+
T cells that produced both IFNγ
and IL-2, which was absent in all
HIV-1 infected individuals studied
(p=0.0005) and the frequency of
these polyfunctional CD4 T cells
correlated with the proliferative
capacity of HIV-2 specific CD4
Figure 1. A subset of HIV-2-specific CD4+ T cells produces both IFN-g and IL-2
T cells. Further studies in the
NIH using multiparameter flow

Figure 2. Frequency, breadth, magnitude and cross-reactivity of Gag-specific IFN-γ responses in HIV-1 (top) and HIV-2
(bottom) infected individuals. Various colours as indicated represent the different Gag peptide sequences. It can be seen
that HIV-2 elicits stronger and broader T-cell responses than HIV-1 but several regions of the gag protein are targeted in
both infections.
Analysis of CD4+ T helper responses in

HIV-1 and HIV-2
Key Investigators at MRC The Gambia:

Beatrice Ondondo, Matthew Cotten, Hilton Whittle, Sarah Rowland-Jones,
Assan Jaye, David Jeffries, Sarah Crozier
Collaborators:
Melody Duvall, Rick Koup, Vaccine Research Centre, NIH, USA; Lucy Dorrell,
Tao Dong, MRC Human Immunology Unit, Oxford University.
Funding:

How do T-cells control HIV-2 infection?
An upgraded laboratory in the gene products was carried out most frequent target (recognized
village of Caio in Guinea Bissau to identify and characterise T cell by 87.5% of patients, (Table 1)
is enabling us to identify which responses in members of a well- and found that the magnitude of
immune responses help to control described HIV-2 community cohort Gag-specific immune responses was
HIV-2 infection. in Caio, Guinea Bissau. This major strongly inversely correlated with
study encouraged the upgrading HIV-2 plasma viral load (p=0.001).
HIV-specific CD8+ T cells play of the Caio ‘bush’ laboratory to a Fine mapping of antigen-specific
an important role in controlling modern facility where cells can now immune responses revealed that the
viral infections by destroying be processed and cultures grown most frequently recognized peptides
virus-infected cells. They may also and tested in assays such as Elispot were clustered in a highly conserved
contribute to the superior control and flow cytometry. This is a major region of the capsid component of
of viral replication in the long-term development from the period when HIV-2 Gag, suggesting that immune
non-progression characteristic of samples had to be transported for responses to this part of the viral
the majority of people with HIV-2 long distances across borders to proteome are a strong marker
infection. carry out the assays at the MRC for control of HIV-2 viraemia.
Fajara site. Qualitative characteristics of such
Similar to the CD4 mapping, a responses are currently being
comprehensive mapping of shorter The testing of CD8+ T cell investigated.
peptides (15-mers) from all HIV-2 responses identified Gag as the
Table 1.
Analysis of CD8+ T cell responses in HIV-2

infection

Aleks Leligdowicz, Sarah Rowland-Jones, Assan Jaye, Hilton Whittle, Matthew
Cotten, Tim Vincent
Collaborators:
Peter Aaby – Bandim Health Project, Guinea Bissau; Tao Dong – MRC Human
Immunology Unit, Oxford
Funding:

HIV-2 and longer life
Diffferences in the immune the activating receptors tested
response between HIV-1 and following stimulation of PBMC
HIV-2 infected patients may with K562 cells, expression of
determine why patients infected NKp44 and NKp46 receptors were
with HIV-2 are more likely to live greater in HIV-2 than in HIV-1
longer than those infected with asymptomatic subjects with CD4
HIV-1. counts >500 cells/ul (p=0.029 and
p=0.032 respectively). Expression
NK cells exert antiviral activity early of the Inhibitory receptor p70
in infection and we postulated was, however, greater in HIV-1
that superior NK cell functional than in HIV-2 infection (p=0.010).
activity early in HIV-2 infection We detected no differences in
could underlie the better clinical expression of the activating receptor
course in most infected people. NKp30 or the inhibitory receptors
We showed that effector function CD158a and CD158b. Work is in
of NK cells is more efficient in progress to assess expression of
asymptomatic HIV-2 than HIV-1 the ligands for NK receptors on
infected subjects and then wanted CD4 T cells in both infections and
to explore whether differential to examine direct cytolytic activity
expression of NK receptors may of NK cells on autologous infected
explain these findings. Amongst CD4 T cells.
Examination of Activating and Inhibitory

Receptor expression by NK Cells in HIV-1
and HIV-2 infections

Victor Nuvor, Hilton Whittle, Sarah Rowland-Jones, Assan Jaye, Matthew
Cotten, Sarah Crozier
Collaborators:
Tao Dong - Human Immunology Unit, Oxford University, Prof Edward Barker
- Department of Microbiology and Immunology, Upstate Medical University,
USA, Dr Domenico Mavilio – NIH, USA
Funding:

Treatment complications
Complications sometimes arise is thought to result from compatible with IRIS. We have
in patients taking antiretroviral paradoxical immune responses developed software to facilitate
therapy for HIV infection. We against previously unrecognised standardized flow cytometric gating
are investigating what happens in pathogens. We postulated that this of T reg markers, are reviewing
the syndrome ‘IRIS’, a common syndrome results from a delayed charts for a final classification, and
complication of therapy in Africa. reconstitution of T regulatory aim to do an interim analysis later
cells (T regs) relative to T effector this year.
MRC collaborated with the Gambia cells. Our primary objectives
Government to initiate the roll out were to identify prospectively the
of anti-retroviral therapy (ART) in occurrence of IRIS among patients
2004 with funding from the Global starting ART and determine the
Fund to fight HIV, TB and malaria. time-course of T reg reconstitution
As part of our studies to understand on therapy, comparing those who
the immunopathogenesis of HIV develop the syndrome and those
infection, we used the opportunity who do not. The study aims to
to study the immunological recruit 70 HIV patients starting ART
basis of Immune Reconstitution at 5 time points over 6 months.
Inflammatory Syndrome (IRIS) Participants who develop symptoms
in patients starting ART in the are examined and the frequency of
MRC clinic. IRIS occurs in 10-25% Treg cells is assessed by both flow
of people between 2 and 8 cytometry and RT-PCR. Among 55
weeks of starting antiretroviral patients recruited thus far, 22 have
therapy (ART) and the syndrome developed symptoms potentially
The role of T regulatory cells in the

immune reconstitution inflammatory
syndrome

Bouke de Jong, Irfan Zaidi, Assan Jaye, Kevin Peterson, Sarah Rowland-Jones,
Hilton Whittle, David Jeffries, Sarah Crozier, Akum Aveika
Funding:

HIV virology
Significant similarities in the response to therapy

A comparison of HIV-1 and HIV-2 both. The study has completed
infected patients during the first enrollment of 30 participants
year of treatment has found who have been followed for
similarities in the fall of virus more than one year. Preliminary
numbers. analysis indicates that in those with
advanced immunosuppression
The rate of replication and the first-phase rapid decline after
clearance of viruses can be anti-retroviral treatment of HIV-2
estimated in studies of viral kinetics is very similar to that of HIV-1.
in the blood following the start of This has major implications for our
anti-retroviral therapy. The unique understanding of the differences in
setting in The Gambia has permitted pathogenesis between HIV-1 and
a comparison of viral kinetics of HIV-2 infection
HIV-1 and HIV-2 in vivo in people
with infection by one virus or by
Comparison of HIV-1 and HIV-2 viral

kinetics in vivo

Abraham Alabi, Akum Aveika, Kevin Peterson, Matthew Cotten, Sarah
Rowland-Jones, Hilton Whittle
Collaborators:
Samuel McConkey, RCSI, Dublin; Ayesha Akinkugbe, Lagos, Nigeria; Avidan
Neumann, Bar-Ilan University
Funding:

Genetic screening for resistance
A new technique has been HIV-1 infection, questions of their
developed which identifies efficacy and mechanisms of drug
mutations in the genes responsible resistance in non-clade B HIV-1 and
for HIV-2 drug resistance in some in HIV-2 infections are important.
people infected with the virus. A study of resistance mechanisms
of HIV-2 to treatment was started
A major change in the direction alongside the ART programme.
of the HIV programme has These studies have demonstrated
accompanied the launch and specific mutations associated with
scale-up of effective anti-retroviral drug resistance in HIV-2-infected
therapy (ART) for people with patients and have developed
HIV infection in partnership with new techniques to detect these
the Gambia Government, which mutations.
began in September 2004. Because
the medications in current use
were initially developed and
optimised for therapy of clade B
Study of HIV-2 resistance to anti-retroviral

drugs

Sabelle Jallow, Matthew Cotten, Sarah Rowland-Jones, GUM clinic staff
Collaborators:
Samuel McConkey, RCSI, Dublin; Steve Kaye, Imperial College, London;
Wouter Janssens, Institute of Tropical Medicine, Antwerp; Marten Schuten,
Erasmus University, Rotterdam
Deenan Pillay, University College, London
Funding:

Learning from natural defences against infection
Mimicking the natural defenses of TRIM5α, which binds to a region measure the quality of the TRIM5α/
some HIV-2 patients could be the of the retrovirus capsid protein to viral capsid interaction. These
key to more effective therapies. block infection at an early stage of sequence and function variabilities
uncoating (panel A). We would will then be correlated with viral
Some people infected with the like to understand why in many replication behavior.
HIV-2 virus do not develop AIDS patients HIV-2 replicates at very low
yet others do. Understanding how levels and does not cause disease, Our hope is that developing a
this happens will help develop more while in other patients HIV-2 molecular understanding of this
effective drugs which work in the infection results in the same tragic important antiviral pathway will help
same way as the natural defence AIDS produced by HIV-1. Our us to improve treatment strategies
system. hypothesis is that variations in the for patients infected with these
HIV-2 capsid binding site allow virus viruses. It will allow us to identify
Retroviruses often can infect a very escape from this inhibition (panel patients at greater or lesser risk
narrow range of cell types. For B). To test this hypothesis, HIV-2 for disease progression and would
example, HIV can infect human p26 capsid genes from rapid HIV-2 facilitate the allocation of anti-
cells but is blocked at some early disease progressors and long-term retroviral drugs. New therapies
stage when attempting to infect non-progressors (LTNP) are being based on improving the function of
cells from many other primates. examined for sequence variation. this innate defense system might be
Part of this strict species limitation Subsequently, functional biochemical identified.
involves the tripartite motif protein studies will be performed to
capsid Trim5α recognition virion destruction

A.
capsid evolves Trim5α no binding infection proceeds

B.

Characterization of variations in the
TRIM5α HIV restriction pathway that
correlate with HIV-2 disease progression
Key Investigators: MRC The Gambia

Clayton Onyango, Aleksandra Leligdowicz, Robert Walton, Assan Jaye, Hilton
Whittle, Sarah Rowland-Jones, Matthew Cotten
Collaborators:
Greg Towers, University College London
Funding:
Forward Look
We are implementing study of the virus. We are planning orally administered deuterated
proposals put forth and approved to test biomarkers of activation glucose.
in the 2005 quinquennial plan that are easily measurable from
and these include continuation serum such as β2-microglobulin 4. Neutralising antibody in HIV-2
of studies of host-mediated and neopterin in a longitudinal infection.
immunosuppressive mechanisms prospective cohort. This will Initial observations made in the
and immune dysfunction : constitute a head-to head Gambia almost 20 years ago
comparison of HIV-1 and HIV-2 suggested that HIV-2 elicited a
1. The role of Regulatory T cells infected subjects that have been potent neutralising antibody (nAb)
in the pathogenesis of HIV-2 followed from the time of entry response, which is rarely seen in
infection. into our cohort with a high HIV-1 infection. We plan to compare
In this project we have begun CD4 count: we have identified the nAb responses of HIV-2 infected
to explore if regulatory T Cells a sub-sample of the Fajara progressors and non-progressors in
(CD4+CD25+) are better cohort for this study, who have order to determine whether this is
preserved and more functional stored sequential serum samples a factor underlying delayed disease
in HIV-2, which could help to and were followed up for a progression in HIV-2 infection.
dampen immune activation: median duration of 5 years for
such suppression of CD4 T evaluation of immune activation 5. Caio serosurvey
cell activation might also limit markers. Studies of HIV-2 infection in a
target cell availability and community cohort in the village
hence reduce HIV replication, 3. Comparison of T lymphocyte of Caio began in 1989: since that
which could be the basis for Kinetics in HIV-1 and HIV-2 time there have been two surveys
preserved CD4 T-cell function infection. of HIV-1 and HIV-2 infection in the
in HIV-2 infection. We are This proposal aims at obtaining entire adult community and more
using markers that allow for quantitative estimates of frequent follow-up of a case-control
accurate identification of Tregs lymphocyte turnover in HIV-2 cohort of HIV-infected subjects and
(CD4+CD127loFoxP3+) and infection with the postulate that matched community controls. The
enumerating their frequency in slower progression of HIV-2 is last full community survey was in
HIV-1 and HIV-2 infection. due to lower rates of naïve CD4 1996-1997 and so a full sero-survey
T cell proliferation and death was planned for 2006-2007 to
2. Immune activation in HIV-2 in HIV-2 infection. We plan to provide up-to-date information about
infection. measure proliferation and death HIV prevalence in the cohort. Led
The mechanism of progressive rates of CD4+ and CD8+ T by Dr Akram Zaman and Dr Carla
decline of CD4 T cells may cells by measuring the kinetics van Tienen, samples were collected
be due to aberrant chronic of incorporation of deuterium from almost 3000 adults in the Caio
immune activation rather than or heavy water into the DNA of community and the data are currently
due to direct cytopathic effects these cells in patients receiving being analysed.

Infant Immunology
In January 2002, a birth cohort
was initiated in the village of
Sukuta, a peri-urban community
approximately 15 km from the
MRC campus at Fajara, in order to
study the development of the infant
immune system as it responds to
infections and vaccinations in early
life. Studies are also performed to
determine whether these vaccines
and infections interact with one
another. As the new generation
of vaccines to prevent infections
such as tuberculosis and malaria will
ultimately be given to infants, it is
important to know that combining
an increasing range of vaccines
in the Extended Programme of
Immunisations (EPI) does not lead
to harmful interactions.
A team comprising nurses,

fieldworkers, a paediatrician and an
epidemiologist work closely with
the Government Health Centre
staff in enrolment and care of study
children. Sukuta has approximately
25,000 inhabitants from a variety
of ethnic groups, although the
Mandinkas make up about half of
the population. Children born in Some members of the infant immunology laboratory team (top) and Sukuta Clinic
the health centre are enrolled into field team (bottom)
various studies, and followed up
according to the study protocol.
Between January 2002 and January Key Investigators at MRC The Gambia:
2007, 1,200 babies were enrolled Dr Jane Adetifa, Dr Melba Palmero, Dr Katie Flanagan, Dr David Miles, Dr
into the cohort. Baseline samples Assan Jaye, Dr Akram Zaman, Ms Sarah Burl, Mr Samuel Nyamweya, Dr Matt
taken at birth include cord blood, Cotten, Prof Hilton Whittle, Prof Sarah Rowland-Jones
placental imprint and biopsy, throat
swabs and urine samples from Collaborators:
babies, and maternal colostrum Sally Savage. Sukuta Health Centre; Kebba Gibba, National EPI Programme,
and blood. The study paediatrician Department of State for Health, The Gambia; Adama Jallow, National TB
assesses the children at birth, and Programme, Dept. of State for Health, The Gambia; Momadou Jammeh, Royal
the children are offered free medical Victoria Teaching Hospital, Banjul, The Gambia
care at the health centre and EPI Arnaud Marchant, Université Libre du Bruxelles, Belgium; Marianne van der
vaccines according to the Gambia Sande, Centre for Infectious Disease Epidemiology, National Institute for Public
Government schedule. Children Health and the Environment, The Netherlands; Jean-Marie Dangou, Institut
are followed up at home by the Pasteur, Dakar, Senegal; Helen McShane, Centre for Clinical Vaccinology and
field workers for morbidity and Tropical Medicine, University of Oxford, UK; Britta Urban, Centre for Clinical
anthropometry. Samples including Vaccinology and Tropical Medicine, University of Oxford, UK; Steve Kaye,
blood, urine and throat swabs Imperial College, London; Tony Holder, National Institute for Medical Research,
from babies and breast milk from Mill Hill, UK; Peter Aaby, Bandim Health Project, Guinea Bissau; Michel Klein,
mothers are then taken in the first Leiden
few years of life according to the
study protocol. Funding:
Medical Research Council, GlaxoSmithKline

Placental malaria risks
When a mother’s placenta is data are available from developing by PCR) of 5.4% in this population
infected with malaria she is more countries. Risk factors for was much higher than reported
likely to pass on a virus to her transmission of CMV infection and in industrialised countries and was
unborn child. clinical outcome were assessed in found to be associated with active
741 children born at Sukuta Health placental malaria infection. Despite
Cytomeglavirus is passed from Centre between January 2002 and this high prevalence, there were
mother to baby in the womb. It is January 2005. Babies were followed no obvious clinical sequelae of
the most common virus of its type up at home monthly for morbidity congenital CMV infection during the
in the world. Epidemiology and and anthropometry, and at one first year of life: the results of 5 year
clinical outcomes of CMV infection year of age a clinical evaluation follow up are awaited.
are known to vary with socio- was performed. The prevalence of
economic background, but few congenital CMV infection (measured
Risk factors for congenital cytomegalovirus

(CMV) infection
Infection by a virus in early life has a big effect

on how the immune system develops
The role of cytomegalovirus (CMV) effects were observed.
infection in development of the
immune response in early life has Other immunological studies include
been studied in detail in Sukuta. A an exploration of the relationship
study of 258 children showed that between the immune response of
almost 90% of Gambian children the mother to vertical transmission
are infected with CMV by 1 year of of CMV, and the relationship
age (Figure 1), representing one of between the viral loads of the
the highest infection rates described. infants and the immune parameters
Detailed immunophenotyping of measured.
CMV specific tetramer positive
T cells by flow cytometry
using sequential blood samples
demonstrated that CMV infection
leads to the accumulation of
terminally differentiated CD27-
CD28- CD8+ T cells (Figure 1).
These terminally differentiated T
cells have been associated with
early death and poor response
to vaccines in the elderly. CMV
specific T cells dominated the T
cell population in many children,
leading to the conclusion that CMV
infection is the main factor driving
T cell differentiation in early life.
It is not known at present if this
large differentiated CMV specific T
cell pool has an impact on survival
or vaccine responses in these
children. A study was performed
to determine whether or not CMV
infection in early life had an adverse
impact on the immune response to
measles vaccine and no significant

Immune response to CMV infection in early
life

Common infection and vaccinations
Infection during infancy by malaria schizont extract, AMA-1
the Epstein Barr virus and and MSP-1 malaria antigens were
cytomegalovirus changes the assessed at both time-points. The
body’s response to some routine data has been analysed to assess the
childhood vaccinations. relationship between EBV and CMV
infection and antibody responses.
This study aimed to analyse We found that EBV infection
whether being infected with EBV suppresses antibody responses
resulted in significantly different to meningococcal polysaccharide
levels of specific antibody to the vaccines and measles vaccine.
antigenic challenges of malaria and Infection with CMV enhances
routine vaccination in early life. measles vaccine antibody responses
Two hundred children were tested but does not affect responses to the
every 3 months for EBV infection by meningococcal vaccine.
throat swab. Blood samples were
taken at 9 months prior to measles,
yellow fever and meningococcal Effect of Epstein Barr virus (EBV) and
vaccination, and again at 11
months, 2 months post vaccination. CMV infection on immunity to malaria and
Antibody levels to measles and
meningococcal vaccines and to responses to vaccines
Malaria in pregnancy
Mother and baby are at a higher Cord blood from the infected
risk of disease and death if the placentas, matched maternal blood
mother’s placenta is infected with samples and uninfected control
malaria, and this could also affect bloods have been analysed for
the immune system. Treg activity: the data is currently
being analysed. Immune responses
Placental malaria is defined as are frequently compartmentalised
infection of the placenta by P. to specific sites of inflammation
falciparum malaria parasites, and in placental malaria, the
commonly during the first malaria-infected red blood cells
pregnancy, and is an important specifically adhere to the placenta.
cause of maternal and neonatal We will assess whether Tregs
morbidity and mortality. Regulatory localise to the placenta during
T cells (Tregs) are increasingly placental malaria and whether
thought to play a vital role in the placental Treg frequencies correlate
regulation of immune responses in with the Treg levels in cord and
health and disease. Functional Tregs maternal blood. The results should
are present in cord blood and likely provide important insights into the
play an important role in controlling mechanism of regulation of the
reactivity to maternal antigens immune response during placental
encountered during pregnancy. malaria infection, and the effect of
Soluble malaria antigens cross the placental malaria on Treg levels
placenta during placental malaria and immune reactivity in newborn
infection, but the effect on Treg babies.
frequencies in the neonate is not
known. The overall aim of this study
is to understand the role that Tregs
play in the immune response to
Effect of placental malaria on regulatory T
placental malaria infection. cells and cellular reactivity at birth
9.4% of 787 placental biopsy
samples from Sukuta that were
processed and analysed for
histological evidence of placental
malaria were found to be infected.

Understanding BCG
The BCG vaccine is given to the immune response to BCG (n=100) or at 4.5 months (n=100).
children to protect them against is attenuated in those with pre- We are examining immunological
tuberculosis. For people who live exposure to environmental responses to various mycobacterial
in the tropics, it does not always mycobacteria, and whether Treg and M tuberculosis specific antigens
protect them against the disease levels are related to the quality at birth, 4.5 and 9 months of
in adulthood. If we understand of the immune response to BCG. age by flow cytometry, cytokine
why this is, we could improve the This study aims to create a better secretion and gene expression. All
vaccine. understanding of the mechanisms participants have a tuberculin skin
responsible for the poor efficacy test at 4.5 months to examine for
BCG is the only available vaccine of BCG in the developing world reactivity which might be explained
against Mycobacterium tuberculosis and should help in the design of by environmental mycobacterial
(TB) but its protective efficacy strategies to increase the protective exposure. Each child is followed
against adult tuberculosis is efficacy of BCG. up monthly during the trial for
highly variable, particularly low in morbidity and anthropometric
tropical countries, for unknown 200 babies are being recruited at assessment and then every three
reasons. The most widely accepted birth and randomised to receive months until 3 years of age.
explanation is that natural immunity BCG vaccination either immediately
to mycobacteria found in the
environment render BCG less
effective. We hypothesise that Regulatory T cells and BCG immunogenicity
Tregs are induced by exposure
to environmental mycobacteria in early life
and attenuate the immunogenicity
of BCG. We will assess whether
Are two doses of measles vaccine better than

one?
An early dose of the measles gamma Elispot counts following at 9 months of age (see Table.)
vaccine, given at four months, stimulation of peripheral blood Children in this study will now be
could stop children dying from mononuclear cells with measles followed until 5 years of age to test
the disease before the routine peptide or measles virus, and whether protection and antibody
immunization is given at nine antibody concentrations. Two persists similarly in the two groups.
months. weeks after a booster dose of If this proves true the early two-
vaccine at 9 months of age antibody dose measles vaccine schedule can
Measles still kills half a million rose rapidly resulting in protective be recommended for routine use in
children per year. Many of these levels in all but two subjects (See countries where measles is endemic.
are young infants below the age Fig. 3). At 18 months of age cell
of 9 months when vaccination mediated immunity, conferred
is recommended (see figure 2). mainly by CD4+ cells, was similar
Previous studies have shown in the two groups. However,
that the Edmonston-Zagreb antibody concentrations were
(E-Z) vaccine is superior to other lower in the two dose group (see
standard measles vaccines in evading fig.) In order to measure duration
neutralization by maternal antibody of immunity we are currently
which is the reason measles repeating these tests at 3 years of
vaccination is delayed to 9 months age before and after another boost
of age. Thus we have conducted with E-Z vaccine. We predict that
randomized immunogenicity and both groups will respond similarly
efficacy trials of two standard doses and quickly suggesting protection
of E-Z vaccine given to infants at 4 following natural exposure.
and 9 months of age. The control
groups were given a standard dose The field trial in Bissau has
of E-Z vaccine at 9 months of age. convincingly shown that the
early dose of E-Z vaccine is very
In Sukuta, The Gambia we showed efficacious in protecting against
that the E-Z vaccine given at 4 measles and against death from
months raised both cell mediated measles in the five month period
immunity, as judged by interferon before the routine dose of vaccine

An infant with severe measles.
HAI antibody levels at 9.5 months

HAI antibody levels at 18 months
E-Z at 4.5 and 9 months Controls E-Z at 9 months Vaccine efficacy (95%
Events
(n=441) only (n=892) confidence interval)
Definite cases measles 2 60 94% (76-99)
Hospitalized cases 0 14 100% (29-100)
Deaths from measles 0 7 100%
Measles Cases, Hospitalization And Deaths Between Enrollment And 9 Months Of Age. In Bandim Guinea-Bissau 2003-4

Hepatitis B
The main focus of the hepatitis
studies is to assess the impact Key Investigators at MRC The Gambia:
of HBV vaccination at birth Maimuna Mendy, Matt Cotten, Hilton Whittle, Akram Zaman, Sarah Rowland-
on protection against chronic Jones
carriage and the development of
hepatocellular carcinoma (HCC) Collaborators:
– liver cancer - in adulthood. We Samuel McConkey (Royal College of Surgeons Ireland, Dublin); Marianne van
conducted studies to assess the der Sande (Centre for Infectious Disease Epidemiology, National Institute for
longevity of the protective immune Public Health and the Environment, The Netherlands); Andy Hall (London
response generated by HBV School of Hygiene and Tropical Medicine, UK); Pierre Hainaut (International
immunisation at birth and to assess Agency for Research on Cancer); Ebrima Bah (Gambia National Cancer
the need for adolescent vaccination. Registry); Steve Kaye (Imperial College, London)
Funding:
Our key questions are: Medical Research Council, International Agency for Research on Cancer
What is the best way of con-

ferring life long protection
against Hepatitis B infection
and its complications in the
liver?
What factors predispose
to the development of
liver cancer in patients with
chronic HBV infection?
Which laboratory and clinical
markers predict the develop-
ment of HBV-related liver
cancer?
Could fewer doses work?

Two doses of the childhood children who had received three
vaccine against hepatitis B gives a doses. After 4–7 years of follow-up,
similar level of protection as the vaccine efficacy among the two-
recommended three doses in the dose group was 86.3% against anti-
short term. We are investigating if HBc positivity (infection) and 92.3%
this is still true over the long term. against HBsAg positivity (carriage),
similar to the vaccine efficacy found
It has been suggested that two or among the participants who had
even one dose of HBV vaccine received three doses. A randomised
might be adequate to confer similar controlled trial with long-term
protection against HBV carriage as follow-up is needed to confirm the
the currently recommended three- results of this study.
dose schedule. This is supported by
several studies among adolescents,
adults and children. If long-term
vaccine efficacy against infection
Similar long-term vaccine efficacy of two
and carriage can be achieved in versus three doses of HBV vaccine in early
infants receiving two rather than
three doses, this would have clear life
benefits for the routine vaccination
schedules. Thus we determined
vaccine efficacy among children who
only received two doses of hepatitis
B vaccine as infants compared to

Childhood vaccination is long lasting
When given during infancy becoming infected during sexual vaccination, fewer than half of the
the hepatitis B vaccine gives exposure in adolescence. An vaccinees had detectable anti-HBs.
long lasting protection into open cohort of HBV vaccinees HBV vaccination early during life
adolescence. from 2 adjacent rural Gambian can provide long-lasting protection
villages in West Kiang (Keneba against carriage, despite decreasing
HBV vaccination provides and Manduar) was studied 19 antibody levels. The role played
protection for 10–15 years after years after the initiation of infant by subclinical boosting and the
infant vaccination despite waning vaccination. Overall vaccine efficacy necessity of a booster need to be
antibodies, suggesting that there (VE) against infection and carriage evaluated.
is no need for a booster before was 83.4% and 96.5%, respectively.
adolescence. The continued Both vaccine efficacy and levels of
protection despite waning antibody hepatitis B surface antibody (anti-
levels may reflect effective HBs) decreased with age, resulting
immunologic memory or a low risk in a vaccine efficacy against infection
of infection in that age group. No and carriage among 20–24-year-old
data are available on the risk for participants of 70.9% and 91.1%,
those vaccinated during infancy of respectively. Fifteen years after
Long-term protection against carriage of

hepatitis B virus after infant vaccination
Application of real-time PCR to quantify

hepatitis B virus (HBV) DNA in chronic carriers
in The Gambia
A new method of measuring how load is important for the clinical
much of the hepatitis B virus is in management of HBV and useful in
the blood of infected people has the detection of genetic variants of
been developed. This will help HBV that affects HBeAg secretion.
doctors treat the disease more Accordingly, we have developed
effectively. and validated a quantitative PCR
(qPCR) method to measure HBV
The detection and quantification DNA in serum; the method was
of HBV DNA has prognostic found to function well to monitor
value for the outcomes of acute HBV DNA levels in patients on
and chronic HBV and it is a useful lamivudine (LMV) therapy.
marker to monitor antiviral therapy.
Accurate quantification of virus

Natural history of chronic HBV infection
In Gambian children infected with high viral loads (>108 DNA copies/
hepatitis B the virus becomes mL). After 19 yrs of follow-up, the
controlled over long periods of average rate of HBsAg clearance
time. was 1.6% per year and the annual
rate for HBeAg clearance was 3.0
A better understanding of the %. Viral load was found to decrease
pathogenic mechanisms of HCC with age with significant (p<0.001)
are the key to prevention and difference between carriers aged
treatment of the disease. High 1-4 yrs and subsequent age groups
level of HBV replication and HBV (Figure 1).
genotype are important risk factors
for disease progression. In conclusion, many chronic HBV
carriers from The Gambia appear to
HBsAg and HBeAg clearance stabilise in an inactive carrier state.
and viral load were determined By the age of 10 years, the majority
in carriers who were aged 1-4 (>80%) have seroconverted to
yrs old at recruitment and then anti-HBe positivity and have low
followed for 19 years in Keneba and levels (<105 copies per mL) of HBV
Manduar villages. These children DNA concentration.
were positive for HBeAg and had
Figure 1. HBV viral load (copies/mL) in relation to age of carriers. The red bars
represent median values.

Screening for people at high risk of liver cancer
A new screening method will help Control study (GLCS) cohort and
us identify the hepatitis B patients showed it to be a reliable method
most at risk of liver cancer. The for detecting these mutations. There
test identifies mutations on specific was 95.8% and 89.3% concordance
genes which are linked to disease between the OLA and DNA
progression. sequencing for pre-C and BCP
mutations respectively.
Double mutations in the basal BCP mutations were detected in
core promoter (BCP) [A1762T 75.7% patients with liver diseases
and G1764] and Pre-core (pre-C) (HCC/Cirrhotic) and in 47.6%
[G1896A] of the virus infecting controls whilst pre-C mutations
chronic HBsAg carriers are thought were detected in 34.5% liver
to exert modulating effects in diseases and 47.6% controls. BCP
hepatocarcinogenesis and are mutations were associated with
associated with high viral load and increased risk for progression to
HCC progression. HBV-related liver disease. The
We developed a simple viral loads in the 1762/4 mutant
oligonucleotide ligation assay (OLA) infected patients were higher (2.0
method for screening and detecting log) compared to wild type (Table
BCP and pre-C/C mutations. We 1). The application of OLA may
then applied OLA to test samples include assessing HCC risk in
from HBV infected carriers recruited epidemiological studies and clinical
from the Gambia Liver Cancer Case care in HBV endemic regions.
Geometric mean HBV DNA viral load by mutation status

Nucleotide 1762/4 Nucleotide 1896
(N=134) (N=139)
1762/4 W 1762/4 M (N=98) 1896 W 1896 M
(N=36) (n=92) (N=47)
1.7 x 105 1.7 x 107 1.3 x 107 4.4 x 106

Genetics of infection
The reason why some people manner by gene or locus. underway, which concentrates
vaccinated against hepatitis B on about ~35 SNPs showing the
during childhood still go on to The analysis identified variants in strongest effect on anti-HBs level.
catch the virus, and others do not seven genes to be associated with
could be genetic. either peak anti-HBs level or anti-
HBc status (p<0.001 and size of
This project builds on the hepatitis effect <0.6 or >1.5). A replication
B studies that have been running study in the remainder of the
at the MRC since the 1980s, and sample cohort (N=421) is currently
aims to assess genetic determinants
of long-term immunity induced by
infant HBV vaccination. The genetic
analysis to date screened 768 SNPs
Genetics of durable vaccine-induced
across 133 genes in 710 individuals immunity to HBV (GoVII)
recruited in the West-Kiang region
and followed up for up to 18 years.
Candidate gene SNPs were selected
on the basis of HapMap frequency
data, validation, distribution across Key Investigators at MRC The Gambia:
loci, and enrichment in coding Maimuna Mendy, Marianne van der Sande, Giorgio Sirugo, Pauline Wraight,
changes. Two outcome measures Akram Zaman, Hilton Whittle,
were assessed, peak anti-HBs level
(as a predictor of long term vaccine Collaborators:
efficacy) and anti-HBc positivity Branwen Hennig, Andrew Hall, Katherine Fielding (London School of Hygiene
(as indication of infection despite and Tropical Medicine, UK); Adrian Hill (Wellcome Trust Centre for Human
vaccination), whilst simultaneously Genetics, Oxford University); Pura Solon (MRC International Nutrition Group,
adjusting for covariates age group, London School of Hygiene and Tropical Medicine, UK)
gender, village, number of doses,
vaccine group and relatedness. Funding:
Genotype data was included in the Medical Research Council, Wellcome Trust Advanced Training Fellowship
regression models in a stepwise
Aflatoxin and liver cancer

A toxin from mouldy peanuts pattern that follows the known
increases the risk of liver cancer seasonal variations in AF exposure
by causing a mutation in an anti- (Figure 1). Previous studies have
cancer protein. shown similar seasonal variation
in ser249 mutation detection in
Chronic Hepatitis B Virus carriage chronic carriers. Presence and
and exposure to Aflatoxin B1 amount of mutant DNA was
(AFB1) have been classified as significantly correlated with HBV
Group 1 carcinogens by the carriage with 44% of HBV+ samples
International Agency for Research containing detectable amounts of
on Cancer and exert a multiplicative mutant DNA copies, in contrast
effect on HCC risk. The presence with 24% of HBV- samples, with an
of a specific mutation induced amount of mutant copies per µL
by AFB1 at codon 249 in TP53 significantly higher in HBV+ samples
detected in over 50% of HCC (p-value<0.0001). These results
cases may provide a useful early suggest that mutagenesis at codon
marker of exposure to AFB1 and 249 in TP53, a mutation considered
hepatocarcinogenesis. as “signature” of DNA damage
induced by AFB1, is a relatively
From testing plasma samples specific event in the context of
from 240 HBV carriers (HBV+) chronic HBV carriage, with seasonal
and 237 non-carriers (HBV-) we variations reflecting exposure to
found that the levels of mutant AFB1.
plasma DNA were significantly
higher in chronic HBV carriers
and exhibited a seasonal variation

A B
C D
Numbers of Ser249 copies/µL of serum in HBV carriers (A,C) and non-carriers (B,D) by month. First quartile (p25), median
(p50) and third quartile (p75) are represented in C and D.
Seasonal variation in plasma load of mutant

TP53 Ser249 DNA in healthy subjects
exposed to AFB1

Maimuna Mendy, Samuel McConkey, Marianne Van der Sande, Hilton Whittle.
Collaborators :
Emilie Le Roux, Stéphanie Villar, Ebrima Bah, Pierre Hainaut, (International
Agency for Research on Cancer)
Funding:
Medical Research Council, International Agency for Research on Cancer

Forward Look
1. Seeking better tumour markers assess the value of each of are now beginning to examine
for HCC detection. Because the tumor markers individually if the tumor specific TP53
of a high level of chronic HBV and in combination to identify 249ser mutation synergizes with
infection and widespread a diagnostic algorithm leading elevated intracellular Aurora A
aflatoxin exposure, The Gambia to a case definition for HCC, kinase activity to promote HCC
presents a high incidence of establish proteomic HCC development.
hepatocellular carcinoma (HCC) fingerprinting capacity and
occurring at a relatively young compare this novel method to 3. HBV genetic studies. We will
age. The availability of sera serological techniques for HCC extend the work on the links
from a well characterised HCC diagnostic accuracy. between viral diversity and the
case control study provides a development of liver cancer to
unique opportunity to develop 2. The role of Aurora A kinase include longitudinal studies using
innovative approaches for in HCC. Elevated levels of serial samples from long term
improving early detection the Aurora A kinase have chronic carriers. We will also
and diagnosis of HCC. We been found in hepatocellular characterize the HBV genome
will evaluate the effectiveness carcinoma (HCC) and the in more detail by examining the
of new diagnostic tools for kinase can phosphorylate and full length genome and HBV
detecting cancer in stored sera, thus destabilize TP53. Studies subtype variation.
Trachoma and Chlamydia Research

Trachoma research projects focus
Leading areas of research:
on the mechanisms by which ocular
infection with Chlamydia trachomatis Quantitation of the expression of human cytokine and pathogen genes
leads to disease and what/or how in the conjunctiva during ocular C. trachomatis infection.
current interventions can interrupt Cellular immunology studies with peripheral blood and conjunctival cells
infection or disease. Trachoma, to investigate T cell immunoregulation, tissue fibrosis and identification
which is the leading cause of of effector cells and their antigenic specificity.
preventable blindness worldwide, is The basis of genetic susceptibility to scarring sequelae of human ocular
declining in The Gambia, surviving chlamydial infection
largely in isolated pockets. Yet it
Determination of the fundamental differences between strains causing
remains a significant problem in
ocular and genital infections with C.trachomatis.
surrounding countries and those
further afield such as Ethiopia. Many Studies of re-emergent infection following mass treatment of affected
of these projects are built on a solid communities and its implications for trachoma control
cooperation with the Gambian
National Eye Care Programme.

Esther Aryee, Nkoyo Faal, Martin Holland, Hassan Joof, Pateh Makalo, Ahmed
Manjang, Isatou Sissoho-Sarr
Collaborators:
David Mabey, Matthew Burton, Robin Bailey, Aura Andreason, Spencer
Polley, Saul Rajak (London School of Hygiene and Tropical Medicine,
UK); Jean-Francois Schemann, (IRD, Dakar, Senegal); Thomas Lietman (F
I Proctor Foundation, University of California San Francisco, USA); Sheila
West (Johns Hopkins University, Baltimore, USA); Rosanna Peeling (WHO);
Grant McClarty (Laboratory Center for Disease Control, Canada); Dominic
Kwiatkowski (University of Oxford, UK); Peng Khaw, Dr Maryse Bailly (Institute
of Ophthalmology, University College London); Dr Helen Lee (University of
Cambridge, UK); Ansumana Sillah and staff (National Eye Care Programme,
The Gambia); Meno Nabicassa (National Blindness Coordinator, Guinea-
Bissau)
Funding:
Medical Research Council, The Wellcome Trust, International Trachoma
Initiative

Treatment gives protection
In the five years since a group of After five years fewer than 10 cleavage by cathepsin-L. It is as yet
villages was treated for trachoma subjects from a community of 1250 unclear how these changes might
there has been a fall in the number of had evidence of infection. We have impact on pathogen ‘fitness’.
cases of the disease. investigated the genetic diversity of
the chlamydial strains in circulation. Population genetic analysis of the
In 2001 a cluster of villages around The ompA gene from each positive baseline pathogen alleles in the
Jareng in the Central River Division sample was sequenced and we community revealed a significant
of The Gambia were treated with a identified 10 genetic ompA types excess of rare mutations (Tajima’s
single dose of azithromycin for the in circulation in the population D = -1.76 ; p = 0.018). This is
control of trachoma. Despite the early (Table 1). Two types dominated, indicative of purifying selection or a
reintroduction of infection into the one of which, A2, was consistently recent selective sweep rather than
community following a pilgrimage to associated with low levels of positive diversifying selection which
Touba in Senegal, both the clinical signs conjunctival infection. This genovar may result from immune selection
of trachoma and ocular infection have has an additional N-glycosylation pressure.
continued to decline without further site and a cathepsin-L cleavage site.
intervention. This could result in several changes
one of which may be alteration of
Genovar VS1 VS1 CSI/II CSI/II VS2 VS2 CSIII/IV VS4 VS4
Nucleotide
278 289 304 353 505 523 790 991 1020
position
Ref.
sequence T (V) G (E) G (A) C (A) G (G) A (I) A A (T) G
HAR13
Baseline
Sample time
(n=77)
A1 . . . . . . G . . 10 (13)
A2 . . A(A→T) . . C(I→L) G . A 57 (74)
A3 . . A(A→T) . . C(I→L) G . . 2 (2.5)
A4 . . . . . . G G(T→A) . 1 (1.3)
A5 A(V→E) C (E→Q) . . A(G S) . G . . 1 (1.3)
A6 . . A(A→T) T(A→V) . C(I→L) G . A 1 (1.3)
A 7* . . A(A→T) . . . G . A -
A8 . . . . . . G . A 1 (1.3)
Genovar B VS2
Nucleotide 511
Ref B
G(G)
(M33636)
B1 A (G→S) 1 (1.3)
B2 . 3 (4)
A4 . . . . . . G G(T→A) . 1 (1.3)
A5 A(V→E) C(E→Q) . . A(G→S) . G . . 1 (1.3)
Table 1. Genovars sequenced in this study. Only single nucleotide polymorphisms and their locations are shown. Reference
strains are C. trachomatis HAR 13 (serovar A) and C. trachomatis M33636 (serovar B). Letters in parenthesis represent the
amino acid and any resulting change. Genovar B2 is identical to the reference strain. VS, variable sequence. CS, constant sequence.
* Genovar A7 isolated from a nasal swab 2 months after treatment.
Quantitative and genotypic diagnosis of

Chlamydial infection following community
wide treatment with Azithromycin.

Genes of infection
Differential host gene transcript the Gambian study villages were
levels in the eyes affect re- followed up and the influence of
occurrence of trichiasis after the expression of these genes at
surgery. the time of surgery was investigated
on the recurrence of trichiasis.
A trial to assess the impact of Highest rates of recurrence appear
azithromycin treatment on the to be associated with bacterial
rate of recurrence of trichiasis after conjunctival infection which is
surgery was completed in 2003 amplified by high levels of pre-
with the Gambia Government operative TNF expression.
National Eye Care Programme
and Senegalese partners. At the
start of this study conjunctival gene
expression was measured for genes Conjunctival gene expression and the rate
which may be important in the
development of trichiasis (IL1, TNF, of recurrence of trichiasis after surgery
MMP2, MMP9, TIMP1 and TIMP2).
Two years after surgery patients in
Age and trachoma

The amount of bacteria as well as and clinical signs and found that
the number of eyes with trachoma those with most severe clinical
disease decreases with age in signs were infected with the largest
communities where the disease is bacterial loads. Work is underway
endemic. to investigate whether functional
T regs can be demonstrated
Using real time qRT-PCR during in subjects from trachoma
episodes of active trachoma and endemic communities. In cross
infection we have confirmed a sectional community studies we
predominantly proinflammatory also demonstrated that there is
conjunctival response during differential expression of extra
infection and have suggested cellular matrix breakdown (MMP
that cytokines such as IFN-γ and 9) and synthesis genes (Collagen)
IL-10 are differentially expressed in the conjunctiva, which results in
during the resolution of clinical scarring and fibrosis.
signs of disease. We also find
expression of FOXP3 is higher at
this time and this may implicate Conjunctival gene expression in the
T regulatory cells in the control
of conjunctival tissue pathology. acquisition and resolution of active
This study also demonstrated
age-related reductions in infection
trachoma

Figure 1. Decline in the prevalence of ocular infection and clinical signs with age in 5 -15 year olds from endemic communities in
the Gambia suggesting that ‘immunity’ to infection and disease might develop through time and exposure.
Risk of scarring
An association has been made collected. We found associations with a reduced risk or increased
between a combination of genes with haplotypes and specific risk of conjunctival scarring. In the
which increases or decreases the SNPs across the following loci - case of MMP9 a reduction in the
risk of scarring from trachoma. A IFNγ, IL10, TNF/LTA and MMP9. risk of scarring was associated with
single mutatation has also been We have attempted to test for an exonic SNP thought to be a
found which is also associated with functional differences in most of ‘loss’ function mutation (Q279R)
reducing the risk of scarring. these genes associated with reduced and work with collaborators at the
risk or susceptibility to disease. wound healing unit at the Institute
A large case-control study of of Ophthalmology in London is
scarred subjects and controls for For IL10 we used allele-specific under way to investigate the role of
genetic susceptibility affecting transcription quantification with this mutation in fibroblasts obtained
outcome in human chlamydial RNA sampled from the conjunctiva from Gambian subjects. In the case
infections is on-going, with the of subjects with active trachoma and of TNF/LTA work at MRC has
overall aim to collect 2000 case- controls. Using this technique we investigated the production of TNF
control pairs for use in a genome found differing transcription rates from cells of subjects with differing
wide scan. Currently we have between IL10 alleles. For MMP9 genetic haplotypes which extend
used a candidate gene approach in and TNF/LTA have also identified across the TNF/LTA loci. Previously
650 case-controls that have been haplotypes at these loci associated a SNP at TNF-308 was associated
with risk of scarring trachoma. In
the current study using extended
Host gene polymorphisms and their role in haplotypes both the TNF-308A
allele and the haplotype containing
resistance or susceptibility to trachoma it were associated with stronger
TNF responses. The most striking
increase in TNF production was
observed among homozygotes for
this risk allele/haplotype (Table 2).

Number of copies of
Haplotype TNF (pg/ml) ANOVA
risk halpotype
F P-value
0 4601 0.51 0.605

HAP1 (ATTGG) 1 5048
2 5178
0 4870 0.43 0.650
HAP2 (TGCGG) 1 5197
2 3832
0 5011 3.34 0.043
HAP3 (TGCAG) 1 4303
2 7194
Table 2. Shows genotyped SNPs used to define common haplotypes spanning a 25 kb region across IkBL, LTA and TNF loci.
SNPs are designated according to the nucleotide position relative to the transcriptional start site. The talbe shows the geometric
mean value of TNF produced by PBMC on stimulation with chlamydial EBs according to the number of copies of the risk
haplotype spanning the TNF locus. Statistics derived from the analysis-of-variance (ANOVA).
Community diagnosis
A new way of diagnosing trachoma is summarized in Tables 3, 4 and
within the community is being 5. Confirmation and follow-up are
tested in The Gambia and Senegal. underway and evaluation in Senegal
(Dr Jean-Francois Schemann of IRD
Evaluation of a chlamydial POC test in Dakar).
is currently underway; once before
mass treatment with azithromycin
and once one year afterwards.
Two divisions, North Bank Division
(NBD) and Lower River Division
(LRD), with the highest active
disease prevalence in the 1996
national survey were selected. Evaluation of a rapid point-of-care (POC)
Trachoma was graded according
to the WHO simplified grading test for C. trachomatis in a community based
system. Two ocular swabs were
taken: one processed by the POC azithromycin treatment programme for the
test in the field, other tested in
the lab by the ‘gold-standard’ PCR elimination of trachoma.
Roche Amplicor. Preliminary data
Division Number of districts Number of children seen

Lower River 19 951
North Bank 41 2046
Total 60 2997
Table 3. Summary of number of children aged 0-9 examined:

Area No. TF either eye TF neither eye TI either eye TI neither eye
LRD 951 109 (11.5) 841 (88.5) 1 (0.1) 950 (99.9)
NBD 2046 197 (9.6) 1849 (90.4) 2 (0.1) 2044 (99.9)
Total 2997 306 (10.2) 2,690 (89.8) 3 (0.1) 2,994 (99.9)
Table 4. Details of WHO simplified grading system clinical signs in LRD and NRD
Area Number PCR Swab A PCR Swab B POC pos Reader 1 POC pos Reader
infection infection (%) 2 (%)
(%) (%)
LRD 951 6 (0.63) 3 (0.32) 1 (0.1%) 4 (0.4%)
Table 5. Preliminary data on prevalence of infection by Amplicor PCR and the POC test in LRD:
Conjunctival gene expression in trichiasis

The biological switch which Scientists are surprised to discover specific tetramers (HLA-A* 6802 is
activates one of the genes that high numbers of immune predominant molecular subtype of
responsible for an immune cells in the blood, as a result of HLA-A28 in Gambian subjects) as
response in the eye is more trachoma bacteria, do not predict well as further functional studies is
strongly activated in people with in the resolution of the disease. on going.
turned eye lashes.
HLA-peptide tetramers specific for
Using mini-gene arrays to screen C. trachomatis MOMP which were
gene expression on site in Fajara, able to bind to CD8+ T cells from
226 genes for extracellular matrix blood were used to enumerate
proteins/adhesion molecules and the number of circulating MOMP
cytokines were tested. Results specific cells. Typical results are
indicate that the transcription factor shown in Figure 4. Tetramer positive
JunB proto-oncogene (JunB) was cells were detected more often in
up-regulated in the conjunctiva subjects who were infected at the
of subjects with in turned lashes. ocular surface and their presence
Interestingly in JunB deficient was associated with infection
mice, delayed wound healing and episodes of longer duration.
epidermal hyperproliferation is Detection of C. trachomatis-specific
observed. In vitro experiments show cells was not associated with the
that JunB is involved in regulatory presence of clinical disease signs or
cytokine networks that control skin with the estimated load of ocular C.
homeostasis and regeneration. trachomatis infection at the time of
sample collection. High frequencies
The results of quantitative of C. trachomatis-specific cells did
expression of JunB and a number of not predict subsequent appearance
other genes known to be involved or resolution of the clinical disease
in other immune mediated fibrotic signs of active trachoma. Further
diseases (TNF, IL1β, IL-11, IL-11Rα, work using HLA-A*6802 MOMP
IL-13 and IL-13Rα2) are currently
being measured by real-time qPCR.
Use of HLA-peptide tretramic complexes

to study MOMP specific CD8+ T cell
responses in a cohort of trachoma subjects
and controls followed longitudinally.
Figure 4. Example FACS plots showing MOMP tetramer staining in whole blood of subjects from trachoma endemic communities in The
Gambia.
Photograph shows Emma Harding-Esch carrying out in the field testing for ocular chlamydial infection using the point of care rapid test in
a typical scene from villages in both the LRD and NRD of the Gambia.
The figure shows the haplotype-tagging SNPs used in genotyping these span a 25 kb region across the IkBL, LTA and TNF loci.
SNPs are designated according to the nucleotide position relative to the transcription start site.

C. trachomatis infected cells HeLa cells (counter stained red) stained with a specific monoclonal antibody for the Major Outer
membrane protein (Yellow/Green)
Field teams search out communities where active trachoma is prevalent. An

experienced team of field supervisors trained in trachoma grading with community
ophthalmic nurses from the NECP identify, treat and refer trachoma and eye
health related problems. Samples are collected for laboratory investigation of
pathogen and host responses to infection and treatment.

Viral Diseases Programme: PhD students
Victor Nuvor
Natural killer cell responses in HIV-1 and HIV-2 infection
Sabelle Jallow
Resistance of HIV-2 to anti-retroviral agents
Melody Duvall:
CD4+ T-cell responses in HIV-1 and HIV-2 infection (awarded 2006)
Rebecca Cassidy
Levels of support and stigma regarding HIV infection and the affect on adherence to medications in a low-prevalence epidemic
context
Beatrice Ondondo
Cross-reactive responses between HIV-1 and HIV-2 (awarded 2007)
Aleksandra Leligdowicz:
CD8+ T-cell responses in HIV-1 and HIV-2 infection
Sarah Burl
Regulation of T-cell responses to BCG and mycobacteria in early life
Irfan Zaidi
Regulatory T-cell responses in HIV-1 and HIV-2 infection
Louis-Marie Yindom
HLA and KIR gene associations with HIV-2 susceptibility and disease progression
Clayton Onyango
The role of TRIM5-alpha in HIV-2 infection
Shamanthi Jayasooriya
How does malaria suppress immunity to EBV infection?
Thushan de Silva
Neutralising antibody responses in HIV-2 infection
Nkoyo Faal
Pathogenic determinations of ocular Chlamydia trachomatis infection
Matthew Burton
Studies of the epidemiology, pathogenesis and control of trachoma in The Gambia (awarded 2005)
Viral Diseases Programme: Publications

2004-2006
01. Duvall MG, Jaye A, Dong T, Brenchley JM, Alabi AS, Jeffries DJ, van der Sande M, Togun TO, McConkey SJ, Douek
DC, McMichael AJ, Whittle HC, Koup RA, Rowland-Jones SL. 2006. Maintenance of HIV-specific CD4+ T cell help
distinguishes HIV-2 from HIV-1 infection. J Immunol 176: 6973-81
02. Eshofonie A, van der Loeff MS, Whittle H, Jaye A. 2006. An adaptation of recombinant vaccinia-based ELISPOT
and intracellular cytokine staining for a comparative measurement of cellular immune responses in HIV-1 and
HIV-2 infections in West Africa. Clin Exp Immunol 146: 471-8
03. Frodsham AJ, Zhang L, Dumpis U, Taib NA, Best S, Durham A, Hennig BJ, Hellier S, Knapp S, Wright M, Chiara-
monte M, Bell JI, Graves M, Whittle HC, Thomas HC, Thursz MR, Hill AV. 2006. Class II cytokine receptor gene
cluster is a major locus for hepatitis B persistence. Proc Natl Acad Sci U S A 103: 9148-53
04. Garly ML, Bale C, Martins CL, Whittle HC, Nielsen J, Lisse IM, Aaby P. 2006. Prophylactic antibiotics to prevent

Publications
pneumonia and other complications after measles: community based randomised double blind placebo controlled
trial in Guinea-Bissau. BMJ 333: 1245
05. Gillespie GM, Pinheiro S, Sayeid-Al-Jamee M, Alabi A, Kaye S, Sabally S, Sarge-Njie R, Njai H, Joof K, Jaye A,
Whittle H, Rowland-Jones S, Dorrell L. 2005. CD8+ T cell responses to human immunodeficiency viruses type 2
(HIV-2) and type 1 (HIV-1) gag proteins are distinguishable by magnitude and breadth but not cellular phenotype.
Eur J Immunol 35: 1445-53
06. Hansmann A, Schim van der Loeff MF, Kaye S, Awasana AA, Sarge-Njie R, O’Donovan D, Ariyoshi K, Alabi A,
Milligan P, Whittle HC. 2005. Baseline plasma viral load and CD4 cell percentage predict survival in HIV-1- and
HIV-2-infected women in a community-based cohort in The Gambia. J Acquir Immune Defic Syndr 38: 335-41
07. Jaffar S, Grant AD, Whitworth J, Smith PG, Whittle H. 2004. The natural history of HIV-1 and HIV-2 infections in
adults in Africa: a literature review. Bull World Health Organ 82: 462-9
08. Jaffar S, Van der Loeff MS, Eugen-Olsen J, Vincent T, Sarje-Njie R, Ngom P, Meyer AM, Berry N, Aaby P, Whit-
tle H. 2005. Immunological predictors of survival in HIV type 2-infected rural villagers in Guinea-Bissau. AIDS Res
Hum Retroviruses 21: 560-4
09. Jaffar S, Govender T, Garrib A, Welz T, Grosskurth H, Smith PG, Whittle H, Bennish ML. 2005. Antiretroviral
treatment in resource-poor settings: public health research priorities. Trop Med Int Health 10: 295-9
10. Jallow S, Kaye S, Alabi A, Aveika A, Sarge-Njie R, Sabally S, Corrah T, Whittle H, Vanham G, Rowland-Jones S,
Janssens W, McConkey SJ. 2006. Virological and immunological response to Combivir and emergence of drug
resistance mutations in a cohort of HIV-2 patients in The Gambia. Aids 20: 1455-8
11. Jaye A, Sarge-Njie R, Schim van der Loeff M, Todd J, Alabi A, Sabally S, Corrah T, Whittle H. 2004. No differences
in cellular immune responses between asymptomatic HIV type 1- and type 2-infected Gambian patients. J Infect
Dis 189: 498-505
12. Jensen ML, Dave S, van der Loeff MS, da Costa C, Vincent T, Leligdowicz A, Benn CS, Roth A, Ravn H, Lisse IM,
Whittle H, Aaby P. 2006. Vaccinia Scars Associated with Improved Survival among Adults in Rural Guinea-Bissau.
PLoS ONE 1: e101
13. Kaye S, Howard M, Alabi A, Hansmann A, Whittle H, Schim van der Loeff M. 2005. No observed effect of GB
virus C coinfection on disease progression in a cohort of African woman infected with HIV-1 or HIV-2. Clin Infect
Dis 40: 876-8
14. Kirk GD, Lesi OA, Mendy M, Akano AO, Sam O, Goedert JJ, Hainaut P, Hall AJ, Whittle H, Montesano R. 2004.
The Gambia Liver Cancer Study: Infection with hepatitis B and C and the risk of hepatocellular carcinoma in West
Africa. Hepatology 39: 211-9
15. Kirk GD, Lesi OA, Mendy M, Szymanska K, Whittle H, Goedert JJ, Hainaut P, Montesano R. 2005. 249(ser) TP53
mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma. Oncogene 24: 5858-67
16. Kirk GD, Turner PC, Gong Y, Lesi OA, Mendy M, Goedert JJ, Hall AJ, Whittle H, Hainaut P, Montesano R, Wild
CP. 2005. Hepatocellular carcinoma and polymorphisms in carcinogen-metabolizing and DNA repair enzymes in a
population with aflatoxin exposure and hepatitis B virus endemicity. Cancer Epidemiol Biomarkers Prev 14: 373-9
17. Marchant A, Pihlgren M, Goetghebuer T, Weiss HA, Ota MO, Schlegel-Hauter SE, Whittle H, Lambert PH, New-
port MJ, Siegrist CA. 2006. Predominant influence of environmental determinants on the persistence and avidity
maturation of antibody responses to vaccines in infants. J Infect Dis 193: 1598-605
18. Mendy M, Kirk GD, van der Sande M, Jeng-Barry A, Lesi OA, Hainaut P, Sam O, McConkey S, Whittle H. 2005.
Hepatitis B surface antigenaemia and alpha-foetoprotein detection from dried blood spots: applications to field-
based studies and to clinical care in hepatitis B virus endemic areas. J Viral Hepat 12: 642-7
19. Mendy ME, Kaye S, van der Sande M, Rayco-Solon P, Waight PA, Shipton D, Awi D, Snell P, Whittle H, McCo-

Publications
nkey SJ. 2006. Application of real-time PCR to quantify hepatitis B virus DNA in chronic carriers in The Gambia.
Virol J 3: 23
20. Newport MJ, Goetghebuer T, Weiss HA, Whittle H, Siegrist CA, Marchant A. 2004. Genetic regulation of immune
responses to vaccines in early life. Genes Immun 5: 122-9
21. Njai HF, Van der Auwera G, Ngong CA, Heyndrickx L, Sawadago S, Whittle H, Nyambi P, Colebunders R, van der
Groen G, Janssens W. 2004. Development, evaluation, and validation of an oligonucleotide probe hybridization
assay to subtype human immunodeficiency virus type 1 circulating recombinant form CRF02_AG. J Clin Microbiol
42: 1428-33
22. Nuvor SV, van der Sande M, Rowland-Jones S, Whittle H, Jaye A. 2006. Natural killer cell function is well pre-
served in asymptomatic human immunodeficiency virus type 2 (HIV-2) infection but similar to that of HIV-1 infec-
tion when CD4 T-cell counts fall. J Virol 80: 2529-38
23. Nwanegbo E, Vardas E, Gao W, Whittle H, Sun H, Rowe D, Robbins PD, Gambotto A. 2004. Prevalence of neu-
tralizing antibodies to adenoviral serotypes 5 and 35 in the adult populations of The Gambia, South Africa, and the
United States. Clin Diagn Lab Immunol 11: 351-7
24. Ota MO, Vekemans J, Schlegel-Haueter SE, Fielding K, Whittle H, Lambert PH, McAdam KP, Siegrist CA, March-
ant A. 2004. Hepatitis B immunisation induces higher antibody and memory Th2 responses in new-borns than in
adults. Vaccine 22: 511-9
25. Rowland-Jones, S. and Dong, T. HIV: Tired T-cells turn around. Nature (news and views) (2006) 443: 282-3
26. Rowland-Jones, S. Protective immunity against HIV infection: lessons from HIV-2 infection. Future Microbiology
(2006)
27. Sarge-Njie R, Schim Van Der Loeff M, Ceesay S, Cubitt D, Sabally S, Corrah T, Whittle H. 2006. Evaluation of the
dried blood spot filter paper technology and five testing strategies of HIV-1 and HIV-2 infections in West Africa.
Scand J Infect Dis 38: 1050-6
28. Szymanska K, Lesi OA, Kirk GD, Sam O, Taniere P, Scoazec JY, Mendy M, Friesen MD, Whittle H, Montesano R,
Hainaut P. 2004. Ser-249TP53 mutation in tumour and plasma DNA of hepatocellular carcinoma patients from a
high incidence area in the Gambia, West Africa. Int J Cancer 110: 374-9
29. van der Loeff MF, Awasana AA, Sarge-Njie R, van der Sande M, Jaye A, Sabally S, Corrah T, McConkey SJ, Whittle
HC. 2006. Sixteen years of HIV surveillance in a West African research clinic reveals divergent epidemic trends of
HIV-1 and HIV-2. Int J Epidemiol 35: 1322-8
30. van der Sande MA, Luong TN, Schim van der Loeff MF, Sabally S, Aveika AA, Corrah T, Sarge-Njie R, Kaye S,
Whittle HC. 2004. Dual HIV-1 and HIV-2 infection in a West African infant. Ann Trop Paediatr 24: 277-8
31. van der Sande MA, Schim van der Loeff MF, Aveika AA, Sabally S, Togun T, Sarge-Njie R, Alabi AS, Jaye A, Corrah
T, Whittle HC. 2004. Body mass index at time of HIV diagnosis: a strong and independent predictor of survival. J
Acquir Immune Defic Syndr 37: 1288-94
32. van der Sande MA, Schim van der Loeff MF, Bennett RC, Dowling M, Aveika AA, Togun TO, Sabally S, Jeffries
D, Adegbola RA, Sarge-Njie R, Jaye A, Corrah T, McConkey S, Whittle HC. 2004. Incidence of tuberculosis and
survival after its diagnosis in patients infected with HIV-1 and HIV-2. Aids 18: 1933-41
33. van der Sande MA, Goetghebuer T, Sanneh M, Whittle HC, Weber MW. 2004. Seasonal variation in respiratory
syncytial virus epidemics in the Gambia, West Africa. Pediatr Infect Dis J 23: 73-4
34. van der Sande MA, Waight P, Mendy M, Rayco-Solon P, Hutt P, Fulford T, Doherty C, McConkey SJ, Jeffries D,
Hall AJ, Whittle HC. 2006. Long-term protection against carriage of hepatitis B virus after infant vaccination. J Infect
Dis 193: 1528-35

Publications
35. van der Sande MA, Mendy M, Waight P, Doherty C, McConkey SJ, Hall AJ, Whittle HC. 2007. Similar long-term
vaccine efficacy of two versus three doses of HBV vaccine in early life. Vaccine 25: 1509-12
36. Viviani S, Mendy M, Jack AD, Hall AJ, Montesano R, Whittle HC. 2004. EPI vaccines-induced antibody prevalence
in 8-9 year-olds in The Gambia. Trop Med Int Health 9: 1044-9
Mulholland EK. 2006. The role of Chlamydia pneumoniae in acute respiratory tract infections in young children in
The Gambia, West Africa. Ann Trop Paediatr 26: 87-94
38. Wojnowski L, Turner PC, Pedersen B, Hustert E, Brockmoller J, Mendy M, Whittle HC, Kirk G, Wild CP. 2004.
Increased levels of aflatoxin-albumin adducts are associated with CYP3A5 polymorphisms in The Gambia, West
Africa. Pharmacogenetics 14: 691-700
2007
39. 1. Jallow S, Kaye S, Schutten M, Brandin E, Albert J, McConkey SJ, Corrah T, Whittle H, Vanham G, Rowland-Jones
S, Janssens W. 2007. Development and evaluation of an Oligonucleotide Ligation Assay for the detection of drug
resistance associated mutations in the HIV-2 pol gene. J Clin Microbiol
40. Rowland-Jones SL, Whittle HC. 2007. Out of Africa: what can we learn from HIV-2 about protective immunity to
HIV-1? Nat Immunol 8: 329-31
41. Miles DJ, van der Sande M, Jeffries D, Kaye S, Ismaili J, Ojuola O, Sanneh M, Touray ES, Waight P, Rowland-Jones
S, Whittle H, Marchant A. 2007. Cytomegalovirus Infection in Gambian Infants Leads to Profound CD8 T Cell Dif-
ferentiation. J Virol 81: 5766-5776
42. van der Sande MA, Mendy M, Waight P, Doherty C, McConkey SJ, Hall AJ, Whittle HC. 2007. Similar long-term
vaccine efficacy of two versus three doses of HBV vaccine in early life. Vaccine 25: 1509-12.
43. van der Sande, M. A., Waight, ., MMendy M, Zaman S, Kaye S, Sam O, Kahn A, Jeffries D, Akum AA, Hall AJ, Bah E,
McConkey SJ, Hainaut P, Whittle HC. Long-term protection against HBV chronic carriage of Gambian adolescents
vaccinated in infancy and immune response in HBV booster trial in adolescence. PLoS ONE 2007; 2:e753.
44. Martinez-Steele E, Awasana AA, Corrah T, Sabally S, van der Sande M, Jaye A, Togun T, Sarge-Njie R, McConkey
SJ, Whittle H, Schim van der Loeff MF. Is HIV-2- induced AIDS different from HIV-1-associated AIDS? Data from a
West African clinic. AIDS 2007; 21:317-324.
45. Van der Sande, M.A.B., Kaye, S., Miles, D.J.C., Waight, P. Jeffries, D.J., Ojuloa, O.O., Palmero, M., Pinder, M., Ismaili,
J., Flanagan, K.F., Aveika, A.A., Zaman, A., Rowland-Jones, S.L., McConkey, S.J., Whittle, H.C. and Marchant, A. Risk
factors and clinical outcome of congenital CMV infection in a peri-urban African birth cohort PLoSOne (2007) 6
e492
46. Leligdowicz, A., Yindom, L-M., Onyango, C., Sarge-Njie, R., Alabi, A., Cotten, M., Vincent, T., da Costa, C, Aaby,
P., Jaye, A., Dong, T., McMichael, A.J., Whittle, H.C. and Rowland-Jones, S.L. Robust gag-specific T-cell responses
characterize viraemia control in HIV-2 infection Journal of Clinical Investigation (2007) (in press)
47. Hammond, A.S., McConkey, S., Hill, P.C., Crozier, S., Klein, M.R., Adegbola, R.A., Rowland-Jones, S.L., Brookes, R.H.,
Whittle, H and Jaye, A. Mycobacterium tuberculosis specific immune responses are maintained across a broad
range of CD4 T-cell counts in patients infected with HIV Journal of Infectious Diseases (2007) (in press)
48. Duvall, M.G., Loré, K., Blaak, H., Ambrozak, D.A., Adams, W.C., Geldmacher, C., Mascola, J.R., McMichael, A.J.,
Hilton C. Whittle, H.C., Rowland-Jones, S.L. and Koup, R.A. Dendritic cells are less susceptible to HIV-2 than HIV-1
infection. J. Virology (2007) (in press)
49. Duvall, M.G., Precopio, M.L., Ambrozak, D.A., Jaye, A., McMichael, A.J., Hilton C. Whittle, H.C., Roederer, M.,
Rowland-Jones, S.L. and Koup, R.A. Polyfunctional T cell responses are a hallmark of HIV-2 infection European
Journal of Immunology (2007) (in press)

Publications
50. Miles D.C., van der Sande, M., Kaye, S., Crozier, S., Ojuola, O., Palmero, M.S., Touray, E.S., Waight, P., Rowland-
Jones, S.L, Whittle, H.C. and Marchant, A. CD4 T-cell responses to CMV mature slowly following infection in
infancy: a prospective birth cohort study Journal of Infectious Diseases (2007) (in press)
51. Emily S Gower, Anthony W. Solomon, Matthew J. Burton, Aura Aguirre, Beatriz Munoz, Robin Bailey, Martin Hol-
land, Pateh Makalo, Patrick Massae, Harran Mkocha, David C. Mabey, Sheila K. West. Chlamydial Positivity of Nasal
Trachoma and Chlamydia

Secretions at Baseline is Associated with Ocular Chlamydial Infection Two Months Following Azithromycin Treat-
ment (IVOS in press)
52. Nkoyo Faal, Robin L. Bailey, Hassan Joof , Isatou Sarr , Mass Laye, David Jeffries, David C. W. Mabey , Martin J.
Holland. Conjunctival FOXP3 expression in trachoma: Is there evidence for a role of T regulatory cells in hu-
man ocular Chlamydia trachomatis infection? ? PLoS Med 3(8): e266. DOI: http://dx.doi.org/10.1371/journal.
pmed.0030266
53. Angels Natividad, Graham Cooke, Martin Holland, Matthew Burton, Hassan Joof, Kirk Rockett, Dominic
Kwiatkowski, David Mabey, Robin Bailey. A coding polymorphism in Matrix metalloproteinase-9 reduces risk
of scarring sequelae of ocular Chlamydia trachomatis infection. BMC Medical Genetics 2006;7:40. http://www.
biomedcentral.com/1471-2350/7/40
54. Martin J Holland, Nkoyo Faal, Isatou Sarr, Hassan Joof, Mass Laye, Ewen Cameron, Frederick Pemberton-Pigott,
Hazel M Dockrell, Robin L Bailey, David CW Mabey. The frequency of Chlamydia trachomatis Major Outer Mem-
brane Protein-specific CD8+ T lymphocytes in active trachoma is associated with current ocular infection. Infect.
Immun. 2006;74(3):1565-1572.
55. M. J. Burton, M. J. Holland, D. Jeffries, D. C. W. Mabey, R. L. Bailey. Conjunctival Chlamydial 16S Ribosomal RNA
Expression in Trachoma: Is Chlamydial Metabolic activity required for disease to Develop. Clinical Infectious Dis-
eases 2006;42:463-470.
56. S.K. West, B. Munoz. H. Mkocha, M. J. Holland, A. Aguirre, A. W. Solomon, A. Foster, R. L. Bailey, D. C. W. Mabey.
Infection with Chlamydia trachomatis after mass treatment of a trachoma hyperendemic community in Tanzania: a
longitudinal study. Lancet 2005; 366: 1296 – 1300.
57. M J Burton, F Kinteh, O Jallow, A Sillah, M Bah, M Faye, E A N Aryee, U N Ikumapayi, N D E Alexander, R A
Adegbola, H Faal, D C W Mabey, A Foster, G J Johnson, and R L Bailey. A randomised controlled trial of azithro-
mycin following surgery for trachomatous trichiasis in the Gambia. Br. J. Ophthalmol., October 1, 2005; 89(10):
1282 - 1288.
58. M J Burton, R J C Bowman, H Faal, E A N Aryee, U N Ikumapayi, N D E Alexander, R A Adegbola, S K West, D

C W Mabey, A Foster, G J Johnson, and R L Bailey. Long term outcome of trichiasis surgery in the Gambia. Br. J.
Ophthalmol., May 2005; 89: 575 - 579.
59. Faal N, Robin L Bailey, Isatou Sarr, Hassan Joof, David CW Mabey and Martin J Holland. Temporal cytokine gene
expression patterns in subjects with trachoma identify distinct conjunctival responses associated with infection.
Clin.Exp.Immunol 2005, 142: 347-353. http://dx.doi.org/10.1111/j.1365-2249.2005.02917.x
60. Esther A.N Aryee, Robin L Bailey, Angels Natividad-Sancho, Steve Kaye, Martin J Holland. Detection, quantification
and genotyping of Herpes Simplex Virus in cervicovaginal secretions by real-time PCR: a cross sectional survey.
Virology Journal 2005, 2:61 http://www.virologyj.com/content/2/1/61
61. Natividad A, Wilson J, Koch O, Holland MJ, Rockett K, Faal N, Jallow O, Joof HM, Burton MJ, Alexander ND,
Kwiatkowski DP, Mabey DC, Bailey RL. Risk of trachomatous scarring and trichiasis in Gambians varies with SNP
haplotypes at the interferon-gamma and interleukin-10 loci. Genes Immun. 2005:1-9. http://dx.doi.org/10.1038/
sj.gene.6364182 http://www.nature.com/gene/journal/v6/n4/abs/6364182a.html

Publications
62. Burton MJ, Holland MJ, Makalo P, Aryee EA, Alexander ND, Sillah A, Faal H, West SK, Johnson GJ, Mabey DC, Bai-
ley RL. Re-emergence of Chlamydia trachomatis infection after mass antibiotic treatment of a trachoma-endemic
Gambian community: a longitudinal study. Lancet 2005;365:1321-28
63. N.D.E. Alexander, A.W. Solomon, M.J. Holland, R.L. Bailey, S.K. West, D.C.W. Mabey, A. Foster. An Index
of Community Ocular Chlamydia trachomatis Load for Control of Trachoma. Trans. R. Soc. Med. Hyg. 2005;
99(3):175-7 http://dx.doi.org/10.1016/j.trstmh.2004.05.003
64. Emily S. West, Sheila K. West, Beatriz Munoz, Harran Mkocha, Martin J. Holland, Aura Aguirre, Anthony W.
Solomon, Robin Bailey, Allen Foster, David Mabey. Mass Treatment and the Effect on the Load of C. trachomatis
Infection in a Trachoma Hyper-endemic Community. Invest Ophthalmol Vis Sci 2005;46(1):83-7 http://dx.doi.
org/10.1167/iovs.04-0327
65. Martin J Holland, Yvonne M Harcus, Adam Balic and Rick M Maizels.Th2 Induction by Nippostrongylus Se-
creted Antigens in Mice Deficient in B cells, Eosinophils or MHC Class I-related Ligands. Immunology Letters
2005:96(1);93-101. http://dx.doi.org/10.1016/j.imlet.2004.08.005
66. Matthew J. Burton, Robin L. Bailey, David Jeffries, David C. W. Mabey and Martin J. Holland. Cytokine and fibro-
genic gene expression in the conjunctivas of subjects from a Gambian Gambian community where trachoma is
endemic. Infect. Immun 2004;72(12):7352-7356 http://dx.doi.org/10.1128/IAI.72.7352-7356.2004
67. A W Solomon, M J Holland, N D E Alexander, P A Massae, A Aguirre, A Natividad-Sancho, S Molina, S Safari, J F

Shao, R W Peeling, S K West, R L Bailey, A Foster, D C W Mabey. High coverage mass treatment with single-dose
azithromycin for trachoma New Eng. J Med 2004;351(19);1962-71
68. Emerson PM Lindsay SW Lowe K Dibba SM Bah M Faal H McAdam K Walraven G Bailey RL. Role of
flies and provision of latrines in trachoma control, a cluster-randomised controlled trial. Lancet. 2004 Apr
3;363(9415):1093-8.
69. Anthony W. Solomon, Emma Harding-Esch, Patrick A. Massae, Neal D. E. Alexander, Aura Aguirre, Martin J. Hol-
land, John F. Shao, Paul Courtright, Robin L. Bailey, Allen Foster, and David C. W. Mabey. Two doses of azithro-
mycin may eliminate ocular chlamydial infection in a Tanzanian community. New Eng. J Med 2007 – in press
70. Angels Natividad, Martin Holland, Kirk Rockett , Julian Forton, Nkoyo Faal, Hassan Joof, David Mabey, Robin Bailey,
Dominic Kwiatkowski. Clinical consequences of allelic variation in the cis-regulation of IL-10 in human Chlamydia
trachomatis infection. Human Mol Genetics 2008; 17(2): 323 – 327. Epub 2007 Oct 18.
71. Laszlo Kari, William M Whitmore, John H Carlson, Deborah Crane, Nathalie Reveneau, David E Nelson, David
CW Mabey, Robin L Bailey, Martin J Holland, Grant McClarty and Harlan D Caldwell. Pathogenic diversity among
Chlamydia trachomatis ocular strains in non-human primates is affected by subtle genomic variations. JID 2007 –
in press
72. Sarah Burl, Philip C Hill, David J Jeffries, Martin Holland, Annette Fox, Moses D Lugos, Richard A Adegbola, Gra-
ham A Rook, Alimuddin Ali Zumla, Keith PWJ McAdam, Roger H Brookes. Recently infected healthy tuberculosis
case contacts have reduced FOXP3 gene expression. Clin. Exp. Immunol 2007; 149(1):117-22. Epub 2007 Apr 26.
73. A. Natividad, N. Hanchard, M.J. Holland, O.S.M. Mahdi, M. Diakite, K. Rockett, O. Jallow, H.M. Joof, D. P.
Kwiatkowski, D.C.W. Mabey, R.L. Bailey .Genetic variation at the TNF locus and the risk of severe sequelae of
ocular Chlamydia trachomatis infection in Gambians. Genes Immun 2007 Jun;8(4):288-95. Epub 2007 Mar 1.
74. Emily S. Gower, Anthony W. Solomon, Matthew J. Burton, Aura Aguirre, Beatriz Munoz, Robin Bailey, Martin
Holland, Pateh Makalo, Patrick Massae, Harran Mkocha, David C. Mabey, Sheila K. West. Chlamydial Positivity of
Nasal Secretions at Baseline is Associated with Ocular Chlamydial Infection Two Months Following Azithromycin
Treatment . IOVS 2006 ;47(11): 4767-71.

Nutrition
Group
Prof Andrew Prentice

Head of Nutrition Group
In addition, we are establishing

The Nutrition Group continues further research projects in areas
to focus its research on the four of both national and international
main topics of: importance. All of our research
seeks to advance our basic
Malnutrition and chronic understanding of the effects of
environmental enteropathy nutrition on health and hence to
Early programming of contribute to health policy and
immunity interventions. We report here some
Calcium and bone health key research outputs during the
Nutrient-gene interactions 2004 to 2007 period together with
a forward look at ongoing research
projects.

Vitamin A – less is more
In The Gambia the World 220 mother-infant pairs to either key interest however, none of the
Health Organization’s (WHO) the IVACG early high-dose protocol outcomes measured showed any
recommended dose for vitamin A (mothers 400,000IU early post- benefit of the high dose protocol
deficient groups is just as effective, partum; infants 50,000IU at 2m, over the existing standard dose,
and safer, than a higher dose of 3m, 4m and 100,000IU at 9m and with no effects detected on mucosal
proposed by the International 200,000IU at 12m) or the standard integrity, systemic infection or
Vitamin A Consultative Group WHO dose (mothers 200,000IU systemic immunity (see examples
(IVACG). early post-partum; infants 100,000IU in Fig 1). There were more clinic
at 9m and 200,000IU at 12m). attendances by the high dose
Universal vitamin A Plasma vitamin A concentration was group in the first 6 months of life
supplementation using the standard assessed in samples of cord blood (p=0.018).
WHO dosing regime has been and then in blood samples collected
adopted as government policy in from both the mothers and infants Our results do not lend support to
most countries in the developing up until the infants reached 12 the proposal to increase the existing
world, including The Gambia. In months of age. Additional data was WHO standard dosing schedule
2002 the International Vitamin collected on levels of vitamin A in for vitamin A in areas of moderate
A Consultative Group (IVACG) breast milk, mammary epithelial vitamin A deficiency. Caution is
Annecy Accord recommended a permeability, nasopharyngeal urged for future studies because
revised early high-dose regime for carriage of S. pneumoniae in both trials have shown possible adverse
mothers and infants. mothers and infants, infant infection effects of higher doses of vitamin A.
with H. pylori, gut permeability and Antibody responses to the standard
We have conducted a study in infant growth and morbidity. EPI vaccines are currently being
six villages in the rural West Kiang measured to examine suggestions
region of The Gambia, an area of In both groups of infants vitamin from Guinea Bissau of potential
moderate vitamin A deficiency. We A status gradually improved from negative interactions between
compared the benefits of these two 60% deficiency in cord blood to vitamin A and DPT vaccines.
protocols on infant health. Within 20% deficiency at 12 months of age
the study, we randomly assigned (plasma retinol <0.70 mol/l). Of

Lack of effect of a
high-dose vitamin A
supplementation regime
on plasma vitamin A
status and markers
of infection in rural
Gambian infants. GGSP
= Gambian Government
Standard Practice; EHD
= Early High Dose; CRP
= C-reactive protein;
AGP = alpha-1-acid
glycoprotein.

Malnutrition and chronic environmental
enteropathy

Richard Adegbola, Momodou Darboe, Conor Doherty, Tony Fulford, Gareth
Morgan, Ousman Secka, Juan Solon, Andrew Prentice
Collaborators:
Sarah Jackson, Christine Northrop-Clewes (MRC Human Nutrition Research,
Cambridge, UK); David Thurnam (University of Ulster, Coleraine, Northern
Ireland)
Funding:

Forward look
Long-chain n-3 polyunsaturated fatty seen in Gambian infants is strongly children aged 3 to 9 months. The
acids in relation to gut integrity and associated with intestinal damage results of this study will add to
growth of rural Gambian children: and malabsorption. Since there our understanding of the role of
is evidence that supplementary essential fatty acids in infant health
Long-chain n-3 polyunsaturated fatty n-3 PUFA’s might ameliorate and will be valuable in contributing
acids (PUFA’s) are vital components this damage by reducing gastro- towards researching an appropriate
of cell membranes, particularly in intestinal inflammation, we plan intervention to reduce the
the brain, and also exert powerful to initiate a randomized, double- widespread enteropathy occurring
immune-modulating effects. blind, controlled trial to investigate in infants in The Gambia and other
Weaning diets fed to infants in rural the physiological functions of developing countries.
Gambia are low in n-3 PUFA’s with dietary n-3 PUFA’s (300mg EPA +
intakes dropping severely once 200mg DHA per day) in relation This project will form the basis of
breastfeeding is terminated. We to infant growth, small bowel Ms Liandré van der Merwe’s PhD
have previously documented that mucosal integrity and inflammation, thesis.
the high degree of growth faltering and infections in rural Gambian
Birthday determines health

Significant research findings in The and release of T-cells (assessed in this large and well-characterised
Gambia have been substantiated by measuring T-cell receptor cohort of Bangladeshi infants will
in Bangladesh. In both countries, rearrangement excision circles), explore the functional consequence
the thymus, an important part indicating that the changes in of these early effects on thymic
of the immune system is smaller thymus size translate into likely development.
in children born during the wet functional effects on immunity.
season compared to those born Measurements in breast milk The effectiveness of the typhoid
during the dry season. showed that levels of the cytokine vaccine during adulthood depends
interleukin-7 (IL-7) were reduced on the individual’s weight at
We continue with our research in the wet season. IL-7 promotes birth. We are investigating if any
programme exploring the early-life thymic development thus suggesting other factors of early life effect
programming of immunity. This that a reduction in the levels of the typhoid and pneumcoccal
programme is driven by our original breast milk proteins during the wet polysaccharide vaccines.
observation that young adults season may mediate the effect on
in rural Gambia who were born thymus size and function. In the last annual report, we
during the annual hungry (wet) presented the findings from our
season have increased mortality Ongoing research in the Nutrition work in Pakistan, which show that
from infectious diseases compared Programme continues to follow up antibody response to typhoid
to those born during the harvest these observations, and we have vaccination is correlated with
(dry) season. This observation recently completed a parallel study size at birth – with subjects born
suggests that long-term immune in a large cohort of infants from the of a lower birth weight having a
function is ‘programmed’ early in rural Matlab region of Bangladesh. weaker response as adults than
life; a hypothesis that has formed Using identical techniques to those those who were heavier at birth.
the basis for our continuing research used in The Gambia, we have Since no such relationship was
in this area. We have developed measured thymic development observed with a rabies vaccine, we
an international programme of in a large cohort of Bangladeshi hypothesised that this finding results
research and the ongoing projects infants. Although the analysis is from a functional deficit in T-cell
in The Gambia run parallel to ongoing, results obtained to date independent antibody responses in
collaborative projects in Bangladesh mirror those observed in The lower birth weight subjects. We
and Pakistan. Gambia with a significant effect of have now shown that this deficit is
month of measurement observed not improved by a second dose of
In our previous annual report, at all ages. In addition, a strong the same typhoid vaccine, and that
we described how thymic size, correlation was observed between no association is observed between
as assessed by ultrasound, is size at birth and thymic size, with size at birth and antibody response
highly correlated to the season infants born of a lower birth to a conjugated-polysaccharide
of measurement, with infants weight having significantly smaller vaccine.
measured in the wet season having thymuses, even after adjustment
significantly smaller thymuses than for current body size. This finding We are now following up these
infants measured in the dry season. supports our previous observations observations with a study in The
We have now shown that this from The Gambia that thymic size Gambia to explore the impact
reduction in size is matched by a is sensitive to critical exposures of early life variables on antibody
reduced production, maturation early in life and follow up studies response to polysaccharide

vaccines. The study in Lahore was morbidity during infancy. Fieldwork
limited by the level of detail of the for this study is now complete, with
information available from early a total of 320 young adults recruited
life. Within our Keneba dataset we and vaccinated with typhoid and
have detailed early-life information pneumococcal polysaccharide
of all individuals born since 1976. vaccines. Antibody analysis is
This includes information on their ongoing, and we hope to report the
mothers during pregnancy, data findings from this study in late 2007.
collected at birth, and growth and
Early life programming of immunity

Sophie Moore, Pa Tamba N’Gom, Andrew Prentice
Collaborators:
Richard Aspinall, Frances Gotch (Imperial College London, UK); Andrew
Collinson (Royal Devon and Exeter Hospital, UK); David Goldblatt (Institute of
Child Health, London, UK); Lars A Hanson (University of Goteborg, Sweden);
Shousun Chen Szu (National Institutes of Health, Maryland, USA)
Funding:
Sanofi-Pasteur, Medical Research Council
Early life predictors of low-grade inflammation

and chronic disease
Feeding mum In parallel to our interests in the
early-life programming of immunity,
What the mother eats during we are also investigating early-
pregnancy can affect the long life predictors of chronic disease.
term health of her child. We are Non-communicable diseases such
studying what effect calcium and as heart disease and diabetes are
protein supplements given to known to be strongly predicted
mothers during pregnancy has on by an individual’s habitual levels of
the risk of disease in their children. low-grade inflammation, which can
be measured using blood markers
In 2006, we completed our such as C-reactive protein (CRP).
component of a European However, very little is known
Union funded study (EARNEST) about the origins and determinants
to explore the long term of these markers. We have now
impact of pre-natal nutritional completed a study investigating
supplementation on the offspring. the determinants of low-grade
In this study, we followed up the inflammation in rural Gambians
children born from two cohorts of and exploring the mechanisms that
women supplemented in pregnancy; link exposures in early life to later
one cohort received a protein- chronic disease risk.
energy rich biscuit supplement
from mid-pregnancy to delivery, This research forms the basis for
whilst the second cohort received Ms Anna Davies’ PhD, due to be
a supplemental dose of calcium (or completed in 2007.
placebo) during pregnancy.

We have successfully traced and
recruited 1,317 children from the Key investigators at MRC The Gambia:
biscuit cohort and 389 children Anna Davies, Tony Fulford, Sophie Hawkesworth, Meaghan Kall, Landing Jarjou,
from the calcium cohort and Sophie Moore, Andrew Prentice, Ann Prentice, Marijke Prins, Yankuba Sawo
measured chronic disease risk
factors including body composition, Collaborators:
blood pressure, blood lipids, glucose Gail Goldberg and Steve Austin (MRC Human Nutrition Research, Cambridge,
and insulin. UK)
Analysis from this study is ongoing, Funding:

and will form part of Ms Sophie European Union, Medical Research Council
Hawkesworth’s PhD thesis.
Forward look
Pre-conceptual multiple among this preconceptional sample
micronutrient supplementation and population during the course of
placental function in rural Gambian the trial. We will assess differences
women. A randomised controlled between intervention and placebo
trial: groups in mid-gestational placental
endothelial activation and blood
Earlier work by the Nutrition flow, and placental active transport
group has described the poor mechanisms at delivery. Secondary
micronutrient status of many outcome measures will include fetal
rural Gambian women during biometry and placental endocrine
pregnancy and lactation, but the capacity in the second trimester of
primary effect of micronutrient pregnancy, neonatal anthropometry
deficiencies on the development at delivery and changes in maternal
of the fetus is unclear. Previous haematological and biochemical
maternal multimicronutrient status from baseline. This study
supplementation trials elsewhere utilises obstetric ultrasound imaging
have tended to target women for the first time in Keneba and
in established pregnancies with will provide a strong platform
inconsistent results. However, for detailed work on our pre-
data describing the impact of pregnancy, pregnancy and birth
maternal micronutrient status in cohorts in the future.
early feto-placental development
are sparse. The placenta is pivotal
in regulating fetal physiology and
we hypothesise that improved
maternal micronutrient status
prior to conception and during
early pregnancy will improve
placental functional parameters,
which are directly relevant to fetal
development. A large, community-
based randomised controlled
trial is now underway throughout
Kiang West, which aims to test
this hypothesis on a sample of
reproductive but non-pregnant
and non-lactating women. The
intervention being used is a daily
dose of 15 vitamins and minerals,
formulated by UNICEF and WHO
as key components in effective
maternal micronutrition and
termed UNIMMAP. We expect Dr Stephen Owens conducting a fetal ultrasound at MRC Keneba
to study 400 pregnancies from

Calcium and bone health
These studies are part of a larger children started in 2007.
The objectives of these studies programme investigating the Growth stunting may result in failure
are to determine the impact environmental, metabolic and to reach optimal peak bone mass
of adaptation to the very low genetic basis of inter-individual and during adolescence. Furthermore,
calcium intake (~200 mg/d in between-population variations in because many young Gambian
children; ~300 mg/d in adults) calcium handling and bone health, women marry soon after menarche,
prevalent in rural areas of The based at MRC Human Nutrition the period of adolescent bone
Gambia on: Research in Cambridge, directed by mineral accretion often coincides
reproductive health Dr Ann Prentice. We report here with pregnancy and lactation.
(pregnancy induced an update on studies completed Follow-up measurements of the
hypertension, lactational and ongoing in the 2004 to 2007 BDS cohort at 10 years post
performance, maternal period. supplementation were completed
bone health, fetal and infant in 2004 and the 12-year follow up
calcium accretion), for the boys in 2006. We plan to
child health (stunting, low Fragile bones follow the boys until they reach
bone mineral content, skeletal maturity. The girls are now
A lack of calcium in the diet can
rickets, blood pressure), followed up more regularly so we
make bones fragile and more likely
health in old age (bone and can study whether pre-pubertal
to break. We are investigating
vascular disease). Ca supplementation has long-
whether calcium supplementation
in children and pregnant women term effects on calcium regulation
has an effect on their bones. during pregnancy and lactation,
and also the implications of low
The global burden of osteoporosis dietary calcium intake, coupled with
is expected to rise 4-fold by 2050 immature skeletal status during
in parallel with increases in life reproductive cycles, for long-term
expectancy, with the greatest maternal and child bone health.
increases predicted for populations
in transition from traditional to
western lifestyles.
Bone deformities
Abnormal bone growth in some
Many recommendations advocate Gambians could be due to
increased calcium intakes as part of misregulation of a vital mineral by
population preventative strategies the body.
which have major economic
implications for countries such as In recent years, children have
The Gambia, but the evidence for presented at MRC clinics in Keneba
the efficacy of such interventions is and Fajara with rickets-like bone
lacking. Data analysis and long- deformities of unknown aetiology.
term follow-up measurements This parallels the emergence of
for two randomised double blind non-vitamin D deficiency rickets
placebo controlled trials of calcium in some other African and Asian
supplementation is ongoing; one of countries with populations that
600 pregnant women in West Kiang have calcium intakes considerably
(PS Study), the other of 160 boys below recommended levels, and
and girls originally aged 8-12 years close to the biological requirement
(BDS Study). for skeletal accretion. Plasma
phosphate tended to be low, and
A subset of 125 women and 70% had an abnormally elevated
their infants in the PS study were plasma concentration of fibroblast
studied in detail. No significant growth factor 23 (FGF23), a
differences were detected between newly discovered phosphate-
the supplementation groups (1500 regulating hormone (Figure 2).
mg Ca/d v placebo) in breast-milk Concentrations remained elevated
calcium concentration, infant birth for 6-12 months, suggesting a
weight, growth or bone mineral long-standing, chronic abnormality
status in the first year of life. There of phosphate regulation. In 2006 a
was evidence of a slower rate of follow up investigation began of the
increase in infant whole-body bone index cases, their parents and full
mineral content and bone area siblings to further characterise this
in the calcium group. A follow up disorder. A prevalence survey of all
study of the bone status of the children under 18 years old in West
Kiang was started in 2007.

Plasma FGF23 concentrations in
rickets patients and community
samples
Rickets-A = patients with signs of
active rickets; Rickets-B = patients
with signs of healed rickets.
The figure shows the maximum
FGF23 concentration recorded for
each patient. The bar represents the
median value for the group. 70% of
rickets patients had a value above
the range of community values.
There was no significant difference
between Groups A and B (P=0.14),
both were significantly different
from the community sample
(P<0.0001).
2004-6 saw major advancements facilities, and new dual energy x-ray
in bone imaging at MRC Keneba absorptiometry and peripheral
with the commissioning of an X-ray quantitative computed tomography
unit in purpose-built research equipment.
Keneba staff with Dr Ann Laskey (second left) holding their training certificates for
the new DXA Prodigy machine.

Landing Jarjou, Ann Prentice, Abdoulie Sanneh, Yankuba Sawo, Helen Smith.
Collaborators:
Stephanie de Bono, Fiona Ginty, Gail Goldberg, Celia Greenberg, Ann Laskey,
Shailja Nigdikar, Inez Schoenmakers, Liya Yan (MRC Human Nutrition Research
Unit, Cambridge, UK); Tom Beck (Johns Hopkins University, Baltimore, USA);
Nick Bishop (University of Sheffield, UK); Tim Cole (Institute of Child Health,
London, UK); Philip Fischer (Mayo Clinic, USA); John Pettifor (Chris Hani-
Baragwanath Hospital and University of Witswatersrand, Johannesburg, South
Africa); Roger Price (Department of Medical Technology & Physics, Sir Charles
Gairdner Hospital, Perth, Australia); Tom Thacher (University of Jos, Nigeria);
Bo Zhou (Shenyang Medical College, China)
Funding:

Forward look
Planned research in the calcium and approaching the age and size where
bone health sub-programme will bone imaging using DXA and
include studies to investigate the pQCT becomes both feasible and
effect of calcium supplementation meaningful. The new DXA has a
during pregnancy on maternal blood number of advantages including
pressure, calciotropic hormones, faster scan times, enabling greater
bone turnover markers, plasma subject throughput and facilitating
and urinary minerals in pregnancy measurements of infants and
and lactation, and on bone mineral children. We will also continue our
in lactation. In addition, we have research into the investigations of
initiated a systematic screening of the long-term consequences for
all children in West Kiang between maternal bone health of repeated
0-17.9 years of age (approximately periods of prolonged lactation.
8000 children) to assess the Future planned studies will also
prevalence, characteristics and focus on calcium handling in adults
disease burden of rickets-like bone and children using stable isotope
deformities. Further research will and other tracer methodologies and
focus on the assessment of bone we will continue our research into
status in the offspring of children the early life influences on bone
born to mothers supplemented growth, size, shape and structural
in the previously highlighted geometry.
PS study. These children are
Nutrient gene interactions

Iron, genetics, Associations between Hp HbAS was protective against
polymorphisms and development malaria in 2003, but less so in 2004.
anaemia and infection of anaemia, iron delocalisation Understanding the variability of
and oxidant stress during malarial response to iron supplementation
Anaemia is generally treated with episodes, and risk of malaria and in malaria-endemic areas could have
iron supplements but a large co-bacteraemia are currently important policy implications for
trial from East Africa showed being analysed and prepared for iron supplementation strategies.
potentially harmful effects. We publication. This study was followed
are investigating the interactions up in 2004 by another prospective Iron supplements should be given at
between genes, anaemia and cohort study in which all children a later stage of malaria treatment
malarial infection to understand aged 6-60 months received iron
this problem and recommend fresh supplementation during the malarial In 2003, we conducted a case-
approaches. transmission season. They were control study of the efficacy of
followed up intensely for the iron absorption after therapeutic
Following on from Dr Sarah incidence of malarial and other supplementation in children
Atkinson’s study, which found infectious episodes – in order to with malaria-associated anaemia
the haptoglobin polymorphism, test if polymorphisms of Hp and compared to non-malarial iron-
Hp2 to be associated with the alleles for sickle haemoglobin deficiency anaemia using stable
malaria-associated anaemia (now and alpha-thalassaemia interact isotope tracers – one of the largest
published in PloS Medicine) we with baseline iron status. We studies of this kind ever performed.
have continued investigations also looked at the effects of iron Results indicate that absorption
of the interactions between Hp supplementation on haemoglobin is impaired for at least 2 weeks
polymorphisms, iron metabolism (Hb) response and susceptibility after completion of treatment
and infection. Laboratory analyses to infection. Initial analyses indicate for malaria, but by 1 month Hb
have been completed from the that iron supplementation was responses are actually greater
large prospective cohort conducted effective in causing a small increase in those with malaria-associated
in 2003. Importantly, this study in mean Hb concentration at the anaemia compared to those with
confirmed the previous finding of end of the malaria transmission iron-deficiency related anaemia
the Hp2 allele being associated with season. This response did not (see Figs 3 & 4). We hypothesise
an increased drop in haemoglobin appear to be altered in those that this is due to the utilization
across a malarial season, even in the with the Hp22 genotype but may of iron from both the supplement
context of follow up and treatment have been reduced in those with and from the release of iron from
of all malarial episodes. alpha-thalassaemia. Additionally, macrophages, occurring after full
preliminary analysis suggests that recovery from malaria. Publication

of this data is awaiting the results of
hepcidin analysis being performed
with a new, fully quantitative, mass-
spectrometry technique, currently
in the last stage of development by
our collaborators at Kings College.
As a result of this study we are

planning future studies, to be
lead by Dr Chidi Nweneka to
investigate malaria therapeutic
combination strategies to assess if
longer duration of chloroquine or
addition of chloroquine to other
anti-malarials in addition to delayed
iron supplementation can promote
the early release of iron from the
reticulo-endothial system and
improvement of recovery of Hb
levels.
Our work in The Gambia has

initiated several other research Haemoglobin response (mean & 95% CI).
projects in which we are seeking
to further expand the scope of
these research hypotheses. Dr
Sarah Atkinson has conducted a
study investigating the role of Hp
polymorphisms, oxidant stress and
severe bacterial infections in the
pathogenesis of severe malnutrition
as treated in the dedicated
severe malnutrition ward in Kilifi,
Kenya. Dr Hala Ghattas is leading
a collaboration with Rebecca
Stoltzfus (Cornell University) and
the Public Health Laboratory, in
Pemba, Zanzibar to test whether
haptoglobin gene polymorphisms
influence anaemia rates in pregnant
women in Zanzibar – a highly
malaria-endemic area.
Haemoglobin response (mean & 95% CI).

Sarah Atkinson, Mamodou Bah, Sharon Cox, Conor Doherty, Tony Fulford,
Andrew Prentice, Joann McDermid, Chidi Nweneka, Giorgio Sirugo, Pura Solon
Collaborators:
Steve Abrams (Baylor College of Medicine, Houston, USA); Hala Ghattas,
Robin Bailey (London School of Hygiene and Tropical Medicine, UK); Adrian
Hill, Dominic Kwiatkowski, Kirk Rockett (Wellcome Centre for Human
Genetics, Oxford, UK); Kevin Marsh, Tom Williams (Kilifi KEMRI-Wellcome
Trust Collaborative Programme, Kenya); Alison May (University Hospital of
Wales, Cardiff)
Funding:

Forward look
Immunological mechanisms we will administer Zn for an
associated with zinc additional 6 months to investigate
supplementation in children less the immunological mechanisms
than 5 years of age and suffering associated with long term Zn
from severe pneumonia: supplementation. At discharge
from hospital and then at 1, 6
In this study, we plan to investigate and 12 months after the start of
the immunological mechanisms supplementation we will measure;
associated with adjuvant zinc thymus size by ultrasound, thymic
treatment for Gambian children output and T cell generation
with severe pneumonia. In The by real time PCR and flow
Gambia, the main source of zinc cytometric analysis of lymphocyte
(Zn) is animal products and the subpopulations, and immune
plant-based diet of Gambians regulation through cell proliferation
puts them at increased risk of Zn and TH1 and TH2 cytokine profiles.
deficiency. Pneumonia is a major Data obtained from this sub-study
killer and Zn supplementation has will add a mechanistic perspective
a potential for improving morbidity to understanding the role of
and mortality. The proposed study, supplementary Zn in the treatment
a collaboration with the Bacterial of severe pneumonia.
Diseases Programme, is part of a
large hospital-based double blind
randomised controlled clinical trial
investigating the effects of daily
Zn supplementation on rates of
recovery from severe pneumonia
and growth. In a subgroup of
children from the main study,

Nutrition: Training achievements 2004-2006;
Mr Mamadou Bah
MSc Medical Molecular Biology, University of Westminster, London, UK.
Mr Buba Jabang
Professional Certificate and Diploma in Management, Open University, UK.
Dr Landing Jarjou
PhD, Open University – “The calcium nutrition of rural pregnant Gambian women habituated to a low calcium diet”
Dr Pa Tamba Ngom
PhD, Imperial College, “The Molecular Mechanisms of Immunosenescence in Nutritional Deprivation”
Dr Chidi Nweneka
MSc Epidemiology, London School of Hygiene & Tropical Medicine, UK.
Mr Yankuba Sawo
MSc Public Health Nutrition, London School of Hygiene & Tropical Medicine, UK.

Nutrition Group: Publications
2004-2007
01. Adair L, Prentice AM (2004) A critical evaluation of the fetal origins hypothesis and its implications for developing
countries. J Nutr 134: 191-193.
02. Allal N, Sear R, Prentice AM, Mace R (2004) An evolutionary model of stature, age at first birth and reproductive
success in Gambia women. Proc Biol Sci 7; 271: 465-70.
03. Allen SJ, Hamer C (2004) Improving quality of care for severe malnutrition. Lancet 363: 2089-90.
04. Allen SJ, Thomas JE, Alexander NDE, Bailey B, Emerson PM (2004) Flies and Helicobacter pylori infection. Arch
Dis Child 89:1037-8.
05. Aspray TJ, Yan L, Prentice A (2005) Parathyroid hormone and rates of bone formation are raised in perimenopau-
sal rural Gambian women. Bone 36:710-20.
06. Atkinson S, Mwangi W, Uyoga SM, Ogada E, Macharia AW, Marsh K, Prentice AM, Williams TN (2007) The Hap-
toglobin 2-2 Genotype is Associated with a Reduced Incidence of Plasmodium falciparum Malaria in Children on
the Coast of Kenya. Clin Infect Dis 44: 802-9.
07. Atkinson S, Rockett K, Sirugo G, Bejon P, Fulford A, O’Connell M, Bailey R, Kwiatkowski D, Prentice AM (2006)
Seasonal Childhood Anaemia in West Africa is Associated with the Haptoglobin 2-2 Genotype. PLOS Medicine: 3;
e172.
08. Bah M (2006) Prevalence of alpha-thalassaemia and effects on malarial anaemia in rural Gambian children, MSc
Dissertation, University of Westminster.
09. Barnard P (2004) Home-based or centre-based treatment for severely malnourished children in West Kiang, The
Gambia? MSc Dissertation, London School of Hygiene & Tropical Medicine.
10. Beavan SR, Prentice A, Stirling DM, Dibba B, Yan L, Harrington DJ, Shearer MJ (2005) Ethnic differences in osteo-
calcin gamma-carboxylation, plasma phylloquinone (vitamin K1) and apolipoprotein E genotype. Eur J Clin Nutr
59:72-81.
11. Brabin BJ, Romagosa C, Abdelgalil S, Menendez C, Verhoeff FH, McGready R, Fletcher KA, Owens S, D’Alessandro
U, Nosten F, Fischer PR, Ordi J (2004) The sick placenta - the role of malaria. Placenta 25: 359-378.
12. Collinson AC, Moore SE, O’Connell MA, Charalambos C, Prentice AM (2005) Developmental changes in leptin as
a measure of energy status in human infants in a natural ecological setting. Am J Clin Nutr 81: 488-94.
13. Cox S (2005) Energy: Metabolism. In Encyclopedia of Human Nutrition, 2nd Edition. Eds: Caballero B, Allen L,
Prentice AM. Elsevier Academic Press: Oxford, Vol 2: 7-13.
14. Cox SE, Arthur P, Kirkwood BR, Yeboah-Antwi K, Riley EM (2006) Vitamin A supplementation increases ratios
of proinflammatory to anti-inflammatory cytokine responses in pregnancy and lactation. Clin & Exp Immunol 144:
392-400.
15. Cox SE, Staalsoe T, Arthur P, Bulmer JN, Hviid L, Yeboah-Antwi K, Kirkwood BR, Riley EM (2005) Rapid acquisi-
tion of isolate-specific antibodies to chondroitin sulfate A-adherent plasmodium falciparum isolates in Ghanaian
primigravidae. Infect Immunol 73: 2841-7.
16. Cox SE, Staalsoe T, Arthur P, Bulmer JN, Tagbor H, Hviid L, Frost C, Riley EM, Kirkwood BR (2005) Maternal
vitamin A supplementation and immunity to malaria in pregnancy in Ghanaian primigravids. Trop Med & Int Health
10: 1286-97.
17. Cox SE, Doherty C, Atkinson SH, Nweneka CV, Fulford AJC, Ghattas H, Rockett KA, Kwiatkowski DP, Prentice

Publications
AM (2007) Haplotype Association between Haptoglobin (Hp2) and Hp Promoter SNP (A-61C) May Explain
Previous Controversy of Haptoglobin and Malaria Protection. PloS ONE 2: e362.
18. Cox SE, Doherty CP, Atkinson SH, Nweneka CV, Fulford AJC, Rockett KA, Kwaitkowski DP, Prentice AM (2007)
Haptoglobin genotype, anaemia and malaria in Gambian children. Trop Med & Int Health 3: e172.
19. Darboe MK, Adegbola R, Secka O, Jackson SJ, Austin S, Fulford AJC, Doherty C, Thurnham DI, Prentice AM
(2005) Effect of standard or early high-dose vitamin A supplementation on nasopharyngeal pneumococcal carriage
and Helicobacter pylori infection among rural Gambian infants. Ann Nutr Metab 49: 145.
20. Darboe MK, Thurnham DI, Morgan G, Adegbola RA, Secka O, Solon J, Jackson SJ, Northrope-Clewes C, Fulford
TJ, Doherty CP, Prentice AM (2007) Effectiveness of the new IVACG early high-dose vitamin A supplementation
scheme compared to the standard WHO protocol: A randomised controlled trial in Gambian mothers and infants.
The Lancet 369: 2088-96.
21. Doherty C (2005) Immunity: Effects of Iron and Zinc. In Encyclopedia of Human Nutrition, 2nd Edition. Eds:
Caballero B, Allen L, Prentice AM. Elsevier Academic Press: Oxford, Vol 3: pp 106-114.
22. Denny A (2005) The effect of the remittance economy on the nutritional status of children in rural Gambia, MSc
Dissertation, London School of Hygiene & Tropical Medicine.
23. Encyclopedia of Human Nutrition, 2nd Edition (2005) Eds: Caballero B, Allen L, Prentice AM. Elsevier Academic
Press: Oxford.
24. Fulford AJC, Rayco-Solon P, Prentice AM (2006) Statistical modelling of the seasonality of preterm delivery and
intrauterine growth restriction in rural Gambia. Paediatr Perinat Epidemiol 20: 251-9.
25. Ghattas H (2005) Infection: Nutritional Interactions. In Encyclopedia of Human Nutrition, 2nd Edition. Eds: Cabal-
lero B, Allen L, Prentice AM. Elsevier Academic Press: Oxford, Vol 3: pp 47-54.
26. Ghattas H, Darboe BH, Wallace DL, Griffin GE, Prentice AM, Macallan DC (2005) Measuring lymphocyte kinetics
in tropical field settings. Trans R Soc Trop Med Hyg 99: 675-85.
27. Ghattas H, Wallace DL, Solon JA, Henson SM, Zhang Y, Ngom PT, Aspinall R, Morgan G, Griffin GE, Prentice AM,
Macallan DC (2007) Long-term effects of perinatal nutrition on T-lymphocyte kinetics in young Gambian men. Am
J Clin Nutr 85: 480-7.
28. Ginty F, Prentice A (2004) Can osteoporosis be prevented with dietary strategies during adolescence? Br J Nutr
92:5-6.
29. Ginty F, Prentice A, McKenna L, Bennett J, Dibba B (2004) An investigation into the effects of calcium carbonate
supplementation on markers of pubertal status and leptin in 8-12 year old Gambian girls. J Bone Miner Res 19:
S450.
30. Grey P (2004) Obesity in Urban Gambia: Generations apart? MSc Dissertation, University of Durham.
31. Gruenewald C (2006) Is there a regulation of infant birth size by maternal body size? Analysis of this relationship
using linear regression, MSc Dissertation, London School of Hygiene & Tropical Medicine.
32. Huidobro LA, Fulford T, Carrasco E (2004) Gestational Diabetes incidence and its relationship with obesity in Chil-
ean pregnant women. Rev Med Chile 132: 931-8.
33. Jackson SJ, Leahy FE, Jebb SA, Prentice AM, Coward WA, Bluck LJ (2006) Frequent feeding delays the gastric emp-
tying of a subsequent meal. Appetite 48: 199-205.
34. Jaffar S, Van der Loeff MS, Eugen-Olsen J, Vincent T, Sarge-Njie R, Ngom P, Meyer AM, Berry N, Aaby P, Whit-
tle H (2005) Immunological predictors of survival in HIV type 2-infected rural villagers in Guinea-Bissau. AIDS Res

Publications
Hum Retroviruses 21: 560-4.
35. Jallow B (2004) Anthropometric status and body fat of Gambian adolescents, MSc Dissertation, London School of
Hygiene & Tropical Medicine.
36. Jarjou LMA (2004) The calcium nutrition of rural pregnant Gambian women habituated to a low calcium diet,
PhD, Open University.
37. Jarjou LMA, Prentice A, Bennett J (2004) Impact of calcium supplementation in the preceding pregnancy on the
human milk calcium concentration of Gambian women. Adv Exp Med Biol 554: 347-9.
38. Jarjou LMA, Prentice A, et al (2004) Impact of calcium supplementation in the preceding pregnancy on the human
milk calcium concentration of Gambian women. Protecting Infants through Human Milk: Advancing the Scientific
Evidence. L. K. Pickering, A. L. Morrow, R. J. Schanler and G. M. Ruiz-Palacios. New York, Kluwer Academic 554:
347-349.
39. Jarjou LMA, Prentice A, Sawo Y, Laskey MA, Bennett J, Goldberg GR, Cole TJ (2006) Randomized, placebo-con-
trolled, calcium supplementation study in pregnant Gambian women: effects on breast-milk calcium concentrations
and infant birth weight, growth, and bone mineral accretion in the first year of life. Am J Clin Nutr 83: 657-666.
40. Jebb SA, Siervo M, Fruhbeck G, Goldberg GR, Murgatroyd PR, Prentice AM (2006) Variability of appetite control
mechanisms in response to 9 weeks of progressive overfeeding in humans. Int J Obes 30:1160-2. Epub 2006 Feb
14.
41. Jebb SA, Siervo M, Murgatroyd PR, Evans S, Fruhbeck G, Prentice AM (2007) Validity of the leg-to-leg bioimped-
ance to estimate changes in body fat during weight loss and regain in overweight women: a comparison with multi-
compartment models. Int J Obes (Lond) 31: 756-62.
42. Jones RT, Darboe MK, Doherty CP, MacKay WG, Weaver LT, Campbell DI, Thomas JE (2007) Evaluation of 13C-
urea breath test and fecal antigen immunoassay to detect Helicobacter pylori infection in Gambian infants. J Pediatr
Gastroenterol Nutr 44: 650-2.
43. Laskey MA, Prentice A (2004) Do appendicular bone measurements reflect changes in the axial skeleton?: the use
of dual-energy X-ray absorptiometry and ultrasound measurements during lactation. J Clin Densitom 7: 296-301.
44. Macallan DC, Wallace D, Zhang Y, De Lara C, Worth AT, Ghattas H, Griffin GE, Beverley PC, Tough DF (2004)
Rapid turnover of effector-memory CD4(+) T cells in healthy humans. J Exp Med 200: 255-60.
45. Macallan DC, Wallace DL, Zhang Y, Ghattas H, Asquith B, de Lara C, Worth A, Panayiotakopoulos G, Griffin GE,
Tough DF, Beverley PC (2005) B-cell kinetics in humans: rapid turnover of peripheral blood memory cells. Blood
105: 3633-40.
46. McCarthy HD, Cole TJ, Fry T, Jebb SA, Prentice AM (2006) Body fat reference curves for children. Int J Obes 30,
598-602.
47. McDermid JM, Jaye A, Schim van der Loeff MF, Todd J, Bates C, Austin S, Jeffries D, Awasana AA, Whittle HC,
Prentice AM (2007) Elevated iron status strongly predicts mortality in West African Adults with HIV infection. J
Acquir Immune Defic Syndr (in press).
48. McDermid JM, Prentice AM (2006) Iron and infection: effects of host iron status and the iron-regulatory genes
haptoglobin and NRAMP1 (SLC11A1) on host-pathogen interactions in tuberculosis and HIV. Clin Sci 110: 503-
524.
49. Moore SE (2006) Commentary: Patterns in mortality governed by the seasons. Int J Epidemiol 35: 435-437.
50. Moore SE, Collinson AC, Fulford AJC, Jalil F, Siegrist CA, Goldblatt D, Hanson LÅ, Prentice AM (2006) Effect of
month of vaccine administration on antibody responses in The Gambia and Pakistan. Trop Med Int Health 11:

Publications
1129-41.
51. Moore SE, Collinson AC, Ngom PT, Aspinall R, Prentice AM (2006) Early immunological development and mortality from
infectious disease in later life. Proc Nutr Soc 65: 311-318.
52. Moore SE, Collinson AC, Ngom PT, Prentice AM (2005) Maternal malnutrition and the risk of infection in later life. In
Hornstra G. Uauy R. Yang X (eds): The impact of Maternal Nutrition on the Offspring, Nestle Nutrition Workshop Series
Pediatric Program, vol 55, pp 153-167, nestec Ltd., Vevey/S. Karger AG, Basel.
53. Moore SE, Falorni A, Bini V, Fulford AJC, O’Connell M, Prentice AM (2004) Ethnic differences in the relationship between
fasting leptin and BMI in children. Int J Obes 28: 17-21.
54. Moore SE, Fulford AJC, Streatfield PK, Persson LA, Prentice AM (2004) Comparative analysis of patterns of survival by
season of birth in rural Bangladeshi and Gambian populations. Int J Epid 33: 137-143.
55. Moore SE, Jalil F, Ashraf R, Szu SC, Prentice AM, Hanson LA (2004) Birth weight predicts response to vaccination in adults
born in an urban slum in Lahore, Pakistan. Am J Clin Nutr 80: 453-9.
56. Moore SE, Mansoor MA, Bates CJ, Prentice AM (2006) Plasma homocysteine, folate and vitamin B12 compared between
rural Gambian and UK adults. Br J Nutr 96: 508-515.
57. Moore SE, Prentice AM, Coward WA, Wright A, Arifeen S, Kabir I (2005) Validation of exclusive breastfeeding in rural
Bangladeshi infants by isotopic methods: findings from the Minimat Study. Ann Nutr Metab 49: 331.
58. Moore SE, Prentice AM, Coward WAC, Wright A, Frongillo EA, Fulford AJC, Mander AP, Arifeen S, Kabir I (2007) Use
of stable isotope techniques to validate infant feeding practices reported by Bangladeshi women receiving breastfeeding
counselling. Am J Clin Nutr 85: 1075-82.
59. Moore SE, Jalil F, Ashraf R, Szu SC, Hahn-Zoric M, Prentice AM & Hanson LÅ. Revaccination does not improve an ob-
served deficit in antibody responses in Pakistani adults born of a lower birth weight. Vaccine (in press).
60. Munday K, Fulford AJC, Bates CJ (2005) Vitamin C status and collagen cross-link ratios in Gambian children. British J Nutri-
tion 93:501-507.
61. Munday K, Ginty F, Fulford A, Bates CJ (2006) Relationships between biochemical bone turnover markers, season, and
inflammatory status indices in prepubertal Gambian boys. Calcif Tissue Int 79: 15-21.
62. Ngom PT (2005) The molecular mechanisms of immunosenescence in nutritional deprivation, PhD, Imperial College.
63. Ngom PT, Collinson AC, Pido-Lopez J, Henson SM, Prentice AM, Aspinall R (2004) Improved thymic function in exclu-
sively breastfed infants is associated with higher interleukin 7 concentrations in their mothers’ breast milk. Am J Clin Nutr
80: 722-8.
64. Nweneka C (2007) Rethinking iron supplementation recommendations in health care (Letter to the Editor). BJOG (in
press).
65. Nweneka C (2007) Delayed recognition of HIV infection in malnourished children is associated with poor clinical outcome
in low HIV prevalence settings - preliminary observations (Letter to the Editor). JAIDS (in press).
66. Nweneka C, Doherty CP, Weaver LT (2007) Malaria and anaemia among children. Postgraduate Doctor Journal (in press).
67. Ofordile ON, Prentice AM, Moore SE, Holladay SD (2005). Early pesticide exposure and later mortality in rural Africa: A
new hypothesis. J Immunotoxicol 2: 33-40.
68. Owens S, Abdel-Rahman IE, Balyejusa S, Musoke P, Cooke RPD, Parry CM, Coulter JBS (2007) Nasopharyngeal aspiration
for the diagnosis of pulmonary tuberculosis. Arch Dis Child 92: 693-6.

Publications
69. Owens S, Chamley LW, Ordi J, Brabin BJ, Johnson PM (2005) The association of anti-phospholipid antibodies with
parity in placental malaria. Clin Exp Imm 142: 512-518.
70. Owens S, Harper G, Amuasi J, Offei-Larbi G, Ordi J, Brabin BJ (2006) Placental malaria and immunity to infant
measles. Arch Dis Child 91: 507–508.
71. Owens S, Stokes E, Mueller J (2007) Debate: Letters to the Editor. Re: Clinical trials in tropical diseases: a politically
incorrect view. Trop Med Int Health 12: 472.
72. Prentice A (2005) Optimisation of vitamin D status. Clin Chim Acta 355: S31.
73. Prentice A, Branca F, Decsi T, Michaelsen KF, Fletcher RJ, Guesry P, Manz F, Vidailhet M, Pannemans D, Samartin
S (2004) Energy and nutrient dietary reference values for children in Europe: methodological approaches and cur-
rent nutritional recommendations. Br J Nutr 92: S83-S146.
74. Prentice A, Laskey MA, Goldberg GR (2006) Letter: Reply to W. Koo [re paper - Randomized, placebo-controlled,
calcium supplementation study in pregnant Gambian women: effects on breast-milk calcium concentrations and
infant birth weight, growth, and bone mineral accretion in the first year of life, Am J Clin Nutr 2006; 83: 657-66].
Am J Clin Nutr 84, 944-945.
75. Prentice A, Schoenmakers I, Laskey MA, de Bono S, Ginty F, Goldberg GR (2006) Nutrition and bone growth
development. Proc Nutr Soc 65: 348-360.
76. Prentice AM (2005) Early influences on human energy regulation: thrifty genotypes and thrifty phenotypes. Phys &
Behav 86: 640-645.
77. Prentice AM (2004) Food and Nutrition. In: Principles of Medicine in Africa: 3rd Edition, Eds: Parry EHO, Godfrey
RC, Mabey DMW, Gill GV; Cambridge University Press, Cambridge, pp. 45-76.
78. Prentice AM (2005) Macronutrients as sources of food energy. Pub Hlth Nutr 8: 932-9.
79. Prentice AM (2004) Nutrition and pregnancy. Women’s Health Medicine 1: 22-24.
80. Prentice AM (2005) Starvation in humans: Evolutionary background and contemporary implications. Mech Ageing
Dev 126: 976-981.
81. Prentice AM (2004) Storing up problems: the medical case for a slimmer nation. Clin Med 4: 99-101.
82. Prentice AM (2006) The emerging epidemic of obesity in developing countries. Int J Epidemiol 35:93-9. Epub
2005 Dec 2.
83. Prentice AM, Jebb SA (2005) Energy intake/physical activity interactions in the homeostasis of body weight regula-
tion. Nutrition Reviews 7: S98-104.
84. Prentice AM, Moore SE (2005) Early Programming of Adult Diseases in Resource Poor Countries. Arch Dis Child
90: 429-32.
85. Prentice AM, Rayco-Solon P, Moore SE (2005) Insights from the developing world: thrifty genotypes and thrifty
phenotypes. Proc Nutr Soc 64: 153-61.
86. Prentice AM, Webb F (2005) Future perspectives on obesity: A short history with a long future. Obesity Metab 1:
1-13.
87. Prentice AM (2006) Are defects in energy expenditure involved in the causation of obesity. Obes Rev 8: 89-91.

Publications
88. Prentice AM (2007) Surviving Famine. In: Survival, ed: Shuckburgh E; Cambridge University Press, Cambridge, 224
p.
89. Prentice AM (2007) Energy. In: Essentials of Human Nutrition, eds: Mann J and Truswell S; Oxford University
Press, Oxford, 640 p.
90. Prentice AM, Darboe MK (2007) Growth and Host-Pathogen interactions. In The Window of Opportunity: Pre-
Pregnancy to 24 months of Age. Nestle Nutrition Workshop Series, Pediatric Programme, Vol 61: p.197.
91. Prentice AM, Ghattas H, Cox SE (2007) Host-pathogen interactions: can micronutrients tip the balance? J Nutr
137: 1334-7.
92. Prentice AM, Ghattas H, Doherty CP, Cox SE (2007) Iron metabolism and malaria. Food & Nutr Bull (in press).
93. Prentice AM, van der Merwe L, Darboe MK, Solon J (2007) Nutrition, Infection and Chronic Enteropathy in Afri-
can Infants. Proceedings of OHUS meeting (in press).
94. Prins M, Hawkesworth S, Wright A, Fulford AJC, Prentice AM, Moore SE (2007) Use of a bioelectrical impedance
analysis to assess body composition in rural African children. Eur J Clin Nutr [Epub ahead of print] 11 July 2007;
doi:10.1038/sj.ejcn.1602830.
95. Raqib R, Alam DS, Sarker P, Meshbahuddin A, Ara G, Yunus M, Moore SE, Fuchs G (2007) Low birth weight is
associated with altered immune function in rural Bangladeshi children: A birth cohort study. Am J Clin Nutr 85:
845-52.
96. Rayco-Solon P, Fulford AJC, Prentice AM (2005) Differential effects of seasonality on preterm birth and intrauter-
ine growth restriction in rural Africans. Am J Clin Nutr 81: 134-139.
97. Rayco-Solon P, Fulford AJC, Prentice AM (2005) Maternal preconceptional weight and gestational length. Am J
Obstet Gynecol 192: 1133-6.
98. Rayco-Solon P, Moore SE, Fulford AJC, Prentice AM (2004) Fifty-year mortality trends in three rural African vil-
lages. Trop Med & Int Hlth 9: 1151-1160.
99. Rennie KL, Livingstone MB, Wells JC, McGloin A, Coward WA, Prentice AM, Jebb SA (2005) Association of
physical activity with body-composition indexes in children aged 6-8 y at varied risk of obesity. Am J Clin Nutr 82:
13-20.
100. Reeve J, Yan L, Prentice A (2004) Importance of geometric factors for hip fracture resistance (Response to the
Letter to the Editor). Bone 35: 1000.
101. Sawo Y (2004) The Long-term effect of lactation on bone mineral content of rural Gambian women, MSc Dis-
sertation, London School of Hygiene & Tropical Medicine.
102. Siervo M, Davies AA, Jebb SA, Jalil F, Moore SE, Prentice AM (2007) Ethnic differences in the association be-
tween body mass index and impedance index (Ht2/Z) in adult women and men using a leg-to-leg bioimpedance
method. Eur J Clin Nutr (in press).
103. Siervo M, Grey P, Nyan OA, Prentice AM (2005) Urbanization and obesity in The Gambia: a country in the early
stages of the demographic transition. Eur J Clin Nutr 60: 455-463.
104. Siervo M, Grey P, Nyan OA, Prentice AM (2006) A pilot study on body image, attractiveness and body size in
Gambians living in an urban community. Eat Weight Disord 11, 100-109.
105. Sirugo G, Schim van der Loeff M, Sam O, Nyan O, Pinder M, Hill AV, Kwiatkowski D, Prentice AM et al (2004)
A national DNA bank in The Gambia, West Africa, and genomic research in developing countries. Nature Genet-
ics 36: 785-86.

Publications
106. Smith H (2004) Influences of maternal nutritional status on the primary and secondary sex ratio in rural Gambia,
MSc Dissertation, London School of Hygiene & Tropical Medicine.
107. Solon JA, Morgan G, Prentice AM (2006) Mucosal immunity in severely malnourished Gambian children. J Pedi-
atr 149: S100-S106.
108. Turner PC, Collinson AC, Cheung YB, Gong Y, Hall AJ, Prentice AM, Wild CP (2007) Aflatoxin exposure in
utero causes growth faltering in Gambian infants. Int J Epidemiol (in press).
109. Van der Merwe L (2005) Long-chain polyunsaturated fatty acids in relation to health and development of rural
African children: research priorities and a possible experimental design, MSc Dissertation, London School of Hy-
giene & Tropical Medicine.
110. van der Sande MA, Waight P, Mendy M, Rayco-Solon P, Hutt P, Fulford AJC, Doherty C, McConkey SJ, Jeffries
D, Hall AJ, Whittle HC (2005) Long-term protection against carriage of hepatitis B virus after infant vaccination. J
Infect Dis 193: 1528-35.
111. Vasavda N, Menzel S, Kondaveeti S, Maytham E, Awogbade M, Bannister S, Cunningham J, Eichholz A, Daniel Y,
Okpala I, Fulford T, Thein SL (2007) The linear effects of alpha-thalassaemia, the UGT1A1 and HMOX1 polymor-
phisms on cholelithiasis in sickle cell disease. Br J of Haematol 138: 263-70.
112. Wallace DL, Zhang Y, Ghattas H, Worth A, Irvine, A, Bennett AR, Griffin GE, Beverley PC, Tough DF, Macallan
DC (2004) Direct measurement of T cell subset kinetics in vivo in elderly men and women. J Immunol 173: 1787-
94.
113. Webb FM, Prentice AM (2005) Obesity amidst poverty. Int J Epidemiol. doi: 10.1093/ije/dyi204

Genetics
Group
Dr Robert Walton
Head of Genetics Group
The period 2004-2007 saw robots and equipment for The period also saw organisational
substantial advances with the determining the quality of DNA changes in genetic research with
introduction of new technology (figure 2) were also installed. From the introduction of a new stream
for medium and high throughput December 2006 to October 2007, of work in Pharmacogenetics
genetic analysis for the first time in the sequencer was used to analyse and the subsequent merging of
the Unit. In addition new genetic 26,688 samples from the three main Pharmacogenetics with Human
research projects began on malaria, disease programmes. Genetics into a single Genetics
liver cancer and tuberculosis. programme with a broader remit
The Gambian National DNA bank under the leadership of Dr Robert
Initially a Taqman instrument was now houses 43,759 specimens Walton. Dr Giorgio Sirugo was
installed for smaller scale projects from 32 epidemiological studies the Head of the Human Genetics
and subsequently an ABI 3730xl and randomised controlled trials. Laboratory and of the DNA Bank
machine which is used for sequence Specimens are bar coded and until August 2006.
analysis, medium scale genotyping collated using the Biobase software
studies and microsatellite analysis and form the largest biorepository
(figure 1). Two liquid handling of its type in Africa.

Dr Giorgio Sirugo, Head of the
Human Genetics Laboratory and of
the DNA Bank until August 2006
Senior staff of the Genetics Group.

From left: Robert Walton, Louis-
Marie Yindom, Ramatoulie Jahna,
Fatoumatta Sisay-Joof, Peter Aka,
Archibald Worwui

EDCTP PhD student Louis Marie
Yindom with ABI3130xl genetic
analyzer
DNA quantitation (Hannah Chap-

man, Laboratory Technologist,
Genetics Group)
Genetic differences could effect antimalarials

Subtle differences in some people’s addition there may be novel African
DNA could make antimalarial alleles that affect function which are
medication less effective. About not present in other populations.
20% of Gambians in this These studies seek to explore the
genomic variations that may affect
study had a genetic difference activation of these antimalarial
which reduced the amount of compounds and to investigate their
active antimalarial drug in the effects on pharmacokinetics and
blood by about a third. clinical efficacy. Initial bioinformatic
analysis of the CYP2C19 gene
The aim of these studies is to which encodes the cytochrome
investigate the effects of common P450 mainly responsible for the
variants in the cytochrome activation of antimalarial biguanides.
P450 enzymes that activate the
antimalarial biguanides proguanil and Preliminary results show that
chlorproguanil. These drugs have genetic differences causing fast
been extensively used worldwide metabolism which are present in
for many years and are components about 20% of our population result
of new therapeutic combinations in a 30% decrease in the amount
such as Malarone and Lapdap. of active antimalarial biguanide in
Studies in Europeans and Asians the blood and half the maximum
suggest that a significant proportion concentration of the drug reached
of the population carry alleles that when people are treated for
lead to poor activation, however malaria.
the frequency of these alleles in
Africa was previously not known. In

Analysis of patterns of linkage disequilibrium in the CYP2C cluster shows two blocks of LD, one containing CYP2C18,
CYP2C19 and CYP2C9 and the other CYP2C8 (Walton et al Nature Genetics 2005)

Forward Look
Future work will involve
typing 600 children treated
for malaria with Lapdap
(chlorproguanil/dapsone)
in a randomised controlled
trial to study whether these
changes in pharmacokinetic
parameters influence the clinical
effectiveness of antimalarial
treatment.
Genetic effects on metabolism of antimalarial biguanides (Janha et al 2007)
Genetic effects on pharmacokinetics of

antimalarial drugs and their effectiveness in
the treatment of malaria in children.

Ramatoulie Janha, Fatoumatta Sisay-Joof, Archibald Worwui, David Conway,
Samuel Dunyo, Giorgio Sirugo
Collaborators:
Munir Pirmohamed, Peter Winstanley Liverpool University, UK; Paul Milligan,
London School of Hygiene and Tropical Medicine, UK
Funding:
Europe Developing Countries Clinical Trial Partnership (EDCTP) PhD
Fellowship

Can DNA affect HIV progression?
A new technology allows genes more time efficient using the haplotypes are shown in figure 5.
differences in the DNA of cells SNPlex system on the 3130xl. This
that control HIV infection to be new method will be used on future SNPlex assays have been designed
identified. Using this information samples and should contribute a for fine resolution genetic typing
novel technological advance in this of the TRIM5 gene encoding an
we will be able to see if different field. antiviral restriction factor thought
genes cause differences in to be important in controlling
susceptibility to HIV 2 and disease The relationship between KIR retroviral infection. Currently reliant
progression. alleles, case status and viral load on information from the HapMap
for HIV 2 will then be investigated database, these assays will be
This project seeks to elucidate together with an exploratory supplemented by including novel
the role of inherited variations in analysis of the effects of KIR variants polymorphisms of the splice variant
receptors on natural killer cells on HIV 1 and HTLV1, although TRIM5alpha which have been
(KIR) in controlling infection with the number of people with HIV 1 identified by sequencing cDNA
the HIV 2 virus. Initial KIR typing in Caio is relatively small. Work from TRIM5alpha mRNA extracted
has now been completed on 347 has commenced on similar studies from peripheral blood lymphocytes
people in the Caio cohort in Guinea in Fajara, The Gambia, for HIV from participants in Caio. Thus
Bissau. 178 of these are cases and 1 where 160 of a target 500 the generic assay will be tailored to
169 are controls. The presence HIV negative controls have been the specific study population. The
or absence of 15 KIR genes in all recruited so far from those who resulting SNPlex assay will be used
participants has been ascertained present for retroviral serology at to explore the relationship between
using PCR with sequence specific the Genito Urinary Medicine clinic. genetic variants of TRIM genes in
primers. Work is now in progress These people will act as controls large scale studies in the Fajara and
to identify the alleles present by for the Fajara HIV 1 cohort which Caio cohorts.
DNA sequencing on the newly has already been established. All
installed 3730xl genetic analyser. 513 people in the study from Caio
Primers have been designed to have now been typed for NK cell
make the detection of the KIR receptor genes. The common KIR
Hap 3DL3 2DS2 2DL2 2DL3 2DL5 2DS3 2DP1 2DL1 2DL4 3DL1 3DS1 2DS5 2DS1 2DS4 3DL2 Total
YA1 145
YA1 54
YA2 35
YA2 16
YA3 15
YA4 11
YA5 11
YA6 10
YA7 10
YA8 9
YA9 9
YA10 9
YA11 8
YA12 8
YA13 8
YA14 7
YA15 7
YA16 7
YA17 6
YA18 5
Common KIR haplotyes in Caio, Guinea-Bissau

Investigating the effects of genetic variants
in the innate immune system and disease
progression in HIV infection.

Louis-Marie Yindom, Peter Aka, Sarah Rowland-Jones, Giorgio Sirugo, Matt
Cotten and Clayton Onyango
Collaborators:
Mary Carrington, National Cancer Institute, Frederick, USA
Funding:
European Developing Countries Clinical Trials Partnership (EDCTP) PhD
Fellowship
TB side effects
The differences in the genes which efficacy. We propose to study In preliminary studies we now have
control patients’ side effects to N-acetyl transferase genotype as complete genomic sequence on
a tuberculosis drug are being a predictor of Elispot reversion. A 87 Gambians for NAT2. Analysis
examined in Gambians. Identifying comprehensive assay for NAT2 will of these sequences is currently
the patients prone to side effects be developed comprising known underway to enable the addition
could enable doctors to prescribe non-functional variants (loci 191, of novel and potentially functionally
more effective medicine to treat 341, 481, 590, 857) in addition to relevant polymorphisms that are
the disease. recently defined haplotype-tagging prevalent in our population to the
SNPs that identify the common SNP typing panel.
The TB case-contact study Caucasian (rs1565684, rs1390358,
comprises 400 sputum smear rs1799930) and Asian (rs2410558)
positive cases with 3000 contacts alleles which may also be present in
in varying degrees of proximity to Africans. It has been reported that
the cases. Very sensitive markers poor metabolisers are significantly
of infection (PPD, ESAT-6/CFP10 more common in African than
Elispot) have been used to identify Caucasian populations for example
sub clinical disease in the contacts. 49, 38 and 52% among Tanzanians,
65% of contacts tested positive Venda and Zimbabweans
for PPD and 31% for ESAT-6/ respectively. Poor metabolisers
CFP10 Elispot and the response may suffer adverse reactions leading
was related to exposure gradient. to therapeutic complications
Work is underway to treat contacts or poor compliance. There is
with isoniazid and monitor immune therefore significant advantage to be
response, seeking to establish an gained by typing for this locus and
‘Elispot reversion’ model for testing tailoring therapy accordingly such
novel therapies. as dose adjustment or alternative
therapy. We hypothesise that slow
Isoniazid is inactivated by N-acetyl metabolisers would derive greater
transferase (NAT2), which is benefit from isoniazid although
highly polymorphic. Genotype they would be at higher risk of side
has been related to frequency of effects such as hepatitis.
side effects but not to treatment

Definition of N-acetyl transferase alleles
in West Africa and assessing their effects
on isoniazid treatment of tuberculosis case
contacts
Peter Aka, Mathurin Diatta, Richard Adegbola, Dayo Adetifa
Collaborators:
Kim Mulholland, London School of Hygiene and Tropical Medicine, UK.
Funding:
Hepatitis B and liver cancer

The Gambia Liver Cancer studies Participants developing cancer are completed for 15 polymorphisms
will look for the effects that likely to be identified at an early that define 62 haplotypes in our
environmental differences and stage and they will be offered population.
genetic variation have on the risk entry into Phase II/III trials of new
of liver cancer. therapeutic agents for liver cancer
currently undergoing Phase I studies
Building on historical strengths in in the UK. People with cancer
hepatitis and liver cancer research, identified through the National
particularly arising from the Gambia Cancer Registry infrastructure will
Hepatitis Intervention Study, a new also be offered treatment as will
programme is being planned to those who present to Gambia
facilitate research into the aetiology Government hospitals and MRC
and treatment of hepatocellular field sites. DNA, blood and tumour
carcinoma. An overview of the tissue will form part of a newly
study is shown in Figure 6. Large established International Liver
scale population screening will be Cancer Biorepository, coordinated
undertaken to establish a cohort of by the International Agency for
people who are chronic carriers of Cancer research (IARC) in France.
hepatitis B virus and thus at high risk
of developing liver cancer. A low SNPlex assays have been developed
cost population based intervention for germ line variants of key
to reduce aflatoxin exposure will genes that are important in the
be rolled out and the effects on pathogenesis of liver cancer (Aurora
cancer risk will be evaluated. The A, P53, XRCC1, ERCC1 and
cohort will be screened regularly ERCC2). The effects of these gene
with a novel array of serum markers variants will be studied for on risk of
currently being developed that developing cancer in archival DNA
predict the development of cirrhosis from the Gambia Liver Cancer
and liver cancer. Screening will Study (GLCS) which has recently
also be offered using the Fibroscan been added to the Gambia National
technique that identifies cirrhosis DNA collection.
which substantially increases cancer
risk. Preliminary typing to obtain pilot
data for XRCC1 has recently been

Active recruitment of liver Screening Gambian male
cancer cases from field sites in population in Western division
Fajara/ Banjul for HBV (n= 7000)
Established
Farafenni
high risk Hepatitis B
Keneba
positive
Bansang
cohorts in Keneba
Basse Hepatitis B positive cohort
and Manduar
(n=1000)
Aflatoxin reduction intervention
Liver Cancer
(n=500)
Regular screening of high risk
cohort with novel diagnostic tool
Liver biopsy
Liver cancer case finding in the
Gambian National Cancer Tissue diagnosis in
Registry. Fajara Liver Clinic
Clinical assessment
Essential for Gambia Hepatitis Ultrasound, Fibroscan and
Intervention study (GHIS) Alpha fetoprotein
Update cancer Histological grading
registry and Clinical staging
Randomised trial of
novel therapeutic agent
Minimum data set Pharmacokinetic and

Pharmacogenetic data
Contribute plasma, serum, Studies on liver cancer
DNA and tissue samples to pathogenesis and markers of
International Liver Cancer treatment response
Biorepository at the at MRC, The Gambia
International Agency for Research Samples and data from other (Aurora, p53, DNA repair
on Cancer, (IARC) Lyon, France. participating centres polymorphisms)
Overview of the Gambia Liver Cancer project
Studies on the prevention, pathogenesis,

early detection and treatment of liver
cancer in The Gambia.

Peter Aka, Matt Cotten, Maimuna Mendy, Ebrima Bah
Collaborators:
Pierre Hainaut, International Agency for Research on Cancer, Lyon, France;
David Kerr Oxford University Department of Clinical Pharmacology, UK; Andy
Hall, London School of Hygiene and Tropical Medicine, UK
Funding:
Application to National Institutes for Health and Cancer Research UK in
preparation.

Banking DNA
Storing samples of DNA is recently been extensively used, The genomic sequencer is in
important for all the research mainly for genetic studies in the TB constant use 24 hours a day
programmes in the MRC. New case control cohort which were providing DNA sequence data on
technology is making this process completed in early 2007. approximately 600 samples each
more efficient. week mainly for studies on malaria,
The SNPlex system for high pneumococcal disease and hepatitis
The DNA Bank provides a service throughput typing will be made B. The sequencer was installed in
for extracting, quantifying and available for use by other December 2006 and has been used
standardising DNA for studies programmes within the Unit in a to sequence 26,688 samples from
conducted by all the programmes in similar fashion. The two systems December 2006 to mid-October
the Unit. are complementary with Taqman 2007. Of these 11,520 were for
being suited for low volume typing the Genetics group, 8,640 for the
DNA samples are bar coded where specific SNPs must be Malaria programme, 4,800 for the
and archived using the Biobase evaluated and SNPlex being used Bacterial Diseases Programme
computer system, which records for larger studies where a haplotype and 1,728 for the Viral Diseases
routine data related to sample tagging approach is used. Thus Programme.
usage such as storage location, both systems will be maintained
when aliquots are taken and the to enable maximum flexibility in
amount of DNA that remains. genotyping as a service to the Unit.
We have recently added routine
information on the purity of
each sample, as measured by the
protein concentration, to the
genetic database. A system has
been recently implemented so that
principal investigators can view
all data on their samples over the
MRC intranet using a web browser
interface.
In 2006 a low volume genotyping

capacity was added to the services
which had previously been provided
solely for DNA sample curation.
The ABI Taqman system using
real-time PCR for genotyping has
Cluster plot of SNPlex typing for XRCC1

Gambian National DNA collection

Mathurin Diatta, Archibald Worwui
Funding:
DNA differences in response to malaria

infection
Slight differences in people’s DNA disrupted by SNPs in the Hapmap for the promoter microsatellite.
could dictate how they respond database which will be typed. These genotypes will be correlated
to malarial infection. We are There are also five exonic splice with functional parameters such
investigating if variation in enhancer sites potentially disrupted as HMOX expression assessed by
by Hapmap SNPs. FACS staining in collaboration with
one particular enzyme affects risk In addition Professor Dominic Dr Michael Walther. The SNPLex
of malaria which may be important Kwiatkowski’s lab has conducted assays will be used to add fine detail
in designing better treatments for studies on HMOX1 expression on to the genetic typing. Thus we will
severe infection. B cells from the Hapmap project be able to assess phenotypic effects
and shown allele specific differences of various HMOX polymorphisms
Haem oxygenase is the rate limiting in expression levels for 4 SNPs and haplotypes. We will use these
enzyme in haem degradation and is which will be included in the studies. assays in a large scale study on
found at high levels in people with All SNPs previously found in the stored samples of 1000 cases and
malaria. This enzyme has been literature to be associated with 1500 controls to assess their effects
implicated in the pathophysiology disease will also be included in the on susceptibility to severe malaria.
of malaria since it acts to produce SNP set.
toxic iron compounds. Genetic
variants affect enzyme activity When the set of potentially
however the small studies to date functionally active SNPs has been
have given conflicting results on defined, these SNPs will be forced
clinical outcome of infection. into the Tagger multilocus algorithm
to define the full set of tagging SNPs
The promoter microsatellite for HMOX1. A low density set of
polymorphism is the most studied tagging SNPs will also be selected to
of the HMOX1 polymorphisms define common haplotypes for the
and will form the main genetic constitutively expressed HMOX2
hypothesis to be tested. Our since functional variants in this
recently completed bioinformatic gene may modify the effect of the
analysis for transcription factor HMOX2 variants.
binding sites shows a FOXP3 site in
the 5’ intergenic region of HMOX1 The assays will be used on
at -9029, NFkappaB at 9620 and prospectively collected samples
HNF-4 at 9655 in an intronic region. from cases around Fajara and about
These sites are all potentially 100 of these have now been typed

Effects of genetic variation in
haemoxygenase on risk of severe malaria

Peter Aka, David Conway, Michael Walther
Collaborators:
Dominic Kwiatkowski (Oxford University)
Funding:

Genetics Group: PhD Studentships
Ramatoulie Janha
‘Genetic effects on pharmacokinetics of antimalarial drugs and their effectiveness in the treatment of malaria in children’
Louis Marie Yindom
‘Investigating the effects of genetic variants in the innate immune system and disease progression in HIV infection’
Genetics Group: Publications
2004
01. Newport MJ, Allen A, Awomoyi AA, Dunstan SJ, McKinney E, Marchant A, Sirugo G. The toll-like receptor 4
Asp299Gly variant: no influence on LPS responsiveness or susceptibility to pulmonary tuberculosis in The Gambia.
Tuberculosis (Edinb) 2004;84(6):347-52.
02. Bornman L, Campbell SJ, Fielding K, Bah B, Sillah J, Gustafson P, Manneh K, Lisse I, Allen A, Sirugo G, Sylla A, Aaby
P, McAdam KP, Bah-Sow O, Bennett S, Lienhardt C, Hill AV. Vitamin D receptor polymorphisms and susceptibility
to tuberculosis in West Africa: a case-control and family study. J Infect Dis 2004;190(9):1631-41.
03. Sirugo G, Ashenbrenner J, Odunsi K, Morakinyo O, Page G. No evidence of association between the genetic pre-
disposition for dizygotic twinning and schizophrenia in West Africa. Schizophr Res 2004;70(2-3):343-4.
04. Sirugo G, Schim van der Loeff M, Sam O, Nyan O, Pinder M, Hill AV, Kwiatkowski D, Prentice A, de Toma C,
Cann HM, Diatta M, Jallow M, Morgan G, Clarke M, Corrah T, Whittle H, McAdam K. A national DNA bank in
The Gambia, West Africa, and genomic research in developing countries. Nat Genet 2004;36(8):785-6.
05. Sirugo G, Schaefer EA, Mendy A, West B, Bailey R, Walraven G, Sabeti P, Macciardi F, Zonta LA. Is G6PD A- defi-
ciency associated with recurrent stillbirths in The Gambia? Am J Med Genet A 2004;128(1):104-5.
06. Cooke GS, Campbell SJ, Fielding K, Sillah J, Manneh K, Sirugo G, Bennett S, McAdam KP, Lienhardt C, Hill
AV. Interleukin-8 polymorphism is not associated with pulmonary tuberculosis in the gambia. J Infect Dis
2004;189(8):1545-6; author reply 1546.
2005
07. Walton R, Kimber M, Rockett K, Trafford C, Kwiatkowski D, Sirugo G. Haplotype block structure of the cyto-
chrome P450 CYP2C gene cluster on chromosome 10. Nat Genet 2005;37(9):915-6; author reply 916.
08. Ackerman H, Usen S, Jallow M, Sisay-Joof F, Pinder M, Kwiatkowski DP. A comparison of case-control and family-
based association methods: the example of sickle-cell and malaria. Ann Hum Genet 2005;69(Pt 5):559-65.
2006
09. Wilson JN, Rockett K, Keating B, Jallow M, Pinder M, Sisay-Joof F, Newport M, Kwiatkowski D. A hallmark of bal-
ancing selection is present at the promoter region of interleukin 10. Genes Immun 2006;7(8):680-3.
10. Tosh K, Campbell SJ, Fielding K, Sillah J, Bah B, Gustafson P, Manneh K, Lisse I, Sirugo G, Bennett S, Aaby P,
McAdam KP, Bah-Sow O, Lienhardt C, Kramnik I, Hill AV. Variants in the SP110 gene are associated with genetic
susceptibility to tuberculosis in West Africa. Proc Natl Acad Sci U S A 2006;103(27):10364-8.

Publications
11. Pinder M, Sutherland CJ, Sisay-Joof F, Ismaili J, McCall MB, Ord R, Hallett R, Holder AA, Milligan P. Immunoglobulin
G antibodies to merozoite surface antigens are associated with recovery from chloroquine-resistant Plasmodium
falciparum in Gambian children. Infect Immun 2006;74(5):2887-93.
12. Hanchard N, Diakite M, Koch O, Keating B, Pinder M, Jallow M, Sisay-Joof F, Nijnik A, Wilson J, Udalova I,
Kwiatkowski D, Rockett K. Implications of inter-population linkage disequilibrium patterns on the approach to a
disease association study in the human MHC class III. Immunogenetics 2006.
13. Hanchard N, Diakite M, Koch O, Keating B, Pinder M, Jallow M, Sisay-Joof F, Nijnik A, Wilson J, Udalova I,
Kwiatkowski D, Rockett K. Implications of inter-population linkage disequilibrium patterns on the approach to a
disease association study in the human MHC class III. Immunogenetics 2006;58(5-6):465-70.
14. Cooke GS, Campbell SJ, Sillah J, Gustafson P, Bah B, Sirugo G, Bennett S, McAdam KP, Sow O, Lienhardt C, Hill
AV. Polymorphism within the interferon-gamma/receptor complex is associated with pulmonary tuberculosis. Am J
Respir Crit Care Med 2006;174(3):339-43.
15. Awomoyi A, Sirugo G, Newport MJ, Tishkoff S. Global distribution of a novel trinucleotide microsatellite polymor-
phism (ATA)n in intron 8 of the SLC11A1 gene and susceptibility to pulmonary tuberculosis. Int J Immunogenet
2006;33(1):11-5.
16. Atkinson SH, Rockett K, Sirugo G, Bejon PA, Fulford A, O’Connell MA, Bailey R, Kwiatkowski DP, Prentice
AM. Seasonal childhood anaemia in West Africa is associated with the haptoglobin 2-2 genotype. PLoS Med
2006;3(5):e172.
2007
17. 2. Olesen R, Wejse C, Velez DR, Bisseye C, Sodemann M, Aaby P, Rabna P, Worwui A, Chapman H, Diatta M,
Adegbola RA, Hill PC, Ostergaard L, Williams SM, Sirugo G. DC-SIGN (CD209), pentraxin 3 and vitamin D recep-
tor gene variants associate with pulmonary tuberculosis risk in West Africans. Genes Immun 2007;8(6):456-67.
18. 3. Khor CC, Chapman SJ, Vannberg FO, Dunne A, Murphy C, Ling EY, Frodsham AJ, Walley AJ, Kyrieleis O, Khan
A, Aucan C, Segal S, Moore CE, Knox K, Campbell SJ, Lienhardt C, Scott A, Aaby P, Sow OY, Grignani RT, Sillah
J, Sirugo G, Peshu N, Williams TN, Maitland K, Davies RJ, Kwiatkowski DP, Day NP, Yala D, Crook DW, Marsh K,
Berkley JA, O’Neill LA, Hill AV. A Mal functional variant is associated with protection against invasive pneumococ-
cal disease, bacteremia, malaria and tuberculosis. Nat Genet 2007;39(4):523-8.
19. 4. Fry AE, Griffiths MJ, Auburn S, Diakite M, Forton JT, Green A, Richardson A, Wilson J, Jallow M, Sisay-Joof F,
Pinder M, Peshu N, Williams TN, Marsh K, Molyneux ME, Taylor TE, Rockett KA, Kwiatkowski DP. Common varia-
tion in the ABO glycosyltransferase is associated with susceptibility to severe Plasmodium falciparum malaria. Hum
Mol Genet 2007.
20. 5. Wellcome Trust Case Control Consortium. Association scan of 14,500 nonsynonymous SNPs in four diseases
identifies autoimmunity variants. Nat Genet 2007;39(11):1329-37.
21. 6. Wellcome Trust Case Control Consortium. Association scan of 14,500 nonsynonymous SNPs in four diseases
identifies autoimmunity variants. Genome-wide association study of 14,000 cases of seven common diseases and
3,000 shared controls. Nature 2007;447(7145):661-78.
22. 7. Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, Timpson NJ, Perry JR, Rayner NW,
Freathy RM, Barrett JC, Shields B, Morris AP, Ellard S, Groves CJ, Harries LW, Marchini JL, Owen KR, Knight B, Car-
don LR, Walker M, Hitman GA, Morris AD, Doney AS, McCarthy MI, Hattersley AT. Replication of genome-wide
association signals in UK samples reveals risk loci for type 2 diabetes. Science 2007;316(5829):1336-41.

Translational
Research
One of the main areas of growth in place to deliver them.

health research over the last decade
has been in the ‘utilisation and We have utilised the platforms of
delivery’ of health care interventions. ongoing public health and clinical
Throughout the twentieth century, trials, as well as the demographic
a series of public health innovations surveillance system (DSS) and
have formed the background to child health surveillance network
a period when life expectancy to look at key questions within this
has risen and child mortality rates paradigm.
have fallen across the world. The
correlation between utilisation rates
of health services and the drop in
mortality rates are striking; implying
that the biggest driver of the
continuing gap between developed
and developing country health
outcomes is due less to the lack of
effective preventative or therapeutic
interventions, and more to the
inefficiencies of the systems set in

Dr Warren Stevens, health economist
and head of the Translational Research
team until 2006
Are Gambians spending their money on the least

effective forms of malaria prevention?
This research aims to investigate how malaria prevention measures aerosols, coils, indoor spraying,
consumers of health care, faced with smoke and other prevention
uncertainty, make decisions about health 2. how expenditure fluctuates through- strategies such as drinking
care consumption based on a range of out the year and herbs and cleaning the outside
preferences, informed or otherwise. It environment.
attempts to quantify a series of proxy 3. the main determinants of expendi-
indices for the working components ture. Expenditure on bed nets, including
of the market for health care within a treatment and repair, constituted
specific population. Initial work centred Cluster-randomised samples of 1,700 only 10% of total expenditure on
on prevention of malaria, and the main households from the North Bank malaria prevention. Of the 442
aims of the work were to provide a region were interviewed about their households that did not own a
better understanding of: expenditure on malaria prevention. bed net, 68% said it was because
Interviews were staggered over 12 they could not afford one,
1. the amounts households in The months. Expenditure was measured for but every 2 months, the same
Gambia spend on a wide variety of bed nets, treating and repairing bed nets, households spent an average

of US 5 dollars - the equivalent
to the cost of an insecticide
treated bed net - on other forms
of prevention, and all year round,
coils were the dominant form of
prevention expenditure, despite
their limited impact on malaria
prevention.
Households in The Gambia spend
considerable amounts on a range
of malaria prevention products and
activities throughout the year. Bed
nets represent a relatively small
proportion of this expenditure even
though they are perceived to be the
most efficient and effective method
of malaria control.
A more concerted effort is needed
to develop appropriate targeting Shops and stalls are the biggest recipients of expenditure on disease prevention in
strategies to encourage bed net use rural Africa.
especially for children under five
years of age.
The Malaria Demand Study Team

Warren Stevens, Lesong Conteh
Collaborators:
Virginia Wiseman (Gates Malaria Partnership); Brendan McIlroy (University
College Cork, Ireland)
Funding:
Gates Malaria Partnership

Culturally sensitive communication is needed to
improve vaccination rates.
Improving childhood vaccination complementing traditional child policy attention to improving the
coverage is a key health policy protection practices. For most rural clinic experiences of vulnerable
objective in Africa, and as mothers, strong social networks social groups in rapidly expanding
availability increases, it will depend encourage routine clinic attendance urban areas.
on addressing issues of demand and vaccination ‘default’ arises only Through discussions with
and timely schedule completion. through day-to-day problems and collaborators, it is hoped that the
This work attempts to explore contingencies. However, more findings will inform and support
vaccination demand in urban pervasive patterns of schedule ongoing efforts to improve mutual
and rural areas of The Gambia non-completion are found amongst understanding and communication
as shaped by prevailing local poorer urban mothers, including processes around vaccines and
vaccination cultures. recent immigrants and also non- related research, between Gambian
A survey of 1,600 mothers migrant transitory workers, who Government institutions, the MRC,
constructed on the basis of prior experience social exclusion at infant and the public they serve.
ethnography finds a high level of welfare clinics. These findings point
social demand for vaccination, to the need for health education
based on lay theories of the dialogue grounded in mothers’ own
general value of immunization in understandings and for particular
Some mothers utilise health services more than others
Key investigator at MRC The Gambia:

Warren Stevens
Collaborators:
Melissa Leach & James Fairhead (Institute of Development Studies University
of Sussex, UK); Mary Small (Gambia Committee on Traditional Practices
-GAMCOTRAP)
Funding:
Department For International Development, UK

Health care utilisation: the compound impact of
health care utilisation on inequalities in health
outcomes.
Gambian health inequalities can strategies. delivery mechanisms as they are,
be improved by understanding the are themselves one of they key
problems with health care delivery. The purpose of this particular study drivers of health inequalities within
is to develop a better understanding developing countries. The main aim
The issue of inequalities in both of the dynamics of health systems of this work is to look empirically
access to health care and utilisation that result in inequalities in at the role of health care delivery
of health care services has once health, concentrating on both the systems in compounding existing
again become an important issue importance of heterogeneity of health inequalities. This will then
in health policy and resource effect and the role of a needs-based allow us to develop better models
allocation. Despite the strong form of the indifference-preference of assessing the true value of
evidence of inequalities of access, hypothesis to address the variance different interventions in different
utilisation and health across in the values of outcomes across contexts, and in time develop
populations, this issue has not different subgroups. The key mechanisms that overcome these
previously been incorporated into to understanding the problem inequities.
the methodologies developed which this work is addressing is
to inform resource allocation the acceptance that health care
Health care utilisation has a significant impact on health outcomes – disease specific population attributable risk and utilisation
rates for primary health care and immunisation for children under five

Warren Stevens, Philip Hill
Collaborators:
Kim Mulholland (London School of Hygiene and Tropical Medicine, UK);
Charles Normand (Trinity College, Dublin, Ireland)
Funding:
MRC

Translational Research: Publications
01. Stevens W. Untangling the debate surrounding strategies for achieving sustainable high coverage of insecticide-
treated nets. Appl Health Econ Health Policy. 2005;4(1):5-8.
02. Stevens W, Wiseman V, Ortiz J, Chavasse D. The costs and effects of a nationwide insecticide-treated net pro-
gramme: the case of Malawi. Malar J. 2005 May 10;4(1):22.
03. Wiseman V, McElroy B, Conteh L, Stevens W. Malaria prevention in The Gambia: patterns of expenditure and
determinants of demand at the household level. Trop Med Int Health. 2006 Apr;11(4):419-31.
04. Wiseman V, Conteh L, Matovu F. Using diaries to collect data in resource-poor settings: questions on design and
implementation. Health Policy Plan. 2005 Nov;20(6):394-404
05. Hill PC, Stevens W, Hill S, Bah J, Donkor SA, Jallow A, Lienhardt C. Risk factors for defaulting from tuberculosis
treatment: a prospective cohort study of 301 cases in the Gambia. Int J Tuberc Lung Dis. 2005 Dec;9(12):1349-54
06. Cassell JA, Leach M, Fairhead JR, Small M, Mercer CH. The social shaping of childhood vaccination practice in rural
and urban Gambia. Health Policy Plan. 2006 Sep;21(5):373-91.
07. Fairhead J, Leach M, Small M. Where techno-science meets poverty: medical research and the economy of blood
in The Gambia, West Africa. Soc Sci Med. 2006 Aug;63(4):1109-20
08. Public engagement with science? Local understandings of a vaccine trial in the Gambia. J Biosoc Sci. 2006
Jan;38(1):103-16.
09. Stevens, W. Evaluating health promotion interventions. In Economic evaluation of health promotion interventions,
Thorogood M. & Coombes, Y. (Editors) Oxford University Press Oxford, UK. 2004.
10. Stevens W, Kaye S, Corrah T. Antiretroviral therapy in Africa. BMJ, 2004; 328: 280-282.
11. Stevens W, Walker D. Adolescent vaccination in the developing world: is it time for consideration? Vaccine 2004;
22(5-6): 782-6.

Clinical
Services
No research without service

The Clinical Services Department, their immediate families.
often referred to as ‘the goodwill
arm’ of the MRC in The Gambia, is The main site is located at Fajara;
recognised locally and internationally limited clinical services are also
for the excellent and cost-effective provided at Keneba, Basse and
health care provided to Gambians Farafenni, where MRC staff work
and other nationals. The provision in close liaison with Gambia
of this service has fostered an Government health service
enduring relationship of trust and providers.
confidence between the MRC and
the people and Government of
The Gambia, resulting in excellent
participation rates in the MRC’s
research activities.
The department also serves

the MRC’s staff complement of
approximately 750 persons and

Ward
other hospitals, clinics and health The number of HIV-associated
The busy 42-bed ward provides centres. morbidities has overtaken severe
in-patient care for both research malaria admissions; there has been
and non-research cases admitted The major causes of admission are a steady rise in the latter over the
through the Outpatients’ pneumonia, HIV/AIDS, malnutrition, years from 7% in 2001 to 24% in
Department/Gate Clinic. The ward gastroenteritis and sepsis. 2006. Although this might represent
also serves as a referral centre for Admissions for severe malaria - a general increase in the number
patients from MRC’s field sites, which took centre stage a few years of HIV cases seen, it could also
ago - have declined substantially. reflect an increase in numbers
Ward admissions for 2006

presenting at our clinics due to is one of the first three approved
the introduction of Highly Active treatment centres for HIV in The
Antiretroviral Treatment (HAART) Gambia; at present, there are about
in 2004, encouraging more sufferers seven treatment centres in the
to come forward for treatment country.
and join the cohort. MRC Fajara
Out Patients’
Department
This includes the general OPD, are seen daily, mainly adult and
staff clinic, Genito-Urinary Medicine paediatric medical cases. Patients
(GUM) clinic (for HIV and STI with surgical problems are referred
referrals) and Tuberculosis clinic. to the Royal Victoria Teaching
Four physicians are in attendance Hospital in Banjul, as well as those
daily. Patients seen at the OPD with chronic medical conditions that
are referred from the MRC Gate have been stabilised. Patients who
Clinic as well as private and other qualify and are willing to participate
hospitals, embassy clinics and in research are recruited at our
health centres. About 150 patients OPD clinics.
OPD Ward
Year Gate Clinic
New Return Total Children Adult Total
2001 51712 18989 15949 34938 2212 1101 3313
2002 50634 12705 12932 25637 1619 858 2474
2003 49259 16000 16583 32583 1548 964 2511
2004 59470 14490 10017 24507 1184 793 1977
2005 59301 14328 12288 26616 897 708 1605
2006 53179 8276 9853 27142* 844 775 1619
* Includes 9013 patients seen at the GUM clinic.
Admissions to the ward and number of patients seen at the OPD and Gate Clinic 2001-2006
Gate Clinic
A rich source for recruiting patients The Clinical Services Department laboratories at MRC Fajara. The
for research and as controls, the provides a number of other UK NEQAS and WHO schemes
Gate Clinic is also used frequently services: provide quality control for the
for piloting questionnaires and haematology/biochemistry
serves as a training ground for Diagnostics and microbiology laboratories
triage. About 250 patients are Our out-patient laboratories have respectively.
seen daily from Mondays to the capacity to carry out detailed
Thursdays, and 200 on Fridays. microbiological, haematological and Facilities exist for both emergency
These are mainly patients with biochemical analysis of specimens and routine fibre-optic upper
minor complaints who are treated from within the department and gastrointestinal video endoscopy,
by state enrolled nurses under the from other hospitals and clinics. as well as fibre-optic video
supervision of the nursing sister. Well-equipped routine laboratories bronchoscopy for adult and
Very ill patients are referred to the are staffed by highly qualified paediatric patients requiring this
OPD (about one third of the total personnel and supported by service.
number seen each day). the more sophisticated research

Ultrasonography, plain and limited and Paediatrics. hospital complex located behind the
contrast radiography are available at main Fajara site. The new site was
the radiology department in Fajara. Nursing students from the commissioned on 4th May 2007
University of The Gambia regularly by MRC UK’s Chief Executive, Prof
Supporting the local health care undertake part of their clinical Colin Blakemore and became fully
sector training at the department. This operational in June 2007.
Support and advice is provided to year, the first batch of auxiliary
other clinics, especially with respect nurses fully trained at the Fajara The former ward is being re-
to travel health, immunization and Clinical Services Department structured to provide dedicated
medical emergencies. graduated. This will no doubt assist space for clinical research.
in MRC’s commitment to building
Clinical support to the Royal local capacity.
Victoria Teaching Hospital, Banjul,
the TB sanatorium and Serrekunda It is also planned that house
Tuberculosis clinic is presently being physician training in internal
strengthened. medicine and paediatrics will be
undertaken at MRC Fajara in the
Training foreseeable future.
The Clinical Services Department
offers excellent undergraduate and Clinical research
postgraduate training opportunities In addition to providing a
in infectious and tropical diseases. continuous flow of patients/clients
Over the years, a large number from the Gate Clinic and OPD for
of medical students from all over the unit’s research projects, the
the world have spent their medical ward is also the base for several
elective periods in internal medicine trials and studies, including Severe
and paediatrics at MRC Fajara, and Pneumonia, Renal Diseases and
in recent times, the pioneer medical H.Pylori studies and the GUM HIV/
students of the University of The HAART cohort studies.
Gambia have undertaken their
electives with us. GCP
Training and re-orientation of
Every year, a number of clinicians clinical staff has been stepped up
and nurses from all over the world to meet Good Clinical Practice
desiring first-hand experience in requirements, improve capacity for
infectious diseases, come to work clinical research and attract funding
for varying periods of time under for clinical trials. The department, in
the supervision of the department. conjunction with the Clinical Trials
For a number of years, the Support Manager, has taken the
department has hosted students lead in the development of standard
taking the Diploma in Tropical management protocols for common
Medicine and Hygiene (London infectious and tropical diseases for
School of Hygiene and Tropical use at the MRC, other hospitals
Medicine) and the visit has come within The Gambia and elsewhere
to be known as ‘The Gambia in the West African sub-region.
Experience’. MSc students from
the Liverpool School of Tropical Records management
Medicine have also spent time at The blue print for an electronic
MRC Fajara in the past. medical records system has
been developed. Presently, it is
Small numbers have come from the being evaluated for its efficiency,
West African College of Physicians speed, accessibility, durability,
(WACP) under the training user-friendliness and superiority
fellowship scheme to acquire over existing systems in the Unit.
some experience in research in The new system will improve
preparation for their final Part 2 confidentiality, access to patient
examinations for the award of medical records and laboratory
the Fellowship of the College. results while transforming
Following an inspection visit by the the service into a paper–free
accreditation team of the WACP in environment.
November 2007, the department
was given joint (with RVTH), partial ...and we have moved
accreditation for post graduate The Clinical Services Department
medical training in Internal Medicine has moved to a new, ultra-modern

Most common causes of admissions in 2006
Causes of Death in 2006

The ward team during ward rounds
Student Nurses at a bedside

teaching session
The new MRC Clinical Services Complex
The new Female Ward

Statistics & Data
Management
Statistics
The Statistics team, managed by training support to the scientific integrity of the data, whether it is
Unit Statistician and Mathematical programmes and has run a number from laboratory or field data. This
Modeller, Dr David Jeffries, supports of statistics and Stata courses. involves work in a number of high-
the unit’s three main programmes: Future plans include establishing level programming languages and
Viral Diseases, Bacterial Diseases an on-line sample size calculator, complements the work of the Data
and Malaria, in collaboration with standardising the many methods Management team.
the TEG (Tropical Epidemiological and packages that staff use at the
Group) at the London School of unit.
Hygiene and Tropical Medicine, UK.
The support begins at the project In addition to supporting the
design stage, with experimental scientific programmes, the Statistics
design and sample size issues, team undertakes applied research
moving through to the analysis relevant to the unit. Current areas
stage at the end of the project. of interest are the processing and
During projects, the Statistics team analysis of laboratory data. Flow
is involved in randomisation tasks cytometry produces huge volumes
and often serve on Data Safety of data and the team is developing
Monitoring Boards to satisfy the algorithms for the automatic and
Good Clinical Practice (GCP) objective analysis of FACS data.
requirements.
The team also works on a number
The Statistics team also offers of coding projects to ensure the
Data Management
The Data Management team, currently implementing this in a
managed by Dr Paul Snell (Senior managed fashion. This will allow us
Data Manager) until August to be more flexible with the use of
2007, continues to oversee the our data entry staff, and free up the
movement to SQL Server based Data Managers’ time to allow them
systems. Many changes have been to concentrate on quality issues
implemented in recent years, within their studies. Data Managers
including the appointment of 3 are being trained to ensure that
full-time Database Developers, who issues relating to data quality are
are helping to move the technical paramount for all our studies.
aspects of our systems considerably.
The Malaria Programme was the
Amongst the innovations have first to pilot the use of handheld
been: a double-entry verification computers to gather data directly
system for SQL Server Databases without the use of paper. The
using a web-based tool in ASP.NET; project has been running since
the evolution of a more generic October 2006 and we are very
approach to studies (enabling keen to see success in this field.
shorter development time and
more standardisation); and the (on-
going) development of an electronic
laboratory sample tracking system.
The unit is moving to the use of

pooled rather than programme-
based Data Entry, and we are

Clinical Trials
Support
GCP in Clinical Research
GCP – Good Clinical Practice research studies. Investigators
is more than only a term of clinical trials and study team
members are trained continuously
The Medical Research Council on GCP and related aspects,
has an honourable tradition of internally as well as externally,
supporting high quality randomised in order to build the necessary
controlled trials. It funded one capacity.
of the most celebrated early
randomised, blinded trials: Several quality assurance measures
streptomycin for pulmonary such as written Standard Operating
tuberculosis, published in the Procedures (SOPs) have been
British Medical Journal (BMJ) in prepared for the running of
1948. The objective of this trial individual clinical trials at Unit,
was to demonstrate unequivocally independent of the scientific
whether streptomycin would be of programmes they are nested in.
any value in treating tuberculosis. Internal and external monitoring of
The use of a control group, the clinical trials are further measures
random allocation of subjects to to ensure the maintenance of high
the investigation and the evaluation quality standards for all clinical trials
of observations, which were sponsored by MRC or by other
introduced in this trial, are still the partners and collaborators.
corner stones of all clinical trials.
The Clinical Trials Support Manager
In 1995 the International monitors adherence to all aspects of
Conference on Harmonisation GCP within projects and requests
(ICH), consisting of representatives for compliance are communicated
of regulatory authorities and the to the scientific programmes and
pharmaceutical industry from departments of the Unit, as well as
Europe, Japan and USA prepared a to the institutions and committees
guideline to provide a unified ethical involved. This includes processes
and scientific quality standard for of approving and overseeing
designing, conducting, recording clinical research projects with
and reporting trials that involve the respect to documentation and
participation of human subjects to quality assurance measures such
facilitate the mutual acceptance of as monitoring, providing training
clinical data on medicinal products to all staff in relevant GCP issues,
by the regulatory authorities (ICH and supporting clinical research
GCP Guideline). committees in terms of GCP
requirements.
Based on the thirteen principles laid
down in this ICH GCP Guideline MRC The Gambia is in the process
the MRC provides guidelines for of employing more staff to help
Good Clinical Practice (MRC GCP ensure the maintenance of GCP
Guideline) that not only apply to standards in accordance with
clinical trials on medicinal products, the MRC GCP Guidelines and
but include any prospective study international requirements.
involving human participants and
the administration of a treatment or
type of management.
The MRC Unit in The Gambia has

also implemented Good Clinical
Practice (GCP) in its clinical

Staff Training &
Development
MRC The Gambia continues Master’s level. At the present time,
to place the highest priority on 14 staff are following programmes
staff training and development ranging from Epidemiology
as the key means of securing to professional management
skills and knowledge to underpin qualifications. Recruitment is
internationally competitive science. underway for new scholarships
Provision ranges from a wide variety for the MSc in Epidemiology, by
of in-house training programmes to distance learning, at the London
an extensive array of qualifications School of Hygiene and Tropical
from diploma level to BSc, MSc Medicine. As with many MRC
and PhD degrees. The Unit initiatives, this is a collaborative
invests almost 10% of its recurrent exercise with the Gambia
expenditure on direct training Government. To add to the one
activities for its staff. student sponsored for a full-time
BSc in the UK a second scholarship
The Unit has strengthened the has been awarded to a young
strategic direction of training promising Gambian. From now
and staff development with on, the scholarship will be available
the appointment in 2006 of a annually. The recognised gap at
dedicated training professional, BSc level is being bridged with
Mrs Christine Croombes. The three staff joining the four already
mission is to facilitate production undertaking distance learning
of the highest quality science in programmes with the University of
the highest quality unit, which South Africa.
continues to forge strong local,
regional and international links. The undergraduate and
One key emphasis is to support postgraduate biomedical sciences
the continuing professional learning pathway is underpinned
development of our senior scientists by the successful diploma run in
to undertake groundbreaking conjunction with the University
research. The strongest focus, of Westminster. January 2007
however, is on capacity building saw the third intake graduating,
and growing tomorrow’s scientists. making a total of 48 successful
Latterly, increased attention has students from the MRC, the
been given to professionalising Gambia Government and other
those staff whose primary purpose local institutions since its inception
is to provide the technical, financial in 2000. At the same time, the
and administrative support which achievement of 12 staff was
makes internationally competitive celebrated in the new Certificate in
science possible. Biomedical Sciences. This in-house
certificate was established in 2005
Over the years the Unit has to provide a firm foundation for the
produced a large number of on-the- diploma level studies. 2007 also
job PhDs and continues to do so. It saw the introduction of the on-line
maintains its productive relationship University of London Foundation
with the Open University in the Degree in Health and Medical
UK with 7 staff currently enrolled Sciences (Applied Blood and
at varying stages of their studies. Tissues Pathway). The qualification
2006-7 has seen three new full-time is awarded by the Faculty of Health
PhD students enrolled in MRC The and Social Care Sciences (FHSCS)
Gambia, an increase on previous Kingston University and St George’s,
years and now the Unit’s quota. University of London, UK.
The Unit continues to offer

excellent opportunities for staff to
pursue professional development at

Tisbeh Faye Joof at the award
ceremony of the University of
Westminster Diploma in Biomedical
Sciences. Tisbeh is currently on a full
time scholarship at the University of
Westminster
Christine Croombes, Head of Training

and Staff Development (left), presenting
a certificate at Keneba Field Site
Students on the distance learning

University of London Foundation
Degree in Health and Medical Sciences
(Applied Blood and Tissues Pathway).
The unit offers many opportunities for

hands-on training

MRC UK The Gambia
Field Sites
Five MRC sites cover 7 Local Government Administrative Divisions in The Gambia. A further field site is situated in Caio, Guinea
Bissau.
MRC Fajara (Kombo St Mary Division). The main base is situated on the coast near the capital Banjul. Features include
laboratories, a hospital, computer centre, offices, workshops and residential accommodation.
MRC Keneba (Lower River Division). Main site for field based nutrition studies
MRC Farafenni (North Bank Division) Main site for field based malaria studies
MRC Wali Kunda (Central River Division) Small site for entomological studies.
MRC Basse (Upper River Division) Site of Pneumococcal Vaccine Trial (concluded in 2005). Current studies include PATH
funded Meningitis Vaccine Project.
Caio (Guinea Bissau). HIV epidemiology studies have been conducted there since 1986. Caio officially became an MRC field
site in 2006.
The unit also operates from Sukuta Health Centre and Sibanor Health Centre in partnership with the Department of State for
Health and Social Welfare.
Fajara Keneba
The Unit’s main operational base MRC Keneba is a rural field site of Station has traditionally been a
is situated in Fajara, approximately situated in the West Kiang region of research scientist working with 2
9 miles down the coast from The Gambia, 4 hours by road from other international staff as well as
the capital Banjul. About half of MRC Fajara. The field site is located West African sub-region and local
the Unit’s overall staff and all the in the village of Keneba; the largest Gambian staff. The clinic provides an
main administrative, procurement, village in an area of predominantly extensive, out-patient based service
infrastructural and technical support subsistence agriculture. The MRC concentrating on maternal and
departments are based here. has had a presence in the area child health provision and working
for almost 60 years and enjoys an closely with the local Gambian
The 100 acre site at Fajara includes excellent relationship with the local Government Divisional Health
a range of research and clinical community. The Nutrition Group Team. Clinics are run 5 days per
laboratory facilities (up to category of the MRC Laboratories, The week and a supplementary feeding
3 containment level). Gambia is also based in Keneba centre for malnourished children
with strong links to the MRC is maintained 7 days per week as
A new clinical trials unit is under International Nutrition Group (ING) well as an emergency out-of-hours
construction at the site of the at the London School of Hygiene service offering medical, midwifery
former MRC ward. and Tropical Medicine and to the and nursing care. The clinic also
MRC Human Nutrition Research supports the local Karantaba Health
in Cambridge. The Head of the Centre and the Maternal and Child
Nutrition Programme, Professor Health trekking teams that deliver
Andrew Prentice, is also head of the healthcare directly to the villages.
ING in London.
The field site has a strong record in
As an isolated rural field site Keneba academic achievement, training for
generates its own electricity, pumps local staff, and heathcare provision
its own water supply and maintains for the residents of West Kiang. A
all the infrastructure required for basic science approach is adopted
the production of internationally to improve our understanding of
competitive science. the effects of nutrition on health,
The field site has a long history contribute to health policy and
of providing medical care to the to design and test interventions.
local population as well as carrying Training and opportunities for local
out a strong nutrition-related staff are extensive and the field site
science programme. The Head is keen to maximise their potential

Farafenni
for scientific achievement with Farafenni was established in 1981
literacy classes through to PhD as the field site for the first trials of sampling studies.
opportunities. The clinical service chemoprophylaxis and insecticide-
provision for the local population treated bed nets for the control evaluations of diagnostic tests.
continues to be improved in of malaria in Africa. It provides an
conjunction with The Gambian excellent platform for the testing trials of interventions
Government. of vaccines and new therapeutic randomised at individual or
combinations and other anti- community level.
The villages of Keneba, Manduar malarial strategies. It also offers
and Kantong-Kunda have an opportunity for high quality the analysis of trends in
traditionally maintained the closest community-based research in all the mortality.
relationship with the field site but programme areas of the Unit. These
increasingly our studies and clinical take advantage of the excellent analyses relying on
service provision involve many infrastructure including the recently demographic data to make
other villages across West Kiang. refurbished laboratories and stable inferences about disease
Currently our studies are active in colony of Anopheles gambiae transmission, eg the relationship
all the local villages and our clinic mosquitoes, with its demographic of HSV-2 seropositivity to
offers care to residents of all West surveillance system, the attendant marriage history.
Kiang villages. In addition, we have data processing capacity, and the
recently initiated a full demographic strong collaborative links with health systems research
survey of all the villages in West Gambia Government health focused on primary health care.
Kiang. The field site maintains a institutions, particularly the Armed
continuous dialogue with the local Forces Provisional Ruling Council anthropological studies of
community to promote a better (AFPRC) Hospital, and the North contraceptive practice and birth
understanding of the research that Bank East District Health Team. spacing.
we are carrying out. Our research is
directly relevant to the health of the The Farafenni Demographic The data derived from the FDSS
local population and this dialogue Surveillance System has also facilitated recruitment of
stresses the co-operative nature The Farafenni Demographic subjects for genetic studies (eg
of the research and the rights of Surveillance System (FDSS) was twins and triplets).
any community or individual to opt established in 1981 as a platform
out. Our staff enjoy working here, for studies of the epidemiology The FDSS has underpinned more
the local communities tell us that of malaria and trials of primary than 100 published papers and
they enjoy hosting us and our field health care level interventions to reports - over 30 since 1996
site continues its track record of reduce malarial morbidity. Initially
excellence as a result. the Demographic Surveillance Area
(DSA) comprised two clusters of
villages stretching from 10 km east
and west of Farafenni respectively.
A third cluster made up of Farafenni
town and its satellite villages within
a 5-km radius was included in the
system in 2002. The system has
undergone a number of major
changes in both the manner of data
collection, and the tools for data
entry and storage. The Farafenni
DSS is one of nine developing
country health-specific DSS
worldwide.
The system tracks the residential

status and main demographic events
in the lives of all individuals resident
within the DSA, together with
genealogical relationships identified
by recording every individual’s
mother and father (where known).
The platform it provides has
proved its value for a wide range of
research activities at the Farafenni
Field Site including:

Basse Caio-Guinea Bissau
Basse is located in the Upper River vaccine which showed a In 1988 Dominic Ricard noticed,
Division (URD) of The Gambia, remarkable reduction in while working in clinics for
the least developed administrative mortality of young infants. commercial sex workers in
area of the country. The division Efficacy trial of artesunate plus Ziguinchor, Southern Senegal, that
consists of a narrow strip of land, pyrimethamine-sulphadoxine. a high number of women who
approximately 50 miles long and 15 were HIV-2 infected came from a
miles wide, which stretches along A randomized controlled trial rural area in N-W Guinea Bissau.
both banks of the River Gambia. of artemether/benflumetol, a Together with Andrew Wilkins, he
URD has an estimated population new antimalarial. set up demographic surveillance
of 183,000 and is characterised by a in Caio, the main village of this
youthful population with about 44% Safety and immunogenicity trial area, to study the epidemiology
below the age of fifteen. of meningococcal conjugate of HIV-2. The Manjago village
vaccine. population which currently numbers
The MRC opened its field site at around 8,000 is dispersed in seven
Basse on 14th December 1982 and Basse offers excellent opportunities settlements among the palm forest.
in recent years the facilities have to carry out clinical trials (phase I, Rice growing, palm oil and palm
been upgraded to accommodate II, III trials) of drugs and vaccines wine production are the main
the pneumococcal vaccine trial relating to malaria, acute respiratory economic activities. Many men have
which was concluded in 2005. infection, meningococcal and to work elsewhere in Guinea-Bissau,
Accommodation, laboratory and diarrhoeal disease in a rural area West Africa or Europe. Women
data management facilities are where the burden of infectious also leave in search of domestic
excellent. disease is very high. It also offers the work or to trade as sex workers in
opportunity to measure the long- the region’s urban centres.
The field site has a long history of term impact of these interventions
collaboration with the Department in a meaningful way in a resource- Since this time unique community-
of State for Health, divisional poor setting. based epidemiological studies of
health team and local government HIV-2 and HTLV-1 have been
authorities and has implemented conducted in Caio on a shoestring
research interventions through budget. An old shop was converted
primary health care facilities. into a laboratory, the shop keeper’s
house was upgraded to offices
Basse field site is one of the very Wali Kunda and living quarters, and under the
few clinical trial sites in rural Africa, guidance of Tim Vincent, the Site
where the burden of infectious This small field site focuses on Head, and Peter Aaby, Director of
disease is highest. As a result of specialist malaria work, and in the Projecto de Saude de Bandim,
many preparatory studies for the particular on entomological studies. Bissau, the site has thrived. Current
large vaccine trials undertaken at the staff consists of site head, clinician,
site, there is excellent background Studies have included investigations data entry clerk, 5 fieldworkers,
data on the epidemiology of malaria to determine the physical, chemical a driver, a laboratory technician,
and respiratory infections in the and optical cues which attract a cleaner and a gardener. The
area. The site is well placed to female Anopheles Gambiae laboratory has been upgraded
provide excellent opportunities mosquitoes to bite some human to allow cell culture and cell
for training in clinical trials, subjects more than others. cryopreservation.Plasma, DNA and
epidemiology, data handling, cells have been cryopreserved and
fieldwork and project management. stored at the MRC Laboratories.
It has established its international Clinical staff have been trained for
reputation by hosting more than the rolling out of Anti Retroviral
10 clinical trials in the last 10 years. Therapy (ART), which has recently
These include: been introduced by the Ministry of
Health. In recent years, community
Safety, immunogenicity and health education using the Stepping
efficacy trials of SPf66 malaria Stones method has been led by Tim
vaccine. Vincent. Anthropological studies
relating to sex work and risk factors
Safety, immunogenicity and for spread of HIV (Lagarde 2003,
efficacy trials of RTS,S/AS02 Buckner 1998) have been part of
malaria vaccine which was first the research effort. Community
to show efficacy of this vaccine participation is excellent; all projects
in a malaria endemic country. are approved by the Guinea-Bissau
Ethics Authority.
Safety, immunogenicity and
efficacy trials of pneumococcal

Sibanor
Building on this remarkable base, a Sibanor is situated in the Western
number of fascinating studies are Division of The Gambia and is
planned. They include a further another developing site. Operating
serosurvey for HIV and HTLV-1 from the WEC Mission-funded
infection in the village; studies of health centre, the MRC conducts
HIV-2 specific CD8 T lymphocyte field research in Sibanor and its
phenotype, function and viral escape surrounding villages. The population
mutants; an examination of the comprises predominantly
interactions of malaria and HIV; and subsistence farmers who grow millet
an investigation of the interaction and maize for home consumption
of HTLV-1 and M. tuberculosis and groundnuts as a cash crop.
infections. They belong mainly to the Jola and
Wollof ethnic groups.
Current research activities focus on

acute lower respiratory infections
Sukuta which account for the majority of
the deaths in children under the
The research at Sukuta is age of five years in most developing
focused on understanding how nations of the world, including the
early life infections influence the Gambia. The study participants are
development of the immune recruited from twenty-one villages.
system, and in particular the Pneumococcal carriage studies
response to vaccinations. There are started in December 2003 and have
still many young children in Africa provided background information
with poor health. Often we do not for an ongoing trial to determine
know why some children do not the impact of immunisation
prosper, but this could be related of a whole community with a
to early asymptomatic infections. pneumococcal polysaccharide/
These could also affect the way a protein conjugate vaccine on
child’s immune system responds nasopharyngeal carriage of
to different vaccinations. These pneumococci.
early infections may make children
more (or less) susceptible to other
infections, or affect their growth.
Other studies look at mother-to-
child transmission of infection and
immunity.
The work done in Sukuta has

contributed substantially already
to what is known about the way
that the immune system of young
children develops. We hope to
learn more, which will be helpful in
understanding how young children
fight disease and respond to
vaccination.
MRC staff work hand in hand with

the Health Centre Staff (Gambia
Government Department of State
for Health) to provide medical care,
growth monitoring, vaccinations,
basic laboratory tests and training.

Map of The Gambia showing MRC UK The Gambia Field Sites
NORTH BANK REGION BRIKAM
KOMBO ST.
NDUNGU KEBBEH FARAFENNI
MARY’S
FAJARA
MRC HQ ESSAU KUNTAYA
KEREWAN
BANJUL MANSAKONKO
SEREKUNDA TANKULAR
KENEBA
SUKUTA MANDUAR
LOWER RIVER REG
BRIKAMA
SIBANOR
WESTERN REGION
MRC Field Site
Minor Field Site
Some major towns and villages

CENTRAL RIVER REGION
MA
KUNTAUR
GEORGETOWN
WALI KUNDA BAJA KUNDA
YORO BAWOL
BANSANG
FATOTO
DIABUGU BASSE
GION
GAMBISARA
UPPER RIVER REGION
Other
information
Photographs have been produced courtesy of:
Fanding P Njie, Webmaster & Desktop Publisher, MRC (UK) The

Gambia
Viral Diseases Programme
Trachoma Group
Bacterial Diseases Programme
Malaria Programme
Nutrition Group
Genetics Group
Dr Warren Stevens
Clinical Services Department
Mr David Cotsell (page 16)
Nutrition Group
Felicia Webb (pages 104 & 145)
Photograph, front page – Marianne Mureithi, PhD student with the

Bacterial Diseases Programme (photograph: Fanding P Njie)
Design, layout and additional images by: Communications Department

Medical Research Council Laboratories (UK) The Gambia
Atlantic Road, Fajara,
P. O. Box 273, Banjul,
The Gambia
www.mrc.gm
Unit Director: Tumani Corrah CBE, PhD, FRCP, PWACP

Tel +220 4495442/6
Fax +220 4494154
© Medical Research Council 2007

www.mrc.gm

MRC 04-07 Review

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MRC (UK) Leading Relevant, Cost-

The Gambia Effective Research

04 Foreword from Unit Director

08 Science Research Overview

12 Science Support Services

22 Bacterial Diseases Programme

150 Statistics & Data Management

Professor Tumani Corrah CBE, MRG, Unit

4 MRC UK The Gambia - 04-07 Review

Under the leadership of Professor Brian Greenwood (1980-1995), field research

Subsequent trials with insecticide impregnated bednets carried out by Bob

The Gambia’s Extended Programme on Immunisation (EPI) is recognized as one

MRC UK The Gambia - 04-07 Review 5

As a Gambian, committed to the continuation of research excellence in this

6 MRC UK The Gambia - 04-07 Review

Professor Tumani Corrah

Professor Sarah Rowland- Mr Mark Radford

MRC UK The Gambia - 04-07 Review 7

Prof Sarah Rowland-Jones

The MRC Gambia Unit is rightly proud of its important contributions to

8 MRC UK The Gambia - 04-07 Review

The Viral Diseases Programme benefited from several long-standing studies

MRC UK The Gambia - 04-07 Review 9

New laboratory and staffing structures

We have endeavoured to increase our collaborative efforts, both within

Although it is still early days in our current quinquennial programme, scientists in

10 MRC UK The Gambia - 04-07 Review

The unit’s science portfolio

MRC UK The Gambia - 04-07 Review 11

The MRC Gambia support, infrastructural and administrative services provide

Power Supply and Utilities

12 MRC UK The Gambia - 04-07 Review

Systems up-time in the last 3 years has averaged at:

As well as coordinating procurement planning, installation and retirement/

MRC UK The Gambia - 04-07 Review 13

Following the set up of a sustainable vehicle replacement policy in 2004, the

The HR Department takes prime responsibility for recruitment, contractual and

HR’s current priorities include a strengthening of our pan-African recruitment

14 MRC UK The Gambia - 04-07 Review

Health Safety & Security

A robust, effective and accountable support and management infrastructure is

MRC UK The Gambia - 04-07 Review 15

16 MRC UK The Gambia - 04-07 Review

A smaller programme was held at Sukuta Health Centre in December 2007, on

18 MRC UK The Gambia - 04-07 Review

The open day programmes include poster presentations, demonstrations from

Entertainment that informs

‘Griots’* of the MRC

MRC UK The Gambia - 04-07 Review 19

Communication workshops for MRC’s fieldworkers commenced in November

(*griot (Mandinka) – story teller, praise singer)

MRC’s face in the community

Partnership built on trust

Gambia Government/MRC Ethics Committee

Gambia Government/MRC Joint Committee

University of The Gambia School of Medicine

20 MRC UK The Gambia - 04-07 Review

Collaboration throughout The Gambia

School students looking at malaria

Sarah Burl and Alice Halliday answering

Professor Tumani Corrah fielding

Rohey John Jallow (centre) explaining

MRC UK The Gambia - 04-07 Review 21

Prof Richard Adegbola