Viral Hemorrhagic Fever - VHF

How are hemorrhagic fever viruses GROUPED?

WHAT
Viral hemorrhagic fevers (VHFs) refer to a group of illnesses that are caused by several distinct families of
viruses. In general, the term "viral hemorrhagic fever" is used to describe a severe multisystem syndrome
(multisystem in that multiple organ systems in the body are aected).
Characteristically, the overall vascular system is damaged, and the body's ability to regulate itself is
impaired. These symptoms are often accompanied by hemorrhage (bleeding); however, the bleeding is itself
rarely life-threatening. While some types of hemorrhagic fever viruses can cause relatively mild illnesses,
many of these viruses cause severe, life-threatening disease.
How are hemorrhagic fever viruses TRANSMITTED?
Viruses causing hemorrhagic fever are initially transmitted to humans when the activities of infected
reservoir hosts or vectors and humans overlap. The viruses carried in rodent reservoirs are transmitted
when humans have contact with urine, fecal matter, saliva, or other body excretions from infected
rodents.
The viruses associated with arthropod vectors are spread most often when the vector mosquito or tick
bites a human, or when a human crushes a tick. However, some of these vectors may spread virus to
animals, livestock, for example. Humans then become infected when they care for or slaughter the animals.
VHFs are caused by viruses of four distinct families: arenaviruses, filoviruses, bunyaviruses,
and flaviviruses.
Each of these families share a number of features:
They are all RNA viruses, and all are covered, or enveloped, in a fatty (lipid) coating.
Their survival is dependent on an animal or insect host, called the natural reservoir.
The viruses are geographically restricted to the areas where their host species live.
Humans are not the natural reservoir for any of these viruses. Humans are infected when
they come into contact with infected hosts. However, with some viruses, after the
accidental transmission from the host, humans can transmit the virus to one another.
Human cases or outbreaks of hemorrhagic fevers caused by these viruses occur
sporadically and irregularly. The occurrence of outbreaks cannot be easily predicted.
With a few noteworthy exceptions, there is no cure or established drug treatment for
VHFs.
In rare cases, other viral and bacterial infections can cause a hemorrhagic fever; scrub typhus is
a good example.
What are the SYMPTOMS of viral hemorrhagic fever illnesses?

Some viruses that cause hemorrhagic fever can spread from one person to another, once an initial person
has become infected. Ebola, Marburg, Lassa and Crimean-Congo hemorrhagic fever viruses are
examples.
This type of secondary transmission of the virus can occur directly, through close contact with infected
people or their body fluids. It can also occur indirectly, through contact with objects contaminated with
infected body fluids. For example, contaminated syringes and needles have played an important role in
spreading infection in outbreaks of Ebola hemorrhagic fever and Lassa fever.
Specific signs and symptoms vary by the type of VHF, but initial signs and symptoms often
include marked fever, fatigue, dizziness, muscle aches, loss of strength, and exhaustion. Patients
with severe cases of VHF often show signs of bleeding under the skin, in internal organs, or from
body orifices like the mouth, eyes, or ears. However, although they may bleed from many sites
around the body, patients rarely die because of blood loss. Severely ill patient cases may also
show shock, nervous system malfunction, coma, delirium, and seizures. Some types of VHF are
associated with renal (kidney) failure.

How can cases of viral hemorrhagic fever be PREVENTED and CONTROLLED?

How are patients with viral hemorrhagic fever
TREATED?
Patients receive supportive therapy, but generally speaking,
there is no other treatment or established cure for VHFs.
Ribavirin, an anti-viral drug, has been eective in treating some
individuals with Lassa fever or HFRS.
Treatment with convalescent-phase plasma has been used
with success in some patients with Argentine hemorrhagic
fever.
With the exception of yellow fever and Argentine hemorrhagic fever, for which vaccines have been developed, no vaccines exist that
can protect against these diseases. Therefore, prevention eorts must concentrate on avoiding contact with host species. If prevention
methods fail and a case of VHF does occur, eorts should focus on preventing further transmission from person to person, if the virus can be
transmitted in this way.
Because many of the hosts that carry hemorrhagic fever viruses are rodents, disease prevention eorts include:
controlling rodent populations;
discouraging rodents from entering or living in homes or workplaces;
encouraging safe cleanup of rodent nests and droppings.
For hemorrhagic fever viruses spread by arthropod vectors, prevention eorts often focus on community-wide insect and arthropod
control. In addition, people are encouraged to use insect repellant, proper clothing, bednets, window screens, and other insect barriers
to avoid being bitten.

For those hemorrhagic fever viruses that can be transmitted from one person to another, avoiding close physical contact with infected
people and their body fluids is the most important way of controlling the spread of disease. Barrier nursing or infection control techniques
include isolating infected individuals and wearing protective clothing. Other infection control recommendations include proper use,
disinfection, and disposal of instruments and equipment used in treating or caring for patients with VHF, such as needles and thermometers.
 DISTINGUISHING CARACTERISTICS Arthropods WHAT?
- an Exoskeleton (a skeleton on the outside of the body) Arthropod, any member of the phylum Arthropoda, the largest phylum in the
- Body divided into distinct parts animal kingdom, which includes such familiar forms as lobsters, crabs,
- Jointed legs and appendages spiders, mites, insects, centipedes, and millipedes. About 84 percent of all
- Bilateral symmetry (both sides of the body are the same) known species of animals are members of this phylum. Arthropods are
represented in every habitat on Earth and show a great variety of adaptations.
Several types live in aquatic environments, and others reside in terrestrial
ones; some groups are even adapted for flight.

Class Distinctions

Insects Arachnids Crustaceans Chilopods Diplopods

Crustaceans (technically a
Mosquitos, Grasshoppers,, subphylum)
Ticks Spiders, scorpions,,
butterflies, beetles, ants, etc. Classes include crabs, shrimps,
mites, etc. 65,000 described
1,000,000 described world lobsters, barnacles, isopods etc.
world species
species 44,000 described world species

Ex Lifecycle Aedes Mosquito Ex Lifecycle Ticks

 WHO$guidelines$for$the$diagnosis$of$dengue$haemorrhagic$fever$(DHF)$and$dengue$shock$
syndrome$(DSS).

Ngo$Thi$Nhan$et$al.$Clin$Infect$Dis.$2001E32:204I213

"2001"by"the"Infectious"Diseases"Society"of"America
 Arbovirus (arthropod-borne virus) applies to any virus that is transmitted to
Arboviruses humans and/or other vertebrates by certain species of blood-feeding
arthropods, chiefly insects (flies and mosquitoes) and arachnids (ticks).
Arbovirus is not part of the current viral classification system, which is
based on the nature and structure of the viral genome. Families in the current
classification system that have some arbovirus members include

Flaviviridae Arenaviridae Filoviridae Bunyaviridae

Phlebo-Virusses Hanta-Virusses

- Yellow Fever
- Lassa Fever
- Dengue - Rift Valley, Phlebotomus - Hantaan, Seoul,
- Machupo, Junin, - Ebola, Marburg
- Japanese Encephalitis Fever Puumala, Sin Nombre
Guanarito, Sabia
- West-Nile Virus

Dengue is a mosquito-borne disease caused by a flavivirus. Dengue

fever usually results in abrupt onset of high fever, headache, myalgias,
arthralgias, and lymphadenopathy, followed by a rash that appears
with a 2nd temperature rise after an afebrile period. Respiratory
symptoms, such as cough, sore throat, and rhinorrhea, can occur.
Dengue can also cause potentially fatal hemorrhagic fever with a
bleeding tendency and shock. Diagnosis involves serologic testing and
PCR. Treatment is symptomatic and, for dengue hemorrhagic fever,
includes meticulously adjusted intravascular volume replacement.
NAME DISEASE Pathogen Pathogen (2) Transmission Vector RESERVOIR INCUBATION PERIOD SYMPTOMS

- MAN is main reservoir Virus circulates in the blood - Begins suddenly with fever Afte
- There is Transovarial of infected humans (viraemia) lasting 2 - 7d => occasionally orbi
transmission of dengue for 2 to 7 days; biphasic beg

DENGUE FEVER Flavivirus - 4 Serogroups - DI, DII, Through bite of a

AEDES AEGYPTI
virus in mosquito, and - No splenomegaly - Rash first
(Flaviviridae) DIII, DIV Mosquito can be repeated for a Aedes mosquitoes may may appear around 3rd to tem
few generations without acquire the virus when they 5th day and
the adults feeding on an feed on humans during this - Leukopenia and Trombo- mac
period cytopenia are the rule.
infected host!!!! and

Follo
feve
DHF - DENGUE - In adults, DHF begins with - Sp
HEMORRHAGIC Flavivirus - 4 Serogroups - DI, DII, Through bite of a
AEDES AEGYPTI IDEM Fever 1 - 4 days
abrupt fever and headache - Se
(Flaviviridae) DIII, DIV Mosquito - DHF initially indistinguis- - Pe
FEVER hable from classic dengue. - Pa
- Dy
- Eff

+ Si
DENGUE SHOCK DENGUE SHOCK SYNDROME
DSSyndrome includes criteria
- Hy
SYNDROME for DHF +++++ =>
- CS

AEDES AEGYPTI
- Non-specific flue-like
(Mosquito is to be => A
- Zoonosis and transmission by mosquito-BITE syndrome
Flavivirus - Transmission can be anthroponotic (human-to-
infected about 2wks
- Sudden fever over 39C
e
(Flaviviridae) => previously by
- Malaise, Headache, Muscle (
vector- to-human).
infects an feeding on a person - Liv
- There are 3 transmission cycles for yellow fever: Nonhuman and human Incubation of 3 - 6 days pain
Arthropod which with AEDES - NO
YELLOW FEVER has to be infected
sylvatic (jungle), intermediate (savannah), and
AEGYPTI
primates are the main => (The Quarantine period is - Red conjunctiva, GBP,
- Pa
urban. reservoirs of the virus, 6 days) Vomiting
by a blood meal on !!!!! an
-> Zoonosis: mosquitos can transmit to monkeys - Skin congestion of Face and
a viraemic - Th
living in the wild => monkey-mosquito-monkey Neck => RED PHASE
vertebrate host!! - HAEMAGOGUS - Ga
cycle. - Possibly Nasal & Gingival
and SABETHES Ex
bleeding
Mosquitos

- Zoonosis with pigs

Through bite of a
and birds (Herons) as - Initial symptoms often - At
Mosquito !! In man usually subclinical include fever, headache, and - In
reservoirs.
infection, but 1/200 develop vomiting. lym
Flavivirus - Humans are incidental
- Infection occurs in foci
Meaning-Encephalitis
(Flaviviridae) JE is the main cause of CULEX in areas where pigs and
or dead-end hosts, - Usually Subclinical - Me
JAPANESE - Asian Arbovirosis viral encephalitis in because they usually
Tritaeniorhynchus people live closely
In persons who develop - Meningo-Encephalitis -> dis
ENCEPHALITIS with mainly many countries of Asia
do not develop high
- breeds in rice together. symptoms, the incubation Incidence 1/200, mortality
neurological with nearly 68 000 fields. - Pigs -> amplifier for the period (time from infection 10-50% - Ne
enough concentrations
symptoms clinical cases every year newborn mosquito until illness) is typically 5-15 - Stupor, coma-convulsions like
of JE virus in their
population because days - Frequent neurologic sequels
bloodstreams to infect
they have a long - Abortion - Se
feeding mosquitoes.
viraemic period!!!

NAME DISEASE Pathogen Pathogen (2) Transmission Vector RESERVOIR INCUBATION PERIOD SYMPTOMS
 SYMPTOMS I SYMPTOMS II DIAGNOSIS TREATMENT

Fever and other symptoms persist 48 to 96 h, Include serologic testing IgM & IgG (Elisa), antigen Treatment is symptomatic -
er After an incubation period of 3 to 15 days, fever, chills, headache, retro- detection on stick (ICT-test), and PCR of blood.
followed by rapid defervescence with profuse Supportive Care
nally orbital pain with eye movement, lumbar backache, and severe prostration CBC may show leukopenia by the 2nd day of
sweating. Patients then feel well for about 24 h, after
begin abruptly. Extreme aching in the legs and joints occurs during the fever; by the 4th or 5th day, the WBC count may
which fever may occur again (saddleback pattern), NO VACCINE
first hours, accounting for the traditional name of breakbone fever. The be 2000 to 4000/L with only 20 to 40%
typically with a lower peak temperature than the first.
o temperature rises rapidly to up to 40 C, with relative bradycardia. Bulbar
Simultaneously, a blanching maculopapular rash granulocytes. Urinalysis may show moderate
and palpebral conjunctival injection and a transient flushing or pale pink albuminuria and a few casts. Thrombocytopenia
spreads from the trunk to the extremities and face. Patients require intensive
macular rash (particularly of the face) may occur. Cervical, epitrochlear, may also be present.
Mild cases of dengue, usually lacking lymph- treatment to maintain euvolemia.
and inguinal lymph nodes are often enlarged
adenopathy, remit in < 72hrs. Both hypovolemia (which can
!! FOUR GRADES:
cause shock) and overhydration
1/ Thrombocytopenia
(which can cause acute respiratory
Following syptoms tend to appear not the 4th or 5th day after the onset of 2/ idem 1 + spontaneous haemorrhages or pos
- Severe Thrombocytopenia distress syndrome) should be
fever, WHEN fever suddenly subsides. Tourniquet test
h - Spontaneous or provoked bleeding - Signs of Plasma leakage => leading to hemo- avoided. Urine output and the
3/ idem 1 or 2 + Hypotension
he - Severe Abdominal pain concentration (>20% above average) degree of hemoconcentration can
4/ idem 3 but blood pressure not measurable
- Persistent vomiting - Hypoproteinemia and pleural eusions be used to monitor intravascular
e. - Painful hepatomegaly - Ascites and/or pericardial eusion (due to OVERT DENGUE HEMORRHAGIC FEVER volume. Ringer Lactate
- Dyspnea, - Lethargy capillary leak syndrome) => Positive Tourniquet test with petechiae - Paracetamol -> NO aspirine
- Effusion (Pleura, pericard, ascites) => Ecchymoses => Purpura - Transfusion of platelets or RBC
=> Bleeding from mucosa (epistaxis, melena) - NO Steroids
+ Sings of circulatory collapse with rapid and weak pulse - Narrow pulse pressure ( <20 mmHg)
eria NO VACCINE
- Hypotension with cold and clammy skin - Cold extremities - Decreased diuresis - Dyspnea and Restlessness or Lethargy
- CSF is usually normal, but occasional raised pressure and Lymphocytosis in the CSF (5-500 x 106 cells/Lter) can be observed.
- Clinical during epidemic !!!!!!!!!NO ASPIRIN!!!!!!!!
- Antigen-detection - Symptomatic: nutrition, fluids,
=> AFTER A SHORT-LIVED IMPROVEMENT (1DAY) a second febrile - No real Encephalitis but Neurological signs such
- Serology from day 5 O2, Transfusion, dopamine
episode occurs (biphasic fever) -> characterised by mild Jaundice as convulsions can occur due petechiae and
- PCR (Polymerase Chain Reaction) - Nasogastric tube: prevention of
cle (YELLOW PHASE) bleeding in the brain as well as to hepatic
- Post mortem: Councilman-bodies in liver stomach dilatation
- Liver and Kidney (proteinuria & oliguria) failure occurs Encephalopathy (Hyperammonaemia)
- Virus isolation: - Cimetidine
- NO Splenomegaly
-> Cell Culture - Avoid component pre-renal
- Patients general condition deteriorates dramatically with hypothension - CSF might show slight increase in protein content.
-> Intrathoracal inoculation of male Kidney failure
and shock
and mosquitos - Temporary Kidney Dialysis
- There is Haemorrhaging (skin - mucosa - uterus - intestines => Death mainly occurs between 7th - 10th day -> if
-> PCR - Isolation
- Gastric bleeding often predominates => VOMITING BLOOD => still alive after 12d, complete recovery can be
l -> Antigen-Capture ELISA - Treat under a mosquito net
Extremely poor prognosis expected. (only 10-20% experience severe form)
-> IgM ELISA
- Formal virus-identification: neutralisation tests VACCINE

No specific treatments have been

- At the beginning there is Leukopenia - Diagnosis can be made by isolating the virus found to benefit patients with JE,
and - In half of the patients the cerebrospinal fluid contains raised protein and from the CSF early in the disease or by but hospitalization for supportive
- Pregnant women risk => intra-uterine infection and
lymphocytes serology. care and close observation is
death of the foetus during the first two trimesters.
generally required.
- Mental status changes, neurologic symptoms, weakness, and movement
- Nipah virus infection can cause a similar clinical !! FOUR GRADES:
disorders might develop over the next few days.
picture - In India -> Chandipura virus (rhabdovirus) 1/ Thrombocytopenia Treatment is symptomatic. Rest,
y
has been responsible for large outbreaks of severe 2/ idem 1 + spontaneous haemorrhages or pos fluids, and use of pain relievers
- Neurological sequelae -> frequent -> such as dystonia and Parkinson-
encephalitis!! => Transmission through Sandflies. Tourniquet test and medication to reduce fever
s like symptoms, due to the basal ganglia being affected.
uels 3/ idem 1 or 2 + Hypotension may relieve some symptoms.
- Seizures are common, esp. among children. 4/ idem 3 but blood pressure not measurable
VACCINE

SYMPTOMS I SYMPTOMS II DIAGNOSIS TREATMENT

 feeding mosquitoes.
viraemic period!!!

NAME DISEASE Pathogen Pathogen (2) Transmission Vector RESERVOIR INCUBATION PERIOD SYMPTOMS
Through bite of a AEDES AEGYPTI
- Fir
Mosquito &
- Fo
Alphavirus ALBOPICTUS Incubation of 2 - 5 days
- Co
- Humans are Primary
CLINICAL PICTURE - Art
Host of Chikungunya Biting throughout => Followed by a sudden
CHIKUNGUNYA virus during epidemic daylight hours, Humans onset fever
RESEMBLES THAT OF to
CLASSIC DENGUE FEVER - An
periods though there may be (typically > 39C)
cau
peaks of activity in
dis
- Blood-borne transm. the early morning
==>
is possible!!! and late afternoon.

Transmission The hepatitis B virus can survive

outside the body for at least 7
- perinatal (from mother to baby at days. During this time, the virus
SYMPTOMS ACUTE S
Hepatitis B virus The virus is transmitted through birth) can still cause infection if it
contact with the blood or other enters the body of a person who PHASE (A,B AND C!!!!)
body fluids of an infected - early childhood infections - is not protected by the vaccine.
Hepatitis B is a viral -y
Hepatitis B person. inapparent infection through close The incubation period of the Most people do not
HEPATITIS B infection that attacks hepatitis B virus is 75 days on e
virus the liver and can
interpersonal contact with infected experience any d
The hepatitis B virus is 50 to household contacts) average, but can vary from 30 symptoms during the
cause both acute e
100 times more infectious than to 180 days. The virus may be acute infection phase.
and chronic disease. n
HIV. - unsafe injection practices detected within 30 to 60 days
a
- unsafe blood transfusions after infection and can persist
and develop into chronic
- unprotected sexual contact. hepatitis B.

=> Adults: N meningitidis (meningococ),

S pneumoniae (pneumococ) Transmission & Incubation The
-as
The bacteria are transmitted from person-to-person through droplets Neisseria meningitidis only infects humans; there is no animal
Bacterial M. => Children: Streptococcus Group B and
of respiratory or throat secretions from carriers. Close and prolonged reservoir. The bacteria can be carried in the throat and
Meningococcal (neonates) Even
contact such as kissing, sneezing or coughing on someone, or living in sometimes, for reasons not fully understood, can overwhelm the
meningitis H influenzae (<5y), S pneumoniae, star
close quarters (such as a dormitory, sharing eating or drinking utensils) body's defenses allowing infection to spread through the
- 4 serogroups: A, N meningitidis the
with an infected person (a carrier) facilitates the spread of the disease. bloodstream to the brain. It is believed that 10% to 20% of the
B, C & W135 dam
The average incubation period is 4 days, but can range between 2 population carries Neisseria meningitidis in their throat at any
=> Gram negatives: Klebsiella, surv
and 10 days. given time. However, the carriage rate may be higher in epidemic
Pseudomonas men
MENINGITIS situations.
char
Meningitis is an => M. Tuberculosis
inflammation of the => Viral H Simplex, H Zoster, Rubella, Measles, It is usually dicult to avoid exposure to human viruses, however
tissue that covers the If you have close contact with a person who has viral meningitis, you may
CMV good hygiene practices such as hand washing after visiting toilets
brain and spinal cord. become infected with the virus that made that person sick. However, you
will minimise the risk of contracting enteroviruses. C
are not likely to develop meningitis as a complication of the illness.
=> Mycosis: Cryptococcus neoformans
For arboviruses, the use of insect repellents, and avoiding
Some viruses are spread from person to person by respiratory secretions,
=> Parasites: P falciparum (Plasmodium exposure to biting insects by avoidance of peak biting times such
Viral falciparum is a protozoan parasite, one of
others through inadvertent contact with faecal matter.
as at dusk, together with use of appropriate clothing during the Feve
the species of Plasmodium that cause Irrita
biting time is also a positive way of reducing the risk of
Some viruses are transmitted to people from blood sucking insects. The Poo
malaria in humans. It is transmitted by the contracting viral illnesses.
way a virus is spread between people depends on the specific virus. Slee
female Anopheles mosquito.
Leth
The incubation period for viral meningitis may range from a few
=> (Malignancy) days to some weeks, depending on the type of virus.

NAME DISEASE Pathogen Transmission RESERVOIR INCUBATION PERIOD

This
 VACCINE

SYMPTOMS I SYMPTOMS II DIAGNOSIS TREATMENT

Most patients recover fully, but in some cases joint
- First sudden onset of fever > 39C - Serological tests: There is no specific antiviral drug
pain may persist for several months, or even years.
- Followed by crippling joint pains that may temp. incapacitate patient -> ELISA (to confirm presence of IgM and IgG treatment for chikungunya.
Occasional cases of eye, neurological and heart
- Conjunctivitis and Skin Rash are common anti-Chikungunya antibodies - IgM levels are
complications have been reported, as well as
- Arthralgias occur in around 70% of the cases, and can persist for weeks highest 3-5 wks after onset of illness and Treatment is directed primarily at
gastrointestinal complaints. Serious complications are
to months persist for about 2 months relieving the symptoms, including
not common, but in older people, the disease can
R - Ankles and wrists are most commonly involved => INTENSE pain -> Samples collected during the first week the joint pain using anti-pyretics,
contribute to the cause of death. Often symptoms in
caused by pressure on the wrist is a strong diagnostic sign of the after onset of symptoms should be tested by optimal analgesics and fluids.
infected individuals are mild and the infection may go
disease!!!! both serological and virological methods (RT-
unrecognized, or be misdiagnosed in areas where
==> If no complications ensue, recovery takes 5 - 7 days. PCR) NO VACCINE
dengue occurs.

- Serology: Hepatitis B Surface Antigen (HBsAg)

- Acute or chronic infection

A small subset of persons with acute hepatitis can Supportive treatment during acute
E Some people have acute illness with symptoms that last
develop acute liver failure which can lead to death. phase
!!) several weeks: - Active or carrier
In some people, the hepatitis B virus can also cause a maintaining comfort and adequate
- yellowing of the skin and - Hepatitis B Surface Antibodies (HBsAb):
t chronic liver infection that can later develop into nutritional balance, including
eyes (jaundice) cirrhosis of the liver or liver cancer. replacement of fluids that are lost
dark urine - Immunity: because of vaccination or
e from vomiting and diarrhea.
extreme fatigue
e. More than 90% of healthy adults who are infected
nausea, vomiting and - Because of natural immunity: patient
with the hepatitis B virus will recover naturally from the Chronic infection: lamivudine (also
abdominal pain. suered from (sub)clinical infection
virus within the first year. used to control HIV)
- PCR-DNA: identifying and measuring the virus
itself
TREATMENT
The most common symptoms are: DIAGNOSIS Meningococcal disease is potentially fatal and should always be viewed as a
- a sti neck, - high fever, - sensitivity to light, - confusion, - headaches medical emergency. Admission to a hospital or health centre is necessary,
mal Initial diagnosis of meningococcal meningitis can be made
and vomiting. although isolation of the patient is not necessary. Appropriate antibiotic
by clinical examination followed by a lumbar puncture
Even when the disease is diagnosed early and adequate treatment is treatment must be started as soon as possible, ideally after the lumbar puncture
he showing a purulent spinal fluid. The bacteria can sometimes
started, 5% to 10% of patients die, typically within 24 to 48 hours after has been carried out if such a puncture can be performed immediately. If
be seen in microscopic examinations of the spinal fluid. The
the onset of symptoms. Bacterial meningitis may result in brain treatment is started prior to the lumbar puncture it may be dicult to grow the
diagnosis is supported or confirmed by growing the bacteria
damage, hearing loss or a learning disability in 10% to 20% of bacteria from the spinal fluid and confirm the diagnosis.
from specimens of spinal fluid or blood, by agglutination
survivors. A less common but even more severe (often fatal) form of
mic tests or by polymerase chain reaction (PCR). The
meningococcal disease is meningococcal septicaemia, which is A range of antibiotics can treat the infection, including penicillin, ampicillin,
identification of the serogroups and susceptibility testing to
characterized by a haemorrhagic rash and rapid circulatory collapse. chloramphenicol and ceftriaxone. Under epidemic conditions in Africa in areas
antibiotics are important to define control measures
with limited health infrastructure and resources, ceftriaxone is the drug of choice.
ver
lets Common symptoms in adults => Bacterial: antibiotics
Common symptoms in infants Supportive
Fever - Headache - Sti neck - Sensitivity to bright light - Sleepiness or trouble waking up - Cephalosporines
from sleep - Nausea - Vomiting - Lack of appetite - Lethargy (a lack of energy) - Gram negatives: gentamycine
=> Reduce intracranial pressure:
Most people with viral meningitis usually get better on their own within 7 to 10 days. - (Chloramphenicol)
uch shunt, mannitol
Fever
e
Irritability Initial symptoms of viral meningitis are similar to those for bacterial meningitis. However, => Viral
=> Antipyretics
Poor eating bacterial meningitis is usually severe and can cause serious complications, such as brain
Sleepiness or trouble waking up from sleep damage, hearing loss, or learning disabilities. It is very important to see a healthcare - Herpesviruses: Aciclovir
=> Anticonvulsants
Lethargy (a lack of energy) provider right away if you think you or your child might have meningitis; a doctor can
w
determine if you have the disease, the type of meningitis, and the best treatment. => Mycosis: Amphotericine

This form is more common. There is increasing anxiety, excitation, hyperactivity, hyperventilation, Viral encephalitis due to herpes simplex or an arbovirosis such as Japanese encephalitis, West Nile fever,
 The incubation period for viral meningitis may range from a few
=> (Malignancy) days to some weeks, depending on the type of virus.

NAME DISEASE Pathogen Transmission RESERVOIR INCUBATION PERIOD

Rabies is a zoonotic disease (a disease that is This

transmitted to humans from animals) that is diso
Lyssavirus Dogs are the source of the vast Incubation is typically 13 months, but may vary from <1
caused by a virus. The disease aects domestic
majority of human rabies week to >1 year. Sym
and wild animals, and is spread to people
Rabies is a viral disease that causes deaths. Hyp
through close contact with infectious material,
acute inflammation of the brain in humans (L. Apers => 20 to 90 days => leaving a window for
RABIES usually saliva, via bites or scratches. (Other involved mammals: curative vaccination)
and other warm-blooded animals In ap
Rabies is caused by lyssaviruses - cat, fox, squirrel, ferret, voca
- Rarely via aerosol !! In dogs saliva becomes infectious at least 2days
skunk, raccoon, sheep, asso
including: rabies virus and Australian bat - Rarely via transplantation BEFORE symptoms of the disease appear!!
cattle, bat..) of th
lyssavirus. - Transmission through contaminated meat??
(aer
conv
stin
and
Pathogenesis
(invo
The
- Entrance of the Virus (e.g. Bite)
- Local Multiplication Myo
- Then crosses the Neuromuscular junction to penetrate a peripheral Nerve neur
- Subsequently spreads along the nerve by retro-axonal flow to the Spinal Cord resp
and Brain dise
- In CNS, the Virus proliferates further
- And from there, it again spreads to almost all organs in the body.
- The Saliva contains high concentrations of infectious viruses

Basically, the patient develops a very aggressive VIRAL ENCEPHALITIS

Deli
=> With few exceptions - 100% Lethal
flapp
- Protein content in CSF is usually normal and in the first week of the disease
Rea
the white blood cell count in the CSF is raised in 70% of cases.
- Antibodies in serum and CSF cannot be detected before there are symptoms
Stry
=> once the Symptoms have begun, antibodies are detectable BUT at that
All ty
moment DEATH is NEAR!!!!!
som
even

Acu
Clinical Features Rabies GENERAL Clinical Features FURIOUS Rabies is un

Incubation lasts 20 to 90 days (extremes of 4 days and 7 years have been described). Anxiousness! hyperactive! Teta
Bites close to the face and with a large inoculum (severe wounds) are associated with the shortest incubation times. mos
Intermittent disorientation hallucinations
A prodromal phase lasting 2 to 10 days then follows.
Spasms : throat, larynx
Bac
The first symptom is an influenza-like syndrome with moderate fever and malaise lasting a few days. This can be associated Hydrofobia
with severe local pruritus leading to scratching and excoriations, headache, pain or paraesthesia at the site of the bite. (Bru
Salivation etc.)
Sometimes there is moderate muscle weakness. Local myoedema after muscle percussion can occur. Agitation and Hyper salivation hyperthermia hypertension etc.
insomnia can occur at a very early stage. Tachycardia
Myocarditis Cere
Afterwards the disease can take two different courses, depending on which features predominate: furious rabies on the Coma colle
one hand (more involvement of the brain) and paralytic rabies (extensive involvement of the spinal cord) on the other.
Mortality is 100%
w
determine if you have the disease, the type of meningitis, and the best treatment.
Clinical Features FURIOUS Rabies II
This form is more common. There is increasing anxiety, excitation, hyperactivity, hyperventilation,
disorientation and/or hallucinations.
m <1
Symptoms occur intermittently and persist for 1 to 5 min, followed by a period of mental calm.
Hyperstimulation occurs as a result of destruction of inhibitory centres in the brain stem.
r Acyclovir can be tried in treatment, but the infection provokes dramatic neurological
In approximately half the patients, painful spasms of the larynx and throat muscles occur (swallowing and
vocal chord spasms). These are triggered for instance by seeing or wanting to drink a glass of water. This is
associated with painful convulsive contractions of the respiratory muscles. The patient is therefore afraid
of this situation (hydrophobia or fear of water). The spasms can also be induced by blowing air over the face
(aerophobia) or by other, often minor, stimuli (compare with tetanus). The spasms develop into generalised
convulsions. There is no trismus or muscle rigidity between convulsions (in contrast to tetanus). Neck
stiness can occur, but is usually not pronounced. There is profound dysautonomia. The patient may sweat
and weep profusely, as well as displaying hypersalivation, hypothermia, hypertension and tachycardia
(involvement of the autonomic nervous system). Fever can occur. There is a pronounced thirst.
The patient is in agony.
Myocarditis can cause cardiac arrhythmias. Coma follows within 10 days after the onset of the acute
neurological symptoms and can persist for hours to months (mostly short-lasting). Finally, cardiac and
respiratory arrest follow. Death occurs in nearly 100% of cases, in general 2-7 days after the onset of the
disease. Medical management can prolong survival up to 133 days.
Dierntial Diagnosis FURIOUS Rabies I
Delirium tremens: chronic alcohol misuse and sudden abstinence, signs of hepatic injury spider naevi,
flapping tremor, gynaecomastia, collateral circulation, etc).
Reaction to some hard drugs (crack, speed). This occurs more often in some large cities.
Strychnine poisoning. This plant product suppresses nerve impulse inhibition and thus causes convulsions.
All types of sensory stimuli can cause convulsions. Consciousness is clear if no asphyxia has occurred. It is
sometimes used as a rodent poison. If the patient survives the first 24-hours, the prognosis is good. In the
event of death, the rapid onset of rigor mortis is characteristic.
Acute psychosis and hysteria. Very common in developing countries. Hysteria: no hydrophobia if the patient
is unaware of the existence of this sign.
Tetanus: portal of entry, trismus, muscle stiness, convulsions on sudden stimulus, clear consciousness,
mostly shorter incubation, no encephalitis, clear CSF.
Bacterial meningitis: lumbar puncture. Note that several organisms can cause lymphocytic pleiocytosis
(Brucella, Listeria, Treponema pallidum (syphilis), Borrelia, tuberculosis, Coxiella burnetii, various rickettsiae,
etc.). Various systemic fungal infections, sarcoidosis, auto-immune diseases (S.L.E.) with cerebral vasculitis
etc. can produce abnormal cerebrospinal fluid.
Cerebral abscess. As a result of septic emboli (subacute bacterial endocarditis) or from penetration of a
collection of pus (sinus, middle ear, etc.). Cerebral toxoplasmosis is common in AIDS.
=> Mycosis: Amphotericine
Dierntial Diagnosis FURIOUS Rabies II
Viral encephalitis due to herpes simplex or an arbovirosis such as Japanese encephalitis, West Nile fever,
tick-borne encephalitis (Russian Spring-Summer meningo-encephalitis) or Venezuelan equine encephalitis.
There are no lucid periods and no typical spasms. For arboviral infections, serology is important. Infections
with Herpes virus B (Herpes simiae virus) are rare. This virus can be transmitted via a bite, scratch or via
body fluids from an infected monkey. Mucocutaneous lesions and encephalitis can follow inoculation.
symptoms.
Cerebral malaria (Plasmodium falciparum)
Post rabies-vaccination encephalitis if vaccination has been given with the old vaccines.
Bite of a cobra or other elapid snake: saliva will dribble out ouf the mouth as a result of
throat paralysis (not from spasms). Ptosis, swelling, pain and tissue injury at the site of the
bite.
DIAGNOSIS RABIES FURIOUS & PARALYTIC
The diagnosis is clinical. Rabies must be suspected in someone who develops neurological symptoms a
week or more after an animal bite. The number of white blood cells in the peripheral blood is normal or
slightly raised, with a slight elevation of monocytes. Albuminuria can occur. An EEG shows abnormalities
consistent with encephalitis. A CT scan or NMR scan of the brain can show surprisingly few
abnormalities. Hydrophobia occurs in approximately half the patients and is pathognomonic (i.e.: highly
specific).
Investigation of contact with animals is important, but no history of exposure can be found in 20% of
patients. The protein content in the cerebrospinal fluid is usually normal and in the first week of the disease
the white blood cell count in the CSF is raised in 70% of cases (highly fluctuating dierential count).
Antibodies in serum and cerebrospinal fluid cannot be detected before there are symptoms. Once the
symptoms have begun, antibodies are detectable but at that moment death is near.
All in all, rabies is a clinical diagnosis, but this has to be supported with arguments, such as:
1. RT-PCR on saliva for rabies RNA
2. Virus isolation from saliva or cerebrospinal fluid
3. Corneal smear for rabies virus antigen
4. Antibodies in serum
5. Skin biopsy for immunofluorescence
Concerning The Animal
The incubation period in dogs is 2 weeks to 6 months. Rabies in dogs (and also in cats and horses) leads to
changes in behaviour, aggressiveness, running away from home, diculty in swallowing with hypersalivation,
and convulsions. The animal usually dies within 7 days. Rabies in animals is not universally fatal. In case of a
bite from a dog suspected of rabies, the dog should be observed for ten days. If it exhibits abnormal
behaviour, the animal's brain can be analysed.
one hand (more involvement of the brain) and paralytic rabies (extensive involvement of the spinal cord) on the other.
Mortality is 100%

Clinical Features PARALYTIC Rabies TREATMENT

This is the most frequent form after a vampire bite (South America). There is a flaccid paralysis (no
tendon reflexes). There are often mild sensory disorders. The paralysis often begins in the bitten
part of the body and then ascends further. Death follows from general paralysis. The course is less
rapid than in the furious form.
Dierntial Diagnosis PARALYTIC Rabies
Polio: initially fever and muscle pain, asymmetrical paralysis, clear consciousness.
Guillain-Barre syndrome: ascending symmetrical paralysis, typical cerebrospinal fluid with large
amount of protein but few cells. Early in this syndrome, the CSF might still be normal. Control
lumbar puncture some days (up to a week) later then shows the albuminocytological dissociation.
There are variants in which the cranial nerves are primarily aected (Fischer syndrome). It should
be noted that initially the cerebrospinal fluid can be normal, but very quickly the protein level in the
CSF will raise substantially.
Often the syndrome follows one or more weeks after Campylobacter enteritis or another infection.
Botulism: descending paralysis (ocular muscles, throat muscles, neck, other muscles, progressive
respiratory paralysis), no fever, dry mucous membranes, large pupils. Is caused by toxins
produced by a specific bacterium (Clostridium botulinum ), related to the organism that causes
tetanus. The organism can be found in a wound or more often in spoilt food ("botulus" = sausage).
Diphtheria: is rare, but poses few diagnostic problems in general in case of throat, nose or
laryngeal infection. Extensive membrane-like coating in the throat ("diphthera" = leather) with
marked cervical lymph node enlargement. This is followed 1 to 2 weeks later by carditis and
progressive paralysis, sometimes also with sensory disorders (peripheral neuropathy).
Cutaneous diphtheria produces painful wounds but rarely paralysis.
Bite of an elapid snake (e.g. cobra): rapidly occurring descending paralysis + local reaction at the
site of the bite.
Metabolic / hypoxic / toxic encephalopathy
Reye syndrome: sudden onset, often after an initial viral syndrome. Vomiting is frequent.
There is hepatomegaly in 40% of cases and liver function tests are abnormal. A liver biopsy is
diagnostic.
Initial : Cleaning of bite-wound (soap)
Anti-tetanus prophylaxis
Antibiotics eventually
Antirabies hyperimmuunglobulins : dose IM and dose round the wound. + Vaccination! (Rabipur) !If vaccinated
before: post-exposure vaccination: two injections: day 1 and 3.
If not vaccinated before: Belgian guidelines: two injections day 1 (each arm), one injection day 7 and 21
Alternative schedule: five injections: day 1, 3, 7, 14 and 28!
Since there is quasi 100% mortality once symptoms have occurred, only palliative therapy can be given at that
time: pain relief (morphine) and reduction of spasms (myorelaxants e.g. diazepam). In most cases, barbiturates and
chlorpromazine are also given. Although no case of transmission from patient to medical personnel has yet been
described, it is recommended that the patient should be isolated and sta should wear masks, goggles and gloves
during the provision of care. Sta should also preferably be vaccinated, but that is not obligatory. In 2004, Jeanna Giese
became the first patient ever to recover from rabies without the vaccine. By early 2009, only two cases of rabies have
been documented to survive with the so-called Wisconsin protocol. In this treatment schema, a multi-drug cocktail is
used, which includes ketamine, amantadine, benzodiazepines and barbiturates.
Clean the wound with a detergent (soap). This is a very eective method of destroying the virus. 0.1% povidone iodine
(Isobetadine) or 70% alcohol (painful!) is also useful.
Oxygenated water or mercurochrome are not indicated. Leave the wound open afterwards (never close bite wounds).
Antibiotics. All bites are by definition bacterially contaminated but do not always become infected. Wound infection with
Pasteurella multocida or Capnocytophaga canimorsus is frequent after dog or cat bites. Routine administration of
antibiotics after bite wound is controversial.
Antirabies hyperimmunoglobulins (BayRab, Imogam Rabies-HT): Previous guidelines advocated to inject IM and
infiltrated around the wound if possible. Recently, preference has been given to injecting as much as possible locally.
The dosage instructions of the immunoglobulines must be observed, since an overdose suppresses the production of
endogenous antibodies. People who have previously been vaccinated against rabies should not receive
hyperimmunoglobulins. They should however receive booster vaccination. If the patient has already been vaccinated
prior to the bite with a correct regimen, a booster is given on day 0 and day 3. Start administration at the same time as
the vaccination, or, in any case, within 7 days. The vaccine should be drawn into a dierent syringe and injected at a
dierent site from the immunoglobulins. There are two types of immunoglobulins:
1. equine serum: cheap but risk of anaphylaxis (40 IU/kg)
2. human serum: expensive but safe (20 IU/kg). A 2 ml ampoule usually contains 300Int'.Units.

Do not touch any sick, paralysed animals, or better still: simply never touch animals in the wild. Kill stray dogs (sometimes problematical in Buddhist countries). Vaccinate dogs (pets).
Vaccination of wild animals: for example in Switzerland and Germany foxes are vaccinated with oral live vaccine incorporated in fishmeal pellets or other bait. Vampire bats can be
vaccinated by catching some and applying the live vaccine to the skin. The animals often lick one another and it would be possible in this way to vaccinate a colony of animals. The
PREVENTION vaccine could also be applied to cattle. Vampires can be controlled by applying coumarins
[rat poison] to their skin and then releasing them again.
Persons in high-risk occupations (e.g. veterinarians, certain laboratory personnel, medical personnel in the infectious diseases departments of hospitals) should be vaccinated. The
antibody titre is determined every 2 years to ascertain whether a booster injection is necessary.

NAME DISEASE Pathogen Pathogen (2) Transmission RESERVOIR INCUBATION PERIOD SYMPTOMS
 antibody titre is determined every 2 years to ascertain whether a booster injection is necessary.

NAME DISEASE Pathogen Pathogen (2) Transmission RESERVOIR INCUBATION PERIOD SYMPTOMS

Most people who get infected

-As
with poliovirus (about 72 out of
- Pharynx: Virus is found in the Cases: the cases are most a
Polioviruses are 100) will not have any visible
oropharyngeal secretions infectious 7 to 10 days before
WPV = Wild relatively resistant symptoms.
(oral-oral -> direct droplet and after the onset of symptoms. ->
Polio Virus and survive for a long About 1 out of 4 people with
infection) In the feaces, the virus is ->
time under suitable poliovirus infection will have
excreted commonly for 2 to 3
environmental flu-like symptoms that may
Human - Small intestine: Virus finds weeks, sometimes as long as to ->
POLIOMYELITIS enteroviruses
conditions, but are
exit in stools => FECAL TO Humans 3 to 4 months.
include:
readily destroyed by - Sore throat - Fever
- 3 Serotypes: ORAL TRANSMISSION ->
heat! - Tiredness - Nausea -
type 1,2,3. Foodborne infection through In Polio cases, infectivity in the - Pa
Headache - Stomach pain
ingestion of contaminated pharyngeal foci is around one an
(e.g. pasteurization of
foods -> Hand to mouth week - and in the intestinal foci be
milk, and chlorination These symptoms usually last 2
infection. 6 - 8 weeks. - Ev
of water). to 5 days then go away on
15
their own.

- Mo
WHO the

- Single-stranded enveloped RNA-virus
- classified as a member of the genus
Morbillivirus in the Paramyxoviridae
family
= > 1 serotype
MEASLES
Measles is one of the most contagious of - The first sign of measles is usually a high fever, which begins - Co
all infectious diseases; approximately 9 out about 10 to12 days after exposure to the virus, and lasts 4 to 7 age
of 10 susceptible persons with close contact days. A runny nose, a cough, red and watery eyes, and small infe
to a measles patient will develop measles. white spots inside the cheeks can develop in the initial stage. ear
Se
Measles is a human
The virus is transmitted by direct contact - After several days, a rash erupts, usually on the face and upper tho
with infectious droplets or by airborne disease and is not known neck. Over about 3 days, the rash spreads, eventually reaching by
spread when an infected person breathes, to occur in animals the hands and feet. The rash lasts for 5 to 6 days, and then fades.
coughs, or sneezes. - In
- On average, the rash occurs 14 days after exposure to the virus up
Measles virus can remain infectious on (within a range of 7 to 18 days). at r
surfaces and in the air for up to two hours del
after an infected person leaves an area.
CDC
Com
- Measles is a systemic infection.
lary
Even
- The primary site of infection is the respiratory epithelium of the
illne
nasopharynx. Two to three days after invasion and replication
in the respiratory epithelium and regional lymph nodes, a
One
primary viremia occurs with subsequent infection of the
enc
reticuloendothelial system.
One
- Following further viral replication in regional and distal reticulo-
resp
endothelial sites, a second viremia occurs 57 days after
initial infection. During this viremia, there may be infection of
Sub
the respiratory tract and other organs. Measles virus is shed
of th
from the nasopharynx beginning with the prodrome until 34
and
days after rash onset.
 SYMPTOMS I SYMPTOMS II DIAGNOSIS TREATMENT

ed
- A smaller proportion of people with poliovirus infection will develop other more serious symptoms that VIRUS ISOLATION: Because no cure for polio exists, the
t of
aect the brain and spinal cord: The likelihood of poliovirus isolation is focus is on increasing comfort,
e
highest from stool specimens, speeding recovery and preventing
-> Paresthesia (feeling of pins and needles in the legs) intermediate from pharyngeal swabs, and complications. Supportive treatments
h
-> Meningitis (infection of the covering of the spinal cord and/or brain) Note that "poliomyelitis" (or low from blood or spinal fluid. include:
e
occurs in about 1 out of 25 people with poliovirus infection "polio" for short) is defined
-> Paralysis (cant move parts of the body) or weakness in the arms, as the paralytic disease. So SEROLOGIC TESTING: ->Bed rest
legs, or both, occurs in about 1 out of 200 people with poliovirus infection only people with Serology may be helpful in supporting -> Pain relievers
the paralytic infection are the diagnosis of paralytic poliomyelitis. -> Portable ventilators to assist
- Paralysis is the most severe symptom associated with polio because it can lead to permanent disability considered to have the An acute serum specimen should be -> breathing
in
and death. Between 2 and 10 out of 100 people who have paralysis from poliovirus infection die disease. obtained as early in the course of disease -> Moderate exercise (physical
because the virus aects the muscles that help them breathe. as possible. therapy) to prevent deformity
st 2
- Even children who seem to fully recover can develop new muscle pain, weakness, or paralysis as adults, and loss of muscle function
15 to 40 years later. This is called post-polio syndrome. Cerebrospinal fluid (CSF) analysis -> A nutritious diet

DIAGNOSIS TREATMENT
- Most measles-related deaths are caused by complications associated with
the disease.

- Complications are more common in children under the age of 5, or adults over the
7 age of 20. The most serious complications include blindness, encephalitis (an
infection that causes brain swelling), severe diarrhoea and related dehydration,
ear-infections, or severe respiratory infections such as pneumonia.
Severe measles is more likely among poorly nourished young children, especially
r those with insucient vitamin A, or whose immune systems have been weakened
g by HIV/AIDS or other diseases.
des.
- In populations with high levels of malnutrition and a lack of adequate health care,
s up to 10% of measles cases result in death. Women infected while pregnant are also
at risk of severe complications and the pregnancy may end in miscarriage or preterm
delivery. People who recover from measles are immune for the rest of their lives.
Complications
Common complications from measles include otitis media, bronchopneumonia,
laryngotracheobronchitis, and diarrhea.
Even in previously healthy children, measles can cause serious
illness requiring hospitalization.
One out of every 1,000 measles cases will develop acute
encephalitis, which often results in permanent brain damage.
One or two out of every 1,000 children who become infected with measles will die from
-
respiratory and neurologic complications.
Healthcare providers should consider measles in patients presenting
with febrile rash illness and clinically compatible measles symptoms,
especially if the person recently traveled internationally or was exposed
No specific antiviral treatment exists for measles
to a person with febrile rash illness. Healthcare providers should report
suspected measles cases to their local health department within 24 virus.
hours.
- Severe complications from measles can be avoided
through supportive care that ensures good nutrition,
Laboratory confirmation is essential for all sporadic measles cases
adequate fluid intake and treatment of dehydration
and all outbreaks. Detection of measles-specific IgM antibody and
with WHO-recommended oral rehydration solution.
measles RNA by real-time polymerase chain reaction (RT-PCR) are the
This solution replaces fluids and other essential
most common methods for confirming measles infection.
elements that are lost through diarrhoea or vomiting.
Healthcare providers should obtain both a serum sample and a throat
Antibiotics should be prescribed to treat eye and ear
swab (or nasopharyngeal swab) from patients suspected to have
infections, and pneumonia.
measles at first contact with them. Urine samples may also contain
virus, and when feasible to do so, collecting both respiratory and urine
- All children in developing countries diagnosed with
samples can increase the likelihood of detecting measles virus.
measles should receive two doses of vitamin A suppl.
given 24 hours apart.
=> This treatment restores low vitamin A levels during
measles that occur even in well-nourished children
and can help prevent eye damage and blindness.
- Vitamin A supplements have been shown to reduce the
number of deaths from measles by 50%.

Subacute sclerosing panencephalitis (SSPE) is a rare, but fatal degenerative disease

of the central nervous system characterized by behavioral and intellectual deterioration
and seizures that generally develop 7 to 10 years after measles infection.