LEPTOSPIROSIS

an update
Dr.T.V.Rao MD

11/27/2010 Dr.T.V.Rao MD 1
 Leptospirosis

Leptospirosis [lep-to-spy-RO-sis].

What is Leptospirosis?

•Leptospirosis is a potentially serious illness that can effect many

parts of the Body.

•Leptospirosis is commonly caused by Leptospira interrogans, a

corkscrew-shaped bacterium (spirochete).

11/27/2010 Dr.T.V.Rao MD 2
 What is Leptospirosis?
• Leptospirosis, also known as canicola fever,
hemorrhagic jaundice, infectious jaundice, mud
fever, spirochetal jaundice, swamp fever,
swineherd's disease, caver's flu or sewerman's
flu, is a bacterial infection resulting from
exposure to the Leptospira interrogans
bacterium.
•
There is an acute form of human infection known
as Weil's disease, where the patient suffers from
jaundice, though this term is often (incorrectly)
used to describe any case of infection..

11/27/2010 Dr.T.V.Rao MD 3
 CDC Definition of Leptospirosis
Clinical description
• An illness characterized by
fever, headache, chills,
myalgia, conjunctival
suffusion, and less
frequently by meningitis,
rash, jaundice, or renal
insufficiency. Symptoms
may be biphasic.

11/27/2010 Dr.T.V.Rao MD 4
 Leptospirosis is still less understood
Disease
• Leptospirosis is a zoonotic disease that has
emerged as an important cause of morbidity and
mortality among impoverished populations. One
hundred years after the discovery of the causative
spirochaetal agent, little is understood about
Leptospira spp. pathogenesis, which in turn has
hampered the development of new intervention
strategies to address this neglected disease

11/27/2010 Dr.T.V.Rao MD 5
 Epidemiology
• In 1886, Weil, a German
doctor observed 4 cases of
Leptospirosis with jaundice,
than this disease is called as
Weil disease
• In China: in 1937, Professor
Tang zeguang discovered
Leptospirosis in Guangzhou
 Early History
• The disease was first described by Adolf Weil in
1886 when he reported an "acute infectious
disease with enlargement of spleen, jaundice and
nephritis". Leptospira was first observed in 1907
from a post mortem renal tissue slice. In 1908,
Inada and Ito first identified it as the causative
organism and in 1916 noted its presence in rats.

11/27/2010 Dr.T.V.Rao MD 7
 Leptospirosis - Zoonosis
• Leptospirosis is an acute anthropo-zoonotic
infection of worldwide significance caused by
spirochete Leptospira interrogans which has 23
serogroups and >200 serovars. Various factors
influencing the animal activity, suitability of the
environment for the survival of the organism and
behavioural and occupational habits of human
beings can be the determinants of incidence and
prevalence of the disease.
11/27/2010 Dr.T.V.Rao MD 8
 Leptospirosis – A Major Zoonotic Infection

• Weil's disease is comparatively rare, though 'mild'

cases of Leptospirosis happen everywhere there
are carriers, and it is believed that Leptospirosis is
one of the most common zoonotic infections in
the world. Millions of people are infected each
year, but information and treatment can be
limited, especially in the developed world where
cases are considered 'rare' by the medical
community.

11/27/2010 Dr.T.V.Rao MD 9
 Leptospirosis can be a Serious Health
Problem
• Leptospirosis, an infectious disease with a wide
global distribution, has been by and large
neglected as a serious health problem till recently.
The increasing reports of outbreaks and clusters of
cases, particularly from Southeast Asia and North
and Central American countries, has brought
attention to the public health problem posed by
this spirocheatal infection

11/27/2010 Dr.T.V.Rao MD 10
 INDIA
• The first of its kind in India was reported in the 1920s from
Andaman and Nicobar Islands.
• In 1993, a serosurvey of conservancy workers in Madras
(using MAT) revealed a prevalence rate of 32.9%.
• In 1994, an increase in the number of individuals with uveitis
was noted at Aravind Eye hospital, Madurai, India after an
epidemic of leptospirosis in South India; the epidemic
followed severe flooding of the Tamil Nadu District in the
autumn of 1993
• In 1995, a seroprevalence rate of 12% leptospirosis was found
among febrile and jaundice patients in Pondicherry
 Major reports on Leptospirosis
India
• The first of its kind in India was reported in the 1920s from
Andaman and Nicobar Islands.
• In 1993, a serosurvey of conservancy workers in Madras (using
MAT) revealed a prevalence rate of 32.9%.
• In 1994, an increase in the number of individuals with uveitis
was noted at Aravind Eye hospital, Madurai, India after an
epidemic of leptospirosis in South India; the epidemic followed
severe flooding of the Tamil Nadu District in the autumn of
1993
• In 1995, a seroprevalence rate of 12% leptospirosis was found
among febrile and jaundice patients in Pondicherry

11/27/2010 Dr.T.V.Rao MD 12
 Animals spread Leptospirosis

Rats, Mice, Wild Rodents,

Dogs, Swine, Cattle are
principle source of
infection
The above animals excrete
Leptospira both in active
infection and
Asymptomatic stage
The Leptospira survive and
remain viable for several
weeks in stagnant water.

11/27/2010 Dr.T.V.Rao MD 13
 Leptospirosis
Reservoir (Maintenance Host)
• Cattle
• Cats (rare)
• Dogs
• Horses
• Pigs
• Rodents
• Wildlife (opossum, raccoons, skunks and many
other species)

11/27/2010 Dr.T.V.Rao MD 14
 What causes Leptospirosis
• Leptospirosis is a bacterial
disease that affects humans
and animals. Leptospira
bacteria are found worldwide
and there are many different
types or serovars capable of
causing disease. Disease
caused by Leptospira bacteria
is most common in temperate
or tropical climates and
appears to be rare in North
America.

11/27/2010 Dr.T.V.Rao MD 15
 Pathogenic strains x Non pathogenic
Leptospirosis
• There are several species of Leptospira only few are
pathogenic to Humans, rest to some Animals and Many in
Nature as saprophytes
• Leptospira Interrogans is Pathogenic there are 200
serovars.
• Leptospira biflexa Non Pathogenic there are 60 serovars
• Further classifications are made on shared antigens

11/27/2010 Dr.T.V.Rao MD 16
 Morphology
• The Leptospira appear tightly
coiled thin flexible Spirochetes
5 – 15 microns long.
• Fine spiral of 0.1 – 0.2 microns
• One end appears bent forms a
hook.
• Actively motile
• Can be Seen with dark field
Microscopy.

11/27/2010 Dr.T.V.Rao MD 17
Important species in Leptospirosis
• The genera Leptospira contains three species,
namely L interrogans, L biflexa and L parva. The first
includes 23 serogroups and more than 250 serovars
and is the principal cause of leptospirosis in humans
and animals. most common being L. canicola, L.
hardjo and L. hebdomadis.
• Two types of leptospirosis:
1. Anicteric leptospirosis or self-limited illness (85% to 90% of
the cases)
2. Icteric leptospirosisor weil’s syndrome (5% to 10)
 Antigenic structure
• All isolates of L.inttterogans from different parts of the
world are serologically related and exhibit cross reactions
in serologic tests.
• Overlapping of Antigens do occur in different species.
• Outer envelop contains large amount of
Lipopolysaccharides ( LPS )
• Antigenic structure varies from one strain to other
• This variation forms the basis of serologic classification

11/27/2010 Dr.T.V.Rao MD 19
 Genome of Leptospira
• L. interrogans serogroup Icterhaemorrhagiae consists of a
4.33 megabase large chromosome and a 359 kilo base
small chromosome, totalling 4,768 predicted genes. A
series of genes have been discovered that could
potentially be related to adhesion. This genome differs
from the two other pathogenic spirochete (Treponema
palladium and Borrelia burgdorferi), though some similar
genes are visible (CHGC, 2004).

11/27/2010 Dr.T.V.Rao MD 20
 Epidemiology - Occupation

Certain occupational
groups such as
agriculture workers in
rice and cane fields,
miners and sever
cleaners are potential
victims
 Pathogenesis

Skin,mucous membranes leptospira

Blood stream leptospiramia Type of Influenza-

typhoid fever
Hemorrhagic
pneumonitis Pulmonary
Hemorrhage
Hepatitis
ieterohemorrhage
Organs
Interstitial
nephritis Renal failure

Meningitis and
Encephalitis Meningoencephalitis
 Leptospirosis
Pathogenesis
• Leptospires penetrate mucous membranes or abraded skin and
multiply rapidly upon entering the blood stream.
• They spread to the kidney, liver, spleen, central nervous system,
eyes and genital tract.
• Initial antibody response clears most organs except the kidneys
where the infection can remain and be shed for weeks to months.
• Leptospirosis causes a severe vasculitis with endothelial damage.
Kidney damage, shock, heart damage with arrhythmias. Liver
damage with icterus and low vit k levels
• Eye disease-Uveitis*

11/27/2010 Dr.T.V.Rao MD 23
 Pathogenesis
• Leptospira are present in the water bodies
• Enter through breaks in the skin ( cuts and abrasions) and
mucous membranes
• Enters through Mouth – Nose – Conjunctive
• Rarely enters though ingestion.
• Incubation period 1 – 2 weeks
• When multiples blood stream produces fever.
• May establish organ involvement in Kidney and Liver,
• May produce hemorrhage and necrosis in the tissues and
initiates dysfunction of these organs

11/27/2010 Dr.T.V.Rao MD 24
 Pathology
• The basic pathological finding is infectious-
infectious-toxic lesion of the
systemic capillary
• In some cases severe damage can be seen in the organs and
tissues
– Liver: cellular infiltration around the portal area
– Kidney: Interstitial nephritis
– Lung: pulmonary congestion and hemorrhage
– Brain: perivascular cuffing
11/27/2010 Dr.T.V.Rao MD 26
11/27/2010 Dr.T.V.Rao MD 27
 LEPTOSPIROSIS
• Clinical features

– incubation period: 7-14 days

– biphasic
– commonly involves CNS, kidneys, and liver
– often misdiagnosed as hepatitis or meningitis
– petechial rash, morbilliform or urticarial in appearance
- in 10-30%of cases within first 2 days, sometimes
pruritic
 LEPTOSPIROSIS
• Clinical features

– acute leptospiremia phase

• abrupt onset of fever
• severe headache
• muscle pain
• nausea
• jaundice in more severe cases
• symptoms persist for up to 7 days
 Incubation period:
Biphasic illness.
2 to 20 days (~ 10).
• Fever, chills and rigors. • Coincides with appearance of
antibodies.
• Myalgia (calf & lumbar0 • Aseptic meningitis.
• Conjunctival suffusion. • Rash and uveitis..
• Haemorrhagic pneumonitis.
• GI symptoms.
• Hepato renal damage.
• Lymphadenitis, • Death due to MOF / pulm hge.
hepatosplenomegaly.
• Leptospires isolated in urine/aqueous
• Leptospires isolated in blood/CSF. humor/kidney.
• Aseptic meningitis –
• Aseptic meningitis – retro-orbital headache/vomiting.
headache and photophobia. • CSF – lymphocytic pleocytosis
• CSF –neutrophilic pleocytosis • Lepto PCR negative.

• Lepto PCR positive.

11/27/2010 Dr.T.V.Rao MD 30
 Clinical Manifestations
Type of Influenza-typhoid fever

3 Symptoms:
Chills and Fever
Myalgia
Fatigue 3 signs:
Conjunctival suffusion
Calf muscle tenderness
Enlargement of lymph nodes
。
 May present with

• Jaundice
• Hemorrhage
• Nitrogen retention
• The Illness is Biphasic with initial temperature when the
second phase comes with raise of IgM titers raise
• Aseptic meningitis – initial headache, stiffness of neck,
pleocytosis of Cerebro spinal fluid

11/27/2010 Dr.T.V.Rao MD 32
 Clinical Manifestations
• Complicated clinical manifestations
• One serotype can result in many kinds of clinical
manifestations
• One clinical type can be caused by many
serotypes
• Clinical manifestations vary greatly in different
patients
• Incubation period: 7-13 days(2-28d)
Weil’s syndrome is said to be present
when the following clinical feature are
present:
• Altered sensorium
• Acute renal failure
• Myocarditis and
hypotension
• Pulmonary hemorrhage
• Features of acute hepatic
failure
 Weil’s Syndrome
• Weil's syndrome is a severe form of Leptospirosis that
causes a continuous fever, stupor, and a reduction in the
blood's ability to clot, which leads to bleeding within
tissues. Blood tests reveal anaemia. By the third to sixth
day, signs of kidney damage and liver injury appear.
Kidney abnormalities may cause blood in the urine and
painful urination. Liver injury tends to be mild and usually
heals completely.

11/27/2010 Dr.T.V.Rao MD 35
 Hepatitis - Leptospirosis
• Hepatitis is the frequent
complication
• Elevation of serum
creatine phosphilipae
enzyme raise
differentiates from Viral
hepatitis where the
enzyme is not raised

11/27/2010 Dr.T.V.Rao MD 36
 Renal manifestations
• Some form of renal
involvement is invariable in
Leptospirosis. It usually
occurs as asymptomatic
urinary abnormality in the
form of mild proteinuria
with few casts & cells in the
urine. Severe renal
involvement in the form of
acute renal failure, (which
occurs in icteric
Leptospirosis) is rare.

11/27/2010 Dr.T.V.Rao MD 37
 Nephritis - Leptospirosis
• Kidney involvement in animals
produce chronic disease of the
kidney and the infected animal
starts shedding large number
of Leptospira and main source
of environmental
contamination of bacteria and
results I human infections
• Human urine also contain
Spirochetes in the second and
third week of infection

11/27/2010 Dr.T.V.Rao MD 38
 Presenting with Jaundice is significant and
Important, Serious Manifestation

11/27/2010 Dr.T.V.Rao MD 39
 May present with Major Complications

• Nephritis
• Hepatitis.
• Manifestations in eye
• Muscular lesions
• Many infections are mild
and subclinical

11/27/2010 Dr.T.V.Rao MD 40
 Ocular manifestations
• Conjunctival suffusion /
hemorrhage
• Late complication
• Anterior uveal tract
inflammation
• Iritis / Iridocyclitis /
chorioretinitis occurs 2
weeks – 1 yr (6 months)

11/27/2010 Dr.T.V.Rao MD 41
 Pulmonary manifestations
• Manifested in most cases
through cough &
• chest pain and in few
cases by hemoptysis.
Severe involvement
leading to
• respiratory failure does
not occur in anicteric
leptospirosis

11/27/2010 Dr.T.V.Rao MD 42
 Clinical Manifestations
Type of pulmonary hemorrhage

1 Type of mild hemorrhage

♦ Cough and hemoptysis
♦ A little bit of moist rale can be heard
♦ Dot
Dot--like or small nodular densities in chest X
X--ray
♦ Prognosis is fine if treatment is given in time
 COMPLICATIONS can be Life Threat

• Azotemia
• Oliguria
• Hemorrhage
• Purpura
• Hemolysis
• Gastrointestinal bleeding
• Hypoprothrombinemia and Thrombocytopenia
 Differential Diagnosis
• Influenza
• Meningitis (encephalitis)
• Viral hepatitis
• Rickettsiosis
• Typhoid fever
• Septicemia
• Toxoplasmosis
• Legionnaire’s disease
• If with jaundice during or after an acute febrile illness,
• Malaria,septicemia, alcoholic hepatitis and typhoid fever
 Leptospirosis
High Risk Situations.
High Risk Situations.
• Swimming and scuba diving.
• Kayaking and canoeing.
• Sailing, windsurfing, fishing and skiing.
• Caving and underground exploration.
• Cleaning and jetting operations.
• Animal handling, control and management.

11/27/2010 Dr.T.V.Rao MD 46
 Medical professional’s Guidance
Leptospirosis
• The infection is extremely easy to miss in initial stages;
often the symptoms are misdiagnosed as influenza, viral
illness or Pyrexia of unknown origin.

• Patients often ignore the significance of their symptoms

unless prior education.

• To allow for correct diagnosis the patient must inform of

having any potential or prior contact with affected areas.
 Other Facts on
Leptospirosis
• An infection from one strain will provide immunity but
only to that strain.

• Exposure to other strains will still cause infection. It is

usual for more than one strain to exist within a specific
population of infected animals.

• Immunity to one type is no great advantage to reducing

your risk
 Laboratory Diagnosis
Specimens
1 Blood to be collected in
a heparin tube
2 CSF, Tissues
Microscopic
examination
3 Urine to be collected
with great care to
avoid contamination
4 Serum for agglutination
tests

11/27/2010 Dr.T.V.Rao MD 49
 Laboratory Diagnosis
• Laboratory diagnostic tests are broadly divided
into two categories via, direct evidences (isolation
of organism or demonstration of leptospires or
amplification of specific fragment of leptospiral
DNA) and indirect evidences (detection of
antibodies to leptospires).

11/27/2010 Dr.T.V.Rao MD 50
 Laboratory Diagnosis
• Alternatively, the
different methods
used in the
laboratory can be
categorized into
bacteriological,
microscopic,
immunological/serological
and molecular techniques.

11/27/2010 Dr.T.V.Rao MD 51
 Diagnosis
• Direct visualization of leptospires in blood (early phase) or
urine (late phase) by dark field microscopic examination
– Low sensitivity (40.2%) and specificity (61.5%)
– Need special media (Fletcher's, Ellinghausen's, polysorbate 80)
– Takes 2-3 weeks to be positive
• IgM antibodies appear in late phase (5-7 days)
– Microscopic agglutination test (MAT), ELISA
– Titer >1:100 helps, but fourfold rise in titer is diagnostic (need
convalescent sample)
 Microscopic Agglutination test
• Serial dilutions of patients sera are reacted with live suspensions
of leptospiral serovars
• The MAT is ready by dark- field microscopy
• Tightly agglutinated clumps of leptospires are seen in cases of
positive sera
• The end point is the highest dilution of serum at which 50%
agglutination occurs
• The end point is determined by presence of approximately 50%
free, unagglutinated leptospires compared to the control
suspension
• Considerable effort is required to reduce the subjective effect of
observer variation, even within laboratories.

11/27/2010 Dr.T.V.Rao MD 53
 Microscopic Agglutination Test
MAT
• The MAT is a complex test to control, perform and
interpret.
• Live cultures of all serovars required to be tested have
to be maintained
• The range of antigens used should include all locally
common serovars
• Cut-off depends on prevalence of antibodies in the
population
• Paired sera (at 2 weeks interval) are required to
confirm a diagnosis with certainty

11/27/2010 Dr.T.V.Rao MD 54
 Serological tests
MAT
• Microscopic agglutination
test (MAT) is the benchmark
test for serodiagnosis of
leptospirosis. It is complex
and time consuming. But it
is an invaluable tool not only
for diagnosis, but for
epidemiology and
serological characterization
of leptospiral isolates.

11/27/2010 Dr.T.V.Rao MD 55
 Culturing of Leptospira
• Leptospira grows best
under aerobic conditions
at 280 to 300c best
demonstrated in
Semisolid agar media
• Optimal Media
Fletchers Media
Stuarts Media
Optimal growth after 1 – 2
weeks
11/27/2010 Dr.T.V.Rao MD 56
 IgM ELISA
• Use broadly reacting antigen
• Serogroup cannot be identified
• Positive earlier than MAT
• Ready made reagents with
long shelf-life
• Need ELISA reader and washer.
• Many commercial kits are now
available to detect IgM
antibodies by plate ELISA e,g.
Serion classic, Panbio

11/27/2010 Dr.T.V.Rao MD 57
Early and Prompt Diagnosis is Highly Essential

• The development of
simpler, rapid assays for
diagnosis has been based
largely on the recognition
that early initiation of
antibiotic therapy is
important in acute disease
but also on the need for
assays which can be used
more widely.

11/27/2010 Dr.T.V.Rao MD 58
 Monitoring of the following laboratory
parameters is essential:
• WBC and platelet counts
• Blood urea and serum
creatinine
• Serum electrolytes
• Electrocardiogram for
Myocarditis
• Serum Amylase for
pancreatitis
 Emerging Trends in Molecular
Diagnostic Methods
• Several PCR-based DNA fingerprinting methods have
become popular and are being used routinely for
characterization of leptospires. Random amplified
polymorphic DNA (RAPD) fingerprinting, arbitrarily
primed PCR (APPCR), single nucleotide polymorphism
of specific PCR products are some of the examples.
REP-PCR (repetitive extragenic PCR) and FAFLP
(fluorescent amplified fragment length
polymorphism) are recent methods in the
characterization of leptospires.

11/27/2010 Dr.T.V.Rao MD 60
 Epidemiology

• Leptospirosis causes several animal infections

• Most wide spread zoonotic infection in Nature
• Human infections are accidental associated with
contamination of water, other materials contaminated
with excreta and animal flesh.
• Animal carriers often excrete up to 100million
Leptospirosis per ml of urine
 Leptospirosis
Epidemiology
• Leptospires are transmitted to incidental hosts by
direct and indirect contact.
• Direct contact (host to host) is via urine, body
secretions, Tran placental and thru the milk.
• Indirect contact (via urine) in water, on bedding or
environmental contaminated products

11/27/2010 Dr.T.V.Rao MD 62
 How Man gets Infected
• Water the great source
Drinking
Swimming
Bathing, as the urine of
Rodents chronically infected
contaminate water sources

Children get infected when in

contact with infected Dogs

11/27/2010 Dr.T.V.Rao MD 63
 Control of Leptospirosis

• Rodent control is most

important.
• Human’s should avoid
contact with water
contaminated with animal
contact.

11/27/2010 Dr.T.V.Rao MD 64
Injection Crystalline penicillin is the drug of
choice in treating weil’s disease because
A. It is a leptospiral disease
B. Organism is uniformly
sensitive to penicillin
C. No resistance against
penicillin is reported so far
D. It is mostly without any
undesirable side effects
E. Earlier the treatment
started, better is the
outcome
 Medications that may be routinely
prescribed in uncomplicated weils :
• Acetaminophen 650 mg
orally SOS
• Doxycycline 100mg twice
daily orally for seven days
OR
• Tetracycline 500mg 6
hourly OR
• Ciprofloxacin 500mg BID
• Frusemide 40mg IV q
12hrly in case of impending
renal failure

11/27/2010 Dr.T.V.Rao MD 66
 Chemoprophylaxis

Doxycycline 200 mg
orally once a week is
simple effective
measure. When heavy
exposure is anticipated

11/27/2010 Dr.T.V.Rao MD 67
 Leptospirosis
Prevention
• Elimination of carrier
• Vaccination for dogs
• Protection is serovar-specific
– Current vaccination is for 3 sero types and is
considered very effective
– Past vaccination was for 2 sero types which are no
longer as important. The past vaccine was not as pure
as current vaccines and was commonly associated with
vaccine allergic reactions….
 Prevention
• Rodent control measures
• Immunization of animals with killed vaccines
short-lived, requires boosters
• Protective clothing, footwear
• Burning canefield prior to harvest (young shoots
can cut hands)
• Doxycycline prophylaxis for high-risk workers
(Takafugi ET, NEJM 1984)
 The following statements regarding
prognosis of Weil’s disease are true:
• Temperature falls by lysis
within 3-4 days of
treatment
• Temperature may rise
again in the anicteric form
• Admission to MICU and close
observation are mandatory
• If untreated mortality in weil’s
syndrome is 15-20%
• Those who recover do so with
residual complications
Medical professional’s should be cautious
Leptospirosis

• “The infection may progress rapidly to fatal

septicemic multisystemic failure or remain as a
barely detectable subclinical illness. There is no
reliable method to identify the final route of the
infection from the initial stage of the disease,
and all cases must be treated as potentially life-
threatening.”
 New Vaccine trails - Leptospira

11/27/2010 Dr.T.V.Rao MD 72
 ICMR contributes to Knowledge on
Leptospirosis
• The Regional Medical Research Centre (ICMR),
Port Blair is the National Leptospirosis Reference
Centre of India and WHO Collaborating Centre for
Diagnosis, Research, Reference and Training in
Leptospirosis. It maintains one of the largest
Leptospira repositories in the world and is the only
facility in India for serological and genetic typing of
Leptospira.

11/27/2010 Dr.T.V.Rao MD 73
 Programme created by Dr.T.V.Rao MD for
benefit of Medical and Paramedical Professionals ,
and Students
Email
doctortvrao@gmail.com

11/27/2010 Dr.T.V.Rao MD 74