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4/5/2015

Background
Most common zoonosis in the world.
Global warming: Re-emerging among animals and
humans
Distributed worldwide (sparing the Polar Regions)
Most common in the tropics.

Leptospirosis
Dr Debasis Biswas

Body fluid/ Urine


Direct Contact

Infected
Animal

24 d
Soil/ Fresh water
Urine

16 d

Indirect
Contact

Skin/ Mucosa

Wide range of animals, including mammals, birds,


amphibians, reptiles and rodents.
Rats are the most common source worldwide
Humans: accidental hosts.
Transmitted via:
Exposure of mucous membranes or abraded skin to
the body fluid of an infected animal
Exposure to soil/ fresh water contaminated with the
urine of an animal that is a chronic carrier.
Accidental
Human
Host

Occupational Risks
Occupational exposure: 30-50% of human leptospirosis.
Agricultural
Veterinarians
workers
Slaughterhouse/
abattoir workers
Milkers
Workers in the
fishing industry

Sewer workers
Plumbers
Coal miners
Military
troops

Body fluid/ Urine


Direct Contact

Infected
Animal

Soil/ Fresh water


Urine

Indirect
Contact

Skin/ Mucosa

Reservoirs & Human Transmission

Accidental
Human
Host

Non- occupational Exposure

Seasonal variation in incidence

Flooding: May lead to outbreaks


Rodent- infested housings
Recreational Exposure: Adventure travel;
Water sports;
Hiking

Leptospires survive best in:


fresh water
damp alkaline soil
vegetation
mud with temperatures higher than 22C.
Most cases occur during the rainy season in the tropics.
Flood conditions increase risk of exposure to the
population at large
Drought causes leptospire concentrations to peak in
isolated pools.

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Manifestations

Antibiotics

Acute febrile illness : 90% of cases


Nonspecific s/s: Fever, headache, nausea, vomiting
Biphasic course
Excellent prognosis.

Uncomplicated infections:
Oral doxycycline decreases duration of fever and
most symptoms.
Hospitalized patients:
IV Penicillin G: treatment of choice.

Icteric Leptospirosis/Weil disease : 10% of cases


More dramatic presentation
Fever, Jaundice, Renal failure, Hemorrhage
May also involve: Resp, CVS, CNS
Mortality rate of 10%.

Bacteria

Axial endoflagella

Spirochetes
Thin, coiled, gram-negative, aerobic: 6-20 m in length.
Motile, with hooked ends and paired axial flagella (one
on each end), enabling them to burrow into tissue.
Continual spinning motion on the long axis.
Only spirochetes to be isolated on artificial media.
Leptospira:
SEM Image

Classification
Traditionally:
Antigenic differences in the LPS envelope
2 species:
Leptospira interrogans pathogenic
218 serovars
Leptospira biflexa nonpathogenic, free-living
60 serovars.
Currently:
DNA homology
> 7 pathogenic species of leptospires.
Organisms that are identical serologically may be
different genetically, and organisms with the same
genetic makeup may differ serologically.

Animal Reservoirs

Many serovars are associated with particular animals.


Symbiotically persist in the renal tubules of animals.
Animals that serve as reservoirs of host-adapted
serovars can shed high concentrations of the organism
in their urine without showing clinical evidence of
disease .
Humans and non-adapted animals are incidental hosts.
L pomona
Cattle & Pigs
L interrogans
L grippotyphosa

Cattle, Sheep, Goats, & Voles

L ballum
L icterohaemorrhagiae

Rats & Mice

L canicola

Dogs

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Pathogenesis

Abrasions in healthy skin


Animal and rodent bites
Sodden and waterlogged skin
Mucous membranes or conjunctiva
Lungs (after inhalation of aerosolized body fluid)
The placenta during pregnancy
Body fluid/ Urine
Direct Contact

Infected
Animal

24 d
Soil/ Fresh water
Urine

16 d

Indirect
Contact

Skin/ Mucosa

Lymphatics . Bloodstream Distant Organs, esp. Liver/ Kidney


Capillary vasculitis: Endotoxin? Hemolysin? Lipase?
Endothelial edema, Necrosis, Lymphocytic infiltration
Loss of RBCs & fluid thru enlarged junctions & fenestrae
Tissue injury

Accidental
Human
Host

Pathologic effects

A b r a s i o n s i n s k i n / S o d d e n o r w a t e r l o g ge d s k i n /
A n i m a l o r R o d e n t B i t e / Mu c o u s m e m b r a n e s o r
Conju nc t i v a/ L u ngs/ Pl acent a

IP: 5-14 days


(3 days- mons.)

Infection

Shock: Capillary leakage, hypovolemia


DIC
HUS
TTP: Thrombocytopenia indicates severe disease and
should raise suspicion for a risk of bleeding.

Liver:
Centrilobular Necrosis
Kupffer Cell Proliferation
JAUNDICE

Immune Response
Opsonizing immunoglobulin: rapid immune clearance
Inflammatory reaction: secondary end-organ injury.
Persistence for weeks to months in immunologically
privileged sites:
Renal tubules, brain, and aqueous humor
Eye: Chronic or recurrent uveitis.

Diagnosis

Lab Tests

Compatible Exposure History


Compatible presentation
Treatment initiated empirically

Purposes:
To confirm the diagnosis
To determine the extent of organ involvement and
severity of complications.
Confirmation:
Isolation of the pathogen
Serology

Lab work-up:
Dark ground Microscopy : In acute cases
Culture: Long incubation; Low recovery
Serology: Microscopic agglutination testing (MAT)
Gold standard
Only at reference laboratories.

4/5/2015

Isolation

Culture Media

Gold standard.
Slow-growing: May be 8 wks
Low recovery rates
Body fluid/ Tissue
Urine: Highest sensitivity
Contains leptospires from the onset of symptoms
till the 3rd week of infection.

Rabbit Serum
Kortoffs/ Stuarts/ Fletchers Media
Semisynthetic: EMJH

Other body fluids contain the organism, but the


window of opportunity to isolate them is shorter.
Blood & CSF: Initial 7-10 days of symptoms.
Viability in anti-coagulated blood: 11 days
Specimens can be transported to a reference laboratory
for culture.

Serology
Paired acute and convalescent sera
Acute sera: 1-2 weeks after onset of symptoms
Convalescent sera: After 2 weeks
Delayed diagnosis
Microscopic agglutination test (MAT)
Gold standard for serodiagnosis
Only in specialized reference labs
Panel of live leptospira belonging to different serovars
Panel to represent circulating serovars in a geographic
area
A 4-fold rise in MAT titer between acute and
convalescent sera with any of these antigens confirms
the diagnosis of leptospirosis.

MAT

MAT

Dilution series of the patient's serum in microtiter plates


Mixed with a suspension of live leptospires
Incubating: 2 hrs at 30C
Results read under the dark-field microscope
Titer: last dilution in which 50% of leptospires agglutinate
Seroconversion or 4-fold titer rise in paired sera
The significance of single titer:
Frequency of residual titers due to past infections
Other Cross-reacting pathogens in the population

A single MAT titer of 1:800 on any sera + appropriate


clinical scenario: Strongly suggestive.

Severity Assessment

Complete blood cell count (CBC)


Mild disease:
Elevated ESR; Leukocytosis with a left shift
Significant anemia: Pulmonary & GI hemorrhage
Thrombocytopenia: as a component of DIC
Coagulation profile deranged: Liver inv/ DIC
Profoundly Elevated BUN & Ser Creatinine
Elevated Serum CK levels (MM fraction): muscular
involvement.
LFT:
Elevated Bilirubin levels: capillaritis in liver.
Alkaline phosphatase: May be elevated 10-fold.
Transaminases: usually < 200 U/L
Jaundice and bilirubinemia disproportional to
hepatocellular damage

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Severity Assessment

Microscopic Agglutination Testing

Urinalysis: Proteinuria
RBCs, WBCs, Hyaline and granular casts

Ab response : After 2nd week of illness


Can be affected by t/t

CSF Analysis: To exclude other causes of bacterial


meningitis.
PMNs initially predominate
Later replaced by monocytes.
Protein: Normal or elevated
Glucose: Normal
Pressure: Normal

False-negative MAT: Testing a single specimen obtained


before the immune phase of disease.
False-positive MAT: Legionella infection, Lyme disease,
and syphilis.

IgM ELISA

PCR

Positive within 3-5 days of disease


Positive results should be confirmed by MAT

Can be +ve before Ab titers are detectable.


Need further standardization
Unable to identify serovar

Histologic Findings
Silver staining & Immunofluorescence
Can identify leptospires in the liver, spleen, kidney,
CNS, muscles, and heart.
During the acute phase of leptospirosis, histology
reveals these organisms without much inflammatory
infiltrate.

Silver stain of liver