2. 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.
During the Egyptian campaign, Napoleon's army suffered from what
was probably infectious jaundice. infectious jaundice occurred among
troops during the American Civil War 1st described by Larrey in 1912
It was also reported among troops at Gallipoli and other battles
of World War I, where the sodden conditions of trench warfare favored
infection
In October 2010 British rower Andy Holmes died after contracting
Weil's Disease. His death has raised awareness of the disease
among the public and medical professionals
3. SYNONYMS
• Mud / Swamp/ rice-field fever
• Canicola Fever
• Autumn Fever
• Japanese 7 day fever
• Spirochete Jaundice
• Black jaundice
• Fort bragg fever
• Swineherd’s Disease
• Nanukayami fever ( in japan )
• RAT-CATCHER’S YELLOWS
• PRETIBIAL FEVER
• 7- day fever
4. Overview
• Most common, underdiagnosed zoonosis
• India : cases are reported from Kerala, Tamil Nadu,
Andhra Pradesh, Karnataka, Maharashtra, Gujarat &
the Andamans.
• The principal reservoirs in our country are rats, pigs,
cattle, bandicoots, dogs and cats.
Epidemiological factors
• Contaminated environment, Rainfall
• High risk groups, endemic in all states of India
5. Overview continued
• Rural = Urban, Developed countries= Developing
countries
• Male > Female (10 : 1)
• Clinical Features –mild to severe life threatening
• Mimics many common febrile illnesses
• Diagnosis - difficult to confirm
• Treatment – effective, if started early (<5 days)
• Not to be confused with Rat-Bite fever
(Streptobacillus monilliformis)
6. LEPTOSPIROSIS IN INDIA
• Most outbreaks of leptospirosis are reported in coastal regions:
Gujarat, Mumbai, Kerala, Chennai and the Andaman Islands.
- High rates have been reported from Valsad district (Gujurat) for
several years.
- Outbreaks of ‘Andaman hemorrhagic fever’ were first reported in
1988, and identified as leptospirosis in 1993.
• Infecting serovars:
The principal strains are Leptospira interrogans serovars.
icterohaemorrhagiae, automnalis, pyrogenes, grippotyphosa,
canicola, copenhageni,etc
- A single infection by serovar javanica was reported in Madras in
1996 – the latter had previously been found only in bandicoots
(Bandikota bengalensis).
- Leptospira interrogans serovar. Valbuzzi has been identified as a
cause of hemorrhagic pneumonia in the Andaman Islands.
7. NOTABLE OUTBREAKS
• 1986 (publication year) – An outbreak of Weil’s disease was reported in a
food-fad commune.
1992 (publication year) – An outbreak (48 cases) in Madras followed a
monsoon.
1993 – An outbreak (18 cases) of leptospirosis with pulmonary involvement
was reported in north Andaman. This was the first report of pulmonary
leptospirosis in India.
1997 – An outbreak (1,127 confirmed cases) was reported in Madras –
40.2% of these Leptospira interrogans serovar. icterohaemorrhagiae,
20.0% serovar. canicola and 14.9% serovar. automnalis.
1997 – Outbreaks (562 cases, total) were reported in Valsad (281 cases, 34
fatal) and Surat (281 cases, 34 fatal).
1999 – An outbreak (143 suspect cases, 28 confirmed cases, 11 fatal) in
Orissa followed a cyclone. Serovars pomona, hebdomadis and canicola
were identified.
2000 – An outbreak (18 children) in Mumbai followed local flooding.
8. NOTABLE OUTBREAKS
(CONTD)
• 2002 – An outbreak (16 fatal cases) was reported in south Gujarat.
2002 (publication year) – An outbreak (74 cases) of Leptospira interrogans
serovar. copenhageni infection was reported in Mumbai.
2002 – An outbreak (143 cases, 11 fatal) of Leptospira interrogans serovars.
canicola, pomona and hebdomadis infection was reported in Orissa 2003 – An
outbreak (27 fatal cases and 177 under treatment) involved 131 villages in
South Gujarat.
2003 (publication year) – An outbreak was reported in a nurses’ hostel in
Chennai.
2004 – An outbreak (550 cases, 75 fatal) of suspected leptospirosis was
reported in South Gujarat.
2005 – An outbreak (100 or more fatal cases) of suspected leptospirosis
was reported in the area of Mumbai following local flooding.
2005 – An outbreak (49 cases) in Chittoor District, Andhra Pradesh was caused
by contact with stagnant water.
2006 – An outbreak (258 cases) was reported in Karnataka.
2006 – An outbreak (11 cases, 1 fatal) was reported in Kerala.
• 2015 – 53 cases reported so far in Mumbai, with 16 fatalities
9. The Causative Bacterium
Order Spirochaetales – Treponema, Borrelia, Leptospira
Family – Leptospiraceae, susceptible to heat, chlorine, acid
Species- interrogans, copenhageni, weilii, borgpetersenii,
santarosai, noguchii, etc
Genus – Leptospira, 22 species (out of which 10 are
pathogenic), 250 serovars
Corkscrew shaped, delicate, flexible spirochete
~0.1 x 6–20 microns, coiled, flagellate, actively motile around its
longitudinal axis
14. Reservoirs of Infection
• Rodents
– (Rattus rattus, Rattus norvegicus,
Mus musculus)
• Dogs
• Wild animals
• Domesticated animals
• Caged game animals
• Leptospira are excreted in the urine
15. Modes of Transmission
1. Direct contact with urine or tissue of
infected animal
Through skin abrasions, intact mucus
membrane
2. Indirect contact
Broken skin with infected soil, water
or vegetation
Ingestion of contaminated food &
water
18. Pathogenesis of Severe Disease
Leptospira
Damage to small
blood vessels
Vasculitis
Direct cytotoxic injury
Immunological injury
Massive migration of fluid from
Intravascular to interstitial compartment
Renal dysfunction, vascular
Injury to internal organs
19. New evidence suggests
• LPS maybe poorly recognised by the innate immune
system.
• TLR-4 isn’t able to bind to the leptospira LPS due to the
presence of methylated phosphate residue of its lipid-A
• Production of hemolytic toxins like sphingomyelinases,
phospholipases,or pore forming proteins cause increased
tissue damage
• HLA-DQ6 IS AN INDEPENDENT RISK FACTOR FOR
THIS DISEASE, as here, there’s production of
superantigen by the leptospira, causing non-specific T-
Cell activation.
• Also, surface lipoproteins, especially LipL32 have been
implicated in the pathogenesis of the disease, especially
tubulo-interstitial nephritis
25. Icteric Leptospirosis
KIDNEYS – Mild to Severe
Urinalysis : Hematuria / Pyuria / Proteinuria
Renal Failure: Pre renal azotemia, ATN / AIN
Oliguric / Non Oliguric
Mechanism
Nephrotoxicity – Endotoxin, (Direct )
Bacterial migration, Toxic Metabolites
Hypoperfusion – Hypotension, Fluid loss/ Fluid shift
G.I. Bleed, Myocarditis
26. Hemorrhagic Manifestations
Hemorrhagic Fever - Vascular injury
• Respiratory, Alimentary, Renal & Genital tracts
• More common in Icteric & with Renal Failure
• Reported in Korea, the Andamans & Brazil
Hemorrhagic Pneumonitis
• Hemoptysis / Respiratory failure
• CXR : Single/ Multiple ill defined opacities
• Occurs in 2nd week (as early as 24-48 hours)
• Reported in Korea, the Andamans & Nicaragua
31. Laboratory Tests
• TC / DC / ESR / Hb / Platelet count
• Serum Bilirubin / SGOT/ SGPT
• Blood Urea, Creatinine & Electrolytes
• Chest X-Ray; ECG
• Tests for diagnosis of Leptospirosis
– Culture for Leptospira: Positive
– MAT; Sero conversion or 4 fold rise/ high
titer
– ELISA / MSAT : positive
• MAT: Microscopic agglutination test
• (M)SAT: Microscopic slide agglutination Test
32. Problems in Diagnosis
Early Diagnosis (1st Week)
• No reliable test
• Delay in culture(usually get positive after 2-4 weeks, but can range
from 1 week to 6 mths)
• After isolation by culture, serovar identification is done by MLST
(Multi-Locus Sequence Typing) or MLVA (Multi-Locus Variable number
tandem repeat Analysis)
• PCR valuable but costly, and effective in acute phase, before IgM
appear
Serological Tests (2nd week)
• Use L.biflexa as source of antigen (non-pathogenic saprophytic
leptospira)
• DOES NOT DETECT SEROVAR, only etects lepto-specific antibody
• Reliable, Current infection, NEGATIVE in 1st 7-10 days
• Gold Standard, Epid studies
• Complicated, Trained personnel, advanced facilities needed for MAT
• Occur late, persist longer
Dip-Sticks (PanBio, Inc; Baltimore, Maryland)
33. Interpretation of Tests
MAT
• GOLD STANDARD
• 4-fold rise in the MAT titre between acute
and convalescent samples -> POSITIVE
• Titre of 1:200 to 1:800, alongwith
symptoms suggests recent infection
ELISA
SAT
• Valuable for Dx of current infection
• IgM antibodies alone are useful
34. Time Relationship of Tests
1 week 1 month 2 months 1 year 5 years
ELISA or SAT
MAT
35. WHO Guide - Faine’s Criteria
• Headache
2
• Fever
2
• Temp > 39 F
2
• Conjn. suffusion
4
• Meningism
4
• Muscle pain
4
• Jaundice
1
• Alb, creatinine
1
• Rain fall
5
• Contaminated
H20
4
• Animal contact
1
• ELISA IgM + ve
15
• SAT positive
15
• MAT high titer
15
• MAT rising titer
25
• Culture positive
Definite
37. TREATMENT
• Mild leptospirosis
• Doxycycline (100 mg PO bid) x 7 days or
• Amoxycillin (500 mg PO tid) x 7 days or
• Ampicillin (500 mg PO tid) x 7 days
• Moderate/severe leptospirosis
• Penicillin (1.5 million units IV or IM q6h) x 7 days or
• Ceftriaxone (1 g/d IV) x 7 days or
• Cefotaxime (1 g IV q6h) x 7 days
• IV Doxy 200 stat, then 100 mg IV bid x 7 days
• Chemoprophylaxis
• Doxycycline (200 mg PO once a week) or
• Azithromycin (250 mg PO once or twice a week)
38. Special Measures
Intensive care, monitoring of vitals
Cardiac, hepatic care
Fluid balance, look for and control bleeding
Platelets and packed cells transfusion
Renal function - dialysis
CNS complications
39. SPECIAL MENTION ON
MANAGEMENT OF ARDS
• In early ARDS, pulse therapy with methyl
prednisolone is useful
• Cyclophosphamide has been successfully
used in severe pulmonary hemorrhage
• ARDS/ pulmonary hemorrhage needs
mechanical ventilation, using low tidal
volume ( 6 ml/kg )
41. POOR PROGNOSTIC FACTORS
• Age > 40 yrs
• Encephalopathy
• ARDS
• Arrhythmias
• Hypotension
• AKI with creatinine > 3 mg/dl
42. Prevention
Prevention is difficult due to wild animal infection
Good sanitation, Immunization of live stock
Personal hygiene, PPE, Water treatment
No useful human vaccines – multiple serovars
Doxycycline 200 mg weekly for at risk groups
