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LeptospirosisbyDrPreetShah.ppt
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- 2. The disease wasfirst 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 OrderSpirochaetales – 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
- 10. Leptospira under theMicroscope Electron Microscope Dark Field Microscopy FL
- 11. Leptospira visualized in Kidneytissue using silver staining techniques
- 12. Epidemiology • Rainfall; Contaminated environment •Poor Sanitation; Inadequate drainage facilities • Presence of rodents, cattle & stray dogs • Walking/ working bare foot poses high risk
- 13. Risk Groups Occupational exposure •Farmers – Rice, Sugarcane, Vegetables, Cattle, Pigs • Sewerage workers; Abattoirs, Butchers • Veterinarians, Lab staff, Miners, Soldiers • Fishermen – Inland (not on the sea) Recreational activities • Swimming, Sailing, Marathon runners, Gardening
- 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
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- 18. Pathogenesis of SevereDisease 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
- 20. Clinical Illnesses Types Anicteric(common 95% recover) Icteric ( Weil’s Syndrome) (rare, fatal) Hepato-renal syndrome Hemorrhagic syndrome with ARF Atypical pneumonia syndrome Aseptic meningo-encephalitis Myocarditis, Chronic uveitis
- 21. Clinical Presentation Anicteric Common, mild <2% Mortality Icteric Rare, Severe 15% Mortality 90% of Cases 10% of Cases
- 23. Anicteric Presentation Leptospiremic Phase(lasts 5-7 days) Fever, Myalgia Severe headache Conjunctival suffusion Abd. pain, Epistaxis Immune Phase (lasts 4-30 days) Mild fever Meningism Uveitis I.P: 5 to 14 days (range is 2-30 days)
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- 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
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- 28. Cardiac Form Cardiac manifestations •Hemorrhagic Myocarditis • Cardiomyopathy / Cardiac failure • Arrhythmias, Hypotension / Death • Atrial fibrillation / Conduction defects ECG changes • Non Specific ST-T changes • Low voltage complexes Reported in Srilanka, Barbados &
- 29. Other Manifestations Aseptic Meningo-encephalitis •It is rare; It occurs in the Immune phase • CSF – proteins , lymphocytes • Convulsions, Polyneuropathy, TM, GBS, Hemiplegia,Coma Ocular manifestations • Late complication • Anterior uveitis, Iritis, Iridocyclitis, chorioretinitis • Occurs in 2 weeks to 1 yr. (average 6 months)
- 30. Fever Influenza, Malaria, Typhus Jaundice Malaria,Viral hepatitis, Sepsis Renal Failure Malaria, Hanta virus, Sepsis Meningitis Bacterial / Viral causes Hemorrhagic Fever Dengue, Hanta virus, Typhus Differential Diagnosis
- 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 EarlyDiagnosis (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 ofTests 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
- 36. Approach to Diagnosis Clinical Features Leptospiremic phase< 7days Blood Culture PCR Immune phase > 7d ELISA MSAT Repeat MAT
- 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 MANAGEMENTOF 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 )
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- 41. POOR PROGNOSTIC FACTORS •Age > 40 yrs • Encephalopathy • ARDS • Arrhythmias • Hypotension • AKI with creatinine > 3 mg/dl
- 42. Prevention Prevention is difficultdue 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