Leptospirosis

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Pathophysiology, clinical and lab features, management of leptospirosis

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Leptospirosis

  1. 1. Leptospirosis DR. ANKIT RAIYANI LTMGH
  2. 2. Introduction Most common, underreported and under diagnosed zoonosis. India - Cases reported from Maharashtra, Gujarat , Kerala, Tamil Nadu, Karnataka, Andaman. Source –Animals ( rodents and domestic animals) or an environment contaminated by their urine Causative org. can survive for months in water & damp soil
  3. 3. Organism Order-Spirochaetales Family-Leptospiraceae Genus-Leptospira Species-17(11 pathogenic-L. interrogans sensu lato) & (6 non-pathogenic-L. biflexa sensu lato) Pathogenic leptospira divided into ›26 serogroups & ›250 serovars. Leptospires are coiled thin highly motile organisms, 6- 20µm long and ~0.1µm wide, obligate aerobes Stain poorly… but seen by dark-field microscopy & by silver impregnation tech. Culture media- EMJH, Fletcher, Korthof
  4. 4. Leptospira interrogansL. Interrogans scanning electron microscope L. Interrogans Silver impregnation L. Interrogans Dark-field microscopy
  5. 5. Epidemiology Etiology: L interrogans Most widespread zoonosis in the world Peak incidence during rainy season Occupational & recreational exposures Source of infection in humans: direct or indirect contact with the urine of an infected animal Portal of entry: abrasions or cuts on skin, conjunctiva & other mucous membranes. Inc. period: 2-30 days(commonly 5-14 days)
  6. 6. Epidemiology Rainfall Contaminated environment Poor Sanitation Inadequate drainage facilities Presence of Rodents, cattle& stray dogs Walking bare foot Specific source of infection cannot be pinpointed with certainty. Males>Females… more chance of exposure
  7. 7. Transmission Rodents (Urine) HumansDomestic Contaminated animals environment
  8. 8. PATHOGENESIS Pathogenesis not completely understood1. Leptospiremia...multiplication in blood, tissues.2. Vasculitis– responsible for most of the manifestations… LOS TNF-α3. Kidneys- interstitial nephritis, tubular injury4. Liver- centrilobular necrosis(usually not extensive)5. Lungs- involvement due to hemorrhage, not to inflammation6. Microcirculation damage, increased vascular permeability….hypovolemia7. Skeletal muscles-necrosis
  9. 9. Clinical Features Biphasic clinical presentation  Acute or bacteremic phase lasting ~1 week  Immune phase, characterized by antibody production and leptospiruria Anicteric Leptospirosis  Abrupt onset of fever, chills, headache, myalgia, abdominal pain, conjunctival suffusion, transient skin rash, Aseptic Meningoencephalitis Icteric Leptospirosis (Weil’s disease) 5-10%  Occurs in 5-15% of patients  Jaundice, Proteinuria, hematuria, oliguria and/or anuria  Pulmonary hemorrhages, ARDS  Myocarditis  Aseptic Meningoencephalitis
  10. 10. Icteric Leptospirosis- LIVER Jaundice -Occurs 4-6 days (2 - 9 days) Sr.Bilirubin –Markedly increased- (20-40 mg/dl) Conjugated bilirubin rise SGOT / SGPT -Mild elevation ALP- moderately elevated Hepatocellular necrosis / Intra hepatic cholestasis Death - Not due to Liver Disease…if no predisposing factors present
  11. 11. Icteric Leptospirosis- G. I. tract Massive spontaneous G. I. bleeding(major cause of death) Pancreatitis Severe abdominal wall tenderness mimicking acute abdomen
  12. 12. Icteric Leptospirosis- Lungs Frequently involved with varying severity Cough, dyspnoea, chest pain, blood stained sputum, hemoptysis Severe pulmonary hemorrhage causing Acute Respiratory Distress Syndrome May cause diffuse or focal interstitial pneumonitis and pneumonia CXR- lesions seen are more extensive than clinical findings, develop ›3-9 days
  13. 13. Microscopy
  14. 14. Hematological disturbances Severe thrombocytopenia…bleeding Anemia- d/t bloodloss, &/or hemolysis Petechiae, purpura, ecchymoses common PT & PTTK time may be normal to moderately elevated…can be corrected with Vit K supplementation. D.I.C.-rare as compared to Gm(-) sepsis Jarisch-Herxheimer reaction- rare
  15. 15. Icteric Leptospirosis- Kidneys Invariably involved --Mild to Severe Urinalysis : Hematuria / Pyuria /Proteinuria Renal Failure: initially non-oliguric with K+ wasting….may become oliguric Prerenal ATN Hypotension Endotoxins Fluid loss/ Fluid shift Toxic Metabolites Myocarditis
  16. 16. Icteric Leptospirosis- HeartHemorrhagic Myocarditis- Arrhythmias,Cardiac failure, Hypotension / DeathArrhythmias- Atrial fibrillation / Conductiondefects (seen in 20-40%)ECG changes- Non Specific ST-T changes, Lowvoltage complexes
  17. 17. Icteric Leptospirosis- CNS Aseptic MeningoEncephalitis- Occurs in the Immune phase CSF – raised proteins , - lymphocytes Rare- Convulsions, Encephalitis Myelitis & Polyneuropathy.
  18. 18. Other manifestations Skeletal Ms involvement- myalgia, raised CPK levels Conjunctival suffusion (pathognomic) Anterior uveal tract inflammation Iritis / Iridocyclitis / chorioretinitis Occurs 2 weeks – 1 yr (6 months)
  19. 19. Modified Faine’s criteria
  20. 20. Diff. Diagnosis Fever-Viral fever/Malaria/Typhoid / UTI Jaundice-Malaria, Viral hepatitis, Sepsis Renal failure-Malaria, Hanta Virus, Sepsis Meningitis-Bacterial / Viral Hemorrhagic Fever-Dengue, Hanta virus, Typhus
  21. 21. Investigations- Routine CBC- low Hb, thrombocytopenia, leucocytosis LFTs- conjugated bilirubinemia, raised ALP, mild elevation of AST/ALT RFTs- raised BUN/Creat…Ratio SE- hypokalemia, hypocalcemia, hypomagnesaemia CPK- elevated PT/PTTK-mild elevation Pl. fibrinogen- normal Urine(R/M)- active sediments, proteinuria, hematuria, Hb/Mb-uria. ECG- conduction defects, non-specific ST changes
  22. 22. Chest radiograph Three radiographic patterns:1.small nodular densities (50-60%);2.confluent areas of consolidation (10-20%); and3.diffuse, ill-defined, ground-glass density (20- 30%). Serial radiographs may show a tendency for the nodular pattern to be followed by confluent consolidation and/or ground-glass density. Abnormalities are bilateral, non-lobar in all cases, and have a marked tendency toward peripheral predominance
  23. 23. Chest radiograph Pulmonary hemorrhage in Leptospirosis
  24. 24. Specific investigations Dark-field microscopy –blood, CSF, urine(Low Sensitivity & Specificity) Culture- blood, CSF, urine…takes up to 4 weeks for diagnosis Serological tests- MAT, ELISA Rapid tests- latex agglutination, ELISA Polymerase Chain Reaction Test
  25. 25. Microscopic Agglutination Test(MAT) Gold Standard, Complicated Titres rise late, but persist longer Valuable in epidemiologic studies Less sensitive for current diagnosis Positive- Seroconversion / 4 fold rise in the titre, High titre(>1:100). Will stay positive for long time after recovery
  26. 26. IgM ELISA and other rapidTests Useful for providing presumptive diagnosis in current infection Sensitivity is low- 39-72% during acute phase illness Repeat sample after 3-4 days.
  27. 27. Polymerase Chain Reaction Test Highly valuable during acute illness(<7 days) Sensitivity decreases as bacteria is cleared from blood Can detect even <10 bacteria in any given sample Primers should cover all prevalent species in given area Recent data - urine sample has more sensitivity then blood sample after 7 days Use limited by less availability
  28. 28. Approach to Diagnosis Clinical features suggestive of current leptospirosisLeptospiremic phase < Immune phase > 7 days 7days Blood culture ELISA / Rapid IgM PCR Positive Negative MAT(if Repeat >3-4 available) days
  29. 29. Biphasic nature of leptospirosis and relevant investigationsat different stages of disease Clin Microbiol Rev. 2001 Apr;14(2):296-326
  30. 30. Management(severeleptospirosis) Prompt triage of high-risk patients and early supportive treatment General management and supportive therapy Specific treatment of various organ system failure  Hemat  RS  Renal  Liver
  31. 31. Contd…Antibiotic therapy  Shortens fever clearance time, leptospiruria  mortalityAntibiotic regimes  Inj. Penicillin G 1.5 million U Q6H (iv) x 7 days(used to be DOC)  Inj. Ceftriaxone 1 Gm OD (iv) x 7 days  Inj. Cefotaxime 1 Gm Q6H (iv) x 7 days  Other agents- Macrolides, fluoroquinolones
  32. 32. Mild Leptospirosis Doxycycline 100 mg BD (po) x 7 days Amoxicillin 500 mg qid (po) x 7days
  33. 33. Prognosis Mortality is high in patients with severe disease Weil’s disease- 5 to 40% Severe pulmonary hemorrhage-> 50% Poor prognostic indicators- age>40 yrs, oliguria, respiratory distress, pulmonary hemorrhage, arrhythmias, altered sensorium, alcoholic patients
  34. 34. Prevention Controlling animal reservoirs, interrupting transmission routes Protective clothing, chemical pesticides.. Chemoprophylaxis- Doxycycline (200 mg po /wk) Doxycycline (100 mg bd ) x 7 days—for postexposure prophylaxis(? Efficacy) Vaccine- Bacterin based vaccine(??efficacy, ?safety)
  35. 35. Thank you!!

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