LEPTOSPIROSIS INFECTION IN CLINICAL ASPECT

leptospirosis infection presentation

1. LEPTOSPIROSIS

2. INTRODUCTION Leptospirosis is a zoonotic disease with protean  manifestations Common synonyms include weils disease , rice field fever Mild disease to extremely fatal Imperative to suspect and treat early in order to prevent complications 

3. EPIDEMIOLOGY Occurs most commonly in tropics and sub tropics Around 1 million cases reported yearly worldwide with mean case fatality rate of about 10%

4. AGENT Leptospira (thin,spiral ) are spirochetes belonging to the order spirochaetales Nearly 64 species have been identified ,divided into 2 clades and 4 sub clades (p1,p2,s1,s2) Traditionally classified as pathogenic (l.Interrogans) and free living (l. Biflexa) 260 serovars

5. LEPTOSPIROSIS 1.6- 20 micron long and 0.1 micron wide  2. Two polar extrusions  3.Dark field microscopy / silver impregnation staining 4.Special culture media ( fletcher's , E llinghausen mccullough – johnson-harris , or polysorbate 80)

6. HOST  Mammals are natural host  Humans are incidental hosts ( animal or environmental exposure) Rodents can persistently shed leptospires in urine throughout their lifespan

7. HOST – RISK FACTORS Men are more commonly infected Low socioeconomic status - overcrowding and unhygenic  Barefoot walking (cuts/abrasions) Recreational exposure - rafting , fresh water swimming Occupational exposure - farmers , sewage workers Domestic animal exposure Travel to endemic areas

8. TRANSMISSION TO HUMANS

9. ENVIRONMENT  Damp soil and water Temperature of 28-32 celsius Tropical regions

10. PATHOGENESIS

11. CLINICAL FEATURES MILD DISEASE Majority of cases are mild and go undiagnosed Acute febrile illness / flu like syndrome Fever,headache,rigors,cough Myalgia- calves,backand abdomen

12. CLINICAL FEATURES  Conjunctival suffusion  Pharyngeal congestion Muscle tenderness Hepatosplenomegaly, lymphadeno pathy Meningismus Transient rash

13. SEVERE LEPTOSPIROSIS AND COMPLICATIONS Onset similar to mild disease May not respect the biphasic course of illness Mortality can be as high as 50%

14. SEVERE LEPTOSPIROSIS Hemorrhage Acute renal failure Acute respiratory failure Multiorgan failure Weil syndrome – Triad of hemorrhage , jaundice and acute kidney injury SHOCK – common presenting sign (45%) due to hypovolemia and microvascular dysregulation

15. CIRCULATORY DYSFUNCTION  Hypovolemia  occurs in sepsis causes vascular leakage or occur as a consequence of hemorahage Shock Multiorgan dysfunction Hemorrhage manifests due to thrombocytopenia , coagulopathy,vascular endothelial damage

16. RENAL INVOLVEMENT Renal impairment attenuated by dehydration from low fluid intake and high fever  Occurs together with jaundice within first 3-4 days presents as non-oliguric ,oliguric or anuric   Hyp onatremia and hypokalemia due to tubulopathy involving    NA-K-2Cl cotransporter Hypokalemia due to impairment of sodium transporter in proximal tubules and spared distal tubules is more common  Hypomagnesemia

17. RENAL INVOLVEMENT POLYURIC PHASE: Develop after 10-18 days S.creatinine begins to fall at the end of second week and normalizes within 3-5 weeks In mild cases the only abnormal findings are in urinary sediment includes albuminuria , microscopic hematuria,pyuria and granular casts

18. PULMONARY INVOLVEMENT Occurs in 20-70% of cases Most common symptom is cough Blood tinged sputum or obvious hemoptysis occur Pulmonary hemorrhage – minimal or severe diffused leading to respiratory failure Pulmonary edema with cardiomegaly due to volume overload or congestive heart failure from myocarditis Diffuse ground glass opacities without cardiomegaly - ARDS

19. CARDIAC INVOLVEMENT  Most commonly non specific st-t changes Myocarditis Conduction abnormality Repolarization abnormalities and arrhthmias

20. CNS INVOLVEMENT Aseptic lymphocytic meningitis Leptospira can be isolated from CSF within 5 days after onset of fever  Raised CSF opening pressure Raised protein with normal CSF glucose level  Lymphocytic pleocytosis Encephalomyelitis Guillain –Barre syndrome  Mononeuritis multiplex  Cranial nerve palsy  Psychiatric syndrome – Mania 

21. LABORATORY DIAGNOSIS  Complete Blood Count Renal Function Tests Liver Function Tests CPK CSF Analysis  Urine Analysis  CXR,ECG PT,APTT TESTS FOR DIAGNOSIS OF LEPTOSPIROSIS 

22. LABORATORY DIAGNOSIS CBC- Leucocytosis ( N- 80%)+thrombocytopenia, anaemia ++ Thrombocytopenia is a indicator of severe disease.  LFT- Elevated billirubin , elevated liver enzymes  Markedly Elevated cpk   PT, APTT- Prolonged.  RFT- AKI+ Urine analysis- proteinuria+, rbcs +  CSF ANALYSIS- ASEPTIC MENINGITIS 

23. SUPPORTIVE TESTS Elevated serum amylase  Elevated creatinine kinase Cardiac  biomarkers Elevated ESR/CRP/Procalcitonin

24. PULMONARY LEPTOSPIROSIS HRCT CHEST Patchy alveolar infiltration Ground glass attenuation Interlobular septa thickening Mediastinal lymphadenitis

25. LABORATORY DIAGNOSIS - SPECIFIC Direct isolation  PCR  -          sensitivity   45-55%                        Specificity   99-100%                        Can detect even in first five days of illness                        Can be done in blood /urine/csf Culture  - specificity-  100%                        Sensitivity  - 25%                        Requires special media                        Time consuming                        Blood /csf - first 10 days                        Urine  -  2nd week to 30 days after resolution of illness

26. SEROLOGICAL DIAGNOSIS Microscopic agglutination test (mat)    Four fold rise in titre or single value of 1:800    Sensitivity – 16-20% Igm-elisa  Simple , sensitive  Single positive sample adequate for diagnosis becomes positive earlier than mat  Indicates current infection   Commonly performed Antigen detection:  Using monoclonal anti –lipl32 antibody based antigen capture ellisa- a cost effective alternative to pcr. 

27. LAB CRITERIA FOR DIAGNOSIS OF CURRENT LEPTOSPIROSIS CULTURE –POSITIVE  MAT-SEROCONVERSION ELISA -POSITIVE 

28. MODIFIED FAINE'S SCORE

29. Presumptive diagnosis of leptospirosis is made of:   Part A or Part A + B Score          : 26 or more  Part A+B+C (Total)                     : 25 or more  A score between 20 and 25 suggests Leptospirosis as a possible diagnosis. Part A+B is useful for diagnosis in the first week as lab tests would be negative. Part A+B+C is valuable in the second week as lab tests would become positive. It is always necessary to confirm the diagnosis with laboratory tests.

30. Reason for Modification Most cases of leptospirosis are reported in the monsoon and post monsoon seasons. Therfore factors such as rainfall,and contact with contaminated environment have been incorporated with appropriate scores Part (B) ELISA and SAT measures IgM antibodies becomes positive by 5th day ,they are the test of choice for diagnosis of current infection and more over a single sample is adequate . High titres and rising titres of MAT have been given appropriate scores Part (C)

31. MANAGEMENT MILD LEPTOSPIROSIS:  FIRST LINE -     Doxycycline 100mg BID PO for 10 days  ALTERNATIVE –         Amoxicillin 500mg QID OR 1g q8h OR   A MPICILLIN 500MG PO tid OR Azithromycin 1g initially followed by 500 mg OD for 2 more days

32. SEVERE LEPTOSPIROSIS(WEIL SYNDROME) PRIMARY : Penicillin G 1.5 million units IV q 6 hrs for 7 days Ceftriaxone 1gm IV OD for 7 days ALTERNATIVE : Ampicillin 0.5-1 gm q6h Azithromycin 500mg OD for 5 days Cefotaxime 1gm q6h Doxycycline 200mg iv loading dose followed by 100mg iv q12h

33. ROLE OF STEROIDS WHY To reduce or delay the need for ventillatory support To reduce mortality WHOM Patients at high risk of pulmonary hemorrhage AKI plus any of the following Platelet count < 1 lakh MAP < 65 mm of Hg Prolonged PT/APTT Need for ionotropes When Initiate as soon as first sign of pulmonary leptospirosis is detected ( tachypnea , hemoptysis , dyspnea )

34. STEROID REGIMENS Methylprednisolone 500mg IV OD for 3 days with first dose given as bolus within first 12 hrs of onset of respiratory involvement For those with renal failure – Methylprednisolone 500mg IV after HD OD for 3 days. After 3 rd MP dose or after any episode of hemoptysis give Cyclophosphamide 1g IV as single dose Bolus Methylprednisolone 1g IV OD for 3 das followed b 1mg/kg/day of oral prednisolone for 7 days

35. PREVENTION AND CONTROL Avoid swimming,bathing ,swallowing or submersing head in potentially contaminated freshwater especially after periods of heavy rainfall or flooding Rodent control measures Chemoprophylaxis with weekly doxycycline 200 mg once weekly for 6 weeks Proper drainage of water bodies Vaccination of domestic animals General protective measures ( proper footwear,eyewear,bandage of cuts ,etc)

36. PROGNOSIS - POOR FACTORS AGE>40 YEARS CNS/PULMONARY /SEVERE RENAL INVOLVEMENT MECHANICAL VENTILATION ARRHYTHMIAS AND REPOLARISATION ABNORMALITIES  SHOCK  LEUCOCYTOSIS

37. REFERENCE MANSON TROPICAL INFECTION HARRISON 21ST EDITION