Leptospirosis

1. Dr. Zubair Sarkar
JR2
Department of Medicine
J. N. Medical College , AMU

2.  Zoonotic disease
 Caused by the spirochete Leptospira
 Historically known as Weil’s disease
 Described in 1885 by Adolf Weil with clinical hallmarks of
 splenomegaly
 jaundice
 nephritis
Introduction

3.  One of the emerging infectious diseases since the late 1990s
 Recent large outbreaks in several Asian, Central and South
American countries
 Becoming an important public health problem, yet it
continues to be under recognized

4. 
 Genus Leptospira, order Spirochetales, family
leptospiraceae
 Can live both in animals and free in the environment
(both pathogenic and saprophytic)
 Around 250 serovars from 20 species cause disease in
humans and animals
Organism

5. 
 All species are morphologically identical
 Tightly and regularly coiled with hooked ends
 Highly motile along the longitudinal axis
Morphology

7.  Not seen by direct light microscopy
 Dark-field or phase contrast microscopy must be used
 In tissues
 silver impregnation (Warthin starry staining),
 immunohistochemistry or
 immunoflourescence microscopy
 Isolation difficult

8. 
 Zoonotic disease
 No human to human transmission
 Most important sources are rats, dogs, cattle and pigs
Epidemiology

9.  Domestic animals : temporary carrier
 Rodents : permanent carrier
 Rodents are therefore considered as the major reservoir of
infection.
 Rat (Rattus norvegicus and Rattus rattus) associated L.
interrogans serovars Icterohaemorrhagic and Copenhageni
are mostly associated with Weil’s disease

10.  Transmitted through contact with infected animal urine
and other excreta (e.g. placenta)
 Contact may be
 direct or
 indirect through surface water or moist soil

12.  Patterns of transmission can be
 Epidemic
 Endemic
 Sporadic

13.  Seasonal rains and flooding are the most important
factors causing epidemics
 Endemic disease is facilitated by
 Tropical humid environment
 Poor sanitation
 Rodent and dog population

14. • Sporadic disease is associated with
 Occupation : veterinary, sewer and slaughterhouse
workers
 Poor hygiene areas e.g. slums
 Adventure travel
 Military training

15.  No precise estimates of the global burden of human
leptospirosis
 Estimated annual incidence (WHO) – 0.1 to 1 per 100 000
per year in temperate climates – 10 or more per 100 000
per year in the humid tropics.
 Estimated case-fatality rates in different parts of the
world have been reported to range from <5% - 30%

16.  Figures are grossly underestimated : Overlooked and
under reported
 Why the lack of recognition?
 Clinical manifestation wide and varied
 May mimic many other diseases, e.g. dengue fever and
other viral haemorrhagic diseases
 Diagnostic capabilities are not readily available
(especially in endemic countries)
 Poor surveillance and reporting of cases

17. 
 Considered a rare zoonotic disease in India with only
sporadic cases being recorded.
 Since 1980’s the disease has been reported from various
states during monsoon months in mini epidemic
proportions.
Indian perspective

18.  In India, urban leptospirosis has been reported from
Chennai & Mumbai while rural leptospirosis has been
reported from Gujarat, Kerala and Andamans
 Non-reporting of leptospirosis from other states of India
does not mean that it is absent in those parts.

19.  The disease is endemic in
 Kerala
 Tamil nadu
 Gujarat
 Andamans
 Karnataka
 Maharashtra
 It has also been reported from Andhra Pradesh, Orissa,
West Bengal, Uttar Pradesh, Delhi & Puducherry

21.  Leptospirosis has been under-reported and under-
diagnosed from India due to
 lack of awareness of the disease and
 lack of appropriate laboratory diagnostic facilities in most
parts of the country

22. 
Organism disappears from blood but remains in
organs including brain , liver, lung, heart and
kidneys
Development of antibodies(5-7 days)
Proliferate in bloodstream and disseminate
hematogenously
Infects through mucosa ( conjunctival , oral) or
through punctured or abraded skin
Pathogenesis

23. Excreted in urine
Adhere to proximal tubule epithelial cells
Penetrate basement membrane of PCT
Traverse interstitial spaces of kidney

24. Hypovolaemic shock and vascular collapse
Loss of fluids into the third space
Vasculitis and leakage : petechiae , intra parenchymal
bleeding and bleeding along serosa and mucosa
Capillary vasculitis (endothelial necrosis and lymphocytic
infiltration)
Attach onto the endothelial cells
Produces endotoxin

25. 
 Clinical expression can be
 Subclinical infection
 Undifferentiated febrile illness
 Weil’s disease
 Incubation period 2-30 days (average 5-14 days)
Clinical features

26.  Classically described as biphasic
 Acute phase:
 3-10 days
 leptospiraemia : blood culture may be positive
 fever responds to antibiotics
 Immune phase :
 fever does not respond to antibiotics
 isolation from urine

27. 
 Conjunctival suffusion
 Jaundice
 Pharyngeal erythema without exudate
 Rashes (maculopapular, erythematous, petechial or
ecchymotic)
 Muscle tenderness
 Rales in lungs
 Meningismus
 Hyporeflexia or areflexia
Physical examination

30. 
 The most severe form of leptospirosis
 Monophasic and fulminant
 Variable combinations of jaundice, acute kidney injury,
hypotension and hemorrhage
 Pulmonary hemorrhage is the most common
 Multisystem involvement occurs
Weil’s disease

31. 
 Presents with jaundice
 Not associated with fulminant hepatic necrosis or liver
cell damage
 LFTs are abnormal (<5 times the upper limit)
 Liver can be enlarged and tender
 Splenomegaly in a minority of patients
Liver involvement

32. 
 Can manifest after several days of illness
 Can be oliguric/nonoliguric
 Dyselectrolytemia is common: hypokalemia and
hypomagnesemia in nonoliguric disease
 Hypotension may cause tubular necrosis and oliguria
 May require vasopressor support and hemodialysis
Kidney involvement

33. 
 Manifests with cough,
chest pain and hemoptysis
 Purulent sputum
uncommon
 Severe pulmonary
hemorrhage occurs in endemic disease
 Alveolar infiltrates are visible on CXR
Pulmonary involvement

34.  Cardiac :
 Myocarditis
 Neurological :
 Aseptic meningitis
 Hypo or areflexia
 Eyes :
 Uveitis
 Skeletal muscles :
 Severe myalgia of calves and abdominal muscles
 Cholecystitis
 Pancreatitis (can cause hypo/hyperglycemia)
Other manifestations

35. 
 High index of suspicion is critical in a setting of
 An appropriate exposure history
 Infection’s protean manifestations
 Biochemical, hematological and urinalysis may suggest
but are not specific for diagnosis
Diagnosis

36.  The disease is usually diagnosed by –
 detecting antibodies using various serological tests
 culturing the bacteria from blood, urine or tissues
 demonstrating the presence of leptospires in tissues using
antibodies labelled with fluorescent markers
 polymerase chain reaction (PCR)
 Immunostaining
 Cultures take many weeks and cannot guide clinical care
 Dark-field microscopy of blood/urine not recommended

37. Dark field microscopy showing Leptospira spp.

38. Immunohistochemical demonstration of leptospira in kidney tissue

39. 
 Microscopic agglutination test (MAT) is the gold
standard : Sensitivity 92% Specificity 95%
 MAT has a very limited availability
Serological tests

40.  The MAT entails growth of a battery of serovars
representing the 26 leptospiral serogroups , incubation of a
standard quantity of leptospires with the patient’s serum
on a microtiter plate, and detection of agglutination by
dark-field microscopy.
 The highest dilution of serum that yields significant (50%)
agglutination is reported as the titer.

41.  When patients have a high pretest probability: a single
antibody titer >1:200 is considered strong evidence of
infection
 In regions where leptospirosis transmission and subclinical
disease are common, higher titers are generally required
 MAT is generally negative in the first 7–10 days after the
onset of infection
 Paired acute- and convalescent-phase serum samples are
preferred to document seroconversion or a fourfold rise in
titer.

42. Microscopic Agglutination Test(MAT)

43.  Genus specific or rapid tests include
 ELISA
 Macroscopic slide agglutination test (MSAT)
 Latex agglutination test
 Dipstick tests ( Lepto dipstick, Lepto Tek lateral flow)
 Lepto Tek Dri-Dot test
 Indirect hemagglutination

44.  These tests are simple, more sensitive and become
positive earlier than MAT (5-6th day) as they detect
specific IgM antibodies
 Use saphrophytic leptospira as antigens
 Are commercially available

45. 
 Leptospires can be cultured from blood and CSF
during first 7-10 days
 Urine culture useful beginning in the 2nd week
 May take 2-4 weeks to be positive
 Urine cultures can remain positive for many
months/years despite therapy
Isolation

49. 
 Malaria
 Enteric fever
 Dengue/ chikungunya
 Hanta virus infection
 Viral hepatitis
 Influenza
 Rickettsial diseases
Differential diagnosis

51. 
 Prompt initiation of antibiotic therapy shortens the
course and prevents progression
 Mild leptospirosis resolves without any treatment
Treatment

53.  Renal involvement may require hemodialysis
 Hypotension can be managed by fluids and vasopressors
 Severe disease should be treated empirically with broad-
spectrum antibiotics before confirmation

54. 
 Advanced age, pulmonary involvement, elevated
creatinine , oliguria and thrombocytopenia indicate poor
prognosis
 Liver dysfunction has not been confirmed to be an
independent risk factor for death
 No permanent sequelae or progressive organ
dysfunction after resolution
Prognosis

55.  No vaccine available currently
 Short-term antibiotic prophylaxis can be used for well-
defined exposures
 Doxycycline 100 mg or Azithromycin 250mg once a week
may be used
 Long-term antibiotic prophylaxis ineffective
 General sanitation measures and avoidance of swimming in
contaminated places
Prevention

56. 
 Adequate history of exposure is most important in
diagnosis
 Possibility of leptospirosis to be kept in d/d of all icteric
illness
 Prompt treatment can prevent life threatening
complications
 Health education and awareness for prevention
Take Home Message