Undergraduate class room lecture

1. Leptospirosis
2008 Batch- V Term
Infectious Diseases Series

2. It’s raining diseases with monsoon in state
Express News Service
Posted: Sep 01, 2010 at 0210 hrs
ISTAhmedabad/Vadodara/Surat
• While the good spell of monsoon has brought in cheer, the health
barometer has been a cause for concern this month. Gujarat health
department recorded outbreak of at least six diseases in a week in
six different areas across the state. Kutch reported 349 suspected
cases of Chikungunya on August 17, a Gandhinagar taluka reported
two cholera cases on August 18, 24-odd cases of gastroenteritis
were reported in Surat district while 35 cases of unknown fever
were reported in Surat on the same day. According to the state
health department, 20 more jaundice cases were reported in
Ahmedabad on August 20. They are unlikely to be due to viral
hepatitis due to the unusual association of kidney failure.
leptospirosis is suspected but not confirmed. In another incident,
10 cases of diarrhoea were reported in Surat on August 21.

3. Leptospirosis: meaning
• Leptospira (from the Greek leptos, meaning
fine or thin, and the Latin spira, meaning coil)
is a genus of spirochaete bacteria, including a
small number of ...

4. Alternate Names
• Weil’s disease
• Ictero-hemorrhagic fever
• Swineherd's disease
• Rice-field fever
• Cane-cutter fever
• Swamp fever
• Mud fever
• Hemorrhagic jaundice
• Stuttgart disease
• Canicola fever

5. Butchers, tourists, residents, animals

6. Butchers, tourists, residents, animals

7. Learning Objectives
• Historical Perspective
• Introduction
• Pathogenesis
• Clinical Features
• Complications
• Diagnosis
• Treatment

8. Historical Perspective
• A syndrome of severe multisystem disease
presenting as profound jaundice and renal
function impairment was described by Weil in
Heidelberg in 1886
• Earlier descriptions also exist
• Leptospires were first visualized in autopsy
specimens in a case thought to be Yellow Fever
• Simultaneously isolated in Japan and Germany
• Many researchers (Stokes, Noguchi, others) died
of the disease

9. Introduction
Zoonosis: Leptospirosis is a bacterial disease that
affects both humans and animals.
Not well documented, often overlooked & under-reported
Emerging Infectious Disease: Several recent
outbreaks in Asia, South America & USA
• In the wake of hurricane Mitch in 1995, an outbreak with pulmonary
hemorrhages was reported in Nicaragua.
• In 1998, there were outbreaks in USA, Peru and Ecuador.
• A post-cyclone outbreak was reported in Orissa, India in 1999
• During outbreaks and in high-risk groups
>100 per 100 000 may be infected.

10. Pathogenesis

11. Pathogenesis- contamination of soil
and water

12. Soil and water contamination

13. Pathogenesis: Agent
• Order:Spirochetales
• Family: Leptospirideae
• Genus: Leptospira
• Species: interrogans (pathogenic) biflexa
• Serovars: > 200
• Serogroups: > 25; icterohemorrhagica,
gryppotyphosa, caniciola, pomona, andmanii,
etc

14. Pathogenesis: Agent

15. Pathogenesis: Agent
• Can survive outside the body for long
• Organism is excreted in the urine even
after clinical infection settles down
(symbiotic)
• Leptospirosis is maintained in nature by
chronic renal infection of carrier animals

16. Animal Urine

17. Pathogenesis: Agent
• Coiled, thin, highly motile
• Hooked ends and flagellae
• Stain poorly
• Seen by DGI & Silver impregnation
• Need special media
• Take long for culture

18. Pathogenesis: Agent
• DGI

19. Pathogenesis: Host
Mammals - wild and domestic
• Animals- Rodents, insectivores, dogs, cattle, pigs,
horses, etc
• Humans
• Direct contact with urine of infected animals
• Urine-contaminated surface water, soil and plants
• Even some birds
• Micro-abrasions, intact skin and mucosa
• Infected animal tissues and blood

20. Pathogenesis: Host
• Occupational hazard: people who work outdoors
/with animals
– rice and sugar-cane field workers, farmers
– sewer workers
– veterinarians and dairy workers
– butchers and abattoirs
– military personnel
• Recreational hazard:
• tourists, Water sports

21. Flooding, Farming, Camping
waterlogging

22. Butchers, tourists, residents, animals

23. Pathogenesis: Environment
• Worldwide
• Both rural and urban areas
• Temperate and tropical climates
• Incidence peaks during the rainy season and
during flooding
• Tourism in tropics with adventure water sports

24. Distribution

25. Environment

26. Pathogenesis
• Entry: through cuts and abrasions in skin &
mucous membranes of the eyes, nose and
mouth
• Inhalation- rare
• Ingestion- rare
• Human-to-human transmission –rare
• Incubation Period: 5 to 14 days (mean 10
days)

27. Pathogenesis
• Leptospiremic/ Septicaemic phase
– Systemic vasculitis
– Migration of organisms into tissues-
inflammation and multi-organ dysfunction
from direct cyto-toxicity
• Immune phase/ Leptospiruric Phase
– Second fever and organ involvement
through immunological mechanisms-
• Persistence of organisms
– Renal tubules, aqueous humor

28. Pathogenesis
Renal Failure:
– Migrate to interstitium,
renal tubules and
tubular lumen –
interstitial nephritis
and tubular necrosis
– Hypovolemia –
dehydration and
leakage

29. Liver
Liver:
– Centrilobular necrosis
and Kupffer cell
hyperplasia
– No hepatocellular
necrosis

30. Pathogenesis
Pulmonary: Hemorrhage
and not much inflammation
- hemoptysis, patchy lung
- infiltrates and ARDS
Muscles: Direct cytotoxicity
CNS: Organisms in the CSF
X 2 weeks with
mild CSF changes
Meningitis in immune phase

31. Jaundice & Red eyes

32. Clinical Features
Wide range of severity and clinical features
A. Subclinical infection
B. Self limited systemic illness 90 %
C. Severe potentially fatal illness consisting of
• Renal failure 15 %
• Liver failure 15%
• Pneumonitis >30 to 40% mortality
• Hemorrhagic diathesis

33. Bimodal illness
• Leptospiremic/ Septicaemic phase
• Immune phase/ Leptospiruric Phase
• Distinction maybe blurred

34. Clinical Features
Factors influencing severity:
• Serovar
• Size of innoculum
• Prior infection
• Early antibiotic use
• Pregnancy

35. Clinical Features- early (5 -7 days)
• High fever and chills
• Severe headache, eyeball pain, photophobia
• Mental confusion
• Muscle pain & tenderness (calves and back)
• Redness in the eyes & conjunctival injection
• Sore throat
• Rash- maculopapular

36. Clinical Features- early (5 to 7 days)
• Abdominal pain
• Vomiting and diarrhea
• Jaundice, hepatosplenomegaly
• Lymphadenopathy -rare
• Hemorrhages in skin and mucous
membranes
• Cough, chest pain & hemoptysis

37. Clinical Features- Late
(A) Anicteric Variety
After 2 to 3 days of seeming recovery
• New fever
• Milder myalgias
• Aseptic meningitis- similar to viral
meningitis- clue- Neutrophilic leucocytosis
• Uveitis (Iridocyclitis)
• Choreoretinitis

38. Clinical Features- Late
(B) Icteric Variety
Severe Leptospirosis (Weil’s Disease)
• Jaundice
• Renal Dysfunction
• Hemorrhagic Diathesis
Mortality 5 to 15 %

39. To Sum Up Clinical Features
• Bacteraemic Leptospirosis
• Aseptic Meningitis
• Icteric Leptospirosis with Renal involvement
• Pulmonary Syndrome

40. Other Complications
• Rhabdomyolysis
• Hemolysis
• Myocarditis
• Pericarditis
• CHF
• Necrotising Pancreatitis
• MOF

41. Differential Diagnosis
• Ac Febrile Syndrome (Dengue, Chick,
Malaria, Influenza, Typhus, Mono, Enteric,
Hanta)
• Jaundice (VH, Yellow Fever, Complicated
Malaria)
• Aseptic Meningitis (.., .., .. )

42. Lab Diagnosis
• Urine: Sediment (RBCs, WBCs, Casts) & proteinuria
• Blood Counts:
– PMN –Leucocytosis,
– ESR elevation
– Thrombocytopenia
• Biochemistry: LFT (Enzymes not very high); KFT
• Coagulation Profile -Vit K dep factors low
• CPK MM
• CSF Abnormalities
• X Ray Chest- patchy alveolar pattern- lower lobes

43. Lab Diagnosis
Antigen Detection:
• DGI and Silver impregnation
staining- urine, CSF
• Culture (EMJH )
• PCR

44. Lab Diagnosis
Antigen Detection:
• DGI and Silver impregnation staining- urine, CSF
• Culture (EMJH )
• PCR
Antibody Detection (second week)
IgM & IgG
• MAT
• ELISA
• Indirect Hemagglutination Test
• Microcapsule Agg test

45. Treatment
• General and Supportive Care
– Antipyretics
– Rest
– Hydration
– Ventilator support
– Liver support
– Renal support
– Transfusion support

46. Treatment
• General and Supportive Care
• Penecillin G
• Amoxycillin
• Ampicillin
• Tetracyclines
• Doxycycline
• Ceftriaxone
• JH Reaction

47. Prevention
• Rodent and wild plus peri-domestic animal
control
• Avoid exposure to urine and tissues of animals
• Avoid wading through water collections
• Vaccination of animals
• Chemoprophylaxis- weekly Doxycycline (200
mg)

48. Take Home Messages
• Leptospirosis is an infectious disease
(zoonosis) caused by a bacterium.
• Leptospirosis is transmitted to humans by direct exposure
to urine or tissue of an infected animal.
• Leptospirosis typically progresses through two phases of
nonspecific symptoms.
• Leptospirosis can be diagnosed by culture of infected
blood, urine, or spinal fluid, as well as using antibody
testing.
• Animals are also at risk for contracting Leptospirosis.
• Leptospirosis is treated with antibiotics and is rarely fatal.

49. Every jaundice is not viral Hepatitis