Leptospirosis2008 Batch- V Term

Infectious Diseases Series

It’s raining diseases with monsoon in stateExpress News ServicePosted: 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.

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 ...

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

Butchers, tourists, residents, animals

Butchers, tourists, residents, animals

Learning Objectives

• Historical Perspective• Introduction• Pathogenesis• Clinical Features• Complications• Diagnosis• Treatment

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

IntroductionZoonosis: 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.

Pathogenesis

Pathogenesis- contamination of soil and water

Soil and water contamination

Pathogenesis: Agent

• Order:Spirochetales• Family: Leptospirideae• Genus: Leptospira • Species: interrogans (pathogenic) biflexa• Serovars: > 200• Serogroups: > 25; icterohemorrhagica,

gryppotyphosa, caniciola, pomona, andmanii, etc

Pathogenesis: Agent

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

Animal Urine

Pathogenesis: Agent

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

Pathogenesis: Agent

• DGI

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

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

Flooding, Farming, Camping waterlogging

Butchers, tourists, residents, animals

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

Distribution

Environment

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)

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

Pathogenesis

Renal Failure: – Migrate to interstitium,

renal tubules and tubular lumen – interstitial nephritis and tubular necrosis

– Hypovolemia – dehydration and leakage

Liver

Liver: – Centrilobular necrosis

and Kupffer cell hyperplasia

– No hepatocellular necrosis

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

Jaundice & Red eyes

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

Bimodal illness

• Leptospiremic/ Septicaemic phase• Immune phase/ Leptospiruric Phase

• Distinction maybe blurred

Clinical Features

Factors influencing severity: • Serovar• Size of innoculum• Prior infection• Early antibiotic use• Pregnancy

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

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

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

Clinical Features- Late(B) Icteric Variety

Severe Leptospirosis (Weil’s Disease)• Jaundice• Renal Dysfunction• Hemorrhagic Diathesis

Mortality 5 to 15 %

To Sum Up Clinical Features

• Bacteraemic Leptospirosis• Aseptic Meningitis• Icteric Leptospirosis with Renal involvement• Pulmonary Syndrome

Other Complications

• Rhabdomyolysis• Hemolysis • Myocarditis • Pericarditis • CHF • Necrotising Pancreatitis • MOF

Differential Diagnosis

• Ac Febrile Syndrome (Dengue, Chick, Malaria, Influenza, Typhus, Mono, Enteric, Hanta)

• Jaundice (VH, Yellow Fever, Complicated Malaria)

• Aseptic Meningitis (.., .., .. )

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

Lab Diagnosis

Antigen Detection:• DGI and Silver impregnation

staining- urine, CSF• Culture (EMJH )• PCR

Lab DiagnosisAntigen 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

Treatment

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

Treatment

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

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)

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.

Every jaundice is not viral Hepatitis