Dr. Zubair SarkarJR2

Department of MedicineJ. N. Medical College , AMU

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

One of the emerging infectious diseases since the late 1990s

Recent large outbreaks in several Asian, Central and SouthAmerican countries

Becoming an important public health problem, yet itcontinues to be under recognized

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 inhumans and animals

Organism

All species are morphologically identical

Tightly and regularly coiled with hooked ends

Highly motile along the longitudinal axis

Morphology

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

Zoonotic disease

No human to human transmission

Most important sources are rats, dogs, cattle and pigs

Epidemiology

Domestic animals : temporary carrier

Rodents : permanent carrier

Rodents are therefore considered as the major reservoir ofinfection.

Rat (Rattus norvegicus and Rattus rattus) associated L.interrogans serovars Icterohaemorrhagic and Copenhageniare mostly associated with Weil’s disease

Transmitted through contact with infected animal urineand other excreta (e.g. placenta)

Contact may be

direct or

indirect through surface water or moist soil

Patterns of transmission can be

Epidemic

Endemic

Sporadic

Seasonal rains and flooding are the most importantfactors causing epidemics

Endemic disease is facilitated by

Tropical humid environment

Poor sanitation

Rodent and dog population

• Sporadic disease is associated with

Occupation : veterinary, sewer and slaughterhouseworkers

Poor hygiene areas e.g. slums

Adventure travel

Military training

No precise estimates of the global burden of humanleptospirosis

Estimated annual incidence (WHO) – 0.1 to 1 per 100 000per year in temperate climates – 10 or more per 100 000per year in the humid tropics.

Estimated case-fatality rates in different parts of theworld have been reported to range from <5% - 30%

Figures are grossly underestimated : Overlooked andunder reported

Why the lack of recognition?

Clinical manifestation wide and varied

May mimic many other diseases, e.g. dengue fever andother viral haemorrhagic diseases

Diagnostic capabilities are not readily available(especially in endemic countries)

Poor surveillance and reporting of cases

Considered a rare zoonotic disease in India with only

sporadic cases being recorded.

Since 1980’s the disease has been reported from variousstates during monsoon months in mini epidemicproportions.

Indian perspective

In India, urban leptospirosis has been reported fromChennai & Mumbai while rural leptospirosis has beenreported from Gujarat, Kerala and Andamans

Non-reporting of leptospirosis from other states of Indiadoes not mean that it is absent in those parts.

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

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 mostparts of the country

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

Excreted in urine

Adhere to proximal tubule epithelial cells

Penetrate basement membrane of PCT

Traverse interstitial spaces of kidney

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

Clinical expression can be

Subclinical infection

Undifferentiated febrile illness

Weil’s disease

Incubation period 2-30 days (average 5-14 days)

Clinical features

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

Conjunctival suffusion

Jaundice

Pharyngeal erythema without exudate

Rashes (maculopapular, erythematous, petechial orecchymotic)

Muscle tenderness

Rales in lungs

Meningismus

Hyporeflexia or areflexia

Physical examination

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

Presents with jaundice

Not associated with fulminant hepatic necrosis or livercell damage

LFTs are abnormal (<5 times the upper limit)

Liver can be enlarged and tender

Splenomegaly in a minority of patients

Liver involvement

Can manifest after several days of illness

Can be oliguric/nonoliguric

Dyselectrolytemia is common: hypokalemia andhypomagnesemia in nonoliguric disease

Hypotension may cause tubular necrosis and oliguria

May require vasopressor support and hemodialysis

Kidney involvement

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

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

High index of suspicion is critical in a setting of

An appropriate exposure history

Infection’s protean manifestations

Biochemical, hematological and urinalysis may suggestbut are not specific for diagnosis

Diagnosis

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 usingantibodies 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

Dark field microscopy showing Leptospira spp.

Immunohistochemical demonstration of leptospira in kidney tissue

Microscopic agglutination test (MAT) is the goldstandard : Sensitivity 92% Specificity 95%

MAT has a very limited availability

Serological tests

The MAT entails growth of a battery of serovarsrepresenting the 26 leptospiral serogroups , incubation of astandard quantity of leptospires with the patient’s serumon a microtiter plate, and detection of agglutination bydark-field microscopy.

The highest dilution of serum that yields significant (50%)agglutination is reported as the titer.

When patients have a high pretest probability: a singleantibody titer >1:200 is considered strong evidence ofinfection

In regions where leptospirosis transmission and subclinicaldisease are common, higher titers are generally required

MAT is generally negative in the first 7–10 days after theonset of infection

Paired acute- and convalescent-phase serum samples arepreferred to document seroconversion or a fourfold rise intiter.

Microscopic Agglutination Test(MAT)

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

These tests are simple, more sensitive and becomepositive earlier than MAT (5-6th day) as they detectspecific IgM antibodies

Use saphrophytic leptospira as antigens

Are commercially available

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

Malaria

Enteric fever

Dengue/ chikungunya

Hanta virus infection

Viral hepatitis

Influenza

Rickettsial diseases

Differential diagnosis

Prompt initiation of antibiotic therapy shortens the

course and prevents progression

Mild leptospirosis resolves without any treatment

Treatment

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

Advanced age, pulmonary involvement, elevated

creatinine , oliguria and thrombocytopenia indicate poorprognosis

Liver dysfunction has not been confirmed to be anindependent risk factor for death

No permanent sequelae or progressive organdysfunction after resolution

Prognosis

No vaccine available currently

Short-term antibiotic prophylaxis can be used for well-defined exposures

Doxycycline 100 mg or Azithromycin 250mg once a weekmay be used

Long-term antibiotic prophylaxis ineffective

General sanitation measures and avoidance of swimming incontaminated places

Prevention

Adequate history of exposure is most important in

diagnosis

Possibility of leptospirosis to be kept in d/d of all ictericillness

Prompt treatment can prevent life threateningcomplications

Health education and awareness for prevention

Take Home Message