LEPTOSPIROSIS
By Dr.R.V.S.N.Sarma, M.D., M.Sc., (Canada)
Etiologic Agent
Leptospirosis is an infectious zoonotic (acquired from animals) diseased caused by pathogenic
bacteria called Leptospires which are long, thin motile spirochetes. Leptospires may be free-living
(non pathogenic) or associated with animal and human hosts (pathogenic) and survive well in fresh
water, soil, and mud in tropical areas. These organisms are antigenically complex, with over 200
known pathogenic serologic variants placed in seven groups. Molecular taxonomic studies at CDC
and elsewhere have identified 13 named and 4 unnamed species of pathogenic leptospires. Although
certain geographic regions contain specific leptospiral serovars and species, the serologic
characterization of an isolate is not an absolute predictor of its species designation.
Incidence
Leptospirosis is a tropical disease and is endemic in our country with peak occurrences during
monsoon season. Although incidence in developed countries is relatively low, leptospirosis is
considered to be the most widespread zoonotic disease in the world. Rodents, especially rats, are the
most important reservoir, although dogs, other wild mammals and birds may harbor the disease.
Leptospires can persist in the renal tubules of the vertebrate host for many years, excreting the
bacteria in urine.
Transmission
Transmission may follow direct contact with infected urine, blood or tissues from an infected animal or
exposure to water and environment contaminated with the above. Direct human-to-human
transmission is rare. Since leptospires are excreted in urine and can survive in water for many
months, contaminated water is the most important vehicle of transmission.
Special risk groups
Workers in rice fields, sugar cane plantations, mines, sewer systems, and slaughterhouses; animal
caretakers and veterinarians; and travelers to tropical parts of the world involved in recreational
activities in fresh water. Children and adults wading through contaminated flooded rainwater are
especially at high risk. Recreational exposures can include rafting, kayaking, and swimming.
Pathogenesis
Leptospires enter the host through abrasions in the skin or through intact mucus membranes of oronaso-pharynx and conjunctiva. Drinking of contaminated water will result in entry of the pathogen
through GI tract. Leptospires multiply in the blood and tissues and target the capillary endothelium
causing vasculitis, liver (causing hepatitis and centrilobular necrosis) and kidneys. Interstitial nephritis
with tubular necrosis is the most common pathologic finding. Pulmonary involvement is a result of
hemorrhage and not due to inflammation. After start of specific anti-microbial therapy, a JarischHerxheimer reaction similar to that seen with Syphilis but less sever may develop - so beware!
Clinical features
After an incubation period of 1 to 2 weeks usually but may range from 2 to 26 days, 15 to 40% of
those exposed develop Inapparent infection only detectable serologically. Typically the disease has
2 phases, namely the initial Leptospiremic phase followed by the Immune phase. In mild cases the
second phase may not be manifest. More than 90% of the symptomatic patients (overt infection) have
relatively mild and anicteric form of leptospirosis. Severe leptospirosis with profound jaundice (Weil’s
syndrome) develops in about 10% of cases.
Anicteric Leptospirosis
Symptoms include fever, headache, chills, muscle aches, vomiting, anemia, but without jaundice and
sometimes a rash. Intense frontal head ache and severe myalgias usually occur. Cough and chest
pain are frequent with hemoptysis in some cases. Fever, conjunctival injection, muscle tenderness,
hepato-splenomegaly, rash – macular, maculopapular, urticarial or hemorrhagic may be seen. Most
patients become a symptomatic with in a week. Often the illness reoccurs after 1-3 days (the immune
phase) coinciding with the development of immune antibodies and the symptoms are similar to the
first leptospiremic phase, except that the fever and mylagia are less severe. Asceptic meningitis may
develop in this phase. This immune phase usually lasts a few days but occasionally persists for
weeks.
Weil’s syndrome (severe leptospirosis)
It is characterized by jaundice, renal dysfunction, hemorrhagic diathesis and high mortality. The onset
of illness is however no different from the milder form described above but 4 to 9 days Jaundice, as
well as renal and vascular dysfunction develops. The biphasic pattern described in milder disease is
lacking. The jaundice may be profound imparting orange colour to the skin, not usually associated with
severe hepatic necrosis. Tender hepatomegaly, right upper quadrant abdominal pain and
splenomegaly develop. Minimal peritoneal and pleural fluid may appear (demonstrable by USG).
Hypolvolemia, renal failure develops in second week. It is hepato-reno-vasculopathy. Pulmonary
involvement with cough, dyspnea and hemoptysis may occur. Hemorrhagic manifestations include
petechiae, purpura, epistaxis and ecchymoses. Severe GI bleed is rare. Less common manifestations
include rabdomyolysis, hemolysis, pericarditis, CHF, cardiogenic shock, Adult Respiratory Distress
Syndrome (ARDS). Case fatality rate is 1 to 5%.
Laboratory diagnosis
Urine sediment shows: Leucocytes, RBC, hyaline and granular casts and proteinuria (+ to ++). ESR is
elevated. Leukocytosis is usual with shift to left. In Weil’s syndrome Leukocytosis is marked.
Increased serum bilirubin, alkaline phosphatase, SGOT and SGPT are also seen. Patchy alveolitis
pattern in the lower lobes on chest X-ray is seen.
Special tests include MAT (microscopic agglutination test) IgM or IgM ELISA for leptospires, which
are diagnostic of recent infection. These are usually positive from the 2nd week onwards. Dark field
examination for the spirochete (cork screw shaped) Leptospira is +ve from the first week.
Differential diagnosis
Malaria, Enteric fever, Dengue, viral hepatitis and Hanta viral and rickettseal disease include the DD.
Treatment
Anicteric Leptospirosis: In milder cases Doxycycline 100 mg orally b.i.d for 7 to 10 days. Or Ampicillin
500 mg orally q.i.d or Amoxycillin in similar doses for 7 to 10 days may be given. In moderately severe
cases Penicillin G 15 to 20 lac units I.V. q.i.d. for 5 to 7 days is the drug of choice. Ampicillin or
Amoxycillin 1 gm I.V. q.i.d. may also be used.
Weil’s Syndrome: Hospitalization is mandatory. I.V. Penicillin G is the drug of choice. In penicillin
sensitive cases Erythromycin 500mg I.V. q.i.d. may be given. Patients will require dialysis for renal
failure and supportive treatment for hepatic failure. Transfusion of whole blood or platelets will be
required for cases of severe vasculopathy. Intensive care is required. Management of JarischHerxheimer reaction is supportive and symptomatic. Chemoprophylaxis with Doxycycline 200 mg
weekly is recommended for travelers from non endemic to endemic zones.
Trends
Leptospirosis continues to re-emerge as a notable source of morbidity and mortality. The largest
recorded outbreak in the continental U.S. (110 cases in a group of 775 exposed persons) occurred in
June and July 1998. Significant increases in incidence were also reported from Peru and Ecuador
following heavy rainfall and flooding in the spring of 1998. India and Thailand have also reported a
rapid increase in incidence between 1995 and 2000.
Challenges
The confirmatory microscopic agglutination test (MAT) is too labour intensive and not widely known
and available. Rapid serologic assays have been shown to be sensitive and specific. The challenge is
to increase awareness of new diagnostic assays and their advantages.
(A Technical Document for Doctors)