leptospirosis

Leptospirosis

Primary Distribution: Worldwide, especially tropical areas and most particularly Latin America and Southeast Asia (Centers for Disease Control [CDC], 1999; Ko, Galvao, Ribeiro, Johnson, & Riley, 1999; World Health Organization [WHO], 2000).

Agent and Vector: Leptospira interrogans is a diverse bacteria (motile spirochette), of which the three most common serovars (causing leptospirosis) are Leptospira icterohaemorrhagiae (carried by rats and causing the most severe form of leptospirosis), L. canicola (carried by dogs), and L. pomona (carried by cattle). Infection is via ingestion of food contaminated by urine from infected vectors or through skin lesions or mucous membranes exposed to contaminated water or soil. The latter is a common means of infection in the tropics, e.g., rice farming in padi plowed with oxen (CDC, 1999; Chin, 2000).

Incubation: 2-28 days, but usually about 10 days.

Clinical Findings and Treatment

Signs and Symptoms: The degree of illness in leptospirosis varies from asymptomatic to a severe or fatal illness. The most common forms are (1) anicteric and (2) icteric or Weil's syndrome. Anicteric leptospirosis is the more common and milder form, and often is biphasic. The first phase is characterized most frequently by sudden onset high fever with chills, headache, conjunctival suffusion (without discharge), cough and pulmonary chest pain, abdominal pain, nausea and vomiting, and myalgia (especially calves and thighs). The abdominal pain may be similar to "surgical abdomen." Other signs include lymphadenopathy, pharyngeal injection, rash of variable presentation, hepatomegaly, and/or splenomegaly. In some cases, the illness resolves after about one week with no further manifestations; and in other cases, after one to three days, the illness recurs. If the second phase occurs, symptoms tend to both milder and more varied than in the first phase - except that aseptic meningitis may occur. This second (immune) phase usually lasts for several days, but may persist for weeks. Icteric leptospirosis or Weil's syndrome is the more severe form and is characterized by symptoms as described above (except not usually biphasic); and after about one week, the development of decreased renal function, pulmonary complications, jaundice, and hemorrhagic manifestations. Renal failure (acute tubular necrosis) with oliguria or anuria may develop after about one week of illness, but does not usually require dialysis, and often returns to normal within months. Early recognition of decreased renal function is critical to patient survival. Pulmonary complications may include the presence of infiltrates, cough, dyspnea, hemoptysis, and/or chest pain. Decreased hepatic function and jaundice are common, but hepatic failure is seldom a cause of death - though the degree of jaundice correlates with risk of death. Hemorrhagic manifestations most often are epistaxis, bleeding gums, purpura, petechiae; and less frequently, gastrointestinal or subarachnoid bleeding (CDC, 1999; Chin, 2000; Jacobs, 1999; Speelman, 1998).

Complications: Aseptic meningitis, myocarditis, pulmonary complications, and renal failure with hepatic involvement occur primarily in severe and untreated disease. Pulmonary complications tends to occur earlier in the illness than other complications. Less common complications include a variety of cardiac problems, ARDS, shock, and multi-organ failure.

Laboratory Findings: Common laboratory findings in anicteric leptospirosis include low, normal, or elevated white blood cell count with neutrophilia regardless of count, elevated erythrocyte sedimentation rate, elevated creatine phosphokinase, anemia, proteinuria, pyuria, and hematuria. Leptospires are present in the blood for about one week after onset of the illness, and then are present in urine. Laboratory findings in icteric leptospirosis are as above except that renal function markers show greater pathology. Serum bilirubin and alkaline phosphatase may be elevated and prothrombin time increased (Jacobs, 1999; Speelman, 1998).

Diagnosis: The index of suspicion is increased by occupational or other exposure to contaminated water or other potential exposure to infected urine. A flu-like illness with very severe myalgia and/or aseptic meningitis is a typical presentation; and conjunctival suffusion and myalgia together is cardinal. As previously noted, leptospires are present in the blood for about one week after onset of the illness, and then are present in urine. Seroconversion or increased antibody titer in the microscopic agglutination test may thus occur after about one week. Other tests (several ELISA) are also available.

Differential Diagnosis: For anicteric leptospirosis, principal differentials are aseptic meningitis related to other entities, fever of unknown origin, influenza, appendicitis, and gastroenteritis. For anicteric leptospirosis, principal differentials are viral hepatitis (see labs above), malaria, typhoid fever, scrub typhus, dengue fever, hemorrhagic fever with renal syndrome.

Treatment: Leptospirosis responds well to treatment, especially if started early in the illness. Anicteric or mild leptospirosis is treated with doxycycline 100 mg po bid for 7 days OR ampicillin 500-750 mg po qid OR amoxicillin 500 mg po qid. Icticteric or anicteric (moderate to severe) leptospirosis is treated with IV penicillin G 1.5 million units qid OR IV ampicillin one gram qid OR IV amoxicillin one gram qid OR IV erythromycin 500 mg qid. Jarisch-Herxheimer reactions to therapy may occur, i.e., acute febrile reaction, accompanied by headache and myalgia due to release of toxic products of killed spirochetes. The reaction usually occurs within 24 hours of initiation of therapy and subsides about 24 hours later. Therapy is continued unless symptoms are severe. Renal failure is treated as in other circumstances. Prophylaxis with doxycycline 200 mg/week is noted as effective in some sources. Doxycycline (200 mg/week) seems to have no effect on disease rates, but that it did reduce morbidity and mortality (Chin, 2000; Sehgal, Sugunan, Murhekar, Sharma, & Vijayachari, 2000; Speelman, 1998).

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References

Centers for Disease Control (1999). Leptospirosis. Available online: http://www.cdc.gov/ncidod/dbmd/diaseaseinfo/leptospirosis_g.htm. Accessed 12/29/99.

Chin, J. (Ed.) (2000). Control of communicable diseases manual (17th ed.). Washington, DC: American Public Health Association.

Jacobs, R.A. (1999). Infectious diseases: Spirochetal. In L.M. Tierney, S.J. McPhee, & M.A. Papadakis (Eds.), Current Medical Diagnosis & Treatment (14th ed.) (pp.1332-1352). Stamford Connecticut: Appleton & Lange.

Ko, A.I., Galvao, M., Ribeiro, C.M., Johnson, W.D., Riley, L.W. (1999) Urban epidemic of severe leptospirosis in Brazil. Salvador Leptospirosis Study Group. Lancet. 354(9181), 820-825.

Sehgal, S.C., Sugunan, A.P., Murhekar, M.V., Sharma, S., & Vijayachari, P. (2000). Randomized controlled trial of doxycycline prophylaxis against leptospirosis in an endemic area. International Journal of antimicrobial agents. 13(4), 249-255.

Speelman, P. (1998). Leptospirosis. In A.S. Fauci, E. Braunwald, K.J. Isselbacher, J.D. Wilson, J.B. Martin, D.L. Kasper, S.L. Hauser, & D.L. Longo (Eds.). Harrison's Principles of Internal Medicine (14th ed.) (pp. 1036-1038). New York: McGraw-Hill.

World Health Organization (2000). Disease outbreak news: Leptospirosis in Canada. Accessed on the World Wide Web 10/16/2000 at http://www.who.int/disease-outbreak-news/index.html. (Readers are encouraged to use this site for current and complete information on major infectious diseases).