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Outbreak of Acute Febrile Illness and Pulmonary Hemorrhage -- Nicaragua, 1995

During the week of October 15, three persons died after presenting to the Achuapa Health Center in Leon state (1995 population: 330,168), Nicaragua, with an acute febrile illness. During the next 2 weeks, at least 400 persons were evaluated at clinics in Achuapa (1995 population: 12,741) and nearby El Sauce (1995 population: 24,289) for acute illnesses characterized by fever, chills, headache, and musculoskeletal pain. As of November 7, approximately 150 of these patients and 150 persons from nearby areas had been hospitalized in the regional medical center in Leon because of more severe manifestations, including intense abdominal pain, hypotension, and/or respiratory distress. At least 13 of the patients have died from respiratory distress and pulmonary hemorrhage. This report summarizes the preliminary findings of the ongoing investigation of this outbreak by the Nicaraguan Ministry of Health, the Pan American Health Organization, and CDC.

Dengue and dengue hemorrhagic fever were initially suspected as the cause of the outbreak but were ruled out in Nicaragua and at CDC by serologic tests and polymerase chain reaction assays of serum specimens. Additional serologic tests found no significant reactions to other arthropodborne and zoonotic pathogens, including New World arenaviruses, lymphocytic choriomeningitis virus, hantaviruses, other Bunyaviridae, Filoviridae, Flaviviridae, Rhabdoviridae, Togaviridae, spotted-fever-group and typhus-group rickettsia, Ehrlichia chaffeensis, and Coxiella burnetii.

Preliminary histopathologic examination at CDC of multiple tissues from four decedents indicates features consistent with leptospirosis. Specifically, silver impregnation staining of autopsy specimens from two patients identified organisms with typical leptospiral morphology in kidney and liver tissue; in a third patient, leptospiral morphology was less typical. These findings were confirmed by immunohistochemical staining using rabbit polyclonal reference antiserum reactive with 16 different leptospiral strains. Leptospiral antigens were seen as intact leptospira, thread-like filaments, and granular forms in liver and kidney tissue from three patients. Immunohistochemical tests of these tissues with polyclonal antibodies were negative for dengue virus, yellow fever virus, hantaviruses, arenaviruses and Ebola virus.

Reported by: F Mućoz, MD, C Jarquin, MD, A Gonzalez, MD, J Amador, MD, J de los Reyes, MD, R Jimenez, MD, Ministry of Health, Nicaragua. F Lamy, MD, N Jiron, MD, Pan American Health Organization, Nicaragua. F Pinheiro, Pan American Health Organization, Washington, DC. US Agency for International Development, Managua, Nicaragua. Div of Vector-Borne Infectious Diseases, Div of Bacterial and Mycotic Diseases, and Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: The preliminary findings of this investigation indicate that leptospirosis was the most likely cause of fatal pulmonary hemorrhage in four hospitalized patients in Nicaragua. Additional studies are under way to confirm the role of leptospiral infection in the outbreak of acute febrile illness, establish animal reservoirs of infection, and identify potentially modifiable risk factors for disease. The investigation has thus far ruled out the potential role of dengue virus and other arthropodborne and rodentborne pathogens; in Central and South America, mosquitoborne dengue is a leading cause of febrile illness, and the increasing circulation of multiple dengue serotypes, including dengue type 3, has been associated with an increase in reported hemorrhagic manifestations of dengue (1,2).

Leptospirosis is a zoonotic disease of worldwide distribution, involving many wild and domestic animals (3). Human infection may result from indirect or direct exposure to infected urine, often through contaminated water or soil. The investigation in Nicaragua is examining the possibility that infection in humans resulted from exposure to water and soil contaminated by animal urine following recent heavy rainfall and flooding in that region.

The spectrum of leptospiral disease is broad and may include fever, headache, chills, myalgia, abdominal pain, and conjunctival suffusion; more severe manifestations include renal failure, jaundice, meningitis, hypotension, hemorrhage, and/or hemorrhagic pneumonitis (4). Severe pulmonary symptoms and pulmonary hemorrhage have not been characteristic of leptospirosis in the Western Hemisphere but have been associated with large outbreaks in Korea and China (5,6). Clinical features of leptospirosis are similar to many other febrile illnesses; in the tropics, the differential diagnosis of such illnesses also may include dengue and malaria. Leptospirosis is diagnosed by isolation of leptospires from blood or cerebrospinal fluid during the acute illness and from urine greater than or equal to 10 days after the onset of symptoms or by documenting rising titers in serologic tests, such as the microagglutination test.

Penicillin is the antibiotic of choice for leptospirosis, and treatment should be initiated early in the course of illness (7). Alternatives are amoxicillin, ampicillin, doxycycline, and tetracycline. Supportive therapy is essential for managing dehydration, hypotension, hemorrhage, renal failure, and pulmonary involvement. For adults with short-term, high-risk exposure to leptospirosis, doxycycline provides effective prophylaxis when administered weekly in a single oral dose of 200 mg (8). Public health measures include controlling rodents, preventing contact with animal urine, wearing protective clothing (e.g., water-resistant boots) when exposure is likely, and avoiding swimming or wading in potentially contaminated water (i.e., with urine of infected animals).

Additional information is available from the CDC Fax Information Service, telephone (404) 332-4565; enter document number 221013# at the prompt.


  1. Gubler DJ, Clark GG. Dengue/dengue hemorrhagic fever: the emergence of a global health problem. Emerging Infectious Diseases 1995;1:55-7.

  2. CDC. Dengue type 3 infection -- Nicaragua and Panama, October- November 1994. MMWR 1995;44:21-4.

  3. Torten M, Marshall RB. Leptospirosis. In: Beran GW, ed. Handbook of zoonoses. Section A: bacterial, rickettsial, chlamydial, and mycotic. Boca Raton, Florida: CRC Press, 1994:245-64.

  4. Farr RW. Leptospirosis. Clin Infect Dis 1995;21:1-8.

  5. Wang CN, Liu J, Chang TF, Cheng WJ, Luo MY, Hung AT. Studies on anicteric leptospirosis: I. Clinical manifestations and antibiotic therapy. Chinese Med J 1965;84:283-391.

  6. Park SK, Lee SH, Rhee YK, et al. Leptospirosis in Chonbuk Province of Korea in 1987: a study of 93 patients. Am J Trop Med Hyg 1989;41:345-51.

  7. Farrar WE. Leptospira species (Leptospirosis). In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases. 4th ed. New York: Churchill Livingstone, 1995:2137-41.

  8. Takafuji ET, Kirkpatrick JW, Miller RN, et al. An efficacy trial of doxycycline chemoprophylaxis against leptospirosis. N Engl J Med 1984;310:497-500.

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