Viscerotropic Leishmaniasis in Persons Returning from Operation Desert Storm -- 1990 - 1991

From November 1990 through December 1991, seven men among the approximately 500,000 military personnel from the United States who participated in Operation Desert Storm had leishmaniasis involving internal organs diagnosed at Walter Reed Army Medical Center. In at least five of the cases, the species of the infecting parasite was Leishmania tropica (previously known as L. tropica minor), a parasite more commonly associated with cutaneous than with visceral leishmaniasis.

The seven men, whose illnesses were termed viscerotropic leishmaniasis, were a median of 30 years of age (range: 21-40 years). They had served in five different military units throughout the eastern province of Saudi Arabia; some were in urban and others in desert settings. Six of the seven men were symptomatic; the asymptomatic man was identified during an epidemiologic investigation of a unit with a symptomatic person. Symptoms developed a median of 7 months (range: 8 weeks-1 year) after the men arrived in the Persian Gulf and within 5 months after they left the area.

Five of the six symptomatic men were febrile. Four had an acute syndrome with high fever (maximum of 103.0-105.6 F (39.4-40.9 C)), chills, and malaise. Of these four men, one had mild hepatosplenomegaly; one had generalized lymphadenopathy; and one, who was found to be coinfected with human immunodeficiency virus (HIV), developed generalized lymphadenopathy after antileishmanial therapy was begun (he was seronegative for HIV infection when tested in February 1990). The other two symptomatic men had predominantly gastrointestinal symptoms, including nausea, low-volume watery diarrhea, and abdominal pain; the abdominal pain initially was nonfocal but later localized to the left upper quadrant and was associated with mild splenomegaly. One of these two men also had a newly diagnosed renal-cell carcinoma. None of the seven men had skin lesions.

At the time leishmaniasis was diagnosed, six of the men (including the asymptomatic one) had modest elevations in their liver enzymes (median for alanine aminotransferase: 131 international units (IU)/L; normal: 5-42 IU/L). Three were mildly anemic (lowest hemoglobin level for these three: 12 g/dL). One had transient hypoalbuminemia. None had leukopenia, thrombocytopenia, or hypergammaglobulinemia.

Leishmania parasites were cultured from bone-marrow aspirates from all seven men. L. tropica was identified by isoenzyme analysis as the infecting species in five men; insufficient numbers of parasites for this analysis were obtained in cultures from the other two men. In addition, parasites were visualized in smears of the bone-marrow aspirates of all seven men using a Leishmania-specific monoclonal antibody (indirect immunofluorescent monoclonal antibody test) (1). Giemsa-stained smears were not routinely prepared; however, in at least one case, no parasites were found when a Giemsa-stained smear was examined.

The five men who were still symptomatic when leishmaniasis was diagnosed were treated with the pentavalent antimonial compound sodium stibogluconate. Although the 30-day course of parenteral therapy was discontinued after 8 and 18 days for two patients (including the HIV-positive patient) who developed reversible thrombocytopenia, all treated patients were clinically well 3 months to 1 year after therapy was stopped. The man who was apparently asymptomatic has remained clinically well during 7 months of follow-up.

Reported by: AJ Magill, MD, RA Gasser, Jr, MD, CN Oster, MD, Infectious Disease Svc, Walter Reed Army Medical Center; M Grogl, PhD, Div of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC. W Sun, MD, Infectious Disease Svc, William Beaumont Army Medical Center, El Paso, Texas. Div of Parasitic Diseases, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: An estimated 12 million persons in the tropics and subtropics have leishmaniasis, a protozoan parasitic disease transmitted by the bite of infected sandflies (2). The major clinical syndromes are visceral, cutaneous, and mucosal leishmaniasis that result from infection of macrophages in the reticuloendothelial system, skin, and nasal and oral mucosae, respectively.

Although the various species and subspecies of the genus Leishmania traditionally have been considered either viscerotropic or dermotropic, exceptions have been reported. Species in the L. donovani complex have been considered primarily viscerotropic but also have been causative agents of cutaneous leishmaniasis without dissemination to the viscera (3-5). L. tropica, an important agent of cutaneous leishmaniasis in the Old World, has reportedly been isolated occasionally from persons with visceral leishmaniasis (6-9). Whether visceral involvement with L. tropica is exceptional or relatively common but only rarely recognized is unknown. Also unknown is whether strains that disseminate to the viscera differ subtly from strains that do not. Host factors, such as lack of previous exposure to the parasite and type of immune response to the parasite, may also play a role in whether strains disseminate to the viscera.

Leishmaniasis was diagnosed for the cases described in this report because of aggressive medical evaluations and the use of specialized laboratory techniques. The soldiers' symptoms and signs, which may have been attributable in part to other medical conditions, were nonspecific. Although five of the men were febrile and several had mild splenomegaly, none had the marked hepatosplenomegaly, pancytopenia, hypergammaglobulinemia, and cachexia classically associated with visceral leishmaniasis (i.e., kala-azar) caused by L. donovani. Because of these differences, the syndrome described in this report has been referred to as viscerotropic rather than visceral leishmaniasis. Whether infection with L. tropica generally results in milder disease than does infection with L. donovani is unknown. However, L. donovani may result in life-threatening disease in only a small proportion of those infected (10,11).

The diagnosis of viscerotropic leishmaniasis should be considered for persons who have been in the Middle East and have an unexplained illness of at least several weeks' duration, especially if the illness is associated with fever or signs of involvement of the reticuloendothelial system. The incubation period for viscerotropic leishmaniasis caused by L. tropica is unknown; if the incubation period is similar to that of visceral leishmaniasis caused by L. donovani, most persons would be expected to become ill within 6 months after exposure. However, the diagnosis of leishmaniasis should not be excluded for persons who become ill later. CDC and the U.S. Department of Defense do not recommend evaluating asymptomatic persons for evidence of infection: effective screening tests are not available, and whether treating asymptomatic persons is beneficial is unknown. Household contacts of persons who were in the Middle East are not at risk for acquiring leishmaniasis.

The diagnosis of cutaneous leishmaniasis should be considered for persons with skin lesions of at least several weeks' duration. Through December 1991, cutaneous leishmaniasis had been diagnosed in 16 military personnel from Operation Desert Storm.

Military and civilian physicians with questions about the diagnostic evaluation of military personnel, including reservists, who were associated with Operation Desert Storm and have persistent signs or symptoms suggestive of leishmaniasis should contact the following: U.S. Army--Walter Reed Army Medical Center, Washington, D.C. (telephone: (800) 423-0231); U.S. Navy/Marines--Naval Hospital, San Diego (telephone: (619) 532-7475 (Duty Station Number (DSN): 522-7475)); U.S. Air Force -- USAF Medical Center, Lackland Air Force Base, San Antonio, Texas (telephone: (512) 670-7444 (DSN: 554-7444)). Physicians caring for civilian employees of the U.S. government stationed in the Middle East and associated with Operation Desert Storm should contact Walter Reed Army Medical Center. Physicians caring for civilians not included in the categories listed above should contact CDC's Parasitic Diseases Branch, Division of Parasitic Diseases, National Center for Infectious Diseases (telephone (404) 488-4050).

Sodium stibogluconate for treating persons confirmed to have leishmaniasis is available to military physicians through Walter Reed Army Medical Center and to civilian physicians through the CDC Drug Service ((404) 639-3670) under an investigational new drug protocol.

References

1. Anthony RL, Grogl M, Sacci JB, Ballou RW. Rapid detection of Leishmania amastigotes in fluid aspirates and biopsies of human tissues. Am J Trop Med Hyg 1987;37:271-6.

2. WHO. Control of the leishmaniases: report of a WHO expert committee. Geneva: World Health Organization, 1990:10. (Technical report series no. 793.)

3. Gramiccia M, Gradoni L, Pozio E. Leishmania infantum sensu lato as an agent of cutaneous leishmaniasis in Abruzzi region (Italy). Trans R Soc Trop Med Hyg 1987;81:235-7.

4. Zeledon R, Hidalgo H, Viquez A, Urbina A. Atypical cutaneous leishmaniasis in a semiarid region of northwest Costa Rica. Trans R Soc Trop Med Hyg 1989;83:786.

5. Ponce C, Ponce E, Morrison A, et al. Leishmania donovani chagasi: new clinical variant of cutaneous leishmaniasis in Honduras. Lancet 1991;1:67-70.

6. Mebrahtu Y, Lawyer P, Githure J, et al. Visceral leishmaniasis unresponsive to Pentostam caused by Leishmania tropica in Kenya. Am J Trop Med Hyg 1989;41:289-94.

7. Schnur LF, Chance ML, Ebert F, Thomas SC, Peters W. The biochemical and serological taxonomy of visceralizing Leishmania. Ann Trop Med Parasitol 1981;75:131-44.

8. Schnur LF. On the clinical manifestations and parasites of Old World leishmaniases and Leishmania tropica causing visceral leishmaniasis. In: Hart DT, ed. Leishmaniasis, the current status and new strategies for control. New York: Plenum Press, 1989:939-43.

9. Oren R, Schnur LF, Yehuda DB, Mayner V, Okon E, Rachmilewitz EA. Visceral leishmaniasis: a difficult diagnosis and unusual causative agent. J Infect Dis 1991;164:746-9.

10. Badaro R, Jones TC, Lorenco R, et al. A prospective study of visceral leishmaniasis in an endemic area of Brazil. J Infect Dis 1986;154:639-49.

11. Badaro R, Jones TC, Carvalho EM, et al. New perspectives on a subclinical form of visceral leishmaniasis. J Infect Dis 1986;154:1003-11.

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