Leishmaniasis

Cutaneous leishmaniasis (CL), a vector-borne parasitic disease, is a risk for persons, including military personnel, who travel to or live in areas of the tropics, subtropics, and southern Europe where the disease is endemic (1-4). This report provides preliminary data about 22 cases of CL in military personnel deployed during 2002-2003 to three countries in Southwest/Central Asia (Afghanistan, Iraq, and Kuwait) (Figure 1). The patients were evaluated and treated at Walter Reed Army Medical Center (WRAMC) in the District of Columbia during August 2002-September 2003. U.S. health-care providers should consider the possibility of CL in persons with chronic skin lesions who were deployed to Southwest/Central Asia or who were in other areas where leishmaniasis is endemic.

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Of the 22 patients with CL that was confirmed parasitologically *, 21 (95%) were men; 19 (86%) were non-Hispanic white, two (9%) were Hispanic, and one (5%) was non-Hispanic black. The median age of the 22 patients was 29 years (range: 21-48 years). The patients represented multiple branches of the U.S. military, including the Active Force, Reserve, and National Guard components of the Army, Air Force, and Marine Corps. On the basis of the patients' histories about their deployments, the majority (18 [82%]) probably were infected in Iraq, particularly in the urban and periurban areas of An Nasiriyah and Baghdad, and two (9%) probably were infected in areas of Kuwait adjacent to Iraq. An additional two (9%) persons were infected in Afghanistan. The patients had been deployed to these areas an estimated median of 60 days (range: 21-150 days) before first noting skin lesions. Self-reported dates of lesion onset ranged from May 2002 to August 2003 (Figure 1).

When first evaluated at WRAMC, the 22 patients had a median of three (range: one to nine) skin lesions, which ranged from 3 mm to 40 mm in diameter. Higher proportions of the lesions were located on the upper (39%) or lower (32%) extremities than on the trunk/back (16%) or face/neck (13%). Typically, the lesions were painless, had enlarged slowly, and ultimately had central ulceration, often covered with eschar and surrounded by an erythematous, indurated border (Figure 2). Regional lymph nodes (e.g., epitrochlear, axillary, and inguinal), if palpable, usually were <1 cm in diameter. None of the patients had systemic symptoms.

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In 17 (77%) of the 22 cases, parasites were noted on light-microscopic examination of tissue. Of the 19 patients who had tissue cultured for parasites, 14 (74%) had positive cultures, of which 13 (93%) had sufficient organisms for species identification by isoenzyme electrophoresis. All nine of the 13 patients whose cultures had been tested as of October 20, 2003, were infected with Leishmania major. Additional evidence that 21 (95%) of the 22 patients had CL was obtained by testing tissue with an investigational, fluorogenic, genus-specific polymerase chain reaction (PCR) assay developed and conducted by staff of WRAMC and Walter Reed Army Institute of Research (Silver Spring, Maryland) (6).

Since 1978, military personnel with potential cases of leishmaniasis have been referred to WRAMC for evaluation and therapy with the pentavalent antimonial compound sodium stibogluconate (Pentostam[R], The Wellcome Foundation, United Kingdom). Although treatment of cases of CL with pentavalent antimonial compounds has been considered the standard of care for over half a century (1), these compounds are not licensed for use in the United States. Therefore, sodium stibogluconate, the pentavalent antimonial compound used in the United States, is provided by WRAMC under Investigational New Drug (IND) protocols that the Surgeon General of the Army holds with the U.S. Food and Drug Administration (FDA). CDC has a separate IND protocol with FDA for providing this drug for civilians with leishmaniasis.

All 22 patients were treated with sodium stibogluconate (20 mg/kg of body weight/day) by intravenous infusion for 20 days (1). The patients' lesions responded to therapy. The patients had predictable, reversible side effects from therapy (e.g., fatigue, arthralgia, myalgia, headache, and chemical pancreatitis) (1).

Surveillance for infected female phlebotomine sand flies, the vectors of leishmanial parasites, has been conducted in and near urban and periurban areas of Iraq where U.S. military personnel have been stationed. Use of light traps facilitated collection of many sand flies in short periods (e.g., up to approximately 1,200 sand flies per trap in a 13-hour period overnight, when sand flies are most active). During April-September 2003, approximately 65,000 sand flies were collected, about half of which were female. Taxonomic analysis indicated that the most common species in the Phlebotomus genus were P.papatasi, P. alexandri, and P. sergenti, all of which can be vectors of leishmanial parasites. As of October 7, approximately 24,000 female phlebotomine sand flies, in pools of one to 15 flies, had been tested for infection by using fluorogenic PCR (6). The overall infection rate in the sand flies was 1.4% (326 of 23,877). The infection rates for sand flies collected in and near specific areas were as follows: 2.3% (nine of 390) for Tikrit, 1.6% (315 of 19,937) for An Nasiriyah, 0.08% (one of 1,307) for Baghdad, 0.06% (one of 1,795) for Balad, and 0% (none of 448) for Diwaniyah. Five percent (eight of 149) of PCR-positive pooled aliquots of sand flies collected from An Nasiriyah were positive by species-specific PCR for L. infantum, which can cause visceral and cutaneons leishmaniasis.

Editorial Note: Leishmaniasis is a vector-borne parasitic disease endemic in parts of the tropics, subtropics, and Southern Europe. The World Health Organization estimates that 1.5 million cases of CL and 500,000 cases of visceral leishmaniasis (VL) occur each year (1).

Both cutaneous and visceral infection can remain asymptomatic or be associated with mild, nonspecific, and nonprogressive symptoms (1). Clinical manifestations, if they develop, typically are first noted weeks to months after exposure. The skin lesions of CL, which can be chronic and disfiguring, typically evolve from papules to nodules to ulcerative lesions but can persist as nodules or plaques (1). Host (e.g., immune status) and parasite (e.g., species and strain) characteristics affect the natural history and the ease and importance of diagnosing and treating cases of CL. Although both L. major and L. tropica are common etiologic agents of CL in Afghanistan, Iraq, and Kuwait (1,7,8), which species has caused a particular case of CL depends on such factors as the geographic area and ecologic setting of exposure and the species of the sand-fly vector. VL is more prevalent in Iraq (8) than in Afghanistan or Kuwait. Manifestations of cases of advanced VL include fever, cachexia, hepatosplenomegaly, pancytopenia, and hypergammaglobulinemia; such cases can be fatal if not treated appropriately and quickly (1).

No FDA-approved vaccines or prophylactic medications to prevent leishmaniasis are available (1). Control measures against vectors or reservoir hosts of infection might be effective in particular settings (1,8,9). Personal protective measures to decrease risk for infection include avoiding, if possible, areas where leishmaniasis is endemic, particularly from dusk through dawn; using permethrin-treated bed nets and clothing; minimizing the amount of exposed skin; and applying insect repellents containing 30%-35% DEET (lower percentages for children) to exposed skin.

Transmission of leishmanial parasites through blood transfusion has not been reported in the United States. However, as a precautionary measure, the Armed Services Blood Program Office of the Department of Defense (DoD) (Falls Church, Virginia) and the American Association of Blood Banks (AABB) (Bethesda, Maryland) are implementing policies to defer prospective blood donors who have been in Iraq from donating blood for 12 months after the last date they left Iraq. Additional information about these deferral policies is available from DoD at http://www-nehc.med.navy.mil/ downloads/prevmed/leishmanAug03.pdf and from AABB at http://www.aabb.org.

In Operations Desert Storm and Shield during 1990 1991, among approximately 697,000 deployed military personnel, WRAMC identified 12 cases of so-called viscerotropic leishmaniasis caused by L. tropica (a syndrome associated with visceral infection but not necessarily the classic clinical manifestations of VL) and 20 cases of CL (3,10; WRAMC, unpublished data, 2003). During August 2002-September 2003, WRAMC identified 22 cases of CL among personnel participating in Operations Iraqi and Enduring Freedom. The apparent decline in numbers of cases of CL with self-reported onset of lesions during July-August 2003 (Figure 1) could reflect delays in persons seeking medical evaluation for skin lesions that might not cause concern initially. U.S. personnel in Iraq have reported being bitten by sand flies (some persons have received >100 bites in a single night), and up to 2% of female phlebotomine sand flies collected in Iraq were infected with leishmanial parasites. As of October 21, WRAMC had identified nine more cases of CL in addition to the 22 cases described in this report. WRAMC is evaluating additional potential cases of CL in deployed personnel, and the number of confirmed cases probably will continue to increase.

U.S. health-care providers should consider the possibility of CL in persons with chronic skin lesions who were deployed to Southwest/Central Asia or who were in other areas where leishmaniasis is endemic and that of VL in such persons with persistent, febrile illnesses, especially if associated with other manifestations suggestive of VL (e.g., splenomegaly and pancytopenia) (1,4,8,10). Information about diagnosing and treating CL and VL has been published (1,5). Both WRAMC and CDC provide diagnostic services and the antileishmanial compound sodium stibogluconate. For treatment of health-care beneficiaries of the military, health-care providers should contact WRAMC, telephone 202-782-6740. For treatment of civilians, providers should contact CDC's Drug Service, telephone 404-639-3670.

Acknowledgments

This report is based in part on data provided by G Albright, MD, P Benson, MD, M Bryan, MD, Landstuhl Regional Medical Center, Landstuhl, Germany. D Burkett, PhD, Tallil Air Base; R Hadley, B Jennings, J McAvin, PhD, 520th Theatre Army Medical Laboratory (Forward), Iraq. K Crosby, C Oster, MD, G Robinson, MS, C Smalls, Walter Reed Army Medical Center; P McEvoy, MD, R Neafie, MS, Armed Forces Institute of Pathology; District of Columbia. E Fleming, MS, L Figueroa, L Hochberg, J Mendez, J Tally, Walter Reed Army Institute of Research, Silver Spring, Maryland.

* Detection of leishmanial parasites in specimens obtained from skin lesions (1,5), either by light-microscopic examination conducted by staff of the Armed Forces institute of Pathology (District of Columbia) of Diff Quik (Dade Diagnostics, Puerto Rico)--stained slides (i.e., thin smears of tissue scrapings from ulcerative lesions or impression smears or tissue sections of skin-biopsy specimens) or by culture (e.g., of skin-biopsy specimens) performed by staff of Walter Reed Army Institute of Research (Silver Spring, Maryland).

References

(l.) Herwaldt BL. Leishmaniasis. Lancet 1999;354:1191-9.

(2.) Martin S, Gambel J, Jackson J, et al. Leishmaniasis in the United States military. Mil Med 1998;163:801-7.

(3.) Hyams KC, Hanson K, Wignall FS, Escamilla J, Oldfield EC 3rd. The impact of infectious diseases on the health of U.S. troops deployed to the Persian Gulf during Operations Desert Shield and Desert Storm. Clin Infect Dis 1995;20:1497-504.

(4.) Herwaldt BL, Stokes SL, Juranek DD. American cutaneous leishmaniasis in U.S. travelers. Ann Intern Med 1993;118:779-84.

(5.) Vega-Lopez F. Diagnosis of cutaneous leishmaniasis. Curr Opin Infect Dis 2003;16:97-101.

(6.) Wortmann G, Sweeney C, Houng H-S, et al. Rapid diagnosis of leishmaniasis by fluorogenic polymerase chain reaction. Am J Trop Med Hyg 2001;65:583-7.

(7.) Ashford RW, Kohestany KA, Karimzad MA. Cutaneous leishmaniasis in Kabul: observations on a 'prolonged epidemic'. Ann Trop Med Parasitol 1992;86:361-71.

(8.) World Health Organization. WHO communicable disease profile for Iraq, 2003:39-43. Available at http://www.who.int/infectious-diseasenews/IDdocs/whocds200317.

(9.) Desjeux P. Leishmaniasis: public health aspects and control. Clin Dermatol 1996;14:417-23.

(10.) Magill AJ, Grogl M, Gasser RA Jr, Sun W, Oster CN. Visceral infection caused by Leishmania tropica in veterans of Operation Desert Storm. N Engl J Med 1993;328:1383-7.

Reported by: N Aronson, MD, Uniformed Svcs Univ of the Health Sciences, Bethesda; R Coleman, PhD, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick; P Coyne, MD, E Rowton, PhD, Walter Reed Army Institute of Research, Silver Spring, Maryland. D Hack, MD, M Polhemus, MD, G Wortmann, MD, Walter Reed Army Medical Center, District of Columbia. K Cox, MD, Air Force Institute for Operational Health, San Antonio, Texas. P Weina, MD, 520th Theatre Army Medical Laboratory (Forward), Iraq. BL Herwaldt, MD, Div of Parasitic Diseases, National Center for Infectious Diseases, CDC.

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