Cutaneous Leishmaniasis in US Military, 2002-2003

Abstract & Commentary

Synopsis: As a result of the recent military conflicts, cutaneous leishmaniasis has emerged as a significant disease among US troops deployed in Iraq, Afghanistan, and Kuwait. Physicians should consider the possibility of cutaneous leishmaniasis in persons with chronic skin lesions who have traveled to or been deployed within areas where leishmaniasis is endemic.

Source: Cutaneous leishmaniasis in US military personnel—Southwest/Central Asia, 2002-2003. MMWR Morb Mortal Wkly Rep. 2003;52(42):1009-1012.

During August 2002 through September 2003, the Walter Reed Army Medical Center (WRAMC) identified 22 cases of cutaneous leishmaniasis (CL) among military personal involved in Operation Iraqi and Enduring Freedom. Of these 22 cases that were parasitologically confirmed, 21 (95%) were males with a median age of 29 years. The cases emerged from within multiple branches of the US military, including the Active Force, Reserve, and National Guard components of the Army, Air Force, and Marine Corps. Eighteen of the 22 cases were most likely infected in Iraq—apparently in the urban and periurban areas of An Nasiriyah and Baghdad. Two cases were probably infected in areas of Kuwait adjacent to Iraq, and the remaining 2 cases were infected in Afghanistan. As of October 20, 2003, those skin cultures with sufficient organisms for species identification were found to contain Leishmania major.

Upon initial evaluation at WRAMC, these 22 cases had a median of 3 skin lesions, ranging in size from 3 mm to 44 mm and were more often located on the upper (39%) or lower (32%) extremities than on the trunk/back (16%) or face/neck (13%). As is typical of CL, the lesions were most often painless, had enlarged slowly with eventual central ulceration, and were sometimes covered by an eschar, surrounded by an erythematous, indurated border. None of the cases had systemic symptoms to suggest either classic visceral leishmaniasis, or the so-called viscerotropic leishmaniasis caused by L tropica described after Operations Desert Storm and Shield during 1990-1991.

As of October 7, 2003, approximately 24,000 female phlebotomine sand flies, the vectors of leishmanial parasites, were collected in Iraq, using light traps, then tested for leishmania organisms by fluorogenic PCR; about 1 in 70 sand flies carried the parasite (1.4%). Many of the US military have reported numerous bites from sand flies, with some personnel reporting more than 100 bites in a single night.

Sodium stibogluconate (Pentostam, 20 mg/kg/d IV for 20 days) was used to treat all 22 patients, and their lesions responded to treatment. Side effects that are well known to be reversible, yet associated with Pentostam, occurred. They included headache, fatigue, myalgias, arthalgias, and chemical pancreatitis.

Comment by Mary-Louise Scully, MD

The most notable clinical syndromes of leishmaniasis may include visceral, cutaneous, and mucosal disease, resulting from the replication of the parasite within macrophages of the mononuclear phagocyte system, dermis, and naso-oropharyngeal mucosa, respectively. About 21 different leishmanial species, transmitted by more than 30 species of phlebotomine sand flies, account for the diversity and complexity of this disease and its treatment.1

For CL, one important component of the decision to treat is assessing the patient’s risk for developing mucosal disease, a disfiguring potential complication of New

World cutaneous leishmaniasis. Other considerations include the location of the lesions (ie, the face), the number of lesions, or their persistence. Old World cutaneous leishmaniasis, such as disease from L major, can heal slowly even without any specific treatment.

There is no ideal therapy identified for all CL, but 2 pentavalent antimonials, either sodium stibogluconate (Pentostam) or meglumine antimoniate (Glucantime), remain the mainstays of treatment. Antimonials must be given parentally; they may be associated with QT prolongation and EKG abnormalities, and have reversible hepatic, renal, and hematologic side effects. Toxicity to pentavalent antimonials usually is cumulative but side effects such as nausea can occur earlier. Myalgias, arthralgias, fatigue, headache, and chemical pancreatitis can occur as well.

There is a plethora of studies regarding other potential treatments of CL, but the studies are often small, uncontrolled, or based on anecdotal data. Therefore, one should be cautious in interpreting these studies and extrapolating the results to other leishmania species in different geographic settings. One randomized, double-blind, placebo-controlled trial of L major in Saudi Arabia assessed the efficacy of 200 mg of fluconazole daily for 6 weeks vs placebo.2 Despite some in vitro studies showing poor activity of fluconazole against various leishmania species, including L major, the authors felt that the long half-life of fluconazole, its high solubility in water and a concentration in skin that is 10 times that of plasma, made it a worthwhile drug to evaluate. The results did show a significantly quicker time to healing in the fluconazole group (8.5 weeks vs 11.2 weeks in controls). Again, this study evaluated CL caused only by L major in Saudi Arabia, and CL lesions of L major do eventually heal without treatment.

Studies of potential treatments have also included itraconazole,3 ketoconazole,4 topical paramomycin, liposomal amphotericin,5 and even thermotherapy;5 all with varying degrees of success. The British have experienced good success rates in many cases of Old World CL using intralesional stibogluconate (personal communication, D. Lockwood). In the United States, the standard remains parenteral Pentostam. However, even Pentostam treatment can result in cases of clinical failure or relapses of New World CL.6 Clearly, this is a disease in need of more straightforward and efficacious treatment.

The World Health Organization estimates that 1.5 million cases of CL occur each year. The military troops returning from Iraq comprise a group at risk for CL. Since this published report a month ago, there have been more than 140 cases of CL reported in the military and this number is expected to rise. In addition, the expanding tourist industry with travel to Costa Rica, Belize, and other parts of Central America, has led to an increase in cases of New World CL in civilian travelers to these areas. CL can occur following relatively short stays in leishmaniasis-endemic areas, and pretravel consultation should include advice to travelers to these destinations to use personal protection measures for the prevention of leishmaniasis. Both the WRAMC and the CDC provide diagnostic services and will provide the sodium stibogluconate for treatment. Health care providers should contact WRAMC (202-782-6740) for treatment of the military or their families, or the CDC’s drug service (404-639-3670) for treatment of civilians.

Dr. Scully, Seattle, WA.

References

1. Herwaldt B. Leishmaniasis. Lancet. 1999;354: 1191-1199.

2. Alrajhi AA, et al. Fluconazole for the treatment of cutaneous leishmaniasis caused by Leishmania major. N Engl J Med. 2002;346:891-895.

3. Momeni AZ. Treatment of cutaneous leishmaniasis with itraconazole. Randomized double-blind study. Arch Dermatol. 1996;132:784-786.

4. Saenz RE. Efficacy of ketoconazole against Leishmania braziliensis panamensis cutaneous leishmaniasis. Am J Med. 1990;89(2):147-155.

5. Berman J. Current treatment approaches to leishmaniasis. Curr Opin Infect Dis. 2003;16(5):397-401.

6. Reithinger R, et al. Am Jour Trop Med Hyg. 2003;69(3):548-549(Abstract # 776).

7. Lawn SD, et al. Am Jour Trop Med Hyg. 2003;69(3):264 (Abstract # 165) .