promastigote form of the parasite into humans. Infection is then established with the amastigote form, which is harbored in human macrophages.

Two transmission cycles have been described. In the zoonotic cycle, dogs are the primary animal reservoir, and humans are an occasional host when they are infected by the bite of the sand fly. In south-central Asia (Afghanistan), great gerbils (Rhombomys opimus) are the vertebrate hosts of L. major and thus determine the clinical distribution of associated CL. In the anthroponotic cycle, humans are the sole reservoir, and sand flies remain the critical vector. Phlebotomus papatasi is the sand fly species that transmits L. major throughout most of the Middle East and is present in south-central Asia. Phlebotomus sergenti was recently identified as the species responsible for transmission of L. tropica in Afghanistan (Wallace et al. 2002).

Sand fly bites are exceedingly common in the Middle East. In August 1943, sand fly fever (caused by a phlebovirus) occurred at a peak rate of 235 per 1,000 military personnel deployed to the Persian Gulf (Hertig and Sabin 1964). Because sand flies are most active during warm months, however, there is seasonal variation in the risk of infection. Only 31 cases of leishmaniasis were diagnosed among 697,000 troops deployed during the Gulf War, and deployment to the open desert during cooler weather was thought to be a partial reason for the low incidence of the disease (Cope et al. 1996). Even in areas that are important foci of Leishmania infection, the prevalence of sand fly-caused infection with Leishmania spp. is unpredictable (Fryauff et al. 1993).

Finally, humans have acquired leishmaniasis through parenteral exposure (because of contaminated injection equipment and blood products) and through sexual contact, but those cases are rare.

Endemicity in Southwest and South-Central Asia

Southwest Asia and south-central Asia are home to Old World CL and VL (Oldfield et al. 1991). The potential for anthroponotic acquisition of CL is especially high in Kabul, Afghanistan, where 270,000 persons (in a population of 2 million) were estimated to be infected in 1996 (World Health Organization as cited in Hewitt et al. 1998). Some 4,700 cases of CL were reported in northern Syria in 1999, an increase from the 3,900 cases reported in 1998 (WHO 2002); most CL in the Middle East is caused by L. major.

Acute Leishmaniasis

Old World CL has an incubation period of 2 weeks to 2 months. The most common etiologic agent is L. major, which causes papular lesions that can ulcerate (Wallace et al. 2002). Most (90-95%) CL lesions heal spontaneously, and they rarely cause persistent disfiguration. L. recidivans can cause a chronic cutaneous (“ring”) lesion.

VL has an incubation period of 2-4 months, although it has been reported to be as long as 2 years. Most infected persons remain asymptomatic during the acute phase. When VL evolves to the clinically evident form, classic symptoms include fever, weight loss, weakness, diarrhea, dysentery, and abdominal swelling. The typical triad of diagnostic findings consists of anemia, fever, and hepatosplenomegaly. Complications of the acute infection arise typically from superimposed bacterial infection, sometimes exacerbated by the neutropenia that can result from bone marrow infiltration. Cytokine disruption is probably critical in determining the clinical presentation and in mediating the outcome of infection, even with treatment (Murray et al. 2005). The predominant cell-mediated immune response is characterized by activity of Th1-type CD4+

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