Leishmaniasis: Recognition and management with a focus on the immunocompromised patient

Leishmaniasis is a protozoan disease whose clinical manifestations depend both on the infecting species of Leishmania and the immune response of the host. Transmission of the disease occurs by the bite of a sandfly infected with Leishmania parasites. Infection may be restricted to the skin in cutaneous leishmaniasis (CL), to the mucous membranes in mucosal leishmaniasis or spread internally in visceral leishmaniasis (VL). In the last 2 decades, leishmaniasis, especially VL, has been recognized as an opportunistic disease in immunocompromised patients, particularly those infected with HIV. Leishmaniasis is characterized by a spectrum of disease phenotypes that correspond to the strength of the host's cell-mediated immune response. Both susceptible and resistant phenotypes exist within human populations. Clinical cutaneous disease ranges from a few spontaneously-healing lesions, to diffuse external or internal disease, to severe mucous membrane involvement. Spontaneously-healing lesions are associated with positive antigen-specific T cell responsiveness, diffuse cutaneous and visceral disease with T cell non-responsiveness, and mucocutaneous disease with T cell hyperresponsiveness. Current research is focused on determining the extent to which this spectrum of host response is genetically determined. In endemic areas, diagnosis is often made on clinical grounds alone including: small number of lesions; on exposed areas; present for a number of months; resistant to all types of attempted treatments; and usually no pain or itching. Multiple diagnostic techniques are available. When evaluating treatment, the natural history of leishmaniasis must be considered. Lesions of CL heal spontaneously over 1 month to 3 years, while lesions of mucocutaneous and VL rarely, if ever, heal without treatment. Consequently, all the latter patients require treatment. Therapy is not always essential in localized CL, although the majority of such patients are treated. Patients with lesions on the face or other cosmetically important areas are treated to reduce the size of the resultant scar. In addition, the species of parasite should be identified so that infection with Leishmania braziliensis and Leishmania panamensis can be treated to reduce the risk of development of mucocutaneous disease. Treating patients with Leishmania and HIV co-infection requires close monitoring for effectiveness of treatment, especially because of the high relapse rates. Proven treatments include: antimonials, pentamidine, amphotericin B, interferon with antimony. Treatments where current clinical experience is too limited include: allopurinol, ketoconazole, itraconazole, immunotherapy, rifampin, dapsone, localized heat, paromomycin ointment and cryotherapy. Investigational treatments include: WR6026, liposomal amphotericin and miltefosine. In addition, vaccines for leishmaniasis are being investigated in clinical trials.