Site of infection: Amastigotes invade macrophage cells of the reticuloendothelial and lymphoid systems of the skin, nasopharynx or viscera depending on the parasite species. The parasites survive within phagosomes but resist digestion by lysosomal enzymes. They multiply and grow, ultimately rupturing the host cell and releasing stages to infect new macrophages, including those which circulate in the blood (monocytes).

Pathogenesis: The parasites cause three distinct types of clinical disease, cutaneous, mucocutaneous and visceral leishmaniasis. Old World cutaneous leishmaniasis is caused by L. tropica and L. aethiopica while New World cutaneous leishmaniasis is caused by L. mexicana and L. braziliensis. Infections generally involve only one or a few lesions at the bite site; they do not spread to other sites. Active lesions appear as open sores/ulcers with pronounced inflammation. Most lesions heal spontaneously, leaving the host with solid protective immunity to re-infection. However, under certain conditions (esp. immuno-compromised hosts), some L. aethiopica infections may spread giving rise to disseminated cutaneous leishmaniasis (not unlike leprosy in appearance). Infections by L. braziliensis are also often confined to single skin lesions, but sometimes they spread to the mucocutaneous junction in the pharynx and may cause severe destructive nasopharyngeal lesions. Visceral leishmaniasis is caused by L. donovani whereby infected macrophages congregate in the viscera, notably the liver and spleen, producing hepatosplenomegaly, oedema and anaemia. It is a slow but progressive illness, with bouts of irregularly recurring fever, and is invariably fatal, unless treated.

Mode of transmission: All species are transmitted by small blood-sucking sandflies, notably Phlebotomus spp. in the Old World and Lutzomyia spp. in the New World. Only the females feed on blood. Amastigotes ingested during feeding transform in the midgut or hindgut into promastigotes which multiply by binary fission. The parasites migrate forward to the foregut and proboscis where some become swept away by saliva into the bite site when the fly feeds.

Differential diagnosis: Amastigotes may be detected microscopically in biopsy tissues, smears or secretions before or after culture. Parasites are best visualized using Giemsa’s or Leishman’s stains, and suitable culture media include conventional nutrient agar-blood mixtures. Serological tests have been developed but there are difficulties in distinguishing between recent and chronic infections and between infections by different parasite species, although a delayed-type hypersensitivity (DTH) skin test has shown good promise as a marker of cured symptomatic or asymptomatic visceral infection. Modern molecular characterization techniques have used the polymerase chain reaction (PCR) to amplify parasite DNA from host tissues.

Treatment and control: Some cutaneous infections require no treatment as lesions may heal within several months. Systemic therapy with pentavalent antimonials (sodium stibogluconate or meglumine antimonate) is the treatment of choice for disfiguring and visceral infections. The development of antimonial drug resistance, however, is a growing problem in many endemic areas, including South America, India and the Middle-East. Pentamidine or amphotericin B can be used if antimonials are ineffective, and miltefosine and aminosidine (paromomycin) have shown promise as treatment options, especially when combined with immunotherapy using the tumour-necrosis factor-alpha (TNF-?) inhibitor pentoxifylline. Preventive measures include protection from sandfly bites but this can be difficult as they are so small that they can penetrate most mosquito nets. Reducing the size of reservoir host populations (especially dogs) has proven beneficial in many endemic urban areas. Many cutaneous infections, however, are acquired in forests away from human habitation, as the reservoir hosts are wild animals (esp. rodents). The prevention of sandfly bites in forest areas is almost impossible but may be minimized by the use of protective clothing, insect repellants and insecticidal sprays in houses.

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