Visceral leishmaniasis (VL), also known as Kala-Azar, is the most severe form of leishmaniasis, a disease caused by parasites of the Leishmania genus. The parasite migrates to the visceral organs such as liver, spleen and bone marrow and if left untreated will almost always result in the death of the mammalian host. Symptoms include fever, weight loss, anaemia and substantial swelling of the liver and spleen. Of particular concern, according to the World Health Organization (WHO) is the emerging problem of HIV/VL co-infection^*.

Species that give rise to VL

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Several species of Leishmania are known to give rise to the visceral form of the disease. The "Old World" (Africa, Asia, Europe) species are L. donovani and L. infantum and the "New World" (South America) species is L. chagasi.

Transmission of the parasite

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As with the cutaneous and mucocutaneous forms, the sandfly is the insect vector for the disease. When the insect takes a blood meal from a potential mammalian host, the parasites which are located in the sandfly mouthparts (and are primed for mammalian cell infectivity) are left behind and taken up by host macrophages. Here, they differentiate into non-motile, dividing amastigote forms that survive within the host cells, thus avoiding the host immune response.

Treatments

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As with many diseases in developing nations, (including trypanosomiasis and malaria) effective and affordable chemotherapy is sorely lacking and parasites or insect vectors are becoming increasingly resistant to existing anti-parasite drugs. Presumably due to the lack of financial return, new drugs are slow to emerge and much of the basic research into potential drug targets takes place in universities, funded by charitable organisations. This may or may not change as a result of infection of members of the armed forces from the "developed" nations that currently occupy nations such as Afghanistan and Iraq, where Leishmania is commonplace.

The traditional treatment is with pentavalent antimonials such as sodium stibogluconate and meglumine antimoniate. Resistance is now common in India, and the treatment of choice for visceral leishmaniasis acquired in India is now Amphotericin B in its various preparations (Ambisome®, Abelcet®, Amphocil®)

• AmBisome dose: total dose 21mg/kg (Mediterranean/Brazilian VL); total dose 7.5mg/kg over 6 days (Indian VL)
• Amphocil dose: total dose 7.5mg/kg over 6 days (Indian VL)

A low dose (0.5–1mg/kg) is given on the first day, increasing to 1–2mg/kg on the second day, followed by 1.5–3mg/kg on the third and subsequent days.

Miltefosine is an oral treatment currently available only in India. Results of trials outside of India have been disappointing. There problems with toxicity (gastrointestinal and renal) as well as the rapid development of resistance. Because it is available as an oral formulation, the expense and inconvenience of hospitalisation is avoided, which makes it an attractive alternative.

References

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Parasitic diseases | Infectious diseases