Visceral Leishmaniasis: New Health Tools Are Needed

Extract from an article in the Public Library of Science Medicine PLoS Med 2{7}:e211.

> Current Treatments: Old, Toxic, and Difficult to Deliver
For many decades, the treatment of VL has been based on pentavalent antimonials, such as sodium stibogluconate or meglumine antimoniate, given intramuscularly or intravenously for one month.

Discovered 60 years ago, sodium stibogluconate remains the mainstay treatment of VL despite its cardiotoxicity in some patients. Treatment requires 30 days of intramuscular or intraveneous injections in a hospital setting. Although it is still effective in most endemic countries, with 95% cure rates, resistance is increasing in some regions, especially in northern Bihar, India, where it is up to 65%.
Other drugs, such as amphotericin B (Fungizone), liposomal amphotericin B (AmBisome), and miltefosine (Impavido), are available for the treatment of VL but are not optimal due to problems of toxicity, high price, or difficulty in administration.

> Developing New Drug
Given the problems associated with the handful of currently available drugs for VL, new and improved treatments to replace or complement existing therapy are needed urgently.
Drug combinations for treating VL should provide advantages of protection from parasite resistance, as well as a reduction in treatment duration and overall toxicity.
Paromomycin (also known as aminosidine), an antibiotic of the aminoglycoside family with proven anti-leishmanial activity, is a candidate drug for treatment of VL. Early clinical studies in Kenya and India have shown that this drug is effective in the treatment of VL. The current treatment regimen for paromomycin is 21 days when used as a single agent, but could be reduced to 17 days when used in combination with sodium stibogluconate, as field experience of Médecins Sans Frontières has shown (unpublished data).

The Drugs for Neglected Diseases Initiative is currently carrying out phase III clinical trials of paromomycin in east Africa with a view to registering the drug in Ethiopia, Sudan, and Kenya.
The Institute for OneWorld Health, a nonprofit pharmaceutical company, has conducted phase III trials of paromomycin and is pursuing registration in India.

> The Challenges Ahead
Progress towards the discovery of an effective vaccine against leishmaniasis has become a snail's race. Therefore, control of leishmaniasis by vaccines remains only a long-term goal.
Many leishmaniasis experts nowadays advocate vector control, especially for areas of anthroponotic transmission.

History relates that in India VL was kept under control, inadvertently, by the large-scale spraying of DDT during anti-malaria campaigns. Recent initiatives of the World Health Organization aim to eliminate VL from the Indian subcontinent by house-to-house spraying of DDT and to reduce epidemic CL in Kabul by a massive provision of insecticide-treated nets. Such nets have been used to reduce transmission of anthroponotic CL in Afghanistan.
Personal protection against the bites of Phlebotomus orientalis by insecticide-treated nets was considered a feasible VL control approach in Sudan]. In Latin America, and even more so in southern Europe, where VL is principally maintained by the domestic dog, opinions about control of VL are divided. In Southern Europe, the situation is further compounded by the increasing incidence of adult VL that is associated with HIV co-infection.
In Africa, VL is transmitted mainly in rural areas either from a zoonotic source (in sporadic endemic areas) or human to human in secondarily anthroponotic foci. Owing to the complexity and diversity of transmission patterns, but also absence of health-care settings, control of VL in the African endemic countries will indeed be challenging.
In Ethiopia, HIV co-infection in some endemic areas of VL ranges from 15%–40%, and is known to be much higher in hospitals in big cities. Significant co-infection rates are being documented in Sudan. In these countries, the surveillance of HIV co-infection in VL endemic areas has to be an integral component of national VL control programmes.
The VL endemic countries provide a unique challenge to clinical research and development. Although the parasite also occurs in poor semi-urban environments, communities of affected patients are generally remote and far from health services. Government budgets are inadequate and health ministries are overstretched with many calls on their resources. In many areas hospital facilities are absent or underdeveloped. Tools for screening and identification of patients are inadequate. Current diagnostic techniques are invasive and complicated, and require trained staff. Treatments are toxic, expensive, and difficult to administer. These limitations have constrained the improvement of access to treatment. On the other hand, treatment possibilities by single-dose regimens of liposomal amphotericin B as well as the availability of miltefosine as an oral treatment of VL may provide opportunities for the development of simplified treatment regimes.

Hailu A., Musa A.M., Royce C., Wasunna M.

VL – visceral leishmaniasis
CL – cutaneous leishmaniasis