Manica Balasegaram: New treatment options for the control of visceral leishmaniasis

Manica BalasegaramA recent report by Médecins Sans Frontières (MSF) of an outbreak of visceral leishmaniasis (VL) in southern Sudan comes at a time when increasing focus is being put on the control and elimination of neglected diseases. However, this outbreak raises questions of how far along we really are in reaching such targets.

VL (also known as kala azar) is one of the deadliest parasitic diseases in the world, with an estimated half a million new cases each year. Spread by the bites of sandflies, VL severely affects the liver, spleen, and bone marrow, and if left untreated is almost always fatal. Yet the disease remains largely unknown in the developed world.

The control of VL, particularly in the anthroponotic areas of transmission (south Asia and east Africa), has focused around vector control and treatment. In terms of treatments, VL appears to be fairly well served in comparison with other neglected diseases. There are several drugs available, including antimonials (eg, sodium stibogluconate or glucantime), amphotericin B, parmomomycin, and miltefosine (the only available oral drug against the disease). However, all these treatments have various problems, including cost, toxicity, long treatment courses, and low feasibility in the field setting. To achieve the objective of elimination, a tailor-made drug for the disease that only would require a few pills of a very cheap (a few dollars), safe, and effective treatment is needed.

Nonetheless, considerable efforts have been made recently to improve options for patients. On the development side, pivotal trials on combinations of these drugs (such as sodium stibogluconate & paromomycin, AmBisome & paromomycin, AmBisome & miltefosine, miltefosine & paromomycin; data in publication) and on a single dose AmBisome have recently been completed in both Africa and Asia. The results of these trials indicate good safety and efficacy. These treatments could be available for use over the next year. There is also ongoing research looking at various promising potential candidates for clinical development. The goal of such research is to develop a safe, short course (7 day) oral treatment that can be used at the most basic healthcare level. These investments could pay off in the near future, since it is possible that a clinical candidate may be available for development within the next 1–2 years.
This sounds all very exciting, except for a couple of major issues. Firstly, drug development does not equate to drug implementation. While resources are required and have been invested in research, it is paramount that much more resources are dedicated towards roll-out of treatment to ensure that patients get access to these life-saving drugs. This is particularly relevant in regions such as south Sudan, where the recent outbreak has been reported. The fact that MSF are so actively involved in treating VL patients in several countries is an illustration in itself that insufficient resources are being invested by both governments and donors (both private and public) towards control and implementation activities including case detection, treatment, surveillance, and prevention. There have been some signs of activity, particularly in south Asia where a regional commitment has been made between India, Nepal, and Bangladesh to eliminate the disease. However, more efforts need to filter down into field level so that sufficient equipment, drugs, and trained personnel are made available to control the disease.

Another major issue is that VL, like so many neglected diseases, is very much a disease of neglected populations; specifically groups that are poor, marginalised, and living in rural, peri-conflict, or unstable environments. The further impoverishing effect of the disease is now also well documented. It is therefore questionable that we can ever truly eliminate these diseases without first a considerable improvement in the lives of the populations in the endemic areas. A recent study I read looking at risk factors for VL in India even concluded that “improving housing conditions for the poor has the potential to reduce VL incidence.” The implication is that the long-term solution to tackling these types of diseases perhaps lies beyond the scope of research and medicine, and that a serious effort needs to be made at a political, social, and economic level to tackle the eternal pandemics of poverty and inequity. In the meantime, it’s best that the rest of us continue our day jobs in trying to find more mundane, “less ambitious” solutions.

Manica Balasegaram is a physician who works for the Drugs for Neglected Diseases initiative where he is the head of the leishmaniasis clinical programme.

This blog also appears on the PLoS Speaking of Medicine site.