Visceral leishmaniasis: elimination with existing interventions

Summary

The world's burden of infectious diseases can be substantially reduced by more-effective use of existing interventions. Advances in case detection, diagnosis, and treatment strategies have made it possible to consider the elimination of visceral leishmaniasis in the Indian subcontinent. The priority must now be to effectively implement existing interventions at the community level by actively finding cases in endemic villages and treating them with single-dose liposomal amphotericin B at primary-health-care centres. Once the elimination target of one case per 10 000 population has been reached, combination therapies involving miltefosine and paromomycin can be introduced to ensure long-term availability of several drugs for visceral leishmaniasis and to protect against resistance.

Introduction

Leishmaniasis is one of the neglected tropical diseases (NTD) of poverty, along with trypanosomiasis, filariasis, schistosomiasis, onchocerciasis, and others.1, 2 NTD are chronic, disfiguring, disabling, and frequently stigmatising disorders. They are largely confined to rural areas of the developing world and contribute to global health disparities between rich and poor countries.³ Many of these diseases, including leishmaniasis and trypanosomiasis, are fatal if left untreated. More than 1 billion people, around a sixth of the worldwide population, are affected by NTD. Whereas there is no shortage of high-quality research on these diseases, the translation of basic scientific discoveries into therapeutic interventions has not met with expectations. This disparity is particularly problematic for NTD where development of treatments would yield low returns on investments for drug companies and an academic culture that frequently rewards publication over the identification of practical solutions to implement available interventions.

Although not ideal, diagnostic methods, treatments, and vector control measures for many of these diseases do exist. Successful implementation of existing interventions requires strong political commitment, close collaboration between scientists, local health-care providers, and policy makers, and support from agencies, such as WHO. The impact of effective implementation would be to reduce the burden of disease through empowering local health-care providers in endemic countries to deliver the best available interventions in an affordable and sustainable way.

An example of where implementation research would have substantial impact is in countries where anthroponotic visceral leishmaniasis caused by Leishmania donovani is endemic. Progress in the development of drugs and diagnostics⁴ has opened a window of opportunity for effective control or even elimination of this lethal disease from the Indian subcontinent. Leishmaniasis overall (including visceral, cutaneous, and mucocutaneous forms) carries the ninth highest disease burden of all infectious diseases worldwide.1, 2, 5 More than 500 000 visceral leishmaniasis cases per year are reported, leading to an estimated 59 000 deaths, predominantly in India, Bangladesh, Nepal, and the Sudan.1, 5 Visceral leishmaniasis is, however, substantially under-reported, with reports of its extent varying not only from country to country, but also from district to district within a country.¹

Visceral leishmaniasis targets the poorest communities, and children, young adults, and women are disproportionately affected.1, 3 Certain epidemiological features of visceral leishmaniasis in the Indian sub-continent, however, make elimination of this disease in the region a realistic goal: human beings are the only reservoir; only one of the sandfly vector species, Phlebotomus argentipes, transmits L donovani, and it is susceptible to insecticides, and the geographic distribution is limited and highly clustered. Implementation of cost-effective, evidence-based, sustainable strategies for control would result in a striking reduction in the number of visceral leishmaniasis infections and, potentially, in the elimination of this disease as a public health problem. Development of such strategies would also establish benchmarks and local human resource expertise while new drugs and vaccines become available for leishmaniasis and other NTD in this region.

Early diagnosis and complete treatment are essential for the management of visceral leishmaniasis, as treatment delay can adversely effect prognosis.⁶ Moreover, untreated infected individuals constitute a reservoir for the parasite, which sustains disease transmission in communities with anthroponotic visceral leishmaniasis. Patients with dermal leishmaniasis after visceral leishmaniasis (termed post-kala-azar dermal leishmaniasis [PKDL]), where L donovani parasites are present in the skin, form another reservoir for transmission. To effectively reduce the human reservoir in south Asia, however, the part latent asymptomatic infections play in transmission needs to be established, since there are more latent infections than acute infections in endemic villages.⁷ Although this issue represents an important gap in knowledge that must be addressed, a programme of elimination with the best available existing interventions should proceed to effectively manage new cases and to continue to reduce the reservoir.