Personal View
Elimination of visceral leishmaniasis on the Indian subcontinent

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Summary

Visceral leishmaniasis is a serious public health problem on the Indian subcontinent, causing high morbidity and mortality. The governments in the region launched a visceral leishmaniasis elimination initiative in 2005. We review knowledge gaps and research priorities. Key challenges include low coverage of health services for those most at risk, drug resistance, the absence of a vaccine, and the complex biology of the sandfly–human host transmission cycle. Vector control is an essential component, but innovation in this field is insufficient. Substantial progress has been made in the area of diagnostic, therapeutic, and vaccine development, but there are still many hurdles to overcome. For visceral leishmaniasis elimination to become a reality, effective deployment of these existing and new tools is essential. A strong commitment at community level is imperative, and appropriate diagnostic and treatment services as well as effective epidemiological surveillance need to be ensured.

Introduction

Among the world's poorest people, more than 1 billion are affected by one or more neglected tropical diseases.1, 2 Visceral leishmaniasis is one the most important disorders in this group, caused by intracellular protozoan parasites of the Leishmania donovani complex. Visceral leishmaniasis is ranked second in mortality and fourth in morbidity among neglected tropical diseases, with 20 000–40 000 deaths annually.3 Over 90% of the visceral leishmaniasis cases occur in India, Bangladesh, Sudan, South Sudan, Ethiopia, and Brazil, and the disease has been a serious impediment to socioeconomic development in these affected areas. Visceral leishmaniasis has never featured as a high priority in drug development programmes funded by the pharmaceutical industry because it is unlikely to yield good returns on research and development costs.

In 2005, the governments of India, Bangladesh, and Nepal launched a regional initiative to eliminate visceral leishmaniasis by 2015.4 Elimination was defined as reducing incidence to a level at which it would cease to be of public health importance—ie, less than one per 10 000 inhabitants per year at sub-district levels (known as blocks in India and Nepal, and upazilas in Bangladesh). Elimination of visceral leishmaniasis was considered to be an achievable goal for the following reasons: L donovani, the causative species, is transmitted in a human-to-human cycle in this region, without animal reservoir; there is only a single sandfly vector species, Phlebotomus argentipes, which is susceptible to insecticides; transmission is geographically restricted to a well-defined number of districts; and recent breakthroughs in diagnosis and treatment have resulted in a rapid diagnostic test and an oral drug, miltefosine.5 At the time of committing to the elimination strategy, the annual incidence of visceral leishmaniasis was as high as 22 per 10 000 people in some endemic districts of Bihar, India, in 2005. A peak was reached in 2007 when 44 533 cases were reported, after which there has been a decreasing trend (figure). To date, more than 70% of endemic blocks have achieved the elimination target.6, 7 Bangladesh has achieved the elimination targets in 90% of their endemic upazilas and has so far been able to sustain these low levels, with the number of visceral leishmaniasis endemic upazilas decreasing from 140 initially in 2005 to 16 in 2012 and six in 2014.8 In Nepal, elimination has been reached at district level, and has been sustained for the past 2 years.7

Although substantial progress has been made by the three countries,9, 10 they clearly fell short of their elimination target. Consequently, as countries remain committed to the goal of visceral leishmaniasis elimination, the original date was extended from 2015 to 2017.11 Why this delay? Were the initial assumptions flawed? Were the tools or the resources inadequate, and if so, what are the research and development needs? What is the outlook for achieving elimination in this region by 2017? Furthermore, is there scope to extend the ambition from eliminating visceral leishmaniasis as a public health problem (ie, reducing incidence to less than a specific threshold) to complete interruption of transmission? In this Personal View, we will assess the technical and operational aspects of visceral leishmaniasis elimination as a public health problem and try to address these questions.

Section snippets

Disease transmission and potential parasite reservoirs: the role of asymptomatically infected people and animals

It is an understatement to say that several factors in the transmission of visceral leishmaniasis are not yet clearly understood. The first assumption underlying the elimination initiative is that visceral leishmaniasis is an anthroponosis—ie, the transmission of the disease occurs between human beings by the sandfly P argentipes. Implicitly, only clinical human visceral leishmaniasis cases have been suggested as the source of pathogen transmission. This theory is not yet proven, and these

Is visceral leishmaniasis elimination operationally achievable?

Visceral leishmaniasis control in the Indian subcontinent has always hinged on two strategies: early case detection and treatment and vector control. Reaching the elimination target once has not much value in public health terms; the importance is in maintaining the incidence to less than that low threshold for the coming years. Case finding and surveillance activities therefore need to be maintained for several years, which will require community awareness and participation. Participation

What are the possible ways forward?

Essentially, successful and sustained visceral leishmaniasis elimination will depend on a better understanding of transmission, optimal use of existing tools, and development of new, more effective tools with which to interrupt the progression of the disease, and patients with PKDL in sustaining transmission. Xenodiagnosis studies are also required to investigate the potential role of domestic animals.

Moreover, concerted efforts should be directed towards the development of highly sensitive,

Concluding remarks

Despite many barriers and obstacles, substantial progress has been made over past years, and the visceral leishmaniasis elimination initiative in the Indian subcontinent has already saved many lives. Keeping visceral leishmaniasis at bay will diminish the cycle of poverty in the community; we believe that visceral leishmaniasis elimination as a public health problem is technically possible and operationally feasible, particularly following the renewed commitment by the three countries'

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