The potential impact of human visceral leishmaniasis vaccines on population incidence.

Epke A Le Rutte,Sake J De Vlas,Stefano Malvolti,Paul M Kaye,Luc E Coffeng,Angamuthu Selvapandiyan

doi:10.1371/journal.pntd.0008468

Abstract

Human visceral leishmaniasis (VL) vaccines are currently under development and there is a need to understand their potential impact on population wide VL incidence. We implement four characteristics from different human VL vaccine candidates into two published VL transmission model variants to estimate the potential impact of these vaccine characteristics on population-wide anthroponotic VL incidence on the Indian subcontinent (ISC). The vaccines that are simulated in this study 1) reduce the infectiousness of infected individuals towards sand flies, 2) reduce risk of developing symptoms after infection, 3) reduce the risk of developing post-kala-azar dermal leishmaniasis (PKDL), or 4) lead to the development of transient immunity. We also compare and combine a vaccine strategy with current interventions to identify their potential role in elimination of VL as a public health problem. We show that the first two simulated vaccine characteristics can greatly reduce VL incidence. For these vaccines, an approximate 60% vaccine efficacy would lead to achieving the ISC elimination target (<1 VL case per 10,000 population per year) within 10 years' time in a moderately endemic setting when vaccinating 100% of the population. Vaccinating VL cases to prevent the development of PKDL is a promising tool to sustain the low incidence elimination target after regular interventions are halted. Vaccines triggering the development of transient immunity protecting against infection lead to the biggest reduction in VL incidence, but booster doses are required to achieve perduring impact. Even though vaccines are not yet available for implementation, their development should be pursued as their potential impact on transmission can be substantial, both in decreasing incidence at the population level as well as in sustaining the ISC elimination target when other interventions are halted.

Highlights

Visceral leishmaniasis (VL), known as kala-azar, is a vector-borne neglected tropical disease
We show that some vaccines have high potential to reduce VL incidence, namely those that reduce the infectiousness of infected individuals to sand flies and those that reduce the chance of developing symptoms once infected
Vaccines that prevent the development of post-kala-azar dermal leishmaniasis are a promising tool to sustain low VL incidence and prevent recrudescence of infection when regular interventions are halted

Summary

Introduction

Visceral leishmaniasis (VL), known as kala-azar, is a vector-borne neglected tropical disease. Infection occurs after successful transmission of the Leishmania protozoa through the bite of an infected female sand fly [1]. Most infected humans remain asymptomatic, and only a small proportion of about 1–10% develop clinical symptoms, resulting in death when left untreated [2,3]. Between 5% and 20% of treated VL cases develop a long-lasting skin condition known as post-kala-azar dermal leishmaniasis (PKDL). Recent studies have identified that individuals with PKDL are infectious towards sand flies as VL cases, making them an important reservoir of infection [4,5]. The contribution of asymptomatic individuals to transmission has not yet been defined [4,6]. A period of immunity follows, of which the duration remains debated

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Conclusion