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Research Project: Biological Control of Invasive Arthropod Pests from the Eastern Hemisphere

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Title: Understanding the transmission dynamics of Leishmania donovani to provide robust evidence for interventions to eliminate visceral leishmaniasis in Bihar, India

item CAMERON, M - London School Of Hygiene & Tropical Medicine
item ACOSTA-SERRANO, A - Liverpool School Of Tropical Medicine
item BERN, C - University Of California
item BOELAERT, M - Institute Of Tropical Medicine
item DEN BOER, MARGRIET - Kalacore
item CHAPMAN, L - University Of Warwick
item CHASKOPOULOU, ALEXANDRA - European Biological Control Laboratory (EBCL)
item COLEMAN, M - Liverpool School Of Tropical Medicine
item CROFT, S - London School Of Hygiene & Tropical Medicine
item COURTNEY, O - University Of Warwick

Submitted to: Parasites & Vectors
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/6/2015
Publication Date: 1/27/2016
Citation: Cameron, M., Acosta-Serrano, A., Bern, C., Boelaert, M., Den Boer, M., Chapman, L., Chaskopoulou, A., Coleman, M., Croft, S., Courtney, O. et al. 2016. Understanding the transmission dynamics of Leishmania donovani to provide robust evidence for interventions to eliminate visceral leishmaniasis in Bihar, India. Parasites & Vectors. 9:25 DOI: 10.1186/s13071-016-1309-8.

Interpretive Summary: Visceral Leishmaniasis (VL), or kala-azar, is a neglected vector-borne disease that affects many people in the world. It is transmitted by biting sand flies, Phlebotomus argentipes, that carry the pathogen, Leishmania donovani. In 2005, the governments of India, Nepal and Bangladesh, in collaboration with the World Health Organization (WHO), developed a strategic framework to eliminate VL as a public health problem by 2015. This was defined as reducing the annual VL incidence below 1/10,000 people. The elimination strategy consists of rapid case detection, treatment of VL cases and vector control using indoor residual spraying (IRS). DDT has been used in India to control the vector; however, it appears to now be ineffective because of development of resistance by the vector and change in its behavior to spend more time outdoors, where insecticides are not applied. The use of alpha-cypermethrin is now being tested as a possible substitute for DDT, but successful elimination of the disease will require a comprehensive epidemiological approach. This paper reviews the current state of knowledge to identify gaps that should be targeted by future research to help design a post elimination surveillance programme.

Technical Abstract: Molecular tools enable the collection of accurate estimates of human blood index (HBI) in P. argentipes. The refinement of a metacyclic-specific qPCR assay to identify L. donovani in P. argentipes would enable quantification of the entomological inoculation rate (EIR) for the first time. Likewise, a set of prototype infection/exposure markers is currently available for which proof of concept and pilot laboratory data are already available and, if proven robust in larger-scale field evaluation, these markers will prove invaluable for future intervention trials of novel vector control methods and will provide essential population-based information on the long-term impact of interventions to inform a successful endgame for VL elimination. A longitudinal study using these tools, in a representative number of intervention and control villages in different endemic districts is needed to determine whether pyrethroid-based IRS can reduce P. argentipes population densities to the critical level required to interrupt disease transmission. In addition to acquiring data to determine whether densities of P. argentipes females are lowered following intervention, precise entomological indices for P. argentipes (HBI and EIR) should be calculated to improve epidemiological models of VL. In parallel, improved diagnostic tools can be used to measure clinical outcomes when the number of active cases is very low. By collecting contemporary entomological and human data in the same geographical locations and over a 2-year period, more precise epidemiological models can be produced, which are essential to inform the NVBDCP during the VL elimination endgame. The refined models will have the following applications: 1) predicting the reduction in disease that can be achieved using different intervention scenarios, 2) identifying hotspots for transmission and control, and 3) determining whether xenomonitoring of P.argentipes can be used in routine surveillance programmes, with an appropriate rapid response, to prevent VL transmission. In addition, the suite of data collected can be used to inform the NVBDCP if supplementary control tools, in addition to IRS, are required to address the issues of people sleeping outside during months when sand fly densities are at their highest. Also, knowing whether the proportion of P. argentipes becoming exophilic, as a consequence of IRS, is increasing would be invaluable. There are a limited number of vector control tools available to roll out in disease control programmes that specifically target exophilic sand flies. One approach has been to treat cattle with systemic insecticide and another is the targeted use of insecticides on localised vegetation or for the development of optimised attractive toxic sugar baits sand flies. Should the refined models indicate that exophilic transmission impedes success at reaching the VL elimination target in endemic areas, further basic research will be required to develop additional tools to tackle this problem.