Model-Based Investigations of Different Vector-Related Intervention Strategies to Eliminate Visceral Leishmaniasis on the Indian Subcontinent

The elimination of infectious diseases requires reducing transmission below a certain threshold. The Visceral Leishmaniasis (VL) Elimination Initiative in Southeast Asia aims to reduce the annual VL incidence rate below 1 case per 10,000 inhabitants in endemic areas by 2015 via a combination of case management and vector control. Using a previously developed VL transmission model, we investigated transmission thresholds dependent on measures reducing the sand fly density either by killing sand flies (e.g., indoor residual spraying and long-lasting insecticidal nets) or by destroying breeding sites (e.g., environmental management). Model simulations suggest that elimination of VL is possible if the sand fly density can be reduced by 67% through killing sand flies, or if the number of breeding sites can be reduced by more than 79% through measures of environmental management. These results were compared to data from two recent cluster randomised controlled trials conducted in India, Nepal and Bangladesh showing a 72% reduction in sand fly density after indoor residual spraying, a 44% and 25% reduction through the use of long-lasting insecticidal nets and a 42% reduction after environmental management. Based on model predictions, we identified the parameters within the transmission cycle of VL that predominantly determine the prospects of intervention success. We suggest further research to refine model-based predictions into the elimination of VL. Author Summary Visceral leishmaniasis is suspected to be the second largest parasitic killer in the world after malaria. On the Indian subcontinent, the vector-borne disease is caused by the protozoan flagellate Leishmania donovani and transmitted by the sand fly Phlebotomus argentipes. The regional elimination programme has suggested as a target line to reduce the annual incidence below 1 case in 10,000 by 2015. Using a previously developed mathematical model, we investigated to what extent the sand fly population must be controlled to achieve elimination. These calculated thresholds were compared to data from two recent trials conducted in India, Nepal and Bangladesh to evaluate the efficacy of different vector control measures. Our results indicate that elimination should be feasible because the evaluated effect of indoor residual spraying exceeds the threshold. However, emerging insecticide resistance may compromise the effectiveness of this measure. The observed effects of long lasting insecticidal nets and environmental management do not seem to be sufficient to reach either threshold. Integrated vector management based on indoor residual spraying combined with long lasting insecticidal nets and more effective environmental management may allow overcoming the limitations of the current vector control methods and should also prevent re-emergence of the infection after local extinction.