Modelling heterogeneity and the impact of chemotherapy and vaccination against human hookworm.

There is a growing emphasis on the development of vaccines against helminths (worms), and mathematical models provide a useful tool to assess the impact of new vaccines under a range of scenarios. The present study describes a stochastic individual-based model to assess the relative impact of chemotherapy and vaccination against human hookworm infection and investigates the implications of potential correlations between risk of infection and vaccine efficacy. Vaccination is simulated as a reduction in susceptibility to infection and the model includes population heterogeneities and dynamical waning of protection. To help identify appropriate measures of vaccine impact, we present a novel framework to quantify the vaccine impact on the infection-associated morbidity and introduce a measure of symmetry to study the correspondence between reduction in intensity and reduction in morbidity. Our modelling shows that, in high-transmission settings, the greatest impact of vaccination will be attained when vaccine efficacy is the greatest among individuals harbouring the heaviest worm burdens, and that the decline of morbidity primarily depends on the level of protection attained in the most at risk 8-12% of the population. We also demonstrate that if risk of infection and vaccine protection are correlated, there is not always a direct correspondence between the reduction in worm burden and in morbidity, with the precise relationship varying according to transmission setting.