Abstract
Malaria transmission remains high in Sub-Saharan Africa despite large-scale implementation of malaria control interventions. A comprehensive understanding of the transmissibility of infections to mosquitoes may guide the design of more effective transmission reducing strategies. The impact of P. falciparum sexual stage immunity on the infectious reservoir for malaria has never been studied in natural settings. Repeated measurements were carried out at start-wet, peak-wet and dry season, and provided data on antibody responses against gametocyte/gamete antigens Pfs48/45 and Pfs230 as anti-gametocyte immunity. Data on high and low-density infections and their infectiousness to anopheline mosquitoes were obtained using quantitative molecular methods and mosquito feeding assays, respectively. An event-driven model for P. falciparum sexual stage immunity was developed and fit to data using an agent based malaria model infrastructure. We found that Pfs48/45 and Pfs230 antibody densities increased with increasing concurrent gametocyte densities; associated with 55–70% reduction in oocyst intensity and achieved up to 44% reduction in proportions of infected mosquitoes. We showed that P. falciparum sexual stage immunity significantly reduces transmission of microscopic (p < 0.001) but not submicroscopic (p = 0.937) gametocyte infections to mosquitoes and that incorporating sexual stage immunity into mathematical models had a considerable impact on the contribution of different age groups to the infectious reservoir of malaria. Human antibody responses to gametocyte antigens are likely to be dependent on recent and concurrent high-density gametocyte exposure and have a pronounced impact on the likelihood of onward transmission of microscopic gametocyte densities compared to low density infections. Our mathematical simulations indicate that anti-gametocyte immunity is an important factor for predicting and understanding the composition and dynamics of the human infectious reservoir for malaria.
Highlights
The 2007 call issued by Bill and Melinda Gates for malaria eradication [1] has rapidly gained momentum
Submicroscopic gametocyte infections are efficiently transmitted from humans to mosquitoes in settings with efficient malaria vectors and may pose challenges for malaria control and elimination efforts
We assess the impact of naturally acquired anti-gametocyte antibodies on malaria transmission to mosquitoes and on the age-dependent composition of the infectious reservoir and seasonal dynamics
Summary
The 2007 call issued by Bill and Melinda Gates for malaria eradication [1] has rapidly gained momentum. More than a dozen countries in SubSaharan Africa, representing approximately 80% of the remaining global malaria burden, still need to considerably improve malaria control interventions substantially to reach levels of transmission that are suitable for elimination strategies [6]. In these countries where climate [7] and ecological conditions favor the vector’s life cycle, malaria transmission remains high and is likely compounded by under-resourced health care systems, resilient vector populations, and, obligatory for ongoing transmission, a reservoir of infectious individuals [8,9,10,11]. Parasite detection or quantification form imperfect proxies for the infectious reservoir of malaria that can currently only be assessed by mosquito feeding assays [18,19,20]
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