Predicting the likelihood and intensity of mosquito infection from sex specific Plasmodium falciparum gametocyte density
- London School of Hygiene and Tropical Medicine, United Kingdom
- Radboud University Medical Center, Netherlands
- Institut de Recherche en Sciences de la Santé, Burkina Faso
- Institut de Recherche pour le Développement, France
- University of Science, Techniques and Technologies of Bamako, Mali
- Centre National de Recherche et de Formation sur le Paludisme, Burkina Faso
- Université de Douala, Cameroon
- University of California, San Francisco, United States
- Imperial College London, United Kingdom
- Cited 26
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Abstract
Understanding the importance of gametocyte density on human-to-mosquito transmission is of immediate relevance to malaria control. Previous work (Churcher et al., 2013) indicated a complex relationship between gametocyte density and mosquito infection. Here we use data from 148 feeding experiments on naturally infected gametocyte carriers to show that the relationship is much simpler and depends on both female and male parasite density. The proportion of mosquitoes infected is primarily determined by the density of female gametocytes though transmission from low gametocyte densities may be impeded by a lack of male parasites. Improved precision of gametocyte quantification simplifies the shape of the relationship with infection increasing rapidly before plateauing at higher densities. The mean number of oocysts per mosquito rises quickly with gametocyte density but continues to increase across densities examined. The work highlights the importance of measuring both female and male gametocyte density when estimating the human reservoir of infection.
Article and author information
Author details
Funding
Bill and Melinda Gates Foundation (AFIRM OPP1034789)
- Chris Drakeley
- Teun Bousema
European Commission (ERC-2014-StG 639776)
- Will Stone
- Teun Bousema
PATH (Malaria Vaccine Iniative)
- Dari FA DA
- Isabelle Morlais
- Anna Cohuet
- Teun Bousema
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Urszula Krzych, Walter Reed Army Institute of Research, United States
Publication history
- Received: December 21, 2017
- Accepted: May 26, 2018
- Accepted Manuscript published: May 31, 2018 (version 1)
- Version of Record published: June 21, 2018 (version 2)
Copyright
© 2018, Bradley et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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Multiple studies have reported a male bias in incidence and/or prevalence of malaria infection in males compared to females. To test the hypothesis that sex-based differences in host-parasite interactions affect the epidemiology of malaria, we intensively followed Plasmodium falciparum infections in a cohort in a malaria endemic area of eastern Uganda and estimated both force of infection (FOI) and rate of clearance using amplicon deep-sequencing. We found no evidence of differences in behavioral risk factors, incidence of malaria, or FOI by sex. In contrast, females cleared asymptomatic infections at a faster rate than males (hazard ratio [HR]=1.82, 95% CI 1.20 to 2.75 by clone and HR = 2.07, 95% CI 1.24 to 3.47 by infection event) in multivariate models adjusted for age, timing of infection onset, and parasite density. These findings implicate biological sex-based differences as an important factor in the host response to this globally important pathogen.
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Case fatality rates in severe falciparum malaria depend on the pattern and degree of vital organ dysfunction. Recent large-scale case-control analyses of pooled severe malaria data reported that glucose-6-phosphate dehydrogenase deficiency (G6PDd) was protective against cerebral malaria but increased the risk of severe malarial anaemia. A novel formulation of the balancing selection hypothesis was proposed as an explanation for these findings, whereby the selective advantage is driven by the competing risks of death from cerebral malaria and death from severe malarial anaemia. We re-analysed these claims using causal diagrams and showed that they are subject to collider bias. A simulation based sensitivity analysis, varying the strength of the known effect of G6PDd on anaemia, showed that this bias is sufficient to explain all of the observed association. Future genetic epidemiology studies in severe malaria would benefit from the use of causal reasoning.
