Heterogeneity in malaria exposure and vaccine response: implications for the interpretation of vaccine efficacy trials

White, MT; Griffin, JT; Drakeley, CJ; Ghani, AC; (2010) Heterogeneity in malaria exposure and vaccine response: implications for the interpretation of vaccine efficacy trials. Malaria Journal, 9. ISSN 1475-2875 DOI: https://doi.org/10.1186/1475-2875-9-82

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Background: Phase III trials of the malaria vaccine, RTS, S, are now underway across multiple sites of varying transmission intensity in Africa. Heterogeneity in exposure, vaccine response and waning of efficacy may bias estimates of vaccine efficacy. Methods: Theoretical arguments are used to identify the expected effects of a) heterogeneity in exposure to infectious bites; b) heterogeneity in individual's response to the vaccine; and c) waning efficacy on measures of vaccine efficacy from clinical trials for an infection-blocking vaccine. Results: Heterogeneity in exposure and vaccine response leads to a smaller proportion of trial participants becoming infected than one would expect in a homogeneous setting. This causes estimates of vaccine efficacy from clinical trials to be underestimated if transmission heterogeneity is ignored, and overestimated if heterogeneity in vaccine response is ignored. Waning of vaccine efficacy can bias estimates of vaccine efficacy in both directions. Conclusions: Failure to account for heterogeneities in exposure and response, and waning of efficacy in clinical trials can lead to biased estimates of malaria vaccine efficacy. Appropriate methods to reduce these biases need to be used to ensure accurate interpretation and comparability between trial sites of results from the upcoming Phase III clinical trials of RTS, S.

Item Type: Article
Keywords: plasmodium-falciparum malaria, circumsporozoite protein vaccine, antibody-responses, mozambican children, african children, public-health, transmission, infection, morbidity, mortality, Animals, Bias (Epidemiology), Biometry, Clinical Trials as Topic, Clinical Trials, Phase III as Topic, Computer Simulation, Humans, Insect Bites and Stings, Malaria Vaccines, immunology, Malaria, Falciparum, immunology, prevention & control, transmission, Models, Theoretical
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Malaria Centre
PubMed ID: 20331863
Web of Science ID: 276657500001
URI: http://researchonline.lshtm.ac.uk/id/eprint/3791


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