Heterogeneity in malaria exposure and vaccine response: implications for the interpretation of vaccine efficacy trials
Abstract 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 t...
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ftdoajarticles:oai:doaj.org/article:fc4207f06a1b446c8bfc8f7f972aa855 2023-05-15T15:07:48+02:00 Heterogeneity in malaria exposure and vaccine response: implications for the interpretation of vaccine efficacy trials Drakeley Chris J Griffin Jamie T White Michael T Ghani Azra C 2010-03-01T00:00:00Z https://doi.org/10.1186/1475-2875-9-82 https://doaj.org/article/fc4207f06a1b446c8bfc8f7f972aa855 EN eng BMC http://www.malariajournal.com/content/9/1/82 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-9-82 1475-2875 https://doaj.org/article/fc4207f06a1b446c8bfc8f7f972aa855 Malaria Journal, Vol 9, Iss 1, p 82 (2010) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2010 ftdoajarticles https://doi.org/10.1186/1475-2875-9-82 2023-01-08T01:29:05Z Abstract 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 9 1 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Drakeley Chris J Griffin Jamie T White Michael T Ghani Azra C Heterogeneity in malaria exposure and vaccine response: implications for the interpretation of vaccine efficacy trials |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract 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. |
format |
Article in Journal/Newspaper |
author |
Drakeley Chris J Griffin Jamie T White Michael T Ghani Azra C |
author_facet |
Drakeley Chris J Griffin Jamie T White Michael T Ghani Azra C |
author_sort |
Drakeley Chris J |
title |
Heterogeneity in malaria exposure and vaccine response: implications for the interpretation of vaccine efficacy trials |
title_short |
Heterogeneity in malaria exposure and vaccine response: implications for the interpretation of vaccine efficacy trials |
title_full |
Heterogeneity in malaria exposure and vaccine response: implications for the interpretation of vaccine efficacy trials |
title_fullStr |
Heterogeneity in malaria exposure and vaccine response: implications for the interpretation of vaccine efficacy trials |
title_full_unstemmed |
Heterogeneity in malaria exposure and vaccine response: implications for the interpretation of vaccine efficacy trials |
title_sort |
heterogeneity in malaria exposure and vaccine response: implications for the interpretation of vaccine efficacy trials |
publisher |
BMC |
publishDate |
2010 |
url |
https://doi.org/10.1186/1475-2875-9-82 https://doaj.org/article/fc4207f06a1b446c8bfc8f7f972aa855 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 9, Iss 1, p 82 (2010) |
op_relation |
http://www.malariajournal.com/content/9/1/82 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-9-82 1475-2875 https://doaj.org/article/fc4207f06a1b446c8bfc8f7f972aa855 |
op_doi |
https://doi.org/10.1186/1475-2875-9-82 |
container_title |
Malaria Journal |
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9 |
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1 |
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1766339219916062720 |