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A novel model fitted to multiple life stages of malaria for assessing efficacy of transmission-blocking interventions
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Sherrard-Smith, Ellie, Churcher, Thomas S., Upton, Leanna M., Sala, Katarzyna A., Zakutansky, Sara E., Slater, Hannah C., Blagborough, Andrew M. and Betancourt, Michael (2017) A novel model fitted to multiple life stages of malaria for assessing efficacy of transmission-blocking interventions. Malaria Journal, 16 (1). 137. doi:10.1186/s12936-017-1782-3 ISSN 1475-2875.
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Official URL: https://doi.org/10.1186/s12936-017-1782-3
Abstract
Transmission-blocking interventions (TBIs) aim to eliminate malaria by reducing transmission of the parasite between the host and the invertebrate vector. TBIs include transmission-blocking drugs and vaccines that, when given to humans, are taken up by mosquitoes and inhibit parasitic development within the vector. Accurate methodologies are key to assess TBI efficacy to ensure that only the most potent candidates progress to expensive and time-consuming clinical trials. Measuring intervention efficacy can be problematic because there is substantial variation in the number of parasites in both the host and vector populations, which can impact transmission even in laboratory settings. A statistically robust empirical method is introduced for estimating intervention efficacy from standardised population assay experiments. This method will be more reliable than simple summary statistics as it captures changes in parasite density in different life-stages. It also allows efficacy estimates at a finer resolution than previous methods enabling the impact of the intervention over successive generations to be tracked. A major advantage of the new methodology is that it makes no assumptions on the population dynamics of infection. This enables both host-to-vector and vector-to-host transmission to be density-dependent (or other) processes and generates easy-to-understand estimates of intervention efficacy. This method increases the precision of intervention efficacy estimates and demonstrates that relying on changes in infection prevalence (the proportion of infected hosts) alone may be insufficient to capture the impact of TBIs, which also suppress parasite density in secondarily infected hosts. The method indicates that potentially useful, partially effective TBIs may require multiple infection cycles before substantial reductions in prevalence are observed, despite more rapidly suppressing parasite density. Accurate models to quantify efficacy will have important implications for understanding how TBI candidates might perform in field situations and how they should be evaluated in clinical trials.
Item Type: | Journal Article | |||||||||||||||
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Subjects: | Q Science > QR Microbiology | |||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Statistics | |||||||||||||||
SWORD Depositor: | Library Publications Router | |||||||||||||||
Library of Congress Subject Headings (LCSH): | Malaria., Malaria vaccine., Antimalarials, Malaria -- Immunological aspects., Malaria -- Prevention., Malaria -- Control, Plasmodium | |||||||||||||||
Journal or Publication Title: | Malaria Journal | |||||||||||||||
Publisher: | BioMed Central Ltd. | |||||||||||||||
ISSN: | 1475-2875 | |||||||||||||||
Official Date: | 4 April 2017 | |||||||||||||||
Dates: |
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Volume: | 16 | |||||||||||||||
Number: | 1 | |||||||||||||||
Article Number: | 137 | |||||||||||||||
DOI: | 10.1186/s12936-017-1782-3 | |||||||||||||||
Status: | Peer Reviewed | |||||||||||||||
Publication Status: | Published | |||||||||||||||
Reuse Statement (publisher, data, author rights): | ** From PubMed via Jisc Publications Router. ** History: ** received: 23-01-2017 ** accepted: 17-03-2017 | |||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
Date of first compliant deposit: | 19 September 2017 | |||||||||||||||
Date of first compliant Open Access: | 20 September 2017 | |||||||||||||||
Funder: | PATH Malaria Vaccine Initiative, Medical Research Council (Great Britain) (MRC), Great Britain. Department for International Development, Engineering and Physical Sciences Research Council (EPSRC) | |||||||||||||||
Grant number: | MR/N00227X/1, EP/J016934/1 | |||||||||||||||
RIOXX Funder/Project Grant: |
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