A novel model fitted to multiple life stages of malaria for assessing efficacy of transmission-blocking interventions
Abstract Background 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 para...
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doaj-ba24cba932b74b068371afce88c841352020-11-24T23:26:36ZengBMCMalaria Journal1475-28752017-04-0116111010.1186/s12936-017-1782-3A novel model fitted to multiple life stages of malaria for assessing efficacy of transmission-blocking interventionsEllie Sherrard-Smith0Thomas S. Churcher1Leanna M. Upton2Katarzyna A. Sala3Sara E. Zakutansky4Hannah C. Slater5Andrew M. Blagborough6Michael Betancourt7MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College LondonMRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College LondonDepartment of Life Sciences, Imperial College LondonDepartment of Life Sciences, Imperial College LondonDepartment of Life Sciences, Imperial College LondonMRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College LondonDepartment of Life Sciences, Imperial College LondonDepartment of Statistics, University of WarwickAbstract Background 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. Methods 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. Results 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. Conclusions 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.http://link.springer.com/article/10.1186/s12936-017-1782-3AtovaquonePlasmodium bergheiTransmission-blocking drugsTransmission-blocking vaccines |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ellie Sherrard-Smith Thomas S. Churcher Leanna M. Upton Katarzyna A. Sala Sara E. Zakutansky Hannah C. Slater Andrew M. Blagborough Michael Betancourt |
spellingShingle |
Ellie Sherrard-Smith Thomas S. Churcher Leanna M. Upton Katarzyna A. Sala Sara E. Zakutansky Hannah C. Slater Andrew M. Blagborough Michael Betancourt A novel model fitted to multiple life stages of malaria for assessing efficacy of transmission-blocking interventions Malaria Journal Atovaquone Plasmodium berghei Transmission-blocking drugs Transmission-blocking vaccines |
author_facet |
Ellie Sherrard-Smith Thomas S. Churcher Leanna M. Upton Katarzyna A. Sala Sara E. Zakutansky Hannah C. Slater Andrew M. Blagborough Michael Betancourt |
author_sort |
Ellie Sherrard-Smith |
title |
A novel model fitted to multiple life stages of malaria for assessing efficacy of transmission-blocking interventions |
title_short |
A novel model fitted to multiple life stages of malaria for assessing efficacy of transmission-blocking interventions |
title_full |
A novel model fitted to multiple life stages of malaria for assessing efficacy of transmission-blocking interventions |
title_fullStr |
A novel model fitted to multiple life stages of malaria for assessing efficacy of transmission-blocking interventions |
title_full_unstemmed |
A novel model fitted to multiple life stages of malaria for assessing efficacy of transmission-blocking interventions |
title_sort |
novel model fitted to multiple life stages of malaria for assessing efficacy of transmission-blocking interventions |
publisher |
BMC |
series |
Malaria Journal |
issn |
1475-2875 |
publishDate |
2017-04-01 |
description |
Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
topic |
Atovaquone Plasmodium berghei Transmission-blocking drugs Transmission-blocking vaccines |
url |
http://link.springer.com/article/10.1186/s12936-017-1782-3 |
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