Prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty
Abstract Background The evolution of drug resistance in malaria parasites highlights a need to identify and evaluate strategies that could extend the useful therapeutic life of anti-malarial drugs. Such strategies are deployed to best effect before resistance has emerged, under conditions of great u...
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ftdoajarticles:oai:doaj.org/article:1cdc094cebb74b4884c0e699eba58087 2023-05-15T15:13:18+02:00 Prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty McKenzie F Ellis Klein Eili Y Smith David L Laxminarayan Ramanan 2010-07-01T00:00:00Z https://doi.org/10.1186/1475-2875-9-217 https://doaj.org/article/1cdc094cebb74b4884c0e699eba58087 EN eng BMC http://www.malariajournal.com/content/9/1/217 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-9-217 1475-2875 https://doaj.org/article/1cdc094cebb74b4884c0e699eba58087 Malaria Journal, Vol 9, Iss 1, p 217 (2010) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2010 ftdoajarticles https://doi.org/10.1186/1475-2875-9-217 2022-12-31T13:10:25Z Abstract Background The evolution of drug resistance in malaria parasites highlights a need to identify and evaluate strategies that could extend the useful therapeutic life of anti-malarial drugs. Such strategies are deployed to best effect before resistance has emerged, under conditions of great uncertainty. Methods Here, the emergence and spread of resistance was modelled using a hybrid framework to evaluate prospective strategies, estimate the time to drug failure, and weigh uncertainty. The waiting time to appearance was estimated as the product of low mutation rates, drug pressure, and parasite population sizes during treatment. Stochastic persistence and the waiting time to establishment were simulated as an evolving branching process. The subsequent spread of resistance was simulated in simple epidemiological models. Results Using this framework, the waiting time to the failure of artemisinin combination therapy (ACT) for malaria was estimated, and a policy of multiple first-line therapies (MFTs) was evaluated. The models quantify the effects of reducing drug pressure in delaying appearance, reducing the chances of establishment, and slowing spread. By using two first-line therapies in a population, it is possible to reduce drug pressure while still treating the full complement of cases. Conclusions At a global scale, because of uncertainty about the time to the emergence of ACT resistance, there was a strong case for MFTs to guard against early failure. Our study recommends developing operationally feasible strategies for implementing MFTs, such as distributing different ACTs at the clinic and for home-based care, or formulating different ACTs for children and adults. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 9 1 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
topic |
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 McKenzie F Ellis Klein Eili Y Smith David L Laxminarayan Ramanan Prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background The evolution of drug resistance in malaria parasites highlights a need to identify and evaluate strategies that could extend the useful therapeutic life of anti-malarial drugs. Such strategies are deployed to best effect before resistance has emerged, under conditions of great uncertainty. Methods Here, the emergence and spread of resistance was modelled using a hybrid framework to evaluate prospective strategies, estimate the time to drug failure, and weigh uncertainty. The waiting time to appearance was estimated as the product of low mutation rates, drug pressure, and parasite population sizes during treatment. Stochastic persistence and the waiting time to establishment were simulated as an evolving branching process. The subsequent spread of resistance was simulated in simple epidemiological models. Results Using this framework, the waiting time to the failure of artemisinin combination therapy (ACT) for malaria was estimated, and a policy of multiple first-line therapies (MFTs) was evaluated. The models quantify the effects of reducing drug pressure in delaying appearance, reducing the chances of establishment, and slowing spread. By using two first-line therapies in a population, it is possible to reduce drug pressure while still treating the full complement of cases. Conclusions At a global scale, because of uncertainty about the time to the emergence of ACT resistance, there was a strong case for MFTs to guard against early failure. Our study recommends developing operationally feasible strategies for implementing MFTs, such as distributing different ACTs at the clinic and for home-based care, or formulating different ACTs for children and adults. |
format |
Article in Journal/Newspaper |
author |
McKenzie F Ellis Klein Eili Y Smith David L Laxminarayan Ramanan |
author_facet |
McKenzie F Ellis Klein Eili Y Smith David L Laxminarayan Ramanan |
author_sort |
McKenzie F Ellis |
title |
Prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty |
title_short |
Prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty |
title_full |
Prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty |
title_fullStr |
Prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty |
title_full_unstemmed |
Prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty |
title_sort |
prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty |
publisher |
BMC |
publishDate |
2010 |
url |
https://doi.org/10.1186/1475-2875-9-217 https://doaj.org/article/1cdc094cebb74b4884c0e699eba58087 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 9, Iss 1, p 217 (2010) |
op_relation |
http://www.malariajournal.com/content/9/1/217 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-9-217 1475-2875 https://doaj.org/article/1cdc094cebb74b4884c0e699eba58087 |
op_doi |
https://doi.org/10.1186/1475-2875-9-217 |
container_title |
Malaria Journal |
container_volume |
9 |
container_issue |
1 |
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1766343872871399424 |