The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data.
dc.contributor.author | Bretscher, MT | en_US |
dc.contributor.author | Dahal, P | en_US |
dc.contributor.author | Griffin, J | en_US |
dc.contributor.author | Stepniewska, K | en_US |
dc.contributor.author | Bassat, Q | en_US |
dc.contributor.author | Baudin, E | en_US |
dc.contributor.author | D'Alessandro, U | en_US |
dc.contributor.author | Djimde, AA | en_US |
dc.contributor.author | Dorsey, G | en_US |
dc.contributor.author | Espié, E | en_US |
dc.contributor.author | Fofana, B | en_US |
dc.contributor.author | González, R | en_US |
dc.contributor.author | Juma, E | en_US |
dc.contributor.author | Karema, C | en_US |
dc.contributor.author | Lasry, E | en_US |
dc.contributor.author | Lell, B | en_US |
dc.contributor.author | Lima, N | en_US |
dc.contributor.author | Menéndez, C | en_US |
dc.contributor.author | Mombo-Ngoma, G | en_US |
dc.contributor.author | Moreira, C | en_US |
dc.contributor.author | Nikiema, F | en_US |
dc.contributor.author | Ouédraogo, JB | en_US |
dc.contributor.author | Staedke, SG | en_US |
dc.contributor.author | Tinto, H | en_US |
dc.contributor.author | Valea, I | en_US |
dc.contributor.author | Yeka, A | en_US |
dc.contributor.author | Ghani, AC | en_US |
dc.contributor.author | Guerin, PJ | en_US |
dc.contributor.author | Okell, LC | en_US |
dc.date.accessioned | 2020-04-03T08:38:09Z | |
dc.date.available | 2020-01-09 | en_US |
dc.date.issued | 2020-02-25 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/63439 | |
dc.description.abstract | BACKGROUND: The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin derivatives have a short half-life, lumefantrine and amodiaquine may give rise to differing durations of post-treatment prophylaxis, an important additional benefit to patients in higher transmission areas. METHODS: We analyzed individual patient data from 8 clinical trials of AL versus AS-AQ in 12 sites in Africa (n = 4214 individuals). The time to PCR-confirmed reinfection after treatment was used to estimate the duration of post-treatment protection, accounting for variation in transmission intensity between settings using hidden semi-Markov models. Accelerated failure-time models were used to identify potential effects of covariates on the time to reinfection. The estimated duration of chemoprophylaxis was then used in a mathematical model of malaria transmission to determine the potential public health impact of each drug when used for first-line treatment. RESULTS: We estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7-15.7) for AL and 15.2 days (95% CI 12.8-18.4) for AS-AQ overall. However, the duration varied significantly between trial sites, from 8.7-18.6 days for AL and 10.2-18.7 days for AS-AQ. Significant predictors of time to reinfection in multivariable models were transmission intensity, age, drug, and parasite genotype. Where wild type pfmdr1 and pfcrt parasite genotypes predominated (<=20% 86Y and 76T mutants, respectively), AS-AQ provided ~ 2-fold longer protection than AL. Conversely, at a higher prevalence of 86Y and 76T mutant parasites (> 80%), AL provided up to 1.5-fold longer protection than AS-AQ. Our simulations found that these differences in the duration of protection could alter population-level clinical incidence of malaria by up to 14% in under-5-year-old children when the drugs were used as first-line treatments in areas with high, seasonal transmission. CONCLUSION: Choosing a first-line treatment which provides optimal post-treatment prophylaxis given the local prevalence of resistance-associated markers could make a significant contribution to reducing malaria morbidity. | en_US |
dc.format.extent | 47 - ? | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | BMC Med | en_US |
dc.rights | This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. | |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.subject | Amodiaquine | en_US |
dc.subject | Artemisinin | en_US |
dc.subject | Crt | en_US |
dc.subject | Drug | en_US |
dc.subject | Lumefantrine | en_US |
dc.subject | Malaria | en_US |
dc.subject | Mathematical model | en_US |
dc.subject | Trial | en_US |
dc.subject | mdr1 | en_US |
dc.title | The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data. | en_US |
dc.type | Article | |
dc.rights.holder | © The Author(s) 2020 | |
dc.identifier.doi | 10.1186/s12916-020-1494-3 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/32098634 | en_US |
pubs.issue | 1 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 18 | en_US |
dcterms.dateAccepted | 2020-01-09 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |
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Except where otherwise noted, this item's license is described as This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.