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http://hdl.handle.net/2445/155078
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DC Field | Value | Language |
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dc.contributor.author | Bretscher, Michael T. | - |
dc.contributor.author | Dahal, Prabin | - |
dc.contributor.author | Griffin, Jamie T. | - |
dc.contributor.author | Stepniewska, Kasia | - |
dc.contributor.author | Bassat Orellana, Quique | - |
dc.contributor.author | Baudin, Elisabeth | - |
dc.contributor.author | Alessandro, Umberto d' | - |
dc.contributor.author | Djimde, Abdoulaye A. | - |
dc.contributor.author | Dorsey, Grant | - |
dc.contributor.author | Espié, Emmanuelle | - |
dc.contributor.author | Fofana, Bakary | - |
dc.contributor.author | González, Raquel | - |
dc.contributor.author | Juma, Elizabeth | - |
dc.contributor.author | Karema, Corine | - |
dc.contributor.author | Lasry, Estrella | - |
dc.contributor.author | Lell, Bertrand | - |
dc.contributor.author | Lima, Nines | - |
dc.contributor.author | Menéndez, Clara | - |
dc.contributor.author | Mombo-Ngoma, Ghyslain | - |
dc.contributor.author | Moreira, Clarissa | - |
dc.contributor.author | Nikiema, Frederic | - |
dc.contributor.author | Ouédraogo, Jean B. | - |
dc.contributor.author | Staedke, Sarah G. | - |
dc.contributor.author | Tinto, Halidou | - |
dc.contributor.author | Valea, Innocent | - |
dc.contributor.author | Yeka, Adoke | - |
dc.contributor.author | Ghani, Azra C. | - |
dc.contributor.author | Guerin, Philippe J. | - |
dc.contributor.author | Okell, Lucy C. | - |
dc.date.accessioned | 2020-04-08T08:39:34Z | - |
dc.date.available | 2020-04-08T08:39:34Z | - |
dc.date.issued | 2020-02-25 | - |
dc.identifier.issn | 1741-7015 | - |
dc.identifier.uri | http://hdl.handle.net/2445/155078 | - |
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. | - |
dc.format.extent | 17 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | BioMed Central | - |
dc.relation.isformatof | Reproducció del document publicat a: http://dx.doi.org/10.1186/s12916-020-1494-3 | - |
dc.relation.ispartof | BMC Medicine, 2020, vol. 18 | - |
dc.relation.uri | http://dx.doi.org/10.1186/s12916-020-1494-3 | - |
dc.rights | cc-by (c) Bretscher et al., 2020 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | - |
dc.source | Articles publicats en revistes (ISGlobal) | - |
dc.subject.classification | Plasmodium falciparum | - |
dc.subject.classification | Malària | - |
dc.subject.other | Plasmodium falciparum | - |
dc.subject.other | Malaria | - |
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 | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2020-04-03T18:01:24Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 32098634 | - |
Appears in Collections: | Articles publicats en revistes (ISGlobal) |
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File | Description | Size | Format | |
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Bretscher_M_BCM_Med_2020.pdf | 1.69 MB | Adobe PDF | View/Open |
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