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BMC Medicine / 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

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العنوان: BMC Medicine / 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
المؤلفون: Okell, Lucy C., Bretscher, Michael T., Dahal, Prabin, Lell, Bertrand, Griffin, Jamie, Stepniewska, Kasia, Bassat, Quique, Baudin, Elisabeth, D’Alessandro, Umberto, Djimde, Abdoulaye A.
بيانات النشر: BMC
سنة النشر: 2020
المجموعة: MedUni Vienna ePub (Medzinische Universität Wien)
مصطلحات موضوعية: Malaria, Artemisinin, Drug, Lumefantrine, Amodiaquine, Trial, Mathematical model, mdr1, Crt
جغرافية الموضوع: UMW:17606
الوصف: 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 ...
نوع الوثيقة: article in journal/newspaper
وصف الملف: text/html
اللغة: English
تدمد: 1741-7015
Relation: vignette : https://repositorium.meduniwien.ac.at/titlepage/urn/urn:nbn:at:at-ubmuw:3-105333/128; urn:nbn:at:at-ubmuw:3-105333; https://resolver.obvsg.at/urn:nbn:at:at-ubmuw:3-105333; local:99148476134803331; system:AC17301259
DOI: 10.1186/s12916-020-1494-3
الاتاحة: https://doi.org/10.1186/s12916-020-1494-3
https://repositorium.meduniwien.ac.at/doi/10.1186/s12916-020-1494-3
https://resolver.obvsg.at/urn:nbn:at:at-ubmuw:3-105333
Rights: cc-by_4
رقم الانضمام: edsbas.73400506
قاعدة البيانات: BASE
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