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    Jan 15, 2021
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    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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    Bretscher et al 2020 The duration ...
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    Authors
    Bretscher, M
    Dahal, P
    Griffin, J
    Bassat, Q
    Baudin, E
    D'Alessandro, U
    Djimde, AA
    Dorsey, G
    Espié, E
    Fofana, B
    González, R
    Juma, E
    Karema, C
    Lasry, E
    Lell, B
    Lima, N
    Menéndez, C
    Mombo-Ngoma, G
    Moreira, C
    Nikiema, F
    Ouédraogo, JB
    Staedke, SG
    Tinto, H
    Valea, I
    Yeka, A
    Ghani, AC
    Guerin, PJ
    Okell, LC
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    Issue Date
    2020-02-25
    Submitted date
    2020-03-06
    
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    Journal
    BMC Medicine
    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.
    Publisher
    BioMed Central
    URI
    http://hdl.handle.net/10144/619612
    DOI
    10.1186/s12916-020-1494-3
    PubMed ID
    32098634
    Type
    Article
    Language
    en
    EISSN
    1741-7015
    ae974a485f413a2113503eed53cd6c53
    10.1186/s12916-020-1494-3
    Scopus Count
    Collections
    Malaria

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