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@article{Okell:2020:10.1186/s12916-020-1494-3,
author = {Okell, L and Bretscher, MT and Dahal, P and Griffin, J and stepniewska, K and Bassat, Q and Baudin, E and D'Alessandro, U and Djimde, A and Dorsey, G and Espie, E and Fofana, B and Gonzalez, R and Juma, E and Karema, C and Lasry, E and Lell, B and Lima, N and Menendez, C and Mombo-Ngoma, G and Moreira, C and Nikiema, F and Ouedraogo, J and Staedke, S and Tinto, H and Valea, I and Yeka, A and Ghani, A and Guerin, P},
doi = {10.1186/s12916-020-1494-3},
journal = {BMC Medicine},
pages = {1--17},
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},
url = {http://dx.doi.org/10.1186/s12916-020-1494-3},
volume = {18},
year = {2020}
}

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TY  - JOUR
AB  - 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 programmes combined with sulfadoxine-pyrimethamine. Whilst 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 re-infection 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 re-infection. 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 re-infection in multivariate 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 protec
AU  - Okell,L
AU  - Bretscher,MT
AU  - Dahal,P
AU  - Griffin,J
AU  - stepniewska,K
AU  - Bassat,Q
AU  - Baudin,E
AU  - D'Alessandro,U
AU  - Djimde,A
AU  - Dorsey,G
AU  - Espie,E
AU  - Fofana,B
AU  - Gonzalez,R
AU  - Juma,E
AU  - Karema,C
AU  - Lasry,E
AU  - Lell,B
AU  - Lima,N
AU  - Menendez,C
AU  - Mombo-Ngoma,G
AU  - Moreira,C
AU  - Nikiema,F
AU  - Ouedraogo,J
AU  - Staedke,S
AU  - Tinto,H
AU  - Valea,I
AU  - Yeka,A
AU  - Ghani,A
AU  - Guerin,P
DO  - 10.1186/s12916-020-1494-3
EP  - 17
PY  - 2020///
SN  - 1741-7015
SP  - 1
TI  - 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
T2  - BMC Medicine
UR  - http://dx.doi.org/10.1186/s12916-020-1494-3
UR  - https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-020-1494-3
UR  - http://hdl.handle.net/10044/1/76878
VL  - 18
ER  -

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