Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

<jats:p>Artemether–lumefantrine (AL) and artesunate–amodiaquine (AS-AQ) are the most commonly used artemisinin-based combination therapies (ACT) for treatment of <jats:italic>Plasmodium falciparum</jats:italic> in Africa. Both treatments remain efficacious, but single nucleotide polymorphisms (SNPs) in the <jats:italic>P<jats:italic>lasmodium</jats:italic> falciparum</jats:italic> multidrug resistance 1 (<jats:italic>Pfmdr1</jats:italic>) gene may compromise sensitivity. AL and AS-AQ exert opposing selective pressures: parasites with genotype 86Y, Y184 and 1246Y are partially resistant to AS-AQ treatment, while N86, 184 F and D1246 are favoured by AL treatment. Through a systematic review, we identified 397 surveys measuring the prevalence of <jats:italic>Pfmdr1</jats:italic> polymorphisms at positions 86 184 or 1246 in 30 countries in Africa. Temporal trends in SNP frequencies after introduction of AL or AS-AQ as first-line treatment were analysed in 32 locations, and selection coefficients estimated. We examined associations between antimalarial policies, consumption, transmission intensity and rate of SNP selection. 1246Y frequency decreased on average more rapidly in locations where national policy recommended AL (median selection coefficient(<jats:italic>s</jats:italic>) of −0.083), compared with policies of AS-AQ or both AL and AS-AQ (median <jats:italic>s</jats:italic>=−0.035 and 0.021, p&lt;0.001 respectively). 86Y frequency declined markedly after ACT policy introduction, with a borderline significant trend for a more rapid decline in countries with AL policies (p=0.055). However, these trends could also be explained by a difference in initial SNP frequencies at the time of ACT introduction. There were non-significant trends for faster selection of N86 and D1246 in areas with higher AL consumption and no trend with transmission intensity. Recorded consumption of AS-AQ was low in the locations and times <jats:italic>Pfmdr1</jats:italic> data were collected. SNP trends in countries with AL policies suggest a broad increase in sensitivity of parasites to AS-AQ, by 7–10 years after AL introduction. Observed rates of selection have implications for planning strategies to cycle drugs or use multiple first-line therapies to maintain drug efficacy.</jats:p>

Original publication

DOI

10.1136/bmjgh-2018-000999

Type

Journal article

Journal

BMJ Global Health

Publisher

BMJ

Publication Date

10/2018

Volume

3

Pages

e000999 - e000999