Genomic epidemiology of the current wave of artemisinin resistant malaria
Amato R., Miotto O., Woodrow C., Almagro-Garcia J., Sinha I., Campino S., Mead D., Drury E., Kekre M., Sanders M., Amambua-Ngwa A., Amaratunga C., Amenga-Etego L., Anderson TJC., Andrianaranjaka V., Apinjoh T., Ashley E., Auburn S., Awandare GA., Baraka V., Barry A., Boni MF., Borrmann S., Bousema T., Branch O., Bull PC., Chotivanich K., Conway DJ., Craig A., Day NP., Djimdé A., Dolecek C., Dondorp AM., Drakeley C., Duffy P., Echeverri-Garcia DF., Egwang TG., Fairhurst RM., Faiz A., Fanello CI., Hien TT., Hodgson A., Imwong M., Ishengoma D., Lim P., Lon C., Marfurt J., Marsh K., Mayxay M., Mobegi V., Mokuolu O., Montgomery J., Mueller I., Kyaw MP., Newton PN., Nosten F., Noviyanti R., Nzila A., Ocholla H., Oduro A., Onyamboko M., Ouedraogo J-B., Phyo AP., Plowe CV., Price RN., Pukrittayakamee S., Randrianarivelojosia M., Ringwald P., Ruiz L., Saunders D., Shayo A., Siba P., Takala-Harrison S., Thanh T-NN., Thathy V., Verra F., White NJ., Htut Y., Cornelius VJ., Giacomantonio R., Muddyman D., Henrichs C., Malangone C., Jyothi D., Pearson RD., Rayner JC., McVean G., Rockett K., Miles A., Vauterin P., Jeffery B., Manske M., Stalker J., MacInnis B., Kwiatkowski DP.
AbstractArtemisinin resistantPlasmodium falciparumis advancing across Southeast Asia in a soft selective sweep involving at least 20 independentkelch13mutations. In a large global survey, we find thatkelch13mutations which cause resistance in Southeast Asia are present at low frequency in Africa. We show that Africankelch13mutations have originated locally, and thatkelch13shows a normal variation pattern relative to other genes in Africa, whereas in Southeast Asia there is a great excess of non-synonymous mutations, many of which cause radical amino-acid changes. Thus,kelch13is not currently undergoing strong selection in Africa, despite a deep reservoir of standing variation that could potentially allow resistance to emerge rapidly. The practical implications are that public health surveillance for artemisinin resistance should not rely onkelch13data alone, and interventions to prevent resistance must account for local evolutionary conditions, shown by genomic epidemiology to differ greatly between geographical regions.