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BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong Subregion, an area of relatively low transmission, but has yet to be reported in Africa. A population-based mathematical model was used to investigate the relationship between P. falciparum prevalence, exposure-acquired immunity and time-to-emergence of artemisinin resistance. The possible implication for the emergence of resistance across Africa was assessed. METHODS: The model included human and mosquito populations, two strains of malaria ("wild-type", "mutant"), three levels of human exposure-acquired immunity (none, low, high) with two types of immunity for each level (sporozoite/liver stage immunity and blood-stage/gametocyte immunity) and drug pressure based on per-capita treatment numbers. RESULTS: The model predicted that artemisinin-resistant strains may circulate up to 10 years longer in high compared to low P. falciparum prevalence areas before resistance is confirmed. Decreased time-to-resistance in low prevalence areas was explained by low genetic diversity and immunity, which resulted in increased probability of selection and spread of artemisinin-resistant strains. Artemisinin resistance was estimated to be established by 2020 in areas of Africa with low (< 10%) P. falciparum prevalence, but not for 5 or 10 years later in moderate (10-25%) or high (> 25%) prevalence areas, respectively. CONCLUSIONS: Areas of low transmission and low immunity give rise to a more rapid expansion of artemisinin-resistant parasites, corroborating historical observations of anti-malarial resistance emergence. Populations where control strategies are in place that reduce malaria transmission, and hence immunity, may be prone to a rapid emergence and spread of artemisinin-resistant strains and thus should be carefully monitored.

Original publication

DOI

10.1186/s12936-018-2418-y

Type

Journal article

Journal

Malar J

Publication Date

02/08/2018

Volume

17

Keywords

Africa, Artemisinin, Drug resistance, Immunity, Malaria, Mathematical model, Africa, Antimalarials, Artemisinins, Drug Resistance, Humans, Malaria, Falciparum, Models, Biological, Plasmodium falciparum