Implications of population-level immunity for the emergence of artemisinin-resistant malaria: a mathematical model

• Published in: Malaria Journal
• Main Authors: Nick Scott, Ricardo Ataide, David P. Wilson, Margaret Hellard, Ric N. Price, Julie A. Simpson, Freya J. I. Fowkes
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2018
• Subjects: Africa; Malaria; Artemisinin; Drug resistance; Immunity; Mathematical model; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-018-2418-y; https://doaj.org/article/629b04b4fdf1459d8566b6e6deb4e73b

Abstract 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.