Abstract
BackgroundArtemisinin-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.MethodsThe 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.ResultsThe 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.ConclusionsAreas 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.
Highlights
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
Using a population-based mathematical model, this study demonstrated that in high prevalence settings, P. falciparum artemisinin-resistant strains may circulate for more than 10 years longer than in low prevalence settings before the areas are classified as having confirmed partial artemisinin resistance according to World Health Organization (WHO) criteria [15]
The time from the emergence of artemisinin resistant malaria falciparum strains to the detection of confirmed partial artemisinin resistance is multifactorial and independently related to malaria prevalence, immunity and drug pressure/relative strain fitness within hosts
Summary
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. The appearance of artemisinin-resistant falciparum malaria in the Greater Mekong Subregion from 2009 poses a significant public health threat [3,4,5,6,7,8,9,10,11] and raises concerns that resistance may emerge and become widespread in high-burden settings, such as Africa. Whilst mutations in the k13 gene have been reported in African isolates, they do not appear to be under strong selection [16] and clinically relevant artemisinin-resistant falciparum malaria is yet to be observed in Africa [17]
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