Assessing the potential impact of artemisinin and partner drug resistance in sub-Saharan Africa

Abstract

Background: Artemisinin and partner drug resistant malaria parasites have emerged in Southeast Asia. If resistance were to emerge in Africa it could have a devastating impact on malaria-related morbidity and mortality. This study estimates the potential impact of artemisinin and partner drug resistance on disease burden in Africa if it were to emerge.

Methods: Using data from Asia and Africa, five possible artemisinin and partner drug resistance scenarios are characterized. An individual-based malaria transmission model is used to estimate the impact of each resistance scenario on clinical incidence and parasite prevalence across Africa. Artemisinin resistance is characterized by slow parasite clearance and partner drug resistance is associated with late clinical failure or late parasitological failure.

Results: Scenarios with high levels of recrudescent infections resulted in far greater increases in clinical incidence compared to scenarios with high levels of slow parasite clearance. Across Africa, it is estimated that artemisinin and partner drug resistance at levels similar to those observed in Oddar Meanchey province in Cambodia could result in an additional 78 million cases over a 5 year period, a 7% increase in cases compared to a scenario with no resistance. A scenario with high levels of slow clearance but no recrudescence resulted in an additional 10 million additional cases over the same period.

Conclusion: Artemisinin resistance is potentially a more pressing concern than partner drug resistance due to the lack of viable alternatives. However, it is predicted that a failing partner drug will result in greater increases in malaria cases and morbidity than would be observed from artemisinin resistance only.

Fig. 1

Malaria transmission model—human dynamics. Susceptible individuals (S) bitten by an infectious mosquito develop either asymptomatic infection (A) or clinical disease (T, T_R, D) according to their level of immunity. Individuals treated for clinical disease with artemisinin-sensitive parasites (T) or artemisinin-resistant parasites (T_R) clear infection (at different rates) and move to the prophylactically protected compartment (P) before returning to the susceptible compartment. Individuals with partner drug-resistant parasites can recrudesce from either the prophylactically protected compartment (P) or the post-treatment sub-patent infection compartment (U₂) to clinical disease or asymptomatic infection. Prophylactically protected individuals can be re-infected, but with a lower probability than those in the fully susceptible state, based on the level of protection from the anti-malarial. Super infection can occur for asymptomatic patent (A) and sub-patent (U) infected individuals

Fig. 2

Impact of three treatment outcomes of ACT resistance on clinical incidence (mean number of cases of malaria per 1000 individuals per year) in five different transmission settings (baseline parasite prevalence in 2–10 year olds = 1, 5, 10, 25 and 50 %). The dark blue bars (LCF) show the situation where recrudescing individuals have a 25 % greater probability of developing clinical infection after recrudescing compared to after a new infection. The medium blue bars (LPF) show the situation where all recrudescing individuals develop late parasitological failure (asymptomatic patent infection). The light blue bars show the situation where individuals clear parasites slowly after treatment but do not go on to recrudesce. The proportion of infections recrudescing or with slow parasite clearance is shown on the x-axis

Fig. 3

Absolute increase in clinical malaria incidence per 1000 individuals over 5 years (2016–2020) using five ACT resistance scenarios compared to a scenario with no artemisinin or partner drug resistance. All maps were created using the maptools package [30] in R

Fig. 4

Absolute increase in malaria prevalence resulting from each ACT resistance scenario—comparing prevalence between 2016 and 2020 for scenarios with and without resistance