Borderless battles: Modelling the spread of artemisinin partial resistance in connected subpopulations in southern Africa

Artemisinin partial resistance has not yet been reported in southern Africa. Therefore, the magnitude of the spread of artemisinin partial resistance in this region is yet to be quantified.

Using a two strain metapopulation modelling framework, we explored possible spread of artemisinin partial resistance in eight connected countries with high level of human movement. We explored three scenarios in which artemisinin partial resistance may first enter circulation: low malaria transmission level country; high malaria transmission level country and all countries and compared to an artemisinin partial resistance free scenario. Partial rank correlation coefficient sensitivity analysis was performed to identify key parameters that drive artemisinin partial resistance spread.

Our model simulations show that high mobility between countries can increase the spread of mutations associated with delayed clearance. Suggesting that artemisinin partial resistance will be confirmed (>5% partial resistant cases) after 14 years of circulation if it is to appear in southern Africa. We confirm that human movement, both human-to-mosquito and mosquito-to-human probabilities of transmission, were significant and highly sensitive parameters in the spread of artemisinin partial resistance.

Human mobility between countries can facilitate the spread of artemisinin partial resistance. More research is needed to identify strategies to preserve the efficacy of artemisinin-based combination therapies in the presence of partial artemisinin resistance, which may eventually lead to treatment failure and necessitate regimen replacement.

Author summary

We developed a two-strain, spatially explicit metapopulation model with eight patches of low, moderate and high levels of malaria transmission. We simulated the spread of artemisinin partial resistance in geographically connected Southern African Development Community Malaria Elimination 8 Initiative (SADC-E8) countries with a high-level of human cross border movement. This study provides a hypothetical reference for future studies necessary to fully understand the spread and impact of artemisinin partial resistance in the malaria elimination process in southern Africa. We found that human movement between countries facilitates the spread of artemisinin partial resistance. The slow parasite clearance and high gametocyte carriage (2-fold of sensitive strain 3 days after ACTs treatment) drive the spread of artemisinin partial resistance within the human population. In the absence of artemisinin partial resistance data in SADC-E8, this study’s simulations inform policy to make decisions on the potential spread of artemisinin partial resistance.