Resurgence of malaria infection after mass treatment: a simulation study

Background: Field studies are evaluating if mass drug administration (MDA) might shorten the time to elimination of Plasmodium falciparum malaria, when vector control measures and reactive surveillance strategies are scaled-up. A concern with this strategy is that there may be resurgence of transmission following MDA.

Methods: A conceptual model was developed to classify possible outcomes of an initial period of MDA, followed by continuously implementing other interventions. The classification considered whether elimination or a new endemic stable state is achieved, and whether changes are rapid, transient, or gradual. These categories were informed by stability analyses of simple models of vector control, case management, and test-and-treat interventions. Individual-based stochastic models of malaria transmission (OpenMalaria) were then used to estimate the probability and likely rates of resurgence in realistic settings. Effects of concurrent interventions, including routine case management and test-and-treat strategies were investigated.

Results: Analysis of the conceptual models suggest resurgence will occur after MDA unless transmission potential is very low, or the post-MDA prevalence falls below a threshold, which depends on both transmission potential and on the induction of bistability. Importation rates are important only when this threshold is very low. In most OpenMalaria simulations the approximately stable state achieved at the end of the simulations was independent of inclusion of MDA and the final state was unaffected by importation of infections at plausible rates. Elimination occurred only with high effective coverage of case management, low initial prevalence, and high intensity test-and-treat. High coverage of case management but not by test-and-treat induced bistability. Where resurgence occurred, its rate depended mainly on transmission potential (not treatment rates).

Conclusions: A short burst of high impact MDA is likely to be followed by resurgence. To avert resurgence, concomitant interventions need either to substantially reduce average transmission potential or to be differentially effective in averting or clearing infections at low prevalence. Case management at high effective coverage has this differential effect, and should suffice to avert resurgence caused by imported cases at plausible rates of importation. Once resurgence occurs, its rate depends mainly on transmission potential, not on treatment strategies.