Intermittent Preventive Treatment (IPT): Its Role in Averting Disease-Induced Mortality in Children and in Promoting the Spread of Antimalarial Drug Resistance.

We develop an age-structured ODE model to investigate the role of intermittent preventive treatment (IPT) in averting malaria-induced mortality in children, and its related cost in promoting the spread of antimalarial drug resistance. IPT, a malaria control strategy in which a full curative dose of an antimalarial medication is administered to vulnerable asymptomatic individuals at specified intervals, has been shown to reduce malaria transmission and deaths in children and pregnant women. However, it can also promote drug resistance spread. Our mathematical model is used to explore IPT effects on drug resistance and deaths averted in holoendemic malaria regions. The model includes drug-sensitive and drug-resistant strains as well as human hosts and mosquitoes. The basic reproduction, and invasion reproduction numbers for both strains are derived. Numerical simulations show the individual and combined effects of IPT and treatment of symptomatic infections on the prevalence of both strains and the number of lives saved. Our results suggest that while IPT can indeed save lives, particularly in high transmission regions, certain combinations of drugs used for IPT and to treat symptomatic infection may result in more deaths when resistant parasite strains are circulating. Moreover, the half-lives of the treatment and IPT drugs used play an important role in the extent to which IPT may influence spread of the resistant strain. A sensitivity analysis indicates the model outcomes are most sensitive to the reduction factor of transmission for the resistant strain, rate of immunity loss, and the natural clearance rate of sensitive infections.