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In a series of models of Plasmodium falciparum dynamics, spontaneous local extinctions of the parasite sometimes occurred under steady, perennial-transmission conditions. These extinctions occurred only with extremely low mosquito densities or when the parameter describing the duration of human infection-blocking immunity was at its maximum value, and, simultaneously, those describing vector survivorship and the duration of human infectivity were at their minimum values. The range and frequency of extinctions increased with seasonal transmission, and decreased with the emergence of recombinant genotypes. Here we extend the immunity parameter up to levels that would describe a successful vaccine, and examine the combined influences of seasonality, genotype cross-reactivity, meiotic recombination, and human population turnover on parasite persistence. As Ross did 90 years ago, we conclude that malaria control programs that encompass several methods and targets of intervention are the most likely to succeed. Success is more likely if programs are cognizant of local circumstances of transmission, and, within that context, aim to reduce vector survivorship and human infectivity as well as augment human immunity.