The spread of Plasmodium falciparum carrying a quadruply mutated dhfr gene to Africa has been widely predicted to have profoundly adverse consequences, as such parasites in vitro are highly resistant to antifolate inhibitiors, still a mainstay of antimalarial drug regimes in this region. Studies of parasites from Southeast Asia demonstrate a strong connection between the I164L-bearing quadruple mutant form and failure of sulfadoxine-pyrimethamine (SP) treatment. However, a recent study reported in this issue of Transactions documents the low-level incidence in an area of Kenya of quadruply mutant parasites which, in the majority of cases, appear to have been cleared by a standard SP treatment regime, contrary to expectations.