Quinine resistant falciparum malaria acquired in east Africa

A 43 year old man with falciparum malaria acquired in East Africa was treated with quinine intravenously at a loading dose of 500 mg and subsequently 500 mg tid. Within 42 hours after initiation of treatment the parasitaemia increased from 2% to 16%. A RIII-resistance against quinine was suspected and therapy was switched to oral administration of halofantrine (500 mg at 6 hourly intervals) which led to complete recovery. Blood samples were cultured for malaria parasites 42 hours after start of therapy with quinine but before initiation of therapy with halofantrine. In vitro resistance testing was performed with samples directly derived from the patient and after 24 and 48 hours of culturing. In repeated tests an in vitro resistance to quinine could be confirmed (IC50: 25.6 x 10(-6) mol/l, IC99: > 51.2 x 10(-6) mol/l) while the strain was fully susceptible to chloroquine (IC50: < 0.4 x 10(-6) mol/l, IC99: 1.6 x 10(-6) mol/l), mefloquine (IC50: < 0.4 x 10(-6) mol/l, IC99: 3.2 x 10(-6) mol/l), tetracycline (IC50: 0.16 x 10(-6) mol/l, IC99: 0.32 x 10(-6) mol/l) and halofantrine (IC50: 0.02 x 10(-6) mol/l, IC99: 0.04 x 10(-6) mol/l). Increased susceptibility to quinine after addition of verapamil was noted. The presence of a specific mutation, on the pfmdr1-gene on chromosome 5, previously associated with chloroquine drug resistance, could be confirmed by polymerase chain reaction. To our knowledge a R III-in vivo and in vitro resistance of Plasmodium falciparum to quinine has not been described yet in East Africa.(ABSTRACT TRUNCATED AT 250 WORDS)