Effect of previous chloroquine intake on in vivo P. Falciparum drug sensitivity

Investigation of the in vivo response of P. falciparum malaria parasites to chloroquine was conducted during 1993/94 in Al-Ain District of Abu Dhabi Emirate, UAE. Sixty seven expatriates who developed falciparum malaria on their return from Pakistan, Oman and Sudan were recruited for the WHO in vivo tests. Of the 67 patients, eight were classified as having RII and RIII responses, while 59 remained aparasitaemic at the end of the seven-day WHO standard test. On continuation into the 28-day WHO extended test, a further 34 patients exhibited RI resistance. Resistance of parasites to chloroquine was confirmed by measurement of plasma chloroquine using High-Performance Liquid Chromatography. In all 67 patients, the level of chloroquine was well above the minimum therapeutic level. The outcome of the in vivo test in patients treated for the first time was significantly different from that in patients who were previously on chloroquine. Among patients treated for the first time, 36 out of 41 (88%) had a resistant response, whereas, among those previously on chloroquine only six out of 26 (23%) had a resistant response. The difference is probably due to the higher initial plasma level of chloroquine among patients who were previously on the drug. Curing more patients with higher plasma chloroquine implies that chloroquine shall continue to be useful, particularly if resistance is at the RI level. Appropriate higher therapeutic levels of chloroquine should be defined for such patients.