A study of chloroquine and desethylchloroquine plasma levels in patients infected with sensitive and resistant malaria parasites.

This study was carried out on 63 patients in the town of Gadaref in eastern Sudan; each patient was given the standard therapeutic dose of chloroquine (CQ). Plasma levels of chloroquine and its major metabolite desethylchloroquine (DCQ) were measured by means of a high-performance liquid chromatographic method (HPLC) in patients infected with sensitive (sensitive group) and resistant (resistant groups) strains of Plasmodium falciparum. The ratios of chloroquine to desethylchloroquine (CQ/DCQ) in different groups were calculated and the results obtained were compared and correlated with the degree of parasitaemia. The statistical analysis of the results showed that the plasma content of CQ and the CQ/DCQ ratio in the majority of the patients fall within the normal mode of distribution. A small group of patients showed a deviation from the normal mode by having a rather high CQ plasma level and a high ratio of CQ/DCQ. The mean plasma levels of CQ and the CQ/DCQ ratio in the sensitive group was found to be higher than that in the resistant groups. However, these differences were found to be not significant. Correlation tests showed that the levels of CQ and the CQ/DCQ ratios increase with the increase of the degree of parasitaemia in the sensitive group but decrease with the increase of parasitaemia in resistant groups.

Chloroquine-resistant Plasmodium falciparum in eastern Sudan.

In vivo testing of the sensitivity of Plasmodium falciparum to chloroquine was carried out in 61 falciparum malaria patients with acute symptoms, in Eastern Sudan. In 26 patients (42%), P. falciparum was resistant to chloroquine. Nine patients (15%) had RI resistance, seven (11%) had RII resistance while ten (16%) had RIII resistance. The persistance of parasitaemia and symptoms were highly correlated in patients with RIII responses. In 21 patients in vitro testing of chloroquine sensitivity was carried out simultaneously with the in vivo testing using the World Health Organization microtest. In vivo and in vitro testing were also highly correlated. Isolates from 12 patients with proven in vivo resistance, grew in vitro in the presence of chloroquine concentrations above 0.8 X 10(-6) mol/l blood. Resistant strains have either been spread by refugees across the borders from Ethiopia or have developed indigenously. Mounting drug pressure, mass movement of non-immune refugees and loss of immunity among local inhabitants, due to the drought, are in favour of development of an indigenous focus. Epidemics with intense transmission caused by heavy rains following the drought could have greatly enhanced the emergence and spread of resistant strains.