Glucose-6-phosphate dehydrogenase A- (G6PD A-) deficiency is a common enzymopathy in Africa that sporadically leads to manifest haemolytic anaemia. It is not exactly known how far the haematological status of individuals with either homozygous or heterozygous G6PD A- deficiency differs from that of individuals with normal G6PD activity. In a field study in Nigeria, we determined G6PD gene variants, the corresponding G6PD and pyruvate kinase (PK) activities, and basic haematological parameters in clinically healthy individuals, who were, in part, asymptomatically infected by malaria parasites. Red blood cell counts and haemoglobin levels were lower in G6PD A- deficient than in G6PD normal subjects. PK activities were higher in G6PD deficients, indicating a younger red cell population in these individuals. These findings suggest that G6PD A- deficiency is accompanied by chronic subclinical haemolysis. As a consequence, the reduced life span of red cells leads to an impaired diagnosis of G6PD heterozygosity when applying routine biochemical methods.

Consumption of chloroquine (CQ) and subtherapeutic drug levels in blood are considered to be widespread in areas where malaria is endemic. A cross-sectional study was performed with 405 Nigerian children to assess factors associated with the presence of CQ in blood and to examine correlations of drug levels with malaria parasite species and densities. Infections with Plasmodium species and parasite densities were determined by microscopy and PCR assays. Whole-blood CQ concentrations were measured by high-performance liquid chromatography. Plasmodium falciparum, P. malariae, and P. ovale were observed in 80, 16, and 9% of the children, respectively, and CQ was detected in 52% of the children. CQ concentrations were >17 and <100 nmol/liter in 25% of the children, 100 to 499 nmol/liter in 14% of the children, and >500 nmol/liter in 13% of the children. Young age, attendance at health posts, and absence of parasitemia were factors independently associated with CQ in blood. With increasing concentrations of CQ, the prevalence of P. falciparum infection and parasite densities decreased. However, at concentrations corresponding to those usually attained during regular prophylaxis (>500 nmol/liter), 62% of children were still harboring P. falciparum parasites. In contrast, no infection with P. malariae and only one infection with P. ovale were observed in children with CQ concentrations of >100 nmol/liter. These data show the high prevalence of subcurative CQ concentrations in Nigerian children and confirm the considerable degree of CQ resistance in that country. Subtherapeutic drug levels are likely to further promote CQ resistance and may impair the development and maintenance of premunition in areas where malaria is endemic.Chloroquine (CQ) is one of the most widely consumed drugs (7). In 1988, an estimated 190 tons of CQ base were used in Africa alone (28). Self-medication, inadequate dosing, and subtherapeutic levels in blood are frequent and are believed to be predominant factors that contribute to CQ resistance in Plasmodium falciparum (25). However, data on actual CQ levels in residents of areas where malaria is endemic are scarce. The validity of history taking with respect to antimalarial drug usage is commonly low (17). Field methods for the detection of CQ in urine such as the Dill-Glazko test (13) suffer from poor sensitivity and specificity (21) and cannot quantify drug concentrations. Nevertheless, tests for detection of CQ in urine were found to be positive at hospital admission for 32% of patients in Malawi (17) and in 33% of patients in Zimbabwe (23). By applying high-performance liquid chromatography (HPLC), CQ was detected in the blood of up to 80% of schoolchildren in Tanzania, with the drug levels in the majority of children being too low to eliminate even CQ-sensitive parasites (9). The whole-blood CQ concentration required to suppress or eliminate P. falciparum is not well recognized. In adults, concentrations in whole blood of Ն500 nmol/liter are usually attained during prophylactic intake of 31...