SUMMARYBackground: Antimalarial drug resistance has been a major contributor to the failure of the battle against malaria in many developing countries. The P. falciparum genes, pfcrt and pfmdr-1, have been implicated in chloroquine resistance. The objective of this study was to determine the presence of mutant alleles of these chloroquine resistance genes among isolates of P. falciparum from children presenting with severe malaria in Ghana. Methods: Venous blood samples were taken from patients, and plasma chloroquine levels measured. P. falciparum chromosomal DNA was isolated from the blood samples, and subjected to PCR, restriction digestion and sequencing. Resulting data were analysed using the STATA statistical software. Results: Of 140 children recruited into the study, 109 (77.9%) had detectable pre-treatment chloroquine levels. PCR and restriction digestion analysis of the pfcrt gene indicated that 124 (88.6%) had the mutant T76 gene, and that this correlated with higher chloroquine levels. Sequence analysis of these showed consistent genetic sequences for chloroquine resistant and sensitive parasites with respect to Pfcrt codons 72 through 76.The Pfcrt T76 mutation was found in 88.4% of isolates having the Pfmdr-1Y86 mutation. The Pfmdr-1 Y86 mutation was found in 67.6% of isolates having the Pfcrt T76 mutation. Conclusion: The study affirms Pfcrt as a better chloroquine resistance marker. Both mutations are independently selected by chloroquine levels and that one mutation (Y86) might modify/increase the effect of the other (T76). This study also depicts the muchoverlooked antimalarial drug resistance situation in the area and emphasizes the need for a proper treatment strategy.

Abstract:Objective: To document the demography of paediatric admissions due to severe malaria, presentation and determinants of clinical symptoms and treatment for the condition at the KNUST Hospital, Ghana.Methods: A prospective, non-randomized, observational study was undertaken at the Children's Ward of the KNUST Hospital, in Kumasi. During a one month period, the symptoms on admission, treatment and treatment outcome of included children were documented. Inclusion criteria were age 0-144 months, verbal informed consent and severe malaria defined by presence of asexual Plasmodium falciparum parasitaemia coupled with at least one criterion suggestive of severe malaria as defined by WHO.Results: Overall, there were 82 malaria admissions with 69 cases being enrolled. On admission, mean haemoglobin levels were consistent for both males and females. Mean body weight was higher for females. Main presentations were anaemia of moderate to severe form (56); fever (52) and convulsions (24). Prostration was observed in all cases. Children under 5 years of age were associated with anaemia (p=0.018) and neurological symptoms (p=0.003). Clinical presentation of severe malaria was found to be independent of patients' sex. Quinine was used as treatment in 17 cases; monotherapy with artemisinin derivatives in 26 cases and artemisinin-amodiaquine combinations in 19 of the cases. No deaths were recorded. Conclusions:Children under 5 years of age presented more often with severe malaria. Prostration, anaemia and neurological symptoms were the most frequent manifestations.