Randomized comparison of the efficacies and tolerabilities of three artemisinin-based combination treatments for children with acute Plasmodium falciparum malaria in the Democratic Republic of the Congo.

An open-label, randomized controlled trial was carried out in 2011-2012 in the Democratic Republic of the Congo to test the efficacy, safety, and tolerability of the artemisinin-based combination treatments dihydroartemisinin-piperaquine, amodiaquine-artesunate, and artemether-lumefantrine. Six hundred eighty-four children aged 3 to 59 months with uncomplicated Plasmodium falciparum malaria were randomly allocated to each study arm. Children were hospitalized for 3 days, given supervised treatment, and followed up weekly for 42 days. All regimens were well tolerated and rapidly effective. The median parasitemia clearance half-life was 2.2 h, and half-lives were similar between arms (P=0.19). The PCR-uncorrected cure rates by day 42 were 73.0% for amodiaquine-artesunate, 70.2% for artemether-lumefantrine, and 86.3% for dihydroartemisinin-piperaquine (P=0.001). Early treatment failure occurred in three patients (0.5%), one in each arm. The PCR-corrected cure rates were 93.4% for amodiaquine-artesunate, 92.7% for artemether-lumefantrine, and 94.3% for dihydroartemisinin-piperaquine (P=0.78). The last provided a longer posttreatment prophylactic effect than did the other two treatments. The day 7 plasma concentration of piperaquine was below 30 ng/ml in 47% of the children treated with dihydroartemisinin-piperaquine, and the day 7 lumefantrine concentration was below 280 ng/ml in 37.0% of children who received artemether-lumefantrine. Thus, although cure rates were all satisfactory, they could be improved by increasing the dose. (This study has been registered with the International Standard Randomized Controlled Trial Number Register [www.isrctn.org] under registration no. ISRCTN20984426.).

Lack of difference in iron status assessed by soluble transferrin receptor between children with cerebral malaria and those with non-cerebral malaria.

We conducted this study to determine whether children with cerebral malaria are less likely to have tissue iron deficiency than those with non-cerebral malaria. Iron status was assessed by soluble transferrin receptor (sTfR), serum ferritin, and haemoglobin in 44 Zaïrian children: 15 with cerebral malaria, 14 with non-cerebral malaria, and 15 without malaria (age range 0.5-16 years). Although there was no significant difference in the mean concentrations of sTfR, serum ferritin, or haemoglobin between either group of patients, a higher percentage of children with cerebral malaria (27 per cent) than those with non-cerebral malaria (14 per cent) or controls (7%) had sTfR levels above 7.3 mg/l (suggestive of tissue iron deficiency). A higher percentage of children with cerebral malaria (40 per cent) than with non-cerebral malaria (29 per cent) or controls (20 per cent) also had either serum ferritin < 100 micrograms/l and inflammation or sTfR > 7.3 mg/l or both. The data suggest that children with cerebral malaria are as likely to have tissue iron deficiency as those with non-cerebral malaria.

Soluble transferrin receptor as an index of iron status in Zaïrian children with malaria.

This study was designed to evaluate soluble transferrin receptor (sTfR) as an index of iron status in 0.5-16-year-old Zaïrian children: 17 with symptomatic malaria, 8 with asymptomatic malaria, and 15 controls. sTfR was also measured in 20 plasma samples obtained from iron sufficient laboratory employees. sTfR, haemoglobin and ferritin were measured by enzyme-immunoassay, cyanmethaemoglobin method, and radioimmunoassay respectively. Mean haemoglobin levels were lower and ferritin higher (P < 0.001) in children with clinical symptoms of malaria than in those without malaria, and they were intermediate in those with asymptomatic malaria. Mean sTfR concentrations were similar among the three groups of children and laboratory controls. There was a considerable overlap in sTfR concentrations between the three groups of children (1.8-10.2, 2.9-11.6 and 2.97-8.95 mg 1(-1) in symptomatic malaria, asymptomatic malaria and control groups, respectively) as well as laboratory controls (1.2-7.30 mg l-1). Despite the overlap, 6 children with malaria (24%) and one control child (6.7%) had sTfR concentrations above the highest concentration found in laboratory controls. No child had serum ferritin < 12 micrograms l-1 (suggestive of iron deficiency). As expected, sTfR negatively correlated with ferritin (r = -0.230) in the overall study population of children, and with haemoglobin in children with asymptomatic malaria (r = -0.943, P < 0.05), as well as in control children (r = -0.363). All children with sTfR above normal were also anaemic. Although the upper limit of normal sTfR concentration in healthy children is unknown, using the cut-off value of adults, we conclude that sTfR might be a more sensitive index of iron deficiency than serum ferritin in patients with malaria.