Of 713 eligible children (one village had only 23 children of the required age group), 709 were enrolled and randomised to either zinc (n=356) or placebo (n=353). The children were not treated for 4349 days in total owing to absence, an average of 6.3 days per child (2163 zinc, 2186 placebo). Overall, 661 of 685 children (96%) were examined during the cross sectional surveys (figure).
Table shows the characteristics of the children at baseline in June. The two groups were similar, except for the children being slightly older in the zinc group (18.7 v 17.5 months, P=0.03). At baseline 26% of the children were aged 6-12 months, 27% were 13-18 months, 26% were 19-24 months, and 21% were 25-31 months.
Characteristics of participants at baseline. Values are numbers (percentages) unless stated otherwise
The prevalence of malnutrition was high at baseline (table ), with 36.3% of children below –2 z score for height for age (stunting) and 24.6% below the –2 z score for weight for height (wasting). The effects of zinc on anthropometric measurements will be published elsewhere.
Clinical and parasitological data at baseline and end of study for cross sectional survey. Values are means (ranges) unless stated otherwise
Serum zinc values paired for June and September were available for 81 children (41 zinc, 40 placebo; table ). Mean zinc concentrations at baseline were 11.7 μmol/l, with no differences between the two groups, and 72% of the children were zinc deficient according to the reference laboratory's threshold of 13.0 μmol/l. After three months (mid-study survey), children in the zinc group had significantly higher serum zinc concentrations than children in the placebo group (15.3 v 12.4 μmol/l, P=0.005), and the proportion of zinc deficient children significantly declined in the zinc group but not in the placebo group (11/41 v 28/40, P=0.0001).
Spleen enlargement (Hackett score >1) was common at baseline and increased significantly until the end of the study (87% in zinc group v 98% in placebo group, P=0.001; table ). At the height of the rainy season (September) a quarter of the children reportedly slept under an untreated mosquito net the night before their visit, with no significant differences between the zinc and placebo groups (24% v 27%). Parasitological results were available for 511 of 661 (77%) and 615 of 661 (93%) children at baseline and at the end of the study, respectively (table ). Overall, P falciparum was the most common parasite (99%), and most of the children who had P malariae (6%) and P ovale (10%) also had P falciparum. The prevalence of falciparum malaria (1.4% in zinc group v 6.2% in placebo group, P=0.001) and of P falciparum, P malariae, and P ovale parasitaemia (62.8% v 89.6%, P=0.001; 4.2% v 13.2%, P=0.001; 0.6% v 20.2%, P=0.001), and the mean density of P falciparum (2909 v 7954, P=0.001) increased significantly over the study. Mean packed cell volume values, measured in 70 children (39 zinc, 31 placebo) at baseline and at follow up, significantly decreased from 32.0 to 29.1 over the study period (P=0.001). No differences were found in clinical or parasitological characteristics between the two groups, either at mid-study (data not shown) or at the end of the study.
Table shows the results for morbidity at follow up in the longitudinal study. Parasitological results were available for 2065 of 2324 (89%) febrile episodes. Over the six months of the study, the mean number of episodes of falciparum malaria a month was 0.38 (parasite density
1/μl), 0.28 (
5.000/μl), and 0.02 (
000/μl), with no differences between the zinc and placebo groups at any of the respective three parasite thresholds (relative risk 0.99, 95% confidence interval 0.89 to 1.11, P=0.94; 0.98, 0.86 to 1.11, P=0.77; 1.00, 0.64 to 1.60, P=0.91). This finding remained the same after analysis of the effects of zinc on the incidence of P falciparum
by age group (data not shown). No difference was found between the two groups for mean temperature (38.3°C in zinc group v
38.3°C in placebo group) and mean parasite density (44
316) during episodes of falciparum malaria (
Effect of zinc supplementation on febrile episodes of falciparum malaria and other causes of morbidity
Table also shows the effects of zinc supplementation on the number of reported days with other morbidity outcomes. No differences were found in the number of days with fever (relative risk 1.01, 0.95 to 1.07, P=0.62) and the number of days with cough (1.05, 0.97 to 1.15, P=0.22) between the two groups, but the number of days with diarrhoea was significantly lower in the zinc group (0.87, 0.79 to 0.95, P=0.002).
More children in the placebo group than zinc group died during the study (12 v 5), but this difference did not reach significance. The estimated relative risk in the survival analysis with a proportional hazards model was 0.41 (0.15 to 1.19, P=0.1). The relative risk did not change appreciably (0.47) when covariates were adjusted for.