We demonstrated in this randomised controlled trial that giving a combination of vitamin A and zinc supplements to children aged 6–24 months led to 27% significantly fewer cases of clinical attacks compared to children who were given vitamin A alone. This finding suggests a role of zinc in reducing malaria morbidity when given in addition to vitamin A; thus confirming the findings of Zeba et al.14 which demonstrated 30% fewer cases of clinical attacks.
Shankar et al.  demonstrated that vitamin A supplementation of children 6 months to 5 years of age in Papua New Guinea resulted in decreased malaria parasite densities, severity of infection and febrile episodes, which we also observed in our study. Several cross-sectional studies have shown a relationship between low zinc status and increased incidence of malaria [24, 25]. Shankar et al.  and Bates et al.  have in a pooled analysis demonstrated a 36% (95%CI:9-55%) reduction in the incidence of clinical malaria in children given daily doses of zinc supplements. However in a study in Gambian children by Muller et al. , there was no significant difference in the incidence of clinical malaria between the daily zinc and placebo groups. Other studies in Ghana by Binka et al. have not shown a significant effect of vitamin A on malaria parasitaemia rates or parasite densities . We observed that at end line a lower percentage of infants in the intervention group had high malaria parasite counts compared to infants in the control group and it is therefore not surprising that infants in the intervention group had a lower incidence of clinical malaria compared to infants in the control group Table 3.
Our study also showed a modest effect of vitamin and zinc supplementation on weight and length/height gain of the children involved in the study but this was not statistically significant and the reasons for this are not clear. This finding is also similar to results obtained by Rahman et al.  in Bangladeshi children between the ages of 12–35 months. The authors concluded that combined short-term zinc supplementation and a single dose of vitamin A had no significant change on weight and length increments in children over a 6-month period. Studies in Danish infants have shown an increase in anthropometric indices between the ages of 6–9 months among infants supplemented with zinc  but two other studies showed that low zinc intake did not impair growth [32, 33]. We did not find any significant differences in the anthropometric indices of those who were supplemented with zinc and the reasons for this are not too clear.
Humans have no body store for zinc, and bioavailable zinc must be supplied on a regular basis . Zinc deficiency in infancy and early childhood in developing countries leads to stunting , infectious disease morbidity  and mortality  especially from diarrhoea and pneumonia.
Pooled analyses of four randomised controlled trials by the Zinc Collaborative Group showed a 41% reduction in the incidence of pneumonia . In a study in Bangladesh assessing the interaction of the combination of vitamin A and zinc in the prevention of acute lower respiratory infections (ALRI), there was an increased relative risk of ALRI in the zinc supplemented children (RR 1.06, 95% CI 1.01-2.25) when compared to placebo  but we are unable to confirm or deny these finding because the number of respiratory diseases reported in our study were low.
There is undisputed evidence of the efficacy of zinc for the treatment of childhood diarrhoea and this has been confirmed by the results of pooled analyses of seven studies in children under the age of five years38. Gupta et al. supplemented children 6–41 months of age with 10 mg zinc five times a week and it was observed that children who received this had significantly lower rates of diarrhoea during the period of supplementation ; however, our study did not demonstrate any significant difference in the incidence of diarrhoea between the intervention and control groups.
We observed a modest increase in plasma zinc levels from baseline to end line, but this was not statistically significant. Similar findings have been described by Lo et al.  who found that plasma zinc concentration increased in children who received daily zinc supplementation for but not in those who received zinc with complementary foods suggesting the role of inhibitors in absorption.
Our study was conducted in an area where the mothers were of low socioeconomic status. More than 90% of children received a dose of vitamin A in the past 6 months. It is important to note that even though the children had been given vitamin A, vitamin A analyses showed that most of them still remained vitamin A deficient Table 2.
A limitation of the study was that the fact that the intervention was self administered, the weekly visits may not have adequately captured compliance to the intervention and the study was powered to look at the incidence of clinical malaria and so may not have been adequately powered to detect the effect of supplementation on other indices.
Our study showed that it was safe to administer vitamin A and zinc to infants as there were no reports of adverse events associated with administering zinc and vitamin A supplements, findings that have been confirmed by Walker and Black .