A systematic review and meta-analysis of the efficacy and safety of intermittent preventive treatment of malaria in children (IPTc)

Abstract

Background: Intermittent preventive treatment of malaria in children less than five years of age (IPTc) has been investigated as a measure to control the burden of malaria in the Sahel and sub-Sahelian areas of Africa where malaria transmission is markedly seasonal.

Methods and findings: IPTc studies were identified using a systematic literature search. Meta-analysis was used to assess the protective efficacy of IPTc against clinical episodes of falciparum malaria. The impact of IPTc on all-cause mortality, hospital admissions, severe malaria and the prevalence of parasitaemia and anaemia was investigated. Three aspects of safety were also assessed: adverse reactions to study drugs, development of drug resistance and loss of immunity to malaria. Twelve IPTc studies were identified: seven controlled and five non-controlled trials. Controlled studies demonstrated protective efficacies against clinical malaria of between 31% and 93% and meta-analysis gave an overall protective efficacy of monthly administered IPTc of 82% (95%CI 75%-87%) during the malaria transmission season. Pooling results from twelve studies demonstrated a protective effect of IPTc against all-cause mortality of 57% (95%CI 24%-76%) during the malaria transmission season. No serious adverse events attributable to the drugs used for IPTc were observed in any of the studies. Data from three studies that followed children during the malaria transmission season in the year following IPTc administration showed evidence of a slight increase in the incidence of clinical malaria compared to children who had not received IPTc.

Conclusions: IPTc is a safe method of malaria control that has the potential to avert a significant proportion of clinical malaria episodes in areas with markedly seasonal malaria transmission and also appears to have a substantial protective effect against all-cause mortality. These findings indicate that IPTc is a potentially valuable tool that can contribute to the control of malaria in areas with markedly seasonal transmission.

Figure 1. Flow Diagram of Study Selection Process.

Figure 2. Effect of IPTc on clinical malaria (any level of parasitaemia) during the intervention period.

NOTE: D+L Overall = Random effect meta-analysis, I–V Overall = Fixed effect meta-analysis. AQ: amodiaquine, AS: artesunate, bi: bimonthly administration, CI: confidence interval, DHA: dihydroartemisinin, PQ: piperaquine, SP: sulphadoxine pyrimethamine.

Figure 3. Effect of IPTc on clinical malaria (any level of parasitaemia) during the subsequent transmission season (following IPTc administration).

NOTE: D+L Overall = Random effect meta-analysis, I–V Overall = Fixed effect meta-analysis. AQ: amodiaquine, AS: artesunate, bi: bimonthly administration, CI: confidence interval, SP: sulphadoxine pyrimethamine.