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

Wilson AL, IPTc Taskfor - PLoS ONE (2011)

Bottom Line: 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.No serious adverse events attributable to the drugs used for IPTc were observed in any of the studies.

View Article: PubMed Central - PubMed

Affiliation: London School of Hygiene and Tropical Medicine, London, United Kingdom.

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.

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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.
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pone-0016976-g003: 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.

Mentions: A further safety concern for IPTc is that it will impair the development of natural immunity making children more susceptible to malaria after treatment is stopped. At the time of this review, data on clinical outcomes in the year after administration of IPTc were available for only three studies [20], [21], [22]. None of these studies demonstrated a statistically significant increase in the incidence of clinical malaria during the transmission season following the intervention. Random effect meta-analysis gave a summary effect measure of 1.11 (95% CI 0.99–1.24, p = 0.07) (Figure 3). A similar result was obtained when a more specific malaria case definition was used (data not shown). At the end of the malaria transmission season in year 2, the prevalence of anaemia in children who had received SP+AS in Niakhar was higher than in children who had received placebo in year 1 (SP+AS 10%, placebo 6%, p = 0.02) [20]. However, the mean Hb concentration (g/dL, 95%CI) was similar in SP+AS and placebo arms (SP+AS: 9.4 (9.3–9.6), placebo: 9.6 (9.4–9.6), p = 0.24). The prevalence of anaemia was similar in IPTc and placebo arms of the Hohoe trial at the end of the transmission season in the post-intervention year (SP bimonthly 12%, AS+AQ bimonthly 15%, AS+AQ monthly 10%, placebo 12%) [22]. The prevalence of parasitaemia at the end of the transmission season in the post-intervention year was similar among children who received IPTc or placebo in the previous year in the Niakhar and Hohoe studies (Niakhar: SP+AS 28%, placebo 30%, Hohoe: SP bimonthly 39%, AS+AQ bimonthly 40%, AS+AQ monthly 42%, placebo 40%) [20], [22].


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

Wilson AL, IPTc Taskfor - PLoS ONE (2011)

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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3038871&req=5

pone-0016976-g003: 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.
Mentions: A further safety concern for IPTc is that it will impair the development of natural immunity making children more susceptible to malaria after treatment is stopped. At the time of this review, data on clinical outcomes in the year after administration of IPTc were available for only three studies [20], [21], [22]. None of these studies demonstrated a statistically significant increase in the incidence of clinical malaria during the transmission season following the intervention. Random effect meta-analysis gave a summary effect measure of 1.11 (95% CI 0.99–1.24, p = 0.07) (Figure 3). A similar result was obtained when a more specific malaria case definition was used (data not shown). At the end of the malaria transmission season in year 2, the prevalence of anaemia in children who had received SP+AS in Niakhar was higher than in children who had received placebo in year 1 (SP+AS 10%, placebo 6%, p = 0.02) [20]. However, the mean Hb concentration (g/dL, 95%CI) was similar in SP+AS and placebo arms (SP+AS: 9.4 (9.3–9.6), placebo: 9.6 (9.4–9.6), p = 0.24). The prevalence of anaemia was similar in IPTc and placebo arms of the Hohoe trial at the end of the transmission season in the post-intervention year (SP bimonthly 12%, AS+AQ bimonthly 15%, AS+AQ monthly 10%, placebo 12%) [22]. The prevalence of parasitaemia at the end of the transmission season in the post-intervention year was similar among children who received IPTc or placebo in the previous year in the Niakhar and Hohoe studies (Niakhar: SP+AS 28%, placebo 30%, Hohoe: SP bimonthly 39%, AS+AQ bimonthly 40%, AS+AQ monthly 42%, placebo 40%) [20], [22].

Bottom Line: 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.No serious adverse events attributable to the drugs used for IPTc were observed in any of the studies.

View Article: PubMed Central - PubMed

Affiliation: London School of Hygiene and Tropical Medicine, London, United Kingdom.

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.

Show MeSH
Related in: MedlinePlus