A Systematic Review and Meta-Analysis of the Efficacy and Safety of Intermittent Preventive Treatment of Malaria in Children (IPTc)

Abstract

BackgroundIntermittent 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 FindingsIPTc 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.ConclusionsIPTc 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.

Impact of Mass Azithromycin Distribution on Malaria Parasitemia during the Low-Transmission Season in Niger: A Cluster-Randomized Trial

“…9,29 Combination therapies for IPTc such as amodiaquine plus sulfadoxine-pyrimethamine or artesunate plus sulfadoxine-pyrimethamine have been effective in areas of seasonal malaria transmission. 9,29,30 Emerging antimicrobial drug resistance has spread through malariaendemic areas and has made treatment difficult. 31 We did not measure resistance to azithromycin in Plasmodium because we were unable to perform cultures at our field site and biochemical assays for this have not been adequately described.…”

Selection of antimalarial drug resistance after intermittent preventive treatment of infants and children (IPTi/c) in Senegal

“…A meta-analysis of 12 clinical IPTc studies in sub-Saharan Africa including Senegal using SP, but always combined with another drug (amodiaquine AQ), have demonstrated impressive protective efficacies against clinical malaria episodes ranging from 31% to 93% (overall protective efficacy of 82% (95% CI = 75-87%). 9 Furthermore, it was shown that IPTc protected against all-cause mortality by 57% (95% CI = 24-76%). 9 Thus, IPTc is highly effective and furthermore, well tolerated.…”

“…9 Furthermore, it was shown that IPTc protected against all-cause mortality by 57% (95% CI = 24-76%). 9 Thus, IPTc is highly effective and furthermore, well tolerated. 10 -12 Therefore, WHO recommended IPTc, 13 now named Seasonal Malaria Chemoprevention (SMC) and the intervention will most likely be adopted large scale in areas where malaria transmission is seasonal.…”

Development of artemether-loaded nanostructured lipid carrier (NLC) formulation for topical application

“…Resistance is occurring as a consequence of several factors, including poor treatment practices, inadequate patient adherence to prescribed antimalarial regimens, widespread availability of artemisininbased monotherapies and substandard forms of the drug [9,10]. In recent years, parasite resistance to artemisinins -the key compounds in artemisinin combination therapy (ACTs) -has been detected in four countries of the Greater Mekong subregion: Cambodia, Myanmar, Thailand and Vietnam in agreement with the prediction of the World Health Organization (WHO) 2010 [6].…”