Intermittent preventive treatment for malaria in infants

Abstract

Background Intermittent preventive treatment could help prevent malaria in infants (IPTi) living in areas of moderate to high malaria transmission in sub‐Saharan Africa. The World Health Organization (WHO) policy recommended IPTi in 2010, but its adoption in countries has been limited. Objectives To evaluate the effects of intermittent preventive treatment (IPT) with antimalarial drugs to prevent malaria in infants living in malaria‐endemic areas. Search methods We searched the following sources up to 3 December 2018: the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library), MEDLINE (PubMed), Embase (OVID), LILACS (Bireme), and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) and the WHO International Clinical Trials Registry Platform (ICTRP) portal for ongoing trials up to 3 December 2018. Selection criteria We included randomized controlled trials (RCTs) that compared IPT to placebo or no intervention in infants (defined as young children aged between 1 to 12 months) in malaria‐endemic areas. Data collection and analysis The primary outcome was clinical malaria (fever plus asexual parasitaemia). Two review authors independently assessed trials for inclusion, evaluated the risk of bias, and extracted data. We summarized dichotomous outcomes and count data using risk ratios (RR) and rate ratios respectively, and presented all measures with 95% confidence intervals (CIs). We extracted protective efficacy values and their 95% CIs; when an included trial did not report this data, we calculated these values from the RR or rate ratio with its 95% CI. Where appropriate, we combined data in meta‐analyses and assessed the certainty of the evidence using the GRADE approach. Main results We included 12 trials that enrolled 19,098 infants; all were conducted in sub‐Saharan Africa. Three trials were cluster‐RCTs. IPTi with sulfadoxine‐pyrimethamine (SP) was evaluated in 10 trials from 1999 to 2013 (n = 15,256). Trials evaluating ACTs included dihydroartemisinin‐piperaquine (1 trial, 147 participants; year 2013), amodiaquine‐artesunate (1 study, 684 participants; year 2008), and SP‐artesunate (1 trial, 676 participants; year 2008). The earlier studies evaluated IPTi with SP, and were conducted in Tanzania (in 1999 and 2006), Mozambique (2004), Ghana (2004 to 2005), Gabon (2005), Kenya (2008), and Mali (2009). One trial evaluated IPTi with amodiaquine in Tanzania (2000). Later studies included three conducted in Kenya (2008), Tanzania (2008), and Uganda (2013), evaluating IPTi in multiple trial arms that included artemisinin‐based combination therapy (ACT). Although the effect size varied over time and between drugs, overall IPTi impacts on the incidence of clinical malaria overall, with a 30% reduction (rate ratio 0.70, 0.62 to 0.80; 10 studies, 10,602 partici...

Perennial malaria chemoprevention with and without malaria vaccination to reduce malaria burden in young children: a modelling analysis

“…The presented analysis includes simplifying assumptions that are relevant to the interpretation of the results. First, the modelled efficacy of PMC-3 in infants was matched to pooled estimates from various clinical trials across Africa conducted between 2000 and 2013 [ 7 ]. This allowed us to make generalizable projections sufficient to describe trends but might underestimate impact as some clinical trials showed higher efficacy [ 51 ].…”

“…The intervention aims to provide protection from malaria disease while allowing for some acquisition of natural immunity [ 5 ]. A pooled analysis of clinical trials conducted in the early 2000s reported a 22–30% reduction in clinical episodes in infants due to malaria chemoprevention with three to four doses [ 6 , 7 ]. In 2010, the World Health Organization (WHO) recommended three doses of sulfadoxine-pyrimethamine (SP) administered at ten weeks, fourteen weeks, and nine months of age, and referred to the intervention as intermittent preventive treatment in infants (IPTi) [ 8 ].…”

Application of mathematical modelling to inform national malaria intervention planning in Nigeria

“…IPTi effects were applied to simulation outputs rather than incorporated dynamically. Protective efficacy parameters for IPTi were extracted from a recent systematic review [ 71 ] and multiplied by LGA-specific coverage in each scenario to generate IPTi effects on prevalence, uncomplicated cases, severe cases, and deaths. LGA-specific expected coverage for IPTi was computed by taking the mean coverage of the first, second and third doses of pentavalent diphtheria, tetanus and pertussis vaccine from the 2018 DHS survey, in anticipation of IPTi administration coupled to the expanded program on immunization for children.…”

Review of intervention products for use in the prevention and control of anemia

“…The WHO recommends perennial malaria chemoprevention (PMC) for children under 2 years of age in areas of moderate to high perennial malaria transmission, although there are limited available data on the safety and efficacy of intermittent preventative treatment (IPT) in children ≤15 months of age 48 . PMC using sulfadoxine‐pyrimethamine (SP) likely decreases the risk of anemia by 18% (moderate‐certainty evidence) but does not appear to increase hemoglobin concentrations 49 . Studies have evaluated a range of 3–6 doses of SP in infants under 12 months of age and 1–11 doses of SP in infants 12–23 months of age 50 .…”