Intermittent preventive treatment of malaria delivered to primary schoolchildren provided effective individual protection in Jinja, Uganda: secondary outcomes of a cluster-randomized trial (START-IPT)

Abstract

Background Intermittent preventive treatment (IPT) of malaria is recommended as policy for certain high-risk populations, but not currently for schoolchildren. A cluster-randomized trial was conducted to evaluate the effect of IPT with dihydroartemisinin–piperaquine (DP) on primary schoolchildren in Jinja, Uganda. Results of the impact of IPT of schoolchildren on community-level transmission have been reported previously. Here, secondary outcomes from a school-based survey are presented. Methods Eighty-four clusters (one primary school plus 100 households) were randomized to intervention and control (1:1 ratio). Participants from intervention schools received monthly IPT with DP for up to 6 rounds (June–December 2014). At endline (November–December 2014), randomly selected children from all 84 schools were surveyed (13 per school) and thick blood smears were done. Those with fever or history of fever were tested with rapid diagnostic tests (RDTs) for malaria. Haemoglobin was measured in every fifth participant. Outcome measures included prevalence of asexual parasites and gametocytes (by microscopy), and prevalence of anaemia. Prevalence outcomes were analysed using generalized linear Poisson models with log link function, incorporating a cluster-level random intercept and quantified using prevalence risk ratios. Results Among 23,280 students listed on the 42 intervention school registers, 10,079 (43.3%) aged 5–20 years were enrolled into the IPT intervention and received at least one dose of DP; of these, 9286 (92.1%) received at least one full (3-day) course. In total, 1092 children were enrolled into the final school survey (546 per arm) and had a thick blood smear done; of these, 255 had haemoglobin measured (129 intervention, 126 control). Children in the intervention arm were less likely to have asexual parasites (9.2% intervention vs 44.1% control, adjusted risk ratio [aRR] 0.22 [95% CI 0.16–0.30] p < 0.001), gametocytes (3.1% intervention vs 9.5% control, aRR 0.34 [95% CI 0.20–0.56] p < 0.001), fever (20.2% intervention vs 56.2% control, aRR 0.35 [95% CI 0.25–0.50] p < 0.001), or symptomatic malaria (5.1% intervention vs 35.7% control, aRR 0.14 [95% CI 0.08–0.26] p < 0.001). Prevalence of anaemia and mean haemoglobin were similar in both study arms. Conclusions School-aged children are a major reservoir of malaria parasites. Delivering IPT to schoolchildren would benefit individual children and may reduce transmission. School-based IPT could help to intensify malaria control toward elimination, and should be considered for policies and programmes. Trial registration Clinicaltrials.gov (NCT02009215), Registered 11 December 2013. https://clinicaltrials.gov/ct2/show/NCT02009215

Preventive malaria treatment among school-aged children in sub-Saharan Africa: a systematic review and meta-analyses

“…School-aged children are significant reservoirs of human-to-mosquito transmission. 16 , 17 Three studies, 27 , 28 , 37 reported that intervention significantly decreased the prevalence of gametocytes, the parasite life-stage required for transmission. Staedke and colleagues 36 found that treating school-aged children decreased infection in the surrounding community by a small but statistically significant proportion.…”

“…Because malaria immunity increases with cumulative exposure to P falciparum parasites, we stratified results by age to explore the effect of intervention among children aged 5 years to less than 10 years versus children aged 10 years or older to less than 15 years. Because two of the larger trials 35 – 37 fundamentally differed from others, we also did sensitivity analyses excluding these datasets. We used Stata/IC 15 software for all analyses.…”

Effect of intermittent preventive treatment for malaria with dihydroartemisinin-piperaquine on immune responses to vaccines among rural Ugandan adolescents: randomised controlled trial protocol B for the ‘POPulation differences in VACcine responses’ (POPVAC) programme

“… 48 We therefore power our study to detect differences of this magnitude (0.2 log 10 ) or (in some cases) smaller. Among 5 to 15 year olds in this study setting, previous studies have reported malaria prevalence of >50% based on microscopy; 21 22 we assume malaria prevalence of > 60% based on PCR.…”

“…20 In a recently concluded trial in Uganda, IPT in schoolchildren was shown to be beneficial in protecting individual children and reducing community transmission of malaria. 21 22 …”

Perception of Malaria Chemoprevention Interventions in Infants and Children in Eight Sub-Saharan African Countries: an End-User Perspective Study

“…Other preventive interventions have been trialed or piloted, including intermittent preventive treatment in school children (IPTsc), mass drug administration (MDA) and post-discharge malaria chemoprevention (PMC) [13,14]. PMC being one of the most recently investigated interventions, we sought to better understand how it could be implemented.…”