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

BACKGROUND: The burden of malaria infection in sub-Saharan Africa among school-aged children aged 5-15 years is underappreciated and represents an important source of human-to-mosquito transmission of Plasmodium falciparum. Additional interventions are needed to control and eliminate malaria. We aimed to assess whether preventive treatment of malaria might be an effective means of reducing P falciparum infection and anaemia in school-aged children and lowering parasite transmission. METHODS: In this systematic review and two meta-analyses, we searched the online databases PubMed, Embase, Cochrane CENTRAL, and Clinicaltrials.gov for intervention studies published between Jan 1, 1990, and Dec 14, 2018. We included randomised studies that assessed the effect of antimalarial treatment among asymptomatic school-aged children aged 5-15 years in sub-Saharan Africa on prevalence of P falciparum infection and anaemia, clinical malaria, and cognitive function. We first extracted data for a study-level meta-analysis, then contacted research groups to request data for an individual participant data meta-analysis. Outcomes of interest included prevalence of P falciparum infection detected by microscopy, anaemia (study defined values or haemoglobin less than age-adjusted and sex-adjusted values), clinical malaria (infection and symptoms on the basis of study-specific definitions) during follow-up, and code transmission test scores. We assessed effects by treatment type and duration of time protected, and explored effect modification by transmission setting. For study-level meta-analysis, we calculated risk ratios for binary outcomes and standardised mean differences for continuous outcomes and pooled outcomes using fixed-effect and random-effects models. We used a hierarchical generalised linear model for meta-analysis of individual participant data. This study is registered with PROSPERO, CRD42016030197. FINDINGS: Of 628 studies identified, 13 were eligible for the study-level meta-analysis (n=16 309). Researchers from 11 studies contributed data on at least one outcome (n=15 658) for an individual participant data meta-analysis. Interventions and study designs were highly heterogeneous; overall risk of bias was low. In the study-level meta-analysis, treatment was associated with reductions in P falciparum prevalence (risk ratio [RR] 0·27, 95% CI 0·17-0·44), anaemia (0·77, 0·65-0·91), and clinical malaria (0·40, 0·28-0·56); results for cognitive outcomes are not presented because data were only available for three trials. In our individual participant data meta-analysis, we found treatment significantly decreased P falciparum prevalence (adjusted RR [ARR] 0·46, 95% CI 0·40-0·53; p<0·0001; 15 648 individuals; 11 studies), anaemia (ARR 0·85, 0·77-0·92; p<0·0001; 15 026 individuals; 11 studies), and subsequent clinical malaria (ARR 0·50, 0·39-0·60; p<0·0001; 1815 individuals; four studies) across transmission settings. We detected a marginal effect on cognitive function in children older than 10 years (adjusted mean difference in standardised test scores 0·36, 0·01-0·71; p=0·044; 3962 individuals; five studies) although we found no significant effect when combined across all ages. INTERPRETATION: Preventive treatment of malaria among school-aged children significantly decreases P falciparum prevalence, anaemia, and risk of subsequent clinical malaria across transmission settings. Policy makers and programme managers should consider preventive treatment of malaria to protect this age group and advance the goal of malaria elimination, while weighing these benefits against potential risks of chemoprevention. FUNDING: US National Institutes of Health and Burroughs Wellcome Fund/ASTMH Fellowship.

Impact of school-based malaria case management on school attendance, health and education outcomes: a cluster randomised trial in southern Malawi.

Introduction: Evidence indicates children who suffer from ill-health are less likely to attend or complete schooling. Malaria is an important cause of morbidity and mortality in school-age children. However, they are less likely to receive malaria treatment at health facilities and evidence for how to improve schoolchildren's access to care is limited. This study aimed to evaluate the impact of a programme of school-based malaria case management on schoolchildren's attendance, health and education. Methods: A cluster randomised controlled trial was conducted in 58 primary schools in Zomba District, Malawi, 2011-2015. The intervention, implemented in 29 randomly selected schools, provided malaria rapid diagnostic tests and artemisinin-based combination therapy to diagnose and treat uncomplicated malaria as part of basic first aid kits known as 'Learner Treatment Kits' (LTK). The primary outcome was school attendance, assessed through teacher-recorded daily attendance registers and independent periodic attendance spot checks. Secondary outcomes included prevalence of Plasmodium spp infection, anaemia, educational performance, self-reported child well-being and health-seeking behaviour. A total of 9571 children from standards 1-7 were randomly selected for assessment of school attendance, with subsamples assessed for the secondary outcomes. Results: Between November 2013 and March 2015, 97 trained teachers in 29 schools provided 32 685 unique consultations. Female schoolchildren were significantly more likely than male to seek a consultation (unadjusted OR=1.78 (95% CI 1.58 to 2.00). No significant intervention effect was observed on the proportion of child-days recorded as absent in teacher registers (n=9017 OR=0.90 (95% CI 0.77 to 1.05), p=0.173) or of children absent during random school visits-spot checks (n=5791 OR=1.09 (95% CI 0.87 to 1.36), p=0.474). There was no significant impact on child-reported well-being, prevalence of Plasmodium spp, anaemia or education scores. Conclusion: Despite high community demand, the LTK programme did not reduce schoolchildren's absenteeism or improve health or education outcomes in this study setting. Trial registration number: ClinicalTrials.gov NCT02213211.

Adherence and acceptability of community-based distribution of micronutrient powders in Southern Mali.

Home fortification with micronutrient powders (MNP) has been shown to reduce anaemia, with high overall acceptability and adherence, but there is limited evidence from West Africa. Around 80% of children younger than 5 years are anaemic in Mali, and new interventions are needed. This paper reports on the adherence and acceptability of a community-led MNP intervention targeting children aged 6-59 months in Southern Mali. The MNP were delivered by a multidisciplinary group of community volunteers using community-based preschools, cooking demonstrations, and traditional communication networks to promote MNP, nutrition, hygiene, and child stimulation. The MNP were delivered alongside early childhood development interventions and seasonal malaria chemoprevention. Adherence and acceptability were evaluated through two cross-sectional surveys in 2014 and 2016 and a qualitative evaluation in 2015. Over 80% of parents reported ever having given MNP to their child, with 65% having given MNP for four or more days in the last week. Likely contributors to uptake include: perceived positive changes in the children following MNP use, the selection of a food vehicle that was already commonly given to children (morning porridge or bouillie) and the community driven, decentralized and integrated delivery approach. These findings support recommendations from recent reviews of MNP implementation to use community-based delivery approaches and behaviour change components.

Using a Community-Based Early Childhood Development Center as a Platform to Promote Production and Consumption Diversity Increases Children's Dietary Intake and Reduces Stunting in Malawi: A Cluster-Randomized Trial.

Background: Children in Malawi face nutritional risks related to low-quality diets and chronic malnutrition. Objective: This study evaluated the impact of a 1-y early childhood development (ECD) center-based agriculture and nutrition intervention aimed at improving household production diversity, maternal knowledge on child nutrition and feeding practices, and children's diets and anthropometric measures. Methods: A longitudinal cluster-randomized controlled trial was implemented in 60 community-based childcare centers (CBCCs), covering 1248 preschool children (aged 36-72 mo) and 304 younger siblings (aged 6-24 mo). CBCCs were randomly assigned to 1) a control group providing the Save the Children's ECD program or 2) a treatment group providing a standard ECD program with additional activities to improve nutritious food production and behavior change communication to improve diets and care practices for young children. Primary outcomes were household production and production diversity, preschooler enrollment and attendance, and dietary intake measured by quantitative 24-h recall and minimum diet diversity for younger siblings. Secondary outcomes included anthropometric measures for preschoolers and younger siblings, child development scores for preschoolers, and women's asset ownership and time use (the latter 2 are not discussed in this article). We used difference-in-difference (DID) estimates to assess impacts. Results: Compared with the control group, preschool children in the intervention group had greater increases in nutrient intakes and in dietary diversity. No impacts on anthropometric measures were seen in preschoolers. Younger siblings in the intervention group had greater increases in height-for-age z scores than did children in the control group (DID: 0.44; P < 0.05) and greater reductions in the prevalence of stunting (DID: -17 percentage points; P < 0.05). The plausibility of the impact on growth in younger siblings was supported by effects along program impact pathways, including production of nutritious foods, caregiver knowledge, and dietary diversity. Conclusion: Implementing an integrated agriculture and nutrition intervention through an ECD platform benefited children's diets and reduced stunting among younger siblings of targeted preschoolers. This trial was registered on the ISRCTN registry as ISCRCTN96497560.

Impact of a malaria intervention package in schools on Plasmodium infection, anaemia and cognitive function in schoolchildren in Mali: a pragmatic cluster-randomised trial.

BACKGROUND: School-aged children are rarely targeted by malaria control programmes, yet the prevalence of Plasmodium infection in primary school children often exceeds that seen in younger children and could affect haemoglobin concentration and school performance. METHODS: A cluster-randomised trial was carried out in 80 primary schools in southern Mali to evaluate the impact of a school-based malaria intervention package. Intervention schools received two interventions sequentially: (1) teacher-led participatory malaria prevention education, combined with distribution of long-lasting insecticidal nets (LLINs), followed 7 months later at the end of the transmission season by (2) mass delivery of artesunate and sulfadoxine-pyrimethamine administered by teachers, termed intermittent parasite clearance in schools (IPCs). Control schools received LLINs as part of the national universal net distribution programme. The impact of the interventions on malaria and anaemia was evaluated over 20 months using cross-sectional surveys in a random subset of 38 schools(all classes), with a range of cognitive measures (sustained attention, visual search, numeracy, vocabulary and writing) assessed in a longitudinal cohort of children aged 9-12 years in all 80 schools. RESULTS: Delivery of a single round of IPCs was associated with dramatic reductions in malaria parasitaemia (OR 0.005, 95% CI 0.002 to 0.011, p<0.001) and gametocyte carriage (OR 0.02, 95% CI 0.00 to 0.17, p<0.001) in intervention compared with control schools. This effect was sustained for 6 months until the beginning of the next transmission season. IPCs was also associated with a significant decrease in anaemia (OR 0.56, 95% CI 0.40 to 0.78, p=0.001), and increase in sustained attention (difference +0.23, 95% CI 0.10 to 0.36, p<0.001). There was no evidence of impact on other cognitive measures. CONCLUSION: The combination of malaria prevention education, LLINs and IPCs can reduce anaemia and improve sustained attention of school children in areas of highly seasonal transmission. These findings highlight the impact of asymptomatic malaria infection on cognitive performance in schoolchildren and the benefit of IPCs in reducing this burden. Additionally, malaria control in schools can help diminish the infectious reservoir that sustains Plasmodium transmission.

School-based diagnosis and treatment of malaria by teachers using rapid diagnostic tests and artemisinin-based combination therapy: experiences and perceptions of users and implementers of the Learner Treatment Kit, southern Malawi.

BACKGROUND: Training teachers to diagnose uncomplicated malaria using malaria rapid diagnostic tests and treat with artemisinin-based combination therapy has the potential to improve the access of primary school children (6-14 years) to prompt and efficient treatment for malaria, but little is known about the acceptability of such an intervention. This qualitative study explored experiences and perceptions of users and implementers of a programme of school-based malaria case management via a first-aid kit-the Learner Treatment Kit (LTK)-implemented as part of a cluster-randomized controlled trial in Zomba district, Malawi. METHODS: From 29 primary schools where teachers were trained to test and treat school children for malaria using the LTK, six schools were purposively selected on the basis of relative intervention usage (low, medium or high); school size and geographical location. In total eight focus group discussions were held with school children, parents and guardians, and teachers; and 20 in-depth interviews were conducted with key stakeholders at the school, district and national levels. Interviews were recorded, transcribed, and analysed using a thematic analysis approach. RESULTS: The LTK was widely perceived by respondents to be a worthwhile intervention, with the opinion that trained teachers were trusted providers of malaria testing and treatment to school children. Benefits of the programme included a perception of improved access to malaria treatment for school children; decreased school absenteeism; and that the programme supported broader national health and education policies. Potential barriers to successful implementation expressed included increased teacher workloads, a feeling of inadequate supervision from health workers, lack of incentives and concerns for the sustainability of the programme regarding the supply of drugs and commodities. CONCLUSION: Training teachers to test for and treat uncomplicated malaria in schools was well received by both users and implementers alike, and was perceived by the majority of stakeholders to be a valuable programme. Factors raised as critical to the success of such a programme included ensuring an effective supervisory system, a reliable supply chain, and the training of greater numbers of teachers per school to manage high consultation numbers, especially during the peak malaria transmission season.

Cost analysis of a school-based comprehensive malaria program in primary schools in Sikasso region, Mali.

BACKGROUND: The expansion of malaria prevention and control to school-aged children is receiving increasing attention, but there are still limited data on the costs of intervention. This paper analyses the costs of a comprehensive school-based intervention strategy, delivered by teachers, that included participatory malaria educational activities, distribution of long lasting insecticide-treated nets (LLIN), and Intermittent Parasite Clearance in schools (IPCs) in southern Mali. METHODS: Costs were collected alongside a randomised controlled trial conducted in 80 primary schools in Sikasso Region in Mali in 2010-2012. Cost data were compiled between November 2011 and March 2012 for the 40 intervention schools (6413 children). A provider perspective was adopted. Using an ingredients approach, costs were classified by cost category and by activity. Total costs and cost per child were estimated for the actual intervention, as well as for a simpler version of the programme more suited for scale-up by the government. Univariate sensitivity analysis was performed. RESULTS: The economic cost of the comprehensive intervention was estimated to $10.38 per child (financial cost $8.41) with malaria education, LLIN distribution and IPCs costing $2.13 (20.5%), $5.53 (53.3%) and $2.72 (26.2%) per child respectively. Human resources were found to be the key cost driver, and training costs were the greatest contributor to overall programme costs. Sensitivity analysis showed that an adapted intervention delivering one LLIN instead of two would lower the economic cost to $8.66 per child; and that excluding LLIN distribution in schools altogether, for example in settings where malaria control already includes universal distribution of LLINs at community-level, would reduce costs to $4.89 per child. CONCLUSIONS: A comprehensive school-based control strategy may be a feasible and affordable way to address the burden of malaria among schoolchildren in the Sahel.

Improving child nutrition and development through community-based childcare centres in Malawi - The NEEP-IE study: study protocol for a randomised controlled trial.

BACKGROUND: The Nutrition Embedded Evaluation Programme Impact Evaluation (NEEP-IE) study is a cluster randomised controlled trial designed to evaluate the impact of a childcare centre-based integrated nutritional and agricultural intervention on the diets, nutrition and development of young children in Malawi. The intervention includes activities to improve nutritious food production and training/behaviour-change communication to improve food intake, care and hygiene practices. This paper presents the rationale and study design for this randomised control trial. METHODS: Sixty community-based childcare centres (CBCCs) in rural communities around Zomba district, Malawi, were randomised to either (1) a control group where children were attending CBCCs supported by Save the Children's Early Childhood Health and Development (ECD) programme, or (2) an intervention group where nutritional and agricultural support activities were provided alongside the routine provision of the Save the Children's ECD programme. Primary outcomes at child level include dietary intake (measured through 24-h recall), whilst secondary outcomes include child development (Malawi Development Assessment Tool (MDAT)) and nutritional status (anthropometric measurements). At household level, primary outcomes include smallholder farmer production output and crop-mix (recall of last production season). Intermediate outcomes along theorised agricultural and nutritional pathways were measured. During this trial, we will follow a mixed-methods approach and undertake child-, household-, CBCC- and market-level surveys and assessments as well as in-depth interviews and focus group discussions with project stakeholders. DISCUSSION: Assessing the simultaneous impact of preschool meals on diets, nutrition, child development and agriculture is a complex undertaking. This study is the first to explicitly examine, from a food systems perspective, the impact of a preschool meals programme on dietary choices, alongside outcomes in the nutritional, child development and agricultural domains. The findings of this evaluation will provide evidence to support policymakers in the scale-up of national programmes. TRIAL REGISTRATION: ISRCTN registry, ID: ISRCTN96497560 . Registered on 21 September 2016.

Design, implementation and evaluation of a training programme for school teachers in the use of malaria rapid diagnostic tests as part of a basic first aid kit in southern Malawi.

BACKGROUND: With increasing levels of enrolment, primary schools present a pragmatic opportunity to improve the access of school children to timely diagnosis and treatment of malaria, increasingly recognised as a major health problem within this age group. The expanded use of malaria rapid diagnostic tests (RDTs) and artemisinin combination therapy (ACT) by community health workers (CHWs) has raised the prospect of whether teachers can provide similar services for school children. We describe and evaluate the training of primary school teachers to use a first aid kit containing malaria RDTs and ACT for the diagnosis and treament of uncomplicated malaria in school children in southern Malawi. METHODS: We outline the development of the intervention as: (1) conception and design, (2) pilot training, (3) final training, and (4) 7-month follow up. The training materials were piloted at a four-day workshop in July 2013 following their design at national stakeholders meetings. The evaluation of the pilot training and materials were assessed in relation to increased knowledge and skill sets using checklist evaluations and questionnaires, the results of which informed the design of a final seven-day training programme held in December 2013. A follow up of trained teachers was carried out in July 2014 following 7 months of routine implementation. A total of 15 teachers were evaluated at four stages: pilot training, two weeks following pilot, final training and seven months following final training. RESULTS: A total of 15 and 92 teachers were trained at the pilot and final training respectively. An average of 93 % of the total steps required to use RDTs were completed correctly at the final training, declining to 87 % after 7 months. All teachers were observed correctly undertaking safe blood collection and handling, accurate RDT interpretation, and correct dispensing of ACT. The most commonly observed errors were a failure to wait 20 minutes before reading the test result, and adding an incorrect volume of buffer to the test cassette. CONCLUSION: Following training, teachers are able to competently use RDTs and ACTs test and treat children at school for uncomplicated malaria safely and accurately. Teachers demonstrate a comparable level of RDT use relative to non-health professional users of RDTs, and sustain this competency over a period of seven months during routine implementation.

The High Burden of Malaria in Primary School Children in Southern Malawi.

Malaria among school children has received increased attention recently, yet there remain few detailed data on the health and educational burden of malaria, especially in southern Africa. This paper reports a survey among school children in 50 schools in Zomba District, Malawi. Children were assessed for Plasmodium infection, anemia, and nutritional status and took a battery of age-appropriate tests of attention, literacy, and numeracy. Overall, 60.0% of children were infected with Plasmodium falciparum, 32.4% were anemic and 32.4% reported sleeping under a mosquito net the previous night. Patterns of P. falciparum infection and anemia varied markedly by school. In multivariable analysis, higher odds of P. falciparum infection were associated with younger age and being stunted, whereas lower odds were associated with reported net use, higher parental education, and socioeconomic status. The odds of anemia were significantly associated with P. falciparum infection, with a dose-response relationship between density of infection and odds of anemia. No clear relationship was observed between health status and cognitive and educational outcomes. The high burden of malaria highlights the need to tackle malaria among school children.

A comparison of the National Center for Health Statistics and new World Health Organization growth references for school-age children and adolescents with the use of data from 11 low-income countries.

BACKGROUND: In 2007 new World Health Organization (WHO) growth references for children aged 5-19 y were introduced to replace the National Center for Health Statistics (NCHS) references. OBJECTIVE: This study aimed to compare the prevalence of stunting, wasting, and thinness estimated by the NCHS and WHO growth references. DESIGN: NCHS and WHO height-for-age z scores were calculated with the use of cross-sectional data from 20,605 schoolchildren aged 5-17 y in 11 low-income countries. The differences in the percentage of stunted children were estimated for each year of age and sex. The z scores of body mass index-for-age and weight-for-height were calculated with the use of the WHO and NCHS references, respectively, to compare differences in the prevalence of thinness and wasting. RESULTS: No systematic differences in mean z scores of height-for-age were observed between the WHO and NCHS growth references. However, z scores of height-for-age varied by sex and age, particularly during early adolescence. In children for whom weight-for-height could be calculated, the estimated prevalence of thinness (WHO reference) was consistently higher than the prevalence of wasting (NCHS reference) by as much as 9% in girls and 18% in boys. CONCLUSIONS: In undernourished populations, the application of the WHO (2007) references may result in differences in the prevalence of stunting for each sex compared with results shown when the NCHS references are used as well as a higher estimated prevalence of thinness than of wasting. An awareness of these differences is important for comparative studies or the evaluation of programs. For school-age children and adolescents across all ranges of anthropometric status, the same growth references should be applied when such studies are undertaken.

Weekly iron supplements given by teachers sustain the haemoglobin concentration of schoolchildren in the Philippines.

OBJECTIVES: To examine the effectiveness of weekly iron supplements given for 10 weeks by teachers to children in rural schools in the Philippines. METHODS: Forty-nine rural primary schools took part in the study and were randomly assigned to two groups: children in 25 schools received a weekly tablet providing 108 mg iron while children in 24 schools acted as controls. All children were dewormed before the start of the iron supplementation. The haemoglobin concentration of a systematic sample of one in three children in two classes in each school was estimated before and 5-17 weeks after the end of the iron supplementation. RESULTS: A total of 1510 children aged 7-12 years were studied at both surveys. The mean haemoglobin concentration of children in the intervention group did not change significantly; in the untreated group it fell by 3.8 g/l and the prevalence of anaemia rose from 14.3% to 25.6%. The difference between study groups was significantly larger amongst the younger children (7-8 years), and was observed in both anaemic and non-anaemic children. CONCLUSION: Even where anaemia is only a mild public health problem, weekly iron supplements given by teachers may prevent a fall in the haemoglobin concentration, and can benefit both anaemic and non-anaemic children.

A randomised trial in Mali of the effectiveness of weekly iron supplements given by teachers on the haemoglobin concentrations of schoolchildren.

OBJECTIVE: To assess the effect on the haemoglobin concentrations of schoolchildren of weekly iron tablets administered by teachers. DESIGN: Sixty schools were randomly assigned to two groups: in 30 schools children were given weekly for 10 weeks a tablet providing 65 mg of iron and 0.25 mg of folic acid; in the other 30 schools no iron tablets were given. All children were dewormed and given vitamin A before the study began. The haemoglobin concentration of up to 20 randomly selected children in each school was estimated before and 2 weeks after the end of treatment. SETTING: Rural community schools in Kolondieba district of Mali. SUBJECTS: Some 1113 schoolchildren aged 6-19 years with a mean of 11.4 years. RESULTS: The haemoglobin concentration of treated children rose on average by 1.8 g l(-1) and the prevalence of anaemia fell by 8.2%; in untreated children the haemoglobin concentration fell by an average of -2.7 g l(-1) and the prevalence of anaemia rose by 9.4%. The fall in haemoglobin concentration among untreated girls of -4.0 g l(-1) was greater than in untreated boys (-0.3 g l(-1) ). CONCLUSIONS: Weekly iron tablets given by teachers prevented a general fall in the haemoglobin concentrations of untreated children, and led to a small but statistically significant rise among treated children. Young children benefited more than children aged >or=12 years, and girls benefited more than boys.