Impact of intermittent screening and treatment for malaria among school children in Kenya: a cluster randomised trial.

BACKGROUND: Improving the health of school-aged children can yield substantial benefits for cognitive development and educational achievement. However, there is limited experimental evidence of the benefits of alternative school-based malaria interventions or how the impacts of interventions vary according to intensity of malaria transmission. We investigated the effect of intermittent screening and treatment (IST) for malaria on the health and education of school children in an area of low to moderate malaria transmission. METHODS AND FINDINGS: A cluster randomised trial was implemented with 5,233 children in 101 government primary schools on the south coast of Kenya in 2010-2012. The intervention was delivered to children randomly selected from classes 1 and 5 who were followed up for 24 months. Once a school term, children were screened by public health workers using malaria rapid diagnostic tests (RDTs), and children (with or without malaria symptoms) found to be RDT-positive were treated with a six dose regimen of artemether-lumefantrine (AL). Given the nature of the intervention, the trial was not blinded. The primary outcomes were anaemia and sustained attention. Secondary outcomes were malaria parasitaemia and educational achievement. Data were analysed on an intention-to-treat basis. During the intervention period, an average of 88.3% children in intervention schools were screened at each round, of whom 17.5% were RDT-positive. 80.3% of children in the control and 80.2% in the intervention group were followed-up at 24 months. No impact of the malaria IST intervention was observed for prevalence of anaemia at either 12 or 24 months (adjusted risk ratio [Adj.RR]: 1.03, 95% CI 0.93-1.13, p = 0.621 and Adj.RR: 1.00, 95% CI 0.90-1.11, p = 0.953) respectively, or on prevalence of P. falciparum infection or scores of classroom attention. No effect of IST was observed on educational achievement in the older class, but an apparent negative effect was seen on spelling scores in the younger class at 9 and 24 months and on arithmetic scores at 24 months. CONCLUSION: In this setting in Kenya, IST as implemented in this study is not effective in improving the health or education of school children. Possible reasons for the absence of an impact are the marked geographical heterogeneity in transmission, the rapid rate of reinfection following AL treatment, the variable reliability of RDTs, and the relative contribution of malaria to the aetiology of anaemia in this setting. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00878007

Challenges for consent and community engagement in the conduct of cluster randomized trial among school children in low income settings: experiences from Kenya.

BACKGROUND: There are a number of practical and ethical issues raised in school-based health research, particularly those related to obtaining consent from parents and assent from children. One approach to developing, strengthening, and supporting appropriate consent and assent processes is through community engagement. To date, much of the literature on community engagement in biomedical research has concentrated on community- or hospital-based research, with little documentation, if any, of community engagement in school-based health research. In this paper we discuss our experiences of consent, assent and community engagement in implementing a large school-based cluster randomized trial in rural Kenya. METHODS: Data collected as part of a qualitative study investigating the acceptability of the main trial, focus group discussions with field staff, observations of practice and authors' experiences are used to: 1) highlight the challenges faced in obtaining assent/consent; and 2) strategies taken to try to both protect participant rights (including to refuse and to withdraw) and ensure the success of the trial. RESULTS: Early meetings with national, district and local level stakeholders were important in establishing their co-operation and support for the project. Despite this support, both practical and ethical challenges were encountered during consenting and assenting procedures. Our strategy for addressing these challenges focused on improving communication and understanding of the trial, and maintaining dialogue with all the relevant stakeholders throughout the study period. CONCLUSIONS: A range of stakeholders within and beyond schools play a key role in school based health trials. Community entry and information dissemination strategies need careful planning from the outset, and with on-going consultation and feedback mechanisms established in order to identify and address concerns as they arise. We believe our experiences, and the ethical and practical issues and dilemmas encountered, will be of interest for others planning to conduct school-based research in Africa. TRIAL REGISTRATION: National Institute of Health NCT00878007

Baseline characteristics of 5,233 study children in the 50 control and 51 IST intervention schools.

a<p>Percent of non-missing children in each study group presented for categorised data. For continuous data mean (SD) [min,max] is presented.</p>b<p>All characteristics have less than 2% missing data with the exception of following indicators (reported as control/intervention): stunted and thin both (138/248 [5.5/9.2%] missing), underweight (1,538/1,744 [61.0/64.4%] missing), net use last night (661/840 [26.2/31.0%] missing).</p>c<p>In Class 1, mean (SD) for age is: 7.8 (1.7) and in Class 5, mean (SD) for age is:12.5 (1.6).</p>d<p>Percentages of treated nets and children sleeping under a net last night are presented only for those children who were reported as usually sleeping under a net.</p>e<p>Study endpoints have less than 5% missing data at baseline with the exception of the following (reported as control/intervention): Hb (147/255 [5.8/9.4%] missing), <i>P. falciparum</i> infection (274 [10.1%] missing in intervention group), class 5 attention (79/72 [6.1/5.2%] missing).</p>f<p>Coefficient of variation (k) estimated for binary outcomes using available baseline (i.e., only using data from IST schools for <i>P. falciparum</i>) and interclass correlation coefficient (ICC) estimated for continuous outcomes using baseline measures.</p>g<p>Not measured at baseline in the control group.</p>h<p>Presented as mean (SD) [min,max].</p>i<p>In class 1 sustained attention was measured by the “pencil tap test” and in class 5 sustained attention was measured by the “two digit code transmission test.”</p

Summary information for 2,710 study children in the IST intervention group by screening round.

<p>Sensitivity and specificity of RDTs compared to expert microscopy is displayed.</p>a<p>Study children are shown as a percentage of the 2,710 initially eligible for the intervention and loss at each stage represents withdrawals and/or deaths. Child transfer events are not included.</p>b<p>Children treated who were directly observed taking doses 1, 3, and 5 in school at the correct time and who reported taking the evening doses.</p>c<p>Microscopy results not available for visit 5.</p

Effect of the IST intervention at 9- and 24-months follow-up on educational achievement (spelling and arithmetic) outcomes for younger (class 1) and older (class 5) children.

<p><a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001594#s3" target="_blank">Results</a> presented (i) for all children with outcome data (unadjusted) and (ii) for those with baseline measurements of each outcome and accounting for age, sex, and stratification effects (adjusted) as the primary pre-specified analysis. <i>N</i>, number of children eligible for follow-up (not withdrawn or deceased). Adjusted: for baseline age, sex, school mean exam score and literacy group (to account for stratification) and baseline measure of the outcome, where available; unadjusted: all children with outcome measures, not adjusted for any baseline or study design characteristics.</p>a<p>Mean difference (intervention-control) for scores on spelling and arithmetic are obtained from GEE analysis accounting for school-level clustering.</p>b<p>Mean score and SD at follow-up.</p>c<p>The same class 1 spelling task was given at baseline, 9- and 24-months follow-ups, with different words used for the 24-month follow-up.</p>d<p>Same addition task conducted at 9-months follow-up and at baseline, hence baseline adjustment is for the same task.</p>e<p>The same class 5 spelling task was given at baseline, 9- and 24-months follow-ups, with different words used for the 24-month follow-up.</p>f<p>Same arithmetic task conducted at baseline, 9- and 24-months follow-ups, with different sums used for the 24-month follow-up.</p>g<p>Addition task conducted at baseline and arithmetic task containing addition, subtraction, multiplication, and division conducted at 24-months follow-up, hence baseline adjustment for different task.</p

Map of the study area and schools.

<p>Schools assigned to the IST intervention are shown in blue and schools assigned to the control group are shown in yellow. Insert shows the location of the study site in Kenya.</p

Study design diagram.

<p>This figure depicts the randomisation procedures.</p

Effect of the IST intervention at 9- and 24-months follow-up on sustained attention outcomes for younger (class 1) and older (class 5) children.

<p><a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001594#s3" target="_blank">Results</a> presented (i) for all children with outcome data (unadjusted) and (ii) for those with baseline measurements of each outcome and accounting for age, sex, and stratification effects (adjusted) as the primary pre-specified analysis. <i>N</i>, number of children eligible for follow-up (not withdrawn or deceased). Adjusted: for baseline age, sex, school mean exam score and literacy group (to account for stratification), and baseline measure of the outcome, where available; unadjusted: all children with outcome measures, not adjusted for any baseline or study design characteristics.</p>a<p>Mean difference (intervention-control) are obtained from GEE analysis accounting for school-level clustering.</p>b<p>Mean score and SD at follow-up.</p>c<p>Pencil tap test was conducted at baseline and single digit code transmission task was conducted at 9- and 24-months follow-ups.</p>d<p>Double digit code transmission was conducted at baseline and both follow-ups.</p

Effect of the IST intervention at 12- and 24-months follow-up on health outcomes anaemia and <i>P. falciparum</i> prevalence for study children.

<p><a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001594#s3" target="_blank">Results</a> presented (i) for all children with outcome data (unadjusted) and (ii) for those with baseline measurements of each outcome and accounting for age, sex, and stratification effects (adjusted) as the primary pre-specified analysis. <i>N</i>, number of children eligible for follow-up (not withdrawn or deceased). Adjusted: for baseline age, sex, school mean exam score and literacy group (to account for stratification), and baseline measure of the outcome, where available; unadjusted: all children with outcome measures, not adjusted for any baseline or study design characteristics.</p>a<p>Risk ratios (intervention/control) presented for binary outcomes (anaemia and <i>P. falciparum</i> prevalence) and are obtained from GEE analysis accounting for school-level clustering.</p>b<p>Number and percentage with outcome.</p>c<p>Age-sex specific anaemia was defined using age and sex corrected WHO thresholds of Hb: <110 g/l in children under 5 years; <115 g/l in children 5 to 11 years; <120 g/l in females 12 years and over and males 12 to 14.99 years old; and <130 g/l in males ≥15 years. All female adolescents are assumed to not be pregnant.</p>d<p>Not including baseline <i>P. falciparum</i> infection.</p