Kaufman Assessment Battery for Children (KABC) memory subtest raw score unadjusted mean (<i>M</i>) and standard deviation (<i>SD</i>) values are presented for the Uganda and Senegal groups.

<p>Also presented are the adjusted Mean (<i>M</i>) and standard error (<i>SE</i>) values for an ANCOVA analysis with age as the covariate. The significance probability (<i>P</i>) value and corresponding effect size for the ANCOVA between-group comparison are presented.</p

For age, education, gender, and physical development measures, the means (M) and standard deviations (<i>SD</i>), Student <i>t</i> test values and significance level probability values (<i>P</i>) for Uganda versus Senegal groups.

a<p>Chi Square test used for statistical <i>P</i> value.</p><p>Physical development <i>Z</i> scores based on CDC2000 norms (Epi Info).</p

Standardized estimates of regression coefficients on the ‘Cognitive ability’ latent variable.

<p>Standardized estimates of regression coefficients on the ‘Cognitive ability’ latent variable.</p

Demographic characteristics of the children.

1<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055653#s3" target="_blank">Results</a> indicate frequency, N (%); HOME = Home observation for the measurement of the environment; N = Number; M = Mean; SD = Standard deviation.</p

Regression coefficients with and without adjusters, excluding other cognitive measures.

*<p>“unadj” is from the unadjusted analysis using a single cognitive scale; “5 adj” is from the analysis using a single cognitive scale adjusting for age, sex, home environment, education level, and weight-for-age z score.</p

Estimates of regression coefficients of an outcome on a scale residual.

<p>Estimates of regression coefficients of an outcome on a scale residual.</p

Galbraith plot analysis to identify outliers among included studies of <i>STH</i> infection and performance in learning tests.

<p>Log SMD: logarithm of standardized mean difference; SE: Standard error. Studies that lie below the– 2 or above the +2 confidence limit are the outliers.</p

Soil-transmitted helminth infection, loss of education and cognitive impairment in school-aged children: A systematic review and meta-analysis

<div><p>Background</p><p>Evidence of an adverse influence of soil transmitted helminth (<i>STH</i>) infections on cognitive function and educational loss is equivocal. Prior meta-analyses have focused on randomized controlled trials only and have not sufficiently explored the potential for disparate influence of <i>STH</i> infection by cognitive domain. We re-examine the hypothesis that <i>STH</i> infection is associated with cognitive deficit and educational loss using data from all primary epidemiologic studies published between 1992 and 2016.</p><p>Methods</p><p>Medline, Biosis and Web of Science were searched for original studies published in the English language. Cognitive function was defined in four domains (learning, memory, reaction time and innate intelligence) and educational loss in two domains (attendance and scholastic achievement). Pooled effect across studies were calculated as standardized mean differences (SMD) to compare cognitive and educational measures for <i>STH</i> infected/non-dewormed children versus <i>STH</i> uninfected /dewormed children using Review Manager 5.3. Sub-group analyses were implemented by study design, risk of bias (ROB) and co-prevalence of <i>Schistosoma</i> species infection. Influential studies were excluded in sensitivity analysis to examine stability of pooled estimates.</p><p>Findings</p><p>We included 36 studies of 12,920 children. <i>STH</i> infected/non-dewormed children had small to moderate deficits in three domains—learning, memory and intelligence (SMD: -0.44 to -0.27, P<0.01–0.03) compared to <i>STH</i>-uninfected/dewormed children. There were no differences by infection/treatment status for reaction time, school attendance and scholastic achievement (SMD: -0.26 to -0.16, P = 0.06–0.19). Heterogeneity of the pooled effects in all six domains was high (P<0.01; I² = 66–99%). Application of outlier treatment reduced heterogeneity in learning domain (P = 0.12; I² = 33%) and strengthened <i>STH</i>-related associations in all domains but intelligence (SMD: -0.20, P = 0.09). Results varied by study design and ROB. Among experimental intervention studies, there was no association between <i>STH</i> treatment and educational loss/performance in tests of memory, reaction time and innate intelligence (SMD: -0.27 to 0.17, P = 0.18–0.69). Infection-related deficits in learning persisted within design/ROB levels (SMD: -0.37 to -52, P<0.01) except for pre-vs post intervention design (n = 3 studies, SMD = -0.43, P = 0.47). Deficits in memory, reaction time and innate intelligence persisted within observational studies (SMD: -0.23 to -0.38, all P<0.01) and high ROB strata (SMD:-0.37 to -0.83, P = 0.07 to <0.01). Further, in S<i>chistosoma</i> infection co-prevalent settings, associations were generally stronger and statistically robust for <i>STH</i>-related deficits in learning, memory and reaction time tests(SMD:-0.36 to -0.55, P = 0.003–0.02). <i>STH</i>-related deficits in school attendance and scholastic achievement was noted in low (SMD:-0.57, P = 0.05) and high ROB strata respectively.</p><p>Interpretation</p><p>We provide evidence of superior performance in five of six educational and cognitive domains assessed for <i>STH</i> uninfected/dewormed versus <i>STH</i> infected/not-dewormed school-aged children from helminth endemic regions. Cautious interpretation is warranted due to high ROB in some of the primary literature and high between study variability in most domains. Notwithstanding, this synthesis provides empirical support for a cognitive and educational benefit of deworming. The benefit of deworming will be enhanced by strategically employing, integrated interventions. Thus, multi-pronged inter-sectoral strategies that holistically address the environmental and structural roots of child cognitive impairment and educational loss in the developing world may be needed to fully realize the benefit of mass deworming programs.</p></div

The association between soil-transmitted helminth infection or no-deworming on tests of learning.

<p>SD: standard deviation; CI: confidence interval; Std: standard; df: degree of freedom; I²: measure of variability expressed in %. Squares indicate the SMD in each study, with square sizes directly proportional to the weight contribution (%) of each study. Horizontal lines represent 95% confidence intervals (CI). The diamond denotes the pooled standardized mean difference (SMD). The Z test for overall effect indicates deficits for <i>STH</i> infected/non treated vs. uninfected/treated children. The chi-square test indicates heterogeneity is high (P <0.00001, I² = 66%) warranting use of the random-effects model.</p

Effect of <i>STH</i> infection/non-treatment on performance in cognitive and educational within strata of study designs, non-outlier investigations and study quality.

<p>Effect of <i>STH</i> infection/non-treatment on performance in cognitive and educational within strata of study designs, non-outlier investigations and study quality.</p