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

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

The association between soil-transmitted helminth infection or no deworming on tests of learning with exclusion of identified outlier investigations.

<p>Diamond denotes the pooled standardized mean difference (SMD). 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 Z test for overall effect indicates non-significance given that <i>P</i> > 0.05. The chi-square test indicates that heterogeneity (P = 0.12, I² = 33%) was reduced by outlier treatment. SD: standard deviation; CI: confidence interval; Std: standard; df: degree of freedom; I²: measure of variability expressed in %.</p

Risk of bias analysis for intervention studies using cochrane collaborations’ tool.

<p>Risk of bias analysis for intervention studies using cochrane collaborations’ tool.</p

Characteristics of the included studies.

<p>Characteristics of the included studies.</p

Summary flowchart of literature search.

<p>Summary flowchart of literature search.</p

Associations between <i>STH</i> infection/non-treatment and performance in cognitive and educational domains among school-aged children following exclusion of outlier investigations using the Galbraith plot method.

<p>Associations between <i>STH</i> infection/non-treatment and performance in cognitive and educational domains among school-aged children following exclusion of outlier investigations using the Galbraith plot method.</p

Risk of bias in observational studies using the Newcastle-Ottawa quality assessment scale.

<p>Risk of bias in observational studies using the Newcastle-Ottawa quality assessment scale.</p

Comparison of pooled effects between <i>STH</i> infection and respective outcomes with and without co-prevalent <i>Schistosoma</i> infection.

<p>Comparison of pooled effects between <i>STH</i> infection and respective outcomes with and without co-prevalent <i>Schistosoma</i> infection.</p

Summary of the impact of publication bias on respective outcome domains.

<p>Summary of the impact of publication bias on respective outcome domains.</p