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Introduction: Over one billion people live with disability worldwide, of whom 80% are in developing countries. Robust childhood disability data are limited, particularly as tools for identifying disability function poorly at young ages. Methods: A subgroup of children enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (a cluster-randomised, community-based, 2x2 factorial trial in two rural districts in Zimbabwe) had neurodevelopmental assessments at 2 years of age. We evaluated functional difficulty prevalence in HIV-exposed and HIV-unexposed children using the Washington Group Child Functioning Module (WGCFM), comparing absolute difference using chi-squared or Fisher's exact tests. Concurrent validity with the Malawi Developmental Assessment Tool (MDAT) was assessed using logistic regression with cohort MDAT score quartiles, linear regression for unit-increase in raw scores and a Generalised Estimating Equation approach (to adjust for clusters) to compare MDAT scores of those with and without functional difficulty. A 3-step, cluster-adjusted multivariable regression model was then carried out to examine risk factors for functional difficulty. Findings: Functional Difficulty prevalence was 4.2% (95%CI: 3.2%, 5.2%) in HIV-unexposed children (n = 1606) versus 6.1% (95%CI: 3.5%, 8.9%) in HIV-exposed children (n = 314) (absolute difference 1.9%, 95%CI: -0.93%, 4.69%; p = 0.14). Functional difficulty score correlated negatively with MDAT: for each unit increase in WGCFM score, children completed 2.6 (95%CI: 2.2, 3.1) fewer MDAT items (p = 0.001). Children from families with food insecurity and poorer housing were more at risk of functional difficulty. Interpretation: Functional difficulty was identified in approximately 1-in-20 children in rural Zimbabwe, which is comparable to prevalence in previous studies. WGCFM showed concurrent validity with the MDAT, supporting its use in early childhood. [ABSTRACT FROM AUTHOR]

Background: Poverty and human capital development are inextricably linked and therefore research on human capital typically incorporates measures of economic well-being. In the context of randomized trials of health interventions, for example, such measures are used to: 1) assess baseline balance; 2) estimate covariate-adjusted analyses; and 3) conduct subgroup analyses. Many factors characterize economic well-being, however, and analysts often generate summary measures such as indices of household socio-economic status or wealth. In this paper, a household wealth index is developed and tested for participants in the cluster-randomized Sanitation, Hygiene, Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe. Methods: Building on the approach used in the Zimbabwe Demographic and Health Survey (ZDHS), we combined a set of housing characteristics, ownership of assets and agricultural resources into a wealth index using principal component analysis (PCA) on binary variables. The index was assessed for internal and external validity. Its sensitivity was examined considering an expanded set of variables and an alternative statistical approach of polychoric PCA. Correlation between indices was determined using the Spearman’s rank correlation coefficient and agreement between quintiles using a linear weighted Kappa statistic. Using the 2015 ZDHS data, we constructed a separate index and applied the loadings resulting from that analysis to the SHINE study population, to compare the wealth distribution in the SHINE study with rural Zimbabwe. Results: The derived indices using the different methods were highly correlated (r>0.9), and the wealth quintiles derived from the different indices had substantial to near perfect agreement (linear weighted Kappa>0.7). The indices were strongly associated with a range of assets and other wealth measures, indicating both internal and external validity. Households in SHINE were modestly wealthier than the overall population of households in rural Zimbabwe. Conclusion: The SHINE wealth index developed here is a valid and robust measure of wealth in the sample. [ABSTRACT FROM AUTHOR]

Background: HIV-infected infants in sub-Saharan Africa have rapid disease progression. We hypothesized that co-infection with cytomegalovirus (CMV) or Epstein Barr virus (EBV) increases mortality in HIV-infected infants. Methods: 257 antiretroviral therapy-naïve HIV-infected Zimbabwean infants were tested for CMV and EBV at 6 weeks of age by real-time PCR; if positive, birth samples were retrieved where available to distinguish congenital and postnatal infection. The impact of co-infection on mortality through 6 months was estimated using Kaplan-Meier and Cox proportional hazards methods. Results: At 6 weeks, 203/257 (79%) HIV-infected infants were CMV-positive; 27 (11%) had congenital CMV, 108 (42%) postnatal CMV and 68 (26%) indeterminate timing of infection. By 6 months, 37/108 (34%) infants with postnatal CMV versus 16/54 (30%) CMV-negative infants died (adjusted hazard ratio (aHR) 1.1 [95%CI 0.6, 2.2]). At 6 weeks, 33/257 (13%) HIV-infected infants had EBV co-infection; 6 (2%) had congenital EBV, 18 (7%) postnatal EBV and 9 (4%) indeterminate timing of infection. By 6 months, 5/18 (28%) infants with postnatal EBV versus 72/224 (32%) EBV-negative infants died (aHR 0.8 [95%CI 0.3, 2.3]). Conclusions: The vast majority of HIV-infants had acquired CMV by 6 weeks, and EBV co-infection occurred earlier than expected, with one in eight HIV-infected infants positive for EBV by 6 weeks. There was a high prevalence of congenital CMV infection and we identified 6 infants with congenital EBV infection, which has not previously been reported in Africa or in the context of HIV infection. Neither CMV nor EBV co-infection was associated with increased mortality. [ABSTRACT FROM AUTHOR]

Background: Stunting affects one-third of children in developing countries, but the causes remain unclear. We hypothesized that enteropathy leads to low-grade inflammation, which suppresses the growth hormone-IGF axis and mediates stunting. Methods: We conducted a case-control study of 202 HIV-unexposed Zimbabwean infants who were stunted (height-for-age Z-score (HAZ) <−2; cases) or non-stunted (HAZ >−0.5; controls) at 18 months. We measured biomarkers of intestinal damage (I-FABP), inflammation (CRP, AGP, IL-6) and growth hormone-IGF axis (IGF-1, IGFBP3) in infant plasma at 6 weeks and 3, 6, 12 and 18 months, and in paired maternal-infant plasma at birth. Adjusted mean differences between biomarkers were estimated using regression models. Multivariate odds ratios of stunting were estimated by logistic regression. Results: At birth, cases were shorter (median (IQR) HAZ −1.00 (−1.53, −0.08) vs 0.03 (−0.57, 0.62,); P<0.001) than controls and their mothers had lower levels of IGF-1 (adjusted mean difference (95%CI) −21.4 (−39.8, −3.1) ng/mL). From 6 weeks to 12 months of age, levels of CRP and AGP were consistently higher and IGF-1 and IGFBP3 lower in cases versus controls; IGF-1 correlated inversely with inflammatory markers at all time-points. I-FABP increased between 3–12 months, indicating extensive intestinal damage during infancy, which was similar in cases and controls. In multivariate analysis, higher log10 levels of CRP (aOR 3.06 (95%CI 1.34, 6.99); P = 0.008) and AGP (aOR 7.87 (95%CI 0.74, 83.74); P = 0.087) during infancy were associated with stunting. There were no associations between levels of I-FABP, IL-6, sCD14 or EndoCAb and stunting. Conclusions: Stunting began in utero and was associated with low maternal IGF-1 levels at birth. Inflammatory markers were higher in cases than controls from 6 weeks of age and were associated with lower levels of IGF-1 throughout infancy. Higher levels of CRP and AGP during infancy were associated with stunting. These findings suggest that an extensive enteropathy occurs during infancy and that low-grade chronic inflammation may impair infant growth. [ABSTRACT FROM AUTHOR]