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Approximately 250 million (43%) children under the age of 5 years in low- and middle-income countries (LMICs) are failing to meet their developmental potential. Risk factors are recognised to contribute to this loss of human potential. Expanding understanding of the risks that lead to poor outcomes and which protective factors contribute to resilience in children may be critical to improving disparities. The Drakenstein Child Health Study is a population-based birth cohort in the Western Cape, South Africa. Pregnant women were enrolled between 20 and 28 weeks' gestation from two community clinics from 2012 to 2015; sociodemographic and psychosocial data were collected antenatally. Mothers and children were followed through birth until 2 years of age. Developmental assessments were conducted by trained assessors blinded to background, using the Bayley-III Scales of Infant and Toddler Development (BSID-III), validated for use in South Africa, at 24 months of age. The study assessed all available children at 24 months; however, some children were not able to attend, because of loss to follow-up or unavailability of a caregiver or child at the correct age. Of 1,143 live births, 1,002 were in follow-up at 24 months, and a total of 734 children (73%) had developmental assessments, of which 354 (48.2%) were girls. This sample was characterised by low household employment (n = 183; 24.9%) and household income (n = 287; 39.1% earning 1 domain affected, and 75 (10.2%) had delay in all domains. Bivariate and multivariable analyses revealed several factors that were associated with developmental outcomes. These included protective factors (maternal education, higher birth weight, and socioeconomic status) and risk factors (maternal anaemia in pregnancy, depression or lifetime intimate partner violence, and maternal HIV infection). Boys consistently performed worse than girls (in cognition [β = -0.74; 95% CI -1.46 to -0.03, p = 0.042], receptive language [β = -1.10; 95% CI -1.70 to -0.49, p < 0.001], expressive language [β = -1.65; 95% CI -2.46 to -0.84, p < 0.001], and fine motor [β = -0.70; 95% CI -1.20 to -0.20, p = 0.006] scales). There was evidence that child sex interacted with risk and protective factors including birth weight, maternal anaemia in pregnancy, and socioeconomic factors. Important limitations of the study include attrition of sample from birth to assessment age and missing data in some exposure areas from those assessed. This study provides reliable developmental data from a sub-Saharan African setting in a well-characterised sample of mother-child dyads. Our findings highlight not only the important protective effects of maternal education, birth weight, and socioeconomic status for developmental outcomes but also sex differences in developmental outcomes and key risk and protective factors for each group.

Infection is an important, preventable cause of maternal morbidity, and pregnancy-related sepsis accounts for 11% of maternal deaths. However, frequency of maternal infection is poorly described, and, to our knowledge, it remains the one major cause of maternal mortality without a systematic review of incidence. Our objective was to estimate the average global incidence of maternal peripartum infection. We searched Medline, EMBASE, Global Health, and five other databases from January 2005 to June 2016 (PROSPERO: CRD42017074591). Specific outcomes comprised chorioamnionitis in labour, puerperal endometritis, wound infection following cesarean section or perineal trauma, and sepsis occurring from onset of labour until 42 days postpartum. We assessed studies irrespective of language or study design. We excluded conference abstracts, studies of high-risk women, and data collected before 1990. Three reviewers independently selected studies, extracted data, and appraised quality. Quality criteria for incidence/prevalence studies were adapted from the Joanna Briggs Institute. We used random-effects models to obtain weighted pooled estimates of incidence risk for each outcome and metaregression to identify study-level characteristics affecting incidence. From 31,528 potentially relevant articles, we included 111 studies of infection in women in labour or postpartum from 46 countries. Four studies were randomised controlled trials, two were before-after intervention studies, and the remainder were observational cohort or cross-sectional studies. The pooled incidence in high-quality studies was 3.9% (95% Confidence Interval [CI] 1.8%-6.8%) for chorioamnionitis, 1.6% (95% CI 0.9%-2.5%) for endometritis, 1.2% (95% CI 1.0%-1.5%) for wound infection, 0.05% (95% CI 0.03%-0.07%) for sepsis, and 1.1% (95% CI 0.3%-2.4%) for maternal peripartum infection. 19% of studies met all quality criteria. There were few data from developing countries and marked heterogeneity in study designs and infection definitions, limiting the interpretation of these estimates as measures of global infection incidence. A limitation of this review is the inclusion of studies that were facility-based or restricted to low-risk groups of women. In this study, we observed pooled infection estimates of almost 4% in labour and between 1%-2% of each infection outcome postpartum. This indicates maternal peripartum infection is an important complication of childbirth and that preventive efforts should be increased in light of antimicrobial resistance. Incidence risk appears lower than modelled global estimates, although differences in definitions limit comparability. Better-quality research, using standard definitions, is required to improve comparability between study settings and to demonstrate the influence of risk factors and protective interventions.

Environmental enteropathy (EE) may increase the risk of diabetes, but data are limited. We assessed the role of EE on markers of glucose metabolism. Cross-sectional study among Tanzanian adults assessing EE and diabetes was conducted between 2019 and 2021. Data on demography, body mass index (BMI), Human immunodeficiency virus (HIV), EE (i.e., fecal myeloperoxidase, lipopolysaccharide binding protein, and markers of intestinal permeability and absorption capacity), glucose and insulin were collected. Data reduction using principal components analysis produced two components: sugar uptake and inflammatory EE. Tertiles were used to define EE severity as: lower, middle, and upper. The main outcome, combined prediabetes and diabetes, was defined as 2-hour oral glucose tolerance test (OGTT) glucose ≥7.8 mmol/L. Lower homeostatic model assessment (HOMA)-β and insulinogenic index, higher HOMA-insulin resistance (HOMA-IR), and lower Matsuda index were secondary outcomes. Logistic regression assessed the associations and HIV and BMI groups were tested as effect modifiers. A total of 612 participants were included. The mean (±SD) age was 42.0 (±11.6) years and 57.2% (350) were females. Eighty (13%) were underweight, 367 (60%) normal weight, 165 (27%) overweight, and 357 (58%) were HIV-infected. We found no overall association of EE on the main outcome, but BMI and HIV modified the associations. Compared to lower tertile of sugar uptake EE, the upper tertile was associated with marginally significant higher odds of prediabetes and diabetes (OR=2.1 (95% CI: 0.9, 4.9; P = 0.06)) and marginally significant higher HOMA-IR (OR=2.6 (1.0, 6.8; P = 0.06)) among overweight and obese participants. Similarly, compared to the lower tertile, the upper tertile of inflammatory EE was associated with higher odds of prediabetes and diabetes (OR=2.1 (1.1, 4.1; P = 0.03)) among HIV-uninfected participants, whereas among HIV-infected participants those in the middle tertile compared to those in the lower tertile had higher odds of lower Matsuda index (OR=2.3 (1.1, 4.7; P = 0.03)). EE may increase the risk of prediabetes and diabetes among those who are overweight and in individuals who are not HIV-infected. Longitudinal studies on the role of EE on diabetes are needed to confirm these results to provide the basis for developing and testing novel interventions to combat diabetes in Africa.

The burden of diabetes is increasing in sub-Saharan Africa, including among people living with HIV. We assessed the prevalence of diabetes and the roles of HIV, antiretroviral therapy (ART) and traditional risk factors among adults in Tanzania. We analysed diabetes-relevant baseline data from 1,947 adult participants in the CICADA study in Mwanza, Tanzania: 655 HIV-uninfected, 956 HIV-infected ART-naïve, and 336 HIV-infected persons on ART. WHO guidelines for haemoglobin A1c (HbA1c) and oral glucose tolerance test (OGTT) were used to define diabetes and prediabetes. Risk factors were evaluated using multinomial logistic regression analysis. Relative risk ratios (RRR) were generated comparing participants with diabetes and prediabetes against the reference of those with no diabetes. Mean age was 41 (SD 12) years; 59% were women. The prevalence of diabetes was 13% by HbA1c and 6% by OGTT, with partial overlap among participants identified by the two tests. Relative to HIV-uninfected, HIV-infected ART-naïve persons had increased relative risks of diabetes (HbA1c: RRR = 1.95, 95% CI 1.25-3.03; OGTT: RRR = 1.90, 95% CI 0.96-3.73) and prediabetes (HbA1c: RRR = 2.89, 95% CI 1.93-4.34; OGTT: RRR = 1.61, 95% CI 1.22-2.13). HIV-infected participants on ART showed increased risk of prediabetes (RRR 1.80, 95% CI 1.09, 2.94) by HbA1c, but not diabetes. CD4 count < 200 cell/μL at recruitment increased risk and physical activity decreased risk of diabetes by both HbA1c and OGTT. The prevalence of diabetes was high, especially among HIV-infected ART-naïve adults. Being more physically active was associated with lower risk of diabetes. HbA1c and OGTT identified different participants as having diabetes or prediabetes. Overall, the finding of high burden of diabetes among HIV-infected persons suggests that health systems should consider integrating diabetes screening and treatment in HIV clinics to optimize the care of HIV patients and improve their health outcomes.

Magnetic resonance imaging (MRI) is an indispensable tool for investigating brain development in young children and the neurobiological mechanisms underlying developmental risk and resilience. Sub-Saharan Africa has the highest proportion of children at risk of developmental delay worldwide, yet in this region there is very limited neuroimaging research focusing on the neurobiology of such impairment. Furthermore, paediatric MRI imaging is challenging in any setting due to motion sensitivity. Although sedation and anesthesia are routinely used in clinical practice to minimise movement in young children, this may not be ethical in the context of research. Our study aimed to investigate the feasibility of paediatric multimodal MRI at age 2–3 years without sedation, and to explore the relationship between cortical structure and neurocognitive development at this understudied age in a sub-Saharan African setting. A total of 239 children from the Drakenstein Child Health Study, a large observational South African birth cohort, were recruited for neuroimaging at 2–3 years of age. Scans were conducted during natural sleep utilising locally developed techniques. T1-MEMPRAGE and T2-weighted structural imaging, resting state functional MRI, diffusion tensor imaging and magnetic resonance spectroscopy sequences were included. Child neurodevelopment was assessed using the Bayley-III Scales of Infant and Toddler Development. Following 23 pilot scans, 216 children underwent scanning and T1-weighted images were obtained from 167/216 (77%) of children (median age 34.8 months). Furthermore, we found cortical surface area and thickness within frontal regions were associated with cognitive development, and in temporal and frontal regions with language development (beta coefficient ≥0.20). Overall, we demonstrate the feasibility of carrying out a neuroimaging study of young children during natural sleep in sub-Saharan Africa. Our findings indicate that dynamic morphological changes in heteromodal association regions are associated with cognitive and language development at this young age. These proof-of-concept analyses suggest similar links between the brain and cognition as prior literature from high income countries, enhancing understanding of the interplay between cortical structure and function during brain maturation. •MRI data are challenging to acquire in the early years of life.•Paediatric MRI without sedation is feasible in sub-Saharan Africa, with 77% success.•The Drakenstein Child Health study has novel MRI data of South African children.•Morphological features of the cortex associate with neurocognitive development.•Structure-cognition relationships in heteromodal association regions at 2–3 years.

Maternal and newborn infections are important causes of mortality but morbidity data from low- and middle-income countries is limited. We used telephone surveillance to estimate infection incidence and risk factors in women and newborns following hospital childbirth in Dar es Salaam. We recruited postnatal women from two tertiary hospitals and conducted telephone interviews 7 and 28 days after delivery. Maternal infection (endometritis, caesarean or perineal wound, or urinary tract infection) and newborn infection (umbilical cord or possible severe bacterial infection) were identified using hospital case-notes at the time of birth and self-reported symptoms. Adjusted Cox regression models were used to assess the association between potential risk-factors and infection. We recruited 879 women and interviewed 791 (90%). From day 0-7, 6.7% (49/791) women and 6.2% (51/762) newborns developed infection. Using full follow-up data, the infection rate was higher in women with caesarean childbirth versus women with a vaginal delivery (aHR 1.93, 95%CI 1.11-3.36). Only 24% of women received pre-operative antibiotic prophylaxis before caesarean section. Infection was higher in newborns resuscitated at birth versus newborns who were not resuscitated (aHR 4.45, 95%CI 2.10-9.44). At interview, 66% (37/56) of women and 88% (72/82) of newborns with possible infection had sought health-facility care. Telephone surveillance identified a substantial risk of postnatal infection, including cases likely to have been missed by hospital-based data-collection alone. Risk of maternal endometritis and newborn possible severe bacterial infection were consistent with other studies. Caesarean section was the most important risk-factor for maternal infection. Improved implementation of pre-operative antibiotic prophylaxis is urgently required to mitigate this risk.

Data on the role of helminths on diabetes in Africa are limited. We investigated whether Schistosoma and geohelminth infections are associated with β-cell function and insulin resistance among adults. A cross-sectional study was conducted among adults during 2016-2017. Demography, Schistosoma and geohelminth infections, HIV and insulin data were collected. Insulin during an oral glucose tolerance test (fasting, 30, and 120-min), overall insulin secretion index, insulinogenic index, HOMA-β, and HOMA-IR were main outcome measures for β-cell function and insulin resistance, respectively. Generalized estimating equations and generalized linear models assessed the association of Schistosoma and geohelminth infections with outcome measures separately by HIV status. Outcomes were presented as marginal means with 95% CI. Data were obtained for 1718 participants. Schistosoma infection was associated with higher 30-min insulin (24.2 mU/L, 95% CI: 6.9, 41.6) and overall insulin secretion index (13.3 pmol/L/mmol/L; 3.7, 22.9) among HIV-uninfected participants but with lower fasting insulin (-0.9 mU/L; -1.6, -0.2), 120-min insulin (-12.0 mU/L; -18.9, -5.1), and HOMA-IR (-0.3 mmol/L; -0.6, -0.05) among HIV-infected participants not yet on antiretroviral therapy (ART). Among HIV-infected participants not on ART, geohelminth infection was associated with lower fasting insulin (-0.9 mU/L; -1.6, -0.2), 120-min insulin (-9.1 mU/L; -17.3, -1.0), HOMA-β (-8.9 mU/L)/(mmol/L; -15.3, -2.6) and overall insulin release index (-5.1 pmol/L/mmol/L; -10.3, 0.02), although this was marginally significant. There was no association among those on ART. Schistosoma infection was associated with higher β-cell function among HIV-uninfected participants whereas Schistosoma and geohelminth infections were associated with reduced β-cell function among HIV-infected participants not on ART.

Introduction Co‐trimoxazole prophylaxis is recommended for children born to women with HIV to protect those who acquire HIV from opportunistic infections, severe bacterial infections and malaria. With scale‐up of maternal antiretroviral therapy, most children remain HIV‐exposed uninfected (HEU) and the benefits of universal co‐trimoxazole are uncertain. We assessed the effect of co‐trimoxazole on mortality and morbidity of children who are HEU. Methods We performed a systematic review (PROSPERO number: CRD42021215059). We systematically searched MEDLINE, Embase, Cochrane CENTRAL, Global Health, CINAHL Plus, Africa‐Wide Information, SciELO and WHO Global Index Medicus for peer‐reviewed articles from inception to 4th January 2022 without limits. Ongoing randomized controlled trials (RCTs) were identified through registries. We included RCTs reporting mortality or morbidity in children who are HEU receiving co‐trimoxazole versus no prophylaxis/placebo. The risk of bias was assessed using the Cochrane 2.0 tool. Data were summarized using narrative synthesis and findings were stratified by malaria endemicity. Results We screened 1257 records and included seven reports from four RCTs. Two trials from Botswana and South Africa of 4067 children who are HEU found no difference in mortality or infectious morbidity in children randomized to co‐trimoxazole prophylaxis started at 2–6 weeks of age compared to those randomized to placebo or no treatment, although event rates were low. Sub‐studies found that antimicrobial resistance was higher in infants receiving co‐trimoxazole. Two trials in Uganda investigating prolonged co‐trimoxazole after breastfeeding cessation showed protection against malaria but no other morbidity or mortality differences. All trials had some concerns or a high risk of bias, which limited the certainty of evidence. Discussion Studies show no clinical benefit of co‐trimoxazole prophylaxis in children who are HEU, except to prevent malaria. Potential harms were identified for co‐trimoxazole prophylaxis leading to antimicrobial resistance. The trials in non‐malarial regions were conducted in populations with low mortality potentially reducing generalizability to other settings. Conclusions In low‐mortality settings with few HIV transmissions and well‐performing early infant diagnosis and treatment programmes, universal co‐trimoxazole may not be required.

Previous studies demonstrated that fewer mosquitoes enter houses which are screened or have closed eaves. There is little evidence about the effect on malaria infection in humans that changes in house construction may have. This study examines the impact of protective housing improvements on malaria infection on Bioko Island. Data from the annual malaria indicator surveys between 2009 and 2012 were used to assess trends in housing characteristics and their effect on RDT confirmed malaria infection in household members. Odds ratios were adjusted for socio-economic status of the household.22726 children between the ages of 2 and 14 years were tested for P. falciparum. Prevalence of infection in those living in houses with open eaves was 23.0% compared to 18.8% for those living in houses with closed eaves (OR = 0.81, 95% CI 0.67 - 0.98). The prevalence of infection for children in screened houses was 9.1% versus 20.1% for those living in unscreened houses (OR = 0.44, 95% CI 0.27 - 0.71). The proportion of houses with closed eaves increased from 66.0% in 2009 to 74.3% in 2012 (test for trend p = 0.01). The proportion of screened houses remained unchanged over time at 1.3%. As a malaria control intervention, house modification has the advantages that it is not affected by the growing threat of insecticide resistance; it protects all household members equally and at all times while indoors; and it offers protection against a number of vector borne diseases. The study provides evidence in support of efforts to regulate or encourage housing improvements which impede vector access into residences as part of an integrated vector control approach to complement existing measures which have been only partially successful in reducing malaria transmission in some parts of Bioko.

Management of co-morbidities among persons living with HIV is an emerging priority, which may require additional medication over and above life-long antiretroviral therapy (ART). We explored factors associated with adherence to the trial drug among children and adolescents with perinatally acquired HIV taking antiretroviral therapy (ART) in the Bronchopulmonary Function in Response to Azithromycin Treatment for Chronic Lung Disease in HIV-Infected Children (BREATHE) trial. The BREATHE trial recruited 6-19 year olds with perinatally acquired HIV and co-morbid chronic lung disease as measured by FEV1. This two-site trial was individually randomised (1:1), double-blind and placebo-controlled. Participants received a once-weekly weight-based dose of 1-5 tablets of azithromycin (AZM: 250mg) or placebo, taken orally. We used pharmacy dispensing records and count of returned pills to measure adherence to study medication. Logistic regression was used to explore factors associated with adherence coverage. Poisson regression with Lexis expansion for time was used to explore whether adherence modified the effect of azithromycin on the incidence of acute respiratory exacerbation, a secondary outcome of the trial. Trial registration: ClinicalTrials.gov NCT02426112. The 347 participants (median age 15.3, 51% male) consumed 14,622 doses of study medication over 16,220 person-weeks under study. Adherence was higher for those randomised to AZM (73.4%) than placebo (68.4%) and declined over the 48 weeks of the study (Score test for trend <0.02). Those with unsuppressed HIV viral load at baseline had 2.08 (95% CI: 1.19, 3.63) times the odds of non-adherence than those with viral suppression. Differences were also observed between trial sites. The majority of children and adolescents tolerated the addition of a once-weekly dose of medication to their pill burden. Barriers in adhering to treatment for co-morbid conditions are likely common to barriers in adhering to ART. Control of co-morbidities will therefore present additional challenges in HIV care.