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There is an urgent need to equip community-based careworkers with the skills to address the mental health needs of orphans and vulnerable children (OVC) as an essential response to shortages in human resources for mental health in Sub-Saharan Africa. We conducted a quasi-experimental feasibility trial in South Africa to adapt and evaluate an established year-long semi-structured, manualized video-feedback caregiver intervention (the Mediational Intervention for Sensitizing Caregivers; MISC) for community-based organizations (CBOs).Following a year-long iterative cross-cultural adaptation of MISC, we recruited 88 OVC (ages 7-11; 45.5% girls) and their CBO careworkers (MISC-CBO was acceptable and feasible in terms of attendance and post-intervention interviews. MISC improved child mental health, as well as the quality of careworker caregiving in terms of interactive effects for affective and cognitive (Expanding) components of MISC, and main effects for the cognitive components of Rewarding and Provision of meaning. MISC components did not mediate the effects of the intervention.The current study shows that laypersons with no tertiary education and virtually no prior training who undergo MISC training can improve caregiving quality and the mental health of OVCs.

OBJECTIVE: Evaluate a computerized-based attention test in early infancy in predicting neurocognitive school-age performance in HIV-exposed uninfected children. METHOD: Thirty-eight Ugandan HIV-exposed/uninfected children (17 boys, 21 girls) were evaluated with the Early Childhood Vigilance Test (ECVT) of attention between 3–5 years of age, which is a 6-minute 44 second animation with colorful animals that greet the child and move across the screen. Attention was proportion of total animation time viewing computer screen, as well as proportion of time tracking the moving animal using eye tracking. These children were then again tested at least two years later (between 5 and 9 years of age) with the Kaufman Assessment Battery for Children, 2nd Edition (KABC-II) and the visual computerized Tests of Variables of Attention (TOVA). RESULTS: Irrespective of whether scored by webcam video scoring or using automated eye tracking to compute proportion of time viewing the animation, ECVT attention was significantly correlated with all TOVA outcomes for vigilance attention. This was still the case when the correlation was adjusted for type of caregiver training for the mother, child gender, SES, and quality of HOME environment – especially for the TOVA response time variability to signal (p=0.03). None of the ECVT attention performance measures correlated significantly with any of the KABC-II cognitive ability outcomes. CONCLUSION: Attention assessment in early childhood is predictive of school-age computer-based measures of attention and can be used to gauge the effects of factors of early risk and resilience in brain/behavior development in African children affected by HIV.

OBJECTIVE: To compare childhood physical growth among antiretroviral drug and maternal HIV-exposed uninfected (AHEU) compared to HIV-unexposed uninfected (HUU) children. DESIGN: Longitudinal follow-up of PROMISE trial (NCT01061151) AHEU and age-matched and sex-matched HUU children, enrolled (September 2013 to October 2014) in Malawi and Uganda. METHOD: We compared WHO population standardized z-scores (Height-for-age (HAZ), weight-for-age (WAZ), weight-for-height (WHZ), head-circumference-for-age (HCAZ) at 12, 24, 36, 48, and 60 months-of-age. We evaluated HUU versus AHEU (in-utero combination antiretroviral treatment (cART) versus Zidovudine alone); stratified by country, using longitudinal linear and generalized linear mixed models. RESULTS: Of 466 Malawian and 477 Ugandan children, median maternal age at enrollment was 24.5 years (Malawi) and 27.8 years (Uganda); more than 90.0% were breastfed (BF) through 12 months except Uganda AHEU (64.0%). HAZ scores (adjusted for maternal age, BF, and socio-economic status) were lower among AHEU versus HUU children at every time point, significant (p

Household survey data from 27 sites in 22 countries were collected in 2017–2018 in order to construct and validate a cross-cultural household-level water insecurity scale. The resultant Household Water Insecurity Experiences (HWISE) scale presents a useful tool for monitoring and evaluating water interventions as a complement to traditional metrics used by the development community. It can also help track progress toward achievement of Sustainable Development Goal 6 ‘clean water and sanitation for all’. We present HWISE scale scores from 27 sites as comparative data for future studies using the HWISE scale in low- and middle-income contexts. Site-level mean scores for HWISE-12 (scored 0–36) ranged from 1.64 (SD 4.22) in Pune, India, to 20.90 (7.50) in Cartagena, Colombia, while site-level mean scores for HWISE-4 (scored 0–12) ranged from 0.51 (1.50) in Pune, India, to 8.21 (2.55) in Punjab, Pakistan. Scores tended to be higher in the dry season as expected. Data from this first implementation of the HWISE scale demonstrate the diversity of water insecurity within and across communities and can help to situate findings from future applications of this tool. HIGHLIGHTS We present comparison scores of the Household Water Insecurity Experiences (HWISE) scale, a novel household water insecurity index validated for use in low- and middle-income countries.; These scores can aid interpretation of future implementation of the HWISE scale.; The HWISE scale should still be evaluated in new contexts, such as high-income settings.

Objective To report vigilance attention outcomes from a cluster randomized controlled trial of early childhood development caregiver training for perinatally HIV-exposed/uninfected preschool-age children in rural Uganda. The Early Childhood Vigilance Test (ECVT) provides a webcam recording of proportion of time a child views an animation periodically moving across a computer screen. Study design Sixty mothers/caregivers received biweekly year-long training sessions of the Mediational Intervention for Sensitizing Caregivers (MISC), and 59 mothers received biweekly training about nutrition, hygiene, and health care. Children were tested for attention at baseline, 6 months, and 12 months with the ECVT, in terms of proportion of time spent viewing a 6-minute animation of animals greeting the child and moving across the computer monitor screen. Time viewing the animation were scored by trained observers using ProCoder program for webcam scoring of proportion of time the child faced the animation. Mixed-effects modeling was used to compare ECVT outcomes for the 2 intervention groups. Results Unadjusted and adjusted (for age, sex, height, and ECVT at baseline) group differences on ECVT significantly favored the MISC arm at 6 months (P = .03; 95% CI (0.01, 0.11), effect size = 0.46) but not at 12 months. Both groups made significant gains in sustained attention across the year-long intervention (P = .021) with no significant interaction effects between time and treatment arms or sex. Conclusions Caregiver early childhood development training enhanced attention in at-risk Ugandan children, which can be foundational to improved working memory and learning, and perhaps related to previous language benefits reported for this cohort. Trial registration Clinicaltrials.gov: NCT00889395 .

Cassava cyanide-related neurocognitive impairment may persist for years in Central African children who rely on cassava as a dietary staple. In the Democratic Republic of the Congo, a cassava processing method, the ‘wetting method’, reduced cyanide in cassava, prevented konzo, and proved a cost-effective intervention to improve children’s cognitive development. Scaling up use of the wetting method may help prevent neurocognitive impairment in millions of at-risk children in sub-Saharan Africa. A wetting method for cassava flour can further reduce cyanide exposure and its disease burden among children. The cost-effectiveness of the method in reducing cognitive disability is assessed in the Democratic Republic of the Congo.

We provide initial evidence that an eye-tracking based measure of infant attention and working memory (gaze preference for novel human faces) can predict aspects of neurocognitive performance years later among Ugandan children. 49 HIV-exposed/uninfected Ugandan children (22 boys, 27 girls) 6-12 months old were tested with the Mullen Scales of Early Learning and a modified Fagan Test of Infant Intelligence (FTII). Modified FTII measures pertaining to attention are correlated to the KABC-II Mental Processing Index (MPI) (rp = -0.40), p Cognitive assessments adapted to eye-tracking instrumentation can be useful to evaluate attention and working memory in HIV-affected children living in low- and middle-income countries.

OBJECTIVE We examined relationships between plasma biomarkers and neurodevelopment in children from sub-Saharan Africa with perinatal HIV (PHIV) with controlled viremia on antiretroviral therapy (ART). DESIGN Longitudinal retrospective cohort study of children with controlled blood HIV replication. METHODS Children (N = 213; 57% girls) started ART at less than 3 years of age, had neurodevelopmental assessments (cognition, attention/impulsivity, motor proficiency, global executive functions) at 5-11 years, and achieved controlled viremia (HIV-1 RNA

Rural children from Benin, west Africa were evaluated with the Mullen Scales of Early Learning (MSEL) at one year of age and then at six years with the Kaufman Assessment Battery for Children (KABC...

Background Neurodevelopmental outcomes of asymptomatic children exposed to Zika virus (ZIKV) in utero are not well characterized. Methods We prospectively followed 129 newborns without evidence of congenital Zika syndrome (CZS) up to 24 months of age. Participants were classified as ZIKV exposed or ZIKV unexposed. The Mullen Scales of Early Learning (MSEL) was administered in the participants’ homes at 6, 12, 15, 18, 21, and 24 months of age by trained psychologists. Sociodemographic data, medical history, and infant anthropometry at birth were collected at each home visit. Our primary outcome was the Mullen Early Learning Composite Score (ECL) at 24 months of age between our 2 exposure groups. Secondary outcomes were differences in MSEL subscales over time and at 24 months. Results Of 129 infants in whom exposure status could be ascertained, 32 (24.8%) met criteria for in utero ZIKV exposure and 97 (75.2%) did not. There were no differences in maternal age, maternal educational attainment, birthweight, or gestational age at birth between the 2 exposure groups. The adjusted means and standard errors (SEs) for the ELC score between the ZIKV-exposed children compared to ZIKV-unexposed children were 91.4 (SE, 3.1) vs 96.8 (SE, 2.4) at 12 months and 93.3 (SE, 2.9) vs 95.9 (SE, 2.3) at 24 months. In a longitudinal mixed model, infants born to mothers with an incident ZIKV infection (P = .01) and low-birthweight infants (, Children with in utero Zika virus exposure and without congenital Zika syndrome in Nicaragua had lower neurocognitive scores at 24 months. Our study includes multiple evaluations over time and a contemporary nonexposed comparator group of children, which is currently lacking in the literature.

Accepted manuscript; International audience; Background - Malaria in pregnancy (MiP) contributes significantly to infant mortality rates in sub-Saharan Africa and has consequences on survivors, such as preterm birth and low birth weight. However, its impact on long-term neurocognitive development in children remains unknown. Methods - Our prospective cohort included pregnant women and their live-born singletons from the Malaria in Pregnancy Preventive Alternative Drugs clinical trial. MiP was assessed using microscopy and real-time quantitative polymerase chain reaction (qPCR). Neurocognitive development in children was assessed using the Mullen Scales of Early Learning and the Kaufman Assessment Battery for Children, 2nd edition (KABC-II), at 1 and 6 years of age, respectively. Results - Of 493 pregnant women, 196 (40%) were infected with malaria at least once: 121 (31%) with placental malaria diagnosed by qPCR. Multiple linear regression B-coefficients showed that impaired gross motor scores were associated with MiP at least once (−2.55; confidence interval [95% CI]: −5.15, 0.05), placental malaria by qPCR (−4.95; 95% CI: −7.65, −2.24), and high parasite density at delivery (−1.92; 95% CI: −3.86, 0.02) after adjustment. Malaria and high parasite density at the second antenatal care visit were associated with lower KABC-II Non-Verbal Index scores at 6 years (−2.57 [95% CI: −4.86, −0.28] and −1.91 [−3.51, −0.32]), respectively. Conclusions This prospective cohort study provides evidence that MiP, particularly late term, could have important negative consequences on child development at 1 and 6 years of age. Mechanisms behind this association must be further investigated and diagnostic methods in low-income countries should be strengthened to provide adequate treatment. Clinical Trials Registration NCT00811421.

Cumulative lifetime adversity and social support were investigated as determinants of psychosocial adjustment (esteem, distress, hopefulness, positive outlook/future aspirations, and sense of purpose) over 12 months in 6-10-years-old HIV-infected, HIV-exposed uninfected and HIV-unexposed uninfected children from Uganda. Each determinant and psychosocial adjustment indicator was self-reported using standardized questionnaires administered at baseline, 6, and 12 months. Linear mixed effects models were used to relate time-varying lifetime adversity and social support to psychosocial adjustment over 12 months. Regardless of HIV status, higher adversity predicted lower esteem (coefficient b = -2.98, 95% confidence interval (CI): [-4.62, -1.35]) and increased distress (b =3.96, 95% CI: [1.29, 6.62]) but was not associated with hopefulness, positive outlook or sense of purpose. Low social support predicted higher distress (b =9.05, 95% CI: [7.36, 10.73]), lower positive outlook (b = -10.56, 95% CI: [-2.34, -8.79]) and low sense of purpose (b = -9.90, 95% CI: [-11.44, -8.36]) over 12 months. Pragmatic interventions that enhance coping with adversity and provide emotional/instrumental support should be tested for effectiveness in promoting resilient psychosocial adjustment trajectory in vulnerable children.

Objectives Maternal depression occurs in 13–20% of women from low-income countries, which is associated with negative child health outcomes, including diarrheal disease. However, few studies have investigated its impact on child risk of infectious disease. We studied the impacts of maternal depressive symptoms and parent–child interactions, independently, on the risk of Plasmodium falciparum malaria and soil-transmitted helminth infection in Beninese children. Methods Our population included mothers and children enrolled in a clinical trial during pregnancy (MiPPAD) in Benin. The Edinburgh Postnatal Depression Scale (EPDS) assessed maternal depressive symptoms and the home observation measurement of the environment (HOME) assessed parent–child interactions. Blood and stool sample analyses diagnosed child malaria and helminth infection at 12, 18, and 24 months. Negative binomial and Poisson regression models with robust variance tested associations. Results Of the 302 mother–child pairs, 39 (12.9%) mothers had depressive symptoms. Median number of malaria episodes per child was 3 (0–14) and 29.1% children had at least one helminth infection. Higher EPDS scores were associated with lower HOME scores; relative risk (RR) 0.97 (95% confidence interval (CI) 0.95, 0.99), particularly with lower acceptance, involvement, and variety subscales; RR 0.92 (95% CI 0.85, 0.99), RR 0.82 (95% CI 0.77, 0.88), RR 0.93 (95% CI 0.88, 0.99), respectively. However, neither exposure was associated with risk of parasitic infection in children. Conclusions for Practice Maternal depressive symptoms are associated with poor parent–child interactions, particularly acceptance of behavior, involvement with children, and variety of interactions, but these exposures do not independently impact risk of parasitic infection in children.

Children in Uganda are at risk for significant cognitive sequelae from severe malaria. Computerized cognitive rehabilitation training (CCRT) represents a potential method to improve working memory, behavior, and executive functioning, cognitive domains most at risk following severe malaria. The primary aim of this study was to complete a secondary analysis of data from a concluded CCRT randomized control trial in order to compare the training efficiency of a commonly used CCRT program under conditions of titrated (adaptive) or non-titrated (non-adaptive) training and with children with increasing malaria severity to determine how various factors may affect potential CCRT improvement. A total of 201 school-aged children (66.2% boys) who were either healthy (n = 102) or previously diagnosed with severe or cerebral malaria (n = 99) were randomized into two active treatment arms (titrated and non-titrated learning). Each child received 24 one-hour sessions of training over 8 weeks using Captain's Log® CCRT by BrainTrain, which includes a comprehensive set of CCRT tasks. Children generally benefited from CCRT over the 24 training sessions, but titrated CCRT showed a clear advantage over non-titrated. Severity of illness or factors such as BMI, did not moderate CCRT performance indicators. These findings support our hypothesis that titrated CCRT would result in steeper improvement in learning, but do not support our hypothesis that history of recent significant illness would affect learning proficiency. Findings were evident across all CCRT performance scores, even given that children were from generally rural, low-resource settings and were generally unfamiliar with computers.ABBREVIATIONS:Computerized Cognitive Rehabilitation Training (CCRT); Mental Processing Index (MPI); Home Observation for the Measurement of the Environment (HOME); Socioeconomic Status (SES); least square means (LSM).

Perinatal HIV and antiretroviral therapy exposure may influence neurocognitive outcomes, although evidence is mixed and most studies are limited to outcomes in the first 24 months. We compared neurocognitive outcomes in school-aged children who were HIV exposed uninfected (CHEU) with those in children who were HIV unexposed uninfected (CHUU).Children were recruited from a health center in Nairobi, Kenya.Key inclusion criteria were children aged 5-12 years and confirmed child and maternal HIV status; for CHEU, mothers reported knowing HIV-positive status before or at delivery of the index child. Children underwent a detailed battery of neuropsychological tests and behavioral assessment, and comparisons of scores between CHEU and CHUU were conducted using linear regression.Among 56 CHEU and 65 CHUU, the median age and sex distributions were 6.8 and 7.0 years (P = 0.8) and 48% and 60% girls (P = 0.2), respectively. In analyses adjusted for child's age and sex and caregiver's age, education, and household rent, CHEU had significantly lower mean z scores for global cognitive ability than CHUU [-0.35, 95% confidence interval (CI): -0.64 to -0.05; P = 0.02], short-term memory (-0.44, 95% CI: -0.76 to -0.12; P = 0.008), delayed memory (-0.43, 95% CI: -0.79 to -0.08; P = 0.02), attention (-0.41, 95% CI: -0.78 to -0.05; P = 0.03), and processing speed (-0.76, 95% CI: -1.37 to -0.16; P = 0.01). Models adjusted for child nutritional status, household food security, and orphanhood yielded similar results.Children exposed to HIV had poorer long-term neurocognitive outcomes than CHUU. These data suggest that long-term studies of neurocognitive and educational attainment in CHEU are warranted.

Introduction Many children living with HIV (CLWH) display impaired cognition. Although early combination antiretroviral therapy (ART) produces improved cognitive outcomes, more long‐term outcome data are needed. After concluding the Children with HIV Early antiRetroviral (CHER) trial in 2011, we investigated cognitive performance, at seven and nine years of age. Participants had been randomized to deferred ART (ART‐Def; n = 22); immediate time‐limited ART for 40 weeks (ART‐40W; n = 30) and immediate time‐limited ART for 96 weeks (ART‐96W; n = 18). We also recruited HIV‐exposed uninfected (CHEU; n = 28) and HIV‐unexposed (CHU; n = 35) children. Methods Data were collected between May 2012 and December 2017. Mixed‐model repeated‐measures ANOVAs assessed differences over time between CLWH (ART‐40W, ART‐96W and ART‐Def) and CHIV‐ CHEU and CHU between ART‐Early (ART‐40W and ART‐96W), ART‐Def, CHEU and CHU; and between ART‐40W, ART‐96W, ART‐Def, CHEU and CHU. Results All comparisons found significant effects of Time for most outcome variables (better scores at nine than at seven years; ps 0.17). Similarly, for motor dexterity, ART‐Def performed worse than ART‐96W, CHEU and CHU at seven years (p 0.20). Conclusions Although neurocognitive developmental trajectories for treatment groups and controls were largely similar (i.e. performance improvements from 7 to 9), all ART‐treated children, regardless of treatment arm, remain at risk for cognitive deficits over early school ages. Although the nature of these deficits may change as cognitive development proceeds, there are potential negative consequences for these children’s future learning, reasoning and adaptive functioning.

Depressive symptoms among HIV-positive (HIV+) women may negatively impact their health and possibly that of their young children through risk of compromised caregiving. We evaluated how depression symptoms in predominantly (97%) female caregivers relate to neurodevelopmental outcomes in their HIV affected children. Data come from the IMPAACT P1104s Study, an observational cohort across six sites in four countries: Zimbabwe, South Africa, Uganda and Malawi. Participants (n=611) were 5-11 year old children with HIV (HIV), HIV exposed uninfected (HEU), or HIV unexposed uninfected (HUU). Primary caregivers were assessed for depression with the Hopkins Symptom Checklist (HSCL) and children with Behavior Rating Inventory for Executive Function (BRIEF) parent-report, Kauffman Assessment Battery for Children II (KABC), Bruininks-Oseretsky Test of Motor Proficiency 2(nd) Ed. (BOT-2), Test of Variables of Attention (TOVA), Multiple Indicators Cluster Survey, Child Disability and Development scales (MICS-4). Caregivers with higher depression scores (> 1.75 mean HSCL score) reported more executive function problems in their children, regardless of HIV status. All executive function scores were significantly (p

Summary Background Antiretroviral medication during pregnancy and breastfeeding substantially decreases the risk of HIV transmission from mothers to infants, but its effects on the child's neurodevelopment are unknown. This study compared neurodevelopmental outcomes of ante-partum and post-partum antiretroviral exposure in HIV-exposed and uninfected children with HIV-unexposed and uninfected children at ages 12, 24, 48, and 60 months. Methods For this study, a prospective cohort of HIV-exposed and uninfected children was identified from two research sites in the PROMISE-BF trial (at Blantyre, Malawi, and Kampala, Uganda), in which pregnant HIV-infected mothers were randomly assigned to triple antiretroviral prophylaxis (lopinavir–ritonavir plus either lamivudine and zidovudine or emtricitabine and tenofovir), versus zidovudine alone. Post partum, the mother–infant pairs were randomly assigned to maternal triple antiretroviral treatment or infant nevirapine during breastfeeding. HIV-unexposed and uninfected children matched for age, sex, and socioeconomic background were enrolled at vaccination and well-child clinics at the study sites. We included only children without a history of documented brain infection or injury or substantial malnutrition, and whose mothers were randomly assigned and maintained within their assigned ante-partum and post-partum phases throughout their treatment arm periods. Primary outcomes were the Mullen Scales of Early Learning (MSEL) cognitive composite score at age 12 months, 24 months, and 48 months; and the mental processing index for the Kaufman Assessment Battery for Children, second edition (KABC-II) global score at 48 months and 60 months. Repeated measures were analysed using a linear mixed-effects model controlling for data collection site. Findings Between Aug 23, 2013, and Dec 17, 2014, we co-enrolled 861 children. For MSEL assessments, 738 were eligible for inclusion at age 12 months, 790 at age 24 months, and 692 at age 48 months. For KABC-II assessments, 685 were eligible for inclusion at age 48 months and 445 at age 60 months. There were no differences in MSEL cognitive composite scores according to exposure at age 12 and 24 months (p=0·19 and 0·24, respectively, for comparison of all groups). At 48 months, MSEL cognitive composite scores were worse for children of mothers who did not remain on triple antiretroviral treatment throughout both the ante-partum and post-partum treatment phases (adjusted means 80·64 [95% CI 77·74–83·54] and 81·34 [78·19–84·48], respectively), compared with those who did remain on triple treatment (adjusted mean 85·93, 95% CI 83·05–88·80; p=0·0486 for the comparison of all groups). The KABC-II composite scores (mental processing index) did not differ at 48 or 60 months according to exposure (p=0·81 and 0·89, respectively, for comparison of all groups). Scores for MSEL and KABC-II for children of mothers on triple antiretrovirals in both the ante-partum and post-partum treatment phases were similar to those for children in the HIV-unexposed and uninfected reference group at all timepoints. Interpretation Maternal triple antiretroviral exposure during both the ante-partum and post-partum phases did not result in greater developmental risks for the mothers' HIV-exposed and uninfected children through age 60 months, compared with children who were HIV-unexposed and uninfected. This might be because ante-partum triple antiretroviral protection of the health of mothers with HIV during pregnancy might be neuroprotective for the child, and when continued post partum, could enhance the quality of caregiving for the child through better clinical care for the mother. Funding National Institutes of Health and Eunice Kennedy Shriver National Institute of Child Health and Human Development.

BACKGROUND. We explored three immunopathogenic biomarkers collected during acute malaria illness as potential moderators of gains from a computerized cognitive rehabilitation training (CCRT) intervention. METHOD. Von Willebrand Factor (vWF), tumor necrosis factor (TNF), and Regulated on Activation, Normal T Expressed and Secreted (RANTES) were assayed from plasma and cerebral spinal fluid (CSF) of children during acute severe malaria anemia or cerebral malaria. Two years after acute malaria illness, 150 surviving children and 150 non-malaria community controls (CC) from their households 6 to 12 years old entered a three-arm randomized controlled trial of titrating and non-titrating CCRT against no CCRT. Tests of cognition (Kaufman Assessment Battery for Children; KABC), Tests of Variables of Attention (TOVA), and Achenbach Child Behavior Checklist (CBCL) were administered before and after 24 CCRT sessions over a 3-month period, and at one-year follow-up. Differences in outcomes by trial arms and biomarker levels were evaluated using linear mixed effects models. RESULTS. Severe malaria survivors with lower levels of vWF, lower CSF levels of TNF, and higher levels of plasma and CSF RANTES had better KABC cognitive performance after both titrating and non-titrating CCRT compared to no CCRT. For the CBCL, high plasma RANTES was associated with no benefit from either the titrating and non-titrating CCRT, while high TNF plasma was predictive of the benefit for both interventions. These biomarker moderating effects were not evident for CC children. CONCLUSION. Severe malaria immunopathogenic biomarkers may be related to poorer long-term brain/behavior function as evidenced by diminished benefit from a computerized cognitive rehabilitation intervention.

BACKGROUND Monocyte activation may contribute to neuronal injury in aviremic HIV-infected adults; data are lacking in children. We examined the relation between monocyte activation markers and early and long-term neurodevelopmental outcomes in early-treated HIV-infected children. SETTING Prospective study of infant and child neurodevelopmental outcomes nested within a randomized clinical trial (NCT00428116) and extended cohort study in Kenya. METHODS HIV-infected infants (N = 67) initiated antiretroviral therapy (ART) at age

We sought to understand social representations of effective parenting and parenting self-efficacy among female HIV-affected caregivers in rural Eastern Uganda. We conducted in-depth interviews (n = 21) to describe parenting experiences and caregivers' perceptions of their own parenting abilities and to create vignettes for use in directed focus groups. We carried out open focus groups (n = 2) to gain social perspectives on parenting, and directed focus groups (n = 2) concentrated on parenting self-efficacy. Analysis involved memoing and inductive and deductive coding of transcripts. Caregivers' perceptions of their own parenting were grounded in parenting values such as providing children with basic needs, having well-behaved children, and having good relationships with children. Caregivers' perceptions were influenced by challenges, including single parenthood, living with HIV, limited family resources, and mental health problems. When facing challenges, caregivers relied on social support and faith as well as their own parenting confidence. Caregivers' perceptions of their parenting abilities were influenced by how they felt others perceived them, their satisfaction in the parenting role, their perseverance despite challenges, and the extent to which they had a vision for their family. Our findings contextualize parenting self-efficacy within parenting values, challenges, and social perceptions among HIV-affected caregivers in rural Uganda.Nos propusimos comprender las representaciones sociales de la crianza eficaz y la auto-efectividad en la crianza entre mujeres afectadas con VIH y que prestan cuidados en el área rural del este de Uganda. Realizamos entrevistas profundas (n = 21) para describir las experiencias de crianza y las percepciones de las cuidadoras sobre sus propias habilidades de crianza y para crear esbozos para usar en grupos de enfoque dirigidos. Llevamos a cabo grupos de enfoque a puertas abiertas (n = 2) para conocer las perspectivas sociales acerca de la crianza y dirigimos los grupos de enfoque (n = 2) concentrados en la auto-efectividad de la crianza. Los análisis incluyeron la toma de notas con reflexión y la codificación inductiva y deductiva de las transcripciones. Las percepciones de las cuidadoras acerca de sus propias crianzas se basaron en los valores de la crianza tales como proveerles a los niños las necesidades básicas, tener niños que se comportan bien, así como mantener buenas relaciones con sus niños. Los retos influyeron las percepciones de las cuidadoras; entre ellos se incluyeron el ser una madre sin pareja, vivir con VIH, los limitados recursos familiares y los problemas de salud mental. Cuando se encontraron con retos, las cuidadoras confiaron en el apoyo social y en la fe, así como en la confianza en su propia crianza. Las percepciones de las cuidadoras acerca de sus habilidades de crianza estuvieron influidas por cómo ellas sentían que otros las veían, su satisfacción en el papel de crianza, su perseverancia a pesar de los retos, así como hasta qué punto tenían una visión para su familia. Nuestros resultados contextualizan la auto-efectividad de la crianza dentro de los valores, retos y perspectivas sociales de la misma entre mujeres afectadas por VIH que prestan cuidado en el área rural de Uganda.Nous avons voulu comprendre la représentation sociale du parentage efficace et de l'auto-efficacité de parentage chez des femmes prenant soin d'enfants et affectées par le VIH dans l'Ouganda rural de l'est. Nous avons conduit des entretiens approfondis (n = 21) afin de décrire les expériences de parentage et les perceptions des personnes prenant soin d'enfants de leurs propres capacités au parentage et afin de créer des vignettes pouvant être utilisées dans des groupes de réflexion et de discussion dirigés (n = 1) se concentrant sur l'auto-efficacité de parentage. L'analyse a inclus l'enregistrement de notes et le codage inductif et déductif des retranscriptions. Les perceptions de personnes prenant soin des enfants de leur propre parentage étaient fondées sur les valeurs de parentage, telles que le fait d'offrir aux enfants les soins de base, d'avoir des enfants sages, et de maintenir de bonnes relations avec les enfants. Les perceptions des personnes prenant soin des enfants étaient influencées par les défis auxquelles elles faisaient face, y compris la monoparentalité, le fait de vivre avec le VIH, les ressources familiales limitées et les problèmes de santé mentale. Quand elles faisaient face à des défis, les femmes prenant soin d'enfants se reposaient sur le soutien social et leur foi, ainsi que sur leur propre confiance de parentage. Les perceptions de leurs capacités de parentage étaient influencées par la manière dont elles pensaient que les autres les percevaient, leur satisfaction dans leur rôle de parentage, leur persévérance en dépit des défis, et le degré auquel elles avaient une vision pour leur famille. Nos résultats contextualisent l'auto-efficacité de parentage au sein des valeurs de parentage, des défis et des perceptions sociales chez les femmes prenant soin d'enfants étant affectées par VIH dans l'Ouganda rural.Wir versuchten ein Verständnis über die sozialen Repräsentationen bezüglich effektiver Erziehung und elterlicher Selbstwirksamkeit von weiblichen HIV-infizierten Bezugspersonen im ländlichen Osten Ugandas zu erlangen. Wir führten ausführliche Interviews durch (n = 21) um Erziehungserfahrungen und die Wahrnehmung der eigenen Erziehungskompetenzen aus Sicht der Bezugspersonen zu beschreiben und um Vignetten für den Einsatz in gezielten Fokusgruppen zu erstellen. Wir führten offene Fokusgruppen (n = 2) durch, um soziale Perspektiven auf die Elternschaft zu gewinnen und gezielte Fokusgruppen (n = 2), die sich auf die elterliche Selbstwirksamkeit konzentrierten. Die Analyse umfasste Memoing und die induktive und deduktive Kodierung von Transkripten. Die Wahrnehmung der eigenen Erziehung durch die Bezugspersonen fundierte auf Erziehungswerten, wie z.B. der Versorgung der Kinder mit Grundbedürfnissen, gut erzogene Kinder und gute Beziehungen zu den Kindern. Die Wahrnehmung der Bezugspersonen wurde durch Herausforderungen beeinflusst, darunter das Alleinerziehen von Kindern, das Leben mit HIV, begrenzte Familienressourcen und psychische Probleme. Bei der Bewältigung von Herausforderungen verließen sich die Bezugspersonen auf soziale Unterstützung, ihren Glauben sowie auf ihr eigenes Vertrauen in ihre Erziehungskompetenz. Die Wahrnehmung der Erziehungskompetenzen der Bezugspersonen wurde beeinflusst von der Art und Weise, wie sie sich von anderen wahrgenommen fühlten, von ihrer Zufriedenheit mit der Elternrolle, von ihrer Ausdauer trotz Herausforderungen und von dem Ausmaß einer Vision für ihre Familie. Unsere Ergebnisse kontextualisieren die elterliche Selbstwirksamkeit innerhalb der elterlichen Werte, Herausforderungen und sozialen Wahrnehmungen bei den von HIV betroffenen Bezugspersonen im ländlichen Uganda.ウガンダ東部の貧困とＨＩＶ罹患状況下における育児の自己効力感:質的研究 我々は、ウガンダ東部の地方に住むＨＩＶに罹患した女性養育者における効果的な育児と、育児の自己効力感を示す社会的表象について解明しようとした。我々は、育児経験と養育者自身の育児能力の認識を描写し、指向型フォーカスグループで使用するビネット (記述された場面) を創ることを目的に心の深層に関するインタビュー (n = 21) を行った。育児についての社会的な考え方を得るオープンフォーカスグループ (n = 2) と、育児の自己効力感に集約した指向型フォーカスグループ (n = 2) を実施した。分析にはメモを作成し、帰納的および演繹的な記録のコード化を行った。養育者自身の自分の育児についての認識は、子どもに基本的なニーズを提供すること、行儀の良い子どもを持つこと、子どもとの良い関係性を持つことなどの、育児の価値観に基づいていた。養育者の認識は、片親であること、ＨＩＶを抱えて生きること、家族の資源が限られていること、メンタルヘルスの問題を含む課題をもつこと、により影響を受けていた。課題に直面したとき、養育者は自分の育児に対する自信と社会的支援と信仰に頼っていた。養育者の育児能力の認識は、他者が自分を認めてくれているときの感じ方、育児役割における満足度、課題の有無にかかわらない忍耐力、そして家族のための展望の程度に影響されていた。我々の調査結果から、ウガンダの地方におけるHIV罹患の養育者において、育児の価値観、課題、そして社会的認識における育児の自己効力感について説明できる。.烏干達東部貧困和艾滋病毒背景下的育兒自我效能:定性研究 我們試圖了解烏干達東部農村地區受艾滋病影響的女性照顧者的有效養育和養育自我效能的社會表徵。我們進行深入訪談 (n = 21) , 以描述育兒經歷和照顧者對自己養育能力的看法, 並創造用於定向焦點小組的短文。我們開展了開放焦點小組 (n = 2) , 以獲得關於養育和定向焦點小組 (n = 2) 的社會觀點, 集中於養育自我效能感。分析涉及成績單的備忘錄, 歸納和演繹編碼。看護者對自己養育子女的看法是基於養育子女的價值觀, 例如為孩子提供基本需求, 教導行為良好的孩子, 及與孩子建立良好的關係。照顧者的看法受到挑戰的影響, 包括單親家庭丶艾滋病病毒丶有限的家庭資源和心理健康問題。面對挑戰時, 照顧者依靠他人支持和信仰, 以及他們自己的養育信心。看護者對其養育能力的看法, 受到其他人對他們看法丶他們對養育子女的滿意度丶他們在遇到挑戰時的毅力以及他們對家庭有遠見程度的影響。我們的研究結果將烏干達農村地區受艾滋病影響的照顧者的養育價值觀丶挑戰和社會認知中的養育自我效能情境化。.الكفاية الذاتية في الرعاية الوالدية في سياق الفقر وفيروس نقص المناعة المكتسبة (HIV) في شرق أوغندا: دراسة وصفية سعت هذه الدراسة إلى فهم التمثيل الاجتماعي للرعاية الوالدية الفعالة والكفاية الوالديه الذاتية بين مقدمي الرعاية من الإناث المصابات بفيروس (HIV) في المناطق الريفية في شرق أوغندا. وتم إجراء مقابلات مفصلة (n = 21) لوصف تجارب الابوه والامومه وتصورات مقدمي الرعاية لقدراتهم في الرعاية الوالدية ولوضع نماذج لاستخدامها في مجموعات التركيز الموجهة. وبذلك تم عقد مجموعات التركيز المفتوحة (n = 2) للحصول على وجهات النظر الاجتماعية حول الابوه والامومه ومجموعات التركيز الموجهة (n = 2) والتي تركز على الكفاية الذاتية الوالدية. تضمن تحليل البيانات الترميز الاستقرائي والاستنتاجي لنص المقابلات الشخصية. وقد استندت تصورات مقدمي الرعاية عن الأبوة والأمومة على قيم الرعاية الوالدية ، مثل توفير الاحتياجات الاساسيه للأطفال ، والحصول على أطفال ذوي سلوكيات جيدة ، وإقامه علاقات جيدة مع الأطفال. وتأثرت تصورات مقدمي الرعاية بالتحديات ، بما في ذلك مشكلة العائل الوحيد ، والتعرض لفيروس (HIV) ، ومحدوديه موارد الاسره ، ومشاكل الصحة النفسية . وعند مواجهه التحديات ، يعتمد مقدمو الرعاية علي الدعم الاجتماعي والإيمان ، فضلا عن ثقتهم في قدراتهم في الرعاية الوالدية . وقد تأثرت تصورات مقدمي الرعاية لقدراتهم الابويه بكيفية إدراكهم لرؤية الآخرين لهم ، ورضاهم عن دور الأبوة والأمومة ، ومثابرتهم علي الرغم من التحديات ، ومدي ما لديهم من رؤية لأسرهم. وتضع نتائج الدراسة الكفاية الذاتية للوالدين في سياق قيم الأبوة والتحديات والتصورات الاجتماعية لدي مقدمي الرعاية المصابين بالفيروس في المناطق الريفية في أوغندا.

The impact of concurrent exposure to neurotoxic metals is a significant threat to brain function, mostly in contexts of multiple exposures as seen in the developing world. Ninety-five children (46 boys and 49 girls, 6 to 11-year old) from Congo-Kinshasa were assessed for cognition using the Kaufman Assessment Battery for Children (2nd edition) and exposure to Cr, Cu, Zn, Co, Mn, As, Cd, Se, Hg, Fe, and Pb by inductively coupled plasma mass spectrometry (ICPMS) in serum and urine collections. Concentrations of elements were all above normal ranges except for Cd, Se and Hg. General linear mixed effects models were used to predict neurocognitive outcomes with variable selection methods including backward elimination, elastic net, or subsets identified based on subject matter expertise. After adjusting for sex, age, and SES, urinary Co > 5 μg/l was associated with poor simultaneous processing (memory) (p = 0.0237). Higher excretion but normal concentration of Cd in serum was associated with better memory (p = 0.03), planning (p = 0.05), and overall performance scores (p < 0.01); thus appeared to be neuroprotective. However, higher excretion of Zn had negative influence on the overall performance scores (p = 0.02). Predictive neurotoxicology is a challenging task in contexts of multiple and concurrent exposures. Urinary Co > 5 μg/l is a risk factor for poor neurodevelopmental outcomes in such contexts. The impact of heavy metals on cognition is dependent on concentrations of and interactions between toxic and essential elements.

Water sharing between households could crucially mitigate short‐term household water shortages, yet it is a vastly understudied phenomenon. Here we use comparative survey data from eight sites in seven sub‐Saharan African countries (Democratic Republic of the Congo, Ethiopia, Ghana, Kenya, Malawi, Nigeria, and Uganda) to answer three questions: With whom do households share water? What is expected in return? And what roles do need and affordability play in shaping those transfers? We find that water is shared predominantly between neighbors, that transfers are more frequent when water is less available and less affordable, and that most sharing occurs with no expectation of direct payback. These findings identify water sharing, as a form of generalized reciprocity, to be a basic and consistent household coping strategy against shortages and unaffordability of water in sub‐Saharan Africa.

Background HIV is a neuropathogenic virus that may result in detrimental neurodevelopmental (ND) outcomes early in life. This is the first study to evaluate the effect of HIV-1 subtype on neurodevelopment of Ugandan preschool children. Methods Neurodevelopment of 87 HIV-1 infected and 221 HIV exposed uninfected Ugandan children 1.8-4.9 years of age was assessed using 4 scales of the Mullen Scales of Early Learning (MSEL), 2 scales of the Color Object Association Test (COAT), and 1 score of the Early Childhood Vigilance Test. HIV-1 subtype was defined by phylogenetic analyses. General linear models were used to relate test scores to HIV-1 subtype (A versus D) while adjusting for relevant covariates. The scores were benchmarked against HIV exposed uninfected group to facilitate the interpretation. Results Seventy-one percentage of children infected with subtype A versus 60% of children with subtype D were currently on antiretroviral therapy (P = 0.49). Children with HIV-1 subtype A infection were older when compared with subtype D (3.29 vs. 2.76 years, respectively, P = 0.03), but similar regarding sex, socioeconomic status, weight-for-age z-score, CD4+ and CD8+ (% and total), viral load. No statistically significant differences by HIV-1 subtype were observed in the MSEL, COAT and Early Childhood Vigilance Test. Differences ≥ 0.33 of the SD were observed for the MSEL Composite Score, Receptive Language (MSEL) and Total Memory (COAT). Conclusions In contrast to previously reported differences in ND outcomes of school-age children by HIV-1 subtype, ND scores among preschool children were similar for subtypes A and D, with few potential differences on language production and memory outcomes that favored subtype A. Further investigation with larger sample sizes and longitudinal follow-up is needed.

We tested a model of dyadic interdependence in depression symptoms experienced by female caregivers living with HIV in Uganda (n = 288) and behavioral problems of their HIV-infected (n = 92) and perinatally HIV-exposed uninfected (HEU) children (n = 196). Three repeated measures of caregiver depression symptoms and child neurodevelopment and behavioral outcomes were related to their own outcomes at a previous time point (actor effects), and the outcomes of the other member of the dyad (partner effects). Caregiver depression and child behavioral problem were interdependent over the 24 months of observation. Caregiver depression at TEvaluamos la interdependencia en relaciones diádicas entre síntomas de depresión en mujeres viviendo con VIH en Uganda (n = 288) y medidas de neurodesarollo y comportamiento en sus hijos no infectados pero expuestos a VIH (HEU) (n = 196). Tres mediciones repetidas de síntomas de depresión en mujeres y de neurodesarollo y comportamiento en niños estuvieron relacionadas con sus propios resultados en mediciones anteriores (efecto de actor), y con los resultados del otro miembro de la pareja (efecto de pareja). Síntomas depresivos y problemas conductuales fueron interdependientes durante los 24 meses de observación. Síntomas depresivos en mujeres en T

Rural children from Benin, west Africa were evaluated with the Mullen Scales of Early Learning (MSEL) at one year of age and then at six years with the Kaufman Assessment Battery for Children (KABC-II), the visual computerized Tests of Variables of Attention (TOVA), and the Bruininks-Oseretsky Test (BOT-2) of motor proficiency (N = 568). Although both the MSEL and KABC-II were available to the assessors in French, instructions to the mother/child were in local language of Fon. Mothers were evaluated with the Edinburgh Postpartum Depression Scale (EPDS), Caldwell HOME Scale, educational level and literacy, and a Socio-Economic Scale - also in their local language (Fon). After adjusting for maternal factors, MSEL cognitive composite was correlated with KABC-II with moderate effect sizes, but not with TOVA scores. Overall eta-squared effect for the multivariate models were moderately to strongly correlated (.07 to .37). Neurodevelopmental assessments in early childhood adapted cross-culturally are predictive of school-age neuropsychological cognitive ability.

Objectives To quantify association between in utero/peripartum antiretroviral (IPA) exposure and cognition, i.e. executive function (EF) and socioemotional adjustment (SEA), in school-aged Ugandan children who were perinatally HIV-infected (CPHIV, n = 100) and children who were HIV-exposed but uninfected (CHEU, n = 101). Methods Children were enrolled at age 6-10 years and followed for 12 months from March 2017 to December 2018. Caregiver-reported child EF and SEA competencies were assessed using validated questionnaires at baseline, 6 and 12 months. IPA type - combination antiretroviral therapy (cART), intrapartum single-dose nevirapine ± zidovudine (sdNVP ± ZDV), nevirapine + zidovudine + lamivudine (sdNVP + ZDV + 3TC) - or no IPA (reference) was verified via medical records. IPA-related standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) in cognitive competencies were estimated from regression models with adjustment for caregiver sociodemographic and contextual factors. Models were fitted separately for CPHIV and CHEU. Results Among CPHIV children, cART (SMD = -0.82, 95% CI: -1.37 to -0.28) and sdNVP ± ZDV (SMD = -0.41, 95% CI: -0.81 to -0.00) vs. no IPA predicted lower executive dysfunction over 12 months. Intrapartum sdNVP + ZDV + 3TC vs. no IPA predicted executive dysfunction (SMD = 0.80, 95% CI: 0.30-1.31), SEA problems (SMD = 0.63-0.76, 95% CI: 0.00-1.24) and lower adaptive skills (SMD = -0.36, 95% CI: -0.75-0.02) over 12 months among CHEU. Further adjustment for contextual factors attenuated associations, although most remained of moderate clinical importance (|SMD| > 0.33). Conclusions Among CPHIV children, cART and sdNVP ± ZDV IPA exposure predicted, on average, lower executive dysfunction 6-10 years later. However, peripartum sdNVP + ZDV + 3TC predicted executive and SEA dysfunction among CHEU 6-10 years later. These data underscore the need for more research into long-term effects of in utero ART to inform development of appropriate interventions so as to mitigate cognitive sequelae.

Background The development of neurocognitive deficits in people infected with HIV is a significant public health problem. Previous cross-sectional studies have shown that performance on central auditory tests (CATs) correlates with cognitive test results in those with HIV, but no longitudinal data exist for confirmation. We have been performing longitudinal assessments of central auditory and cognitive function on a cohort of HIV-positive and HIV-negative individuals in Dar es Salaam, Tanzania to understand how the central auditory system could be used to study and track the progress of central nervous system dysfunction. Objective The goal of the project was to determine if CATs can track the trajectory of cognitive function over time in people diagnosed with HIV. Methods Tests of peripheral and central auditory function as well as cognitive performance were performed on 382 individuals over the course of 3.5 years. Visits were scheduled every 6 months. CATs included tests of auditory temporal processing (gap detection) and speech perception in noise (Hearing in Noise Test and Triple Digit Test). Cognitive tests included the Montreal Cognitive Assessment (MoCA), Test of Variables of Attention (TOVA), and subtests from the Cogstate battery. HIV-positive subjects were divided into groups based on their CAT results at their final visit (bottom 20%, top 20%, middle 60%). Primary analyses focused on the comparison between HIV-positive individuals that performed worse on CATs (bottom 20%) and the overall HIV-positive group (middle 60%). Data were analyzed using linear mixed-effect models with time as the main fixed effect. Results The group with the worst (bottom 20%) CAT performance showed a difference in trajectory for the MoCA (P=.003), TOVA (P Conclusions The results of this study support the ability for CATs to track cognitive function over time, suggesting that central auditory processing can provide a window into central nervous system performance. CATs can be simple to perform, and are relatively insensitive to education and socioeconomic status because they only require repeating sentences, numbers, or detecting gaps in noise. These tests could potentially provide a time-efficient, low-cost method to screen for and monitor cognitive decline in patients with HIV, making them a useful surveillance tool for this major public health problem.

BACKGROUND Few studies have assessed neurodevelopmental outcomes in normocephalic infants born to women with Zika virus (ZIKV) infection during pregnancy in Mexico. We sought to evaluate ZIKV exposed infants in Yucatan, Mexico, with performance-based and eye-gaze measures of neurodevelopment, removing observer bias. METHODS We enrolled 60 infants about 6-month old born to women with PCR + test for ZIKV during pregnancy. Infants were normocephalic and asymptomatic. Sixty infants born to women without a history of ZIKV infection were included as comparison. Children were assessed with the Mullen scales of early learning (MSEL), a test with scales in motor, language, and overall cognitive skills development, and the Fagan test of infant intelligence (FTII) using automated eye-tracking instrumentation to evaluate infant visual preference of human faces, where longer gaze lengths to unfamiliar (i.e., new) faces are expected. RESULTS All MSEL subscale scores, except expressive language, were significantly lower among ZIKV exposed children compared to controls, including the overall standard composite (80 ± 10 vs. 87 ± 7.4, respectively; p < 0.001). FTII eye-tracking measures of fixation and gaze length were in the expected direction, with longer times recorded among infants in the control group (i.e., higher attention), but none reached statistical significance. In adjusted linear regressions, the FTII high novelty score (expected preference for a novel face) predicted fine motor (β = 3.61, p = 0.04) and receptive language (β = 2.55, p = 0.03) scores. CONCLUSIONS Nonmicrocephalic children born to women with ZIKV during pregnancy in Mexico merit early neurodevelopmental evaluation to allow for appropriate interventions and clinical follow-up. It is possible that long-term monitoring of cognitive deficits may need to be established for a proportion of affected cases.

In March 2020, the World Health Organization (WHO) issued a set of public guidelines for Coronavirus Disease 2019 (COVID-19) prevention measures that highlighted handwashing, physical distancing, and household cleaning. These health behaviors are severely compromised in parts of the world that lack secure water supplies, particularly in low- and middle-income countries (LMICs). We used empirical data gathered in 2017-2018 from 8,297 households in 29 sites across 23 LMICs to address the potential implications of water insecurity for COVID-19 prevention and response. These data demonstrate how household water insecurity presents many pathways for limiting personal and environmental hygiene, impeding physical distancing and exacerbating existing social and health vulnerabilities that can lead to more severe COVID-19 outcomes. In the four weeks prior to survey implementation, 45.9% of households in our sample either were unable to wash their hands or reported borrowing water from others, which may undermine hygiene and physical distancing. Further, 70.9% of households experienced one or more water-related problems that potentially undermine COVID-19 control strategies or disease treatment, including insufficient water for bathing, laundering, or taking medication; drinking unsafe water; going to sleep thirsty; or having little-to-no drinking water. These findings help identify where water provision is most relevant to managing COVID-19 spread and outcomes.