Intimate partner violence, HIV and sexually transmitted infections in fishing, trading and agrarian communities in Rakai, Uganda.

BackgroundIntimate partner violence (IPV), HIV and sexually transmitted infections (STI) can contribute to disparities in population health, depending on the individual, social and environmental factors characterizing a setting. To better understand the place-based determinants and patterns of these key interrelated public health problems in Uganda, we compared risk factors for IPV, HIV and STI in fishing, trading and agrarian communities in Rakai, Uganda by gender.MethodThis study used cross-sectional data collected from 14,464 sexually active men (n = 6531) and women (n = 7933) as part of the Rakai Community Cohort Study, a population-based open cohort study of men and women aged 15-49 years. We used multilevel modified poisson regression models, which incorporated random intercepts for community and households. Factors associated with IPV, HIV and STI were assessed separately for men and women in fishing, trading and agrarian communities.ResultsA larger proportion of participants in the fishing communities than those in trading and agrarian communities were HIV positive, engaged in HIV risk behaviors, had STI symptoms and reported perpetration of or victimization by IPV. Female gender was a shared correlate of IPV, HIV and STI in the fishing communities. Engagement in multiple sexual relationships or partner's engagement in multiple relationships were shared correlates of IPV, and HIV in agrarian communities and IPV and STI in trading communities.ConclusionPrograms should target factors at multiple levels to reduce risk for syndemic conditions of HIV, STI and IPV in Rakai, Uganda particularly among men and women in fishing communities

Polymorphisms in ARMS2/HTRA1 and complement genes and age-related macular degeneration in India: findings from the INDEYE study.

PURPOSE: Association between genetic variants in complement factor H (CFH), factor B (CFB), component 2 (C2), and in the ARMS2/HTRA1 region with age-related macular degeneration (AMD) comes mainly from studies of European ancestry and case-control studies of late-stage disease. We investigated associations of both early and late AMD with these variants in a population-based study of people aged 60 years and older in India. METHODS: Fundus images were graded using the Wisconsin Age-Related Maculopathy Grading System and participants assigned to one of four mutually exclusive stages based on the worse affected eye (0 = no AMD, 1-3 = early AMD, 4 = late AMD). Multinomial logistic regression was used to derive risk ratios (RR) accounting for sampling method and adjusting for age, sex, and study center. RESULTS: Of 3569 participants, 53.2% had no signs of amd, 45.6% had features of early amd, and 1.2% had late amd. CFH (RS1061170), C2 (RS547154), OR CFB (RS438999) was not associated with early or late AMD. In the ARMS2 locus, RS10490924 was associated with both early (adjusted RR 1.22, 95% confidence interval [CI]: 1.13-1.33, P < 0.0001) and late AMD (adjusted RR 1.81, 95% CI: 1.15-2.86; P = 0.01); rs2672598 was associated only with early AMD (adjusted RR 1.12, 95% CI: 1.02-1.23; P = 0.02); rs10490923 was not associated with early or late AMD. CONCLUSIONS: Two variants in ARMS2/HTRA1 were associated with increased risk of early AMD, and for one of these, the increased risk was also evident for late AMD. The study provides new insights into the role of these variants in early stages of AMD in India

Application of two machine learning algorithms to genetic association studies in the presence of covariates

BACKGROUND: Population-based investigations aimed at uncovering genotype-trait associations often involve high-dimensional genetic polymorphism data as well as information on multiple environmental and clinical parameters. Machine learning (ML) algorithms offer a straightforward analytic approach for selecting subsets of these inputs that are most predictive of a pre-defined trait. The performance of these algorithms, however, in the presence of covariates is not well characterized. METHODS AND RESULTS: In this manuscript, we investigate two approaches: Random Forests (RFs) and Multivariate Adaptive Regression Splines (MARS). Through multiple simulation studies, the performance under several underlying models is evaluated. An application to a cohort of HIV-1 infected individuals receiving anti-retroviral therapies is also provided. CONCLUSION: Consistent with more traditional regression modeling theory, our findings highlight the importance of considering the nature of underlying gene-covariate-trait relationships before applying ML algorithms, particularly when there is potential confounding or effect mediation

Serologic Responses in Childhood Pulmonary Tuberculosis.

BACKGROUND: Identification of the Mycobacterium tuberculosis immunoproteome and antigens associated with serologic responses in adults has renewed interest in developing a serologic test for childhood tuberculosis (TB). We investigated IgG antibody responses against M. tuberculosis antigens in children with well-characterized TB. METHODS: We studied archived sera obtained from hospitalized children with suspected pulmonary TB, and classified as having confirmed TB (culture-confirmed), unlikely TB (clinical improvement without TB treatment), or unconfirmed TB (all others). A multiplexed bead-based assay for IgG antibodies against 119 M. tuberculosis antigens was developed, validated and used to test sera. The area under the curves (AUCs) of the empiric receiver-operator characteristic curves were generated as measures of predictive ability. A cross-validated generalized linear model was used to select the most predictive combinations of antigens. RESULTS: For the confirmed TB versus unlikely TB comparison, the maximal single antigen AUC was 0.63, corresponding to sensitivity 0.60 and specificity 0.60. Older (age: 60+ months old) children's responses were better predictive of TB status than younger (age: 12-59 months old) children's, with a maximal single antigen AUC of -0.76. For the confirmed TB versus unlikely TB groups, the most predictive combinations of antigens assigned TB risk probabilities of 0.33 and 0.33, respectively, when all ages were considered, and 0.57 (interquartile range: 0.48-0.64) and 0.35 (interquartile range: 0.32-0.40) when only older children were considered. CONCLUSION: An antigen-based IgG test is unlikely to meet the performance characteristics required of a TB detection test applicable to all age groups

Factors associated with delay in care–seeking for fatal neonatal illness in the Sylhet district of Bangladesh: results from a verbal and social autopsy study

We conducted a social and verbal autopsy study to determine cultural–, social– and health system–related factors that were associated with the delay in formal care seeking in Sylhet district, Bangladesh

A trial of nurturing care among children who are HIV‐exposed and uninfected in eSwatini

Abstract Introduction Children who are HIV‐exposed and uninfected (CHEU) are a growing population at potential risk of poor neurocognitive development. We tested a nurturing care intervention on children's neurocognitive development and maternal depressive symptoms (primary) with mediation through caregiving activities (secondary). Methods This study was conducted among six intervention and nine comparison antenatal‐care/prevention of vertical transmission (ANC/PVT) HIV clinics in eSwatini. We enrolled pregnant women and measured infant development at 9 and 18 months. mothers2mothers (m2m) designed and implemented the clinic‐home‐community‐based intervention. We measured infants’ neurodevelopment, maternal depressive symptoms and caregiving activities with the Mullen Scales of Early Learning (MSEL), Edinburgh Postnatal Depression Scale, HOME Inventory and Family Care Indicators. We fitted linear mixed effects regression models with clinic random effects to compare intervention versus comparison arms, and generalised structural equation models to evaluate mediation, adjusting for confounders. Results Mother‐infant pairs (n = 429) participated between January 2016 through May 2018. Socio‐demographic characteristics were balanced between arms except for higher rates of peri‐urban versus rural residence and single versus married mothers in the comparison group. The 18 month retention was 82% (180/220) intervention, 79% (166/209) comparison arm, with 25 infant deaths. Intervention MSEL scores were significantly, and modestly, higher in receptive language (55.7 [95% CI 54.6, 56.9] vs. 53.7 [95% CI 52.6, 54.8]), expressive language (42.5 [95% CI 41.6, 39.8] vs. 40.8 [95% CI 39.8, 41.7]) and composite MSEL (85.4 [95% CI 83.7, 84.5] vs. 82.7 [95% CI 81.0, 84.5]), with no difference in maternal depressive symptoms or in observations of mother‐child interactions. Intervention book‐sharing scores were higher (0.63 vs. 0.41) and mediated the effect on MSEL scores (indirect effect, p‐values ≤ 0.024). The direct effects on visual reception and expressive language scores were significantly higher in the intervention compared to the comparison arm (coefficients 1.93 [95% CI 0.26, 3.60] and 1.66 [95% CI 0.51, 2.79, respectively]). Conclusions Nurturing care interventions can be integrated into ANC/PVT clinic‐home‐community programmes. The intervention, mediated through interactive caregiving activities, increased language development scores among CHEU. Partnering with a local team, m2m, to design and implement a culturally relevant intervention illustrates the ability to impact parent‐child play and learning activities that are associated with children's neurodevelopment

Longitudinal study reveals HIV-1-infected CD4+ T cell dynamics during long-term antiretroviral therapy

Proliferation of CD4+ T cells harboring HIV-1 proviruses is a major contributor to viral persistence in people on antiretroviral therapy (ART). To determine whether differential rates of clonal proliferation or HIV-1-specific cytotoxic T lymphocyte (CTL) pressure shape the provirus landscape, we performed an intact proviral DNA assay (IPDA) and obtained 661 near-full-length provirus sequences from 8 individuals with suppressed viral loads on ART at time points 7 years apart. We observed slow decay of intact proviruses but no changes in the proportions of various types of defective proviruses. The proportion of intact proviruses in expanded clones was similar to that of defective proviruses in clones. Intact proviruses observed in clones did not have more escaped CTL epitopes than intact proviruses observed as singlets. Concordantly, total proviruses at later time points or observed in clones were not enriched in escaped or unrecognized epitopes. Three individuals with natural control of HIV-1 infection (controllers) on ART, included because controllers have strong HIV-1-specific CTL responses, had a smaller proportion of intact proviruses but a distribution of defective provirus types and escaped or unrecognized epitopes similar to that of the other individuals. This work suggests that CTL selection does not significantly check clonal proliferation of infected cells or greatly alter the provirus landscape in people on ART