Undernutrition as a risk factor for tuberculosis disease.

BACKGROUND: Tuberculosis (TB) is a leading cause of mortality due to an infectious disease, with an estimated 1.6 million deaths due to TB in 2022. Approximately 25% of the global population has TB infection, giving rise to 10.6 million episodes of TB disease in 2022. Undernutrition is a key risk factor for TB and was linked to an estimated 2.2 million TB episodes in 2022, as outlined in the World Health Organization (WHO) Global Tuberculosis Report. OBJECTIVES: To determine the prognostic value of undernutrition in the general population of adults, adolescents, and children for predicting tuberculosis disease over any time period. SEARCH METHODS: We searched the literature databases MEDLINE (via PubMed) and WHO Global Index Medicus, as well as the WHO International Clinical Trials Registry Platform (ICTRP) on 3 May 2023 (date of last search for all databases). We placed no restrictions on the language of publication. SELECTION CRITERIA: We included retrospective and prospective cohort studies, irrespective of publication status or language. The target population comprised adults, adolescents, and children from diverse settings, encompassing outpatient and inpatient cohorts, with varying comorbidities and risk of exposure to tuberculosis. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and the Quality In Prognosis Studies (QUIPS) tool to assess the risk of bias of the studies. Prognostic factors included undernutrition, defined as wasting, stunting, and underweight, with specific measures such as body mass index (BMI) less than two standard deviations below the median for children and adolescents and low BMI scores (< 18.5) for adults and adolescents. Prognostication occurred at enrolment/baseline. The primary outcome was the incidence of TB disease. The secondary outcome was recurrent TB disease. We performed a random-effects meta-analysis for the adjusted hazard ratios (HR), risk ratios (RR), or odds ratios (OR), employing the restricted maximum likelihood estimation. We rated the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 51 cohort studies with over 27 million participants from the six WHO regions. Sixteen large population-based studies were conducted in China, Singapore, South Korea, and the USA, and 25 studies focused on people living with HIV, which were mainly conducted in the African region. Most studies were in adults, four in children, and three in children and adults. Undernutrition as an exposure was usually defined according to standard criteria; however, the diagnosis of TB did not include a confirmatory culture or molecular diagnosis using a WHO-approved rapid diagnostic test in eight studies. The median follow-up time was 3.5 years, and the studies primarily reported an adjusted hazard ratio from a multivariable Cox-proportional hazard model. Hazard ratios (HR) The HR estimates represent the highest certainty of the evidence, explored through sensitivity analyses and excluding studies at high risk of bias. We present 95% confidence intervals (CI) and prediction intervals, which present between-study heterogeneity represented in a measurement of the variability of effect sizes (i.e. the interval within which the effect size of a new study would fall considering the same population of studies included in the meta-analysis). Undernutrition may increase the risk of TB disease (HR 2.23, 95% CI 1.83 to 2.72; prediction interval 0.98 to 5.05; 23 studies; 2,883,266 participants). The certainty of the evidence is low due to a moderate risk of bias across studies and inconsistency. When stratified by follow-up time, the results are more consistent across < 10 years follow-up (HR 2.02, 95% CI 1.74 to 2.34; prediction interval 1.20 to 3.39; 22 studies; 2,869,077 participants). This results in a moderate certainty of evidence due to a moderate risk of bias across studies. However, at 10 or more years of follow-up, we found only one study with a wider CI and higher HR (HR 12.43, 95% CI 5.74 to 26.91; 14,189 participants). The certainty of the evidence is low due to the moderate risk of bias and indirectness. Odds ratio (OR) Undernutrition may increase the odds of TB disease, but the results are uncertain (OR 1.56, 95% CI 1.13 to 2.17; prediction interval 0.61 to 3.99; 8 studies; 173,497 participants). Stratification by follow-up was not possible as all studies had a follow-up of < 10 years. The certainty of the evidence is very low due to the high risk of bias and inconsistency. Contour-enhanced funnel plots were not reported due to the few studies included. Risk ratio (RR) Undernutrition may increase the risk of TB disease (RR 1.95, 95% CI 1.72 to 2.20; prediction interval 1.49 to 2.55; 4 studies; 1,475,867 participants). Stratification by follow-up was not possible as all studies had a follow-up of < 10 years. The certainty of the evidence is low due to the high risk of bias. Contour-enhanced funnel plots were not reported due to the few studies included. AUTHORS' CONCLUSIONS: Undernutrition probably increases the risk of TB two-fold in the short term (< 10 years) and may also increase the risk in the long term (> 10 years). Policies targeted towards the reduction of the burden of undernutrition are not only needed to alleviate human suffering due to undernutrition and its many adverse consequences, but are also an important part of the critical measures for ending the TB epidemic by 2030. Large population-based cohorts, including those derived from high-quality national registries of exposures (undernutrition) and outcomes (TB disease), are needed to provide high-certainty estimates of this risk across different settings and populations, including low and middle-income countries from different WHO regions. Moreover, studies including children and adolescents and state-of-the-art methods for diagnosing TB would provide more up-to-date information relevant to practice and policy. FUNDING: World Health Organization (203256442). REGISTRATION: PROSPERO registration: CRD42023408807 Protocol: https://doi.org/10.1002/14651858.CD015890.

Is social support related to better mental health, treatment continuation and success rates among individuals undergoing in-vitro fertilization? Systematic review and meta-analysis protocol.

Infertility and its treatment via in-vitro fertilization (IVF) represent a global health area of increasing importance. However, the physical and psychological burden of IVF can negatively impact psychological wellbeing, as well as treatment retention and success. Social support has been found to have positive health effects among populations facing health-related stressors worldwide, and its potential protective role for IVF patients merits further attention. We present a protocol for a systematic review of peer-reviewed published studies quantitatively investigating associations between social support and i) mental health; ii) the decision to (dis)continue with IVF treatment cycles and; iii) IVF success (pregnancy and birth rates); among individuals who are undertaking or have undertaken IVF cycles. Studies will be included if they work with human subjects, provide correlation coefficients between measures of social support and at least one of the outcomes of interest, and are in the English language. Social support may derive from both naturally occurring networks and more formalized sources or interventions. The protocol for this systematic review was developed according to the PRISMA-P guidelines. Ten health-, psychology- and sociology-related databases will be searched using composite search terms that include keywords for 'IVF' and 'social support'. To assess methodological quality, the authors will use a modified version of the Newcastle-Ottawa Scale. Should three or more moderate or good quality studies be identified for any one outcome of interest, correlation meta-analyses, using the Hedges-Olkin method, will be conducted to pool effect sizes and heterogeneity will be assessed. Should the number, quality and characteristics of eligible studies not allow for reliable quantitative synthesis, the authors will limit the analysis to qualitative synthesis, with a focus on implications of findings for future research and programming.

Recent Interventions to Improve Retention in HIV Care and Adherence to Antiretroviral Treatment Among Adolescents and Youth: A Systematic Review.

Adolescents represent a growing proportion of people living with HIV worldwide and the highest risk population group for treatment attrition and AIDS-related mortality. There is an urgent need to design, implement, and test interventions that keep young people in HIV treatment and care. However, previous systematic reviews show scarce and inconclusive evidence of effective interventions for this age group. Recent years have seen an increase in focus on adolescent health and a rapidly changing programmatic environment. This systematic review article provides an evidence update by synthesizing empirical evaluations of interventions designed to improve antiretroviral therapy adherence and retention among adolescents (10-19) and youth (15-24) living with HIV, published between January 2016 and June 2018. A search of 11 health and humanities databases generated 2425 citations and 10 relevant studies, the large majority conducted in sub-Saharan Africa. These include six clinic-level interventions, one individual-level m-Health trial, and three community- or household-level interventions. Implications of their findings for future programming and research with young adults are discussed, in relation to previous reviews and the broader empirical evidence in this area. Findings highlight the need to further develop and test multi-faceted interventions that go beyond health facilities, to address broader social barriers to adherence and retention. In particular, further intervention studies with adolescents (10-19) should be a priority, if we are to retain these young people in treatment and care and aspire to achieve the United Nation's Sustainable Development Goals and 90-90-90 targets.

Improving lives by accelerating progress towards the UN Sustainable Development Goals for adolescents living with HIV: a prospective cohort study.

BACKGROUND: Low-income and middle-income countries (LMICs) face major challenges in achieving the UN's Sustainable Development Goals (SDGs) for vulnerable adolescents. We aimed to test the UN Development Programme's proposed approach of development accelerators-provisions that lead to progress across multiple SDGs-and synergies between accelerators on achieving SDG-aligned targets in a highly vulnerable group of adolescents in South Africa. METHODS: We did standardised interviews and extracted longitudinal data from clinical records at baseline (2014-15) and 18-month follow-up (2016-17) for adolescents aged 10-19 years living with HIV in the Eastern Cape province of South Africa. We used standardised tools to measure 11 SDG-aligned targets-antiretroviral therapy adherence, good mental health, no substance use, HIV care retention, school enrolment, school progression, no sexual abuse, no high-risk sex, no violence perpetration, no community violence, and no emotional or physical abuse. We also assessed receipt at both baseline and follow-up of six hypothesised development accelerators-government cash transfers to households, safe schools (ie, without teacher or student violence), free schools, parenting support, free school meals, and support groups. Associations of all provisions with SDG-aligned targets were assessed jointly in a multivariate path model, controlling for baseline outcomes and sociodemographic and HIV-related covariates, and adjusted for multiple outcome testing. Cumulative effects were tested by marginal effects modelling. FINDINGS: 1063 (90%) of 1176 eligible adolescents were interviewed. Three provisions were shown to be development accelerators. Parenting support was associated with good mental health (odds ratio 2·13, 95% CI 1·43-3·15, p<0·0001), no high-risk sex (2·44, 1·45-5·03, p=0·005), no violence perpetration (2·59, 1·63-4·59, p<0·0001), no community violence (2·43, 1·65-3·86, p<0·0001), and no emotional or physical abuse (2·38, 1·65-3·76; p<0·0001). Cash transfers were associated with HIV care retention (1·87, 1·15-3·02, p=0·010), school progression (2·05, 1·33-3·24, p=0·003), and no emotional or physical abuse (1·76, 1·12-3·02, p=0·025). Safe schools were associated with good mental health (1·74, 1·30-2·34, p<0·0001), school progression (1·57, 1·17-2·13, p=0·004), no violence perpetration (2·02, 1·45-2·91, p<0·0001), no community violence (1·81, 1·30-2·55, p<0·0001), and no emotional or physical abuse (2·20, 1·58-3·17, p<0·0001). For five of 11 SDG-aligned targets, a combination of two or more accelerators showed cumulative positive associations, suggesting accelerator synergies of combination provisions. For example, the fitted probability of adolescents reporting no emotional or physical abuse (SDG 16.2) with no safe schools, cash transfers, or parenting support was 0·25 (0·16-0·34). With cash transfer alone it was 0·37 (0·33-0·42), with safe school alone 0·42 (0·30-0·55), and with parenting support alone 0·44 (0·30-0·59). With all three development accelerators combined, the probability of adolescents reporting no emotional or physical abuse was 0·76 (0·67-0·84). After correcting for multiple tests, four of the SDG-aligned targets (antiretroviral therapy adherence, no substance use, school enrolment, and no sexual abuse) were not associated with any hypothesised accelerators. INTERPRETATION: The findings suggest the UN's accelerator approach for this high-risk adolescent population has policy and potential financing usefulness. Services that simultaneously promote several SDG targets, or combine to support particular targets, might be important to meet not only health-related targets, but also to ensure that adolescents in LMICs thrive within a new development framework. FUNDING: Nuffield Foundation, UK Research and Innovation Global Challenges Research Fund, UKAID, Janssen Pharmaceutica, International AIDS Society, John Fell Fund, European Research Council, Economic and Social Research Council, Philip Leverhulme Trust, and UNICEF.

Evaluation of the NucliSens EasyQ v2.0 assay in comparison with the Roche Amplicor v1.5 and the Roche CAP/CTM HIV-1 Test v2.0 in quantification of C-clade HIV-1 in plasma.

Human immunodeficiency virus type 1 (HIV-1) genetic diversity poses a challenge to reliable viral load monitoring. Discrepancies between different testing platforms have been observed, especially for non-clade-B virus. Therefore we compare, in antiretroviral therapy (ART)-naïve South African subjects predominantly infected with HIV-1 clade-C, three commercially available assays: the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test version 2.0 by Roche (CAP/CTM v2.0), the BioMérieux NucliSens Version 2.0 Easy Q/Easy Mag (NucliSens v2.0) and the Roche COBAS Amplicor HIV-1 Monitor Test Version 1.5 (Amplicor v1.5). Strong linear correlation was observed and Bland-Altman analyses showed overall good agreement between the assays with mean viral load differences of 0.078 log cp/ml (NucliSens v2.0 - Amplicor v1.5), 0.260 log cp/ml (CAP/CTM v2.0 - Amplicor v1.5) and 0.164 log cp/ml (CAP/CTM v2.0 - NucliSens v2.0), indicating lower mean viral load results for the Amplicor v1.5 and higher mean readings for the CAP/CTM v2.0. Consistent with observations following previous comparisons of CAP/CTM v2.0 versus Amplicor v1.5, the CAP/CTM v2.0 assay detected low-level viremia (median 65 cp/ml) in more than one-third of those in whom viremia had been undetectable (<20 cp/ml) in assays using the NucliSens platform. These levels of viremia are of uncertain clinical significance but may be of importance in early detection of ART resistance in those on treatment. Overall the three assays showed good comparability of results but with consistent, albeit relatively small, discrepancies for HIV-1 clade-C samples, especially in the low-viremic range that should be taken into account when interpreting viral load data.