Abstract Background Tuberculosis (TB) is a stigmatised disease due to its associations with poverty, HIV, transmission risk and mortality. The use of visible TB infection prevention and control (IPC) measures, such as masks or isolation, can contribute to stigma. Methods To explore stigma in this condition, we conducted in-depth individual interviews with 18 health workers and 15 patients in the rural Eastern Cape of South Africa using a semi-structured interview guide and narrative approach. We used reflexive thematic analysis and applied Link and Phelan’s theoretical model of stigma. Results Participants shared poignant narratives of TB stigma, often entailing TB IPC, with some feeling ‘less than human’. We found TB IPC measures sometimes exacerbated stigma, for example through introducing physical isolation that became prolonged, or through a mask marking the person out as being ill with TB. In this context, stigma emerged from the narrow definition of what mask-wearing symbolises, in contrast with broader uses of masks as a preventative measure. In this way, the health facility itself was shown to play an important role in generating and perpetuating IPC related stigma. We applied ‘ubuntu’ as African humanist conceptual framework to develop recommendations of how TB IPC implementation could be destigmatised. Conclusion Health facilities may unwittingly perpetuate stigma, but they also have the potential to reduce it. Ubuntu emphases shared humanity and collective wellbeing and could engage with some of the deep-rooted contributors to TB stigma. An ubuntu-informed approach could underpin a local policy change to universal masking, thereby destigmatising an important IPC practice.

Background. Progressive interventions have recently improved programmatic outcomes in drug-resistant tuberculosis (DR-TB) care in South Africa (SA). Amidst these, a shorter regimen was introduced in 2017 with weak evidence, and has shown mixed results. Outcomes still fall short of national targets, and the coronavirus disease 2019 pandemic has undermined progress to date. Objectives. To describe the outcomes of participants treated for DR-TB using a shorter, compared with a longer, regimen in a deeply rural SA setting, and to explore other factors affecting these outcomes. Methods. This retrospective cohort study describes outcomes in short and long DR-TB treatment regimens, over 5 years, at two rural treatment sites in SA. Characteristics were analysed for outcome correlates using multivariable logistic regression models. Results. Of 282 treatment episodes, 62% were successful, with higher success in shorter (69%) compared with longer regimens (58%). Mortality was approximately 21% in both groups. Characteristics included high proportions of HIV co-infection (61%). Injectables (adjusted odds ratio (aOR) 3.00, 95% confidence interval (CI) 1.48 - 6.09), bedaquiline (aOR 3.16, 95% CI 1.36 - 7.35), increasing age (aOR 0.97, 95% CI 0.95 - 0.99) and HIV viraemia defined as final HIV-RNA viral load >1 000 copies/mL (aOR 0.16, 95% CI 0.07 - 0.37) were all significantly and independently associated with treatment success. Injectables (aOR 0.22, 95% CI 0.08 - 0.57), bedaquiline (aOR 0.05, 95% CI 0.01 - 0.19), increasing age (aOR 1.09, 95% CI 1.05 - 1.13), extra-pulmonary TB (aOR 8.15, 95% CI 1.62 - 41.03) and HIV viraemia (aOR 9.20, 95% CI 3.22 - 26.24) were all significantly and independently associated with mortality. Conclusion. In a rural context, treating DR-TB amid limited resources and a high burden of HIV co-infection, we found that after considering controls, a short regimen was no different to a longer regimen in terms of success or mortality. Therefore, by alleviating burdens on multiple stakeholders, a short regimen is likely to be favourable for rural patients, clinicians, and healthcare systems. Besides other previously described correlates of outcomes, HIV viraemia emerged as a novel marker for reliably predicting poor outcomes in DR-TB with HIV co-infection, and a pragmatic target for intervention.

Deploying Community Health Workers is a crucial strategy to improve health at a community level in low and middle income countries. While there is substantial evidence for CHW effectiveness, there is a need for more research on the mechanisms through which these programs work. Understanding CHWs experiences of how programmes function is important. This article examines CHW's experiences of three key programmatic domains; training, logistical support and supervision. Data were gathered using a qualitative study embedded within a cluster randomized controlled trial of an enhanced supervision package delivered to government-employed CHWs in the rural Eastern Cape, South Africa. We interviewed CHWs (n = 16) and two supervisors. Three overarching areas and five sub-themes emerged from our interviews. CHW knowledge and confidence increased through additional training, that CHW motivation and community acceptance improved because of added logistical support, and that CHW supervision led to improved sense of accountability, feelings of respect, and sense of being supported. Our findings highlight the importance of a functional support system within which CHWs can operate, in a context where most CHWs operate in isolation and without support. CHWs receiving supportive supervision reported positive impacts on their motivation and ability to carry out their work effectively.

Abstract Aims: This study evaluates the changes of brain spontaneous activity in patients with anisometropia amblyopia compared with healthy controls. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data of 18 children patients with anisometropia amblyopia（PAA group）and 14 healthy children (control group) were collected. Fractional amplitude of low frequency fluctuation (fALFF) was used to assess brain spontaneous activity changes between the two groups. Two-sample t test was used for statistical analysis of fALFF value between groups. Pearson correlation was used to analyze the correlation between fALFF value in anisometropic amblyopia and clinical information. Results: Compared with healthy controls, children with anisometropia amblyopia showed higher fALFF values in the middle right occipital gyrus and left central paracentric lobule. While fALFF value in the left middle frontal gyrus in children with anisometropic amblyopia was lower than that of healthy controls. There were no significant correlations between clinical information and mean fALFF values in PAA group. Conclusion: Rs-fMRI fALFF analysis of children with anisometropic amblyopia reflects brain spontaneous activity changes in the visual cortex.

Community health workers (CHWs) can supplement professional medical providers, especially in rural settings where resources are particularly scarce. Yet, outcomes of studies evaluating CHWs effectiveness have been highly variable and lack impact when scaled nationally. This study examines if child and maternal outcomes are better when existing government CHWs, who are perinatal home visitors, receive ongoing enhanced supervision and monitoring, compared to standard care. A cluster randomized controlled effectiveness trial was conducted comparing outcomes over 2 years when different supervision and support are provided. Primary health clinics were randomized by clinic to receive monitoring and supervision from either (1) existing supervisors (Standard Care (SC); n = 4 clinics, 23 CHWs, 392 mothers); or (2) supervisors from a nongovernmental organization that provided enhanced monitoring and supervision (Accountable Care [AC]; n = 4 clinic areas, 20 CHWs, 423 mothers). Assessments were conducted during pregnancy and at 3, 6, 15, and 24 months post-birth with high retention rates (76% to 86%). The primary outcome was the number of statistically significant intervention effects among 13 outcomes of interest; this approach allowed us to evaluate the intervention holistically while accounting for correlation among the 13 outcomes and considering multiple comparisons. The observed benefits were not statistically significant and did not show the AC's efficacy over the SC. Only the antiretroviral (ARV) adherence effect met the significance threshold established a priori (SC mean 2.3, AC mean 2.9, p < 0.025; 95% CI = [0.157, 1.576]). However, for 11 of the 13 outcomes, we observed an improvement in the AC compared to the SC. While the observed outcomes were not statistically significant, benefits were observed for 4 outcomes: increasing breastfeeding for 6 months, reducing malnutrition, increasing ARV adherence, and improving developmental milestones. The major study limitation was utilizing existing CHWs and being limited to a sample of 8 clinics. There were no major study-related adverse events. Supervision and monitoring were insufficient to improve CHWs' impact on maternal and child outcomes. Alternative strategies for staff recruitment and narrowing the intervention outcomes to the specific local community problems are needed for consistently high impact. Clinicaltrials.gov, NCT02957799.

Self-testing for COVID-19 may be a preferable strategy for identifying SARS-CoV-2 infection among populations in low- and middle-income settings. To determine South Africans’ values related to COVID-19 self-testing should it become widely available, a cross-sectional survey was administered in Durban, KwaZulu-Natal Province and the King Sabata Dalindyebo sub-district of the Eastern Cape.A 35-question survey was administered to 531 participants (268 female) in one urban and one rural setting of South Africa. Survey participants were randomly selected by household in the rural setting, while in the urban setting participants were approached in randomly selected public places. The survey assessed participants’ likelihood of using and willingness to pay for a COVID-19 self-test and actions they would take following a COVID-19 self-test. The results were analysed using descriptive statistics and bivariate and multivariate regression.Overall, 93.03% of participants supported COVID-19 self-testing, 61.62% of participants were willing to pay for self-testing, and 90.15% indicated they would communicate their results if they tested positive. Rural participants were more positively associated with each of these outcomes compared with urban-based participants. Should they test positive, most participants said they would: go in-person to a health facility for counselling (76.45%), self-isolate (95.85%), notify close contacts (97.74%), and inform their employer (95.14%).COVID-19 self-testing was a preferable option for most participants, although this varied with setting and demographic characteristics. Self-testing may overcome barriers to care for South Africans, but to achieve this, policies for self-testing and delivery methods must not exacerbate individuals’ underlying economic vulnerabilities.

Our objective was to assess differences in TB treatment outcomes between individuals who were HIV negative, HIV positive on anti-retroviral treatment (ART) and HIV positive not on ART, at TB treatment initiation at a rural district hospital in Eastern Cape, South Africa. This was a retrospective cohort study of individuals diagnosed with TB between January 2017 and April 2020 at a district hospital. Adults 15 years and over with reported HIV status and treatment outcome were included (N = 711). A categorical outcome with three levels was considered: unfavorable, down referral, and success. We report descriptive statistics for the association between HIV and ART status and treatment outcome using Chi-square and Fisher's exact tests. A multinomial baseline logit model was used to estimate odds ratios for treatment outcomes. Overall, 59% of included patients were HIV positive with 75% on ART. Eighty-eight patients 12% had an unfavorable outcome. Half of all patients were down referred with an additional 37% having a successful outcome. Individuals without HIV were more likely to be down referred (versus unfavorable) compared to individuals with untreated HIV (2.90 OR, 1.36, 6.17 95% CI). There was a greater likelihood for individuals without HIV having a successful TB treatment outcome compared to individuals with untreated HIV (4.98 OR, 2.07, 11.25 95% CI). The majority of individuals had positive TB treatment outcomes (down referred or success). However, people without HIV had nearly five times greater odds of having successful outcomes than those with untreated HIV.

Background: Amongst HIV-positive adults in South Africa with initial negative Xpert results, we compared the yield from repeating Xpert MTB/RIF (“Xpert”) on sputum to guideline-recommended investigation for tuberculosis (TB). Methods: A systematic sample of adults attending for HIV care were enrolled in a cohort exploring TB investigation pathways. This substudy was restricted to those at highest risk of TB (CD4&lt;200 cells/mm3 or unknown) who had a negative initial Xpert result. At attendance for the Xpert result, a repeat sputum sample was stored, and further investigations facilitated per national guidelines. Participants were reviewed monthly, with reinvestigation if indicated, for at least three months, when sputum and blood were cultured for mycobacteria, and the stored sputum tested using Xpert. We defined TB as “confirmed” if Xpert, line probe assay or Mycobacterium tuberculosis culture within six months of enrolment were positive, and “clinical” if TB treatment was started without microbiological confirmation. Results: Amongst 227 participants with an initial negative Xpert result (63% female, median age 37 years, median CD4 count 100 cells/mm3), 28 (12%) participants had TB diagnosed during study follow-up (16 confirmed, 12 clinical); stored sputum tested positive on Xpert in 5/227 (2%). Amongst 27 participants who started TB treatment, the basis was bacteriological confirmation 11/27 (41%); compatible imaging 11/27 (41%); compatible symptoms 2/27 (7%); and unknown 3/27 (11%). Conclusions: Amongst HIV-positive individuals at high risk of active TB with a negative Xpert result, further investigation using appropriate diagnostic modalities is more likely to lead to TB treatment than immediately repeating sputum for Xpert. TB diagnostic tests with improved sensitivity are needed.

Atopic dermatitis (AD) is one of the most common diseases in pediatric patients, with over 12.5% of US children diagnosed with the condition.1 Previous studies have shown that the impaired skin barrier caused by AD leads to the development of other atopic conditions later in life.2 The rate of AD among black children in Africa is similar to reported rates among African Americans (AA), while the rate of other atopic diseases such as asthma and food allergy (FA) in black children living in African countries are lower compared to most western populations. 3 The lower rate of asthma and FA, despite similar AD rates among rural African children, calls into question the critical role environment plays in protection against the progression of the atopic march. Previous evidence suggests gut microbiota differences are linked to the initiation and progression of atopic diseases.4 It is possible that changes in the environment including diet, exposure to microbes, and lifestyle factors result in alteration in the gut microbiome and contribute to the risk of atopic diseases. In certain African countries, many individuals still live in completely natural settings. Studying these populations provides the opportunity to evaluate the protective role of environment and lifestyle on gut microbiota and atopic diseases.

This study investigates the association of 5 single nucleotide polymorphisms (SNPs) in selected genes (ABO, VEGFA, BDKRB2, NOS3, and ADRB2) with blood pressure (BP) response to enalapril. The study further assessed genetic interactions that exist within these genes and their implications in enalapril treatment response among South African adults with hypertension.A total of 284 participants belonging to the Nguni tribe of South Africa on continuous treatment for hypertension were recruited. Five SNPs in enalapril pharmacogenes were selected and genotyped using MassArray. Uncontrolled hypertension was defined as BP ≥140/90 mm Hg. The association between genotypes, alleles, and BP response to treatment was determined by fitting multivariate logistic regression model analysis, and genetic interactions between SNPs were assessed by multifactor dimensionality reduction.Majority of the study participants were female (75.00%), Xhosa (78.87%), and had uncontrolled hypertension (69.37%). All 5 SNPs were exclusively detected among Swati and Zulu participants. In the multivariate (adjusted) logistic model analysis, ADRB2 rs1042714 GC (adjusted odds ratio [AOR] = 2.31; 95% confidence interval [CI] 1.02–5.23; P = .044) and BDKRB2 rs1799722 CT (AOR = 2.74; 95% CI 1.19–6.28; P = .017) were independently associated with controlled hypertension in response to enalapril. While the C allele of VEGFA rs699947 (AOR = 0.37; 95% CI 0.15–0.94; P = .037) was significantly associated with uncontrolled hypertension. A significant interaction between rs699947, rs495828, and rs2070744 (cross-validation consistency = 10/10; P = .0005) in response to enalapril was observed.We confirmed the association of rs1042714 (ADRB2) and rs1799722 (BDKRB2) with controlled hypertension and established an interaction between rs699947 (VEGFA), rs495828 (ABO), and rs2070744 (NOS3) with BP response to enalapril. Our findings have provided substantial evidence for the use of SNPs as predictors for enalapril response among South Africans adults with hypertension.