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Vertebral, Cardiac, Renal and Limb Defect Syndrome (VCRL), is a very rare congenital malformation syndrome. Pathogenic variants in HAAO (3-Hydroxyanthranilate 3,4-dioxygenase), NADSYN1 (NAD+ Synthetase-1) and KYNU (Kynureninase) have been identified in a handful of affected individuals. All three genes encode for enzymes essential for the NAD+ de novo synthesis pathway. Using Trio-Exome analysis and CGH array analysis in combination with long range PCR, we have identified a novel homozygous copy number variant (CNV) encompassing exon 5 of KYNU in an individual presenting with overlapping features of VCRL and Catel–Manzke Syndrome. Interestingly, only the mother, not the father carried the small deletion in a heterozygous state. High-resolution SNP array analysis subsequently delineated a maternal isodisomy of chromosome 2 (UPD2). Increased xanthurenic acid excretion in the urine confirmed the genetic diagnosis. Our findings confirm the clinical, genetic and metabolic phenotype of VCRL1, adding a novel functionally tested disease allele. We also describe the first patient with NAD+ deficiency disorder resulting from a UPD. Furthermore, we provide a comprehensive review of the current literature covering the genetic basis and pathomechanisms for VCRL and Catel–Manzke Syndrome, including possible phenotype/genotype correlations as well as genetic causes of hypoplastic left heart syndrome.

Hypomethylation of H19 and IGF2 can cause Silver–Russell syndrome (SRS), a clinically and genetically heterogeneous condition characterized by intrauterine growth restriction, poor postnatal growth, relative macrocephaly, craniofacial abnormalities, body asymmetry, hypoglycemia and feeding difficulties. Isolated hypomethylation of IGF2 has been reported in single cases of SRS as well. Here, we report on a 19-month-old patient who presented with two episodes of hypoglycemic seizures. No intrauterine growth restriction was observed, the patient did not present with SRS-typical facial features, and postnatal growth in the first months of life was along the lower normal percentiles. Exome sequencing did not reveal any likely pathogenic variants explaining the phenotype; however, hypomethylation studies revealed isolated hypomethylation of IGF2, while the methylation of H19 appeared normal. Hypoglycemia responded well to growth hormone therapy, and the boy showed good catch-up growth. Our case demonstrates that SRS and isolated IGF2 hypomethylation should be considered early in the diagnosis of recurrent hypoglycemia in childhood, especially in combination with small gestational age and poor growth.

Mycobacterium tuberculosis and nontuberculous mycobacteria such as Mycobacterium abscessus cause diseases that are becoming increasingly difficult to treat due to emerging antibiotic resistance. The development of new antimicrobial molecules is vital for combating these pathogens. Carbon nanomaterials (CNMs) are a class of carbon-containing nanoparticles with promising antimicrobial effects. Fullertubes (C 90 ) are novel carbon allotropes with a structure unique among CNMs. The effects of fullertubes on any living cell have not been studied. In this study, we demonstrate that pristine fullertube dispersions show antimicrobial effects on Mycobacterium smegmatis and M. abscessus. Using scanning electron microscopy, light microscopy, and molecular probes, we investigated the effects of these CNMs on mycobacterial cell viability, cellular integrity, and biofilm formation. C 90 fullertubes at 1 µM inhibited mycobacterial viability by 97%. Scanning electron microscopy revealed that the cell wall structure of M. smegmatis and M. abscessus was severely damaged within 24 h of exposure to fullertubes. Additionally, exposure to fullertubes nearly abrogated the acid-fast staining property of M. smegmatis. Using SYTO-9 and propidium iodide, we show that exposure to the novel fullertubes compromises the integrity of the mycobacterial cell. We also show that the permeability of the mycobacterial cell wall was increased after exposure to fullertubes from our assays utilizing the molecular probe dichlorofluorescein and ethidium bromide transport. C 90 fullertubes at 0.37 µM and C 60 fullerenes at 0.56 µM inhibited pellicle biofilm formation by 70% and 90%, respectively. This is the first report on the antimycobacterial activities of fullertubes and fullerenes., (© 2024 The Authors. Cell Biochemistry and Function published by John Wiley & Sons Ltd.)

Health-related quality of life (HRQoL) assesses the perceived impact of health status across life domains. Although research has explored the relationship between specific conditions, including HIV, and HRQoL in low-resource settings, less attention has been paid to the association between multimorbidity and HRQoL. In a secondary analysis of cross-sectional data from the Vukuzazi ("Wake up and know ourselves" in isiZulu) study, which identified the prevalence and overlap of non-communicable and infectious diseases in the uMkhanyakunde district of KwaZulu-Natal, we (1) evaluated the impact of multimorbidity on HRQoL; (2) determined the relative associations among infectious diseases, non-communicable diseases (NCDs), and HRQoL; and (3) examined the effects of controlled versus non-controlled disease on HRQoL. HRQoL was measured using the EQ-5D-3L, which assesses overall perceived health, five specific domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and three levels of problems (no problems, some problems, and extreme problems). Six diseases and disease states were included in this analysis: HIV, diabetes, stroke, heart attack, high blood pressure, and TB. After examining the degree to which number of conditions affects HRQoL, we estimated the effect of joint associations among combinations of diseases, each HRQoL domain, and overall health. Then, in one set of ridge regression models, we assessed the relative impact of HIV, diabetes, stroke, heart attack, high blood pressure, and tuberculosis on the HRQoL domains; in a second set of models, the contribution of treatment (controlled vs. uncontrolled disease) was added. A total of 14,008 individuals were included in this analysis. Having more conditions adversely affected perceived health (r = -0.060, p<0.001, 95% CI: -0.073 to -0.046) and all HRQoL domains. Infectious conditions were related to better perceived health (r = 0.051, p<0.001, 95% CI: 0.037 to 0.064) and better HRQoL, whereas non-communicable diseases (NCDs) were associated with worse perceived health (r = -0.124, p<0.001, -95% CI: 0.137 to -0.110) and lower HRQoL. Particular combinations of NCDs were detrimental to perceived health, whereas HIV, which was characterized by access to care and suppressed viral load in the large majority of those affected, was counterintuitively associated with better perceived health. With respect to disease control, unique combinations of uncontrolled NCDs were significantly related to worse perceived health, and controlled HIV was associated with better perceived health. The presence of controlled and uncontrolled NCDs was associated with poor perceived health and worse HRQoL, whereas the presence of controlled HIV was associated with improved HRQoL. HIV disease control may be critical for HRQoL among people with HIV, and incorporating NCD prevention and attention to multimorbidity into healthcare strategies may improve HRQoL., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Stanton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Stroke is a major cause of death and disability worldwide and is also a leading cause of vascular dementia and Alzheimer's disease, with older women experiencing accelerated decline. Our previous studies show that intravenous (iv) injections of miR-20a-3p, a small noncoding RNA (miRNA) delivered after stroke improves acute stroke outcomes in middle-aged male and female rats. The present study tested whether mir-20a-3p treatment would also ameliorate stroke-induced cognitive decline in the chronic phase. Acyclic middle-aged females and age-matched male Sprague Dawley rats were subjected to middle cerebral artery occlusion using endothelin-1 or sham surgery, and treated iv with miR-20a-3p mimics or scrambled oligos at 4 hours, 24 hours, and 70 days post-stroke. Stroke resulted in a significant sensory motor deficit, while miR-20a-3p treatment reduced these deficits in both sexes. Cognitive impairment was assessed periodically for 3 months after stroke using contextual fear conditioning and the novel object recognition task. Overall, the tests of associative and episodic memory were affected by focal ischemia only in female rats, and miR-20a-3p ameliorated the rate of decline., Competing Interests: Declarations of interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The convergence of infectious diseases and non-communicable diseases in South Africa is challenging to health systems. In this analysis, we assessed the multimorbidity health needs of individuals and communities in rural KwaZulu-Natal and established a framework to quantify met and unmet health needs for individuals living with infectious and non-communicable diseases., Methods: We analysed data collected between May 25, 2018, and March 13, 2020, from participants of a large, community-based, cross-sectional multimorbidity survey (Vukuzazi) that offered community-based HIV, hypertension, and diabetes screening to all residents aged 15 years or older in a surveillance area in the uMkhanyakude district in KwaZulu-Natal, South Africa. Data from the Vukuzazi survey were linked with data from demographic and health surveillance surveys with a unique identifier common to both studies. Questionnaires were used to assess the diagnosed health conditions, treatment history, general health, and sociodemographic characteristics of an individual. For each condition (ie, HIV, hypertension, and diabetes), individuals were defined as having no health needs (absence of condition), met health needs (condition that is well controlled), or one or more unmet health needs (including diagnosis, engagement in care, or treatment optimisation). We analysed met and unmet health needs for individual and combined conditions and investigated their geospatial distribution., Findings: Of 18 041 participants who completed the survey (12 229 [67·8%] were female and 5812 [32·2%] were male), 9898 (54·9%) had at least one of the three chronic diseases measured. 4942 (49·9%) of these 9898 individuals had at least one unmet health need (1802 [18·2%] of 9898 needed treatment optimisation, 1282 [13·0%] needed engagement in care, and 1858 [18·8%] needed a diagnosis). Unmet health needs varied by disease; 1617 (93·1%) of 1737 people who screened positive for diabetes, 2681 (58·2%) of 4603 people who screened positive for hypertension, and 1321 (21·7%) of 6096 people who screened positive for HIV had unmet health needs. Geospatially, met health needs for HIV were widely distributed and unmet health needs for all three conditions had specific sites of concentration; all three conditions had an overlapping geographical pattern for the need for diagnosis., Interpretation: Although people living with HIV predominantly have a well controlled condition, there is a high burden of unmet health needs for people living with hypertension and diabetes. In South Africa, adapting current, widely available HIV care services to integrate non-communicable disease care is of high priority., Funding: Fogarty International Center and the National Institutes of Health, the Bill & Melinda Gates Foundation, the South African Department of Science and Innovation, the South African Medical Research Council, the South African Population Research Infrastructure Network, and the Wellcome Trust., Translation: For the isiZulu translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: This study aims to assess the efficacy of current measurement strategies for lung sizing and the feasibility of future use of computed tomography (CT)-derived lung volumes to predict a donor-recipient lung size match during bilateral lung transplants., Methods: We reviewed the data of 62 patients who underwent bilateral lung transplantation for interstitial lung disease and/or idiopathic pulmonary fibrosis from 2018 to 2019. Data for recipients was retrieved from the department's transplant database and medical records, and the donor's data was retrieved from the DonorNet. The data included demographic data, lung heights, measured total lung capacity (TLC) from plethysmography for recipients and estimated TLC for donors, clinical data, and CT-derived lung volumes in both pre- and post-transplant recipients. The post-transplant CT-derived lung volume in recipients was used as a surrogate for donor lung CT volumes due to inadequate or poor donor CT data. Computed tomography-derived lung volumes were calculated using thresholding, region growing, and cutting techniques on Computer-Aided Design and Mimics (Materialise NV, Leuven, Belgium) programs. Preoperative CT-derived lung volumes in recipients were compared with the plethysmography TLC, Frustum Model, and donor-predicted TLC. The ratio of the recipient's pre-and postoperative CT-derived volumes, the ratio of preoperative CT-derived lung volume, and donor-estimated TLC were studied to detect a correlation with 1-year outcomes., Results: The recipient preoperative CT-derived volume correlated with the recipient preoperative plethysmography TLC (Pearson correlation coefficient [PCC] of 0.688) and with the recipient Frustum model volume (PCC of 0.593). The recipient postoperative CT-derived volume correlated with the recipient's postoperative plethysmography TLC (PCC of 0.651). There was no statistically significant correlation between recipients' CT-derived pre- or postoperative volume with donor-estimated TLC. The ratio of preoperative CT-derived volume to donor-estimated TLC correlated inversely with the length of ventilation (P value = .0031). The ratio of postoperative CT-derived volume to preoperative CT-derived volume correlated inversely with delayed sternal closure (P = .0039). No statistically significant correlations were found in evaluating outcomes related to lung oversizing in the recipient (defined as a postoperative to preoperative CT-derived lung volume ratio of >1.2)., Conclusions: Generating CT-derived lung volumes is a valid and convenient method for evaluating lung volumes for transplantation in patients with ILD and/or IPF. Donor-estimated TLC should be interpreted carefully. Further studies should derive donor lung volumes from CT scans for a more accurate evaluation of lung size matching., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Universal health coverage (UHC) aims to ensure people have access to the health services they need. Sixteen tracer indicators were developed for implementation by countries to measure UHC in the health system. South Africa uses 15 of the proposed 16 indicators. Operational managers in the public health care sector collect data and report on these indicators at a primary health clinic level. This qualitative study explored the knowledge and attitudes of managers toward data and UHC service indicators in a sub-district in Ugu, KwaZulu-Natal, South Africa. Operational managers saw data collection as information gathering, measuring performance and driving action. They understood UHC indicators as 'health for all' linking them to National Department of Health Strategic plans and saw the value of indicators for health promotion. They found the lack of training, inadequate numeracy skills, requests for data from multiple spheres of government and the indicator targets that they had to reach as challenging and untenable. While operational managers made the link between data, measuring performance and action, the limited training, skills gaps and pressures from higher levels of government may impede their ability to use data for local level planning and decision making.

Non-communicable diseases (NCDs) account for half of all deaths in South Africa, partly reflecting unmet NCDs healthcare needs. Leveraging existing HIV infrastructure is touted as a strategy to alleviate this chronic care gap. We evaluated whether HIV care platforms are associated with improved NCDs care. We conducted a community-based screening of adults in rural KwaZulu-Natal, collecting BP, HbA1c, and health services utilization data. Care cascade indicators for hypertension and diabetes mellitus were defined as: 1) aware, if previously diagnosed, 2) in care, if seeing a provider within last 6 months; 3) treated, if reporting medication use within preceding 2 weeks; and 4) controlled, if BP<140/90mmHg or HbA1c<6.5%. We fit multivariable adjusted logistic regression models to compare successful completion of each step of the care cascade for hypertension and diabetes between people with virally suppressed HIV and HIV-negative comparators. Inverse probability sampling weights were applied to derive population-level estimates. The analytic sample included 4,933 individuals [mean age 58.4 years; 77% female]. Compared to being HIV-negative, having suppressed HIV was associated with lower adjusted prevalence of being aware (-6.0% [95% CI: -11.0, -1.1%]), in care (-5.7% [-10.6, -0.8%]), and in treatment (-4.8% [-9.7, 0.1%]) for diabetes; but higher adjusted prevalence of controlled diabetes (3.2% [0.2-6.2%]). In contrast, having suppressed HIV was associated with higher adjusted prevalence of being aware (7.4% [5.3-9.6%]), in care (8.0% [5.9-10.2%]), in treatment (8.4% [6.1-10.6%]) and controlled (9.0% [6.2-11.8%]), for hypertension. Overall, disease control was achieved for 40.0% (38.6-40.8%) and 6.8% (5.9-7.8%) of individuals with hypertension and diabetes, respectively. Engagement in HIV care in rural KwaZulu-Natal was generally associated with worse diabetes care and improved hypertension care. While further work should explore how success of HIV programs can be translated to NCD care, strengthening of primary healthcare will also be needed to respond to the growing NCDs epidemic., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Magodoro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Tuberculosis (TB) case finding efforts typically target symptomatic people attending health facilities. We compared the prevalence of Mycobacterium tuberculosis (Mtb) sputum culture-positivity among adult clinic attendees in rural South Africa with a concurrent, community-based estimate from the surrounding demographic surveillance area (DSA)., Methods: Clinic: Randomly selected adults (≥18 years) attending 2 primary healthcare clinics were interviewed and requested to give sputum for mycobacterial culture. Human immunodeficiency virus (HIV) and antiretroviral therapy (ART) status were based on self-report and record review. Community: All adult (≥15 years) DSA residents were invited to a mobile clinic for health screening, including serological HIV testing; those with ≥1 TB symptom (cough, weight loss, night sweats, fever) or abnormal chest radiograph were asked for sputum., Results: Clinic: 2055 patients were enrolled (76.9% female; median age, 36 years); 1479 (72.0%) were classified HIV-positive (98.9% on ART) and 131 (6.4%) reported ≥1 TB symptom. Of 20/2055 (1.0% [95% CI, .6-1.5]) with Mtb culture-positive sputum, 14 (70%) reported no symptoms. Community: 10 320 residents were enrolled (68.3% female; median age, 38 years); 3105 (30.3%) tested HIV-positive (87.4% on ART) and 1091 (10.6%) reported ≥1 TB symptom. Of 58/10 320 (0.6% [95% CI, .4-.7]) with Mtb culture-positive sputum, 45 (77.6%) reported no symptoms. In both surveys, sputum culture positivity was associated with male sex and reporting >1 TB symptom., Conclusions: In both clinic and community settings, most participants with Mtb culture-positive sputum were asymptomatic. TB screening based only on symptoms will miss many people with active disease in both settings., Competing Interests: Potential conflicts of interest. I. G. reports salary support from the UK Economic and Social Research Council (grant awarded to the London School of Hygiene and Tropical Medicine [LSHTM]). A. S. K. reports support from The Bloomsbury SET (Research England) (grant awarded to their institution, London School of Hygiene & Tropical Medicine), the National Institute for Health Research (UK), Colt Foundation (UK), ViiV Healthcare (USA), Queen Margaret University (UK), World Health Organization, Medical Research Council (UK), London School of Hygiene and Tropical Medicine (UK), and grants awarded to their employer/institution; reports consulting fees from the University of Cape Town (South Africa), South African National TB Think Tank (funded by the Bill and Melinda Gates Foundation, USA), Center for Health Policy and Studies (Republic of Moldova), Vital Strategies (Singapore; funded by Bloomberg Philanthropies, USA), The Aurum Institute (South Africa), and Edanz Group (Japan); reports travel and accommodation costs from Africa Health Research Institute (South Africa), Kyoto University (Japan), University College London (UK), Vital Strategies (Singapore), and Open Access publishing costs from the Bill and Melinda Gates Foundation (USA). K. K. reports salary support and travel expenses and support towards article-processing charges received for a role on the Umoya Omuhle project (from which the paper draws its data) from the UK Economic and Social Research Council (payments made to Queen Margaret University), grant received from the Joint Health Systems Research Initiative (Medical Research Council/Economic and Social Research Council/Department for International Development/Wellcome Trust) and a grant received from the National Institute for Health Research (NIHR; payments made to Queen Margaret University). O. K. reports salary support through grant to the institutions (Africa Health Research Institute [AHRI] and LSHTM) from Wellcome Trust (core grant 082384/Z/07/Z) and the Bill and Melinda Gates Foundation (OPP1175182). T. N. reports support from Wellcome Trust African Academy of Sciences and the South African National Research Foundation, the Bill and Melinda Gates Foundation and Max Planck Society and reports serving as member of the External Advisory Committee for HIV Vaccine Trials Network. E. B. W. reports support from Massachusetts General Hospital, the Africa Health Research Institute, University of Alabama at Birmingham, Bill and Melinda Gates Foundation, Wellcome Trust and National Institutes of Health. A. G. reports funding for other projects paid to their institution by the National Institutes of Allergy and Infectious Diseases, Bill and Melinda Gates Foundation, Research England, Wellcome Trust, and Medical Research Council and reports travel support paid to their institution by Wellcome Trust and Economic and Social Research Council. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Limited research has been conducted on explanations and understandings of biobanking for future genomic research in African contexts with low literacy and limited healthcare access. We report on the findings of a sub-study on participant understanding embedded in a multi-disease community health screening and biobank platform study known as 'Vukuzazi' in rural KwaZulu-Natal, South Africa., Methods: Semi-structured interviews were conducted with research participants who had been invited to take part in the Vukuzazi study, including both participants and non-participants, and research staff that worked on the study. The interviews were transcribed, and themes were identified from the interview transcripts, manually coded, and thematically analysed., Results: Thirty-nine individuals were interviewed. We found that the research team explained biobanking and future genomic research by describing how hereditary characteristics create similarities among individuals. However, recollection and understanding of this explanation seven months after participation was variable. The large volume of information about the Vukuzazi study objectives and procedures presented a challenge to participant recall. By the time of interviews, some participants recalled rudimentary facts about the genetic aspects of the study, but many expressed little to no interest in genetics and biobanking., Conclusion: Participant's understanding of information related to genetics and biobanking provided during the consent process is affected by the volume of information as well as participant's interest (or lack thereof) in the subject matter being discussed. We recommend that future studies undertaking biobanking and genomic research treat explanations of this kind of research to participants as an on-going process of communication between researchers, participants and the community and that explanatory imagery and video graphic storytelling should be incorporated into theses explanations as these have previously been found to facilitate understanding among those with low literacy levels. Studies should also avoid having broader research objectives as this can divert participant's interest and therefore understanding of why their samples are being collected., (© 2022. The Author(s).)

Purpose: Prisons in Africa face unprecedented challenges during Coronavirus disease 2019 (COVID-19). In July 2020, the first prison system case of COVID-19 was notified in Zimbabwe. Subsequently, the Zimbabwe Prisons and Correctional Services released their COVID-19 operational plan. The purpose of the study was to assess preparedness, prevention and control of COVID-19 in selected prisons in Zimbabwe., Design/methodology/approach: A multi-method situation assessment of COVID-19 preparedness was conducted across three Zimbabwean prisons. The World Health Organization checklist to evaluate preparedness, prevention and control of COVID-19 in prisons was administered to frontline health managers. Information garnered was further explored during site observation and in multi-stakeholder key informant interviews with policymakers, prison health directorate, frontline health-care professionals, officers in charge and non-governmental organizations ( n = 26); focus group discussions with correctional officers ( n = 18); and male/female prisoners ( n = 36). Data was triangulated and analyzed using content thematic analysis., Findings: Outdated infrastructure, severe congestion, interrupted water supply and inadequate hygiene and sanitation were conducive to ill-health and spread of disease. Health professionals had been well-trained regarding COVID-19 disease control measures. COVID-19 awareness among prisoners was generally adequate. There was no routine COVID-19 testing in place, beyond thermo scanning. Access to health care was good, but standards were hindered by inadequate medicines and personnel protective equipment supply. Isolation measures were compromised by accommodation capacity issues. Flow of prison entries constituted a transmission risk. Social distancing was impossible during meals and at night., Originality/value: This unique situation assessment of Zimbabwean prisons' preparedness and approach to tackling COVID-19 acknowledges state and prison efforts to protect prisoners and staff, despite infrastructural constraints and inadequate resourcing from government., (© Emerald Publishing Limited.)

Background: Cross-sectional screening programs are used to detect and refer individuals with non-communicable diseases to healthcare services. We evaluated the positive predictive value of cross-sectional measurements for Diabetes Mellitus (DM) and hypertension (HTN) as part of a community-based disease screening study, 'Vukuzazi' in rural South Africa., Methods: We conducted community-based screening for HTN and DM using the World Health Organization STEPS protocol and glycated haemoglobin A1c (HbA1c) testing, respectively. Nurses conducted follow-up home visits for confirmatory diagnostic testing among individuals with a screening BP above 140/90 mmHg and/or HbA1c above 6.5% at the initial screen, and without a prior diagnosis. We assessed the positive predictive value of the initial screening, compared to the follow up measure. We also sought to identify a screening threshold for HTN and DM with greater than 90% positive predictive value., Results: Of 18,027 participants enrolled, 10.2% (1,831) had a screening BP over 140/90 mmHg. Of those without a prior diagnosis, 871 (47.6%) received follow-up measurements. Only 51.2% (451) of those with completed follow-up measurements had a repeat BP>140/90 mmHg at the home visit and were referred to care. To achieve a 90% correct referral rate, a systolic BP threshold of 192 was needed at first screening. For DM screening, 1,615 (9.0%) individuals had an HbA1c > 6.5%, and of those without a prior diagnosis, 1,151 (71.2%) received a follow-up blood glucose. Of these, only 34.1% (395) met criteria for referral for DM. To ensure a 90% positive predictive value i.e. a screening HbA1c of >16.6% was needed., Conclusions: A second home-based screening visit to confirm a diagnosis of DM and HTN reduced health system referrals by 48% and 66%, respectively. Two-day screening programmes for DM and HTN screening might save individual and healthcare resources and should be evaluated carefully in future cost effectiveness evaluations., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2021 The Author(s).)

Accurate reporting of antiretroviral therapy (ART) uptake is crucial for measuring the success of epidemic control. Programs without linked electronic medical records are susceptible to duplicating ART initiation events. We assessed the prevalence of undisclosed ART use at the time of treatment initiation and explored its correlates among people presenting to public ambulatory clinics in South Africa. Data were analyzed from the community-based delivery of ART (DO ART) clinical trial, which recruited people living with HIV who presented for ART initiation at two clinics in rural South Africa. We collected data on socioeconomic factors, clinical factors, and collected blood as part of study screening procedures. We estimated the proportion of individuals presenting for ART initiation with viral load suppression (< 20 copies/mL) and fitted regression models to identify social and clinical correlates of non-disclosure of ART use. We also explored clinical and national databases to identify records of ART use. Finally, to confirm surreptitious ART use, we measured tenofovir (TDF) and emtricitabine (FTC) levels in dried blood spots. A total of 193 people were screened at the two clinics. Approximately 60% (n = 114) were female, 40% (n = 78) reported a prior HIV test, 23% (n = 44) had disclosed to a partner, and 31% (n = 61) had a partner with HIV. We found that 32% (n = 62) of individuals presenting for ART initiation or re-initiation had an undetectable viral load. In multivariable regression models, female sex (AOR 2.16, 95% CI 1.08-4.30), having a prior HIV test and having disclosed their HIV status (AOR 2.48, 95% CI 1.13-5.46), and having a partner with HIV (AOR 1.94, 95% CI 0.95-3.96) were associated with having an undetectable viral load. In records we reviewed, we found evidence of ART use from either clinical or laboratory databases in 68% (42/62) and detected either TDF or FTC in 60% (37/62) of individuals with an undetectable viral load. Undisclosed ART use was present in approximately one in three individuals presenting for ART initiation or re-initiation at ambulatory HIV clinics in South Africa. These results have important implications for ART resource use and planning in the region. A better understanding of reasons for non-disclosure of ART at primary health care clinics in such settings is needed., (© 2021. The Author(s).)

Computer-aided digital chest radiograph interpretation (CAD) can facilitate high-throughput screening for tuberculosis (TB), but its use in population-based active case-finding programs has been limited. In an HIV-endemic area in rural South Africa, we used a CAD algorithm (CAD4TBv5) to interpret digital chest x-rays (CXR) as part of a mobile health screening effort. Participants with TB symptoms or CAD4TBv5 score above the triaging threshold were referred for microbiological sputum assessment. During an initial pilot phase, a low CAD4TBv5 triaging threshold of 25 was selected to maximize TB case finding. We report the performance of CAD4TBv5 in screening 9,914 participants, 99 (1.0%) of whom were found to have microbiologically proven TB. CAD4TBv5 was able to identify TB cases at the same sensitivity but lower specificity as a blinded radiologist, whereas the next generation of the algorithm (CAD4TBv6) achieved comparable sensitivity and specificity to the radiologist. The CXRs of people with microbiologically confirmed TB spanned a range of lung field abnormality, including 19 (19.2%) cases deemed normal by the radiologist. HIV serostatus did not impact CAD4TB's performance. Notably, 78.8% of the TB cases identified during this population-based survey were asymptomatic and therefore triaged for sputum collection on the basis of CAD4TBv5 score alone. While CAD4TBv6 has the potential to replace radiologists for triaging CXRs in TB prevalence surveys, population-specific piloting is necessary to set the appropriate triaging thresholds. Further work on image analysis strategies is needed to identify radiologically subtle active TB.