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Increasing evidence suggests that urban health objectives are best achieved through a multisectoral approach. This approach requires multiple sectors to consider health and well-being as a central aspect of their policy development and implementation, recognising that numerous determinants of health lie outside (or beyond the confines of) the health sector. However, collaboration across sectors remains scarce and multisectoral interventions to support health are lacking in Africa. To address this gap in research, we conducted a mixed-method systematic review of multisectoral interventions aimed at enhancing health, with a particular focus on non-communicable diseases in urban African settings. Africa is the world’s fastest urbanising region, making it a critical context in which to examine the impact of multisectoral approaches to improve health. This systematic review provides a valuable overview of current knowledge on multisectoral urban health interventions and enables the identification of existing knowledge gaps, and consequently, avenues for future research. We searched four academic databases (PubMed, Scopus, Web of Science, Global Health) for evidence dated 1989–2019 and identified grey literature from expert input. We identified 53 articles (17 quantitative, 20 qualitative, 12 mixed methods) involving collaborations across 22 sectors and 16 African countries. The principle guiding the majority of the multisectoral interventions was community health equity (39.6%), followed by healthy cities and healthy urban governance principles (32.1%). Targeted health outcomes were diverse, spanning behaviour, environmental and active participation from communities. With only 2% of all studies focusing on health equity as an outcome and with 47% of studies published by first authors located outside Africa, this review underlines the need for future research to prioritise equity both in terms of research outcomes and processes. A synthesised framework of seven interconnected components showcases an ecosystem on multisectoral interventions for urban health that can be examined in the future research in African urban settings that can benefit the health of people and the planet. Paper Context Main findings: Multisectoral interventions were identified in 27.8% of African countries in the African Union, targeted at major cities with five sectors present at all intervention stages: academia or research, agriculture, government, health, and non-governmental. Added knowledge: We propose a synthesised framework showcasing an ecosystem on multisectoral interventions for urban health that can guide future research in African urban settings. Global health impact for policy and action: This study reveals a crucial gap in evidence on evaluating the long-term impact of multisectoral interventions and calls for partnerships involving various sectors and robust community engagement to effectively deliver and sustain health-promoting policies and actions.

Introduction Leveraging data science could significantly advance the understanding of the health impacts of climate change and air pollution to meet health systems’ needs and improve public health in Africa. This scoping review will aim to identify and synthesise evidence on the use of data science as an intervention to address climate change and air pollution-related health challenges in Africa.Methods and analysis The search strategy will be developed, and the search will be conducted in the Web of Science, Scopus, CAB Abstracts, MEDLINE and EMBASE electronic databases. We will also search the reference lists of eligible articles for additional records. We will screen titles, technical reports, abstracts and full texts and select studies reporting the use of data science in relation to the health effects and interventions associated with climate change and air pollution in Africa.Ethics and dissemination There are no formal ethics requirements as we are not collecting primary data. Results, once published, will be disseminated via conferences and shared with policy-makers and public health, air pollution and climate change key stakeholders in Africa.

IntroductionSouth Africa, grappling with the complexities of malnutrition, faces a dual challenge of undernutrition in children and overnutrition in adults, particularly among women. This situation is exacerbated by high rates of food insecurity, affecting nearly one-fourth of households. In this context, the role of Rotating Savings and Credit Associations (ROSCAs), locally known as stokvels, becomes increasingly significant. These informal, often women-led, savings and borrowing groups present a unique opportunity to address dietary challenges and promote healthier eating practices in urban, low-income settings. This study explores the potential of stokvels in mitigating the dual burden of malnutrition by facilitating access to healthy, affordable foods.MethodsWe conducted stakeholder mapping to understand the roles and influences of various actors within South Africa's food system, particularly their interactions with stokvels. Our research focuses on how these groups, deeply embedded in the community fabric, can leverage their collective power to negotiate better access to nutritious food and influence healthier dietary choices. Stakeholders identified in the study span diverse sectors, including retail, agriculture, finance, and community organizations.ResultsThe research reveals that stokvels are perceived as vital social and economic entities capable of maximizing value through partnerships and networks. However, challenges such as the informal nature of stokvels and the lack of formal legal agreements often hinder their ability to form partnerships with formal institutions. The findings emphasize the importance of understanding and leveraging the social dynamics within stokvels, recognizing their role in enhancing food security and contributing to economic empowerment, especially for women. The study also identifies the need for formalizing stokvel structures to enhance their operational efficiency and increase their impact on food systems.DiscussionIn conclusion, this research highlights the untapped potential of stokvels in addressing South Africa's nutritional challenges. By fostering stronger connections between stokvels and various food system actors, there is a significant opportunity to improve food security and promote healthier eating habits in low-income communities. Future research should aim to include unrepresented stakeholders and explore strategies to enhance the role of ROSCAs in promoting healthier food choices and addressing affordability and accessibility barriers.

Abstract Background In South Africa, overweight and obesity affect 17% of children aged 15–18. School food environments play a vital role in children’s health, influencing dietary behaviours and resulting in high obesity rates. Interventions targeting schools can contribute to obesity prevention if evidence-based and context-specific. Evidence suggests that current government strategies are inadequate to ensure healthy school food environments. The aim of this study was to identify priority interventions to improve school food environments in urban South Africa using the Behaviour Change Wheel model. Methods A three-phased iterative study design was implemented. First, we identified contextual drivers of unhealthy school food environments through a secondary framework analysis of 26 interviews with primary school staff. Transcripts were deductively coded in MAXQDA software using the Behaviour Change Wheel and the Theoretical Domains Framework. Second, to identify evidence-based interventions, we utilised the NOURISHING framework and matched interventions to identified drivers. Third, interventions were prioritised using a Delphi survey administered to stakeholders (n = 38). Consensus for priority interventions was defined as an intervention identified as being 'somewhat' or ‘very' important and feasible with a high level of agreement (quartile deviation ≤ 0.5). Results We identified 31 unique contextual drivers that school staff perceived to limit or facilitate a healthy school food environment. Intervention mapping yielded 21 interventions to improve school food environments; seven were considered important and feasible. Of these, the top priority interventions were to: 1) “regulate what kinds of foods can be sold at schools”, 2) “train school staff through workshops and discussions to improve school food environment”, and affix 3) “compulsory, child-friendly warning labels on unhealthy foods”. Conclusion Prioritising evidence-based, feasible and important interventions underpinned by behaviour change theories is an important step towards enhanced policy making and resource allocation to tackle South Africa’s childhood obesity epidemic effectively.

Background: This cross-sectional study examined the relationship between socioeconomic status (SES), dietary knowledge and patterns, and physical activity level with body mass index of urban South African young women. Methods: Data were collected on 160 black South African women (aged 18–24 years) and included household SES, food frequency and nutritional knowledge questionnaires, self-reported physical activity and anthropometry. To assess household SES index, 1–7 assets were categorised as a lower household SES and those with 8–13 assets as a higher household SES. Structural equation modelling analysis was used to determine the direct, indirect and total effects on adiposity of household SES, age, education, nutrition knowledge score, dietary patterns and physical activity. Results: The prevalence of overweight and obesity was similar among women from high SES households compared with their low SES peers (48.4 vs. 44.8%). More than half (53%) of the women had poor dietary knowledge. Women from low SES households spent more time in moderate to vigorous intensity exercise (MVPA) compared with their high SES counterparts. Two distinct dietary patterns (Western and mixed) were identified. SEM results show that a unit increase in adherence to the ‘Mixed’ dietary pattern compared with ‘Western’ was associated with a 0.81 lower BMI kg/m2 (95% CI −1.54; −0.08), while ≥ 150 minutes’ MVPA per week was associated with a 1.94 lower BMI kg/m2 (95% CI −3.48; −0.41). Conclusion: The associations of SES, diet and physical activity on BMI must be taken into account when developing and designing interventions that target improvement in young women’s health.

No abstract available.

Physical activity (PA) can reduce the risk of non-communicable diseases like heart diseases and diabetes. However, exposure to poor air quality (AQ) when engaging in PA could negate the health benefits. The risk associated with air pollution is relatively severe during physical activities because a higher inhaled pollution dose is experienced during PA compared to when sedentary. We conducted a yearlong AQ monitoring using a commercial low-cost AQ device. The devices were deployed near a public space used for PA as part of a study to understand the health risks encountered by people informally appropriating public spaces for PA in Lagos, Nigeria and Yaoundé, Cameroon. The parameters monitored included CO, NO, NO2, O3, PM2.5, PM10, CO2, pressure, temperature and relative humidity. We detected unique pollutant temporal profiles at the two locations, with a distinct weekday-to-weekend effect observed for the gaseous pollutants but not for the PM. Transboundary emissions related to the Harmattan haze dominated the background PM concentration in both cities in the dry season. Our findings underscore the importance of long-term AQ monitoring to inform action and offer insights into simple behavioural changes that can maximise the health benefits of PA while minimising the risk of air pollution exposure.

Abstract Purpose Quantitative epidemiological tools are routinely used to assess adolescent diet and physical activity (PA) constructs (behaviour, knowledge, and awareness) as risk factors for non-communicable diseases. This study sought to synthesize evidence on the quantitative epidemiological tools that have been used to assess adolescent diet and PA constructs in low to middle-income countries (LMIC). Methods A systematised review was conducted using 3 databases (EbscoHost, Scopus and Web of Science). Results We identified 292 LMIC studies assessing adolescent diet and PA. Identified studies predominantly explored behavioural (90%) constructs with a paucity of studies investigating knowledge and awareness. The majority of studies used subjective (94%) and self-administered (78%) tools. Only 39% of LMIC studies used tools validated for their contexts. Conclusions The findings highlight the need for more contextual tools for assessing adolescent diet and PA in LMICs. Diet and PA measurement tools used in future research will need to incorporate measures of knowledge and awareness for a more comprehensive understanding of the epidemiology of diet and PA in adolescents. Furthermore, there is a need for more evidence on the reliability and validity of these tools for use, in both cross sectional and longitudinal studies, in LMIC contexts.

BackgroundChronic non-communicable disease comorbidities are a major problem faced by people living with HIV (PLHIV). Obesity is an important factor contributing to such comorbidities and PLHIV face an elevated risk of obesity. However, there is data paucity on the intersection of obesity and HIV in adolescents and youth living with HIV (AYLHIV) in sub-Saharan Africa. We therefore aimed to investigate the prevalence of abdominal obesity and associated multilevel factors in AYLHIV in peri-urban Cape Town, South Africa.MethodsWe conducted a cross-sectional study enrolling AYLHIV aged 15-24 years attending primary healthcare facilities in peri-urban Cape Town in 2019. All measures, except for physical examination measures, were obtained via self-report using a self-administered electronic form. Our outcome of interest was abdominal obesity (waist-to-height ratio ≥ 0.5). We collected individual-level data and data on community, built and food environment factors. Data was summarized using descriptive statistics, stratified by obesity status. Multilevel logistic regression was conducted to investigate factors associated with abdominal obesity, adjusted for sex and age.FindingsA total of 87 participants were interviewed, 76% were female and the median age was 20.7 (IQR 18.9-23.0) years. More than two fifths had abdominal obesity (41%; 95% CI: 31.0-51.7%), compared to published rates for young people in the general population (13.7-22.1%). In multilevel models, skipping breakfast (aOR = 5.42; 95% CI: 1.32-22.25) was associated with higher odds of abdominal obesity, while daily wholegrain consumption (aOR = 0.20; 95% CI: 0.05-0.71) and weekly physical activity (aOR = 0.24; 95% CI: 0.06-0.92) were associated with lower odds of abdominal obesity. Higher anticipated stigma was associated with reduced odds of obesity (aOR = 0.58; 95% CI: 0.33-1.00). Land-use mix diversity (aOR = 0.52; 95% CI: 0.27-0.97), access to recreational places (aOR = 0.37; 95% CI: 0.18-0.74), higher perceived pedestrian and traffic safety (aOR = 0.20; 95% CI: 0.05-0.80) and having a non-fast-food restaurant within walking distance (aOR = 0.30; 95% CI: 0.10-0.93) were associated with reduced odds of abdominal obesity. The main limitations of the study were low statistical power and possible reporting bias from self-report measures.ConclusionsOur findings demonstrate a high prevalence of abdominal obesity and highlight multilevel correlates of obesity in AYLHIV in South Africa. An intersectoral approach to obesity prevention, intervening at multiple levels is necessary to intervene at this critical life stage.

One of the major consequences of Africa’s rapid urbanisation is the worsening air pollution, especially in urban centres. However, existing societal challenges such as recovery from the COVID-19 pandemic, poverty, intensifying effects of climate change are making prioritisation of addressing air pollution harder.We undertook a scoping review of strategies developed and/or implemented in Africa to provide a repository to stakeholders as a reference that could be applied for various local contexts. The review includes strategies assessed for effectiveness in improving air quality and/or health outcomes, co-benefits of the strategies, potential collaborators, and pitfalls.An international multidisciplinary team convened to develop well-considered research themes and scope from a contextual lens relevant to the African continent. From the initial 18,684 search returns, additional 43 returns through reference chaining, contacting topic experts and policy makers, 65 studies and reports were included for final analysis.Three main strategy categories obtained from the review included technology (75%), policy (20%) and education/behavioural change (5%). Most strategies (83%) predominantly focused on household air pollution compared to outdoor air pollution (17%) yet the latter is increasing due to urbanisation. Mobility strategies were only 6% compared to household energy strategies (88%) yet motorised mobility has rapidly increased over recent decades.A cost effective way to tackle air pollution in African cities given the competing priorities could be by leveraging and adopting implemented strategies, collaborating with actors involved whilst considering local contextual factors. Lessons and best practices from early adopters/implementers can go a long way in identifying opportunities and mitigating potential barriers related to the air quality management strategies hence saving time on trying to “reinvent the wheel” and prevent pitfalls. We suggest collaboration of various stakeholders, such as policy makers, academia, businesses and communities in order to formulate strategies that are suitable and practical to various local contexts.

Abstract Background The growing burden of the HIV and non-communicable disease (NCD) syndemic in Sub- Saharan Africa has necessitated introduction of integrated models of care in order to leverage existing HIV care infrastructure for NCDs. However, there is paucity of literature on treatment outcomes for multimorbid patients attending integrated care. We describe 12-month treatment outcomes among multimorbid patients attending integrated antiretroviral treatment (ART) and NCD clubs in Cape Town, South Africa. Methods As part of an integrated clubs (IC) model pilot implemented in 2016 by the local government at two primary health care clinics in Cape Town, we identified all multimorbid patients who were enrolled for IC for at least 12 months by August 2017. Mean adherence percentages (using proxy of medication collection and attendance of club visits) and optimal disease control (defined as the proportion of participants achieving optimal blood pressure, glycosylated haemoglobin control and HIV viral load suppression where appropriate) were calculated at 12 months before, at the point of IC enrolment and 12 months after IC enrolment. Predictors of NCD control 12 months post IC enrolment were investigated using multivariable logistic regression. Results As of 31 August 2017, 247 HIV-infected patients in total had been enrolled into IC for at least 12 months. Of these, 221 (89.5%) had hypertension, 4 (1.6%) had diabetes mellitus and 22 (8.9%) had both diseases. Adherence was maintained before and after IC enrolment with mean adherence percentages of 92.2% and 94.2% respectively. HIV viral suppression rates were 98.6%, 99.5% and 99.4% at the three time points respectively. Retention in care was high with 6.9% lost to follow up at 12 months post IC enrolment. Across the 3 time-points, optimal blood pressure control was achieved in 43.1%, 58.9% and 49.4% of participants while optimal glycaemic control was achieved in 47.4%, 87.5% and 53.3% of participants with diabetes respectively. Multivariable logistic analyses showed no independent variables significantly associated with NCD control. Conclusion Multimorbid adults living with HIV achieved high levels of HIV control in integrated HIV and NCD clubs. However, intensified interventions are needed to maintain NCD control in the long term.

Objectives The Cardiff Model of data sharing for violence prevention is premised on the idea that the majority of injury cases presenting at health facilities as a result of interpersonal violence will not be reported to the police. The aim of this study was to determine the concordance between violent crimes reported to the police with violence-related injuries presenting at health facilities in Cape Town, South Africa.Methods We conducted a retrospective analysis of secondary cross-sectional health and police data, from three health facilities and three police stations in the community of Khayelitsha, Cape Town. 781 cases of injuries arising from interpersonal violence seen at health facilities were compared with 739 violence-related crimes reported at police stations over five separate week-long sampling periods from 2013 to 2015. Personal identifiers, name and surname, were used to match cases.Results Of the 708 cases presenting at health facilities, 104 (14.7%) were matched with police records. The addition of non-reported cases of violence-related injuries from the health dataset to the police-reported crime statistics resulted in an 81.7% increase in potential total violent crimes over the reporting period. Compared with incidents reported to the police, those not reported were more likely to involve male patients (difference: +47.0%; p

Objectives: To present the protocol for a systematic review synthesising quantitative and qualitative evidence in academic and grey literature on intersectoral interventions to address non-communicable disease risk factors in urban Africa. Study design: This protocol is developed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analyses Protocols guidelines. Databases to be searched include PubMed, Global Health, SCOPUS, and Web of Science. Grey literature will be sourced from Google, local, regional, and international agencies, colleagues within the GDAR network, international organisations such as the WHO and UN-Habitat, UNICEF's Child Friendly Cities Initiative, Partnership for Healthy Cities, WHO Alliance for Healthy Cities, the African Centre for Cities, as well as grey literature databases such as Greynet and Opengrey. Methods: We will include all quantitative and qualitative study designs that describe any initiatives to address non-communicable disease risk factors through intersectoral interventions, and those that describe associations between such interventions and behavioural health or wellbeing outcomes. We will also include health service interventions that have an intersectoral component and are focused on non-communicable disease prevention. Studies must have been conducted in African countries, published in the past 30 years, and contain primary or secondary data as well as an analysis of these data. Results: We will use the qualitative checklist and the cohort study checklist of the Critical Appraisal Skills Programme (CASP), to appraise the quality of each study included in this review. While the specific framework for data synthesis will be concluded after reviewing the extracted data, we anticipate using a parallel convergent method to synthesise the parallel strands of our study, as it involves analysing the qualitative and quantitative papers separately and then integrating them. Conclusions: This will be the first systematic review to explore intersectoral interventions to address non-communicable disease risk in African cities, thus filling a crucial gap in the literature. The findings of this study will be disseminated across global organisations whose mandates cut across non-communicable diseases prevention, health promotion and healthy urban development. These include but are not limited to the World Health Organization, UN-Habitat, the UN Interagency Task Force on Noncommunicable Diseases Prevention and Control and the NCD Global Coordination Mechanism. We also plan to disseminate our findings to national and provincial stakeholders such as local governments, Ministries of Health and grassroots organisations; intergovernmental organisations such as the African Development Bank, and local and international private foundations such as Dangote Foundation and the Gates Foundation. The pan-African scope of this study makes it eligible to serve as a regional body of work and a resource to inform future interventions, practices, and policies.

Objective This study aimed to examine the prevalence of adolescent active travel to school (ATS) across 31 countries and territories in Asia, overall and by age group, sex and body mass index (BMI) category.Design Cross-sectional study.Setting 31 Asian countries.Participants 152 368 adolescents aged 13–17 years with complete data for age, sex, measured weight and height and active travel to school from 31 Asian countries from the Global School-based student Health Survey (GSHS).Primary outcome Self-reported active travel to school categorised into passive (0 days) and active (1–7 days).Results Overall prevalence of adolescent ATS in Asia based on random-effect meta-analysis was 55%, ranging from 18% (UAE) to 84% (Myanmar). There was limited subregional variation: 47% in the Eastern Mediterranean (EM), 56% in the South East Asia and 64% in the Western Pacific. Summarised by random-effect meta-analysis, being an older adolescent aged 16 years and older (vs younger age below 16 years: OR: 1.08; 95% CI: 1.00 to 1.16) was positively associated with ATS. This association was strongest in EM countries. Summarised by random-effect meta-analysis, females (vs males: OR: 0.79; 95% CI: 0.71 to 0.89) and adolescents with overweight/obesity (vs underweight and normal BMI: OR: 0.92; 95% CI: 0.86 to 0.99) were less likely to use ATS. Association with sex was strongest in EM countries. Heterogeneity was considerable in all meta-analyses.Conclusion The prevalence of adolescent ATS in Asia varies substantially. Overall, older and male adolescents, and adolescents with underweight and normal BMI category are more likely to actively travel to school. However, the main contributor to differences in ATS between and within regions remain unknown. Although there is substantial scope for improving ATS rates in Asia, any policy actions and interventions should be cognisant of local built, social and natural environmental contexts that may influence active travel behaviour.

Abstract Background Non-communicable diseases (NCDs) are the leading cause of death globally. While upstream approaches to tackle NCD risk factors of poor quality diets and physical inactivity have been trialled in high income countries (HICs), there is little evidence from low and middle-income countries (LMICs) that bear a disproportionate NCD burden. Sub-Saharan Africa and the Caribbean are therefore the focus regions for a novel global health partnership to address upstream determinants of NCDs. Partnership The Global Diet and Activity research Network (GDAR Network) was formed in July 2017 with funding from the UK National Institute for Health Research (NIHR) Global Health Research Units and Groups Programme. We describe the GDAR Network as a case example and a potential model for research generation and capacity strengthening for others committed to addressing the upstream determinants of NCDs in LMICs. We highlight the dual equity targets of research generation and capacity strengthening in the description of the four work packages. The work packages focus on learning from the past through identifying evidence and policy gaps and priorities, understanding the present through adolescent lived experiences of healthy eating and physical activity, and co-designing future interventions with non-academic stakeholders. Conclusion We present five lessons learned to date from the GDAR Network activities that can benefit other global health research partnerships. We close with a summary of the GDAR Network contribution to cultivating sustainable capacity strengthening and cutting-edge policy-relevant research as a beacon to exemplify the need for such collaborative groups.

Perceived quality of care is a determinant of uptake of health services. This study aimed to assess the determinants of quality of care of enrollees in the National Health Insurance Scheme (NHIS) in Nigeria. The outcome was satisfaction with health care services, which was used as a proxy for quality. Findings will assist in the intervention to enhance enrollment in the scheme and for universal health coverage attainment. This was a descriptive cross-sectional study conducted among enrollees in selected NHIS facilities in Ibadan, Nigeria. Data on satisfaction with health care were collected among selected 432 enrollees with the aid of an adapted semi-structured WHO-USAID interviewer-administered questionnaire. Data were analyzed using chi-square and multiple logistic regression models (α = 0.05). Among predictors of satisfaction with health services were younger age (OR = 1.85, 95% CI = 1.05–3.25, p = .024), working in the private sector (OR = 1.84, 95% CI = 1.03–3.28, p = .022), and seeking information about quality of services prior enrollment (OR = 1.63, 95% CI = 1.04−2.53, p = .013). Targeted intervention based on the findings of this study should be implemented to improve satisfaction with the services offered.

Abstract Background Chronic care models like the Integrated Chronic Disease Management (ICDM) model strive to improve the efficiency and quality of care for patients with chronic diseases. However, there is a dearth of studies assessing the moderating factors of fidelity during the implementation of the ICDM model. The aim of this study is to assess moderating factors of implementation fidelity of the ICDM model. Methods This was a cross-sectional mixed method study conducted in two health districts in South Africa. The process evaluation and implementation fidelity frameworks were used to guide the assessment of moderating factors influencing implementation fidelity of the ICDM model. We interviewed 30 purposively selected healthcare workers from four facilities (15 from each of the two facilities with lower and higher levels of implementation fidelity of the ICDM model). Data on facility characteristics were collected by observation and interviews. Linear regression and descriptive statistics were used to analyse quantitative data while qualitative data were analysed thematically. Results The median age of participants was 36.5 (IQR: 30.8–45.5) years, and they had been in their roles for a median of 4.0 (IQR: 1.0–7.3) years. The moderating factors of implementation fidelity of the ICDM model were the existence of facilitation strategies (training and clinical mentorship); intervention complexity (healthcare worker, time and space integration); and participant responsiveness (observing operational efficiencies, compliance of patients and staff attitudes). One feature of the ICDM model that seemingly compromised fidelity was the inclusion of tuberculosis patients in the same stream (waiting areas, consultation rooms) as other patients with non-communicable diseases and those with HIV/AIDS with no clear infection control guidelines. Participants also suggested that poor adherence to any one component of the ICDM model affected the implementation of the other components. Contextual factors that affected fidelity included supply chain management, infrastructure, adequate staff, and balanced patient caseloads. Conclusion There are multiple (context, participant responsiveness, intervention complexity and facilitation strategies) interrelated moderating factors influencing implementation fidelity of the ICDM model. Augmenting facilitation strategies (training and clinical mentorship) could further improve the degree of fidelity during the implementation of the ICDM model.

Abstract Background Epidemiological transition in high HIV-burden settings is resulting in a rise in HIV/NCD multimorbidity. The majority of NCD risk behaviours start during adolescence, making this an important target group for NCD prevention and multimorbidity prevention in adolescents with a chronic condition such as HIV. However, there is data paucity on NCD risk and prevention in adolescents with HIV in high HIV-burden settings. The aim of this study was to investigate the extent to which NCD comorbidity (prevention, diagnosis, and management) is incorporated within existing adolescent HIV primary healthcare services in Cape Town, South Africa. Methods We reviewed medical records of 491 adolescents and youth living with HIV (AYLHIV) aged 10–24 years across nine primary care facilities in Cape Town from November 2018–March 2019. Folders were systematically sampled from a master list of all AYLHIV per facility and information on HIV management and care, NCDs, NCD risk and NCD-related health promotion extracted. Results The median age was 20 years (IQR: 14–23); median age at ART initiation 18 years (IQR: 6–21) and median duration on ART 3 years (IQR: 1.1–8.9). Fifty five percent of participants had a documented comorbidity, of which 11% had an NCD diagnosis with chronic respiratory diseases (60%) and mental disorders (37%) most common. Of those with documented anthropometrics (62%), 48% were overweight or obese. Fifty nine percent of participants had a documented blood pressure, of which 27% were abnormal. Twenty-six percent had a documented health promoting intervention, 42% of which were NCD-related; ranging from alcohol or substance abuse (13%); smoking (9%); healthy weight or diet (9%) and mental health counselling (10%). Conclusions Our study demonstrates limited NCD screening and health promotion in AYLHIV accessing healthcare services. Where documented, our data demonstrates existing NCD comorbidity and NCD risk factors highlighting a missed opportunity for multimorbidity prevention through NCD screening and health promotion. Addressing this missed opportunity requires an integrated health system and intersectoral action on upstream NCD determinants to turn the tide on the rising NCD and multimorbidity epidemic.

Abstract Background The Integrated Chronic Disease Management (ICDM) model has been implemented in South Africa to enhance quality of clinical services in Primary Healthcare (PHC) clinics in a context of a high prevalence of chronic conditions and multi-morbidity. This study aimed to assess the implementation fidelity (adherence to guidelines) of the ICDM model. Methods A cross-sectional study in 16 PHC clinics in two health districts in South Africa: Dr. Kenneth Kaunda (DKK) and West Rand (WR). A fidelity assessment tool with 89 activities and maximum score of 158 was developed from the four interrelated ICDM model components: facility re-organization, clinical supportive management, assisted self-management and strengthening of support systems. Value stream mapping of patient flow was conducted to analyse waiting time and identify operational inefficiencies. ICDM items were scored based on structured observations, facility document reviews and structured questionnaires completed by healthcare workers. Fidelity scores were summarized using medians and proportions and compared by facilities and districts using Chi-Square and Kruskal Wallis test. Results The monthly patient headcount over a six-month period in these 16 PHC clinics was a median of 2430 (IQR: 1685–2942) individuals over 20 years. The DKK district had more newly diagnosed TB patients per month [median 5.5 (IQR: 4.00–9.33) vs 2.0 (IQR: 1.67–2.92)], and fewer medical officers per clinic [median 1 (IQR: 1–1) vs 3.5 (IQR:2–4.5)] compared to WR district. The median fidelity scores in both districts for facility re-organization, clinical supportive management, assisted self-management and strengthening of support systems were 78% [29/37, IQR: 27–31)]; 77% [30/39 (IQR: 27–34)]; 77% [30/39 (IQR: 28–34)]; and 80% [35/44 (IQR: 30–37)], respectively. The overall median implementation fidelity of the ICDM model was 79% (125/158, IQR, 117–132); WR was 80% (126/158, IQR, 123–132) while DKK was 74% (117/158, IQR, 106–130), p = 0.1409. The lowest clinic fidelity score was 66% (104/158), while the highest was 86% (136/158). A patient flow analysis showed long (2–5 h) waiting times and one stream of care for acute and chronic services. Conclusion There was some variability of scores on components of the ICDM model by PHC clinics. More research is needed on contextual adaptations of the model.

# Background High rates of non-communicable diseases (NCD) among people living with human immunodeficiency virus (HIV) have been reported in high HIV burden, low-resource settings. The growing dual burden of HIV and NCD epidemics has necessitated introduction of integrated models of HIV and NCD care in order to leverage existing HIV care infrastructure for NCDs. There is a paucity of evidence on the effects of integrated care on long-term patient outcomes. We sought to review literature that described effects of integration on long-term patient outcomes. # Methods We reviewed literature published between 01 Jan 2000 to 25 September 2019, that described long-term patient outcomes in HIV and NCD integrated models of care in order to understand the effects of integration on long-term patient outcomes. Relevant literature was searched in PubMed, Scopus, EBSCOhost and Web of Science. A manual search of abstracts in the International AIDS Society and the Journal of Acquired Immunodeficiency Syndrome was also conducted. # Results One thousand six hundred and sixty articles were identified, 31 of which were read in full, with 11 meeting eligibility criteria. Patient outcomes in four models of integrated care were identified: (i) integration of NCD screening and treatment services into established HIV centres; (ii) integration of HIV screening and treatment services into established NCD centres; (iii) simultaneous integration of HIV and NCD services at health facilities; and (iv) integrated HIV and NCD care specifically for multi-morbid patients. Studies reported high rates of control of HIV and NCD across the various models of integrated care. However, majority of studies lacked comparator groups required to ascertain non-inferiority of integrated care over non-integrated care. # Conclusions There is limited evidence on the effect of integrated HIV and NCD models of care on long-term patient outcomes especially in low-resource, high-burden settings. Randomized clinical trials with clearly defined comparator groups and standardized measures of HIV and NCD outcomes are needed to demonstrate non-inferiority of integrated against non-integrated care.

BackgroundThe increasing burden of noncommunicable diseases that are prevalent in low- and middle-income countries (LMICs) is largely attributed to modifiable behavioral risk factors such as unhealthy diets and insufficient physical activity (PA). The adolescent stage, defined as 10 to 24 years of age, is an important formative phase of life and offers an opportunity to reduce the risk of noncommunicable diseases across the life course and for future generations. ObjectiveThe aim of this paper is to describe a protocol for a study using a convergent mixed methods design to explore exposures in the household, neighborhood, school, and the journey from home to school that may influence diet and PA behaviors in adolescents from LMICs. MethodsMale and female adolescents (n≥150) aged between 13 and 24 years will be recruited from selected high schools or households in project site countries to ensure the socioeconomic diversity of perspectives and experiences at the individual, home, and neighborhood levels. The project will be conducted at 5 sites in 4 countries: Kenya, Cameroon, Jamaica, and South Africa (Cape Town and Johannesburg). Data on anthropometric measures, food intake, and PA knowledge and behavior will be collected using self-report questionnaires. In addition, a small number of learners (n=30-45) from each site will be selected as citizen scientists to capture data (photographs, audio notes, text, and geolocations) on their lived experiences in relation to food and PA in their homes, the journey to and from school, and the school and neighborhood environments using a mobile app, and for objective PA measurements. In-depth interviews will be conducted with the citizen scientists and their caregivers to explore household experiences and determinants of food intake and foodways, as well as the PA of household members. ResultsThe study described in this protocol paper was primarily funded through a UK National Institute for Health Research grant in 2017 and approved by the relevant institutional ethics review boards in the country sites (South Africa, Cameroun, and Jamaica in 2019, and Kenya in 2020). As of December 23, 2020, we had completed data collection from adolescents (n≥150) in all the country sites, except Kenya, and data collection for the subgroup (n=30-45) is ongoing. Data analysis is ongoing and the output of findings from the study described in this protocol is expected to be published by 2022. ConclusionsThis project protocol contributes to research that focuses on adolescents and the socioecological determinants of food intake and PA in LMIC settings. It includes innovative methodologies to interrogate and map the contexts of these determinants and will generate much-needed data to understand the multilevel system of factors that can be leveraged through upstream and downstream strategies and interventions to improve health outcomes. International Registered Report Identifier (IRRID)DERR1-10.2196/26739

Abstract The African continent is predicted to be home to over half of the expected global population growth between 2015 and 2050, highlighting the importance of addressing population health in Africa for improving public health globally. By 2050, nearly 60% of the population of the continent is expected to be living in urban areas and 35–40% of children and adolescents globally are projected to be living in Africa. Urgent attention is therefore required to respond to this population growth - particularly in the context of an increasingly urban and young population. To this end, the Research Initiative for Cities Health and Equity in Africa (RICHE Africa) Network aims to support the development of evidence to inform policy and programming to improve urban health across the continent. This paper highlights the importance of action in the African continent for achieving global public health targets. Specifically, we argue that a focus on urban health in Africa is urgently required in order to support progress on the Sustainable Development Goals (SDGs) and other global and regional public health targets, including Universal Health Coverage (UHC), the new Urban Agenda, and the African Union’s Agenda 2063. Action on urban public health in Africa is critical for achieving global public health targets. Four key research and training priorities for improving urban health in Africa, are outlined: (1) increase intersectoral urban health literacy; (2) apply a healthy urban governance and systems approach; (3) develop a participatory and collaborative urban health planning process; and, (4) produce a new generation of urban health scholars and practitioners. We argue that acting on key priorities in urban health is critical for improving health for all and ensuring that we ‘leave no-one behind’ when working to achieve these regional and global agendas to improve health and wellbeing.

Recently, host whole blood gene expression signatures have been identified for diagnosis of tuberculosis (TB). Absolute quantification of the concentrations of signature transcripts in blood have not been reported, but would facilitate diagnostic test development. To identify minimal transcript signatures, we applied a transcript selection procedure to microarray data from African adults comprising 536 patients with TB, other diseases (OD) and latent TB (LTBI), divided into training and test sets. Signatures were further investigated using reverse transcriptase (RT)—digital PCR (dPCR). A four-transcript signature (GBP6, TMCC1, PRDM1, and ARG1) measured using RT-dPCR distinguished TB patients from those with OD (area under the curve (AUC) 93.8% (CI95% 82.2–100%). A three-transcript signature (FCGR1A, ZNF296, and C1QB) differentiated TB from LTBI (AUC 97.3%, CI95%: 93.3–100%), regardless of HIV. These signatures have been validated across platforms and across samples offering strong, quantitative support for their use as diagnostic biomarkers for TB.

Accurate and affordable point-of-care diagnostics for tuberculosis (TB) are needed. Host serum protein signatures have been derived for use in primary care settings, however validation of these in secondary care settings is lacking. We evaluated serum protein biomarkers discovered in primary care cohorts from Africa reapplied to patients from secondary care. In this nested case-control study, concentrations of 22 proteins were quantified in sera from 292 patients from Malawi and South Africa who presented predominantly to secondary care. Recruitment was based upon intention of local clinicians to test for TB. The case definition for TB was culture positivity for Mycobacterium tuberculosis; and for other diseases (OD) a confirmed alternative diagnosis. Equal numbers of TB and OD patients were selected. Within each group, there were equal numbers with and without HIV and from each site. Patients were split into training and test sets for biosignature discovery. A nine-protein signature to distinguish TB from OD was discovered comprising fibrinogen, alpha-2-macroglobulin, CRP, MMP-9, transthyretin, complement factor H, IFN-gamma, IP-10, and TNF-alpha. This signature had an area under the receiver operating characteristic curve in the training set of 90% (95% CI 86–95%), and, after adjusting the cut-off for increased sensitivity, a sensitivity and specificity in the test set of 92% (95% CI 80–98%) and 71% (95% CI 56–84%), respectively. The best single biomarker was complement factor H [area under the receiver operating characteristic curve 70% (95% CI 64–76%)]. Biosignatures consisting of host serum proteins may function as point-of-care screening tests for TB in African hospitals. Complement factor H is identified as a new biomarker for such signatures.

At the time of writing, it is unclear how the COVID-19 pandemic will play out in rapidly urbanising regions of the world. In these regions, the realities of large overcrowded informal settlements, a high burden of infectious and non-communicable diseases, as well as malnutrition and precarity of livelihoods, have raised added concerns about the potential impact of the COVID-19 pandemic in these contexts. COVID-19 infection control measures have been shown to have some effects in slowing down the progress of the pandemic, effectively buying time to prepare the healthcare system. However, there has been less of a focus on the indirect impacts of these measures on health behaviours and the consequent health risks, particularly in the most vulnerable. In this current debate piece, focusing on two of the four risk factors that contribute to >80% of the NCD burden, we consider the possible ways that the restrictions put in place to control the pandemic, have the potential to impact on dietary and physical activity behaviours and their determinants. By considering mitigation responses implemented by governments in several LMIC cities, we identify key lessons that highlight the potential of economic, political, food and built environment sectors, mobilised during the pandemic, to retain health as a priority beyond the context of pandemic response. Such whole-of society approaches are feasible and necessary to support equitable healthy eating and active living required to address other epidemics and to lower the baseline need for healthcare in the long term.

Objective To assess whether organisational culture influences the fidelity of implementation of the Integrated Chronic Disease Management (ICDM) model at primary healthcare (PHC) clinics.Design A cross-sectional study.Setting The ICDM model was introduced in South African clinics to strengthen delivery of care and improve clinical outcomes for patients with chronic conditions, but the determinants of its implementation have not been assessed.Participants The abbreviated Denison organisational culture (DOC) survey tool was administered to 90 staff members to assess three cultural traits: involvement, consistency and adaptability of six PHC clinics in Dr. Kenneth Kaunda and West Rand (WR) health districts.Primary and secondary outcome measures Each cultural trait has three indices with five items, giving a total of 45 items. The items were scored on a Likert scale ranging from one (strongly disagree) to five (strongly agree), and mean scores were calculated for each item, cultural traits and indices. Descriptive statistics were used to describe participants and clinics, and Pearson correlation coefficient to asses association between fidelity and culture.Results Participants’ mean age was 38.8 (SD=10.35) years, and 54.4% (49/90) were nurses. The overall mean score for the DOC was 3.63 (SD=0.58). The involvement (team orientation, empowerment and capability development) cultural trait had the highest (3.71; SD=0.72) mean score, followed by adaptability (external focus) (3.62; SD=0.56) and consistency (3.56; SD=0.63). There were no statistically significant differences in cultural scores between PHC clinics. However, culture scores for all three traits were significantly higher in WR (involvement 3.39 vs 3.84, p=0.011; adaptability 3.40 vs 3.73, p=0.007; consistency 3.34 vs 3.68, p=0.034).Conclusion Leadership intervention is required to purposefully enhance adaptability and consistency cultural traits of clinics to enhance the ICDM model’s principles of coordinated, integrated, patient-centred care.

BackgroundA cost analysis of implementation of interventions informs budgeting and economic evaluations.ObjectiveTo estimate the cost of implementing the integrated chronic disease management (ICDM) model in primary healthcare (PHC) clinics in South Africa.MethodsCost data from the provider's perspective were collected in 2019 from four PHC clinics with comparable patient caseloads (except for one). We estimated the costs of implementing the ICDM model current activities for three (facility reorganization, clinical supportive management and assisted self-management) components and additional costs of implementing with enhanced fidelity. Costs were estimated based on budget reviews, interviews with management teams, and other published data. The standard of care activities such as medication were not included in the costing. One-way sensitivity analyses were carried out for key parameters by varying patient caseloads, required infrastructure and staff. Annual ICDM model implementation costs per PHC clinic and per patient per visit are presented in 2019 US dollars.ResultsThe overall mean annual cost of implementing the ICDM model was $148 446.00 (SD: $65 125.00) per clinic. Current ICDM model activities cost accounted for 84% ($124 345.00) of the annual mean cost, while additional costs for higher fidelity were 16% ($24 102.00). The mean cost per patient per visit was $6.00 (SD:$0.77); $4.94 (SD:0.70) for current cost and $1.06 (SD:0.33) for additional cost to enhance ICDM model fidelity. For the additional cost, 49% was for facility reorganization, 31% for adherence clubs and 20% for training of nursing staff. In the sensitivity analyses, the major cost drivers were the proportion of effort of assisted self-management staff and the number of patients with chronic diseases receiving care at the clinic.ConclusionMinimal additional cost are required to implement the ICDM model with higher fidelity. Further research on the cost-effectiveness of the ICDM model in middle-income countries is required.

IntroductionThe South African Department of Health has developed and implemented the Integrated Chronic Disease Management (ICDM) model to respond to the increased utilisation of primary healthcare services due to a surge of non-communicable diseases coexisting with a high prevalence of communicable diseases. However, some of the expected outcomes on implementing the ICDM model have not been achieved. The aims of this study are to assess if the observed suboptimal outcomes of the ICDM model implementation are due to lack of fidelity to the ICDM model, to examine the contextual factors associated with the implementation fidelity and to calculate implementation costs.Methods and analysisA process evaluation, mixed methods study in 16 pilot clinics from two health districts to assess the degree of fidelity to four major components of the ICDM model. Activity scores will be summed per component and overall fidelity score will be calculated by summing the various component scores and compared between components, facilities and districts. The association between contextual factors and the degree of fidelity will be asseseed by multivariate analysis, individual and team characteristics, facility features and organisational culture indicators will be included in the regression. Health system financial and economic costs of implementing the four components of the ICDM model will be calculated using an ingredient approach. The unit of implementation costs will be by activity of each of the major components of the ICDM model. Sensitivity analysis will be carried out using clinic size, degree of fidelity and different inflation situations.Ethics and disseminationThe protocol has been approved by the University of Cape Town and University of the Witwatersrand Human Research ethics committees. The results of the study will be shared with the Department of Health, participating health facilities and through scientific publications and conference presentations.

Current South African health policy for chronic disease management proposes integration of chronic services for better outcomes for chronic conditions; that is based on the Integrated Chronic Disease Model (ICDM). However, scant data exist on how patients with chronic multimorbidities currently experience the (re)-organisation of health services and what their perceived needs are in order to enhance the management of their conditions.A qualitative study was conducted in a community health centre treating both HIV and diabetes patients in Cape Town. The study was grounded in the Shippee's Cumulative Complexity Model (CCM) and explored "patient workload" and "patient capacity" to manage chronic conditions. Individual interviews were conducted with 10 adult patient-participants with HIV and type two diabetes (T2D) multimorbidity and 6 healthcare workers who provided health services to these patient-participants.Patient-participants in this study experienced clinic-related workload such as: two separate clinics for HIV and T2D and perceived and experienced power mismatch between patients and healthcare workers. Self-care related workloads were largely around nutritional requirements, pill burden, and stigma. Burden of these demands varied in difficulty among patient-participants due to capacity factors such as: positive attitudes, optimal health literacy, social support and availability of economic resources. Strategies mentioned by participants for improved continuity of care and self-management of multi-morbidities included integration of chronic services, consolidated guidelines for healthcare workers, educational materials for patients, improved information systems and income for patients.Using the CCM to explore multimorbidity captured most of the themes around "patient workload" and "patient capacity", and was thus a suitable framework to explore multimorbidity in this high HIV/T2D burden setting. Integration of chronic services and addressing social determinants of health may be the first steps towards alleviating patient burden and improving their access and utilisation of these services. Further studies are necessary to explore multimorbidity beyond the context of HIV/T2D.

Cardiovascular disorders are common in HIV-1 infected persons in Africa and presentation is often insidious. Development of screening algorithms for cardiovascular disorders appropriate to a resource-constrained setting could facilitate timely referral. Cardiothoracic ratio (CTR) on chest radiograph (CXR) has been suggested as a potential screening tool but little is known about its reproducibility and stability. Our primary aim was to evaluate the stability and the inter-observer variability of CTR in HIV-1 infected outpatients. We further evaluated the prevalence of cardiomegaly (CTR≥0.5) and its relationship with other risk factors in this population.HIV-1 infected participants were identified during screening for a tuberculosis vaccine trial in Khayelitsha, South Africa between August 2011 and April 2012. Participants had a digital posterior-anterior CXR performed as well as history, examination and baseline observations. CXRs were viewed using OsiriX software and CTR calculated using digital callipers.450 HIV-1-infected adults were evaluated, median age 34 years (IQR 30-40) with a CD4 count 566/mm3 (IQR 443-724), 70% on antiretroviral therapy (ART). The prevalence of cardiomegaly was 12.7% (95% C.I. 9.6%-15.8%). CTR was calculated by a 2nd reader for 113 participants, measurements were highly correlated r = 0.95 (95% C.I. 0.93-0.97) and agreement of cardiomegaly substantial κ = 0.78 (95% C.I 0.61-0.95). CXR were repeated in 51 participants at 4-12 weeks, CTR measurements between the 2 time points were highly correlated r = 0.77 (95% C.I 0.68-0.88) and agreement of cardiomegaly excellent κ = 0.92 (95% C.I. 0.77-1). Participants with cardiomegaly had a higher median BMI (31.3; IQR 27.4-37.4) versus 26.9; IQR 23.2-32.4); p

BackgroundA major impediment to tuberculosis control in Africa is the difficulty in diagnosing active tuberculosis (TB), particularly in the context of HIV infection. We hypothesized that a unique host blood RNA transcriptional signature would distinguish TB from other diseases (OD) in HIV-infected and -uninfected patients, and that this could be the basis of a simple diagnostic test.Methods and findingsAdult case-control cohorts were established in South Africa and Malawi of HIV-infected or -uninfected individuals consisting of 584 patients with either TB (confirmed by culture of Mycobacterium tuberculosis [M.TB] from sputum or tissue sample in a patient under investigation for TB), OD (i.e., TB was considered in the differential diagnosis but then excluded), or healthy individuals with latent TB infection (LTBI). Individuals were randomized into training (80%) and test (20%) cohorts. Blood transcriptional profiles were assessed and minimal sets of significantly differentially expressed transcripts distinguishing TB from LTBI and OD were identified in the training cohort. A 27 transcript signature distinguished TB from LTBI and a 44 transcript signature distinguished TB from OD. To evaluate our signatures, we used a novel computational method to calculate a disease risk score (DRS) for each patient. The classification based on this score was first evaluated in the test cohort, and then validated in an independent publically available dataset (GSE19491). In our test cohort, the DRS classified TB from LTBI (sensitivity 95%, 95% CI [87-100]; specificity 90%, 95% CI [80-97]) and TB from OD (sensitivity 93%, 95% CI [83-100]; specificity 88%, 95% CI [74-97]). In the independent validation cohort, TB patients were distinguished both from LTBI individuals (sensitivity 95%, 95% CI [85-100]; specificity 94%, 95% CI [84-100]) and OD patients (sensitivity 100%, 95% CI [100-100]; specificity 96%, 95% CI [93-100]). Limitations of our study include the use of only culture confirmed TB patients, and the potential that TB may have been misdiagnosed in a small proportion of OD patients despite the extensive clinical investigation used to assign each patient to their diagnostic group.ConclusionsIn our study, blood transcriptional signatures distinguished TB from other conditions prevalent in HIV-infected and -uninfected African adults. Our DRS, based on these signatures, could be developed as a test for TB suitable for use in HIV endemic countries. Further evaluation of the performance of the signatures and DRS in prospective populations of patients with symptoms consistent with TB will be needed to define their clinical value under operational conditions. Please see later in the article for the Editors' Summary.

Studies on Mycobacterium tuberculosis (MTB) antigens are of interest in order to improve vaccine efficacy and to define biomarkers for diagnosis and treatment monitoring. The methodologies used for these investigations differ greatly between laboratories and discordant results are common. The IFN-gamma response to two well characterized MTB antigens ESAT-6 and CFP-10, in the form of recombinant proteins and synthetic peptides, was evaluated in HIV-1 uninfected persons in both long-term (7 day) and 24 hour, commercially available QuantiFERON TB Gold in Tube (QFT-GIT), whole blood assays. Our findings showed differences in the IFN-gamma response between 24 hour and 7 day cultures, with recombinant proteins inducing a significantly higher response than the peptide pools in 7 day whole blood assays. The activity of peptides and recombinant proteins did not differ in 24 hour whole blood or peripheral blood mononuclear cell (PBMC) based assays, nor in the ELISpot assay. Further analysis by SELDI-TOF mass spectrometry showed that the peptides are degraded over the course of 7 days of incubation in whole blood whilst the recombinant proteins remain intact. This study therefore demonstrates that screening antigenic candidates as synthetic peptides in long-term whole blood assays may underestimate immunogenicity.

Despite high rates of successful treatment TB incidence in South Africa remains high, suggesting ongoing transmission and a large reservoir of latently infected persons. Isoniazid preventive therapy (IPT) is recommended as preventive therapy in HIV-infected persons. However, implementation has been slow, impeded by barriers and challenges including the fear of non-adherence.The aim was to evaluate predictors of IPT non-completion. One hundred and sixty four antiretroviral therapy (ART)-naïve HIV-infected patients with tuberculin skin test ≥5 mm were recruited from Khayelitsha day hospital and followed up monthly. A questionnaire was used to collect demographic information.The overall completion rate was 69%. In multivariable analysis, there was a 29% decrease in risk of non-completion for every year after HIV diagnosis (OR 0.81; 95% C.I. 0.68-0.98). Self-reported alcohol drinkers (OR 4.05; 95% C.I. 1.89-9.06) also had a four-fold higher risk of non-completion, with a strong association between alcohol drinkers and smoking (χ(2) 27.08; p

BACKGROUND:The increased susceptibility to latent tuberculosis infection (LTBI) of HIV-1-infected persons represents a challenge in TB epidemic control. However few studies have evaluated LTBI predictors in a generalized HIV/TB epidemic setting. METHODS:The study recruited 335 HIV-infected participants from Khayelitsha, Cape Town between February 2008 and November 2010. Tuberculin skin tests and interferon-gamma release assays were performed on all participants and active TB excluded using a symptom screen, TB microscopy and culture. RESULTS:LTBI prevalence was 52.7% and 61.2% (TST and IGRA respectively). Being a recent TB contact (OR 2.07; 95% C.I. 1.15-3.69) was associated with TST positivity. Participants with a CD4>200 had a two-fold higher risk of IGRA positivity compared to those with CD4 counts

Globally there are approximately 9 million new active tuberculosis cases and 1.4 million deaths annually. Effective antituberculosis treatment monitoring is difficult as there are no existing biomarkers of poor adherence or inadequate treatment earlier than 2 months after treatment initiation. Inadequate treatment leads to worsening disease, disease transmission and drug resistance.To determine if blood transcriptional signatures change in response to antituberculosis treatment and could act as early biomarkers of a successful response.Blood transcriptional profiles of untreated active tuberculosis patients in South Africa were analysed before, during (2 weeks and 2 months), at the end of (6 months) and after (12 months) antituberculosis treatment, and compared to individuals with latent tuberculosis. An active-tuberculosis transcriptional signature and a specific treatment-response transcriptional signature were derived. The specific treatment response transcriptional signature was tested in two independent cohorts. Two quantitative scoring algorithms were applied to measure the changes in the transcriptional response. The most significantly represented pathways were determined using Ingenuity Pathway Analysis.An active tuberculosis 664-transcript signature and a treatment specific 320-transcript signature significantly diminished after 2 weeks of treatment in all cohorts, and continued to diminish until 6 months. The transcriptional response to treatment could be individually measured in each patient.Significant changes in the transcriptional signatures measured by blood tests were readily detectable just 2 weeks after treatment initiation. These findings suggest that blood transcriptional signatures could be used as early surrogate biomarkers of successful treatment response.

M. tuberculosis (MTB) species-specific antigenic determinants of the human T cell response are important for immunodiagnosis and vaccination. As hypoxia is a stimulus in chronic tuberculosis infection, we analyzed transcriptional profiles of MTB subject to 168 hours of hypoxia to test the hypothesis that upregulation by hypoxia might result in gene products being recognized as antigens. We identified upregulation of two region of difference (RD) 11 (Rv2658C and Rv2659c), and one RD2 (Rv1986) absent from commonly used BCG strains. In MTB infected persons, the IL-2 ELISpot response to Rv1986 peptides was several times greater than the corresponding IFN-γ response to the reference immunodominant ESAT-6 or CFP-10 antigens. The IL-2 response was confined to two epitopic regions containing residues 61-80 and 161-180. The biggest population of IL-2 secreting T cells was single cytokine positive central memory T cells. The IL-2 response to live MTB bacilli lacking Rv1986 was significantly lower than the response to wild type or mutant complemented with Rv1986. In addition, the IL-2 response to Rv1986 was significantly lower in HIV-TB co-infected persons than in HIV uninfected persons, and significantly increased during antiretroviral therapy. These findings demonstrate that Rv1986 is an immunodominant target of memory T cells and is therefore of relevance when considering the partial efficacy of currently used BCG vaccines and provide evidence for a clinical trial comparing BCG strains.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to a subgroup of coronaviruses rampant in bats for centuries. It caused the coronavirus disease 2019 (COVID-19) pandemic. Most patients recover, but a minority of severe cases experience acute respiratory distress or an inflammatory storm devastating many organs that can lead to patient death. The spread of SARS-CoV-2 was facilitated by the increasing intensity of air travel, urban congestion and human contact during the past decades. Until therapies and vaccines are available, tests for virus exposure, confinement and distancing measures have helped curb the pandemic. Vision: The COVID-19 pandemic calls for safeguards and remediation measures through a systemic response. Self-organizing initiatives by scientists and citizens are developing an advanced collective intelligence response to the coronavirus crisis. Their integration forms Olympiads of Solidarity and Health. Their ability to optimize our response to COVID-19 could serve as a model to trigger a global metamorphosis of our societies with far-reaching consequences for attacking fundamental challenges facing humanity in the 21 st century. Mission: For COVID-19 and these other challenges, there is no alternative but action. Meeting in Paris in 2003, we set out to 'rethink research to understand life and improve health.' We have formed an international coalition of academia and industry ecosystems taking a systems medicine approach to understanding COVID-19 by thoroughly characterizing viruses, patients and populations during the pandemic, using openly shared tools. All results will be publicly available with no initial claims for intellectual property rights. This World Alliance for Health and Wellbeing will catalyze the creation of medical and health products such as diagnostic tests, drugs and vaccines that become common goods accessible to all, while seeking further alliances with civil society to bridge with socio-ecological and technological approaches that characterise urban systems, for a collective response to future health emergencies.