Population health outcomes in Nigeria compared with other west African countries, 1998-2019: a systematic analysis for the Global Burden of Disease Study.

BACKGROUND: Population-level health and mortality data are crucial for evidence-informed policy but scarce in Nigeria. To fill this gap, we undertook a comprehensive assessment of the burden of disease in Nigeria and compared outcomes to other west African countries. METHODS: In this systematic analysis, using data and results of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, we analysed patterns of mortality, years of life lost (YLLs), years lived with disability (YLDs), life expectancy, healthy life expectancy (HALE), and health system coverage for Nigeria and 15 other west African countries by gender in 1998 and 2019. Estimates of all-age and age-standardised disability-adjusted life-years for 369 diseases and injuries and 87 risk factors are presented for Nigeria. Health expenditure per person and gross domestic product were extracted from the World Bank repository. FINDINGS: Between 1998 and 2019, life expectancy and HALE increased in Nigeria by 18% to 64·3 years (95% uncertainty interval [UI] 62·2-66·6), mortality reduced for all age groups for both male and female individuals, and health expenditure per person increased from the 11th to third highest in west Africa by 2018 (US$18·6 in 2001 to $83·75 in 2018). Nonetheless, relative outcomes remained poor; Nigeria ranked sixth in west Africa for age-standardised mortality, seventh for HALE, tenth for YLLs, 12th for health system coverage, and 14th for YLDs in 2019. Malaria (5176·3 YLLs per 100 000 people, 95% UI 2464·0-9591·1) and neonatal disorders (4818·8 YLLs per 100 000, 3865·9-6064·2) were the leading causes of YLLs in Nigeria in 2019. Nigeria had the fourth-highest under-five mortality rate for male individuals (2491·8 deaths per 100 000, 95% UI 1986·1-3140·1) and female individuals (2117·7 deaths per 100 000, 1756·7-2569·1), but among the lowest mortality for men older than 55 years. There was evidence of a growing non-communicable disease burden facing older Nigerians. INTERPRETATION: Health outcomes remain poor in Nigeria despite higher expenditure since 2001. Better outcomes in countries with equivalent or lower health expenditure suggest health system strengthening and targeted intervention to address unsafe water sources, poor sanitation, malnutrition, and exposure to air pollution could substantially improve population health. FUNDING: The Bill & Melinda Gates Foundation.

Participatory prioritisation of interventions to improve primary school food environments in Gauteng, South Africa.

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.

Comparing travel behaviour characteristics and correlates between large and small Kenyan cities (Nairobi versus Kisumu).

Understanding urban travel behaviour is crucial for planning healthy and sustainable cities. Africa is urbanising at one of the fastest rates in the world and urgently needs this knowledge. However, the data and literature on urban travel behaviour, their correlates, and their variation across African cities are limited. We aimed to describe and compare travel behaviour characteristics and correlates of two Kenyan cities (Nairobi and Kisumu). We analysed data from 16,793 participants (10,000 households) in a 2013 Japan International Cooperation Agency (JICA) household travel survey in Nairobi and 5790 participants (2760 households) in a 2016 Institute for Transportation and Development Policy (ITDP) household travel survey in Kisumu. We used the Heckman selection model to explore correlations of travel duration by trip mode. The proportion of individuals reporting no trips was far higher in Kisumu (47% vs 5%). For participants with trips, the mean number [lower - upper quartiles] of daily trips was similar (Kisumu (2.2 [2-2] versus 2.4 [2-2] trips), but total daily travel durations were lower in Kisumu (65 [30-80] versus 116 [60-150] minutes). Walking was the most common trip mode in both cities (61% in Kisumu and 42% in Nairobi), followed by motorcycles (17%), matatus (minibuses) (11%), and cars (5%) in Kisumu; and matatus (28%), cars (12%) and buses (12%) in Nairobi. In both cities, females were less likely to make trips, and when they did, they travelled for shorter durations; people living in households with higher incomes were more likely to travel and did so for longer durations. Gender, income, occupation, and household vehicle ownership were associated differently with trip making, use of transport modes and daily travel times in cities. These findings illustrate marked differences in reported travel behaviour characteristics and correlates within the same country, indicating setting-dependent influences on travel behaviour. More sub-national data collection and harmonisation are needed to build a more nuanced understanding of patterns and drivers of travel behaviour in African cities.

Assessing adolescent diet and physical activity behaviour, knowledge and awareness in low- and middle-income countries: a systematised review of quantitative epidemiological tools.

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.

Treatment outcomes among adults with HIV/non-communicable disease multimorbidity attending integrated care clubs in Cape Town, South Africa.

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.

Tuberculosis, Human Immunodeficiency Virus, and the Association With Transient Hyperglycemia in Periurban South Africa.

BACKGROUND: Diabetes mellitus (DM) increases tuberculosis (TB) risk. We assessed the prevalence of hyperglycemia (DM and impaired glucose regulation [IGR]) in persons with TB and the association between hyperglycemia and TB at enrollment and 3 months after TB treatment in the context of human immunodeficiency virus (HIV) infection. METHODS: Adults presenting at a Cape Town TB clinic were enrolled. TB cases were defined by South African guidelines, while non-TB participants were those who presented with respiratory symptoms, negative TB tests, and resolution of symptoms 3 months later without TB treatment. HIV status was ascertained through medical records or HIV testing. All participants were screened for DM using glycated hemoglobin and fasting plasma glucose at TB treatment and after 3 months. The association between TB and DM was assessed. RESULTS: Overall DM prevalence was 11.9% (95% confidence interval [CI], 9.1%-15.4%) at enrollment and 9.3% (95% CI, 6.4%-13%) at follow-up; IGR prevalence was 46.9% (95% CI, 42.2%-51.8%) and 21.5% (95% CI, 16.9%-26.3%) at enrollment and follow-up. TB/DM association was significant at enrollment (odds ratio [OR], 2.41 [95% CI, 1.3-4.3]) and follow-up (OR, 3.3 [95% CI, 1.5-7.3]), whereas TB/IGR association was only positive at enrollment (OR, 2.3 [95% CI, 1.6-3.3]). The TB/DM association was significant at enrollment in both new and preexisting DM, but only persisted at follow-up in preexisting DM in patients with HIV-1 infection. CONCLUSIONS: Our study demonstrated high prevalence of transient hyperglycemia and a significant TB/DM and TB/IGR association at enrollment in newly diagnosed DM, but persistent hyperglycemia and TB/DM association in patients with HIV-1 infection and preexisting DM, despite TB therapy.

Slum Health: Arresting COVID-19 and Improving Well-Being in Urban Informal Settlements.

The informal settlements of the Global South are the least prepared for the pandemic of COVID-19 since basic needs such as water, toilets, sewers, drainage, waste collection, and secure and adequate housing are already in short supply or non-existent. Further, space constraints, violence, and overcrowding in slums make physical distancing and self-quarantine impractical, and the rapid spread of an infection highly likely. Residents of informal settlements are also economically vulnerable during any COVID-19 responses. Any responses to COVID-19 that do not recognize these realities will further jeopardize the survival of large segments of the urban population globally. Most top-down strategies to arrest an infectious disease will likely ignore the often-robust social groups and knowledge that already exist in many slums. Here, we offer a set of practice and policy suggestions that aim to (1) dampen the spread of COVID-19 based on the latest available science, (2) improve the likelihood of medical care for the urban poor whether or not they get infected, and (3) provide economic, social, and physical improvements and protections to the urban poor, including migrants, slum communities, and their residents, that can improve their long-term well-being. Immediate measures to protect residents of urban informal settlements, the homeless, those living in precarious settlements, and the entire population from COVID-19 include the following: (1) institute informal settlements/slum emergency planning committees in every urban informal settlement; (2) apply an immediate moratorium on evictions; (3) provide an immediate guarantee of payments to the poor; (4) immediately train and deploy community health workers; (5) immediately meet Sphere Humanitarian standards for water, sanitation, and hygiene; (6) provide immediate food assistance; (7) develop and implement a solid waste collection strategy; and (8) implement immediately a plan for mobility and health care. Lessons have been learned from earlier pandemics such as HIV and epidemics such as Ebola. They can be applied here. At the same time, the opportunity exists for public health, public administration, international aid, NGOs, and community groups to innovate beyond disaster response and move toward long-term plans.

The global diet and activity research (GDAR) network: a global public health partnership to address upstream NCD risk factors in urban low and middle-income contexts.

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.

Missed opportunities for NCD multimorbidity prevention in adolescents and youth living with HIV in urban South Africa.

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.

A mixed methods approach to exploring the moderating factors of implementation fidelity of the integrated chronic disease management model in South Africa.

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.

Urban health in Africa: a critical global public health priority.

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.

Food insecurity in relation to obesity in peri-urban Cape Town, South Africa: Implications for diet-related non-communicable disease.

In urban informal areas of South Africa, obesity and hunger represent two sides of food insecurity. Despite this, public health and clinical obesity interventions focus on nutrition education, implying dietary choice and thereby overlooking food insecurity. The objective of this paper is to explore peri-urban residents' perspectives of changing food environments, framed by the Food Aid Organization (FAO) definition of food security and demonstrating the interconnectedness of dimensions of food security. We conducted three-part in-depth interviews with 21 participants and nine focus group discussions with a total of 57 participants, consisting primarily of women aged 20-84, in a peri-urban township and informal settlement outside of Cape Town, South Africa. Participants' encounters in clinical settings framed choice as a driver of diet-related non-communicable disease (NCD). Yet participants lacked economic access to food, particularly at the end of the month. Diets consisted of fewer green leafy vegetables relative to their diets in rural areas, despite affirming a preference for these foods. They described consuming more meat, which was also perceived as unhealthy. Based on self-report, residents within this peri-urban area of South Africa were food insecure: they lacked access to food at specific times of the month, they were unable to consume foods they preferred, and they felt that their diets were neither nutritious nor enabled an active and healthy life. When viewed in terms of multiple facets of food security, participants' concurrent experiences of hunger and obesity were unsurprising. Health interventions related to diet should incorporate an understanding of food security as shaped by the interactions of access, availability, utilization and stability.

Process evaluation of implementation fidelity of the integrated chronic disease management model in two districts, South Africa.

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.

The Influence of HIV on the Evolution of Mycobacterium tuberculosis.

HIV significantly affects the immunological environment during tuberculosis coinfection, and therefore may influence the selective landscape upon which M. tuberculosis evolves. To test this hypothesis whole genome sequences were determined for 169 South African M. tuberculosis strains from HIV-1 coinfected and uninfected individuals and analyzed using two Bayesian codon-model based selection analysis approaches: FUBAR which was used to detect persistent positive and negative selection (selection respectively favoring and disfavoring nonsynonymous substitutions); and MEDS which was used to detect episodic directional selection specifically favoring nonsynonymous substitutions within HIV-1 infected individuals. Among the 25,251 polymorphic codon sites analyzed, FUBAR revealed that 189-fold more were detectably evolving under persistent negative selection than were evolving under persistent positive selection. Three specific codon sites within the genes celA2b, katG, and cyp138 were identified by MEDS as displaying significant evidence of evolving under directional selection influenced by HIV-1 coinfection. All three genes encode proteins that may indirectly interact with human proteins that, in turn, interact functionally with HIV proteins. Unexpectedly, epitope encoding regions were enriched for sites displaying weak evidence of directional selection influenced by HIV-1. Although the low degree of genetic diversity observed in our M. tuberculosis data set means that these results should be interpreted carefully, the effects of HIV-1 on epitope evolution in M. tuberculosis may have implications for the design of M. tuberculosis vaccines that are intended for use in populations with high HIV-1 infection rates.

Effect of HIV on the Frequency and Number of Mycobacterium tuberculosis-Specific CD4+ T Cells in Blood and Airways During Latent M. tuberculosis Infection.

Human immunodeficiency virus type 1 (HIV) infection substantially increases the risk of developing tuberculosis. There is extensive depletion of Mycobacterium tuberculosis-specific CD4+ T cells in blood during early HIV infection, but little is known about responses in the lungs at this stage. Given that mucosal organs are a principal target for HIV-mediated CD4+ T-cell destruction, we investigated M. tuberculosis-specific responses in bronchoalveolar lavage (BAL) from persons with latent M. tuberculosis infection and untreated HIV coinfection with preserved CD4+ T-cell counts. M. tuberculosis-specific CD4+ T-cell cytokine (interferon γ, tumor necrosis factor α, and interleukin 2) responses were discordant in frequency and function between BAL and blood. Responses in BAL were 15-fold lower in HIV-infected persons as compared to uninfected persons (P = .048), whereas blood responses were 2-fold lower (P = .006). However, an increase in T cells in the airways in HIV-infected persons resulted in the overall number of M. tuberculosis-specific CD4+ T cells in BAL being similar. Our study highlights the important insights gained from studying M. tuberculosis immunity at the site of disease during HIV infection.

Trilateral overlap of tuberculosis, diabetes and HIV-1 in a high-burden African setting: implications for TB control.

The diabetes mellitus burden is growing in countries where tuberculosis (TB) and HIV-1 remain major challenges, threatening TB control efforts. This study determined the association between TB and diabetes/impaired glucose regulation in the context of HIV-1.A cross-sectional study was conducted at a TB clinic in Cape Town (South Africa). Participants were screened for diabetes and impaired glucose regulation using fasting plasma glucose, oral glucose tolerance test and glycated haemoglobin (HbA1c).414 TB and 438 non-TB participants were enrolled. In multivariable analysis, diabetes was associated with TB (OR 2.4, 95% CI 1.3-4.3; p=0.005), with 14% population-attributable risk fraction; however, this association varied by diagnostic test (driven by HbA1c). The association remained significant in HIV-1-infected individuals (OR 2.4, 95% CI 1.1-5.2; p=0.030). A high prevalence of impaired glucose regulation (65.2% among TB cases) and a significant association with TB (OR 2.3, 95% CI 1.6-3.3; p<0.001) was also found.Diabetes and impaired glucose regulation prevalence was high and associated with TB, particularly in HIV-1-infected individuals, highlighting the importance of diabetes screening. The variation in findings by diagnostic test highlights the need for better glycaemia markers to inform screening in the context of TB and HIV-1.

QuantiFERON conversion following tuberculin administration is common in HIV infection and relates to baseline response.

BACKGROUND: HIV-1 infection impairs tuberculosis (TB) specific immune responses affecting the diagnosis of latent TB. We aimed to (1) determine the proportion of HIV-1-infected adults with a negative QuantiFERON®-TB Gold in-tube (QFT-GIT) and Tuberculin skin testing (TST) that convert to QFT-GIT positive following TST, and (2) evaluate the relationship between conversion and baseline QFT-GIT results. METHODS: HIV-1 infected adults being screened for a TB vaccine study in South Africa underwent QFT-GIT followed by TST. As per protocol, QFT-GIT was repeated if randomization was delayed allowing for evaluation of TST boosting in a proportion of participants. RESULTS: Of the 22 HIV-1 infected, TST and QFT-GIT negative adults (median CD4 477/mm3 IQR 439-621) who had QFT-GIT repeated after median 62 days (IQR 49-70), 40.9 % (95 % CI 18.6-63.2 %) converted. Converters had a significantly greater increase in the background subtracted TB antigen response (TBAg-Nil - all units IU/mL) following TST, 0.82 (IQR 0.39-1.28) vs 0.03 (IQR -0.05-0.06), p = 0.0001. Those who converted also had a significantly higher baseline TBAg-Nil 0.21(IQR 0.17-0.26) vs 0.02(IQR 0.01-0.07), p = 0.002. Converters did not differ with regard to CD4 count or ART status. ROC analysis showed a baseline cut off of 0.15 correctly classified 86.4 % of converters with 88.9 % sensitivity. CONCLUSIONS: Our findings support the possibility that there are 2 distinct groups in an HIV-1 infected population with negative QFT-GIT and TST; a true negative group and a group showing evidence of a weak Mtb specific immune response that boosts significantly following TST resulting in conversion of the test result that may represent false negatives. Further evaluation of whether a lower cut off may improve sensitivity of QFT-GIT in this population is warranted.