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BACKGROUND: Growing evidence suggests that chronic inflammation caused by tuberculosis (TB) may increase the incidence of diabetes. However, the relationship between post-TB pulmonary abnormalities and diabetes has not been well characterized. METHODS: We analyzed data from a cross-sectional study in KwaZulu-Natal, South Africa, of people 15 years and older who underwent chest X-ray and diabetes screening with hemoglobin A1c testing. The analytic sample was restricted to persons with prior TB, defined by either (1) a self-reported history of TB treatment, (2) radiologist-confirmed prior TB on chest radiography, and (3) a negative sputum culture and GeneXpert. Chest X-rays of all participants were evaluated by the study radiologist to determine the presence of TB lung abnormalities. To assess the relationships between our outcome of interest, prevalent diabetes (HBA1c ≥6.5%), and our exposure of interest, chest X-ray abnormalities, we fitted logistic regression models adjusted for potential clinical and demographic confounders. In secondary analyses, we used the computer-aided detection system CAD4TB, which scores X-rays from 10 to 100 for detection of TB disease, as our exposure interest, and repeated analyses with a comparator group that had no history of TB disease. RESULTS: In the analytic cohort of people with prior TB (n = 3,276), approximately two-thirds (64.9%) were women, and the average age was 50.8 years (SD 17.4). The prevalence of diabetes was 10.9%, and 53.0% of people were living with HIV. In univariate analyses, there was no association between diabetes prevalence and radiologist chest X-ray abnormalities (OR 1.23, 95%CI 0.95-1.58). In multivariate analyses, the presence of pulmonary abnormalities was associated with an 29% reduction in the odds of prevalent diabetes (aOR 0.71, 95%CI 0.53-0.97, p = 0.030). A similar inverse relationship was observed for diabetes with each 10-unit increase in the CAD4TB chest X-ray scores among people with prior TB (aOR 0.92, 95%CI 0.87-0.97; p = 0.002), but this relationship was less pronounced in the no TB comparator group (aOR 0.96, 95%CI 0.94-0.99). CONCLUSIONS: Among people with prior TB, pulmonary abnormalities on digital chest X-ray are inversely associated with prevalent diabetes. The severity of radiographic post-TB lung disease does not appear to be a determinant of diabetes in this South African population.
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Diabetes Mellitus , População Rural , Humanos , África do Sul/epidemiologia , Feminino , Masculino , Adulto , Estudos Transversais , Pessoa de Meia-Idade , Diabetes Mellitus/epidemiologia , População Rural/estatística & dados numéricos , Prevalência , Adulto Jovem , Radiografia Torácica , Adolescente , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/complicações , Pulmão/diagnóstico por imagem , Radiografia , Idoso , Tuberculose/epidemiologia , Tuberculose/diagnóstico por imagemRESUMO
Tuberculosis is a leading cause of death from an infectious agent globally. Infectious subclinical tuberculosis accounts for almost half of all tuberculosis cases in national tuberculosis prevalence surveys, and possibly contributes to transmission and might be associated with morbidity. Modelling studies suggest that new tuberculosis vaccines could have substantial health and economic effects, partly based on the assumptions made regarding subclinical tuberculosis. Evaluating the efficacy of prevention of disease tuberculosis vaccines intended for preventing both clinical and subclinical tuberculosis is a priority. Incorporation of subclinical tuberculosis as a composite endpoint in tuberculosis vaccine trials can help to reduce the sample size and duration of follow-up and to evaluate the efficacy of tuberculosis vaccines in preventing clinical and subclinical tuberculosis. Several design options with various benefits, limitations, and ethical considerations are possible in this regard, which would allow for the generation of the evidence needed to estimate the positive global effects of tuberculosis vaccine trials, in addition to informing policy and vaccination strategies.
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Background: Tuberculosis (TB), a leading cause of infectious death, is curable when patients complete a course of multi-drug treatment. Because entry into the TB treatment cascade usually relies on symptomatic individuals seeking care, little is known about linkage to care and completion of treatment in people with subclinical TB identified through community-based screening. Methods: Participants of the Vukuzazi study, a community-based survey that provided TB screening in the rural uMkhanyakude district of KwaZulu-Natal from May 2018 - March 2020, who had a positive sputum (GeneXpert or Mtb culture, microbiologically-confirmed TB) or a chest x-ray consistent with active TB (radiologically-suggested TB) were referred to the public health system. Telephonic follow-up surveys were conducted from May 2021 - January 2023 to assess linkage to care and treatment status. Linked electronic TB register data was accessed. We analyzed the effect of baseline HIV and symptom status (by WHO 4-symptom screen) on the TB treatment cascade. Results: Seventy percent (122/174) of people with microbiologically-confirmed TB completed the telephonic survey. In this group, 84% (103/122) were asymptomatic and 46% (56/122) were people living with HIV (PLWH). By self-report, 98% (119/122) attended a healthcare facility after screening, 94% (115/122) started TB treatment and 93% (113/122) completed treatment. Analysis of electronic TB register data confirmed that 67% (116/174) of eligible individuals started TB treatment. Neither symptom status nor HIV status affected linkage to care. Among people with radiologically-suggested TB, 48% (153/318) completed the telephonic survey, of which 80% (122/153) were asymptomatic and 52% (79/153) were PLWH. By self-report, 75% (114/153) attended a healthcare facility after screening, 16% (24/153) started TB treatment and 14% (22/153) completed treatment. Nine percent (28/318) of eligible individuals had TB register data confirming that they started treatment. Conclusions: Despite high rates of subclinical TB, most people diagnosed with microbiologically-confirmed TB after community-based screening were willing to link to care and complete TB treatment. Lower rates of linkage to care in people with radiologically-suggested TB highlight the importance of streamlined care pathways for this group. Clearer guidelines for the management of people who screen positive during community-based TB screening are needed. Supplementary Information: The online version contains supplementary material available at 10.1186/s44263-024-00059-0.
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BACKGROUND: Estimation of prevalence and diagnostic test accuracy in tuberculosis (TB) prevalence surveys suffer from reference standard and verification biases. The former is attributed to the imperfect reference test used to bacteriologically confirm TB disease. The latter occurs when only the participants screening positive for any TB-compatible symptom or chest X-ray abnormality are selected for bacteriological testing (verification). Bayesian latent class analysis (LCA) alleviates the reference standard bias but suffers verification bias in TB prevalence surveys. This work aims to identify best-practice approaches to simultaneously alleviate the reference standard and verification biases in the estimates of pulmonary TB prevalence and diagnostic test performance in TB prevalence surveys. METHODS: We performed a secondary analysis of 9869 participants aged ≥15 years from a community-based multimorbidity screening study in a rural district of KwaZulu-Natal, South Africa (Vukuzazi study). Participants were eligible for bacteriological testing using Xpert Ultra and culture if they reported any cardinal TB symptom or had an abnormal chest X-ray finding. We conducted Bayesian LCA in five ways to handle the unverified individuals: (i) complete-case analysis, (ii) analysis assuming the unverified individuals would be negative if bacteriologically tested, (iii) analysis of multiply-imputed datasets with imputation of the missing bacteriological test results for the unverified individuals using multivariate imputation via chained equations (MICE), and simultaneous imputation of the missing bacteriological test results in the analysis model assuming the missing bacteriological test results were (iv) missing at random (MAR), and (v) missing not at random (MNAR). We compared the results of (i)-(iii) to the analysis based on a composite reference standard (CRS) of Xpert Ultra and culture. Through simulation with an overall true prevalence of 2.0%, we evaluated the ability of the models to alleviate both biases simultaneously. RESULTS: Based on simulation, Bayesian LCA with simultaneous imputation of the missing bacteriological test results under the assumption that the missing data are MAR and MNAR alleviate the reference standard and verification biases. CRS-based analysis and Bayesian LCA assuming the unverified are negative for TB alleviate the biases only when the true overall prevalence is <3.0%. Complete-case analysis produced biased estimates. In the Vukuzazi study, Bayesian LCA with simultaneous imputation of the missing bacteriological test results under the MAR and MNAR assumptions produced overall PTB prevalence of 0.9% (95% Credible Interval (CrI): 0.6-1.9) and 0.7% (95% CrI: 0.5-1.1) respectively alongside realistic estimates of overall diagnostic test sensitivity and specificity with substantially overlapping 95% CrI. The CRS-based analysis and Bayesian LCA assuming the unverified were negative for TB produced 0.7% (95% CrI: 0.5-0.9) and 0.7% (95% CrI: 0.5-1.2) overall PTB prevalence respectively with realistic estimates of overall diagnostic test sensitivity and specificity. Unlike CRS-based analysis, Bayesian LCA of multiply-imputed data using MICE mitigates both biases. CONCLUSION: The findings demonstrate the efficacy of these advanced techniques in alleviating the reference standard and verification biases, enhancing the robustness of community-based screening programs. Imputing missing values as negative for bacteriological tests is plausible under realistic assumptions.
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Teorema de Bayes , Análise de Classes Latentes , Programas de Rastreamento , Padrões de Referência , Humanos , Adulto , Feminino , África do Sul/epidemiologia , Masculino , Programas de Rastreamento/normas , Programas de Rastreamento/métodos , Prevalência , Pessoa de Meia-Idade , Viés , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto Jovem , IdosoRESUMO
Despite expanded antiretroviral therapy (ART) in South Africa, HIV-1 transmission persists. Integrase strand transfer inhibitors (INSTI) and long-acting injectables offer potential for superior viral suppression, but pre-existing drug resistance could threaten their effectiveness. In a community-based study in rural KwaZulu-Natal, prior to widespread INSTI usage, we enroled 18,025 individuals to characterise HIV-1 drug resistance and transmission networks to inform public health strategies. HIV testing and reflex viral load quantification were performed, with deep sequencing (20% variant threshold) used to detect resistance mutations. Phylogenetic and geospatial analyses characterised transmission clusters. One-third of participants were HIV-positive, with 21.7% having detectable viral loads; 62.1% of those with detectable viral loads were ART-naïve. Resistance to older reverse transcriptase (RT)-targeting drugs was found, but INSTI resistance remained low (<1%). Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, particularly to rilpivirine (RPV) even in ART-naïve individuals, was concerning. Twenty percent of sequenced individuals belonged to transmission clusters, with geographic analysis highlighting higher clustering in peripheral and rural areas. Our findings suggest promise for INSTI-based strategies in this setting but underscore the need for RPV resistance screening before implementing long-acting cabotegravir (CAB) + RPV. The significant clustering emphasises the importance of geographically targeted interventions to effectively curb HIV-1 transmission.
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Farmacorresistência Viral , Infecções por HIV , HIV-1 , Filogenia , População Rural , Carga Viral , Humanos , Infecções por HIV/transmissão , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Infecções por HIV/epidemiologia , Farmacorresistência Viral/genética , África do Sul/epidemiologia , HIV-1/genética , HIV-1/efeitos dos fármacos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Carga Viral/efeitos dos fármacos , Adulto Jovem , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Adolescente , Mutação , Inibidores da Transcriptase Reversa/uso terapêutico , Inibidores da Transcriptase Reversa/farmacologia , Inibidores de Integrase de HIV/farmacologia , Inibidores de Integrase de HIV/uso terapêuticoRESUMO
This study investigated the presence of Mycobacterium bovis (M. bovis) DNA in archived human sputum samples previously collected from residents who reside adjacent to the M. bovis-endemic Hluhluwe-iMfolozi wildlife park, South Africa (SA). Sixty-eight sputum samples were GeneXpert MTB/RIF Ultra-positive for M. tuberculosis complex (MTBC) DNA but culture negative for M. tuberculosis. Amplification and Sanger sequencing of hsp65 and rpoB genes from DNA extracted from stored heat-inactivated sputum samples confirmed the presence of detectable amounts of MTBC from 20 out of the 68 sputum samples. Region of difference PCR, spoligotyping and gyrB long-read amplicon deep sequencing identified M. bovis (n = 10) and M. tuberculosis (n = 7). Notably, M. bovis spoligotypes SB0130 and SB1474 were identified in 4 samples, with SB0130 previously identified in local cattle and wildlife and SB1474 exclusively in African buffaloes in the adjacent park. M. bovis DNA in sputum, from people living near the park, underscores zoonotic transmission potential in SA. Identification of spoligotypes specifically associated with wildlife only and spoligotypes found in livestock as well as wildlife, highlights the complexity of TB epidemiology at wildlife-livestock-human interfaces. These findings support the need for integrated surveillance and control strategies to curb potential spillover and for the consideration of human M. bovis infection in SA patients with positive Ultra results.
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Health-related quality of life (HRQoL) assesses the perceived impact of health status across life domains. Although research has explored the relationship between specific conditions, including HIV, and HRQoL in low-resource settings, less attention has been paid to the association between multimorbidity and HRQoL. In a secondary analysis of cross-sectional data from the Vukuzazi ("Wake up and know ourselves" in isiZulu) study, which identified the prevalence and overlap of non-communicable and infectious diseases in the uMkhanyakunde district of KwaZulu-Natal, we (1) evaluated the impact of multimorbidity on HRQoL; (2) determined the relative associations among infectious diseases, non-communicable diseases (NCDs), and HRQoL; and (3) examined the effects of controlled versus non-controlled disease on HRQoL. HRQoL was measured using the EQ-5D-3L, which assesses overall perceived health, five specific domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and three levels of problems (no problems, some problems, and extreme problems). Six diseases and disease states were included in this analysis: HIV, diabetes, stroke, heart attack, high blood pressure, and TB. After examining the degree to which number of conditions affects HRQoL, we estimated the effect of joint associations among combinations of diseases, each HRQoL domain, and overall health. Then, in one set of ridge regression models, we assessed the relative impact of HIV, diabetes, stroke, heart attack, high blood pressure, and tuberculosis on the HRQoL domains; in a second set of models, the contribution of treatment (controlled vs. uncontrolled disease) was added. A total of 14,008 individuals were included in this analysis. Having more conditions adversely affected perceived health (r = -0.060, p<0.001, 95% CI: -0.073 to -0.046) and all HRQoL domains. Infectious conditions were related to better perceived health (r = 0.051, p<0.001, 95% CI: 0.037 to 0.064) and better HRQoL, whereas non-communicable diseases (NCDs) were associated with worse perceived health (r = -0.124, p<0.001, -95% CI: 0.137 to -0.110) and lower HRQoL. Particular combinations of NCDs were detrimental to perceived health, whereas HIV, which was characterized by access to care and suppressed viral load in the large majority of those affected, was counterintuitively associated with better perceived health. With respect to disease control, unique combinations of uncontrolled NCDs were significantly related to worse perceived health, and controlled HIV was associated with better perceived health. The presence of controlled and uncontrolled NCDs was associated with poor perceived health and worse HRQoL, whereas the presence of controlled HIV was associated with improved HRQoL. HIV disease control may be critical for HRQoL among people with HIV, and incorporating NCD prevention and attention to multimorbidity into healthcare strategies may improve HRQoL.
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Doenças Transmissíveis , Diabetes Mellitus , Infecções por HIV , Hipertensão , Infarto do Miocárdio , Doenças não Transmissíveis , Acidente Vascular Cerebral , Humanos , Multimorbidade , Qualidade de Vida , África do Sul/epidemiologia , Doenças não Transmissíveis/epidemiologia , Estudos Transversais , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Diabetes Mellitus/epidemiologia , Doenças Transmissíveis/complicações , Hipertensão/epidemiologia , Infarto do Miocárdio/complicações , Acidente Vascular Cerebral/complicaçõesRESUMO
INTRODUCTION: As people living with HIV (PLHIV) are experiencing longer survival, the co-occurrence of HIV and non-communicable diseases has become a public health priority. In response to this emerging challenge, we aimed to characterise the spatial structure of convergence of chronic health conditions in an HIV hyperendemic community in KwaZulu-Natal, South Africa. METHODS: In this cross-sectional study, we used data from a comprehensive population-based disease survey conducted in KwaZulu-Natal, South Africa, which collected data on HIV, diabetes and hypertension. We implemented a novel health needs scale to categorise participants as: diagnosed and well-controlled (Needs Score 1), diagnosed and suboptimally controlled (Score 2), diagnosed but not engaged in care (Score 3) or undiagnosed and uncontrolled (Score 4). Scores 2-4 were indicative of unmet health needs. We explored the geospatial structure of unmet health needs using different spatial clustering methods. RESULTS: The analytical sample comprised 18 041 individuals. We observed a similar spatial structure for HIV among those with combined needs Score 2-3 (diagnosed but uncontrolled) and Score 4 (undiagnosed and uncontrolled), with most PLHIV with unmet needs clustered in the southern urban and peri-urban areas. Conversely, a high prevalence of need Scores 2 and 3 for diabetes and hypertension was mostly distributed in the more rural central and northern part of the surveillance area. A high prevalence of need Score 4 for diabetes and hypertension was mostly distributed in the rural southern part of the surveillance area. Multivariate clustering analysis revealed a significant overlap of all three diseases in individuals with undiagnosed and uncontrolled diseases (unmet needs Score 4) in the southern part of the catchment area. CONCLUSIONS: In an HIV hyperendemic community in South Africa, areas with the highest needs for PLHIV with undiagnosed and uncontrolled disease are also areas with the highest burden of unmet needs for other chronic health conditions, such as diabetes and hypertension. Our study has revealed remarkable differences in the distribution of health needs across the rural to urban continuum even within this relatively small study site. The identification and prioritisation of geographically clustered vulnerable communities with unmet health needs for both HIV and non-communicable diseases provide a basis for policy and implementation strategies to target communities with the highest health needs.
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Diabetes Mellitus , Infecções por HIV , Hipertensão , Doenças não Transmissíveis , Humanos , África do Sul/epidemiologia , Infecções por HIV/epidemiologia , Doenças não Transmissíveis/epidemiologia , Estudos Transversais , Diabetes Mellitus/epidemiologia , Hipertensão/epidemiologiaRESUMO
Diversity, equity and inclusion (DEI) in science is vital to improve the scientific process and ensure societal uptake and application of scientific results. DEI challenges include a full spectrum of issues from the lack of, and promotion of, women in science, to the numerous barriers in place that limit representation of African scientists in global scientific efforts. DEI principles in African science remain relatively underdeveloped, with limited engagement and discussion among all stakeholders to ensure that initiatives are relevant to local environments. The Sub-Saharan African Network for TB/HIV research Excellence (SANTHE) is a network of African-led research in HIV, tuberculosis (TB), associated co-morbidities, and emerging pathogens, now based in eight African countries. Our aim, as a scientific capacity strengthening network, was to collaboratively produce a set of DEI guidelines and to represent them visually as a DEI compass. We implemented a consortium-wide survey, focus group discussions and a workshop where we were able to identify the key DEI challenges as viewed by scientists and support staff within the SANTHE network. Three thematic areas were identified: 1. Conquering Biases, 2. Respecting the Needs of a Diverse Workforce (including mental health challenges, physical disability, career stability issues, demands of parenthood, and female-specific challenges), and 3. Promotion of African Science. From this we constructed a compass that included proposed steps to start addressing these issues. The use of the compass metaphor allows 're-adjustment/re-positioning' making this a dynamic output. The compass can become a tool to establish an institution's DEI priorities and then to progress towards them.
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Introduction: Several low-and middle-income countries are undergoing rapid epidemiological transition with a rising burden of non-communicable diseases (NCDs). South Africa (SA) is a country with one of the largest HIV epidemics worldwide and a growing burden of NCDs where the collision of these epidemics poses a major public health challenge. Methods: Using data from a large nationally representative survey, the South Africa Demographic and Health Survey (SADHS 2016), we conducted a geospatial analysis of several diseases including HIV, tuberculosis (TB), cardiovascular, respiratory, and metabolic diseases to identify areas with a high burden of co-morbidity within the country. We explored the spatial structure of each disease and associations between diseases using different spatial and visual data methodologies. We also assessed the individual level co-occurrence of HIV and the other diseases included in the analysis. Results: The spatial distribution for HIV prevalence showed that this epidemic is most intense in the eastern region of the country, mostly within the Gauteng, Mpumalanga, and Kwazulu-Natal provinces. In contrast, chronic diseases had their highest prevalence rates the southern region of the country, particularly in the Eastern and Western Cape provinces. Individual-level analyses were consistent with the spatial correlations and found no statistically significant associations between HIV infection and the presence of any NCDs. Conclusions: We found no evidence of geospatial overlap between the HIV epidemic and NCDs in SA. These results evidence the complex epidemiological landscape of the country, characterized by geographically distinct areas exhibiting different health burdens. The detailed description of the heterogenous prevalence of HIV and NCDs in SA reported in this study could be a useful tool to inform and direct policies to enhance targeted health service delivery according to the local health needs of each community.
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Valid screening and diagnostic algorithms are needed to achieve 2030 targets proposed by the WHO's Global Diabetes Compact. We explored anthropometric thresholds to optimally screen and refer individuals for diabetes testing in rural South Africa. We evaluated screening thresholds for waist circumference (WC), body mass index (BMI), and waist-hip ratio (WHR) to detect dysglycemia based on a glycated hemoglobin (HbA1C) ≥6.5% among adults in a population-based study in South Africa using weighted, non-parametric ROC regression analyses. We then assessed the diagnostic validity of traditional obesity thresholds, explored optimal thresholds for this population, and fit models stratified by sex, age, and HIV status. The prevalence of dysglycemia in the total study population (n = 17,846) was 7.7%. WC had greater discriminatory capacity than WHR to detect dysglycemia in men (p-value<0.001) and women (p<0.001). WC had greater discriminatory capacity than BMI to detect dysglycemia in women (p<0.001). However, BMI and WC performed similarly for men (p = 0.589). Whereas traditional WC thresholds for women (>81cm) performed well (sensitivity 91%, positive predictive value [PPV] 14.9%), substantially lower thresholds were needed to achieve acceptable sensitivity and PPV among men (traditional >94cm, derived >79.5cm). WC outperforms BMI as an anthropometric screening measure for dysglycemia in rural South Africa. Whereas WC guideline thresholds are appropriate for women, male-derived WC cutoffs performed better at lower thresholds. In this rural South African population, thresholds that maximize specificity and PPV for efficient resource allocation may be preferred.
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Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Cirurgia de Mohs , Mamilos/cirurgia , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Carcinoma Basocelular/cirurgiaRESUMO
BACKGROUND: The convergence of infectious diseases and non-communicable diseases in South Africa is challenging to health systems. In this analysis, we assessed the multimorbidity health needs of individuals and communities in rural KwaZulu-Natal and established a framework to quantify met and unmet health needs for individuals living with infectious and non-communicable diseases. METHODS: We analysed data collected between May 25, 2018, and March 13, 2020, from participants of a large, community-based, cross-sectional multimorbidity survey (Vukuzazi) that offered community-based HIV, hypertension, and diabetes screening to all residents aged 15 years or older in a surveillance area in the uMkhanyakude district in KwaZulu-Natal, South Africa. Data from the Vukuzazi survey were linked with data from demographic and health surveillance surveys with a unique identifier common to both studies. Questionnaires were used to assess the diagnosed health conditions, treatment history, general health, and sociodemographic characteristics of an individual. For each condition (ie, HIV, hypertension, and diabetes), individuals were defined as having no health needs (absence of condition), met health needs (condition that is well controlled), or one or more unmet health needs (including diagnosis, engagement in care, or treatment optimisation). We analysed met and unmet health needs for individual and combined conditions and investigated their geospatial distribution. FINDINGS: Of 18 041 participants who completed the survey (12 229 [67·8%] were female and 5812 [32·2%] were male), 9898 (54·9%) had at least one of the three chronic diseases measured. 4942 (49·9%) of these 9898 individuals had at least one unmet health need (1802 [18·2%] of 9898 needed treatment optimisation, 1282 [13·0%] needed engagement in care, and 1858 [18·8%] needed a diagnosis). Unmet health needs varied by disease; 1617 (93·1%) of 1737 people who screened positive for diabetes, 2681 (58·2%) of 4603 people who screened positive for hypertension, and 1321 (21·7%) of 6096 people who screened positive for HIV had unmet health needs. Geospatially, met health needs for HIV were widely distributed and unmet health needs for all three conditions had specific sites of concentration; all three conditions had an overlapping geographical pattern for the need for diagnosis. INTERPRETATION: Although people living with HIV predominantly have a well controlled condition, there is a high burden of unmet health needs for people living with hypertension and diabetes. In South Africa, adapting current, widely available HIV care services to integrate non-communicable disease care is of high priority. FUNDING: Fogarty International Center and the National Institutes of Health, the Bill & Melinda Gates Foundation, the South African Department of Science and Innovation, the South African Medical Research Council, the South African Population Research Infrastructure Network, and the Wellcome Trust. TRANSLATION: For the isiZulu translation of the abstract see Supplementary Materials section.
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Diabetes Mellitus , Infecções por HIV , Hipertensão , Doenças não Transmissíveis , Estados Unidos , Humanos , Feminino , Masculino , África do Sul/epidemiologia , Estudos Transversais , Multimorbidade , Diabetes Mellitus/epidemiologia , Hipertensão/epidemiologia , Infecções por HIV/epidemiologiaRESUMO
Tuberculosis is the leading bacterial cause of death globally. In 2021, 10·6 million people developed symptomatic tuberculosis and 1·6 million died. Seven promising vaccine candidates that aim to prevent tuberculosis disease in adolescents and adults are currently in late-stage clinical trials. Conventional phase 3 trials provide information on the direct protection conferred against infection or disease in vaccinated individuals, but they tell us little about possible indirect (ie, transmission-reducing) effects that afford protection to unvaccinated individuals. As a result, proposed phase 3 trial designs will not provide key information about the overall effect of introducing a vaccine programme. Information on the potential for indirect effects can be crucial for policy makers deciding whether and how to introduce tuberculosis vaccines into immunisation programmes. We describe the rationale for measuring indirect effects, in addition to direct effects, of tuberculosis vaccine candidates in pivotal trials and lay out several options for incorporating their measurement into phase 3 trial designs.
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Vacinas contra a Tuberculose , Tuberculose , Adulto , Adolescente , Humanos , Tuberculose/prevenção & controle , Vacinação , Programas de Imunização , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Mechanisms by which HIV causes susceptibility to respiratory pathogens remain incompletely understood. We obtained whole blood and bronchoalveolar lavage (BAL) from people with latent TB infection in the presence or absence of antiretroviral-naïve HIV co-infection. Transcriptomic and flow cytometric analyses demonstrated HIV-associated cell proliferation plus type I interferon activity in blood and effector memory CD8 T-cells in BAL. Both compartments displayed reduced induction of CD8 T-cell-derived IL-17A in people with HIV, associated with elevated T-cell regulatory molecule expression. The data suggest that dysfunctional CD8 T-cell responses in uncontrolled HIV contribute to susceptibility to secondary bacterial infections, including tuberculosis.
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Background: South Africa is facing a convergence of communicable diseases (CDs) and non-communicable diseases (NCDs). The contribution of tobacco use to the burden of these conditions is unknown. Methods: We analyzed the associations between current tobacco smoking and four important CDs and NCDs in Vukuzazi, a cross-sectional study of individuals aged 15 years and older conducted between 2018-2020 in a demographic surveillance area in KwaZulu-Natal, South Africa. Data on HIV, active tuberculosis (TB), hypertension and diabetes mellitus were collected via direct measurement from participants. Results: Of 18,024 participants (68% female, median age 37 years [interquartile rage 23-56 years]), 1,301 (7.2%) reported current smoking. Prevalence of HIV infection was similarly high among people who currently smoked (34.6%) and people who had never smoked (33.9%). However, among people living with HIV (PLWH), there was a higher prevalence of detectable viremia in people reporting current smoking compared to people who reported never smoking (28.8% vs. 16.6%; p-value < 0.001). Active TB was more prevalent in people who currently smoked than in people who never smoked (3.1% vs 1.3%, p < 0.001). In contrast, the prevalence of hypertension and diabetes mellitus were lower in people reporting current smoking than in people reporting never smoking (17.1% vs 26.0% (p < 0.001), and 2.5% vs 10.2% (p < 0.001), respectively). In sex-stratified multivariable analyses that were adjusted for potential confounding factors (including body mass index for the NCDs), the magnitude of differences in CD prevalence between people who currently smoked and people who never smoked decreased, whereas the lower prevalence of NCDs among people reporting current smoking persisted. Conclusions: In rural South Africa, smoking is associated with higher rates of active TB, and people with HIV who smoke have worse disease control. In contrast, hypertension and diabetes mellitus are less common in those who smoke. Interventions to screen for TB among those who smoke and to address smoking among people with HIV may be particularly impactful.
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Background: As people living with HIV (PLHIV) are experiencing longer survival, the co-occurrence of HIV and non-communicable diseases has become a public health priority. In response to this emerging challenge, we aimed to characterize the spatial structure of convergence of chronic health conditions in a HIV hyperendemic community in KwaZulu-Natal, South Africa. Methods: We utilized data from a comprehensive population-based disease survey conducted in KwaZulu-Natal, South Africa, which collected data on HIV, diabetes, and hypertension. We implemented a novel health needs scale to categorize participants as: diagnosed and well-controlled (Needs Score 1), diagnosed and sub-optimally controlled (Score 2), diagnosed but not engaged in care (Score 3), or undiagnosed and uncontrolled (Score 4). Scores 2-4 were indicative of unmet health needs. We explored the geospatial structure of unmet health needs using different spatial clustering methods. Findings: The analytical sample comprised of 18,041 individuals. We observed a similar spatial structure for HIV among those with a combined needs Score 2-3 (diagnosed but uncontrolled) and Score 4 (undiagnosed and uncontrolled), with most PLHIV with unmet needs clustered in the southern peri-urban area, which was relatively densely populated within the surveillance area. Multivariate clustering analysis revealed a significant overlap of all three diseases in individuals with undiagnosed and uncontrolled diseases (unmet needs Score 4) in the southern part of the catchment area. Interpretation: In a HIV hyperendemic community in South Africa, areas with the highest needs for PLHIV with undiagnosed and uncontrolled disease are also areas with the highest burden of unmet needs for other chronic health conditions, such as diabetes and hypertension. The identification and prioritization of geographically clustered vulnerable communities with unmet health needs for both HIV and non-communicable diseases provide a basis for policy and implementation strategies to target communities with the highest health needs. Funding: Research reported in this publication was supported by the Fogarty International Center (R21 TW011687; D43 TW010543), the National Institute of Mental Health, the National Institute of Allergy and Infectious Diseases (K24 HL166024; T32 AI007433) of the National Institutes of Health, and Heart Lung and Blood Institute (K24 HL166024, T32 AI007433). The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the funders.
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BACKGROUND: Tuberculosis (TB) is a leading infectious cause of death worldwide and treating latent TB infection (LTBI) with TB preventative therapy is a global priority. This study aimed to measure interferon gamma (IFN-γ) release assay (IGRA) positivity (the current reference standard for LTBI diagnosis) and Mtb-specific IgG antibodies in otherwise healthy adults without HIV and those living with HIV (PLWH). METHODS: One-hundred and eighteen adults (65 without HIV and 53 antiretroviral-naïve PLWH), from a peri-urban setting in KwaZulu-Natal, South Africa were enrolled. IFN-γ released following stimulation with ESAT-6/CFP-10 peptides and plasma IgG antibodies specific for multiple Mtb antigens were measured using the QuantiFERON-TB Gold Plus (QFT) and customized Luminex assays, respectively. The relationships between QFT status, relative concentrations of anti-Mtb IgG, HIV-status, sex, age and CD4 count were analysed. FINDINGS: Older age, male sex and higher CD4 count were independently associated with QFT positivity (p = 0.045, 0.05 and 0.002 respectively). There was no difference in QFT status between people with and without HIV infection (58% and 65% respectively, p = 0.06), but within CD4 count quartiles, people with HIV had higher QFT positivity than people without HIV (p = 0.008 (2nd quartile), <0.0001 (3rd quartile)). Concentrations of Mtb-specific IFN-γ were lowest, and relative concentrations of Mtb-specific IgGs were highest in PLWH in the lowest CD4 quartile. INTERPRETATION: These results suggest that the QFT assay underestimates LTBI among immunosuppressed people with HIV and Mtb-specific IgG may be a useful alternative biomarker for Mtb infection. Further evaluation of how Mtb-specific antibodies can be leveraged to improve LTBI diagnosis is warranted, particularly in HIV-endemic areas. FUNDINGS: NIH, AHRI, SHIP: SA-MRC and SANTHE.
Assuntos
Infecções por HIV , Mycobacterium tuberculosis , Tuberculose , Adulto , Masculino , Humanos , Interferon gama , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , África do Sul/epidemiologia , Tuberculose/diagnóstico , Anticorpos , Contagem de Linfócito CD4RESUMO
OBJECTIVE: Tuberculosis (TB) may predispose individuals to the development of diabetes. Such a relationship could have an outsized impact in high-prevalence TB settings. However, few studies have explored this relationship in populations heavily burdened by diabetes and TB. METHODS: We analyzed data from a community-based population cohort that enrolled adults in rural South Africa. Individuals were considered to have prior TB if they self-reported a history of TB treatment. We fitted sex-specific logistic regression models, adjusted for potential clinical and demographic confounders, to estimate relationships between dysglycemia (HBA1c ≥6.5%) and prior TB. Propensity score-matched cohorts accounted for the differential age distributions between comparator groups. We examined the interactions between sex, prior TB, and HIV status. RESULTS: In the analytic cohort (n = 17,593), the prevalence of prior TB was 13.8% among men and 10.7% among women. Dysglycemia was found in 9.1% of the population, and HIV prevalence was 34.0%. We found no difference in dysglycemia prevalence by prior TB (men OR 0.96, 95% CI 0.60-1.56: women OR 1.05, 95% CI 0.79-1.39). However, there was a qualitative interaction by HIV serostatus, such that among men without HIV, those with a history of TB had a greater prevalence of dysglycemia than those without prior TB (10.1% vs. 4.6%, p = 0.0077). An inverse relationship was observed among men living with HIV (prior TB 3.3% vs. no TB 7.3%, p = 0.0073). CONCLUSIONS: Treated TB disease was not associated with dysglycemia in an HIV-endemic, rural South African population. However, we found a significant interaction between prior TB and HIV status among men, suggesting distinct pathophysiological mechanisms between the two infections that may impact glucose metabolism. Longitudinal studies are needed to better establish a causal effect and underlying mechanisms related to resolved TB, HIV, and diabetes.