Browsing by Person "Karat, Aaron S."
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Item Algorithm-guided empirical tuberculosis treatment for people with advanced HIV (TB Fast Track): An open-label, cluster-randomised trial(Elsevier, 2019-11-11) Grant, Alison D.; Charalambous, Salome; Tlali, Mpho; Karat, Aaron S.; Dorman, Susan E.; Hoffmann, Christopher J.; Johnson, Suzanne; Vassall, Anna; Churchyard, Gavin J.; Fielding, Katherine L.Background Tuberculosis, which is often undiagnosed, is the major cause of death among HIV-positive people. We aimed to test whether the use of a clinical algorithm enabling the initiation of empirical tuberculosis treatment by nurses in primary health-care clinics would reduce mortality compared with standard of care for adults with advanced HIV disease.Item All non-adherence is equal, but is some more equal than others? TB in the digital era(European Respiratory Society, 2020-11-02) Stagg, Helen R.; Flook, Mary; Martinecz, Antal; Kielmann, Karina; Abel Zur Wiesch, Pia; Karat, Aaron S.; Lipman, Marc; Sloan, Derek J.; Walker, Elizabeth F.; Fielding, Katherine L.Adherence to treatment for tuberculosis (TB) has been a concern for many decades, resulting in the World Health Organization’s recommendation of the direct observation of treatment in the 1990s. Recent advances in digital adherence technologies (DATs) have renewed discussion on how to best address non-adherence, as well as offering important information on dose-by-dose adherence patterns and their variability between countries and settings. Previous studies have largely focussed on percentage thresholds to delineate sufficient adherence, but this is misleading and limited, given the complex and dynamic nature of adherence over the treatment course. Instead, we apply a standardised taxonomy- as adopted by the international adherence community- to dose-by-dose medication-taking data, which divides missed doses into a) late/non-initiation (starting treatment later than expected/not starting), b) discontinuation (ending treatment early), and c) suboptimal implementation (intermittent missed doses). Using this taxonomy, we can consider the implications of different forms of non-adherence for intervention and regimen design. For example, can treatment regimens be adapted to increase the ‘forgiveness’ of common patterns of suboptimal implementation to protect against treatment failure and the development of drug resistance? Is it reasonable to treat all missed doses of treatment as equally problematic and equally common when deploying DATs? Can DAT data be used to indicate the patients that need enhanced levels of support during their treatment course? Critically, we pinpoint key areas where knowledge regarding treatment adherence is sparse and impeding scientific progress.Item Autopsy prevalence of tuberculosis and other potentially treatable infections among adults with advanced HIV enrolled in out-patient care in South Africa(PLOS, 2016-11-09) Karat, Aaron S.; Omar, Tanvier; von Gottberg, Anne; Tlali, Mpho; Chihota, Violet N.; Churchyard, Gavin J.; Fielding, Katherine L.; Johnson, Suzanne; Martinson, Neil A.; McCarthy, Kerrigan; Wolter, Nicole; Wong, Emily B.; Charalambous, Salome; Grant, Alison D.; Cardona, Pere-JoanBackground Early mortality among HIV-positive adults starting antiretroviral therapy (ART) remains high in resource-limited settings, with tuberculosis (TB) the leading cause of death. However, current methods to estimate TB-related deaths are inadequate and most autopsy studies do not adequately represent those attending primary health clinics (PHCs). This study aimed to determine the autopsy prevalence of TB and other infections in adults enrolled at South African PHCs in the context of a pragmatic trial of empiric TB treatment (“TB Fast Track”).Item Commentary: Time to change the way we think about tuberculosis infection prevention and control in health facilities: insights from recent research(Cambridge University Press, 2023-07-17) Yates, Tom A.; Karat, Aaron S.; Bozzani, Fiammetta; McCreesh, Nicky; MacGregor, Hayley; Beckwith, Peter G.; Govender, Indira; Colvin, Christopher J.; Kielmann, Karina; Grant, Alison D.In clinical settings where airborne pathogens, such as Mycobacterium tuberculosis, are prevalent, they constitute an important threat to health workers and people accessing healthcare. We report key insights from a 3-year project conducted in primary healthcare clinics in South Africa, alongside other recent tuberculosis infection prevention and control (TB-IPC) research. We discuss the fragmentation of TB-IPC policies and budgets; the characteristics of individuals attending clinics with prevalent pulmonary tuberculosis; clinic congestion and patient flow; clinic design and natural ventilation; and the facility-level determinants of the implementation (or not) of TB-IPC interventions. We present modeling studies that describe the contribution of M. tuberculosis transmission in clinics to the community tuberculosis burden and economic evaluations showing that TB-IPC interventions are highly cost-effective. We argue for a set of changes to TB-IPC, including better coordination of policymaking, clinic decongestion, changes to clinic design and building regulations, and budgeting for enablers to sustain implementation of TB-IPC interventions. Additional research is needed to find the most effective means of improving the implementation of TB-IPC interventions; to develop approaches to screening for prevalent pulmonary tuberculosis that do not rely on symptoms; and to identify groups of patients that can be seen in clinic less frequently.Item Cost of point-of-care lateral flow urine lipoarabinomannan antigen testing in HIV-positive adults in South Africa(International Union Against Tuberculosis and Lung Disease, 2018-09-01) Mukora, R.; Tlali, M.; Monkwe, S.; Charalambous, S.; Karat, Aaron S.; Fielding, K. L.; Grant, A. D.; Vassall, A.INTRODUCTION: The World Health Organization recommends point-of-care (POC) lateral flow urine lipoarabinomannan (LF-LAM) for tuberculosis (TB) diagnosis in selected human immunodeficiency virus (HIV) positive people. South Africa had 438 000 new TB episodes in 2016, 58.9% of which were contributed by HIV-positive people. LF-LAM is being considered for scale-up in South Africa.Item Cryptococcal-related mortality despite fluconazole preemptive treatment in a cryptococcal antigen (CrAg) screen-and-treat programme(Oxford University Press, 2019-06-08) Wake, Rachel M.; Govender, Nelesh P.; Omar, Tanvier; Nel, Carolina; Mazanderani, Ahmad Haeri; Karat, Aaron S.; Ismail, Nazir A.; Tiemessen, Caroline T.; Jarvis, Joseph N.; Harrison, Thomas S.Background. Cryptococcal antigen (CrAg) screening and treatment with preemptive fluconazole reduces the incidence of clinically evident cryptococcal meningitis in individuals living with advanced human immunodeficiency virus (HIV) disease. However, mortality remains higher in CrAg-positive than in CrAg-negative patients with similar CD4+ T-lymphocyte counts.Item Determinants of non-adherence to anti-TB treatment in high income, low TB incidence settings: A scoping review(The Union, 2021-06-01) Jones, Annie; Bidad, Natalie; Horne, Rob; Stagg, Helen R.; Wurie, Fatima; Kielmann, Karina; Karat, Aaron S.; Kunst, Heinke; Campbell, Colin N. J.; Darvell, Marcia; Clarke, Amy Louise; Lipman, MarcBackground Improving adherence to anti-tuberculosis (TB) treatment is a public health priority in high income, low incidence (HILI) regions. We conducted a scoping review to identify reported determinants of non-adherence in HILI settings.Item Development and description of a theory-driven, evidence-based, complex intervention to improve adherence to treatment for tuberculosis in the UK: the IMPACT study(Informa UK Limited, 2023-11-27) Jones, Annie S. K.; Horne, Rob; White, Jacqui; Costello, Trish; Darvell, Marcia; Karat, Aaron S.; Kielmann, Karina; Stagg, Helen R.; Hill, Adam T.; Kunst, Heinke; Campbell, Colin N. J.; Lipman, Marc C. I.Background Tuberculosis (TB) has a significant treatment burden for patients, requiring at least six months of anti-TB treatment (ATT) with multiple medicines. Ensuring good adherence to ATT is central to global TB strategies, including those in high-income, low-TB incidence (HILI) settings. For adherence interventions to be successful and deliverable, they need to address the personal and environmental factors influencing patient and provider behaviour. Purpose This paper describes the application of theory and research evidence to inform the design process of the IMPACT manualised intervention to support ATT adherence for adults with TB disease in the United Kingdom (UK). It also provides a full description of the resulting intervention. Methods We synthesised findings from our formative research (qualitative and quantitative scoping reviews and patient and carer interviews) and supplemented these with clinic observations, a literature review, and healthcare provider interviews. Findings were mapped to the guiding theoretical framework (Perceptions and Practicalities Approach) which was operationalised to design the intervention components and content. An Intervention Development Group (IDG) of relevant stakeholders were consulted to adapt the intervention to local clinical settings. Results The pragmatic, deliverable components and content for the IMPACT intervention included: (1) an enhanced, structured, risk assessment to systematically identify risk factors for non-adherence plus locally-adapted guidance to mitigate these; and (2) patient educational materials (an animated video and interactive patient booklet) about TB and its treatment, to communicate the need for treatment and address common concerns. Conclusions Using a theory– and evidence– based approach incorporating stakeholder input, we have developed a multi-component, pragmatic, manualised intervention, which addresses patients’ personal barriers to adherence within local service resources to improve adherence to ATT within UK TB services.Item Direct estimates of absolute ventilation and estimated Mycobacterium tuberculosis transmission risk in clinics in South Africa(Public Library of Science, 2022-11-02) Beckwith, Peter G.; Karat, Aaron S.; Govender, Indira; Deol, Arminder K.; McCreesh, Nicky; Kielmann, Karina; Baisley, Kathy; Grant, Alison D.; Yates, Tom A.Healthcare facilities are important sites for the transmission of pathogens spread via bioaerosols, such as Mycobacterium tuberculosis. Natural ventilation can play an important role in reducing this transmission. We aimed to measure rates of natural ventilation in clinics in KwaZulu-Natal and Western Cape provinces, South Africa, then use these measurements to estimate Mycobacterium tuberculosis transmission risk. We measured ventilation in clinic spaces using a tracer-gas release method. In spaces where this was not possible, we estimated ventilation using data on indoor and outdoor carbon dioxide levels. Ventilation was measured i) under usual conditions and ii) with all windows and doors fully open. Under various assumptions about infectiousness and duration of exposure, measured absolute ventilation rates were related to risk of Mycobacterium tuberculosis transmission using the Wells-Riley Equation. In 2019, we obtained ventilation measurements in 33 clinical spaces in 10 clinics: 13 consultation rooms, 16 waiting areas and 4 other clinical spaces. Under usual conditions, the absolute ventilation rate was much higher in waiting rooms (median 1769 m3/hr, range 338–4815 m3/hr) than in consultation rooms (median 197 m3/hr, range 0–1451 m3/hr). When compared with usual conditions, fully opening existing doors and windows resulted in a median two-fold increase in ventilation. Using standard assumptions about infectiousness, we estimated that a health worker would have a 24.8% annual risk of becoming infected with Mycobacterium tuberculosis, and that a patient would have an 0.1% risk of becoming infected per visit. Opening existing doors and windows and rearranging patient pathways to preferentially use better ventilated clinic spaces result in important reductions in Mycobacterium tuberculosis transmission risk. However, unless combined with other tuberculosis infection prevention and control interventions, these changes are insufficient to reduce risk to health workers, and other highly exposed individuals, to acceptable levels.Item Estimating the contribution of transmission in primary healthcare clinics to community-wide TB disease incidence, and the impact of infection prevention and control interventions, in KwaZulu-Natal, South Africa(BMJ, 2022-04-08) McCreesh, Nicky; Karat, Aaron S.; Govender, Indira; Baisley, Kathy; Diaconu, Karin; Yates, Tom A.; Houben, Rein M. G. J.; Kielmann, Karina; Grant, Alison D.; White, RichardBackground: There is a high risk of Mycobacterium tuberculosis (Mtb) transmission in healthcare facilities in high burden settings. WHO guidelines on tuberculosis (TB) infection prevention and control (IPC) recommend a range of measures to reduce transmission in healthcare settings. These were evaluated primarily based on evidence for their effects on transmission to healthcare workers in hospitals. To estimate the overall impact of IPC interventions, it is necessary to also consider their impact on community-wide TB incidence and mortality. Methods: We developed an individual-based model of Mtb transmission in households, primary healthcare (PHC) clinics, and all other congregate settings. The model was parameterised using data from a high HIV prevalence community in South Africa, including data on social contact by setting, by sex, age, and HIV/antiretroviral therapy status; and data on TB prevalence in clinic attendees and the general population. We estimated the proportion of disease in adults that resulted from transmission in PHC clinics, and the impact of a range of IPC interventions in clinics on community-wide TB. Results: We estimate that 7.6% (plausible range 3.9%–13.9%) of non-multidrug resistant and multidrug resistant TB in adults resulted directly from transmission in PHC clinics in the community in 2019. The proportion is higher in HIV-positive people, at 9.3% (4.8%–16.8%), compared with 5.3% (2.7%–10.1%) in HIV-negative people. We estimate that IPC interventions could reduce incident TB cases in the community in 2021–2030 by 3.4%–8.0%, and deaths by 3.0%–7.2%. Conclusions: A non-trivial proportion of TB results from transmission in clinics in the study community, particularly in HIV-positive people. Implementing IPC interventions could lead to moderate reductions in disease burden. We recommend that IPC measures in clinics should be implemented for their benefits to staff and patients, but also for their likely effects on TB incidence and mortality in the surrounding community.Item Estimating ventilation rates in rooms with varying occupancy levels: Relevance for reducing transmission risk of airborne pathogens(PLoS, 2021-06-24) Deol, Arminder K.; Scarponi, Danny; Beckwith, Peter; Yates, Tom A.; Karat, Aaron S.; Yan, Ada W. C.; Baisley, Kathy S.; Grant, Alison D.; White, Richard G.; McCreesh, Nicky; Lo Iacono, GiovanniBackground: In light of the role that airborne transmission plays in the spread of SARS-CoV-2, as well as the ongoing high global mortality from well-known airborne diseases such as tuberculosis and measles, there is an urgent need for practical ways of identifying congregate spaces where low ventilation levels contribute to high transmission risk. Poorly ventilated clinic spaces in particular may be high risk, due to the presence of both infectious and susceptible people. While relatively simple approaches to estimating ventilation rates exist, the approaches most frequently used in epidemiology cannot be used where occupancy varies, and so cannot be reliably applied in many of the types of spaces where they are most needed. Methods: The aim of this study was to demonstrate the use of a non-steady state method to estimate the absolute ventilation rate, which can be applied in rooms where occupancy levels vary. We used data from a room in a primary healthcare clinic in a high TB and HIV prevalence setting, comprising indoor and outdoor carbon dioxide measurements and head counts (by age), taken over time. Two approaches were compared: approach 1 using a simple linear regression model and approach 2 using an ordinary differential equation model. Results: The absolute ventilation rate, Q, using approach 1 was 2407 l/s [95% CI: 1632–3181] and Q from approach 2 was 2743 l/s [95% CI: 2139–4429]. Conclusions: We demonstrate two methods that can be used to estimate ventilation rate in busy congregate settings, such as clinic waiting rooms. Both approaches produced comparable results, however the simple linear regression method has the advantage of not requiring room volume measurements. These methods can be used to identify poorly-ventilated spaces, allowing measures to be taken to reduce the airborne transmission of pathogens such as Mycobacterium tuberculosis, measles, and SARS-CoV-2.Item Estimating waiting times, patient flow, and waiting room occupancy density as part of tuberculosis infection prevention and control research in South African primary health care clinics(Public Library of Science, 2022-07-20) Karat, Aaron S.; McCreesh, Nicky; Baisley, Kathy; Govender, Indira; Kallon, Idriss I.; Kielmann, Karina; MacGregor, Hayley; Vassall, Anna; Yates, Tom A.; Grant, Alison D.Transmission of respiratory pathogens, such as Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2, is more likely during close, prolonged contact and when sharing a poorly ventilated space. Reducing overcrowding of health facilities is a recognised infection prevention and control (IPC) strategy; reliable estimates of waiting times and ‘patient flow’ would help guide implementation. As part of the Umoya omuhle study, we aimed to estimate clinic visit duration, time spent indoors versus outdoors, and occupancy density of waiting rooms in clinics in KwaZulu-Natal (KZN) and Western Cape (WC), South Africa. We used unique barcodes to track attendees’ movements in 11 clinics, multiple imputation to estimate missing arrival and departure times, and mixed-effects linear regression to examine associations with visit duration. 2,903 attendees were included. Median visit duration was 2 hours 36 minutes (interquartile range [IQR] 01:36–3:43). Longer mean visit times were associated with being female (13.5 minutes longer than males; p<0.001) and attending with a baby (18.8 minutes longer than those without; p<0.01), and shorter mean times with later arrival (14.9 minutes shorter per hour after 0700; p<0.001). Overall, attendees spent more of their time indoors (median 95.6% [IQR 46–100]) than outdoors (2.5% [IQR 0–35]). Attendees at clinics with outdoor waiting areas spent a greater proportion (median 13.7% [IQR 1–75]) of their time outdoors. In two clinics in KZN (no appointment system), occupancy densities of ~2.0 persons/m2 were observed in smaller waiting rooms during busy periods. In one clinic in WC (appointment system, larger waiting areas), occupancy density did not exceed 1.0 persons/m2 despite higher overall attendance. In this study, longer waiting times were associated with early arrival, being female, and attending with a young child. Occupancy of waiting rooms varied substantially between rooms and over the clinic day. Light-touch estimation of occupancy density may help guide interventions to improve patient flow.Item Fatigue after stroke: Frequency and effect on daily life(Taylor & Francis, 2011-10-07) Crosby, Gail A.; Munshi, Sunil; Karat, Aaron S.; Worthington, Esme; Lincoln, Nadina B.Purpose: An audit was conducted to assess the frequency of fatigue after stroke, to determine the impact on daily life, and whether it was discussed with clinicians. Method: Patients were recruited from Nottingham University Hospitals NHS Trust stroke service. Patients were interviewed about their fatigue, and the Fatigue Severity Subscale (FSS-FAI), Brief Assessment Schedule for Depression Cards (BASDEC), Barthel Index and Nottingham Extended Activities of Daily Living (EADL) Scale were administered. Results: 64 patients were recruited, with a mean age 73.5 years (SD 14.0, range 37–94 years), 37 (58%) as in-patients and 27 (42%) as outpatients. There were 41 (64%) who reported significant levels of fatigue and 31 (48%) with significant fatigue on the Fatigue Severity Scale. Demographic and clinical variables were not significantly related to fatigue (p > 0.05), apart from gender, with women reporting significantly more fatigue than men (p = 0.006). There was a moderate correlation between the BASDEC and FSS (rs = 0.41, p = 0.002). Of the 41 participants who reported fatigue, 33 (81%) had not discussed this with their clinician. Conclusions: Fatigue was a common problem after stroke. There was a lack of awareness in both patients and clinicians and little advice being given to patients with fatigue.Item Health system determinants of tuberculosis mortality in South Africa: A causal loop model(BMC, 2021-04-26) Osman, Muhammad; Karat, Aaron S.; Khan, Munira; Meehan, Sue-Ann; von Delft, Arne; Brey, Zameer; Charalambous, Salome; Hesseling, Anneke C.; Naidoo, Pren; Loveday, MarianBackground: Tuberculosis (TB) is a major public health concern in South Africa and TB-related mortality remains unacceptably high. Numerous clinical studies have examined the direct causes of TB-related mortality, but its wider, systemic drivers are less well understood. Applying systems thinking, we aimed to identify factors underlying TB mortality in South Africa and describe their relationships. At a meeting organised by the ‘Optimising TB Treatment Outcomes’ task team of the National TB Think Tank, we drew on the wide expertise of attendees to identify factors underlying TB mortality in South Africa. We generated a causal loop diagram to illustrate how these factors relate to each other. Results: Meeting attendees identified nine key variables: three ‘drivers’ (adequacy & availability of tools, implementation of guidelines, and the burden of bureaucracy); three ‘links’ (integration of health services, integration of data systems, and utilisation of prevention strategies); and three ‘outcomes’ (accessibility of services, patient empowerment, and socio-economic status). Through the development and refinement of the causal loop diagram, additional explanatory and linking variables were added and three important reinforcing loops identified. Loop 1, ‘Leadership and management for outcomes’ illustrated that poor leadership led to increased bureaucracy and reduced the accessibility of TB services, which increased TB-related mortality and reinforced poor leadership through patient empowerment. Loop 2, ‘Prevention and structural determinants’ describes the complex reinforcing loop between socio-economic status, patient empowerment, the poor uptake of TB and HIV prevention strategies and increasing TB mortality. Loop 3, ‘System capacity’ describes how fragmented leadership and limited resources compromise the workforce and the performance and accessibility of TB services, and how this negatively affects the demand for higher levels of stewardship. Conclusions: Strengthening leadership, reducing bureaucracy, improving integration across all levels of the system, increasing health care worker support, and using windows of opportunity to target points of leverage within the South African health system are needed to both strengthen the system and reduce TB mortality. Further refinement of this model may allow for the identification of additional areas of intervention.Item Lessons learnt conducting minimally invasive autopsies in private mortuaries as part of HIV and tuberculosis research in South Africa(International Union Against Tuberculosis and Lung Disease, 2019-12-21) Karat, Aaron S.; Omar, T.; Tlali, M.; Charalambous, S.; Chihota, V. N.; Churchyard, G. J.; Fielding, K. L.; Martinson, N. A.; McCarthy, K. M.; Grant, A. D.Current estimates of the burden of tuberculosis (TB) disease and cause-specific mortality in human immunodeficiency virus (HIV) positive people rely heavily on indirect methods that are less reliable for ascertaining individual-level causes of death and on mathematical models. Minimally invasive autopsy (MIA) is useful for diagnosing infectious diseases, provides a reasonable proxy for the gold standard in cause of death ascertainment (complete diagnostic autopsy) and, used routinely, could improve cause-specific mortality estimates. From our experience in performing MIAs in HIV-positive adults in private mortuaries in South Africa (during the Lesedi Kamoso Study), we describe the challenges we faced and make recommendations for the conduct of MIA in future studies or surveillance programmes, including strategies for effective communication, approaches to obtaining informed consent, risk management for staff and efficient preparation for the procedure.Item Measuring mortality due to HIV-associated tuberculosis among adults in South Africa: Comparing verbal autopsy, minimally-invasive autopsy, and research data(PLOS, 2017-03-23) Karat, Aaron S.; Tlali, Mpho; Fielding, Katherine L.; Charalambous, Salome; Chihota, Violet N.; Churchyard, Gavin J.; Hanifa, Yasmeen; Johnson, Suzanne; McCarthy, Kerrigan; Martinson, Neil A.; Omar, Tanvier; Kahn, Kathleen; Chandramohan, Daniel; Grant, Alison D.; Isaakidis, PetrosBackground The World Health Organization (WHO) aims to reduce tuberculosis (TB) deaths by 95% by 2035; tracking progress requires accurate measurement of TB mortality. International Classification of Diseases (ICD) codes do not differentiate between HIV-associated TB and HIV more generally. Verbal autopsy (VA) is used to estimate cause of death (CoD) patterns but has mostly been validated against a suboptimal gold standard for HIV and TB. This study, conducted among HIV-positive adults, aimed to estimate the accuracy of VA in ascertaining TB and HIV CoD when compared to a reference standard derived from a variety of clinical sources including, in some, minimally-invasive autopsy (MIA).Item Modelling the effect of infection prevention and control measures on rate of Mycobacterium tuberculosis transmission to clinic attendees in primary health clinics in South Africa(BMJ, 2021-10-25) McCreesh, Nicky; Karat, Aaron S.; Baisley, Kathy; Diaconu, Karin; Bozzani, Fiammetta; Govender, Indira; Beckwith, Peter; Yates, Tom A.; Deol, Arminder K.; Houben, Rein M. G. J.; Kielmann, Karina; White, Richard G.; Grant, Alison D.Background Elevated rates of tuberculosis in health care workers demonstrate the high rate of Mycobacterium tuberculosis (Mtb) transmission in health facilities in high burden settings. In the context of a project taking a whole systems approach to tuberculosis infection prevention and control (IPC), we aimed to evaluate the potential impact of conventional and novel IPC measures on Mtb transmission to patients and other clinic attendees.Item Performance of verbal autopsy methods in estimating HIV-associated mortality among adults in South Africa(BMJ, 2018-07-03) Karat, Aaron S.; Maraba, Noriah; Tlali, Mpho; Charalambous, Salome; Chihota, Violet N.; Churchyard, Gavin J.; Fielding, Katherine L.; Hanifa, Yasmeen; Johnson, Suzanne; McCarthy, Kerrigan M.; Kahn, Kathleen; Chandramohan, Daniel; Grant, Alison D.; Topp, Stephanie M.Introduction Verbal autopsy (VA) can be integrated into civil registration and vital statistics systems, but its accuracy in determining HIV-associated causes of death (CoD) is uncertain. We assessed the sensitivity and specificity of VA questions in determining HIV status and antiretroviral therapy (ART) initiation and compared HIV-associated mortality fractions assigned by different VA interpretation methods.Item Prevalence of Mycobacterium tuberculosis in sputum and reported symptoms among clinic attendees compared to a community survey in rural South Africa(Oxford University Press, 2022-01-12) Govender, Indira; Karat, Aaron S.; Olivier, Stephen; Baisley, Kathy; Beckwith, Peter; Dayi, Njabulo; Dreyer, Jaco; Gareta, Dickman; Gunda, Resign; Kielmann, Karina; Koole, Olivier; Mhlongo, Ngcebo; Modise, Tshwaraganang; Moodley, Sashen; Mpofana, Xolile; Ndung’u, Thumbi; Pillay, Deenan; Siedner, Mark J.; Smit, Theresa; Surujdeen, Ashmika; Wong, Emily B.; Grant, Alison D.Background Tuberculosis (TB) case finding efforts typically target symptomatic people attending health facilities. We compared the prevalence of Mycobacterium tuberculosis (Mtb) sputum culture-positivity among adult clinic attendees in rural South Africa with a concurrent, community-based estimate from the surrounding demographic surveillance area (DSA). Methods Clinic: Randomly-selected adults (≥18 years) attending two primary healthcare clinics were interviewed and requested to give sputum for mycobacterial culture. HIV and antiretroviral therapy (ART) status were based on self-report and record review. Community: All adult (≥15 years) DSA residents were invited to a mobile clinic for health screening, including serological HIV testing; those with ≥1 TB symptom (cough, weight loss, night sweats, fever) or abnormal chest radiograph were asked for sputum. Results Clinic: 2,055 patients were enrolled (76.9% female, median age 36 years); 1,479 (72.0%) were classified HIV-positive (98.9% on ART) and 131 (6.4%) reported ≥1 TB symptom. Of 20/2,055 (1.0% [95% CI 0.6–1.5]) with Mtb culture-positive sputum, 14 (70%) reported no symptoms. Community: 10,320 residents were enrolled (68.3% female, median age 38 years); 3,105 (30.3%) tested HIV-positive (87.4% on ART) and 1,091 (10.6%) reported ≥1 TB symptom. Of 58/10,320 (0.6% [95% CI 0.4–0.7]) with Mtb culture-positive sputum, 45 (77.6%) reported no symptoms. In both surveys, sputum culture positivity was associated with male sex and reporting >1 TB symptom. Conclusions In both clinic and community settings, most participants with Mtb culture-positive sputum were asymptomatic. TB screening based only on symptoms will miss many people with active disease in both settings.Item Relational dynamics of treatment behavior among individuals with tuberculosis in high-income countries: A scoping review(Dove Press, 2021-09-21) Arakelyan, Stella; Karat, Aaron S.; Jones, Annie S. K.; Vidal, Nicole L.; Stagg, Helen R.; Darvell, Marcia; Horne, Rob; Lipman, Marc C. I.; Kielmann, KarinaAlthough tuberculosis (TB) incidence has significantly declined in high-income, low-incidence (HILI) countries, challenges remain in managing TB in vulnerable populations who may struggle to stay on anti-TB treatment (ATT). Factors associated with non-adherence to ATT are well-documented; however, adherence is often narrowly conceived as a fixed binary variable that places emphasis on individual agency and the act of taking medicines, rather than on the demands of being on treatment more broadly. Further, the mechanisms through which documented factors act upon the experience of ‘being on treatment’ are poorly understood. Adopting a relational approach that emphasizes the embeddedness of individuals within dynamic social, structural, and systems contexts, this scoping review aims to synthesize qualitative evidence on experiences of being on ATT and mechanisms through which socio-ecological factors influence adherence in HILI countries. Six electronic databases were searched for peer-reviewed literature published in English between January 1990 and May 2020. Additional studies were obtained by searching references and citations of included studies. Narrative synthesis was used to analyze qualitative data extracted from included studies. Of 28 included studies, the majority (86%) reported on health systems factors, followed by personal characteristics (82%), structural influences (61%), social factors (57%), and treatment-related factors (50%). Included studies highlighted three points that underpin a relational approach to ATT behavior: (1) individual motivation and capacity to take ATT is dynamic and intertwined with, rather than separate from, social, health systems, and structural factors; (2) individuals’ pre-existing experiences of health-seeking influenced their views on treatment and their ability to commit to long-term regular medicine-taking; and (3) social, cultural, and political contexts play an important role in mediating how specific factors work to support or hinder ATT adherence behavior in different settings. Based on our analysis, we suggest that person-centered clinical management of tuberculosis should (a) acknowledge the ways in which ATT both disrupts and is managed within the everyday lives of individuals with TB; (b) appreciate that circumstances and the support and resources that individuals can access may change over the course of treatment; and (c) display sensitivity towards context-specific social and cultural norms affecting individual and collective experiences of being on ATT.