Intimate Partner Violence (IPV) and Associated Factors in HPTN 071 (PopART) Study Communities in Zambia and South Africa-A Comparison by HIV Status.

The HPTN 071(PopART) study was a community-randomised trial in Zambia and South Africa, examining the impact of combination-prevention including universal testing and treatment (UTT), on HIV-incidence. This sub-study evaluated factors associated with IPV (physical and/or sexual) to identify differences by HIV status. During 2015-16, a random subset of adults who participated in the first year of the PopART intervention were recruited and standardised questionnaires were administered. Logistic regression was performed to estimate odds ratios of factors associated with IPV. Among > 700 women studied (300 HIV-negative;400 HIV-positive), ~ 20% reported experiencing physical and/or sexual violence in the last 12-months. Sexual violence was similar by HIV status, but physical violence and reporting both physical/sexual violence was more common among HIV-positive women. Spending nights away from the community in the last 12-months was associated with higher odds of IPV among both HIV-negative (aOR 3.17, 95% CI 1.02-9.81) and HIV-positive women (aOR 1.79, 95% CI 0.99-3.24). Among HIV-positive women, financial autonomy was associated with reduced IPV (aOR:0.41,95%CI:0.23-0.75) while pregnancy in the last 12-months (aOR 2.25, 95% CI 1.07-4.74), risk of alcohol dependence (aOR 2.75, 95% CI 1.51-5.00) and risk of mental distress (aOR 2.62, 95% CI 1.33-5.16) were associated with increased IPV. Among HIV-negative women reporting sex in the last 12-months, transactional sex (aOR 3.97, 95% CI 1.02-15.37) and not knowing partner's HIV status (aOR 3.01, 95% CI 1.24-7.29) were associated with IPV. IPV was commonly reported in the study population and factors associated with IPV differed by HIV status. The association of mobility with IPV warrants further research. The high prevalence of harmful alcohol use and mental distress, and their association with IPV among HIV-positive women require urgent attention.

RESUMEN: El estudio HPTN 071 (PopART) fue un ensayo aleatorio-comunitario realizado en Zambia y Sudáfrica, que examinó el impacto de la prevención combinada, incluyendo las pruebas y tratamiento universal (UTT), en la incidencia del VIH. Este subestudio evaluó los factores asociados con la IPV (físicos y / o sexuales) para identificar diferencias en el estado del VIH. Durante 2015-16, un subconjunto aleatorio de adultos fueron reclutados para participar en el primer año de intervención de PopART, donde se administraron cuestionarios estandarizados. Se realizó una regresión logística para estimar las ratios de probabilidad de los factores asociados con la VPI. Entre las > 700 mujeres estudiadas (300 VIH negativas; 400 VIH positivas), ~ 20% informó haber experimentado violencia física y / o sexual en los últimos 12 meses. La violencia sexual fue similar en cuanto al estado del VIH. La denuncia de violencia física y sexual fue más común entre las mujeres VIH positivas. Pasar noches fuera de la comunidad en los últimos 12 meses, se asoció con mayores probabilidades de VPI entre las mujeres VIH negativas (ORa 3,17, 95% IC 1,02­9,81) y las mujeres VIH positivas (ORa 1,79, 95% IC 0,99­3,24). Entre las mujeres VIH positivas, la autonomía financiera se asoció con una reducción de la VPI (ORa 0,41; IC del 95% 0,23-0,75) mientras que en el embarazo en los últimos 12 meses (ORa 2,25; IC del 95% 1,07­4,74), riesgo a la dependencia del alcohol (ORa 2,75% IC 1,51­5,00) y el riesgo de angustia mental (ORa 2,62% IC del 95% 1,33­5,16) se asociaron con un aumento de la VPI. Entre las mujeres VIH negativas que informaron haber tenido relaciones sexuales en los últimos 12 meses, el sexo transaccional (ORa 3.97, 95% CI 1.02­15.37) y el desconocimiento del estado de VIH de la pareja (ORa 3.01, 95% CI 1.24­7.29) se asociaron con IPV. La IPV fue notificada mayoritariamente en la población de estudio y los factores asociados con la IPV diferían según el estado del VIH. La asociación de la movilidad con la IPV justifica una mayor investigación. La alta prevalencia de l consumo nocivo de alcohol y la angustia mental, y su asociación con la VPI entre las mujeres seropositivas, requieren atención urgente.

Is home-based HIV testing universally acceptable? Findings from a case-control study nested within the HPTN 071 (PopART) trial.

OBJECTIVE: The HPTN 071 (PopART) trial is examining the impact of a package including universal testing and treatment on community-level HIV incidence in Zambia and South Africa. We conducted a nested case-control study to examine factors associated with acceptance of home-based HIV testing and counselling (HB-HTC) delivered by community HIV-care providers (CHiPs) in PopART intervention communities. METHODS: Of 295 447 individuals who were offered testing, random samples of individuals who declined HB-HTC (cases) and accepted HB-HTC (controls), stratified by gender and community, were selected. Odds ratios comparing cases and controls were estimated using multivariable logistic regression. RESULTS: Data from 642 participants (313 cases, 329 controls) were analysed. There were no differences between cases and controls by demographic or behavioural characteristics including age, marital or socio-economic position. Participants who felt they could be open with CHiPs (AOR: 0.46, 95% CI: 0.30-0.71, P < 0.001); self-reported as not previously tested (AOR: 0.64; 95% CI: 0.43-0.95, P = 0.03); considered HTC at home to be convenient (AOR: 0.38, 95% CI: 0.27-0.54, P = 0.001); knowing others who had accepted HB-HTC from the CHiPs (AOR: 0.49, 95% CI: 0.31-0.77, P = 0.002); or were motivated to get treatment without delay (AOR: 0.60, 95% CI: 0.43-0.85, P = 0.004) were less likely to decline the offer of HB-HCT. Those who self-reported high-risk sexual behaviour were also less likely to decline HB-HCT (AOR: 0.61, 95% CI: 0.39-0.93, P = 0.02). Having stigmatising attitudes about HB-HTC was not an important barrier to HB-HCT uptake. Men who reported fear of HIV were more likely to decline HB-HCT (AOR: 2.68, 95% CI: 1.33-5.38, P = 0.005). CONCLUSION: Acceptance of HB-HTC was associated with lack of previous HIV testing, positive attitudes about HIV services/treatment and perception of high sexual risk. Uptake of HB-HCT among those offered it was similar across a range of demographic and behavioural subgroups suggesting it was 'universally' acceptable.

Perspectives from the 2nd International Post-Tuberculosis Symposium: mobilising advocacy and research for improved outcomes.

In 2020, it was estimated that there were 155 million survivors of TB alive, all at risk of possible post TB disability. The 2nd International Post-Tuberculosis Symposium (Stellenbosch, South Africa) was held to increase global awareness and empower TB-affected communities to play an active role in driving the agenda. We aimed to update knowledge on post-TB life and illness, identify research priorities, build research collaborations and highlight the need to embed lung health outcomes in clinical TB trials and programmatic TB care services. The symposium was a multidisciplinary meeting that included clinicians, researchers, TB survivors, funders and policy makers. Ten academic working groups set their own goals and covered the following thematic areas: 1) patient engagement and perspectives; 2) epidemiology and modelling; 3) pathogenesis of post-TB sequelae; 4) post-TB lung disease; 5) cardiovascular and pulmonary vascular complications; 6) neuromuscular & skeletal complications; 7) paediatric complications; 8) economic-social and psychological (ESP) consequences; 9) prevention, treatment and management; 10) advocacy, policy and stakeholder engagement. The working groups provided important updates for their respective fields, highlighted research priorities, and made progress towards the standardisation and alignment of post-TB outcomes and definitions.

En 2020, il est estimé qu'il y a 155 millions de survivants de la TB dans le monde, tous exposés à un risque d'invalidité post-TB. Le deuxième Symposium International Post-Tuberculose (Stellenbosch, Afrique du Sud) a été organisé dans le but de sensibiliser davantage à l'échelle mondiale et de permettre aux communautés touchées par la TB de contribuer activement à la mise en œuvre de l'agenda. De plus, nous avons entrepris de mettre à jour les connaissances sur la vie et les maladies post-TB, de déterminer les domaines de recherche prioritaires, d'établir des partenariats de recherche et de souligner l'importance d'intégrer les résultats sur la santé pulmonaire dans les essais cliniques et les services de soins de la TB. Le symposium était une réunion de travail pluridisciplinaire rassemblant des praticiens, des chercheurs, des personnes ayant survécu à la TB, des donateurs, des décideurs politiques et d'autres acteurs clés. Dix groupes de travail académiques ont établi leurs propres objectifs et ont abordé les sujets thématiques suivants : 1) engagement et perspectives des patients ; 2) épidémiologie et modélisation ; 3) pathogénie des séquelles post-TB ; 4) maladie pulmonaire post-TB (PTLD, pour l'anglais «post-TB lung disease ¼) ; 5) complications cardiovasculaires et vasculaires pulmonaires ; 6) complications neuromusculaires et squelettiques ; 7) complications pédiatriques ; 8) conséquences économiques, sociales et psychologiques (ESP, pour l'anglais «economic-social and psychological¼) ; 9) prévention, traitement et gestion ; 10) plaidoyer, politique et engagement des parties prenantes. Les groupes de travail académiques ont apporté des mises à jour significatives dans leurs domaines respectifs, ont mis en évidence les priorités de recherche et ont avancé vers la normalisation et l'harmonisation des résultats et des définitions de la post-TB.

TB programme stakeholder views on lessons from the COVID-19 response in South Africa.

BACKGROUND: The global COVID-19 pandemic has reversed many of the hard-won gains made in TB programmes and the associated reduction in the number of TB deaths, case notifications and incidence over the last three decades. Modelling estimates show that the impact will be lasting. There are global calls to recover the shortfalls along the TB care cascade that have resulted from COVID-19, with the recognition that the COVID-19 response holds lessons to inform more robust and comprehensive TB programmes and services. OBJECTIVE: To explore lessons from response measures to the COVID-19 pandemic in two high TB burden South African provinces. DESIGN: This was an exploratory qualitative study. We conducted interviews with TB programme stakeholders (managers and facility-level staff: n = 35) between February and June 2022. RESULTS: We identified eight facilitators of the COVID-19 response, including political will, rapid policy development, multi-sectoral collaboration, patient-centred models of care delivery, community engagement, mHealth and telehealth technologies, rigorous contact tracing and widespread mask wearing. Political will was singled out as a critical driver of the response. CONCLUSION: Leveraging COVID-19 inspired collaborations, technologies and avenues for health service delivery is an opportunity to maximise benefits for the TB programme. Reinvestment in national TB programmes and political prioritisation of TB are critical.

CONTEXTE: La pandémie mondiale de COVID-19 a réduit à néant une grande partie des gains durement acquis dans les programmes de lutte contre la TB et la réduction associée du nombre de décès dus à la TB, de notifications de cas et d'incidence au cours des trois dernières décennies. Les estimations de la modélisation montrent que l'impact sera durable. Des appels ont été lancés au niveau mondial pour combler les lacunes dans la chaîne de soins de la TB qui ont résulté de la pandémie de COVID-19, en reconnaissant que la réponse à cette pandémie est porteuse d'enseignements qui permettront d'élaborer des programmes et des services de lutte contre la TB plus solides et plus complets. OBJECTIF: Etudier les enseignements tirés des mesures prises en réponse à la pandémie de COVID-19 dans deux provinces sud-africaines à forte charge de morbidité TB. MÉTHODE: Il s'agit d'une étude qualitative exploratoire. Nous avons mené des entretiens avec les parties prenantes des programmes de lutte contre la TB (responsables et personnel au niveau des établissements : n = 35) entre février et juin 2022. RÉSULTATS: Nous avons identifié huit facilitateurs de la riposte au COVID-19, notamment la volonté politique, l'élaboration rapide de directives, la collaboration multisectorielle, les modèles de prestation de soins centrés sur le patient, l'engagement communautaire, les technologies de mHealth et de télésanté, la recherche rigoureuse des contacts et le port généralisé de masques. La volonté politique a été désignée comme un moteur essentiel de la riposte. CONCLUSION: L'exploitation des collaborations, des technologies et des moyens inspirés du COVID-19 pour la prestation de services de santé est une occasion de maximiser les avantages pour le programme de lutte contre la TB. Il est essentiel de réinvestir dans les programmes nationaux de lutte contre la TB et d'en faire une priorité politique.

Extemporaneously compounded liquid formulations of clofazimine.

BACKGROUND: Clofazimine (CFZ) is routinely used worldwide for the treatment of leprosy and TB. However, no liquid or dispersible tablet formulations of CFZ are currently available commercially for patients with challenges ingesting soft gelatin capsules or solid formulations. The aim of this research was to develop stable extemporaneous liquid formulations of CFZ that can be stored at room temperature for several weeks to enable practical dosing in the field. METHODS: Two formulations were prepared in syrup and sugar-free vehicles with CFZ tablets using a simple method that can be used in a routine pharmacy. Suspensions were stored at room temperature and at 30°C for 30 days. Formulation aliquots were tested on Days 0, 15 and 30 for appearance, pH, potency and microbial counts. RESULTS: Appearance remained unchanged during storage. The pH of both formulations was between 4.0 and 6.0. Potency was between 90% and 110% for 30 days in the syrup formulation and for 15 days in the sugar-free formulation. Microbial counts met United States Pharmacopeia 1111 limits for oral aqueous liquids and specific organisms were absent. CONCLUSIONS: A simple field-friendly method was successfully developed for the preparation of CFZ liquid formulations using commonly available ingredients. This will permit practical dosing and titration for children and other patients with swallowing challenges.

Sugar and sugar-free liquid formulations of delamanid for patients with rifampicin-resistant TB.

BACKGROUND: Delamanid (DLM) tablets are recommended for the treatment of rifampicin-resistant TB. However, no liquid or dispersible tablet formulation of DLM is currently commercially available for patients with challenges ingesting these tablets. The aim of this study was to develop stable extemporaneous liquid formulations of DLM that can be stored at room temperature for several weeks.METHODS: DLM tablets were suspended in 1) simple syrup and 2) a specially formulated sugar-free vehicle. These suspensions containing DLM 5 mg/mL were stored in plastic prescription bottles at room temperature or 30°C for 30 days. These suspensions were evaluated for appearance, potency, pH, and microbial counts at Days 0, 15, and 30.RESULTS: The potency of DLM in each formulation remained at 98-104% of the theoretical concentration for 30 days. The appearance, pH, and microbial count did not change for the sugar-free formulation during the 30-day storage period. Microbial growth, however, was observed in the simple syrup formulation on Day 30 but not on Day 15.CONCLUSION: DLM can be formulated in sugar or sugar-free suspensions and stored at room temperature or 30°C for at least 15 and 30 days, respectively.

Children´s priorities to improve the acceptability of MDR-TB treatment: qualitative data from South Africa.

BACKGROUND: Multidrug-resistant TB (MDR-TB) treatment for children frequently includes unpalatable drugs with low overall acceptability. This can negatively impact children and their caregivers´ treatment experiences and is an important contributor to poor adherence, and potentially, poor treatment outcomes. Children and their caregivers´ preferences for MDR-TB treatment are not well documented. We describe children and caregivers´ priorities to inform future MDR-TB treatment regimens.METHODS: We conducted a cross-sectional qualitative study at a TB hospital in South Africa using semi-structured interviews and participatory research activities with caregivers and children routinely diagnosed and treated for MDR-TB between June and August 2018.RESULTS: We conducted 15 interviews with children and their caregivers. Children ranged from 2 to 17 years of age (median age: 8.3 years). Children and caregivers had an overall negative experience of MDR-TB treatment. Children and caregivers described how future MDR-TB drugs and regimens should prioritise sweeter flavours, fewer pills, brighter colours, and formulations that are easy to prepare and administer and dispensed in colourful, small and discrete packaging.CONCLUSIONS: MDR-TB treatment acceptability remains low, and negatively impacts children and their caregivers´ treatment experiences. Improving the overall acceptability of MDR-TB treatment requires engaging with children and their caregivers to better understand their priorities for new treatment regimens and child-friendly formulations.

TB preventive therapy preferences among children and adolescents.

BACKGROUND: TB preventive therapy (TPT) is critical for ending TB, yet implementation remains poor. With new global guidelines expanding TPT eligibility and regimens, we aimed to understand TPT preferences among children, adolescents and caregivers.METHODS: We undertook a discrete choice experiment among 131 children, 170 adolescents and 173 caregivers, and conducted 17 in-depth interviews in 25 clinics in Cape Town, South Africa. The design included attributes for location, waiting time, treatment duration, dosing frequency, formulation/size, side effects, packaging and taste. Mixed-effects logistic regression models were used for analysis.RESULTS: Among children and caregivers, the number and size of pills, taste and side effects were important drivers of preferences. Among adolescents and caregivers, clinic waiting times and side effects were significant drivers of preferences. Adolescents expressed concerns about being stigmatised, and preferred services from local clinics to services delivered in the community. Dosing frequency and treatment duration were only significant drivers of choice among adolescents, and only if linked to fewer clinic visits.CONCLUSIONS: Introducing shorter TPT regimens in isolation without consideration of preferences and health services may not have the desired effect on uptake and completion. Developing TPT delivery models and formulations that align with preferences must be prioritised.

Lessons for TB from the COVID-19 response: qualitative data from Brazil, India and South Africa.

BACKGROUND: Brazil, India and South Africa are among the top 30 high TB burden countries globally and experienced high rates of SARS-CoV-2 infection and mortality. The COVID-19 response in each country was unprecedented and complex, informed by distinct political, economic, social and health systems contexts. While COVID-19 responses have set back TB control efforts, they also hold lessons to inform future TB programming and services. METHODS: This was a qualitative exploratory study involving interviews with TB stakeholders (n = 76) in Brazil, India and South Africa 2 years into the COVID-19 pandemic. Interview transcripts were analysed using an inductive coding strategy. RESULTS: Political will - whether national or subnational - enabled implementation of widespread prevention measures during the COVID-19 response in each country and stimulated mobile and telehealth service delivery innovations. Participants in all three countries emphasised the importance of mobilising and engaging communities in public health responses and noted limited health education and information as barriers to implementing TB control efforts at the community level. CONCLUSIONS: Building political will and social mobilisation must become more central to TB programming. COVID-19 has shown this is possible. A similar level of investment and collaborative effort, if not greater, as that seen during the COVID-19 pandemic is needed for TB through multi-sectoral partnerships.

CONTEXTE: Le Brésil, l'Inde et l'Afrique du Sud figurent parmi les 30 pays les plus touchés par la TB dans le monde et ont connu des taux élevés d'infection et de mortalité dus au SARS-CoV-2. La réponse au COVID-19 dans chacun de ces pays a été sans précédent et complexe, en raison de contextes politiques, économiques, sociaux et de systèmes de santé distincts. Si les réponses au COVID-19 ont fait reculer les efforts de lutte contre la TB, elles permettent également de tirer des enseignements pour les futurs programmes et services de lutte contre la TB. MÉTHODES: Il s'agit d'une étude exploratoire qualitative comprenant des entretiens avec des acteurs de la lutte contre la TB (n = 76) au Brésil, en Inde et en Afrique du Sud, 2 ans après le début de la pandémie de COVID-19. Les transcriptions des entretiens ont été analysées à l'aide d'une stratégie de codage inductive. RÉSULTATS: La volonté politique ­ qu'elle soit nationale ou infranationale ­ a permis la mise en œuvre de mesures de prévention généralisées au cours de la riposte au COVID-19 dans chaque pays et a stimulé les innovations en matière de prestation de services mobiles et de télésanté. Les participants des trois pays ont souligné l'importance de la mobilisation et de l'engagement des communautés dans les réponses de santé publique et ont noté que l'éducation et l'information sanitaires limitées constituaient des obstacles à la mise en œuvre des efforts de lutte contre la TB au niveau communautaire. CONCLUSIONS: La volonté politique et la mobilisation sociale doivent occuper une place plus centrale dans les programmes de lutte contre la TB. La conférence COVID-19 a montré que c'était possible. Un niveau d'investissement et de collaboration similaire, voire supérieur, à celui observé lors de la pandémie de COVID-19 est nécessaire pour lutter contre la TB par le biais de partenariats multisectoriels.

A novel home-based method for preparing suspensions of anti-TB drugs.

BACKGROUND: Tablets are the most widely available dosage form for the treatment of TB; however, adult tablets fail to meet the needs of young children who cannot swallow these tablets or require dose titration. We tested a new, simple device (XTEMP-R®) and the methodology for converting tablets of TB drugs into a homogeneous suspension for home use by children and caregivers.METHODS: XTEMP-R is a new device used for converting tablets into liquid preparations. Four TB drugs - pretomanid, delamanid, clofazimine and bedaquiline - were dispersed in the device utilizing water and simple syrup. The reproducibility of accurately delivering aliquots from the suspension upon preparation and upon redispersion after storing for 2 days was studied.RESULTS: Suspensions of each of the drugs tested were easily prepared in about 10 min and were visually uniform in consistency. Dosages in 2 and 5 mL were assessed in suspension, and those in 5 mL tested upon redispersion after 2 days. The observed range for these dosages spanned from 94.6% to 101.1% of the theoretical concentration for the suspensions under examination. The cleaned device had no detectable residual drug.CONCLUSION: XTEMP-R can be used at home by caregivers to prepare doses of suspensions accurately for children and patients who cannot swallow tablets.

Stable, compounded bedaquiline suspensions to support practical implementation of pediatric dosing in the field.

BACKGROUND: Bedaquiline (BDQ) tablets are indicated as part of a combination regimen for the treatment of multidrug-resistant TB in adults, adolescents and children. A dispersible tablet formulation is now approved but is not currently available in all settings. The aim of this study was to develop stable extemporaneous liquid formulations of BDQ that can be stored at room temperature or 30°C for several weeks, to support pragmatic pediatric dosing in the field and reduce wastage.METHODS: BDQ tablets were suspended in simple syrup and a sugar-free vehicle. Each 20 mg/mL formulation was stored at room temperature or 30°C for 30 days in amber dispensing bottles. Appearance, BDQ potency, pH and microbial counts were determined on Days 0, 15 and 30.RESULTS: The BDQ potency in both formulations remained at 98-101% of the theoretical concentration for 30 days. The appearance, pH and microbial count of sugar-free formulation did not change during the 30-day storage. The simple syrup formulation was stable for 15 days as microbial growth was observed on Day 30.CONCLUSIONS: BDQ may be prepared in syrup or sugar-free suspensions: syrup suspensions can be stored for 15 days at room temperature and 30C, whereas sugar-free suspensions can be stored for 30 days at room temperature and 30C. This information will support practical BDQ dosing for children in the field.

Post-TB health and wellbeing.

TB affects around 10.6 million people each year and there are now around 155 million TB survivors. TB and its treatments can lead to permanently impaired health and wellbeing. In 2019, representatives of TB affected communities attending the '1st International Post-Tuberculosis Symposium´ called for the development of clinical guidance on these issues. This clinical statement on post-TB health and wellbeing responds to this call and builds on the work of the symposium, which brought together TB survivors, healthcare professionals and researchers. Our document offers expert opinion and, where possible, evidence-based guidance to aid clinicians in the diagnosis and management of post-TB conditions and research in this field. It covers all aspects of post-TB, including economic, social and psychological wellbeing, post TB lung disease (PTLD), cardiovascular and pericardial disease, neurological disability, effects in adolescents and children, and future research needs.

Clinical standards for drug-susceptible TB in children and adolescents.

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.

Early interactions with newly diagnosed TB patients in hospital can support linkage to care.

BACKGROUND: In South Africa, failure to link individuals diagnosed with TB to care remains an important gap in the TB care cascade. Compared to people diagnosed at primary healthcare (PHC) facilities, people diagnosed in hospitals are more likely to require additional support to be linked with PHC TB treatment services. We describe a patient interaction process to support linkage to TB care. METHODS: We implemented a step-by-step early patient interaction process with 84 adults newly diagnosed with TB in one district hospital in Khayelitsha, Cape Town, South Africa (August 2020-March 2021). We confirmed patient contact details, provided TB and health information, shared information on accessing care at PHC facilities and answered patients' questions in their home language. RESULTS: Most patients (54/84, 64%) provided updated telephone numbers, and 19/84 (23%) reported changes in their physical address. Patients welcomed practical and health information in their home language. The majority (74/84, 88%) were linked to care after hospital discharge. CONCLUSIONS: A simple early patient interaction process implemented as part of routine care is a feasible strategy to facilitate early TB treatment initiation and registration.

CONTEXTE: En Afrique du Sud, l'incapacité à relier les personnes dont la TB a été diagnostiquée aux soins reste une lacune importante dans la cascade des soins antituberculeux. Comparativement aux personnes diagnostiquées dans les établissements de soins de santé primaires (PHC), les personnes diagnostiquées dans les hôpitaux sont plus susceptibles d'avoir besoin d'un soutien supplémentaire pour être reliées aux services de traitement de la TB des PHC. Nous décrivons un processus d'interaction avec le patient pour favoriser le lien avec les soins antituberculeux. MÉTHODES: Nous avons mis en œuvre un processus d'interaction précoce, étape par étape, avec 84 adultes chez qui la TB a été récemment diagnostiquée dans un hôpital de district de Khayelitsha, au Cap, en Afrique du Sud (août 2020­mars 2021). Nous avons confirmé les coordonnées des patients, fourni des informations sur la TB et la santé, partagé des informations sur l'accès aux soins dans les établissements de PHC et répondu aux questions des patients dans leur langue maternelle. RÉSULTATS: La plupart des patients (54/84 ; 64%) ont fourni des numéros de téléphone actualisés, et 19/84 (23%) ont signalé des changements dans leur adresse physique. Les patients ont apprécié les informations pratiques et ceux ayant trait à la santé dans leur langue maternelle. La majorité d'entre eux (74/84 ; 88%) ont été reliés aux soins après leur sortie de l'hôpital. CONCLUSIONS: Un processus simple d'interaction précoce avec le patient, mis en œuvre dans le cadre des soins de routine, est une stratégie réalisable pour faciliter l'initiation et l'enregistrement précoce du traitement de la TB.

Use of interactive messaging to reduce pre-diagnosis loss to follow-up for TB care.

OBJECTIVE: To investigate the uptake and usage of a WhatsApp-based interactive communication strategy to avert pre-diagnosis loss to follow-up (LTFU) from TB care in a high-incidence setting.METHODS: We enrolled adults (≥18 years) who underwent routine sputum TB testing in two primary healthcare clinics in Khayelitsha, Cape Town, South Africa. The intervention consisted of structured WhatsApp-based reminders (prompts) sent prior to a routine clinic appointment scheduled 2-3 days after the diagnostic visit. Pre-diagnosis LTFU was defined as failure to return for the scheduled appointment and within 10 days.RESULTS: We approached 332 adults with presumptive TB, of whom 103 (31%) were successfully enrolled; 213 (64%) did not own a WhatsApp-compatible phone. Of 103 participants, 74 (72%) actively responded to WhatsApp prompts; 69 (67%) opted to include a close contact in group communication to co-receive reminders. Pre-diagnosis LTFU was low overall (n = 7, 6.8%) and was not associated with failure to respond to WhatsApp prompts.CONCLUSION: In this high-incidence setting, enrolment in a WhatsApp-based communication intervention among adults with presumptive TB was low, mainly due to low availability of WhatsApp-compatible phones. Among participants, we observed high message response rates and low LTFU, suggesting potential for interactive messaging services to support pre-diagnosis TB care.

Stable sugar and sugar-free suspensions of pretomanid.

BACKGROUND: Pretomanid (PMD) tablets are indicated as part of a combination regimen for the treatment of adults with pulmonary extensively drug-resistant, treatment-intolerant or non-responsive multidrug-resistant TB. No commercial liquid formulation is currently available for patients unable to swallow these tablets.OBJECTIVE: To develop stable extemporaneous liquid formulations of PMD that can be stored at room temperature or 30°C for at least 4 weeks.METHODS: Crushed PMD tablets were formulated into 20 mg/mL suspensions in a simple syrup and sugar-free formulation. The PMD formulations were stored at room temperature and at 30°C for 30 days in dispensing bottles. Appearance, pH, potency and microbial counts of the suspensions were determined on Days 0, 15 and 30.RESULTS: The potency of PMD remained at 99.7-103.4% of the theoretical concentration in each formulation. The appearance, pH and microbial count did not change during the 30-day storage period. Simple syrup formulations did not require preservatives for microbial stability.CONCLUSIONS: PMD oral suspension formulations in simple syrup or in sugar-free vehicle were easily prepared by utilising commonly available equipment and ingredients and were stable for 30 days. These formulations are appropriate alternatives for patients with swallowing difficulties.

Reasons for poor uptake of TB preventive therapy in South Africa.

BACKGROUND: South Africa has one the highest TB and HIV burdens globally. TB preventive therapy (TPT) reduces the risk of TB disease and TB-related mortality in adults and children living with HIV and is indicated for use in TB-exposed HIV-negative individuals and children. TPT implementation in South Africa remains suboptimal. METHODS: We conducted a pragmatic review of TPT implementation using multiple data sources, including informant interviews (n = 134), semi-structured observations (n = 93) and TB patient folder reviews in 31 health facilities purposively selected across three high TB burden provinces. We used case descriptive analysis and thematic coding to identify barriers and facilitators to TPT implementation. RESULTS: TPT programme implementation was suboptimal, with inadequate monitoring even in health districts with well-functioning TB services. Health workers reported scepticism about TPT effectiveness, deprioritised TPT in practice and expressed divergent opinions about the cadres of staff responsible for implementation. Service- and facility-level barriers included ineffective contact tracing, resource shortages, lack of standardised reporting mechanisms and insufficient patient education on TPT. Patient-level barriers included socio-economic factors. CONCLUSIONS: Improving TPT implementation will require radically simplified and more feasible systems and training for all cadres of health workers. Partnership with communities to stimulate demand driven service uptake can potentially facilitate implementation.

CONTEXTE: L'Afrique du Sud a l'une des charges de TB et de VIH les plus élevées au monde. La thérapie préventive contre la TB (TPT) réduit le risque de TB maladie et de mortalité liée à la TB chez les adultes et les enfants vivant avec le VIH et est indiquée chez les personnes et les enfants séronégatifs exposés à la TB. La mise en œuvre du TPT en Afrique du Sud reste sous-optimale. MÉTHODES: Nous avons procédé à un examen pragmatique de la mise en œuvre du TPT à l'aide de plusieurs sources de données, notamment des entretiens avec des informateurs (n = 134), des observations semi-structurées (n = 93) et des examens de dossiers de patients atteints de TB dans 31 établissements de santé sélectionnés à dessein dans trois provinces fortement touchées par la TB. Nous avons utilisé une analyse descriptive des cas et un codage thématique pour identifier les obstacles et les facilitateurs de la mise en œuvre du programme TPT. RÉSULTATS: La mise en œuvre du programme TPT était sousoptimale, avec un suivi inadéquat, y compris dans les districts sanitaires où les services de lutte contre la TB fonctionnaient correctement. Les agents de santé ont fait part de leur scepticisme quant à l'efficacité de la TPT, n'ont pas accordé la priorité à la TPT dans la pratique et ont exprimé des opinions divergentes sur les cadres du personnel responsables de la mise en œuvre. Les obstacles au niveau des services et des établissements comprennent l'inefficacité de la recherche des contacts, la pénurie de ressources, l'absence de mécanismes de déclaration standardisés et l'insuffisance de l'éducation des patients sur la TPT. Les obstacles au niveau des patients comprenaient des facteurs socio-économiques. CONCLUSIONS: L'amélioration de la mise en œuvre des TPT nécessitera des systèmes radicalement simplifiés et plus réalisables ainsi qu'une formation pour tous les cadres du personnel de santé. Un partenariat avec les communautés pour stimuler l'adoption de services axés sur la demande peut potentiellement faciliter la mise en œuvre.

Caregivers' perspectives on health-related quality of life in young children with TB and respiratory illnesses.

BACKGROUND: There is a lack of holistic health-related quality of life (HRQoL) measures for young children with respiratory disease, especially in low- and middle-income countries (LMICs). We aimed to understand caregivers' perceptions of the relevance of common HRQoL domains for children with respiratory diseases, including TB. METHODS: This study was nested in a prospective observational cohort of children presenting with respiratory symptoms presumptive of pulmonary TB. We conducted 10 semi-structured interviews to explore caregivers' perceptions of the five commonly measured HRQoL domains: physical health, social support, emotional and psychological wellbeing, and schooling. We used case descriptive analysis and thematic coding. RESULTS: Caregivers considered all five domains to be relevant. The socio-economic context framed their responses, with QoL requiring sufficient basic resources for children. HRQoL experiences varied according to the severity of the child's symptoms, but not between TB and non-TB illnesses. Manifestations in the psychological domain were difficult to distinguish from the emotional domain. Social support included broad support for family members, indirectly benefiting the children. Caregivers were concerned about their children's early developmental milestones and future schooling. CONCLUSION: This exploratory study shows that HRQoL domains are relevant but require adaptation to be applicable for young children affected by respiratory illnesses living in LMICs.

CONTEXTE: Il existe un manque de mesures holistiques de la qualité de vie liée à la santé (HRQoL) pour les jeunes enfants atteints de maladies respiratoires, en particulier dans les pays à revenu faible ou intermédiaire (LMIC). Nous avons cherché à comprendre la perception qu'ont les soignants de la pertinence des domaines communs de la HRQoL pour les enfants atteints de maladies respiratoires, dont la TB. MÉTHODES: Cette étude était imbriquée dans une cohorte observationnelle prospective d'enfants présentant des symptômes respiratoires présomptifs de TB pulmonaire. Nous avons mené 10 entretiens semi-structurés pour explorer les perceptions des soignants sur les cinq domaines de la HRQoL communément mesurés : santé physique, soutien social, bien-être émotionnel et psychologique, et scolarité. Nous avons utilisé une analyse descriptive des cas et un codage thématique. RÉSULTATS: Les soignants considèrent que les cinq domaines sont pertinents. Le contexte socio-économique encadrait leurs réponses, la QoL nécessitant des ressources de base suffisantes pour les enfants. Les expériences de QoL variaient en fonction de la gravité des symptômes de l'enfant, mais pas entre les maladies TB et non TB. Les manifestations dans le domaine psychologique étaient difficiles à distinguer du domaine émotionnel. Le soutien social comprenait un large soutien aux membres de la famille, ce qui profitait indirectement aux enfants. Les soignants étaient préoccupés par les premiers stades de développement de leurs enfants et par leur future scolarité. CONCLUSION: Cette étude exploratoire montre que les domaines de la QoL sont pertinents mais nécessitent une adaptation pour être applicables aux jeunes enfants atteints de maladies respiratoires vivant dans les LMIC.

Persistent chronic respiratory symptoms despite TB cure is poorly correlated with lung function.

BACKGROUND: Persistent respiratory symptoms and lung function deficits are common after patients with TB. We aimed to define the burden of post-TB lung disease (PTLD) and assess associations between symptoms and impairment in two high TB incidence communities.METHODS: This was a cross-sectional survey of adults in Cape Town, South Africa who completed TB treatment 1-5 years previously. Questionnaires, spirometry and 6-minute walking distance (6MWD) were used to assess relationships between outcome measures and associated factors.RESULTS: Of the 145 participants recruited (mean age: 42 years, range: 18-75; 55 [38%] women), 55 (38%) had airflow obstruction and 84 (58%) had low forced vital capacity (FVC); the mean 6MWD was 463 m (range: 240-723). Respiratory symptoms were common: chronic cough (n = 27, 19%), wheeze (n = 61, 42%) and dyspnoea (modified MRC dyspnoea score 3 or 4: n = 36, 25%). There was poor correlation between FVC or obstruction and 6MWD. Only low body mass index showed consistent association with outcomes on multivariable analyses. Only 19 (13%) participants had a diagnosis of respiratory disease, and 16 (11%) currently received inhalers.CONCLUSION: There was substantial burden of symptoms and physiological impairment in this "cured" population, but poor correlation between objective outcome measures, highlighting deficits in our understanding of PTLD.

Clinical standards for the assessment, management and rehabilitation of post-TB lung disease.

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.