"It's about time they taught us": a qualitative study evaluating the barriers to finding and screening child contacts under five at risk for TB in Gauteng Province, South Africa from the provider and caregiver perspectives.

BACKGROUND: Inadequate numbers of children under five years of age who are exposed to tuberculosis (TB) in the home (child contact) are initiated on TB preventive treatment (TPT) in South Africa. We assessed barriers of initiating isoniazid preventive therapy (IPT) in this age group. METHODS: We conducted a qualitative study at two primary health clinics in the Ekurhuleni district in Gauteng Province. Between April and July 2019, we enrolled facility managers, TB staff and parents or legal guardians of child contacts (caregivers) attending for care, at the two facilities. Semi-structured questionnaires, facility observations and in-depth interviews using a semi-structured interview guide were used to collect data. Findings from the semi-structured questionnaires with facility staff and facility observations were summarized. Thematic analysis with a deductive approach was used to analyse the data from the in-depth interviews with caregivers. RESULTS: Two facility managers took part in the study and were assisted to complete the semi-structured questionnaires by TB staff. Fifteen caregivers aged between 18 and 43 years were interviewed of which 13 (87%) were female. Facility managers and TB staff (facility staff) felt that even though caregivers knew of family members who were on TB treatment, they delayed bringing their children for TB screening and TPT. Facility staff perceived caregivers as not understanding the purpose and benefits of TB prevention strategies such as TPT. Caregivers expressed the desire for their children to be screened for TB. However, caregivers lacked knowledge on TB transmission and the value of TB prevention in children at high risk of infection. CONCLUSION: While facility staff perceived caregivers to lack responsibility, caregivers expressed limited knowledge on the value of screening their children for TB as reasons for not accessing TB preventive services. Health education on TB transmission, screening, and TB prevention strategies at a community level, clinics, creches, schools and via media are important to achieve the global end TB goal of early detection and prevention of TB.

Performance of spirometry assessment at TB diagnosis.

BACKGROUND: Spirometry is considered relevant for the diagnosis and monitoring of post-TB lung disease. However, spirometry is rarely done in newly diagnosed TB patients.METHODS: Newly diagnosed, microbiologically confirmed TB patients were recruited for the study. Spirometry was performed within 21 days of TB treatment initiation according to American Thoracic Society/European Respiratory Society guidelines. Spirometry analysis was done using Global Lung Initiative equations for standardisation.RESULTS: Of 1,430 eligible study participants, 24.7% (353/1,430) had no spirometry performed mainly due to contraindications and 23.0% (329/1,430) had invalid results; 52.3% (748/1,430) of participants had a valid result, 82.8% (619/748) of whom had abnormal spirometry. Of participants with abnormal spirometry, 70% (436/619) had low forced vital capacity (FVC), 6.1% (38/619) had a low ratio of forced expiratory volume in 1 sec (FEV1) to FVC, and 19.1% (118/619) had low FVC, as well as low FEV1/FVC ratio. Among those with abnormal spirometry, 26.3% (163/619) had severe lung impairment.CONCLUSIONS: In this population, a high proportion of not performed and invalid spirometry assessments was observed; this was addressed by removing tachycardia as a (relative) contraindication from the study guidance and retraining. The high proportion of patients with severe pulmonary impairment at the time of TB diagnosis suggests a huge morbidity burden and calls for further longitudinal studies on the relevance of spirometry in predicting chronic lung impairment after TB.

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.

Delivery of TB preventive therapy to incarcerated people living with HIV in southern African correctional facilities.

TB preventive treatment (TPT) is recommended for high-risk and hard-to-reach populations such as incarcerated people living with HIV (PLHIV). To assess implementation of TPT delivery in correctional settings, we conducted an exploratory analysis of data from a multisite cohort study in South Africa and Zambia. From 975 participants, 648 were screened for TB, and 409 initiated TPT mostly within a month after initiation of antiretroviral therapy (190/409, 46.5%). We observed a median gap of one month (IQR 0.6-4.7) in TPT delivery to incarcerated PLHIV. Future research should examine standardised quality improvement tools and new strategies such as short-course regimens to improve TPT initiation in this population.

Le traitement préventif antituberculeux (TPT) est recommandé pour les populations à haut risque et difficiles à atteindre, telles que les personnes vivant avec le VIH (PLHIV) qui sont incarcérées. Afin d'évaluer la mise en place du TPT en centres correctionnels, nous avons réalisé une analyse exploratoire des données d'une étude de cohorte multisites en Afrique du Sud et en Zambie. Sur 975 participants, 648 ont subi un test de dépistage de la TB et 409 ont été mis sous TPT, dans le mois ayant suivi l'instauration du traitement antirétroviral pour la plupart (190/409 ; 46,5%). Nous avons observé un écart médian d'un mois (IQR 0,6­4,7) en matière de dispense du TPT aux PLHIV incarcérées. Les études futures devraient analyser l'utilisation d'outils standardisés d'amélioration de la qualité ainsi que de nouvelles stratégies, telles que les schémas thérapeutiques de courte durée, afin d'améliorer l'instauration du TPT dans cette population.

A position statement and practical guide to the use of particulate filtering facepiece respirators (N95, FFP2, or equivalent) for South African health workers exposed to respiratory pathogens including Mycobacterium tuberculosis and SARS-CoV-2.

SUMMARY: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is transmitted mainly by aerosol in particles <10 µm that can remain suspended for hours before being inhaled. Because particulate filtering facepiece respirators ('respirators'; e.g. N95 masks) are more effective than surgical masks against bio-aerosols, many international organisations now recommend that health workers (HWs) wear a respirator when caring for individuals who may have COVID-19. In South Africa (SA), however, surgical masks are still recommended for the routine care of individuals with possible or confirmed COVID-19, with respirators reserved for so-called aerosol-generating procedures. In contrast, SA guidelines do recommend respirators for routine care of individuals with possible or confirmed tuberculosis (TB), which is also transmitted via aerosol. In health facilities in SA, distinguishing between TB and COVID-19 is challenging without examination and investigation, both of which may expose HWs to potentially infectious individuals. Symptom-based triage has limited utility in defining risk. Indeed, significant proportions of individuals with COVID-19 and/or pulmonary TB may not have symptoms and/or test negative. The prevalence of undiagnosed respiratory disease is therefore likely significant in many general clinical areas (e.g. waiting areas). Moreover, a proportion of HWs are HIV-positive and are at increased risk of severe COVID-19 and death. RECOMMENDATIONS: Sustained improvements in infection prevention and control (IPC) require reorganisation of systems to prioritise HW and patient safety. While this will take time, it is unacceptable to leave HWs exposed until such changes are made. We propose that the SA health system adopts a target of 'zero harm', aiming to eliminate transmission of respiratory pathogens to all individuals in every healthcare setting. Accordingly, we recommend: the use of respirators by all staff (clinical and non-clinical) during activities that involve contact or sharing air in indoor spaces with individuals who: (i) have not yet been clinically evaluated; or (ii) are thought or known to have TB and/or COVID-19 or other potentially harmful respiratory infections;the use of respirators that meet national and international manufacturing standards;evaluation of all respirators, at the least, by qualitative fit testing; andthe use of respirators as part of a 'package of care' in line with international IPC recommendations. We recognise that this will be challenging, not least due to global and national shortages of personal protective equipment (PPE). SA national policy around respiratory protective equipment enables a robust framework for manufacture and quality control and has been supported by local manufacturers and the Department of Trade, Industry and Competition. Respirator manufacturers should explore adaptations to improve comfort and reduce barriers to communication. Structural changes are needed urgently to improve the safety of health facilities: persistent advocacy and research around potential systems change remain essential.

An economic evaluation of an intervention to increase demand for medical male circumcision among men aged 25-49 years in South Africa.

BACKGROUND: Studies estimate that circumcising men between the ages of 20-30 years who have exhibited previous risky sexual behaviour could reduce overall HIV prevalence. Demand creation strategies for medical male circumcision (MMC) targeting men in this age group may significantly impact these prevalence rates. OBJECTIVES: The objective of this study is to evaluate the cost-effectiveness and cost-benefit of an implementation science, pre-post study designed to increase the uptake of male circumcision for ages 25-49 at a fixed MMC clinic located in Gauteng Province, South Africa. METHODS: A health care provider perspective was utilised to collect all costs. Costs were compared between the standard care scenario of routine outreach strategies and a full intervention strategy. Cost-effectiveness was measured as cost per mature man enrolled and cost per mature man circumcised. A cost-benefit analysis was employed by using the Bernoulli model to estimate the cases of HIV averted due to medical male circumcision (MMC), and subsequently translated to averted medical costs. RESULTS: In the 2015 intervention, the cost of the intervention was $9445 for 722 men. The total HIV treatment costs averted due to the intervention were $542,491 from a public care model and $378,073 from a private care model. The benefit-cost ratio was 57.44 for the public care model and 40.03 for the private care model. The net savings of the intervention were $533,046 or $368,628 - depending on treatment in a public or private setting. CONCLUSIONS: The intervention was cost-effective compared to similar MMC demand interventions and led to statistically significant cost savings per individual enrolled.

Data quality assessment of a South African electronic registry for drug-resistant TB, 2015-2016.

SETTING: Assessment of bedaquiline roll-out in South Africa requires accurate patient data in EDRWeb, a national case-based rifampicin-resistant TB (RR-TB) surveillance register. OBJECTIVE: To ensure EDRWeb data reflect programmatic DR-TB source data, we implemented a data quality improvement initiative. DESIGN: We conducted data quality assessments of EDRWeb data compared to paper patient folders at two South African RR-TB treatment facilities in 2015 and 2016. We assessed 80 patient records before the intervention for completeness of clinically relevant data fields, and 80 different records after the intervention for completeness and concordance. The intervention involved reviewing and updating EDRWeb along with data quality audits with direct feedback to sites. RESULTS: At baseline data completeness per site was lowest for variables related to electrocardiogram (ECG) data, adverse events, and concomitant medications (completeness for these fields ranged from 0% to 80%). Post-intervention data completeness and concordance were high for all fields except those related to ECG data (ECG-related field completeness ranged from 10% to 100%). CONCLUSION: After a data quality initiative, data completeness improved at each site with the exception of ECG data fields. Our findings suggest that data quality interventions may improve patient clinical registries, ultimately enabling better evidence-based decision making for TB programmes.

CONTEXTE: L'évaluation du lancement de la bédaquiline en Afrique du Sud requiert des données précises relatives aux patients sur EDRWeb, notamment grâce à un registre de surveillance national de cas de la TB résistante à la rifampicine (RR-TB). OBJECTIF: Pour s'assurer que les données d'EDRWeb reflètent les sources des données de programme de TB résistante, nous avons mis en œuvre une initiative d'amélioration de la qualité des données. SCHÉMA: Nous avons réalisé des évaluations de qualité des données d'EDRWeb comparés aux dossiers papier des patients dans deux structures de traitement de RR-TB en Afrique du Sud en 2015 et 2016. Nous avons évalué 80 dossiers de patients avant l'intervention pour l'exhaustivité des données des domaines pertinents et 80 autres dossiers après l'intervention à la recherche d'exhaustivité et de concordance. L'intervention a consisté à revoir et à mettre à jour EDRWeb avec des audits de qualité des données directement renvoyés aux sites. RÉSULTATS: Au départ, l'exhaustivité des données dans chaque site était la plus faible en ce qui concerne les variables liées à l'électrocardiogramme (ECG), aux effets secondaires et aux médicaments concomitants ; elle allait de 0% à 80%. L'exhaustivité des données post-intervention et leur concordance ont été élevées pour tous les champs excepté ceux liés aux données de l'ECG qui allaient de 10% to 100%. CONCLUSION: Après une initiative de qualité des données, leur exhaustivité s'est améliorée dans chaque site à l'exception des données relatives à l'ECG. Nos résultats suggèrent que les interventions de qualité des données pourraient améliorer les dossiers cliniques des patients, ce qui permettrait des meilleures prises de décision, basées sur des preuves, pour les programmes TB.

Symptom and digital chest X-ray TB screening in South African prisons: yield and cost-effectiveness.

BACKGROUND: Correctional inmates are at a high risk of tuberculosis (TB). The optimal approach to screening this population is unclear.METHODS: We retrospectively reviewed records from TB screening in 64 correctional facilities in South Africa between January 2015 and July 2016. Inmates received symptom screening (any of cough, fever, weight loss, or night sweats) combined with digital chest X-ray (CXR), when available. CXRs were assessed as 'abnormal' or with no abnormalities. Inmates with either a symptom or an 'abnormal' CXR were asked to provide a single spot sputum for Xpert® MTB/RIF testing. We estimated the incremental cost-effectiveness ratio (ICER) per additional TB case detected using CXR screening among asymptomatic inmates.RESULTS: Of 61 580 inmates, CXR screening was available for 41 852. Of these, 19 711 (47.1%) had TB symptoms. Among 22 141 inmates without symptoms, 1939/19 783 (9.8%) had an abnormal CXR, and 8 (1.2%) were Xpert-positive among those with Xpert tests done. Of 14 942 who received symptom screening only and had symptoms, 84% (12 616) had an Xpert result, and 105 (0.8%) were positive. The ICER for CXR screening was US$22 278.CONCLUSION: Having CXR in addition to symptom screening increased yield but added considerable cost. A major limitation of screening was the low specificity of the symptom screen.

'They are inconveniencing us' - exploring how gaps in patient education and patient centred approaches interfere with TB treatment adherence: perspectives from patients and clinicians in the Free State Province, South Africa.

BACKGROUND: Tuberculosis (TB) treatment loss to follow up (LTFU) plays an important contributory role to the staggering TB epidemic in South Africa. Reasons for treatment interruption are poorly understood. Treatment interruption appears to be the culmination of poor health literacy of patients and inadequate health education provided by clinicians. We explored clinician and patient perspectives of the gaps in TB messaging that influence TB treatment LTFU. METHODS: We conducted semi-structured in-depth interviews between January and May 2018 with a sample of 15 clinicians managing TB and 7 patients identified as LTFU in public clinics in the Free State Province, South Africa. Thematic analysis using a mixed deductive/inductive thematic approach was used. RESULTS: Limited occupational opportunities, fear of disclosure and stigmatization all contributed to treatment LTFU. Patients felt that the TB messaging received was inadequate. Many of the clinicians interviewed felt that improving patient's TB knowledge would reinforce adherence to treatment and thus focused on sharing information on treatment completion, side effects and infection control. However, the inability of clinicians to establish rapport with patients or to identify social support challenged TB treatment adherence by patients. Clinicians perceived this as patients not following their instructions despite what they considered lengthy TB education. Having said this, clinicians concurred that their medical management of TB lacked the psycho-social dimension to treat a social disease of this magnitude. CONCLUSIONS: Limited occupational opportunities, fear of disclosure and stigmatization all contributed to treatment LTFU. Clinicians concurred that poor patient understanding of TB and that biomedical management lacking a psycho-social dimension further exacerbated the poor treatment outcome. TB remains a social disease, the successful management of which hinges on patient-centred care.

Prevalence and risk factors of tuberculosis disease in South African correctional facilities in 2015.

SETTING: Sixteen South African correctional facilities.OBJECTIVE: To determine the prevalence of and risk factors for tuberculosis (TB) in South African correctional facilities using data collected during a TB screening program in South African correctional facilities in 2015.DESIGN: Inmates in 16 South African correctional facilities were screened for TB from January to December 2015. Inmates reporting ≥1 TB symptom or having an abnormal computer-assisted digital chest X-ray (CXR) provided sputum. Abnormal CXRs were interpreted by a radiologist. Sputum was tested for Mycobacterium tuberculosis using Xpert® MTB/RIF. Data from 16 South African correctional facilities were used in regression analysis, and prevalence estimates calculated for 12 South African correctional facilities with >30% screening coverage.RESULTS: In 12 South African correctional facilities included in the prevalence estimates, 837 inmates had TB disease (2653/100 000) as indicated by current TB treatment or screening-identified TB by radiologist or Xpert. Previous TB was associated with increased odds of screening-identified TB in HIV-positive inmates (OR 4.3, 95%CI 2.5-7.3). For HIV-negative inmates, previous TB (adjusted OR [aOR] 4.9, 95%CI 1.7-14.1) and self-reported symptoms vs. none (1 symptom, aOR 8.8, 95%CI 1.2-67.7; >2 symptoms, aOR 21.7, 95%CI 3.0-158.8) were independently associated with increased odds of screening-identified TB.CONCLUSIONS: Routine TB screening, including CXR, is needed in South African correctional facilities to identify and refer inmates with active TB.

What causes symptoms suggestive of tuberculosis in HIV-positive people with negative initial investigations?

OBJECTIVE: To identify the causes of symptoms suggestive of tuberculosis (TB) among people living with the human immunodeficiency virus (PLHIV) in South Africa. METHODS: A consecutive sample of HIV clinic attendees with symptoms suggestive of TB (1 of cough, weight loss, fever or night sweats) at enrolment and at 3 months, and negative initial TB investigations, were systematically evaluated with standard protocols and diagnoses assigned using standard criteria. TB was 'confirmed' if Mycobacterium tuberculosis was identified within 6 months of enrolment, and 'clinical' if treatment started without microbiological confirmation. RESULTS: Among 103 participants, 50/103 were pre-antiretroviral therapy (ART) and 53/103 were on ART; respectively 68% vs. 79% were female; the median age was 35 vs. 45 years; the median CD4 count was 311 vs. 508 cells/mm³. Seventy-two (70%) had 5% measured weight loss and 50 (49%) had cough. The most common final diagnoses were weight loss due to severe food insecurity (n = 20, 19%), TB (n = 14, 14%: confirmed n = 7; clinical n = 7), other respiratory tract infection (n = 14, 14%) and post-TB lung disease (n = 9, 9%). The basis for TB diagnosis was imaging (n = 7), bacteriological confirmation from sputum (n = 4), histology, lumbar puncture and other (n = 1 each). CONCLUSION: PLHIV with persistent TB symptoms require further evaluation for TB using all available modalities, and for food insecurity in those with weight loss.

Lessons learnt conducting minimally invasive autopsies in private mortuaries as part of HIV and tuberculosis research in South Africa.

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.

Les estimations actuelles du poids de la tuberculose (TB) maladie et de la mortalité qui lui est due parmi les patients positifs à l'infection par le virus de l'immunodéficience humaine (VIH) dépendent beaucoup de méthodes indirectes, qui sont moins fiables pour vérifier les causes de décès au niveau individuel et de modèles mathématiques. Une autopsie peu invasive (MIA) est utile au diagnostic de maladies infectieuses, fournit une approximation raisonnable de l'étalon or de la vérification de la cause du décès c'est-à-dire une autopsie diagnostique complète. Si elle est utilisée en routine, elle pourrait améliorer les estimations de mortalité spécifique d'une cause. A partir de nos expériences de MIA sur des adultes positifs au VIH dans des morgues privées d'Afrique du Sud (au cours de l'étude Lesedi Kamoso), nous décrivons les défis rencontrés et faisons des recommandations pour la réalisation de MIA dans des études futures ou des programmes de surveillance, incluant des stratégies de communication efficaces, des approches visant à obtenir un consentement éclairé, une prise en charge du risque pour le personnel et une préparation efficace de la procédure.

Las estimaciones actuales de morbilidad por tuberculosis (TB) y de mortalidad por causas específicas en las personas positivas frente al virus de la inmunodeficiencia humana (VIH) se fundamentan en su mayor parte en métodos indirectos que son menos fiables para determinar las causas de muerte individuales y en modelizaciones matemáticas. La autopsia mínimamente invasiva (MIA) es útil en el diagnóstico de las enfermedades infecciosas, ofrece un sustituto aceptable al método de referencia para determinar la causa de muerte (que es la autopsia diagnóstica completa), y cuando se usa de manera sistemática, mejora las estimaciones de la mortalidad por causas específicas. A partir de su experiencia con la MIA en adultos con infección por el VIH en empresas fúnebres privadas en Suráfrica (durante el estudio Lesedi Kamoso), los autores describen las dificultades que encontraron y formulan recomendaciones que se pueden aplicar en el futuro al realizar la autopsia mínimamente invasiva en estudios de investigación o en programas de vigilancia; se preconizan estrategias de comunicación efectivas, métodos de obtención del consentimiento informado, la gestión de riesgos para el personal y la preparación eficiente del procedimiento.

Cost of point-of-care lateral flow urine lipoarabinomannan antigen testing in HIV-positive adults in South Africa.

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. METHODS: We estimated the costs of using LF-LAM in HIV-positive adults with CD4 counts  150 cells/µl enrolled in the TB Fast Track Trial in South Africa. We also estimated costs of POC haemoglobin (Hb), as this was used in the study algorithm. Data on clinic-level (10 intervention clinics) and above-clinic-level costs were collected. RESULTS: A total of 1307 LF-LAM tests were performed at 10 clinics over 24 months. The mean clinic-level costs were US$12.80 per patient for LF-LAM and POC Hb; LF-LAM costs were US$11.49 per patient. The mean above-clinic-level unit costs for LF-LAM were US$12.06 for clinic preparation, training, coordination and mentoring. The mean total cost of LF-LAM was US$23.55 per patient. CONCLUSION: At clinic level, the cost of LF-LAM was comparable to other TB diagnostics in South Africa. It is important to consider above-clinic-level costs for POC tests, as these may be required to support roll-out and ensure successful implementation.

An intervention to optimise the delivery of integrated tuberculosis and HIV services at primary care clinics: results of the MERGE cluster randomised trial.

OBJECTIVES: To evaluate the effect of an intervention to optimize TB/HIV integration on patient outcomes. METHODS: Cluster randomised control trial at 18 primary care clinics in South Africa. The intervention was placement of a nurse (TB/HIV integration officer) to facilitate provision of integrated TB/HIV services, and a lay health worker (TB screening officer) to facilitate TB screening for 24 months. Primary outcomes were i) incidence of hospitalisation/death among individuals newly diagnosed with HIV, ii) incidence of hospitalisation/death among individuals newly diagnosed with TB and iii) proportion of HIV-positive individuals newly diagnosed with TB who were retained in HIV care 12 months after enrolment. RESULTS: Of 3328 individuals enrolled, 3024 were in the HIV cohort, 731 in TB cohort and 427 in TB-HIV cohort. For the HIV cohort, the hospitalisation/death rate was 12.5 per 100 person-years (py) (182/1459py) in the intervention arm vs. 10.4/100py (147/1408 py) in the control arms respectively (Relative Risk (RR) 1.17 [95% CI 0.92-1.49]).For the TB cohort, hospitalisation/ death rate was 17.1/100 py (67/ 392py) vs. 11.1 /100py (32/289py) in intervention and control arms respectively (RR 1.37 [95% CI 0.78-2.43]). For the TB-HIV cohort, retention in care at 12 months was 63.0% (213/338) and 55.9% (143/256) in intervention and control arms (RR 1.11 [95% 0.89-1.38]). CONCLUSIONS: The intervention as implemented failed to improve patient outcomes beyond levels at control clinics. Effective strategies are needed to achieve better TB/HIV service integration and improve TB and HIV outcomes in primary care clinics. TRIAL REGISTRATION: South African Register of Clinical Trials (registration number DOH-27-1011-3846).

Evidence-informed policy making at country level: lessons learned from the South African Tuberculosis Think Tank.

BACKGROUND: National Tuberculosis Programmes (NTPs) require specialist input to support the development of policy and practice informed by evidence, typically against tight deadlines. OBJECTIVE: To describe lessons learned from establishing a dedicated tuberculosis (TB) think tank to advise the South African NTP on TB policy. INTERVENTION AND EVALUATION METHODS: A national TB think tank was established to advise the NTP in support of evidence-informed policy. Support was provided for activities, including meetings, modelling and regular telephone calls, with a wider network of unpaid expert advisers under an executive committee and working groups. Intervention evaluation used desktop analysis of documentary evidence, interviews and direct observation. RESULTS: The TB Think Tank evolved over time to acquire three key roles: an 'institution', a 'policy dialogue forum' and an 'interface'. Although enthusiasm was high, motivating participation among the NTP and external experts proved challenging. Motivation of working groups was most successful when aligned to a specific need for NTP decision making. Despite challenges, the TB Think Tank contributed to South Africa's first ever TB and human immunodeficiency virus (HIV) investment case, and the decision to create South Africa's first ever ring-fenced grant for TB. The TB Think Tank also assisted the NTP in formulating strategy to accelerate progress towards reaching World Health Organization targets. DISCUSSION: With partners, the TB Think Tank achieved major successes in supporting evidence-informed decision making, and garnered increased funding for TB in South Africa. Identifying ways to increase the involvement of NTP staff and other experts, and keeping the scope of the Think Tank well defined, could facilitate greater impact. Think tank initiatives could be replicated in other settings to support evidence-informed policy making.

Tuberculosis among HIV-infected population: incidence and risk factors in rural Tanzania.

BACKGROUND: The incidence of tuberculosis among HIV-infected populations with high CD4 count in high burden countries has not been well studied. OBJECTIVE: To assess the TB incidence in HIV-infected adults and its associated risk factors. METHOD: A cohort study with retrospective review of medical records and prospective follow-up of HIV-infected adult participants attending CTC who were 18-55 years old, had CD4 count more than 250 cells/mm3 in the period of 2008-2010 and were not on ART at enrolment. Cox proportional hazard regression was used to explore the predictors of incident TB. RESULTS: Overall 777 (24%) of 3,279 CTC enrolled HIV-infected adults fulfilled the inclusion criteria of the study. The incidence of TB in the study population ranged from 0.8/100 per person years (PY) at risk (95% CI 0.5-1.3) in the main analysis to 1.7/100 PY at risk (95% CI 1.0-2.6) in sensitivity analyses. Only prior history of TB disease was found to have a significant association with an increased risk of TB, hazard ratio 5.7 (95% CI 2.0-16.4, p value 0.001). CONCLUSION: Tuberculosis incidence among HIV-infected adults with medium/high CD4 count in Bagamoyo is lower than in other high TB burden countries. Previously TB treated patients have a much higher risk of getting TB again than those who never had TB before.

Chronic hepatitis B increases mortality and complexity among HIV-coinfected patients in South Africa: a cohort study.

OBJECTIVES: To assess the effect of chronic hepatitis B on survival and clinical complexity among people living with HIV following antiretroviral therapy (ART) initiation. METHODS: We evaluated mortality and single-drug substitutions up to 3 years from ART initiation (median follow-up 2.75 years; interquartile range 2-3 years) among patients with and without chronic hepatitis B (CHB) enrolled in a workplace HIV care programme in South Africa. RESULTS: Mortality was increased for CHB patients with hepatitis B virus (HBV) DNA levels > 10 000 copies/mL (adjusted hazard ratio 3.1; 95% confidence interval 1.2-8.0) compared with non-CHB patients. We did not observe a similar difference between non-CHB patients and those with CHB and HBV DNA < 10 000 copies/mL (adjusted hazard ratio 0.70; 95% confidence interval 0.2-2.3). Single-drug substitutions occurred more frequently among coinfected patients regardless of HBV DNA level. CONCLUSIONS: Our findings suggest that CHB may increase mortality and complicate ART management.

Pooling sputum from multiple individuals for Xpert® MTB/RIF testing: a strategy for screening high-risk populations.

SETTING: Symptom-based screening for tuberculosis (TB) disease is limited by poor performance of symptom screening in several key populations. We tested the hypothesis that pooling sputum from multiple individuals for Xpert(®) MTB/RIF testing would reduce the number of tests required while retaining an acceptable sensitivity, thus allowing the use of Xpert for TB screening. METHODS: We compared pooling ratios that would require the least number of assays using Xpert and determined that for a population with a TB prevalence of approximately 3%, a 1:5 pooling ratio is optimal. To evaluate sensitivity, we generated pools of one specimen with known Mycobacterium tuberculosis culture positivity (smear microscopy-positive or -negative) with four culture-negative specimens. RESULTS: All 20 of the pools generated from a smear- and culture-positive sputum sample were positive using Xpert. Of the 22 pools with a smear-negative, culture-positive sample, we included 17 in the analysis, of which 13 (76%) were Xpert-positive. CONCLUSIONS: Pooling of sputum samples using Xpert achieved reasonable sensitivity and warrants further evaluation of the systematic screening of high TB prevalence populations.

A cluster randomised trial to evaluate the effect of optimising TB/HIV integration on patient level outcomes: the "merge" trial protocol.

INTRODUCTION: We describe the design of the MERGE trial, a cluster randomised trial, to evaluate the effect of an intervention to optimise TB/HIV service integration on mortality, morbidity and retention in care among newly-diagnosed HIV-positive patients and newly-diagnosed TB patients. DESIGN: Eighteen primary care clinics were randomised to either intervention or standard of care arms. The intervention comprised activities designed to optimise TB and HIV service integration and supported by two new staff cadres-a TB/HIV integration officer and a TB screening officer-for 24 months. A process evaluation to understand how the intervention was perceived and implemented at the clinics was conducted as part of the trial. Newly-diagnosed HIV-positive patients and newly-diagnosed TB patients were enrolled into the study and followed up through telephonic interviews and case note abstractions at six monthly intervals for up to 18 months in order to measure outcomes. The primary outcomes were incidence of hospitalisations or death among newly diagnosed TB patients, incidence of hospitalisation or death among newly diagnosed HIV-positive patients and retention in care among HIV-positive TB patients. Secondary outcomes of the study included measures of cost-effectiveness. DISCUSSION: Methodological challenges of the trial such as implementation of a complex multi-faceted health systems intervention, the measurement of integration at baseline and at the end of the study and an evolving standard of care with respect to TB and HIV are discussed. The trial will contribute to understanding whether TB/HIV service integration affects patient outcomes.