Risk factors for and timing of presumptive recurrent TB.

Understanding factors associated with increased risk for tuberculosis (TB) recurrence is essential in lowering the TB burden. We aimed to quantify the burden, risk factors, and timing of TB presumptive recurrence.We analyzed test results from 2013 to 2017 in the South African National Health Laboratory Service's database. We defined a person's TB episode to start with their first positive TB test. In the absence of treatment outcome data, we assumed the episode concluded 6 months later for rifampicin-susceptible TB (RS-TB) and 18 months later for rifampicin-resistant TB (RR-TB), provided that at least one negative smear or culture test was recorded within this period. We defined a presumptive recurrent TB episode to start with a positive TB test after the completion of a prior episode. We calculated recurrence measures stratified by various demographics and RR-TB status.Of 574,316 people with RS-TB, 4.7% experienced at least one presumptive recurrent TB episode. Higher local TB notification rates, HIV coinfection, and males experienced higher recurrence rates. Most (89.4%) of the first RS-TB recurrences occurred within a year of the initial episode.Our findings of when and among whom recurrent TB is more likely to occur can be used to assist early interventions and inform impact on patient care..

Xpert MTB/XDR implementation in South Africa: cost outcomes of centralised vs. decentralised approaches.

INTRODUCTION: In South Africa, Xpert® MTB/RIF Ultra (Ultra) is the recommended diagnostic assay for TB with line-probe assays for first- (LPAfl) and second-line drugs (LPAsl) providing additional drug susceptibility testing (DST) for samples that were rifampicin-resistant (RR-TB). To guide implementation of the recently launched Xpert® MTB/XDR (MTB/XDR) assay, a cost-outcomes analysis was conducted comparing total costs for genotypic DST (gDST) for persons diagnosed with RR-TB considering three strategies: replacing LPAfl/LPAsl (centralised level) with MTB/XDR vs. Ultra reflex testing (decentralised level). Further, DST was performed using residual specimen following RR-TB diagnosis. METHODS: The total cost of gDST was determined for three strategies, considering loss to follow-up (LTFU), unsuccessful test rates, and specimen volume. RESULTS: For 2019, 9,415 persons were diagnosed with RR-TB. A 35% LTFU rate between RR-TB diagnosis and LPAfl/LPAsl-DST was estimated. Unsuccessful test rates of 37% and 23.3% were reported for LPAfl and LPAsl, respectively. The estimated total costs were $191,472 for the conventional strategy, $122,352 for the centralised strategy, and $126,838 for the decentralised strategy. However, it was found that sufficient residual volume for reflex MTB/XDR testing is a limiting factor at the decentralised level. CONCLUSION: Centralising the implementation of XDR testing, as compared to LPAfl/LPAsl, leads to significant cost savings.

INTRODUCTION: En Afrique du Sud, Xpert® MTB/RIF Ultra (Ultra) est le test de diagnostic recommandé pour la TB avec des tests par sonde de ligne pour les médicaments de première (LPAfl) et de deuxième ligne (LPAsl) fournissant des tests de sensibilité aux médicaments (DST) supplémentaires pour les échantillons résistants à la rifampicine (RR-TB). Afin d'orienter la mise en œuvre du test Xpert® MTB/XDR (MTB/XDR) récemment lancé, une analyse coûts-résultats a été réalisée en comparant les coûts totaux de la DST génotypique (gDST) pour les personnes diagnostiquées avec une RR-TB en tenant compte de trois stratégies : remplacer le LPAfl/LPAsl (niveau centralisé) par le MTB/XDR par rapport au test Ultra reflex (niveau décentralisé). De plus, l'heure d'été a été réalisée à l'aide d'un échantillon résiduel après le diagnostic de RR-TB. MÉTHODES: Le coût total de la gDST a été déterminé pour trois stratégies, en tenant compte de la perte de suivi (LTFU), des taux d'échec des tests et du volume d'échantillons. RÉSULTATS: En 2019, 9 415 personnes ont reçu un diagnostic de RR-TB. Un taux de LTFU de 35% entre le diagnostic de RR-TB et le diagnostic de LPAfl/LPAsl-DST a été estimé. Des taux d'échec de 37% et de 23,3% ont été signalés pour LPAfl et LPAsl, respectivement. Les coûts totaux estimés étaient de 191 472 dollars pour la stratégie conventionnelle, de 122 352 dollars pour la stratégie centralisée et de 126 838 dollars pour la stratégie décentralisée. Cependant, il a été constaté qu'un volume résiduel suffisant pour les tests réflexes MTB/XDR est un facteur limitant au niveau décentralisé. CONCLUSION: La centralisation de la mise en œuvre des tests XDR, par rapport à LPAfl/LPAsl, permet de réaliser d'importantes économies.

Death trends for 2010 - 2022 for members of a large private medical scheme in South Africa.

BACKGROUND: In the absence of more recent national data on underlying causes of death in South Africa (SA), we examined mortality trends from 2010 to 2022 among members of a large private medical scheme. This analysis sheds light on the health profile of this specific demographic. OBJECTIVE: To investigate trends in Discovery Health Medical Scheme (DHMS) members' death rates and underlying cause of death patterns between 2010 and 2022. METHODS: All-cause deaths were compared across years accounting for demographic changes, by analysing age- and sex-standardised rates using 2019 age and sex population weightings. We used underlying cause-of-death data from death notifications. RESULTS: The 2019 age- and sex-standardised death rate was lower than the 2010 rate by 10%, with a steady decline experienced between 2010 and 2019. We have seen reduced age- and sex-standardised death rates from HIV/AIDS during this period, and despite the high prevalence, reduced age- and sex-standardised death rates from non-communicable diseases. Malignant neoplasms and cardiovascular disease have been and remained the two leading causes of death for Discovery Health Medical Scheme (DHMS) clients between 2012 and 2022. Age- and sex- standardised death rates, however, reached historic high levels during the first 2 years of the COVID-19 pandemic in SA. In 2020, overall age- and sex-standardised death rates for DHMS members increased to 542 deaths per 100 000 life years, which was higher than pre-pandemic levels. Age- and sex-standardised death rates went on to reach their highest level in the history of the scheme in 2021, at 767 deaths per 100 000 life years. Age- and sex-standardised death rates, however, had returned to near 2019 (pre-pandemic) levels by 2022, at 477 deaths per 100 000 life years. Males experienced a higher increase in age-standardised death rates during 2020 and remained at an increased risk of death in 2022 compared with pre-pandemic levels. When COVID-19 -related deaths are excluded, the age-standardised rates for both females and males in 2022 was lower than observed in the pre-pandemic years. While the low mortality experience could be related to competing causes and mortality displacement, further analysis over a longer period is needed to confirm this. CONCLUSION: DHMS experienced the highest level of age- and sex-standardised death rates during 2020 and 2021, the initial 2 years of the COVID-19 pandemic. Most of this increase was explained by COVID-19 deaths.

Undiagnosed comorbidities among individuals hospitalised with COVID-19 in South African public hospitals.

BACKGROUND: Previous studies have reported comorbid disease, including hypertension, diabetes mellitus, chronic cardiac and renal disease, malignancy, HIV, tuberculosis (TB) and obesity, to be associated with COVID­19 mortality. National demographic surveys have reported a high proportion of undiagnosed and untreated comorbid disease in South Africa (SA). OBJECTIVES: To determine the number of individuals with previously undiagnosed HIV, TB and non-communicable diseases (NCDs) among patients hospitalised with COVID­19, and the level of medical control of these chronic diseases. METHODS: We conducted a sentinel surveillance study to collect enhanced data on HIV, TB and NCDs among individuals with COVID­19 admitted to 16 secondary-level public hospitals in six of the nine provinces of SA. Trained surveillance officers approached all patients who met the surveillance case definition for inclusion in the study, and consenting patients were enrolled. The data collection instrument included questions on past medical history to determine the self-reported presence of comorbidities. The results of clinical and laboratory testing introduced as part of routine clinical care for hospitalised COVID­19 patients were collected for the study, to objectively determine the presence of hypertension, diabetes, HIV and TB and the levels of control of diabetes and HIV. RESULTS: On self-reported history, the most prevalent comorbidities were hypertension (n=1 658; 51.5%), diabetes (n=855; 26.6%) and HIV (n=603; 18.7%). The prevalence of self-reported active TB was 3.1%, and that of previous TB 5.5%. There were 1 254 patients admitted with COVID­19 (39.0%) who met the body mass index criteria for obesity. On clinical and laboratory testing, 87 patients were newly diagnosed with HIV, 29 with TB, 215 with diabetes and 40 with hypertension during their COVID­19 admission. There were 151/521 patients living with HIV (29.0%) with a viral load >1 000 copies/mL and 309/570 (54.2%) with a CD4 count <200 cells/µL. Among 901 patients classified as having diabetes, 777 (86.2%) had a glycated haemoglobin (HbA1c) level ≥6.5%. CONCLUSION: The study revealed a high prevalence of comorbid conditions among individuals with COVID­19 admitted to public hospitals in SA. In addition, a significant number of patients had previously undiagnosed hypertension, diabetes, HIV and active TB, and many and poorly controlled chronic disease, as evidenced by high HbA1c levels in patients with diabetes, and high viral loads and low CD4 levels in patients with HIV. The findings highlight the importance of strengthening health systems and care cascades for chronic disease management, which include prevention, screening for and effectively treating comorbidities, and ensuring secure and innovative supplies of medicines in primary healthcare during the COVID­19 pandemic.

Leveraging epidemiology as a decision support tool during the COVID-19 epidemic in South Africa.

By May 2021, South Africa (SA) had experienced two 'waves' of COVID-19 infections, with an initial peak of infections reached in July 2020, followed by a larger peak of infections in January 2021. Public health decisions rely on accurate and timely disease surveillance and epidemiological analyses, and accessibility of data at all levels of government is critical to inform stakeholders to respond effectively. In this paper, we describe the adaptation, development and operation of epidemiological surveillance and modelling systems in SA in response to the COVID-19 epidemic, including data systems for monitoring laboratory-confirmed COVID-19 cases, hospitalisations, mortality and recoveries at a national and provincial level, and how these systems were used to inform modelling projections and public health decisions. Detailed descriptions on the characteristics and completeness of individual datasets are not provided in this paper. Rapid development of robust data systems was necessary to support the response to the SA COVID-19 epidemic. These systems produced data streams that were used in decision-making at all levels of government. While much progress was made in producing epidemiological data, challenges remain to be overcome to address gaps to better prepare for future waves of COVID-19 and other health emergencies.

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.

Advancing TB research using digitized programmatic data.

The use of real-world data from national TB care programs has great potential to answer key research questions in TB control and is now opportune due to increasing digital data collection and storage. We summarize an expert stakeholder workshop conducted on this topic in October 2019, with perspectives from academics, national TB program officers, and data managers. We discuss challenges and opportunities in the use of TB programmatic data for research and describe digital data availability in two large, high TB burden countries, Brazil and South Africa. From this, we posit that with a standardized data collection set, improved data management, and greater collaboration, more TB programmatic data can be used for research with measurable public health impact.

Evaluation of the intensified tuberculosis case finding guidelines for children living with HIV.

SETTING: Out-patient paediatric human immunodeficiency virus (HIV) clinic in Soweto, South Africa. OBJECTIVE: To evaluate the yield of symptom screening for intensified tuberculosis (TB) case finding (ICF) and potential eligibility for isoniazid preventive therapy (IPT) in children living with HIV on antiretroviral treatment (ART). DESIGN: A cohort of 247 children (age 0-8 years) was systematically screened for TB symptoms during the first 2 years of ART. Children with symptoms were assessed using chest X-ray, smear microscopy and culture. RESULTS: Over 2 years, 1346 TB symptom screens were performed in 220 children not on anti-tuberculosis treatment. Only 48 (3.6%) screens in 39 children were positive for current cough, current fever, weight loss (>5%) or contact with a TB patient. The positive predictive value of symptom screening was 8.9% (95%CI 2.5-21.2); the sensitivity was 57.1% (95%CI 18.4-90.1). Most children (85.8%) were IPT-eligible according to World Health Organization guidelines; however, few (1.2%) were eligible according to South African guidelines. CONCLUSIONS: The yield of TB symptom screening was relatively poor in children on ART, highlighting the need for future research on paediatric TB symptom screening approaches in this population. The vastly different criteria for IPT eligibility between guidelines suggest that research is also needed to define the optimal use of IPT in children on ART.

Microbiological investigation for tuberculosis among HIV-infected children in Soweto, South Africa.

SETTING: A paediatric human immunodeficiency virus (HIV) clinic in an academic hospital in Soweto, South Africa. OBJECTIVES: 1) To describe and compare the clinical, immunological and virological characteristics of HIV-infected children co-treated for tuberculosis (TB), and 2) to compare those investigated microbiologically with those who were not, with a description of the results of the microbiological TB investigation. DESIGN: Retrospective analysis of TB-HIV-infected children aged <15 years treated for TB between 1 October 2007 and 15 March 2009. RESULTS: Anti-tuberculosis treatment was initiated in 616/3358 (18%) children during the study period. Microbiological TB investigation results were available for 399/616 (65%), among whom culture-confirmed TB was diagnosed in 49 (12%). Drug susceptibility testing was performed in 29/49 (59%) children: 5/29 (17%) were isoniazid-resistant, and 3 had multidrug-resistant TB. Children aged >8 years and those between 3 and 8 years were more likely to have culture-confirmed TB than those aged <3 years (aOR 9.4, 95%CI 2.26-39.08 vs. aOR 6.7, 95%CI 1.60-27.69), as were those with CD4 count <200 cells/mm(3) compared to those with >500 cells/mm(3) (aOR 3.95, 95%CI 1.23-12.72). CONCLUSION: Our study in HIV-infected children showed a high TB case rate, a low rate of definite TB and a high rate of drug-resistant TB based on World Health Organization case definitions. Increased uptake of available TB tests and availability of new diagnostic tests remains a priority in high TB-HIV burden settings.

HAART and risk of tuberculosis in HIV-infected South African children: a multi-site retrospective cohort.

SETTING: Four human immunodeficiency virus (HIV) clinics located at South African tertiary hospitals. OBJECTIVE: To assess the effectiveness of highly active antiretroviral therapy (HAART) in reducing incident tuberculosis (TB) in HIV-infected children. DESIGN: Retrospective cohort. RESULTS: A total of 1132 children's records were included in the study. At entry to the cohort, the median (interquartile range [IQR]) age, CD4%, CD4 count and viral load of all children was respectively 6.3 years (4.1-8.8), 15% (9.0-22.2), 576 cells/mm(3) (287-960) and 160 000 copies/ml (54 941.5-449 683); 75.9% were started on HAART. The male:female ratio was 1:1, and median follow-up time was 1.7 years. In children whose follow-up included both pre-HAART and on-HAART periods, the incidence of clinically diagnosed TB was respectively 21.1 per 100 person-years (py; 95%CI 18.2-24.4) and 6.4/100 py (95%CI 4.8-8.1), and when restricted to confirmed cases, respectively 3.1/100 py (95%CI 2.2-4.2) and 0.8/100 py (95%CI 0.5-1.4). Only 23% of all cases of TB were microbiologically confirmed. Multivariate analyses showed that HAART reduced incident TB by approximately 70%, both for confirmed and all TB cases. CONCLUSIONS: In this high TB burden country, the incidence of diagnosis of TB in HIV-infected children is at least as high as that of adults. HAART reduces incident TB, but further prospective TB preventive and diagnostic studies are urgently needed in children.