Tuberculosis control in South Africa : Successes challenges and recommendations

PKTuberculosis (TB) remains a global health threat, and South Africa (SA) has one of the world’s worst TB epidemics driven by HIV. Among the 22 countries with the highest burden of TB, SA has the highest estimated incidence and prevalence of TB, the second highest number of diagnosed multidrug-resistant TB cases, and the largest number of HIV-associated TB cases. Although SA has made notable progress in reducing TB prevalence and deaths and improving treatment outcomes for new smear-positive TB cases, the burden of TB remains enormous. SA has the means to overcome this situation. In addition to better implementing the basics of TB diagnosis and treatment,scaling up the use of Xpert MTB/RIF as a replacement for sputum smear microscopy, strengthening case finding in and beyond healthcare facilities and a greater focus on TB prevention for people living with HIV, particularly earlier initiation of and scaling up antiretroviral therapy and scaling up continuous isoniazid preventive therapy, will have a substantial impact on TB control. New TB drugs, diagnostics and vaccines are required to further accelerate progress towards improved TB control in SA and beyon

Tuberculosis control in South Africa: Successes, challenges and recommendations

Tuberculosis (TB) remains a global health threat, and South Africa (SA) has one of the world’s worst TB epidemics driven by HIV. Among the 22 countries with the highest burden of TB, SA has the highest estimated incidence and prevalence of TB, the second highest number of diagnosed multidrug-resistant TB cases, and the largest number of HIV-associated TB cases. Although SA has made notable progress in reducing TB prevalence and deaths and improving treatment outcomes for new smear-positive TB cases, the burden of TB remains enormous. SA has the means to overcome this situation. In addition to better implementing the basics of TB diagnosis and treatment, scaling up the use of Xpert MTB/RIF as a replacement for sputum smear microscopy, strengthening case finding in and beyond healthcare facilities and a greater focus on TB prevention for people living with HIV, particularly earlier initiation of and scaling up antiretroviral therapy and scaling up continuous isoniazid preventive therapy, will have a substantial impact on TB control. New TB drugs, diagnostics and vaccines are required to further accelerate progress towards improved TB control in SA and beyond.

Xpert MTB/RIF versus sputum microscopy as the initial diagnostic test for tuberculosis: a cluster-randomised trial embedded in South African roll-out of Xpert MTB/RIF

Background In South Africa, sputum smear microscopy has been replaced with Xpert MTB/RIF as the initial diagnostic test for tuberculosis. In a pragmatic parallel cluster-randomised trial, we evaluated the eff ect on patient and programme outcomes. Methods We randomly allocated 20 laboratories (clusters) in medium-burden districts of South Africa to either an Xpert (immediate Xpert) or microscopy (Xpert deferred) group (1:1), stratifi ed by province. At two primary care clinics per laboratory, a systematic sample of adults giving sputum for tuberculosis investigation was assessed for eligibility. The primary outcome was mortality at 6 months from enrolment. Masking of participants’ group allocation was not possible because of the pragmatic trial design. The trial is registered with the ISRCTN registry (ISRCTN68905568) and the South African Clinical Trial Register (DOH-27-1011-3849). Findings Between June and November, 2012, 4972 people were screened, and 4656 (93·6%) enrolled (median age 36 years; 2891 [62%] female; 2212 [62%] reported being HIV-positive). There was no diff erence between the Xpert and microscopy groups with respect to mortality at 6 months (91/2324 [3·9%] vs 116/2332 [5·0%], respectively; adjusted risk ratio [aRR] 1·10, 95% CI 0·75–1·62]). Interpretation Xpert did not reduce mortality at 6 months compared with sputum microscopy. Improving outcomes in drug-sensitive tuberculosis programmes might require not only better diagnostic tests but also better linkage to care

Xpert MTB/RIF versus sputum microscopy as the initial diagnostic test for tuberculosis: a cluster-randomised trial embedded in South African roll-out of Xpert MTB/RIF.

BACKGROUND: In South Africa, sputum smear microscopy has been replaced with Xpert MTB/RIF as the initial diagnostic test for tuberculosis. In a pragmatic parallel cluster-randomised trial, we evaluated the effect on patient and programme outcomes. METHODS: We randomly allocated 20 laboratories (clusters) in medium-burden districts of South Africa to either an Xpert (immediate Xpert) or microscopy (Xpert deferred) group (1:1), stratified by province. At two primary care clinics per laboratory, a systematic sample of adults giving sputum for tuberculosis investigation was assessed for eligibility. The primary outcome was mortality at 6 months from enrolment. Masking of participants' group allocation was not possible because of the pragmatic trial design. The trial is registered with the ISRCTN registry (ISRCTN68905568) and the South African Clinical Trial Register (DOH-27-1011-3849). FINDINGS: Between June and November, 2012, 4972 people were screened, and 4656 (93·6%) enrolled (median age 36 years; 2891 [62%] female; 2212 [62%] reported being HIV-positive). There was no difference between the Xpert and microscopy groups with respect to mortality at 6 months (91/2324 [3·9%] vs 116/2332 [5·0%], respectively; adjusted risk ratio [aRR] 1·10, 95% CI 0·75-1·62]). INTERPRETATION: Xpert did not reduce mortality at 6 months compared with sputum microscopy. Improving outcomes in drug-sensitive tuberculosis programmes might require not only better diagnostic tests but also better linkage to care. FUNDING: Bill & Melinda Gates Foundation

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 COVID‑19 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 COVID‑19, 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 COVID‑19 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 COVID‑19 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 COVID‑19 (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 COVID‑19 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 COVID‑19 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 COVID‑19 pandemic

What did we learn from South Africa’s first-ever tuberculosis prevalence survey?

The World Health Organization (WHO) has urged countries to conduct tuberculosis (TB) prevalence surveys to better understand the burden of TB and to enable the WHO to conduct global estimates. Until the report from the first-ever prevalence survey in South Africa (SA), the country had to rely on WHO estimates. The recently published report on the SA TB prevalence survey provides important estimates of the burden of TB disease as well as information on health-seeking behaviour. This review notes the key findings of the 2018 prevalence survey. The high prevalence of TB in SA continues to be a major cause for concern, and calls for a significantly improved response to reach the End TB targets set by the WHO

Implementation and Operational Research: What Happens After a Negative Test for Tuberculosis? Evaluating Adherence to TB Diagnostic Algorithms in South African Primary Health Clinics.

INTRODUCTION AND BACKGROUND: Diagnostic tests for tuberculosis (TB) using sputum have suboptimal sensitivity among HIV-positive persons. We assessed health care worker adherence to TB diagnostic algorithms after negative sputum test results. METHODS: The XTEND (Xpert for TB-Evaluating a New Diagnostic) trial compared outcomes among people tested for TB in primary care clinics using Xpert MTB/RIF vs. smear microscopy as the initial test. We analyzed data from XTEND participants who were HIV positive or HIV status unknown, whose initial sputum Xpert MTB/RIF or microscopy result was negative. If chest radiography, sputum culture, or hospital referral took place, the algorithm for TB diagnosis was considered followed. Analysis of intervention (Xpert MTB/RIF) effect on algorithm adherence used methods for cluster-randomized trials with small number of clusters. RESULTS: Among 4037 XTEND participants with initial negative test results, 2155 (53%) reported being or testing HIV positive and 540 (14%) had unknown HIV status. Among 2155 HIV-positive participants [684 (32%) male, mean age 37 years (range, 18-79 years)], there was evidence of algorithm adherence among 515 (24%). Adherence was less likely among persons tested initially with Xpert MTB/RIF vs. smear [14% (142/1031) vs. 32% (364/1122), adjusted risk ratio 0.34 (95% CI: 0.17 to 0.65)] and for participants with unknown vs. positive HIV status [59/540 (11%) vs. 507/2155 (24%)]. CONCLUSIONS: We observed poorer adherence to TB diagnostic algorithms among HIV-positive persons tested initially with Xpert MTB/RIF vs. microscopy. Poor adherence to TB diagnostic algorithms and incomplete coverage of HIV testing represents a missed opportunity to diagnose TB and HIV, and may contribute to TB mortality

Tuberculosis control in South Africa : successes, challenges and recommendations

Please cite as follows: Churchyard, G. J. et al. 2014. Tuberculosis control in South Africa: successes, challenges and recommendations. South African Medical Journal, 104(3 Suppl 1):244-248, doi:10.7196/SAMJ.7689.The original publication is available at http://www.samj.org.zaTuberculosis (TB) remains a global health threat, and South Africa (SA) has one of the world’s worst TB epidemics driven by HIV. Among the 22 countries with the highest burden of TB, SA has the highest estimated incidence and prevalence of TB, the second highest number of diagnosed multidrug-resistant TB cases, and the largest number of HIV-associated TB cases. Although SA has made notable progress in reducing TB prevalence and deaths and improving treatment outcomes for new smear-positive TB cases, the burden of TB remains enormous. SA has the means to overcome this situation. In addition to better implementing the basics of TB diagnosis and treatment, scaling up the use of Xpert MTB/RIF as a replacement for sputum smear microscopy, strengthening case finding in and beyond healthcare facilities and a greater focus on TB prevention for people living with HIV, particularly earlier initiation of and scaling up antiretroviral therapy and scaling up continuous isoniazid preventive therapy, will have a substantial impact on TB control. New TB drugs, diagnostics and vaccines are required to further accelerate progress towards improved TB control in SA and beyond.http://www.samj.org.za/index.php/samj/article/view/7689Publisher's versio

Key issues in the clinical development and implementation of TB vaccines in South Africa.

Geneeskunde en GesondheidswetenskappePediatrie En KindergesondheidPlease help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]

Key issues in the clinical development and implementation of TB vaccines in South Africa.

Significant progress has been made in advancing the development pipeline for a new and more effective TB vaccine with some candidate vaccines now in late stage clinical evaluation. However, progress has been hampered by an incomplete understanding of the components of a protective immune response and limited animal models, rendering the field unable to reliably predict vaccine efficacy earlier in preclinical development, including by evaluation in animal models, and limiting the predictive utility of comparing immunogenic effects across vaccine candidates in phase I/II studies. Consequently, new candidate vaccines have to be evaluated for efficacy in large-scale phase II/III trials using clinical endpoints. Apart from the technical challenges of characterising TB incidence in target populations at high risk of acquiring TB disease and standardising case definitions in order to improve both the sensitivity and more importantly the specificity of trial endpoints, there is an urgency in expanding and supporting the considerable trial infrastructure that will be required to evaluate and ultimately license a new TB vaccine. In the longer term, implementation strategies are dependent on what policy makers most value. Economic analyses will be essential to guide policy and implementation. This paper outlines the gaps and challenges and identifies solutions for effectively developing and efficiently introducing a new TB vaccine