Leisha Genade

Background: Tuberculosis preventive therapy (TPT) reduces tuberculosis incidence among people living with HIV (PLHIV), yet uptake has been sub-optimal. We evaluated trends of TPT prescribing among people initiated on antiretroviral therapy (ART). Setting: Thirty-six public sector clinics in South Africa. Methods: We retrospectively analyzed individual-level clinical data abstracted from clinics in the Free State and North West provinces, South Africa. We included PLHIV who initiated ART 2005-2022 and had ≥1 HIV-related clinic visits on or after 15 September 2021. The timing of TPT prescribing was defined by the earliest recorded TPT prescription date as: (1) TPT prescription within ≤6 months, (2) TPT prescription >6 months, or (3) no recorded TPT prescription on or after ART initiation. Results: Among 48,718 ART initiators, 23,168 (47.6%) were prescribed TPT on or after ART initiation; 15,510 (31.8%) were prescribed TPT ≤6 months and 7,658 (15.7%) were prescribed TPT >6 months after ART initiation. Early TPT prescribing increased from 0.7% in the 2005-2010 cohort to 71.3% in 2022 ART initiators, while TPT prescribing >6 months after ART initiation declined from 28.5% in the 2005-2010 cohort to 1.3% among those who initiated ART in 2022. Cumulative TPT prescribing was 29.2% in the 2005-2010 cohort, 34.2% in the 2011-2015 cohort, and 72.6% in the 2022 cohort. Conclusions: Over 2005-2022, TPT prescribing shifted markedly toward initiation near the time of ART initiation, with early prescribing exceeding 70% by 2022. Cumulative prescribing remained low among people from earlier ART cohorts, underscoring the need for targeted catch-up strategies.

Background/Objectives: Tuberculosis (TB) and SARS-CoV-2 share similar symptoms and transmission routes. In early 2021, USAID and Stop TB Partnership recommended an integrated approach for simultaneous COVID-19 and TB testing in high TB burden countries for individuals with respiratory symptoms. In this evaluation, we tested a single sputum for both SARS-CoV-2 and Mycobacterium tuberculosis complex (MTBC) from participants at two healthcare facilities in South Africa. The diagnostic accuracy of the Xpert Xpress SARS-CoV-2 (Xpress) assay using a sputum swab capture method was assessed by comparing the results with routine SARS-CoV-2 testing, while also determining the prevalence of TB and TB-COVID-19 co-infection in the study population. Methods: A total of 2274 individuals were screened for enrolment. Eligibility included the presence of respiratory symptoms, close contact with a person with TB, TB diagnosis in the last two years or a person living with HIV. Sputum from 1032 participants was tested on the Xpress assay using a swab capture method while residual sputum was tested on the Xpert MTB/RIF Ultra assay for MTBC and rifampicin-resistance detection. Concordance between the Xpress assay and routine SARS-CoV-2 testing was assessed. Results: The Xpress assay detected SARS-CoV-2 in 183/1032 (18%) participants, TB was detected in 35/1032 (3%) participants and 10/1032 (1%) participants were co-infected with TB and COVID-19. The Xpress assay showed substantial agreement with routine testing (Kappa: 0.755). Conclusions: The study findings underscore a substantial identification of TB and rifampicin-resistant TB that would have been missed if bi-disease testing was not performed. In addition, the sputum swab capture method demonstrated reliable performance for SARS-CoV-2 detection.

Background/Objectives: Both tuberculosis (TB) and SARS-CoV-2 share similar symptoms and transmission routes. In early 2021, USAID and Stop TB Partnership recommended an integrated approach for simultaneous COVID-19 and TB testing in high TB burden countries, using a nasopharyngeal swab and sputum for individuals with respiratory symptoms. We extended this in a clinical evaluation, testing a single sputum for both SARS-CoV-2 and Mycobacterium tuberculosis complex (MTBC) at two healthcare facilities in South Africa. Methods: A total of 2274 individuals were screened for enrolment. Eligibility included the presence of symptoms suggestive of either TB or COVID-19 infection, close contact with a person with TB, TB diagnosis in the last two years or a person living with HIV. Sputum from 1032 participants were tested on the Xpert Xpress SARS CoV-2 assay (Xpress) using a swab capture method while residual sputum was tested on the Xpert MTB/RIF Ultra assay for MTBC and rifampicin-resistance detection. Results: The Xpress assay detected SARS CoV-2 in 183/1032 (18%) participants, TB was detected in 35/1032 (3%) participants and 10/1032 (1%) participants were co-infected with TB and COVID-19. Conclusions: The study findings underscore a substantial identification of TB and Rifampicin-resistant TB that would have been missed if bi-disease testing was not performed. In addition, the sputum swab capture method for SARS-CoV-2 detection showed substantial agreement with routine testing.

Background: The World Health Organization (WHO) recommends systematic symptom screening for tuberculosis (TB). However, TB prevalence surveys suggest that this strategy does not identify millions of TB patients, globally. Undiagnosed or delayed diagnosis of TB contribute to TB transmission and exacerbate morbidity and mortality. We conducted a cluster-randomized trial of large urban and rural primary healthcare clinics in 3 provinces of South Africa to evaluate whether a novel intervention of targeted universal testing for TB (TUTT) in high-risk groups diagnosed more patients with TB per month compared to current standard of care (SoC) symptom-directed TB testing. Methods and findings: Sixty-two clinics were randomized; with initiation of the intervention clinics over 6 months from March 2019. The study was prematurely stopped in March 2020 due to clinics restricting access to patients, and then a week later due to the Coronavirus Disease 2019 (COVID-19) national lockdown; by then, we had accrued a similar number of TB diagnoses to that of the power estimates and permanently stopped the trial. In intervention clinics, attendees living with HIV, those self-reporting a recent close contact with TB, or a prior episode of TB were all offered a sputum test for TB, irrespective of whether they reported symptoms of TB. We analyzed data abstracted from the national public sector laboratory database using Poisson regression models and compared the mean number of TB patients diagnosed per clinic per month between the study arms. Intervention clinics diagnosed 6,777 patients with TB, 20.7 patients with TB per clinic month (95% CI 16.7, 24.8) versus 6,750, 18.8 patients with TB per clinic month (95% CI 15.3, 22.2) in control clinics during study months. A direct comparison, adjusting for province and clinic TB case volume strata, did not show a significant difference in the number of TB cases between the 2 arms, incidence rate ratio (IRR) 1.14 (95% CI 0.94, 1.38, p = 0.46). However, prespecified difference-in-differences analyses showed that while the rate of TB diagnoses in control clinics decreased over time, intervention clinics had a 17% relative increase in TB patients diagnosed per month compared to the prior year, interaction IRR 1.17 (95% CI 1.14, 1.19, p < 0.001). Trial limitations were the premature stop due to COVID-19 lockdowns and the absence of between-arm comparisons of initiation and outcomes of TB treatment in those diagnosed with TB. Conclusions: Our trial suggests that the implementation of TUTT in these 3 groups at extreme risk of TB identified more TB patients than SoC and could assist in reducing undiagnosed TB patients in settings of high TB prevalence. Trial registration: South African National Clinical Trials Registry DOH-27-092021-4901.