Pren Naidoo

The End Tuberculosis (TB) programme has set ambitious targets to reduce TB incidence by 80% and mortality by 90% globally, by 2030 (both relative to 2015 levels) [1]. Many new TB interventions have...

Every person diagnosed with tuberculosis (TB) needs to initiate treatment. The WHO estimated 61% of people who developed TB in 2021 were included in a TB treatment registration system. Initial loss to follow up (ILTFU) is the loss of persons to care between diagnosis and treatment initiation/registration. LINKEDin, a quasi-experimental study, evaluated the effect of two interventions (hospital-recording and an alert-and-response patient management intervention) in six sub-districts across three high-TB burden provinces of South Africa. Using integrated electronic reports, we identified all persons diagnosed with TB (Xpert MTB/RIF positive) in hospital and at primary healthcare facilities. We prospectively determined linkage to care at 30 days after TB diagnosis. We calculated the risk of ILTFU during the baseline and intervention periods and the relative risk reduction in ILTFU between these periods. We found a relative reduction in ILTFU of 42.4% (95%CI:28.5,53.7) in KwaZulu Natal (KZN) and 22.3% (95%CI:13.3,30.4) in the Western Cape (WC) with no significant change in Gauteng. In KZN and the WC, the relative reduction in ILTFU appeared greater in sub-districts where the alert-and-response patient management intervention was implemented; KZN (49.3% (95%CI:32.4,62) vs 32.2% (95%CI:5.4,51.4)); and WC (34.2% (95%CI:20.9,45.3) vs 13.4% (95%CI:0.7,24.4)). We reported a notable reduction in ILTFU in two provinces using existing routine health service data and applying a simple intervention to trace and recall those not linked to care. TB programs need to consider ILTFU as a priority and develop interventions specific to their context to ensure improved linkage to care.

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.

Objectives The tuberculosis (TB) MATE study evaluated whether a differentiated care approach (DCA) based on tablet-taking data from Wisepill evriMED digital adherence technology could improve TB treatment adherence. The DCA entailed a stepwise increase in adherence support starting from short message service (SMS) to phone calls, followed by home visits and motivational counselling. We explored feasibility of this approach with providers in implementing clinics. Design Between June 2020 and February 2021, in-depth interviews were conducted in the provider’s preferred language, audiorecorded, transcribed verbatim and translated. The interview guide included three categories: feasibility, system-level challenges and sustainability of the intervention. We assessed saturation and used thematic analysis. Setting Primary healthcare clinics in three provinces of South Africa. Participants We conducted 25 interviews with 18 staff and 7 stakeholders. Results Three major themes emerged: First, providers were supportive of the intervention being integrated into the TB programme and were eager to be trained on the device as it helped to monitor treatment adherence. Second, there were challenges in the adoption system such as shortage of human resources which could serve as a barrier to information provision once the intervention is scaled up. Healthcare workers reported that some patients received incorrect SMS’s due to delays in the system that contributed to distrust. Third, DCA was considered as a key aspect of the intervention by some staff and stakeholders since it allowed for support based on individual needs. Conclusions It was feasible to monitor TB treatment adherence using the evriMED device and DCA. To ensure successful scale-up of the adherence support system, emphasis will need to be placed on ensuring that the device and the network operate optimally and continued support on adhering to treatment which will enable people with TB to take ownership of their treatment journey and help overcome TB-related stigma. Trial registration number Pan African Trial Registry PACTR201902681157721.

Background: South Africa has achieved drug-susceptible TB (DS-TB) treatment success of only 77% among people with new and previously treated TB. Alternative approaches are required to improve medication adherence and treatment completion to limit transmission, TB relapse and the development of resistance. This study aims to implement and evaluate the use of adherence medication monitors (Wisepill evriMED 1000) with a differentiated response to patient care, among DS-TB patients in three provinces of South Africa. Methods: In total, 18 public health clinics across three provinces were selected. Clinics were randomised to intervention or standard of care clinics. In each clinic, approximately 145 DS-TB patients are being enrolled to reach a total of 2610. All patients have their daily adherence monitored using medication monitors. In the intervention arm, patients are receiving medication monitor reminders and differentiated care in response to adherence data. This weekly review of daily real-time monitoring will be undertaken from a central database. The differentiated care model includes automated SMS reminders with a missed dose, research staff-initiated phone call to the patient with a second or third missed dose, a home visit if four or more doses are missed, and motivational counselling if four or more doses are missed repeatedly. Fidelity of the intervention will be measured through process evaluation. Patients in control clinics will receive medication monitors for adherence tracking, standard of care TB education, and normal clinic follow-up procedures. The primary outcome is the proportion of patients by arm with >80% adherence, as measured by the medication monitor. The feasibility and acceptability of the intervention will be assessed by in-depth interviews with patients, stakeholders, and study staff. A cost effectiveness analysis of the intervention and standard of care clinics will be conducted. Significance: This trial will provide evidence for the use of an intervention, including medication monitors and differentiated care package, to improve adherence to TB treatment. Improved adherence should also improve TB treatment completion rates, thus reducing loss to follow-up rates, and TB relapse among people with TB. The intervention is intended to ultimately improve overall TB control and reduce TB transmission in South Africa. Trial registration: Pan African Trial Registry PACTR201902681157721. Registered on 11 February 2019.

While tuberculosis incidence and mortality are declining in South Africa, meeting the goals of the End TB Strategy requires an invigorated programmatic response informed by accurate data. Enumerating the losses at each step in the care cascade enables appropriate targeting of interventions and resources. We estimated the tuberculosis burden; the number and proportion of individuals with tuberculosis who accessed tests, had tuberculosis diagnosed, initiated treatment, and successfully completed treatment for all tuberculosis cases, for those with drug-susceptible tuberculosis (including human immunodeficiency virus (HIV)–coinfected cases) and rifampicin-resistant tuberculosis. Estimates were derived from national electronic tuberculosis register data, laboratory data, and published studies. The overall tuberculosis burden was estimated to be 532005 cases (range, 333760–764480 cases), with successful completion of treatment in 53% of cases. Losses occurred at multiple steps: 5% at test access, 13% at diagnosis, 12% at treatment initiation, and 17% at successful treatment completion. Overall losses were similar among all drug-susceptible cases and those with HIV coinfection (54% and 52%, respectively, successfully completed treatment). Losses were substantially higher among rifampicin- resistant cases, with only 22% successfully completing treatment. Although the vast majority of individuals with tuberculosis engaged the public health system, just over half were successfully treated. Urgent efforts are required to improve implementation of existing policies and protocols to close gaps in tuberculosis diagnosis, treatment initiation, and successful treatment completion.

Primary health services in Cape Town, South Africa where the introduction of Xpert^® MTB/RIF (Xpert) enabled simultaneous screening for tuberculosis (TB) and drug susceptibility in all presumptive cases. To compare the proportion of TB cases with drug susceptibility tests undertaken and multidrug-resistant tuberculosis (MDR-TB) diagnosed pre-treatment and during the course of 1st line treatment in the previous smear/culture and the newly introduced Xpert-based algorithms. TB cases identified in a previous stepped-wedge study of TB yield in five sub-districts over seven one-month time-points prior to, during and after the introduction of the Xpert-based algorithm were analysed. We used a combination of patient identifiers to identify all drug susceptibility tests undertaken from electronic laboratory records. Differences in the proportions of DST undertaken and MDR-TB cases diagnosed between algorithms were estimated using a binomial regression model. Pre-treatment, the probability of having a DST undertaken (RR = 1.82)(p<0.001) and being diagnosed with MDR-TB (RR = 1.42)(p<0.001) was higher in the Xpert-based algorithm than in the smear/culture-based algorithm. For cases evaluated during the course of 1st-line TB treatment, there was no significant difference in the proportion with DST undertaken (RR = 1.02)(p = 0.848) or MDR-TB diagnosed (RR = 1.12)(p = 0.678) between algorithms. Universal screening for drug susceptibility in all presumptive TB cases in the Xpert-based algorithm resulted in a higher overall proportion of MDR-TB cases being diagnosed and is an important strategy in reducing transmission. The previous strategy of only screening new TB cases when 1st line treatment failed did not compensate for cases missed pre-treatment.

Primary health services in Cape Town, South Africa. To compare tuberculosis (TB) diagnostic yield in an existing smear/culture-based and a newly introduced Xpert^® MTB/RIF-based algorithm. TB diagnostic yield (the proportion of presumptive TB cases with a laboratory diagnosis of TB) was assessed using a non-randomised stepped-wedge design as sites transitioned to the Xpert^® based algorithm. We identified the full sequence of sputum tests recorded in the electronic laboratory database for presumptive TB cases from 60 primary health sites during seven one-month time-points, six months apart. Differences in TB yield and temporal trends were estimated using a binomial regression model. TB yield was 20.9% (95% CI 19.9% to 22.0%) in the smear/culture-based algorithm compared to 17.9% (95%CI 16.4% to 19.5%) in the Xpert^® based algorithm. There was a decline in TB yield over time with a mean risk difference of -0.9% (95% CI -1.2% to -0.6%) (p® based algorithm with a risk difference of 0.3% (95% CI -1.8% to 2.3%) (p = 0.796). Culture tests were undertaken for 35.5% of smear-negative compared to 17.9% of Xpert^® negative low MDR-TB risk cases and for 82.6% of smear-negative compared to 40.5% of Xpert^® negative high MDR-TB risk cases in respective algorithms. Introduction of an Xpert^® based algorithm did not produce the expected increase in TB diagnostic yield. Studies are required to assess whether improving adherence to the Xpert^® negative algorithm for HIV-infected individuals will increase yield. In light of the high cost of Xpert^®, a review of its role as a screening test for all presumptive TB cases may be warranted.

The South African government is striving for universal access to HIV counselling and testing (HCT), a fundamental component of HIV care and prevention. In the Cape Town district, Western Cape Province of South Africa, HCT is provided free of charge at publically funded primary health care (PHC) facilities and through non-governmental organizations (NGOs). This study investigated the availability and accessibility of HCT services; comparing health seeking behaviour and client experiences of HCT across public PHC facilities (fixed sites) and NGO mobile services. This qualitative study used semi-structured interviews. Systematic sampling was used to select 16 participants who accessed HCT in either a PHC facility (8) or a NGO mobile service (8). Interviews, conducted between March and June 2011, were digitally recorded, transcribed and where required, translated into English. Constant comparative and thematic analysis was used to identify common and divergent responses and themes in relation to the key questions (reasons for testing, choice of service provider and experience of HCT). The sample consisted of 12 females and 4 males with an age range of 19–60 years (median age 28 years). Motivations for accessing health facilities and NGO services were similar; opportunity to test, being affected by HIV and a perceived personal risk for contracting HIV. Participants chose a particular service provider based on accessibility, familiarity with and acceptability of that service. Experiences of both services were largely positive, though instances of poor staff attitude and long waiting times were reported at PHC facilities. Those attending NGO services reported shorter waiting times and overall positive testing experiences. Concerns about lack of adequate privacy and associated stigma were expressed about both services. Realised access to HCT is dependent on availability and acceptability of HCT services. Those who utilised either a NGO mobile service or a public PHC facility perceived both service types as available and acceptable. Mobile NGO services provided an accessible opportunity for those who would otherwise not have tested at that time. Policy makers should consider the perceptions and experiences of those accessing HCT services when increasing access to HCT.

SETTING: Ten primary health care facilities in Cape Town, South Africa, 2010–2013. OBJECTIVE: A comparison of costs incurred by patients in GenoType^® MDRTBplus line-probe assay (LPA) and Xpert^® MTB/RIF-based diagnostic algorithms from symptom onset until treatment initiation for multidrug-resistant tuberculosis (MDR-TB). METHODS: Eligible patients identified from laboratory and facility records were interviewed 3–6 months after treatment initiation and a cost questionnaire completed. Direct and indirect costs, individual and household income, loss of individual income and change in household income were recorded in local currency, adjusted to 2013 costs and converted to $US. RESULTS: Median number of visits to initiation of MDR-TB treatment was reduced from 20 to 7 (P < 0.001) and median costs fell from US$68.1 to US$38.3 (P = 0.004) in the Xpert group. From symptom onset to being interviewed, the proportion of unemployed increased from 39% to 73% in the LPA group (P < 0.001) and from 53% to 89% in the Xpert group (P < 0.001). Median household income decreased by 16% in the LPA group and by 13% in the Xpert group. CONCLUSION: The introduction of an Xpert-based algorithm brought relief by reducing the costs incurred by patients, but loss of employment and income persist. Patients require support to mitigate this impact.