Abstract Background In the high disease burden and resource-constrained contexts of sub-Saharan Africa (SSA), health workers experience a range of psychosocial stressors that leave them vulnerable to developing burnout, which can reduce service quality and negatively impact their own health and wellbeing. As universal testing and treatment (UTT) for HIV scales up across SSA, we sought to understand the implications of this human resource-intensive approach to HIV prevention to inform decision-making about health workforce staffing and support needs. Methods Using the Maslach Burnout Inventory-Human Services Survey (MBI-HSS), we assessed the prevalence of three domains of burnout—emotional exhaustion, depersonalization, and personal accomplishment—among three cadres of health workers delivering health services in areas receiving a UTT intervention in Zambia and South Africa. These cadres included health facility workers (n = 478), community health workers (n = 159), and a study-specific cadre of community HIV care providers (n = 529). We used linear regression to assess risk factors associated with emotional exhaustion, the only domain with sufficient variation in our sample. Results The MBI-HSS was completed by 1499/2153 eligible participants (69.6% response rate). Less than 1% of health workers met Maslach’s definition for burnout. All groups of health workers reported lower levels of emotional exhaustion than found in previous studies of this type (mean score scores ranged from 10.7 to 15.4 out of 54 across health cadres). Higher emotional exhaustion was associated with higher educational attainment (βadj = 2.24, 95% CI 0.76 to 3.72), greater years providing HIV services (βadj = 0.20, 95% CI 0.03 to 0.36), and testing negative for HIV at last HIV test (βadj = − 3.88 − 95% CI 5.69 to − 2.07). Working as a CHW was significantly associated with lower emotional exhaustion (βadj = − 2.52, 95% CI − 4.69 to − 0.35). Among all health workers, irrespective of HIV status, witnessing stigmatizing behaviors towards people living with HIV among their co-workers was associated with significantly increased emotional exhaustion (βadj = 3.38, 95% CI 1.99 to 4.76). Conclusions The low level of burnout detected among health workers is reassuring. However, it remains important to assess how UTT may affect levels of emotional exhaustion among health workers over time, particularly in the context of emerging global pandemics, as burnout may impact the quality of HIV services they provide and their own mental health and wellbeing. Interventions to reduce HIV stigma in health facilities may protect against emotional exhaustion among health workers, as well as interventions to increase mindfulness and resilience among health workers at risk of burnout. Trial registration ClinicalTrials.gov number: NCT01900977.

OBJECTIVES:To evaluate diagnostic yield and feasibility of integrating testing for TB and COVID-19 using molecular and radiological screening tools during community-based active case-finding (ACF).METHODS:Community-based participants with presumed TB and/or COVID-19 were recruited using a mobile clinic. Participants underwent simultaneous point-of-care (POC) testing for TB (sputum; Xpert Ultra) and COVID-19 (nasopharyngeal swabs; Xpert SARS-CoV-2). Sputum culture and SARS-CoV-2 RT-PCR served as reference standards. Participants underwent ultra-portable POC chest radiography with computer-aided detection (CAD). TB infectiousness was evaluated using smear microscopy, cough aerosol sampling studies (CASS), and chest radiographic cavity detection. Feasibility of POC testing was evaluated via user-appraisals.RESULTS:Six hundred and one participants were enrolled, with 144/601 (24.0%) reporting symptoms suggestive of TB and/or COVID-19. 16/144 (11.1%) participants tested positive for TB, while 10/144 (6.9%) tested positive for COVID-19 (2/144 [1.4%] had concurrent TB/COVID-19). Seven (7/16 [43.8%]) individuals with TB were probably infectious. Test-specific sensitivity and specificity (95% CI) were: Xpert Ultra 75.0% (42.8-94.5) and 96.9% (92.4-99.2); Xpert SARS-CoV-2 66.7% (22.3-95.7) and 97.1% (92.7-99.2). Area under the curve (AUC) for CAD4TB was 0.90 (0.82-0.97). User appraisals indicated POC Xpert to have 'good' user-friendliness.CONCLUSIONS:Integrating TB/COVID-19 screening during community-based ACF using POC molecular and radiological tools is feasible, has a high diagnostic yield, and can identity probably infectious persons.

Background Almost 40% of persons newly diagnosed with TB are unreported. Detecting cases in TB/HIV endemic communities have been restricted by a lack of sensitive and user-friendly point-of-care (POC) diagnostic tools. Computer-aided detection (CAD) has been recommended by the WHO for screening for TB, however, implementation of CAD in community-based active case finding (ACF) is unclear. We aimed determine the adjunctive role of CAD in Xpert-orientated community-based ACF for TB. Methods In this ongoing, EDCTP-funded (RIA2020S-3295), open-labelled randomised controlled trial (RCT), high-risk persons (symptomatic and/or HIV-infected) with presumed TB were recruited from TB/HIV endemic communities in South Africa and Zambia (Zimbabwe is an additional site). Using a low-cost mobile van staffed by three healthcare workers and equipped with an ultra-portable x-ray and GeneXpert® system, participants were randomized into either ‘CAD + POC Xpert’ (Arm 1: CAD followed by Xpert MTB/RIF Ultra in CAD-positive participants using a CAD4TB v7 threshold of 10 [South Africa] and 50 [Zambia] based on prior population-specific calibration), or ‘POC Xpert alone’ (Arm 2: POC Xpert MTB/RIF Ultra only). The primary outcome was time to detection of microbiologically proven TB (Xpert and/or culture positivity). Here we present an interim trial progress report. Results From Feb 2022, a total of 505 participants have been enrolled (256 [50.7%] from South Africa and 249 [49.3%] from Zambia). 26.9% (136/505) of participants were HIV-infected (median CD4 of 609). 33/505 (6.5%) tested positive for TB (25/256 [9.8%] in South Africa and 8/249 [3.2%] in Zambia). 15 participants underwent screening to detect 1 case of TB. Of TB-positive participants, 7/33 (21.2%) were smear positive. Conclusion Community-based ACF detected a high burden of TB, of which a significant minority (~20%) was probably infectious. These data have implications for ACF strategies in high burden settings.

The performance of the Xpert© MTB/RIF and MTBDRplus assays for the detection of rifampicin resistant Mycobacterium tuberculosis was compared to culture-based drug susceptibility testing in 30 specimens with rifampicin-resistant and rifampicin-indeterminate Xpert MTB/RIF results collected between March 2012 and March 2014. Xpert MTB/RIF and MTBDRplus were 100% sensitive and 100% concordant for rifampicin resistance detection, but 3 of 13 samples (23%) positive for rifampicin resistance on Xpert MTB/RIF and MTBDRplus were negative for rifampicin resistance on mycobacteria growth indicator tube drug susceptibility testing. Specificity was 72% for Xpert MTB/RIF and 80% for MTBDRplus. Positive predictive value for Xpert MTB/RIF for multidrug resistant tuberculosis was 47.8% for new patients and 77.8% for previously treated patients; negative predictive value was 100% for both new and previously treated patients. The discordant rifampicin resistance test results indicate a need to fully characterise circulating rifampicin resistant Mycobacterium tuberculosis strains in Zambia and to inform the development of guidelines for decision-making in relation to diagnosis of drug-resistant tuberculosis.

BACKGROUND:Household (HH) contact tracing is a strategy that targets high risk groups for TB. Symptom based screening is the standard used to identify HH contacts at risk for TB during HH contact tracing for TB. However, this strategy may be limited due to poor performance in predicting TB. The objective of this study was to compare CXR with Computer Aided Diagnosis (CAD) against symptom screen for defining presumptive TB and how TB detection changes with each method.METHODS:Household contacts of consecutive index bacteriologically confirmed TB cases were visited by study teams and given TB/HIV education to raise awareness of the risk of TB following close contact with a TB patient. Contacts were encouraged to visit the health facility for screening; where symptoms history was obtained and opt out HIV testing was provided as part of the screening process. CXR was offered to all regardless of symptoms, followed by definitive sputum test with either Xpert MTB RIF or smear microscopy.RESULTS:Among 919 HH contacts that presented for screening, 865 were screened with CXR and 464 (53.6%) had an abnormal CXR and the rest had a normal CXR. Among 444 HH contacts with valid sputum results, 274 (61.7%) were symptom screen positive and 255 (57.4%) had an abnormal CXR. Overall, TB was diagnosed in 32/444 (7.2%); 13 bacteriologically unconfirmed and 19 bacteriologically confirmed. Of 19 bacteriologically confirmed TB 8 (42.1%) were symptom screen negative contacts with an abnormal CXR and these 6/8 (75.0%) were HIV positive. Among the 13 bacteriologically unconfirmed TB cases, 7 (53.8%) were HIV positive and all had an abnormal CXR.CONCLUSION:Symptom screen if used alone with follow on definitive TB testing only for symptom screen positive individuals would have missed eight of the 19 confirmed TB cases detected in this study. There is need to consider use of other screening strategies apart from symptom screen alone for optimal rule out of TB especially in HIV positive individuals that are at greatest risk of TB and present atypically.

Background Combination of genotypic assays (Xpert MTB/ RIF and MTBDRplus (LiPA) would be a powerful tool to shorten the time for diagnosis of MDR tuberculosis (TB). However, the algorithm used for these assays in Zambia has not yet been implemented and the most widely used drug susceptibility testing (DST) method remains MGIT DST. Missed rifampicin resistance on the MGIT 960 system has been reported by several studies due to silent rpoB gene mutations. We report comparative observations made on the performance of Xpert, LiPA and MGIT DST methods for detection of rifampicin resistance (RR) at the ZAMBART Central Laboratory (ZCL). Methods Specimens were collected from consecutive patients with Xpert rifampicin resistance positive (RR+) or rifampicin resistance indeterminate (RRI) results at peripheral site laboratories for further testing at the ZCL. Each sample was tested using Xpert, LiPA and MGIT culture/DST. Results 30 patient samples were received and 17 were RR+, 8 were rifampicin-sensitive (RR-) and 5 were TB-negative by Xpert. All 17 RR+ on Xpert were RR+ on LiPA and all 8 Xpert RR – were sensitive on LiPA giving a 100% concordance for diagnosis of RR. Three isolates that were rifampicin sensitive by the MGIT system (Gold standard) were RR+ by both genotypic tests. Genotypic tests showed evidence of mutation in the codon 526 region of the rpoB gene for all the three isolates with discordant RR MGIT DST results. Xpert positive predictive value for Multidrug Resistance (MDR) TB was 62.5% and 81.2% compared to MGIT DST and LiPA, respectively. Conclusions There is need for Zambia to perform a full classification of rpoB mutations to determine the prevalence of silent mutations. This will optimise national guidelines for diagnosis of RR – and MDR-TB.

Background The current cost of Xpert MTB RIF (Xpert) consumables is such that algorithms are needed to select which patients to prioritise for testing with Xpert. Objective To evaluate two algorithms for prioritisation of Xpert in primary health care settings in a high TB and HIV burden setting. Method Consecutive, presumptive TB patients with a cough of any duration were offered either Xpert or Fluorescence microscopy (FM) test depending on their CXR score or HIV status. In one facility, sputa from patients with an abnormal CXR were tested with Xpert and those with a normal CXR were tested with FM (“CXR algorithm”). CXR was scored automatically using a Computer Aided Diagnosis (CAD) program. In the other facility, patients who were HIV positive were tested using Xpert and those who were HIV negative were tested with FM (“HIV algorithm”). Results Of 9482 individuals pre-screened with CXR, Xpert detected TB in 2090/6568 (31.8%) with an abnormal CXR, and FM was AFB positive in 8/2455 (0.3%) with a normal CXR. Of 4444 pre-screened with HIV, Xpert detected TB in 508/2265 (22.4%) HIV positive and FM was AFB positive in 212/1920 (11.0%) in HIV negative individuals. The notification rate of new bacteriologically confirmed TB increased; from 366 to 620/ 100,000/yr and from 145 to 261/100,000/yr at the CXR and HIV algorithm sites respectively. The median time to starting TB treatment at the CXR site compared to the HIV algorithm site was; 1(IQR 1-3 days) and 3 (2-5 days) (p<0.0001) respectively. Conclusion Use of Xpert in a resource-limited setting at primary care level in conjunction with pre-screening tests reduced the number of Xpert tests performed. The routine use of Xpert resulted in additional cases of confirmed TB patients starting treatment. However, there was no increase in absolute numbers of patients starting TB treatment. Same day diagnosis and treatment commencement was achieved for both bacteriologically confirmed and empirically diagnosed patients where Xpert was used in conjunction with CXR.

ObjectiveTo determine the sensitivity and specificity of a Computer Aided Diagnosis (CAD) program for scoring chest x-rays (CXRs) of presumptive tuberculosis (TB) patients compared to Xpert MTB/RIF (Xpert).MethodConsecutive presumptive TB patients with a cough of any duration were offered digital CXR, and opt out HIV testing. CXRs were electronically scored as normal (CAD score ≤ 60) or abnormal (CAD score > 60) using a CAD program. All patients regardless of CAD score were requested to submit a spot sputum sample for testing with Xpert and a spot and morning sample for testing with LED Fluorescence Microscopy-(FM).ResultsOf 350 patients with evaluable data, 291 (83.1%) had an abnormal CXR score by CAD. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CXR compared to Xpert were 100% (95%CI 96.2-100), 23.2% (95%CI 18.2-28.9), 33.0% (95%CI 27.6-38.7) and 100% (95% 93.9-100), respectively. The area under the receiver operator curve (AUC) for CAD was 0.71 (95%CI 0.66-0.77). CXR abnormality correlated with smear grade (r = 0.30, p<0.0001) and with Xpert CT(r = 0.37, p<0.0001).ConclusionsTo our knowledge this is the first time that a CAD program for TB has been successfully tested in a real world setting. The study shows that the CAD program had high sensitivity but low specificity and PPV. The use of CAD with digital CXR has the potential to increase the use and availability of chest radiography in screening for TB where trained human resources are scarce.