Capacity Building in Sub-Saharan Africa as Part of the INTENSE-TBM Project During the COVID-19 Pandemic.

Tuberculous meningitis (TBM) is the most severe and disabling form of tuberculosis (TB), with at least 100,000 cases per year and a mortality rate of up to 50% in individuals co-infected with human immunodeficiency virus type 1 (HIV-1). To evaluate the efficacy and safety of an intensified anti-tubercular regimen and an anti-inflammatory treatment, the INTENSE-TBM project includes a phase III randomised clinical trial (TBM-RCT) in four countries in sub-Saharan Africa (SSA). Within this framework, we designed a comprehensive capacity-building work package ensuring all centres had, or would acquire, the ability to conduct the TBM-RCT and developing a network of skilled researchers, clinical centres and microbiology laboratories. Here, we describe these activities, identify strengths/challenges and share tools adaptable to other projects, particularly in low- and lower-middle income countries with heterogeneous settings and during the coronavirus disease 2019 (COVID-19) pandemic. Despite major challenges, TBM-RCT initiation was achieved in all sites, promoting enhanced local healthcare systems and encouraging further clinical research in SSA. In terms of certified trainings, the achievement levels were 95% (124/131) for good clinical practice, 91% (39/43) for good clinical laboratory practice and 91% (48/53) for infection prevention and control. Platform-based research, developed as part of capacity-building activities for specific projects, may be a valuable tool in fighting future infectious diseases and in developing high-level research in Africa.

The INTENSE-TBM project aimed to design a comprehensive work-package on capacity building, ensuring all centres would acquire the ability to conduct a phase III randomised clinical trial on TBM in sub-Saharan Africa, to reduce tuberculous meningitis mortality and morbidity in patients with/without HIV-1 co-infection. Therefore, the INTENSE-TBM project is an example of how an international clinical research consortium can provide opportunities to enhance local capacity building and promote centres without previous experience in clinical research. This article provides practical approaches for implementing effective capacity-building programmes. We highlight how to overcome limitations imposed by the COVID-19 pandemic to successfully complete clinics, laboratory set-ups and personnel training, so as to optimise resources and empower African institutions on a local level. At the same time, our experience shows how capacity-building programmes can deliver long-lasting impact that extends beyond the original aims of the project (e.g. HIV and TB), and support local health systems in fighting other infectious disease (e.g. COVID-19). Research projects in low- and lower-middle income countries with heterogeneous settings could stand to benefit the most.

Effect of previous treatment and sputum quality on diagnostic accuracy of Xpert® MTB/RIF.

SETTING: In early studies, Xpert® MTB/RIF accurately detected culture-proven pulmonary tuberculosis (TB). Recent reports have, however, found a lower than expected specificity in previously treated TB patients. OBJECTIVE: To investigate the diagnostic accuracy of Xpert in presumptive pulmonary TB patients in Southwestern Uganda. DESIGN: We obtained demographic and clinical information and collected three sputum samples from each patient for smear microscopy, Xpert and culture. We estimated Xpert sensitivity and specificity against culture, and stratified the analysis by previous treatment and sputum quality status. RESULTS: We analyzed results from 860 presumptive TB patients, including 109 (13%) with a previous history of anti-tuberculosis treatment; 205 (24%) were culture-positive. Xpert specificity was lower (91.8%, 95%CI 84.9-96.2) in previously treated than in new TB patients (97.5%, 95%CI 96.1-98.5; P = 0.01). In an adjusted analysis, patients with culture-, Xpert+ results were more likely to have been previously treated for TB (OR 8.3, 95%CI 2.1-32.0; P = 0.002), and to have mucosalivary sputum (OR 4.1, 95%CI 1.1-14.6; P = 0.03), but were less likely to self-report fever (OR 0.23, 95%CI 0.1-0.7; P = 0.008) than patients with concordant positive results. CONCLUSION: Xpert specificity was lower in previously treated patients with suspected TB. The clinical and programmatic impact of culture-, Xpert+ results requires evaluation in future studies.

Xpert(®) MTB/RIF for detection of Mycobacterium tuberculosis from frozen string and induced sputum sediments.

SETTING: Although it is now widely used for tuberculosis (TB) diagnosis, Xpert(®) MTB/RIF availability remains inadequate in low-resource settings. Moreover, its accuracy in testing stored samples from non-expectorating patients has not been evaluated. OBJECTIVE: To assess the performance of Xpert in frozen samples of induced sputum (IS) and sputum from string test (ST) from non-expectorating individuals with presumed TB. DESIGN: This was a laboratory-based study of 377 ST and IS samples collected between March 2010 and March 2013 at a referral hospital in Uganda. Samples were decontaminated, centrifuged and cultured, and the resultant samples were frozen at -20°C before Xpert evaluation. RESULTS: TB was detected in ST and IS samples from 19/163 (11.7%) children and 63/201 (29.4%) adults using culture. Xpert sensitivity in frozen sediments from children was 37.5% (95%CI 8.5-75.5) in ST and 41.7% (95%CI 15.2-72.3) in IS samples, with specificities of respectively 100% (95%CI 94.9-100) and 98.6% (95%CI 92.7-100). In adults, sensitivity was respectively 50% (95%CI 31.3-68.7) and 48.5% (95%CI 30.8-66.4) in ST and IS samples, with specificities of respectively 100% (95%CI 95.5-100) and 98.6% (95%CI 92.4-100). CONCLUSION: Given these results, and particularly the high specificity, the use of Xpert on frozen ST and IS sediment samples from both children and adults is promising.