RESUMEN
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.
RESUMEN
BACKGROUND: Meticillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA) are responsible for outbreaks in intensive care units. MSSA infections have the same morbidity and mortality rate as MRSA infections but are studied less often. Whole-genome sequencing (WGS) is used increasingly for outbreak monitoring, but still requires specific installation and trained personnel to obtain and analyse the data. AIM: To evaluate the workflow and benefits of EpiSeq solution (bioMérieux, Marcy l'Etoile, France) in exploring the increased incidence of S. aureus bloodstream infections in a neonatal intensive care unit (NICU). METHODS: Four S. aureus bacteraemia isolates and 27 colonization isolates obtained between January and July 2016 were submitted to the 'all in one solution' EpiSeq [WGS, quality data assessment, multi-locus sequence typing (MLST), spa typing, virulome and resistome characterization, and phylogenetic tree construction]. More in-depth analyses were performed (whole-genome MLST and whole-genome single nucleotide polymorphism (wgSNP)] with BioNumerics software (Applied Maths, Sint-Martens-Latem, Belgium). FINDINGS: Nine different sequence types and 13 different spa types were found among the 31 isolates studied. Among those isolates, 11 (seven patients) were ST146 spa type t002, five (four patients) were ST30 and four (four patients) were ST398. The 11 ST146 isolates had a maximum of seven pairwise SNP differences. CONCLUSION: Use of EpiSeq solution allowed fast demonstration of the polyclonal profile of the MSSA population in neonates, and enabled the suspicion of a global outbreak to be ruled out. However, wgSNP analysis showed the transmission and persistence of one sequence type for over six months in the NICU, and enabled the infection control team to adapt its response.
