RESUMO
Background: The first wave of the SARS-CoV-2 global pandemic in early 2020 required a rapid roll-out of infection prevention and control (IPC) training for healthcare workers (HCW), including use of appropriate personal protective equipment (PPE). Education about respiratory droplet and aerosol transmission was of paramount importance to ensure safe working practices and improve confidence. Methods: A joint working group of Infectious Diseases and IPC staff developed a 'train the trainers' programme, to be rapidly deployed over a three-week period. This model utilised a snowballing approach, training selected staff with the intention that they would train their teams, facilitating swift cascading of information. Targeted invitations prompted staff from diverse departments of the hospital to attend. Pre- and post-session questionnaires evaluated staff confidence with regard to appropriate PPE use. Results: The programme trained 130 HCW over a three week period, was well received and led to increased confidence with PPE use amongst staff. Real-time evaluation ensured content could be adapted to the specific needs of HCW involved. We highlight perceived gaps in training despite existing and enhanced training structures. Conclusion: Provision of face-to-face training in transmission-based precautions, including PPE use, is required to maintain confidence in safe and appropriate IPC amongst hospital staff. We highlight the importance of including non-clinical staff in PPE educational programmes, recognising that these roles are vital for patient care and are frequently patient-facing. We recommend adopting the train the trainers model to facilitate rapid dissemination of education, with interactive multidisciplinary training in future outbreaks to improve HCW confidence and effective IPC.
RESUMO
BACKGROUND: Despite being highly prevalent in hospitalised patients with severe HIV-associated tuberculosis (TB) and sepsis, little is known about the mycobacteriology of Mycobacterium tuberculosis bloodstream infection (MTBBSI). We developed methods to serially measure bacillary load in blood and used these to characterise MTBBSI response to anti-TB therapy (ATT) and relationship with mortality. METHODS: We established a microscopy method for direct visualisation of M. tuberculosis bacilli in blood using a novel lysis-concentration protocol and the fluorescent probe, 4-N,N-dimethylaminonaphthalimide-trehalose (DMN-Tre). We tested blood using GeneXpert® MTB/RIF-Ultra (Xpert-ultra) and Myco/F lytic culture after processing blood through lysis-wash steps to remove PCR inhibitors and anti-microbial drug carry-over. HIV-positive patients predicted to have MTBBSI gave blood samples 0, 4, 24, 48 and 72 h after ATT initiation. Bacillary loads were quantified using microscopy, Xpert-ultra cycle threshold, and culture time-to-positivity. Pharmacodynamics were modelled using these measures combined on an ordinal scale, including association with 12-week mortality. FINDINGS: M. tuberculosis was detected in 27 of 28 recruited participants; 25 (89%) by blood Xpert-ultra, 22 (79%) by DMN-Tre microscopy, and 21 (75%) by Myco/F lytic blood culture. Eight (29%) participants died by 12-week follow-up. In a combined pharmacodynamic model, predicted probabilities of negative DMN-Tre microscopy, blood Xpert-ultra, or blood culture after 72 h treatment were 0·64, 0·27, and 0·94, respectively, in those who survived, compared with 0·23, 0·06, and 0·71 in those who died (posterior probability of slower clearance of MTBBSI in those that died >0·99). DMN-Tre microscopy of blood demonstrated heterogenous bacillary morphologies, including microcolonies and clumps. Bacillary cell-length varied significantly with ATT exposure (mean cell-length increase 0·13 log-µm/day; 95%CrI 0·10-0·16). INTERPRETATION: Pharmacodynamics of MTBBSI treatment can be captured using DMN-Tre microscopy, blood Xpert-ultra and culture. This could facilitate interventional trials in severe HIV-associated TB. FUNDING: Wellcome Trust, NIH Fogarty International Center, South African MRC, NIHR(UK), National Research Foundation of South Africa.
