Preferences of healthcare workers using tongue swabs for tuberculosis diagnosis during COVID-19.

Healthcare workers (HCWs) who come into contact with tuberculosis (TB) patients are at elevated risk of TB infection and disease. The collection and handling of sputum samples for TB diagnosis poses exposure risks to HCWs, particularly in settings where aerosol containment is limited. An alternative sample collection method, tongue swabbing, was designed to help mitigate this risk, and is under evaluation in multiple settings. This study assessed risk perceptions among South African HCWs who used tongue swabbing in TB diagnostic research during the COVID-19 pandemic. We characterized their context-specific preferences as well as the facilitators and barriers of tongue swab use in clinical and community settings. Participants (n = 18) were HCWs with experience using experimental tongue swabbing methods at the South African Tuberculosis Vaccine Initiative (SATVI). We used key informant semi-structured interviews to assess attitudes toward two tongue swab strategies: Provider-collected swabbing (PS) and supervised self-swabbing (SSS). Responses from these interviews were analyzed by rapid qualitative analysis and thematic analysis methods. Facilitators included aversion to sputum (PS and SSS), perceived safety of the method (SSS), and educational resources to train patients (SSS). Barriers included cultural stigmas, as well as personal security and control of their work environment when collecting swabs in community settings. COVID-19 risk perception was a significant barrier to the PS method. Motivators for HCW use of tongue swabbing differed substantially by use case, and whether the HCW has the authority and agency to implement safety precautions in specific settings. These findings point to a need for contextually specific educational resources to enhance safety of and adherence to the SSS collection method.

Safety and Immunogenicity of Newborn MVA85A Vaccination and Selective, Delayed Bacille Calmette-Guerin for Infants of Human Immunodeficiency Virus-Infected Mothers: A Phase 2 Randomized, Controlled Trial.

Background: Vaccination of human immunodeficiency virus (HIV)-infected infants with bacille Calmette-Guérin (BCG) is contraindicated. HIV-exposed newborns need a new tuberculosis vaccination strategy that protects against tuberculosis early in life and avoids the potential risk of BCG disease until after HIV infection has been excluded. Methods: This double-blind, randomized, controlled trial compared newborn MVA85A prime vaccination (1 × 108 PFU) vs Candin® control, followed by selective, deferred BCG vaccination at age 8 weeks for HIV-uninfected infants and 12 months follow-up for safety and immunogenicity. Results: A total of 248 HIV-exposed infants were enrolled. More frequent mild-moderate reactogenicity events were seen after newborn MVA85A vaccination. However, no significant difference was observed in the rate of severe or serious adverse events, HIV acquisition (n = 1 per arm), or incident tuberculosis disease (n = 5 MVA85A; n = 3 control) compared to the control arm. MVA85A vaccination induced modest but significantly higher Ag85A-specific interferon gamma (IFNγ)+ CD4+ T cells compared to control at weeks 4 and 8 (P < .0001). BCG did not further boost this response in MVA85A vaccinees. The BCG-induced Ag85A-specific IFNγ+ CD4+ T-cell response at weeks 16 and 52 was of similar magnitude in the control arm compared to the MVA85A arm at all time points. Proliferative capacity, functional profiles, and memory phenotype of BCG-specific CD4 responses were similar across study arms. Conclusions: MVA85A prime vaccination of HIV-exposed newborns was safe and induced an early modest antigen-specific immune response that did not interfere with, or enhance, immunogenicity of subsequent BCG vaccination. New protein-subunit and viral-vectored tuberculosis vaccine candidates should be tested in HIV-exposed newborns. Clinical Trials Registration: NCT01650389.

Knowledge and acceptability of patient-specific infection control measures for pulmonary tuberculosis.

BACKGROUND: Effective infection control measures are essential to reduce tuberculosis (TB) transmission in domestic, workplace, and health care settings. Acceptability of infection control measures is key to patient adherence. METHODS: We used a prospective questionnaire study to determine knowledge and acceptability of potential patient-specific TB infection control measures in a rural South African community. Fifty adult TB suspects were interviewed at investigation, and 50 newly diagnosed TB patients were interviewed at the start and at the end of TB treatment. RESULTS: TB patients and TB suspects had similar knowledge of infection control measures at baseline. Fifty-seven percent of all participants reported knowing the cause of TB, but only 25% correctly identified microbial etiology. Basic cough hygiene was accepted by 98% of participants. Most participants (89%) accepted wearing of face masks in health facilities, but only 42% of TB suspects and 66% of TB patients (P = .016) would accept wearing face masks at home. Only 68% of participants accepted separate cohorting in health facilities and avoidance of co-sleeping with uninfected household members. At the end of treatment, TB patients demonstrated increased knowledge of TB and increased acceptability of certain household infection control measures. CONCLUSION: Acceptability of patient-specific infection control measures within households increases with acquired knowledge of TB. National control programs should maximize early TB education to improve adherence to infection control measures.

Moxifloxacin population pharmacokinetics in patients with pulmonary tuberculosis and the effect of intermittent high-dose rifapentine.

We described the population pharmacokinetics of moxifloxacin and the effect of high-dose intermittent rifapentine in patients with pulmonary tuberculosis who were randomized to a continuation-phase regimen of 400 mg moxifloxacin and 900 mg rifapentine twice weekly or 400 mg moxifloxacin and 1,200 mg rifapentine once weekly. A two-compartment model with transit absorption best described moxifloxacin pharmacokinetics. Although rifapentine increased the clearance of moxifloxacin by 8% during antituberculosis treatment compared to that after treatment completion without rifapentine, it did not result in a clinically significant change in moxifloxacin exposure.