Exhaled Mycobacterium tuberculosis output and detection of subclinical disease by face-mask sampling: prospective observational studies.

BACKGROUND: Tuberculosis remains a global health challenge, with early diagnosis key to its reduction. Face-mask sampling detects exhaled Mycobacterium tuberculosis. We aimed to investigate bacillary output from patients with pulmonary tuberculosis and to assess the potential of face-mask sampling as a diagnostic method in active case-finding. METHODS: We did a 24-h longitudinal study in patients from three hospitals in Pretoria, South Africa, with microbiologically confirmed pulmonary tuberculosis. Patients underwent 1 h of face-mask sampling eight times over a 24-h period, with contemporaneous sputum sampling. M tuberculosis was detected by quantitative PCR. We also did an active case-finding pilot study in inhabitants of an informal settlement near Pretoria. We enrolled individuals with symptoms of tuberculosis on the WHO screening questionnaire. Participants provided sputum and face-mask samples that were tested with the molecular assay Xpert MTB/RIF Ultra. Sputum-negative and face-mask-positive individuals were followed up prospectively for 20 weeks by bronchoscopy, PET-CT, and further sputum analysis to validate the diagnosis. FINDINGS: Between Sept 22, 2015, and Dec 3, 2015, 78 patients with pulmonary tuberculosis were screened for the longitudinal study, of whom 24 completed the study (20 had HIV co-infection). M tuberculosis was detected in 166 (86%) of 192 face-mask samples and 38 (21%) of 184 assessable sputum samples obtained over a 24-h period. Exhaled M tuberculosis output showed no diurnal pattern and did not associate with cough frequency, sputum bacillary content, or chest radiographic disease severity. On May 16, 2018, 45 individuals were screened for the prospective active case-finding pilot study, of whom 20 had tuberculosis symptoms and were willing to take part. Eight participants were diagnosed prospectively with pulmonary tuberculosis, of whom six were exclusively face-mask positive at screening. Four of these participants (three of whom were HIV-positive) had normal findings on chest radiography but had treatment-responsive early tuberculosis-compatible lesions on PET-CT scans, with Xpert-positive sputum samples after 6 weeks. INTERPRETATION: Face-mask sampling offers a highly efficient and non-invasive method for detecting exhaled M tuberculosis, informing the presence of active infection both with greater consistency and at an earlier disease stage than with sputum samples. The approach shows potential for diagnosis and screening, particularly in difficult-to-reach communities. FUNDING: Wellcome Trust, CARA (Council for At-Risk Academics), University of Leicester, the UK Medical Research Council, and the National Institute for Health Research. VIDEO ABSTRACT.

Antimicrobial susceptibility of organisms causing community-acquired urinary tract infections in Gauteng Province, South Africa.

BACKGROUND: Patients with community-acquired urinary tract infections (UTIs) frequently present to healthcare facilities in South Africa (SA). AIM: To provide information on UTI aetiology and antimicrobial susceptibility of pathogens. METHODS: We recruited women with UTI-related symptoms, who tested positive for ≥2 urine dipstick criteria (proteinuria, blood, leucocytes or nitrites) at 1 public and 5 private primary healthcare facilities in 2011. Demographic and clinical data were recorded and mid-stream urine (MSU) specimens were cultured. UTI pathogens were Gram-stained and identified to species level. Etest-based antimicrobial susceptibility testing was performed for amoxicillin/clavulanic acid, cefixime, cefuroxime, ciprofloxacin, fosfomycin, levofloxacin, nitrofurantoin, norfloxacin and trimethoprim/sulphamethoxazole. RESULTS: Of the 460 women recruited, 425 MSU samples were processed and 204 UTI pathogens were identified in 201 samples. Most pathogens were Gram-negative bacilli (GNB) (182; 89.2%) and 22 (10.8%) were Gram-positive cocci (GPC). Escherichia coli was the most frequent GNB (160; 79.6%), while Enterococcus faecalis was the predominant GPC (8; 4.0%). The UTI pathogens had similar susceptibility profiles for fosfomycin (95.5%; 95% confidence interval (CI) 92.6 - 98.4), the 3 fluoroquinolones (94.1%; 95% CI 90.8 - 97.4), nitrofurantoin (91.7%; 95% CI 87.8 - 95.6), cefuroxime (90.1%; 95% CI 86.0 - 94.3) and cefixime (88.2%; 95% CI 83.7 - 92.6). UTI pathogens were less susceptible to amoxicillin/clavulanic acid (82.8%; 95% CI 77.5 - 88.0) when compared with fluoroquinolones and fosfomycin. Trimethoprim/ sulphamethoxazole was the least efficacious antimicrobial agent (44.3% susceptible; 95% CI 37.4 - 51.2). CONCLUSION: This study provides relevant data for the empirical treatment of community-acquired UTIs in SA.