Délégation Midi Pyrénées

IntroductionThe WHO estimates a gap of about 30% between the incident (10.6 million) and notified (7.5 million) cases of tuberculosis (TB). Combined with the growing recognition in prevalence surveys of the high proportion of cases identified who are asymptomatic or paucisymptomatic, these data underscore how current symptom screening approaches and use of diagnostic tests with suboptimal performance on sputum miss large numbers of cases. Thus, the development of sputum-free biomarker-based tests for diagnosis is becoming necessary, which the WHO has already identified as a priority for new TB diagnostics.The objective of this study is to evaluate a combination of exhaled breath condensate (EBC) samples and mycobacterial lipoarabinomannan (LAM) as point-of-care (POC) assays to identify TB patients.Methods and analysisThis prospective diagnostic accuracy study is conducted at the TB Screening and Treatment Centre of International Center for Diarrhoeal Disease Research, Bangladesh, on a cohort of adults and adolescents >11 years of age. A total of 614 individuals with presumptive pulmonary TB based on TB signs, symptoms and radiography are being recruited from 28 August 2023. Spot sputum is collected for standard reference testing (L-J culture, GeneXpert MTB/Rif, acid-fast Bacilli microscopy) to fine-tune categorisation of TB disease status for each participant, defined as (1) definite TB (at least one positive standard reference test); (2) probable TB (not microbiologically confirmed but under TB treatment); (3) possible TB (no TB treatment but signs, symptoms and radiography suggestive of TB); (4) other respiratory disease (microbiologically not confirmed and no radiography presenting abnormalities compatible with TB); and (5) unknown (no microbiological evidence with normal/no TB abnormalities with radiography). Urine and EBC specimens will be subjected to LAM POC testing and biobanked for further investigation. Statistical analyses will include an assessment of diagnostic accuracy by constructing receiver operating curves and calculating sensitivity and specificity, as well as post-test probabilities.Ethics and disseminationThe study protocol was approved by the Research Review Committee as well as the Ethical Review Committee of icddr,b and recorded under a protocol reference number, PR-2301. Results will be submitted to open-access peer-reviewed journals, presented at academic meetings, and shared with national and international policymaking bodies.

We present a detailed study of SMM 02399-0136, a hyperluminous, active galaxy selected from a sub-mm survey of the distant Universe. This galaxy is the brightest source in the fields of seven rich, lensing clusters - total area 0.01 deg^2 - that we have mapped with a sensitivity of ~2 mJy/bm at 850um. We identify a compact optical counterpart with B ~ 23 and a LSB companion 3" away. Our spectroscopy shows that components have the same redshift; z = 2.803 +/- 0.003. The emission lines widths, FWHM ~ 1000-1500 km/s, and line ratios, along with the compact morphology and high luminosity (M_B ~ -24.0) of the galaxy indicate that SMM 02399-0136 contains a rare dust-embedded, narrow-line or type-2 AGN. The source is lensed by the foreground cluster, amplifying its apparent luminosity by a factor of 2.5. Taking this into account, we estimate that SMM 02399-0136 is five times more luminous than F10214+4724. Its far-IR and H-alpha luminosities and LSB radio emission are indicative of an extremely high SFR - several thousand Mo/yr. This assumes that a starburst is the dominant source of energy, but we cannot yet determine the relative contributions of the starburst and the buried AGN. A dust mass of 5-7 x 10^8 Mo is indicated by our data for T(dust) ~ 40-50K, independent of whether the dominant energy source is an AGN or a starburst. We estimate the possible space density of such luminous sub-mm sources and find that while a very large population of these obscured sources could be detected in future wide-field sub-mm surveys, they are unlikely to dominate the faint counts in this waveband. Galaxies such as SMM 02399-0136 and F10214+4724 cannot be easily detected in conventional AGN/QSO surveys, and so estimates of the prevalence of AGN in the early Universe may require significant revision.