A pilot cross-sectional study of non-communicable diseases in TB household contacts.

BACKGROUND: Data on the prevalence of non-communicable diseases (NCDs) in TB household contacts (HHCs) are limited, yet important to inform integrated screening and care for NCD within contact investigations. It is also unclear if screening these contacts reveals more people with NCDs than individuals in the same neighbourhood. METHOD: We conducted a pilot cross-sectional study in South Africa and Tanzania, enrolling adult HHCs of TB and individuals in neighbourhood households (controls). We inquired about known NCD and systematically measured blood pressure, and tested for spot blood glucose and haemoglobin A1c. RESULTS: We enrolled 203 adult contacts of 111 persons with TB and 160 controls. Among contacts, respectively 12.2% (95% CI 8.3-17.6) and 39.7% (95% CI 33.1-46.7) had diabetes and hypertension, compared to 14.1% (95% CI 9.2-21.0) and 44.7% (95% CI 36.9-52.7) among controls. More than half of NCDs were newly identified. We did not find a significant difference in the prevalence of at least one NCD between the two groups (OR 0.85, 95% CI 0.50-1.45, adjusted for age and sex). CONCLUSIONS: We found a high prevalence of undiagnosed NCDs among contacts, suggesting a potential benefit of integrating NCD screening and care within contact investigations. Screening in the same community might similarly find undiagnosed NCDs.

CONTEXTE: Les données sur la prévalence des maladies non transmissibles (NCD, pour l'anglais « non-communicable diseases ¼) chez les contacts familiaux (HHC, pour l'anglais « household contacts ¼) de personnes atteintes de TB sont restreintes, mais elles revêtent une grande importance pour le dépistage et la prise en charge intégrée des NCD dans le cadre des enquêtes sur les contacts. De plus, on ignore si le dépistage de ces contacts permet de détecter davantage de personnes atteintes de NCD par rapport aux les individus résidant dans le même quartier. MÉTHODE: Nous avons réalisé une étude pilote transversale en Afrique du Sud et en Tanzanie, au cours de laquelle nous avons recruté des adultes HHC de personnes atteintes de TB et des individus vivant dans les ménages voisins (témoins). Nous les avons interrogés sur les NCD connues et avons systématiquement mesuré la pression artérielle, ainsi que réalisé des tests de de glycémie et d'hémoglobine glyquée. RÉSULTATS: Un total de 203 contacts adultes de 111 personnes atteintes de TB et 160 témoins ont été répertoriés. Parmi ces contacts, respectivement 12,2% (IC à 95% 8,3­17,6) et 39,7% (IC à 95% 33,1­46,7) souffraient de diabète et d'hypertension, contre 14,1% (IC à 95% 9,2­21,0) et 44,7% (IC à 95% 36,9­52,7) chez les témoins. Plus de la moitié des NCD ont été récemment découvertes. Aucune disparité significative n'a été observée dans la prévalence d'au moins une NCD entre les deux groupes (OR 0,85 ; 95% CI 0,50­1,45, ajusté pour l'âge et le sexe). CONCLUSIONS: Nous avons observé une fréquence élevée de NCDs non diagnostiquées parmi les contacts, ce qui indique qu'il pourrait être potentiellement bénéfique d'inclure le dépistage et les soins des NCD dans les enquêtes sur les contacts. Le dépistage au sein de la même communauté pourrait également révéler des NCD non diagnostiquées.

A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis.

BACKGROUND: Linezolid is an effective, but toxic anti-tuberculosis drug that is currently recommended for the treatment of drug-resistant tuberculosis. Improved oxazolidinones should have a better safety profile, while preserving efficacy. Delpazolid is a novel oxazolidinone developed by LegoChem Biosciences Inc. that has been evaluated up to phase 2a clinical trials. Since oxazolidinone toxicity can occur late in treatment, LegoChem Biosciences Inc. and the PanACEA Consortium designed DECODE to be an innovative dose-ranging study with long-term follow-up for determining the exposure-response and exposure-toxicity relationship of delpazolid to support dose selection for later studies. Delpazolid is administered in combination with bedaquiline, delamanid and moxifloxacin. METHODS: Seventy-five participants with drug-sensitive, pulmonary tuberculosis will receive bedaquiline, delamanid and moxifloxacin, and will be randomized to delpazolid dosages of 0 mg, 400 mg, 800 mg, 1200 mg once daily, or 800 mg twice daily, for 16 weeks. The primary efficacy endpoint will be the rate of decline of bacterial load on treatment, measured by MGIT liquid culture time to detection from weekly sputum cultures. The primary safety endpoint will be the proportion of oxazolidinone class toxicities; neuropathy, myelosuppression, or tyramine pressor response. Participants who convert to negative liquid media culture by week 8 will stop treatment after the end of their 16-week course and will be observed for relapse until week 52. Participants who do not convert to negative culture will receive continuation phase treatment with rifampicin and isoniazid to complete a six-month treatment course. DISCUSSION: DECODE is an innovative dose-finding trial, designed to support exposure-response modelling for safe and effective dose selection. The trial design allows assessment of occurrence of late toxicities as observed with linezolid, which is necessary in clinical evaluation of novel oxazolidinones. The primary efficacy endpoint is the change in bacterial load, an endpoint conventionally used in shorter dose-finding trials. Long-term follow-up after shortened treatment is possible through a safety rule excluding slow-and non-responders from potentially poorly performing dosages. TRIAL REGISTRATION: DECODE was registered in ClinicalTrials.gov before recruitment start on 22 October 2021 (NCT04550832).

Evaluation of Diagnos TB AG, a flow-through immunoassay for rapid detection of pulmonary tuberculosis.

We evaluated the diagnostic performance of the Diagnos TB AG immunoassay in 171 Tanzanians with suspected pulmonary tuberculosis (TB). The sensitivity and specificity, and positive and negative predictive values of the rapid test for the detection of pulmonary TB in this population were respectively 60.0%, 33.3%, 40.3% and 52.6%. In its current configuration, this test will not help overcome difficulties in the rapid diagnosis of TB.