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Background: Several neonatal intensive care units (NICU) have reported exposure to sputum smear positive tuberculosis (TB). NICE guidelines give support regarding investigation and treatment intervention, but not for contact definitions. Data regarding the reliability of any interferon gamma release assay (IGRA) in infants as a screening test for TB infection is scarce. We report an investigation and management strategy and evaluated the viability of IGRA (T-Spot) in infants and its concordance to the tuberculin skin test (TST).
Methods: We performed an outbreak investigation of incident TB infection in a NICU after prolonged exposure to sputum smear positive miliary TB by an infant's mother. We defined individual contact definitions and interventions and assessed secondary attack rates. In addition, we evaluated the technical performance of T-Spot in infants and compared the results with the TST at baseline investigation.
Results: Overall, 72 of 90 (80%) exposed infants were investigated at baseline, in 51 (56.7%) of 54 (60%) infants, follow-up TST at the age of 6 months was performed. No infant in our cohort showed a positive TST or T-Spot at baseline. All blood samples from infants except one responded to phytohemagglutinin (PHA), which was used as a positive control of the T-Spot, demonstrating that cells are viable and react upon stimulation. 149 of 160 (93.1%) exposed health care workers (HCW) were investigated. 1 HCW was tested positive, having no other reason than this exposure for latent TB infection. 5 of 92 (5.5%) exposed primary contacts were tested positive, all coming from countries with high TB incidences. In total, 1 of 342 exposed contacts was newly diagnosed with latent TB infection. The secondary attack rate in this study including pediatric and adult contacts was 0.29%.
Conclusion: This investigation highlighted the low transmission rate of sputum smear positive miliary TB in a particularly highly susceptible population as infants. Our expert definitions and interventions proved to be helpful in terms of the feasibility of a thorough outbreak investigation. Furthermore, we demonstrated concordance of T-Spot and TST. Based on our findings, we assume that T-Spot could be considered a reliable investigation tool to rule out TB infection in infants.
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http://dx.doi.org/10.1186/s13756-022-01179-8 | DOI Listing |
Contemp Clin Trials
September 2025
Weill Cornell Medicine Center for Global Health, New York, NY, USA.
Introduction: Preclinical and clinical study data show that combining bedaquiline (B or BDQ), moxifloxacin (M), and pyrazinamide (Z), known as BMZ, has potent antimicrobial activity that might shorten treatment duration for drug-susceptible pulmonary tuberculosis.
Methods/design: We describe the design of Tuberculosis Trials Consortium (TBTC) Study 38/CRUSH-TB (NCT05766267), an open-label multicenter international randomized controlled phase 2C trial that compares two four-month regimens, BMZ plus rifabutin (Rb) (2BMZRb/2BMRb) or BMZ plus delamanid (D or DLM) (2BMZD/2BMD), with standard 6-months isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE). All drugs are administered seven days per week, under direct observation, at least five days per week.
Lancet Infect Dis
September 2025
The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Background: Based on results from preclinical and clinical studies, a five-drug combination of isoniazid, rifapentine, pyrazinamide, ethambutol, and clofazimine was identified with treatment shortening potential for drug-susceptible tuberculosis; the Clo-Fast trial aimed to determine the efficacy and safety of this regimen. We compared 3 months of isoniazid, rifapentine, pyrazinamide, ethambutol, and clofazimine, administered with a clofazimine loading dose, to the standard 6 month regimen of isoniazid, rifampicin, pyrazinamide, and ethambutol in drug-susceptible tuberculosis.
Methods: Clo-Fast was a phase 2c open-label trial recruiting participants at six sites in five countries.
PLoS One
September 2025
Department of Microbiology, Immunology and Parasitology, College of Health Sciences, Addis Ababa University, Ethiopia.
Background: Tuberculosis is a major public health challenge in the resource-limited endemic setting of sub-Saharan Africa. The diagnostic challenge becomes worse for smear-negative TB cases. Even if efforts for non-sputum-based TB diagnostic and prognostic biomarkers, there was limited data on blood-based immunological biomarkers among smear-negative PTB patients.
View Article and Find Full Text PDFMicrobiol Spectr
September 2025
Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, China.
Unlabelled: This study aimed to investigate the epidemic status and distribution characteristics of drug-resistant in Urumqi. From January 2019 to July 2024, all sputum culture-positive strains were collected in Urumqi. Using the traditional solid-state proportion method for drug-sensitivity testing, we determined the resistance of to first-line antituberculosis (TB) drugs.
View Article and Find Full Text PDFJ Clin Tuberc Other Mycobact Dis
December 2025
Maseno University, School of Public and Community Development, Department of Biomedical Sciences and Technology, Kisumu, Kenya.
Introduction: Nontuberculous Mycobacteria (NTM) species are emerging pathogens causing Pulmonary diseases with no definitive treatment. Molecular techniques enable characterization and drug resistance profiling, this study sought to determine NTM prevalence, circulating species, and distribution factors among presumptive multidrug-resistant tuberculosis (MDR-TB) patients in western Kenya.
Method: Sputum samples were collected between March through October 2022, and transported for testing at Kenya Medical Research Institute (KEMRI) TB laboratory, in Kisumu.