Household contacts (HHCs) of pulmonary tuberculosis patients are at high risk of Mycobacterium tuberculosis infection and early disease development. Identification of individuals at risk of tuberculosis disease is a desirable goal for tuberculosis control. Interferon-gamma release assays (IGRAs) using specific M. tuberculosis antigens provide an alternative to tuberculin skin testing (TST) for infection detection. Additionally, the levels of IFNγ produced in response to these antigens may have prognostic value. We estimated the prevalence of M. tuberculosis infection by IGRA and TST in HHCs and their source population (SP), and assessed whether IFNγ levels in HHCs correlate with tuberculosis development. A cohort of 2060 HHCs was followed for 2–3 years after exposure to a tuberculosis case. Besides TST, IFNγ responses to mycobacterial antigens: CFP, CFP-10, HspX and Ag85A were assessed in 7-days whole blood cultures and compared to 766 individuals from the SP in Medellín, Colombia. Isoniazid prophylaxis was not offered to child contacts because Colombian tuberculosis regulations consider it only in children under 5 years, TST positive without BCG vaccination. Using TST 65.9% of HHCs and 42.7% subjects from the SP were positive (OR 2.60, p<0.0001). IFNγ response to CFP-10, a biomarker of M. tuberculosis infection, tested positive in 66.3% HHCs and 24.3% from the SP (OR = 6.07, p<0.0001). Tuberculosis incidence rate was 7.0/1000 person years. Children <5 years accounted for 21.6% of incident cases. No significant difference was found between positive and negative IFNγ responders to CFP-10 (HR 1.82 95% CI 0.79–4.20 p = 0.16). However, a significant trend for tuberculosis development amongst high HHC IFNγ producers was observed (trend Log rank p = 0.007). CFP-10-induced IFNγ production is useful to establish tuberculosis infection prevalence amongst HHC and identify those at highest risk of disease. The high tuberculosis incidence amongst children supports administration of chemoprohylaxis to child contacts regardless of BCG vaccination.

Tuberculosis (TB) remains one of the most deadly infectious diseases. One-third to one-fourth of the human population is estimated to be infected with Mycobacterium tuberculosis (Mtb) without showing clinical symptoms, a condition called latent TB infection (LTBI). Diagnosis of Mtb infection is based on the immune response to a mixture of mycobacterial antigens (PPD) or to Mtb specific ESAT-6/CFP10 antigens (IGRA), highly expressed during the initial phase of infection. However, the immune response to PPD and IGRA antigens has a low power to discriminate between LTBI and PTB. The T-cell response to a group of so-called latency (DosR-regulon-encoded) and Resuscitation Promoting (Rpf) antigens of Mtb has been proved to be significantly higher in LTBI compared to active TB across many populations, suggesting their potential use as biomarkers to differentiate latent from active TB. PBMCs from a group LTBI (n = 20) and pulmonary TB patients (PTB, n = 21) from an endemic community for TB of the city of Medellín, Colombia, were in vitro stimulated for 7 days with DosR- (Rv1737c, Rv2029c, and Rv2628), Rpf- (Rv0867c and Rv2389c), the recombinant fusion protein ESAT-6-CFP10 (E6-C10)-, or PPD-antigen. The induced IFNγ levels detectable in the supernatants of the antigen-stimulated cells were then used to calculate specificity and sensitivity in discriminating LTBI from PTB, using different statistical approaches. IFNγ production in response to DosR and Rpf antigens was significantly higher in LTBI compared to PTB. ROC curve analyses of IFNγ production allowed differentiation of LTBI from PTB with areas under the curve higher than 0.70. Furthermore, Multiple Correspondence Analysis (MCA) revealed that LTBI is associated with higher levels of IFNγ in response to the different antigens compared to PTB. Analysis based on decision trees showed that the IFNγ levels produced in response to Rv2029c was the leading variable that best-classified disease status. Finally, logistic regression analysis predicted that IFNγ produced by PBMCs in response to E6-C10, Rv2029c, Rv0867c (RpfA) and Rv2389c (RpfA) antigens correlates best with the probability of being latently infected. The Mtb antigens E6-C10, Rv2029c (PfkB), Rv0867c (RpfA) and Rv2389c (RpfA), may be potential candidates to discriminate LTBI from PTB.

To determine the incidence of pulmonary tuberculosis (TB) in inmates, factors associated with TB, and the time to sputum smear and culture conversion during TB treatment. Prospective cohort study. All prisoners with respiratory symptoms (RS) of any duration were evaluated. After participants signed consent forms, we collected three spontaneous sputum samples on consecutive days. We performed auramine-rhodamine staining, culturing with the thin-layer agar method, Löwestein-Jensen medium and MGIT, susceptibility testing for first-line drugs; and HIV testing. TB cases were followed, and the times to smear and culture conversion to negative were evaluated. Of 9,507 prisoners held in four prisons between April/30/2010 and April/30/2012, among them 4,463 were screened, 1,305 were evaluated for TB because of the lower RS of any duration, and 72 were diagnosed with TB. The annual incidence was 505 cases/100,000 prisoners. Among TB cases, the median age was 30 years, 25% had <15 days of cough, 12.5% had a history of prior TB, and 40.3% had prior contact with a TB case. TB-HIV coinfection was diagnosed in three cases. History of prior TB, contact with a TB case, and being underweight were risk factors associated with TB. Overweight was a protective factor. Almost a quarter of TB cases were detected only by culture; three cases were isoniazid resistant, and two resistant to streptomycin. The median times to culture conversion was 59 days, and smear conversion was 33. The TB incidence in prisons is 20 times higher than in the general Colombian population. TB should be considered in inmates with lower RS of any duration. Our data demonstrate that patients receiving adequate anti-TB treatment remain infectious for prolonged periods. These findings suggest that current recommendations regarding isolation of prisoners with TB should be reconsidered, and suggest the need for mycobacterial cultures during follow-up.

Two prisons in Medellín and Itagüí, Colombia.

Rapidly urbanizing cities in Latin America experience high levels of air pollution which are known risk factors for population health. However, the estimates of long-term exposure to air pollution are scarce in the region. We developed intraurban land use regression (LUR) models to map long-term exposure to fine particulate matter (PM_2.5) and nitrogen dioxide (NO₂) in the five largest cities in Colombia. We conducted air pollution measurement campaigns using gravimetric PM_2.5 and passive NO₂ sensors for 2 weeks during both the dry and rainy seasons in 2021 in the cities of Barranquilla, Bucaramanga, Bogotá, Cali, and Medellín, and combined these data with geospatial and meteorological variables. Annual models were developed using multivariable spatial regression models. The city annual PM_2.5 mean concentrations measured ranged between 12.32 and 15.99 µg/m³ while NO₂ concentrations ranged between 24.92 and 49.15 µg/m³. The PM_2.5 annual models explained 82% of the variance (R²) in Medellín, 77% in Bucaramanga, 73% in Barranquilla, 70% in Cali, and 44% in Bogotá. The NO₂ models explained 65% of the variance in Bucaramanga, 57% in Medellín, 44% in Cali, 40% in Bogotá, and 30% in Barranquilla. Most of the predictor variables included in the models were a combination of specific land use characteristics and roadway variables. Cross-validation suggests that PM_2.5 outperformed NO₂ models. The developed models can be used as exposure estimate in epidemiological studies, as input in hybrid models to improve personal exposure assessment, and for policy evaluation.