Tuberculosis, Pulmonary
Conditions
Interventions
In the hospitalized arm of the study, 1,118 participants under 15 years of age hospitalized for lower respiratory tract infection will be included. They will undergo induced sputum collection for labo
an IGRA and tuberculin skin test (to detect M. tuberculosis infection)
and a nasal swab for viral and bacterial panel testing. As this is a cross-sectional study, there will be no longitudinal follow-up of participants. After completing the study procedures, hospitalized
and a tuberculin skin test (for detection of M. tuberculosis infection). As this is a cross-sectio
Sponsors
Hospital Moinhos de Vento
Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde (PROADI-SUS) do Hospital Moinhos de Vento
Eligibility
Age
6 Months to 14 Years
Inclusion criteria
Inclusion criteria: In the Hospital-based study arm we include patients aged from 6 months to less than 15 years are eligible if admitted for less than 7 days, have a chest radiograph performed during the current admission, and present at least one of the following signs at enrollment: age-specific tachypnea (6 months to 1 year: 50 breaths per minute, 1 to 4 years: 40 breaths per minute; 5 to 14 years: 30 breaths per minute) or respiratory retractions and/or; lower respiratory signs of wheezing, crackling, or diminished breath sounds and/or; danger signs of severe pneumonia according to World Health Organization guidelines and/or; radiographic signs suggestive of intrathoracic TB (tracheal compression and/or displacement; soft tissue opacity suggestive of adenomegaly; alveolar opacity; nodular infiltrate suggestive of miliary TB; cavitation; calcification of the lung parenchyma; or pleural effusion. In the Outpatient-based study arm we include participants aged 6 months to 15 years at TB referral clinics are eligible if they have 1 of the following: persistent, unremitting cough for more than two weeks and/or; unexplained axillary temperature above 37.8 °C for more than one week and/or; persistent, unexplained lethargy and/or; decrease in playfulness/activity reported by the parent/caregiver and/or; weight loss/failure to thrive (weight loss is defined as >5% reduction in weight compared with the highest weight recorded in the last three months, and failure to thrive is defined as clear deviation from a previous growth trajectory), and/or documented crossing percentile lines in the preceding 3 months, and/or weight-for-age z score of = -2 in the absence of information on previous/recent growth trajectory, and/or weight-for-height z score of = -2 in the absence of information on previous/recent growth trajectory and not responding to nutritional rehabilitation (or antiretroviral therapy if HIV infected).
Exclusion criteria
Exclusion criteria: In the Hospital-based study arm, exclusion criteria include: diagnosis of pleural TB without lung parenchymal involvement on radiology. When it is not possible to obtain samples for the detection of M. tuberculosis through Xpert MTB/RIF Ultra analysis and liquid culture. Participants will also be excluded if, at the time of inclusion, they present a clinical diagnosis of laryngotracheobronchitis, cystic fibrosis, bronchiolitis obliterans, and/or asthma in crisis without clinical signs suggestive of associated infection; treatment for active TB for more than 72 hours at the time of respiratory secretion collection; previous history of active TB treatment; presence of tracheostomy and use of non-invasive and mechanical ventilation; presence of conditions that prevent the respiratory secretion collection procedure; patients with a diagnosis of healthcare-associated infection. In the outpatient study arm, exclusion criteria will apply when it is not possible to obtain samples for the detection of M. tuberculosis by Xpert MTB/RIF Ultra analysis or liquid culture. Participants undergoing treatment for active TB for more than 72 hours at the time of respiratory secretion collection will also be excluded, as will those with a prior history of active TB treatment, those with a tracheostomy, and those with a known impediment to respiratory secretion collection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| In the hospitalized arm of the study, the primary outcome is the prevalence of pulmonary tuberculosis among children under 15 years of age hospitalized for lower respiratory tract infection. Pulmonary tuberculosis (PTB) is defined as the detection of M tuberculosis in liquid culture, by molecular biology tests (GeneXpert Ultra), or clinical diagnosis by the attending physician without microbiological confirmation.;The primary outcome in the outpatient study arm is the accuracy of the rapid molecular test (Xpert MTB/RIF Ultra) with induced sputum samples versus liquid culture (gold standard) for M. tuberculosis detection. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and 95% confidence intervals for all estimates will be calculated. | — |
Secondary
| Measure | Time frame |
|---|---|
| Prevalence of M. tuberculosis infection (TBI) detected by IGRA or positive tuberculin skin test (= 5 mm). This outcome applies to both study arms and will be analyzed independently.;Accuracy of the rapid molecular test (Xpert MTB/RIF Ultra) with induced sputum samples versus liquid culture for M. tuberculosis (gold standard) in the hospital study arm. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and 95% confidence intervals for all estimates will be calculated.;Risk factors associated with pulmonary tuberculosis (PTB). Demographic, socioeconomic, environmental, as well as time of symptom onset and chest radiography results, will be analyzed by logistic modeling. This outcome applies to both study arms and will be analyzed independently.;Risk factors associated with M. tuberculosis infection (TBI). Demographic, socioeconomic, environmental, as well as time of symptom onset and chest radiography results, will be analyzed by logistic modeling. This outcome applies to both study arms and will be analyzed independently.;Accuracy of the Brazilian Ministry of Health score system for prediction of PTB versus laboratory diagnosis (Ultra and/or liquid culture - obtained through sputum collection) (gold standard). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and 95% confidence intervals for all estimates will be calculated. This outcome applies to both study arms, and analysis will be conducted jointly and independently for each study arm. ;Accuracy of GeneXpert Ultra results (with induced sputum samples) versus presumptive diagnosis or liquid culture results. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and 95% confidence intervals for all estimates will be calculated. This outcome applies to both study arms, and analysis will be conducted jointly and independently for each study arm. ;Accuracy of GeneXpert Ultra results from tongue swab | — |
Countries
Brazil
Contacts
Public ContactRenato Stein
Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde (PROADI-SUS) do Hospital Moinhos de Vento
Outcome results
None listed