The consortium sites represent a diverse population and are enrolling into a protocol that is harmonized with the RePORT International Common Protocol (https://reportinternational.org/common-protocol-toolkit/).
Three sites in Rio de Janeiro, one in Manaus, and one in Salvador enrolled approximately 1,000 culture-confirmed pulmonary TB cases and 2,000 close contacts of those TB cases (RePORT-Brazil phase 1). During phase 2 of enrollment (from 2022 to 2027), our plan is to enroll 1,000 new TB cases and 2,000 close contacts.
RePORT-Brazil Phase 1 (finalized; 2015-2021)
- Adults only, pulmonary culture-confirmed TB, mostly drug-susceptible (DS-TB), 20% HIV co-infected, 62% with dysglycemia at baseline, 70% received DOT.
- 963 culture-confirmed DS-TB enrolled, followed for up to 24 months.
- Visits with data and specimen collection at Baseline, Month 1, Month 2 and at End of Treatment (Month 6). Also, at time of TB recurrence/failure.
- Follow up telephone calls at Months 12, 18 and 24.
- Specimens available: DNA, RNA, sputum, Mtb isolates, whole blood, plasma, PBMCs, urine at all visits.
- All patients had smear, culture (solid-LJ on everyone, plus MGIT in a sub-group; drug susceptibility testing (DST) in all), HIV, HbA1C, Hepatitis serologies, CBC, etc.
- Data also available and produced from other related projects: human low pass-whole genome sequencing (WGS), Mtb HAIN second- line, MIC, and whole genome sequencing of select Mtb isolates, human Ancestry Informative Markers, genotyping (TB/HIV drug metabolism SNPs), Xpert cycle threshold (Ct values), plasma drug levels (for all patients; drug levels in ~500 patients), whole blood RNA signatures in a subset, etc.
- Main endpoints: 33 treatment failures, 9 recurrences, 5% culture+ at Month 2.
- Adults and children, contacts of TB cases enrolled in Cohort A, 3% HIV co-infected, 5% diabetes.
- 1,839 contacts of a culture confirmed case in Cohort A enrolled, followed for up to 24 months.
- Visits with data and specimen collection at Baseline and at End of prophylaxis or Month 6. Also, at time of TB activation.
- Follow up telephone calls at Month 12, 18 and 24.
- Specimens available: DNA, RNA, Whole Blood, Plasma, PBMCs, Urine and QuantiFERON supernatants at all visits.
- All participants had HIV, CBC, IGRA testing done. Most participants have information on quantification of TB exposure (sleeping in the same room, bed or 5h per day of contact with TB patient).
- Data available and produced from other related projects: low pass-WGS in all participants, HLA in a subgroup, whole blood RNA signature work (TB progression) on all participants, Ancestry Informative Markers (work is ongoing), plasma metabolomics in subgroup (ongoing), WGS of Mtb isolates (from those who progressed to active disease), T-cell receptor (TCR) frequency, single-cell work on all TB progressors, etc.
- Main endpoints: 25 participants developed active TB. Among all close contacts, 37% IGRA positive at Baseline, 6% IGRA converters, 45% IGRA negative at Baseline and Month 6.
RePORT-Brazil Phase 2 (2022-2027; ongoing)
- Adults and children, Drug Susceptible TB, pulmonary and/or extra-pulmonary TB, with or without microbiological confirmation.
- We will also enroll TB suspects.
- 250 TB cases/year, for 4 years (1000 total)
- 250 TB suspects (no TB)/year, for 4 years (1000 total)
- Expected to be 25-30% HIV co-infected
- Adults and children, contacts will only be enrolled if their index case have microbiologically confirmed pulmonary TB.
- 400 close-contacts/year, for 4 years (1600 total)