Mycobacterium Tuberculosis Infection, Tuberculosis, Pulmonary
Conditions
Brief summary
This five-year study will evaluate two strategies for conducting tuberculosis (TB) active case finding (ACF) and linkage to TB treatment or TB preventive therapy (TPT) in peri-urban Uganda. The two strategies differ in the location where ACF activities are performed: A "facility-based" ACF/TPT strategy will perform ACF, plus linkage to TPT, in the immediate vicinity of a large public health facility and will primarily recruit individuals who are attending the health facility, irrespective of TB suspicion or symptoms. Alternatively, a "hotspot-based" strategy will use routine notification data and local expertise to identify local TB hotspots - defined as the geographic areas though to have the highest burden of undiagnosed TB per estimated population. The same infrastructure (personnel, equipment, supplies, etc.) for ACF/TPT will then be placed in those zones for a period of four months at a time, and the general population will be recruited for screening and linkage to TPT. The two interventions will be compared in a Type 1 hybrid effectiveness-implementation trial with a cluster-randomized, multiple-period crossover design. The study will evaluate whether hotspot-focused ACF/TPT results in a greater number of TB patients diagnosed and linked to care, and a greater number of individuals started on preventive therapy, than facility-based ACF/TPT. Secondarily, it will also compare the two interventions in terms of number of people initiated on TPT, and it will compare TB cases detected in regions performing ACF/TPT (either approach) against cases detected in regions that continue to perform the standard of care.
Interventions
OTHERActive TB case finding with linkage to preventive therapy (ACF/TPT)
ACF/TPT in both intervention arms will consist of TB screening by mobile chest X-ray (with artificial intelligence-based reading, followed by confirmatory sputum testing with Xpert MTB/RIF Ultra for participants with abnormal x-rays), and linkage to preventive therapy for those who are TB-negative and eligible for TPT (limited in April 2024 to those with close TB contact or known HIV infection).
Sponsors
Johns Hopkins University
National Heart, Lung, and Blood Institute (NHLBI)
Walimu
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SCREENING
Masking
SINGLE (Investigator)
Intervention model description
Twelve clusters or study regions (of which eight will be randomized to receive interventions) will be defined according to the catchment areas of twelve participating Ugandan district hospitals/major health centers. Eight study areas will receive a total of six 4-month intervention periods (alternating between the facility-based and the hotspot focused strategy, for three periods of each type) over a four-year period, with a 4-month wash-out period after each intervention period. Four additional areas will be used as control sites; the only involvement of participants in these sites will be through retrospective collection of de-identified data.
Eligibility
Sex/Gender
ALL
Age
5 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age ≥15 years, OR age 5-14 and a close contact of someone diagnosed with TB, * Provision of oral informed consent, or, if age \<18 years and not legally emancipated, oral informed assent (if ages 8-17) and parental informed consent (ages 5-17) to participate in the study * Ability to communicate with study staff in English or Luganda, or availability of a capable interpreter who is acceptable to the participant
Exclusion criteria
* On treatment for, or diagnosed with but not yet treated for, active TB
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary bacteriologically confirmed TB notifications, hotspot vs facility | From the start to two weeks after the end of each four-month intervention period | Number of study region residents notified as initiating treatment for bacteriologically confirmed new or relapsed pulmonary TB, comparing periods in which regions performed hotspot-focused ACF/TPT to those in which facility-based ACF/TPT was performed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TPT initiations, hotspot vs facility | From the start to two weeks after the end of each four-month intervention period | Number of study region residents initiating TPT during intervention periods, comparing periods in which regions performed hotspot-focused ACF/TPT to those in which facility-based ACF/TPT was performed. |
| Pulmonary bacteriologically confirmed TB notifications, ACF/TPT vs control | 48 months from start of interventions in each "triplet" of clusters | Number of study region residents notified as initiating treatment for bacteriologically confirmed new or relapsed pulmonary TB, comparing intervention regions to control regions. |
| TB notification trend (intervention vs control) | Approximately 38 to 46 months per cluster (5 to 6 four-month intervention periods, plus intervening washout periods) | Trend in TB notification rate over the span of study intervention involvement, comparing intervention clusters to control clusters |
| Study-initiated TB notifications, hotspot vs facility | From the start to two weeks after the end of each four-month intervention period | Number of people diagnosed with TB through study participation and initiating treatment for TB, hotspot-focused and facility-based ACF/TPT. |
| Number screened by study | During four-month intervention periods (6 periods per cluster over 48 months) | Total number of people screened for TB with each intervention. |
| Number diagnosed by study | During four-month intervention periods (6 periods per cluster over 48 months) | Number of study participants found to have Xpert-positive sputum. |
| Cost effectiveness (hotspot vs facility) as assessed by cost per disability-adjusted life year averted | From the start to two weeks after the end of each four-month intervention period | Incremental cost per disability-adjusted life year (DALY) averted, comparing the more to the less effective ACF/TPT intervention (if an effectiveness difference is found). |
| Cost effectiveness (ACF/TPT vs no intervention) as assessed by cost per disability-adjusted life year averted | From the start to two weeks after the end of each four-month intervention period | Incremental cost per disability-adjusted life year (DALY) averted, comparing ACF/TPT to no ACF/TPT. |
| Number evaluated for latent tuberculosis infection (LTBI) with tuberculin skin testing (TST) | During four-month intervention periods (6 periods per cluster over 48 months) | Total number of people completing TST placement and reading by the study |
| Number referred for TPT | During four-month intervention periods (6 periods per cluster over 48 months) | Number of participants referred for TB preventive therapy based on TST result or other eligibility criteria |
| Contacts screened | During four-month intervention periods (6 periods per cluster over 48 months) | Number of people screened for TB who are identified as contacts of a person diagnosed with TB through the study |
Countries
Uganda
Contacts
PRINCIPAL_INVESTIGATOREmily Kendall, MD PhD
Johns Hopkins University
Outcome results
None listed