Kharituwe TB Contact Tracing Study

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to characterize the role of human mobility in fueling TB epidemics and estimate the potential impact of innovative case finding interventions tailored to mobile populations

Detailed Description
-----------------
The investigators propose a randomized trial of two novel TB case-finding interventions among household members of patients diagnosed with active TB: holiday-based screening in a rural South African province (Limpopo) and off-peak (weekend/evening) screening in an urban settlement into which many residents of Limpopo migrate for work. The investigators will enroll index cases of TB plus their household contacts in each setting and randomize them to novel versus standard contact investigation. In Specific Aim 1, investigators will use whole genome sequencing of all cases, overlaying transmission trees with data on human movement, to evaluate associations between mobility and TB transmission in this population. In Specific Aim 2, investigators will employ a multidisciplinary approach to compare novel versus standard contact investigation in each setting along the following dimensions: (a) effectiveness (number of secondary TB cases diagnosed and starting treatment); (b) implementation (reach, fidelity, and maintenance of contact investigation outside of business hours); (c) cost-effectiveness (cost per disability-adjusted life year) and budget impact; and (d) projected population-level impact on TB incidence. Successful completion of these aims will have long-term impact by characterizing the role of mobility in fueling TB epidemics and testing two tailored approaches to improve TB control in highly mobile populations - an underserved group that is increasingly recognized as playing a major role in global TB transmission.

Official Title
-----------------
Innovative Contact Tracing Strategies for Detecting TB in Mobile Rural and Urban South African Populations

Conditions
-----------------
Hiv, Tuberculosis

Intervention / Treatment
-----------------
* Behavioral: Household contact tracing


Participation Criteria
=================
Eligibility Criteria
-----------------
TB index cases: Inclusion criteria: Age 0-99 years (Including those recently deceased) Diagnosed with pulmonary TB at a study hospital or clinic (microbiological and/or chest x-ray diagnosis) Exclusion criteria: Unwilling/unable to provide informed consent (including next of kin, for those recently deceased) Plan not to pursue TB treatment within the study district Unwilling/unable to comply with study procedures Contacts: Inclusion criteria: Age 0-99 years Currently resides with or visiting eligible TB index case Exclusion Criteria: Unwilling/unable to provide informed consent Unwilling/unable to comply with study procedures

Ages Eligible for Study
-----------------
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Tracing<br>Households of tuberculosis index patients receive standard household contact tracing during regular weekday business hours. | Behavioral: Household contact tracing<br>* Household contact tracing to test and diagnose Tuberculosis of household contacts of Tuberculosis patients.<br>|
| Experimental: Holiday Tracing<br>Households of tuberculosis index patients in rural South Africa receive household contact tracing during holidays (Christmas and Easter). | Behavioral: Household contact tracing<br>* Household contact tracing to test and diagnose Tuberculosis of household contacts of Tuberculosis patients.<br>|
| Experimental: Evening / Weekend Tracing<br>Households of tuberculosis index patients in urban South Africa receive household contact tracing during evenings and weekends. | Behavioral: Household contact tracing<br>* Household contact tracing to test and diagnose Tuberculosis of household contacts of Tuberculosis patients.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness: ratio of secondary TB identified and started on treatment per index case in novel strategy arm compared to standard contact investigation arm | The ratio of the number of secondary TB cases identified and started on treatment per index case in the novel strategy arm (off-peak screening in Soshanguve and holiday screening in Limpopo) compared to index cases receiving standard contact investigation. | Duration of study (30 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The TB prevalence ratio, comparing highly mobile to less mobile index patients | The TB prevalence ratio, comparing highly mobile to less mobile individuals, measuring mobility on two scales (neighborhood/intra-urban and regional/intra-national). For the analysis: amount of time spent in transit, truncating long excursions at 50km (one hour). | Duration of study (30 months) | 
| TB strain relatedness using maximum likelihood transmission trees. | TB natural history, epidemiological, and whole genome sequencing (WGS)-derived phylogenetic data will be integrated into a statistical modeling framework to draw probabilistic conclusions about the likelihood of transmission between persons. Transmitters will be defined as individuals from whom at least one secondary case most likely originated. | Duration of study (30 months) | 
| Relative acceptability of each novel strategy compared to standard contact investigation | Relative acceptability of each novel strategy, compared against routine contact investigation. Acceptability of the intervention will be measured among index cases and contacts using a short questionnaire given to a randomly selected participant at a randomly selected 15% of the households visited. The interview will cover acceptability of the visit timing, notification, visit activities (TB screening, HIV testing) and study team interaction among others. | Duration of study (30 months) | 
| Feasibility of each strategy: proportion of potentially eligible index cases for whom a household visit was conducted | Feasibility of each strategy as the proportion of potentially eligible index cases for whom a household visit was conducted. All reasons why visits were unable to be conducted will be recorded (e.g. could not find household, no one ever home, visit not conducted during expected off-peak period). | Duration of study (30 months( | 
| Relative fidelity of each novel strategy compared to standard contact investigation | Relative fidelity of each novel strategy using a process checklist for each index case and household, including whether the household visit was offered and accepted, whether the visit was attempted, whether the visit was successful (i.e., enrolled at least one contact), whether symptom screening and sputum collection were completed and whether newly identified TB cases were notified and referred for treatment. | Duration of study (30 months) | 
| Sustainability of each novel strategy relative to standard contact tracing | Sustainability of each novel strategy by reporting the primary outcome and fidelity measures according to six-month time period over the course of the study. | Duration of study (30 months) | 
| Incremental cost-effectiveness ratio for each novel strategy relative to standard contact tracing | Defined as (cost of contact tracing strategy 2 - cost of strategy 1)/(effectiveness of strategy 2 - effectiveness of strategy 1), where effectiveness is modeled as the number of disability-adjusted life years (DALYs) averted by the intervention. The primary cost-effectiveness measures will be the incremental cost per DALY averted using novel strategies (holiday and off-hours contact tracing) compared to routine contact tracing in each setting separately. | Duration of study (30 months) |