Kharituwe TB Contact Tracing Study

Not Applicable

Completed

Conditions: Hiv
Tuberculosis

Interventions: Behavioral: Household contact tracing

Registration Number: NCT04520113

Lead Sponsor: Johns Hopkins Bloomberg School of Public Health

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10579

Inclusion Criteria

Not provided

Exclusion Criteria

Unwilling/unable to provide informed consent
Unwilling/unable to comply with study procedures

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Evening / Weekend Tracing	Household contact tracing	Households of tuberculosis index patients in urban South Africa receive household contact tracing during evenings and weekends.
Standard Tracing	Household contact tracing	Households of tuberculosis index patients receive "standard" household contact tracing during regular weekday business hours.
Holiday Tracing	Household contact tracing	Households of tuberculosis index patients in rural South Africa receive household contact tracing during holidays (Christmas and Easter).

Primary Outcome Measures

Name	Time	Method
Effectiveness: Mean Number of Secondary TB Cases Identified and Started on Treatment Per Index Case in Each Arm	Up to 35 months	The mean number of secondary TB cases identified and started on treatment per index case for each arm.

Secondary Outcome Measures

Name	Time	Method
Relative Fidelity of Each Novel Strategy Compared to Standard Contact Investigation	Duration of study (30 months)	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.
Sustainability of Each Novel Strategy Relative to Standard Contact Tracing	Duration of study (30 months)	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.
Feasibility of Each Strategy: Proportion of Potentially Eligible Index Cases for Whom a Household Visit Was Conducted	Duration of study (30 months(	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).
Relative Acceptability of Each Novel Strategy Compared to Standard Contact Investigation	Duration of study (30 months)	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.
The TB Prevalence Ratio, Comparing Highly Mobile to Less Mobile Index Patients	Duration of study (30 months)	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).
TB Strain Relatedness Using Maximum Likelihood Transmission Trees.	Duration of study (30 months)	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.
Incremental Cost-effectiveness Ratio for Each Novel Strategy Relative to Standard Contact Tracing	Duration of study (30 months)	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.