Comparative Effectiveness/Implementation of TB Case Finding in Rural South Africa

NCT02808507 | Completed Results DMC

• 2 other identifiers: 15-0005R01AI116787-02
• Study Type: interventional
• Target: 4,852
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to compare three strategies for finding TB cases in a rural Sub-Saharan African setting: 1) Screening all attendees of primary care clinics for TB; 2) Conducting household contact investigations of newly diagnosed TB cases; 3) Providing incentives to newly diagnosed TB cases and their contacts to promote contact screening for TB. For each intervention, investigators will measure comparative effectiveness in terms of cases identified as well as the cost-effectiveness and feasibility of implementation.

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (2)

• Treatment Initiation Ratio in Facility Versus Contact Investigation Clinics

  The primary analysis was based on the facility- level rate ratio, and we first calculated an unadjusted ratio of the treatment initiation rates between the two arms and the corresponding 95% confidence interval (CI). We then adjusted for any residual confounding by district stratification and the historical annual number of people started on TB following a two-stage approach. The first step of this approach fits a Poisson regression to the facility-level counts and the district and historical volume covariates irrespective of study arm. The residuals ratios, calculated as the ratio of the observed over the expected counts, are then used in the second stage to estimate the between-arm rate ratio and the corresponding 95% CI.

  18 months

• Comparative Treatment Initiation Ratio in the Incentive-based Versus Household-based Contact Investigation Arms

  The primary outcome of the study was the comparative number of people with incident TB diagnosed and started on treatment at study clinics in the two contact tracing arms, excluding the six-month washout period.

  36 months

Secondary Outcomes (5)

• Comparative Number of Secondary TB Cases Identified in Incentive-based Versus Household-based Contact Tracing

  36 months

• Total Cost of Household Contact Investigation Strategies

  36 months

• Estimated Costs Per Contact Person Screened in the Household-based and Incentive-based Contact Investigation Arms

  36 months

• Cost Per Secondary Case of TB Identified Among Contacts, Per Arm

  36 months

• Incremental Cost-effectiveness Ratio

  36 months

Study Arms (2)

Facility-based screening

EXPERIMENTAL

This strategy will be implemented at all clinics (n=28) within this arm for 18 months. Study staff will encourage providers at each of the clinics to screen all consenting patients attending the clinic, regardless of the original reason for clinic presentation. Upon presenting for care (e.g., while waiting for their healthcare provider), patients will be informed about the study and screened for cough of any duration, fever, weight loss, or night sweats. Participants who are symptomatic and provide a sputum specimen (according to the clinic standard of care) will be given a study flyer informing them that they may be contacted by study staff, and a brief summary of the study. Per standard of care, all sputum samples will be sent to the local National Health Laboratory Service laboratory for Xpert testing.

Other: Active TB case finding

Contact screening

EXPERIMENTAL

This arm is comprised of two sub-arms: In the household contact screening sub-arm, a mobile field team visits the household of each consenting newly diagnosed pulmonary TB index case. Each visit consists of a household census, consent of all eligible household members for TB screening, administration of a brief questionnaire, sputum collection for testing with Xpert Mycobacterium tuberculosis (MTB)/rifampin (RIF) and the offer of HIV testing. In the incentive-based contact screening sub-arm, all consenting newly diagnosed active TB cases are provided with 10 coupons for free TB screening to give to close contacts. When a contact presents at clinic with a coupon, they and the index case each receive a small amount of money. If the contact is diagnosed with active TB and starts treatment, the index case receives an additional larger amount of money. Each contact receives a brief questionnaire, TB symptom screen, optional HIV testing, and sputum sample collection for Xpert MTB/RIF.

Other: Active TB case finding

Interventions

Active TB case finding OTHER

Active TB case finding (ACF) refers to any number of strategies used to identify individuals with active TB disease, outside of passive case finding. In passive case finding, individuals with symptoms present at health centers for diagnosis. In active case finding, the health system makes an effort to identify TB cases before they present passively.

Contact screening; Facility-based screening

Eligibility Criteria

• Age: 0 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Facility-based screening arm
• Age 0-99 years
• Informed consent provided (or assent plus parent/guardian consent)
• Attending any of the study 28 study clinics in the facility-based screening arm
• Contact tracing arm- Index Case
• Age 0-99 years
• Informed consent provided (or assent plus parent/guardian consent)
• Newly diagnosed (last 2 months) with TB at any of the 28 study clinics in the contact tracing arm
• Contact tracing arm- Household Contact
• Age 0-99 years
• Informed consent provided (or assent plus parent/guardian consent)
• Living in the same household as an enrolled Index case (see above)
• Contact tracing arm- Non-household Close Contact
• Age 0-99 years
• Informed consent provided (or assent plus parent/guardian consent)

You may not qualify if:

• Unable to provide informed consent.

Sponsors & Collaborators

• Johns Hopkins Bloomberg School of Public Health: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Perinatal HIV Research Unit of the University of the Witswatersrand: collaborator

Study Sites (2)

Vhembe health subdistrict

Louis Trichardt, Limpopo, South Africa

Location

Waterberg health subdistrict

Mokopane, Limpopo, South Africa

Location

Related Publications (3)

• Baik Y, Hanrahan CF, Mmolawa L, Nonyane BAS, Albaugh NW, Lebina L, Siwelana T, Martinson N, Dowdy DW. Conditional Cash Transfers to Incentivize Tuberculosis Screening: Description of a Novel Strategy for Contact Investigation in Rural South Africa. Clin Infect Dis. 2022 Mar 23;74(6):957-964. doi: 10.1093/cid/ciab601.

  PMID: 34212181 DERIVED

• Hanrahan CF, Nonyane BAS, Mmolawa L, West NS, Siwelana T, Lebina L, Martinson N, Dowdy DW. Contact tracing versus facility-based screening for active TB case finding in rural South Africa: A pragmatic cluster-randomized trial (Kharitode TB). PLoS Med. 2019 Apr 30;16(4):e1002796. doi: 10.1371/journal.pmed.1002796. eCollection 2019 Apr.

  PMID: 31039165 DERIVED

• Kerrigan D, West N, Tudor C, Hanrahan CF, Lebina L, Msandiwa R, Mmolawa L, Martinson N, Dowdy D. Improving active case finding for tuberculosis in South Africa: informing innovative implementation approaches in the context of the Kharitode trial through formative research. Health Res Policy Syst. 2017 May 30;15(1):42. doi: 10.1186/s12961-017-0206-8.

  PMID: 28558737 DERIVED

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Limitations and Caveats

* Clinics were purposively chosen based on having larger historical TB patient volume; findings may not generalize to smaller, more remote clinics. * Clinics and patients not blinded to allocation, so cannot rule out possibility of resultant bias. * 1/3 of the index patients with TB whom we approached for enrollment refused or were unable to be enrolled, and cannot rule out that they may have differed in some way associated with TB incidence among their contacts from those able to be enrolled.

Results Point of Contact

• Title: Colleen Hanrahan
• Organization: Johns Hopkins Bloomberg School of Public Health

chanrah1@jhu.edu

410-502-9289

Study Officials

• David Dowdy, MD, PhD

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2016
• First Posted: June 21, 2016
• Study Start: July 18, 2016
• Primary Completion: January 17, 2018
• Study Completion: January 30, 2020
• Last Updated: September 5, 2024
• Results First Posted: December 2, 2022

Record last verified: 2024-08

Locations

ZA (2)