Transmission of Tuberculosis Among Illicit Drug Use Linkages

NCT04151602 | Completed DMC

• 2 other identifiers: H-389101R01AI147316-01
• Study Type: observational
• Target: 802
• Locations: 1 country
• Sites: 1

Brief Summary

Tuberculosis (TB) is the leading infectious disease killer globally and leading cause of death in persons with HIV. The most effective way to reduce TB incidence and mortality is to interrupt transmission. This requires finding and treating individuals with TB disease early, including those with subclinical disease. Molecular epidemiologic studies and mathematical models have shown that the primary approach to case finding-household contact tracing-identifies only 8-19% of transmissions in high TB and TB/HIV burden settings. Thus there is a clear need to identify new groups and settings where TB transmission occurs. Spatial clustering of individuals with higher rates of progression from infection to disease, such as those with HIV and malnourishment, can also form transmission hotspots. Illicit drug (i.e., methamphetamines, crack/cocaine, opiates) users have higher TB infection prevalence and disease incidence compared to non-users, likely due to significant within-group transmission and/or clustered vulnerability. Increased transmission among people who use illicit drugs (PWUD) could result from creation of more efficient TB transmitters, increased close contact among transmitters, increased rates of primary progression from infection to disease among contacts, or a combination. Interrogation of illicit drug user networks for TB transmission, therefore, holds great potential as a target for early case identification and linkage to treatment, with potential benefit for halting transmission to the broader population.

Conditions

Tuberculosis; Illicit Drug Use

Outcome Measures

Primary Outcomes (4)

• TB disease prevalence

  Percentage of persons with TB disease based on results from Xpert Ultra and sputum culture

  At baseline

• Incipient TB prevalence

  Percentage of persons with incipient TB based on host RNA signature

  At baseline

• Proportion of active TB cases resulting from recent transmission within this network of PWUD

  Proportion of linked TB cases based on whole genome sequencing of the mycobacterium tuberculosis (Mtb) isolate and overlaying social epidemiological ties

  At baseline

• Quantity of aerosolized Mtb in exhaled breath: amount of aerosolized Mtb exhaled in one hour

  The amount of aerosolized Mtb exhaled in one hour in a specialized bio-aerosol capturing booth

  One hour

Study Arms (3)

PWUD with active TB

People who use smoked illicit drugs (methamphetamine and/or methaqualone (mandrax)) with active TB disease

Behavioral: Smoked illicit drug use

PWUD with no active TB

People who use smoked illicit drugs (methamphetamine and/or methaqualone (mandrax)) with no active TB disease

Behavioral: Smoked illicit drug use

non-PWUD with active TB

People who do not use meth/mandrax who have active TB disease

Interventions

Smoked illicit drug use BEHAVIORAL

The exposure of interest is current smoked illicit drug use, particularly methamphetamine and/or methaqualones

PWUD with active TB; PWUD with no active TB

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

750 PWUD in the Western Cape, South Africa will be enrolled into Aim 1. An anticipated 45-75 will have active TB disease and enrolled into Aim 2 and Aim 3 Arm 1 of the study. 50 people who do not smoke illicit drugs with active TB disease will be enrolled into Aim 3 Arm 2.

You may qualify if:

• at least 15 years old
• resident of the study community
• intact mental status at enrollment (i.e., no acute intoxication)
• provide written, informed consent to participate in the study if ≥18 years or written assent and parental consent if \<18 years.
• agree to comply with all study requirements, including provision of contact information and study appointments attendance
• And for Aim 1:
• self-reported meth or Mandrax use in the past month
• urine drug screen positive for meth and/or Mandrax
• all participants other than the seeds must also have evidence that they have been recruited by a peer (the coupon)
• (1) Have evidence of active TB disease on Xpert Ultra from their Aim 1 visit testing or report a recent TB diagnosis (within the past month)

You may not qualify if:

• No current pregnancy by urine pregnancy test
• Not yet started on TB medication
• Attend the Worcester Community Day Clinic, the Empilisweni Clinic, or any other clinic and live in the general Worcester area
• Have newly diagnosed TB
• No self-reported drug use or evidence of drug use by urine test
• No current pregnancy by urine pregnancy test
• Not yet started TB medication
• Current drug or alcohol intoxication
• Mental incapacitation to providing informed consent
• Not currently or previously enrolled in any prophylactic TB therapy studies
• Participants may also be excluded from the study under discretion of the Principal Investigator if the PI believes participation in the study may prove harmful to the participant or the research staff.
• Participants will be enrolled from the main cohort (n=750) (Aim 1) into the additional cohorts under Aims 2 and Aim 3 Arm 1. Aim 3 Arm 2 will be recruited external to the main cohort (Aim 1)

Sponsors & Collaborators

• Boston Medical Center: lead
• University of Stellenbosch: collaborator
• Desmond Tutu HIV Foundation: collaborator
• Boston University: collaborator
• Medical Research Council, South Africa: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Privately Rented Facility

Worcester, South Africa

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Sputum, exhaled bio-aerosols

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Karen Jacobson, MD MPH

  Boston Medical Center/ BUMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2019
• First Posted: November 5, 2019
• Study Start: April 22, 2021
• Primary Completion: October 26, 2023
• Study Completion: August 22, 2024
• Last Updated: April 3, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)