Transmission and Acquisition of Nontuberculous Mycobacteria Outbreak Investigation (TrANsMIt) (TrANsMIt)

The goal of this observational study is to support U.S. healthcare centers in determining if they may have an NTM outbreak among patients receiving care at the healthcare center. The study applies a standardized, reproducible outbreak investigation approach across diverse healthcare settings. This study focuses on patients with NTM isolates suspected to be part of an outbreak, receiving care at a specific U.S. healthcare center.

The main questions it aims to answer are:

Can application of a standardized epidemiologic investigation framework support evaluation of whether clustered NTM infections may be consistent with healthcare-associated exposure? Are respiratory NTM isolates genetically related to environmental NTM isolates identified within healthcare settings or shared home water sources?

Researchers will compare clinical, epidemiologic, molecular, and infection prevention data from suspected NTM isolates to determine whether patterns are consistent with healthcare-associated transmission or acquisition.

Participants (healthcare centers and selected patients) will:

• Implement a standardized epidemiologic investigation using the Healthcare-Associated Links in Transmission of Nontuberculous Mycobacteria (HALT-NTM) toolkit
• Submit available respiratory and environmental NTM isolates for molecular comparison, when applicable
• Optionally collect dust and water biofilm samples within the healthcare setting
• Complete a survey to provide home address history for watershed mapping, when clustered infections are identified

Study Overview

• Status: Recruiting
• Conditions: Mycobacterium Infections; Healthcare Associated Infection; Nontuberculous Mycobacterial Pulmonary Infection; Outbreak Investigation
• Intervention / Treatment: Other: Epidemiologic investigation

Detailed Description

This study is a parallel multi-site study of people cared for in a healthcare center who are identified with highly similar respiratory nontuberculous mycobacteria (NTM) isolates. All study activities described herein are optional and conducted at the discretion of each participating site.

This is an outbreak investigation and involves no more than minimal risk, which is commensurate with those inherent in the actual or expected care of a patient with pulmonary NTM. No samples will be collected from the identified participants outside of routine clinical care. As with any research study, there is a potential risk of breach of individual patient confidentiality. Linked to the samples will be clinical data, specifically NTM culture results and designation of NTM disease status, as well as data captured routinely in the course of clinical care. There is no additional testing required for this protocol beyond what is recommended for standard care, and no additional research visits beyond normally scheduled clinic visits.

The Transmission and Acquisition of Nontuberculous Mycobacteria Outbreak Investigation (TrANsMIt) study is designed to provide resources to systematically collect data to perform an outbreak investigation on people in a suspected healthcare-associated NTM outbreak. Respiratory NTM isolates will undergo WGS to identify infections that are highly related and falling into clusters in order to determine if the source of NTM infection may be a healthcare-associated outbreak. The investigators integrated clinical and epidemiological research methods to adapt a CDC standardized, and validated Healthcare-Associated Infection Outbreak Investigation Toolkit to retrospectively collect data for suspected healthcare-associated NTM outbreak investigations. Through consultation with subject matter experts and scientific literature review, the investigators modified the CDC Healthcare-Associated Infection Outbreak Investigation Abstraction Form, designed to be utilized in local investigations of common healthcare-associated infections to develop the Healthcare-associated links in transmission of NTM (HALT NTM) study Outbreak Investigation Abstraction Toolkit. The HALT NTM Toolkit is a Health Insurance Portability and Accountability Act (HIPAA) compliant, web-based, branching logic questionnaire that uses integrated clinical and epidemiological research methods to perform an epidemiologic investigation to identify overlaps in space and time with mapping of visits and source(s) of care among patients with highly similar NTM isolates in a Center. Additionally, the Toolkit assesses detailed Center-specific IP&C measures utilized the healthcare system. Utilizing the HALT NTM toolkit, the TrANsMit study facilitates a standardized, stepwise process by which healthcare centers perform an internal epidemiologic evaluation of patients identified as part of an NTM cluster. Since clustered NTM isolates could originate from a shared healthcare source, dust and water biofilms from the healthcare environment are collected. NTM are recovered, identified, and sequenced as described to determine if the respiratory NTM strain genotype is similar to those recovered from the healthcare environment. Through a collaborative agreement, TrANsMIt is available to U.S. healthcare centers to conduct a standardized, independent, confidential NTM outbreak investigation.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Principal Investigator; Phone Number: 919-445-4240; Email: Jane_gross@med.unc.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina- Chapel Hill
      • Contact: Jane Gross; Phone Number: 919-445-4240; Email: jane_gross@med.unc.edu
      • Contact: Silvia Caceres; Phone Number: 919-445-4240; Email: silvia_caceres@med.unc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Male or female participant of any age who has a history of respiratory NTM or a first positive NTM culture collected as part of routine clinical care from expectorated sputum, induced sputum and/or bronchoalveolar lavage.

Description

Inclusion Criteria:

• Male or female participant of any age who has a history of NTM or a first positive NTM culture collected as part of routine clinical care from expectorated sputum, induced sputum and/or bronchoalveolar lavage.

Exclusion Criteria:

• No NTM respiratory culture

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
People infected with related NTM isolates identified as having membership in a related cluster; Characterize the source(s) of acquisition and/or direct or indirect patient-to-patient transmission of NTM within a healthcare setting among participants with highly related isolates.	Other: Epidemiologic investigation; Identification of: overlaps in source(s) of care between participants with NTM isolates in a healthcare center.; environmental NTM isolates that are highly related to respiratory isolates.; common water source exposure among subjects with clustered NTM infections via shared home of residence watershed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epidemiologic Investigation	Identification of a shared healthcare-associated source(s) between patients in a healthcare center.	5 years
Dust and Water Biofilm Collection	Identification of healthcare dust and water biofilm NTM isolates that are highly related to the isolates recovered from subjects within a healthcare system.	5 years
Home of Residence Watershed Mapping	The primary endpoint is identification of common watersheds among subjects infected with clustered NTM isolates.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geographic Patterns and Genetic Relatedness of Nontuberculous Mycobacteria Across Healthcare Centers	Incidence and prevalence of NTM species/subspecies by geographical region. Between Center comparisons of genetic similarity and patterns of potential transmission. Banking of isolates for ex vivo analysis.	5 years
Regional Incidence and Prevalence of Nontuberculous Mycobacteria Identified in Healthcare Dust and Water Biofilm	Incidence and prevalence of healthcare-associated dust and water biofilm NTM species/subspecies by geographical region.	5 years

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: University of Texas at Tyler; National Jewish Health
• Investigators: Principal Investigator: Jane Gross, MD, PhD, University of North Carolina, Chapel Hill

Publications and helpful links

General Publications

• Gross JE, Caceres S, Poch K, Hasan NA, Davidson RM, Epperson LE, Lipner E, Vang C, Honda JR, Strand M, Strong M, Saiman L, Prevots DR, Olivier KN, Nick JA. Healthcare-associated links in transmission of nontuberculous mycobacteria among people with cystic fibrosis (HALT NTM) study: Rationale and study design. PLoS One. 2021 Dec 20;16(12):e0261628. doi: 10.1371/journal.pone.0261628. eCollection 2021.
• Gross JE, Caceres S, Poch K, Hasan NA, Jia F, Epperson LE, Lipner E, Vang C, Honda JR, Strand M, Calado Nogueira de Moura V, Daley CL, Strong M, Davidson RM, Nick JA. Investigating Nontuberculous Mycobacteria Transmission at the Colorado Adult Cystic Fibrosis Program. Am J Respir Crit Care Med. 2022 May 1;205(9):1064-1074. doi: 10.1164/rccm.202108-1911OC.
• Gross JE, Teneback CC, Sweet JG, Caceres SM, Poch KR, Hasan NA, Jia F, Epperson LE, Lipner EM, Vang CK, Honda JR, Strand MJ, Calado Nogueira de Moura V, Daley CL, Strong M, Davidson RM, Nick JA. Molecular Epidemiologic Investigation of Mycobacterium intracellulare Subspecies chimaera Lung Infections at an Adult Cystic Fibrosis Program. Ann Am Thorac Soc. 2023 May;20(5):677-686. doi: 10.1513/AnnalsATS.202209-779OC.
• Ankrum AL, Caceres SM, Torsell M, Epperson E, Calado Nogueira de Moura V, Gilick JJ, Strong M, Liu Q, Strand MJ, Wilsey RN, Honda JR, Gross JE, Scaggs-Huang FA. Mycobacterium chelonae outbreak investigation at a quaternary pediatric hospital following the opening of a LEED-certified critical care tower: where does water sustainability intersect with infection control? Infect Control Hosp Epidemiol. 2026 Feb;47(2):161-169. doi: 10.1017/ice.2025.10344. Epub 2025 Nov 24.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Estimated): December 28, 2036
• Study Completion (Estimated): December 28, 2036

Study Registration Dates

• First Submitted: May 5, 2023
• First Submitted That Met QC Criteria: December 1, 2023
• First Posted (Actual): December 4, 2023

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Epidemiology; Infection transmission; Nontuberculous Mycobacterial Pulmonary Infection; Healthcare Associated Infection; Outbreak investigation; Infection acquisition
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Iatrogenic Disease; Actinomycetales Infections; Pathological Conditions, Signs and Symptoms; Mycobacterium Infections; Cross Infection
• Other Study ID Numbers: 25-0472; HS-4062 (Other Identifier: National Jewish Health)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: There is a plan to make de-identified IPD and related data dictionaries available. All IPD will be made available upon reasonable request. Requests will be reviewed to ensure alignment with the original informed consent and applicable ethical and regulatory requirements.
• IPD Sharing Time Frame: De-identified IPD and supporting documentation will become available 6 months after publication and will remain available for a period of 3 years thereafter.

IPD Sharing Access Criteria

Access to de-identified IPD will be granted to qualified researchers upon reasonable request. Requests must include a methodologically sound research proposal and will be reviewed for consistency with the original informed consent, ethical considerations, and applicable regulatory requirements.

Prior to data release, approval by the University of North Carolina at Chapel Hill (UNC) and execution of a UNC Data Use Agreement (DUA) will be required. Data will be shared only after confirmation that all required institutional approvals and agreements are fully executed. Requests should be directed to the corresponding author.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No