Bioaerosol Sampling in Suspected Pulmonary Tuberculosis

Bioaerosol Sampling of Patients With Suspected Pulmonary Tuberculosis: A Study Protocol

Tuberculosis (TB) is transmitted in bioaerosols containing Mycobacterium tuberculosis (Mtb). Mtb-containing bioaerosols are likely related to host infectiousness and central to ongoing TB transmission. No routine diagnostic assay exists to measure Mtb in bioaerosols. Furthermore, published studies of Mtb in bioaerosol samples, have been limited to individuals with sputum-positive pulmonary TB. Currently TB diagnosis is based on clinical symptoms and sputum laboratory findings. However, approximately half of all patients commencing TB treatment are sputum negative resulting in a high proportion of presumptive treatments. We therefore propose to use a sensitive sampling protocol to investigate the prevalence of Mtb-containing bioaerosols in both sputum-positive and sputum-negative TB suspects.

Study Overview

• Status: Completed
• Conditions: Pulmonary Tuberculosis Confirmation by Sputum Microscopy With or Without Culture
• Intervention / Treatment: Diagnostic test: Bioaerosol Sampling

Detailed Description

Our pragmatic, parallel-group design is aimed at identifying viable Mtb in bioaerosols produced by individuals attending a TB clinic in Cape Town, South Africa. Bioaerosol sampling will be performed on all eligible individuals presenting with symptoms indicative of TB and repeated at 14 days if initially positive for viable Mtb. Participants will be classified into three distinct groups based on the National TB Control Program (NTBCP) criteria: Group A, TB notification with sputum-based laboratory confirmation; Group B, TB notification with empiric diagnosis; and Group C, individuals not notified. Group C individuals with detectable Mtb bioaerosol will be monitored until resolution of clinical and laboratory status. Collection of bioaerosol specimens will be via two consecutive sampling modalities: (1) direct sampling of a specific respiratory manoeuvre; and (2) indirect sampling following passive respiratory activity and environmental sampling. microscopy. Mtb genomes and mycobacterial and host lipids will be detected using droplet digital PCR and mass spectrometry analyses, respectively. The primary objective is to determine the prevalence of Mtb bioaerosols in all TB clinic attendees and in each of the mutually exclusive groups A, B and C. Secondary objectives are to investigate differences in prevalence of Mtb bioaerosol by HIV status, current isoniazid preventive therapy (IPT) use and pre and post initiation of anti-TB chemotherapy.

• Study Type: Observational
• Enrollment (Actual): 102

Contacts and Locations

Study Locations

• South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa
      • Aerobiology Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 100 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients with respiratory and/or constitutional symptoms suggestive of pulmonary TB who self-present to two TB clinics in high density peri-urban settlements in Cape Town, South Africa will be offered recruitment to the study

Description

Inclusion Criteria:

• age over 13 years
• person with suspected TB
• provision of written, informed consent (parental consent and patient assent for those aged under 18yrs)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
A: Notified TB with sputum laboratory confirmation; Bioaerosol Sampling: (1) direct sampling of a specific respiratory manoeuvre; and (2) indirect, following passive respiratory activity and environmental sampling. Repeat bioaerosol sampling will be conducted at 14 days.	Diagnostic test: Bioaerosol Sampling; Cyclone collection of exhaled bioaerosol
B: Notified TB without sputum laboratory confirmation; Bioaerosol Sampling: (1) direct sampling of a specific respiratory manoeuvre; and (2) indirect, following passive respiratory activity and environmental sampling. Repeat bioaerosol sampling will be conducted at 14 days.	Diagnostic test: Bioaerosol Sampling; Cyclone collection of exhaled bioaerosol
C: Not Notified for TB; Bioaerosol Sampling: (1) direct sampling of a specific respiratory manoeuvre; and (2) indirect, following passive respiratory activity and environmental sampling. Repeat bioaerosol sampling will be conducted at 14 days.	Diagnostic test: Bioaerosol Sampling; Cyclone collection of exhaled bioaerosol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Aim	The difference in prevalence proportions of Mtb-containing bioaerosol in sputum positive and sputum negative pulmonary TB cases (Groups A & B)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Aim (1)	The difference in numbers of viable MTB organisms in bioaerosols per liter of air sampled and per nano-liter of bioaerosol particulate volume collected in both sputum positive and sputum negative pulmonary TB cases (Groups A & B).	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Aim (1)	The prevalence of MTB containing bioaerosols in TB suspects not diagnosed with clinical TB (Group C)	12 months
Exploratory Aim (2)	The difference in prevalence and numbers of viable MTB in subjects receiving and not receiving IPT prophylaxis.	12 months
Exploratory Aim (3)	The difference in prevalence and numbers of viable MTB in subjects with and without HIV-infection.	12 months
Exploratory Aim (4)	The difference in prevalence and numbers of viable MTB in subjects before and after TB therapy.	12 months
Exploratory Aim (5)	The difference in numbers of viable MTB in bioaerosol collected by direct and indirect sampling.	12 months
Exploratory Aim (6)	The ratio of MTB genomes (ddPCR) to viable MTB organisms (DMN-tre-positive) in MTB containing bioaerosol	12 months
Exploratory Aim (7)	Which MTB lipids are present in MTB containing bioaerosol	12 months

Collaborators and Investigators

• Sponsor: Desmond Tutu HIV Foundation
• Collaborators: National Institutes of Health (NIH); University of Cape Town; Zeteo Tech Incorporated

Publications and helpful links

General Publications

• Patterson B, Koch A, Gessner S, Dinkele R, Gqada M, Bryden W, Cobelens F, Little F, Warner DF, Wood R. Bioaerosol sampling of patients with suspected pulmonary tuberculosis: a study protocol. BMC Infect Dis. 2020 Aug 8;20(1):587. doi: 10.1186/s12879-020-05278-y. Erratum In: BMC Infect Dis. 2020 Aug 24;20(1):624.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2020
• Primary Completion (Actual): May 27, 2022
• Study Completion (Actual): May 27, 2022

Study Registration Dates

• First Submitted: November 27, 2019
• First Submitted That Met QC Criteria: January 22, 2020
• First Posted (Actual): January 27, 2020

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary
• Other Study ID Numbers: R01AI147347-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The outcomes of the analysis in addition to the unprocessed data will be submitted for publication in open-source peer-reviewed journals and presented at international conferences.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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