Nanodisk-MS Assay for the Diagnosis of Active Pulmonary and Extrapulmonary Tuberculosis in Hospitalized Patients

Detection of Circulating Mycobacterium Tuberculosis Antigen Peptides for the Diagnosis of Active Pulmonary and Extrapulmonary Tuberculosis in Hospitalized Patients

Diagnosis and treatment of tuberculosis are often delayed in hospitalized patients, leading to worse outcomes. Rapid diagnosis of tuberculosis currently relies on microscopy and molecular techniques, which have limitations including low sensitivity and high cost.Highly sensitive diagnostic technique is needed for more accurate rapid diagnosis of tuberculosis to aid earlier initiation of antituberculous therapy. Detection of Mycobacterium tuberculosis (MTB) antigens in the bloodstream can potentially allow early diagnosis of tuberculosis. This study aims to evaluate the diagnostic performance of a novel assay using nanotechnology to detect MTB antigens in patients admitted to hospital with suspected pulmonary and/or extrapulmonary tuberculosis. Blood will be taken from eligible patients, and will be sent to the School of Biological and Health Systems Engineering, Arizona State University, for detection of 10-kDa culture filtrate protein (CFP-10) and the 6 kDa early secretory antigenic target (ESAT-6), two antigens specific for MTB, using the Nanodisk-MS assay. Investigations, including microscopy, culture, MTB polymerase chain reaction (PCR), and imaging, will be performed for diagnosis of tuberculosis. The diagnostic performance of Nanodisk-mass spectrometry (MS) assay will be evaluated.

Study Overview

• Status: Completed
• Conditions: Tuberculosis, Pulmonary; Active Tuberculosis; Tuberculosis, Extrapulmonary
• Intervention / Treatment: Diagnostic test: Nanodisk-MS assay

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

Contacts and Locations

Study Locations

• Hong Kong
  • Sha Tin, Hong Kong
    • Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients admitted to the Prince of Wales Hospital and the Alice Ho Miu Ling Nethersole Hospital with suspected pulmonary and extrapulmonary TB will be identified by Infectious Diseases physician and recruited.

Description

Inclusion Criteria:

• Adult patients aged 18 or above,
• Assessed by an Infectious Diseases physician to have clinical and/or radiological suspicion of pulmonary and/or extrapulmonary TB.

Exclusion Criteria:

• Refusal to consent from patients or next of kins for incompetent patients.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic test correlation	Sensitivity, specificity, positive predictive value, and negative predictive value, will be calculated to determine accuracy of Nanodisk-MS assay, in diagnosing "culture-positive" and "culture-negative" pulmonary and/or extrapulmonary TB.	One year from the date of recruitment

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Collaborators: Prince of Wales Hospital, Shatin, Hong Kong; Alice Ho Miu Ling Nethersole Hospital

Publications and helpful links

General Publications

• Liu C, Zhao Z, Fan J, Lyon CJ, Wu HJ, Nedelkov D, Zelazny AM, Olivier KN, Cazares LH, Holland SM, Graviss EA, Hu Y. Quantification of circulating Mycobacterium tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring. Proc Natl Acad Sci U S A. 2017 Apr 11;114(15):3969-3974. doi: 10.1073/pnas.1621360114. Epub 2017 Mar 27.
• Lui G, Wong RY, Li F, Lee MK, Lai RW, Li TC, Kam JK, Lee N. High mortality in adults hospitalized for active tuberculosis in a low HIV prevalence setting. PLoS One. 2014 Mar 18;9(3):e92077. doi: 10.1371/journal.pone.0092077. eCollection 2014.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 28, 2017
• Primary Completion (ACTUAL): July 31, 2019
• Study Completion (ACTUAL): December 31, 2019

Study Registration Dates

• First Submitted: September 1, 2017
• First Submitted That Met QC Criteria: September 1, 2017
• First Posted (ACTUAL): September 5, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 26, 2020
• Last Update Submitted That Met QC Criteria: February 25, 2020
• Last Verified: February 1, 2020

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: TB Protocol ver.1

Drug and device information, study documents

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