Examination of Optimal Culture Methodologies and Conditions for Tuberculosis Treatment Trials Öffentlichkeit

Abstract

Abstract

Examination of Optimal Culture Methodologies and Conditions for Tuberculosis Treatment Trials

By: Keun O. Lee

Introduction: Tuberculosis (TB) is a contagious and airborne disease of the lungs caused by Mycobacterium tuberculosis (Mtb) that continues to be a one of top ten causes of death worldwide. In efforts to eliminate TB epidemic, the Tuberculosis Trials Consortium (TBTC) conducts clinical trials, which relies on culture media for assessment of treatment efficacy. The purpose of this study is to examine three different culture systems, Löwenstein-Jensen medium (LJ), selective Middlebrook agar (7H11S), and BACTEC MGIT 960 (MGIT), for the identification of methods and conditions that are optimal for Mtb growth and robust against contamination in detection of Mtb.

Methods: LJ, 7H11S, and MGIT were compared on sensitivity, proportions of Mtb positivity, contamination, and discordance of media results. The two solid culture media, LJ and 7H11S, were additionally stratified by exposure to 8-10% carbon dioxide (CO2) during incubation. Secondly, independent generalized linear mixed effects models (GLMMs) were used to simultaneously assess the effects of solid medium type, CO2 exposure, total sputum sample volume, participant HIV status, and time on treatment on culture positivity and Mtb recovery against contamination.

Results: MGIT had the highest sensitivity (98.5%), followed by 72.2% and 77.6% for 7H11S and 7H11S/CO2, and 67.8% and 69.2% for LJ and LJ/CO2, respectively. Similarly, Mtb yield was highest for MGIT with 55%, followed by 7H11S/CO2, 7H11S, LJ/CO2, and LJ. Contamination varied across different sites. Modeling result showed statistically significant negative effects on solid culture positivity for LJ method, HIV-positive status, and increase in treatment time with adjusted odds ratio (OR) of 0.514 (95% CI: 0.401, 0.658), 0.227 (0.082, 0.629), and 0.379 (0.351, 0.409), respectively. CO2 exposure showed a positive effect on solid culture positivity with OR=1.367 (1.073, 1.818). In addition, treatment time and sputum sample volume >3mL showed significantly negative effects on Mtb recovery for both solid and liquid media (p<0.05).

Discussion: Results indicated that the higher odds of Mtb-positive cultures are associated with 7H11S medium compared to LJ, CO2 incubation, HIV-negative individuals, and earlier weeks of TB treatment. There were reduced odds of Mtb-positive cultures due to contamination associated with sputum volume > 3mL and longer time on treatment.

Table of Contents

Table of Contents

1. Introduction………………………………………………………………………………………………………...1

1.1 Problem Statement…………………………………………………………….…………………...……...2

1.2 Purpose Statement………………………………………………………………………………..………...3

1.3 Significance Statement…………………………………………………………………………….……...3

2. Background………………………………………………………………………………………………...……...4

2.1 TB Overview……………………………………………………………………………………….......……...4

2.2 TB Diagnostic Tests…………………………………………………………………………………..……...5

3. Data Description & Methodology………………………………………..……………………………...6

3.1 Setting and Specimen Collection…………………………………..……………...………..……...7

3.2 Data Analysis…………………………………..…………….....................................……...8

3.2.1 Sensitivity, Mtb Yield, Contamination, and Discordance Analysis……….……...8

3.2.2 Nested Logistic Regression Mixed Effects Models……………………….……….……...9

4. Results………………………………………………………………………………..…………………....……...12

4.1 Sensitivity, Mtb Yield, Contamination, and Discordance Analysis Results……..12

4.2 Modeling Results & Interpretations……………………………………………...……...……....17

5. Discussion………………………………………………………………………..…..………...……...……....21

5.1 Implications…………………………………………………………………..….………...……...…….....26

5.2 Strength and Limitations……………………………………………..…………..………...……...…26

5.3 Recommendations……………………………………………..…………..……..………...……...……28

References………………………………………………………………………………..………...……...……....30

Appendix…………………………………………………………………………..……..………...……...……....32

About this Master's Thesis

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School	Rollins School of Public Health
Department	Biostatistics and Bioinformatics
Subfield / Discipline	Biostatistics - MPH & MSPH
Degree	MSPH
Submission	Master's Thesis
Language	English
Research Field	Statistics Health Sciences, Public Health Biology, Molecular
Stichwort	Tuberculosis GLMM Culture systems
Committee Chair / Thesis Advisor	Waller, Lance, Emory University
Committee Members	Reynolds, Sue, CDC
Partnering Agencies	CDC

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