Whole Blood Mycobacterial Growth Assays And Tuberculosis Susceptibility Open Access

Abstract

Background: Developing a valid and simple biomarker test to predict tuberculosis (TB) susceptibility is necessary for reversing recent trends and ending TB. Whole blood mycobacterial growth assays (WBMGA) have demonstrated potential to be used in low resource settings in order to direct screening and preventative care to those most at risk. While WBMGA have been linked to determinants of TB, this thesis explores the association between WBMGA results and the risk of incipient TB disease.

Method: A secondary analysis was conducted with the permission of Innovation for Health and Development (IFHAD) in Lima, Peru on an anonymous, unlinked dataset. Participants were healthy, TB-negative adults who were close contacts of TB index cases.

Results: Mycobacterial growth in blood relative to plasma at or below the median log difference in luminosity of 0.53 relative light units (RLU) was significantly associated with a 3.0 (95% confidence interval= 1.0, 8.0) times increase in risk of developing TB disease within six months (p=0.031).

Conclusions: The results from this analysis demonstrate the potential of WBMGA to be used as a predictive tool of TB susceptibility within six months. Future research is necessary to explore the implementation of WBMGA for use in point-of-care risk evaluation and its potential contribution to the global campaign against TB.

Table of Contents

Introduction 1

Definition of terms 2

Literature Review 3

Determining who is at Risk of TB 4

Importance of biomarkers in disease control and eradication 6

Importance of cost and ease of use in TB control 6

The search for TB biomarkers 7

The potential of WBMGA 8

Objectives 14

Methods 15

Sample population 15

Measuring mycobacterial growth 16

Assessing the relationship of WBMGA results and operational variables 17

Assessing the relationship of WBMGA results and variables associated with TB 17

Incorporating long-term TB epidemiological follow-up data 18

Analysis Strategy 18

Ethical considerations 19

Results 20

Mycobacterial growth in each medium 20

Selecting a comparison for growth in blood 22

WBMGA association with operational, demographic, and TB-associated variables 23

Outcome of interest: Secondary TB 24

Survival analysis 26

Proportional hazards assumption for incipient TB 27

Discussion 27

Limitations 29

Conclusion 30

References 30

About this Master's Thesis

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School	Rollins School of Public Health
Department	Hubert Department of Global Health
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health
Keyword	Susceptibility Tuberculosis Mycobacterial growth inhibition assay Risk Mycobacterial growth assay
Committee Chair / Thesis Advisor	Matthew Magee, Emory University Carlton A. Evans, Imperial College London
Committee Members	Sumona Datta, Liverpool School of Tropical Medicine

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