TB sensitization measured by interferon gamma and non-interferon gamma cytokines among South African Infants Restricted; Files Only

Abstract

Background: Young children infected with Mycobacterium tuberculosis (Mtb), the bacteria that causes Tuberculosis disease (TB), are more likely to progress from latent TB infection (LTBI) to TB disease than older children older than 5 and adults. Additionally, the two methods of diagnosing Mtb infection that are currently in use, the tuberculin skin test (TST) and the interferon gamma release assay (IGRA), face limitations in test specificity and sensitivity that are unique to the immune response of pediatric screening recipients. The use of novel diagnostics that measure cytokines in addition to interferon gamma to detect early immune Mtb sensitization may increase diagnostic sensitivity from that of standard IGRA methods, and research on these diagnostics is ongoing to identify the most useful cytokines for predicting Mtb infection and cofactors to sensitization. 

Methods: Pairs of mothers and infants in Khayelitsha, South Africa, were recruited within a few hours after birth and enrolled in a longitudinal cohort study for one year of follow-up. This nested case-control study collected IGRA and non-IGRA testing data using the T.SPOT TB and Luminex assays on cryopreserved biospecimens collected during study follow-up visits. Data analyses were conducted to find prevalence of TB infection, test agreement based on Cohen’s kappa statistic, and measures of association for select clinical cofactors based on univariate linear regression. 

Results: Of the 159 infants sampled (150 with valid IGRA tests), 7 infants (4.7%) were positive for TB infection based on IGRA testing. Non-IGRA criteria for possible TB infection detected an additional 24 infants with positive results, bringing the prevalence of TB infection based on combined IGRA and non-IGRA results to 31 infants (19%). Overall, IGRA and non-IGRA test results demonstrated substantial agreement (κ = 0.63). Measures of association for breastfeeding exclusivity demonstrated a possible positive correlation to positive test outcomes, but these measures were not shown to be statistically significant. 

Conclusion: Non-IGRA cytokine measurement may increase test sensitivity for detecting possible TB infection among infants when combined with IGRA testing. Future studies should further evaluate the best TB-specific cytokine and chemokine biomarkers for prognostic value and possible cofactors of interaction to immune sensitization. 

Table of Contents

Chapter 1: Introduction 1

Chapter 2: Background 2

Chapter 3: Methods & Results 15

Methods 15

Results 20

Chapter 4: Discussion, Conclusion & Recommendations 27

Discussion 27

Conclusion 29

Recommendations 29

References 29 

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 Health Sciences, Epidemiology Health Sciences, Immunology
Palabra Clave	Tuberculosis, immunology, South Africa, pediatric TB
Committee Chair / Thesis Advisor	Kenneth G. Castro, MD, Emory University
Committee Members	Lisa Marie Cranmer, MD, MPH, Emory University

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