Assessment of IgA responses to Chlamydia trachomatis antigens among children from trachoma - endemic communities Pubblico
Morgan, Sheri Maria (2013)
Abstract
Trachoma, caused by the bacteria, Chlamydia trachomatis, affects millions of individuals worldwide, and is a leading cause of visual impairment and blindness. Nucleic acid amplifications tests are being used to confirm infection, but tests are expensive and are not routinely available in trachoma - endemic areas. After the introduction of mass drug administration (MDA), trachoma infection diminishes, but clinical signs may continue for a long period of time after infection prevalence declines, requiring new tools to determine if MDA is still warranted, and to carry out surveillance when MDA has stopped. We have previously shown that IgG response against the trachoma antigens, pgp3 and CT694, were associated with ocular pathology and active infection; however, many children with IgG antibody lacked evidence of either pathology or infection, indicating past exposure. In this study, we analyzed IgA responses to pgp3 and CT694 to determine if these provided a better marker of recent infection than IgG responses. Bloodspots were analyzed from a cohort of Tanzanian children (n=155) using an antibody - based multiplex assay to determine associations between IgA antibody responses, infection status, and ocular pathology. A second set of bloodspots were analyzed from a cohort of Tanzanian children (n=173) using an antibody - based multiplex assay to determine the kinetics of IgA antibody responses over time after MDA. Ocular swabs were analyzed for presence of C. trachomatis infection using Amplicor®. Antibody responses to both antigens were associated with infection status as determined by PCR. Only pgp3 antibody responses were significant when observing normal and TF/TI ocular pathology (pgp3 p = 0.0207, CT694 p = 0.4691). For children without evidence of trachoma or infection, 23% tested IgA-positive to pgp3, and 6% tested IgA-positive to CT694. These results suggest that IgA responses are not specific indicators of active infection. The results of the kinetics of IgA responses show a significant decline in both antigens six months after treatment for most age groups. Further studies with larger sample sizes are required to verify the findings of the kinetics of IgA antibody responses.
Table of Contents
Table of Contents
Chapter 1: Introduction........................................................1
1.1 Introduction and Rationale................................................1
1.2 Statement of the Problem.................................................1
1.3 Purpose Statement..........................................................2
1.4 Significance Statement.....................................................3
1.5 Hypothesis......................................................................3
1.6 Definition of Terms............................................................4
Chapter 2: Literature Review....................................................6
2.1 Introduction.....................................................................6
2.2 Trachoma Worldwide..........................................................7
2.2.1 Global Prevalence of Trachoma - the number........................8
2.2.2 Economic Burden and Disability due to Infection...................11
2.3 Trachoma Prevention.........................................................12
2.3.1 Focusing on the 'A' in SAFE...............................................13
2.4 Diagnostic tools for C. trachomatis - ocular and genital studies..19
2.4.1 The Multiplex Bead Assay.................................................20
2.4.2 Serological tools for public health programs..........................21
2.4.3 The trachoma antigens pgp3 and CT694..............................23
2.4.4 Candidate Antigens: MOMP and CPAF..................................24
2.5 Conclusion........................................................................27
Chapter 3: Manuscript.............................................................28
3.1 Title................................................................................29
3.2 Contribution of the Student.................................................30
3.3 Abstract..........................................................................31
3.4 Introduction.....................................................................32
3.5 Methods..........................................................................34
3.6 Results............................................................................36
3.7 Discussion........................................................................40
3.8 Tables and Figures.............................................................46
Chapter 4: Conclusion and Recommendations................................56
4.1 Implementation..................................................................56
4.2 Recommendations...............................................................58
4.3 Conclusion.........................................................................59
References..............................................................................60
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