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Title: Chlamydia trachomatis : quantification, immunological investigation and co-infection with HIV-1
Author: Broadbent, Andrew James
ISNI:       0000 0004 2694 1079
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2010
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Three aspects of Chlamydia trachomatis translational research were explored in this thesis. Firstly, as over 75% of patients with LGV are also HIV-1 sero-positive, a cell-culture model was established to investigate whether HIV-1 altered the replication of C. trachomatis serovar L2 in vitro. Inclusion size was significantly increased in the presence of HIV-1, but there was no significant alteration in chlamydial growth kinetics, infectivity, morphology, or transcription of 16sRNA, ompA or euo, suggesting that viral co-infection did not induce chlamydial persistence. It is, therefore, unlikely that the association of HIV-1 and LGV in vivo is due to an impact of HIV-1 on chlamydial replication in co-infected cells. Secondly, as there is no information on the chlamydial load shed by individuals with a rectal C. trachomatis infection, a qPCR assay was developed and used to determine the number of C. trachomatis organisms per rectal swab in NAAT-positive patients. The geometric mean chlamydial load was 5.0 x 105 organisms per swab (Standard Deviation, 152) and load was associated with proctitis, but not symptoms or HIV-1 infection. Asymptomatic individuals shed as much C. trachomatis as patients with rectal symptoms and might maintain transmission in the community. Finally, an ex vivo IFN-γ ELISpot assay was developed to characterise human cellular immune responses to the C. trachomatis-specific protein, Pgp3. T-cell epitopes were found along the length of the protein, but the magnitude of the immune responses was low. The Pgp3- induced IFN-γ response correlated with C. trachomatis exposure and was dynamic, decreasing after effective treatment. These observations suggest that Pgp3- induced IFN-γ may be useful as a biomarker for current infection, although the sensitivity and specificity of the ELISpot assay need improvement.
Supervisor: McClure, Myra Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral