Chlamydia trachomatis: strain distribution and host response in relation to gynaecological complications.

Lead Research Organisation: University of Edinburgh
Department Name: MRC Centre for Inflammation Research

Abstract

Chlamydia trachomatis is the commonest sexually transmitted infection in the UK and is estimated to cost the NHS over #100 million per year. The number of cases continues to increase in young adults. Laboratory diagnoses in Scotland for Jan-Jun 2007 show that two thirds were female with an overall 6% increase between the first and second quarters. Control measures rely on a combination of increased public awareness, diagnosis, antibiotic treatment and partner notification but are clearly failing to prevent spread of infection. C. trachomatis infection is often asymptomatic and goes untreated but can have serious implications for subsequent female reproductive health. Primary infection can resolve without intervention, presumably due to protective immunity. In some individuals C. trachomatis infection can be episodic although it is unclear whether this is due to failure of antibiotic control, bacterial persistence or to reinfection due to inadequate protective immunity in the reproductive tract. The National Chlamydia Screening Programme in England reports that 10-30% of women infected by C. trachomatis develop pelvic inflammatory disease [PID]. The risk of developing PID and other reproductive sequelae increases with each recurrence of C. trachomatis infection and infection is associated with increased risk of tubal infertility, reproductive failure and ectopic pregnancy. There is controversy as to whether some strains of C. trachomatis are more virulent than others and whether persistent infection is responsible for reproductive disease. Hitherto studies have been conducted in isolation by different groups. This disconnection has contributed to lack of clear understanding how natural history of infection and the host response translate into risk of gynaecological problems. We propose to integrate an internationally competitive, UK group of clinicians and basic scientists to investigate outcomes of C. trachomatis infection on female reproductive health.

Technical Summary

We wish to develop a consortium of UK-wide clinicians and scientists to combine expertise and access to defined patient samples in order to investigate how sexually transmitted infection [STI] with the intracellular bacterium Chlamydia trachomatis [Ctrach] causes damage to the female reproductive tract. Ctrach is the commonest UK STI and current control measures fail to prevent spread. Infection is often asymptomatic and untreated but it can have serious implications for subsequent female reproductive health. In some individuals infection can be episodic although it is unclear whether this is due to failure of antibiotic control, bacterial persistence or to reinfection due to inadequate protective immunity. 10-30% of women infected by Ctrach develop pelvic inflammatory disease [PID] and the risk of developing PID and other reproductive sequelae [tubal infertility, reproductive failure and ectopic pregnancy] increases with each recurrence. Our hypothesis is that PID leading to tubal damage and scarring represents non-resolving inflammation triggered by C. trachomatis infection. Mutant variants and concern over development of antibiotic resistance raise the level of concern. There is no vaccine. Current therapy assumes that all strains are equally pathogenic. Through better understanding of the incidence of infection in women and their partners and of the host response in female patients who do and do not have reproductive pathology, we wish to determine whether or not all chlamydial subtypes cause similar female reproductive damage so that future therapy and prevention, including by vaccination, can be better targeted.

Publications

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Iredale JP (2016) BREXIT and science, where do we go from here. in QJM : monthly journal of the Association of Physicians

 
Description British Fertility Society Guidelines for Practice
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
 
Description "project grant"
Amount £210,818 (GBP)
Organisation Chief Scientist Office 
Sector Public
Country United Kingdom
Start 02/2012 
End 01/2014
 
Title Collaborative grant applications 
Description Grant applications will be submitted based on the research discussions that took part - the first of these will be submitted in december 2010 
Type Of Material Improvements to research infrastructure 
Provided To Others? No  
Impact To be determined 
 
Description Does Chlamydia trachomatis increase miscarriage rate? 
Organisation University of Bristol
Department Bristol Sexual Health Services
Country United Kingdom 
Sector Academic/University 
PI Contribution PhD supervision use of lab facilities
Collaborator Contribution PhD supervision use of lab facilities
Impact PhD studentship - Edinburgh Tommy's Centre Dr A Horne, Prof S Howie Prof G Entrican
Start Year 2012
 
Description Does Chlamydia trachomatis increase miscarriage rate? 
Organisation University of Edinburgh
Department MRC Centre for Reproductive Health
Country United Kingdom 
Sector Public 
PI Contribution PhD supervision use of lab facilities
Collaborator Contribution PhD supervision use of lab facilities
Impact PhD studentship - Edinburgh Tommy's Centre Dr A Horne, Prof S Howie Prof G Entrican
Start Year 2012
 
Description Public Lecture 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact Lecture on the Let's Talk series run by the Centre for Reproductive Biology http://www.crb.ed.ac.uk/letstalk. "Pregnancy in the wrong place: causes and diagnosis of ectopic pregnancy." Dr Andrew Horne and Dr Gary Entrican. Wednesday 12th November 2008 at 5.30-6.30pm. The lecture was held at Edinburgh University, the audience had to pre-register and on the day was over 350, including school students. The feedback was very positive.

School requested work placements in laboratory
Year(s) Of Engagement Activity 2008