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

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.

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.