Chlamydia screening Is it worth it? Dr. Phillip Hay Reader in Sexual Health & HIV Medicine St. George’s, University of London

More or less ? 35% Coverage £ 23/test + cost of Rx and PN for those testing positive £ 50 Million

Overview Reminder of PID and Chlamydia Outline CSP Latest updates

Chlamydia trachomatis Common sexually transmitted infection Majority of infections are asymptomatic Highest rates of infection among young people Easy to detect using NAAT tests Easy to treat with antibiotics Chlamydia infected culture (Wellcome Images)

Rationale for chlamydia screening Chlamydia infection is a known risk factor for a number of serious health problems: –Pelvic inflammatory disease –Ectopic pregnancy –Tubal factor infertility –Neonatal pneumonia and neonatal conjunctivitis –Epididymitis in men Treating chlamydia infections prevents the development of sequelae –RCT showed 83% reduction in PID among treated compared to untreated chlamydia infection (p>0.05) [1] [1] Oakeshott et al. BMJ 2010;340:c1642

Rationale for chlamydia screening Asymptomatic screening to detect chlamydia trachomatis should: –Reduce the prevalence and incidence of infection –Reduce the risk of developing health problems

What do we want to know? Impact of widespread screening for asymptomatic chlamydia infections on –Prevalence and incidence of chlamydia –The incidence of complications –Young adults’ sexual health and wellbeing The predicted impact The impact in practice

Chlamydia prevalence among year olds: Modelling the effectiveness of screening NAO, Based on: Turner et al. STI 2006 Key assumptions: Baseline prevalence 6.5%; PN 20%; few cases treated in absence of screening programme Testing coverage: 9% Testing coverage: 26% Testing coverage: 43% Years after introduction of the screening programme Chlamydia prevalence (%)

Randomised controlled trial of chlamydia screening, Netherlands RCT among >300, year old men and women Annual postal invitation to chlamydia screening for 3 years Lower than expected uptake (10% -16%) No significant fall in prevalence was observed some evidence for a fall in South Limburg Van den Broek et al. BMJ 2012

Number of tests and proportion testing positive by gender (NCSP tests)

Ectopic Pregnancy Tubal Factor Infertility Pelvic Inflammatory Disease Chlamydia infection Chlamydia is an important cause of reproductive health problems in women 1% / 10% / 30% 7.6% 10.8% Source: Adams et al. STI 2007; 83;

Chlamydia is an important cause of reproductive health problems in women ~10% to 20% risk of developing PID after a chlamydia infection [1,2] ~45% of tubal factor infertility is caused by chlamydia [3] [1] Oakeshott et al. BMJ 2010;340:c1642; [2] Price et al. Am J Epi. In press; [3] Price STD 2012;39(8)

Can chlamydia screening prevent ‘PID’? [4] Scholes NEJM:1996;334:1362-6; [5] Ostergaard CID:2000;31:951–7; [6] Oakeshott BMJ:2010;340:c1642

Rate of PID diagnoses* in General Practice by age group (Females 16 to 44 years old) *Definite/probable PID diagnoses Source: French et al. STD 2011: 38(3):158-62

Question Should the NCSP routinely recommend repeat testing following a positive chlamydia test result?

Risk of re-infection following a positive chlamydia test [1]Lamontagne. STI 2007; [2] PLoS.One. 2012;[3] Batteiger JID Young people who test positive for chlamydia are at higher risk of subsequently testing positive for chlamydia [1-3]

Time between treatment and repeat testing The optimum interval for repeat testing has not been established This will depend on logistical and biological considerations CountryRecommended re-testing interval USAApproximately 3 months Canada6 months Australia3 months New Zealand6 months Scotland3-12 months, or sooner if there is a change of partner

Summary: What do we know? Young people who test positive for chlamydia are at increased risk of subsequent infection High rates of repeat infection are consistently reported Repeat infections may be important causes of morbidity and maintaining chlamydia epidemics Rates of repeat testing in England are moderate, but could be higher Mailed screening kits, and telephone or text message reminders appear to increase repeat testing rates

PID Important sequelae Clinical diagnosis poor specificity Microbiological aetiology often unknown Treatment trials base is poor Evolving antimicrobial resistance Pretty Imprecise Diagnosis

Pelvic Inflammatory Disease Acute clinical episode Ascending spread of microorganisms from vagina/cervix To endometrium, fallopian tubes and/or contiguous structures

Complications of PID Ruptured tubo-ovarian abscess Tubal infertility 12.8% after 1 episode 35.5% after 2 episodes 75% after 3 or more episodes Chronic pelvic pain 18% Westrom L. Am J Obstet Gynecol Mar 1;121(5):707-13

Ectopic pregnancy Risk increased 7-10 fold 1/16 in pregnancy following an episode of PID 1/147 in control group Westrrom L. Am J Obstet Gynecol Mar 1;121(5):707-13

PID Diagnosed in STI Clinics in England

Pelvic pain > 90% Deep dyspareunia Abnormal vaginal bleeding Lower genital tract infection Cervical motion/adnexal tenderness +/- fever >38 0 Raised CRP, ESR, WCC Diagnosis of PID

Pelvic Inflammatory Disease Jacobson L, Westrom L. Am J Obstet Gynecol Dec 1;105(7):

Am J Obstet Gynecol 1993;168:1503-9

Chlamydia trachomatis Ascending infection PID Perihepatitis (Fitz-Hugh Curtis Syndrome) Epididymo-orchitis Ectopic pregnancy Infertility Tubal factor Male ? Reiter’s syndrome/SARA

Prevalence of Chlamydia trachomatis in women with PID Simms Sex Trans Inf 2000;76:80-87

Heterotypic resistance in Chlamydia Conventional antimicrobial resistance has only rarely been observed with C. trachomatis clinical isolates. At high infection loads, in vitro persistence can often be demonstrated to antimicrobials—heterotypic resistance. The subsequently recovered isolates do not possess antimicrobial resistance at low loads 8% ( 95% CI 5% to 11%) failure rate using recommended treatment regimens for uncomplicated genital C trachomatis infection in 289 women who had not subsequently been sexually active. Golden et al N Engl J Med 2005;352:676–85

Yeh Sex Trans Dis 2003;30:369-78

2529 women (mean age 20.9) outcome data on 2377 (94%) 38 probable or possible PID: 1.3% (15/1191) in the intervention group 1.9% (23/1186) in the control group RR 0.65, (95% CI 0.34 to 1.22). The reduction in PID among women with chlamydia at baseline (1/63 in the intervention group vs 7/74 in the control group, RR 0.17, 95% CI 0.03 to 1.01) is also encouraging.

the 10 reported cases of chlamydia-positive PID among women who were chlamydia-negative at baseline could not have been prevented by the screening intervention. These cases highlight ongoing chlamydia transmission as the underlying problem; infections acquired in new relationships and reinfections within ongoing partnerships that result from failed partner notification still need to be tackled.

Obtaining specimens at follow-up for chlamydia testing and Controlling chlamydia transmission is proving much more difficult to deal with than gonorrhoea in the 1970s. The characteristics of C trachomatis, including the long duration of asymptomatic infection and prolonged life cycle, contribute to sustaining transmission and reinfection which drive the progression to PID. The results of the POPI trial suggest that current levels of chlamydia screening uptake in England are unlikely to have a measurable impact on the overall incidence of PID. The interventions being evaluated now should prioritise both screening and prevention of reinfection to maximise the impact on chlamydia transmission.

Int J Epidemiol.Int J Epidemiol Apr;38(2): doi: /ije/dyn222. Epub 2008 Dec 5. Effectiveness of chlamydia screening: systematic review. Low N. et al Two randomized trials: register-based screening of women at high risk of chlamydia and of female and male high school students reduced the incidence of pelvic inflammatory disease in women at 1 year. One randomized trial: opportunistic screening before TOP reduced post-abortal rates of PID. There is an absence of evidence supporting opportunistic chlamydia screening in the general population younger than 25 years, the most commonly recommended approach. Equipoise remains, so high-quality randomized trials of multiple rounds of screening with biological outcome measures are still needed to determine the balance of benefits and harms of chlamydia screening.

International Journal of Epidemiology Volume 42, Issue 2 International Journal of Epidemiology Volume 42, Issue 2 Pp The risk of TFI in individuals with past or current chlamydial infection is low (0.9– 1.4%) and varies little with age. Using a broader infertility definition (24 months primary or secondary infertility) the risk increases to 4.5%.

Is it worth it? Likely that we overestimated rates of complications associated with chlamydia diagnosed by NAATs Efficacy of Rx is not 100% Prevalence does not yet appear to be dropping Should we invest in more/better targeted screening to have more effect?