Has the incidence of pelvic inflammatory disease following chlamydial infection been overestimated?

Sir: Risser and Risser are to be congratulated on their review of the incidence of pelvic inflammatory disease (PID) in untreated women after infection with Chlamydia trachomatis. This measure is crucial to the assessment of the importance of genital chlamydial infection as a human pathogen, from counselling patients to evaluating the impact and cost-effectiveness of screeningprogrammes. Unfortunately, there is a paucity of high quality evidence. We undertook a similar literature review and findings from our study re-enforce Risser and Risser’s conclusion concerning the reliability of current estimates. However, we also suggest that it may not be valid to conclude that asymptomatic chlamydiapositive women attending clinical settings other than sexually transmitted disease clinics are at lower risk of developing PID. We would like to make a number of additional observations based on the evidence. The study by Morre et al. suffers from a number of methodological weaknesses in addition to those outlined by Risser and Risser. The primary endpoint used was the existence of clinical symptoms, which prompted patients to contact their general practitioner (GP) or the gynaecologist. Patients with selfreported symptoms were assumed to be asymptomatic. All 216 women included in the study, 30 chlamydia positives and 186 negatives, were advised in the information leaflet to contact their GP or gynaecologist, if they had any of the following; lower abdominal pain, intermenstrual bleeding, post-coital bleeding, abnormal vaginal discharge or frequency and/or dysuria. At one month approximately 50% of patients reported such symptoms, but were described as asymptomatic because they had not contacted their GP or gynaecologist. Only three (1.4%) women, all of whom were chlamydia-negative, appear to have consulted their GP during the study period and were treated for suspected chlamydial infection without diagnostic testing. In addition, of the chlamydia-positive women 7 (23%) women were lost to follow-up after six months and nine (30%) by one year. Consequently, it is possible that at least 10% of chlamydia-positive women may have had PID at one month, and it cannot be excluded that over 10% did not develop acute PID during the following 11 months. In the prospective cohort study by Scholes et al. Risser and Risser assume 17% of PID cases in the non-intervention group was due to chlamydia as seven out of 42 women with PID had positive tests for chlamydia or gonorrhoea. This assumes that all women with a diagnosis of PID were tested prior to treatment. It is unlikely to be the case as the study was undertaken between 1990 and 1992 when not all physicians would have been aware of chlamydia as a cause of PID. Thus, their calculations may underestimate the incidence of PID. If we assume a similar prevalence of 7% in the non-screened women compared with those offered screening and that the reduction of 0.012 episodes per year in the screened group is due to treated chlamydia then the incidence of PID, if chlamydiapositive is 17% (0.012/.07) per year. The authors could have included results from two further studies. Ostergaard et al. in a randomized controlled trial of chlamydial screening among women attending educational establishments observed a prevalence of genital chlamydial infection of approximately 5% in the intervention group. After a one-year follow-up, 2.1% of the intervention group developed PID, compared with 4.2% of the non-intervention group. If, as with the Scholes study, we assume that reduction in PID is attributable to treated chlamydial infection then the estimated incidence of PID if chlamydia-positive is 42% (0.021/ 0.05). Tait et al. undertook laparoscopy on 10 chlamydia-positive women with no clinical evidence of upper genital tract disease prior to treatment. C. trachomatis was detected in the upper genital tract of four women, two women had evidence of severe inflammation with hyperaemia and exudates and three had evidence ofmilderupper genital tract inflammationwith hyperaemia or oedema. There was no association between the detection of chlamydia and the observable upper genital tract inflammation. This suggests that silent PID may occur in the absence of clinical symptoms or signs. Finally, the duration of follow-up differed between the studies cited by Risser and Risser, some being as little as four weeks. Whether a longer duration of follow-up would increase the likelihood of developing PID is unknown as the incubation period following genital chlamydial infection has not been determined. Investigators have suggested that the rate of progression from genital chlamydial infection to complications may be lower than previously suggested. The review by Risser and Risser in conjunction with the evidence provided above does not support the conclusion that population-based studies consistently estimate lower incidence rates of PID than clinic-based studies. From the evidence presented a reasonable estimate of PID incidence, until more reliable evidence becomes available, is in the range 5–30%, most likely 10–20%. An accurate estimate of the rate of progression of genital chlamydial infection to PID is urgently required. Any such estimate needs to be agreed by researchers in the field and standardized in future modelling and cost-effectiveness studies. Given the problems in diagnosing PID, and the fact that it is widely considered unethical to withhold treatment from infected individuals, any future definitive studies require careful planning and assessment. However, these issues need to be discussed now if we are to provide an evidence-base with which to accurately evaluate chlamydial screening programmes.