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Chlamydial salpingitis and pelvic inflammatory disease

Introduction

Pelvic inflammatory disease (PID) is infection of the uterus, fallopian tubes, and adjacent pelvic structures that is not associated with either surgery or pregnancy. It is caused by ascending infection from the lower genital tract of bacteria associated either with sexually transmitted disease (gonococci, C. trachomatis), Mycoplasma genitalium [Cohen et al., 2002] or vaginosis (various anaerobic bacteria) resulting in inflammation of the uterine lining [endometritis] and of the fallopian tubes [salpingitis]. While it is clear that C. trachomatis and N. gonorrhoeae are common and important causes of PID, there is less information on the role of M. genitalium. However, in a case control study, Simms et al., 2003 using real time PCR to detect M. genitalium infection and LCR for C. trachomatis found that in 45 PID cases 13% had  M genitalium infection and 27% C. trachomatis infection compared to none of 37 controls. This association of these organisms with PID was significant (p<0.001) and largely independent of each other.

Diagnosis, risk factors, treatment

The clinical spectrum of pelvic inflammatory disease ranges from virtually asymptomatic endometritis to severe salpingitis, pyosalpinx, tubo-ovarian abscess, pelvic peritonitis, and perihepatitis [Paavonen, 1998]. Clinical signs include: low grade fever; exudate from the cervix [the neck of the womb]; sensitivity of the cervix to movement and abdominal tenderness due to locally enlarged lymph nodes. However these clinical criteria are insensitive and non-specific criteria of infection, with false-positive and false-negative diagnosis common  [Washington et al., 1990]. Where possible, laboratory tests should be performed to determine if lower genital tract infection with gonococci or C. trachomatis is present. 

For many years the direct visual examination of potentially inflamed tubes in symptomatic patients by laparoscopic examination of the abdominal cavity using a fibre optic device was the  diagnostic method of choice. The main findings at laparoscopy in women with pelvic infection are either a)  tubal occlusion and moderate to severe adhesions; b) the presence of a pelvic-abdominal exudate which collects in the Pouch of Douglas ; or a combination thereof [Eschenbach et al., 1997]. Among women with acute salpingitis, tubal occlusion was associated positively with older age, palpable adnexal mass, and moderate to severe pelvic adhesions. Free exudate was associated with abdominal rebound tenderness, elevated white blood cell count and recovery of gonococci. [Eschenbach et al., 1997].  Unfortunately, laparoscopy necessitates general anaesthesia, is not always feasible or without risk, and is costly and relatively insensitive [Paavonen, 1998; Washington et al., 1990].  Fortunately, the presence of an endometritis with plasma cells in a small biopsy of the uterine lining is an alternative and less traumatic  marker of upper genital tract infection with chlamydiae [Paavonen, 1987].  PID is often clinically diagnosed on the basis of cervical motion tenderness or uterine / adnexal tenderness. Additional criteria include oral temperature > 101 F (38.3 C), abnormal cervical or vaginal mucopurulent discharge, the presence of white blood cells on saline microscopy of vaginal secretions, an elevated erythrocyte sedimentation rate or C-reactive protein or laboratory evidence of cervical infection with C. trachomatis or N. gonorrhoeae. Transvaginal sonography or magnetic resonance imaging techniques that show thickened, fluid filled tubes or a tubo-ovarian abscess are also indicative. However the positive predictive value of a clinical diagnosis of symptomatic pelvic inflammatory disease is of the order of 65 - 95% compared with laparoscopy [itself an imperfect standard], depending on local epidemiological characteristics and the clinical setting [it's highest in sexually active young women]. However in all settings no single historical, clinical or laboratory finding is both sensitive and specific for the diagnosis of acute pelvic inflammatory disease [CDC STD Guidelines, 2002]. Moreover it seems likely that  the vast majority of patients with low grade salpingitis never seek medical investigation and are unaware that they are at risk of infertility.  A cross-sectional study among women attending a sexually transmitted diseases or ambulatory gynecology clinic without a diagnosis of acute pelvic inflammatory disease found that subclinical PID was present in 27% of women with Chlamydia trachomatis (odds ratio 3.4; 95% confidence interval [CI] 1.8, 6.3) and in 26% of women infected with Neisseria gonorrhoeae (odds ratio 2.4; 95% CI 1.1, 5.1) where PID was defined as histological evidence of endometritis [Wissenfeld et al., 2002]. Prospective studies would be necessary to determine the reproductive impact of these asymptomatic upper genital tract infections.

Although the risk factors and markers for the initial sexually transmitted infection in women are well known [see: chlamydial cervicitis] those for the subsequent development of pelvic infection are not. The oestrogen-progesterone oral contraceptive pill is associated with a high prevalence of lower genital tract C. trachomatis infection but paradoxically, in oral contraceptive users, pelvic inflammatory disease is less frequent and  is associated with milder pelvic lesions. There is, however, a question as to whether oral contraceptives favour the development of asymptomatic endometritis / salpingitis  [Henry-Suchet, 1997]. Douching is considered a risk factor for both lower and upper genital tract chlamydial infection [Scholes et al., 1998]. Repeated pelvic infection greatly increases the likelihood of infertility or ectopic pregnancy [see: complications of pelvic inflammatory disease] and host genotypic factors are also likely to influence disease severity [see: pathogenesis of pelvic inflammatory disease; repeated infection; host genotypic factors].

Currently the main strategy for the prevention of pelvic inflammatory disease in most countries is health education plus "bug and drug" treatment of those cases that are identified. Various models have been proposed to evaluate the cost effectiveness of actively screening key populations for chlamydial infection [Welte et al., 2000]. There is evidence that C. trachomatis screening using laboratory tests for infection is cost-effective. The selection of the diagnostic laboratory tests used in such screening programs needs to be carefully evaluated relative to cost, feasibility, specificity and sensitivity, and should be adapted to the presumed prevalence in screened populations. Systematic screening of women becomes economically worthwhile when the prevalence of infection is 5% or more [Henry-Suchet, 1997; Welte et al., 2000]. 

Treatment: Optimal treatment regimens and the long-term outcome of the early treatment of women with aysymptomatic or atypical pelvic inflammatory disease are unknown. The  CDC STD Guidelines, 2002 recommend  that empiric treatment should be instituted if either uterine / adnexal or cervical motion tenderness is present, and that therapy should include coverage of possible anaerobic bacterial agents.  Criteria for considering inpatient as opposed to outpatient treatment were where:

• surgical emergencies such as appendicitis could not be ruled out;

• the patient is pregnant;

• the patient has not responded to or cannot tolerate outpatient oral antibiotic regimes;

• the patient has severe illness, nausea and vomiting or fever;

• the patient has a tubo-ovarian abscess.

There are no data comparing the efficacy of oral versus parenteral therapy. The parenteral regimes recommended were Cefotetan or Cefoxitin 2 grams intravenously every 12 hours plus Doxycycline 100 mg, preferably orally because of the pain of intravenous doxycycline infusion. An alternative regime, particularly where tubo-ovarian abscess is present, is Clindamycin 900 mg intravenously every eight hours plus Gentamicin: loading dose 2mg/kg body weight intravenous or intramuscular followed by a maintenance dose of 1.5mg/kg every eight hours. It was recommended that parenteral therapy be continued for 24 hours after the patient improves clinically and then be changed for continuing oral therapy of doxycycline 100 mg orally twice a day or clindamycin 450 mg orally four times a day. Several other parenteral regimes involving quinolones and or metronidazole are also suggested. For oral treatment the suggested regimes were Ofloxacin 400 mg twice a day for 14 days or Levofloxacin 500 mg orally once daily for 14 days, with or without metronidazole 500 mg orally twice a day for 14 days. For a further discussion of the issues, see the CDC STD Guidelines and other guidelines.

NEXT:  Infertility and ectopic pregnancy

[MEW] September 2003

References

Bevan, C. D., Johal, B. J., Mumtaz, G., Ridgway, G. L. & Siddle, N. C. (1995). Clinical, laparoscopic and microbiological findings in acute salpingitis: report on a United Kingdom cohort. British Journal of Obstetrics and Gynaecology 102, 407 - 414.

Bjartling, C., Osser, S. & Persson, K. (2000). The frequency of salpingitis and ectopic pregnancy as epidemiologic markers of Chlamydia trachomatis. Acta Obstetrica Gynecologica Scandinavica 79, 123 - 128.

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Cohen CR, Manhart LE, Bukusi EA et al., (2002). Association between Mycoplasma genitalium and acute endometritis. Lancet 359, 765 - 766.

Eschenbach, D. A., Wolner-Hanssen, P., Hawes, S. E., Pavletic, A., Paavonen, J. & Holmes, K. K. (1997). Acute pelvic inflammatory disease: associations of clinical and laboratory findings with laparoscopic findings. Obstetrics &  Gynecology 89, 184 - 192.

Gaydos, C. A., Howell, M. R., Pare, B., Clark, K. L., Ellis, D. A., Hendrix, R. M., Gaydos, J. C., McKee, K. T. Jr. & Quinn, T. C. (1998). Chlamydia trachomatis infections in female military recruits. New England Journal of Medicine 339, 739 - 744.

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Paavonen, J. (1998). Pelvic inflammatory disease. From diagnosis to prevention. Dermatology Clinics 16, 747 - 756.

Paavonen J, Teisala K, Heinonen PK, Aine R, Laine S, Lehtinen M, Miettinen A, Punnonen R, Gronroos P. (1987). Microbiological and histopathological findings in acute pelvic inflammatory disease. British Journal of Obstetrics & Gynaecology 94, 454 - 460.

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Robertson, J. N., Ward, M. E., Conway, D. & Caul, E. O. (1987). Chlamydial and gonococcal antibodies in sera of infertile women with tubal obstruction. Journal of Clinical Pathology 40, 377 - 383.

Schachter, J. (1999). Infection and disease epidemiology. Pages 139 - 169. In: (Stephens, R. S. ed.,) Chlamydia: Intracellular biology, pathogenesis and immunity. American Society of Microbiology Press, Washington D.C., ISBN 1-55581-155-8.

Scholes, D., Stergachis, A., Ichikawa, L. E., Heidrich, F. E., Holmes, K. K. & Stamm WE. (1998). Vaginal douching as a risk factor for cervical Chlamydia trachomatis infection. Obstetrics and Gynecology 91, 993 - 997.

Simms, I., Eastick, K., Mallinson, H., Thomas, K., Gokhale, R., Hay, P., Herring, A. & Rogers, P. A. (2003). Associations between Mycoplasma genitalium, Chlamydia trachomatis and pelvic inflammatory disease. Sexually Transmitted Infections 79, 154 - 156 (2003). [An identical paper by the same authors is syndicated by the same publishing group in J. Clin. Path. 56, 616 - 618 (2003). In the interests of information overload this site hopes that the double publishing of papers is not going to be a regular practice of publishers ].

Washington, A. E., Aral, S. O., Wolner-Hanssen, P., Grimes, D. A.. &  Holmes, K. K. (1990). Assessing risk for pelvic inflammatory disease and its sequelae. Journal of the American Medical Association (JAMA) 266, 2581 - 2586. [Thorough study].

Welte, R., Kretzschmar, M., Leidl, R., van den Hoek, A., Jager, J. C. Postma, M. J. (2000). Cost-effectiveness of screening programs for Chlamydia trachomatis: a population-based dynamic approach. Sexually Transmitted Diseases 27, 518 - 529.

Westrom, L. R., Joesoef, R., Reynolds, G., Hagdu, A. & Thompson, S. E. (1992). Pelvic inflammatory disease and fertility. A cohort study of 1,844 women with laparoscopically verified disease and 657 control women with normal laparoscopic results. Sexually Transmitted Diseases 19, 185 - 192. 

Wiesenfeld, H. C., Hillier, S. L., Krohn, M. A., Amortegui, A. J., Heine, R. P., Landers,  D. V, & Sweet, R. L. (2002). Lower genital tract infection and endometritis: insight into subclinical pelvic inflammatory disease. Obstetrics and Gynecology 100, 456 - 463.

NEXT: Infertility and ectopic pregnancy