Per-Anders Mårdh

Chlamydia trachomatis infection in patients with acute salpingitis.

Abstract We examined the prevalence of Chlamydia trachomatis in the cervix and the fallopian tubes of patients with acute salpingitis. Cycloheximide-treated McCoy cells were used as the growth medium. For purposes of comparison, women with infections confined to the lower genital tract and women without signs of genital infections were also studied. C. trachomatis was isolated from the cervix in 19 of 53 patients with acute salpingitis, in one of 18 lower-genital-tract infections and in none of 12 without signs of genital infection. C. trachomatis was recovered from six of the 20 valid specimens from the fallopian tubes of the patients with acute salpingitis. Our results indicate that chlamydia is a common etiologic agent in acute salpingitis. (N Engl J Med 296:1377–1379, 1977)

THE RISK OF PELVIC INFLAMMATORY DISEASE IN WOMEN USING INTRAUTERINE CONTRACEPTIVE DEVICES AS COMPARED TO NON-USERS

The frequency of women using an intrauterine contraceptive device (I.U.D.) among 515 patients presenting with acute, laparoscopically verified salpingitis, has been compared with the corresponding frequency in 741 sexually active women who were matched to the patients by date of birth, domicile, and socioeconomic status. The frequency of I.U.D. use was significantly (P less than 0-001) higher in the patients than in the controls. It was estimated that the relative risk of acute salpingitis for any woman using an I.U.D. was 3-fold as compared to non-users. For women using I.U.D.s who had not been pregnant at any time, the corresponding risk was found to be 7-fold.

The accuracy and efficacy of screening tests for Chlamydia trachomatis: a systematic review

Screening women for lower genital tract infection with Chlamydia trachomatis is important in the prevention of pelvic inflammatory disease, ectopic pregnancy and infertility. This systematic review aims to state clearly which of the available diagnostic tests for the detection of C. trachomatis would be most effective in terms of clinical effectiveness. The review included all studies published from 1990 onward that evaluated diagnostic tests in asymptomatic, young, sexually active populations. Medline and Embase were searched electronically and key journals were hand-searched. Further studies were identified through the Internet and contact with experts in the field. All studies were reviewed by two reviewers and were scored by Irwigs assessment criteria. Additional quality assessment criteria included a documented sexual history and recording of previous chlamydial infection. The reviews were subjected to meta-analysis and meta-regression. The 30 studies that were included examined three types of DNA-based test--ligase chain reaction (LCR), PCR and gene probe--as well as enzyme immuno-assay (EIA). The results showed that while specificities were high, sensitivities varied widely across the tests and were also dependent on the specimen tested. Pooled sensitivities for LCR, PCR, gene probe and EIA on urine were 96.5%, 85.6%, 92% and 38%, respectively, while on cervical swabs the corresponding sensitivities of PCR, gene probe and EIA were 88.6%, 84% and 65%. Meta-analysis demonstrated that DNA amplification techniques performed best for both urine and swabs in low prevalence populations. We conclude that nucleic acid amplification tests used on non-invasive samples such as urine are more effective at detecting asymptomatic chlamydial infection than conventional tests, but there are few data to relate a positive result with clinical outcome.

A Cost-effectiveness Analysis of Screening and Treatment for Chlamydia trachomatis Infection in Asymptomatic Women

In recent decades, Chlamydia trachomatis has been recognized as one of the most widespread sexually transmitted organisms [1]. In women, it can cause urethritis, cervicitis, pelvic inflammatory disease (for example, endometritis and salpingitis), and the sequelae of these conditions, such as infertility, ectopic pregnancy, and chronic pelvic pain. In men, C. trachomatis infection can cause urethritis and epididymitis, which may rarely result in urethral strictures and decreased fertility. Neonates passing through the birth canal of an infected woman can become infected, leading to chlamydial conjunctivitis and pneumonia. Chlamydial infections of the genital tract do not invariably cause symptoms that would prompt a person to seek medical aid. Identification and treatment of infected persons is important not only for their own well-being but also to prevent the spread of C. trachomatis in society. We assess the cost-effectiveness of some commonly used diagnostic tests and treatment regimens, including the recently introduced DNA amplification assays and a single oral dose of azithromycin, for identifying and treating asymptomatic female carriers of C. trachomatis. Methods Eligible Patients We considered a cohort of 1000 sexually active, nonpregnant women of reproductive age who had no clinical signs or symptoms of a genital tract infection. We assumed that these women attend youth, gynecology, and family planning clinics for either contraceptive advice or routine gynecologic care. We derived the assumptions on their demographic characteristics from the Swedish Womens Health Study [2], which focused on the same group of women considered in our analysis. These assumptions include the following: The mean age of the women is 26 years (range, 15 to 48 years); most are nonparous (68%), are either married or cohabiting (52%), have a steady partner (85%), and have had some training beyond the compulsory 9 years of education (88%); they have had a mean of 11 sex partners; and the prevalence of genital tract infection with C. trachomatis and Neisseria gonorrhoeae is 8.5% and 0.1%, respectively. We believe that these women are representative of the general Swedish female population who are of reproductive age and are at moderate risk for chlamydial infections of the genital tract. Intervention We compared a no-screening strategy with tissue cell culture, confirmed enzyme immunoassay, and DNA amplification assays that were based on either polymerase chain reaction (Amplicor C. trachomatis, Roche Diagnostic Systems, Elizabeth, New Jersey) or ligase chain reaction (LCR Assay C. trachomatis, Abbott Diagnostics, North Chicago, Illinois) for screening asymptomatic chlamydial infections of the genital tract. We assumed that all samples with positive or equivocal enzyme immunoassay results would be tested with a blocking assay [3]. Positive results that become blocked would be reported as confirmed positive, and equivocal results that become blocked would be further evaluated with a direct fluorescent assay. If chlamydial elementary bodies are found in the pellet obtained by centrifugation of the sample tested by enzyme immunoassay, the result would again be reported as confirmed positive. In the screening strategies, endocervical samples are collected from women during a pelvic examination. Any woman with laboratory-confirmed chlamydial infection is referred to a disease intervention specialist, who attempts to confidentially notify infected women and arrange a visit to the clinic. Notification efforts include telephone calls, letters, and visits to the patients residence. When the patient returns to the clinic, an antibiotic regimen is prescribed, and counseling regarding the disease and its treatment as well as notification of the patients partner are done. Partner notification is mandatory by law in Sweden; the disease intervention specialist informs the index patient of the importance of revealing her sex partner or partners and interviews her extensively to obtain the names, addresses, and telephone numbers of her sex partners. The disease intervention specialist then contacts these partners to motivate them to be examined at the clinic. This procedure is repeated until the partner comes to the clinic for examination. At this visit, the same steps are followed as with the index patient: physical examination, partner notification, counseling, and prescription of an antibiotic regimen for empiric treatment of uncomplicated chlamydial genital infection. In our analysis, we assumed that a 7-day, twice-daily course of doxycycline was prescribed to treat uncomplicated chlamydial genital tract infection in both women and their sex partners. We also evaluated the effect of administering a single oral 1-g dose of azithromycin under supervision in the clinic on the outcomes of the screening strategies. We assumed that only persons who seek medical help because of the presence of signs and symptoms of chlamydial diseases and their sequelae receive medical care in the no-screening strategy. Decision-Analysis Model We used two decision trees to graphically structure our decision-analysis model (Figure 1 and Figure 2). The branches in the decision trees represent the strategies of screening and no screening. The square at the point of branching indicates a decision node: a point at which a decision must be madefor example, whether or not to screen a woman. The nodes represented by circles are used if subsequent outcomes occur by chancefor example, if the physician cannot control the results of the test, which therefore branch from a chance node. We used the Bayes theorem to assign probabilities within the ranges presented in Table 1 to the chance nodes of the decision trees. We varied the prevalence of C. trachomatis among women from 0% to 100% to determine the prevalence above which one strategy is preferred to another [break-even analysis] Figure 1, node 1). Figure 1. Decision tree showing the outcomes of screening strategies for Chlamydia trachomatis among women and the outcomes of no screening. Figure 2. Decision tree showing the outcomes of tracing and treating contacts of women with a diagnosis of chlamydial infection of the genital tract and the outcomes of no contact tracing. Table 1. Ranges of Probabilities Assigned to the Chance Nodes of the Decision Trees We derived the estimates on the sensitivity and specificity of the laboratory tests from multicenter clinical evaluations in which a positive diagnosis was made when tissue cell culture was positive or when the results of one nonculture test (enzyme immunoassay, direct fluorescence assay, polymerase chain reaction assay, or ligase chain reaction assay) verified those of another. The estimates on follow-up rates for women with positive results and their partners were derived from data obtained from medical centers in North America and Sweden, which do follow-up procedures similar to those considered in our analysis. We obtained data on the prevalence of infection in male partners of women infected with C. trachomatis from studies in which tissue cell culture or the polymerase chain reaction assay was used for diagnosis. Compliance with a 7-day, twice-daily course of doxycycline is nearly 100% among Swedish patients but may be as low as 50% in other countries. We assumed that administering a single dose of azithromycin ensures full compliance and that noncompliance is synonymous with treatment failure. We also assumed that each woman would disclose one or two male sex partners [13]. Case-finding and partner notification yielded six groups of male partners (Figure 2, node 8). The probabilities for these outcomes were obtained from the probabilities of the corresponding outcomes of screening in women (Figure 1). In the no-screening strategy, the partners can be divided into two groups: contacts of infected women and contacts of healthy women. The probability of a man having an infected female partner is the same as that of a woman being infected (Figure 2, node 9). Costs Table 2 presents the direct and indirect cost estimates associated with medical services used in our analysis. Direct costs included salaries of health care personnel and costs of hospitals, drugs, equipment, and so forth; indirect costs were lost wages and lost value of household management due to participation in a health care program or sickness. We obtained these cost estimates from reported calculations that were based on average salaries and costs of medical care in Sweden [15, 21]. Using upper and lower limits for input salaries and costs, we made these calculations yield the widest range of monetary value for each cost category. The ranges of direct costs were extended in either direction by 20% to include any regional differences in medical care costs. The cost of sample collection, which included the cost of the sample collection materials, wages of the personnel collecting the endocervical swabs, and the cost of storing and transporting the specimens to the laboratory, were added to the cost of doing a diagnostic test. Table 2. Cost Assumptions Used in the Decision Analysis* We included no cost for the womans initial clinic visit because the test was not the primary reason for consultation. We assumed that the cost of informing a patient of her test result and arranging a visit to the clinic included the salary of a disease intervention specialist plus the cost of equipment and the setting. Because patient follow-up may be difficult and time-consuming in certain settings, we estimated that a disease intervention specialist spends an average of 30 minutes for the follow-up of each patient. The cost of medical care for uncomplicated genital chlamydial infection includes those of a physicians appointment, antibiotic treatment, a 1-week course of clotrimazole for the 20% of female patients who develop moniliasis from antibiotic therapy, and partner notification. We obtained the average cost of an unt

Cost effectiveness of screening for Chlamydia trachomatis: a review of published studies.

Objective: Screening for Chlamydia trachomatis in the lower genital tract may contribute to the prevention of pelvic inflammatory disease in women. The purpose of this review was to critically appraise, and summarise studies of the cost effectiveness of screening for C trachomatis. Methods: A literature search was conducted on Medline and in Health Star from 1990–2000. Keywords were C trachomatis, screening, cost effectiveness. Bibliographies of reviewed articles were also searched. The population studied was asymptomatic sexually active women under 30 years of age in a primary care setting. The intervention assessed was screening for lower genital tract infection with C trachomatis and the outcomes studied were cases of C trachomatis detected, cases of PID prevented, and associated costs. Studies were assessed using the Drummond criteria for economic evaluations. They were assessed qualitatively as they were too heterogeneous to allow quantitative analysis. Results: 10 studies were included. All were modelled scenarios and all found screening to be more cost effective than simply testing symptomatic women, although all were based on probabilities that were assumed. Six of the studies focused on DNA based testing, three of them using urine. The models showed screening to be cost effective at prevalences of 3.1–10.0%, and cost saving (overtesting symptomatic women) at a prevalence as low as 1.1%, if age was used as a selection factor and DNA based tests were used in urine samples. Conclusions: At the prevalence of infection expected in the target population, all studies suggest screening is cost effective. However, the assumptions used in the models have been difficult to confirm and there is a need for more data, particularly on the risk of complications in women with asymptomatic lower tract infection.

Differences in some clinical and laboratory parameters in acute salpingitis related to culture and serologic findings

Women with laparoscopically verified acute salpingitis (AS) were studied, and 151 were classified as having: chlamydia-associated AS (C-AS), gonococcal-associated AS (G-AS), and nonchlamydial, nongonococcal-associated AS (NCNG-AS). Patients with G-AS were more often febrile (rectal temperature greater than 38 degrees C) and more often had a moderately elevated erythrocyte sedimentation rate (ESR) (16 to 30 mm/hr) compared to other patients. Women with NCNG-AS were more likely to have a normal ESR and a mild inflammatory reaction laparoscopically. C-AS women were more likely to have had pelvic pain for more than 3 days before seeking treatment and to have an ESR of greater than 30 mm/hr on admission. Predisposing factors to AS, such as insertion of intrauterine device, hysterosalpingography, and curettage within 4 weeks of admission, were more common in the C-AS group. The tubal inflammatory changes in the C-AS group were generally more severe than expected from the relatively benign clinical course.

Facts and myths on recurrent vulvovaginal candidosis-a review on epidemiology, clinical manifestations, diagnosis, pathogenesis and therapy.

Approximately three-quarters of all women will experience an episode of vulvovaginal candidosis at least once in their life and 5-10% of them will have more than one attack. Women suffering from three to four attacks within 12 months will be diagnosed with recurrent vulvovaginal candidosis (RVVC). This review covers the large number of proposed aetiological factors for RVVC. The diagnosis of the condition made by conventional means by health providers is often false and is also often misdiagnosed by the affected woman herself. The review covers various methods of diagnosing RVVC and the current knowledge on potential pathogenetic mechanisms proposed for genital candida infections. Treatment of RVVC, including local and systemic antimicrobial therapy and behaviour modification to decrease the risk of recurrences, are discussed. Recent knowledge on drug resistance in candida is also included.

Bacterial vaginosis: Microbiological and clinical findings

A prospective study was performed involving 101 women who consecutively attended a primary health care unit for complaints of genital malodour and/or abnormal vaginal discharge. Bacterial vaginosis was diagnosed in 34 women on the basis of four diagnostic criteria: vaginal pH > 4.7, homogeneous vaginal discharge, a positive amine test and clue cells. The sensitivity of these criteria was > 90 % except for homogeneous discharge (82 %). Their specificity was > 90% except for vaginal pH > 4.7 (46%); a specificity of 87% could have been achieved by using the criterion for vaginal pH ⩾ 5.0. There was a strong association between diagnosis of bacterial vaginosis and the concomitant occurrence ofGardnerella vaginalis, Mobiluncusspp. andBacteroidesspp. There was no difference between women with or without bacterial vaginosis as regards contraception methods (except for use of an intrauterine device), age at first intercourse, or earlier episodes of vaginal discharge. Sexual transmission of the predominant bacteria was not supported by data collected from the male consorts.

An overview of infectious agents of salpingitis, their biology, and recent advances in methods of detection.

It was only in the decade of the 1970s that more extensive research into the etiology of acute salpingitis (pelvic inflammatory disease) was performed. Recently the development of new laboratory diagnostic methods and the detection and taxonomic differentiation of new organisms such as strictly anerobic bacteria chlamydiae and microplasms have contributed to an understanding of the etiology of acute salpingitis (AS). In this discussion AS and pelvic inflammatory disease (PID) are used synonymously. In reviewing infectious agents of salpingitis their biology and recent advances in methods of detection attention is directed to the following: 1) nontuberculous salpingitis (Neisseria gonorrhea anerobic infections mycoplasma hominis and Ureaplasma urealyticum Chlamydia trachomatis Chlamydial perihepatitis in acute salpingitis and miscellaneous and uncommon etiologic agents); 2) tuberculous salpingitis; 3) obtaining specimens in AS (lower genital tract uterine cavity and cul-de-sac and fallopian tubes); and 4) recent advances in laboratory diagnostic methods (tests for tubal isoamylases Neisseria gonorrhea anerobic bacteria mycoplasma hominis and Ureaplasma urealyticum Chlamydia trachomatis and mycobacteria. A common condition AS is on the increase in many countries as exemplified by studies from Lund Sweden. This increase in the incidence of PID appears to be associated with the pandemic situation of gonorrhea and other sexually transmitted diseases that has prevailed over the last 20 years. Most cases of AS are the result of an infection ascending from the cervix and in a large percentage of all women who develop AS the cervix is colonized by organisms known to be spread by sexual intercourse.

Infertility after acute salpingitis with special reference to Chlamydia trachomatis

Of 552 women with laparoscopically verified acute salpingitis (AS), 299 were reviewed 2.5 to 7.5 years later. Cervical secretions from these women had been cultured for the presence of Chlamydia trachomatis and Neisseria gonorrhoeae. For 49 of 82 women with visually normal pelvic organs, such cultures were also performed; these women served as control subjects. In women exposing themselves to pregnancy, 50 (23.3%) of 197 AS patients and 2 (6.7%) of 30 control women were infertile for at least 1 year (P less than 0.02). After one episode of AS, women harboring chlamydiae, gonococci, both, or neither of these microorganisms in the cervix on admission seemed to have the same fertility prognosis. Infertility was correlated with the number of AS episodes, the erythrocyte sedimentation rate (millimeters per hour) at admission, and the severity of the inflammatory reactions of the tubes. The use of oral contraceptives at admission was found to be a positive prognostic factor regarding fertility. Oral contraceptives might protect the patient from severe tubal inflammatory reactions.