Ultrasound for diagnosing acute salpingitis: a prospective observational diagnostic study.

STUDY QUESTION: What are the diagnostic benefits of using ultrasound in patients with a clinical suspicion of acute salpingitis and signs of pelvic inflammatory disease (PID)? SUMMARY ANSWER: In patients with a clinical suspicion of acute salpingitis, the absence of bilateral adnexal masses at ultrasound decreases the odds of mild-to-severe acute salpingitis about five times, while the presence of bilateral adnexal masses increases the odds about five times. WHAT IS KNOWN ALREADY: PID is difficult to diagnose because the symptoms are often subtle and mild. The diagnosis is usually based on clinical findings, and these are unspecific. The sensitivity and specificity of ultrasound with regard to salpingitis have been reported in one study (n = 30) of appropriate design, where most patients had severe salpingitis (i.e. pyosalpinx) or tubo-ovarian abscess. STUDY DESIGN, SIZE, DURATION: This diagnostic test study included 52 patients fulfilling the clinical criteria of PID. Patients were recruited between October 1999 and August 2008. PARTICIPANTS/MATERIALS, SETTING, METHODS: The patients underwent a standardized transvaginal gray scale and Doppler ultrasound examination by one experienced sonologist (index test) before diagnostic laparoscopy by a laparoscopist blinded to the ultrasound results. The final diagnosis was determined by laparoscopy, histology of the endometrium and other histology where relevant (reference standard). MAIN RESULTS AND THE ROLE OF CHANCE: Of the 52 patients, 23 (44%) had a final diagnosis unrelated to genital infection, while the other 29 had cervicitis (n = 3), endometritis (n = 9) or salpingitis (n = 17; mild n = 4, moderate n = 8, severe, i.e. pyosalpinx n = 5). Bilateral adnexal masses and bilateral masses lying adjacent to the ovary were seen more often on ultrasound in patients with salpingitis than with other diagnoses (bilateral adnexal masses: 82 versus 17%, i.e. 14/17 versus 6/35, P = 0.000, positive likelihood ratio 4.8, negative likelihood ratio 0.22; bilateral masses adjacent to ovary: 65 versus 17%, i.e.11/17 versus 6/35, P = 0.001, positive likelihood ratio 3.8, negative likelihood ratio 0.42). In cases of salpingitis, the masses lying adjacent to the ovaries were on average 2-3 cm in diameter, solid (n = 14), unilocular cystic (n = 4), multilocular cystic (n = 3) or multilocular solid (n = 1), with thick walls and well vascularized at colour Doppler. In no case were the cogwheel sign or incomplete septae seen. All 13 cases of moderate or severe salpingitis were diagnosed with ultrasound (detection rate 100%, 95% confidence interval 78-100%) compared with 1 of 4 cases of mild salpingitis. Three of six cases of appendicitis, and two of two ovarian cysts were correctly diagnosed with ultrasound, and one case of adnexal torsion was suspected and then verified at laparoscopy. LIMITATIONS, REASONS FOR CAUTION: The sample size is small. This is explained by difficulties with patient recruitment. There are few cases of mild salpingitis, which means that we cannot estimate with any precision the ability of ultrasound to detect very early salpingitis. The proportion of cases with salpingitis of different grade affects the sensitivity and specificity of ultrasound, and the sensitivity and specificity that we report here are applicable only to patient populations similar to ours. WIDER IMPLICATIONS OF THE FINDINGS: The information provided by transvaginal ultrasound is likely to be of help when deciding whether or not to proceed with diagnostic laparoscopy in patients with symptoms and signs suggesting PID and, if laparoscopy is not performed, to select treatment and plan follow-up. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by funds administered by Malmö University Hospital and two Swedish governmental grants (ALF-medel and Landstingsfinansierad Regional Forskning). The authors have no conflict of interest

Plasmid deficiency in urogenital isolates of Chlamydia trachomatis reduces infectivity and virulence in a mouse model.

We hypothesized that the plasmid of urogenital isolates of Chlamydia trachomatis would modulate infectivity and virulence in a mouse model. To test this hypothesis, we infected female mice in the respiratory or urogenital tract with graded doses of a human urogenital isolate of C. trachomatis, serovar F, possessing the cognate plasmid. For comparison, we inoculated mice with a plasmid-free serovar F isolate. Following urogenital inoculation, the plasmid-free isolate displayed significantly reduced infectivity compared with the wild-type strain with the latter yielding a 17-fold lower infectious dose to yield 50% infection. When inoculated via the respiratory tract, the plasmid-free isolate exhibited reduced infectivity and virulence (as measured by weight change) when compared to the wild-type isolate. Further, differences in infectivity, but not in virulence were observed in a C. trachomatis, serovar E isolate with a deletion within the plasmid coding sequence 1 when compared to a serovar E isolate with no mutations in the plasmid. We conclude that plasmid loss reduces virulence and infectivity in this mouse model. These findings further support a role for the chlamydial plasmid in infectivity and virulence in vivo

Co-evolution of genomes and plasmids within Chlamydia trachomatis and the emergence in Sweden of a new variant strain.

BACKGROUND: Chlamydia trachomatis is the most common cause of sexually transmitted infections globally and the leading cause of preventable blindness in the developing world. There are two biovariants of C. trachomatis: 'trachoma', causing ocular and genital tract infections, and the invasive 'lymphogranuloma venereum' strains. Recently, a new variant of the genital tract C. trachomatis emerged in Sweden. This variant escaped routine diagnostic tests because it carries a plasmid with a deletion. Failure to detect this strain has meant it has spread rapidly across the country provoking a worldwide alert. In addition to being a key diagnostic target, the plasmid has been linked to chlamydial virulence. Analysis of chlamydial plasmids and their cognate chromosomes was undertaken to provide insights into the evolutionary relationship between chromosome and plasmid. This is essential knowledge if the plasmid is to be continued to be relied on as a key diagnostic marker, and for an understanding of the evolution of Chlamydia trachomatis. RESULTS: The genomes of two new C. trachomatis strains were sequenced, together with plasmids from six C. trachomatis isolates, including the new variant strain from Sweden. The plasmid from the new Swedish variant has a 377 bp deletion in the first predicted coding sequence, abolishing the site used for PCR detection, resulting in negative diagnosis. In addition, the variant plasmid has a 44 bp duplication downstream of the deletion. The region containing the second predicted coding sequence is the most highly conserved region of the plasmids investigated. Phylogenetic analysis of the plasmids and chromosomes are fully congruent. Moreover this analysis also shows that ocular and genital strains diverged from a common C. trachomatis progenitor. CONCLUSION: The evolutionary pathways of the chlamydial genome and plasmid imply that inheritance of the plasmid is tightly linked with its cognate chromosome. These data suggest that the plasmid is not a highly mobile genetic element and does not transfer readily between isolates. Comparative analysis of the plasmid sequences has revealed the most conserved regions that should be used to design future plasmid based nucleic acid amplification tests, to avoid diagnostic failures

Recent Developments of Chlamydia trachomatis and Mycoplasma Infections in Women

The aim of this thesis was to elucidate developments in epidemiology, clinical manifestations and complications in Chlamydia trachomatis (C.trachomatis) and Mycoplasma genitalium (M.genitalium) infection. In study I the frequencies of non-gonococcal salpingitis, gonococcal salpingitis and ectopic pregnancy (EP) were observed over a period of 28 years and correlated to the prevalence of Neisseria gonorrhoeae (N.gonorrhoeae) and C.trachomatis. The frequency of acute salpingitis reflected the prevalence of N.gonorrhoeae and C.trachomatis in our population. The frequency of acute salpingitis and ectopic pregnancy might be used to estimate the occurrence of C.trachomatis during the 1970s and early 1980s before diagnostic facilities became available. In study II we explored the possible presence of C.trachomatis DNA at the time of EP using freshly frozen tubal tissue and analyzing for C.trachomatis with PCR and a highly sensitive real time PCR test. We also investigated the correlation between c-hsp60 antibodies and h-hsp60. C.trachomatis DNA could not be detected in any of the tubal tissue specimens from our patients with EP although highly sensitive diagnostic methods were used. Prior EP /PID was associated with ct-hsp60 antibodies but not with human hsp60. Comparison of the antibody levels of chlamydial hsp60 and human hsp60 in our patients with EP showed no correlation. In study III we compared clinical manifestations of infections with nvCT and wild type C.trachomatis (wtCT) in both men and women and estimated the frequency of ascending infections (PID) in women. The mean age of patients with nvCT infection was slightly lower than in patients with wtCT infection although nvCT was distributed in all age groups. Men and women with nvCT or wtCT infection were similar with regard to sexual lifestyle parameters and they had the same frequency of previous chlamydial infection. Asymptomatic infection seemed more common in women with nvCT infection than in women with wtCT infection. No case of PID associated with nvCT was found. Our findings suggest a difference in virulence between the nvCT and the wtCT. Study IV was performed to investigate the prevalence, clinical findings and complications of M.genitalium in women. In 7,598 women tested for M.genitalium and C.trachomatis the prevalence was 2.1 % and 2.6 % respectively. M.genitalium was associated with cervicitis and the observed association was independent of age and C.trachomatis infection. The frequency of symptoms and clinical signs were higher in patients with C.trachomatis infection suggesting that M.genitalium is a less aggressive pathogen in terms of symptoms and clinical signs. M.genitalium was clearly associated with PID in patients requesting termination of pregnancy

Cervical myoma causing colonic obstruction in the first trimester of pregnancy – a case report

A 39-year-old nulliparous woman with a previously known cervical myoma was admitted to the obstetrics department during the first trimester with complaints of severe abdominal pain, lack of bowel movements and the suspicion of a clinical bowel obstruction. Because no literature on this exact condition could be found, clinical decisions were based on reports and practice in similar situations. Ultrasound revealed the progression of a cervical myoma (previously 9 cm across), now 12 × 12 × 11 cm in size and a distended large bowel. Sigmoidoscopy excluded intraluminal obstruction. The patient was treated with oral laxatives and enema without success and her condition deteriorated. The myomatous cervix was examined vaginally (bimanual manoeuvre) with the patient under anaesthesia; however, attempts to dislodge the obstruction proved unsuccessful. After surgical consultation the patient was planned for an emergency laparoscopic sigmoidostomy. The post-operative course was uneventful and the patient discharged. She delivered a healthy child with caesarean section in gestation week 36. Bowel continuity was later laparoscopically restored in conjunction with a hysterectomy. This case illustrates the importance of active multidisciplinary management in a case of severe colonic obstruction caused by pregnancy-related obstruction in the small pelvis. In this case, colonic perforation and abortion of the fetus were both avoided

Deoxyribonucleic acid of Chlamydia trachomatis in fresh tissue from the Fallopian tubes of patients with ectopic pregnancy.

Objectives: The role of persistent chlamydial infection of the Fallopian tubes in ectopic pregnancy is still unresolved. Therefore, we examined tissue of the Fallopian tubes from patients with ectopic pregnancy for the presence of Chlamydia trachomatis. In addition, other markers of C. trachomatis infection implicated in the pathogenesis of tubal damage were studied including antibodies to heat shock protein 60 of chlamydial and human origin. Study design: Fresh frozen tubal tissue from 55 patients with ectopic pregnancy in a hospital setting were examined for the presence of C. trachomatis DNA by polymerase chain reaction (PCR) and blood sample were analysed for antibodies to C. trachomatis including heat shock protein 60 (hsp60). Results: Chlamydial DNA was not detected in any of the 55 tubal specimens using a commercial test, Cobas Amplicor, Roche, and an in-house real time PCR able to detect a few copies of the organism. Logistic regression showed that chlamydial IgG antibodies were more common in a subgroup of patients with previous PID than in controls (OR = 7.84, CI 1.78-34.6). Specific antibodies to hsp60 of chlamydial (OR = 7.00, CI 1.50-32.6) but not of human origin (OR = 2.13, CI 0.14-31.6) were associated with ectopic pregnancy in this group. Conclusions: No evidence of persistent infection of C. trachomatis in the fallopian tubes at the time of ectopic pregnancy was found in this study. (C) 2006 Elsevier Ireland Ltd. All rights reserved

The association between Mycoplasma genitalium and pelvic inflammatory disease after termination of pregnancy

The prevalence and complications of Mycoplasma genitalium and Chlamydia trachomatis infections among women undergoing termination of pregnancy were studied in this nested case-control study at Malmo University Hospital, Sweden, during 2003 to 2007. The study comprised 2079 women presenting for termination of pregnancy. Forty-nine women with M. genitalium infection and 51 women with C. trachomatis infection, together with 168 negative control women, were evaluated. The prevalences of M. genitalium and C. trachomatis were 2.5% and 2.8%, respectively. The M. genitalium was strongly associated with post-termination pelvic inflammatory disease (odds ratio 6.29, 95% CI 1.56-25.2). The increased risk for pelvic inflammatory disease associated with M. genitalium infection after termination of pregnancy suggests a causal relationship

Mycoplasma genitalium in cervicitis and pelvic inflammatory disease among women at a gynecologic outpatient service.

OBJECTIVE: We sought to analyze the prevalence and clinical manifestations of Mycoplasma genitalium infection in a heterogeneous population of women. STUDY DESIGN: The study was designed as a cross-sectional case-control study. Women attending a gynecological outpatient service from 2003 through 2008 were invited to participate. RESULTS: The prevalence of M genitalium was 2.1% and of Chlamydia trachomatis was 2.8% among 5519 tested women. A total of 679 women were included. Both pelvic inflammatory disease (PID) and cervicitis were independently associated with M genitalium (odds ratio, 9.00; 95% confidence interval, 1.62-49.89 and odds ratio, 3.80; 95% confidence interval, 2.06-7.03, respectively). Women with C trachomatis had a higher frequency of both PID (18.3% vs 4.9%, P < .001) and cervicitis (33.4% vs 22.3%, P < .001) than women with M genitalium. CONCLUSION: M genitalium was an independent and strong risk factor for both cervicitis and PID although, compared to C trachomatis, clinical manifestations were less frequent

Clinical Manifestations and Epidemiology of the New Genetic Variant of Chlamydia trachomatis.

BACKGROUND:: In 2006, a new genetic variant of Chlamydia trachomatis (nvCT) was discovered in Sweden. Clinical manifestations of this infection were studied in a high-risk population. METHODS:: During 2007, a prospective case-control study on sexual lifestyle and urogenital infections was performed at the Centre for Sexual Health (CSH), affiliated to Malmo University Hospital. A total of 629 C. trachomatis positive cases and 1252 negative controls were included. At Malmo University Hospital, Department of Obstetrics and Gynecology, all cases of pelvic inflammatory disease (PID) were assessed and correlated to the prevalence of nvCT. RESULTS:: Patients with nvCT or wild type C. trachomatis (wtCT) infection did not differ regarding their sexual lifestyle. Men with nvCT or wtCT infection did not differ in uro-genital symptoms or clinical findings. Women with nvCT infection reported painful urination (12.2% vs. 25.8%, P = 0.02) and were diagnosed with urethritis (11.1% vs. 40.0%, P = 0.04) less often than women with wtCT infection. The ratio of lower abdominal pain in women with nvCT infection was only half of that in women with wtCT infection (13.4% vs. 27.8%, P = 0.02). PID was detected in 0.8% of women with C. trachomatis infection in Malmo. All these cases were due to wtCT infection. CONCLUSIONS:: Symptomatic urethral infection and lower abdominal pain was less common in women with nvCT as compared to wtCT. Infection with nvCT was more frequently asymptomatic suggesting a possible difference in virulence between the nvCT strain and the wtCT strain