Lars Falk

Signs and symptoms of urethritis and cervicitis among women with or without Mycoplasma genitalium or Chlamydia trachomatis infection.

Objectives: To study the prevalence, symptoms, and signs of Mycoplasma genitalium and Chlamydia trachomatis infections in women attending a Swedish STD clinic, accessible for both sexes, and in a group of young women called in the cervical cancer screening programme. Methods: A cross sectional study among female STD clinic attendees in Örebro and a study among women called for Papanicolaou smear screening. Attendees were examined for urethritis and cervicitis. First void urine and endocervical samples were tested for M genitalium and C trachomatis. Results: The prevalence of C trachomatis and M genitalium in the STD clinic population was 10% (45/465) and 6% (26/461), respectively. Dual infection was diagnosed in four women. In the cancer screening group of women the corresponding prevalence was 2% (1/59) and 0%, respectively. Among the STD clinic attendees there were no significant differences in symptoms (32% v 23%, RR 1.4, 95% CI 0.6 to 3.4) or signs (71% v 50%, RR 1.4, 95% CI 0.9 to 2.3) between C trachomatis and M genitalium infections. Microscopic signs of cervicitis were significantly more common among M genitalium and C trachomatis infected women than in the cancer screening group of women. 56% (15/27) of male partners of M genitalium infected women were infected with M genitalium compared to 59% of male partners of C trachomatis infected women who were infected with C trachomatis (p = 0.80). Conclusions:M genitalium is a common infection associated with cervicitis and with a high prevalence of infected sexual partners supporting its role as a cause of sexually transmitted infection.

Symptomatic urethritis is more prevalent in men infected with Mycoplasma genitalium than with Chlamydia trachomatis

Objectives: To study the prevalence, symptoms, and signs of Mycoplasma genitalium and Chlamydia trachomatis infections in men attending a Swedish STD clinic and to study the criteria for urethritis. Methods: A cross sectional study among STD clinic attendees in Örebro, Sweden. Attendees were examined for microscopic urethritis and first void urine (FVU) was tested for M genitalium and C trachomatis. Results: The prevalence of M genitalium and C trachomatis was 7% (34/512) and 12% (61/512), respectively. Dual infection was diagnosed in four men. In both infections 90% of the patients had signs of microscopic urethritis. M genitalium positive men had symptomatic urethritis significantly more often than those infected with C trachomatis (73% v 40%, RR 1.8; 95% CI 1.2 to 2.7). 63% of female partners of men infected with M genitalium were infected with M genitalium compared with chlamydial infection in 67% of female partners of men infected with C trachomatis. Non-chlamydial non-gonococcal urethritis without evidence of M genitalium infection was diagnosed in 180 men (35%). Symptoms and/or visible discharge were reported in 49% in this group. Conclusions:M genitalium is a common infection associated with symptomatic urethritis and with a high prevalence of infected sexual partners supporting its role as a sexually transmitted infection.

Characterization of Chlamydia trachomatis omp1 Genotypes among Sexually Transmitted Disease Patients in Sweden

ABSTRACT A method for detection and genotyping of genital Chlamydia trachomatis infections based on omp1 gene amplification and sequencing was developed. DNA was extracted from urogenital or urine samples using a Chelex-based method, and an approximately 1,100-bp-long fragment from the omp1 gene was directly amplified and sequenced. Genotyping was performed by BLAST similarity search, and phylogenetic tree analysis was used to illustrate the evolutionary relationships between clinical isolates and reference strains. The method was used to determine the genotypes ofC. trachomatis in 237 positive urogenital and/or urine specimens collected at a Swedish sexually transmitted disease clinic during 1 year. The most common genotypes corresponded to serotypes E (47%) and F (17%). The omp1 gene was highly conserved for genotype E (106 of 112 samples without any mutation) and F (41 of 42 samples without any mutation) strains but appear slightly less conserved for genotypes G (n = 6) and H (n = 6), where the sequences displayed one to four nucleotide substitutions relative to the reference sequence. Genotyping of samples collected at the follow-up visit indicated that two patients had become reinfected, while three other patients suffered treatment failure or reinfection. One woman appeared to have a mixed infection with two different C. trachomatis strains. Thisomp1 genotyping method had a high reproducibility and could be used for epidemiological characterization of sexually transmitted Chlamydia infections.

Sequence-Based Typing of Mycoplasma genitalium Reveals Sexual Transmission

ABSTRACT Mycoplasma genitalium causes male nonchlamydial, nongonococcal urethritis and is associated with cervicitis and pelvic inflammatory disease in women. Epidemiological studies indicate that M. genitalium is sexually transmitted, and the aim of the present study was to further substantiate this by means of a DNA typing system. A typing assay based on a diagnostic mgpB gene PCR was developed, evaluated, and applied directly to urogenital specimens. The assay had a low limit of detection and hence a high typeability. Sequences of isolates from 52 unrelated patients were divided into 29 different sequence types, giving a discriminatory index of 0.95. Two to six M. genitalium-positive specimens were collected from each of 44 patients over a median interval of 56 days (range, 11 to 1,395). Forty had the same sequence type in consecutive specimens. Specimens collected from two men were repeatedly positive at intervals of 472 and 1,395 days, respectively, but the sequence types had changed. A new strain was introduced in one sexual dyad, and the sequence types changed subsequently. Seventy-nine M. genitalium-positive specimens from 19 couples were investigated, and all partners initially had concordant sequence types, but one couple had discordant types at one time point before a newly introduced strain took over. The present typing system is simple and reproducible and has an excellent discriminatory capacity which might prove useful in studies of sexual networks and for evaluation of treatment failures. In the laboratory, this system may document the uniqueness of newly isolated M. genitalium strains.

Young women requesting emergency contraception are, despite contraceptive counseling, a high risk group for new unintended pregnancies

Since its introduction in Sweden in 1994, emergency contraception has become a welcome addition to the campaign against unwanted pregnancy. In addition to an unplanned pregnancy, unprotected sexual intercourse may also involve the risk of contracting sexually transmitted diseases (STD). The aim of this study was to assess the short- and long-term risk of unintended pregnancy and to determine the frequency of chlamydia infections in women receiving emergency contraception. Between September 1998 and February 1999 young women aged 15-25 years had the opportunity to obtain emergency contraception (Yuzpe method) at a youth clinic in the city of Orebro where the opening hours were extended to include Saturdays and Sundays. A follow-up visit 3 weeks after treatment, which included contraceptive counseling, was offered to all participants. At both visits, a pregnancy test and a chlamydia test were performed, and the women completed a questionnaire. After the initial visit, the young women where monitored for new pregnancies during the following 12 months. One pregnancy occurred in the 134 young women who received emergency contraception during the study period. None of the women had a positive chlamydia test. Of those requesting emergency contraception, 54% did so because no contraception was used, 32% because of a ruptured condom, 11% because of missed oral contraceptives (OC), and 5% had mixed reasons. At long-term follow-up 1 year after the initial visit, 10 of the 134 young women had experienced an unplanned pregnancy that terminated in legal abortion in 9 women. All these women had either started and terminated OC or had never commenced the prescribed OC. Young women who request emergency contraception are, despite a planned follow-up with contraceptive counseling, a high risk group for new unintended pregnancies. In Sweden they do not seem to be a high risk group for STD.

A comparative study of three different PCR assays for detection of Mycoplasma genitalium in urogenital specimens from men and women

The aim of this study was to compare conventional 16S rRNA gene PCR, real-time 16S rRNA gene PCR and real-time Mycoplasma genitalium adhesin protein (MgPa) gene PCR as detection methods for M. genitalium infection. The study also determined the prevalence of M. genitalium in male and female patients attending a sexually transmitted infections clinic in a rural area in the west of Sweden. First void urine (FVU) and/or urethral swabs were collected from 381 men, and FVU and/or cervical swabs and/or urethral swabs were collected from 298 women. A total of 213 specimens were used in the PCR comparative study: 98 consecutively sampled specimens from patients enrolled in the prevalence study, 36 consecutively sampled specimens from patients with symptoms of urethritis and 79 specimens from patients positive for M. genitalium by real-time MgPa gene PCR in the prevalence study. A true-positive M. genitalium DNA specimen was defined as either a specimen positive in any two PCR assays or a specimen whose PCR product was verified by DNA sequencing. The prevalence of M. genitalium infection in men and women was 27/381 (7.1 %) and 23/298 (7.7 %), respectively. In the PCR comparative study, M. genitalium DNA was detected in 61/76 (80.3 %) of true-positive specimens by conventional 16S rRNA gene PCR, in 52/76 (68.4 %) by real-time 16S rRNA gene PCR and in 74/76 (97.4 %) by real-time MgPa gene PCR. Real-time MgPa gene PCR thus had higher sensitivity compared with conventional 16S rRNA gene PCR and had considerably increased sensitivity compared with real-time 16S rRNA gene PCR for detection of M. genitalium DNA. Real-time MgPa gene PCR is well suited for the clinical diagnosis of M. genitalium.

Sampling for Chlamydia trachomatis infection – a comparison of vaginal, first-catch urine, combined vaginal and first-catch urine and endocervical sampling

Summary The aim of the study was to evaluate the sensitivity of patients’ self-sampled vaginal specimens, first-catch urine (FCU), combined vaginal/FCU specimens and endocervical specimens for detecting chlamydial infection in women. Women attending sexually transmitted disease clinics, youth clinics and a womens health clinic were enrolled. They self-collected a vaginal specimen with two swabs, which were placed into a sterile tube and into a tube containing a buffer medium, respectively. An FCU sample was collected and aliquoted into both an empty tube and the tube containing the vaginal swab. A clinician collected an endocervical swab. The samples were sent to laboratories for analysis using polymerase chain reaction testing and strand displacement amplification testing, respectively. The sensitivities calculated in all 171 Chlamydia trachomatis-infected women were equal for endocervical specimens (97.1 %), vaginal specimens (96.5%) and combined vaginal/FCU specimens (95.3%), whereas the sensitivity for FCU was significantly lower (87.7%). The sensitivity of vaginal specimens for the detection of C. trachomatis is as high as that of combined vaginal/FCU specimens.

2016 European guideline on the management of non-gonococcal urethritis.

We present the updated International Union against Sexually Transmitted Infections (IUSTI) guideline for the management of non-gonococcal urethritis in men. This guideline recommends confirmation of urethritis in symptomatic men before starting treatment. It does not recommend testing asymptomatic men for the presence of urethritis. All men with urethritis should be tested for Chlamydia trachomatis and Neisseria gonorrhoeae and ideally Mycoplasma genitalium using a nucleic acid amplification test (NAAT) as this is highly likely to improve clinical outcomes. If a NAAT is positive for gonorrhoea, a culture should be performed before treatment. In view of the increasing evidence that azithromycin 1 g may result in the development of antimicrobial resistance in M. genitalium, azithromycin 1 g is no longer recommended as first line therapy, which should be doxycycline 100 mg bd for seven days. If azithromycin is to be prescribed an extended course of 500 mg stat, then 250 mg daily for four days is to be preferred over 1 g stat. In men with persistent NGU, M. genitalium NAAT testing is recommended if not previously undertaken, as is Trichomonas vaginalis NAAT testing in populations where T. vaginalis is detectable in >2% of symptomatic women.

Time to eradication of Mycoplasma genitalium after antibiotic treatment in men and women.

OBJECTIVES The objectives of this study were to evaluate the time to a Mycoplasma genitalium-negative test after start of treatment and to monitor if and when antibiotic resistance developed. METHODS Sexually transmitted disease (STD) clinic attendees with suspected or verified M. genitalium infection were treated with azithromycin (5 days, 1.5 g; n = 85) or moxifloxacin (n = 5). Subjects with symptomatic urethritis or cervicitis of unknown aetiology were randomized to either doxycycline (n = 49) or 1 g of azithromycin as a single dose (n = 51). Women collected vaginal specimens and men collected first-catch urine 12 times during 4 weeks. Specimens were tested for M. genitalium with a quantitative MgPa PCR and for macrolide resistance-mediating mutations with a PCR targeting 23S rRNA. CLINICAL TRIALS REGISTRATION NCT01661985. RESULTS Ninety M. genitalium cases were enrolled. Of 56 patients with macrolide-susceptible strains before treatment with azithromycin (1.5 g, n = 46; 1 g single oral dose, n = 10), 54 (96%) had a negative PCR test within 8 days. In four patients, M. genitalium converted from macrolide susceptible to resistant after a 10 day lag time with negative tests (azithromycin 1.5 g, n = 3; 1 g single oral dose, n = 1). Moxifloxacin-treated subjects (n = 4) were PCR negative within 1 week. Six of eight (75%) remained positive despite doxycycline treatment. CONCLUSIONS PCR for M. genitalium rapidly became negative after azithromycin treatment. Macrolide-resistant strains were detected after initially negative tests. Test of cure should be recommended no earlier than 3-4 weeks.

Genotyping of Chlamydia trachomatis Would Improve Contact Tracing

Background The reported number of genital Chlamydia trachomatis infections has increased 15% annually since 1997 in Sweden. Inaccurate partner notification might be one reason. Goal The goals were to determine if genotyping of C trachomatis would improve partner notification and to study the duration of infection. Study Design Sexual networks were constructed. C trachomatis isolates from 231 individuals attending the Örebro STD clinic during 1 year were typed by sequencing of the omp1 gene. Results All individuals were traced and diagnoses were established in 30 of 161 networks. More than one genotype was seen in seven networks. The mean duration of C trachomatis infection in each network was calculated to be 23 weeks. Conclusion Genotyping could be a useful tool in partner notification when there are discrepant or uncommon genotypes. Limited clinic catchment areas create information difficulties that obstruct accurate contact tracing.