Arne Wikström

Mycoplasma genitalium: a common cause of persistent urethritis among men treated with doxycycline

Background/objective: Persistent or recurrent non-gonococcal urethritis (NGU) is commonly observed in men attending sexually transmitted diseases clinics. The aim of this study was to determine the importance of Mycoplasma genitalium in this condition and to monitor the effect of treatment with macrolides. Methods: 78 male patients with persistent or recurrent symptomatic non-chlamydial NGU after treatment with doxycycline 200 mg day 1 and 100 mg for the following 8 days were enrolled. The patients had a first void urine specimen examined for the presence of M genitalium DNA by an inhibitor controlled PCR. Treatment with azithromycin and/or erythromycin and/or repeat doxycycline was prescribed at the doctor’s discretion to the M genitalium positive men. Microbiological cure rate was determined at a 3 week follow up visit. Results:M genitalium was detected in 32 (41%) men and those infected had more often a high grade urethritis (>10 PMNLs/hpf) than those negative for M genitalium (p = 0.01). 22 men had been treated with azithromycin, 19 of whom received 1.5 g over 5 days and three received 1 g as a single dose. All 20 who came back after treatment were M genitalium negative. Only two of five erythromycin treated controlled cases were M genitalium negative after treatment compared to all six given azithromycin at inclusion (p = 0.12). Six of nine female partners were M genitalium positive; they were treated with 1.5 g azithromycin given over 5 days, and the four tested were M genitalium negative after treatment. Conclusions:M genitalium is a common cause of persistent or recurrent urethritis among men treated with doxycycline and erythromycin appears to be less efficient than azithromycin in eradicating the infection.

Identification of human papillomavirus seroconversions

The temporal relationship between primary genital human papillomavirus (HPV) infections and the induction of antibodies against viral antigens has not been established. In order to address this question we studied a cohort of 110 women and 48 men with multiple heterosexual partners, who were followed for 220 person-years during which they made 583 visits to the sexually transmitted diseases clinic of the Amsterdam Public Health Service. At each visit spatula or brush samples from multiple anogenital and oral sites were collected for HPV DNA analysis by PCR. Serum samples were also collected and analysed for serological reactivity to peptides derived from the L1, L2 and E2 regions of HPV types 6, 16 and 18 as well as to bovine papillomavirus and HPV-16 virus-like particles. Seroconversions for at least three antigens were found among 16/158 patients. Of these, 10/16 were HPV-positive and in 5/16 cases seroconversions occurred concomitantly with the detection of HPV DNA. Analysis of participants who were HPV-negative at entry, but became HPV DNA-positive during follow-up revealed that antibodies against several HPV antigens were regularly induced at the time of a new HPV infection, in particular the IgG responses against HPV-16 virus-like particles and against the HPV-16 E2-derived peptide 245. Whereas the responses induced among the women with new HPV-16 infection tended to continuously increase, the responses among the men with any type of new HPV infection were mostly transient and disappeared during follow-up. In conclusion, we find that antibody responses to multiple viral antigens are often induced following the detection of genital HPV infection, that the type-specificity of the response is limited and that transient responses are common.

High occurrence of a new variant of Chlamydia trachomatis escaping diagnostic tests among STI clinic patients in Stockholm, Sweden.

Background: In 2006, a genetic variant of Chlamydia trachomatis not detectable with the most commonly used diagnostic tests was identified. Initial reports suggested that as many as 10% to 13% of all chlamydia cases would have remained undiagnosed. The aim of the study was to find the occurrence and clinical findings of this genetic variant among a high-risk population in Stockholm, Sweden. Methods: Samples were analyzed using the Cobas TaqMan CT test (Roche Diagnostics). To detect the new variant, an additional PCR-analysis, artus C. trachomatis LC MOMP PCR Kit (Qiagen) was performed on all negative samples. Positive results in the artus test were confirmed by a mutant specific PCR. Clinical data were retrospectively collected from medical records. Results: Among 1009 samples analyzed, 115 were positive for C. trachomatis and among those, 27 were found to belong to the genetic altered strain. This variant constituted 23% of all chlamydia cases diagnosed, and 29% were found in the age group 20 to 29 years. Women with the new variant were younger and had more often performed another chlamydia test within the previous 6 months compared with those infected with the wild type. Conclusion: These results indicate that a large number of sexually active individuals might be infected despite a negative chlamydia test, thus facilitating a rapid transmission of the new variant. Accordingly, it is of great importance to be aware of limitations of the diagnostic methods used.

Efficacy of chemical and/or surgical therapy against condylomata acuminata: a retrospective evaluation.

In order to estimate treatment resistance of condylomas, standardized records of 230 males aged 17–80 years (mean 27) attending at an STD clinic were analysed retrospectively. Anal warts occurred in 38 (17%) men; in 19 (50%) intra-anal warts were extensive enough to require further referral to the Department of Surgery. Urinary meatal warts occurred in 30 men; 9 of them (30%) were referred to the Department of Urology. The remaining 202 (88%) men were treated in the STD clinic with simple surgery and/or home-treatment with 0.5% podophyllotoxin-ethanol twice a day for one or more 3 day sessions. After a follow-up of at least one year, 46 (23%) patients still had condylomas. However, 77 (49%) of the remaining 156 men were cured after a single therapeutic session, and after 1–4 sessions the cumulative cure rate was 77%.

Papillomavirus-associated balanoposthitis.

OBJECTIVE--To assess whether there might be an association between genital papillomavirus infection (GPVI) and balanoposthitis. DESIGN--Retrospective HPV DNA examination of biopsy specimens from 23 men suffering from balanoposthitis and exhibiting acetowhite lesions that were penoscopically and histologically concurrent with HPV infection. SETTING--The STD clinics at Karolinska Hospital and South Hospital, Stockholm, Sweden. PARTICIPANTS--Randomly selected men attending with long-lasting and/or recurrent penile symptoms and exhibiting a clinical picture of balanoposthitis, who revealed a penoscopical and histopathological picture of epidermal lesions that were concordant with accepted criteria for typical or conspicuous GPVI. Asymptomatic controls were selected retrospectively on the basis of identical penoscopy and histology criteria. RESULTS--A history of previous condylomata was obtained in eight (35%) of 23 men. At penoscopic evaluation tiny condylomatous lesions were observed in five (22%) patients. The in situ hybridisation (ISH) assay using specific probes for the HPV types 6/11, 16/18, 31/33 and 42 was positive in 13/23 (56%) of the patient samples, but in only 26% of the 19 control samples. In patient biopsies the oncogenic HPV types 16/18 and/or 31/33 were found in 7/13 samples, whereas HPV 6/11 and/or 42 were present in another six cases. PCR performed on the ten ISH negative patient biopsies, were negative in all cases. CONCLUSION--Symptoms included redness, itching, burning, tenderness, dyspareunia, fissuring and in two cases penile oedema and inguinal adenopathy. All patients fulfilled penoscopical and histopathological criteria for HPV infection. We demonstrate some tentative evidence that HPV might be associated with long-lasting balanoposthitis, although our data still are circumstantial for a causative association. The results also elucidate the diversity in clinical presentation of GPVI.

Penile intraepithelial neoplasia: histopathological evaluation, HPV typing, clinical presentation and treatment

Background  Genital human papillomavirus (HPV) infection in male patients can cause great variety of lesions, most of which are benign, but some are categorised as penile intraepithelial neoplasia (PIN).

Antibodies against human papillomavirus type 6 capsids are elevated in men with previous condylomas.

Serum samples from 47 men with current condylomas, 32 men with a history of condylomas and from 205 men with no history of genital wart disease, who were attending sexually transmitted disease (STD) clinics at two different hospitals in Stockholm, were analyzed for the presence of immunoglobulin G (IgG) and A (IgA) antibodies to capsids of human papillomavirus types 6 and 11. IgG to HPV type 6 was found among 35% of patients with a history of condylomas compared to 10% of controls (p=0.0003), but only among 27% of patients with current condylomas. Antibodies to HPV 6 and to HPV 11 showed a very limited correlation, suggesting that the antibodies are HPV‐type restricted. The results strengthen conclusions from a previous serological study indicating that IgG antibodies against HPV 6 develop late during condylomatous disease and mostly reflect previous exposure to the virus.

Urethritis-associated Pathogens in Urine from Men with Non-gonococcal Urethritis: A Case-control Study.

The aetiology of non-gonococcal urethritis (NGU) remains unexplained in 30-40% of patients. Urine samples from men attending Swedish sexually transmitted disease clinics were examined by species-specific quantitative PCRs for Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, Ureaplasma urealyticum, U. parvum, adenovirus, herpes simplex virus, Neisseria meningitidis, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae. A total of 187 men with acute NGU (symptoms ≤ 30 days) and 24 with chronic NGU (symptoms < 30 days) were cases, and 73 men without NGU were controls. Number of lifetime sexual partners was negatively associated with U. urealyticum bacterial load. C. trachomatis and M. genitalium were associated with NGU, as was U. urealyticum, with bacterial loads ≥ 1.3 × 103 genome equivalents/ml urine. Virus and H. influenzae might explain a few NGU cases, but the aetiology in at least 24% of patients with acute NGU was unexplained. In multivariate analysis, detection of U. urealyticum was significantly more common in acute NGU (20%) compared with controls (11%).

Occurrence of pharyngeal Chlamydia trachomatis is uncommon in patients with a suspected or confirmed genital infection

Objective. To evaluate how common pharyngeal Chlamydia trachomatis (CT) is among mainly heterosexual women and men with a confirmed or a highly suspicious genital infection having had recent unprotected active oral sex. Design. Prospective observational study. Setting. Out‐patient clinics for sexually transmitted infections in Stockholm. Population. A total of 143 women and 138 men with a confirmed or suspected genital CT infection and a history of active oral sex. Methods. Pharyngeal samples from men and women in the study population were analyzed for the presence of CT. Main outcome measures. Number of positive CT in pharyngeal samples in relation to positive CT in genital samples. Results. Of the women, 9/128 (7.0%) were positive in the pharyngeal samples. None were exclusively positive in the pharynx. Three of 110 men (2.7%) had pharyngeal involvement. One man was positive in the pharynx as well as in the urine sample, and two men were exclusively pharyngeal CT positive. Conclusions. The finding of CT in the pharynx is not common in spite of the presence of a genital infection and a history of active oral sex.

The spectrum of genital human papillomavirus infection among men attending a Swedish sexually-transmitted infections clinic: human papillomavirus typing and clinical presentation of histopathologically benign lesions.

There have been a number of Swedish studies on human papillomavirus (HPV) typing in men, most of which have used less sensitive HPV-typing techniques. The present study included male patients with genital HPV-induced lesions planned for surgery. Samples were prepared for histopathology and PCR. HPV was detected in 233/253 (92%) and HPV 6 or 11 in 89% of the HPV-positive lesions. There were statistically significant differences regarding morphology (p=0.002), location (p=0.000001) and colour (p=0.005) of the lesions for low- vs. mixed or high-risk HPV types. For example, acuminate lesions were mostly found among men with low-risk HPV types, whereas macular lesions were over-represented among them with mixed or high-risk types. The HPV type distribution is similar to that in earlier studies, but we also found correlations with some clinical parameters.