Harald Moi

Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males.

BACKGROUND Infection with human papillomavirus (HPV) and diseases caused by HPV are common in boys and men. We report on the safety of a quadrivalent vaccine (active against HPV types 6, 11, 16, and 18) and on its efficacy in preventing the development of external genital lesions and anogenital HPV infection in boys and men. METHODS We enrolled 4065 healthy boys and men 16 to 26 years of age, from 18 countries in a randomized, placebo-controlled, double-blind trial. The primary efficacy objective was to show that the quadrivalent HPV vaccine reduced the incidence of external genital lesions related to HPV-6, 11, 16, or 18. Efficacy analyses were conducted in a per-protocol population, in which subjects received all three vaccinations and were negative for relevant HPV types at enrollment, and in an intention-to-treat population, in which subjects received vaccine or placebo, regardless of baseline HPV status. RESULTS In the intention-to-treat population, 36 external genital lesions were seen in the vaccine group as compared with 89 in the placebo group, for an observed efficacy of 60.2% (95% confidence interval [CI], 40.8 to 73.8); the efficacy was 65.5% (95% CI, 45.8 to 78.6) for lesions related to HPV-6, 11, 16, or 18. In the per-protocol population, efficacy against lesions related to HPV-6, 11, 16, or 18 was 90.4% (95% CI, 69.2 to 98.1). Efficacy with respect to persistent infection with HPV-6, 11, 16, or 18 and detection of related DNA at any time was 47.8% (95% CI, 36.0 to 57.6) and 27.1% (95% CI, 16.6 to 36.3), respectively, in the intention-to-treat population and 85.6% (97.5% CI, 73.4 to 92.9) and 44.7% (95% CI, 31.5 to 55.6) in the per-protocol population. Injection-site pain was significantly more frequent among subjects receiving quadrivalent HPV vaccine than among those receiving placebo (57% vs. 51%, P<0.001). CONCLUSIONS Quadrivalent HPV vaccine prevents infection with HPV-6, 11, 16, and 18 and the development of related external genital lesions in males 16 to 26 years of age. (Funded by Merck and others; ClinicalTrials.gov number, NCT00090285.).

Antibiotic treatment of symptomatic Mycoplasma genitalium infection in Scandinavia: a controlled clinical trial

Objectives: To evaluate the microbiological cure rate after treatment with tetracyclines or azithromycin in patients infected with M genitalium. Methods: One hundred and fifty-two men and 60 women positive for M genitalium were recruited. Patients treated either with doxycyline for 9 days or with azithromycin 1 g stat. were compared. Those still positive for M genitalium after primary doxycycline treatment received an extended course of azithromycin 500 mg on day 1 followed by 250 mg daily for the following 4 days, whereas those with treatment failure after azithromycin received doxycycline 100 mg twice daily for 15 days. Results: The eradication rate after azithromycin 1 g stat. was 85% (95% CI 69 to 94) in men (n = 39) and 88% (95% CI 64 to 99) in women (n = 17) and after doxycycline 17% (95% CI 9 to 27) in men (n = 76) and 37% (95% CI 19 to 58) in women (n = 27). Extended azithromycin eradicated M genitalium from 96% (95% CI 85 to 99) of the men (n = 47) and from all six women who failed on doxycycline. Extended doxycycline treatment was insufficient. Persistent urethral inflammation was seen in a substantial portion of the men after eradication of M genitalium regardless of the antibiotic drug, indicating a poor predictive value of urethral smears in evaluation of persistent or recurrent infection. Conclusions: Azithromycin was more effective than doxycycline in treating patients infected with M genitalium. The extended course of azithromycin was highly effective but was given after the initial treatment with doxycycline. Randomised clinical trials are needed to compare the different dosages of azithromycin.

External Genital Human Papillomavirus Prevalence and Associated Factors Among Heterosexual Men on 5 Continents

BACKGROUND We examined the baseline prevalence of penile, scrotal, and perineal/perianal human papillomavirus (HPV) in heterosexual men (HM). We also evaluated baseline characteristics of HM to assess factors associated with prevalent HPV detection. METHODS We tested serum samples from 3463 HM aged 16-24 years with 1-5 lifetime female sexual partners for antibodies to HPV 6, 11, 16, and 18. We collected baseline swab specimens for the detection of DNA of HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59 from 3 areas: penile, scrotal, and perineal/perianal. Risk factors for prevalent HPV DNA detection were evaluated. RESULTS The prevalence of any tested HPV type was 18.7% at the penis, 13.1% at the scrotum, 7.9% at the perineal/perianal region, and 21.0% at any site. Having >3 lifetime female sexual partners had the greatest impact on HPV prevalence: odds ratio (OR) 3.2 (95% confidence interval (CI) 2.1-4.9) for HPV 6, 11, 16, and 18; and OR 4.5 (95% CI 3.3-6.1) for all HPV types tested. HPV DNA detection was highest in Africa. Neither condom usage nor circumcision was associated with HPV DNA prevalence. CONCLUSION Genital-HPV DNA detection is common in young, sexually active HM. We found HPV to be most prevalent in African men and least prevalent in men from the Asia-Pacific region. Increased numbers of sexual partners was an important risk factor for HPV DNA prevalence.

Genital Ulcers as Initial Manifestation of Epstein-Barr Virus Infection: Two New Cases and a Review of the Literature

Genital ulceration is an uncommon manifestation of primary Epstein-Barr virus (EBV) infection. We present here two cases of genital ulcers probably caused by EBV. The first case is a 12-year-old girl with a genital ulcer appearing before specific EBV serology could identify a primary infection. However, serology was positive 13 days after the ulcer appeared. Polymerase chain reaction for EBV was positive in the biopsy from the ulcer as well. The second case is an 18-year-old female in whom the specific EBV serology was positive 8 days after appearance of the ulcer. The ulcers in both cases healed after 21 days. We reviewed the literature and a total of 26 cases of EBV-associated genital ulcers in females are now published. Median age of the 26 cases is 14.5 years of whom only 6 reports previous sexual contact. Mean healing time for the ulcers is 18 days. Our two cases correspond well with clinical reports of 24 EBV-associated genital ulcers in the literature.

Seroreactivity to Human Papillomavirus Type 16 Virus-like Particles Is Lower in High-Risk Men than in High-Risk Women

Seroreactivity to human papillomavirus type 16 (HPV-16) virus-like particles (VLPs) in men attending clinics for sexually transmitted diseases (STDs) in Denmark (n = 219) and Greenland (n = 88) was compared with seroreactivity in women attending the same clinics and was furthermore related to epidemiologic variables and concurrent HPV DNA detection. Risk factors for male seropositivity in Denmark were lifetime number of sex partners, a history of STDs, and sexual preference and in Greenland were ever having had syphilis and years at school. Although men reported significantly more sex partners, the mean seroreactivity was significantly lower in men than in women: 0.50 and 0.75, respectively, in Denmark and 0.53 and 0.86 in Greenland (P = .0001). Male seropositivity was not correlated with concurrent HPV DNA detection, but only 15 Danish and 6 Greenlandic men had HPV-16 DNA. Presence of HPV-16 VLP antibodies appears to be a biomarker for exposure to genital HPVs in men but is less sensitive than in women.

Risk factors for HPV infection in women from sexually transmitted disease clinics : Comparison between two areas with different cervical cancer incidence

We have compared risk factors for human papillomavirus (HPV) infection in very sexually active women [attenders of clinics for sexually transmitted diseases (STDs)] living in 2 areas with a 4‐fold difference in cervical cancer incidence, i.e., Greenland and Denmark. The results were compared with findings of HPV infection in men attending the STD clinics during the same period. Overall, 204 Greenlandic women (GW), 187 Danish women (DW), 103 Greenlandic men and 216 Danish men were included. A similar age distribution was found in the 2 female populations. The GW reported significantly more sexual partners, earlier first intercourse and more STDs, but HPV was less frequently detected in the GW (25%) than in the DW (35%). However, this could be explained by a difference in the age pattern of HPV prevalence seen in the 2 areas. In each geographical area, the age pattern of HPV prevalence in men was very similar to that seen in women. The most important risk factors for HPV detection were the same in both female populations, i.e., age, years since first sexual intercourse and number of partners in the last years. In conclusion, the pattern of risk factors for HPV infection was the same in STD women from a high‐risk area and a low‐risk area for cervical cancer. Our results also show that the use of an overall HPV prevalence for comparing populations is meaningless, even in populations with similar age distribution. Int. J. Cancer 75:1–8, 1998.© 1998 Wiley‐Liss, Inc.

2016 European guideline on Mycoplasma genitalium infections

Mycoplasma genitalium infection contributes to 10–35% of non‐chlamydial non‐gonococcal urethritis in men. In women, M. genitalium is associated with cervicitis and pelvic inflammatory disease (PID). Transmission of M. genitalium occurs through direct mucosal contact. Asymptomatic infections are frequent. In women, symptoms include vaginal discharge, dysuria or symptoms of PID – abdominal pain and dyspareunia. In men, urethritis, dysuria and discharge predominates. Besides symptoms, indication for laboratory test is a high‐risk sexual behaviour. Diagnosis is achievable only through nucleic acid amplification testing (NAAT). If available, NAAT diagnosis should be followed with an assay for macrolide resistance. Therapy for M. genitalium is indicated if M. genitalium is detected or on an epidemiological basis. Doxycycline has a low cure rate of 30–40%, but does not increase resistance. Azithromycin has a cure rate of 85–95% in macrolide susceptible infections. An extended course appears to have a higher cure rate. An increasing prevalence of macrolide resistance, most likely due to widespread use of azithromycin 1 g single dose without test of cure, is drastically decreasing the cure rate. Moxifloxacin can be used as second‐line therapy, but resistance is increasing. Uncomplicated M. genitalium infection should be treated with azithromycin 500 mg on day one, then 250 mg on days 2–5 (oral), or josamycin 500 mg three times daily for 10 days (oral). Second line treatment and treatment for uncomplicated macrolide resistant M. genitalium infection is moxifloxacin 400 mg od for 7–10 days (oral). For third line treatment of persistent M. genitalium infection after azithromycin and moxifloxacin doxycycline 100 mg two times daily for 14 days can be tried and may cure 30%. Pristinamycin 1 g four times daily for 10 days (oral) has a cure rate of app. 90%. Complicated M. genitalium infection (PID, epididymitis) is treated with moxifloxacin 400 mg od for 14 days.

Mycoplasma genitalium in women with lower genital tract inflammation

Objectives: To examine the prevalence of Mycoplasma genitalium in a large number of female patients attending a sexually transmitted infections (STI) clinic and to determine if there is an association with signs or symptoms of lower genital tract inflammation (LGTI). Methods: Altogether, 7646 female patients who had symptoms or microscopic signs of LGTI or were perceived to be at high risk of exposure to an STI were tested for both M genitalium and Chlamydia trachomatis. Urethral and cervical smears were examined quantitatively for polymorphic mononuclear leucocytes (PMNLs). Results: The prevalence of C trachomatis and M genitalium was 10.1% and 4.5%, respectively. We found a clear association between detecting M genitalium in first void urine (FVU) of patients and signs of urethral inflammation. The strongest association was between detecting M genitalium in FVU and number of PMNLs in urethral smears (n = 6790; OR 2.1; 95 % CI 1.5 to 2.9). The association was less significant between detecting M genitalium in cervical swabs and the number of PMNLs in urethral smears (n = 6785; OR 1.4; 95% CI 1.1 to 1.9), although cervical swabs gave higher sensitivity than FVU in detecting M genitalium (86% vs 62%). C trachomatis detection in FVU and cervical swabs was highly concordant and both significantly associated with urethritis (n = 6790; OR 3.6; 95% CI 3.0 to 4.4). Conclusions: This data support the hypothesis that M genitalium causes urethritis in women and that M genitalium infection of the genitourinary tract leads to different clinical manifestations depending on whether the site of infection is the urethral or the cervical epithelium.

The genital econiche: focus on microbiota and bacterial vaginosis

Ecological and evolutionary forces shaping the normal and abnormal microflora of the genital econiche are discussed, in particular those related to bacterial vaginosis, which worldwide is the most common vaginal infection, with numerous obstetrical and gynecological complications, including acquisition and transmission of HIV and other sexually transmitted infections (STIs). Characterized by a heavy overgrowth of Gram‐negative and Gram‐positive anaerobes with no signs of inflammation, bacterial vaginosis has been regarded a microbiological and immunological enigma. Immune tolerance to both normal and abnormal vaginal microbiota, mainly derived from gut microflora, as a result of coevolution with humans might explain the absence of inflammation, supported by short‐chain fatty acids, known to modulate immune responses, that are produced in large quantities by anaerobes. Recent studies have implicated the development of a vaginal biofilm with Gardnerella vaginalis and Atopobium vaginae as main players in the pathogenesis of bacterial vaginosis. Supporting this conclusion are data such as those demonstrating heavy growth of G. vaginalis and diversified anaerobes with numerous “clue cells” that are sloughing off from the biofilm. Gardnerella and Atopobium organisms attached to these clue cells can be demonstrated in the male genital econiche, likely reflecting a heterosexual transmission of the disorder.

Mycoplasma genitalium is associated with symptomatic and asymptomatic non-gonococcal urethritis in men

Objectives: To examine the prevalence of Mycoplasma genitalium in a large number of male patients attending a sexually transmitted infections (STI) clinic and to determine if there is an association with objective non-gonococcal urethritis (NGU) in patients with and without clinical symptoms. Methods: Patients were tested for both M genitalium and Chlamydia trachomatis if they had symptoms or microscopic signs of NGU or if they were perceived to be at high-risk of exposure to a STI (n = 8468). Urethral smears were examined for polymorphic mononuclear leucocytes. Results: We found that M genitalium infection was associated with symptoms of non-chlamydial NGU (discharge and dysuria; OR 4.3; 95% CI 3.4 to 5.5). We also found that M genitalium infection was associated with signs of non-chlamydial NGU independently with or without symptoms of NGU (with symptoms: OR 4.7; 95% CI 3.2 to 6.7; without symptoms: OR 3.1; 95% CI 2.0 to 4.6). Prevalence of M genitalium was also associated with severity of urethritis as quantified by microscopic examination of urethral smears. Conclusions: These data add further evidence to the association of M genitalium infection with NGU and should allow better risk analysis of recent recommendations of not performing urethral smears in asymptomatic men attending STI clinics.