Improvement in Neisseria gonorrhoeae culture rates by bedside inoculation and incubation at a clinic for sexually transmitted infections.

BACKGROUND: Culture of Neisseria gonorrhoeae is essential for surveillance of complete antimicrobial susceptibility profiles. In 2014, the culture success rate of N. gonorrhoeae from samples taken at the clinic for sexually transmitted infections (STI clinic), Oslo University Hospital, Norway, was only 20%. The present study aimed to improve gonococcal culture rates using bedside inoculation of patient samples on gonococcal agar plates and incubation at the STI clinic. METHODS: This prospective quality improvement study was conducted by the STI clinic and the Department of Microbiology at Oslo University Hospital from May 2016 - October 2017. When culture of N. gonorrhoeae was clinically indicated, we introduced a parallel 'bedside culture' at the STI clinic and compared results with the standard culture at the microbiology department. Samples were taken from urethra, anorectum, pharynx and cervix. Culture rates were compared across symptomatic and asymptomatic anatomical sites. RESULTS: From 596 gonococcal-positive PCR samples, bedside culture had a significantly higher success rate of 57% compared to 41% with standard culture (p < 0.05). Overall, culture rate from symptomatic sites was 91% v. 45% from asymptomatic sites. The culture rates from different anatomical sites were as follows: urethra 93%, anorectum 64%, pharynx 28% and cervix 70%. Bedside culture significantly (p < 0.05) improved the culture rates for symptomatic urethral and asymptomatic pharyngeal samples. CONCLUSIONS: Where feasible, bedside inoculation on gonococcal agar plates and incubation of samples from patients with gonorrhoea is recommended. This will improve the culture diagnostics and provide additional gonococcal isolates for antimicrobial resistance surveillance.

Clinical and analytical evaluation of the new Aptima Mycoplasma genitalium assay, with data on M. genitalium prevalence and antimicrobial resistance in M. genitalium in Denmark, Norway and Sweden in 2016.

OBJECTIVES: Mycoplasma genitalium (MG) causes urethritis and cervicitis, potentially causing reproductive complications. Resistance in MG to first-line (azithromycin) and second-line (moxifloxacin) treatment has increased. We examined the clinical and analytical performance of the new Conformité Européene (CE)/in vitro diagnostics (IVD) Aptima Mycoplasma genitalium assay (CE/IVD AMG; Hologic); the prevalence of MG, Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); and MG resistance to azithromycin and moxifloxacin in Denmark, Norway and Sweden in 2016. METHODS: From February 2016 to February 2017, urogenital and extragenital (only in Denmark) specimens from consecutive attendees at three sexually transmitted disease clinics were tested with the CE/IVD AMG, the research-use-only MG Alt TMA-1 assay (Hologic), Aptima Combo 2 (CT/NG) assay and a laboratory-developed TaqMan real-time mgpB quantitative real-time PCR (qPCR). Resistance-associated mutations were determined by sequencing. Strains of MG and other mycoplasma species in different concentrations were also tested. RESULTS: In total 5269 patients were included. The prevalence of MG was 7.2% (382/5269; 4.9-9.8% in the countries). The sensitivity of the CE/IVD AMG, MG Alt TMA-1 and mgpB qPCR ranged 99.13-100%, 99.13-100% and 73.24-81.60%, respectively, in the countries. The specificity ranged 99.57-99.96%, 100% and 99.69-100%, respectively. The prevalence of resistance-associated mutations for azithromycin and moxifloxacin was 41.4% (120/290; 17.7-56.6%) and 6.6% (18/274; 4.1-10.2%), respectively. Multidrug resistance was found in all countries (2.7%; 1.1-4.2%). CONCLUSIONS: Both transcription-mediated amplification (TMA)-based MG assays had a highly superior sensitivity compared to the mgpB qPCR. The prevalence of MG and azithromycin resistance was high. Validated and quality-assured molecular tests for MG, routine resistance testing of MG-positive samples and antimicrobial resistance surveillance are crucial.

Identification of macrolide-resistant Mycoplasma genitalium using real-time PCR.

OBJECTIVES: Mycoplasma genitalium is a common cause of non-gonococcal urethritis (NGU) in Western Europe, but is not routinely tested for in all clinics. A high prevalence of macrolide-resistant M. genitalium has been reported. An easy to use test that can predict likely macrolide treatment failure is potentially very valuable. We report the development of a rapid and reliable real-time PCR-assay which detects all relevant resistance loci in the M. genitalium 23S rRNA gene. METHODS: Mycoplasma genitalium-positive clinical samples were collected between December 2012 and May 2013, from samples sent routinely to the laboratory for diagnostic testing for M. genitalium. The real-time PCR assay was designed using forward amplification primers complementary to all relevant commonly identified 23s rRNA gene mutations, a common reverse amplification primer and a common TaqMan Probe. RESULT: We report a Taqman assay for detection of common 23S rRNA genotypes at position 2058 and 2059 (Escherichia coli numbering) associated with macrolide resistance, directly from clinical samples. We validated the assay by comparison with DNA sequence determination. CONCLUSION: Our TaqMan assay detects common genotypes associated with macrolide-resistant M. genitalium, namely, A2058G, A2059G and A2058C. We show association between the presence of resistant M. genitalium and treatment failure, thereby confirming the validity of testing for these mutants to prevent further spread of antimicrobial resistance and to allow informed choice of antibiotics for treatment.

Elevated odds of metabolic syndrome in psoriasis: a population-based study of age and sex differences.

BACKGROUND: Questions remain concerning to what extent age and sex may modify the suggested association between psoriasis and the metabolic syndrome in the general population. OBJECTIVES: To investigate the association between psoriasis and the metabolic syndrome within a large population-based cohort by age and sex. METHODS: A cross-sectional study including 10 521 participants aged 30-79 years from the Tromsø Study cohort was performed; 1137 participants reported lifetime psoriasis of a mainly mild character. The new harmonized definition of metabolic syndrome was used in the multivariable logistic regression analysis. RESULTS: There was a uniformly higher prevalence of metabolic syndrome in men and women with psoriasis compared with those without across all age groups. In women, psoriasis was associated with a 3·8-times higher odds of metabolic syndrome at age 30 years (95% confidence interval 1·5-9·7), with a decreasing odds ratio with increasing age. In men, psoriasis was associated with a stable 1·35-times higher odds of metabolic syndrome (95% confidence interval 1·1-1·6) at all ages. Abdominal obesity was the most frequent metabolic syndrome component in women in this study, and there was indication of a dose-response relationship between psoriasis severity, indicated through treatment, and having a high waistline in women. CONCLUSIONS: This study suggests age and sex variations in the risk of metabolic syndrome among individuals with psoriasis. Given the high prevalence of psoriasis and the significantly elevated burden of metabolic syndrome in this patient group, there may be a benefit from targeted screening of metabolic syndrome among individuals with psoriasis regardless of age and disease severity.

Anatomic distribution of Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium infections in men who have sex with men.

BACKGROUND: New cases of gonorrhoea (Neisseria gonorrhoeae) and chlamydia (Chlamydia trachomatis) infections have been steadily increasing in Scandinavian countries over the last decade. There is a particular urgency in reducing new infections as isolation of multiple drug resistant strains of gonorrhoea is becoming more frequent. The aim of this study was to determine the prevalence and sites of infection of common sexually transmissible infections (STIs) in men who have sex with men (MSM). METHODS: We have performed a retrospective analysis of the three major STIs, gonorrhoea, chlamydia and Mycoplasma genitalium in urogenital, anorectal and oropharyngeal samples from MSM that attended two STI clinics in Oslo. RESULTS: One hundred and thirty-six men (6.0%) out of 2289 MSM tested were found to be positive for gonorrhoea using a porA gene targeted nucleic acid amplification test (NAAT). Of these, 106 (77.9%) would not have been identified through testing first-void urine alone. Two hundred and twenty eight (10.0%) patients from 2289 tested were found to be positive for chlamydia, 164 (71.9%) of which were identified through anorectal specimens. Ninety-one (5.1%) patients from 1778 tested were found to be positive for M. genitalium, with 65 (71.4%) identified through testing of anorectal specimens. CONCLUSIONS: Our results supports the European findings that the MSM population carries a high burden of STIs and that testing the anorectum and oropharynx will identify a significantly higher percentage of infected patients and reservoirs of STIs.

Is the prevalence of psoriasis increasing? A 30-year follow-up of a population-based cohort.

BACKGROUND: There is indication of an increasing prevalence of psoriasis in some western populations. However, the results are not conclusive. OBJECTIVES: To analyse trends in the prevalence of psoriasis over the past 30 years, separating age, birth cohort and time period effects. METHODS: Five population-based surveys in North Norway, the Tromsø Studies 2-6, collected between 1979 and 2008, were studied. Participants aged 20-79 years with self-reported psoriasis data in at least one of the surveys were included, yielding a total of 69,539 observations from 33,387 unique individuals born between 1915 and 1977. Trends in psoriasis prevalence were examined using cross-sectional, time lag and longitudinal designs of graphical plots. Observed trends were further evaluated in generalized linear-regression models. RESULTS: The self-reported lifetime prevalence of psoriasis increased from 4·8% in 1979-1980 to 11·4% in 2007-2008. Graphical plots showed an increasing prevalence of psoriasis with each consecutive survey in all examined age groups and birth cohorts, leaving time period effects as the explanation for the increase. The odds for psoriasis in the cohort were 2·5 times higher in 2007-2008 than in 1979-1980 (adjusted odds ratio 2·49, 95% confidence interval 2·08-2·99). The prevalence of persons reporting a doctor's diagnosis of psoriasis was 9·9% in the last survey. In subgroups of the study population, psoriasis was associated with higher body mass index, lower physical activity during work and leisure time, lower educational level and smoking. CONCLUSIONS: Our findings indicate an increasing prevalence of self-reported psoriasis. This could represent a true increase in prevalence, possibly due to changes in lifestyle and environmental factors, or an increased awareness of the disease.

Psoriasis in Norwegian twins: contribution of genetic and environmental effects.

BACKGROUND: Psoriasis is a chronic T-cell-mediated immunological skin disease with a complex pathogenesis where both genetic and environmental factors are involved. OBJECTIVE: To study the conditional and relative risk of developing psoriasis in identical and fraternal twins whose co-twin has a positive history of the disease and to estimate the relative contribution of genetic and environmental factors on the liability for psoriasis in Norway. METHODS: Self-reported history of psoriasis in twins from the population-based Norwegian Twin Panel (N = 8045) was studied. Absolute and relative risks of developing psoriasis conditioned on the positive history of psoriasis in a co-twin were calculated by Kaplan-Meier survival analysis and Cox regression, respectively. Structural equation modelling was used to estimate genetic and environmental variance components. RESULTS: Altogether, 334 (4.2%) of the twins reported having psoriasis. No difference in prevalence of the disease across sexes and zygosity groups was found. Identical twins were more likely to develop psoriasis than fraternal twins if a co-twin reported having the disease. The best-fitting model showed that additive genetic effects could explain 66% of the variation in liability for psoriasis in this population, and the remaining 34% was due to non-shared environmental influences. CONCLUSIONS: High heritability due to additive genetic effects together with considerable environmental contribution to the liability of psoriasis support the current opinion on the multifactorial aetiology of the disease. No sex-specific patterns of heritability of psoriasis were found.

Psoriasis in Norway as observed in a population-based Norwegian twin panel.

BACKGROUND: Psoriasis is a chronic T-cell-mediated immunological skin disease. The occurrence of the disease appears to differ with geography and ethnicity. There is a need for epidemiological data obtained from defined population-based studies, and the sex-specific differences observed in the natural history of the disease require more attention. OBJECTIVES: To describe the occurrence and risk of psoriasis in Norway by age and sex. PATIENTS/METHODS: A population-based health survey was conducted in 1998 in Norwegian twins aged 19-31 years. The present study is based upon the self-reported history of psoriasis among the 8045 questionnaire responders. RESULTS: Altogether, 334 (4.2%) reported a positive history of psoriasis. There were no sex differences in the overall prevalence rates, but significantly higher point-prevalences emerged in females in the teenage-year intervals. A fairly linear increase in incidence rates by every 4-year age-interval peaked at a lower age in females. The mean age at onset was also significantly lower in females (14.8 years) than in males (17.3 years). The absolute risk of developing psoriasis appeared higher for females across the entire age range. However, by the age of 31 the cumulative risks were similar in females and males (0.056 and 0.053, respectively). CONCLUSIONS: In this historical cohort of Norwegian twins, we find a high prevalence of psoriasis in congruence with previously reported data among whites in north-western Europe. We have found sex-specific characteristics in point-prevalences and incidence rates which may contribute to the understanding of the earlier age at onset of the disease in females.

Association between the HLA DQB1*0301 gene and human papillomavirus infection in high-grade cervical intraepithelial neoplasia.

This study describes the distribution of DQB1genes in Norwegian women treated for high-grade cervical intraepithelial neoplasia (CIN). Formalin-fixed, paraffin-embedded tissue sections from 170 biopsy specimens with diagnoses of CIN II (n = 54) or CIN III (n = 116) were DQB1-typed using allele-specific polymerase chain reaction. The follow-up period for cases was 13 to 15 years. The control material comprised blood samples and endocervical brushes from 213 women without CIN. Both cases and controls had previously been human papillomavirus (HPV)-typed. The DQB1*0301 allele was overrepresented among cases compared with controls (odds ratio [OR] = 1.8). Presence of CIN was related to HPV infection, and HPV 16 positivity was significantly associated with the presence of DQB1*0301 (OR 1.8). The DQBI*0301 allele was significantly more prevalent in CIN III than in CIN II cases. The lesions in two women recurred in the follow-up period, one of whom was carrying the DQB1*0301 allele. Women carrying the HLA-DQB1*0301 allele have an increased risk of developing CIN when infected by HPV 16, although there was not an increased frequency of recurrent disease among women carrying this allele.

Combined effect of smoking and human papillomavirus type 16 infection in cervical carcinogenesis.

To study the combined effect of smoking and human papillomavirus (HPV) type 16 infection in high-grade cervical intraepithelial neoplasia, we analyzed data from a Norwegian population-based case-control study including 90 patients and 216 controls, 20-44 years of age. We assessed HPV-16 status both by polymerase chain reaction detecting virus DNA and by enzyme-linked immunosorbent assay detecting antibodies against virus capsid. Smoking was associated with cervical intraepithelial neoplasia grade II-III in HPV-16-positive individuals. Using the jointly unexposed (HPV-16 DNA-negative never-smokers) as the reference group, we determined the risk of cervical intraepithelial neoplasia grade II-III in HPV-16 DNA-positive never-smokers and HPV-16 DNA-positive ever-smokers (odds ratio = 15.7; 95% confidence limits = 3.2, 76.5, and odds ratio = 65.9; 95% confidence limits = 22.3, 194.3, respectively). The estimated proportion of cases among HPV-16-positive smokers that is attributable to the interaction between the two causes is 74%, based on HPV-16 DNA positivity.

Herpes simplex virus and human papillomavirus in a population-based case-control study of cervical intraepithelial neoplasia grade II-III.

In order to evaluate the association between seropositivity for herpes simplex virus (type 1 and type 2) and cervical intraepithelial neoplacia (CIN), we analysed data from a population-based case-control study of CIN grade II-III which included Norwegian women aged 20 to 44 years, 94 cases and 228 controls. Our objectives were to determine if HSV-1 and/or HSV-2 seropositivity were independent risk factors for CIN, taking human papillomavirus exposure into account, and to elucidate the combined effect of HPV positivity and seropositivity for HSV In logistic regression analyses, the association between HSV-2 or HSV-1 seropositivity and CIN II-III was not explained by HPV (adjusted OR 3.0; 95%, CI 1.3-7.2 and adjusted OR 3.3; 95% CI 1.3-8.4, respectively). In analyses restricted to HPV-16 DNA-positive individuals, seropositivity for HSV-2 increased the risk of CIN (OR 11.1; 95% CI 1.2-105.7), whereas HSV-1 seropositivity was not significantly associated with CIN. In women positive for other HPV types, only HSV-1 seropositivity was associated with CIN (OR 8.5; 95% CI 1.3-55.8). In analyses of the HPV-16-seropositive individuals, neither HSV-1 nor HSV-2 seropositivity was associated with CIN. Compared to the reference group of jointly unexposed subjects, the HPV-16 DNA-positive women who were anti-HSV-2 negative had an increased risk of CIN (OR 29; 95% CI 12-67), whereas the risk in women who were both HPV-16 DNA-positive and HSV-2 was OR=247 (95% CI 31-1996). The estimate of interaction was strong, but did not reach significance, and our findings may suggest that the combined effect of the two viruses is of aetiological importance in cervical carcinogenesis. Furthermore, the results indicate that HPV DNA positivity is not sufficient to explain the sexual behaviour-associated risk of cervical neoplasia and that further studies on the role of genital HSV (type 1 as well as type 2) and other STDs are warranted.

An increased risk of cervical intra-epithelial neoplasia grade II-III among human papillomavirus positive patients with the HLA-DQA1*0102-DQB1*0602 haplotype: a population-based case-control study of Norwegian women.

Several recent studies have reported different associations between HLA specificities and human papillomavirus (HPV)-associated disease of the cervix. We report the distribution of DQA1 and DQB1 genes and HPV infection in a population-based case-control study including 92 patients with histologically verified cervical intraepithelial neoplasia grade II-III (CIN II-III) (thus including moderate and severe dysplasia and carcinoma in situ) and 225 control subjects. We found an overrepresentation of the DQA1*0102-DQB1*0602 haplotype among HPV-positive cases compared with controls. The association was even stronger when comparing HPV-16-positive cases with HPV-16-positive controls. In addition, among HPV-16-positive individuals, we observed a decreased frequency of DQA1*0102-DQB1*0604 in cases compared with controls. We were not able to detect any association between CIN II-III and DQB1*03. Compared with previous findings in cervical cancer, our data indicate that carrying the DQA1*0102-DQB1*0602 haplotype gives an increased risk of developing CIN when infected with HPV-16, without influencing progression to cancer.

Seropositivity against HPV 16 capsids: a better marker of past sexual behaviour than presence of HPV DNA.

OBJECTIVES: To assess if seropositivity to human papillomavirus type 16 capsids is a better marker of sexual history than the presence of HPV DNA. STUDY DESIGN: A population based age stratified random sample of 234 Norwegian women (mean age 32.8 years, range 20-44) was examined for HPV serum antibodies, cervical HPV DNA, cytology and age in relation to sexual behaviour. RESULTS: Neither age nor age at first sexual intercourse was associated with HPV 16 antibodies. Adjusted ORs for 4-5; 6-10 and > 10 versus 0-1 lifetime sexual partners, were 13.1 (95% CI 1.5-110.8), 8.2 (1.0-69.6) and 10.5 (1.2-94.0) for HPV 16 seropositivity, respectively; and 2.6 (0.2-27.8), 3.4 (0.4-31.7) and 4.1 (0.4-42.8) for HPV 16 DNA positivity, respectively. CONCLUSION: Seropositivity to HPV 16 capsids is positively associated with the number of sexual partners, suggesting that HPV 16 is predominantly sexually transmitted. The fact that serology had a stronger association with number of sexual partners than viral DNA suggests that seroreactivity is a better measure of lifetime history of HPV infection.

Screening for ESR mutations in breast and ovarian cancer patients.

In the present study, leukocyte DNA from 143 patients with familial clustering of breast and/or ovarian cancer and tumour DNA from 96 breast carcinomas were screened for base mutations in the estrogen receptor gene (ESR). Three patients with a family history of cancer were carrying a Gly160Cys germline substitution. This alteration was also detected in eight (four females and four males) of 729 controls (366 female, 363 males), indicating that the substitution probably represents a polymorphism. However, in the 229 female controls in whom family history of cancer was known, one of two who had a sister with breast cancer was carrying the variant allele. Hence, a possible clinical significance of the glycine into cysteine cannot be completely ruled out and should be further investigated. Somatic mutations were not detected in any of the tumours studied, and the present data do not provide support for somatic ESR base mutations as an important mechanism for hormonal therapy resistance in estrogen receptor-positive breast carcinomas.

Correlation between polymerase chain reaction and cervical cytology for detection of human papillomavirus infection in women with and without dysplasia.

The aim of this study was to compare the ability of two methods, the polymerase chain reaction (PCR) and cervical cytology, to detect HPV infection. The study population included 222 randomly selected women without dysplasia (controls) and 91 women with histologically confirmed dysplasia (CIN II-III) (cases). In women without dysplasia, 8.6% had cytological signs of HPV infection, whereas 15.3% were HPV DNA positive by PCR. In women with dysplasia, 72.5% had cytological signs of HPV infection, whereas 90.1% were HPV PCR positive. The statistical agreement between the two diagnostic methods was low (controls: kappa = 0.26, cases: kappa = -0.03). In total, PCR failed to detect 17 of 85 women with cytological signs of HPV infection, whereas cervical cytology failed to detect 48 of 116 HPV PCR-positive women. In women with dysplasia, but not in women without dysplasia, the oncogenic HPV types were associated with cytological signs of HPV infection.

A population-based case-control study of human papillomavirus-type-16 seropositivity and incident high-grade dysplasia of the uterine cervix.

In order to study the association between seropositivity against human papillomavirus-type-16 capsids and CIN II-III in the general population in ages at which high-grade cervical dysplasia arises, 90 cases and 216 controls participating in a population-based case-control study of incident CIN II-III, were analyzed for the presence of HPV antibodies, HPV DNA and for the influence of behavioral factors. A significantly higher proportion of cases than controls were seropositive. Of HPV-16-DNA-positive cases and controls, 42 and 14% respectively were seropositive. A similar proportion of seropositivity was found among the 172 cytologically normal, HPV-DNA-negative controls. However, seropositivity was closely linked to the sexual history of the women. Logistic-regression analyses, adjusting for sexual behavior, smoking history and educational level, revealed that CIN II-III was associated with HPV-16 seropositivity and with HPV DNA. Controlling for the presence of HPV DNA indicated that antibodies were not independently associated with CIN. The low correlation between the presence of HPV antibodies and DNA, the finding that the association between seropositivity and CIN depended on the presence of HPV DNA, and the association of seropositivity with sexual history, may be explained by serology detecting both past and present persistent infections and presence of HPV DNA, reflecting mostly transient infections in controls and persistent infections in cases.

Prevalence of human papillomavirus in cervical scrapes, as analyzed by PCR, in a population-based sample of women with and without cervical dysplasia.

HPV is suspected of being a major cause of cancer of the uterine cervix. To understand the risk of disease in the general population of women, it is important to estimate the prevalence of HPV infection in a random population-based sample of women without disease. In this study, a total of 231 randomly selected women without dysplasia (controls) were examined, and compared with 103 women with histologically confirmed CIN II-III (patients). The prevalence of HPV DNA in cervical scrapes was determined by general nested PCR, which was expected to detect any relevant HPV type commonly found in cervical samples. The nested positive samples were typed with type-specific PCR. In the general nested PCR, 15% of the controls were positive, compared to 91% of the patients. In the population-based sample, 2.2% had HPV types 6 and 11 and 10% had types 16, 18, 31, and 33. In both groups, HPV DNA was observed less frequently in women above than below the age of 30. The results are among the few population-based figures on the prevalence of HPV in women, and provide a baseline for understanding the risk of developing cancer of the uterine cervix, and determining the proportion of women to be included in intervention studies.

Human papillomavirus and cervical intraepithelial neoplasia grade II-III: a population-based case-control study.

The association between certain human papillomaviruses (HPV) and cervical intraepithelial neoplasia (CIN) is well documented, but there is uncertainty about the strength of association and the role of co-factors is unclear. This population-based case-control study in Norwegian women 20-44 years of age included 103 cases with histologically confirmed CIN II-III and 234 age-matched and randomly selected controls. Cytological specimens from the cervix were analyzed using the polymerase chain reaction (PCR). In all, 91% of the cases and 15% of the controls were HPV DNA positive, giving a crude odds ratio (OR) of 67.2 (95% confidence interval: 28.6-157.5). The association between HPV 16 and CIN II-III was even stronger (crude OR = 123.9; 46.7 - 328.5). In logistic regression analysis, additional to HPV, only a high number of sexual partners and a low educational level contributed independently to the risk. The adjusted OR for the association between HPV and CIN II-III was 72.8 (95% CI: 27.6-191.9). The association between HPV and CIN remains very strong even after adjustment for proposed confounding factors. The results therefore support the role of HPV as a causative agent in the development of CIN.