Impact of HPV Vaccination on the Incidence of High-Grade Cervical Intraepithelial Neoplasia (CIN2+) in Women Aged 20-25 in the Northern Part of Norway: A 15-Year Study.

BACKGROUND: Human papillomavirus (HPV), the most prevalent sexually transmitted infection globally, is a key risk factor for high-grade cervical lesions and cervical cancer. Since 2009, HPV vaccination has been part of the national immunization program for girls in 7th grade in Norway (women born 1997 and later). This study aimed to assess the impact of HPV vaccination on the incidence of high-grade cervical precursors (CIN2+) among women aged 20-25 in Troms and Finnmark over a 15-year period. MATERIALS AND METHODS: In this time series study, we analyzed cervical screening data from 15,328 women aged 20-25 in Troms and Finnmark, collected between 2008 and 2022. Statistical methods, including linear and logistic regression, were employed to evaluate changes in cervical intraepithelial neoplasia grade 2 and worse (CIN2+) incidence and compare risks between vaccine-offered cohorts and pre-vaccine cohorts. RESULTS: The incidence of CIN2+ initially increased from 31 cases per year in 2008 to 110 cases in 2018, then significantly decreased to 44 cases per year by 2022 (p < 0.01). Women in pre-vaccine cohorts had a substantially higher risk of CIN2+ (OR 9.02, 95% CI 5.9-13.8) and CIN3+ (OR 19.6, 95% CI 7.3-52.6). Notably, no vaccinated women with CIN2+ tested positive for HPV types 16 or 18. Furthermore, none of the 13 cervical cancer cases recorded during the study were from the vaccinated cohorts. INTERPRETATION: The findings suggest a significant reduction in the incidence of high-grade cervical precursors following the introduction of the HPV vaccine in Norway's national immunization program, highlighting its effectiveness in cervical cancer prevention among young women in Northern Norway.

Incidence of invasive infections with Group B streptococcus in adults in Norway 1996-2019: a nationwide registry-based case-control study.

PURPOSE: Group B streptococcus (GBS) colonizes the gastrointestinal and vaginal mucosa in healthy adults, but has also become an increasing cause of invasive infection. The aims of this study were to describe the incidence and factors associated with the occurrence of invasive GBS disease in adults in Norway. METHODS: We performed a nationwide retrospective case-control study of invasive GBS infections during 1996-2019, with two control groups; invasive Group A streptococcal disease (GAS) to control for changes in surveillance and diagnostics, and a second representing the general population. RESULTS: A total of 3710 GBS episodes were identified. The age-standardized incidence rate increased steadily from 1.10 (95% CI 0.80-1.50) in 1996 to 6.70 (95% CI 5.90-7.50) per 100,000 person-years in 2019. The incidence rate had an average annual increase of 6.44% (95% CI 5.12-7.78). Incidence rates of GAS varied considerably, and there was no evidence of a consistent change over the study period. GBS incidence was highest among adults > 60 years of age. Cardiovascular disease, cancer, and diabetes were the most common comorbid conditions. There was a shift in the distribution of capsular serotypes from three dominant types to more equal distribution among the six most common serotypes. CONCLUSIONS: The incidence of invasive GBS disease in adults increased significantly from 1996 to 2019. The increasing age of the population with accompanying underlying comorbid conditions might contribute to the increasing burden of invasive GBS disease. Interestingly, type 1 diabetes was also associated with the occurrence of invasive GBS disease.

Explaining sex differences in risk of bloodstream infections using mediation analysis in the population-based HUNT study in Norway.

Previous studies indicate sex differences in incidence and severity of bloodstream infections (BSI). We examined the effect of sex on risk of BSI, BSI mortality, and BSI caused by the most common infecting bacteria. Using causal mediation analyses, we assessed if this effect is mediated by health behaviours (smoking, alcohol consumption), education, cardiovascular risk factors (systolic blood pressure, non-HDL cholesterol, body mass index) and selected comorbidities. This prospective study included 64,040 participants (46.8% men) in the population-based HUNT2 Survey (1995-1997) linked with hospital records in incident BSI. During median follow-up of 15.2 years, 1840 (2.9%) participants (51.3% men) experienced a BSI and 396 (0.6%) died (56.6% men). Men had 41% higher risk of first-time BSI (95% confidence interval (CI), 28-54%) than women. Together, health behaviours, education, cardiovascular risk factors and comorbidities mediated 34% of the excess risk of BSI observed in men. The HR of BSI mortality was 1.87 (95% CI 1.53-2.28), for BSI due to S. aureus 2.09 (1.28-2.54), S. pneumoniae 1.36 (1.05-1.76), E. coli 0.97 (0.84-1.13) in men vs women. This study shows that men have higher risk of BSI and BSI mortality than women. One-third of this effect was mediated by potential modifiable risk factors for incident BSI.

Risk of cervical intraepithelial neoplasia grade 3 or higher (CIN3+) among women with HPV-test in 1990-1992, a 30-year follow-up study.

BACKGROUND/OBJECTIVE: Having a 30-year follow-up of a cohort of women tested for HPV is a unique opportunity to further study long-term risk of CIN3+. The study objective was to compare HPV status at baseline with the risk of CIN3+ in the follow-up period of 30 years. METHODS: All women (n = 642) referred to the HPV outpatient clinic at the University Hospital of North Norway (UNN) in 1990-1992, with an HPV test at baseline, were included in a prospective cohort. HPV-testing was performed by two different HPV-DNA tests, and genotypes 6, 11, 16, 18, 31 and 33 were identified. High-risk (HR) HPV genotypes (16, 18, 31 and 33) were classified as HPV positive, whereas low-risk (LR) genotypes (6 and 11) in addition to absent HPV were classified as HPV negative. A single cohort in which women were classified for their HPV status underwent follow-up prospectively to the last time-point of observation of 30 years. RESULTS: During follow-up, 148 (148/642) cases of CIN3+ were detected, of whom 70.3% (104/148) were HPV positive and 29.7% (44/148) were HPV negative at baseline. The proportions of women who developed CIN3+ following a positive and a negative test were 46.6% (104/223) and 10.5% (44/419), respectively. Most cases of CIN3+ were seen shortly after the baseline HPV test, with 112 cases of CIN3+ diagnosed within the first year. In total, 48.6% (72/148) with HPV 16 and 57.6% (19/33) with HPV 33 developed CIN3+. Within the first year, CIN3+ was detected in 37.8% (56/148) with HPV 16, and 51.5% (17/33) with HPV 33. The long-term risk of CIN3+ was significantly lower than the short-term risk, and mainly associated with HPV 16. Overall, eight cases of cervical cancer were detected. Five were HPV positive, harboured HPV 16 at baseline and developed cervical cancer after 3, 4, 5, 11 and 24 years of follow-up. CONCLUSION AND CONSEQUENCES: HPV status at baseline is predictive for the subsequent risk of developing CIN3+. Women with a positive HPV test in 1990-1992 had a significantly higher risk of CIN3+ during 30 years of follow-up than those with a negative test. HPV 16 was associated with the greatest long-term risk of cervical cancer. All patients with a positive HPV test at baseline should be followed up until negative. TRIAL REGISTRATION: ISRCTN, ISRCTN10836802 . Registered 14 December 2020 - Retrospectively registered.

Hormonal contraceptive use and Staphylococcus aureus nasal and throat carriage in a Norwegian youth population.

BACKGROUND: Use of hormonal contraceptives has been associated with Staphylococcus aureus nasal carriage in adult women. However, the role of hormonal contraceptives in S. aureus colonization among adolescents and associations with progestin only contraceptives are unknown. METHODS: We obtained nasal and throat swab samples from 439 girls aged 17-21 years in the population-based Tromsø study Fit Futures, 2012-2013, Norway, with information on lifestyle, health and biomarkers. We used multivariable logistic regression to study the association between use of hormonal contraceptives and Staphylococcus aureus carriage while adjusting for potential confounding factors. RESULTS: Staphylococcus aureus nasal carriage prevalence were 34%, 42%, and 61% among progestin-only users, non-users, and progestin-estrogen combination contraceptive users, respectively (P<0.001). Use of combination contraceptives doubled the odds of nasal carriage (non-users reference; OR = 2.31, 95%CI = 1.43-3.74). The OR of nasal carriage was 0.29 among progestin-only users compared to combination contraceptives users (95% CI = 0.12-0.67). DISCUSSION: In this study, use of combination hormonal contraceptives was associated with higher risk of Staphylococcus aureus nasal carriage in adolescent girls. Experimental design studies are needed to establish the role of exogenous sex steroids in Staphylococcus aureus colonization in women.

Systemic antibiotic prophylaxis prior to gastrointestinal surgery - is oral administration of doxycycline and metronidazole adequate?

BACKGROUND: Antibiotic prophylaxis is recommended prior to a wide range of gastrointestinal operations to reduce the rate of surgical site infections (SSIs). Traditional intravenous (IV) drugs are costly and their preparation strains nursing resources at the wards. While oral administration may attenuate these limitations, its use remains limited. We aimed to assess whether a dual oral antibiotic prophylaxis regimen provides adequate serum concentrations throughout the surgical procedure. METHODS: We measured serum concentrations of doxycycline and metronidazole following single oral doses of 400 mg doxycycline and 1200 mg metronidazole at first incision and repeated at wound closure in a cohort of patients undergoing elective gastrointestinal surgery. Both drugs were dispensed at least two hours before skin incision. Serum concentrations were compared to minimum inhibitory concentrations (MIC) and epidemiological cut-off values (ECOFFs) for relevant pathogens. RESULTS: Mean serum concentrations of doxycycline at first incision and at wound closure were 5.75 mg/L and 4.66 mg/L and of metronidazole 18.88 mg/L and 15.56 mg/L, respectively. Metronidazole concentrations were above ECOFF (2 mg/L) for relevant anaerobic species in 103/104 of patients in both samples. Doxycycline serum concentrations were above the ECOFF for common Enterobacteriaceae species (4 mg/L) in both samples in 58/104 patients (55.8%). CONCLUSIONS: A single dose of orally administered metronidazole provides adequate concentrations throughout surgery in a heterogeneous cohort of patients. Uncertainty persists regarding the adequacy of doxycycline concentrations, as the optimal serum level of doxycycline in a prophylactic setting has not been established.

Cluster of linezolid-resistant Enterococcus faecium ST117 in Norwegian hospitals.

A linezolid-resistant, vancomycin-susceptible Enterococcus faecium strain was isolated from 3 patients who had not received linezolid. The first patient was hospitalized in the same hospitals and wards as the 2 following patients. The E. faecium isolates were resistant to linezolid (minimum inhibitory concentration 8-32 mg/l), ampicillin, and high levels of gentamicin. Resistance to linezolid was associated with a G2576T mutation in 23S rDNA. The cfr linezolid resistance gene was not detected. The 3 isolates showed identical DNA fingerprints by pulsed-field gel electrophoresis, belonged to ST117, and harboured virulence genes esp, hyl, acm, efaAfm, srgA, ecbA, scm, pilA, pilB, and pstD typically associated with high-risk E. faecium genotypes. The linezolid-resistant E. faecium high-risk clone caused bacteraemia in the first 2 cancer patients and survived in the hospital environment for more than a year before appearing in the urethral catheter of the third patient.

Factors associated with Chlamydia trachomatis testing in a high school based screening and previously in clinical practice: a cross-sectional study in Norway.

BACKGROUND: High school based chlamydia screening has been shown to increase uptake and detect hidden infections among sexually active adolescents. Our study aimed to: i) examine the proportions of 15-20 year-olds tested in a high school based screening and previously in clinical practice, ii) determine chlamydia prevalence according to testing pattern, and iii) examine factors associated with testing in the two settings. METHODS: A population based cross-sectional study was conducted in 5 high schools in Norway in 2009, using web-questionnaires and Chlamydia trachomatis PCR in first-void urine (800 girls/818 boys, mean age 17.2 years). Only sexually active participants at risk for chlamydia infections were included in the analyses. Crude and multivariable logistic regression models were applied with 'clinic based testing' and 'school based screening' as outcome variables. RESULTS: 56% of girls and 21% of boys reported previous clinic based testing. In the school based screening, 93% were tested with no gender difference. 42% of girls and 74% of boys were tested for the first time at school ('school-only test'). Both girls with clinic based testing and girls with school-only test had high chlamydia prevalence (7.3% vs 7.2%). Boys with clinic based testing had twice the prevalence of those with school-only test (6.2% vs 3.0%, p = 0.01). Half of infections were detected in participants with school-only test. One-fifth were repeat infections. In multivariable analysis of girls and boys combined, female gender, older age, early sexual debut, no condom use at first and last intercourse, steady relationship, and higher number of lifetime partners increased the odds of clinic based testing. The odds of school based screening increased with male gender, academic affiliation, later sexual debut, condom use at first intercourse, and current urogenital symptoms in multivariable analysis. CONCLUSIONS: More than half the girls had been tested prior to the school based screening and had high prevalence independent of previous clinic based testing. School screening was mostly associated with factors unknown to increase chlamydia infection risk, while clinic based testing was associated with traditional risk factors. The unusually high and equal participation between genders and the detection of a large chlamydia reservoir confirms the value of school based screening suggesting this approach to be further explored in Norway.

Age- and gender-associated Staphylococcus aureus spa types found among nasal carriers in a general population: the Tromso Staph and Skin Study.

Staphylococcus aureus nasal carriers risk autoinfection; however, knowledge about the factors that make specific strains successful colonizers is limited. This study was undertaken to identify the most successful S. aureus clones in nasal carriers and compare their distribution among host groups. The population structure of S. aureus isolates from healthy adults was investigated by spa typing 1,981 isolates from persistent and intermittent nasal carriers participating in a health survey. In the baseline screening (1,113 isolates), the most common spa types were t012 (8.4%), t084 (7.6%), and t065 (4.9%). Three large spa clonal complexes (spa CC012, spa CC065, and spa CC084) comprised 62.4% of the isolates. In multivariate models adjusted for age and smoking status, male sex was associated with higher risk for spa type t084 (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.06 to 2.77), and lower risk of spa type t012 (OR, 0.60; 95% CI, 0.39 to 0.92) colonization. The prevalence of spa type t012 decreased significantly with increasing age (P = 0.03), with a prevalence almost twice as high in the youngest group (age 30 to 44 years, prevalence = 11.1%) as in the oldest group (age, 60 to 87 years; prevalence = 5.6%). Among baseline isolates, spa type t084 had a twofold-higher prevalence among intermittent carriers than among persistent carriers (10.6% versus 5.5%; P = 0.04). In summary, the two most prevalent spa types found in this study were significantly associated with age and/or gender. This may provide valuable clues to the multifactorial mechanisms, among them bacterial factors, involved in nasal colonization with S. aureus.

Febrile neutropenia in children with cancer: a retrospective Norwegian multicentre study of clinical and microbiological outcome.

Our objective was to describe clinical and laboratory characteristics, treatment and outcome among Norwegian children with cancer suffering from chemotherapy-induced febrile neutropenia (FN). We retrospectively reviewed data on paediatric FN episodes in 7 Norwegian hospitals during a 2.5-y period. A total of 236 episodes of FN occurred in 95 children. Acute lymphoblastic leukaemia was the most common diagnosis (49 patients). Blood cultures yielded growth in 39 episodes (17%). Primary empirical antibiotic regimens could be assigned to 2 main groups: 1) benzylpenicillin or ampicillin and an aminoglycoside (58%) or 2) a regimen based on third-generation cephalosporins (42%). There were no statistically significant differences in outcome between the 2 regimens in terms of need to change initial antibiotic treatment, d of fever or maximum C-reactive protein values. One infection-related death (fungal septicaemia) occurred during the study period. We conclude that incidence of septicaemia and clinical outcome is similar to recent international trials on paediatric FN, but antibiotic treatment in Norway differs from international guidelines. However, patients in our study were successfully and safely treated, irrespective of the primary empirical antibiotic regimen.