The 'Finnish new variant of Chlamydia trachomatis' escaping detection in the Aptima Combo 2 assay is widespread across Norway, June to August 2019.

The 'Finnish new variant of Chlamydia trachomatis' (FI-nvCT), escaping detection in the Aptima Combo 2 assay (AC2), is widespread across Norway. From June to August 2019, 84% (81/97) of available AC2/Aptima CT discordant samples from five laboratories were confirmed as FI-nvCT. Two additional CT variants (CT 23S rRNA C1514T and G1523A) also escaped AC2 detection. The high FI-nvCT proportion might indicate a long-term national spread and it cannot be excluded that FI-nvCT emerged in Norway.

Large outbreak of mumps virus genotype G among vaccinated students in Norway, 2015 to 2016.

From 6 September 2015-May 2016, a large mumps outbreak occurred among vaccinated students in Norway. A case was defined as a person presenting with a clinical mumps infection, notified between 1 September 2015 and 30 June 2016. Confirmed cases had positive laboratory confirmation and probable cases had an epidemiological link; PCR-positive specimens were genotyped. A total of 232 cases were notified (230 confirmed) with median age of 23 years (range 4-81) and 61% were male. Of 68 (30%) confirmed cases that were genotyped, 66 were genotype G and associated with the outbreak. Cases that had received two doses of the measles-mumps-rubella (MMR) vaccine had reduced risk of hospitalisation (adjusted relative risk (aRR): 0.14; 95%CI: 0.03-0.57), mumps-related orchitis (aRR: 0.21; 95% CI: 0.08-0.55) and severe outcome (aRR: 0.25; 95% CI: 0.10-0.62) compared with those unvaccinated. A third dose of the vaccine was offered to approximately 1,300 fully vaccinated close contacts and subsequently reported cases decreased. This large outbreak, occurring among predominately vaccinated students, suggests the current genotype A vaccine offers suboptimal protection against mumps genotype G. We recommend maintaining high vaccination coverage and offering the vaccine to all unvaccinated individuals.

[A 4-year-old girl with diarrhoea, paresis and mutism]. / En fire år gammel jente med diaré, kraftsvikt og mutisme.

BACKGROUND Rotavirus is a common cause of gastroenteritis in children. Neurological manifestations associated with rotavirus infections are well described and range from benign afebrile convulsions to lethal encephalopathy or encephalitis.CASE PRESENTATION We present an uncommon neurological manifestation in a Caucasian child in the course of a rotavirus infection. A 4-year old girl presented with mutism, hypotonia and reduced consciousness. Magnetic resonance imaging revealed diffusion abnormalities in the splenium corpus callosum and bilaterally in the nuclei dentate in the cerebellum. She was diagnosed with rotavirus cerebellitis.INTERPRETATION Her clinical symptoms and the magnetic resonance imaging abnormalities were uncommon and previously described in only a few Caucasian children. The outcome has varied, and some children have shown long term neurological sequela. Treatment with immunoglobulins and corticosteroids has been used in similar cases, but there is no established treatment for this condition.

Antibodies to Epstein-Barr virus and MRI disease activity in multiple sclerosis.

BACKGROUND: Previous reports indicate an association between Epstein-Barr virus (EBV) antibody levels and multiple sclerosis (MS) disease activity, but the results have been conflicting. OBJECTIVES: The objective of this paper is to study if EBV antibody levels reflect MRI disease activity in MS and examine the potential for EBV antibody levels as biomarkers for treatment response. METHODS: A total of 87 MS patients were followed for two years prior to and during interferon beta (IFNB) treatment, with MRI examinations and serum measurement of IgM and IgG antibodies to viral capsid antigen (VCA), EBV nuclear antigen 1 (EBNA-1) and early antigen (EA). Associations between EBV antibody levels and MRI activity were assessed by a logistic regression model. RESULTS: Higher anti-EBNA-1 IgG levels were associated with increased MRI activity, OR = 2.95 (95% CI 1.07-8.10; p = 0.036) for combined unique activity (CUA; the sum of T1Gd+ lesions and new or enlarging T2 lesions). Although most patients were anti-VCA IgM negative, there was an inverse association, OR = 0.32 (95% CI 0.12-0.84; p = 0.021) with CUA during IFNB treatment. CONCLUSIONS: This study supports an association between anti-EBNA-1 IgG levels and MS disease activity. We also found an inverse association with anti-VCA IgM levels during IFNB treatment not previously described, indicating anti-VCA IgM as a possible biomarker for IFNB treatment response.

Humoral response to Epstein-Barr virus in patients with multiple sclerosis treated with B cell depletion therapy.

BACKGROUND: B cell depletion therapy is highly effective in relapsing-remitting multiple sclerosis (RRMS). However, the precise underlying mechanisms of action for its biological effects in MS have still not been clarified. Epstein-Barr virus (EBV) is a known risk factor for MS and seems to be a prerequisite for disease development. EBV resides latently in the memory B cells, and may not only increase the risk of developing MS, but also contribute to disease activity and disability progression. Therefore, the effects of B cell depletion in MS could be associated with the depletion of EBV-infected cells and the altered immune response to the virus. In this study, we investigate the impact of B cell depletion on the humoral immune response specific to EBV in patients with MS. METHODS: Newly diagnosed, treatment-naïve patients with RRMS were followed up to 18 months after initiation of B-cell depletion therapy in the Overlord-MS study, a phase III trial (NCT04578639). We analyzed serum sampled before treatment and after 3, 6, 12 and 18 months for immunoglobulin γ (IgG) against Epstein-Barr nuclear antigen 1 (EBNA1) and Epstein-Barr viral capsid antigen (VCA). We analyzed antibodies to cytomegalovirus (CMV) and total IgG in serum, as controls for viral and overall humoral immunity. The risk allele, HLA-DRB1*15:01, and the protective allele, HLA-A*02:01, were determined in all participants. In addition, polymerase chain reaction (PCR) for circulating EBV-DNA was performed in the first 156 samples drawn. The associations between time on B cell-depletion therapy and serum anti-EBV antibody levels were estimated using linear mixed-effects models. RESULTS: A total of 290 serum samples from 99 patients were available for analysis. After 6, 12 and 18 months, the EBNA1 IgG levels decreased by 12.7 % (95 % CI -18.8 to -6.60, p < 0.001), 12.1 % (95 % CI -19.8 to -3.7, p = 0.006) and 14.6 % (95 % CI to -25.3 to -2.4, p = 0.02) respectively, compared to baseline level. Carriers of the HLA-DRB1*15:01 allele had higher EBNA1 IgG levels at baseline (p = 0.02). The VCA IgG levels significantly increased by 13.7 % (95 % CI 9.4 to 18.1, p < 0.001) after 3 months, compared to baseline, and persisted at this level throughout the follow-up. CMV IgG levels decreased, but to a lesser extent than the decrease of EBNA1 IgG, and total IgG levels decreased during therapy. Circulating EBV-DNA was found in only three of 156 samples from 64 patients. CONCLUSIONS: EBNA1 IgG levels decreased, while VCA IgG levels increased, during B cell depletion therapy. This supports the hypothesis that the mechanism of action for B cell depletion therapy might be mediated by effects on EBV infection, which, in turn, mitigate immune cross-reactivity and disease perpetuation.

Cytomegalovirus High-risk Kidney Transplant Recipients Show No Difference in Long-term Outcomes Following Preemptive Versus Prophylactic Management.

BACKGROUND: Following kidney transplantation (KT), cytomegalovirus (CMV) infection remains an important challenge. Both prophylactic and preemptive antiviral protocols are used for CMV high-risk kidney recipients (donor seropositive/recipient seronegative; D+/R-). We performed a nationwide comparison of the 2 strategies in de novo D+/R- KT recipients accessing long-term outcomes. METHODS: A nationwide retrospective study was conducted from 2007 to 2018, with follow-up until February 1, 2022. All adult D+/R- and R+ KT recipients were included. During the first 4 y, D+/R- recipients were managed preemptively, changing to 6 mo of valganciclovir prophylaxis from 2011. To adjust for the 2 time eras, de novo intermediate-risk (R+) recipients, who received preemptive CMV therapy throughout the study period, served as longitudinal controls for possible confounders. RESULTS: A total of 2198 KT recipients (D+/R-, n = 428; R+, n = 1770) were included with a median follow-up of 9.4 (range, 3.1-15.1) y. As expected, a greater proportion experienced a CMV infection in the preemptive era compared with the prophylactic era and with a shorter time from KT to CMV infection ( P < 0.001). However, there were no differences in long-term outcomes such as patient death (47/146 [32%] versus 57/282 [20%]; P = 0.3), graft loss (64/146 [44%] versus 71/282 [25%]; P = 0.5), or death censored graft loss (26/146 [18%] versus 26/282 [9%]; P = 0.9) in the preemptive versus prophylactic era. Long-term outcomes in R+ recipients showed no signs of sequential era-related bias. CONCLUSIONS: There were no significant differences in relevant long-term outcomes between preemptive and prophylactic CMV-preventive strategies in D+/R- kidney transplant recipients.

Influenza-like illness in Norway: clinical course, attitudes towards vaccination and preventive measures during the 2009 pandemic.

OBJECTIVES: To document clinical characteristics of influenza-like illness, reported use of health preventive measures and attitudes towards vaccination among patients with influenza-like illness in general practice during the influenza pandemic in 2009. METHODS: Cross-sectional survey in general practice. Patients, who were identified as having influenza-like illness during the peak of the influenza pandemic activity in Norway, were eligible for inclusion in the study. A questionnaire was sent 2-4 weeks after the patients visit to the GP with influenza-like illness diagnosis during October to December 2009, from general practices in Norway. A sample of responders >18 years also had a blood test to check for serological response to the pandemic H1N1 virus. RESULTS: Questionnaires were sent to 1324 patients, and 357 (27%) were returned. Fever (91% versus 49%, P < 0.01), cough (85% versus 73%, P = 0.016) and gastrointestinal symptoms (58% versus 38%, P < 0.01) were more frequent in the age group <18 years compared to older patients. Serological H1N1 responses were analysed in 72 patients; 34 (47%) were positive (haemagglutination inhibition assay titres ≥ 40). There were no statistically significant differences in symptoms between seropositive and seronegative patients. Women reported better adherence to personal protective measures, such as hand washing and cough etiquette than men. Women were also more concerned about possible adverse effects of the pandemic influenza vaccine than men. CONCLUSIONS: Discrimination between influenza and other viral upper respiratory tract infections is difficult in daily clinical practice, even during an influenza pandemic. A gender difference was found in reported precautions to prevent influenza.

Detection and characterization of group A rotaviruses in children hospitalized with acute gastroenteritis in Norway, 2006-2008.

To assess the genetic diversity of rotavirus strains in Norway, the distribution of rotavirus genotypes was studied in children admitted to hospital with acute gastroenteritis. The detection of rotavirus in stool samples was compared using an enzyme-linked immunosorbent assay (ELISA), an immunochromatographic test and RT-PCR. Children <5 years of age admitted to hospital with diarrhea in three large hospitals were enrolled prospectively from March 2006 to February 2008. Rotavirus was detected in 58% of the children by the immunochromatographic test, in 63% by ELISA and 72% by RT-PCR. A total of 219 (70%) rotavirus isolates were characterized in order to determine the genotype. The predominant G types included G1 (53%), G9 (16%), and G3 (13%), and the frequency of G3 varied more than G9 between seasons (8-20%). The P[8] genotype was identified in 188 (86%) of samples, and the globally common genotype combinations G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8] accounted together for >80% of infection. No unusual rotavirus strains were detected, and only four samples contained mixed infections. This study demonstrates that ELISA has similar specificity but lower sensitivity compared to RT-PCR. The immunochromatographic test had the lowest sensitivity and specificity compared to the other assays. Rotaviruses causing severe gastroenteritis leading to hospitalization of children <5 years of age in Norway include the common genotypes, however, a considerable geographical and seasonal variation was observed in the distribution of these genotypes. These data may be important for assessing the need for introducing rotavirus vaccines into immunization programs in Norway.

Rotavirus gastroenteritis in Norway: analysis of prospective surveillance and hospital registry data.

We aimed to evaluate rotavirus morbidity and describe rotavirus epidemiology in hospitalized children in Norway to provide information before the introduction of new rotavirus vaccines. We retrospectively reviewed 14,973 gastroenteritis hospitalizations in children aged <5 y for the period 1995 to 2004, and prospectively surveyed for rotavirus in 311 children aged <5 y admitted with diarrhoea to 3 hospitals in 2006-2008. The proportion of rotavirus among all gastroenteritis hospitalizations was estimated at 14.5% from the retrospective data and at 62.9% in the prospective data. The annual incidence of rotavirus hospitalizations is estimated to be 3 per 1000 children <5 y of age, corresponding to approximately 900 (range 735-1092) hospitalizations each year. Children aged 6-23 months accounted for 61% of all confirmed rotavirus cases, and average duration of hospital stay for rotavirus cases was 1.3 days. We observed a predominance of rotavirus infections from March through May, similar to the seasonality of diarrhoea-associated hospitalizations with viral and unspecified aetiology. No rotavirus-associated deaths were reported. It is estimated that two thirds of all gastroenteritis hospitalizations in children <5 y of age may be attributable to rotavirus in Norway. Continued surveillance and further studies are needed to assess the full burden of rotavirus disease and its economic impact in Norway.

Identification of a Natural Killer Cell Receptor Allele That Prolongs Survival of Cytomegalovirus-Positive Glioblastoma Patients.

By affecting immunological presentation, the presence of cytomegalovirus in some glioblastomas may impact progression. In this study, we examined a hypothesized role for natural killer (NK) cells in impacting disease progression in this setting. We characterized 108 glioblastoma patients and 454 healthy controls for HLA-A,-B,-C, NK-cell KIR receptors, and CMV-specific antibodies and correlated these metrics with clinical parameters. Exome sequences from a large validation set of glioblastoma patients and control individuals were examined from in silico databases. We demonstrated that the KIR allele KIR2DS4*00101 was independently prognostic of prolonged survival. KIR2DS4*00101 displayed 100% concordance with cognate HLA-C1 ligands in glioblastoma patients, but not controls. In the context of both HLA-C1/C2 ligands for the KIR2DS4 receptor, patient survival was further extended. Notably, all patients carrying KIR2DS4*00101 alleles were CMV seropositive, but not control individuals, and exhibited increased NK-cell subpopulations, which expressed the cytotoxicity receptors CD16, NKG2D, and CD94/NKG2C. Finally, healthy controls exhibited a reduced risk for developing glioblastoma if they carried two KIR2DS4*00101 alleles, where protection was greatest among Caucasian individuals. Our findings suggest that KIR2DS4*00101 may offer a molecular biomarker to identify intrinsically milder forms of glioblastoma. Cancer Res; 76(18); 5326-36. ©2016 AACR.

[Parvovirus B19 infection--dangerous for the fetus]. / Parvovirus B19-infeksjon--en livstruende fostersykdom.

BACKGROUND: Human parvovirus B19 infection is a common and usually benign disease in children, but may cause severe complications in pregnancy. We determined the proportion of the pregnant population at risk of infection and present a recent cluster of cases with fetal complications, hoping to raise the general awareness. MATERIAL AND METHODS: Five cases of fetal parvovirus B19 infection during 2001--2 illustrate the delay in diagnosis, treatment and outcome. During the same period, the number of positive and negative serological tests was noted for the catchment area and the entire country. Additionally, 206 consecutive pregnant women were tested to determine susceptibility. RESULTS: Out of the five cases of fetal complications, all had cardiac involvement, three had anaemia, and two fetuses died. Lag-time to fetal diagnosis was six, eight, and 13 weeks for those with known maternal disease. In Norway, seroconversion is similar to that found in other Nordic countries; 36 % (74/206) of the pregnant population is seronegative. In Norway, parvovirus B19 infection is more frequently reported in the January-June period. A third of the pregnant population is susceptible to infection. Early testing in cases of exposure or suspected infection in pregnancy is recommended in order to ensure appropriate follow-up and treatment.

Post-cholecystectomy symptoms were caused by persistence of a functional gastrointestinal disorder.

AIM: To classify gallstone disease as a basis for assessment of post-cholecystectomy symptoms. METHODS: One hundred and fifty three patients with a clinical and ultrasonographic diagnosis of gallstones filled out a structured questionnaire on abdominal pain symptoms and functional gastrointestinal disorder (FGID) before and at six months after cholecystectomy. Symptom frequency groups (SFG) were categorized according to frequency of pain attacks. According to certain pain characteristics in gallstone patients, a gallstone symptom score was accorded on a scale from one to ten. A visual analogue scale was used to quantify pain. Operative specimens were examined for size and magnitude of stone contents as well as presence of bacteria. Follow-up took place after six months with either a consultation or via a mailed questionnaire. Results were compared with those obtained pre-operatively to describe and analyze symptomatic outcome. RESULTS: SFG groups were categorized as severe (24.2%), moderate (38.6%), and mild (22.2%) attack frequency, and a chronic pain condition (15%). Pain was cured or improved in about 90% of patients and two-thirds of patients obtained complete symptom relief. Patients with the most frequent pain episodes were less likely to obtain symptom relief. FGID was present in 88% of patients pre-operatively and in 57% post-operatively (P = 0.244). Those that became asymptomatic or improved with regard to pain also had most relief from FGID (P = 0.001). No pre-operative FGID meant almost complete cure. CONCLUSION: Only one third of patients with FGID experienced postoperative relief, indicating that FGID was a dominant cause of post-cholecystectomy symptoms.