Tick-borne encephalitis virus (TBEV) is transferred to humans by ticks. The virus causes tick-borne encephalitis (TBE) with symptoms such as meningitis and meningoencephalitis. About one third of the patients suffer from long-lasting sequelae after clearance of the infection. Studies of the immune response during TBEV-infection are essential to the understanding of host responses to TBEV-infection and for the development of therapeutics. Here, we studied in detail the primary CD8 T cell response to TBEV in patients with acute TBE. Peripheral blood CD8 T cells mounted a considerable response to TBEV-infection as assessed by Ki67 and CD38 co-expression. These activated cells showed a CD45RA-CCR7-CD127- phenotype at day 7 after hospitalization, phenotypically defining them as effector cells. An immunodominant HLA-A2-restricted TBEV epitope was identified and utilized to study the characteristics and temporal dynamics of the antigen-specific response. The functional profile of TBEV-specific CD8 T cells was dominated by variants of mono-functional cells as the effector response matured. Antigen-specific CD8 T cells predominantly displayed a distinct Eomes+Ki67+T-bet+ effector phenotype at the peak of the response, which transitioned to an Eomes-Ki67-T-bet+ phenotype as the infection resolved and memory was established. These transcription factors thus characterize and discriminate stages of the antigen-specific T cell response during acute TBEV-infection. Altogether, CD8 T cells responded strongly to acute TBEV infection and passed through an effector phase, prior to gradual differentiation into memory cells with distinct transcription factor expression-patterns throughout the different phases.

We evaluated the performance of 11 SARS-CoV-2 antibody tests using a reference set of heat-inactivated samples from 278 unexposed persons and 258 COVID-19 patients, some of whom contributed serial samples. The reference set included samples with a variation in SARS-CoV-2 IgG antibody titers, as determined by an in-house immunofluorescence assay (IFA). The five evaluated rapid diagnostic tests had a specificity of 99.0% and a sensitivity that ranged from 56.3 to 81.6% and decreased with low IFA IgG titers. The specificity was > 99% for five out of six platform-based tests, and when assessed using samples collected ≥ 22 days after symptom onset, two assays had a sensitivity of > 96%. These two assays also detected samples with low IFA titers more frequently than the other assays. In conclusion, the evaluated antibody tests showed a heterogeneity in their performances and only a few tests performed well with samples having low IFA IgG titers, an important aspect for diagnostics and epidemiological investigations.

Early-life infections with persistent Epstein–Barr virus (EBV) and cytomegalovirus (CMV) are delayed in affluent countries, probably due to alterations in early environmental exposures, such as maternal age, siblings, and day-care attendance. We have previously reported that the timing of EBV and CMV contraction is related both to allergic sensitization and changes in functional competence of immune cells, while the presence/absence of lactobacilli [Lactobacillus (L.) casei, L. paracasei, and L. rhamnosus] or Staphylococcus (S.) aureus in feces is related to the risk for allergy. Here, we used the same prospective longitudinal birth cohort of children to investigate early-life environmental exposures and their influence on EBV and CMV contraction over time. Since gut microbes also belong to this category of early exposures, we investigated their association with herpesvirus contraction. Our results show that these two viruses are acquired with different kinetics and that EBV and CMV seroprevalence at 10 years of age was 47 and 57%, respectively. We also observed that a delayed EBV or CMV infection was associated with older maternal age [time ratio (TR) 1.14, 95% confidence interval (CI) 1.07–1.21, Padj < 0.001 and TR 1.09, CI 1.03–1.16, Padj = 0.008, respectively]. Further, we present the novel finding that S. aureus colonization reduced the time to CMV acquisition (TR 0.21, CI 0.06–0.78, Padj = 0.02). Together, these findings suggest that there is a relationship between timing of herpesvirus acquisition and early-life immune modulating exposures, which interestingly also includes the early infant gut microbiota.

A serum immunoglobulin G enzyme immunoassay (EIA) forHelicobacter pylori antibodies already in use in adults was evaluated with 99 pediatric serum samples to determine its usefulness for the study of H. pylori disease in children. The reference method used was either the 13C-urea breath test or a biopsy culture of gastric mucosa. In children, an EIA cutoff of 0.35 absorbancy unit yielded sensitivity, specificity, and positive and negative predictive values of 93, 97, 93, and 97%, respectively. The cutoff recommended when this EIA was published for use in adults was 0.70 absorbancy unit (H. Gnarpe, P. Unge, C. Blomqvist, and S. Mäkitalo, APMIS 96:128–132, 1988). Another subset of 169 serum samples taken from children was analyzed by four serological tests in order to compare the performance of the in-house EIA with the Pyloriset, HM-CAP, and Helico-G kits. For the 169 samples, 10 (5.9%) false-positives and no false-negatives occurred with the Helico-G, 3 (1.8%) false-positives and no false-negatives occurred with the Pyloriset, and 3 (1.8%) false-positives and 1 (0.6%) false-negative occurred with the HM-CAP. For the 169 samples, 1 (0.6%) false-positive and no false-negatives occurred with the in-house EIA. Serological detection of H. pylori antibodies with our EIA seems to be valuable in diagnosing H. pylori infection in children, but only if a lowered, specific pediatric cutoff is established. The commercial kits, particularly the Helico-G, seem to overdiagnose pediatric H. pylori infection. A positive serological test for H. pylori infection, particularly for children, needs to be confirmed by a reference method because of the possibility of spontaneous eradication of infection, with a lingering serological response.

Laboratory testing for Human T‐lymphotropic Virus type 1 and 2 (HTLV‐1 and ‐2) infections has become routine in blood transfusion, tissue transplantation and clinical diagnoses in many countries worldwide. Screening is usually based on the detection of antibodies to HTLV‐1 and/ or ‐2. The number of commercially available assays is limited, and among them, ELISA tests based on microtiter format are most commonly used. Recently, the new rHTLV‐I/II assay (Abbott Laboratories, Abbott Park, IL) was released; this assay was developed for an automatic large‐scale screening platform. This assay was evaluated using pre‐characterized serum panels and routine samples from the clinical laboratory. The sensitivity was 100% for HTLV‐1 and ‐2 (99/99 and 42/42, respectively, including one sample that was dually reactive, HTLV‐1 + 2). To test assay specificity, panels of blood donor sera, specimens from patients with autoimmune diseases and some viral infections were used. False‐reactive samples from previous HTLV diagnoses were also included. With these panels, the specificity was 99.4% (619/623). However, the four false‐reactive samples all belonged to the group of samples that were previously considered as false‐reactive for HTLV‐antibodies. All other samples were negative by the rHTLV‐I/II assay, and thus 100% specificity was obtained. The 1,412 samples tested in the clinic by this assay in routine use were all negative (100% specificity). Taken together, the overall specificity was 99.8%. The assay was sensitive, specific and appropriate for the large‐scale screening of samples for HTLV‐1/2 antibodies. J. Med. Virol. 82:1606–1611, 2010. © 2010 Wiley‐Liss, Inc.

Quantiferon-TB Gold Plus (QFT-Plus) is an interferon gamma release assay used to diagnose latent tuberculosis (LTB). A borderline range (0.20-0.99 IU/mL) around the cut off (0.35 IU/ml) has been suggested for the earlier QFT version. Our aims were to evaluate the borderline range for QFT-Plus and the contribution of the new TB2 antigen tube. QFT-Plus results were collected from clinical laboratories in Sweden and linked to incident active TB within 3-24 months using the national TB registry. Among QFT-Plus results from 58539 patients, 83% were negative (<0.20 IU/ml), 2.4% borderline negative (0.20-0.34 IU/ml), 3.4% borderline positive (0.35-0.99 IU/ml), 9.6% positive (≥1.0 IU/ml) and 1.6% indeterminate. Follow-up tests after initial borderline results were negative (<0.20 IU/ml) in 38.3% without any cases of incident active TB within 2 years. Applying the 0.35 IU/ml cut-off, 1.5% of TB1 and TB2 results were discrepant whereof 52% within borderline range. A TB2≥0.35 IU/ml with TB1<0.20 IU/ml was found in 0.4% (231/58539) of all included baseline QFT-Plus test results, including 1.8% (1/55) of incident TB cases. A borderline range for QFT-Plus is clinically useful as more than one third of those with borderline results are convincingly negative upon retesting, without developing incident active TB. The TB2 tube contribution for LTB diagnosis appears limited.

The frequency of Helocobacter pylori (Hp.) infection and active chronic antral gastritis among people with excessive alcohol consumption is not known. A high alcohol intake regularly causes acute gastroduodenitis. In this study, the prevalence of Hp. infection and active chronic antral gastritis in alcoholics compared with nonalcoholic controls was studied. Further, the frequency of gastrointestinal symptoms was registered. Diagnostic methods for Hp. were compared. Twenty-four alcoholics admitted to the hospital for detoxification underwent upper gastrointestinal endoscopy regardless of symptoms. Twelve individuals admitted to upper endoscopy mainly for dyspepsia, with low alcohol consumption and without gross pathology by upper endoscopy, were chosen as controls. Three diagnostic methods for Hp. were used: culture, direct microscopy, and histology. Hp. infection was found in 7 of the 24 alcoholics (29%) according to culture. In controls, 4 of 12 (33%) had a positive Hp. culture. In the alcoholic group, culture was more sensitive than histology. There was a good correlation between the different diagnostic methods in the control group. Histologically active chronic antral gastritis was found in 6 of the alcoholics (25%) and in 5 of the controls (42%). Five of the 7 Hp.-positive alcoholics and all of the Hp.-positive controls had an active chronic antral gastritis. Hp. infection is not more frequent in alcoholics than in controls. In both groups, there was a good correlation between Hp. infection and histologically, active chronic antral gastritis.

Background: Previous seroprevalence studies have demonstrated higher anti-SARS-CoV-2 IgG seroprevalence in healthcare workers (HCWs) than in the background population during the first phase of the 2020 COVID-19 pandemic. These studies, however, focussed mainly on hospital employees. Aim: To perform a cross-sectional study comparing the seroprevalence of hospital-based HCWs with those employed in elderly care (home care and nursing homes). Methods: Employees (n ¼ 4955) in the county of V€ armland, Sweden, were recruited between weeks 27 and 42 and tested for IgG antibodies against SARS-CoV-2. Serological results were combined with self-reported questionnaire data. Findings: IgG seroprevalence was 5.7% in the total group of HCWs, and was higher among those employed in hospitalbased healthcare than among those working in elderly care (8.4% vs. 3.7%, p < .001). Being employed as an assistant nurse, working in a COVID-19 unit, and being exposed via co-workers or private acquaintances were all associated with IgG seropositivity. Conclusion:The difference in seroprevalence between HCWs in the two settings suggests that not only the profession but also factors in the workplace environment may be of importance. As all studied exposures were associated with IgG seropositivity, and asymptomatic infection was detected in 7.5% of participants, preventing outbreaks among HCWs is challenging. Adequate use of personal protective equipment when working with patients regardless of COVID-19 status, source control in situations with co-workers in which distancing is not possible, and routines enabling symptomatic staff to isolate pending PCR results are required to prevent healthcare-associated outbreaks of