Nephropathia Epidemica Caused by Puumala Virus in Bank Voles, Scania, Southern Sweden.

In 2018, a local case of nephropathia epidemica was reported in Scania, southern Sweden, more than 500 km south of the previously known presence of human hantavirus infections in Sweden. Another case emerged in the same area in 2020. To investigate the zoonotic origin of those cases, we trapped rodents in Ballingslöv, Norra Sandby, and Sörby in southern Sweden during 2020‒2021. We found Puumala virus (PUUV) in lung tissues from 9 of 74 Myodes glareolus bank voles by screening tissues using a hantavirus pan-large segment reverse transcription PCR. Genetic analysis revealed that the PUUV strains were distinct from those found in northern Sweden and Denmark and belonged to the Finnish PUUV lineage. Our findings suggest an introduction of PUUV from Finland or Karelia, causing the human PUUV infections in Scania. This discovery emphasizes the need to understand the evolution, cross-species transmission, and disease outcomes of this newly found PUUV variant.

Surveillance of tick-borne encephalitis in emerging risk areas in southern Sweden: a retrospective case finding study.

Tick-borne encephalitis (TBE) is an emerging infection causing CNS infection of various severity. Good knowledge of the incidence in the population and defined risk areas is important in risk communication and vaccination recommendations. The aim of this study was to investigate potential underreporting by retrospectively diagnose TBE among patients with viral CNS infections of unknown etiology in a region with emerging risk areas for TBE, and define variables associated with performed TBE serology at the time of infection. Epidemiological data and microbiological diagnostics of cases with viral CNS infection of unknown etiology treated at departments of infectious diseases and pediatrics in Skåne County during 2000-2012 were investigated. Analyses to evaluate variables associated with performed TBE serology at the time of infection were performed. Retrospective TBE serology was performed on stored blood samples when available. TBE serology was already performed at the time of CNS infection in 193 out of 761 cases. Department, type of clinical manifestation, time period of illness, and whether Borrelia serology had been performed were independent variables associated with having had TBE serology performed or not at the time of illness. Only one of 137 cases, where samples could be retrospectively analyzed for TBE, turned out positive. This study shows a low frequency of TBE sampling among patients with meningoencephalitis in a region with emerging risk for TBE. A higher awareness of TBE as differential diagnosis could contribute to earlier detection of new risk areas and adequate preventive advice to the public.

Methotrexate reduces circulating Th17 cells and impairs plasmablast and memory B cell expansions following pneumococcal conjugate immunization in RA patients.

Methotrexate (MTX) impairs antibody response after pneumococcal vaccination. We aimed to investigate differences in phenotypes of circulating B and T cells after pneumococcal conjugate vaccine (PCV) in rheumatoid arthritis (RA) patients on MTX (MTX group), RA without disease-modifying drugs (0DMARD), and controls (HC). MTX group (n = 11), 0DMARD (n = 12) and HC (n = 13) were studied. Blood samples were collected: before MTX, ≥ 4 weeks on stable MTX dose (prevaccination), and 7 days postvaccination (MTX group), and pre- and 7 days postvaccination (0DMARD and HC). Phenotypes of B- and T cell subsets were determined using flow cytometry. Serotype-specific IgG were quantified using multiplex bead assay, pre- and 4-6 weeks postvaccination. Concentrations of plasmablasts and switched memory B cells increased after PCV in HC (both p = 0.03) and the 0DMARD group (p = 0.01 and p = 0.02), but not in the MTX group. Postimmunization plasmablasts were lower in MTX group, compared to the 0DMARD group and HC (p = 0.002 and p < 0.001). Th17 cells decreased after MTX start (p = 0.02), and increased in HC after immunization (p = 0.01). Postimmunization plasmablasts correlated with mean antibody response ratio in all RA patients (R = 0.57, p = 0.035). Methotrexate reduced Th17 cells and blocked activation of plasmablasts and switched memory B cells following polysaccharide-protein conjugate antigen challenge in RA.

Correction to: Prime-boost vaccination strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients receiving conventional DMARDs, to some extent in abatacept but not in rituximab-treated patients.

An amendment to this paper has been published and can be accessed via the original article.

Prime-boost vaccination strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients receiving conventional DMARDs, to some extent in abatacept but not in rituximab-treated patients.

OBJECTIVE: To explore whether a prime-boost vaccination strategy, i.e., a dose of pneumococcal conjugate vaccine (PCV) and a dose of 23-valent polysaccharide vaccine (PPV23), enhances antibody response compared to single PCV dose in patients with inflammatory rheumatic diseases treated with different immunosuppressive drugs and controls. METHODS: Patients receiving rituximab (n = 30), abatacept (n = 23), monotherapy with conventional disease-modifying antirheumatic drugs (cDMARDs, methotrexate/azathioprine/mycophenolate mofetil, n = 27), and controls (n = 28) were immunized with a dose PCV followed by PPV23 after ≥ 8 weeks. Specific antibodies to 12 serotypes included in both vaccines were determined using a multiplex microsphere immunoassay in blood samples before and 4-8 weeks after each vaccination. Positive antibody response was defined as ≥ 2-fold increase from pre- to postvaccination serotype-specific IgG concentration and putative protective level as IgG ≥ 1.3 µg/mL. The number of serotypes with positive antibody response and IgG ≥ 1.3 µg/mL, respectively, after PCV and PCV + PPV23 were compared within each treatment group and to controls. Opsonophagocytic activity (OPA) assay was performed for serotypes 6B and 23F. RESULTS: Compared to single-dose PCV, prime-boost vaccination increased the number of serotypes with positive antibody response in patients with abatacept, cDMARDs, and controls (p = 0.02, p = 0.01, and p = 0.01), but not in patients on rituximab. After PCV + PPV23, the number of serotypes with positive antibody response was significantly lower in all treatment groups compared to controls but lowest in rituximab, followed by the abatacept and cDMARD group (p < 0.001). Compared to PCV alone, the number of serotypes with putative protective levels after PCV + PPV23 increased significantly only in patients in cDMARDs (p = 0.03) and controls (p = 0.001). Rituximab treatment was associated with large reduction (coefficient - 8.6, p < 0.001) and abatacept or cDMARD with moderate reductions (coefficients - 1.9 and - 1.8, p = 0.005, and p < 0.001) in the number of serotypes with positive antibody response to PCV + PPV23 (multivariate linear regression model). OPA was reduced in rituximab (Pn6B and Pn23F, p < 0.001), abatacept (Pn23F, p = 0.02), and cDMARD groups (Pn6B, p = 0.02) compared to controls. CONCLUSIONS: Prime-boost strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients with inflammatory rheumatic diseases receiving cDMARDs, to some extent in abatacept but not in patients on rituximab. Pneumococcal vaccination should be encouraged before the initiation of treatment with rituximab. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03762824. Registered on 4 December 2018, retrospectively registered.

Vaccination status and immune response to 13-valent pneumococcal conjugate vaccine in asplenic individuals.

Overwhelming post-splenectomy infection (OPSI) is immediately life-threatening and vaccination against encapsulated bacteria, in particular pneumococci, decreases its incidence. First, we investigated the adherence to vaccination guidelines in a retrospective study of the hospital records of splenectomised patients. Second, patients were asked to complete a questionnaire and invited to participate in a study where 12-valent pneumococcal serotype-specific IgG concentrations were determined before and 4 to 6 weeks after vaccination with PCV13. Of 79 individuals who underwent splenectomy between 2000 and 2012: 81.0% received pneumococcal vaccine, 51.9% received vaccine against Haemophilus influenzae type B and 22.8% received meningococcal vaccine. 31 individuals were deceased. 33 individuals completed questionnaires and accepted participation in the second part of the study. The participants consisted of two groups: (1) prior PPV23 (n=24) and (2) prior PPV23+PCV13 (n=9). In group 1, pre-PCV13 GMC's≥0.35µg/mL were observed for serotypes 1, 4, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F, and GMC's<0.35µg/mL for serotypes 3 and 5, significant increases pre- to post-PCV13 were found for serotypes 1, 3, 4, 5, 7F, 18C, 19A, 23F (p≤0.001) and 19F (p=0.01) and all 12 serotypes-specific GMC were above 0.35µg/mL after vaccination. Group 2 did not receive vaccine in this study, but blood tests showed all 12 serotype-specific GMC>0.35µg/mL. Adherence to guidelines regarding primary pneumococcal vaccination was adequate but only a minority received the recommended meningococcal vaccination. High levels of pneumococcal serotype-specific antibodies were observed in the previous PPV23 vaccinated group, and more pronounced in the previous PCV13 group, and our data suggests that PCV13 is immunogenic for serotypes 1, 3, 4, 5, 7F, 18C, 19A, 19F and 23F, if used as a booster dose in asplenic patients with previous PPV23 vaccination.

Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial.

BACKGROUND: Acute pyelonephritis is a common infection in adult women, but there is a paucity of controlled trials of its treatment and the optimum duration of antibiotic treatment has not been properly defined. We compared the efficacy of ciprofloxacin for 7 days and 14 days in women with community-acquired acute pyelonephritis. METHODS: In a prospective, non-inferiority trial undertaken at 21 centres of infectious diseases in Sweden, women (aged ≥18 years) who were not pregnant and had a presumptive diagnosis of acute pyelonephritis were randomly assigned to oral treatment with ciprofloxacin 500 mg twice daily for 7 days or 14 days. The first week was open label. A computer-generated randomisation list in block sizes of two was used for treatment allocation in a 1:1 ratio. The study was double-blind and placebo-controlled during the second week of treatment, which was either continuation of ciprofloxacin 500 mg or placebo tablets twice daily according to the randomisation code. Patients, carers, site investigators, and trial coordinating centre staff were masked to group assignment. The primary endpoint was the clinical and bacteriological outcome 10-14 days after completion of treatment with active drug. Analysis was by per protocol. This trial is registered with EudraCT, number 2005-004992-39, and ClinicalTrials.gov, number ISRCTN73338924. FINDINGS: 126 of 248 patients were randomly assigned to 7 days and 122 to 14 days of ciprofloxacin. 73 and 83 patients, respectively, were analysed. Short-term clinical cure occurred in 71 (97%) patients treated with ciprofloxacin for 7 days and 80 (96%) treated for 14 days (difference -0·9%; 90% CI -6·5 to 4·8; p=0·004; non-inferiority test). Cumulative efficacy at long-term follow-up was 93% in each group (68 of 73 vs 78 of 84; -0·3%; -7·4 to 7·2; p=0·015). Both regimens were well tolerated. Two patients discontinued ciprofloxacin because of myalgia with 7 days of treatment and itching exanthema with 14 days. Four (5%) of 86 patients assigned to 7 days of treatment who complied with study criteria and six (6%) of 93 assigned to 14 days reported an adverse event after the first week of treatment that was possibly or probably related to the study drug. In those assigned to 7 days, no patient had mucosal candida infection after the first week versus five treated for 14 days (p=0·036). INTERPRETATION: Our results show that acute pyelonephritis in women, including older women and those with a more severe infection, can be treated successfully and safely with oral ciprofloxacin for 7 days. Short courses of antibiotics should be favoured in an era of increasing resistance. FUNDING: Swedish Strategic Programme against Antibiotic Resistance (Strama).

Characterization of hemorrhagic fever with renal syndrome caused by hantaviruses, Estonia.

Thirty cases of hemorrhagic fever with renal syndrome (HFRS) due to Puumala virus (PUUV), Saaremaa virus (SAAV), and Dobrava virus infection were confirmed in Estonia. Except for the levels of serum creatinine, no remarkable differences were found in the clinical course of HFRS caused by PUUV and SAAV.

Cat bite wound infections: a prospective clinical and microbiological study at three emergency wards in Stockholm, Sweden.

OBJECTIVE: The rate of infection following cat bites appears to be greater than that from dog bites. To study the clinical picture, complications and microbiology (in humans and cats), this prospective study was performed. METHODS: A prospective study with patients with clinical symptoms of infection due to cat bites from three emergency wards during two years in Stockholm, Sweden. Aerobic and anaerobic cultures from the wounds were performed as well as cultures from the biting cat's mouth. Clinical data and complications were registered. RESULTS: Seventy-nine episodes in 78 patients with infective cat bites were included. Pasteurella multocida was isolated in 70% of the patients; in addition anaerobic pathogens were isolated in 16% concurrently with P. multocida, while Staphylococcus aureus was isolated in only two patients. Pasteurella spp. was also isolated from 80% of the pharynx of the biting cats. The dominating symptoms of infection were erythema, pain and oedema, often emerging as early as 3h after the bite. Complications such as tendosynovitis, arthritis, abscesses and septicaemia occurred in 18% of the patients. No patient died due to the infection. The majority of the patients received penicillin or amoxicillin as antibiotic treatment. CONCLUSIONS: P. multocida was the dominating pathogen among patients with infected cat bites and antibiotic treatment should cover P. multocida.

Report of the Meningitis Program of the International Scientific Working Group on TBE. Serological screening of patients with viral CNS-infection of unknown etiology in search of undiagnosed TBE cases.

The endemicity of tick-borne encephalitis (TBE) in Europe is changing. Potential undetected or emerging TBEV foci and the risk of underdiagnosis due to a low awareness among the medical community form the background of this retrospective multicenter follow-up study. We investigated the possibility of undiagnosed TBE cases among patients with presumed viral central nervous system (CNS)-infection of unknown etiology. Eight centers in four European countries provided sera and/or cerebrospinal fluid (CSF) samples from 233 individuals. The samples were screened with a commercial TBEV ELISA test system (IgM and IgG). Positive or borderline samples were re-evaluated at the Institute of Virology in Vienna by an in-house ELISA test and a neutralization test (NT). Two previously undiagnosed Swedish TBE patients were verified. Three additional individuals from Swedish centers were IgG ELISA and NT positive. No NT positive individuals were found from France, Belgium or The Netherlands. Nineteen individuals were found IgG TBE ELISA positive, but negative in NT, indicating unspecific reactivity. At least four of those patients were vaccinated against yellow fever. The probable reason for the reactivity seen in these individuals is the well-known cross-reactivity existing among flaviviruses.

[Several cases of tick-borne encephalitis in Skane. Should high-risk groups be vaccinated?]. / Flera fall av fästingburen hjärninflammation i Skåne. Bör riskgrupper vaccineras?

Three cases of tick-borne encephalitis from the non-endemic southern Swedish region of Skåne is reported. The clinical course was moderate to severe including neurological sequelae. The question is raised whether risk groups also in southern Sweden should be vaccinated.