The Public Health Agency of Sweden

Stockholm, Sweden

The Public Health Agency of Sweden

Stockholm, Sweden
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Kaden R.,Uppsala University | Ferrari S.,National Veterinary Institute | Alm E.,The Public Health Agency of Sweden | Wahab T.,Swedish Forum for Biopreparedness Diagnostics | Wahab T.,The Public Health Agency of Sweden
BMC Infectious Diseases | Year: 2017

Background: Brucellosis is a zoonosis that occurs worldwide. The disease has been completely eradicated in livestock in Sweden in 1994, and all cases of confirmed human brucellosis are imported into Sweden from other countries. However, due to an increase in the number of refugees and asylum seekers from the middle-east to Sweden, there is a need to improve the current diagnostic methodology for Brucella melitensis. Whilst culture of Brucella species can be used as a diagnostic tool, real-time PCR approaches provide a much faster result. The aim of this study was to set up a species-specific real-time PCR for the detection of all biovars of Brucella melitensis, which could be used routinely in diagnostic laboratories. Methods: A Brucella melitensis real-time PCR assay was designed using all available genomes in the public database of Brucella (N = 96) including all complete genomes of Brucella melitensis (N = 17). The assay was validated with a collection of 37 Brucella species reference strains, 120 Brucella melitensis human clinical isolates, and 45 clinically relevant non-Brucella melitensis strains. Results: In this study we developed a single real-time PCR for the specific detection of all biovars of Brucella melitensis. Conclusions: This new real-time PCR method shows a high specificity (100%) and a high sensitivity (1.25 GE/μl) and has been implemented in the laboratories of four governmental authorities across Sweden. © 2017 The Author(s).

Schmitz M.,German Center for Neurodegenerative Diseases | Ebert E.,German Center for Neurodegenerative Diseases | Stoeck K.,German Center for Neurodegenerative Diseases | Karch A.,German Center for Neurodegenerative Diseases | And 14 more authors.
Molecular Neurobiology | Year: 2016

At present, the testing of 14-3-3 protein in cerebrospinal fluid (CSF) is a standard biomarker test in suspected sporadic Creutzfeldt-Jakob disease (sCJD) diagnosis. Increasing 14-3-3 test referrals in CJD reference laboratories in the last years have led to an urgent need to improve established 14-3-3 test methods. The main result of our study was the validation of a commercially available 14-3-3 ELISA next to the commonly used Western blot method as a high-throughput screening test. Hereby, 14-3-3 protein expression was quantitatively analyzed in CSF of 231 sCJD and 2035 control patients. We obtained excellent sensitivity/specificity values of 88 and 96 % that are comparable to the established Western blot method. Since standard protocols and preanalytical sample handling have become more important in routine diagnostic, we investigated in a further step the reproducibility and stability of 14-3-3 as a biomarker for human prion diseases. Ring trial data from 2009 to 2013 revealed an increase of Fleiss’ kappa from 0.51 to 0.68 indicating an improving reliability of 14-3-3 protein detection. The stability of 14-3-3 protein under short-term and long-term storage conditions at various temperatures and after repeated freezing/thawing cycles was confirmed. Contamination of CSF samples with blood appears likely to be an important factor at a concentration of more than 2500 erythrocytes/μL. Hemolysis of erythrocytes with significant release of 14-3-3 protein started after 2 days at room temperature. We first define clear standards for the sample handling, short- and long-term storage of CSF samples as well as the handling of blood- contaminated samples which may result in artificially elevated CSF levels of 14-3-3. © 2015, Springer Science+Business Media New York.

Gudo E.S.,National Institute of Health | Pinto G.,National Institute of Health | Vene S.,The Public Health Agency of Sweden | Mandlaze A.,National Institute of Health | And 4 more authors.
PLoS Neglected Tropical Diseases | Year: 2015

Background: In the last two decades, chikungunya virus (CHIKV) has rapidly expanded to several geographical areas, causing frequent outbreaks in sub-Saharan Africa, South East Asia, South America, and Europe. Therefore, the disease remains heavily neglected in Mozambique, and no recent study has been conducted. Methods: Between January and September 2013, acute febrile patients with no other evident cause of fever and attending a health center in a suburban area of Maputo city, Mozambique, were consecutively invited to participate. Paired acute and convalescent serum samples were requested from each participant. Convalescent samples were initially screened for anti-CHIKV IgG using a commercial indirect immunofluorescence test, and if positive, the corresponding acute sample was screened using the same test. Results: Four hundred patients were enrolled. The median age of study participants was 26 years (IQR: 21–33 years) and 57.5% (224/391) were female. Paired blood samples were obtained from 209 patients, of which 26.4% (55/208) were presented anti-CHIKV IgG antibodies in the convalescent sample. Seroconversion or a four-fold titer rise was confirmed in 9 (4.3%) patients. Conclusion: The results of this study strongly suggest that CHIKV is circulating in southern Mozambique. We recommend that CHIKV should be considered in the differential diagnosis of acute febrile illness in Mozambique and that systematic surveillance for CHIKV should be implemented. © 2015 Gudo et al.

PubMed | Centers for Disease Control and Prevention and The Public Health Agency of Sweden
Type: | Journal: Epidemiology and infection | Year: 2017

In 2013-2014, the Public Health Agency of Sweden developed a web-based participatory surveillance system, Hlsorapport, based on a random sample of individuals reporting symptoms weekly online, to estimate the community incidence of self-reported acute gastrointestinal (AGI), acute respiratory (ARI) and influenza-like (ILI) illnesses and their severity. We evaluated Hlsorapports acceptability, completeness, representativeness and its data correlation with other surveillance data. We calculated response proportions and Spearman correlation coefficients (r) between (i) incidence of illnesses in Hlsorapport and (ii) proportions of specific search terms to medical-advice website and reasons for calling a medical advice hotline. Of 34 748 invitees, 3245 (93%) joined the cohort. Participants answered 81% (139 013) of the weekly questionnaires and 90% (16 351) of follow-up questionnaires. AGI incidence correlated with searches on winter-vomiting disease [r = 081, 95% confidence interval (CI) 069-089], and ARI incidence correlated with searches on cough (r = 077, 95% CI 062-086). ILI incidence correlated with the web query-based estimated incidence of ILI patients consulting physicians (r = 063, 95% CI 042-077). The high response to different questionnaires and the correlation with other syndromic surveillance systems suggest that Hlsorapport offers a reasonable representation of AGI, ARI and ILI patterns in the community and can complement traditional and syndromic surveillance systems to estimate their burden in the community.

Carlsson R.M.,The Public Health Agency of Sweden | Carlsson R.M.,Sahlgrenska University Hospital | von Segebaden K.,The Public Health Agency of Sweden | Bergstrom J.,The Public Health Agency of Sweden | And 3 more authors.
Eurosurveillance | Year: 2015

In Sweden, pertussis was excluded from the national vaccination programme in 1979 until acellular vaccination was introduced in a highly endemic setting in 1996. The general incidence dropped 10-fold within a decade, less in infants. Infant pertussis reached 40–45 cases per 100,000 in 2008 to 2012; few of these cases were older than five months. We present an observational 15-year study on the severity of infant pertussis based on 1,443 laboratory-confirmed cases prospectively identified from 1998 to 2012 in the national mandatory reporting system and followed up by telephone contact. Analyses were made in relation to age at onset of symptoms and vaccination history. Pertussis decreased in non-vaccinated infants (2003 to 2012, p < 0.001), indicating herd immunity, both in those too young to be vaccinated and those older than three months. The hospitalisation rates also decreased (last five-year period vs the previous five-year periods, p <0.001), but 70% of all cases in under three month-old infants and 99% of cases with apnoea due to pertussis were admitted to hospital in 1998 to 2012. Median duration of hospitalisation was seven days for unvaccinated vs four days for vaccinated infants aged 3–5 months. Nine unvaccinated infants died during the study period. © 2015, European Centre for Disease Prevention and Control (ECDC). All rights reserved.

Andersen F.H.,MORE Health | Andersen F.H.,Norwegian University of Science and Technology | Flaatten H.,University of Bergen | Klepstad P.,Norwegian University of Science and Technology | And 4 more authors.
Annals of Intensive Care | Year: 2015

Background: Comparison of survival and quality of life in a mixed ICU population of patients 80 years of age or older with a matched segment of the general population. Methods: We retrospectively analyzed survival of ICU patients ≥80 years admitted to the Haukeland University Hospital in 2000–2012. We prospectively used the EuroQol-5D to compare the health-related quality of life (HRQOL) between survivors at follow-up and an age- and gender-matched general population. Follow-up was 1–13.8 years. Results: The included 395 patients (mean age 83.8 years, 61.0 % males) showed an overall survival of 75.9 (ICU), 59.5 (hospital), and 42.0 % 1 year after the ICU. High ICU mortality was predicted by age, mechanical ventilator support, SAPS II, maximum SOFA, and multitrauma with head injury. High hospital mortality was predicted by an unplanned surgical admission. One-year mortality was predicted by respiratory failure and isolated head injury. We found no differences in HRQOL at follow-up between survivors (n = 58) and control subjects (n = 179) or between admission categories. Of the ICU non-survivors, 63.2 % died within 2 days after ICU admission (n = 60), and 68.3 % of these had life-sustaining treatment (LST) limitations. LST limitations were applied for 71.3 % (n = 114) of the hospital non-survivors (ICU 70.5 % (n = 67); post-ICU 72.3 % (n = 47)). Conclusions: Overall 1-year survival was 42.0 %. Survival rates beyond that were comparable to those of the general octogenarian population. Among survivors at follow-up, HRQOL was comparable to that of the age- and sex-matched general population. Patients admitted for planned surgery had better short- and long-term survival rates than those admitted for medical reasons or unplanned surgery for 3 years after ICU admittance. The majority of the ICU non-survivors died within 2 days, and most of these had LST limitation decisions. © 2015, Andersen et al.

Salata C.,University of Padua | Baritussio A.,University of Padua | Munegato D.,University of Padua | Calistri A.,University of Padua | And 6 more authors.
Pathogens and disease | Year: 2015

Ebola virus disease (EVD) is one of the most lethal transmissible infections characterized by a high fatality rate, and a treatment has not been developed yet. Recently, it has been shown that cationic amphiphiles, among them the antiarrhythmic drug amiodarone, inhibit filovirus infection. In the present work, we investigated how amiodarone interferes with Ebola virus infection. Wild-type Sudan ebolavirus and recombinant vesicular stomatitis virus, pseudotyped with the Zaire ebolavirus glycoprotein, were used to gain further insight into the ability of amiodarone to affect Ebola virus infection. We show that amiodarone decreases Ebola virus infection at concentrations close to those found in the sera of patients treated for arrhythmias. The drug acts by interfering with the fusion of the viral envelope with the endosomal membrane. We also show that MDEA, the main amiodarone metabolite, contributes to the antiviral activity. Finally, studies with amiodarone analogues indicate that the antiviral activity is correlated with drug ability to accumulate into and interfere with the endocytic pathway. Considering that it is well tolerated, especially in the acute setting, amiodarone appears to deserve consideration for clinical use in EVD. © FEMS 2015. All rights reserved. For permissions, please e-mail:

PubMed | National Health Research Institute, the Public Health Agency of Sweden and HU University of Applied Sciences Utrecht
Type: | Journal: International journal of mycobacteriology | Year: 2017

Pyrazinamide (PZA) is included in the 2016 World Health Organization multidrug-resistant tuberculosis treatment guidelines and is a key component of most ongoing clinical trials investigating novel antibiotic combinations. PZA resistance is associated with worse tuberculosis treatment outcomes. Unfortunately, for such an important drug, phenotypic susceptibility testing is extremely challenging. The exacting bacterial growth conditions required to induce susceptibility to the drug reduce the accuracy of the susceptibility assay, even in experienced laboratories, and widespread testing is not performed. This situation is unacceptable for such a valuable and important drug. A more complete understanding of the mechanism of action of PZA would be expected to lead to improvements in this situation. Although the exact mechanism of action of PZA is not known yet, it is widely accepted that PZA is a prodrug requiring transformation to pyrazinoic acid, the active form, by the mycobacterial enzyme encoded by the pncA gene. Most clinical resistance indeed appears to be a result of a diverse range of mutations in this gene and sequencing of the pncA gene has been shown to have excellent predictive power for PZA resistance. The wider availably of pncA sequencing in combination with databases of the phenotypic implications of these mutations has helped make genetic testing for PZA resistance a practical proposition. For the past decades, it has been generally accepted that an extracellular low pH is required for PZA activity but work in our laboratory [1] and others [2] has recently challenged this assumption. Alternative bacterial stresses, apart from a reduced pH of the growth media (such as reduced temperature), can also induce a PZA-susceptible phenotype. The characterization of spontaneous in vitro-resistant pyrazinoic acid mutants selected under neutral pH conditions suggests a key role for the pantothenate/coenzyme A biosynthetic pathway. This has profound implications for the mechanism of action of PZA as well as potentially the bacterial population against which PZA is active in the host. These findings will be discussed as well as their implications for further research and the future of PZA susceptibility testing.

Desvars A.,Umeå University | Furberg M.,Umeå University | Hjertqvist M.,The Public Health Agency of Sweden | Vidman L.,Umeå University | And 3 more authors.
Emerging Infectious Diseases | Year: 2015

The zoonotic disease tularemia is endemic in large areas of the Northern Hemisphere, but research is lacking on patterns of spatial distribution and connections with ecologic factors. To describe the spatial epidemiology of and identify ecologic risk factors for tularemia incidence in Sweden, we analyzed surveillance data collected over 29 years (1984–2012). A total of 4,830 cases were notified, of which 3,524 met all study inclusion criteria. From the first to the second half of the study period, mean incidence increased 10-fold, from 0.26/100,000 persons during 1984–1998 to 2.47/100,000 persons during 1999–2012 (p<0.001). The incidence of tularemia was higher than expected in the boreal and alpine ecologic regions (p<0.001), and incidence was positively correlated with the presence of lakes and rivers (p<0.001). These results provide a comprehensive epidemiologic description of tularemia in Sweden and illustrate that incidence is higher in locations near lakes and rivers. © 2015, Centers for Disease Control and Prevention (CDC). All rights reserved.

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