| 1. |
- Andersson, T, et al.
(author)
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Syndromic surveillance for local outbreak detection and awareness : evaluating outbreak signals of acute gastroenteritis in telephone triage, web-based queries and over-the-counter pharmacy sales
- 2014
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In: Epidemiology and Infection. - : Cambridge University Press. - 0950-2688 .- 1469-4409. ; 142:2, s. 303-313
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Journal article (peer-reviewed)abstract
- For the purpose of developing a national system for outbreak surveillance, local outbreak signals were compared in three sources of syndromic data - telephone triage of acute gastroenteritis, web queries about symptoms of gastrointestinal illness, and over-the-counter (OTC) pharmacy sales of antidiarrhoeal medication. The data sources were compared against nine known waterborne and foodborne outbreaks in Sweden in 2007-2011. Outbreak signals were identified for the four largest outbreaks in the telephone triage data and the two largest outbreaks in the data on OTC sales of antidiarrhoeal medication. No signals could be identified in the data on web queries. The signal magnitude for the fourth largest outbreak indicated a tenfold larger outbreak than officially reported, supporting the use of telephone triage data for situational awareness. For the two largest outbreaks, telephone triage data on adult diarrhoea provided outbreak signals at an early stage, weeks and months in advance, respectively, potentially serving the purpose of early event detection. In conclusion, telephone triage data provided the most promising source for surveillance of point-source outbreaks.
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| 2. |
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| 3. |
- Bjelkmar, Par, et al.
(author)
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Early outbreak detection by linking health advice line calls to water distribution areas retrospectively demonstrated in a large waterborne outbreak of cryptosporidiosis in Sweden
- 2017
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In: BMC Public Health. - : BIOMED CENTRAL LTD. - 1471-2458. ; 17
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Journal article (peer-reviewed)abstract
- Background: In the winter and spring of 2011 a large outbreak of cryptosporidiosis occurred in Skelleftea municipality, Sweden. This study summarizes the outbreak investigation in terms of outbreak size, duration, clinical characteristics, possible source(s) and the potential for earlier detection using calls to a health advice line. Methods: The investigation included two epidemiological questionnaires and microbial analysis of samples from patients, water and other environmental sources. In addition, a retrospective study based on phone calls to a health advice line was performed by comparing patterns of phone calls between different water distribution areas. Results: Our analyses showed that approximately 18,500 individuals were affected by a waterborne outbreak of cryptosporidiosis in Skelleftea in 2011. This makes it the second largest outbreak of cryptosporidiosis in Europe to date. Cryptosporidium hominis oocysts of subtype IbA10G2 were found in patient and sewage samples, but not in raw water or in drinking water, and the initial contamination source could not be determined. The outbreak went unnoticed to authorities for several months. The analysis of the calls to the health advice line provides strong indications early in the outbreak that it was linked to a particular water treatment plant. Conclusions: We conclude that an earlier detection of the outbreak by linking calls to a health advice line to water distribution areas could have limited the outbreak substantially.
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| 4. |
- Fontana, Robert J., et al.
(author)
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Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection
- 2016
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In: Liver transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 1527-6465 .- 1527-6473. ; 22:4, s. 446-458
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Journal article (peer-reviewed)abstract
- Daclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) or simeprevir (SMV) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection. Herein, we report efficacy and safety data for DCV-based all-oral antiviral therapy in liver transplantation (LT) recipients with severe recurrent HCV. DCV at 60mg/day was administered for up to 24 weeks as part of a compassionate use protocol. The study included 97 LT recipients with a mean age of 59.3 +/- 8.2 years; 93% had genotype 1 HCV and 31% had biopsy-proven cirrhosis between the time of LT and the initiation of DCV. The mean Model for End-Stage Liver Disease (MELD) score was 13.0 +/- 6.0, and the proportion with Child-Turcotte-Pugh (CTP) A/B/C was 51%/31%/12%, respectively. Mean HCV RNA at DCV initiation was 14.3x6 log(10) IU/mL, and 37% had severe cholestatic HCV infection. Antiviral regimens were selected by the local investigator and included DCV+SOF (n=77), DCV+SMV (n=18), and DCV+SMV+SOF (n=2); 35% overall received RBV. At the end of treatment (EOT) and 12 weeks after EOT, 88 (91%) and 84 (87%) patients, respectively, were HCV RNA negative or had levels <43 IU/mL. CTP and MELD scores significantly improved between DCV-based treatment initiation and last contact. Three virological breakthroughs and 2 relapses occurred in patients treated with DCV+SMV with or without RBV. None of the 8 patient deaths (6 during and 2 after therapy) were attributed to therapy. In conclusion, DCV-based all-oral antiviral therapy was well tolerated and resulted in a high sustained virological response in LT recipients with severe recurrent HCV infection. Most treated patients experienced stabilization or improvement in their clinical status.
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| 5. |
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| 6. |
- Gherasim, Alin, et al.
(author)
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Risk factors and potential preventive measures for nephropatia epidemica in Sweden 2011-2012 : a case-control study
- 2015
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In: Infection Ecology & Epidemiology. - : Informa UK Limited. - 2000-8686. ; 5
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Nephropatia epidemica (NE), a relatively mild form of hemorrhagic fever with renal syndrome caused by the Puumala virus (PUUV), is endemic in northern Sweden. We aim to study the risk factors associated with NE in this region.METHODS: We conducted a matched case-control study between June 2011 and July 2012. We compared confirmed NE cases with randomly selected controls, matched by age, sex, and place of infection or residence. We analyzed the association between NE and several occupational, environmental, and behavioral exposures using conditional logistic regression.RESULTS: We included in the final analysis 114 cases and 300 controls, forming 246 case-control pairs. Living in a house with an open space beneath, making house repairs, living less than 50 m from the forest, seeing rodents, and smoking were significantly associated with NE.CONCLUSION: Our results could orient public health policies targeting these risk factors and subsequently reduce the NE burden in the region.
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| 7. |
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| 8. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 9. |
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| 10. |
- Lindgren, Helena, 1969-, et al.
(author)
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Distinct roles of reactive nitrogen and oxygen species to control infection with the facultative intracellular bacterium Francisella tularensis.
- 2004
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In: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 72:12, s. 7172-7182
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Journal article (peer-reviewed)abstract
- Reactive nitrogen species (RNS) and reactive oxygen species (ROS) are important mediators of the bactericidal host response. We investigated the contribution of these two mediators to the control of infection with the facultative intracellular bacterium Francisella tularensis. When intradermally infected with the live vaccine strain F. tularensis LVS, mice deficient in production of RNS (iNOS(-/-) mice) or in production of ROS by the phagocyte oxidase (p47(phox-/-) mice) showed compromised resistance to infection. The 50% lethal dose (LD(50)) for iNOS(-/-) mice was <20 CFU, and the LD(50) for p47(phox-/-) mice was 4,400 CFU, compared to an LD(50) of >500,000 CFU for wild-type mice. The iNOS(-/-) mice survived for 26.4 +/- 1.8 days, and the p47(phox-/-) mice survived for 10.1 +/- 1.3 days. During the course of infection, the serum levels of gamma interferon (IFN-gamma) and interleukin-6 were higher in iNOS(-/-) and p47(phox-/-) mice than in wild-type mice. Histological examination of livers of iNOS(-/-) mice revealed severe liver pathology. Splenocytes obtained 5 weeks after primary infection from antibiotic-treated iNOS(-/-) mice showed an in vitro recall response that was similar in magnitude and greater secretion of IFN-gamma compared to cells obtained from wild-type mice. In summary, mice lacking expression of RNS or ROS showed extreme susceptibility to infection with F. tularensis LVS. The roles of RNS and ROS seemed to be distinct since mice deficient in production of ROS showed dissemination of infection and died during the early phase of infection, whereas RNS deficiency led to severe liver pathology and a contracted course of infection.
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| 11. |
- Lundin, Karin E, et al.
(author)
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Susceptibility to infections, without concomitant hyper-IgE, reported in 1976, is caused by hypomorphic mutation in the phosphoglucomutase 3 (PGM3) gene
- 2015
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In: Clinical Immunology. - : Elsevier. - 1521-6616 .- 1521-7035. ; 161:2, s. 366-372
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Journal article (peer-reviewed)abstract
- Phosphoglucomutase 3 (PGM3) is an enzyme converting N-acetyl-glucosamine-6-phosphate to N-acetylglucosamine-l-phosphate, a precursor important for glycosylation. Mutations in the PGM3 gene have recently been identified as the cause of novel primary immunodeficiency with a hyper-IgE like syndrome. Here we report the occurrence of a homozygous mutation in the PGM3 gene in a family with immunodeficient children, described already in 1976. DNA from two of the immunodeficient siblings was sequenced and shown to encode the same homozygous missense mutation, causing a destabilized protein with reduced enzymatic capacity. Affected individuals were highly prone to infections, but lack the developmental defects in the nervous and skeletal systems, reported in other families. Moreover, normal IgE levels were found. Thus, belonging to the expanding group of congenital glycosylation defects, PGM3 deficiency is characterized by immunodeficiency, with or without increased IgE levels, and with variable forms of developmental defects affecting other organ systems.
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| 12. |
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| 13. |
- Rehn, Moa, et al.
(author)
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Post-infection symptoms following two large waterborne outbreaks of Cryptosporidium hominis in Northern Sweden, 2010-2011
- 2015
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In: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 15
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Journal article (peer-reviewed)abstract
- Background: In 2010-2011, two large waterborne outbreaks caused by Cryptosporidium hominis affected two cities in Sweden, Ostersund and Skelleftea. We investigated potential post-infection health consequences in people who had reported symptoms compatible with cryptosporidiosis during the outbreaks using questionnaires. Methods: We compared cases linked to these outbreaks with non-cases in terms of symptoms present up to eleven months after the initial infection. We examined if cases were more likely to report a list of symptoms at follow-up than non-cases, calculating odds ratios (OR) and 95 % confidence intervals (CI) obtained through logistic regression. Results: A total of 872 (310 cases) and 743 (149 cases) individuals responded to the follow-up questionnaires in Ostersund and Skelleftea respectively. Outbreak cases were more likely to report diarrhea (Ostersund OR: 3.3, CI: 2.0-5.3. Skelleftea OR: 3.6, CI: 2.0-6.6), watery diarrhea (Ostersund OR: 3.4, CI: 1.9-6.3. Skelleftea OR: 2.8, CI: 1.5-5.1) abdominal pain (Ostersund OR: 2.1, CI: 1.4-3.3, Skelleftea OR: 2.7, CI: 1.5-4.6) and joint pain (Ostersund OR: 2.0, CI: 1.2-3.3, Skelleftea OR: 2.0, CI: 1.1-3.6) at follow-up compared to non-cases. Conclusions: Our findings suggest that gastrointestinal-and joint symptoms can persist several months after the initial infection with Cryptosporidium and should be regarded as a potential cause of unexplained symptoms in people who have suffered from the infection.
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| 14. |
- Stenmark, Stephan, 1965-
(author)
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Cutaneous resistance against Francisella tularensis
- 2004
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Doctoral thesis (other academic/artistic)abstract
- Francisella tularensis, the causative agent of tularemia, is a potent pathogen in humans and other mammals. The ulceroglandular form of the disease is the most common expression in humans with a clinical picture characterized by a skin ulcer, enlarged regional lymph nodes and fever. Despite being a preferred route of infection, the skin also affords an effective defense barrier against F. tularensis. Doses required to induce infection by intradermal inoculation are several logs higher than those needed for infection by other routes. In the present thesis, the requirements for the local and systemic host defense to intradermal infection with F. tularensis was studied in experimental mouse models. Naïve mice and mice immunized by previous infection were challenged, mostly with the live vaccine strain F. tularensis LVS but also with a clinical isolate of F. tularensis. In naïve mice, intradermal inoculation of F. tularensis LVS resulted in a rapid increase of bacterial numbers during the first few days in the skin, lymph nodes, spleen and liver, followed by a decrease and eradication of the bacteria within two weeks of inoculation. Immune mice controlled the infection at the site of infection and very few bacteria spread to internal organs. When immunohistochemical staining of skin specimens was performed during the first 3 days, naïve mice showed a weak or barely discernible local expression of TNF-α, IL-12 and IFN-γ. In immune mice, the expression of all three cytokines was strongly enhanced, TNF-α and IL-12 within 24 h and IFN-γ within 72 h of inoculation. To investigate the role of T cells in the defense against intradermal infection with F. tularensis LVS, naïve and immune T-cell knockout mice (e.g., αβ TCR-/-, γδ TCR-/-, αβγδ TCR-/-) were used. Naïve mice lacking the αβ TCR had persistently high bacterial numbers in all organs and died at 4 weeks. Mice lacking the γδ TCR, on the other hand, controlled the infection as effectively as did wild-type mice. To enable αβ TCR-/- and αβγδ TCR-/- mice to survive, antibiotic treatment was given from day 10 to 20 of infection. When intradermally challenged 2 weeks later, these animals were found to control a secondary infection, resulting in decreasing viable counts in skin and lymph nodes and prevention of spread to liver and spleen. The results indicated the presence of a T-cell independent mechanism of resistance and analyses of serum showed high levels of F. tularensis-specific IgM, findings suggesting a role for antibodies in the protection against cutaneous tularemia. To study the effect of F. tularensis-specific antibodies on host resistance, we adoptively transferred immune serum to B-cell-deficient mice. After receiving immune serum, both naïve and immunized mice became capable of surviving an otherwise lethal dose of F. tularensis LVS. Moreover, transfer of immune serum to wild type mice, afforded significant protection to a lethal dose of a wild-type strain of F. tularensis subsp. holarctica, as disclosed by reduced bacterial counts in spleen and liver. Finally, we studied the effect of immune serum on the local expression of proinflammatory cytokines and neutrophils in response to an intradermal injection of F. tularensis LVS. As compared to normal serum, transfer of immune serum resulted in increased expression of TNF-α, IL-12 and neutrophils. These findings afford a possible explanation for the effect of specific antibodies in the local host protection in the skin against tularemia.
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| 19. |
- Westin, Johan, 1965, et al.
(author)
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Management of hepatitis B virus infection, updated Swedish guidelines
- 2020
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In: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 52:1, s. 1-22
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Journal article (peer-reviewed)abstract
- Despite access to effective antiviral drugs and vaccines, hepatitis B virus (HBV) infection remains a major health issue worldwide. HBV is highly infectious and may cause chronic infection, progressive liver damage, hepatocellular cancer (HCC) and death. Early diagnosis, proper management and timing of treatment are crucial. The Swedish Reference group for Antiviral Treatment (RAV) here provides updated evidence-based guidelines for treatment and management of HBV infection which may be applicable also in other countries. Tenofovir alafenamide (TAF) has been introduced as a novel treatment option and new principles regarding indication and duration of treatment and characterization of hepatitis B have been gradually introduced which justifies an update of the previous guidelines from 2007. Updated guidelines on HCC surveillance in HBV-infected patients, treatment and prophylaxis for patients undergoing liver transplantation as well as management of pregnant women and children with HBV infection are also provided.
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