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  • 1.
    Abioye, Ajibola I.
    et al.
    Brown Univ, RI 02912 USA.
    McDonald, Emily A.
    Brown Univ, RI 02912 USA.
    Park, Sangshin
    Brown Univ, RI 02912 USA; Univ Seoul, South Korea.
    Joshi, Ayush
    Brown Univ, RI 02912 USA.
    Kurtis, Jonathan D.
    Brown Univ, RI 02912 USA.
    Wu, Hannah
    Brown Univ, RI 02912 USA.
    Pond-Tor, Sunthorn
    Brown Univ, RI 02912 USA.
    Sharma, Surendra
    Brown Univ, RI 02912 USA; Women and Infants Hosp Rhode Isl, RI 02908 USA.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Baltazar, Palmera
    Remedios Trinidad Romualdez Hosp, Philippines.
    Acosta, Luz P.
    Res Inst Trop Med, Philippines.
    Olveda, Remigio M.
    Res Inst Trop Med, Philippines.
    Tallo, Veronica
    Res Inst Trop Med, Philippines.
    Friedman, Jennifer F.
    Brown Univ, RI 02912 USA.
    Maternal, placental and cord blood cytokines and the risk of adverse birth outcomes among pregnant women infected with Schistosoma japonicum in the Philippines2019In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 13, no 6, article id e0007371Article in journal (Refereed)
    Abstract [en]

    Background The objectives of this study were to 1) evaluate the influence of treatment with praziquantel on the inflammatory milieu in maternal, placental, and cord blood, 2) assess the extent to which proinflammatory signatures in placental and cord blood impacts birth outcomes, and 3) evaluate the impact of other helminths on the inflammatory micro environment. Methods/Findings This was a secondary analysis of samples from 369 mother-infant pairs participating in a randomized controlled trial of praziquantel given at 12-16 weeks gestation. We performed regression analysis to address our study objectives. In maternal peripheral blood, the concentrations of CXCL8, and TNF receptor I and II decreased from 12 to 32 weeks gestation, while IL-13 increased. Praziquantel treatment did not significantly alter the trajectory of the concentration of any of the cytokines examined. Hookworm infection was associated with elevated placental IL-1, CXCL8 and IFN-gamma. The risk of small-for-gestational age increased with elevated IL-6, IL-10, and CXCL8 in cord blood. The risk of prematurity was increased when cord blood sTNFRI and placental IL-5 were elevated. Conclusions Our study suggests that fetal cytokines, which may be related to infectious disease exposures, contribute to poor intrauterine growth. Additionally, hookworm infection influences cytokine concentrations at the maternal-fetal interface. Clinical Trial Registry number and website ClinicalTrials.gov (NCT00486863). Author summary Schistosomiasis is one of the most prevalent parasitic tropical diseases, and it is primarily treated with the drug praziquantel. This study examined the effects of praziquantel treatment for schistosomiasis and the presence of geohelminth infections during pregnancy on cytokines in maternal, placental, and cord blood, and examined the effects of pro-inflammatory signatures at the maternal-fetal interface on perinatal outcomes. We analyzed the data of 369 mother-infant pairs obtained from a randomized controlled trial of praziquantel given at 12-16 weeks gestation. Praziquantel treatment did not significantly alter the trajectory of the concentration of any of the cytokines examined. Elevated levels of both Th1 and Th2 cytokines were associated with the risk of adverse perinatal outcomes (small-for-gestational age and prematurity). Hookworm coinfection at 12 weeks gestation was, however, related to elevated levels of certain cytokines in the placenta (IL-1, IL-5, CXCL8 and IFN-gamma).

  • 2.
    Ahle, Margareta
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Magnusson, Amanda
    Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
    Elfvin, Anders
    Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
    Andersson, Roland
    Department of Surgery, County Hospital Ryhov, Jönköping, Sweden.
    Space-time clustering of necrotizing enterocolitis supports the existence of transmissible causes.2017Conference paper (Other academic)
    Abstract [en]

    Problem Statement: Despite great efforts to prevent necrotizing enterocolitis (NEC) the incidence may in fact be increasing, and changes in the patient population over time seem to lead to changes in clinical presentation and risk factor spectrum as well. The presence of bacteria is an important prerequisite in the pathogenesis, but, rather than being caused by specific pathogens, inflammation and bacterial invasion are thought to be mediated through erroneous interaction between microbiota and innate immunity during colonization of the gut. There are, however, reports of episodic outbreaks of NEC, seasonal variation in incident rates, and clustering, suggesting a role for transmissible infectious agents or other environmental factors around the pregnant mother or newborn infant. In order to investigate evidence for such factors we have analyzed the occurrence of space-time clusters in Sweden over 23 years. Methods: A national register-based cohort of all children born between 1987 and 2009 in Sweden, diagnosed with NEC, was identified. The Knox test and Kulldorff’s scan method were used to analyze signs of space-time clusters at two geographical levels; the mother’s residential address and the delivery hospital. Time windows of seven, 14 and 21 days were used for closeness in time. Results: The Knox test showed clustering on hospital level in all studied temporal windows; seven days (p=0.022) 14 days (p=0.011) and 21 days (p=0.006), and Kulldorff’s scan method found seven significant clusters. On residential level, there was no indication of space-time interaction. When comparing two time periods, significant clustering on hospital level was found during 1987-1997, but not during 1998-2009. Conclusion: Space-time clustering was found on hospital level, but not on community level, suggesting a contagious environmental effect at and after delivery but not in the materno-fetal environment outside the hospital before birth. The decrease in clustering over time suggests that improved routines in neonatal care have minimized the risk of NEC precipitating contagions spreading between patients in the neonatal intensive care unit. The importance of such routines should not be forgotten while our efforts to bring down NEC incidence are directed towards other challenges.

  • 3.
    Andersson, Anna-Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Andersson, Blanka
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lorell, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Raffetseder, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Autophagy induction targeting mTORC1 enhances Mycobacterium tuberculosis replication in HIV co-infected human macrophages2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 28171Article in journal (Refereed)
    Abstract [en]

    To survive and replicate in macrophages Mycobacterium tuberculosis (Mtb) has developed strategies to subvert host defence mechanisms, including autophagy. Autophagy induction has the potential to clear Mtb, but little is known about its effect during controlled tuberculosis and HIV co-infection. Mammalian target of rapamycin complex1 (mTORC1) inhibitors were used to induce autophagy in human macrophages pre-infected with HIV-1(BaL) and infected with a low dose of Mtb (co-infected), or single Mtb infected (single infected). The controlled Mtb infection was disrupted upon mTOR inhibition resulting in increased Mtb replication in a dose-dependent manner which was more pronounced during co-infection. The increased Mtb replication could be explained by the marked reduction in phagosome acidification upon mTOR inhibition. Autophagy stimulation targeting mTORC1 clearly induced a basal autophagy with flux that was unlinked to the subcellular environment of the Mtb vacuoles, which showed a concurrent suppression in acidification and maturation/flux. Overall our findings indicate that mTOR inhibition during Mtb or HIV/Mtb co-infection interferes with phagosomal maturation, thereby supporting mycobacterial growth during low-dose and controlled infection. Therefore pharmacological induction of autophagy through targeting of the canonical mTORC1-pathway should be handled with caution during controlled tuberculosis, since this could have serious consequences for patients with HIV/Mtb co-infection.

  • 4.
    Askling, Helena H
    et al.
    Karolinska Institute, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Lesko, Birgitta
    Swedish National Board of Health & Welfare, Stockholm, Sweden; Swedish Institute for Infectious Disease Control, Stockholm.
    Vene, Sirkka
    Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
    Berndtson, Angerd
    Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
    Björkman, Per
    Malmö University Hospital, Malmö, Sweden.
    Bläckberg, Jonas
    Lund University Hospital, Lund, Sweden.
    Bronner, Ulf
    Karolinska University Hospital, Stockholm, Sweden.
    Follin, Per
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Hellgren, Urban
    Karolinska University Hospital, Stockholm, Sweden.
    Palmerus, Maria
    County Hospital Ryhov, Jönköping, Sweden.
    Ekdahl, Karl
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Tegnell, Anders
    Swedish National Board of Health & Welfare, Stockholm, Sweden.
    Struwe, Johan
    Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
    Serologic Analysis of Returned Travelers with Fever, Sweden2009In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 15, no 11, p. 1805-1808Article in journal (Refereed)
    Abstract [en]

    We studied 1,432 febrile travelers from Sweden who had returned from malaria-endemic areas during March 2005-March 2008. In 383 patients, paired serum samples were blindly analyzed for influenza and 7 other agents. For 21% of 115 patients with fever of unknown origin, serologic analysis showed that influenza was the major cause.

  • 5.
    Balkhed Östholm, Åse
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Duration of travel-associated faecal colonisation with ESBL-producing Enterobacteriaceae - A one year follow-up study2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 10Article in journal (Refereed)
    Abstract [en]

    In a previous study, we found that 30% of individuals travelling outside Scandinavia acquired extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) in their faecal flora. The aim of this study was to determine the duration of travel-associated faecal colonisation with ESBL-PE, to assess risk factors for prolonged colonisation and to detect changes in antibiotic susceptibility during prolonged colonisation.

  • 6.
    Baroni de Moraes, Marcia Terezinha
    et al.
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Olivares Olivares, Alberto Ignacio
    Univ Fed Roraima, Brazil; Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Fialho, Alexandre Madi
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Malta, Fabio Correia
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    da Silva e Mouta Junior, Sergio
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Bispo, Romanul de Souza
    Univ Fed Roraima, Brazil.
    Velloso, Alvaro Jorge
    Oswaldo Cruz Fdn FIOCRUZ, Brazil; Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Alves Leitao, Gabriel Azevedo
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Cantelli, Carina Pacheco
    Oswaldo Cruz Fdn FIOCRUZ, Brazil; Oswaldo Cruz Fdn FIOCRUZ, Brazil; Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Miagostovich, Marize Pereira
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Gagliardi Leite, Jose Paulo
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Phenotyping of Lewis and secretor HBGA from saliva and detection of new FUT2 gene SNPs from young children from the Amazon presenting acute gastroenteritis and respiratory infection2019In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 70, p. 61-66Article in journal (Refereed)
    Abstract [en]

    The Histo-blood group antigens (HBGA) are host genetic factors associated with susceptibility to rotavirus (RV) and human norovirus (HuNoV), the major etiological agents of viral acute gastroenteritis (AGE) worldwide. The FUT2 gene expressing the alpha-1, 2-L- fucosyltransferase enzyme is important for gut HBGA expression, and also provides a composition of the phenotypic profile achieved through mutations occurring in populations with different evolutionary histories; as such, it can be considered a genetic population marker. In this study, Lewis and secretor HBGA phenotyping was performed using 352 saliva samples collected from children between three months and five years old born in the Amazon (Brazil, Venezuela and English Guyana) presenting AGE or acute respiratory infection (ARI), the latter considered as control samples. The total of children phenotyped as secretors was 323, corresponding to 91.80%. From these, 207 (58.80%) had a Le (a + b +) profile. The HBGA profiles were equally found in children with AGE as well as with ARI. The rs1047781 of the FUT2 gene was not detected in DNA from saliva cells with a Le (a + b +) profile. However, mutations not yet described in the FUT2 gene were observed: missense 325A amp;gt; T, 501C amp;gt; T, 585C amp;gt; T, 855A amp;gt; T and missense substitutions 327C amp;gt; T [S (Ser) amp;gt; C (Cys)], 446 T amp;gt; C [L(Leu) amp;gt; P(Pro)], 723C amp;gt; A [N(Asn) amp;gt; K(Lys)], 724A amp;gt; T [I(Ile) amp;gt; F(Phe)], 736C amp;gt; A [H(His) amp;gt; N(Asn)]. The SNP distribution in the FUT2 gene of the analyzed samples was very similar to that described in Asian populations, including indigenous tribes.

  • 7.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Bich Hoang, Ngoc Thi
    Vietnam Natl Childrens Hosp, Vietnam.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Kien Le, Ngai
    Vietnam Natl Childrens Hosp, Vietnam.
    Svartström, Olov
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Khanh Khu, Dung Thi
    Vietnam Natl Childrens Hosp, Vietnam.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Thanh Le, Hai
    Vietnam Natl Childrens Hosp, Vietnam.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Olson, Linus
    TRAC, Sweden; TRAC, Vietnam; Karolinska Inst, Sweden.
    Larsson, Mattias
    TRAC, Sweden; TRAC, Vietnam; Karolinska Inst, Sweden.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. TRAC, Sweden; TRAC, Vietnam.
    Insertion sequence transpositions and point mutations in mgrB causing colistin resistance in a clinical strain of carbapenem-resistant Klebsiella pneumoniae from Vietnam2018In: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 51, no 5, p. 789-793Article in journal (Refereed)
    Abstract [en]

    Resistance among Klebsiella pneumoniae to the last-resort antibiotics carbapenems and colistin is increasing worldwide. In this study, whole-genome sequencing was used to determine the colistin resistance mechanisms in clinical isolates of carbapenem-and colistin-resistant K. pneumoniae from Vietnam. Alterations in the regulatory gene mgrB, via mutations and insertion sequence transpositions, were found in 30 of 31 isolates, emphasising the importance of this resistance mechanism in colistin-resistant K. pneumoniae. (c) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  • 8.
    Bonkoungou, Isidore Juste O.
    et al.
    Univ Ouaga, Burkina Faso; Natl Publ Hlth Lab, Burkina Faso.
    Ouedraogo, Nafissatou
    Univ Ouaga, Burkina Faso.
    Tamini, Laure
    Univ Ouaga, Burkina Faso; Charles de Gaulle Pediat Univ Hosp, Burkina Faso.
    Teguera, Rabieta Kouboura
    Natl Publ Hlth Lab, Burkina Faso.
    Yameogo, Pouire
    Natl Publ Hlth Lab, Burkina Faso.
    Drabo, Maxime Koine
    Natl Publ Hlth Lab, Burkina Faso.
    Medah, Isaie
    Minist Hlth, Burkina Faso.
    Barro, Nicolas
    Univ Ouaga, Burkina Faso.
    Sharma, Sumit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Rotavirus and norovirus in children with severe diarrhea in Burkina Faso before rotavirus vaccine introduction2018In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 90, no 9, p. 1453-1460Article in journal (Refereed)
    Abstract [en]

    Burkina Faso introduced rotavirus vaccine (RotaTeq) to the national immunization program in November 2013. This study describes the detection rates, clinical profiles, and molecular epidemiology of rotavirus and norovirus (NoV) infections among children amp;lt;5 years hospitalized (n=154) because of acute diarrhea in Ouagadougou, Burkina Faso, from December 2012 to November 2013, just before the start of vaccination. Overall, 44% and 23% of fecal samples were positive for rotavirus and NoV, respectively, most of them detected during the cold dry season (December-March). The predominant G/P combinations were G12P[8] (47%) and G6P[6] (30%). G2P[4] (n=3), G12P[6] (n=3), and G6P[8] (n=1) werealso detected. Nearly all (94%) successfully genotyped NoV strains belonged to genotype GII.4. The predominance of rotavirus and NoV was noteworthy in the age group 6 months, with 67% rotavirus and 22% NoV, respectively. Vomiting was significantly more common among rotavirus-infected children. To conclude, this study shows high detection rates of both rotavirus and NoV in children with severe diarrhea in Burkina Faso just before the introduction of rotavirus group A vaccination. The results can be used for estimating the impact of rotavirus group A vaccination, which started in the end of 2013. Furthermore, this study shows that the G6P[6] rotavirus strains emerging in Burkina Faso in 2010 is now established as a regionally important genotype.

  • 9.
    Borg, O.
    et al.
    Uppsala University, Sweden.
    Wille, M.
    Uppsala University, Sweden.
    Kjellander, P.
    Swedish University of Agriculture Science, Sweden.
    Bergvall, U. A.
    Swedish University of Agriculture Science, Sweden; Stockholm University, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Chirico, J.
    SVA, Sweden.
    Lundkvist, A.
    Uppsala University, Sweden; Uppsala University Hospital, Sweden.
    Expansion of spatial and host range of Puumala virus in Sweden: an increasing threat for humans?2017In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 145, no 8, p. 1642-1648Article in journal (Refereed)
    Abstract [en]

    Hantaviruses are globally distributed and cause severe human disease. Puumala hantavirus (PUUV) is the most common species in Northern Europe, and the only hantavirus confirmed to circulate in Sweden, restricted to the northern regions of the country. In this study, we aimed to further add to the natural ecology of PUUV in Sweden by investigating prevalence, and spatial and host species infection patterns. Specifically, we wanted to ascertain whether PUUV was present in the natural reservoir, the bank vole (Myodes glareolus) further south than Dalalven river, in south-central Sweden, and whether PUUV can be detected in other rodent species in addition to the natural reservoir. In total, 559 animals were collected at Grimso (59 degrees 43 N; 15 degrees 28 E), Sala (59 degrees 55 N; 16 degrees 36 E) and Bogesund (59 degrees 24 N; 18 degrees 14 E) in south-central Sweden between May 2013 and November 2014. PUUV ELISA-reactive antibodies were found both in 2013 (22/295) and in 2014 (18/264), and nine samples were confirmed as PUUV-specific by focus reduction neutralization test. Most of the PUUV-specific samples were from the natural host, the bank vole, but also from other rodent hosts, indicating viral spill-over. Finally, we showed that PUUV is present in more highly populated central Sweden.

  • 10.
    Bucardo, F.
    et al.
    Department of Microbiology, University of León (UNAN-León), León, Nicaragua.
    Mercado, J.
    National Center for Diagnostic and Reference, Ministry of Health, Managua, Nicaragua.
    Reyes, Y.
    Department of Microbiology, University of León (UNAN-León), León, Nicaragua.
    González, F.
    Department of Microbiology, University of León (UNAN-León), León, Nicaragua.
    Balmaseda, A
    National Center for Diagnostic and Reference, Ministry of Health, Managua, Nicaragua.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Large increase of rotavirus diarrhoea in the hospital setting associated with emergence of G12 genotype in a highly vaccinated population in Nicaragua.2015In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 21, no 6, p. 603.e1-603.e7Article in journal (Refereed)
    Abstract [en]

    Rotaviruses (RVs) are a major cause of severe diarrhoea in young children. Nicaragua introduced routine immunization with the pentavalent RV vaccine (RV5) in 2006, which greatly reduced the incidence of diarrhoea. A remaining concern has been the possible emergence of new RV strains to which the vaccination has less effect. In this study, 837 children with diarrhoea in hospital settings were investigated for RV between May 2011 and July 2013. RVs were subsequently typed by multiplex PCR and/or sequencing. Fecal anti-RV IgA titres for a subset of RV-infected (n = 137) and noninfected children (n = 52) were determined with an in-house enzyme-linked immunosorbent assay. The RV detection rate was 8% in 2011, followed by a sharp increase to 29% in 2012 and 19% in 2013. This was associated with emergence and predominance of genotype G12 RV, from 0% in 2011 to 66% in 2012 and 82% in 2013, infecting children from 1 month to 10 years of age. Two sequenced G12 strains showed a Wa-like genome with genotype G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, similar to the globally emerging G12 strains. Fecal anti-RV IgA analysis showed that most G12-infected and noninfected children had been in contact with either vaccine or wild RV strains, but such antibodies did not prevent symptomatic G12 infection. A marked increase of RV was evident in the hospital setting associated with a nationwide emergence and predominance of RV G12 genotype in a population with high RV5 vaccine coverage.

  • 11.
    Bucardo, Filemon
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Department of Microbiology, University of León, UNAN-León, Nicaragua.
    Carlsson, Beatrice
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Larson, Göran
    University of Gothenburg, Göteborg, Sweden.
    Blandon, Patricia
    Department of Microbiology University of León, Nicaragua (UNAN-León).
    Vilchez, Samuel
    Department of Microbiology University of León, Nicaragua (UNAN-León).
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Susceptibility of Children to Sapovirus Infections, Nicaragua, 2005–20062012In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 18, no 11, p. 1875-1878Article in journal (Refereed)
    Abstract [en]

    We describe the genetic diversity of sapovirus (SaV) in children in Nicaragua and investigate the role of host genetic factors and susceptibility to SaV infections. Our results indicate that neither ABO blood group, Lewis phenotype, nor secretor status affects susceptibility to SaV infection in Nicaragua.

  • 12.
    Bucardo, Filemon
    et al.
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Reyes, Yaoska
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Gonzalez, Fredman
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Sharma, Sumit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    The Lewis A phenotype is a restriction factor for Rotateq and Rotarix vaccine-take in Nicaraguan children2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 1502Article in journal (Refereed)
    Abstract [en]

    Histo-blood group antigens (HBGAs) and the Lewis and secretor antigens are associated with susceptibility to rotavirus infection in a genotype-dependent manner. Nicaraguan children were prospectively enrolled in two cohorts vaccinated with either RotaTeq RV5 (n = 68) or Rotarix RV1 (n = 168). Lewis and secretor antigens were determined by saliva phenotyping and genotyping. Seroconversion was defined as a 4-fold increase in plasma IgA antibody titer 1 month after administration of the first dose of the vaccine. Regardless of the vaccine administered, significantly fewer of the children with Lewis A phenotype (0/14) seroconverted after receiving the first vaccine dose compared to 26% (45/175) of those with the Lewis B phenotype and 32% (15/47) of the Lewis negative individuals (P amp;lt; 0.01). Furthermore, following administration of the RV1 vaccine, secretor-positive ABO blood group B children seroconverted to a significantly lesser extent (5%) compared to secretor-positive children with ABO blood groups A (26%) and O (27%) (P amp;lt; 0.05). Other factors such as pre-vaccination titers, sex, breastfeeding, and calprotectin levels did not influence vaccine-take. Differences in HBGA expression appear to be a contributing factor in the discrepancy in vaccine-take and thus, in vaccine efficacy in different ethnic populations.

  • 13.
    Bucardo, Filemon
    et al.
    National Autonomous University of Nicaragua, Nicaragua.
    Reyes, Yaoska
    National Autonomous University of Nicaragua, Nicaragua.
    Becker-Dreps, Sylvia
    University of N Carolina, NC USA.
    Bowman, Natalie
    University of N Carolina, NC USA.
    Gruber, Joann F.
    University of N Carolina, NC USA.
    Vinje, Jan
    National Centre Immunizat and Resp Disease, GA USA.
    Espinoza, Felix
    National Autonomous University of Nicaragua, Nicaragua.
    Paniagua, Margarita
    National Autonomous University of Nicaragua, Nicaragua.
    Balmaseda, Angel
    Minist Heatlh, Nicaragua.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Pediatric norovirus GII.4 infections in Nicaragua, 1999-20152017In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 55, p. 305-312Article in journal (Refereed)
    Abstract [en]

    Objectives: Investigate clinical and epidemiological factors of pediatric GII.4 norovirus infections in children with acute gastroenteritis (AGE) in Nicaragua between 1999 and 2015. Methods: We retrospectively analyzed laboratory and epidemiologic data from 1,790 children amp;lt;= 7 years with AGE from 6 hospitals in Nicaragua (n = 538), and 3 community clinics (n = 919) and households (n = 333) in Leon, between 1999 and 2015. Moreover, asymptomatic children from community clinics (n = 162) and households (n = 105) were enrolled. Norovirus was detected by real-time PCR and genotyped by sequencing the N-terminal and shell region of the capsid gene. Results: Norovirus was found in 19% (n = 338) and 12% (n = 32) of children with and without AGE, respectively. In total, 20 genotypes including a tentatively new genotype were detected. Among children with AGE, the most common genotypes were GII.4 (53%), GII.14 (7%), GII.3 (6%) and GI.3 (6%). In contrast, only one (1.4%) GII.4 was found in asymptomatic children. The prevalence of GII.4 infections was significantly higher in children between 7 and 12 months of age. The prevalence of GII.4 was lowest in households (38%), followed by community clinics (50%) and hospitals (75%). Several different GII.4 variants were detected and their emergence followed the global temporal trend. Conclusions: Overall our study found the predominance of pediatric GII.4 norovirus infections in Nicaragua mostly occurring in children between 7 and 12 months of age, implicating GII.4 as the main norovirus vaccine target.

  • 14.
    Bucardo, Filemon
    et al.
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Reyes, Yaoska
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Rönnelid, Ylva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Gonzalez, Fredman
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Sharma, Sumit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Histo-blood group antigens and rotavirus vaccine shedding in Nicaraguan infants2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 10764Article in journal (Refereed)
    Abstract [en]

    ABO, Lewis and secretor histo-blood group antigens (HBGA) are susceptibility factors for rotavirus in a P-genotype dependent manner and can influence IgA seroconversion rates following rotavirus vaccination. To investigate the association between HBGA phenotypes and rotavirus vaccine shedding fecal samples (n = 304) from a total of 141 infants vaccinated with Rotarix (n = 71) and RotaTeq (n = 70) were prospectively sampled in three time frames (= 3, 4-7 and = 8 days) after first vaccination dose. Rotavirus was detected with qPCR and genotypes determined by G/P multiplex PCR and/or sequencing. HBGAs were determined by hemagglutination and saliva based ELISA. Low shedding rates were observed, with slightly more children vaccinated with RotaTeq (19%) than Rotarix (11%) shedding rotavirus at = 4 days post vaccination (DPV). At = 4 DPV no infant of Lewis A (n = 6) or nonsecretor (n = 9) phenotype in the Rotarix cohort shed rotavirus; the same observation was made for Lewis A infants (n = 7) in the RotaTeq cohort. Putative in-vivo gene reassortment among RotaTeq strains occurred, yielding mainly G1P[8] strains. The bovine derived P[5] genotype included in RotaTeq was able to replicate and be shed at long time frames (amp;gt;13 DPV). The results of this study are consistent with that HBGA phenotype influences vaccine strain shedding as similarly observed for natural infections. Due to the low overall shedding rates observed, additional studies are however warranted.

  • 15.
    Carlander, Christina
    et al.
    Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    Wagner, Philippe
    Uppsala Univ, Sweden.
    van Beirs, Astrid
    Linköping University, Faculty of Medicine and Health Sciences.
    Yilmaz, Aylin
    Univ Gothenburg, Sweden.
    Elfgren, Kristina
    Karolinska Univ Hosp Huddinge, Sweden.
    Dillner, Joakim
    Karolinska Inst, Sweden.
    Sonnerborg, Anders
    Karolinska Inst, Sweden.
    Sparen, Par
    Karolinska Inst, Sweden.
    Suppressive antiretroviral therapy associates with effective treatment of high-grade cervical intraepithelial neoplasia2018In: AIDS (London), ISSN 0269-9370, E-ISSN 1473-5571, Vol. 32, no 11, p. 1475-1484Article in journal (Refereed)
    Abstract [en]

    Objectives: To assess if women living with HIV (WLWH) have poorer outcome after treatment of cervical intraepithelial neoplasia grade 2, grade 3, adenocarcinoma in situ or cervical cancer (CIN2+) than HIV-negative women (HNW) and to identify predictors of CIN2+ treatment failure and recurrence in WLWH. Design: Population-based cohort study with follow-up between 1983 and 2015. Methods: The Swedish National HIV Registry, the Swedish Population Registry and the Swedish National Cervical Screening Registry were linked to identify all women in Stockholm and Gothenburg counties (Sweden) living with HIV and diagnosed with CIN2+ (n = 179) sometime between 1983 and 2014. For each WLWH, two HNW resident in the same counties and matched for country of birth, diagnosed with CIN2+, were chosen as controls. Treatment failure was defined as the presence of CIN2+ at initial follow-up. Recurrence was defined as the presence of CIN1+ subsequent to an initial normal follow-up. Results: WLWH were three times more likely to have treatment failure (odds ratio (OR) 3.7 [95% confidence interval (CI) 2.0-6.8]) and five times more likely to recur (hazard ratio 5.0 [95% CI 2.1-11.6]) than HNW. Suppressive antiretroviral therapy (ART) at time of treatment of CIN2+ was associated with reduced OR of treatment failure (OR 0.3 [95% CI 0.1-0.8]). Immunosuppression (CD4(+) cell count amp;lt; 200 cells/mu l) associated strongly with treatment failure (OR compared with CD4 (+) cell count amp;gt;= 500: 8.5 [95% CI 2.3-30.7]). Conclusion: Suppressive ART is associated with effective treatment of CIN2+. Early HIV diagnosis and ART are essential for successful CIN2+ treatment. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

  • 16.
    Carlsson, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Kalmar Cty Hosp, Sweden.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Jonsson Henningsson, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar Cty Hosp, Sweden.
    Tjernberg, Ivar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar Cty Hosp, Sweden.
    Subclinical Lyme borreliosis is common in south-eastern Sweden and may be distinguished from Lyme neuroborreliosis by sex, age and specific immune marker patterns2018In: Ticks and Tick-borne Diseases, ISSN 1877-959X, E-ISSN 1877-9603, Vol. 9, no 3, p. 742-748Article in journal (Refereed)
    Abstract [en]

    Background: Determinants of a subclinical course of Lyme borreliosis (LB) remain largely unknown. The aim of this study was to assess the extent, sex and age profiles of subclinical Borrelia seroconversion in a LB endemic area in Sweden and to map blood cellular Borrelia-specific immune marker patterns in individuals with a previous subclinical LB course compared with patients previously diagnosed with Lyme neuroborreliosis (LNB). Methods: A large group of 1113 healthy blood donors was screened for multiple IgG anti-Borrelia antibodies and asked to complete a health inquiry regarding previous LB. A group of subjects with anti-Borrelia-specific IgG antibodies but no previous history of LB (subclinical LB, n = 60) was identified together with 22 cases of previous LNB. Whole Borrelia spirochetes, strains B. afzelii ACA1 and B. garinii Ip90, were used for ex vivo whole blood stimulations, whereas outer surface protein enriched fractions of the same strains were used for stimulation of peripheral blood mononuclear cells (PBMCs). An extensive panel of immune markers was analysed in the supernatants after stimulation using multiplex bead arrays, and Borrelia-specific secretion was determined by subtracting the spontaneous secretion. Results: A total of 125/1113 blood donors reported previous clinical LB. In contrast, 66 donors denied previous LB but showed multiple IgG anti-Borrelia antibodies; these were defined as subclinical subjects, of whom 60 were available for further studies. The subclinical subjects consisted of significantly more men and had a younger age compared with the LNB patients (p amp;lt;= 0.01). Discriminant analysis revealed a distinct pattern of sex, age and PBMC B. garinii-specific levels of IL-10, IL-17A and CCL20 discriminating subclinical subjects from LNB patients. Conclusions: This study confirms that subclinical Borrelia seroconversion is common in south-eastern Sweden. The findings further suggest that male sex, younger age together with B. gariniii induced levels of IL-10, IL-17A and CCL20 may be associated with a subclinical course.

  • 17.
    Carlsson, R. M.
    et al.
    Public Health Agency Sweden, Sweden; Sahlgrens University Hospital, Sweden.
    von Segebaden, K.
    Public Health Agency Sweden, Sweden.
    Bergstrom, J.
    Public Health Agency Sweden, Sweden.
    Kling, A. M.
    Public Health Agency Sweden, Sweden.
    Nilsson, Lennart J
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Surveillance of infant pertussis in Sweden 1998-2012; severity of disease in relation to the national vaccination programme2015In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 20, no 6, article id 21032Article in journal (Refereed)
    Abstract [en]

    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.

  • 18.
    Crawford, Sue E.
    et al.
    Baylor Coll Med, TX 77030 USA.
    Ramani, Sasirekha
    Baylor Coll Med, TX 77030 USA.
    Tate, Jacqueline E.
    US Centre Disease Control and Prevent, GA USA.
    Parashar, Umesh D.
    US Centre Disease Control and Prevent, GA USA.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Hagbom, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Franco, Manuel A.
    Pontificia University of Javeriana, Colombia.
    Greenberg, Harry B.
    Stanford University, CA 94305 USA.
    ORyan, Miguel
    University of Chile, Chile; University of Chile, Chile.
    Kang, Gagandeep
    Translat Health and Science Technology Institute, India; Christian Medical Coll and Hospital, India.
    Desselberger, Ulrich
    University of Cambridge, England.
    Estes, Mary K.
    Baylor Coll Med, TX 77030 USA.
    Rotavirus infection2017In: NATURE REVIEWS DISEASE PRIMERS, ISSN 2056-676X, Vol. 3, article id 17083Article in journal (Refereed)
    Abstract [en]

    Rotavirus infections are a leading cause of severe, dehydrating gastroenteritis in children amp;lt;5 years of age. Despite the global introduction of vaccinations for rotavirus over a decade ago, rotavirus infections still result in amp;gt;200,000 deaths annually, mostly in low-income countries. Rotavirus primarily infects enterocytes and induces diarrhoea through the destruction of absorptive enterocytes (leading to malabsorption), intestinal secretion stimulated by rotavirus non-structural protein 4 and activation of the enteric nervous system. In addition, rotavirus infections can lead to antigenaemia (which is associated with more severe manifestations of acute gastroenteritis) and viraemia, and rotavirus can replicate in systemic sites, although this is limited. Reinfections with rotavirus are common throughout life, although the disease severity is reduced with repeat infections. The immune correlates of protection against rotavirus reinfection and recovery from infection are poorly understood, although rotavirus-specific immunoglobulin A has a role in both aspects. The management of rotavirus infection focuses on the prevention and treatment of dehydration, although the use of antiviral and anti-emetic drugs can be indicated in some cases.

  • 19.
    Crisci, Elisa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ellegård, Rada
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nyström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Rondahl, Elin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Serrander, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Bergström, Tomas
    University of Gothenburg, Gothenburg, Sweden.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Eriksson, Kristina
    University of Gothenburg, Gothenburg, Sweden.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Complement opsonization promotes HSV-2 infection of human dendritic cells2016In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 90, no 10, p. 4939-4950Article in journal (Refereed)
    Abstract [en]

    Herpes virus type 2 (HSV2) is one of the most common sexually transmitted infections globally with a very high prevalence in many countries. During HSV2 infection viral particles become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. In genital mucosa, the primary target cells for HSV2 infection are epithelial cells, but resident immune cells such as dendritic cells (DCs) are also infected. The DCs are the activators of the ensuing immune responses directed against HSV2, and the aim of this study was to examine the effects opsonization of HSV2, either with complement alone or with complement and antibodies, had on the infection of immature DCs and their ability to mount inflammatory and antiviral responses. Complement opsonization of HSV2 enhanced both the direct infection of immature DCs and their production of new infectious viral particles. The enhanced infection required activation of the complement cascade and functional complement receptor 3. Furthermore, HSV2 infection of DCs required endocytosis of viral particles and their delivery into an acid endosomal compartment. The presence of complement in combination with HSV1 or HSV2 specific antibodies more or less abolished the HSV2 infection of DCs.Our results clearly demonstrate the importance of studying HSV2 infection under conditions that ensue in vivo, i.e. when the virions are covered in complement fragments and complement fragments and antibodies, as this will shape the infection and the subsequent immune response and needs to be further elucidated.

    IMPORTANCE: During HSV2 infection viral particles should become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. The dendritic cells are the activators of the immune responses directed against HSV2, and the aim of this study was to examine the effects of complement alone or complement and antibodies, on the HSV2 infection of dendritic cells and their ability to mount inflammatory and antiviral responses.Our results demonstrate that the presence of antibodies and complement in the genital environment can influence HSV2 infection under in vitro conditions that reflect the in vivo situation. We believe that our findings are highly relevant for the understanding of HSV2 pathogenesis.

  • 20.
    Deshpande, Devyani
    et al.
    Baylor Univ, TX USA.
    Alffenaar, Jan-Willem C.
    Univ Groningen, Netherlands.
    Koser, Claudio U.
    Univ Cambridge, England.
    Dheda, Keertan
    Univ Cape Town, South Africa.
    Chapagain, Moti L.
    Baylor Univ, TX USA.
    Simbar, Noviana
    Univ Groningen, Netherlands.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Sturkenboom, Marieke G. G.
    Univ Groningen, Netherlands.
    McIlleron, Helen
    Univ Cape Town, South Africa.
    Lee, Pooi S.
    Baylor Univ, TX USA.
    Koeuth, Thearith
    Baylor Univ, TX USA.
    Mpagama, Stellah G.
    Kibongoto Infect Dis Hosp, Tanzania.
    Banu, Sayera
    Int Ctr Diarrhoeal Dis Res, Bangladesh.
    Foongladda, Suporn
    Mahidol Univ, Thailand.
    Ogarkov, Oleg
    Sci Ctr Family Hlth and Human Reprod Problem, Russia.
    Pholwat, Suporn
    Univ Virginia, VA USA.
    Houpt, Eric R.
    Univ Virginia, VA USA.
    Heysell, Scott K.
    Univ Virginia, VA USA.
    Gumbo, Tawanda
    Baylor Univ, TX USA.
    D-Cycloserine Pharmacokinetics/Pharmacodynamics, Susceptibility, and Dosing Implications in Multidrug-resistant Tuberculosis: A Faustian Deal2018In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 67, p. S308-S316Article in journal (Refereed)
    Abstract [en]

    Background. D-cycloserine is used to treat multidrug-resistant tuberculosis. Its efficacy, contribution in combination therapy, and best clinical dose are unclear, also data on the D-cycloserine minimum inhibitory concentration (MIC) distributions is scant. Methods. We performed a systematic search to identify pharmacokinetic and pharmacodynamic studies performed with D-cycloserine. We then performed a combined exposure-effect and dose fractionation study of D-cycloserine in the hollow fiber system model of tuberculosis (HFS-TB). In parallel, we identified D-cycloserine MICs in 415 clinical Mycobacterium tuberculosis (Mtb) isolates from patients. We utilized these results, including intracavitary concentrations, to identify the clinical dose that would be able to achieve or exceed target exposures in 10 000 patients using Monte Carlo experiments (MCEs). Results. There were no published D-cycloserine pharmacokinetics/pharmacodynamics studies identified. Therefore, we performed new HFS-TB experiments. Cyloserine killed 6.3 log(10) colony-forming units (CFU)/mL extracellular bacilli over 28 days. Efficacy was driven by the percentage of time concentration persisted above MIC (% T-MIC), with 1.0 log(10) CFU/mL kill achieved by % T-MIC = 30% (target exposure). The tentative epidemiological cutoff value with the Sensititre MYCOTB assay was 64 mg/L. In MCEs, 750 mg twice daily achieved target exposure in lung cavities of 92% of patients whereas 500 mg twice daily achieved target exposure in 85% of patients with meningitis. The proposed MCE-derived clinical susceptibility breakpoint at the proposed doses was 64 mg/L. Conclusions. Cycloserine is cidal against Mtb. The susceptibility breakpoint is 64 mg/L. However, the doses likely to achieve the cidality in patients are high, and could be neurotoxic.

  • 21.
    Dessau, R. B.
    et al.
    Slagelse Hosp, Denmark.
    van Dam, A. P.
    OLVG Gen Hosp, Netherlands; Publ Hlth Lab, Netherlands.
    Fingerle, V.
    Natl Reference Ctr Borrelia, Germany.
    Gray, J.
    Univ Coll Dublin, Ireland.
    Hovius, J. W.
    Univ Amsterdam, Netherlands.
    Hunfeld, K-P
    Goethe Univ, Germany; INSTAND eV, Germany.
    Jaulhac, B.
    Hop Univ Strasbourg, France.
    Kahl, O.
    Tick Radar GmbH, Germany.
    Kristoferitsch, W.
    Karl Landsteiner Inst Neuroimmunol and Neurodegener, Austria.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Markowicz, M.
    Med Univ Vienna, Austria.
    Mavin, S.
    Raigmore Hosp, Scotland.
    Ornstein, K.
    Skanevard Kryh, Sweden.
    Rupprecht, T.
    HELIOS Klinikum Munchen West, Germany.
    Stanek, G.
    Med Univ Vienna, Austria.
    Strle, F.
    Univ Med Ctr Ljubljana, Slovenia.
    To test or not to test? Laboratory support for the diagnosis of Lyme borreliosis: a position paper of ESGBOR, the ESCMID study group for Lyme borreliosis2018In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 24, no 2, p. 118-124Article, review/survey (Refereed)
    Abstract [en]

    Background: Lyme borreliosis (LB) is a tick-borne infection caused by Borrelia burgdorferi sensu lato. The most frequent clinical manifestations are erythema migrans and Lyme neuroborreliosis. Currently, a large volume of diagnostic testing for LB is reported, whereas the incidence of clinically relevant disease manifestations is low. This indicates overuse of diagnostic testing for LB with implications for patient care and cost-effective health management. Aim: The recommendations provided in this review are intended to support both the clinical diagnosis and initiatives for a more rational use of laboratory testing in patients with clinically suspected LB. Sources: This is a narrative review combining various aspects of the clinical and laboratory diagnosis with an educational purpose. The literature search was based on existing systematic reviews, national and international guidelines and supplemented with specific citations. Implications: The main recommendations according to current European case definitions for LB are as follows. Typical erythema migrans should be diagnosed clinically and does not require laboratory testing. The diagnosis of Lyme neuroborreliosis requires laboratory investigation of the spinal fluid including intrathecal antibody production, and the remaining disease manifestations require testing for serum antibodies to B. burgdorferi. Testing individuals with non-specific subjective symptoms is not recommended, because of a low positive predictive value. (C) 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  • 22.
    Dessau, Ram B
    et al.
    Slagelse Hospital, Slagelse, Denmark.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Nyman, Dag
    Åland University, Mariehamn, Finlad.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Study of a Cohort of 1,886 Persons To Determine Changes in Antibody Reactivity to Borrelia burgdorferi 3 Months after a Tick Bite2015In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 22, no 7, p. 823-827Article in journal (Refereed)
    Abstract [en]

    Lyme borreliosis is a tick-borne disease caused by the bacterium Borrelia burgdorferi. The most frequent clinical manifestation is a rash called erythema migrans. Changes in antibody reactivity to B. burgdorferi 3 months after a tick bite are measured using enzyme-linked immunosorbent assays (ELISAs). One assay is based on native purified flagellum antigen (IgG), and the other assay is based on a recombinant antigen called C6 (IgG or IgM). Paired samples were taken at the time of a tick bite and 3 months later from 1,886 persons in Sweden and the Åland Islands, Finland. The seroconversion or relative change is defined by dividing the measurement units from the second sample by those from the first sample. The threshold for the minimum level of significant change was defined at the 2.5% level to represent the random error level. The thresholds were a 2.7-fold rise for the flagellar IgG assay and a 1.8-fold rise for the C6 assay. Of 1,886 persons, 102/101 (5.4%) had a significant rise in antibody reactivity in the flagellar assay or the C6 assay. Among 40 cases with a diagnosis of Lyme borreliosis, the sensitivities corresponding to a rise in antibodies were 33% and 50% for the flagellar antigen and the C6 antigen, respectively. Graphical methods to display the antibody response and to choose thresholds for a rise in relative antibody reactivity are shown and discussed. In conclusion, 5.4% of people with tick bites showed a rise in Borrelia-specific antibodies above the 2.5% threshold in either ELISA but only 40 (2.1%) developed clinical Lyme borreliosis.

  • 23.
    Dettenkofer, Markus
    et al.
    University of Freiburg, Germany.
    Humphreys, Hilary
    Royal Coll Surg, Ireland; Beaumont Hospital, Ireland.
    Saenz, Henri
    European Soc Clin Microbiol and Infect Disease, Switzerland.
    Carlet, Jean
    Grp Hospital Paris St Joseph, France.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Ruef, Christian
    Hirslanden Klin, Switzerland.
    Widmer, Andreas
    University of Basel Hospital, Switzerland.
    Wolkewitz, Martin
    University of Freiburg, Germany.
    Cookson, Barry
    UCL, England.
    Key priorities in the prevention and control of healthcare-associated infection: a survey of European and other international infection prevention experts2016In: Infection. Zeitschrift für Klinik und Therapie der Infektionen, ISSN 0300-8126, E-ISSN 1439-0973, Vol. 44, no 6, p. 719-724Article in journal (Refereed)
    Abstract [en]

    Purpose Prevention and control of healthcare-associated infection (HCAI) are important within and beyond Europe. However, it is unclear which areas are considered important by HCAI prevention and control professionals. This study assesses the priorities in the prevention and control of HCAI as judged by experts in the field. Methods A survey was conducted by the European Society of Clinical Microbiology and Infectious Diseases focussing on seven topics using SurveyMonkey (R). Through a newsletter distributed by email, about 5000 individuals were targeted throughout the world in February and March 2013. Participants were asked to rate the importance of particular topics from one (low importance) to ten (extraordinary importance), and there was no restriction on giving equal importance to more than one topic. Results A total of 589 experts from 86 countries participated including 462 from Europe (response rate: 11.8 %). Physicians accounted for 60 % of participants, and 57 % had ten or more years experience in this area. Microbial epidemiology/resistance achieved the highest priority scoring with 8.9, followed by surveillance 8.2, and decolonisation/disinfection/antiseptics with 7.9. Under epidemiology/resistance, highly resistant Gram-negative bacilli scored highest (9.0-9.2). The provision of computerised healthcare information systems for the early detection of outbreaks was accorded the top priority under surveillance. The prevention of surgical site and central line infections ranked highest under the category of specific HCAI and HCAI in certain settings. Differences between regions are described. Conclusion These findings reflect the concerns of experts in HCAI prevention and control. The results from this survey should inform national and international agencies on future action and research priorities.

  • 24.
    Edlund, Charlotta
    et al.
    Folkhälsomyndigheten, Sverige.
    Skoog, Gunilla
    Folkhälsomyndigheten, Sverige.
    Grape, Malin
    Folkhälsomyndigheten, Sverige.
    Hedin, Katarina
    FoU, Region Kronoberg, Sverige.
    Sundvall, Pär-Daniel
    FoU primärvård, Västra Götalandsregionen, Sverige.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Dags att fylla kunskapsluckor om antibiotikaanvändning i praxis2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no 12Article in journal (Other academic)
  • 25.
    Ehlersson, Gustaf
    et al.
    Örebro University, Sweden; Örebro University Hospital, Sweden.
    Hellmark, Bengt
    Örebro University, Sweden; Örebro University Hospital, Sweden.
    Svartström, Olov
    Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Stenmark, Bianca
    Örebro University, Sweden; Örebro University Hospital, Sweden.
    Soderquist, Bo
    Örebro University, Sweden; Örebro University Hospital, Sweden.
    Phenotypic characterisation of coagulase-negative staphylococci isolated from blood cultures in newborn infants, with a special focus on Staphylococcus capitis2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no 10, p. 1576-1582Article in journal (Refereed)
    Abstract [en]

    Aim: This Swedish study determined which species of coagulase-negative staphylococci (CoNS) were found in neonatal blood cultures and whether they included Staphylococcus capitis clones with decreased susceptibility to vancomycin. Methods: CoNS isolates (n = 332) from neonatal blood cultures collected at orebro University Hospital during 1987-2014 were identified to species level with matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). The antibiotic susceptibility pattern of S. capitis isolates was determined by the disc diffusion test and Etest, and the presence of heterogeneous glycopeptide-intermediate S. capitis (hGISC) was evaluated. Results: Staphylococcus epidermidis (67.4%), Staphylococcus haemolyticus (10.5%) and S. capitis (9.6%) were the most common CoNS species. Of the S. capitis isolates, 75% were methicillin-resistant and 44% were multidrug-resistant. No isolate showed decreased susceptibility to vancomycin, but at least 59% displayed the hGISC phenotype. Staphylococcus capitis isolates related to the strain CR01 displaying pulsotype NRCS-A were found. Conclusion: Staphylococcus epidermidis, S. haemolyticus and S. capitis were the predominant species detected in neonatal blood cultures by MALDI-TOF MS. The number of episodes caused by S. capitis increased during the study period, but no isolates with decreased susceptibility to vancomycin were identified. However, S. capitis isolates related to the strain CR01 displaying pulsotype NRCS-A were found.

  • 26.
    Elmasry, Moustafa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Suez Canal Univ, Plast Surg Unit, Dept Surg, Ismailia, Egypt.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Thorfinn, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Abbas, Ashraf H.
    Suez Canal University, Egypt.
    Abdelrahman, Islam
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Suez Canal University, Egypt.
    Adly, Osama A.
    Suez Canal University, Egypt.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Treatment of Children With Scalds by Xenografts: Report From a Swedish Burn Centre2016In: Journal of Burn Care & Research, ISSN 1559-047X, E-ISSN 1559-0488, Vol. 37, no 6, p. E586-E591Article in journal (Refereed)
    Abstract [en]

    Scalds are the most common type of burn in children, and one way to treat them is with xenografts with no topical antimicrobials in line with the recommendations of a recent review. However, this treatment has not been examined in detail. Our aim was to describe the treatment of such children when biological dressings (xenografts) were used without local antimicrobials. We reviewed the medical records of all children admitted to a Swedish National Burn Centre during the period 2010-2012 with scalds who were treated with xenografts. Percentage TBSA injured, age, length of hospital stay, number of operations, antibiotics given, duration of antibiotic treatment, and pain score during the first 3 days, application of xenografts, and clinical notes of wound infection were recorded. We studied 67 children, (43 of whom were boys), with a median (interquartile range [IQR]) age of 1 (1-2) year and median (IQR) TBSA% 6.2 (4-11). Twenty children (30%) required operation. Twelve (18%) developed a wound infection, 29 (43%) had other infections, and 26 (39%) were free from infection. The median (IQR) duration of systemic antibiotics was 10 (6-13) days. On the day that the xenografts were applied 10 of the children had a Face, Legs, Activity, Cry, and Consolability (FLACC) score between 3 and 7, and during the following 2 days, only four children scored in this range. The remaining 57 children had scores amp;lt;3 on the day that xenografts were applied and on the following 2 days. Median (IQR) length of stay/TBSA% was 0.7 (0.4-1.0). Treatment with xenografts was associated with median length of stay/TBSA% amp;lt; 1 and low pain scores. Despite a high rate of prescription of systemic antibiotics, most were for reasons other than wound infection.

  • 27.
    Enkirch, Theresa
    et al.
    European Programme for Public Health Microbiology Training (EUPHEM), European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden; Public Health Agency of Sweden, Solna, Sweden.
    Eriksson, Ronnie
    National Food Agency, Uppsala, Sweden.
    Persson, Sofia
    National Food Agency, Uppsala, Sweden.
    Schmid, Daniela
    Austrian Agency for Health and Food Safety, Vienna, Austria.
    Aberle, Stephan W
    Center for Virology, Medical University of Vienna, Vienna, Austria.
    Löf, Emma
    European Programme for Intervention Epidemiology Training (EPIET), European Centre for Disease Prevention and Control, (ECDC), Stockholm, Sweden; Public Health Agency of Sweden, Solna, Sweden.
    Wittesjö, Bengt
    Department of Communicable Disease Control and Prevention, Blekinge County, Sweden.
    Holmgren, Birgitta
    Department of Communicable Disease Control and Prevention, Skåne County, Sweden.
    Johnzon, Charlotte
    The Environment and Health Administration of Stockholm Municipality, Stockholm, Sweden.
    Gustafsson, Eva X
    Department of Communicable Disease Control and Prevention, Skåne County, Sweden.
    Svensson, Lena M.
    Region Östergötland, Center for Business support and Development, Department of Communicable Disease and Infection Control.
    Sandelin, Lisa Labbé
    Department of Communicable Disease Control and Prevention, Kalmar County, Sweden.
    Richter, Lukas
    Austrian Agency for Health and Food Safety, Vienna, Austria.
    Lindblad, Mats
    National Food Agency, Uppsala, Sweden.
    Brytting, Mia
    Public Health Agency of Sweden, Solna, Sweden.
    Maritschnik, Sabine
    Austrian Agency for Health and Food Safety, Vienna, Austria.
    Tallo, Tatjana
    Public Health Agency of Sweden, Solna, Sweden.
    Malm, Therese
    Department of Communicable Disease Control and Prevention, Gävleborg County, Sweden.
    Sundqvist, Lena
    Public Health Agency of Sweden, Solna, Sweden.
    Ederth, Josefine Lundberg
    Public Health Agency of Sweden, Solna, Sweden.
    Hepatitis A outbreak linked to imported frozen strawberries by sequencing, Sweden and Austria, June to September 20182018In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 23, no 41, article id 1800528Article in journal (Refereed)
    Abstract [en]

    Between June-September 2018, 20 hepatitis A cases were notified in six counties in Sweden. Combined epidemiological and microbiological investigations identified imported frozen strawberries produced in Poland as the source of the outbreak. Sequence analysis confirmed the outbreak strain IB in the strawberries with 100 % identity and the respective batch was withdrawn. Sharing the sequence information internationally led to the identification of 14 additional cases in Austria, linked to strawberries from the same producer.

  • 28.
    Eriksson, Henrik
    et al.
    Linköping University, Department of Computer and Information Science, Human-Centered systems. Linköping University, Faculty of Science & Engineering.
    Timpka, Toomas
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Center for Public Health. Linköping University, Department of Computer and Information Science, Human-Centered systems. Linköping University, Faculty of Science & Engineering.
    Spreco, Armin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Dahlström, Örjan
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Strömgren, Magnus
    Dept. of Social and Economic Geography, Umeå University, Umeå, Sweden.
    Holm, Einar
    Dept. of Social and Economic Geography, Umeå University, Umeå, Sweden.
    Dynamic Multicore Processing for Pandemic Influenza Simulation.2016In: AMIA Annual Symposium Proceedings, American Medical Informatics Association , 2016, Vol. 2016, p. 534-540Conference paper (Refereed)
    Abstract [en]

    Pandemic simulation is a useful tool for analyzing outbreaks and exploring the impact of variations in disease, population, and intervention models. Unfortunately, this type of simulation can be quite time-consuming especially for large models and significant outbreaks, which makes it difficult to run the simulations interactively and to use simulation for decision support during ongoing outbreaks. Improved run-time performance enables new applications of pandemic simulations, and can potentially allow decision makers to explore different scenarios and intervention effects. Parallelization of infection-probability calculations and multicore architectures can take advantage of modern processors to achieve significant run-time performance improvements. However, because of the varying computational load during each simulation run, which originates from the changing number of infectious persons during the outbreak, it is not useful to us the same multicore setup during the simulation run. The best performance can be achieved by dynamically changing the use of the available processor cores to balance the overhead of multithreading with the performance gains of parallelization.

  • 29.
    Erlandsson, Marcus
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Surveillance of Antibiotic Consumption and Antibiotic Resistance in Swedish Intensive Care Units2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: Nosocomial infections remain a major cause of mortality and morbidity. The problem is most apparent in intensive care units (ICUs). Most ICU patients are compromised and vulnerable as a result of disease or severe trauma. One in ten people admitted to hospital is given an antibiotic for infection. The risk of acquiring a nosocomial infection in a European ICU is approximately 20%. It is vitally important that ways are found to prevent transmission between patients and personnel, and that local hygiene routines and antibiotic policies are developed. This thesis is a holistic work focused particularly on antimicrobial antibiotic resistance, antibiotic consumption and to some extent on hygiene in Swedish ICUs.

    Aims: The general aim of this thesis was to investigate bacterial resistance and antibiotic consumption in Swedish ICUs and to try to correlate ICU demographic data with antibiotic consumption and antibiotic resistance. Additional aims were to investigate on which clinical indications antibacterial drugs are prescribed in the ICU, and to investigate the emergence of resistance and transmission of Pseudomonas aeruginosa in the ICU using cluster analysis based on antibiograms and genotype data obtained by AFLP.

    Material and methods: In paper 1-3, antibiotic consumption data together with bacterial antibiotic resistance data and specific ICU-demographic data were collected from an increasing number of ICUs over the years 1997-2001. Data from ICUs covering up to six million out of Sweden’s nine million inhabitants were included. In paper 4, the indications for antibiotic prescribing were studied during two weeks in 2000. Paper 5 investigated Pseudomonas aeruginosa isolates in order to detect cross-transmission with genotype obtained by AFLP, and antibiogram-based cluster analysis was also performed in order to see if this could be a quicker and easier substitute for AFLP.

    Results: This thesis has produced three important findings. Firstly, antibiotic consumption in participating ICUs was relatively high during the study period, and every patient received on average more than one antimicrobial drug per day (I-IV). Secondly, levels of antimicrobial drug resistance seen in S. aureus, E. coli and Klebsiella spp remained low when data were pooled from all ICUs throughout the study period, despite relatively high antibiotic consumption (I-V). Thirdly, the prevalence of antibiotic resistance in CoNS and E. faecium, cefotaxime resistance in Enterobacter, and ciprofloxacin and imipenem resistance in P. aeruginosa was high enough to cause concern.

    Conclusion: For the period studied, multidrug resistance in Swedish ICUs was not a major problem. Signs of cross-transmission with non-multiresistant bacteria were observed, indicating a hygiene problem and identifying simple improvements that could be made in patient care guidelines and barrier precautions. A need for better follow up of prescribed antibiotics was evident. With further surveillance studies and monitoring of antibiotics and bacterial resistance patterns in the local setting as well as on a national and international level, some of the strategic goals in the prevention and control of the emergence of antimicrobial-resistant microbes may be achievable.

    List of papers
    1. Surveillance of Antibiotic Resistance in ICUs in Southeastern Sweden
    Open this publication in new window or tab >>Surveillance of Antibiotic Resistance in ICUs in Southeastern Sweden
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    1999 (English)In: Acta Anaesthesiol Scand, Vol. 43, no 8, p. 815-820Article in journal (Refereed) Published
    Abstract [en]

    Background: A study was designed to assess a computer-based program for continuous registration of antibiotic resistance, statistics concerning severity of illness, and consumption of antibacterial drugs.

    Methods: The frequency of antibiotic resistance among bacteria in eight ICUs in southeastern Sweden was investigated yearly from 1995 through 1997. The antibiotic consumption in the ICUs was registered as defined daily doses (DDD) and compared to severity of illness (APACHE-II scores).

    Results: There was a statistically significant increase in ampicillin resistance among Enterococcus spp. between 1996 and 1997, which was due to a shift from Enterococcus faecalis to Enterococcus faecium. A high prevalence of resistance among coagulase-negative staphylococci to oxacillin (≈ 70%), ciprofloxacin (≈ 50%), fucidic acid (≈ 50%) and netilmicin (≈ 30%) was seen in all ICUs during the whole study period. There was a statistically significant increase in ciprofloxacin resistance among Escherichia coli and Enterococcus spp. The resistance among Enterobacter spp. to cefotaxime decreased but this change was not statistically significant. Efforts were made to avoid betalactam antibiotics, except carbapenems, for treatment of infections caused by Enterobacter spp. and the consumption of cephalosporins decreased whereas the consumption of carbapenems increased. The total antibiotic consumption decreased by 2.5% during the study period. There was no correlation between APACHE II scores and antibiotic consumption.

    Conclusions: Each ICU within a hospital ought to have a program for "on-line" antibiotic resistance surveillance of drugs used in that unit so that changes in empirical treatment can be made when there is an increase in antibiotic-resistant isolates within that unit.

    Keywords
    Antibiotic resistance, intensive care units, antibiotic consumption, ICU-infections
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12662 (URN)10.1034/j.1399-6576.1999.430806.x (DOI)
    Available from: 2007-10-18 Created: 2007-10-18 Last updated: 2009-08-18
    2. Antibiotic prescription practices, consumption and bacterial resistance in a cross section of Swedish intensive care units
    Open this publication in new window or tab >>Antibiotic prescription practices, consumption and bacterial resistance in a cross section of Swedish intensive care units
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    2002 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, Vol. 46, no 9, p. 1075-1081Article in journal (Refereed) Published
    Abstract [en]

    Background: The purpose of this work was to study usage of antibiotics, its possible determinants, and patterns of bacterial resistance in Swedish intensive care units (ICUs).

    Methods: Prospectively collected data on species and antibiotic resistance of clinical isolates and antibiotic consumption specific to each ICU in 1999 were analyzed together with answers to a questionnaire. Antibiotic usage was measured as defined daily doses per 1000 occupied bed days (DDD1000).

    Results: Data were obtained for 38 ICUs providing services to a population of approximately 6 million. The median antibiotic consumption was 1257 DDD1000 (range 584–2415) and correlated with the length of stay but not with the illness severity score or the ICU category. Antibiotic consumption was higher in the ICUs lacking bedside devices for hand disinfection (2193 vs. 1214 DDD1000, p=0.05). In the ICUs with a specialist in infectious diseases responsible for antibiotic treatment the consumption pattern was different only for use of glycopeptides (58% lower usage than in other ICUs: 26 vs. 11 DDD1000,P=0.02). Only 21% of the ICUs had a written guideline on the use of antibiotics, 57% received information on antibiotic usage at least every 3 months and 22% received aggregated resistance data annually. Clinically significant antimicrobial resistance was found among Enterbacter spp. to cephalosporins and among Enterococcus spp. to ampicillin.

    Conclusions: Availability of hand disinfection equipment at each bed and a specialist in infectious diseases responsible for antibiotic treatment were factors that correlated with lower antibiotic consumption in Swedish ICUs, whereas patient-related factors were not associated with antibiotic usage.

    Keywords
    Anti-infective agents, critical care, cross infection, multiple drug resistance
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12663 (URN)10.1034/j.1399-6576.2002.460904.x (DOI)
    Available from: 2007-10-18 Created: 2007-10-18 Last updated: 2009-08-21
    3. High Antibiotic Susceptibility Among Bacterial Pathogens In Swedish ICUs
    Open this publication in new window or tab >>High Antibiotic Susceptibility Among Bacterial Pathogens In Swedish ICUs
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    2004 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, Vol. 36, no 1, p. 24-30Article in journal (Refereed) Published
    Abstract [en]

    Local infection control measures, antibiotic consumption and patient demographics from 1999-2000 together with bacteriological analyses were investigated in 29 ICUs participating in the ICU-STRAMA programme. The median antibiotic consumption per ICU was 1147 (range 605-2143) daily doses per 1000 occupied bed d (DDD1000). Antibiotics to which >90% of isolates of an organism were susceptible were defined as treatment alternatives (TA90). The mean number of TA90 was low (1-2 per organism) for Enterococcus faecium (vancomycin:VAN), coagulase negative staphylococci (VAN), Pseudomonas aeruginosa (ceftazidime:CTZ, netilmicin: NET) and Stenotrophomonas maltophilia (CTZ, trimethoprim-sulfamethoxazole: TSU), but higher (3-7) for Acinetobacter spp. (imipenem:IMI, NET, TSU), Enterococcus faecalis (ampicillin:AMP, IMI, VAN), Serratia spp. (ciprofloxacin:CIP, IMI, NET), Enterobacter spp. (CIP, IMI, NET, TSU), E. coli (cefuroxime:CXM, cefotaxime/ceftazidime:CTX/CTZ, CIP, IMI, NET, piperacillin-tazobactam:PTZ, TSU), Klebsiella spp. (CTX/CTZ CIP, IMI, NET, PTZ, TSU) and Staphylococcus aureus (clindamycin, fusidic acid, NET, oxacillin, rifampicin, VAN). Of S. aureus isolates 2% were MRSA. Facilities for alcohol hand disinfection at each bed were available in 96% of the ICUs. The numbers of TA90 available were apparently higher than in ICUs in southern Europe and the US, despite a relatively high antibiotic consumption. This may be due to a moderate ecological impact of the used agents and the infection control routines in Swedish ICUs.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12664 (URN)10.1080/00365540310017429 (DOI)
    Available from: 2007-10-18 Created: 2007-10-18 Last updated: 2009-08-18
    4. Prescription of antibiotic agents in Swedish intensive care units is empiric and adequate
    Open this publication in new window or tab >>Prescription of antibiotic agents in Swedish intensive care units is empiric and adequate
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    2007 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 39, no 1, p. 63-69Article in journal (Refereed) Published
    Abstract [en]

    Since the prescription of antibiotics in the hospital setting is often empiric, particularly in the critically ill, and therefore fraught with potential error, we analysed the use of antibiotic agents in Swedish intensive care units (ICUs). We examined indications for antibiotic treatment, agents and dosage prescribed among 393 patients admitted to 23 ICUs at 7 tertiary care centres, 11 secondary hospitals and 5 primary hospitals over a 2-week period in November 2000. Antibiotic consumption was higher among ICU patients in tertiary care centres with a median of 84% (range 58-87%) of patients on antibiotics compared to patients in secondary hospitals (67%, range 35-93%) and in primary hospitals (38%, range 24-80%). Altogether 68% of the patients received antibiotics during the ICU stay compared to 65% on admission. Cefuroxime was the most commonly prescribed antibiotic before and during admission (28% and 24% of prescriptions, respectively). A date for decision to continue or discontinue antibiotic therapy was set in 21% (6/29) of patients receiving prophylaxis, in 8% (16/205) receiving empirical treatment and in 3% (3/88) when culture-based therapy was given. No correlation between antibiotic prescription and laboratory parameters such as CRP levels, leukocyte and thrombocyte counts, was found. The treatment was empirical in 64% and prophylactic in 9% of cases. Microbiological data guided prescription more often in severe sepsis (median 50%, range 40-60% of prescriptions) than in other specified forms of infection (median 32%, range 21-50%). The empirically chosen antibiotic was found to be active in vitro against the pathogens found in 55 of 58 patients (95%) with a positive blood culture. This study showed that a high proportion of ICU patients receive antimicrobial agents and, as expected, empirical-based therapy is more common than culture-based therapy. Antibiotics given were usually active in vitro against the pathogen found in blood cultures. We ascribe this to a relatively modest antibiotic resistance problem in Swedish hospitals.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12665 (URN)10.1080/00365540600740504 (DOI)
    Available from: 2007-10-18 Created: 2007-10-18 Last updated: 2017-12-14
    5. Antibiotic susceptibility patterns and clones of Pseudomonas aeruginosa in Swedish ICUs
    Open this publication in new window or tab >>Antibiotic susceptibility patterns and clones of Pseudomonas aeruginosa in Swedish ICUs
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    2008 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 40, no 6-7, p. 487-494Article in journal (Refereed) Published
    Abstract [en]

    Pseudomonas aeruginosa is 1 of the bacteria most adaptive to anti-bacterial treatment. Previous studies have shown nosocomial spread and transmission of clonal strains of P. aeruginosa in European hospitals. In this study we investigated antibiotic susceptibility and clonality in 101 P. aeruginosa isolates from 88 patients admitted to 8 Swedish ICUs during 2002. We also compared phenotypes and genotypes of P. aeruginosa and carried out cluster analysis to determine if phenotypic data can be used for surveillance of clonal spread. All isolates were collected on clinical indication as part of the NPRS II study in Sweden and were subjected to AFLP analysis for genotyping. 68 isolates with unique genotypes were found. Phenotyping was performed using MIC values for 5 anti-pseudomonal agents. Almost 6% of the isolates were multi-drug resistant (MDR), and this figure rose to almost 8% when intermediate isolates were also included. We found probable clonal spread in 9 cases, but none of them was found to be an MDR strain. Phenotypical cluster analysis produced 40 clusters. Comparing partitions did not demonstrate any significant concordance between the typing methods. The conclusion of our study is that cross-transmission and clonal spread of MDR P. aeruginosa does not present a clinical problem in Swedish ICUs, but probable cross-transmission of non-MDR clones indicate a need for improved hygiene routines bedside. The phenotype clusters were not concordant with genotype clusters, and genotyping is still recommended for epidemiological tracking.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12666 (URN)10.1080/00365540701864641 (DOI)
    Available from: 2007-10-18 Created: 2007-10-18 Last updated: 2017-12-14
  • 30.
    Esteves, Aida
    et al.
    NOVA University of Lisbon, Portugal.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Pereira, Joana
    NOVA University of Lisbon, Portugal.
    Fortes, Filomeno
    National Institute Public Heatlh, Angola.
    Dimbu, Rafael
    National Institute Public Heatlh, Angola.
    Saraiva, Nilton
    National Institute Public Heatlh, Angola.
    Mendes, Cristina
    NOVA University of Lisbon, Portugal.
    Istrate, Claudia
    NOVA University of Lisbon, Portugal.
    Molecular Epidemiology of Rotavirus in Four Provinces of Angola Before Vaccine Introduction2016In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 88, no 9, p. 1511-1520Article in journal (Refereed)
    Abstract [en]

    Angola is a sub-Saharan country in southern Africa highly affected by diarrhoeal disease with limited epidemiological data regarding etiologic agents. This study was performed during 2012-2013, prior to rotavirus vaccine introduction, with the objective to detect and characterize the rotavirus strains circulating in four provinces of the country: Huambo, Luanda, Zaire, and Cabinda. A high rotavirus detection rate (35%, 117/334) was observed. G1 was the most common G-genotype (83.6%), whereas P[8] (50.9%) followed by P[6] (38.8%) were the most common P-types. G1P[8] was identified as the predominant combination (50%), followed by the unusual G1P[6] (29.3%). Strains such G2P[4], G8P[6], G9P[6], and G12P[6] were also found in lower frequencies (5.2-1.7%). The P[6] strains did not cluster in the phylogenetic trees according to their geographic origin or even the corresponding G-genotype, suggesting a limited number of recent introductions and extensive reassortment events. Our results represent the first report on rotavirus genotype profiles in Angola, showing a wide circulation of the unusual genotype G1P[6], and underline the importance of RV surveillance after the vaccine introduction. (C) 2016 Wiley Periodicals, Inc.

  • 31.
    Flodin, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Paues, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Åkerlind, Britt
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Business support and Development, Department of Communicable Disease and Infection Control.
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Sjögren, Bengt
    Karolinska Institutet, Arbetsmiljötoxikologi, Institutet för miljömedicin Stockholm, Sweden Institutet för miljömedicin, Karolinska Institutet - Arbetsmiljötoxikologi Stockholm, Sweden.
    Svetsare – en riskgrupp för septisk pneumoni [Welders - a risk group for septic pneumonia]: Vaccination mot pneumokocker kan vara motiverat för yrkesgruppen2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no 6Article in journal (Refereed)
  • 32.
    Fransen, Jian
    et al.
    Uppsala University, Sweden.
    Huss, Fredrik R. M.
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Rydell, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Surveillance of antibiotic susceptibility in a Swedish Burn Center 1994-20122016In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 42, no 6, p. 1295-1303Article in journal (Refereed)
    Abstract [en]

    Patients with burn trauma are at risk for infections caused by antibiotic resistant bacteria (ABR) with subsequent increase in morbidity and mortality. As part of the Swedish strategic program against antibiotic resistance in intensive care (ICU-Strama), we have surveyed the distribution of species and ABR in isolates from patients admitted to a Swedish burn center at Linkoping University Hospital from 1994 through 2012. In an international comparison Strama has been successful in reducing the antibiotic consumption among animals and humans in primary care. The aim of this study was to investigate the antibiotic consumption pressure and resistance rates in a Swedish burn unit. Methods: Microbiology data, total body surface area (TBSA), patient days, and mortality were collected from a hospital database for all patients admitted to the Burn Center at the University Hospital of Linkoping from April 1994 through December 2012. Results: A total of 1570 patients were admitted with a mean annual admission rate of 83 patients (range: 57-152). 15,006 microbiology cultures (approximately 10 per patient) were collected during the study period and of these 4531 were positive (approximately 3 per patient). The annual mean total body surface area (TBSA) was 13.4% (range 9.5-18.5) with an annual mortality rate of 5.4% (range 1-8%). The MRSA incidence was 1.7% (15/866) which corresponds to an MRSA incidence of 0.34/1000 admission days (TAD). Corresponding figures were for Escherichia coli resistant to 3rd generation cephalosporins (ESBL phenotype) 8% (13/170) and 0.3/TAD, Klebsiella spp. ESBL phenotype 5% (6/134) and 0.14/TAD, carbapenem resistant Pseudomonas aeruginosa 26% (56/209) and 1.28/TAD, and carbapenem resistant Acinetobacter spp. 3% (2/64) and 0.04/TAD. Conclusions: Our results show a sustained low risk for MRSA and high, although not increasing, risk for carbapenem resistant P. aeruginosa. (C) 2016 Elsevier Ltd and ISBI. All rights reserved.

  • 33.
    Gideskog, Maria
    et al.
    Region Östergötland, Center for Business support and Development, Department of Communicable Disease and Infection Control.
    Melhus, Asa
    Region Östergötland, Center for Business support and Development, Department of Communicable Disease and Infection Control. Uppsala Univ Hosp, Sweden.
    Outbreak of Methicillin-resistant Staphylococcus aureus in a Hospital Center for Childrens and Womens Health in a Swedish County2019In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 127, no 4, p. 181-186Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to investigate a sudden increase in methicillin-resistant Staphylococcus aureus (MRSA) cases primarily in one maternity ward at the Center for Childrens and Womens Health at Linkoping University Hospital, Sweden. Approximately 300 individuals including patients, their family members, and healthcare workers were screened for MRSA. The antibiotic susceptibility was tested and isolates polymerase chain reaction (PCR)-positive for the mecA gene were spa typed. Isolates with the same antibiogram and spa type were further whole genome sequenced. Compliance to current cleaning and hygiene routines was also controlled, and environmental samples collected. The results showed that a total of 13 individuals were involved in the outbreak. It was caused by a t386 MRSA strain (ST-1, NCBI-accession AB505628) with additional resistance to erythromycin and clindamycin. All cases were epidemiologically connected to the index patient, who had recently emigrated from a high-endemic area for MRSA. With improved cleaning and better compliance to basic hygiene routines, no further cases were reported. This study demonstrates how rapid an MRSA strain can disseminate in a ward with susceptible patients and insufficient cleaning and hygiene. For a better control of MRSA, clinical cultures and screening samples need to be obtained early and more extensively than according to the current recommendations.

  • 34.
    Gustavsson, O.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology. Innlandet Hospital Trust, Norway.
    Johansson, A. V.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Monstein, Hans-Jurg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Bredberg, A.
    Innlandet Hospital Trust, Norway; Lund University, Sweden.
    A wide spectrum of fastidious and ampicillin-susceptible bacteria dominate in animal-caused wounds2016In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 35, no 8, p. 1315-1321Article in journal (Refereed)
    Abstract [en]

    The main purpose of this study was to assess the actual occurrence of Gram-negative oxidase-positive bacteria (GNOP) in human wounds caused by animals, mostly cat and dog bites and scratches, and with signs of infection. We report a prospective series of 92 wound samples. Routine culturing was combined with a procedure optimised for fastidious GNOP. All GNOP isolates were identified by 16S rDNA sequencing to the species level. We observed a more prominent role of GNOP, including at least 30 species mostly in the families Flavobacteriaceae, Neisseriaceae and Pasteurellaceae, and less of Staphylococcus aureus and streptococci. The antibiotic susceptibility pattern was investigated, as GNOP are associated with sudden onset of serious infections, making an early decision on antibiotic treatment vital. All GNOP isolates judged to be clinically relevant displayed susceptibility to ampicillin and meropenem, but resistance to oxacillin, clindamycin and gentamicin was frequent. Our findings emphasise the need to cover GNOP as recommended in guidelines, and not only common wound pathogens, when treating an animal-caused wound.

  • 35.
    Gyllemark, Paula
    et al.
    Department of Infectious Diseases, Region Jönköping County, Jönköping, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Henningsson, Anna J.
    Clinical Microbiology, Division of Medical Services, Jönköping, Region Jönköping County, Sweden.
    Intrathecal Th17- and B cell-associated cytokine and chemokine responses in relation to clinical outcome in Lyme neuroborreliosis: a large retrospective study.2017In: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 14, no 1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: B cell immunity, including the chemokine CXCL13, has an established role in Lyme neuroborreliosis, and also, T helper (Th) 17 immunity, including IL-17A, has recently been implicated.

    METHODS: We analysed a set of cytokines and chemokines associated with B cell and Th17 immunity in cerebrospinal fluid and serum from clinically well-characterized patients with definite Lyme neuroborreliosis (group 1, n = 49), defined by both cerebrospinal fluid pleocytosis and Borrelia-specific antibodies in cerebrospinal fluid and from two groups with possible Lyme neuroborreliosis, showing either pleocytosis (group 2, n = 14) or Borrelia-specific antibodies in cerebrospinal fluid (group 3, n = 14). A non-Lyme neuroborreliosis reference group consisted of 88 patients lacking pleocytosis and Borrelia-specific antibodies in serum and cerebrospinal fluid.

    RESULTS: Cerebrospinal fluid levels of B cell-associated markers (CXCL13, APRIL and BAFF) were significantly elevated in groups 1, 2 and 3 compared with the reference group, except for BAFF, which was not elevated in group 3. Regarding Th17-associated markers (IL-17A, CXCL1 and CCL20), CCL20 in cerebrospinal fluid was significantly elevated in groups 1, 2 and 3 compared with the reference group, while IL-17A and CXCL1 were elevated in group 1. Patients with time of recovery <3 months had lower cerebrospinal fluid levels of IL-17A, APRIL and BAFF compared to patients with recovery >3 months.

    CONCLUSIONS: By using a set of markers in addition to CXCL13 and IL-17A, we confirm that B cell- and Th17-associated immune responses are involved in Lyme neuroborreliosis pathogenesis with different patterns in subgroups. Furthermore, IL-17A, APRIL and BAFF may be associated with time to recovery after treatment.

  • 36.
    Hammarskjöld, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Berg, Sören
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Taxbro, Knut
    Ryhov County Hospital, Sweden .
    Malmvall, Bo-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Jonkoping Cty Council, Futurum Acad Hlth Care, Jonkoping, Sweden.
    Sustained low incidence of central venous catheter-related infections over six years in a Swedish hospital with an active central venous catheter team2014In: American Journal of Infection Control, ISSN 0196-6553, E-ISSN 1527-3296, Vol. 42, no 2, p. 122-128Article in journal (Refereed)
    Abstract [en]

    Background: There are limited data on the long-term effects of implementing a central venous catheter (CVC) program for prevention of CVC infections. The aims of this study were to evaluate the incidence of CVC colonization, catheter-related infections (CRI), catheter-related bloodstream infections (CRBSI), and their risk factors over a 6-year period in a hospital with an active CVC team. Methods: We conducted a continuous prospective study aiming to include all CVCs used at our hospital during the years 2004 to 2009, evaluating colonization, CRI, CRBSI, and possible risk factors. Results: A total of 2,772 CVCs was used during the study period. Data on culture results and catheterization time were available for 2,045 CVCs used in 1,674 patients. The incidences of colonization, CRI, and CRBSI were 7.0, 2.2, and 0.6 per 1,000 CVC-days, respectively. Analysis of quarterly incidences revealed 1 occasion with increasing infection rates. Catheterization time was a risk factor for CRI but not for CRBSI. Other risk factors for CRI were hemodialysis and CVC use in the internal jugular vein compared with the subclavian vein. Hemodialysis was the only risk factor for CRBSI. Conclusion: We found that a CRI prevention program led by an active CVC team and adhered to by the entire staff at a county hospital is successful in keeping CVC infections at a low rate over a long period of time.

  • 37.
    Hanberger, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Giske, Christian G
    Clinical microbiology — Karolinska Institutet, Karolinska University Hospital, Stockholm.
    Giamarellou, Helen
    Athens University Medical School, Athens, Greece.
    When and how to cover for resistant gram-negative bacilli in severe sepsis and septic shock.2011In: Current Infectious Disease Reports, ISSN 1523-3847, E-ISSN 1534-3146, Vol. 13, no 5, p. 416-425Article in journal (Refereed)
    Abstract [en]

    In the 80s and 90s, increasing antibiotic resistance was met by the introduction of new effective agents with broader antibacterial spectra for the empirical treatment of severe infections. In recent years, however, few novel antimicrobials have been developed, and this has critically weakened our strength in the fight against resistant bacteria, especially Gram-negative bacilli. It has been well proven that mortality increases if initial empirical antibiotic treatment for severe infection is inappropriate due to resistance of the pathogen. Physicians are already faced with the increasing challenge of untreatable or almost untreatable Gram-negative infections due to antibiotic resistance. Empirical treatment with broader spectra and high antibiotic pressure both in- and outside hospital is the driving force behind resistance. Since new efficient drugs against Gram-negative bacilli will not be available for some time, the best we can do to stop infections caused by multidrug-resistant bacteria is to improve infection control and choice of antibiotics, which should be based on surveillance of local antibiotic consumption and resistance. We must learn more about the revived antibacterial agents colistin and fosfomycin, and the few next generation Gram-negative antibiotics that have been developed. The aim of this review is to give an update on present therapeutic options in the fight against multidrug-resistant Gram-negative bacteria.

  • 38.
    Hedenstierna, M
    et al.
    Karolinska Universitetssjukhuset Huddinge, Stockholm.
    Weiland, O
    Karolinska Universitetssjukhuset Huddinge, Stockholm.
    Brass, A
    Karolinska Institutet, Stockholm .
    Bankwitz, D
    Twincore Centre for Experimental and Clinical Infection Research, Hannover, Germany.
    Behrendt, P
    Twincore Centre for Experimental and Clinical Infection Research, Hannover, Germany.
    Uhnoo, I
    Akademiska Universitetssjukhuset, Uppsala .
    Aleman, S
    Karolinska Universitetssjukhuset Huddinge och Solna, Stockholm.
    Cardell, Kristina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Frydén, Aril
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Norkrans, G
    Sahlgrenska Universitetssjukhuset, Göteborg .
    Eilard, A
    Sahlgrenska Universitetssjukhuset, Göteborg .
    Glaumann, H
    Karolinska Universitetssjukhuset Huddinge .
    Pietschmann, T
    Twincore Centre for Experimental and Clinical Infection Research, Hannover, Germany.
    Sällberg, M
    Karolinska Institutet, Stockholm .
    Brenndörfer, E D
    Karolinska Institutet, Stockholm.
    Long-term follow-up of successful hepatitis C virus therapy: waning immune responses and disappearance of liver disease are consistent with cure.2015In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 41, no 6, p. 532-543Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A sustained viral response (SVR) after interferon-based therapy of chronic hepatitis C virus (HCV) infection is regarded to represent a cure. Previous studies have used different markers to clarify whether an SVR truly represents a cure, but no study has combined a clinical work-up with highly sensitive HCV RNA detection, and the determination of immune responses.

    AIM: To determine clinical, histological, virological and immunological markers 5-20 years after SVR.

    METHODS: In 54 patients, liver biochemistry, histology and elastography were evaluated. Liver biopsies, plasma and peripheral blood mononuclear cells (PBMCs) were tested for minute amounts of HCV RNA. HCV-specific T-cell responses were monitored by ELISpot and pentamer staining, and humoral responses by measuring HCV nonstructural (NS)3-specific antibodies and virus neutralisation.

    RESULTS: Liver disease regressed significantly in all patients, and 51 were HCV RNA-negative in all tissues tested. There was an inverse association between liver disease, HCV-specific T-cell responses and HCV antibody levels with time from SVR, supporting that the virus had been cleared. The three patients, who all lacked signs of liver disease, had HCV RNA in PBMCs 5-9 years after SVR. All three had HCV-specific T cells and NS3 antibodies, but no cross-neutralising antibodies.

    CONCLUSIONS: Our combined data confirm that a SVR corresponds to a long-term clinical cure. The waning immune responses support the disappearance of the antigenic stimulus. Transient HCV RNA traces may be detected in some patients up to 9 years after SVR, but no marker associates this with an increased risk for liver disease.

  • 39.
    Hedin Skogman, Barbro
    et al.
    Center for Clinical Research, Falun, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Vene, Sirkka
    Smittskyddsinstutet .
    Åkerlind, Britt
    Östergötlands Läns Landsting, Center for Health and Developmental Care, Department of Infection Control.
    Are There Undiagnosed TBE-, Herpes- or Enteroviral Infections among Children Being Evaluated for Lyme Neuroborreliosis?2014In: Open Journal of Clinical Diagnostics, ISSN 2162-5816, E-ISSN 2162-5824, Vol. 4, no 3, p. 123-129Article in journal (Refereed)
    Abstract [en]

    Lyme neuroborreliosis (LNB) in children is a challenging diagnosis based on clinical manifestations and laboratory findings. The aim of this study was to investigate whether herpes simplex virus (HSV) 1 or 2, varicella zoster virus (VZV), enterovirus or tick-borne encephalitis virus (TBEV) could be identified in cerebrospinal fluid (CSF) or serum from children being evaluated for LNB, in order to elucidate whether such infectious diseases may be missed by the clinician. Methods: Ninety-nine pediatric patients (n = 99) were retrospectively included from a previous study on LNB in southeast of Sweden. They had been diagnosed as “Possible LNB” or “Not determined” due to negative Borrelia antibody index in CSF. Routine polymerase chain reaction (PCR) methods were used for detection of herpes viral RNA or enteroviral DNA in CSF. An ELISA assay was used for detection of anti-TBEV antibodies (IgM and IgG) in serum. Results: One patient showed elevated anti-TBEV IgM and IgG antibodies in serum, indicating a current TBE infection. No positive PCR reactions for HSV 1 or 2, VZV or enterovirus were detected in CSF from any of the patients. In conclusion, our results suggest that undiagnosed herpes- or enteroviral infections are unlikely to explain CNS symptoms in children being evaluated for LNB, whereas missed TBE infections may occur. TBEV serology should be included when evaluating children for LNB in TBE endemic areas.

  • 40.
    Henningsson, A J
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Malmvall, Bo-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Matussek, Andreas
    Klinisk mikrobiologi, Länssjuhuset Ryhov, Jönköping.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Neuroborreliosis-an epidemiological, clinical and healthcare cost study from an endemic area in the south-east of Sweden2010In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 16, no 8, p. 1245-1251Article in journal (Refereed)
    Abstract [en]

    We studied retrospectively the medical records of all patients (n = 150) diagnosed, by cerebrospinal fluid (CSF) analysis, with neuroborreliosis (NB) in Jonkoping County, Sweden during 2000-2005. The number of NB cases increased from 5/100 000 to 10/100 000 inhabitants/year. In 17% of the patients, anti-Borrelia antibodies were found in CSF but not in serum at the time of diagnosis. Facial palsy, headache and fever were frequent manifestations in children, whereas unspecific muscle and joint pain were the most commonly reported symptoms in older patients. Post-treatment symptoms persisting for more than 6 months occurred in 13%, and the patients concerned were significantly older, had longer-lasting symptoms prior to treatment, had higher levels of Borrelia-specific IgG in CSF, and more often had radiculitis. The total cost of NB-related healthcare was estimated to be euro500 000 for the entire study group (euro3300 per patient), and the cost of social benefits was estimated to be euro134 000 (euro2000 per patient). CSF analysis is necessary for the diagnosis of NB, because some patients develop antibodies in serum later than in CSF. Early diagnosis of borreliosis would result in reduced human suffering and in economic gain.

  • 41.
    Henningsson, A. J.
    et al.
    Regional Jönköping County, Sweden.
    Nilsson Bowers, A.
    Regional Jönköping County, Sweden.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Quttineh, M.
    Regional Jonköping County, Sweden.
    Matussek, A.
    Regional Jonköping County, Sweden; Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Haglund, S.
    Regional Jonköping County, Sweden.
    Rapid diagnosis of acute norovirus-associated gastroenteritis: evaluation of the Xpert Norovirus assay and its implementation as a 24/7 service in three hospitals in Jonkoping County, Sweden2017In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 36, no 10, p. 1867-1871Article in journal (Refereed)
    Abstract [en]

    Noroviruses are a leading cause of epidemic and sporadic cases of acute gastroenteritis worldwide. The rapid diagnosis of norovirus infection is important for prompt infection control measures and may reduce the need for additional diagnostic testing. Here we evaluated the performance of the rapid Xpert Norovirus assay, and assessed the turn-around time (TAT) before and after the implementation of the analysis as a 24/7 service at all the three hospitals in Jonkoping County, Sweden. We describe the implementation process which was performed in two steps during 2014. A total number of 276 clinical samples (stool and vomitus) from patients with symptoms of acute gastroenteritis were included in 2014-2015. The samples were analysed with the Xpert Norovirus assay and the already existing routine method: an in-house reverse transcription real-time PCR. Samples showing discrepant results with the two assays were further analysed by a third PCR method. The Xpert Norovirus assay performed well with a sensitivity of 100% and a specificity of 93% compared to the gold standard (defined as the result obtained by at least two of the three PCR methods). The median TAT decreased from 22 hours in 2013 to 2.4 hours in 2015 (p amp;lt; 0.001). We conclude that the performance of the Xpert Norovirus assay was excellent, and that the implementation of the analysis as a 24/7 service at all three hospitals in the county has greatly reduced the time to diagnosis which is beneficial for both patients and healthcare providers.

  • 42.
    Henningsson, Anna J
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Clinical, epidemiological and immunological aspects of Lyme borreliosis with special focus on the role of the complement system2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Lyme borreliosis (LB) is the most common vector-borne disease in the Northern Hemisphere. The infection is caused by spirochetes belonging to the Borrelia burgdorferi sensu lato complex, and it is transmitted to humans by ticks. LB is associated with several clinical manifestations, of which erythema migrans (EM) and neuroborreliosis (NB) are the most common inEurope. The course of the disease is usually benign, but can vary between individuals. The underlying pathogenic mechanisms are not fully understood, but the prognosis is probably determined by a complex interplay between the bacteria and the host’s immune response. Previous studies have indicated that a strong initial T helper (Th) 1-response followed by a Th2 response is beneficial for the clinical outcome in LB.

    The aims of this thesis were to follow the incidence of NB inJönköping County,Sweden, over time, to search for clinical and laboratory markers associated with the risk of developing long-lasting post-treatment symptoms, and to explore the role of the complement system as well as the relative balance between Th-associated cytokine/chemokine responses in LB.

    The number of NB cases, diagnosed by cerebrospinal fluid (CSF) analysis, increased from 5 to 10/100,000 inhabitants/year in Jönköping County during 2000-2005. Post-treatment symptoms persisting more than 6 months occurred in 13 %, and were associated with higher age, longer-lasting symptoms prior to treatment, higher levels of Borrelia-specific IgG in CSF, and reported symptoms of radiculitis. Facial palsy, headache and fever were frequent manifestations in children, whereas unspecific muscle and joint pain were the most commonly reported symptoms in older patients.

    Complement activation occurred both locally in the skin in EM and in CSF of NB patients. However, no activation could be detected in blood in NB patients. Elevated levels of C1q, C4 and C3a in CSF, along with correlation between C1q and C3a levels, suggest complement activation via the classical pathway locally in the central nervous system in NB. In vitro experiments with two clinical Borrelia isolates revealed that B. garinii LU59 induced higher complement activation in human plasma compared to B. afzelii K78 that recruited more of complement regulator factor H. To elucidate the role of complement in the phagocytosis process, experiments were performed using whole blood from healthy donors incubated with fluorescence-labelled spirochetes and different complement inhibitors. The results illustrated a central role of complement for phagocytosis of Borrelia spirochetes.

    We also studied the relative contribution of different Th-associated cytokines/chemokine responses in NB. The results support the notion that early NB is dominated by a Th1 response, eventually accompanied by a Th2 response. IL-17A was increased in CSF in half of the patients with confirmed NB, suggesting a hitherto unknown role of Th17 in NB.

    In conclusion, the risk of developing long-lasting post-treatment symptoms tend to increase mainly with age and duration of symptoms prior to treatment in NB. The complement system seems to play an important role in host defence to recognize and kill Borrelia spirochetes. However, complement activation in inappropriate sites or to an excessive degree may cause tissue damage, and therefore, the role of complement in relation to disease course needs to be studied further. Likewise, the role of Th17 in LB pathogenesis and host defence should be further evaluated in prospective studies.

    List of papers
    1. Neuroborreliosis-an epidemiological, clinical and healthcare cost study from an endemic area in the south-east of Sweden
    Open this publication in new window or tab >>Neuroborreliosis-an epidemiological, clinical and healthcare cost study from an endemic area in the south-east of Sweden
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    2010 (English)In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 16, no 8, p. 1245-1251Article in journal (Refereed) Published
    Abstract [en]

    We studied retrospectively the medical records of all patients (n = 150) diagnosed, by cerebrospinal fluid (CSF) analysis, with neuroborreliosis (NB) in Jonkoping County, Sweden during 2000-2005. The number of NB cases increased from 5/100 000 to 10/100 000 inhabitants/year. In 17% of the patients, anti-Borrelia antibodies were found in CSF but not in serum at the time of diagnosis. Facial palsy, headache and fever were frequent manifestations in children, whereas unspecific muscle and joint pain were the most commonly reported symptoms in older patients. Post-treatment symptoms persisting for more than 6 months occurred in 13%, and the patients concerned were significantly older, had longer-lasting symptoms prior to treatment, had higher levels of Borrelia-specific IgG in CSF, and more often had radiculitis. The total cost of NB-related healthcare was estimated to be euro500 000 for the entire study group (euro3300 per patient), and the cost of social benefits was estimated to be euro134 000 (euro2000 per patient). CSF analysis is necessary for the diagnosis of NB, because some patients develop antibodies in serum later than in CSF. Early diagnosis of borreliosis would result in reduced human suffering and in economic gain.

    Place, publisher, year, edition, pages
    Blackwell Publishing Ltd, 2010
    Keywords
    Clinical, epidemiology, healthcare economy, Lyme disease, neuroborreliosis
    National Category
    Infectious Medicine
    Identifiers
    urn:nbn:se:liu:diva-58536 (URN)10.1111/j.1469-0691.2009.03059.x (DOI)000280359900034 ()
    Note
    This is the pre-reviewed version of the following article: A J Henningsson, Bo-Eric Malmvall, Jan Ernerudh, A Matussek and Pia Forsberg, Neuroborreliosis-an epidemiological, clinical and healthcare cost study from an endemic area in the south-east of Sweden, 2010, CLINICAL MICROBIOLOGY AND INFECTION, (16), 8, 1245-1251. which has been published in final form at: http://dx.doi.org/10.1111/j.1469-0691.2009.03059.x Copyright: Blackwell Publishing Ltd http://eu.wiley.com/WileyCDA/Brand/id-35.html Available from: 2010-08-13 Created: 2010-08-13 Last updated: 2017-12-12Bibliographically approved
    2. Complement activation in Lyme neuroborreliosis - Increased levels of C1q and C3a in cerebrospinal fluid indicate complement activation in the CNS
    Open this publication in new window or tab >>Complement activation in Lyme neuroborreliosis - Increased levels of C1q and C3a in cerebrospinal fluid indicate complement activation in the CNS
    Show others...
    2007 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 183, no 01-Feb, p. 200-207Article in journal (Refereed) Published
    Abstract [en]

    A strong initial inflammatory response is important in neuroborreliosis. Since complement is a main player in early inflammation, we monitored the concentration and activation of complement in plasma and cerebrospinal fluid from 298 patients, of whom 23 were diagnosed with neuroborreliosis. Using sandwich ELISAs, we found significantly elevated levels of C1q, C4, C3, and C3a in cerebrospinal fluid, but not in plasma, in patients with neuroborreliosis. This finding indicates that complement plays a role in the human immune response in neuroborreliosis, that the immunologic process is compartmentalized to the CNS, and that complement activation may occur via the classical pathway.

    Keywords
    complement, neuroborreliosis, inflammation, Lyme borreliosis, cerebrospinal fluid
    National Category
    Infectious Medicine
    Identifiers
    urn:nbn:se:liu:diva-45964 (URN)10.1016/j.jneuroim.2006.10.022 (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13Bibliographically approved
    3. Early Immune Responses to Borrelia garinii and Borrelia afzeliiin Lyme Borreliosis: Local Complement Activation in Erythema Migrans and in vitro Studies ofComplement Activation, Phagocytosis and Cytokine Profile
    Open this publication in new window or tab >>Early Immune Responses to Borrelia garinii and Borrelia afzeliiin Lyme Borreliosis: Local Complement Activation in Erythema Migrans and in vitro Studies ofComplement Activation, Phagocytosis and Cytokine Profile
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    An optimal eradication of spirochetes in Lyme borreliosis depends on the early immune response, including the potent actions of the complement system. We here assessed possible differences between two Borrelia burgdorferi genospecies in their ability to activate complement, and the consequences of complement activation in terms of phagocytosis and induction of cytokines.

    Early local complement activation was assessed immunohistochemically in skin biopsies from patients with erythema migrans (EM) caused by B. afzelii or B. garinii. Complement activation, phagocytosis and early cytokine and chemokine release were studied in vitro by incubating clinical isolates of B. afzelii (K78 from a human skin biopsy) and B. garinii (LU59 from human cerebrospinal fluid) in human whole blood.

    B. afzelii and B. garinii were detected in skin biopsies from EM and deposition of C3-fragments and IgG was found adjacent to the spirochetes. In vitro, B. garinii LU59 induced higher complement activation (measured as the generation of C3a and C5b-9), while B. afzelii K78 recruited more factor H. Phagocytosis by granulocytes and monocytes was demonstrated to be largely dependent on complement activation since phagocytosis was substantially reduced by addition of the C3 inhibitor compstatin or a C5a receptor antagonist. The early cytokine and chemokine release in human blood in response to live spirochetes revealed a rapid and pronounced pro-inflammatory response, mainly associated with the Th1- and Th17-types.

    We conclude that complement is activated locally in the skin in EM, and that B. garinii LU59 activates complement more than B. afzelii K78. Complement activation is pivotal for efficient phagocytosis of Borrelia spirochetes, especially in early infection before specific antibodies are produced. Both B. garinii LU59 and B. afzelii K78 induce proinflammatory cytokines rapidly, but no clear differences were seen between the two genospecies in this respect.

    Keywords
    Lyme borreliosis, erythema migrans, inflammation, complement, cytokine, chemokine, phagocytosis
    National Category
    Infectious Medicine
    Identifiers
    urn:nbn:se:liu:diva-71065 (URN)
    Available from: 2011-09-29 Created: 2011-09-29 Last updated: 2012-08-23Bibliographically approved
    4. Indications of Th1 and Th17 responses in cerebrospinal fluid from patients with Lyme neuroborreliosis: a large retrospective study
    Open this publication in new window or tab >>Indications of Th1 and Th17 responses in cerebrospinal fluid from patients with Lyme neuroborreliosis: a large retrospective study
    Show others...
    2011 (English)In: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 8, no 36Article in journal (Refereed) Published
    Abstract [en]

    Background: Previous studies indicate that successful resolution of Lyme neuroborreliosis (NB) is associated with a strong T helper (Th) 1-type cytokine response in the cerebrospinal fluid (CSF) followed by a down-regulating Th2 response, whereas the role of the recently discovered Th17 cytokine response is unknown. Methods: To investigate the relative contribution of different Th associated cytokine/chemokine responses, we used a multiple bead array to measure the levels of CXCL10 (Th1 marker), CCL22 (Th2 marker), IL-17 (Th17 marker) and CXCL8 (general inflammation marker), in serum and in CSF from untreated patients with confirmed NB (n = 133), and non-NB patients (n = 96), and related the findings to clinical data. Samples from patients with possible early NB (n = 15) and possible late NB (n = 19) were also analysed, as well as samples from an additional control group with orthopaedic patients (n = 17), where CSF was obtained at spinal anaesthesia. Results: The most prominent differences across groups were found in the CSF. IL-17 was elevated in CSF in 49% of the patients with confirmed NB, but was not detectable in the other groups. Patients with confirmed NB and possible early NB had significantly higher CSF levels of CXCL10, CCL22 and CXCL8 compared to both the non-NB group and the control group (p andlt; 0.0001 for all comparisons). Patients in the early NB group, showing a short duration of symptoms, had lower CCL22 levels in CSF than did the confirmed NB group (p andlt; 0.0001). Furthermore, patients within the confirmed NB group showing a duration of symptoms andlt; 2 weeks, tended to have lower CCL22 levels in CSF than did those with longer symptom duration (p = 0.023). Cytokine/chemokine levels were not correlated with clinical parameters or to levels of anti-Borrelia-antibodies. Conclusion: Our results support the notion that early NB is dominated by a Th1-type response, eventually accompanied by a Th2 response. Interestingly, IL-17 was increased exclusively in CSF from patients with confirmed NB, suggesting a hitherto unknown role for Th17 in NB. However, for conclusive evidence, future prospective studies are needed.

    Place, publisher, year, edition, pages
    BioMed Central, 2011
    Keywords
    Lyme neuroborreliosis, cerebrospinal fluid, T helper cell, cytokine, chemokine
    National Category
    Infectious Medicine
    Identifiers
    urn:nbn:se:liu:diva-69177 (URN)10.1186/1742-2094-8-36 (DOI)000291317900001 ()
    Note

    Original Publication: Anna J Henningsson, Ivar Tjernberg, Bo-Eric Malmvall, Pia Forsberg and Jan Ernerudh, Indications of Th1 and Th17 responses in cerebrospinal fluid from patients with Lyme neuroborreliosis: a large retrospective study, 2011, JOURNAL OF NEUROINFLAMMATION, (8), 36. http://dx.doi.org/10.1186/1742-2094-8-36 Licensee: BioMed Central http://www.biomedcentral.com/

    Available from: 2011-06-17 Created: 2011-06-17 Last updated: 2017-12-11Bibliographically approved
  • 43.
    Henningsson, Anna J.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Department of Infectious Diseases, Ryhov County Hospital, Jönköping.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Sandholm, Kerstin
    Department of Chemistry and Biomedical Sciences, University of Kalmar, Kalmar.
    Carlsson, Sten-Anders
    Åland Borrelia Group, Åland Central Hospital, Finland.
    Granlund, Hans
    Åland Borrelia Group, Åland Central Hospital, Finland.
    Jansson, Christian
    Åland Borrelia Group, Åland Central Hospital, Finland.
    Nyman, Dag
    Åland Borrelia Group, Åland Central Hospital, Finland.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Nilsson Ekdahl, Kristina
    Department of Chemistry and Biomedical Sciences, University of Kalmar, Kalmar.
    Complement activation in Lyme neuroborreliosis - Increased levels of C1q and C3a in cerebrospinal fluid indicate complement activation in the CNS2007In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 183, no 01-Feb, p. 200-207Article in journal (Refereed)
    Abstract [en]

    A strong initial inflammatory response is important in neuroborreliosis. Since complement is a main player in early inflammation, we monitored the concentration and activation of complement in plasma and cerebrospinal fluid from 298 patients, of whom 23 were diagnosed with neuroborreliosis. Using sandwich ELISAs, we found significantly elevated levels of C1q, C4, C3, and C3a in cerebrospinal fluid, but not in plasma, in patients with neuroborreliosis. This finding indicates that complement plays a role in the human immune response in neuroborreliosis, that the immunologic process is compartmentalized to the CNS, and that complement activation may occur via the classical pathway.

  • 44.
    Henningsson, Anna J.
    et al.
    Regional Jonköping County, Sweden.
    Lindqvist, Richard
    Umeå University, Sweden.
    Norberg, Peter
    University of Gothenburg, Sweden.
    Lindblom, Pontus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Roth, Anette
    University of Gothenburg, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Bergstrom, Tomas
    University of Gothenburg, Sweden.
    Overby, Anna K.
    Umeå University, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Regional Jonköping County, Sweden.
    Human Tick-Borne Encephalitis and Characterization of Virus from Biting Tick2016In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 22, no 8, p. 1485-1487Article in journal (Refereed)
    Abstract [en]

    We report a case of human tick-borne encephalitis (TBE) in which the TBE virus was isolated from the biting tick. Viral growth and sequence were characterized and compared with those of a reference strain. Virus isolation from ticks from patients with TBE may offer a new approach for studies of epidemiology and pathogenicity.

  • 45.
    Henningsson, Anna J
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Ryhov County Hospital, Jönköping.
    Tjernberg, Ivar
    Kalmar County Hospital, Kalmar.
    Malmvall, Bo-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Indications of Th1 and Th17 responses in cerebrospinal fluid from patients with Lyme neuroborreliosis: a large retrospective study2011In: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 8, no 36Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies indicate that successful resolution of Lyme neuroborreliosis (NB) is associated with a strong T helper (Th) 1-type cytokine response in the cerebrospinal fluid (CSF) followed by a down-regulating Th2 response, whereas the role of the recently discovered Th17 cytokine response is unknown. Methods: To investigate the relative contribution of different Th associated cytokine/chemokine responses, we used a multiple bead array to measure the levels of CXCL10 (Th1 marker), CCL22 (Th2 marker), IL-17 (Th17 marker) and CXCL8 (general inflammation marker), in serum and in CSF from untreated patients with confirmed NB (n = 133), and non-NB patients (n = 96), and related the findings to clinical data. Samples from patients with possible early NB (n = 15) and possible late NB (n = 19) were also analysed, as well as samples from an additional control group with orthopaedic patients (n = 17), where CSF was obtained at spinal anaesthesia. Results: The most prominent differences across groups were found in the CSF. IL-17 was elevated in CSF in 49% of the patients with confirmed NB, but was not detectable in the other groups. Patients with confirmed NB and possible early NB had significantly higher CSF levels of CXCL10, CCL22 and CXCL8 compared to both the non-NB group and the control group (p andlt; 0.0001 for all comparisons). Patients in the early NB group, showing a short duration of symptoms, had lower CCL22 levels in CSF than did the confirmed NB group (p andlt; 0.0001). Furthermore, patients within the confirmed NB group showing a duration of symptoms andlt; 2 weeks, tended to have lower CCL22 levels in CSF than did those with longer symptom duration (p = 0.023). Cytokine/chemokine levels were not correlated with clinical parameters or to levels of anti-Borrelia-antibodies. Conclusion: Our results support the notion that early NB is dominated by a Th1-type response, eventually accompanied by a Th2 response. Interestingly, IL-17 was increased exclusively in CSF from patients with confirmed NB, suggesting a hitherto unknown role for Th17 in NB. However, for conclusive evidence, future prospective studies are needed.

  • 46.
    Heyckendorf, Jan
    et al.
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany; Univ Lubeck, Germany.
    Andres, Soenke
    Res Ctr Borstel, Germany.
    Koser, Claudio U.
    Univ Cambridge, England.
    Olaru, Ioana D.
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar Cty Hosp, Sweden.
    Sturegard, Erik
    Lund Univ, Sweden.
    Beckert, Patrick
    German Ctr Infect Res DZIF, Germany; Karolinska Inst, Sweden.
    Schleusener, Viola
    Karolinska Inst, Sweden.
    Kohl, Thomas A.
    German Ctr Infect Res DZIF, Germany; Karolinska Inst, Sweden.
    Hillemann, Doris
    Res Ctr Borstel, Germany.
    Moradigaravand, Danesh
    Wellcome Trust Sanger Inst, England.
    Parkhill, Julian
    Wellcome Trust Sanger Inst, England.
    Peacock, Sharon J.
    Wellcome Trust Sanger Inst, England; London Sch Hyg and Trop Med, England.
    Niemann, Stefan
    German Ctr Infect Res DZIF, Germany; Univ Cambridge, England; Res Ctr Borstel, Germany.
    Lange, Christoph
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany; Univ Lubeck, Germany; Karolinska Inst, Sweden; Univ Namibia, Namibia.
    Merker, Matthias
    German Ctr Infect Res DZIF, Germany; Res Ctr Borstel, Germany.
    What Is Resistance? Impact of Phenotypic versus Molecular Drug Resistance Testing on Therapy for Multi-and Extensively Drug-Resistant Tuberculosis2018In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 62, no 2, article id e01550-17Article in journal (Refereed)
    Abstract [en]

    Rapid and accurate drug susceptibility testing (DST) is essential for the treatment of multi-and extensively drug-resistant tuberculosis (M/XDR-TB). We compared the utility of genotypic DST assays with phenotypic DST (pDST) using Bactec 960 MGIT or Lowenstein-Jensen to construct M/XDR-TB treatment regimens for a cohort of 25 consecutive M/XDR-TB patients and 15 possible anti-TB drugs. Genotypic DST results from Cepheid GeneXpert MTB/RIF (Xpert) and line probe assays (LPAs; Hain GenoType MTBDRplus 2.0 and MTBDRsl 2.0) and whole-genome sequencing (WGS) were translated into individual algorithmderived treatment regimens for each patient. We further analyzed if discrepancies between the various methods were due to flaws in the genotypic or phenotypic test using MIC results. Compared with pDST, the average agreement in the number of drugs prescribed in genotypic regimens ranged from just 49% (95% confidence interval [ CI], 39 to 59%) for Xpert and 63% (95% CI, 56 to 70%) for LPAs to 93% (95% CI, 88 to 98%) for WGS. Only the WGS regimens did not contain any drugs to which pDST showed resistance. Importantly, MIC testing revealed that pDST likely underestimated the true rate of resistance for key drugs (rifampin, levofloxacin, moxifloxacin, and kanamycin) because critical concentrations (CCs) were too high. WGS can be used to rule in resistance even in M/XDR strains with complex resistance patterns, but pDST for some drugs is still needed to confirm susceptibility and construct the final regimens. Some CCs for pDST need to be reexamined to avoid systematic false-susceptible results in low-level resistant isolates.

  • 47.
    Hoffman, Tove
    et al.
    Uppsala Univ, Sweden.
    Lindeborg, Mats
    Uppsala Univ, Sweden.
    Barboutis, Christos
    Hellen Ornithol Soc Birdlife, Greece.
    Erciyas-Yavuz, Kiraz
    Ondokuz Mayis Univ, Turkey.
    Evander, Magnus
    Umeå Univ, Sweden.
    Fransson, Thord
    Swedish Museum Nat Hist, Sweden.
    Figuerola, Jordi
    Estn Biol Donana, Spain; Ciber Epidemil and Salud Publ, Spain.
    Jaenson, Thomas G. T.
    Uppsala Univ, Sweden.
    Kiat, Yosef
    Hebrew Univ Jerusalem, Israel.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lundkvist, Ake
    Uppsala Univ, Sweden.
    Mohamed, Nahla
    Umea Univ, Sweden.
    Moutailler, Sara
    Agence Natl Secur Sanit Alimentat, France.
    Nyström, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Olsen, Bjorn
    Uppsala Univ, Sweden.
    Salaneck, Erik
    Uppsala Univ, Sweden.
    Alkhurma Hemorrhagic Fever Virus RNA in Hyalomma rufipes Ticks Infesting Migratory Birds, Europe and Asia Minor2018In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 24, no 5, p. 879-882Article in journal (Refereed)
    Abstract [en]

    Alkhurma hemorrhagic fever virus RNA was detected in immature Hyalomma rufipes ticks infesting northward migratory birds caught in the North Mediterranean Basin. This finding suggests a role for birds in the ecology of the Alkhurma hemorrhagic fever virus and a potential mechanism for dissemination to novel regions. Increased surveillance is warranted.

  • 48.
    Horner, Patrick J
    et al.
    School of Social and Community Medicine, University of Bristol, UK.
    Karla, Blee
    Bristol Sexual Health Centre, University Hospitals Bristol NHS Foundation Trust, UK.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    van der Meijden, W
    Department of Dermatology, New Cross Hospital, UK..
    Moi, H.
    Olafia Clinic, Oslo University Hospital, Institute of Medicine, University of Oslo, Norway.
    2016 European Guideline on the management of non-gonococcal urethritis2016In: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, Vol. 27, no 11, p. 928-937Article in journal (Refereed)
    Abstract [en]

    We present the updated International Union against Sexually Transmitted Infections guideline for the management of non-gonococcal urethritis in men. This guideline recommends confirmation of urethritis in symptomatic men before starting treatment. It does not recommend testing asymptomatic men for the presence of urethritis. All men with urethritis should be tested for Chlamydia trachomatis and Neisseria gonorrhoeae and ideally M. genitalium using a NAAT as this is highly likely to improve clinical outcomes. If a NAAT is positive for gonorrhoea, a culture should be performed before treatment. In view of the increasing evidence that azithromycin 1 g may result in the development of antimicrobial resistance in Mycoplasma genitalium azithromycin 1 g is no longer recommended as first line therapy, which should be doxycycline 100 mg bd for 7 days. If azithromycin is to be prescribed an extended of 500 mg, then 250 mg daily for 4 days is to be preferred over 1 g stat. In men with persistent NGU, M. genitalium NAAT testing is recommended if not previously undertaken, as is Trichomonas vaginalis NAAT testing in populations where T. vaginalis is detectable in >2% of symptomatic women.

  • 49.
    Hwei Yap, Siew
    et al.
    University of Malaya, Malaysia.
    Kamila Abdullah, Noor
    University of Malaya, Malaysia.
    McStea, Megan
    University of Malaya, Malaysia.
    Takayama, Kozo
    Hoshi University, Japan.
    Li Chong, Meng
    University of Malaya, Malaysia.
    Crisci, Elisa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Azwa, Iskandar
    University of Malaya, Malaysia; University of Malaya, Malaysia.
    Kamarulzaman, Adeeba
    University of Malaya, Malaysia; University of Malaya, Malaysia.
    Hoong Leong, Kok
    University of Malaya, Malaysia.
    Ling Woo, Yin
    University of Malaya, Malaysia; University of Malaya, Malaysia.
    Rajasuriar, Reena
    University of Malaya, Malaysia; University of Malaya, Malaysia; University of Melbourne, Australia.
    HIV/Human herpesvirus co-infections: Impact on tryptophan-kynurenine pathway and immune reconstitution2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 10, article id e0186000Article in journal (Refereed)
    Abstract [en]

    Background Co-infections with human herpesvirus (HHV) have been associated with residual chronic inflammation in antiretroviral (ART)-treated human immunodeficiency virus (HIV)-infected individuals. However, the role of HHV in modulating the tryptophan-kynurenine pathway and clinical outcomes in HIV-infected individuals is poorly understood. Thus, we investigated the seroprevalence of four common HHVs among treated HIV-infected participants and their impact on kynurenine/tryptophan (K/T) ratio and long-term CD4 T-cell recovery in HIV/HHV co-infected participants. Method In this cross-sectional study, HIV-infected participants receiving suppressive ART for a minimum of 12 months were recruited from the University Malaya Medical Centre (UMMC), Malaysia. Stored plasma was analyzed for CMV, VZV, HSV-1 and HSV-2 IgG antibody levels, immune activation markers (interleukin-6, interferon-gamma, neopterin and sCD14), kynurenine and tryptophan concentrations. The influence of the number of HHV co-infection and K/T ratio on CD4 T-cell recovery was assessed using multivariate Poisson regression. Results A total of 232 HIV-infected participants were recruited and all participants were seropositive for at least one HHV; 96.1% with CMV, 86.6% with VZV, 70.7% with HSV-1 and 53.9% with HSV-2. K/T ratio had a significant positive correlation with CMV (rho = 0.205, p = 0.002), VZV (rho = 0.173, p = 0.009) and a tendency with HSV-2 (rho = 0.120, p = 0.070), with CMV antibody titer demonstrating the strongest modulating effect on K/T ratio among the four HHVs assessed in SOM analysis. In multivariate analysis, higher K/T ratio (p = 0.03) and increasing number of HHV co-infections (pamp;lt;0.001) were independently associated with poorer CD4 T-cell recovery following 12 months of ART initiation. Conclusion Multiple HHV co-infections are common among ART-treated HIV-infected participants in the developing country setting and associated with persistent immune activation and poorer CD4 T-cell recovery.

  • 50.
    Hällgren, Anita
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Borgström, S.
    Department of Anaesthesia and Intensive Care, Kalmar County Hospital, Kalmar, Sweden.
    Kullberg, F.
    Department of Anaesthesia and Intensive Care , Central Hospital , Växjö Sweden.
    Wimmerstedt, A.
    Department of Infectious Diseases, Central Hospital, Växjö, Sweden.
    Oscarsson, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Nordlund, P.
    Department of Anaesthesia and Intensive Care, Ryhov Hospital, Jönköping Sweden.
    Lindholm, M-L.
    Department of Anaesthesia and Intensive Care, Kalmar County Hospital, Kalmar, Sweden.
    Bonnedahl, J.
    Department of Infectious Diseases, Kalmar County Hospital, Kalmar, Sweden.
    Brudin, L.
    Department of Clinical Physiology, Kalmar County Hospital, Kalmar Sweden.
    Carlsson, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    High target attainment for β-lactam antibiotics in intensive care unit patients when actual minimum inhibitory concentrations are applied.2017In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 36, no 3, p. 11p. 553-563Article in journal (Refereed)
    Abstract [en]

    Patients in the intensive care unit (ICU) are at risk for suboptimal levels of β-lactam antibiotics, possibly leading to poor efficacy. Our aim was to investigate whether the actual minimum inhibitory concentration (MIC) compared to the more commonly used arbitrary epidemiological cut-off values (ECOFFs) would affect target attainment in ICU patients on empirical treatment with broad-spectrum β-lactam antibiotics and to identify risk factors for not reaching target. In a prospective, multicenter study, ICU patients ≥18 years old and treated with piperacillin/tazobactam, meropenem, or cefotaxime were included. Clinical and laboratory data were recorded. Serum trough antibiotic levels from three consecutive days were analyzed by liquid chromatography-mass spectrometry (LC-MS). The target was defined as the free trough concentration above the MIC (100% fT). MIC was used as the target and, when available, the actual MIC (MIC) was applied. The median age of the patients was 70 years old, 52% (58/111) were males, and the median estimated glomerular filtration rate (eGFR) was 48.0 mL/min/1.73 m. The rate of patients reaching 100% fT greater than MIC was higher (89%, 31/35) compared to the same patients using MIC (60%, p = 0.002). In total, 55% (61/111) reached 100% fT greater than MIC. Increased renal clearance was independently associated to not reaching 100% fT greater than MIC. On repeated sampling, greater than77% of patients had stable serum drug levels around the MIC. Serum concentrations of β-lactam antibiotics vary extensively between ICU patients. The rate of patients not reaching target was markedly lower for the actual MIC than when the arbitrary MIC based on the ECOFF was used, which is important to consider in future studies. [ABSTRACT FROM AUTHOR]

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