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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).

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  • 2.
    Abou Ghayda, Ramy
    et al.
    Case Western Reserve Univ, OH 44106 USA.
    Lee, Keum Hwa
    Yonsei Univ, South Korea.
    Han, Young Joo
    Inje Univ, South Korea.
    Ryu, Seohyun
    Yonsei Univ, South Korea.
    Hong, Sung Hwi
    Yonsei Univ, South Korea.
    Yoon, Sojung
    Yonsei Univ, South Korea.
    Jeong, Gwang Hum
    Gyeongsang Natl Univ, South Korea.
    Yang, Jae Won
    Yonsei Univ, South Korea.
    Lee, Hyo Jeong
    Yonsei Univ, South Korea.
    Lee, Jinhee
    Yonsei Univ, South Korea.
    Lee, Jun Young
    Yonsei Univ, South Korea.
    Effenberger, Maria
    Med Univ Innsbruck, Austria.
    Eisenhut, Michael
    Luton & Dunstable Univ Hosp NHS Fdn Trust, England.
    Kronbichler, Andreas
    Med Univ Innsbruck, Austria.
    Solmi, Marco
    Univ Ottawa, Canada; Ottawa Hosp, Canada; Univ Ottawa, Canada; Univ Ottawa, Canada.
    Li, Han
    Univ Florida, FL USA.
    Jacob, Louis
    Univ Versailles St Quentin En Yvelines, France; CIBERSAM, Spain.
    Koyanagi, Ai
    CIBERSAM, Spain; ICREA, Spain.
    Radua, Joaquim
    Inst Invest Biomed August Pi & Sunyer IDIBAPS, Spain; Kings Coll London, England; Karolinska Inst, Sweden.
    Park, Myung Bae
    Pai Chai Univ, South Korea.
    Aghayeva, Sevda
    Azerbaijan Med Univ, Azerbaijan.
    Ahmed, Mohamed L. C. B.
    Univ Nouakchott Al Aasriya, Mauritania.
    Al Serouri, Abdulwahed
    Yemen Field Epidemiol Training Program, Yemen.
    Al-Shamsi, Humaid O.
    Univ Sharjah, U Arab Emirates; Burjeel Canc Inst, U Arab Emirates.
    Amir-Behghadami, Mehrdad
    Tabriz Univ Med Sci, Iran; Tabriz Univ Med Sci, Iran; Tabriz Univ Med Sci, Iran.
    Baatarkhuu, Oidov
    Mongolian Natl Univ Med Sci, Mongolia.
    Bashour, Hyam
    Damascus Univ, Syria.
    Bondarenko, Anastasiia
    Shupyk Natl Healthcare Univ Ukraine, Ukraine.
    Camacho-Ortiz, Adrian
    Univ Autonoma Nuevo Leon, Mexico.
    Castro, Franz
    Gorgas Mem Inst Hlth Studies, Panama.
    Cox, Horace
    Minist Hlth Guyana, Guyana.
    Davtyan, Hayk
    TB Res & Prevent Ctr NGO, Armenia.
    Douglas, Kirk
    Univ West Indies, Barbados.
    Dragioti, Elena
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ebrahim, Shahul
    Univ Sci Tech & Technol, Mali.
    Ferioli, Martina
    IRCCS Azienda Osped Univ Bologna, Italy.
    Harapan, Harapan
    Univ Syiah Kuala, Indonesia.
    Mallah, Saad I
    Royal Coll Surg Ireland Bahrain, Indonesia.
    Ikram, Aamer
    Natl Inst Hlth, Pakistan.
    Inoue, Shigeru
    Tokyo Med Univ, Japan.
    Jankovic, Slobodan
    Univ Kragujevac, Serbia.
    Jayarajah, Umesh
    Univ Colombo, Sri Lanka.
    Jesenak, Milos
    Comenius Univ, Slovakia.
    Kakodkar, Pramath
    Natl Univ Galway Ireland, Ireland.
    Kebede, Yohannes
    Jimma Univ, Ethiopia.
    Kifle, Meron
    Univ Oxford, England.
    Koh, David
    Natl Univ Singapore, Singapore.
    Males, Visnja K.
    Sch Med Split, Croatia.
    Kotfis, Katarzyna
    Pomeranian Med Univ, Poland.
    Lakoh, Sulaiman
    Univ Sierra Leone, Sierra Leone.
    Ling, Lowell
    Chinese Univ Hong Kong, Peoples R China.
    Llibre-Guerra, Jorge
    Washington Univ, MO USA.
    Machida, Masaki
    Tokyo Med Univ, Japan.
    Makurumidze, Richard
    Univ Zimbabwe, Zimbabwe.
    Mamun, Mohammed
    Chinese Univ Hong Kong, Peoples R China; Jahangirnagar Univ, Bangladesh; Daffodil Int Univ, Bangladesh; CHINTA Res Bangladesh, Bangladesh.
    Masic, Izet
    Acad Med Sci Bosnia & Herzegovina, Bosnia & Herceg.
    Van Minh, Hoang
    Hanoi Univ Publ Hlth, Vietnam.
    Moiseev, Sergey
    Sechenov First Moscow State Med Univ, Russia.
    Nadasdy, Thomas
    St Parascheva Clin Hosp Infect Dis, Romania.
    Nahshon, Chen
    Carmel Hosp, Israel.
    Namendys-Silva, Silvio A.
    Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico.
    Yongsi, Blaise N.
    Univ Yaounde II, Cameroon.
    Nielsen, Henning B.
    Zealand Univ Hosp Roskilde, Denmark.
    Nodjikouambaye, Zita A.
    Mobile Lab Hemorrhag & Resp Viruses Ndjamena, Chad.
    Ohnmar, Ohnmar
    Myanmar Hlth Minist, Myanmar.
    Oksanen, Atte
    Tampere Univ, Finland.
    Owopetu, Oluwatomi
    Univ Coll Hosp, Nigeria.
    Parperis, Konstantinos
    Univ Cyprus Med Sch, Cyprus.
    Perez, Gonzalo E.
    Clin Olivos, Argentina.
    Pongpirul, Krit
    Chulalongkorn Univ, Thailand.
    Rademaker, Marius
    Auckland Univ Med Sch, New Zealand.
    Rosa, Sandro
    Fed Fluminense Univ, Brazil; Natl Inst Ind Property, Brazil.
    Sah, Ranjit
    Natl Publ Hlth Lab, Nepal.
    Sallam, Dina
    Ain Shams Univ, Egypt.
    Schober, Patrick
    Vrije Univ Amsterdam, Netherlands.
    Singhal, Tanu
    Kokilaben Dhirubhai Ambani Hosp & Med Res Inst, India.
    Tafaj, Silva
    Univ Hosp Shefqet Ndroqi, Albania.
    Torres, Irene
    Fdn Octaedro, Ecuador.
    Smith Torres-Roman, J.
    Univ Cient Sur, Peru.
    Tsartsalis, Dimitrios
    Hippokrateion Hosp, Greece.
    Tsolmon, Jadamba
    Mongolian Natl Univ Med Sci, Mongolia.
    Tuychiev, Laziz
    Tashkent Med Acad, Uzbekistan.
    Vukcevic, Batric
    Univ Montenegro, Montenegro.
    Wanghi, Guy
    Univ Kinshasa, DEM REP CONGO.
    Wollina, Uwe
    Stadt Klinikum Dresden, Germany.
    Xu, Ren-He
    Univ Macau, Peoples R China.
    Yang, Lin
    Alberta Hlth Serv, Canada; Univ Calgary, Canada; Univ Calgary, Canada.
    Zaidi, Zoubida
    Univ Ferhat Abbas, Algeria.
    Smith, Lee
    Anglia Ruskin Univ, England.
    Shin, Jae Il
    Yonsei Univ, South Korea.
    The global case fatality rate of coronavirus disease 2019 by continents and national income: A meta-analysis2022In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 94, no 6, p. 2402-2413Article in journal (Refereed)
    Abstract [en]

    The aim of this study is to provide a more accurate representation of COVID-19s case fatality rate (CFR) by performing meta-analyses by continents and income, and by comparing the result with pooled estimates. We used multiple worldwide data sources on COVID-19 for every country reporting COVID-19 cases. On the basis of data, we performed random and fixed meta-analyses for CFR of COVID-19 by continents and income according to each individual calendar date. CFR was estimated based on the different geographical regions and levels of income using three models: pooled estimates, fixed- and random-model. In Asia, all three types of CFR initially remained approximately between 2.0% and 3.0%. In the case of pooled estimates and the fixed model results, CFR increased to 4.0%, by then gradually decreasing, while in the case of random-model, CFR remained under 2.0%. Similarly, in Europe, initially, the two types of CFR peaked at 9.0% and 10.0%, respectively. The random-model results showed an increase near 5.0%. In high-income countries, pooled estimates and fixed-model showed gradually increasing trends with a final pooled estimates and random-model reached about 8.0% and 4.0%, respectively. In middle-income, the pooled estimates and fixed-model have gradually increased reaching up to 4.5%. in low-income countries, CFRs remained similar between 1.5% and 3.0%. Our study emphasizes that COVID-19 CFR is not a fixed or static value. Rather, it is a dynamic estimate that changes with time, population, socioeconomic factors, and the mitigatory efforts of individual countries.

  • 3.
    Adams, Yvonne
    et al.
    Univ Copenhagen, Denmark.
    Clausen, Anne Skovsbo
    Copenhagen Univ Hosp, Denmark; Copenhagen Univ Hosp, Denmark.
    Jensen, Peter Ostrup
    Lager, Malin
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Natl Reference Lab Borrel, Div Clin Microbiol, Other Tick Borne Bacter, Lab Med, Reg Jonkoping Cty, Jonkoping, Sweden.
    Wilhelmsson, Peter
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Natl Reference Lab Borrel, Div Clin Microbiol, Other Tick Borne Bacter, Lab Med, Reg Jonkoping Cty, Jonkoping, Sweden.
    Jonsson Henningsson, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology. Natl Reference Lab Borrel, Div Clin Microbiol, Other Tick Borne Bacter, Lab Med, Reg Jonkoping Cty, Jonkoping, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Natl Reference Lab Borrel, Div Clin Microbiol, Other Tick Borne Bacter, Lab Med, Reg Jonkoping Cty, Jonkoping, Sweden.
    Faurholt-Jepsen, Daniel
    Copenhagen Univ Hosp, Denmark.
    Mens, Helene
    Copenhagen Univ Hosp, Denmark.
    Kraiczy, Peter
    Goethe Univ Frankfurt, Germany.
    Kragh, Kasper Norskov
    Copenhagen Univ Hosp, Denmark; Univ Copenhagen, Denmark.
    Bjarnsholt, Thomas
    Copenhagen Univ Hosp, Denmark; Univ Copenhagen, Denmark.
    Kjaer, Andreas
    Copenhagen Univ Hosp, Denmark; Copenhagen Univ Hosp, Denmark.
    Lebech, Anne-Mette
    Copenhagen Univ Hosp, Denmark; Univ Copenhagen, Denmark.
    Jensen, Anja R.
    Univ Copenhagen, Denmark.
    3D blood-brain barrier-organoids as a model for Lyme neuroborreliosis highlighting genospecies dependent organotropism2023In: ISCIENCE, ISSN 2589-0042, Vol. 26, no 1, article id 105838Article in journal (Refereed)
    Abstract [en]

    Lyme neuroborreliosis (LNB), a tick-borne infection caused by spirochetes within the Borrelia burgdorferi sensu lato (s.L.) complex, is among the most prevalent bacterial central nervous system (CNS) infections in Europe and the US. Here we have screened a panel of low- passage B. burgdorferi s.l. isolates using a novel, human-derived 3D blood-brain barrier (BBB)-organoid model. We show that human-derived BBB-organoids support the entry of Borrelia spirochetes, leading to swelling of the organoids and a loss of their structural integrity. The use of the BBB-organoid model highlights the organotropism between B. burgdorferi s.l. genospecies and their ability to cross the BBB contributing to CNS infection.

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  • 4.
    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.

  • 5.
    Al Abri, Seif
    et al.
    Minist Hlth, Oman.
    Kasaeva, Thereza
    Who Global TB Programme, Switzerland.
    Migliori, Giovanni Battista
    Ist Clin Sci Maugeri IRCCS, Italy.
    Goletti, Delia
    Natl Inst Infect Dis Lazzaro Spallanzani IRCCS, Italy; ESCMID Study Grp Mycobacteria, Switzerland.
    Zenner, Dominik
    IOM, Belgium.
    Denholm, Justin
    Royal Melbourne Hosp, Australia; Victorian TB Programme, Australia.
    Al Maani, Amal
    Royal Hosp, Oman; Minist Hlth, Oman.
    Cirillo, Daniela Maria
    San Rafaele Sci Inst, Italy.
    Schön, Thomas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Kalmar Cty Hosp, Sweden.
    Lillebaek, Troels
    Univ Copenhagen, Denmark.
    Al-Jardani, Amina
    Minist Hlth, Oman.
    Go, Un-Yeong
    Int TB Res Ctr, South Korea.
    Dias, Hannah Monica
    WHO Global TB Programme Unit Policy Strategy and In, Switzerland.
    Tiberi, Simon
    Barts Hlth NHS Trust, England; Queen Mary Univ London, England.
    Al Yaquobi, Fatma
    Minist Hlth, Oman.
    Khamis, Faryal Ali
    Minist Hlth, Oman.
    Kurup, Padmamohan
    Muscat Governorate, Oman.
    Wilson, Michael
    Zero TB Initiat, South Africa.
    Memish, Ziad
    Alfaisal Univ, Saudi Arabia; Emory Univ, GA 30322 USA.
    Al Maqbali, Ali
    North Bathinah Governorate, Oman.
    Akhtar, Muhammad
    WHO MENA Reg TB Programme, Egypt.
    Wejse, Christian
    Univ Aarhus, Denmark; ESCMID Study Grp Travel and Migrat, Switzerland.
    Petersen, Eskild
    Minist Hlth, Oman; Univ Aarhus, Denmark; ESCMID Emerging Infect Task Force, Switzerland.
    Tools to implement the World Health Organization End TB Strategy: Addressing common challenges in high and low endemic countries2020In: International Journal of Infectious Diseases, ISSN 1201-9712, E-ISSN 1878-3511, Vol. 92, p. S60-S68Article in journal (Refereed)
    Abstract [en]

    Aim: The purpose of this viewpoint is to summarize the advantages and constraints of the tools and strategies available for reducing the annual incidence of tuberculosis (TB) by implementing the World Health Organization (WHO) End TB Strategy and the linked WHO TB Elimination Framework, with special reference to Oman. Methods: The case-study was built based on the presentations and discussions at an international workshop on TB elimination in low incidence countries organized by the Ministry of Health, Oman, which took place from September 5 to September 7, 2019, and supported by the WHO and European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Results: Existing tools were reviewed, including the screening of migrants for latent TB infection (LTBI) with interferon-gamma release assays, clinical examination for active pulmonary TB (APTB) including chest X-rays, organization of laboratory services, and the existing centres for mandatory health examination of pre-arrival or arriving migrants, including examination for APTB. The need for public-private partnerships to handle the burden of screening arriving migrants for active TB was discussed at length and different models for financing were reviewed. Conclusions: In a country with a high proportion of migrants from high endemic countries, screening for LTBI is of high priority. Molecular typing and the development of public-private partnerships are needed. (C) 2020 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

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  • 6.
    Alfsnes, Kristian
    et al.
    Norwegian Inst Publ Hlth, Norway.
    Lagerqvist, Nina
    Publ Hlth Agcy Sweden, Sweden.
    Vene, Sirkka
    Publ Hlth Agcy Sweden, Sweden.
    Bohlin, Jon
    Norwegian Inst Publ Hlth, Norway.
    Verner-Carlsson, Jenny
    Publ Hlth Agcy Sweden, Sweden.
    Ekqvist, David
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Brave, Andreas
    Publ Hlth Agcy Sweden, Sweden.
    Holmes, Edward C.
    Univ Sydney, Australia; Univ Sydney, Australia.
    Shi, Weifeng
    Shandong First Med Univ & Shandong Acad Med Sci, Peoples R China.
    Pettersson, John H-O
    Publ Hlth Agcy Sweden, Sweden; Univ Sydney, Australia; Univ Sydney, Australia; Uppsala Univ, Sweden.
    Retrospective meta-transcriptomic identification of severe dengue in a traveller returning from Africa to Sweden, 19902021In: One Health, ISSN 2352-7714, Vol. 12, article id 100217Article in journal (Refereed)
    Abstract [en]

    Pathogens associated with haemorrhagic fever commonly have zoonotic origins. The first documented imported case of likely viral severe haemorrhagic fever in Sweden occurred in 1990. Despite extensive study, no aetiological agent was identified. Following retrospective investigation with total RNA-sequencing of samples collected between 7 and 36 days from onset of symptoms we identified dengue virus 3 (DENV-3) and a human pegivirus (HPgV). We conclude that the patient likely suffered from haemorrhagic symptoms due to an atypical severe and undiagnosed dengue infection.

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  • 7.
    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, 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.

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  • 8.
    Andersson, Martin
    et al.
    Reg Kronoberg, Sweden.
    Pallon, Jon
    Reg Kronoberg, Sweden; Lund Univ, Sweden.
    Cronberg, Olof
    Reg Kronoberg, Sweden; Lund Univ, Sweden.
    Sundqvist, Martin
    Orebro Univ, Sweden.
    Hedin, Katarina
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Lund Univ, Sweden; Reg Jönköping Cty, Sweden.
    Seasonal variations in use and outcome of rapid antigen detection tests and cultures in pharyngotonsillitis: a register study in primary care2021In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 21, no 1, article id 1104Article in journal (Refereed)
    Abstract [en]

    Background Diagnosis and treatment of pharyngotonsillitis are commonly focused on group A streptococci (GAS), although the disease is often associated with other pathogens. While the incidence of pharyngotonsillitis is known to vary with season, seasonal variations in the prevalence of potential pathogens are sparsely explored. The aim of this study was to explore any seasonal variations in the use and outcome of rapid antigen detection tests (RADTs) for GAS and throat cultures among patients diagnosed with pharyngotonsillitis in primary care. Methods We retrieved and combined retrospective data from the electronic medical record system and the laboratory information system in Kronoberg County, Sweden. Primary care visits resulting in a diagnosis of tonsillitis or pharyngitis were included, covering the period 2013-2016. The monthly rate of visits was measured, along with the use and outcome of RADTs for GAS and throat cultures obtained on the date of diagnosis. The variations between calendar months were then analysed. Results We found variations between calendar months, not only in the mean rate of visits resulting in a diagnosis of pharyngotonsillitis (p < 0.001), but in the mean proportion of RADTs being positive for GAS among the diagnosed (p < 0.001), and in the mean proportion of visits associated with a throat culture (p < 0.001). A lower mean rate of visits in August and September coincided with a lower proportion of RADTs being positive for GAS among them, which correlated with a higher proportion of visits associated with a throat culture. Conclusions This study suggests that the role of GAS in pharyngotonsillitis in Sweden is less prominent in August and September than during the rest of the year.

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  • 9. Antimycobacterial Susceptibility Testing Group,
    Updating the approaches to define susceptibility and resistance to anti-tuberculosis agents: implications for diagnosis and treatment2022In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 59, no 4Article in journal (Other academic)
    Abstract [en]

    Inappropriately high breakpoints have resulted in systematic false-susceptible AST results to anti-TB drugs. MIC, PK/PD and clinical outcome data should be combined when setting breakpoints to minimise the emergence and spread of antimicrobial resistance.

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  • 10.
    Arnason, Sigurdur
    et al.
    Dept Clin Sci Intervent & Technol CLINTEC, Sweden; Astrid Lindgrens Childrens Hosp, Sweden.
    Molewijk, Kesia
    Orebro Univ, Sweden.
    Henningsson, Anna J.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology. Laboratory Medicine, Region Jönköping County, Sweden.
    Tjernberg, Ivar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Reg Kalmar Cty, Sweden.
    Skogman, Barbro H.
    Orebro Univ, Sweden; Uppsala Univ, Sweden; Karolinska Inst, Sweden.
    Brain damage markers neuron-specific enolase (NSE) and S100B in serum in children with Lyme neuroborreliosis-detection and evaluation as prognostic biomarkers for clinical outcome2022In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 41, p. 1051-1057Article in journal (Refereed)
    Abstract [en]

    Lyme borreliosis (LB) is the most common tick-borne infection in Europe, with Lyme neuroborreliosis (LNB) its second most frequent clinical manifestation. Prognostic factors for clinical outcomes in LNB have not been identified. Elevated serum levels of the brain damage markers neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) have been associated with poor clinical outcomes in other disorders of the central nervous system. The aim of this study is to assess NSE and S100B in serum as prognostic biomarkers for clinical outcomes in paediatric LNB patients. Children evaluated for LNB (n= 121) in Sweden were prospectively included during 2010-2014, serum samples were collected on admission, and all children underwent a 2-month follow-up. Patients with pleocytosis and anti-Borrelia antibodies in cerebrospinal fluid (CSF) were classified as having LNB (n= 61). Controls were age- and gender-matched non-LNB patients (n= 60). NSE was elevated in 38/61 (62%) LNB patients and in 31/60 (52%) controls. S100B was elevated in 3/60 (5%) LNB patients and 0/59 (0%) controls. NSE and S100B concentrations did not differ significantly when comparing LNB patients with controls. No differences were found in the concentrations when comparing the clinical recovery of LNB patients at the 2-month follow-up. NSE was detectable in the majority of LNB patients and controls, whereas S100B was detectable in only a few LNB patients and no controls. NSE and S100B in serum cannot be recommended as prognostic biomarkers for clinical outcomes in children with LNB.

  • 11.
    Arvidsson, Åsa
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Lafta, Gihan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Sönnerbrandt, Martina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Sundelin, Karin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Paues, Jakob
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    The cascade of care for pregnant women with latent tuberculosis infection in a high-income country2023In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 55, no 9, p. 635-645Article in journal (Refereed)
    Abstract [en]

    Background: Pregnant women have an increased risk of developing active tuberculosis (TB). The Public Health Agency of Sweden recommends screening of active TB and latent tuberculosis infection (LTBI) among pregnant women from countries with high TB incidence at Maternal Health Care (MHC) clinics. In ostergotland County, Sweden, a screening program has been active since 2013. The aim of this study was to evaluate this screening program and the cascade of care for LTBI among pregnant women in ostergotland county.Methods: Data were obtained from pregnant women screened for TB at MHC clinics and subsequently referred to the pulmonary medicine clinic or the clinic of infectious diseases in ostergotland County between 2013 and 2018. The Public Health Agency of Swedens national database for active TB was used to analyse if any women developed active TB up to two years after the screening process.Results: A total of 439 women were included. Nine cases of active TB were discovered during the screening process and two developed active TB afterward. 177 women were recommended LTBI treatment and variables significantly associated with a decreased likelihood of being recommended treatment were increasing age, time in Sweden, and parity. 137 women received and 112 (82%) completed treatment. 14 women discontinued treatment due to adverse effects.Conclusion: Screening of pregnant women from countries with high TB incidence at MHC clinics led to the discovery of several cases of active TB. The completion rate of LTBI treatment was high and few discontinued due to adverse effects.

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  • 12.
    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.

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  • 13.
    Atterby, Clara
    et al.
    Uppsala University.
    Ramey, Andrew M.
    US Geological Survey, USA.
    Hall, Gabriel Gustafsson
    Uppsala University.
    Järhult, Josef
    Uppsala University.
    Börjesson, Stefan
    National Veterinary Institute.
    Bonnedahl, Jonas
    Linnéuniversitetet, Institutionen för biologi och miljö (BOM).
    Increased prevalence of antibiotic-resistant E. coli in gulls sampled in Southcentral Alaska is associated with urban environments2016In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 6, no 1, p. 1-7, article id 32334Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Antibiotic-resistant bacteria pose challenges to healthcare delivery systems globally; however, limited information is available regarding the prevalence and spread of such bacteria in the environment. The aim of this study was to compare the prevalence of antibiotic-resistant bacteria in large-bodied gulls (Larus spp.) at urban and remote locations in Southcentral Alaska to gain inference into the association between antibiotic resistance in wildlife and anthropogenically influenced habitats.

    METHODS: Escherichia coli was cultured (n=115 isolates) from fecal samples of gulls (n=160) collected from a remote location, Middleton Island, and a more urban setting on the Kenai Peninsula.

    RESULTS: Screening of E. coli from fecal samples collected from glaucous-winged gulls (Larus glaucescens) at Middleton Island revealed 8% of isolates were resistant to one or more antibiotics and 2% of the isolates were resistant to three or more antibiotics. In contrast, 55% of E. coli isolates derived from fecal samples collected from large-bodied gulls (i.e. glaucous, herring [Larus argentatus], and potentially hybrid gulls) on the Kenai Peninsula were resistant to one or more antibiotics and 22% were resistant to three or more antibiotics. In addition, total of 16% of the gull samples from locations on the Kenai Peninsula harbored extended-spectrum cephalosporin-resistant E. coli isolates (extended-spectrum beta-lactamases [ESBL] and plasmid-encoded AmpC [pAmpC]), in contrast to Middleton Island where no ESBL- or pAmpC-producing isolates were detected.

    CONCLUSION: Our findings indicate that increased prevalence of antibiotic resistance is associated with urban environments in Southcentral Alaska and presumably influenced by anthropogenic impacts. Further investigation is warranted to assess how migratory birds may maintain and spread antimicrobial-resistant bacteria of relevance to human and animal health.

  • 14.
    Bai, Xiangning
    et al.
    Oslo Univ Hosp, Norway; Karolinska Inst, Sweden.
    Ylinen, Elisa
    Univ Helsinki, Finland; Helsinki Univ Hosp, Finland.
    Zhang, Ji
    Minist Primary Ind, New Zealand.
    Salmenlinna, Saara
    Finnish Inst Hlth & Welf, Finland.
    Halkilahti, Jani
    Finnish Inst Hlth & Welf, Finland.
    Saxen, Harri
    Univ Helsinki, Finland; Helsinki Univ Hosp, Finland.
    Narayanan, Aswathy
    Karolinska Inst, Sweden.
    Jahnukainen, Timo
    Univ Helsinki, Finland; Helsinki Univ Hosp, Finland.
    Matussek, Andreas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Oslo Univ Hosp, Norway; Karolinska Inst, Sweden; Univ Oslo, Norway; Laboratory Medicine, Jönköping Region County, Jönköping, Sweden.
    Comparative Genomics of Shiga Toxin-Producing Escherichia coli Strains Isolated from Pediatric Patients with and without Hemolytic Uremic Syndrome from 2000 to 2016 in FinlandIn: Microbiology Spectrum, E-ISSN 2165-0497Article in journal (Refereed)
    Abstract [en]

    Shiga toxin-producing Escherichia coli (STEC) is a serious public health burden worldwide which causes outbreaks of gastrointestinal diseases and the fatal hemolytic uremic syndrome (HUS) characterized by the triad of mechanical hemolytic anemia, thrombocytopenia, and acute renal failure. Understanding the mechanism underlying the disease severity and patient outcome is of high importance. Shiga toxin-producing Escherichia coli (STEC) infection can cause mild to severe illness, such as nonbloody or bloody diarrhea, and the fatal hemolytic uremic syndrome (HUS). The molecular mechanism underlying the variable pathogenicity of STEC infection is not fully defined so far. Here, we performed a comparative genomics study on a large collection of clinical STEC strains collected from STEC-infected pediatric patients with and without HUS in Finland over a 16-year period, aiming to identify the bacterial genetic factors that can predict the risk to cause HUS and poor renal outcome. Of 240 STEC strains included in this study, 52 (21.7%) were from pediatric patients with HUS. Serotype O157:H7 was the main cause of HUS, and Shiga toxin gene subtype stx2a was significantly associated with HUS. Comparative genomics and pangenome-wide association studies identified a number of virulence and accessory genes overrepresented in HUS-associated STEC compared to non-HUS STEC strains, including genes encoding cytolethal distending toxins, type III secretion system effectors, adherence factors, etc. No virulence or accessory gene was significantly associated with risk factors for poor renal outcome among HUS patients assessed in this study, including need for and duration of dialysis, presence and duration of anuria, and leukocyte counts. Whole-genome phylogeny and multiple-correspondence analysis of pangenomes could not separate HUS STEC from non-HUS STEC strains, suggesting that STEC strains with diverse genetic backgrounds may independently acquire genetic elements that determine their varied pathogenicity. Our findings indicate that nonbacterial factors, i.e., characteristics of the host immunity, might affect STEC virulence and clinical outcomes. IMPORTANCE Shiga toxin-producing Escherichia coli (STEC) is a serious public health burden worldwide which causes outbreaks of gastrointestinal diseases and the fatal hemolytic uremic syndrome (HUS) characterized by the triad of mechanical hemolytic anemia, thrombocytopenia, and acute renal failure. Understanding the mechanism underlying the disease severity and patient outcome is of high importance. Using comparative genomics on a large collection of clinical STEC strains from STEC-infected patients with and without HUS, our study provides a reference of STEC genetic factors/variants that can be used as predictors of the development of HUS, which will aid risk assessment at the early stage of STEC infection. Additionally, our findings suggest that nonbacterial factors may play a primary role in the renal outcome in STEC-infected patients with HUS; further studies are needed to validate this.

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  • 15.
    Balata, Dilan
    et al.
    Region Östergötland, Heart Center, Department of Cardiology in Linköping.
    Mellergård, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping.
    Ekqvist, David
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Baranowski, Jacek
    Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Garcia, Isidro Albert
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Volosyraki, Marina
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Broqvist, Mats
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Cardiology in Linköping.
    Non-Bacterial Thrombotic Endocarditis: A Presentation of COVID-192020In: European journal of case reports in internal medicine, ISSN 2284-2594, Vol. 7, no 8Article in journal (Refereed)
    Abstract [en]

    The SARS-CoV-2 virus is a newly emergent pathogen first identified in Wuhan, China, and responsible for the COVID-19 global pandemic. In this case report we describe a manifestation of non-bacterial thrombotic endocarditis with continuous peripheral embolization in a COVID-19-positive patient. The patient responded well to high-dose LMWH treatment with cessation of the embolic process.

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  • 16.
    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, 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.

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  • 17.
    Barathan, Muttiah
    et al.
    Univ Malaya, Malaysia.
    Riazalhosseini, Behnaz
    Univ Malaya, Malaysia.
    Iyadorai, Thevambiga
    Univ Malaya, Malaysia.
    Vellasamy, Kumutha Malar
    Univ Malaya, Malaysia.
    Vadivelu, Jamuna
    Univ Malaya, Malaysia.
    Chang, Li-Yen
    Univ Malaya, Malaysia.
    Zulpa, Ahmad Khusairy
    Univ Malaya, Malaysia.
    Larsson, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Shankar, Esaki M.
    Cent Univ Tamil Nadu, India.
    Mohamed, Rosmawati
    Univ Malaya, Malaysia.
    Comparative expression of pro-inflammatory and apoptotic biosignatures in chronic HBV-infected patients with and without liver cirrhosis2021In: Microbial Pathogenesis, ISSN 0882-4010, E-ISSN 1096-1208, Vol. 161, article id 105231Article in journal (Refereed)
    Abstract [en]

    The interplay of immune mediators is paramount to optimal host anti-viral immune responses, especially against chronic hepatitis B virus (HBV) infection. Here, we investigated the dynamic changes in host immune responses in chronic HBV-infected individuals with and without liver cirrhosis by examining the signatures of apoptosis and plasma levels of pro-inflammatory cytokines, chemokines, and cytotoxic proteins. A total of 40 chronic HBV patients with and without liver cirrhosis were studied for plasma levels of immune mediators, and signatures of apoptosis in peripheral blood mononuclear cells (PBMCs). The intracellular concentrations of reactive oxygen species (ROS) in patients with chronic HBV with liver cirrhosis was relatively higher as compared to chronic HBV patients. The onset of apoptosis was sustained due to ongoing liver inflammation in concert with plasma TNF-alpha and IL-6 levels. Plasma VEGF was upregulated among chronic HBV patients with liver cirrhosis, whereas CCL2, CCL5 and granzyme B levels were down-regulated. High levels of ROS, IL-6 and TNF-alpha correlated with ongoing inflammation among chronic HBV patients with liver cirrhosis, which likely attributed to the expression of biosignatures of apoptosis and activation in immune cells.

  • 18.
    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, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology.
    Svensson, Lennart
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology.
    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.

  • 19.
    Barraud, Damien
    et al.
    CHR Metz Thionville, France.
    Besançon, Lonni
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Bik, Elisabeth M.
    Harbers Bik LLC, CA USA.
    Billy, Eric
    Strasbourg, France.
    Clarot, Franck
    Univ Rouen, France.
    Frank, Fabrice
    Essaouira, Morocco.
    Guihur, Anthony
    Univ Lausanne UNIL, Switzerland.
    Hajage, David
    Sorbonne Univ, France.
    Lacombe, Karine
    Sorbonne Univ, France.
    Maisonneuve, Herve
    Univ Paris Cite, France.
    Molimard, Mathieu
    Univ Bordeaux, France; Univ Neuchatel, Switzerland.
    Mulot, Matthieu
    Univ Neuchatel, Switzerland.
    Samuel, Alexander
    Nice, France.
    Why the article that led to the widespread use of hydroxychloroquine in COVID-19 should be retracted2023In: Therapie (Paris), ISSN 0040-5957, E-ISSN 1958-5578, Vol. 78, no 4, p. 437-440Article in journal (Other academic)
  • 20.
    Bengtsson, Torbjorn
    et al.
    Orebro Univ, Sweden.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering. Orebro Univ, Sweden.
    Musa, Amani
    Orebro Univ, Sweden.
    Hultenby, Kjell
    Karolinska Inst, Sweden.
    Utterström, Johanna
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Sivler, Petter
    S2Medical AB, SE-58273 Linkoping, Sweden.
    Skog, Marten
    S2Medical AB, SE-58273 Linkoping, Sweden.
    Nayeri, Fariba
    PEAS Res Inst, Dept Infect Control, SE-58273 Linkoping, Sweden.
    Hellmark, Bengt
    Orebro Univ Hosp, Sweden.
    Soderquist, Bo
    Orebro Univ, Sweden; Orebro Univ Hosp, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Khalaf, Hazem
    Orebro Univ, Sweden.
    Plantaricin NC8 alpha beta exerts potent antimicrobial activity against Staphylococcus spp. and enhances the effects of antibiotics2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 3580Article in journal (Refereed)
    Abstract [en]

    The use of conventional antibiotics has substantial clinical efficacy, however these vital antimicrobial agents are becoming less effective due to the dramatic increase in antibiotic-resistant bacteria. Novel approaches to combat bacterial infections are urgently needed and bacteriocins represent a promising alternative. In this study, the activities of the two-peptide bacteriocin PLNC8 alpha beta were investigated against different Staphylococcus spp. The peptide sequences of PLNC8 alpha and beta were modified, either through truncation or replacement of all L-amino acids with D-amino acids. Both L- and D-PLNC8 alpha beta caused rapid disruption of lipid membrane integrity and were effective against both susceptible and antibiotic resistant strains. The D-enantiomer was stable against proteolytic degradation by trypsin compared to the L-enantiomer. Of the truncated peptides, beta 1-22, beta 7-34 and beta 1-20 retained an inhibitory activity. The peptides diffused rapidly (2min) through the bacterial cell wall and permeabilized the cell membrane, causing swelling with a disorganized peptidoglycan layer. Interestingly, sub-MIC concentrations of PLNC8 alpha beta substantially enhanced the effects of different antibiotics in an additive or synergistic manner. This study shows that PLNC8 alpha beta is active against Staphylococcus spp. and may be developed as adjuvant in combination therapy to potentiate the effects of antibiotics and reduce their overall use.

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  • 21.
    Bengtsson, Torbjörn
    et al.
    Örebro University, Sweden.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering. Örebro University, Sweden.
    Musa, Amani
    Örebro University, Sweden.
    Hultenby, Kjell
    Karolinska Institutet, Sweden.
    Utterström, Johanna
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Sivlér, Petter
    S2Medical AB, 58273, Linköping, Sweden.
    Skog, Mårten
    S2Medical AB, 58273, Linköping, Sweden.
    Nayeri, Fariba
    Department of Infection Control, PEAS Research Institute, Linköping, Sweden.
    Hellmark, Bengt
    Department of Clinical Microbiology, Örebro University Hospital, Sweden.
    Söderquist, Bo
    Cardiovascular Research Centre, School of Medical Sciences, Örebro University, 70362, Örebro, Sweden; Department of Clinical Microbiology, Örebro University Hospital, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Khalaf, Hazem
    Cardiovascular Research Centre, School of Medical Sciences, Örebro University, Sweden.
    Author Correction: Plantaricin NC8 aß exerts potent antimicrobial activity against Staphylococcus spp. and enhances the effects of antibiotics2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1Article in journal (Other academic)
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  • 22.
    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.

  • 23.
    Bewket, Gezahegn
    et al.
    Univ Gondar, Ethiopia.
    Kiflie, Amare
    Univ Gondar, Ethiopia.
    Abate, Ebba
    Univ Gondar, Ethiopia; Ethiopian Publ Hlth Inst, Ethiopia.
    Stendahl, Olle
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Schön, Thomas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases. Kalmar Cty Hosp, Sweden.
    Blomgran, Robert
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Helminth species specific expansion and increased TNF-alpha production of non-classical monocytes during active tuberculosis2021In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 15, no 3, article id e0009194Article in journal (Refereed)
    Abstract [en]

    Author summary Monocytes are important cells for the early innate immune response and play an integral part during inflammation and infection. Classical monocytes, the dominant monocyte subset during homeostasis and health, have been linked to efficient TB protection. Intermediate or non-classical monocytes have instead been associated with uncontrolled inflammation (TNF-alpha), cell death, and poor protection against Mycobacterium tuberculosis. In areas endemic for intestinal helminths, the immunoregulatory effects of monocytes may affect development or progression of TB disease. The role of monocyte subsets during helminth/TB coinfection have not been studied. In Gondar, Ethiopia, we show that in patients with helminth infection, a helminth species dependent expansion of non-classical monocytes is triggered, where Ascaris and hookworm had the strongest effect in coinfected pulmonary TB-patients. The increase in non-classical monocytes was mainly detected in coinfected patients with a low-to-intermediate disease severity. Only coinfection with helminths and TB induced an increased TNF-alpha response in monocytes. Thus, we found a helminth species-specific dysregulation of monocyte subset distribution and functionality in coinfected TB-patients which could affect TB pathogenesis. Both Mycobacterium tuberculosis infection and helminths may affect innate immune mechanisms such as differential effects on monocytes towards the non-classical and intermediate subsets that favor bacterial persistence. Our aim, was to investigate helminth species specific effects on the frequency and functional activity of monocyte subsets in patients with active tuberculosis and healthy subjects. HIV-negative patients with active pulmonary tuberculosis (PTB) and community controls (CCs) in Gondar, Ethiopia were screened for helminth infection by stool microscopy. Flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and ex vivo stimulation with purified protein derivative (PPD) and helminth antigens were used to characterize the distribution of monocyte subsets and their function. A total of 74 PTB patients and 57 CCs with and without helminth infection were included. Non-classical monocytes were increased in PTB patients with Ascaris and hookworm infection but not in Schistosoma-infected patients. Ascaris had the strongest effect in increasing the frequency of non-classical monocytes in both PTB patients and CCs, whereas PTB without helminth infection did not affect the frequency of monocyte subsets. There was a helminth specific increase in the frequency of TNF-alpha producing non-classical monocytes in hookworm infected PTB patients, both with and without PPD-stimulation. Low-to-intermediate TB disease severity associated with increased frequency of non-classical monocytes only for helminth-positive PTB patients, and the frequency of TNF-alpha producing monocytes were significantly higher in intermediate and non-classical monocytes of helminth positive PTB patients with an intermediate disease score. Helminth infection affected the frequency of monocyte subsets and function both in TB patients and controls which was helminth species dependent in TB patients. The clinical role of this potential immunomodulatory effect needs further study and may affect the response and protection to tuberculosis in areas where helminth infections are endemic.

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  • 24.
    Bewket, Gezahegn
    et al.
    Univ Gondar, Ethiopia.
    Kiflie, Amare
    Univ Gondar, Ethiopia.
    Tajebe, Fitsumbrhan
    Univ Gondar, Ethiopia.
    Abate, Ebba
    Ethiopian Publ Hlth Inst, Ethiopia.
    Schön, Thomas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Blomgran, Robert
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Helminth species dependent effects on Th1 and Th17 cytokines in active tuberculosis patients and healthy community controls2022In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 16, no 8, article id e0010721Article in journal (Refereed)
    Abstract [en]

    Despite that the impact of different helminth species is not well explored, the current dogma states that helminths affect the Th1/Th2 balance which in turn affects the risk of tuberculosis (TB) reactivation and severity of disease. We investigated the influence of helminth species on cytokine profiles including IL-17A in TB patients and healthy community controls (CCs). In total, 104 newly diagnosed pulmonary TB patients and 70 HIV negative and Quanti-FERON negative CCs in Gondar, Ethiopia were included following helminth screening by stool microscopy. Plasma samples and ex vivo stimulation of peripheral blood mononuclear cells (PBMCs) with purified protein derivative (PPD) and Staphylococcus enterotoxin B (SEB) was used to determine cytokine profiles by cytometric bead array. In CCs, Ascaris lumbricoides or Schistosoma mansoni infections were associated with an impaired Th1-type response (IFN-gamma, IL-6 and TNF-alpha) in PBMCs mainly with SEB stimulations, whereas in TB patients only hookworm infection showed a similar pattern. Among CCs, the IL-17A response in PBMCs stimulated with SEB was higher only for S. mansoni, whereas in TB patients, the elevated systemic IL-17A plasma level was significantly suppressed in hookworm infected TB patients compared to patients without helminth coinfection. Following treatment of TB and helminth infection there was a general decrease in ex vivio IL-10 and TNF-alpha production in unstimulated, PPD or SEB stimulated PBMCs that was the most pronounced and significant in TB patients infected with S. mansoni, whereas the follow-up levels of IFN-gamma and IL-17A was significantly increased only in TB patients without helminth coinfection from PBMCs stimulated mainly with SEB. In summary, in addition to confirming helminth specific effects on the Th1/Th2 response before and after TB treatment, our novel finding is that IL-17A was impaired in helminth infected TB patients especially for hookworm, indicating a helminth species-specific immunoregulatory effect on IL-17A which needs to be further investigated.

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  • 25.
    Bladh, Oscar
    et al.
    Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Marking, Ulrika
    Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Havervall, Sebastian
    Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Norin, Nina Greilert
    Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Aguilera, Katherina
    Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Hober, Sophia
    Department of Protein Science, KTH Royal Institute of Technology, SciLifeLab, Stockholm, Sweden.
    Smed-Sörensen, Anna
    Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Gordon, Max
    Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Blom, Kim
    Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden; Public Health Agency of Sweden, Solna, Sweden.
    Åberg, Mikael
    Department of Medical Sciences, Clinical Chemistry and SciLifeLab Affinity Proteomics, Uppsala University, Uppsala, Sweden.
    Klingström, Jonas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences. Public Health Agency of Sweden, Solna, Sweden.
    Thålin, Charlotte
    Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Mucosal immune responses following a fourth SARS-CoV-2 vaccine dose2023In: The Lancet Microbe, ISSN 2666-5247, Vol. 4, no 7, p. e488-e488Article in journal (Refereed)
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  • 26.
    Bläckberg, Jonas
    et al.
    Infectious Diseases - Lund, Sweden.
    Asgeirsson, Hilmir
    Karolinska Universitetssjukhuset - Infektionssjukdomar Stockholm, Sweden .
    Glimåker, Kajsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Lier, Tore
    Folkhälsomyndigheten - Enheten för parasitologi Solna, Sweden.
    Sasor, Agata
    Region Skåne - Labmedicin, Patologi Lund, Sweden .
    Flera svenska fall av infektion med rävens dvärgbandmask [Echinococcus multilocularis infection - six cases during two years in Sweden]2020In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 117Article, review/survey (Refereed)
    Abstract [en]

    Alveolar echinococcosis (AE) caused by the fox tapeworm Echinococcus multilocularis is a zoonosis presenting with focal liver lesions and has a poor prognosis without treatment. The disease is common in Central and Eastern Europe but has been highly unusual in Sweden. A suspicion of AE usually arises through radiology and the diagnosis may be confirmed by histology and/or serological antibody detection. AE is treated with radical surgery in combination with anti-helminthic drug therapy. During the last two years six cases of AE have been diagnosed in Sweden. In no case was AE suspected clinically before biopsy. A heightened awareness of AE is needed among Swedish physicians, including radiologists, surgeons and pathologists.

  • 27.
    Boateng, Irene
    et al.
    Univ Southampton, England.
    Stuart, Beth
    Univ Southampton, England; Queen Mary Univ London, England.
    Becque, Taeko
    Univ Southampton, England.
    Barrett, Bruce
    Univ Wisconsin, WI USA.
    Bostock, Jennifer
    Univ Southampton, England.
    Bruyndonckx, Robin
    Hasselt Univ, Belgium.
    Carr-Knox, Lucy
    Queen Mary Univ London, England.
    Ciccone, Emily J.
    Univ North Carolina Chapel Hill, NC USA.
    Coenen, Samuel
    Univ Antwerp, Belgium; Univ Antwerp, Belgium.
    Ebell, Mark
    Univ Georgia, GA 30602 USA.
    Gillespie, David
    Cardiff Univ, Wales.
    Hayward, Gail
    Univ Oxford, England.
    Hedin, Katarina
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Futurum, Sweden.
    Hood, Kerenza
    Cardiff Univ, Wales.
    Lau, Tin Man Mandy
    Cardiff Univ, Wales.
    Little, Paul
    Univ Southampton, England.
    Merenstein, Dan
    Georgetown Univ, DC 20007 USA.
    Mulogo, Edgar
    Mbarara Univ Sci & Technol, Uganda.
    Ordonez-Mena, Jose
    Univ Oxford, England.
    Muir, Peter
    UK Hlth Secur Agcy, England.
    Samuel, Kirsty
    Univ Southampton, England.
    Shaikh, Nader
    Univ Pittsburgh, PA USA.
    Tonner, Sharon
    Univ Oxford, England.
    van der Velden, Alike W.
    Univ Med Ctr Utrecht, Netherlands.
    Verheij, Theo
    Univ Med Ctr Utrecht, Netherlands.
    Wang, Kay
    Univ Southampton, England.
    Hay, Alastair D.
    Univ Bristol, England.
    Francis, Nick
    Univ Southampton, England.
    Using microbiological data to improve the use of antibiotics for respiratory tract infections: A protocol for an individual patient data meta-analysis2023In: PLOS ONE, E-ISSN 1932-6203, Vol. 18, no 11, article id e0294845Article in journal (Refereed)
    Abstract [en]

    BackgroundResistance to antibiotics is rising and threatens future antibiotic effectiveness. 'Antibiotic targeting' ensures patients who may benefit from antibiotics receive them, while being safely withheld from those who may not. Point-of-care tests may assist with antibiotic targeting by allowing primary care clinicians to establish if symptomatic patients have a viral, bacterial, combined, or no infection. However, because organisms can be harmlessly carried, it is important to know if the presence of the virus/bacteria is related to the illness for which the patient is being assessed. One way to do this is to look for associations with more severe/prolonged symptoms and test results. Previous research to answer this question for acute respiratory tract infections has given conflicting results with studies has not having enough participants to provide statistical confidence.AimTo undertake a synthesis of IPD from both randomised controlled trials (RCTs) and observational cohort studies of respiratory tract infections (RTI) in order to investigate the prognostic value of microbiological data in addition to, or instead of, clinical symptoms and signs.MethodsA systematic search of Cochrane Central Register of Controlled Trials, Ovid Medline and Ovid Embase will be carried out for studies of acute respiratory infection in primary care settings. The outcomes of interest are duration of disease, severity of disease, repeated consultation with new/worsening illness and complications requiring hospitalisation. Authors of eligible studies will be contacted to provide anonymised individual participant data. The data will be harmonised and aggregated. Multilevel regression analysis will be conducted to determine key outcome measures for different potential pathogens and whether these offer any additional information on prognosis beyond clinical symptoms and signs.Trial registrationPROSPERO Registration number: CRD42023376769.

  • 28.
    Bogelund Hansen, Matilde
    et al.
    Univ Copenhagen, Denmark.
    Arpi, Magnus
    Univ Copenhagen, Denmark.
    Hedin, Katarina
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Futurum, Reg Jonkoping Cty, Linkoping, Sweden; Lund Univ, Sweden.
    Melander, Eva
    Skane Reg, Sweden; Lund Univ, Sweden.
    Hertz, Frederik Boetius
    Univ Copenhagen, Denmark; Slagelse Hosp, Denmark.
    Thorsted, Anne Bonde
    Univ Southern Denmark, Denmark.
    Jakobsen, Helle Neel
    Bispebjerg and Frederiksberg Hosp, Denmark.
    Hyllebusk, Lena
    Dept Clin Microbiol, Sweden.
    Brogaard, Emma
    Skane Reg, Sweden.
    Jensen, Jette Nygaard
    Univ Copenhagen, Denmark; Capital Reg Denmark, Denmark.
    Antibiotic-prescribing and antibiotic-resistance patterns among elderly citizens residing in two Nordic regions2020In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 52, no 4, p. 257-265Article in journal (Refereed)
    Abstract [en]

    Objective: The objective of this study was to compare antibiotic-prescribing rates in 2016 and antibiotic-resistance rates in 2017 among citizens aged amp;gt;= 85 years between the Capital Region in Denmark and the Skane Region in Sweden, with regards to overall antibiotic use and antibiotics of choice for urinary tract infections (UTIs) and skin and soft tissue infections (SSTIs). Methods: Inhabitants amp;gt;= 85 year old on the date of prescription during 2016 and residing in the Capital Region or the Skane Region were included for antibiotic-prescription analyses. Samples from 2017 from residents of the same regions who were amp;gt;= 85 years old were included for antibiotic-resistance analyses. Antimicrobial use was determined according to the drugs of choice for UTIs and SSTIs in Denmark and Sweden. Students t-tests were used to compare antibiotic prescribing while a Chi-Squared test was performed to compare antibiotic resistance. Results: There was a significantly higher overall prescription rate among citizens amp;gt;= 85 years in the Capital Region than in the Skane Region. The same pattern was evident for the antibiotics of choice for UTIs and SSTIs except for clindamycin. Antibiotic resistance against all antibiotics included was more prominent in the Capital Region than in the Skane Region. Conclusion: Considerable variation in antibiotic prescribing and resistance exists among elderly citizens between these two adjacent Nordic regions. Information and reflection on current practices and resistance patterns may direct attention towards antimicrobial stewardship as a higher priority and may help inform and motivate prescribing behaviours.

  • 29.
    Bogelund Hansen, Matilde
    et al.
    Univ Copenhagen, Denmark.
    Thorsted, Anne Bonde
    Univ Southern Denmark, Denmark.
    Ivarsson, Stina
    Lundbergsgatan Primary Hlth Care Ctr, Sweden.
    Tyrstrup, Mia
    Lund Univ, Sweden.
    Hedin, Katarina
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Lund Univ, Sweden.
    Melander, Eva
    Lund Univ, Sweden; Reg Ctr Communicable Dis Control, Sweden.
    Arpi, Magnus
    Univ Copenhagen, Denmark.
    Jakobsen, Helle Neel
    Bispebjerg & Frederiksberg Hosp, Denmark.
    Brogaard, Emma
    Region Skåne, Sweden.
    Nygaard Jensen, Jette
    Univ Copenhagen, Denmark; Comm Prevent Hosp Infect, Denmark.
    Antibiotic use in pre-school children and the correlation with adult educational levels in two Nordic counties: a replication of a 20-year-old study2021In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 53, no 4, p. 281-290Article in journal (Refereed)
    Abstract [en]

    Objective The aim of this study was to describe the change of antibiotic prescribing in pre-school children in the municipalities of the former Copenhagen County in Denmark and Skane County in Sweden after 20 years of antibiotic stewardship effort. Furthermore, the variation in the prescribing of antibiotics between the municipalities and the correlation between municipal adult educational level and antibiotic prescribing in pre-school children was assessed. Methods In this ecological study, information on antibiotic prescribing in pre-school children was obtained from a central pharmacy settlement system in each Region. The antibiotic prescribing rate was expressed in defined daily doses per 1,000 inhabitants per day (DDD/TID) and number of prescriptions/1000 inhabitants. Information on municipal adult educational levels was obtained from Statistics Denmark and Statistics Sweden. Results The antibiotic prescribing rate during 2017 was higher in the municipalities of Copenhagen County (5.6-7.9 DDD/TID) compared to the municipalities of Skane County (4.2-6.6 DDD/TID). In 1998 a higher rate was found in Skane County (9.6-17.7 DDD/TID) compared to Copenhagen County (8.0-12.9 DDD/TID). A non-significant negative correlation between adult educational levels and antibiotic prescribing was observed in the municipalities of Copenhagen County (r= -0.233, p = .352) while the correlation was positive in the municipalities of Skane County (r= +0.410, p = .018). The same correlations were observed in 1998. Conclusion We found higher antibiotic prescribing in pre-school children in the municipalities of Copenhagen County compared to Skane County in 2017, suggesting a possible overuse of antibiotics in Denmark. Further research should try to elucidate the reasons for the observed variation.

  • 30.
    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.

  • 31.
    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.

  • 32.
    Borsa, Baris Ata
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Sudagidan, Mert
    Konya Food & Agr Univ, Turkey.
    Aldag, Mehmet E.
    Corlu State Hosp, Turkey.
    Baris, Isik I.
    Cakmak Erdem Hosp, Turkey.
    Acar, Elif E.
    Konya Food & Agr Univ, Turkey.
    Acuner, Cagatay
    Yeditepe Univ, Turkey.
    Kavruk, Murat
    Turkish Stand Inst TSE, Turkey.
    Ozalp, Veli C.
    Atilim Univ, Turkey.
    Antibiotic administration in targeted nanoparticles protects the faecal microbiota of mice2021In: RSC MEDICINAL CHEMISTRY, ISSN 2632-8682, Vol. 12, no 3, p. 380-383Article in journal (Refereed)
    Abstract [en]

    Antibiotic therapy comes with disturbances on human microbiota, resulting in changes of bacterial communities and thus leading to well-established health problems. In this study, we demonstrated that targeted teicoplanin administration maintains the faecal microbiota composition undisturbed in a mouse model while reaching therapeutic improvements for S. aureus infection.

  • 33.
    Bowman, Natalie M.
    et al.
    Univ North Carolina Chapel Hill, NC 27599 USA.
    Bucardo, Filemon
    Univ Nacl Autonoma Nicaragua Leon, Nicaragua.
    Collins, Matthew H.
    Emory Univ, GA 30033 USA.
    Reyes, Yaoska
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences. Univ Nacl Autonoma Nicaragua Leon, Nicaragua.
    Cuadra, Edwing Centeno
    Univ Nacl Autonoma Nicaragua Leon, Nicaragua.
    Blette, Bryan
    Univ North Carolina atChapelHill, NC 27515 USA.
    Lakshmanane, Premkumar
    Univ N Carolina, NC 27515 USA.
    Guerra, Enrique Paulo
    Univ N Carolina, NC 27515 USA.
    Rubinstein, Rebecca
    Univ N Carolina, NC 27515 USA.
    Liou, Guei-Jiun Alice
    Kansas City Univ, MO USA.
    de Silva, Aravinda M.
    Univ N Carolina, NC 27515 USA.
    Becker-Dreps, Sylvia
    Univ N Carolina, NC 27515 USA; Univ N Carolina, NC 27515 USA.
    Clinical and Epidemiological Features of Acute Zika Virus Infections in Leon, Nicaragua2021In: American Journal of Tropical Medicine and Hygiene, ISSN 0002-9637, E-ISSN 1476-1645, Vol. 105, no 4, p. 924-930Article in journal (Refereed)
    Abstract [en]

    The American Zika virus (ZIKV) epidemic has highlighted the need to gain a better understanding of this emerging virus. The goal of this study was to describe the clinical symptoms, laboratory findings, and risk factors for symptomatic ZIKV infection in an area with ongoing transmission of other arboviral infections. We recruited patients at least 2 years of age seeking care at public health centers in Leon, Nicaragua, between January 2016 and August 2017, for fever, maculopapular rash, and/or nonsuppurative conjunctivitis with a duration of less than 1 week. A laboratory diagnosis of ZIKV was established using a combination of molecular and serological tests. Clinical and laboratory findings and potential risk factors were compared between participants with and without acute ZIKV infection. Fifty-eight (26%) of the 225 participants included in the analysis were found to have acute ZIKV infection. Pregnancy and reports of previous arboviral infection were associated with a higher risk of ZIKV infection. Rash, conjunctivitis, sore throat, and lower absolute neutrophil counts were associated with acute ZIKV infection. The clinical characteristics and risk factors identified were consistent with those identified by previous studies; however, we found sore throat to be a feature of ZIKV infection. We also found that neutrophil counts were lower in ZIKV-infected subjects. These clinical symptoms and laboratory datamay help clinicians suspect ZIKV infection during future outbreaks.

  • 34.
    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.

  • 35.
    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.

  • 36.
    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, 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.

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  • 37.
    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.

  • 38.
    Bucardo, Filemon
    et al.
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Reyes, Yaoska
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Morales, Marlen
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Briceno, Rafaela
    Minist Hlth Leon, Nicaragua.
    Gonzalez, Fredman
    Natl Autonomous Univ Nicaragua, Nicaragua.
    Lundkvist, Ake
    Uppsala Univ, Sweden.
    Svensson, Lennart
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Nordgren, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Association of Genetic Polymorphisms in DC-SIGN, Toll-Like Receptor 3, and Tumor Necrosis Factor a Genes and the Lewis-Negative Phenotype With Chikungunya Infection and Disease in Nicaragua2021In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 223, no 2, p. 278-286Article in journal (Refereed)
    Abstract [en]

    Background. Chikungunya infections range from subclinical infection to debilitating arthralgia and to chronic inflammatory rheumatism. Tumor necrosis factor (TNF) alpha, DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin), Toll-like receptor (TLR) 3, and blood groups have been directly or indirectly implicated in the susceptibility and pathogenesis of chikungunya. Methods. To test the hypothesis that polymorphisms in genes coding for these molecules determine clinical outcomes of chikungunya infection, a retrospective case-control study was performed in Leon, Nicaragua. The study included 132 case patients and 132 controls, matched for age, sex and neighborhood. Case patients had clinical symptoms of chikungunya, which was diagnosed by means of polymerase chain reaction. Controls were individuals not reporting abrupt presentation of clinical chikungunya-like symptoms. Polymorphisms were identified by TaqMan single-nucleotide polymorphism genotyping assays. Results. After adjustment for sociodemographic risk factors, chikungunya disease was associated with polymorphism in DC-SIGN and TLR3 genes (odds ratios, 5.2 and 3.3, respectively), and TNF-alpha with reduced persistent joint pain (0.24). Persistent joint pain was also associated with age, female sex and other comorbid conditions. Most interestingly, the Lewis-negative phenotype was strongly associated with both symptomatic chikungunya and immunoglobulin G seropositivity (odds ratios, 2.7, and 3.3, respectively). Conclusion. This study identified polymorphisms in DC-SIGN, TLR3, and TNF-alpha genes as well as Lewis-negative phenotype as risk factors for chikungunya infection and disease progression.

  • 39.
    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, 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.

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  • 40.
    Bujila, Ioana
    et al.
    Publ Hlth Agcy Sweden, Sweden.
    Troell, Karin
    Natl Vet Agcy, Sweden; Norwegian Vet Inst, Norway.
    Ögren, Jessica
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Lab Med, Sweden.
    Hansen, Anette
    Publ Hlth Agcy Sweden, Sweden.
    Killander, Gustav
    Publ Hlth Agcy Sweden, Sweden.
    Agudelo, Lady
    Publ Hlth Agcy Sweden, Sweden.
    Lebbad, Marianne
    Publ Hlth Agcy Sweden, Sweden.
    Beser, Jessica
    Publ Hlth Agcy Sweden, Sweden.
    Cryptosporidium species and subtypes identified in human domestic cases through the national microbiological surveillance programme in Sweden from 2018 to 20222024In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 24, no 1, article id 146Article in journal (Refereed)
    Abstract [en]

    Background The intestinal protozoan parasite Cryptosporidium is an important cause of diarrheal disease worldwide. A national microbiological surveillance programme was implemented in Sweden in 2018 in order to increase knowledge of the molecular epidemiology of human cryptosporidiosis to better understand transmission patterns and potential zoonotic sources. This article summarises the results of the first five years of the surveillance programme. Methods Cryptosporidium-positive faecal and DNA samples from domestically acquired infections were collected from clinical microbiological laboratories in Sweden. Species and subtype determination was performed using 60 kDa glycoprotein and/or small subunit ribosomal RNA gene analysis. Results Between 2018 and 2022, 1654 samples were analysed and 11 different species were identified: C. parvum (n = 1412), C. mortiferum (n = 59), C. hominis (n = 56), C. erinacei (n = 11), C. cuniculus (n = 5), C. meleagridis (n = 3), C. equi (n = 2), C. ubiquitum (n = 2), and one each of C. canis, C. ditrichi and C. felis. Subtyping revealed seven subtype families of C. parvum (new subtype families IIy and IIz) and 69 different subtypes (11 new subtypes). The most common C. parvum subtypes were IIdA22G1c, IIdA24G1, IIdA15G2R1 and IIaA16G1R1b. For C. hominis, four different subtype families and nine different subtypes (two new subtypes) were identified. For additional species, two new subtype families (IIIk and VId) and nine new subtypes were identified. All successfully subtyped C. mortiferum cases were subtype XIVaA20G2T1, confirming previous findings in Sweden. Several outbreaks were identified of which the majority were foodborne and a few were due to direct contact with infected animals. Conclusion Infection with C. parvum is the leading cause of human cryptosporidiosis acquired in Sweden, where more than 90% of domestic cases are caused by this zoonotic species and only a small proportion of cases are due to infection with other species. The rodent-associated C. mortiferum is considered an emerging zoonotic species in Sweden and the number of domestically acquired human cases has surpassed that of infection with C. hominis. A high diversity of species and subtypes, as well as diversity within the same subtype, was detected. Also, cryptosporidiosis appears to affect adults to a great extent in Sweden.

  • 41.
    Börjesson, Stefan
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Natl Vet Inst SVA, Sweden.
    Gunnarsson, Lotta
    Natl Vet Inst SVA, Sweden.
    Landen, Annica
    Natl Vet Inst SVA, Sweden.
    Gronlund, Ulrika
    AniCura, Sweden.
    Low occurrence of extended-spectrum cephalosporinase producing Enterobacteriaceae and no detection of methicillin-resistant coagulase-positive staphylococci in healthy dogs in Sweden2020In: Acta Veterinaria Scandinavica, ISSN 0044-605X, E-ISSN 1751-0147, Vol. 62, no 1, article id 18Article in journal (Refereed)
    Abstract [en]

    Sweden has a long tradition of monitoring occurrence of antibiotic resistant bacteria in both animals and humans, but there currently is no organised and harmonized monitoring on carriage of Enterobacteriaceae producing extended-spectrum beta-lactamase (ESBL), plasmid-mediated AmpC beta-lactamase (pAmpC), or methicillin-resistant coagulase positive staphylococci e.g. methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP) in dogs. The aim of the current study was therefore to determine the prevalence of ESBL/pAmpC producing Enterobacteriaceae and methicillin-resistant coagulase positive staphylococci in healthy dogs in Sweden, and to phenotypically and genotypically characterize any identified isolates. It was shown that 0.9% (95% confident interval 0.3-2.7%) of the dogs (n = 325) carried multi-resistant ESBL-producing Escherichia coli, but that no methicillin-resistant coagulase positive staphylococci could be detected. In conclusion, the occurrence of multi-drug resistant bacteria remains rare among healthy dogs in Sweden. In addition, the ESBL-producing E. coli identified showed genetic characteristics related to those reported from humans.

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  • 42.
    Cantelli, Carina Pacheco
    et al.
    Fiocruz MS, Brazil.
    Fumian, Tulio Machado
    Fiocruz MS, Brazil.
    Malta, Fabio Correia
    Fiocruz MS, Brazil.
    da Cunha, Denise Cotrim
    Fiocruz MS, Brazil.
    Brasil, Patricia
    Fiocruz MS, Brazil.
    Nordgren, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Svensson, Lennart
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Miagostovich, Marize Pereira
    Fiocruz MS, Brazil.
    Baroni de Moraes, Marcia Terezinha
    Fiocruz MS, Brazil.
    Gagliardi Leite, Jose Paulo
    Fiocruz MS, Brazil.
    Norovirus infection and HBGA host genetic susceptibility in a birth community-cohort, Rio de Janeiro, Brazil2020In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 82, article id 104280Article in journal (Refereed)
    Abstract [en]

    Norovirus has emerged as an important viral agent of acute pediatric gastroenteritis, with a growing genetic diversity reported in the last decades. Histo-blood group antigens (HBGAs) present on the surface of enterocytes are susceptibility factors for norovirus infection and differ between populations which could affects the epidemiology and evolution of these viruses. This study investigated the frequency, incidence and genetic diversity of noroviruses in a cohort of rotavirus A vaccinated children in association to the host HBGA (Secretor/Lewis) genetic susceptibility profile. Norovirus genogroups I and II (GI/GII) were screened by RT-qPCR in 569 stool samples from 132 children followed-up from birth to 11 months of age during 2014-2018. Noroviruses were identified in 21.2% of children enrolled in this study, with a norovirus detection rate of 5.6% (32/569), in 17.1% and 4.7% of acute diarrheic episodes (ADE) and non-ADE, respectively. The norovirus incidence was 5.8 infections per 100 child-months. Partial nucleotide sequencing characterized six different norovirus genotypes, with GII.4 Sydney 2012 being detected in 50% associated with three different polymerase genotypes (GII.31, GII.P16 and GII.P4 New Orleans 2009). FUT3 genotyping was yielded seven new mutations in this population. A significant association between symptomatic norovirus infection and secretor profile could be inferred.

  • 43.
    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, 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.

  • 44.
    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.

  • 45.
    Carlsson, Hanna
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Reg Kalmar Cty, Sweden.
    Sandholm, Kerstin
    Linnaeus Univ, Sweden.
    Haddish, Haben Woldu
    Reg Kalmar Cty, Sweden.
    Brudin, Lars
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Reg Kalmar Cty, Sweden.
    Ekdahl, Kristina Nilsson
    Linnaeus Univ, Sweden; Uppsala Univ, Sweden.
    Tjernberg, Ivar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Reg Kalmar Cty, Sweden.
    Complement activation in individuals with previous subclinical Lyme borreliosis and patients with previous Lyme neuroborreliosis2020In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 39, no 5, p. 855-862Article in journal (Refereed)
    Abstract [en]

    Lyme borreliosis (LB) is caused by Borrelia burgdorferi and infection may lead to not only a large variety of clinical manifestations but also a subclinical outcome. The aim of the present study was to investigate if there is a constitutional difference in complement activation between individuals with previous subclinical Lyme borreliosis (SB) and patients previously diagnosed with Lyme neuroborreliosis (LNB). Lepirudin plasma for activation studies was collected from 60 SB individuals and from 22 patients pre-diagnosed with LNB. The plasma was incubated with live Borrelia spirochetes of two strains (complement sensitive B. garinii Lu59 and complement resistant B. afzelii ACA1). Complement factor C3 was measured in non-activated lepirudin plasma with immune-nephelometry and C3a and sC5b-9 generated during complement activation were measured by enzyme-linked immunosorbent assay. We found that the complement sensitive Lu59 induced higher complement activation than the complement resistant ACA1 when measuring activation products C3a and sC5b-9 in SB and LNB patients, p < 0.0001. No significant difference was found between SB and LNB patients in systemic levels of C3. Furthermore, SB individuals generated a higher activation of C3 cleavage to C3a (C3a/C3 ratio) than LNB patients after activation with ACA1, p < 0.001, but no significant differences were found in response to Lu59. In conclusion, Lu59 induced higher complement activation than ACA1 and individuals with previous SB showed increased generation of C3a compared with patients with previous LNB. In our study population, this mechanism could lead to less elimination of spirochetes in LNB patients and thereby be a factor contributing to the clinical outcome.

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  • 46.
    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.

  • 47.
    Carlströmer Berthén, Nellie
    et al.
    Borrelia Research Group of the Aland Islands, The Aland Islands, Finland; Bimelix AB, The Aland Islands, Finland.
    Tompa, Eszter
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Olausson, Susanne
    Borrelia Research Group of the Aland Islands,The Aland Islands, Finland;Bimelix AB, The Aland Islands, Finland.
    Nyberg, Clara
    Borrelia Research Group of the Aland Islands, The Aland Islands, Finland.
    Nyman, Dag
    Borrelia Research Group of the Aland Islands, The Aland Islands, Finland;Bimelix AB, The Aland Islands, Finland.
    Ringbom, Malin
    Borrelia Research Group of the Aland Islands, The Aland Islands, Finland;The Aland Islands Healthcare Services, The Aland Islands, Finland.
    Perander, Linda
    Borrelia Research Group of the Aland Islands, The Aland Islands, Finland;The Aland Islands Healthcare Services, The Aland Islands, Finland.
    Svärd, Joel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Lindgren, Per-Eric
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Clinical Microbiology, Laboratory Medicine, County Hospital Ryhov, Sweden.
    Forsberg, Pia
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection.
    Wilhelmsson, Peter
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Clinical Microbiology, Laboratory Medicine, County Hospital Ryhov, 551 85 Jonkoping, Sweden.
    Sjöwall, Johanna
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Nordberg, Marika
    Borrelia Research Group of the Aland Island, The Aland Islands, Finland;The Aland Islands Healthcare Services, The Aland Islands, Finland.
    The AxBioTick Study: Borrelia Species and Tick-Borne Encephalitis Virus in Ticks, and Clinical Responses in Tick-Bitten Individuals on the Aland Islands, Finland2023In: Microorganisms, E-ISSN 2076-2607, Vol. 11, no 5, article id 1100Article in journal (Refereed)
    Abstract [en]

    The AxBioTick Study: Borrelia Species and Tick-Borne Encephalitis Virus in Ticks, and Clinical Responses in Tick-Bitten Individuals on the Aland Islands, Finlandby  Nellie Carlströmer Berthén 1,2,*,† , Eszter Tompa 3,† , Susanne Olausson 1,2, Clara Nyberg 1, Dag Nyman 1,2, Malin Ringbom 1,4, Linda Perander 1,4, Joel Svärd 3, Per-Eric Lindgren 3,5, Pia Forsberg 3, Peter Wilhelmsson 3,5,‡, Johanna Sjöwall 3,6,‡  and Marika Nordberg 1,4,‡  1Borrelia Research Group of the Aland Islands, 22100 Mariehamn, The Aland Islands, Finland2Bimelix AB, 22100 Mariehamn, The Aland Islands, Finland3Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Linkoping University, 581 83 Linkoping, Sweden4The Aland Islands Healthcare Services, 22100 Mariehamn, The Aland Islands, Finland5Clinical Microbiology, Laboratory Medicine, County Hospital Ryhov, 551 85 Jonkoping, Sweden6Department of Infectious Diseases, Vrinnevi Hospital, 603 79 Norrkoping, Sweden*Author to whom correspondence should be addressed.†These authors contributed equally to the study.‡These authors contributed equally to the study.Microorganisms 2023, 11(5), 1100; https://doi.org/10.3390/microorganisms11051100Received: 30 March 2023 / Revised: 17 April 2023 / Accepted: 19 April 2023 / Published: 22 April 2023(This article belongs to the Special Issue Research on Ticks and Tick-Borne Pathogens)

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    AbstractThe AxBioTick study was initiated to investigate the prevalence of ticks and tick-borne pathogens and their impact on antibody and clinical responses in tick-bitten individuals on the Aland Islands. This geographical area is hyperendemic for both Lyme borreliosis (LB) and Tick-borne encephalitis (TBE). Blood samples and ticks were collected from 100 tick-bitten volunteers. A total of 425 ticks was collected, all determined to Ixodes ricinus using molecular tools. Of them 20% contained Borrelia species, of which B. garinii and B. afzelii were most common. None contained the TBE virus (TBEV). Blood samples were drawn in conjunction with the tick bite, and eight weeks later. Sera were analyzed for Borrelia- and TBEV-specific antibodies using an ELISA and a semiquantitative antibody assay. In total 14% seroconverted in Borrelia C6IgG1, 3% in TBEV IgG, and 2% in TBEV IgM. Five participants developed clinical manifestations of LB. The high seroprevalence of both Borrelia (57%) and TBEV (52%) antibodies are likely attributed to the endemic status of the corresponding infections as well as the TBE vaccination program. Despite the similar prevalence of Borrelia spp. detected in ticks in other parts of Europe, the infection rate in this population is high. The AxBioTick study is continuing to investigate more participants and ticks for co-infections, and to characterize the dermal immune response following a tick bite.

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  • 48.
    Charitakis, Emmanouil
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Karlsson, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Papageorgiou, Joanna-Maria
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Walfridsson, Ulla
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Echocardiographic and Biochemical Factors Predicting Arrhythmia Recurrence After Catheter Ablation of Atrial Fibrillation-An Observational Study2019In: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 10, article id 1215Article in journal (Refereed)
    Abstract [en]

    Background: RFA is a well-established treatment for symptomatic patients with AF. However, the success rate of a single procedure is low. We aimed to investigate the association between the risk of recurrence of atrial fibrillation (AF) after a single radiofrequency ablation (RFA) procedure and cardiac neurohormonal function, left atrial (LA) mechanical function as well as proteins related to inflammation, fibrosis, and apoptosis. Methods and Results: We studied 189 patients undergoing RFA between January 2012 and April 2014, with a follow-up period of 12 months. A logistic regression analysis was performed to investigate the association between pre-ablation LA emptying fraction (LAEF), MR-proANP, Caspase-8 (CASP8), Neurotrophin-3 (NT3), and the risk for recurrence of AF after a single RFA procedure. 119 (63.0%) patients had a recurrence during a mean follow-up of 402 +/- 73 days. An increased risk of recurrence was associated with: Elevated MR-proANP (fourth quartile vs. first quartile: HR, 2.80 (95% CI, 1.14-6.90]; P = 0.025); Low LAEF (fourth quartile vs. first quartile: hazard ratio [HR], 2.41 [95% CI, 1.01-5.79]; P = 0.045); Elevated CASP8 (fourth quartile vs. first quartile: HR 12.198 95% CI 2.216-67.129; P = 0.004); Elevated NT-3 (fourth quartile vs. first quartile: HR 7.485 95% CI 1.353-41.402; P = 0.021). In a receiver operating characteristic curve analysis, the combination of MR-proANP, CASP8, and NT3 produced an area under the curve of 0.819; CI 95% (0.710-0.928). Conclusions: Patients with better LA mechanical function and lower levels of atrial neurohormones as well as of proteins related to fibrosis and apoptosis, have a better outcome after an RFA procedure.

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  • 49.
    Chiappa, Giulia
    et al.
    Univ Milan, Italy.
    Perini, Matteo
    Univ Milan, Italy.
    Cafiso, Alessandra
    Univ Milan, Italy.
    Nodari, Riccardo
    Univ Milan, Italy.
    Wilhelmsson, Peter
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Dept Clin Microbiol, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Dept Clin Microbiol, Sweden.
    Omazic, Anna
    Natl Vet Inst, Sweden.
    Ullman, Karin
    Natl Vet Inst, Sweden.
    Moutailler, Sara
    Ecole Natl Vet Alfort, France.
    Kjellander, Petter
    Swedish Univ Agr Sci, Sweden.
    Bazzocchi, Chiara
    Univ Milan, Italy.
    Grandi, Giulio
    Natl Vet Inst, Sweden; Swedish Univ Agr Sci, Sweden.
    A Novel High Discriminatory Protocol for the Detection of Borrelia afzelii, Borrelia burgdorferi Sensu Stricto and Borrelia garinii in Ticks2022In: Pathogens, E-ISSN 2076-0817, Vol. 11, no 11, article id 1234Article in journal (Refereed)
    Abstract [en]

    Bacteria of the Borrelia burgdorferi sensu lato complex are the causative agents of Lyme borreliosis (LB). Even if the conventional diagnosis of LB does not rely on the species itself, an accurate species identification within the complex will provide a deepened epidemiological scenario, a better diagnosis leading to a more targeted therapeutic approach, as well as promote the general publics awareness. A comparative genomics approach based on the 210 Borrelia spp. genomes available in 2019 were used to set up three species-specific PCR protocols, able to detect and provide species typing of Borrelia afzelii, Borrelia burgdorferi sensu stricto (s.s.) and Borrelia garinii, the three most common and important human pathogenic Lyme Borrelia species in Europe. The species-specificity of these protocols was confirmed on previously identified B. afzelii, B. burgdorferi s.s. and B. garinii specimens detected in Ixodes ricinus samples. In addition, the protocols were validated on 120 DNA samples from ticks collected in Sweden, showing 88% accuracy, 100% precision, 72% sensitivity and 100% specificity. The proposed approach represents an innovative tool in epidemiological studies focused on B. burgdorferi s.l. occurrence in ticks, and future studies could suggest its helpfulness in routine diagnostic tests for health care.

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  • 50.
    Cho, Kyuyeon
    et al.
    Yonsei Univ, South Korea.
    Park, Seoyeon
    Yonsei Univ, South Korea.
    Kim, Eun-Young
    Chung Ang Univ, South Korea.
    Koyanagi, Ai
    ICREA, Spain; CIBERSAM, Spain.
    Jacob, Louis
    CIBERSAM, Spain; Univ Versailles St Quentin En Yvelines, France.
    Yon, Dong K.
    Seoul Natl Univ, South Korea.
    Lee, Seung Won
    Sejong Univ, South Korea.
    Kim, Min Seo
    Sungkyunkwan Univ, South Korea.
    Radua, Joaquim
    Kings Coll London, England; Mental Hlth Networking Biomed Res Ctr CIBERSAM, Spain; Karolinska Inst, Sweden; Inst Invest Biomed August Pi & Sunyer IDIBAPS, Spain.
    Dragioti, Elena
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Il Shin, Jae
    Yonsei Univ, South Korea.
    Smith, Lee
    Anglia Ruskin Univ, England.
    Immunogenicity of COVID-19 vaccines in patients with diverse health conditions: A comprehensive systematic review2022In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 94, no 9, p. 4144-4155Article, review/survey (Refereed)
    Abstract [en]

    It remains unclear how effective COVID-19 vaccinations will be in patients with weakened immunity due to diseases, transplantation, and dialysis. We conducted a systematic review comparing the efficacy of COVID-19 vaccination in patients with solid tumor, hematologic malignancy, autoimmune disease, inflammatory bowel disease, and patients who received transplantation or dialysis. A literature search was conducted twice using the Medline/PubMed database. As a result, 21 papers were included in the review, and seropositivity rate was summarized by specific type of disease, transplantation, and dialysis. When different papers studied the same type of patient group, a study with a higher number of participants was selected. Most of the solid tumor patients showed a seropositivity rate of more than 80% after the second inoculation, but a low seropositivity was found in certain tumors such as breast cancer. Research in patients with certain types of hematological malignancy and autoimmune diseases has also reported low seropositivity, and this may have been affected by the immunosuppressive treatment these patients receive. Research in patients receiving dialysis or transplantation has reported lower seropositivity rates than the general population, while all patients with inflammatory bowel disease have converted to be seropositive. Meta-analysis validating these results will be needed, and studies will also be needed on methods to protect patients with reduced immunity from COVID-19.

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