| 1. |
- Kerkman, Priscilla, et al.
(author)
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Generation of plasma cells and CD27-IgD- B cells during hantavirus infection is associated with distinct pathological findings
- 2021
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In: Clinical & Translational Immunology (CTI). - : John Wiley & Sons. - 2050-0068. ; 10
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Journal article (peer-reviewed)abstract
- Objective: Human hantavirus infections can cause haemorrhagic fever with renal syndrome (HFRS). The pathogenic mechanisms arenot fully understood, nor if they affect the humoral immune system. The objective of this study was to investigate humoral immune responses to hantavirus infection and to correlate them to the typical features of HFRS: thrombocytopenia and transient kidney dysfunction.Methods: We performed a comprehensive characterisation of longitudinal antiviral B-cell responses of 26 hantavirus patients and combined this with paired clinical data. In addition, we measured extracellular adenosine triphosphate (ATP)and its breakdown products in circulation and performed in vitro stimulations to address its effect on B cells.Results: We found that thrombocytopenia was correlated to an elevated frequency of plasmablasts in circulation. In contrast, kidney dysfunction was indicative of an accumulation of CD27-IgD- B cells and CD27/low plasmablasts. Finally, we provide evidence that high levels of extracellular ATP and matrix metalloproteinase 8 can contribute to shedding of CD27 during human hantavirus infection.Conclusion: Our findings demonstrate that thrombocytopenia and kidneydysfunction associate with distinctly different effects on the humoral immune system. Moreover, hantavirus-infectedindividuals have significantly elevated levels of extracellular ATP incirculation.
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| 2. |
- Kerkman, Priscilla, et al.
(author)
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The B cell response towards Puumala virus infection : can B cells be infected?
- 2017
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In: Scandinavian Journal of Immunology. - : John Wiley & Sons. - 0300-9475 .- 1365-3083. ; 86:4, s. 260-260
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Journal article (other academic/artistic)abstract
- Hantavirus infections are rodent-borne viruses causing potential lethal infections in humans. Different hantaviruses exist worldwide, reporting a fatality rate of up to 40%. The Puumala hantavirus (PUUV) is endemic in northern Sweden. This hantavirus strain has a relatively low fatality rate but the hospitalisation rate is high. No vaccine to the virus and no treatment for the disease exist. Despite differences in severity, the immune-mediated pathogenesis of Puumala virus infection is similar to that of highly lethal strains of hantavirus. It is currently unknown how the humoral immune system is affected during hantavirus infection.The aim of this study is to characterise how the humoral immune response is affected during Puumala virus infection. A large number of longitudinal patient samples have been collected. Here, we demonstrate the longitudinal kinetics of the B cell response during Puumala virus infection and show that there is a change in B cell populations during the course of the disease. Furthermore we show that B cells carry known hantavirus receptors. This suggests that Puumala virus may directly infect B cells. Infection of the B cells could affect their function and or phenotype explaining a different immune response. Importantly, in approximately 10–15% of Puumala infected patients we could detect antibodies that could neutralise other hantaviruses in vitro. Samples from these patients could help to generate a monoclonal antibody treatment potentially treating diseases caused by several hantavirus.
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| 3. |
- Obanda, Vincent, et al.
(author)
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Epidemiology and ecology of the sylvatic cycle of African swine fever virus in Kenya
- 2024
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In: Virus Research. - : Elsevier. - 0168-1702 .- 1872-7492. ; 348
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Journal article (peer-reviewed)abstract
- African Swine Fever (ASF) is caused by a DNA virus (AFSV) maintained and transmitted by the Argasid ticks. The re-emergence of the disease in Africa coupled with its rapid spread globally is a threat to the pig industry, food security and livelihoods. The ecology and epidemiology of the ASFV sylvatic cycle, especially in the face of changing land use and land cover, further compounds the menace and impacts of this disease in Kenya. The study aimed to determine the occurrence and distribution of ASFV seroprevalence in warthog populations, the tick vectors and extent of tick infestation of warthog burrows, and the genotypes of ASFV in soft ticks in Kenya. Warthogs from different parts of Kenya were captured and venous blood was centrifuged to harvest sera. Warthog burrows were examined for their conditions and to extract ticks. Sera were analyzed for antibodies against ASFV using a commercial ELISA kit coated with p32 ASFV recombinant protein. Ticks were pooled, DNA extracted and the p72 gene of the ASFV was amplified by qPCR and conventional PCR. The overall seroprevalence of ASFV in warthogs was 87.5 %. A total of 228 warthog burrows were examined and 2154 argasid ticks were extracted from the burrows. Tick pools from Kigio Farm and Lewa Wildlife Conservancies were ASFV-positive by qPCR and conventional PCR. ASFV was further confirmed by the Twist Comprehensive Viral Research Panel (TCVRP), which also identified the argasid ticks as Ornithodoros porcinus. The ticks were infected with virus genotype IX, and their occurrence overlaps with regions of previous ASF outbreaks in domestic pigs. Further, Viruses that could be tick endosymbionts/commensals or due to bloodmeal were detected in ticks by TCVRP; Porcine type-C oncovirus; Pandoravirus neocaledonia; Choristoneura fumiferana granulovirus; Enterobacteria phage p7; Leporid herpesvirus 4 isolate; 5; Human Lymphotropic virus; Human herpesvirus 5. In conclusion, our results suggest that infected Ornithodoros spp. seems to have a rich virome, which has not been explored but could be exploited to inform ASF control in Kenya. Further, the ecology of Ornithodoros spp. and burrow-use dynamics are complex and more studies are needed to understand these dynamics, specifically in the spread of ASFV at the interface of wild and domestic pigs. Further, our results provide evidence of genotype IX ASFV sylvatic cycle which through O. porcinus tick transmission has resulted in high exposure of adult common warthogs. Finally, the co-circulation of ASFV genotype IX in the same location with past ASF outbreaks in domestic pigs and presently in ticks brings to focus the role of the interface and ticks on virus transmission to pigs and warthogs.
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| 4. |
- Rosenbaum, William, et al.
(author)
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Hybrid capture-based next-generation sequencing of new and old world Orthohantavirus strains and wild-type Puumala isolates from humans and bank voles
- 2024
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In: Journal of Clinical Virology. - : Elsevier. - 1386-6532 .- 1873-5967. ; 172
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Journal article (peer-reviewed)abstract
- Orthohantaviruses, transmitted primarily by rodents, cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome in the Americas. These viruses, with documented human-to-human transmission, exhibit a wide case-fatality rate, 0.5–40 %, depending on the virus species, and no vaccine or effective treatment for severe Orthohantavirus infections exists. In Europe, the Puumala virus (PUUV), carried by the bank vole Myodes glareolus, causes a milder form of HFRS. Despite the reliance on serology and PCR for diagnosis, the three genomic segments of Swedish wild-type PUUV have yet to be completely sequenced.We have developed a targeted hybrid-capture method aimed at comprehensive genomic sequencing of wild-type PUUV isolates and the identification of other Orthohantaviruses. Our custom-designed panel includes >11,200 probes covering the entire Orthohantavirus genus. Using this panel, we sequenced complete viral genomes from bank vole lung tissue, human plasma samples, and cell-cultured reference strains. Analysis revealed that Swedish PUUV isolates belong to the Northern Scandinavian lineage, with nucleotide diversity ranging from 2.8 % to 3.7 % among them. Notably, no significant genotypic differences were observed between the viral sequences from reservoirs and human cases except in the nonstructural protein.Despite the high endemicity of PUUV in Northern Sweden, these are the first complete Swedish wild-type PUUV genomes and substantially increase our understanding of PUUV evolution and epidemiology. The panel's sensitivity enables genomic sequencing of human samples with viral RNA levels reflecting the natural progression of infection and underscores our panel's diagnostic value, and could help to uncover novel Orthohantavirus transmission routes.
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| 5. |
- Tuiskunen-Bäck, Anne, et al.
(author)
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Acute myocarditis caused by Francisella tularensis : a case report
- 2023
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In: SN Comprehensive Clinical Medicine. - : Springer Science and Business Media LLC. - 2523-8973. ; 5:1
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Journal article (other academic/artistic)abstract
- Myocarditis is an inflammatory disease of the myocardium with either focal or diffuse involvement and usually gives rise to chest pain, dyspnea, palpitations, and fatigue. In severe cases, arrythmias, syncope, and cardiogenic shock may occur. Acute myocarditis is most commonly caused by a variety of viruses with cardiotropic properties. Rare causes of myocarditis include bacterial infections. We, herein, describe a case of acute myocarditis caused by the intracellular bacterium Francisella tularensis. A young and previously healthy male in Northern Sweden was referred to the emergency department due to intense upper-chest pain and dyspnea. ECG exhibited minimal ST-segment elevations and laboratory parameters revealed pathological levels of high-sensitivity cardiac troponin and C-reactive protein. Radiological imaging showed increased metabolism in enlarged lymph nodes in the chest and signs that could be compatible with increased metabolism in the left ventricular of the heart. The combination of acute myocarditis and enlarged lymph nodes was believed to be caused by the intracellular bacterium Francisella tularensis, endemic in the Northern Sweden, and was verified with positive serology. The patient showed full recovery after antimicrobial treatment. As this is the fifth published case of myocarditis associated with Francisella tularensis, we suggest considering tularemia in acute myocarditis in tularemia-endemic area.
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| 6. |
- Tuiskunen-Bäck, Anne, et al.
(author)
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Clinical and genomic characterisation of a fatal Puumala orthohantavirus case with low levels of neutralising antibodies
- 2022
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In: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 54:10, s. 766-772
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Journal article (peer-reviewed)abstract
- BACKGROUND: Orthohantaviruses are rodent-borne emerging viruses that cause haemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome in America. Transmission between humans have been reported and the case-fatality rate ranges from 0.4% to 40% depending on virus strain. There is no specific and efficient treatment for patients with severe HFRS. Here, we characterised a fatal case of HFRS and sequenced the causing Puumala orthohantavirus (PUUV).METHODS: PUUV RNA and virus specific neutralising antibodies were quantified in plasma samples from the fatal case and other patients with non-fatal PUUV infection. To investigate if the causing PUUV strain was different from previously known strains, Sanger sequencing was performed directly from the patient's plasma. Biopsies obtained from autopsy were stained for immunohistochemistry.RESULTS: The patient had approximately tenfold lower levels of PUUV neutralising antibodies and twice higher viral load than was normally seen for patients with less severe PUUV infection. We could demonstrate unique mutations in the S and M segments of the virus that could have had an impact on the severity of infection. Due to the severe course of infection, the patient was treated with the bradykinin receptor inhibitor icatibant to reduce bradykinin-mediated vessel permeability and maintain vascular circulation.CONCLUSIONS: Our data suggest that bradykinin receptor inhibitor may not be highly efficient to treat patients that are at an advanced stage of HFRS. Low neutralising antibodies and high viral load at admission to the hospital were associated with the fatal outcome and may be useful for future predictions of disease outcome.
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| 7. |
- Tuiskunen-Bäck, Anne
(author)
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Dengue gaining ground
- 2015
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In: Journal of Human Virology & Retrovirology. - : MedCrave. - 2373-6453. ; 2:2, s. 51-52
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Journal article (peer-reviewed)
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| 8. |
- Tuiskunen-Bäck, Anne, et al.
(author)
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Dengue viruses – an overview
- 2013
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In: Infection Ecology & Epidemiology. - : Taylor & Francis. - 2000-8686. ; 3:1
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Journal article (peer-reviewed)abstract
- Dengue viruses (DENVs) cause the most common arthropod-borne viral disease in man with 50–100 million infections per year. Because of the lack of a vaccine and antiviral drugs, the sole measure of control is limiting the Aedes mosquito vectors. DENV infection can be asymptomatic or a self-limited, acute febrile disease ranging in severity. The classical form of dengue fever (DF) is characterized by high fever, headache, stomach ache, rash, myalgia, and arthralgia. Severe dengue, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) are accompanied by thrombocytopenia, vascular leakage, and hypotension. DSS, which can be fatal, is characterized by systemic shock. Despite intensive research, the underlying mechanisms causing severe dengue is still not well understood partly due to the lack of appropriate animal models of infection and disease. However, even though it is clear that both viral and host factors play important roles in the course of infection, a fundamental knowledge gap still remains to be filled regarding host cell tropism, crucial host immune response mechanisms, and viral markers for virulence.dengue virusdengue feverdengue hemorrhagic feverdengue shock syndromeflavivirus
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| 9. |
- Tuiskunen-Bäck, Anne, et al.
(author)
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Extensive spinal epidural hematoma as the cause of postpartum headache and neck pain after epidural anesthesia : a case-based report
- 2022
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In: SN Comprehensive Clinical Medicine. - : Springer Science and Business Media LLC. - 2523-8973. ; 4:1
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Journal article (peer-reviewed)abstract
- Spinal epidural hematomas (SEH) are a rare hemorrhagic event occurring after trauma, epidural anesthesia, or operative inventions. However, in 40–50% of cases, they occur spontaneously. Spontaneous spinal epidural hematomas (SSEH) are rare in occurrence with an estimated incidence of 1 case per million annually. Pregnancy is an independent risk factor. Sudden neck or back pain, often in combination with a rapid onset of neurological symptoms, is the most common presentation of SEH (1). A 36-year-old Caucasian female with rheumatoid arthritis (RA) presented to the emergency department approximately 48 h after an uncomplicated vaginal delivery. She sought medical attention due to constant headaches and neck pain that started during active labor. An MRI of the spine revealed an extensive SEH spreading from C1 to L5. The patient was without neurological symptoms or deficits and was successfully treated conservatively without any sequelae. Even though the definitive cause of this case of SEH will remain unknown, several possible synergistic mechanisms have been identified. These include female gender, full-term pregnancy, physical activity with increased intraabdominal pressure (i.e., Valsalva maneuver), systemic administration of platelet aggregation inhibitor (PAI), and iatrogenic manipulation such as spinal epidural anesthesia. Even though autoimmune and inflammatory disorders have been described in the literature to be rare sources of hemorrhage in the spinal canal, it is unclear whether the patient’s RA should be regarded as an individual risk factor.
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| 10. |
- Tuiskunen-Bäck, Anne, et al.
(author)
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Phenotypic and genotypic characterization of dengue virus isolates differentiates dengue fever and dengue hemorrhagic fever from dengue shock syndrome
- 2011
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In: Archives of Virology. - : Springer Science and Business Media LLC. - 0304-8608 .- 1432-8798. ; 156:11, s. 2023-2032
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Journal article (peer-reviewed)abstract
- Dengue viruses (DENV) cause 50-100 million cases of acute febrile disease every year, including 500,000 reported cases of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Viral factors have been proposed to influence the severity of the disease, but markers of virulence have never been identified on DENV. Three DENV serotype-1 isolates from the 2007 epidemic in Cambodia that are derived from patients experiencing the various clinical forms of dengue were characterized both phenotypically and genetically. Phenotypic characteristics in vitro, based on replication kinetics in different cell lines and apoptosis response, grouped isolates from DF and DHF patients together, whereas the virus isolate from a DSS patient showed unique features: a lower level of replication in mammalian cells and extensive apoptosis in mosquito cells. Genomic comparison of viruses revealed six unique amino acid residues in the membrane, envelope, and in non-structural genes in the virus isolated from the DSS patient.
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