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  • 1.
    Abdelrahim, Nada A.
    et al.
    Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, Nile University, Khartoum, Sudan.
    Mohamed, Nahla
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Fadl-Elmula, Imad M.
    Department of Pathology and Clinical Genetics, Faculty of Medicine, Al-Neelain University, Khartoum, Sudan; Assafa Academy, Kartoum, Sudan.
    Human herpes virus type-6 is associated with central nervous system infections in children in Sudan2022In: African Journal of Laboratory Medicine, ISSN 2225-2002, E-ISSN 2225-2010, Vol. 11, no 1, article id a1718Article in journal (Refereed)
    Abstract [en]

    Background: Human herpes virus type-6 (HHV-6) is increasingly recognised as a febrile agent in children. However, less is known in sub-Saharan African countries, including Sudan.

    Objective: We investigated the involvement of HHV-6 in paediatric central nervous system (CNS) infections in Khartoum, Sudan.

    Methods: Febrile patients aged up to 15 years with suspected CNS infections at Omdurman Hospital for Children from 01 December 2009 to 01 August 2010 were included. Viral DNA was extracted from leftover cerebrospinal fluid (CSF) specimens and quantitatively amplified by real-time polymerase chain reaction (PCR) at Umeå University in Sweden.

    Results: Of 503 CSF specimens, 13 (2.6%) were positive for HHV-6 (33.0% [13/40 of cases with proven infectious meningitis]). The median thermal cycle threshold for all HHV-6-positive specimens was 38 (range: 31.9-40.8). The median number of virus copies was 281.3/PCR run (1 × 105 copies/mL CSF; range: 30-44 × 103 copies/PCR run [12 × 103 - 18 × 106 copies/mL CSF]). All positive patients presented with fever and vomiting; 86.0% had seizures. The male-to-female ratio was 1:1; 50.0% were toddlers, 42.0% infants and 8.0% teenagers. Most (83.0%) were admitted in the dry season and 17.0% in the rainy season. Cerebrospinal fluid leukocytosis was seen in 33.0%, CSF glucose levels were normal in 86.0% and low in 14.0%, and CSF protein levels were low in 14.0% and high in 43.0%.

    Conclusion: Among children in Sudan with CNS infections, HHV-6 is common. Studies on the existence and spread of HHV-6 chromosomal integration in this population are needed.

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  • 2.
    Abdelrahim, Nada Abdelghani
    et al.
    Department of Pathology-Medical Microbiology, Faculty of Medicine, University of Medical Sciences and Technology, Khartoum, Sudan.
    Mohamed, Nahla
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Fadl-Elmula, Imad Mohammed
    Department of Pathology & Clinical Genetics, Al-Neelain University & Assafa Academy, Khartoum, Sudan.
    Viral meningitis in Sudanese children: differentiation, etiology and review of literature2022In: Medicine, ISSN 0025-7974, E-ISSN 1536-5964, Vol. 101, no 46, article id e31588Article, review/survey (Refereed)
    Abstract [en]

    Diagnosis of viral meningitis (VM) is uncommon practice in Sudan and there is no local viral etiological map. We therefore intended to differentiate VM using standardized clinical codes and determine the involvement of herpes simplex virus types-1 and 2 (HSV-1/2), varicella zoster virus, non-polio human enteroviruses (HEVs), and human parechoviruses in meningeal infections in children in Sudan. This is a cross-sectional hospital-based study. Viral meningitis was differentiated in 503 suspected febrile attendee of Omdurman Hospital for Children following the criteria listed in the Clinical Case Definition for Aseptic/Viral Meningitis. Patients were children age 0 to 15 years. Viral nucleic acids (DNA/RNA) were extracted from cerebrospinal fluid (CSF) specimens using QIAamp® UltraSens Virus Technology. Complementary DNA was prepared from viral RNA using GoScriptTM Reverse Transcription System. Viral nucleic acids were amplified and detected using quantitative TaqMan® Real-Time and conventional polymerase chain reactions (PCRs). Hospital diagnosis of VM was assigned to 0%, when clinical codes were applied; we considered 3.2% as having VM among the total study population and as 40% among those with proven infectious meningitis. Two (0.4%) out of total 503 CSF specimens were positive for HSV-1; Ct values were 37.05 and 39.10 and virus copies were 652/PCR run (261 × 103/mL CSF) and 123/PCR run (49.3 × 103/mL CSF), respectively. Other 2 (0.4%) CSF specimens were positive for non-polio HEVs; Ct values were 37.70 and 38.30, and the approximate virus copies were 5E2/PCR run (~2E5/mL CSF) and 2E2/PCR run (~8E4/mL CSF), respectively. No genetic materials were detected for HSV-2, varicella zoster virus, and human parechoviruses. The diagnosis of VM was never assigned by the hospital despite fulfilling the clinical case definition. Virus detection rate was 10% among cases with proven infectious meningitis. Detected viruses were HSV-1 and non-polio HEVs. Positive virus PCRs in CSFs with normal cellular counts were seen.

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  • 3. Affognon, Hippolyte
    et al.
    Mburu, Peter
    Hassan, Osama Ahmed
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kingori, Sarah
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Sang, Rosemary
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ethnic groups' knowledge, attitude and practices and Rift Valley fever exposure in Isiolo County of Kenya2017In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 11, no 3, article id e0005405Article in journal (Refereed)
    Abstract [en]

    Rift Valley fever (RVF) is an emerging mosquito-borne viral hemorrhagic fever in Africa and the Arabian Peninsula, affecting humans and livestock. For spread of infectious diseases, including RVF, knowledge, attitude and practices play an important role, and the understanding of the influence of behavior is crucial to improve prevention and control efforts. The objective of the study was to assess RVF exposure, in a multiethnic region in Kenya known to experience RVF outbreaks, from the behavior perspective. We investigated how communities in Isiolo County, Kenya were affected, in relation to their knowledge, attitude and practices, by the RVF outbreak of 2006/2007. A cross-sectional study was conducted involving 698 households selected randomly from three different ethnic communities. Data were collected using a structured questionnaire regarding knowledge, attitudes and practices that could affect the spread of RVF. In addition, information was collected from the communities regarding the number of humans and livestock affected during the RVF outbreak. This study found that better knowledge about a specific disease does not always translate to better practices to avoid exposure to the disease. However, the high knowledge, attitude and practice score measured as a single index of the Maasai community may explain why they were less affected, compared to other investigated communities (Borana and Turkana), by RVF during the 2006/2007 outbreak. We conclude that RVF exposure in Isiolo County, Kenya during the outbreak was likely determined by the behavioral differences of different resident community groups. We then recommend that strategies to combat RVF should take into consideration behavioral differences among communities.

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  • 4.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Distribution of puumala virus in Sweden1997Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Puumala virus, belonging to the genus hantavirus, is the causative agent of nephropathia epidemica (NE), a relatively mild form of hemorrhagic fever with renal syndrome. Puumala virus occurs endemically in Central and Northern Europe and Western Russia. In Sweden, NE is reported from the northern and central parts but virtually not at all from the southern part of the country. The bank vole (Clethrionomys glareolus) is the main reservoir of Puumala virus and humans are infected by inhalation of aerosolized animal secreta. In northern Sweden, the density of the bank vole population varies cyclically in intervals of 3-4 years and the incidence of NE shows a covariation.

    The prevalence of serum antibodies to hantaviruses in northern Sweden was studied in a stratified and randomly selected adult population sample comprising 1538 subjects. As expected, the prevalence increased with age. There was no difference between men and women, which was unexpected based on a male:female ratio of > 2:1 in clinical reports. By use of an immunofiuorescent assay, a seroprevalence of 5.4% and by a newly developed enzyme-linked immunosorbent assay (ELISA) with recombinant Puumala virus nucleocapsid protein as antigen, a prevalence of 8.9% was recorded. This is about or more than ten times higher than what would be calculated from clinical reports.

    By use of the ELISA, an occupational risk of acquisition of Puumala virus infection was demonstrated. Serum samples from 910 farmers and 663 referent subjects living in various rural parts of Sweden were tested. Among farmers from the Puumala virus-endemic northern and central parts of the country, the seroprevalence (12.9%) was higher (p=0.01) than in referents (6.8%). In the southern part of Sweden, only 2/459 persons had antibodies. Only a limited number of children with NE had been previously reported. In a separate study, 32 children with Puumala virus infection were identified and the clinical picture of NE in children was found to be similar to that of adult cases.

    Variations in the prevalence of Puumala virus in the bank vole population within an endemic region are not well known. Here, a higher mean rodent density and a higher prevalence of Puumala virus-specific serum antibodies were recorded in the vicinity of households afflicted with NE than in rural control areas. The data indicated that the risk of exposure locally within an endemic region may vary widely and tentatively suggested that a threshold density of bank voles might be necessary to achieve before effective spread of Puumala virus within the rodent population may occur.

    There is no firm evidence of the occurrence of Puumala virus among wild living animals other than rodents. A study of Swedish moose, an animal which is ecologically well characterized, was performed. Convincing evidence of past Puumala virus infection was found in 5/260 moose originating from Puumala virus-endemic areas but in none of 167 animals from nonendemic areas. Based on the low seroprevalence recorded, moose seemed to serve as endstage hosts rather than being active parts of the enzootic circle of transmission.

    In conclusion, the present investigations confirmed that the exposure to Puumala virus is geographically well restricted in Sweden. Seroprevalence studies indicated that only a minor proportion of individuals infected with Puumala virus are clinically reported, with a bias in favour of men. NE was confirmed to occur in children, with a clinical picture similar to that of adults. An occupational risk was defined for acquisition of Puumala virus infection. Studies in rodents suggested that there may be wide local variations within a limited area in the risk of exposure to Puumala virus. The studies validated the usefulness of a newly developed ELISA based on recombinant nucleocapsid peptides of hantaviruses and finally, methodological progress was reached when Puumala virus was, for the first time, successfully isolated from a Scandinavian patient.

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  • 5.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Norrländska infektionssjukdomar2011In: Infektionssjukdomar: Epidemiologi, klinik, terapi / [ed] Ivarsson-Norrby, Sundbyberg: Säve förlag , 2011, 5Chapter in book (Other academic)
  • 6.
    Ahlm, Clas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Alexeyev, O A
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Aava, Birgitta
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Tärnvik, Arne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Juto, Per
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Palo, T
    High prevalence of hantavirus antibodies in bank voles (Clethrionomys glareolus) captured in the vicinity of households afflicted with nephropathia epidemica.1997In: American Journal of Tropical Medicine and Hygiene, ISSN 0002-9637, E-ISSN 1476-1645, Vol. 56, no 6, p. 674-8Article in journal (Refereed)
    Abstract [en]

    Puumala virus, the causative agent of nephropathia epidemica (NE), occurs endemically in Europe and is spread mainly by the bank vole (Clethrionomys glareolus). In the vicinity of each of four households afflicted with NE, we studied rodents with regard to population density and prevalence of Puumala virus-specific antibodies. For each case area, a control area was randomly selected 10 km away, without regard to the presence of human settlement. During 6,000 trap nights, 328 rodents were caught, of which 299 were C. glareolus. The mean rodent densities of case and control areas were 6.6 and 3.7 animals per 100 trap nights (P < 0.001). The prevalence of serum antibodies was 15.9% in case areas compared with 5.6% in control areas (P < 0.05). In three of the case areas, where NE had occurred 3-10 weeks before trapping, the rodent density and seroprevalence were much higher than in the fourth area, where NE occurred 38 weeks before trapping. In conclusion, C. glareolus seropositive for Puumala virus occurred more frequently near households afflicted with NE than in control areas 10 km away.

  • 7.
    Ahlm, Clas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Axelsson, I
    Jansson, B
    [Maternal health care must improve its tracing of hepatitis B virus carriers].1990In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 87, no 37, p. 2865-6Article in journal (Refereed)
  • 8.
    Ahlm, Clas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Vapalahti, O.
    University of Helsinki and Helsinki University Central Hospital Laboratory, Finland.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Seroprevalence of Sindbis virus and associated risk factors in northern Sweden2014In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 142, no 7, p. 1559-1565Article in journal (Refereed)
    Abstract [en]

    Mosquito-borne Sindbis virus (SINV) cause disease characterized by rash, fever and arthritis which often leads to long-lasting arthralgia. To determine the seroprevalence of SINV and associated risk factors in northern Sweden, a randomly selected population aged between 25 and 74 years were invited to join the MONICA study. Serum from 1611 samples were analysed for specific IgG antibodies. Overall, 2·9% had IgG against SINV. More men (3·7%) than women (2·0%) were SINV seropositive (P = 0·047) and it was more common in subjects with a lower educational level (P = 0·013) and living in small, rural communities (P < 0·001). Seropositivity was associated with higher waist circumference (P = 0·1), elevated diastolic blood pressure (P = 0·037), and history of a previous stroke (P = 0·011). In a multiple logistic regression analysis, adjusting for known risk factors for stroke, seropositivity for SINV was an independent predictor of having had a stroke (odds ratio 4·3, 95% confidence interval 1·4–13·0,P = 0·011).

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  • 9.
    Ahlm, Clas
    et al.
    Infektionskliniken, Norrlands universitetssjukhus, Umeå, Sweden.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Missfall orsakades av det myggburna Rift Valley-feberviruset2016In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 113, no 42, article id EAUZArticle in journal (Other academic)
  • 10.
    Ahlm, Clas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Herlitz, H
    Säll, C
    Eriksson, C
    Settergren, B
    [Is vole fever (nephropathia epidemica) spreading in the south of Sweden?].1992In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 89, no 40, p. 3275-Article in journal (Refereed)
  • 11.
    Ahlm, Clas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Juto, Per
    Settergren, Bo
    [Nephropathia epidemica--a current disease in Norrland].1990In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 87, no 43, p. 3521-2, 3527Article in journal (Refereed)
  • 12.
    Ahlm, Clas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Juto, Per
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Stegmayr, Birgitta
    Settergren, Bo
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Tärnvik, Arne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Prevalence of serum antibodies to hantaviruses in northern Sweden as measured by recombinant nucleocapsid proteins.1997In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 29, no 4, p. 349-54Article in journal (Refereed)
    Abstract [en]

    An enzyme-linked immunosorbent assay (ELISA) based on recombinant nucleocapsid protein (rN delta) (aa 1-117) of Hantaan, Seoul, Dobrava, Sin Nombre and Puumala hantaviruses was used to determine the prevalence of antibodies among randomized and stratified individuals from northern Sweden. In total, 137/1533 individuals (8.9%) had specific serum IgG antibodies to Puumala virus, the only hantavirus known to occur in the region. The prevalence of antibodies to Puumala virus (8.9%) was determined to be higher than previously reported (5.4%) in the same serum material, by use of immunofluorescence assay. As expected, sera reactive to Puumala virus rN delta did frequently cross-react with Sin Nombre virus protein. Unexpectedly, 21/1533 (1.4%) individuals recognized the Sin Nombre virus rN delta exclusively. Another 8 subjects showed reactivity in the ELISA to Hantaan, Seoul, or Dobrava virus-derived rN delta but not Puumala virus or Sin Nombre virus rN delta. The present demonstration in some individuals of antibodies specifically recognizing the Sin Nombre, Dobrava, Hantaan and Seoul virus protein justifies an awareness of the possibility that hantaviruses antigenically different from Puumala virus might occur in the region.

  • 13.
    Ahlm, Clas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Linderholm, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Juto, Per
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Stegmayr, Birgitta
    Settergren, Bo
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Prevalence of serum IgG antibodies to Puumala virus (haemorrhagic fever with renal syndrome) in northern Sweden.1994In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 113, no 1, p. 129-36Article in journal (Refereed)
    Abstract [en]

    A stratified and randomly-selected population sample was identified in 1990 in order to study the seroprevalence of nephropathia epidemica (haemorrhagic fever with renal syndrome) in Northern Sweden. Sera from 1538 subjects (750 men, 788 women), 25-64 years of age, were analysed for the presence of Puumala virus (PUV) specific-IgG by the indirect immunofluorescence antibody test. Specific IgG was detected in sera from 83 subjects (5.4%). Men and women had similar seroprevalence rates. The highest seroprevalences were found in subjects 55 years or older (8.0%) and among farmers and forestry workers (15.9%). The geographic distribution of seropositive individuals was uneven and there were significantly more seropositive persons in rural than in urban areas (P < 0.05).

  • 14.
    Ahlm, Clas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Linderholm, M
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Alexeyev, O A
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Billheden, J
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Fagerlund, M
    Zetterlund, B
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neurophysiology.
    Settergren, B
    Central nervous system and ophthalmic involvement in nephropathia epidemica (European type of haemorrhagic fever with renal syndrome)1998In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 36, no 2, p. 149-155Article in journal (Refereed)
    Abstract [en]

    Central nervous system (CNS) - related symptoms occur in haemorrhagic fever with renal syndrome (HFRS). To study the CNS and ophthalmic involvement in nephropathia epidemica (NE), the European type of HFRS, we included 26 patients in a prospective study. Most common CNS-related symptoms were headache (96%), insomnia (83%), vertigo (79%), nausea (79%), and vomiting (71%). Ophthalmic symptoms were reported by 82% of patients; 41% had photophobia and 50% had impaired vision. A transient loss of vision was recorded in one patient, who also had a generalized seizure. Minor white matter lesions were found in about half of the patients investigated with brain magnetic resonance imaging (MRI). Electroencephalography (EEG) showed severe alterations in only one patient, and slight and reversible patterns in another two patients. Neopterin, interleukin-6 and interferon-gamma levels in the cerebrospinal fluid (CSF) were elevated, which may indicate immune activation. However, we found no evidence of intrathecal NE virus replication. We conclude that CNS-related symptoms are common in NE, and transient ophthalmic involvement can be demonstrated in about half of the patients.

  • 15.
    Ahlm, Clas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Lundberg, Sonia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Fessé, Kerstin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Wiström, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Health problems and self-medication among Swedish travellers.1994In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 26, no 6, p. 711-7Article in journal (Refereed)
    Abstract [en]

    500 consecutive travellers seeking pre-travel health advice were issued a questionnaire before leaving Sweden to continuously record health problems and use of medication during travel. Of 442 subjects who turned in assessable questionnaires (232 male and 210 female, mean age 37 years), 81% travelled to areas at high risk for the acquisition of diarrhea. The mean duration of travel was 4 weeks. During travel 218 (49% at 95% CI 44.3 to 53.7%) of the travellers experienced some illness and 61 (14%) had symptoms of more than one illness. The mean duration of illness was 4.5 days, and 65 subjects (30% of ill travellers) were confined to bed for a mean duration of 2 days. The incidence of illness was significantly (p < 0.01) higher among travellers to high risk than to low risk areas (55% vs 26%), among young travellers than among elderly (65% vs 33%), and among those going on adventure tours compared with recreational tourists (74% vs 41%). Diarrhea was reported by 36% (95% CI 31.6 to 40.5%), and respiratory tract infection by 21% (95% CI 17.2 to 24.8%). Self-medication with one or several drugs was initiated by 163 (75%) travellers experiencing illness during travel. Thus, every second Swedish traveller to tropical and subtropical areas experienced some kind of travel-related, often incapacitating, health problem.

  • 16.
    Ahlm, Clas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Olsen, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Koskinen, Lars Ove
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Monsen, Tor
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Brain abscess caused by methicillin-resistant Staphylococcus aureus2000In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 32, no 5, p. 562-563Article in journal (Refereed)
    Abstract [en]

    A Swedish tourist was admitted to a Cuban hospital due to epileptic seizures caused by brain tumors. Upon return to Sweden and admission to our hospital, methicillin-resistant Staphylococcus aureus (MRSA) was isolated. He was later considered to be free of MRSA but then developed a brain abscess from which MRSA was isolated.

  • 17.
    Ahlm, Clas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Settergren, Bo
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Gothefors, Leif
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Juto, Per
    Nephropathia epidemica (hemorrhagic fever with renal syndrome) in children: clinical characteristics.1994In: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 13, no 1, p. 45-9Article in journal (Refereed)
    Abstract [en]

    The clinical characteristics of serologically verified nephropathia epidemica, the Scandinavian form of hemorrhagic fever with renal syndrome, were studied in Swedish children who were < 15 years of age. In 1990 to 1992, 14 cases were prospectively followed. A retrospective survey during 1984 to 1990 disclosed another 18 cases. Among the 32 cases (20 boys, 12 girls, 3 to 15 years of age; median age, 11 years), the most common symptoms were fever (100%), headache (100%), abdominal pain (93%), vomiting (91%) and back pain (76%). Laboratory findings included elevated serum creatinine concentration (19 of 28) and thrombocytopenia (7 of 22). Urinalysis showed proteinuria (31 of 31 patients) and hematuria (24 of 30). Six children had mild hemorrhagic manifestations (epistaxis, metrorrhagia, and petechiae). No severe complications occurred. The clinical symptoms of children with nephropathia epidemica seem to be similar to those found among adult nephropathia epidemica cases.

  • 18.
    Ahlm, Clas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Thelin, Anders
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Juto, Per
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Stiernström, E L
    Holmberg, S
    Tärnvik, Arne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Prevalence of antibodies specific to Puumala virus among farmers in Sweden1998In: Scandinavian Journal of Work, Environment and Health, ISSN 0355-3140, E-ISSN 1795-990X, Vol. 24, no 2, p. 104-108Article in journal (Refereed)
    Abstract [en]

    Serological evidence confirmed that the exposure of humans to Puumala virus is firmly restricted to the northern and central parts of Sweden. In addition the evidence indicated that, in this region, farming is associated with an increased risk of contracting hantavirus infection.

  • 19.
    Ahlm, Clas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Wallin, Kjell
    Skoglig zooekologi, SLU, Umeå.
    Lundkvist, Åke
    Smittskyddsinstitutet.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Juto, Per
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Merza, Malik
    Virologi, SVA, Uppsala.
    Tärnvik, Arne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Serologic evidence of Puumala virus infection in wild moose in northern Sweden2000In: American Journal of Tropical Medicine and Hygiene, ISSN 0002-9637, E-ISSN 1476-1645, Vol. 62, no 1, p. 106-111Article in journal (Refereed)
    Abstract [en]

    Puumala (PUU) virus is the causative agent of nephropathia epidemica, the Scandinavian form of hemorrhagic fever with renal syndrome. The infection is acquired by airborne transmission of PUU virus from its rodent reservoir, the bank vole. Besides serologic data indicating that the virus may spread also to heterologous rodents, there is little information on the susceptibility of wild living animals to PUU virus. We studied the occurrence of antibodies to PUU virus in serum samples from 427 wild-living moose, of which 260 originated from the PUU virus-endemic northern and central parts of Sweden and 167 originated from the southern, nonendemic part of Sweden. Samples from 5 animals showed reactivity in an ELISA for recombinant PUU virus nucleocapsid protein, an immunofluorescent assay, and a neutralization test. These 5 animals all originated from the PUU virus-endemic northern part of Sweden. In conclusion, 5 of 260 moose from the endemic region showed convincing serologic evidence of past PUU virus infection. The seroprevalence was low, suggesting that the moose is subjected to endstage infection rather than being part of an enzootic transmission cycle.

  • 20.
    Ahlm, Clas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Wiström, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Carlsson, Hans
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Chloroquine-Resistant Plasmodium vivax Malaria in Borneo.1996In: Journal of Travel Medicine, ISSN 1195-1982, E-ISSN 1708-8305, Vol. 3, no 2, p. 124-Article in journal (Refereed)
  • 21.
    Ahmad, Irma
    et al.
    Department of Radiation Oncology, Stanford University, Stanford, CA, United States.
    Edin, Alicia
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Granvik, Christoffer
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Kumm Persson, Lowa
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Tevell, Staffan
    Department of Infectious Diseases, Karlstad Hospital, Karlstad, Sweden; Centre for Clinical Research and Education, Region Värmland, Karlstad, Sweden; School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Månsson, Emeli
    Centre for Clinical Research, Region Västmanland—Uppsala University, Västmanland Hospital Västerås, Västerås, Sweden.
    Magnuson, Anders
    Center for Clinical Epidemiology and Biostatistics, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Marklund, Ingela
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation. Centre for Clinical Research and Education, Region Värmland, Karlstad, Sweden.
    Persson, Ida-Lisa
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Kauppi, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Sundh, Josefin
    Department of Respiratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lange, Anna
    Department of Radiation Oncology, Stanford University, Stanford, CA, United States.
    Cajander, Sara
    Department of Radiation Oncology, Stanford University, Stanford, CA, United States.
    Normark, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    High prevalence of persistent symptoms and reduced health-related quality of life 6 months after COVID-192023In: Frontiers In Public Health, ISSN 2296-2565, Vol. 11, article id 1104267Article in journal (Refereed)
    Abstract [en]

    Background: The long-term sequelae after COVID-19 constitute a challenge to public health and increased knowledge is needed. We investigated the prevalence of self-reported persistent symptoms and reduced health-related quality of life (HRQoL) in relation to functional exercise capacity, 6 months after infection, and explored risk factors for COVID-19 sequalae. Methods: This was a prospective, multicenter, cohort study including 434 patients. At 6 months, physical exercise capacity was assessed by a 1-minute sit-to-stand test (1MSTST) and persistent symptoms were reported and HRQoL was evaluated through the EuroQol 5-level 5-dimension (EQ-5D-5L) questionnaire. Patients with both persistent symptoms and reduced HRQoL were classified into a new definition of post-acute COVID syndrome, PACS+. Risk factors for developing persistent symptoms, reduced HRQoL and PACS+ were identified by multivariable Poisson regression. Results: Persistent symptoms were experienced by 79% of hospitalized, and 59% of non-hospitalized patients at 6 months. Hospitalized patients had a higher prevalence of self-assessed reduced overall health (28 vs. 12%) and PACS+ (31 vs. 11%). PACS+ was associated with reduced exercise capacity but not with abnormal pulse/desaturation during 1MSTST. Hospitalization was the most important independent risk factor for developing persistent symptoms, reduced overall health and PACS+. Conclusion: Persistent symptoms and reduced HRQoL are common among COVID-19 survivors, but abnormal pulse and peripheral saturation during exercise could not distinguish patients with PACS+. Patients with severe infection requiring hospitalization were more likely to develop PACS+, hence these patients should be prioritized for clinical follow-up after COVID-19.

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  • 22.
    Alexeyev, O A
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Billheden, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Settergren, Bo
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Juto, Per
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Elevated levels of total and Puumala virus-specific immunoglobulin E in the Scandinavian type of hemorrhagic fever with renal syndrome.1994In: Clinical and diagnostic laboratory immunology, ISSN 1071-412X, Vol. 1, no 3, p. 269-72Article in journal (Refereed)
    Abstract [en]

    In a previous study, it was reported that the total immunoglobulin E (IgE) level was increased in patients with hemorrhagic fever with renal syndrome (HFRS). The aim of the present study was to investigate whether specific IgE is synthesized during the course of the disease. For this purpose, an epsilon-capture enzyme-linked immunosorbent assay was developed. A total of 72 patients with HFRS caused by Puumala virus were studied. Three different control groups were included: 20 blood donors, 20 patients with other viral diseases (influenza A and B virus, acute Epstein-Barr virus, and acute cytomegalovirus infections), and 5 subjects with high levels of total IgE (median, 1,070 kU/liter; range, 773 to 5,740 kU/liter). The levels of total IgE were significantly higher during the acute phase of HFRS than those of blood donors (P < 0.01) and of patients with other viral diseases (P < 0.001). All patients developed a specific IgE response (median, 55 arbitrary units; range 24 to 123 arbitrary units) in the acute phase of the disease, whereas in the different control groups no specific IgE was detectable. Both total and specific IgE levels decreased during convalescence compared with those during the acute phase of HFRS (P < 0.001 and P < 0.001, respectively). In conclusion, we have shown that both total and specific IgE levels are increased in patients with HFRS compared with levels in patients with other viral diseases. The possible pathogenetic role of the specific IgE response in HFRS is discussed.

  • 23.
    Alexeyev, O A
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Stigbrand, Torgny
    Settergren, Bo
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Juto, Per
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Hantavirus antigen detection using human serum immunoglobulin M as the capturing antibody in an enzyme-linked immunosorbent assay.1996In: American Journal of Tropical Medicine and Hygiene, ISSN 0002-9637, E-ISSN 1476-1645, Vol. 54, no 4, p. 367-71Article in journal (Refereed)
    Abstract [en]

    An enzyme-linked immunosorbent assay (ELISA) was developed to detect different hantavirus antigens in cell culture; i.e. Puumala (PUU), Hantaan (HTN), and Dobrava (DOB) viruses. The assay was based on binding human serum immunoglobulin M (IgM) antibodies to the solid phase by use of goat anti-IgM antibodies. The captured IgM antibodies were present in the acute phase serum from two patients: one infected in Sweden and the other in Bosnia. Antigens being bound to the solid phase by the human anti-PUU and anti-DOB/HTN IgM antibodies were detected by a broadly reacting polyclonal rabbit anti PUU-recombinant nucleocapsid protein antiserum. The IgM isotype was proven to be at least five times more efficient than IgG when used as the capturing antibody. The sensitivity of the PUU antigen ELISA was approximately 0.5 ng/ml, as measured by titration with a PUU recombinant nucleoprotein antigen. Cell-associated PUU antigen in tissue culture was seen after 48 hr by the PUU-ELISA and after 96 hr by immunofluorescent assay. When tested for capacity to discriminate between PUU, DOB, and HTN viruses, significant differences were found: the Swedish serum detected PUU antigen at high titers, whereas no reactivity was found against DOB and HTN; the Bosnian serum detected both DOB and HTN at high titers but had a low reactivity to PUU. The method was also tested for its usefulness in detecting PUU antigen in bank vole (clethrionomys glareolus) lungs. Of 59 animals captured from the surroundings of patients with nephropathia epidemica, three became positive with a high activity in the PUU-ELISA, but with low reactivity in the DOB/HTN-ELISA. It is concluded that a sensitive ELISA has been developed to detect different hantaviruses in cell culture and lungs of bank voles.

  • 24. Alexeyev, O A
    et al.
    Settergren, B
    Billheden, Jan
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Suzdaltsev, A
    Tsaig, M
    Laboratory findings in patients with hemorrhagic fever with renal syndrome in western Russia.1993In: Infection. Zeitschrift für Klinik und Therapie der Infektionen, ISSN 0300-8126, E-ISSN 1439-0973, Vol. 21, no 6, p. 412-Article in journal (Refereed)
  • 25.
    Alexeyev, Oleg A
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Aava, Birgitta
    Skoglig Zooekologi, SLU, Umeå.
    Palo, Thomas
    Skoglig Zooekologi, SLU, Umeå.
    Settergren, Bo
    Tärnvik, Arne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Juto, Per
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    A minority of seropositive wild bank voles (Clethrionomys glareolus) show evidence of current Puumala virus infection1998In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 121, no 2, p. 419-425Article in journal (Refereed)
    Abstract [en]

    Bank voles (Clethrionomys glareolus) serve as the reservoir for Puumala (PUU) virus, the aetiologic agent of nephropathia epidemica. The animals are believed to be persistently infected and the occurrence of serum antibodies is usually taken as an evidence of active infection. We found serum antibodies to PUU virus in 42 of 299 wild bank voles captured in a PUU virus endemic area. PUU virus RNA was demonstrated in lung specimens of 11 of these 42 animals and in 2 of them antigen was also found. Thus in the lungs of 31 of 42 seropositive animals neither PUU virus RNA nor antigen was detected. In 2 of 257 seronegative animals, lung specimens showed presence of PUU virus antigen and RNA. Isolation of PUU virus from lung tissue was successful in all 4 antigen-positive bank voles but in none of 16 tested antigen-negative animals. In conclusion, only a minority of bank voles with serum antibodies to PUU virus showed evidence of current infection.

  • 26. Alm, Erik
    et al.
    Lesko, Birgitta
    Lindegren, Gunnel
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Soderholm, Sandra
    Falk, Kerstin I.
    Lagerqvist, Nina
    Universal Single-Probe RT-PCR Assay for Diagnosis of Dengue Virus Infections2014In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 8, no 12, p. e3416-Article in journal (Refereed)
    Abstract [en]

    Background: Dengue is a mosquito-borne viral disease that has become more prevalent in the last few decades. Most patients are viremic when they present with symptoms, and early diagnosis of dengue is important in preventing severe clinical complications associated with this disease and also represents a key factor in differential diagnosis. Here, we designed and validated a hydrolysis-probe-based one-step real-time RT-PCR assay that targets the genomes of dengue virus serotypes 1-4. Methodology/Principal Findings: The primers and probe used in our RT-PCR assay were designed to target the 39 untranslated region of all complete genome sequences of dengue virus available in GenBank (n=3,305). Performance of the assay was evaluated using in vitro transcribed RNA, laboratory-adapted virus strains, external control panels, and clinical specimens. The linear dynamic range was found to be 10(4)-10(11) GCE/mL, and the detection limit was between 6.0x10(2) and 1.1x10(3) GCE/mL depending on target sequence. The assay did not cross-react with human RNA, nor did it produce false-positive results for other human pathogenic flaviviruses or clinically important etiological agents of febrile illnesses. We used clinical serum samples obtained from returning travelers with dengue-compatible symptomatology (n = 163) to evaluate the diagnostic relevance of our assay, and laboratory diagnosis performed by the RT-PCR assay had 100% positive agreement with diagnosis performed by NS1 antigen detection. In a retrospective evaluation including 60 archived serum samples collected from confirmed dengue cases 1-9 days after disease onset, the RT-PCR assay detected viral RNA up to 9 days after appearance of symptoms. Conclusions/Significance: The validation of the RT-PCR assay presented here indicates that this technique can be a reliable diagnostic tool, and hence we suggest that it be introduced as the method of choice during the first 5 days of dengue symptoms.

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  • 27. Amada, Takako
    et al.
    Yoshimatsu, Kumiko
    Koma, Takaaki
    Shimizu, Kenta
    Gamage, Chandika D.
    Shiokawa, Kanae
    Nishio, Sanae
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Arikawa, Jiro
    Development of an immunochromatography strip test based on truncated nucleocapsid antigens of three representative hantaviruses2014In: Virology Journal, E-ISSN 1743-422X, Vol. 11, p. 87-Article in journal (Refereed)
    Abstract [en]

    Background: Hantaviruses are causative agents of hemorrhagic fever with renal syndrome (HFRS) and nephropathia epidemica (NE) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. There is a need for time-saving diagnostic methods. In the present study, recombinant N antigens were used as antigens in an immunochromatography strip (ICG) test to detect specific IgG antibodies. Methods: The N-terminal 103 amino acids (aa) of Hantaan virus (HTNV), Puumala virus (PUUV) and Andes virus (ANDV) nucleocapsid (N) protein were expressed in E. coli as representative antigens of three groups (HFRS, NE and HPS-causing viruses) of hantavirus. Five different types of ICG test strips, one antigen line on one strip for each of the three selected hantaviruses (HTNV, PUUV and ANDV), three antigen lines on one strip and a mixed antigen line on one strip, were developed and sensitivities were compared. Results: A total of 87 convalescent-phase patient sera, including sera from 35 HFRS patients, 36 NE patients and 16 HPS patients, and 25 sera from healthy seronegative people as negative controls were used to evaluate the ICG test. Sensitivities of the three-line strip and mixed-line strip were similar to those of the single antigen strip (97.2 to 100%). On the other hand, all of the ICG test strips showed high specificities to healthy donors. Conclusion: These results indicated that the ICG test with the three representative antigens is an effective serodiagnostic tool for screening and typing of hantavirus infection in humans.

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  • 28. Baharom, Faezzah
    et al.
    Rankin, Gregory
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Scholz, Saskia
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Smed-Sörensen, Anna
    Human lung dendritic cells: spatial distribution and phenotypic identification in endobronchial biopsies using immunohistochemistry and flow cytometry2017In: Journal of Visualized Experiments, E-ISSN 1940-087X, no 119, article id e55222Article in journal (Refereed)
    Abstract [en]

    The lungs are constantly exposed to the external environment, which in addition to harmless particles, also contains pathogens, allergens, and toxins. In order to maintain tolerance or to induce an immune response, the immune system must appropriately handle inhaled antigens. Lung dendritic cells (DCs) are essential in maintaining a delicate balance to initiate immunity when required without causing collateral damage to the lungs due to an exaggerated inflammatory response. While there is a detailed understanding of the phenotype and function of immune cells such as DCs in human blood, the knowledge of these cells in less accessible tissues, such as the lungs, is much more limited, since studies of human lung tissue samples, especially from healthy individuals, are scarce. This work presents a strategy to generate detailed spatial and phenotypic characterization of lung tissue resident DCs in healthy humans that undergo a bronchoscopy for the sampling of endobronchial biopsies. Several small biopsies can be collected from each individual and can be subsequently embedded for ultrafine sectioning or enzymatically digested for advanced flow cytometric analysis. The outlined protocols have been optimized to yield maximum information from small tissue samples that, under steady-state conditions, contain only a low frequency of DCs. While the present work focuses on DCs, the methods described can directly be expanded to include other (immune) cells of interest found in mucosal lung tissue. Furthermore, the protocols are also directly applicable to samples obtained from patients suffering from pulmonary diseases where bronchoscopy is part of establishing the diagnosis, such as chronic obstructive pulmonary disease (COPD), sarcoidosis, or lung cancer.

  • 29. Baharom, Faezzah
    et al.
    Thomas, Saskia
    Rankin, Gregory
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lepzien, Rico
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Smed-Sorensen, Anna
    Dendritic Cells and Monocytes with Distinct Inflammatory Responses Reside in Lung Mucosa of Healthy Humans2016In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 196, no 11, p. 4498-4509Article in journal (Refereed)
    Abstract [en]

    Every breath we take contains potentially harmful pathogens or allergens. Dendritic cells (DCs), monocytes, and macrophages are essential in maintaining a delicate balance of initiating immunity without causing collateral damage to the lungs because of an exaggerated inflammatory response. To document the diversity of lung mononuclear phagocytes at steady-state, we performed bronchoscopies on 20 healthy subjects, sampling the proximal and distal airways (bronchial wash and bronchoalveolar lavage, respectively), as well as mucosal tissue (endobronchial biopsies). In addition to a substantial population of alveolar macrophages, we identified subpopulations of monocytes, myeloid DCs (MDCs), and plasmacytoid DCs in the lung mucosa. Intermediate monocytes and MDCs were highly frequent in the airways compared with peripheral blood. Strikingly, the density of mononuclear phagocytes increased upon descending the airways. Monocytes from blood and airways produced 10-fold more proinflammatory cytokines than MDCs upon ex vivo stimulation. However, airway monocytes were less inflammatory than blood monocytes, suggesting a more tolerant nature. The findings of this study establish how to identify human lung mononuclear phagocytes and how they function in normal conditions, so that dysregulations in patients with respiratory diseases can be detected to elucidate their contribution to immunity or pathogenesis.

  • 30.
    Baudin, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Jumaa, Ammar M.
    Jomma, Huda J. E.
    Karsany, Mubarak S.
    Bucht, Göran
    Näslund, Jonas
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Mohamed, Nahla
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Association of Rift Valley fever virus infection with miscarriage in Sudanese women: a cross-sectional study2016In: The Lancet Global Health, E-ISSN 2214-109X, Vol. 4, no 11, p. e864-e871Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Rift Valley fever virus is an emerging mosquito-borne virus that causes infections in animals and human beings in Africa and the Arabian Peninsula. Outbreaks of Rift Valley fever lead to mass abortions in livestock, but such abortions have not been identified in human bezings. Our aim was to investigate the cause of miscarriages in febrile pregnant women in an area endemic for Rift Valley fever.

    METHODS: Pregnant women with fever of unknown origin who attended the governmental hospital of Port Sudan, Sudan, between June 30, 2011, and Nov 17, 2012, were sampled at admission and included in this cross-sectional study. Medical records were retrieved and haematological tests were done on patient samples. Presence of viral RNA as well as antibodies against a variety of viruses were analysed. Any association of viral infections, symptoms, and laboratory parameters to pregnancy outcome was investigated using Pearson's χ(2) test.

    FINDINGS: Of 130 pregnant women with febrile disease, 28 were infected with Rift Valley fever virus and 31 with chikungunya virus, with typical clinical and laboratory findings for the infection in question. 15 (54%) of 28 women with an acute Rift Valley fever virus infection had miscarriages compared with 12 (12%) of 102 women negative for Rift Valley fever virus (p<0·0001). In a multiple logistic regression analysis, adjusting for age, haemorrhagic disease, and chikungunya virus infection, an acute Rift Valley fever virus infection was an independent predictor of having a miscarriage (odds ratio 7·4, 95% CI 2·7-20·1; p<0·0001).

    INTERPRETATION: This study is the first to show an association between infection with Rift Valley fever virus and miscarriage in pregnant women. Further studies are warranted to investigate the possible mechanisms. Our findings have implications for implementation of preventive measures, and evidence-based information to the public in endemic countries should be strongly recommended during Rift Valley fever outbreaks.

    FUNDING: Schlumberger Faculty for the Future, CRDF Global (31141), the Swedish International Development Cooperation Agency, the County Council of Västerbotten, and the Faculty of Medicine, Umeå University.

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  • 31.
    Bergqvist, Joakim
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Forsman, Oscar
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Larsson, Pär
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Näslund, Jonas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Lilja, Tobias
    Engdahl, Cecilia
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lindström, Anders
    Gylfe, Åsa
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Arctic Research Centre at Umeå University.
    Bucht, Göran
    [ 1 ] CBRN Def & Secur, Swedish Def Res Agcy, SE-90182 Umea, Sweden.
    Detection and Isolation of Sindbis Virus from Mosquitoes Captured During an Outbreak in Sweden, 20132015In: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 15, no 2, p. 133-140Article in journal (Refereed)
    Abstract [en]

    Mosquito-borne alphaviruses have the potential to cause large outbreaks throughout the world. Here we investigated the causative agent of an unexpected Sindbis virus (SINV) outbreak during August-September, 2013, in a previously nonendemic region of Sweden. Mosquitoes were collected using carbon dioxide-baited CDC traps at locations close to human cases. The mosquitoes were initially screened as large pools by SINV-specific quantitative RT-PCR, and the SINV-positive mosquitoes were species determined by single-nucleotide polymorphism (SNP) analysis, followed by sequencing the barcoding region of the cytochrome oxidase I gene. The proportion of the collected mosquitoes was determined by a metabarcoding strategy. By using novel strategies for PCR screening and genetic typing, a new SINV strain, Lovanger, was isolated from a pool of 1600 mosquitoes composed of Culex, Culiseta, and Aedes mosquitoes as determined by metabarcoding. The SINV-positive mosquito Culiseta morsitans was identified by SNP analysis and sequencing. After whole-genome sequencing and phylogenetic analysis, the SINV Lovanger isolate was shown to be most closely similar to recent Finnish SINV isolates. In conclusion, within a few weeks, we were able to detect and isolate a novel SINV strain and identify the mosquito vector during a sudden SINV outbreak.

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  • 32.
    Bergstedt Oscarsson, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Brorstad, Alette
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Baudin, Maria
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Forssén, Annika
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Human Puumala hantavirus infection in northern Sweden: increased seroprevalence and association to risk and health factors2016In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 16, article id 566Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The rodent borne Puumala hantavirus (PUUV) causes haemorrhagic fever with renal syndrome in central and northern Europe. The number of cases has increased and northern Sweden has experienced large outbreaks in 1998 and 2006-2007 which raised questions regarding the level of immunity in the human population.

    METHODS: A randomly selected population aged between 25 and 74 years from northern Sweden were invited during 2009 to participate in a WHO project for monitoring of trends and determinants in cardiovascular disease. Health and risk factors were evaluated and sera from 1,600 participants were available for analysis for specific PUUV IgG antibodies using a recombinant PUUV nucleocapsid protein ELISA.

    RESULTS: The overall seroprevalence in the investigated population was 13.4 %, which is a 50 % increase compared to a similar study only two decades previously. The prevalence of PUUV IgG increased with age, and among 65-75 years it was 22 %. More men (15.3 %) than women (11.4 %) were seropositive (p < 0.05). The identified risk factors were smoking (OR = 1.67), living in rural areas (OR = 1.92), and owning farmland or forest (OR = 2.44). No associations were found between previous PUUV exposure and chronic lung disease, diabetes, hypertension, renal dysfunction, stroke or myocardial infarction.

    CONCLUSIONS: PUUV is a common infection in northern Sweden and there is a high life time risk to acquire PUUV infection in endemic areas. Certain risk factors as living in rural areas and smoking were identified. Groups with increased risk should be targeted for future vaccination when available, and should also be informed about appropriate protection from rodent secreta.

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  • 33.
    Bergstedt-Oskarsson, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Brorstad, Alette
    Baudin, Maria
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lindberg, Anne
    Forssén, Annika
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Seroepidemiology, comorbidity and riskfactors for Puumula hantavirus in a highly endemic area of Sweden2011Conference paper (Other academic)
  • 34. Björkström, Niklas K
    et al.
    Lindgren, Therese
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Stoltz, Malin
    Fauriat, Cyril
    Braun, Monika
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Michaëlsson, Jakob
    Malmberg, Karl-Johan
    Klingström, Jonas
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Ljunggren, Hans-Gustaf
    Rapid expansion and long-term persistence of elevated NK cell numbers in humans infected with hantavirus2011In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 208, no 1, p. 13-21Article in journal (Refereed)
    Abstract [en]

    Natural killer (NK) cells are known to mount a rapid response to several virus infections. In experimental models of acute viral infection, this response has been characterized by prompt NK cell activation and expansion followed by rapid contraction. In contrast to experimental model systems, much less is known about NK cell responses to acute viral infections in humans. We demonstrate that NK cells can rapidly expand and persist at highly elevated levels for >60 d after human hantavirus infection. A large part of the expanding NK cells expressed the activating receptor NKG2C and were functional in terms of expressing a licensing inhibitory killer cell immunoglobulin-like receptor (KIR) and ability to respond to target cell stimulation. These results demonstrate that NK cells can expand and remain elevated in numbers for a prolonged period of time in humans after a virus infection. In time, this response extends far beyond what is considered normal for an innate immune response.

  • 35.
    Björsell, Tove
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Infectious Diseases, Karlstad Hospital, Karlstad, Sweden; Centre for Clinical Research and Education, Region Värmland, Karlstad, Sweden.
    Sundh, Josefin
    Department of Respiratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lange, Anna
    Department of Infectious Diseases, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Tevell, Staffan
    Department of Infectious Diseases, Karlstad Hospital, Karlstad, Sweden; Centre for Clinical Research and Education, Region Värmland, Karlstad, Sweden; Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Edin, Alicia
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Normark, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Cajander, Sara
    Department of Infectious Diseases, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Risk factors for impaired respiratory function post COVID-19: a prospective cohort study of nonhospitalized and hospitalized patients2023In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 293, no 5, p. 600-614Article in journal (Refereed)
    Abstract [en]

    Background: Severe COVID-19 increases the risk for long-term respiratory impairment, but data after mild COVID-19 are scarce. Our aims were to determine risk factors for reduced respiratory function 3–6 months after COVID-19 infection and to investigate if reduced respiratory function would relate to impairment of exercise performance and breathlessness. Methods: Patients with COVID-19 were enrolled at the University Hospitals of Umeå and Örebro, and Karlstad Central Hospital, Sweden. Disease severity was defined as mild (nonhospitalized), moderate (hospitalized with or without oxygen treatment), and severe (intensive care). Spirometry, including diffusion capacity (DLCO), was performed 3–6 months after hospital discharge or study enrollment (for nonhospitalized patients). Breathlessness (defined as ≥1 according to the modified Medical Research Council scale) and functional exercise capacity (1-min sit-to-stand test; 1-MSTST) were assessed. Results: Between April 2020 and May 2021, 337 patients were enrolled in the study. Forced vital capacity and DLCO were significantly lower in patients with severe COVID-19. Among hospitalized patients, 20% had reduced DLCO, versus 4% in nonhospitalized. Breathlessness was found in 40.6% of the participants and was associated with impaired DLCO. A pathological desaturation or heart rate response was observed in 17% of participants during the 1-MSTST. However, this response was not associated with reduced DLCO. Conclusion: Reduced DLCO was the major respiratory impairment 3–6 months following COVID-19, with hospitalization as the most important risk factor. The lack of association between impaired DLCO and pathological physiological responses to exertion suggests that these physiological responses are not primarily related to decreased lung function.

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  • 36.
    Blanco-Penedo, Isabel
    et al.
    Unit of Veterinary Epidemiology, Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Obanda, Vincent
    Veterinary Services Department, Kenya Wildlife Service, Nairobi, Kenya; Department of Research Permitting and Compliance, Wildlife Research and Training Institute, Naivasha, Kenya.
    Kingori, Edward
    Veterinary Services Department, Kenya Wildlife Service, Nairobi, Kenya; Department of Research Permitting and Compliance, Wildlife Research and Training Institute, Naivasha, Kenya.
    Agwanda, Bernard
    Mammalogy Section, National Museums of Kenya, Nairobi, Kenya.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Lwande, Olivia Wesula
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Seroepidemiology of Crimean-Congo Hemorrhagic Fever Virus (CCHFV) in cattle across three livestock pastoral regions in Kenya2021In: Dairy, E-ISSN 2624-862X, Vol. 2, no 3, p. 425-434Article in journal (Refereed)
    Abstract [en]

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonotic disease, endemic in Africa, with a high case fatality rate. There is no efficient treatment or licensed vaccine. This study aimed to determine the prevalence of CCHFV in cattle in extensive grazing systems (both pastoralism and ranching) within the Maasai Mara ecosystem, Nanyuki, and the Ol Pejeta Conservancy in Kenya. We conducted a seroepidemiological study of the sera of 148 cattle from 18 households from the three ecosystems in 2014, 2016, and 2019. Sera from 23 sheep and 17 goats were also obtained from the same households during the same period. Sera were analyzed for the presence of antibodies to CCHFV using the commercially available double-antigen ELISA kit. Overall, 31.5% CCHFV seropositivity was observed. The prevalence of CCHF was analyzed using a multiple logistic mixed model with main predictors. Risk factors associated with exposure to CCHFV were age (p = 0.000) and season (p = 0.007). Our findings suggest exposure to CCHFV and point to cattle as likely reservoirs of CCHFV in Kenya. The findings might play a role in providing better insights into disease risk and dynamics where analysis of tick populations in these regions should be further investigated.

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  • 37.
    Bortz, Robert H.
    et al.
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, NY, Bronx, United States.
    Florez, Catalina
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, NY, Bronx, United States; Department of Chemistry and Life Science, United States Military Academy at West Point, West Point, NY, United States.
    Laudermilch, Ethan
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, NY, Bronx, United States.
    Wirchnianski, Ariel S.
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, NY, Bronx, United States; Department of Biochemistry, Albert Einstein College of Medicine, NY, Bronx, United States.
    Lasso, Gorka
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, NY, Bronx, United States.
    Malonis, Ryan J.
    Department of Biochemistry, Albert Einstein College of Medicine, NY, Bronx, United States.
    Georgiev, George I.
    Department of Biochemistry, Albert Einstein College of Medicine, NY, Bronx, United States.
    Vergnolle, Olivia
    Department of Biochemistry, Albert Einstein College of Medicine, NY, Bronx, United States.
    Herrera, Natalia G.
    Department of Biochemistry, Albert Einstein College of Medicine, NY, Bronx, United States.
    Morano, Nicholas C.
    Department of Biochemistry, Albert Einstein College of Medicine, NY, Bronx, United States.
    Campbell, Sean T.
    Department of Pathology, Albert Einstein College of Medicine, NY, Bronx, United States; Montefiore Medical Center, NY, Bronx, United States.
    Orner, Erika P.
    Department of Pathology, Albert Einstein College of Medicine, NY, Bronx, United States; Montefiore Medical Center, NY, Bronx, United States.
    Mengotto, Amanda
    Montefiore Medical Center, NY, Bronx, United States; Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, NY, Bronx, United States.
    Dieterle, M. Eugenia
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, NY, Bronx, United States.
    Fels, J. Maximilian
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, NY, Bronx, United States.
    Haslwanter, Denise
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, NY, Bronx, United States.
    Jangra, Rohit K.
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, NY, Bronx, United States.
    Celikgil, Alev
    Department of Biochemistry, Albert Einstein College of Medicine, NY, Bronx, United States.
    Kimmel, Duncan
    Montefiore Medical Center, NY, Bronx, United States; Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, NY, Bronx, United States.
    Lee, James H.
    Department of Biochemistry, Albert Einstein College of Medicine, NY, Bronx, United States.
    Mariano, Margarette C.
    Department of Biochemistry, Albert Einstein College of Medicine, NY, Bronx, United States.
    Nakouzi, Antonio
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, NY, Bronx, United States; Montefiore Medical Center, NY, Bronx, United States; Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, NY, Bronx, United States.
    Quiroz, Jose
    Montefiore Medical Center, NY, Bronx, United States; Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, NY, Bronx, United States.
    Rivera, Johanna
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, NY, Bronx, United States; Montefiore Medical Center, NY, Bronx, United States; Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, NY, Bronx, United States.
    Szymczak, Wendy A.
    Department of Pathology, Albert Einstein College of Medicine, NY, Bronx, United States; Montefiore Medical Center, NY, Bronx, United States.
    Tong, Karen
    Department of Biochemistry, Albert Einstein College of Medicine, NY, Bronx, United States.
    Barnhill, Jason
    Department of Chemistry and Life Science, United States Military Academy at West Point, West Point, NY, United States.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Stein, Daniel T.
    Montefiore Medical Center, NY, Bronx, United States; Division of Endocrinology and Diabetes, Department of Medicine, Albert Einstein College of Medicine, NY, Bronx, United States.
    Pirofski, Liise-Anne
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, NY, Bronx, United States; Montefiore Medical Center, NY, Bronx, United States; Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, NY, Bronx, United States.
    Goldstein, D Yitzchak
    Department of Pathology, Albert Einstein College of Medicine, NY, Bronx, United States; Montefiore Medical Center, NY, Bronx, United States.
    Garforth, Scott J.
    Department of Biochemistry, Albert Einstein College of Medicine, NY, Bronx, United States.
    Almo, Steven C.
    Department of Biochemistry, Albert Einstein College of Medicine, NY, Bronx, United States.
    Daily, Johanna P.
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, NY, Bronx, United States; Montefiore Medical Center, NY, Bronx, United States; Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, NY, Bronx, United States.
    Prystowsky, Michael B.
    Department of Pathology, Albert Einstein College of Medicine, NY, Bronx, United States; Montefiore Medical Center, NY, Bronx, United States.
    Faix, James D.
    Department of Pathology, Albert Einstein College of Medicine, NY, Bronx, United States; Montefiore Medical Center, NY, Bronx, United States.
    Fox, Amy S.
    Department of Pathology, Albert Einstein College of Medicine, NY, Bronx, United States; Montefiore Medical Center, NY, Bronx, United States.
    Weiss, Louis M.
    Montefiore Medical Center, NY, Bronx, United States; Department of Pathology, Albert Einstein College of Medicine, NY, Bronx, United States.
    Lai, Jonathan R.
    Department of Biochemistry, Albert Einstein College of Medicine, NY, Bronx, United States.
    Chandran, Kartik
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, NY, Bronx, United States.
    Single-Dilution COVID-19 Antibody Test with Qualitative and Quantitative Readouts2021In: mSphere, E-ISSN 2379-5042, Vol. 6, no 2, article id e00224-21Article in journal (Refereed)
    Abstract [en]

    The coronavirus disease 2019 (COVID-19) global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to place an immense burden on societies and health care systems. A key component of COVID-19 control efforts is serological testing to determine the community prevalence of SARS-CoV-2 exposure and quantify individual immune responses to prior SARS-CoV-2 infection or vaccination. Here, we describe a laboratory-developed antibody test that uses readily available research-grade reagents to detect SARS-CoV-2 exposure in patient blood samples with high sensitivity and specificity. We further show that this sensitive test affords the estimation of viral spike-specific IgG titers from a single sample measurement, thereby providing a simple and scalable method to measure the strength of an individual's immune response. The accuracy, adaptability, and cost-effectiveness of this test make it an excellent option for clinical deployment in the ongoing COVID-19 pandemic.IMPORTANCE Serological surveillance has become an important public health tool during the COVID-19 pandemic. Detection of protective antibodies and seroconversion after SARS-CoV-2 infection or vaccination can help guide patient care plans and public health policies. Serology tests can detect antibodies against past infections; consequently, they can help overcome the shortcomings of molecular tests, which can detect only active infections. This is important, especially when considering that many COVID-19 patients are asymptomatic. In this study, we describe an enzyme-linked immunosorbent assay (ELISA)-based qualitative and quantitative serology test developed to measure IgG and IgA antibodies against the SARS-CoV-2 spike glycoprotein. The test can be deployed using commonly available laboratory reagents and equipment and displays high specificity and sensitivity. Furthermore, we demonstrate that IgG titers in patient samples can be estimated from a single measurement, enabling the assay's use in high-throughput clinical environments.

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  • 38. Braun, Monika
    et al.
    Bjorkström, Niklas K.
    Gupta, Shawon
    Sundström, Karin
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Klingström, Jonas
    Ljunggren, Hans-Gustaf
    NK Cell Activation in Human Hantavirus Infection Explained by Virus-Induced IL-15/IL15R alpha Expression2014In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 10, no 11, p. e1004521-Article in journal (Refereed)
    Abstract [en]

    Clinical infection with hantaviruses cause two severe acute diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). These diseases are characterized by strong immune activation, increased vascular permeability, and up to 50% case-fatality rates. One prominent feature observed in clinical hantavirus infection is rapid expansion of natural killer (NK) cells in peripheral blood of affected individuals. We here describe an unusually high state of activation of such expanding NK cells in the acute phase of clinical Puumala hantavirus infection. Expanding NK cells expressed markedly increased levels of activating NK cell receptors and cytotoxic effector molecules. In search for possible mechanisms behind this NK cell activation, we observed virus-induced IL-15 and IL-15R alpha on infected endothelial and epithelial cells. Hantavirus-infected cells were shown to strongly activate NK cells in a cell-cell contact-dependent way, and this response was blocked with anti-IL-15 antibodies. Surprisingly, the strength of the IL-15-dependent NK cell response was such that it led to killing of uninfected endothelial cells despite expression of normal levels of HLA class I. In contrast, hantavirus-infected cells were resistant to NK cell lysis, due to a combination of virus-induced increase in HLA class I expression levels and hantavirus-mediated inhibition of apoptosis induction. In summary, we here describe a possible mechanism explaining the massive NK cell activation and proliferation observed in HFRS patients caused by Puumala hantavirus infection. The results add further insights into mechanisms behind the immunopathogenesis of hantavirus infections in humans and identify new possible targets for intervention.

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  • 39.
    Brorstad, Alette
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Oscarsson, Kristina Bergstedt
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Early diagnosis of hantavirus infection by family doctors can reduce inappropriate antibiotic use and hospitalization2010In: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 28, no 3, p. 179-184Article in journal (Refereed)
    Abstract [en]

    Raised awareness in general practice regarding emerging infections and better diagnostic tools are desirable. This study of a Hantavirus outbreak shows that general practitioners are frontline doctors during outbreaks and through early and correct diagnosis they can reduce antibiotic treatment and hospitalization.

  • 40.
    Brundin, Peik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Department of Biosciences and Nutrition, Karolinska Institutet, NOVUM, Huddinge, Stockholm, Sweden.
    Zhao, Chunyan
    Dahlman-Wright, Karin
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evengård, Birgitta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Gene Expression of Estrogen Receptors in Pbmc From Patients With Puumala-Virus Infection2012In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 37, no 4, p. 355-359Article in journal (Refereed)
    Abstract [en]

    The influence of estrogen signaling on infectious diseases is not fully known. Males seem to be more susceptible to infections than females. This has also been noted for the Scandinavian form of hemorrhagic fever with renal syndrome caused by Puumala hantavirus (PUUV). To investigate the differences in estrogen receptors in relation to sex and clinical severity, 20 patients (10 males, 10 females) with confirmed PUUV infection were studied. Real-time polymerase chain reaction was performed for analyzing mRNA expression of estrogen receptor-alpha (ERV), ER beta, and ER beta 2 (ER beta cx) in peripheral blood mononuclear cells from patients and healthy age-and sex-matched blood donors. Blood chemistry and peripheral blood mononuclear cells sampling were performed during the acute and convalescent phases. None or very small amounts of ER beta were detected, and ER alpha and ER beta 2 mRNA were elevated in the patient group. The samples from the males were correlated with ER beta 2; the female samples, with ER alpha. Furthermore, the female and male samples are partly separated using multivariate statistic analysis (principal component analysis), supporting findings that clinical symptoms differ depending on sex.

  • 41.
    Cagigi, Alberto
    et al.
    Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Yu, Meng
    Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Österberg, Björn
    Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Svensson, Julia
    Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Falck-Jones, Sara
    Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Vangeti, Sindhu
    Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Åhlberg, Eric
    Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Azizmohammadi, Lida
    Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Warnqvist, Anna
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Falck-Jones, Ryan
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
    Gubisch, Pia C.
    Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Ödemis, Mert
    Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Ghafoor, Farangies
    Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Eisele, Mona
    Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Lenart, Klara
    Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Bell, Max
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
    Johansson, Niclas
    Division of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital Solna, Stockholm, Sweden.
    Albert, Jan
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Division of Clinical Microbiology, Karolinska University Laboratory, Karolinska University Hospital Solna, Stockholm, Sweden.
    Sälde, Jörgen
    Närakut SLSO, Karolinska University Hospital Solna, Stockholm, Sweden.
    Pettie, Deleah D.
    Department of Biochemistry, University of Washington, WA, Seattle, United States; Institute for Protein Design, University of Washington, WA, Seattle, United States.
    Murphy, Michael P.
    Department of Biochemistry, University of Washington, WA, Seattle, United States; Institute for Protein Design, University of Washington, WA, Seattle, United States.
    Carter, Lauren
    Department of Biochemistry, University of Washington, WA, Seattle, United States; Institute for Protein Design, University of Washington, WA, Seattle, United States.
    King, Neil P.
    Department of Biochemistry, University of Washington, WA, Seattle, United States; Institute for Protein Design, University of Washington, WA, Seattle, United States.
    Ols, Sebastian
    Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Normark, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Forsell, Mattias N.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Färnert, Anna
    Division of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital Solna, Stockholm, Sweden.
    Loré, Karin
    Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Smed-Sörensen, Anna
    Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination2021In: JCI Insight, ISSN 2379-3708, Vol. 6, no 22, article id e151463Article in journal (Refereed)
    Abstract [en]

    Understanding the presence and durability of antibodies against SARS-CoV-2 in the airways is required to provide insights into the ability of individuals to neutralize the virus locally and prevent viral spread. Here, we longitudinally assessed both systemic and airway immune responses upon SARS-CoV-2 infection in a clinically well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity, from asymptomatic infection to fatal disease. In addition, we evaluated how SARS-CoV-2 vaccination influenced the antibody responses in a subset of these individuals during convalescence as compared with naive individuals. Not only systemic but also airway antibody responses correlated with the degree of COVID-19 disease severity. However, although systemic IgG levels were durable for up to 8 months, airway IgG and IgA declined significantly within 3 months. After vaccination, there was an increase in both systemic and airway antibodies, in particular IgG, often exceeding the levels found during acute disease. In contrast, naive individuals showed low airway antibodies after vaccination. In the former COVID-19 patients, airway antibody levels were significantly elevated after the boost vaccination, highlighting the importance of prime and boost vaccinations for previously infected individuals to obtain optimal mucosal protection.

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  • 42.
    Connolly-Andersen, Anne-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Sorkfeber ökar risken för stroke och hjärtinfarkt2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 6Article in journal (Other academic)
  • 43.
    Connolly-Andersen, Anne-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Hammargren, Edvin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Whitaker, Heather
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Holmgren, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Klingstrom, Jonas
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Increased Risk of Acute Myocardial Infarction and Stroke During Hemorrhagic Fever With Renal Syndrome A Self-Controlled Case Series Study2014In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 129, no 12, p. 1295-1302Article in journal (Refereed)
    Abstract [en]

    Background We recently observed that cardiovascular causes of death are common in patients with hemorrhagic fever with renal syndrome (HFRS), which is caused by hantaviruses. However, it is not known whether HFRS is a risk factor for the acute cardiovascular events of acute myocardial infarction (AMI) and stroke. Methods and Results Personal identification numbers from the Swedish HFRS patient database (1997-2012; n=6643) were cross-linked with the National Patient Register from 1987 to 2011. Using the self-controlled case series method, we calculated the incidence rate ratio of AMI/stroke in the 21 days after HFRS against 2 different control periods either excluding (analysis 1) or including (analysis 2) fatal AMI/stroke events. The incidence rate ratios for analyses 1 and 2 for all AMI events were 5.53 (95% confidence interval [CI], 2.6-11.8) and 6.02 (95% CI, 2.95-12.3) and for first AMI events were 3.53 (95% CI, 1.25-9.96) and 4.64 (95% CI, 1.83-11.77). The incidence rate ratios for analyses 1 and 2 for all stroke events were 12.93 (95% CI, 5.62-29.74) and 15.16 (95% CI, 7.21-31.87) and for first stroke events were 14.54 (95% CI, 5.87-36.04) and 17.09 (95% CI, 7.49-38.96). The majority of stroke events occurred in the first week after HFRS. Seasonal effects were not observed, and apart from 1 study, neither sex nor age interacted with the associations observed in this study. Conclusions There is a significantly increased risk for AMI and stroke in the immediate time period after HFRS. Therefore, HFRS patients should be carefully monitored during the acute phase of disease to ensure early recognition of symptoms of impending AMI or stroke.

  • 44.
    Connolly-Andersen, Anne-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Rasmuson, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Öman, Mikael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Mesenteric Vein Thrombosis Following Platelet Transfusion in a Patient with Hemorrhagic Fever with Renal Syndrome: A Case Report2018In: TH open : companion journal to thrombosis and haemostasis, ISSN 2567-3459, Vol. 2, no 3, p. e261-e264Article in journal (Refereed)
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  • 45.
    Connolly-Andersen, Anne-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Sundberg, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Baudin, Maria
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Larsson, Johanna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Dunne, Eimear
    Clinical Research Centre, Royal College of Surgeons in Ireland, Dublin .
    Kenny, Dermot
    Clinical Research Centre, Royal College of Surgeons in Ireland, Dublin .
    Lindahl, Tomas L.
    Department of Clinical and Experimental Medicine, Linköping University, Sweden.
    Ramström, Sofia
    Department of Clinical and Experimental Medicine, Linköping University, Sweden.
    Nilsson, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Increased Thrombopoiesis and Platelet Activation in Hantavirus-Infected Patients2015In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 212, no 7, p. 1061-1069Article in journal (Refereed)
    Abstract [en]

    Background. Thrombocytopenia is a common finding during viral hemorrhagic fever, which includes hemorrhagic fever with renal syndrome (HFRS). The 2 main causes for thrombocytopenia are impaired thrombopoiesis and/or increased peripheral destruction of platelets. In addition, there is an increased intravascular coagulation risk during HFRS, which could be due to platelet activation. Methods. Thrombopoiesis was determined by quantification of platelet counts, thrombopoietin, immature platelet fraction, and mean platelet volume during HFRS. The in vivo platelet activation was determined by quantification of soluble P-selectin (sP-selectin) and glycoprotein VI (sGPVI). The function of circulating platelets was determined by ex vivo stimulation followed by flow cytometry analysis of platelet surface-bound fibrinogen and P-selectin exposure. Intravascular coagulation during disease was determined by scoring for disseminated intravascular coagulation (DIC) and recording thromboembolic complications. Results. The levels of thrombopoietin, immature platelet fraction, and mean platelet volume all indicate increased thrombopoiesis during HFRS. Circulating platelets had reduced ex vivo function during disease compared to follow-up. Most interestingly, we observed significantly increased in vivo platelet activation in HFRS patients with intravascular coagulation (DIC and thromboembolic complications) as shown by sP-selectin and sGPVI levels. Conclusions. HFRS patients have increased thrombopoiesis and platelet activation, which contributes to intravascular coagulation.

  • 46.
    Connolly-Andersen, Anne-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Thunberg, Therese
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Endothelial activation and repair during hantavirus infection: association with disease outcome2014In: Open forum infectious diseases, ISSN 2328-8957, Vol. 1, no 1, article id ofu027Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Endothelial activation and dysfunction play a central role in the pathogenesis of sepsis and viral hemorrhagic fevers. Hantaviral disease is a viral hemorrhagic fever and is characterized by capillary dysfunction, although the underlying mechanisms for hantaviral disease are not fully elucidated.

    METHODS: The temporal course of endothelial activation and repair were analyzed during Puumala hantavirus infection and associated with disease outcome and a marker for hypoxia, insulin-like growth factor binding protein 1 (IGFBP-1). The following endothelial activation markers were studied: endothelial glycocalyx degradation (syndecan-1) and leukocyte adhesion molecules (soluble vascular cellular adhesion molecule 1, intercellular adhesion molecule 1, and endothelial selectin). Cytokines associated with vascular repair were also analyzed (vascular endothelial growth factor, erythropoietin, angiopoietin, and stromal cell-derived factor 1).

    RESULTS: Most of the markers we studied were highest during the earliest phase of hantaviral disease and associated with clinical and laboratory surrogate markers for disease outcome. In particular, the marker for glycocalyx degradation, syndecan-1, was significantly associated with levels of thrombocytes, albumin, IGFBP-1, decreased blood pressure, and disease severity.

    CONCLUSIONS: Hantaviral disease outcome was associated with endothelial dysfunction. Consequently, the endothelium warrants further investigation when designing future medical interventions.

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  • 47.
    Connolly-Andersen, Anne-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Whitaker, Heather
    Klingstrom, Jonas
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Risk of venous thromboembolism following hemorrhagic fever with renal syndrome: a self-controlled case series study2018In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 66, no 2, p. 268-273Article in journal (Refereed)
    Abstract [en]

    Background: Bleeding is associated with viral hemorrhagic fevers; however, thromboembolic complications have received less attention. Hemorrhagic fever with renal syndrome (HFRS) is a mild viral hemorrhagic fever caused by Puumala hantavirus. We previously identified HFRS as a risk factor for myocardial infarction and stroke, but the risk for venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is unknown.

    Methods: Personal identity numbers from the Swedish HFRS database were cross-linked with the National Patient register to obtain information on all causes for hospitalization during 1964 to 2013. The self-controlled case series method was used to calculate the incidence rate ratio (IRR) for first VTE, DVT, and PE during 1998 to 2013.

    Results: From 7244 HFRS patients, there were 146 with a first VTE of which 74 were DVT and 78 were PE, and 6 patients had both DVT and PE. The overall risk for a VTE was significantly higher during the first 2 weeks following HFRS onset, with an IRR of 64.3 (95% confidence interval [CI], 36.3-114). The corresponding risk for a DVT was 45.9 (95% CI, 18-117.1) and for PE, 76.8 (95% CI, 37.1-159). Sex interacted significantly with the association between HFRS and VTE, with females having a higher risk compared with males.

    Conclusions: A significantly increased risk for VTE was found in the time period following HFRS onset. It is important to keep this in mind and monitor HFRS patients, and possibly other viral hemorrhagic fever patients, for early symptoms of VTE.

  • 48.
    Connolly-Andersson, Anne-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Ahlm, Kristin
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Forensic Medicine.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Klingström, Jonas
    Puumala virus infections associated with cardiovascular causes of death2013In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 19, no 1, p. 126-128Article in journal (Refereed)
    Abstract [en]

    We studied the causes of death of patients in Sweden with diagnoses of hemorrhagic fever with renal syndrome (HFRS) during 1997–2009. Cardiovascular disorders were a common cause of death during acute-phase HFRS and were the cause of death for >50% of those who died during the first year after HFRS.

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  • 49.
    Dernstedt, Andy
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Leidig, Jana
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Holm, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Kerkman, Priscilla
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Mjösberg, Jenny
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Henriksson, Johan
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Regulation of Decay Accelerating Factor Primes Human Germinal Center B Cells for Phagocytosis2021In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 11, article id 599647Article in journal (Refereed)
    Abstract [en]

    Germinal centers (GC) are sites for extensive B cell proliferation and homeostasis is maintained by programmed cell death. The complement regulatory protein Decay Accelerating Factor (DAF) blocks complement deposition on host cells and therefore also phagocytosis of cells. Here, we show that B cells downregulate DAF upon BCR engagement and that T cell-dependent stimuli preferentially led to activation of DAF(lo) B cells. Consistent with this, a majority of light and dark zone GC B cells were DAF(lo) and susceptible to complement-dependent phagocytosis, as compared with DAF(hi) GC B cells. We could also show that the DAF(hi) GC B cell subset had increased expression of the plasma cell marker Blimp-1. DAF expression was also modulated during B cell hematopoiesis in the human bone marrow. Collectively, our results reveal a novel role of DAF to pre-prime activated human B cells for phagocytosis prior to apoptosis.

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  • 50.
    Engdahl, Cecilia
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Larsson, Pär
    Swedish Defense Research Agency, CBRN Defense and Security, Umeå, Sweden.
    Näslund, Jonas
    Swedish Defense Research Agency, CBRN Defense and Security, Umeå, Sweden.
    Bravo, Mayra
    Swedish Defense Research Agency, CBRN Defense and Security, Umeå, Sweden.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lundström, Jan O.
    Department of Ecology and Genetics, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Bucht, Göran
    Swedish Defense Research Agency, CBRN Defense and Security, Umeå, Sweden.
    Identification of Swedish mosquitoes based on molecular barcoding of the COI gene and SNP analysis2014In: Molecular Ecology Resources, ISSN 1755-098X, E-ISSN 1755-0998, Vol. 14, no 3, p. 478-488Article in journal (Refereed)
    Abstract [en]

    Mosquito-borne infectious diseases are emerging in many regions of the world. Consequently, surveillance of mosquitoes and concomitant infectious agents is of great importance for prediction and prevention of mosquito-borne infectious diseases. Currently, morphological identification of mosquitoes is the traditional procedure. However, sequencing of specified genes or standard genomic regions, DNA barcoding, has recently been suggested as a global standard for identification and classification of many different species. Our aim was to develop a genetic method to identify mosquitoes and to study their relationship. Mosquitoes were captured at collection sites in northern Sweden and identified morphologically before the cytochrome c oxidase subunit I (COI) gene sequences of 14 of the most common mosquito species were determined. The sequences obtained were then used for phylogenetic placement, for validation and benchmarking of phenetic classifications and finally to develop a hierarchical PCR-based typing scheme based on single nucleotide polymorphism sites (SNPs) to enable rapid genetic identification, circumventing the need for morphological characterization. The results showed that exact phylogenetic relationships between mosquito taxa were preserved at shorter evolutionary distances, but at deeper levels, they could not be inferred with confidence using COI gene sequence data alone. Fourteen of the most common mosquito species in Sweden were identified by the SNP/PCR-based typing scheme, demonstrating that genetic typing using SNPs of the COI gene is a useful method for identification of mosquitoes with potential for worldwide application.

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