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  • 1. 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.

  • 2.
    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.

  • 3.
    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)
  • 4.
    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.

  • 5.
    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)
  • 6.
    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).

  • 7.
    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)
  • 8.
    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)
  • 9.
    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.

  • 10.
    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).

  • 11.
    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.

  • 12.
    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.

  • 13.
    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.

  • 14.
    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.

  • 15.
    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.

  • 16.
    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.

  • 17.
    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)
  • 18.
    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.

  • 19.
    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.

  • 20. 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)
  • 21.
    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.

  • 22. 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.

  • 23. 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, ISSN 1743-422X, 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.

  • 24. 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: Jove-journal pf visualized experiments, 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.

  • 25. 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.

  • 26.
    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.

  • 27.
    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.

  • 28.
    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, ISSN 1471-2334, 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.

  • 29.
    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)
  • 30. 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.

  • 31. 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.

  • 32.
    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.

  • 33.
    Brundin, Peik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    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.

  • 34.
    Bystrom, Julia Wigren
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Näslund, Jonas
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Trulsson, Fredrik
    Umeå University, Faculty of Science and Technology, European CBRNE Center. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Wesula Lwande, Olivia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Bucht, Göran
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Quantification and kinetics of viral RNA transcripts produced in Orthohantavirus infected cells2018In: Virology Journal, ISSN 1743-422X, E-ISSN 1743-422X, Vol. 15, p. 1-7, article id 18Article in journal (Refereed)
    Abstract [en]

    Background: Rodent borne viruses of the Orthohantavirus genus cause hemorrhagic fever with renal syndrome among people in Eurasia, and hantavirus cardiopulmonary syndrome in the Americas. At present, there are no specific treatments or efficient vaccines against these diseases. Improved understanding of viral transcription and replication may instigate targeted treatment of Orthohantavirus infections. For this purpose, we investigated the kinetics and levels of viral RNA transcription during an ongoing infection in-vitro. Methods: Vero E6 cells were infected with Puumala Orthohantavirus (strain Kazan) before cells and supernatants were collected at different time points post infection for the detection of viral RNAs. A plasmid containing primer binding sites of the three Orthohantavirus segments small (S), medium (M) and large (L) was constructed and standard curves were generated to calculate the copy numbers of the individual transcripts in the collected samples. Results: Our results indicated a rapid increase in the copy number of viral RNAs after 9 h post infection. At peak days, 2-6 days after infection, the S- and M-segment transcripts became thousand and hundred-fold more abundant than the copy number of the L-segment RNA, respectively. The presence of viral RNA in the cell culture media was detected at later time-points. Conclusions: We have developed a method to follow RNA transcription in-vitro after synchronous infection of Vero cells. The obtained results may contribute to the understanding of the viral replication, and may have implications in the development of antiviral drugs targeting transcription or replication of negative stranded RNA viruses.

  • 35.
    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.

  • 36.
    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.

  • 37.
    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.

  • 38.
    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.

  • 39.
    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.

  • 40.
    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.

  • 41.
    Engdahl, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Näslund, Jonas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Lindgren, Lena
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Bucht, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    The Rift Valley Fever virus protein NSm and putative cellular protein interactions2012In: Virology Journal, ISSN 1743-422X, Vol. 9, p. 139-Article in journal (Refereed)
    Abstract [en]

    Rift Valley Fever is an infectious viral disease and an emerging problem in many countries of Africa and on the Arabian Peninsula. The causative virus is predominantly transmitted by mosquitoes and high mortality and abortion rates characterize outbreaks in animals while symptoms ranging from mild to life-threatening encephalitis and hemorrhagic fever are noticed among infected humans. For a better prevention and treatment of the infection, an increased knowledge of the infectious process of the virus is required. The focus of this work was to identify protein-protein interactions between the non-structural protein (NSm), encoded by the M-segment of the virus, and host cell proteins. This study was initiated by screening approximately 26 million cDNA clones of a mouse embryonic cDNA library for interactions with the NSm protein using a yeast two-hybrid system. We have identified nine murine proteins that interact with NSm protein of Rift Valley Fever virus, and the putative protein-protein interactions were confirmed by growth selection procedures and beta-gal activity measurements. Our results suggest that the cleavage and polyadenylation specificity factor subunit 2 (Cpsf2), the peptidyl-prolyl cistrans isomerase (cyclophilin)-like 2 protein (Ppil2), and the synaptosome-associated protein of 25 kDa (SNAP-25) are the most promising targets for the NSm protein of the virus during an infection.

  • 42. Esbjörner, E
    et al.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Clinical quiz. Nephropathia epidemica. Specific IgM antibodies against Puumalavirus can be found in serum.1994In: Pediatric nephrology (Berlin, West), ISSN 0931-041X, E-ISSN 1432-198X, Vol. 8, no 2, p. 257-8Article in journal (Refereed)
  • 43.
    Evander, Magnus
    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.
    Milder winters in northern Scandinavia may contribute to larger outbreaks of haemorrhagic fever virus2009In: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 2Article in journal (Refereed)
    Abstract [en]

    The spread of zoonotic infectious diseases may increase due to climate factors such as temperature, humidity and precipitation. This is also true for hantaviruses, which are globally spread haemorrhagic fever viruses carried by rodents. Hantaviruses are frequently transmitted to humans all over the world and regarded as emerging viral diseases. Climate variations affect the rodent reservoir populations and rodent population peaks coincide with increased number of human cases of hantavirus infections. In northern Sweden, a form of haemorrhagic fever called nephropathia epidemica (NE), caused by the Puumala hantavirus (PUUV) is endemic and during 2006-2007 an unexpected, sudden and large outbreak of NE occurred in this region. The incidence was 313 cases/100,000 inhabitants in the most endemic areas, and from January through March 2007 the outbreak had a dramatic and sudden start with 474 cases in the endemic region alone. The PUUV rodent reservoir is bank voles and immediately before and during the peak of disease outbreak the affected regions experienced extreme climate conditions with a record-breaking warm winter, registering temperatures 6-9 degrees C above normal. No protective snow cover was present before the outbreak and more bank voles than normal came in contact with humans inside or in close to human dwellings. These extreme climate conditions most probably affected the rodent reservoir and are important factors for the severity of the outbreak.

  • 44.
    Evander, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Eriksson, Irene
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Pettersson, Lisa
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Juto, Per
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Olsson, Gert E
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Bucht, Göran
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Allard, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Puumala hantavirus viremia diagnosed by real-time reverse transcriptase PCR using samples from patients with hemorrhagic fever and renal syndrome.2007In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 45, no 8, p. 2491-7Article in journal (Refereed)
    Abstract [en]

    Puumala virus (PUUV) is the endemic hantavirus in northern Sweden and causes nephropathia epidemica (NE), a milder form of hemorrhagic fever with renal syndrome. There is a need for fast and reliable diagnostics to differentiate the disease from other infections. By aligning virus RNA sequences isolated from 11 different bank voles and one human patient, we designed a real-time reverse transcriptase (RT) PCR method for detection of PUUV RNA. The real-time RT-PCR assay showed linearity from 20 to 2 x 10(6) virus copies with a correlation coefficient above 0.98 to 0.99 for all experiments. The detection threshold for PUUV cDNA was two copies per reaction. A two-step qualitative RT-PCR to detect PUUV RNA showed 100% concordance with the real-time RT-PCR assay. PUUV RNA viremia was detected in 33 of 34 PUUV immunoglobulin M (IgM)-positive patients with typical clinical NE disease from the region of endemicity. One PUUV IgM-negative sample had PUUV RNA, and 4 days later, the patient was IgM positive. Of samples with indeterminate IgM, 43% were PUUV RNA positive. The kinetics of antibody titers and PUUV viremia were studied, and five of six NE patients displayed a decrease in PUUV viremia a few days after disease outbreak coupled with an increase in PUUV IgM and IgG. In one patient with continuously high PUUV RNA levels but low IgM and no IgG response, the infection was lethal. These findings demonstrated that real-time RT-PCR is a useful method for diagnosis of PUUV viremia and for detecting PUUV RNA at early time points, before the appearance of IgM antibodies.

  • 45.
    Evander, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Putkuri, Niina
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lwande, Olivia Wesula
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Vapalahti, Olli
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Seroprevalence and Risk Factors of Inkoo Virus in Northern Sweden2016In: American Journal of Tropical Medicine and Hygiene, ISSN 0002-9637, E-ISSN 1476-1645, Vol. 94, no 5, p. 1103-1106Article in journal (Refereed)
    Abstract [en]

    The mosquito-borne Inkoo virus (INKV) is a member of the California serogroup in the family Bunyaviridae, genus Orthobunyavirus These viruses are associated with fever and encephalitis, although INKV infections are not usually reported and the incidence is largely unknown. The aim of the study was to determine the prevalence of anti-INKV antibodies and associated risk factors in humans living in northern Sweden. Seroprevalence was investigated using the World Health Organization Monitoring of Trends and Determinants in Cardiovascular Disease study, where a randomly selected population aged between 25 and 74 years (N = 1,607) was invited to participate. The presence of anti-INKV IgG antibodies was determined by immunofluorescence assay. Seropositivity for anti-INKV was significantly higher in men (46.9%) than in women (34.8%; P < 0.001). In women, but not in men, the prevalence increased somewhat with age (P = 0.06). The peak in seropositivity was 45-54 years for men and 55-64 years for women. Living in rural areas was associated with a higher seroprevalence. In conclusion, the prevalence of anti-INKV antibodies was high in northern Sweden and was associated with male sex, older age, and rural living. The age distribution indicates exposure to INKV at a relatively early age. These findings will be important for future epidemiological and clinical investigations of this relatively unknown mosquito-borne virus.

  • 46.
    Furberg, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Xijia, Liu
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Nystedt, Anders
    Stenmark, Stephan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Elisasson, Mats
    Sellin, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Johansson, Andersson
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Tularemia in northern Sweden - sero-prevalence and a case-control study of risk factorsArticle in journal (Refereed)
  • 47. Gherasim, Alin
    et al.
    Hjertqvist, Marika
    Lundkvist, Åke
    Kühlmann-Berenzon, Sharon
    Verner Carlson, Jenny
    Stenmark, Stephan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Widerström, Mikael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Department of Communicable Disease Control and Prevention, Jämtland County Council, Östersund, Sweden.
    Österlund, Anders
    Boman, Hans
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Wallensten, Anders
    Risk factors and potential preventive measures for nephropatia epidemica in Sweden 2011-2012: a case-control study2015In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 5, article id 27698Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Nephropatia epidemica (NE), a relatively mild form of hemorrhagic fever with renal syndrome caused by the Puumala virus (PUUV), is endemic in northern Sweden. We aim to study the risk factors associated with NE in this region.

    METHODS: We conducted a matched case-control study between June 2011 and July 2012. We compared confirmed NE cases with randomly selected controls, matched by age, sex, and place of infection or residence. We analyzed the association between NE and several occupational, environmental, and behavioral exposures using conditional logistic regression.

    RESULTS: We included in the final analysis 114 cases and 300 controls, forming 246 case-control pairs. Living in a house with an open space beneath, making house repairs, living less than 50 m from the forest, seeing rodents, and smoking were significantly associated with NE.

    CONCLUSION: Our results could orient public health policies targeting these risk factors and subsequently reduce the NE burden in the region.

  • 48. Gnann, John W, Jr
    et al.
    Sköldenberg, Birgit
    Hart, John
    Aurelius, Elisabeth
    Schliamser, Silvia
    Studahl, Marie
    Eriksson, Britt-Marie
    Hanley, Daniel
    Aoki, Fred
    Jackson, Alan C
    Griffiths, Paul
    Miedzinski, Lil
    Hanfelt-Goade, Diane
    Hinthorn, Daniel
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Aksamit, Allen
    Cruz-Flores, Salvador
    Dale, Ilet
    Cloud, Gretchen
    Jester, Penelope
    Whitley, Richard J
    Herpes Simplex Encephalitis: Lack of Clinical Benefit of Long-term Valacyclovir Therapy2015In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 61, no 5, p. 683-691Article in journal (Refereed)
    Abstract [en]

    Background: Despite the proven efficacy of acyclovir (ACV) therapy, herpes simplex encephalitis (HSE) continues to cause substantial morbidity and mortality. Among patients with HSE treated with ACV, the mortality rate is approximately 14%-19%. Among survivors, 45%-60% have neuropsychological sequelae at 1 year. Thus, improving therapeutic approaches to HSE remains a high priority. Methods: Following completion of a standard course of intravenous ACV, 87 adult patients with HSE (confirmed by positive polymerase chain reaction [PCR] for herpes simplex virus DNA in cerebrospinal fluid) were randomized to receive either valacyclovir (VACV) 2 g thrice daily (n = 40) or placebo tablets (n = 47) for 90 days (12 tablets of study medication daily). The primary endpoint was survival with no or mild neuropsychological impairment at 12 months, as measured by the Mattis Dementia Rating Scale (MDRS). Logistic regression was utilized to assess factors related to the primary endpoint. Results: The demographic characteristics of the 2 randomization groups were statistically similar with no significant differences in age, sex, or race. At 12 months, there was no significant difference in the MDRS scoring for VACV-treated vs placebo recipients, with 85.7% and 90.2%, respectively, of patients demonstrating no or mild neuropsychological impairment (P = .72). No significant study-related adverse events were encountered in either treatment group. Conclusions: Following standard treatment with intravenous ACV for PCR-confirmed HSE, an additional 3-month course of oral VACV therapy did not provide added benefit as measured by neuropsychological testing 12 months later in a population of relatively high-functioning survivors.

  • 49. Grankvist, Olof
    et al.
    Juto, Per
    Settergren, Bo
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Bjermer, L
    Linderholm, M
    Tärnvik, A
    Wadell, G
    Detection of nephropathia epidemica virus RNA in patient samples using a nested primer-based polymerase chain reaction.1992In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 165, no 5, p. 934-7Article in journal (Refereed)
    Abstract [en]

    A nested primer-based polymerase chain reaction was constructed for the detection of Puumala virus RNA in patient samples. Puumala virus RNA was detected in cells from the urinary and the respiratory tracts and in peripheral blood mononuclear cells of patients with nephropathia epidemica. After inoculation with nephropathia epidemica patient material on Vero E6 cells and propagation for nine passages (4 months), Puumala virus RNA was detected at every passage. Hybridization under high-stringency conditions revealed that the overall nucleotide homology between the different patient isolates and the prototype strain (Puumala) is high. Using cDNA from Hällnäs B1 strain as a probe, hybridization occurred only under low-stringency conditions.

  • 50. Hansson, Marit
    et al.
    Stockfelt, Leo
    Urazalin, Marat
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Andersson, Rune
    HIV/AIDS awareness and risk behavior among students in Semey, Kazakhstan: a cross-sectional survey.2008In: BMC International Health and Human Rights, ISSN 1472-698X, E-ISSN 1472-698X, Vol. 8, p. 14-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Until recently, young people in Kazakhstan have been only moderately affected by the global HIV epidemic. Today, however, the HIV epidemic in Central Asia is one of the most rapidly increasing epidemics in the world. It is mainly concentrated to vulnerable groups such as intravenous drug users, sex workers, the purchasers of sexual services and the financially marginalized. Young, sexually active people may however be the gateway for the epidemic to the general population, and knowledge about their attitudes and behavior is therefore important in planning preventive measures. METHODS: To gather information about young students and their attitudes and knowledge about HIV/AIDS, we collected 600 structured questionnaires and made 23 semi-structured interviews among three groups of students. Response rate was 99%. RESULTS: Almost 99% of the respondents had heard of HIV/AIDS, and 89% could identify ways to protect oneself against sexually transmitted HIV/AIDS. The main routes of transmission, sexual contact without condom and intravenous drug use, were both identified by 97% of the students. Twenty-five percent of the female students and 75% of the male students had had one or more sexual partners. More than 30% of the young men had purchased sex, and homosexuality was widely stigmatized. CONCLUSION: Risks for the spread of HIV/AIDS among young people in Kazakhstan include prostitution as well as stigmatization of the HIV positive and of homosexuals. Protective factors are good knowledge about risks and protection, and opportunities to talk and gather information about sexuality and HIV/AIDS.

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