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O Vapalahti

Publications and source records attributed to O Vapalahti.

At least 19 recordsLinked to original sources

Rapid field test for detection of hantavirus antibodies in rodents.

Puumala virus (PUUV) is the causative agent of nephropathia epidemica, a mild form of haemorrhagic fever with renal syndrome. PUUV is transmitted to humans via aerosolized excreta of the infected bank vole (Clethrionomys glareolus). Current methods for screening of the PUUV prevalence among bank vole populations are laborious, combining sampling in the field and subsequent analyses in the laboratory. In order to facilitate animal testing, a new serological immunochromatographic rapid test was developed. The test uses PUUV nucleocapsid protein as antigen, and it detects anti-PUUV IgG antibodies in rodents. With fresh and undiluted bank-vole blood samples (n = 105) the efficacy of the test was 100%, and with frozen and diluted samples (n = 78) the efficacy was 91%. The test was also shown to detect related hantavirus infections in Norway lemmings and sibling voles (n = 31) with 99% efficacy. The test provides an applicable tool for studying PUUV and related hantavirus infections in arvicoline rodents.

Animals↗

Patterns of Puumala virus infection in Finland.

Puumala hantavirus infection is prevalent throughout most of Europe, and in endemic areas it may be the most common cause of acute renal failure. To evaluate trends in incidence of Puumala virus infections in Finland, we analysed national surveillance data in 12-month periods from March 1995 to February 2002. During this time, 8184 laboratory-confirmed cases were notified to the National Infectious Disease Register. Three epidemic periods were identified, for which the number of cases was more than 1400 (there were approximately 600-900 cases per non-epidemic period). The incidence of Puumala hantavirus infection varied by geographic region during the study period, and the overall number of cases may be increasing.

Adolescent↗

Epidemiology of Sindbis virus infections in Finland 1981-96: possible factors explaining a peculiar disease pattern.

Pogosta disease (PD), an epidemic rash-arthritis occurring in late summer is caused by Sindbis virus (SINV) and is transmitted to humans by mosquitoes. Altogether 2183 PD cases were serologically confirmed 1981-96 in Finland, with an annual incidence of 2.7/100000 (18 in the most endemic area of Northern Karelia). The annual average was 136 (varying from 1 to 1282) with epidemics occurring in August-September with a 7-year interval. Studies on 6320 patients with suspected rubella (1973-89) revealed 107 PD cases. The depth of snow cover and the temperature in May-July seemed to predict the number of cases. The morbidity was highest in 45- to 65-year-old females and lowest in children. Subclinical SINV infections were 17 times more common than the clinical ones. The SINV-antibody prevalence in fertile-age females was 0.6% in 1992; the estimated seroprevalence in Finland is about 2%. Among game animals the tetraonids (black grouse and capercaillie) had the highest seroprevalence (65%) in the epidemic year of 1981.

Adolescent↗

Prevalence of tick-borne encephalitis virus in Ixodes ricinus ticks in Finland.

Approximately 20 cases of tick-borne encephalitis (TBE) occur annually in Finland. The known endemic areas are situated mainly in the archipelago and coastal regions of Finland, with highest incidence in Aland islands. Ixodes ricinus panels collected in 1996-1997 from two endemic areas were screened for the presence of RNA. Two distinct RT-PCR methods were applied, and were shown to have an approximate detection limit of 10 focus forming doses (FFD)/100 microl. One out of 20 pools (a total of 139 ticks) from Helsinki Isosaari Island and one out of 48 pools (a total of 450 ticks) from Aland were positive with both methods, whereas the remaining pools were negative. The observed overall frequency (0.34%) in ticks in endemic areas of Finland, was similar to the low incidence found by virus isolation in mice in the 1960s (0.5%). Viral RNA was detectable in a diluted sample representing 0.005% of a positive pool of ten nymphs suggesting that the viral RNA load within an infected tick pool was approximately equivalent to 20,000-200,000 FFD. Sequence analysis did not show geographical clustering of the Finnish strains, suggesting an independent emergence of different TBE foci from the south. TBE virus RNA positive ticks were not found in I. ricinus panels consisting of 130 pools (726 ticks) from Helsinki city parks or 41 pools (197 ticks) from Võrmsi Island in Estonia.

Animals↗

Comparison of a new immunochromatographic rapid test with a commercial EIA for the detection of Puumala virus specific IgM antibodies.

BACKGROUND: Hantaviruses are associated with two human diseases: haemorrhagic fever with renal syndrome (HFRS) and Hantavirus pulmonary syndrome (HPS). Puumala virus (PUUV), which is one of the Hantaviruses, is a causative agent of nephropathia epidemica (NE), a mild form of HFRS. OBJECTIVE: a new 5 min rapid test, POC PUUMALA (Erilab Ltd, Finland), for detecting IgM antibodies to PUUV was evaluated and compared with the commercially available Hantavirus (Puumala) IgM ELISA test (Progen, Germany). Discrepant test results between the two tests were confirmed by a mu-capture reference EIA. STUDY DESIGN: Two hundred and thirty five serum samples, which had earlier been analyzed with the Progen IgM ELISA, were assayed with the POC PUUMALA rapid test. Five persons, without knowing the Progen IgM ELISA test results, interpreted independently the rapid test results. In addition, a panel of 48 serum samples was analyzed in parallel with the rapid test and the Progen IgM ELISA by one technician in daily routine diagnostics in a clinical microbiology laboratory. RESULTS: the agreement between the results of the five interpreters was 95%, and the congruence of the results between individual readers and commercial ELISA test varied from 93 to 96%. Diagnostic efficacy of the rapid test varied between 98 and 99% compared with 96% of the Progen IgM ELISA. The POC PUUMALA rapid test showed higher or similar sensitivity compared with the Progen IgM ELISA, whereas both the tests had similar levels of specificity. CONCLUSIONS: the analytical performance of the POC PUUMALA rapid test was found to be as good or even slightly better than the analytical performance of the Progen IgM ELISA. In addition, the rapid and straightforward procedure makes the POC PUUMALA a feasible tool for the diagnosis of the acute PUUV infection.

Antibodies, Viral↗

Polymorphism of the cytokine genes in hospitalized patients with Puumala hantavirus infection.

BACKGROUND: Nephropathia epidemica (NE) is a mild type of haemorrhagic fever with renal syndrome caused by Puumala (PUU) hantavirus. The clinical course of NE varies from asymptomatic to fatal. The aim of this study was to establish whether polymorphisms in the cytokine genes are associated with susceptibility to and outcome of NE. METHODS: The genotypes of the genes of tumour necrosis factor alpha (TNFalpha), interleukin-1alpha (IL-1alpha), IL-1beta and IL-1 receptor antagonist (IL-1RA) were analysed by polymerase chain reaction in 87 subjects, all hospital-treated for serologically confirmed acute NE. The control group comprised 400 healthy blood donors. Nineteen out of these 400 (5%) controls were PUU virus-seropositive. RESULTS: IL-1RA allele 2 and IL-1beta (base exchange polymorphism at position -511) allele 2 were strongly associated with each other in both groups. NE patients were more often IL-1RA-2 negative/IL-1beta-2 negative than PUU-seronegative blood donors (38 vs 27%, odds ratio 1.65, 95% confidence interval 1.0-2.7). However, there were no differences in the clinical severity of NE between the IL-1RA-2 negative/IL-1beta-2 negative and the other patients. The other allele frequencies studied evinced no statistically significant differences between the groups. Thirty-three out of 87 (38%) patients and 121 out of 381 (32%) seronegative controls were carriers of the high-producer genotype TNF2 allele. Several parameters showed the clinical course of NE to be more severe in TNF2 carriers than in non-carriers. CONCLUSIONS: These data suggest that non-carriage of the IL-1RA allele 2 and IL-1beta (-511) allele 2 may contribute to susceptibility to NE. Furthermore, TNFalpha polymorphism seems to be associated with the outcome of NE.

Adolescent↗

New immunochromatographic rapid test for diagnosis of acute Puumala virus infection.

A new immunochromatographic rapid test, POC PUUMALA (Erilab Ltd., Kuopio, Finland), for detection of acute-phase Puumala virus (PUUV) infection was developed based on a highly purified baculovirus-expressed PUUV nucleocapsid protein antigen and lateral immunodiffusion techniques. After addition of sample (5 microl of serum, plasma, or fingertip blood) and buffer, PUUV-specific immunoglobulin M (IgM) antibodies, if present, together with the gold-conjugated anti-human IgM, formed a specific colored line in 5 min. The sensitivity and specificity of the test were evaluated with 200 serum samples and 30 fingertip blood samples. The reference method for the serum samples was a micro-capture enzyme immunoassay (EIA) for IgM and an immunofluorescence assay (IFA) for IgG antibodies. The analytical sensitivity and specificity of the rapid test were 100 and 99%, respectively, for unfrozen serum samples (n = 103; 12 PUUV IgM-positive samples). When freeze-thawed serum samples were used, the sensitivity and specificity were each 97.1% (n = 70; 35 PUUV IgM-positive samples). The specificity of the test was 96.2% for 27 serum samples with nonspecific IgM antibodies or rheumatoid factor (RF). The fingertip blood samples (n = 30) were negative, but they gave clear positive results when spiked with IgM-positive sera (n = 20). The results were in good agreement with the standard diagnostic methods. The rapid performance, the lack of need for refined laboratory equipment, and the high specificity with fresh serum and fingertip blood samples indicate that the developed POC PUUMALA rapid test is a useful tool for fast diagnosis of acute PUUV infection.

Antibodies, Viral↗

Isolation of Dobrava virus from Apodemus flavicollis in Greece.

Dobrava virus (DOBV) carried by Apodemus flavicollis is the causative agent of severe hemorrhagic fever with renal syndrome (HFRS). DOBV was isolated from an A. flavicollis mouse trapped in northeastern Greece. This is the third DOBV cell culture isolate in the world, clustering together with other Greek DOBV sequences from HFRS patients and rodents.

Animals↗

Human immune response to Puumala virus glycoproteins and nucleocapsid protein expressed in mammalian cells.

Puumala hantavirus (PUUV) glycoproteins G1 and G2 and nucleocapsid protein (N) were expressed in BHK-21 cells by transfection of a plasmid producing a recombinant alphavirus replicon. Coexpression of G1 and G2 from separate constructs seemed to be important for the optimal folding of the glycoproteins, as evaluated by a panel of MAbs detecting conformational epitopes. To evaluate the human antibody response against recombinant G1, G2 and N, several panels of sera were tested by immunofluorescence assay (IFA). Also human sera showed the best reactivity towards G1 and G2 coexpressed from separate transcripts (G1 + G2). Notably, only 2% of the acute sera (total number = 133) contained IgG antibodies against G1 + G2, whereas of old-immunity sera (total number = 100) 87% were G1 + G2 positive. Analysis of a panel of serial patient sera showed that as the immunity matured, IgG antibodies against the recombinant glycoproteins appeared and the titers increased in the course of time, while antibodies against the recombinant N were present already in the acute phase in high titers. The granular fluorescence pattern in PUUV IgG-IFA, associated with the acute phase of immunity, was linked to the presence of antibodies against N, whereas the diffuse fluorescence pattern associated with old-immunity, was linked to the development of antibodies against G1 + G2. The granular fluorescence pattern in PUUV IgG-IFA had a predictive value of 100% for acute PUUV infection. Weak cross-reaction with PUUV glycoproteins was observed in 36% of old-immunity DOBV-specific human sera.

Adolescent↗

Systemic inflammation in hemorrhagic fever with renal syndrome correlates with hypotension and thrombocytopenia but not with renal injury.

Systemic inflammation is common in patients with nephropathia epidemica (NE), a European form of hemorrhagic fever. Markers of inflammation were studied in a patient with NE with respiratory insufficiency (patient 1), 18 other patients with NE, and 13 patients with a viral infectious disease other than NE. Neutrophil and monocyte CD11b expression levels, determined by flow cytometry; soluble interleukin (IL)-2 receptor (sIL-2R), IL-6, and IL-8 concentrations, determined by means of Immulite; and soluble E-selectin, determined by ELISA, were higher in patients with NE than in healthy subjects. The findings were not specific for NE and did not correlate with serum creatinine levels, but the findings correlated inversely with mean arterial pressure (sIL-2R and monocyte CD11b expression) and minimum platelet count (sIL-2R, IL-6, neutrophil, and monocyte CD11b expression). Monocyte CD11b expression in patient 1 was extremely high, suggesting that monocytes may contribute to development of lung injury. Severity of inflammation in patients with NE is related to hypotension and platelet consumption but not to renal injury.

Adolescent↗

Renal function and blood pressure five years after puumala virus-induced nephropathy.

BACKGROUND: Nephropathia epidemica (NE) is a mild form of hemorrhagic fever with renal syndrome caused by Puumala hantavirus. Its long-term prognosis is considered favorable. Some reports suggest, however, that a previous hantavirus infection increases the risk of hypertension. METHODS: We studied 46 previously healthy subjects (26 males and 20 females, mean age of 44 years) who had serologically confirmed NE three to seven years previously, and 38 healthy, seronegative controls (22 males and 16 females, mean age of 44 years). Ambulatory blood pressure (ABP) was monitored. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by 51CrEDTA and 131I-hippurate clearances, respectively. The filtration fraction (FF) was calculated. Quantitative 24-hour urinary protein excretion (UprotE) and timed overnight urinary excretion of alpha1-microglobulin were measured. RESULTS: The NE patients had a higher mean ambulatory systolic BP than the controls (123 +/- 13 vs. 117 +/- 9 mm Hg, P = 0. 008). GFR and FF were increased in patients compared with controls (GFR, 120 +/- 20 vs. 109 +/- 14 mL/min/1.73 m2, P = 0.006; FF, 19 +/- 3 vs. 18 +/- 3%, P = 0.030), but ERPF did not differ between the groups. The patients also had higher UPE than the controls (median 0. 18 g/day, range 0.12 to 0.38 vs. median 0.14 g/day, range 0.09 to 0. 24, P < 0.001, respectively). The overnight urinary excretion rate of alpha1-microglobulin exceeded 7 microg/min in nine patients. CONCLUSION: Three to seven years after NE, the patients had higher GFR and FF, more proteinuria, and higher ambulatory systolic BP compared with the healthy controls. NE may thus cause mild renal lesions and alterations in BP in some patients.

Acute Kidney Injury↗

Antigenic properties and diagnostic potential of recombinant dobrava virus nucleocapsid protein.

Dobrava hantavirus (DOBV) causes severe hemorrhagic fever with renal syndrome in the Balkan region and has been detected recently also in Russia, Estonia, and Germany. DOBV nucleocapsid protein (N) was produced in insect cells, using the baculovirus expression system (bac-DOBV-N), and in E. coli as a truncated (aa 1-165) glutathione-S transferase fusion protein (DOBV-dN-GST). The antigenic properties of bac-DOBV-N were found identical to native DOBV-N when examined by a panel of hantavirus-specific monoclonal antibodies. Enzyme immunoassays for detection of IgM and IgG antibodies were set up using DOBV recombinant N proteins and compared with those based on recombinant Hantaan and Puumala virus N, using panels of sera collected from DOBV, Hantaan and Puumala virus-infected patients. Full-length N protein (bac-DOBV-N) was found to be a more sensitive antigen than DOBV-dN-GST. The sensitivity values for sera from DOBV-infected patients were 100% for bac-DOBV-N and 86% for DOBV-dN-GST by IgM assays, and 98% for bac-DOBV-N and 88% for DOBV-dN-GST by IgG assays. The specificity values were 100% for bac-DOBV-N and 99% for DOBV-dN-GST by IgM assays, and 100% for both antigens by IgG assays.

Antigens, Viral↗

Puumala virus infections in Finland: increased occupational risk for farmers.

Puumala hantavirus, transmitted by bank voles (Clethrionomys glareolus), causes a mild-type hemorrhagic fever with renal syndrome. The disease is common in Finland and is considered an occupational hazard for farmers, but the actual risk has not been assessed by analytical studies. Data on 5,132 serologically confirmed Puumala virus infections during 1989-1994 were analyzed, and cases among farmers and the population living in similar conditions were compared. The farmers contracted the disease earlier and more often than did the comparison group. In the province of Mikkeli with the highest incidence (70/100,000), the risk ratio was 5.1 (95% confidence interval (CI) 3.0-8.4) for 20- to 29-year-old farmers; in the older age groups, the risk was still increased but the risk ratios were lower. The peak incidence in the comparison group was 10 years later (age group 30-39 years). For the whole country, the result was similar although less marked. The average risk ratio adjusted by age, sex, and geographic variation was 1.7 (95% CI 1.5-1.8) for the whole country and 1.9 (95% CI 1.5-2.3) for the Mikkeli province, where 80% of Puumala virus infections among young farmers could be estimated to be attributable to occupation.

Adult↗

Epidemiological study of nephropathia epidemica in Finland 1989-96.

This study presents data on 33,000 serum samples studied from July 1989 to June 1996 in Finland, with 6,701 serologically confirmed Puumala virus (PUU) infections. In addition, a PUU serosurvey of 8,000 sera from Finland is presented. On average, 957 PUU infections were detected annually, resulting in an incidence of 19/100,000; mortality was less than 0.1%. The infection was most common in the district of Ita-Savo with an incidence of 90/100,000. The seasonal peak was in November-December; however, the urban population had its incidence peak in August. Local epidemics mirrored bank vole densities, with 3-4-y cycles. Males contracted the disease at a mean age of 40 y, females at 44 y (male:female ratio 2:1). The disease was relatively rare in children and elderly people. The nationwide PUU antibody prevalence for women entering Finnish maternity clinics was 3%, suggesting 5% for the total population. The highest prevalences (7% for young women) were encountered in eastern Finland. In the district with the highest clinical alert, approximately 30% of all PUU infections were estimated to lead to clinical disease with serological confirmation.

Adolescent↗