[Show abstract][Hide abstract] ABSTRACT: Here, we report 40 new whole-genome sequences of influenza A(H1N1)pdm09 viruses isolated from Finnish patients during 2009 to 2014. A preliminary analysis of these and 186 other whole genomes of influenza A(H1N1)pdm09 viruses isolated from hospitalized and nonhospitalized patients during 2009 to 2014 in Finland revealed several viral mutations that might be associated with patient hospitalizations.
[Show abstract][Hide abstract] ABSTRACT: Here, we report 40 complete genome sequences of influenza A/H1N1 strains isolated from 33 nonhospitalized and 7 hospitalized
patients during the 2013-2014 epidemic season in Finland. An analysis of the aligned sequences revealed no oseltamivir-resistant
genotypes. As a whole, the recent viruses have drifted from the prototype A/California/7/2009 virus by ca. 1.3%.
[Show abstract][Hide abstract] ABSTRACT: Virus strains in the seasonal influenza vaccine for the 2014/15 northern hemisphere season remained unchanged from those in 2013/14. During spring 2014, drifted influenza A(H3N2) viruses, subgroup 3C.3a, were detected in Finland; another subgroup, 3C.2a, emerged in the 2014/15 season and has predominated. We monitored antibody responses against vaccine and epidemic strains (2013/14 and 2014/15) among Finnish healthcare workers after influenza vaccination with the 2013/14 vaccine. The data suggest reduced cross-protection towards both subgroups of drifted A(H3N2) viruses.
Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 02/2015; 20(5):21028. DOI:10.2807/1560-7917.ES2015.20.5.21028 · 5.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The influenza season 2014/15 started in Europe in week 50 2014 with influenza A(H3N2) viruses predominating. The majority of the A(H3N2) viruses characterised antigenically and/or genetically differ from the northern hemisphere vaccine component which may result in reduced vaccine effectiveness for the season. We therefore anticipate that this season may be more severe than the 2013/14 season. Treating influenza with antivirals in addition to prevention with vaccination will be important.
Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 01/2015; 20(4):1-5. · 5.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Influenza B virus strains in trivalent influenza vaccines are frequently mismatched to the circulating B strains, but the population-level impact of such mismatches is unknown. We assessed the impact of vaccine mismatch on the epidemiology of influenza B during 12 recent seasonal outbreaks of influenza in Finland.
We analyzed all available nationwide data on virologically confirmed influenza infections in all age groups in Finland between 1 July 1999 and 30 June 2012, with the exclusion of the pandemic season of 2009-2010. We derived data on influenza infections and the circulation of different lineages of B viruses during each season from the Infectious Diseases Register and the National Influenza Center, National Institute for Health and Welfare, Finland.
A total of 34 788 cases of influenza were recorded. Influenza A accounted for 74.0% and influenza B for 26.0% of all typed viruses. Throughout the 12 seasons, we estimated that 41.7% (3750 of 8993) of all influenza B infections were caused by viruses representing the other genetic lineage than the one in the vaccine. Altogether, opposite-lineage influenza B viruses accounted for 10.8% of all influenza infections in the population, the proportion being highest (16.8%) in children aged 10-14 years and lowest (2.6%) in persons aged ≥70 years.
The population-level impact of lineage-level mismatch between the vaccine and circulating strains of influenza B viruses is substantial, especially among children and adolescents. The results provide strong support for the inclusion of both influenza B lineages in seasonal influenza vaccines.
[Show abstract][Hide abstract] ABSTRACT: The influenza pH1N1 virus caused a global flu pandemic in 2009 and continues manifestation as a seasonal virus. Better understanding of the virus-host cell interaction could result in development of better prevention and treatment options. Here we show that Akt inhibitor MK2206, blocks influenza pH1N1 virus infection in vitro. In particular, at non-cytotoxic concentrations MK2206 alters Akt signaling and inhibits endocytic uptake of the virus. Interestingly, MK2206 is unable to inhibit H3N2, H7N9 and H5N1 viruses indicating that pH1N1 evolved specific requirements for efficient infection. Thus, Akt signaling could be exploited further for development of better therapeutics against pH1N1 virus.
[Show abstract][Hide abstract] ABSTRACT: Here we report full-length sequencing of the first large set of influenza A(H1N1)pdm09 virus genomes isolated in Finland between the years 2009 and 2013 and discuss the advantages and needs of influenza virus sequencing efforts.
[Show abstract][Hide abstract] ABSTRACT: Swine influenza is an infectious acute respiratory disease of pigs caused by influenza A virus. In this retrospective serological study we investigated the time of entry of swine influenza into the Finnish pig population. We also describe the molecular detection of two types of influenza A (H1N1) viruses in porcine samples submitted in 2009 and 2010.This retrospective study was based on three categories of samples: blood samples collected for disease monitoring from pigs at major slaughterhouses from 2007 to 2009; blood samples from pigs in farms with a special health status taken in 2008 and 2009; and diagnostic blood samples from pigs in farms with clinical signs of respiratory disease in 2008 and 2009.The blood samples were tested for influenza A antibodies with an antibody ELISA. Positive samples were further analyzed for H1N1, H3N2, and H1N2 antibodies with a hemagglutination inhibition (HI) test.Diagnostic samples (lungs, nasal swabs) for virus detection were subjected to influenza A M-gene-specific real-time RT-PCR and to pandemic influenza A H1N1-specific real-time RT-PCR. Positive samples were further analyzed with RT-PCRs designed for this purpose, and the PCR products were sequenced. Phylogenetic analyses were carried out to characterize the viruses more precisely.
In the blood samples from pigs in special health class farms producing replacement animals and in diagnostic blood samples, the first serologically positive samples originated from the period July--August 2008. In samples collected for disease monitoring, < 0.1%, 0% and 16% were positive for antibodies against influenza A H1N1 in the HI test in 2007, 2008, and 2009, respectively.Swine influenza A virus of avian-like H1N1 was first detected in diagnostic samples in February 2009. In 2009 and 2010, the avian-like H1N1 virus was detected on 12 and two farms, respectively. The pandemic H1N1 virus (A(H1N1)pdm09) was detected on one pig farm in 2009 and on two farms in 2010.
Based on our study, swine influenza of avian-like H1N1 virus was introduced into the Finnish pig population in 2008 and A(H1N1)pdm09 virus in 2009. The source of avian-like H1N1 infection could not be determined. Cases of pandemic H1N1 in pigs coincided with the period when the A(H1N1)pdm09 virus was spread in humans in Finland.
[Show abstract][Hide abstract] ABSTRACT: The clinical picture of influenza may vary from mild respiratory infection to pneumonia requiring intensive care. Annual epidemics are most commonly caused by H3N2 or H1N1 type influenza A or influenza B viruses. The population's immune protection against a new virus type is low, whereupon morbidity and mortality may be high. Vaccinations are the most important means to decrease influenza morbidity. Annual variation and quick intercontinental migration of influenza viruses, combined with the possibility of the creation of reassortant viruses, are significant challenges for the development of influenza vaccines.
[Show abstract][Hide abstract] ABSTRACT: Background Influenza A(H1N1)pdm09 virus has been circulating in human population for three epidemic seasons. During this time, monovalent pandemic and trivalent seasonal influenza vaccination against this virus have been offered to Finnish healthcare professionals. It is, however, unclear how well vaccine-induced antibodies recognize different strains of influenza A(H1N1)pdm09 circulating in the population and whether the booster vaccination with seasonal influenza vaccine would broaden the antibody cross-reactivity.
Objectives Influenza vaccine-induced humoral immunity against several isolates of influenza A(H1N1)pdm09 virus was analyzed in healthcare professionals. Age-dependent responses were also analyzed.
Methods Influenza viruses were selected to represent viruses that circulated in Finland during two consecutive influenza epidemic seasons 2009–2010 and 2010–2011. Serum samples from vaccinated volunteers, age 20–64 years, were collected before and after vaccination with AS03-adjuvanted pandemic and non-adjuvanted trivalent seasonal influenza vaccine that was given 1 year later.
Results Single dose of pandemic vaccine induced a good albeit variable antibody response. On day 21 after vaccination, depending on the virus strain, 14–75% of vaccinated had reached antibody titers (≥1:40) considered seroprotective. The booster vaccination 1 year later with a seasonal vaccine elevated the seroprotection rate to 57–98%. After primary immunization, younger individuals (20–48 years) had significantly higher antibody titers against all tested viruses than older persons (49–64 years) but this difference disappeared after the seasonal booster vaccination.
Conclusions Even a few amino acid changes in influenza A HA may compromise the vaccine-induced antibody recognition. Older adults (49 years and older) may benefit more from repeated influenza vaccinations.
Influenza and Other Respiratory Viruses 08/2012; 7(3). DOI:10.1111/j.1750-2659.2012.00415.x · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Timely identification of respiratory pathogens is essential for appropriate patient care and cohorting. In order to do rapid identification-technology near the patient we utilized the field-deployable RAZOR EX-thermocycler with a reverse transcription real-time PCR assay that detects all subtypes of influenza A virus. In addition, we developed a RT PCR assay for specific detection of influenza A(H1N1)pdm09 virus. These assays amplified segments of the matrix (M)- and the hemagglutinin (HA)-gene, respectively. Detection limits of the M-gene and the influenza A(H1N1)pdm09-specific HA-gene assays were 0.15 PFU and 8.8 PFU per reaction, respectively. With 18 influenza A viruses of different subtypes and influenza B, C, and 7 other respiratory viruses the RAZOR EX and standard real-time PCR assay results were in total agreement. From 104 clinical samples identical results were obtained by both PCR methods. Additional 21 clinical samples were tested under field conditions with the RAZOR EX instrument. Results were achieved in 90 min, including 45 min for sample preparation and they were in complete agreement with those obtained by standard real-time PCR under laboratory conditions. These methods enable highly sensitive and rapid on-site diagnostics to reliably identify patients infected with influenza A, including the influenza A(H1N1)pdm09-virus.
[Show abstract][Hide abstract] ABSTRACT: The influenza A(H1N1)2009 virus has been the dominant type of influenza A virus in Finland during the 2009-2010 and 2010-2011 epidemic seasons. We analyzed the antigenic characteristics of several influenza A(H1N1)2009 viruses isolated during the two influenza seasons by analyzing the amino acid sequences of the hemagglutinin (HA), modeling the amino acid changes in the HA structure and measuring antibody responses induced by natural infection or influenza vaccination.
Based on the HA sequences of influenza A(H1N1)2009 viruses we selected 13 different strains for antigenic characterization. The analysis included the vaccine virus, A/California/07/2009 and multiple California-like isolates from 2009-2010 and 2010-2011 epidemic seasons. These viruses had two to five amino acid changes in their HA1 molecule. The mutation(s) were located in antigenic sites Sa, Ca1, Ca2 and Cb region. Analysis of the antibody levels by hemagglutination inhibition test (HI) indicated that vaccinated individuals and people who had experienced a natural influenza A(H1N1)2009 virus infection showed good immune responses against the vaccine virus and most of the wild-type viruses. However, one to two amino acid changes in the antigenic site Sa dramatically affected the ability of antibodies to recognize these viruses. In contrast, the tested viruses were indistinguishable in regard to antibody recognition by the sera from elderly individuals who had been exposed to the Spanish influenza or its descendant viruses during the early 20(th) century.
According to our results, one to two amino acid changes (N125D and/or N156K) in the major antigenic sites of the hemagglutinin of influenza A(H1N1)2009 virus may lead to significant reduction in the ability of patient and vaccine sera to recognize A(H1N1)2009 viruses.
PLoS ONE 10/2011; 6(10):e25848. DOI:10.1371/journal.pone.0025848 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The first infection caused by pandemic influenza A(H1N1)2009 virus was confirmed in Finland on 10 May 2009. The spread of the disease and its impact were monitored using several surveillance systems, such as the national infectious disease register, notifications of clusters of influenza, influenza-like or influenzarelated illnesses, as well as virological, hospital, casebased and mortality surveillance. The epidemic started in early October in the north and then spread to the south about two weeks later. Based on the data from laboratory-confirmed cases, the morbidity was highest in children. The daily number of patients hospitalized with influenza A(H1N1)2009 reached a maximum of over 400 in late November. Of the 1,580 hospitalised patients (median age 32 years), 672 (43%) had at least one chronic underlying illness, 35 (2%) were pregnant, 132 (8%) were treated in intensive care units and 74 (5%) required mechanical ventilation. The median age of patients admitted to intensive care units was 48 years and 78 (59%) of them had at least one chronic underlying disease, none were pregnant. Altogether 44 deaths related to influenza A(H1N1)2009 were recorded (median age 56 years): 40 belonged to high-risk groups on the basis of underlying chronic diseases. Combining data from different surveillance systems gave timely information about the spread of the pandemic and contributed to identifying risk groups.
Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 07/2011; 16(27). · 5.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Real-time reverse transcription-PCR assays specific for the nonstructural (NS) and hemagglutinin (HA) genes of the 2009 pandemic influenza A (H1N1) virus were developed and evaluated with clinical samples from infected patients. The tests are characterized by high sensitivity and specificity and performed well throughout the first year of the 2009 pandemic.
[Show abstract][Hide abstract] ABSTRACT: In Finland, the first infections caused by the 2009 pandemic influenza A(H1N1) virus were identified on May 10. During the next three months almost all infections were found from patients who had recently traveled abroad. In September 2009 the pandemic virus started to spread in the general population, leading to localized outbreaks and peak epidemic activity was reached during weeks 43-48.
The nucleotide sequences of the hemagglutinin (HA) and neuraminidase (NA) genes from viruses collected from 138 patients were determined. The analyzed viruses represented mild and severe infections and different geographic regions and time periods. Based on HA and NA gene sequences, the Finnish pandemic viruses clustered in four groups. Finnish epidemic viruses and A/California/07/2009 vaccine virus strain varied from 2-8 and 0-5 amino acids in HA and NA molecules, respectively, giving a respective maximal evolution speed of 1.4% and 1.1%. Most amino acid changes in HA and NA molecules accumulated on the surface of the molecule and were partly located in antigenic sites. Three severe infections were detected with a mutation at HA residue 222, in two viruses with a change D222G, and in one virus D222Y. Also viruses with change D222E were identified. All Finnish pandemic viruses were sensitive to oseltamivir having the amino acid histidine at residue 275 of the neuraminidase molecule.
The Finnish pandemic viruses were quite closely related to A/California/07/2009 vaccine virus. Neither in the HA nor in the NA were changes identified that may lead to the selection of a virus with increased epidemic potential or exceptionally high virulence. Continued laboratory-based surveillance of the 2009 pandemic influenza A(H1N1) is important in order to rapidly identify drug resistant viruses and/or virus variants with potential ability to cause severe forms of infection and an ability to circumvent vaccine-induced immunity.
PLoS ONE 10/2010; 5(10):e13329. DOI:10.1371/journal.pone.0013329 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oseltamivir provides modest clinical benefits to children with influenza when started within 48 hours of symptom onset. The effectiveness of oseltamivir could be substantially greater if the treatment were started earlier during the course of the illness.
We carried out a randomized, double-blind, placebo-controlled trial of the efficacy of oseltamivir started within 24 hours of symptom onset in children 1-3 years of age with laboratory-confirmed influenza during the seasons of 2007-2008 and 2008-2009. Eligible children received either orally administered oseltamivir suspension or a matching placebo twice daily for 5 days. The children received clinical examinations, and the parents filled out detailed symptom diaries for 21 days.
Of 408 randomized children who received the study drug (oseltamivir, 203, and placebo, 205), 98 had laboratory-confirmed influenza (influenza A, 79, and influenza B, 19). When started within 12 hours of the onset of symptoms, oseltamivir decreased the incidence of acute otitis media by 85% (95% confidence interval, 25%-97%), but no significant reduction was observed with treatment started within 24 hours. Among children with influenza A, oseltamivir treatment started within 24 hours shortened the median time to resolution of illness by 3.5 days (3.0 vs 6.5 days; P = .006) in all children and by 4.0 days (3.4 vs 7.3; P = .006) in unvaccinated children and reduced parental work absenteeism by 3.0 days. No efficacy was demonstrated against influenza B infections.
Oseltamivir treatment started within 24 hours of symptom onset provides substantial benefits to children with influenza A infection. Clinical trials registration. ClinicalTrials.gov identifier: NCT00593502.
[Show abstract][Hide abstract] ABSTRACT: Since May 2009, the pandemic influenza A(H1N1) virus has been spreading throughout the world. Epidemiological data indicate that the elderly are underrepresented among the ill individuals. Approximately 1,000 serum specimens collected in Finland in 2004 and 2005 from individuals born between 1909 and 2005, were analysed by haemagglutination-inhibition test for the presence of antibodies against the 2009 pandemic influenza A(H1N1) and recently circulating seasonal influenza A viruses. Ninety-six per cent of individuals born between 1909 and 1919 had antibodies against the 2009 pandemic influenza virus, while in age groups born between 1920 and 1944, the prevalence varied from 77% to 14%. Most individuals born after 1944 lacked antibodies to the pandemic virus. In sequence comparisons the haemagglutinin (HA) gene of the 2009 pandemic influenza A(H1N1) virus was closely related to that of the Spanish influenza and 1976 swine influenza viruses. Based on the three-dimensional structure of the HA molecule, the antigenic epitopes of the pandemic virus HA are more closely related to those of the Spanish influenza HA than to those of recent seasonal influenza A(H1N1) viruses. Among the elderly, cross-reactive antibodies against the 2009 pandemic influenza virus, which likely originate from infections caused by the Spanish influenza virus and its immediate descendants, may provide protective immunity against the present pandemic virus.
Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 02/2010; 15(5). · 5.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In less than 3 months after the first cases of swine origin 2009 influenza A (H1N1) virus infections were reported from Mexico, WHO declared a pandemic. The pandemic virus is antigenically distinct from seasonal influenza viruses, and the majority of human population lacks immunity against this virus. We have studied the activation of innate immune responses in pandemic virus-infected human monocyte-derived dendritic cells (DC) and macrophages. Pandemic A/Finland/553/2009 virus, representing a typical North American/European lineage virus, replicated very well in these cells. The pandemic virus, as well as the seasonal A/Brisbane/59/07 (H1N1) and A/New Caledonia/20/99 (H1N1) viruses, induced type I (alpha/beta interferon [IFN-alpha/beta]) and type III (IFN-lambda1 to -lambda3) IFN, CXCL10, and tumor necrosis factor alpha (TNF-alpha) gene expression weakly in DCs. Mouse-adapted A/WSN/33 (H1N1) and human A/Udorn/72 (H3N2) viruses, instead, induced efficiently the expression of antiviral and proinflammatory genes. Both IFN-alpha and IFN-beta inhibited the replication of the pandemic (H1N1) virus. The potential of IFN-lambda3 to inhibit viral replication was lower than that of type I IFNs. However, the pandemic virus was more sensitive to the antiviral IFN-lambda3 than the seasonal A/Brisbane/59/07 (H1N1) virus. The present study demonstrates that the novel pandemic (H1N1) influenza A virus can readily replicate in human primary DCs and macrophages and efficiently avoid the activation of innate antiviral responses. It is, however, highly sensitive to the antiviral actions of IFNs, which may provide us an additional means to treat severe cases of infection especially if significant drug resistance emerges.
Journal of Virology 11/2009; 84(3):1414-22. DOI:10.1128/JVI.01619-09 · 4.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Influenza A virus nonstructural protein 1 (NS1A protein) is a virulence factor which is targeted into the nucleus. It is a
multifunctional protein that inhibits host cell pre-mRNA processing and counteracts host cell antiviral responses. We show
that the NS1A protein can interact with all six human importin α isoforms, indicating that the nuclear translocation of NS1A
protein is mediated by the classical importin α/β pathway. The NS1A protein of the H1N1 (WSN/33) virus has only one N-terminal
arginine- or lysine-rich nuclear localization signal (NLS1), whereas the NS1A protein of the H3N2 subtype (Udorn/72) virus
also has a second C-terminal NLS (NLS2). NLS1 is mapped to residues 35 to 41, which also function in the double-stranded RNA-binding
activity of the NS1A protein. NLS2 was created by a 7-amino-acid C-terminal extension (residues 231 to 237) that became prevalent
among human influenza A virus types isolated between the years 1950 to 1987. NLS2 includes basic amino acids at positions
219, 220, 224, 229, 231, and 232. Surprisingly, NLS2 also forms a functional nucleolar localization signal NoLS, a function
that was retained in H3N2 type virus NS1A proteins even without the C-terminal extension. It is likely that the evolutionarily
well-conserved nucleolar targeting function of NS1A protein plays a role in the pathogenesis of influenza A virus.
Journal of Virology 07/2007; 81(11):5995-6006. DOI:10.1128/JVI.01714-06 · 4.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The first sporadic cases of Fujian/411/02-lineage viruses were recorded in Finland in winter 2001-2002. The first protracted but low-intensity outbreak occurred here during the first half of 2003, and the second outbreak early in autumn 2003, after detection of sporadic influenza A cases in the summer. The calculated incidence of influenza A in the Finnish army was 515/10000 during the first outbreak and 2066/10000 during the second outbreak. During the 2003-2004 epidemic season, the isolates fell into three groups for their haemagglutinin (HA1) sequences. In groups I and II, the strains were reassortants which differed for their neuraminidase (NA) sequences from the viruses of the previous spring. Group II viruses, which predominated in Finland during the 2003-2004 season, were characterized by loss of the glycosylation site at position 126 in HA1. The relevance of this loss to the epidemiology is discussed, as well as the frequent appearance of codominant amino acid mixtures at position 151 lining the catalytic cavity of the NA. Group III viruses, genetically related to Wellington/1/2004, the drift variant predominant in 2004 in the southern hemisphere, caused some localized outbreaks in Finland towards the end of the 2003-2004 epidemic. The antigenic match between the vaccine virus (Panama/2007/99) and the Fujian-lineage epidemic viruses in winter 2003-2004 was far from optimal. Nevertheless, high levels of prevaccination and postvaccination antibodies to the predomi- nant group II virus were recorded. Lower antibody levels were detected to the group III virus, which turned out to be a herald strain that reappeared in Finland during the following epidemic season.
Archives of Virology 03/2006; 151(2):241-54. DOI:10.1007/s00705-005-0635-5 · 2.39 Impact Factor