Publications by authors named "Niina Ikonen"

34 Publications

Detection of SARS-CoV-2 Infection in Gargle, Spit, and Sputum Specimens.

Microbiol Spectr 2021 09 25;9(1):e0003521. Epub 2021 Aug 25.

Infectious Disease Control and Vaccinations Unit, Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland.

The gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis is reverse transcription (RT)-PCR from a nasopharyngeal swab specimen (NPS). Its collection involves close contact between patients and health care workers, requiring a significant amount of workforce and putting them at risk of infection. We evaluated self-collection of alternative specimens and compared their sensitivity and cycle threshold () values to those of NPS. We visited acute coronavirus disease 2019 (COVID-19) outpatients to collect concomitant NPS and gargle specimens and had patients self-collect gargle and either sputum or spit specimens the next morning. We included 40 patients and collected 40 concomitant NPS and gargle specimens, as well as 40 gargle, 22 spit, and 16 sputum specimens the next day (2 patients could not produce sputum). All specimens were as sensitive as NPS. Gargle specimens had a sensitivity of 0.97 (95% confidence interval [CI], 0.92 to 1.00), whether collected concomitantly with NPS or the next morning. Next-morning spit and sputum specimens showed sensitivities of 1.00 (95% CI, 1.00 to 1.00) and 0.94 (95% CI, 0.87 to 1.00]), respectively. The gargle specimens had significantly higher mean values of 29.89 (standard deviation [SD], 4.63; < 0.001) and 29.25 (SD, 3.99; < 0.001) when collected concomitantly and the next morning, respectively, compared to NPS (22.07 [SD, 4.63]). values obtained with spit (23.51 [SD, 4.57]; = 0.11) and sputum (25.82 [SD, 9.21]; = 0.28) specimens were close to those of NPS. All alternative specimen collection methods were as sensitive as NPS, but spit collection appeared more promising, with a low value and ease of collection. Our findings warrant further investigation. Control of the COVID-19 pandemic relies heavily on a test-trace-isolate strategy. The most commonly used specimen for diagnosis of SARS-CoV-2 infection is a nasopharyngeal swab. However, this method is quite uncomfortable for the patient, requires specific equipment (nose swabs and containers), and requires close proximity to health care workers, putting them at risk of infection. Developing alternative sampling strategies could decrease the burden for health care workers, help overcome potential shortages of equipment, and improve acceptability of testing by reducing patient discomfort.
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http://dx.doi.org/10.1128/Spectrum.00035-21DOI Listing
September 2021

An outbreak caused by the SARS-CoV-2 Delta variant (B.1.617.2) in a secondary care hospital in Finland, May 2021.

Euro Surveill 2021 07;26(30)

Finnish Institute for Health and Welfare, Helsinki, Finland.

An outbreak caused by the SARS-CoV-2 Delta variant (B.1.617.2) spread from one inpatient in a secondary care hospital to three primary care facilities, resulting in 58 infections including 18 deaths in patients and 45 infections in healthcare workers (HCW). Only one of the deceased cases was fully vaccinated. Transmission occurred despite the use of personal protective equipment by the HCW, as advised in national guidelines, and a high two-dose COVID-19 vaccination coverage among permanent staff members in the COVID-19 cohort ward.
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http://dx.doi.org/10.2807/1560-7917.ES.2021.26.30.2100636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323455PMC
July 2021

Characteristics of SARS-CoV-2 variants of concern B.1.1.7, B.1.351 or P.1: data from seven EU/EEA countries, weeks 38/2020 to 10/2021.

Euro Surveill 2021 04;26(16)

Health Board, Tallinn, Estonia.

We compared 19,207 cases of SARS-CoV-2 variant B.1.1.7/S gene target failure (SGTF), 436 B.1.351 and 352 P.1 to non-variant cases reported by seven European countries. COVID-19 cases with these variants had significantly higher adjusted odds ratios for hospitalisation (B.1.1.7/SGTF: 1.7, 95% confidence interval (CI): 1.0-2.9; B.1.351: 3.6, 95% CI: 2.1-6.2; P.1: 2.6, 95% CI: 1.4-4.8) and B.1.1.7/SGTF and P.1 cases also for intensive care admission (B.1.1.7/SGTF: 2.3, 95% CI: 1.4-3.5; P.1: 2.2, 95% CI: 1.7-2.8).
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http://dx.doi.org/10.2807/1560-7917.ES.2021.26.16.2100348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063589PMC
April 2021

Epidemiology of laboratory-confirmed influenza among kidney transplant recipients compared to the general population-A nationwide cohort study.

Am J Transplant 2021 05 19;21(5):1848-1856. Epub 2021 Feb 19.

Abdominal Center, Nephrology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Seasonal influenza causes morbidity and mortality after organ transplantation. We quantified the detection of laboratory-confirmed influenza among kidney transplant recipients compared to the general population in a nationwide cohort. All laboratory-confirmed cases of influenza and hospitalizations due to influenza among all kidney transplant recipients in our country between 1995 and 2017 were captured with database linkage from statutory national registries. Data from the general population of Finland, population 5.5 million, were used for comparisons. Annual incidences of influenza and hospitalizations due to influenza, and standardized incidence ratios (SIR) were calculated. Altogether 3904 kidney transplant recipients with a total follow-up of 37 175 patient-years were included. Incidence of laboratory-confirmed influenza was 9.0 per 1000 patient years in 2003-2019, and 18.0 per 1000 patient years during 2015-2019. The risk of laboratory-confirmed influenza was significantly higher among kidney transplant recipients compared to the general population (SIR 5.1, 95% CI 4.5-5.7). SIR for hospitalization due to influenza was 4.4 (95% CI 3.4-4.7). Mortality of the hospitalized patients was 9%, and 5% of the patients with laboratory-confirmed influenza. Detection of laboratory-confirmed influenza is increased fivefold and risk of hospitalization due to influenza more than fourfold among kidney transplant recipients compared to the general population.
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http://dx.doi.org/10.1111/ajt.16421DOI Listing
May 2021

Long-lasting heterologous antibody responses after sequential vaccination with A/Indonesia/5/2005 and A/Vietnam/1203/2004 pre-pandemic influenza A(H5N1) virus vaccines.

Vaccine 2021 01 24;39(2):402-411. Epub 2020 Nov 24.

Expert Microbiology Unit, Department of Health Security, Finnish Institute for Health and Welfare (THL), POB 30, 00271 Helsinki, Finland; Institute of Biomedicine, University of Turku and Turku University Hospital, Kiinamyllynkatu 10, 20520 Turku, Finland.

Background: Avian influenza A(H5N1) viruses have caused sporadic infections in humans and thus they pose a significant global health threat. Among symptomatic patients the case fatality rate has been ca. 50%. H5N1 viruses exist in multiple clades and subclades and several candidate vaccines have been developed to prevent A(H5N1) infection as a principal measure for preventing the disease.

Methods: Serum antibodies against various influenza A(H5N1) clade viruses were measured in adults by ELISA-based microneutralization and haemagglutination inhibition tests before and after vaccination with two different A(H5N1) vaccines in 2009 and 2011.

Results: Two doses of AS03-adjuvanted A/Indonesia/5/2005 vaccine induced good homologous but poor heterologous neutralizing antibody responses against different clade viruses. However, non-adjuvanted A/Vietnam/1203/2004 booster vaccination in 2011 induced very strong and long-lasting homologous and heterologous antibody responses while homologous response remained weak in naïve subjects.

Conclusions: Sequential vaccination with two different A(H5N1) pre-pandemic vaccines induced long-lasting high level cross-clade immunity against influenza A(H5N1) strains, thus supporting a prime-boost vaccination strategy in pandemic preparedness plans.
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http://dx.doi.org/10.1016/j.vaccine.2020.11.041DOI Listing
January 2021

Comparison of the clinical characteristics and outcomes of hospitalized adult COVID-19 and influenza patients - a prospective observational study.

Infect Dis (Lond) 2021 02 10;53(2):111-121. Epub 2020 Nov 10.

Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: We compared the clinical characteristics, findings, and outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19) or influenza to detect relevant differences.

Methods: From December 2019 to April 2020, we recruited all eligible hospitalized adults with respiratory infection to a prospective observational study at a tertiary care hospital in Finland. Influenza and SARS-CoV-2 infections were confirmed by RT-PCR. Follow-up lasted for 3 months from admission.

Results: We included 61 patients, of whom 28 were COVID-19 and 33 influenza patients with median ages of 53 and 56 years. Majority of both COVID-19 and influenza patients were men (61% vs. 67%) and had at least one comorbidity (68% vs. 85%). Pulmonary diseases and current smoking were less common among COVID-19 than influenza patients (5 [18%] vs. 15 [45%], =.03 and 1 [4%] vs. 10 [30%], =.008). In chest X-ray at admission, ground-glass opacities (GGOs) and consolidations were more frequent among COVID-19 than influenza patients (19 [68%] and 7 [21%], <.001). Severe disease and intensive care unit (ICU) admission occurred more often among COVID-19 than influenza patients (26 [93%] vs. 19 [58%], =.003 and 8 [29%] vs. 2 [6%], =.034). COVID-19 patients were hospitalized longer than influenza patients (six days [IQR 4-21] vs. 3 [2-4], <.001).

Conclusions: Bilateral GGOs and consolidations in chest X-ray may help to differentiate COVID-19 from influenza. Hospitalized COVID-19 patients had more severe disease, required longer hospitalization and were admitted to ICU more often than influenza patients, which has important implications for public health policies.
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http://dx.doi.org/10.1080/23744235.2020.1840623DOI Listing
February 2021

Determinants of Fatal Outcome in Patients Admitted to Intensive Care Units With Influenza, European Union 2009-2017.

Open Forum Infect Dis 2019 Nov 29;6(11):ofz462. Epub 2019 Oct 29.

Office of the Chief Scientist, European Centre for Disease Prevention and Control (ECDC), Solna, Sweden.

Background: Morbidity, severity, and mortality associated with annual influenza epidemics are of public health concern. We analyzed surveillance data on hospitalized laboratory-confirmed influenza cases admitted to intensive care units to identify common determinants for fatal outcome and inform and target public health prevention strategies, including risk communication.

Methods: We performed a descriptive analysis and used Poisson regression models with robust variance to estimate the association of age, sex, virus (sub)type, and underlying medical condition with fatal outcome using European Union data from 2009 to 2017.

Results: Of 13 368 cases included in the basic dataset, 2806 (21%) were fatal. Age ≥40 years and infection with influenza A virus were associated with fatal outcome. Of 5886 cases with known underlying medical conditions and virus A subtype included in a more detailed analysis, 1349 (23%) were fatal. Influenza virus A(H1N1)pdm09 or A(H3N2) infection, age ≥60 years, cancer, human immunodeficiency virus infection and/or other immune deficiency, and heart, kidney, and liver disease were associated with fatal outcome; the risk of death was lower for patients with chronic lung disease and for pregnant women.

Conclusions: This study re-emphasises the importance of preventing influenza in the elderly and tailoring strategies to risk groups with underlying medical conditions.
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http://dx.doi.org/10.1093/ofid/ofz462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105050PMC
November 2019

Serological and molecular findings during SARS-CoV-2 infection: the first case study in Finland, January to February 2020.

Euro Surveill 2020 03;25(11)

Department of Health Security, Finnish Institute for Health and Welfare (THL), Helsinki, Finland.

The first case of coronavirus disease (COVID-19) in Finland was confirmed on 29 January 2020. No secondary cases were detected. We describe the clinical picture and laboratory findings 3-23 days since the first symptoms. The SARS-CoV-2/Finland/1/2020 virus strain was isolated, the genome showing a single nucleotide substitution to the reference strain from Wuhan. Neutralising antibody response appeared within 9 days along with specific IgM and IgG response, targeting particularly nucleocapsid and spike proteins.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.11.2000266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096774PMC
March 2020

Vaccine effectiveness against influenza A(H3N2) and B among laboratory-confirmed, hospitalised older adults, Europe, 2017-18: A season of B lineage mismatched to the trivalent vaccine.

Influenza Other Respir Viruses 2020 05 5;14(3):302-310. Epub 2020 Feb 5.

Epiconcept, Paris, France.

Background: Influenza A(H3N2), A(H1N1)pdm09 and B viruses co-circulated in Europe in 2017-18, predominated by influenza B. WHO-recommended, trivalent vaccine components were lineage-mismatched for B. The I-MOVE hospital network measured 2017-18 seasonal influenza vaccine effectiveness (IVE) against influenza A(H3N2) and B among hospitalised patients (≥65 years) in Europe.

Methods: Following the same generic protocol for test-negative design, hospital teams in nine countries swabbed patients ≥65 years with recent onset (≤7 days) severe acute respiratory infection (SARI), collecting information on demographics, vaccination status and underlying conditions. Cases were RT-PCR positive for influenza A(H3N2) or B; controls: negative for any influenza. "Vaccinated" patients had SARI onset >14 days after vaccination. We measured pooled IVE against influenza, adjusted for study site, age, sex, onset date and chronic conditions.

Results: We included 3483 patients: 376 influenza A(H3N2) and 928 B cases, and 2028 controls. Most (>99%) vaccinated patients received the B lineage-mismatched trivalent vaccine. IVE against influenza A(H3N2) was 24% (95% CI: 2 to 40); 35% (95% CI: 6 to 55) in 65- to 79-year-olds and 14% (95% CI: -22 to 39) in ≥80-year-olds. Against influenza B, IVE was 30% (95% CI: 16 to 41); 37% (95% CI: 19 to 51) in 65- to 79-year-olds and 19% (95% CI: -7 to 38) in ≥80-year-olds.

Conclusions: IVE against influenza B was similar to A(H3N2) in hospitalised older adults, despite trivalent vaccine and circulating B lineage mismatch, suggesting some cross-protection. IVE was lower in those ≥80 than 65-79 years. We reinforce the importance of influenza vaccination in older adults as, even with a poorly matched vaccine, it still protects one in three to four of this population from severe influenza.
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http://dx.doi.org/10.1111/irv.12714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182608PMC
May 2020

Seasonal influenza vaccines induced high levels of neutralizing cross-reactive antibody responses against different genetic group influenza A(H1N1)pdm09 viruses.

Vaccine 2019 05 4;37(20):2731-2740. Epub 2019 Apr 4.

Expert Microbiology Unit, Department of Health Security, National Institute for Health and Welfare (THL), POB 30, 00271 Helsinki, Finland; Institute of Biomedicine, University of Turku and Turku University Hospital, Kiinamyllynkatu 10, 20520 Turku, Finland.

Influenza A(H1N1)pdm09 viruses have been circulating throughout the world since the 2009 pandemic. A/California/07/2009 (H1N1) virus was included in seasonal influenza vaccines for seven years altogether, providing a great opportunity to analyse vaccine-induced immunity in relation to the postpandemic evolution of the A(H1N1)pdm09 virus. Serum antibodies against various epidemic strains of influenza A(H1N1)pdm09 viruses were measured among health care workers (HCWs) by haemagglutination inhibition and microneutralization tests before and after 2010 and 2012 seasonal influenza vaccinations. We detected high responses of vaccine-induced neutralizing antibodies to six distinct genetic groups. Our results indicate antigenic similarity between vaccine and circulating A(H1N1)pdm09 strains, and substantial vaccine-induced immunity against circulating epidemic viruses.
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http://dx.doi.org/10.1016/j.vaccine.2019.03.078DOI Listing
May 2019

Deposition of respiratory virus pathogens on frequently touched surfaces at airports.

BMC Infect Dis 2018 Aug 29;18(1):437. Epub 2018 Aug 29.

Department of Health Security, National Institute for Health and Welfare, P.O.Box 30, 00271, Helsinki, Finland.

Background: International and national travelling has made the rapid spread of infectious diseases possible. Little information is available on the role of major traffic hubs, such as airports, in the transmission of respiratory infections, including seasonal influenza and a pandemic threat. We investigated the presence of respiratory viruses in the passenger environment of a major airport in order to identify risk points and guide measures to minimize transmission.

Methods: Surface and air samples were collected weekly at three different time points during the peak period of seasonal influenza in 2015-16 in Finland. Swabs from surface samples, and air samples were tested by real-time PCR for influenza A and B viruses, respiratory syncytial virus, adenovirus, rhinovirus and coronaviruses (229E, HKU1, NL63 and OC43).

Results: Nucleic acid of at least one respiratory virus was detected in 9 out of 90 (10%) surface samples, including: a plastic toy dog in the children's playground (2/3 swabs, 67%); hand-carried luggage trays at the security check area (4/8, 50%); the buttons of the payment terminal at the pharmacy (1/2, 50%); the handrails of stairs (1/7, 14%); and the passenger side desk and divider glass at a passport control point (1/3, 33%). Among the 10 respiratory virus findings at various sites, the viruses identified were: rhinovirus (4/10, 40%, from surfaces); coronavirus (3/10, 30%, from surfaces); adenovirus (2/10, 20%, 1 air sample, 1 surface sample); influenza A (1/10, 10%, surface sample).

Conclusions: Detection of pathogen viral nucleic acids indicates respiratory viral surface contamination at multiple sites associated with high touch rates, and suggests a potential risk in the identified airport sites. Of the surfaces tested, plastic security screening trays appeared to pose the highest potential risk, and handling these is almost inevitable for all embarking passengers.
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http://dx.doi.org/10.1186/s12879-018-3150-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116441PMC
August 2018

Low 2016/17 season vaccine effectiveness against hospitalised influenza A(H3N2) among elderly: awareness warranted for 2017/18 season.

Euro Surveill 2017 10;22(41)

The members of the I-Move+ hospital working group are listed at the end of the article.

In a multicentre European hospital study we measured influenza vaccine effectiveness (IVE) against A(H3N2) in 2016/17. Adjusted IVE was 17% (95% confidence interval (CI): 1 to 31) overall; 25% (95% CI: 2 to 43) among 65-79-year-olds and 13% (95% CI: -15 to 30) among those ≥ 80 years. As the A(H3N2) vaccine component has not changed for 2017/18, physicians and public health experts should be aware that IVE could be low where A(H3N2) viruses predominate.
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http://dx.doi.org/10.2807/1560-7917.ES.2017.22.41.17-00645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710120PMC
October 2017

2015/16 seasonal vaccine effectiveness against hospitalisation with influenza A(H1N1)pdm09 and B among elderly people in Europe: results from the I-MOVE+ project.

Euro Surveill 2017 07;22(30)

EpiConcept, Paris, France.

We conducted a multicentre test-negative case-control study in 27 hospitals of 11 European countries to measure 2015/16 influenza vaccine effectiveness (IVE) against hospitalised influenza A(H1N1)pdm09 and B among people aged ≥ 65 years. Patients swabbed within 7 days after onset of symptoms compatible with severe acute respiratory infection were included. Information on demographics, vaccination and underlying conditions was collected. Using logistic regression, we measured IVE adjusted for potential confounders. We included 355 influenza A(H1N1)pdm09 cases, 110 influenza B cases, and 1,274 controls. Adjusted IVE against influenza A(H1N1)pdm09 was 42% (95% confidence interval (CI): 22 to 57). It was 59% (95% CI: 23 to 78), 48% (95% CI: 5 to 71), 43% (95% CI: 8 to 65) and 39% (95% CI: 7 to 60) in patients with diabetes mellitus, cancer, lung and heart disease, respectively. Adjusted IVE against influenza B was 52% (95% CI: 24 to 70). It was 62% (95% CI: 5 to 85), 60% (95% CI: 18 to 80) and 36% (95% CI: -23 to 67) in patients with diabetes mellitus, lung and heart disease, respectively. 2015/16 IVE estimates against hospitalised influenza in elderly people was moderate against influenza A(H1N1)pdm09 and B, including among those with diabetes mellitus, cancer, lung or heart diseases.
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http://dx.doi.org/10.2807/1560-7917.ES.2017.22.30.30580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553054PMC
July 2017

Mid-season real-time estimates of seasonal influenza vaccine effectiveness in persons 65 years and older in register-based surveillance, Stockholm County, Sweden, and Finland, January 2017.

Euro Surveill 2017 Feb;22(8)

Department of Communicable Disease Control and Prevention, Stockholm County Council, and Karolinska Institutet, Department of Medicine Karolinska Solna, Unit of Infectious Diseases, Stockholm, Sweden.

Systems for register-based monitoring of vaccine effectiveness (VE) against laboratory-confirmed influenza (LCI) in real time were set up in Stockholm County, Sweden, and Finland, before start of the 2016/17 influenza season, using population-based cohort studies. Both in Stockholm and Finland, an early epidemic of influenza A(H3N2) peaked in week 52, 2016. Already during weeks 48 to 50, analyses of influenza VE in persons 65 years and above showed moderately good estimates of around 50%, then rapidly declined by week 2, 2017 to 28% and 32% in Stockholm and Finland, respectively. The sensitivity analyses, where time since vaccination was taken into account, could not demonstrate a clear decline, neither by calendar week nor by time since vaccination. Most (68%) of the samples collected from vaccinated patients belonged to the 3C.2a1 subclade with the additional amino acid substitution T135K in haemagglutinin (64%) or to subclade 3C.2a with the additional haemagglutinin substitutions T131K and R142K (36%). The proportion of samples containing these alterations increased during the studied period. These substitutions may be responsible for viral antigenic change and part of the observed VE drop. Another possible cause is poor vaccine immunogenicity in older persons. Improved influenza vaccines are needed, especially for the elderly.
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http://dx.doi.org/10.2807/1560-7917.ES.2017.22.8.30469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356437PMC
February 2017

Improving influenza virological surveillance in Europe: strain-based reporting of antigenic and genetic characterisation data, 11 European countries, influenza season 2013/14.

Euro Surveill 2016 Oct;21(41)

European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden.

Influenza antigenic and genetic characterisation data are crucial for influenza vaccine composition decision making. Previously, aggregate data were reported to the European Centre for Disease Prevention and Control by European Union/European Economic Area (EU/EEA) countries. A system for collecting case-specific influenza antigenic and genetic characterisation data was established for the 2013/14 influenza season. In a pilot study, 11 EU/EEA countries reported through the new mechanism. We demonstrated feasibility of reporting strain-based antigenic and genetic data and ca 10% of influenza virus-positive specimens were selected for further characterisation. Proportions of characterised virus (sub)types were similar to influenza virus circulation levels. The main genetic clades were represented by A/StPetersburg/27/2011(H1N1)pdm09 and A/Texas/50/2012(H3N2). A(H1N1)pdm09 viruses were more prevalent in age groups (by years) < 1 (65%; p = 0.0111), 20-39 (50%; p = 0.0046) and 40-64 (55%; p = 0.00001) while A(H3N2) viruses were most prevalent in those ≥ 65 years (62%*; p = 0.0012). Hospitalised patients in the age groups 6-19 years (67%; p = 0.0494) and ≥ 65 years (52%; p = 0.0005) were more frequently infected by A/Texas/50/2012 A(H3N2)-like viruses compared with hospitalised cases in other age groups. Strain-based reporting enabled deeper understanding of influenza virus circulation among hospitalised patients and substantially improved the reporting of virus characterisation data. Therefore, strain-based reporting of readily available data is recommended to all reporting countries within the EU/EEA.
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http://dx.doi.org/10.2807/1560-7917.ES.2016.21.41.30370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073191PMC
October 2016

Effectiveness of the live attenuated and the inactivated influenza vaccine in two-year-olds - a nationwide cohort study Finland, influenza season 2015/16.

Euro Surveill 2016 Sep;21(38)

Vaccine Programme Unit, Department of Health Protection, National Institute for Health and Welfare, Finland.

Although widely recommended, influenza vaccination of children is part of the national vaccination programme only in few countries. In addition to Canada and the United States (US), in Europe Finland and the United Kingdom have introduced live attenuated influenza vaccine (LAIV) for healthy children in their programmes. On 22 June 2016, the US Advisory Committee on Immunizations Practices, voted against further use of LAIV due to no observed vaccine effectiveness (VE) over three consecutive influenza seasons (2013/14 to 2015/16). We summarise the results of a nationwide, register-based cohort study (N=55,258 of whom 8,086 received LAIV and 4,297 TIV); all outcome (laboratory-confirmed influenza), exposure (vaccination) and confounding variable data were retrieved from four computerised national health registers, which were linked via a unique personal identity code assigned to all permanent Finnish residents regardless of nationality. Our study provides evidence of moderate effectiveness against any laboratory-confirmed influenza of the quadrivalent LAIV vaccine (VE: 51%; 95% confidence interval (CI): 28-66%) as well as the inactivated trivalent vaccine (VE: 61%; 95% CI: 31-78%) among two-year-olds during the influenza season 2015/16 in Finland. Based on these data, Finland will continue using LAIV for young children in its National Immunisation Programme this coming influenza season.
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http://dx.doi.org/10.2807/1560-7917.ES.2016.21.38.30346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073199PMC
September 2016

Comparative Analysis of Whole-Genome Sequences of Influenza A(H1N1)pdm09 Viruses Isolated from Hospitalized and Nonhospitalized Patients Identifies Missense Mutations That Might Be Associated with Patient Hospital Admissions in Finland during 2009 to 2014.

Genome Announc 2015 Jul 30;3(4). Epub 2015 Jul 30.

The Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland

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.
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http://dx.doi.org/10.1128/genomeA.00676-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520887PMC
July 2015

Complete Genome Sequences of Influenza A/H1N1 Strains Isolated from Patients during the 2013-2014 Epidemic Season in Finland.

Genome Announc 2015 Mar 12;3(2). Epub 2015 Mar 12.

The Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland

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%.
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http://dx.doi.org/10.1128/genomeA.01523-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357768PMC
March 2015

Impact of influenza B lineage-level mismatch between trivalent seasonal influenza vaccines and circulating viruses, 1999-2012.

Clin Infect Dis 2014 Dec 19;59(11):1519-24. Epub 2014 Aug 19.

National Influenza Center, National Institute for Health and Welfare, Helsinki, Finland.

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.

Methods: 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1093/cid/ciu664DOI Listing
December 2014

Akt inhibitor MK2206 prevents influenza pH1N1 virus infection in vitro.

Antimicrob Agents Chemother 2014 Jul 21;58(7):3689-96. Epub 2014 Apr 21.

Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland Department of Environmental Research, Siauliai University, Siauliai, Lithuania

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 the Akt inhibitor MK2206 blocks influenza pH1N1 virus infection in vitro. In particular, at noncytotoxic 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.
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http://dx.doi.org/10.1128/AAC.02798-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068572PMC
July 2014

Autophagy is needed for the growth of pancreatic adenocarcinoma and has a cytoprotective effect against anticancer drugs.

Eur J Cancer 2014 May 3;50(7):1382-90. Epub 2014 Feb 3.

Tampere Pancreas Laboratory, Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Teiskontie 35, P.O. Box 2000, 33521 Tampere, Finland. Electronic address:

Background And Aim: Autophagy is a regulated process of degradation and recycling of cellular constituents. The role of autophagy in pancreatic cancer is still not clear. Some studies indicate that in pancreatic cancer autophagy exerts cytoprotective effects, whereas others suggest that autophagy positively contributes to cell death by enhancing cytotoxicity of anticancer drugs. The aim of this study was to investigate the role of autophagy in pancreatic cancer, and to provide insights into new strategies for treatment.

Materials And Methods: Pancreatic cancer cell lines PANC-1 and BxPC-3 were treated with anticancer drugs (5-fluorouracil or gemcitabine) alone and in combination with autophagy inhibitors (chloroquine or wortmannin). Biopsy samples were retrieved from patients from pancreatic normal tissue and adenocarcinoma. Western blot of microtubule-associated protein 1 light chain 3 (LC3)-II was performed to investigate the degree of autophagy and cell proliferation was assessed by a crystal violet assay.

Results: Autophagy was active in PANC-1 cells under basal conditions. Autophagy was significantly induced in pancreatic ductal adenocarcinoma compared to healthy pancreatic tissue in patients. Inhibition of autophagy by chloroquine suppressed the growth of PANC-1 and BxPC-3. Autophagy was markedly increased after treatment with 5-fluorouracil or gemcitabine. Inhibition of autophagy by chloroquine potentiated the inhibition of cell proliferation of PANC-1 and BxPC-3 by 5-fluorouracil and gemcitabine.

Conclusions: Our results with pancreatic cancer cell lines and human pancreatic adenocarcinoma suggest that autophagy contributes to pancreatic cancer cell growth. Autophagy has a cytoprotective effect against 5-fluorouracil and gemcitabine in pancreatic cancer cells. Combination therapy of these anticancer drugs and chloroquine should be investigated.
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http://dx.doi.org/10.1016/j.ejca.2014.01.011DOI Listing
May 2014

Full-Genome Sequences of Influenza A(H1N1)pdm09 Viruses Isolated from Finnish Patients from 2009 to 2013.

Genome Announc 2014 Jan 16;2(1). Epub 2014 Jan 16.

The Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.

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.
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http://dx.doi.org/10.1128/genomeA.01004-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894269PMC
January 2014

The first detection of influenza in the Finnish pig population: a retrospective study.

Acta Vet Scand 2013 Sep 18;55:69. Epub 2013 Sep 18.

Finnish Food Safety Authority Evira, Mustialankatu 3, FI-00790 Helsinki, Finland.

Background: Swine influenza is an infectious acute respiratory disease of pigs caused by influenza A virus. 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 test. Diagnostic samples 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 and sequences analyzed phylogenetically.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1186/1751-0147-55-69DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850993PMC
September 2013

[Influenza viruses--a challenge for vaccinations].

Duodecim 2012 ;128(18):1919-28

Virologin yksikkö ja kansallinen influenssakeskus, Tartuntatautiseurannan ja -torjunnan osasto, Terveyden ja hyvinvoinnin Iaitos.

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.
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December 2012

Antibody responses against influenza A(H1N1)pdm09 virus after sequential vaccination with pandemic and seasonal influenza vaccines in Finnish healthcare professionals.

Influenza Other Respir Viruses 2013 May 23;7(3):431-8. Epub 2012 Aug 23.

Virology Unit, Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare, Helsinki, Finland.

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.
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http://dx.doi.org/10.1111/j.1750-2659.2012.00415.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5779819PMC
May 2013

Detection of influenza A viruses with a portable real-time PCR instrument.

J Virol Methods 2012 May 22;181(2):188-91. Epub 2012 Feb 22.

Centres for Military Medicine and for Biological Threat Preparedness, Tukholmankatu 8A, FI-00290 Helsinki, Finland.

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.
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http://dx.doi.org/10.1016/j.jviromet.2012.02.001DOI Listing
May 2012

Minor changes in the hemagglutinin of influenza A(H1N1)2009 virus alter its antigenic properties.

PLoS One 2011 11;6(10):e25848. Epub 2011 Oct 11.

Viral Infections Unit, Department of Vaccines and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland.

Background: 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.

Methods/results: 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.

Conclusions: 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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0025848PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191144PMC
February 2012

Validation and diagnostic application of NS and HA gene-specific real-time reverse transcription-PCR assays for detection of 2009 pandemic influenza A (H1N1) viruses in clinical specimens.

J Clin Microbiol 2011 May 2;49(5):2009-11. Epub 2011 Mar 2.

Viral Infections Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare (THL),Helsinki, Finland.

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.
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http://dx.doi.org/10.1128/JCM.00259-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122666PMC
May 2011

Genetic diversity of the 2009 pandemic influenza A(H1N1) viruses in Finland.

PLoS One 2010 Oct 20;5(10):e13329. Epub 2010 Oct 20.

Viral Infections Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare THL, Helsinki, Finland.

Background: 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.

Methods/results: 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.

Conclusions: 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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0013329PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958116PMC
October 2010

Early oseltamivir treatment of influenza in children 1-3 years of age: a randomized controlled trial.

Clin Infect Dis 2010 Oct;51(8):887-94

Departments of Pediatrics, Turku University Hospital, University of Turku, Turku, Finland.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1086/656408DOI Listing
October 2010
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