Browsing by Author "Correia, Lurdes"
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- Cross-protection to new drifted influenza A(H3) viruses and prevalence of protective antibodies to seasonal influenza, during 2014 in PortugalPublication . Guiomar, Raquel; Pereira da Silva, Susana; Conde, Patrícia; Cristóvão, Paula; Maia, Ana Carina; Pechirra, Pedro; Rodrigues, Ana Paula; Nunes, Baltazar; Milho, Luís; Coelho, Ana Paula; Fernandes, Aida; Caseiro, Paula; Rodrigues, Fernando; Correia, Lurdes; Pereira-Vaz, João; Almeida, Sofia; Branquinho, Paula; Côrte-Real, Rita; Viseu, Regina; Peres, Maria João; Sanches, Raquel; Dantas, Filipa; Freitas, Ludovina; Andrade, Graça; Maurílio, Manuel; Caldeira, Filomena; Cabral Veloso, Rita; Mota-Vieira, Luísa; Soares, Marta; Couto, Ana Rita; Bruges-Armas, Jácome; Mouro Pinto, Rita; Sobrinho Simões, Joana; Rosário Costa, Maria; Guimarães, João Tiago; Martins, Luís; Cunha, MárioIntroduction: Immune profile for influenza viruses is highly changeable over time. Serological studies can assess the prevalence of influenza, estimate the risk of infection, highlight asymptomatic infection rate and can also provide data on vaccine coverage. The aims of the study were to evaluate pre-existing cross-protection against influenza A(H3) drift viruses and to assess influenza immunity in the Portuguese population. Materials and methods: We developed a cross-sectional study based on a convenience sample of 626 sera collected during June 2014, covering all age groups, both gender and all administrative health regions of Portugal. Sera antibody titers for seasonal and new A(H3) drift influenza virus were evaluated by hemagglutination inhibition assay (HI). Seroprevalence to each seasonal influenza vaccine strain virus and to the new A(H3) drift circulating strain was estimated by age group, gender and region and compared with seasonal influenza-like illness (ILI) incidence rates before and after the study period. Results: Our findings suggest that seroprevalences of influenza A(H3) (39.9%; 95% CI: 36.2–43.8) and A(H1)pdm09 (29.7%; 95% CI: 26.3–33.4) antibodies were higher than for influenza B, in line with high ILI incidence rates for A(H3) followed by A(H1)pdm09, during 2013/2014 season. Low pre-existing crossprotection against new A(H3) drift viruses were observed in A(H3) seropositive individuals (46%). Both against influenza A(H1)pdm09 and A(H3) seroprotection was highest in younger than 14-years old. Protective antibodies against influenza B were highest in those older than 65 years old, especially for B/Yamagata lineage, 33.3% (95% CI: 25.7–41.9). Women showed a high seroprevalence to influenza, although without statistical significance, when compared to men. A significant decreasing trend in seroprotection from north to south regions of Portugal mainland was observed. Conclusions: Our results emphasize that low seroprotection increases the risk of influenza infection in the following winter season. Seroepidemiological studies can inform policy makers on the need for vaccination and additional preventive measures.
- Cross-protection to new drifted influenza A(H3) viruses and prevalence of protective antibodies to seasonal influenza, during 2014 in PortugalPublication . Guiomar, Raquel; Pereira da Silva, Susana; Conde, Patrícia; Cristóvão, Paula; Maia, Ana Carina; Pechirra, Pedro; Rodrigues, Ana Paula; Nunes, Baltazar; Milho, Luís; Coelho, Ana Paula; Fernandes, Aida; Caseiro, Paula; Rodrigues, Fernando; Correia, Lurdes; Pereira-Vaz, João; Almeida, Sofia; Branquinho, Paula; Côrte-Real, Rita; Viseu, Regina; Peres, Maria João; Sanches, Raquel; Dantas, Filipa; Freitas, Ludovina; Andrade, Graça; Maurílio, Manuel; Caldeira, Filomena; Cabral Veloso, Rita; Mota-Vieira, Luísa; Soares, Marta; Couto, Ana Rita; Bruges-Armas, Jácome; Mouro Pinto, Rita; Sobrinho Simões, Joana; Costa, Maria do Rosário; Guimarães, João Tiago; Martins, Luís; Cunha, MárioIntroduction: Immune profile for influenza viruses is highly changeable over time. Serological studies can assess the prevalence of influenza, estimate the risk of infection, highlight asymptomatic infection rate and can also provide data on vaccine coverage. The aims of the study were to evaluate pre-existing cross-protection against influenza A(H3) drift viruses and to assess influenza immunity in the Portuguese population. Materials and methods: We developed a cross-sectional study based on a convenience sample of 626 sera collected during June 2014, covering all age groups, both gender and all administrative health regions of Portugal. Sera antibody titers for seasonal and new A(H3) drift influenza virus were evaluated by hemagglutination inhibition assay (HI). Seroprevalence to each seasonal influenza vaccine strain virus and to the new A(H3) drift circulating strain was estimated by age group, gender and region and compared with seasonal influenza-like illness (ILI) incidence rates before and after the study period. Results: Our findings suggest that seroprevalences of influenza A(H3) (39.9%; 95% CI: 36.2-43.8) and A(H1)pdm09 (29.7%; 95% CI: 26.3-33.4) antibodies were higher than for influenza B, in line with high ILI incidence rates for A(H3) followed by A(H1)pdm09, during 2013/2014 season. Low pre-existing cross-protection against new A(H3) drift viruses were observed in A(H3) seropositive individuals (46%). Both against influenza A(H1)pdm09 and A(H3) seroprotection was highest in younger than 14-years old. Protective antibodies against influenza B were highest in those older than 65 years old, especially for B/ Yamagata lineage, 33.3% (95% CI: 25.7-41.9). Women showed a high seroprevalence to influenza, although without statistical significance, when compared to men. A significant decreasing trend in seroprotection from north to south regions of Portugal mainland was observed. Conclusions: Our results emphasize that low seroprotection increases the risk of influenza infection in the following winter season. Seroepidemiological studies can inform policy makers on the need for vaccination and additional preventive measures.
- Influenza seroprotection correlates with predominant circulating viruses during 2014/15 and 2015/16 seasons in PortugalPublication . Guiomar, Raquel; Cristóvão, Paula; Conde, Patrícia; Costa, Inês; Pechirra, Pedro; Rodrigues, Ana Paula; Pereira da Silva, Susana; Nunes, Baltazar; Mouro Pinto, Rita; Sobrinho Simões, Joana; Costa, Maria do Rosário; Guimarães, João Tiago; Rodrigues, Fernando; Correia, Lurdes; Pereira-Vaz, João; Caseiro, Paula; Cabral Veloso, Rita; Mota Vieira, Luísa; Pimentel Couto, Ana Rita; Santos, Margarida; Bruges Armas, Jácome; Branquinho, Paula; Corte-Real, Rita; Martins, Luís; Cunha, Mário; Almeida, Sofia; Viseu, Regina; Inácio, Filipe; Peres, Maria João; Milho, Luís; Fernandes, Aida; Maurílio, Manuel; Caldeira, Filomena; Sanches, Raquel; Dantas, Filipa; Freitas, Ludivina; Andrade, Graça; Mota, PaulaBACKGROUND: Population immune profile for influenza is highly affected by circulating influenza viruses, thus changing the risk of infection for influenza. This study aims to assess influenza immunity in the Portuguese population by age groups, during 2014 and 2015 and establish a relationship between seroprotection and circulating influenza viruses in 2014/15 and 2015/16 seasons. METHODS: Two cross-sectional studies were developed based on a convenience serum sample collected in June 2014 (n=626) and July 2015 (n=675) in hospitals from mainland and Azores and Madeira.Serums equally represent all age groups. Antibody titers were evaluated by HI assay for strains recommended for seasonal influenza vaccine northern hemisphere,2014/15 and 2015/2016. Seroprevalences were estimated for each strain by age group and the association with seasonal cumulative influenza-like illness (ILI) rates for influenza virus during both seasons was analised. RESULTS: In June 2014 the highest seroprotection was observed for influenza A(H3) (39.0%; 95% CI: 36.2-43.8%) and A(H1)pdm09 (29.7; 95% CI: 26.3-33.4%), with higher levels in children 5-14 years old. In 2014/2015 a dominant circulation of influenza B/Yamagata was observed with high incidence rates in individuals under 65 years old, the ones that had lower seroprotection. Although before the start of the season high protection for A(H3) was observed, the circulation of the new drift A(H3) strains had gained an immunological advantage,in accordance with A(H3) elevated incidence rates observed during 2014/15. In July 2015 the highest seroprotection was observed for influenza B/ Yamagata (55.1%; 95% CI: 51.4-58.9%), 2.4 times the estimated 2014.This increase was even more pronounced in younger (≤ 4 years old), 6.3 times increase in 2015.This fact is in agreement with the predominant influenza B virus detected and the high ILI incidence rate observed in children during 2014/2015 epidemic. Seroprotection levels for influenza A in July 2015 were not significantly different from 2014.During 2015/16 season, influenza A(H1N1)pdm09 was predominant, with high incidence rate in < 65 year old. Influenza B/Victoria lineage,although detected at low levels increased in frequency, in agreement with the lowest level of seroprotection detected in the general population before the start of 2015/2016 season (21.8%; 95% CI: 18.7-24.0%). CONCLUSIONS There was a correlation between virus circulation, incidence rates for each age group and the previous seroprotection for seasonal influenza viruses.Our study highlights the value of measuring the serological profile for influenza to establishe risk groups for infection for which an increase preventive measures, including vaccination, should be fostered.
- Influenza severe cases in hospitals, between 2014 and 2016 in PortugalPublication . Guiomar, Raquel; Pechirra, Pedro; Cristóvão, Paula; Costa, Inês; Conde, Patrícia; Corte-Real, Rita; Branquinho, Paula; Silvestre, Maria José; Almeida Santos, Madalena; Fernandes, Isabel; Dias, Isabel; Rodrigues, Sónia; Sena, Nadir; Lazzara, Daniela; Sobrinho Simões, Joana; Costa, Maria do Rosário; Guimarães, João Tiago; Rodrigues, Fernando; Pereira-Vaz, João; Correia, Lurdes; Andrade, Graça; Freitas, Ludivina; Figueira, Neuza; Sanches, Raquel; Marques, Mónica; Barros, Margarida; Mota Vieira, Luísa; Cabral Veloso, Rita; Castelo Branco, Cláudia; Pimentel, Sílvia; Duarte, Joana; Pereirinha, Tânia; Bulhões, Sara; Moniz, Raquel; Brilhante, Maria José; Bruges Armas, Jácome; Pimentel Couto, Ana Rita; Santos, Margarida; Soares, Marta; Melo Cristino, José; Ribeiro, Carlos; Carvalho, Dinah; Barreto, Rosário; Ramos, Maria Helena; Castro, Ana Paula; Matos Santos, Ana Cláudia; Cunha, Mário; Martins, Luís; Almeida, Sofia; Peres, Maria João; Viseu, Regina; Inácio, Filipe; Mota, PaulaBackground: Since 2009, the Portuguese Laboratory Network (PLNID) for Influenza Diagnosis has integrated 15 Laboratories in mainland and Atlantic Islands of Azores and Madeira. This PLNID added an important contribute to the National Influenza Surveillance Program regarding severe and hospitalized influenza cases. The present study aims to describe influenza viruses detected in influenza like illness (ILI) cases: outpatients (Outp), hospitalized (Hosp), and intensive care units (ICU), between 2014 and 2016. Methods: The PLNID performs influenza virus diagnosis by biomolecular methodologies. Weekly reports to the National Influenza Reference Laboratory ILI cases tested for influenza. Reports include data on detecting viruses, hospital assistance, antiviral therapeutics, and information on death outcome. Were reported during two winter seasons 8059 ILI cases,being 3560 cases in 2014/15 (1024 in Outp, 1750 Hosp, and 606 in ICU) and 4499 cases in 2015/2016 (1933 in Outp, 1826 Hosp, and 740 in ICU). Results: The higher percentage of influenza positive cases were detected in Outp in both seasons, 18% during 2014/15 and 20% in 2015/16. In 2014/15,influenza cases were more frequent in individuals older than 65 years old and these required more hospitalizations,even in ICU. In 2015/16,the influenza cases were mainly detected in individuals between 15-64 years old. A higher proportion of influenza positive cases with hospitalization in ICU were observed in adults between 45-64 years old.During the study period,the predominant circulating influenza viruses were different in the two seasons: influenza B and A(H3) co-circulated in 2014/15,and influenza A(H1)pdm09 was predominant during 2015/16. Even when influenza A is notthe dominant virus, A(H3) and A(H1)pdm09 subtypes correlate with higher detection rate in hospitalized cases (Hosp and UCI), with higher frequencies in adults older than 45. Influenza B,detected in higher proportion in outpatients, was frequently relatedwith influenza cases in younger age groups: 0-4 and 5-14 years old. Conclusions: This study highlights the correlation of theinfluenza virus type/subtype that circulates in each season with the possible need for hospitalization and intensive care in special groups of the population. Circulation of influenza A subtypes can cause more frequentdisease in individuals older than 45, with need of hospitalization including intensive care. On the other hand, influenza B is more frequently associated with less severe cases and with infection in children and younger adults. Influenza B circulation might predict lower number of hospitalizations.The identification of influenza type in circulation,byPLNID ineach season, could guide action planning measures in population health care.
- Molecular characterization of respiratory syncycial virus during 2015-2016 season in PortugalPublication . Cristóvão, Paula; Pereira, Diogo; Pechirra, Pedro; Pereira-Vaz, João; Correia, Lurdes; Rodrigues, Fernando; Andrade, Graça; Corte-Real, Rita; Branquinho, Paula; Peres, Maria João; Viseu, Regina; Balseiro, Maria Jesus; Mota, Paula; Guiomar, RaquelBackground: Respiratory syncytial virus (RSV) is one of the most frequent and important respiratory viral agent that causes respiratory infection complications in younger children and elderly. RSV has an autumn / winter seasonality. Genetic diversity in both of RSV A and B subtypes increased in last years with the spread of new genotypes. This study aims to describe the genetic variability of RSV during 2015/2016 season in Portugal and correlate the circulating genotypes with detected ones in previous seasons. Will also be evaluated the association between genotype, clinical diagnosis and age. Methods: During 2015/16 winter season, between November/2015 and February/2016, 45 RSV were genetically characterized. RSV positive respiratory samples were collected in two settings: children under 5 years old diagnosed by hospital laboratories from the Portuguese Laboratory Network for the Diagnosis of Influenza Infection, and all age Influenza-like illness (ILI) patients reported by primary care health services and diagnosed by the National Influenza Reference Laboratory. All samples were irreversibly anonymized. Demographic and clinical data were collected. RSV detection was performed by real-time PCR and other biomolecular methods. RSV genotype was assigned by the nucleotide sequence of the hypervariable C-terminal region of the G protein gene and the phylogenetic analysis was performed in MEGA 6.0. Results: From 45 RSV genetically characterized, 31 (69%) were reported by hospitals, patients age ranged from newborn to 4 years old. From these, 25 (81%; 25/31) patients were hospitalized, being the bronchiolitis the most frequent diagnosis. While 14 (31%) RSV cases came from primary care health services, patients age ranged from 3 to 83 and all had a clinical diagnosis of ILI. Were included patients from both genders in equal proportions. RSV A and B co-circulated during 2015/2016 season. Were genetically characterized 21 (47%) RSV A and 24 (53%) RSV B. 90% (19/21) of RSV A clustered in ON1 genotype, the others 2 clustered with NA1 genotype. All RSV B present a BA-like genotype, 70% (17/24) were similar to BA9 and 30% (7/24) clustered with BA10 genotype. Conclusions: During 2015/2016 season was observed a co-circulation of RSVA and RSVB. In present study ON1genotype was predominant in circulation among RSVA, this was also detected as the major RSVA genotype at the global level. Only two RSVA belonged to NA1 genotype. In Portugal, NA1 was in circulation during 2010-2012 period. Undetected since 2012, it seems to reappear during 2015/16 season. All RSVB characterized belonged to BA genotypes, the majority clustered within BA9 genotype. BA10 genotype was also identified in circulation at low frequency. BA9 and BA10 were being found in co-circulation since 2011/12. No association was found between age, clinical diagnosis and RSVA and B genotypes. RSV has an important impact in children in high-risk groups highlighting the need off a continuous RSV surveillance each winter.
- Rede Portuguesa de Laboratórios para o Diagnóstico da Gripe: inverno 2013/2014Publication . Guiomar, Raquel; Pechirra, Pedro; Conde, Patrícia; Cristóvão, Paula; Maia, Ana Carina; Silvestre, Maria José; Almeida Santos, Madalena; Sobrinho Simões, Joana; Costa, Maria do Rosário; Pinto, Rita; Guimarães, João Tiago; Ribeiro, Graça; Pereira-Vaz, João; Correia, Lurdes; Fernandes, Paula Luísa; Andrade, Graça; Mota Vieira, Luísa; Cabral Veloso, Rita; Moniz, Raquel; Pereirinha, Tânia; Bruges Armas, Jácome; Pimentel Couto, Ana Rita; Soares, Marta; Melo Cristino, José; Ribeiro, Carlos; Carvalho, Dinah; Barreto, Raquel; Côrte-Real, Rita; Branquinho, Paula; Ramos, Maria Helena; Castro, Ana Paula; Cunha, Mário; Martins, Luís; Almeida, Sofia; Peres, Maria João; Viseu, Regina; Inácio, FilipeA Rede Portuguesa de Laboratórios para o Diagnóstico da Gripe (RPLDG) integra, atualmente, 15 laboratórios maioritariamente hospitalares e é coordenada pelo Laboratório Nacional de Referência para o Vírus da Gripe (LNRVG) do Departamento de Doenças Infecciosas do Instituto Nacional de Saúde Doutor Ricardo Jorge, I.P. A RPLDG realiza o diagnóstico laboratorial do vírus da gripe assim como de outros vírus respiratórios, permitindo um conhecimento mais preciso da etiologia das infeções respiratórias, particularmente em casos hospitalizados de infeção respiratória aguda grave, constituindo um complemento valioso para o PNVG. Os casos de SG provenientes de emergências hospitalares e casos de Infecção Respiratória Aguda Grave, incluindo casos com internamento em unidade de cuidados intensivos, foram notificados pelos laboratórios da Rede ao LNRVG. Dos 15 laboratórios da Rede, 13 notificaram casos de doença respiratória durante a época de 2013/2014. Os dados recolhidos foram inseridos em suporte informático tendo as bases de dados sido agregadas numa base de dados comum submetida a um processo de validação de congruência de dados. Os dados analisados correspondem ao período que decorreu entre a semana 38 de 2013 e a semana 21 de 2014. Foram notificados pelos Laboratórios da Rede um total de 3790 casos de infeção respiratória. O maior número de notificações foi observado no mês de janeiro e fevereiro (semanas 2/2014 a 8/2014), com um pico de ocorrência na semana 4/2014 com a notificação de 454 casos de infeção respiratória. O vírus da gripe foi detetado em 822 casos de infeção respiratória. O vírus influenza A foi identificado em 807 (98,2%) dos casos positivos, destes 403 (49,0%) pertencem ao subtipo A(H1)pdm09, 98 (12,0%) ao subtipo A(H3) e 306 (37,0%) vírus influenza A não foram subtipados. O vírus influenza B foi detetado em 14 (2,0%) casos. Foi identificada 1 infecção mista por vírus influenza A(H1)pdm09 e A(H3) (0,1%). A maior percentagem de casos de gripe foi observada em indivíduos entre os 15 e os 64 anos sendo o vírus influenza A(H1)pdm09 o predominantemente detetado. Nas crianças com menos de 4 anos o vírus influenza foi detetado numa proporção reduzida, apenas em 8,8% dos casos analisados laboratorialmente, sendo o agente mais detetado neste grupo etário, o vírus sincicial respiratório (dados não mostrados). A Rede Portuguesa de Laboratórios para o Diagnóstico da Gripe permitiu a deteção dos vírus da gripe em meio hospitalar, incluindo doentes em internamento e UCI. Os vírus influenza A foram predominantes e detetados em maior percentagem nos jovens e adultos.
- Severe acute respiratory infections in the 2012/2013 season studied by the Portuguese Laboratory Network for Influenza DiagnosisPublication . Guiomar, Raquel; Pechirra, Pedro; Conde, Patrícia; Cristóvão, Paula; Silvestre, Maria José; Almeida Santos, Madalena; Sobrinho Simões, Joana; Costa, Maria do Rosário; Amaral, Susana; Guimarães, João Tiago; Ribeiro, Graça; Correia, Lurdes; Fernandes, Aida; Milho, Luís; Fernandes, Paula Luísa; Andrade, Graça; Mota Vieira, Luísa; Cabral, Rita; Moniz, Raquel; Pereirinha, Tania; Bruges Armas, Jacome; Pimentel Couto, Ana Rita; Soares, Marta; Melo Cristino, José; Carvalho, Dinah; Ribeiro, Carlos; Barreto, Rosário; Côrte-Real, Rita; Branquinho, Paula; Ramos, Maria Helena; Castro, Ana Paula; Caldeira, Filomena; Maurílio, Manuel; Cunha, Mário; Ornelas, Carmo; Almeida, SofiaDuring the 2009/10 influenza pandemic, a network of 14 laboratories located in the main reference hospitals from Portugal mainland, Madeira and Azores was established for the diagnosis of the new influenza A(H1N1)2009 pandemic strain. Since then, the network performs laboratory diagnosis of influenza as well as other respiratory pathogens, thus contributing to the laboratory diagnosis of respiratory disease in Portugal. This network is a valuable complement of the National Influenza Surveillance Programme (mainly based on primary healthcare units), enabling a more accurate knowledge of the aetiology of the severe respiratory infections, especially in hospitalized cases. The present study describes the severe acute respiratory infections, in the 2012/2013 season, diagnosed by the laboratory network. From the 14 laboratories, 11 reported cases of respiratory disease during 2012/2013 season. The laboratory network performs diagnosis of influenza A and B viruses and other respiratory agents by PCR based methods, also enabling the detection of mixed infections. All 14 laboratories perform the detection of influenza A(H1)pdm09, 4 perform the influenza A(H1) seasonal and A(H3) subtyping, and 10 participants also detect influenza B. Eight laboratories implemented methodologies for the detection of other infectious agents associated with respiratory disease. The antigenic characterization of 8 isolated viruses [3 A(H1)pdm09 and 5 B/Yamagata] was performed at the National Influenza Reference Laboratory. The genetic analysis of the HA1 subunit of the haemagglutinin gene was performed in 17 viruses [7 A(H1)pdm09, 1 A(H3) and 9 B/Yamagata]. Twenty nine A(H1)pdm09 and 5 B/Yamagata were tested for antiviral susceptibility [PCR(NA)-H275Y and/or MUNANA phenotypic assays for oseltamivir and zanamivir]. The 11 laboratories reported a total of 1470 respiratory disease cases, from week 39/2012 to 21/2013 [peak of 205 (13.9%) cases during week 10/2013]. Influenza was identified in 504 cases. Influenza A was detected in 352 (70.0%) cases: 297 (59.0%) cases were A(H1)pdm09, 48 (10.0%) cases were not subtyped, and 7 (1.0%) cases were A(H3). Influenza B was identified in 152 (30%) of the influenza cases. During the 2012/2013 season, 311 (21.2%) reported cases were hospitalized in intensive care units (ICU), the majority of them had between 50-54 years (34; 10.9%), followed by the age groups 45-49 and 55-59 years old (28; 9.0% each). The causal agent was identified in 160 (51.4%) ICU cases. Influenza was identified in 120 (38.5%) patients, other respiratory agents were detected in 40 (12.8%), within these, multiple infections were present in 18 (5.7%). Bacteria were identified in 31 (10.0%) cases mainly associated with RSV and hRV. Among ICU influenza cases, the most detected virus was A(H1)pdm09 (82; 62.0%). However, cases of A(H3) (3; 2.0%), A unsubtyped (8; 7.0%) and B (27; 23.0%) were also detected. As expected, the highest number of ICU influenza positive cases was detected in week 10/2013 (18; 15.0%), coincident with the highest number of influenza cases during all season. ICU flu cases were detected predominantly in individuals between 50-54 years (18; 15.0%). From the ICU reported cases, 6 (1.9%) died. The influenza A(H1)pdm09 virus was detected in 2 man between 50-59 years old from these 6 fatal outcomes. The isolated influenza A viruses were similar to the 2012/2013 vaccine strains. The influenza B/Yamagata viruses showed a greater antigenic and genetic variability. The Portuguese Laboratory Network for Influenza Diagnosis plays a major role in the diagnosis of acute respiratory infections in Portugal, providing a more accurate knowledge of the respiratory agents involved. During the 2012/2013 season, the influenza A(H1)pdm09 virus predominated in co-circulation with influenza B virus. The A(H1)pdm09 virus was the responsible for the majority of the flu cases admitted in the ICU and may have been the cause of death in two cases. Bacterial and other viral agents have been identified in some of the severe cases reported. The majority of the characterized influenza viruses were similar to the vaccine strains and none of the virus showed reduced susceptibility to oseltamivir or zanamivir.