Streptococcus Pneumoniae coinfection is correlated with the severity of H1N1 pandemic Influenza

Fil: Palacios, Gustavo. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Hornig, Mady. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Cisterna, Daniel. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Savji, Nazir. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Bussetti, Ana Valeria. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Kapoor, Vishal. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Hui, Jeffrey. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Tokarz, Rafal. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Briese, Thomas. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Baumeister, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Lipkin, W. Ian. Columbia University. Center for Infection and Immunity; Estados Unidos.Background Initial reports in May 2009 of the novel influenza strain H1N1pdm estimated a case fatality rate (CFR) of 0.6%, similar to that of seasonal influenza. In July 2009, however, Argentina reported 3056 cases with 137 deaths, representing a CFR of 4.5%. Potential explanations for increased CFR included virus reassortment or genetic drift, or infection of a more vulnerable population. Virus genomic sequencing of 26 Argentinian samples representing both severe and mild disease indicated no evidence of reassortment, mutations associated with resistance to antiviral drugs, or genetic drift that might contribute to virulence. Furthermore, no evidence was found for increased frequency of risk factors for H1N1pdm disease. Methods/Principal Findings We examined nasopharyngeal swab samples (NPS) from 199 cases of H1N1pdm infection from Argentina with MassTag PCR, testing for 33 additional microbial agents. The study population consisted of 199 H1N1pdm-infected subjects sampled between 23 June and 4 July 2009. Thirty-nine had severe disease defined as death (n = 20) or hospitalization (n = 19); 160 had mild disease. At least one additional agent of potential pathogenic importance was identified in 152 samples (76%), including Streptococcus pneumoniae (n = 62); Haemophilus influenzae (n = 104); human respiratory syncytial virus A (n = 11) and B (n = 1); human rhinovirus A (n = 1) and B (n = 4); human coronaviruses 229E (n = 1) and OC43 (n = 2); Klebsiella pneumoniae (n = 2); Acinetobacter baumannii (n = 2); Serratia marcescens (n = 1); and Staphylococcus aureus (n = 35) and methicillin-resistant S. aureus (MRSA, n = 6). The presence of S. pneumoniae was strongly correlated with severe disease. S. pneumoniae was present in 56.4% of severe cases versus 25% of mild cases; more than one-third of H1N1pdm NPS with S. pneumoniae were from subjects with severe disease (22 of 62 S. pneumoniae-positive NPS, p = 0.0004). In subjects 6 to 55 years of age, the adjusted odds ratio (OR) of severe disease in the presence of S. pneumoniae was 125.5 (95% confidence interval [CI], 16.95, 928.72; p<0.0001). Conclusions/Significance The association of S. pneumoniae with morbidity and mortality is established in the current and previous influenza pandemics. However, this study is the first to demonstrate the prognostic significance of non-invasive antemortem diagnosis of S. pneumoniae infection and may provide insights into clinical management

Streptococcus pneumoniae Coinfection Is Correlated with the Severity of H1N1 Pandemic Influenza

Initial reports in May 2009 of the novel influenza strain H1N1pdm estimated a case fatality rate (CFR) of 0.6%, similar to that of seasonal influenza. In July 2009, however, Argentina reported 3056 cases with 137 deaths, representing a CFR of 4.5%. Potential explanations for increased CFR included virus reassortment or genetic drift, or infection of a more vulnerable population. Virus genomic sequencing of 26 Argentinian samples representing both severe and mild disease indicated no evidence of reassortment, mutations associated with resistance to antiviral drugs, or genetic drift that might contribute to virulence. Furthermore, no evidence was found for increased frequency of risk factors for H1N1pdm disease.We examined nasopharyngeal swab samples (NPS) from 199 cases of H1N1pdm infection from Argentina with MassTag PCR, testing for 33 additional microbial agents. The study population consisted of 199 H1N1pdm-infected subjects sampled between 23 June and 4 July 2009. Thirty-nine had severe disease defined as death (n = 20) or hospitalization (n = 19); 160 had mild disease. At least one additional agent of potential pathogenic importance was identified in 152 samples (76%), including Streptococcus pneumoniae (n = 62); Haemophilus influenzae (n = 104); human respiratory syncytial virus A (n = 11) and B (n = 1); human rhinovirus A (n = 1) and B (n = 4); human coronaviruses 229E (n = 1) and OC43 (n = 2); Klebsiella pneumoniae (n = 2); Acinetobacter baumannii (n = 2); Serratia marcescens (n = 1); and Staphylococcus aureus (n = 35) and methicillin-resistant S. aureus (MRSA, n = 6). The presence of S. pneumoniae was strongly correlated with severe disease. S. pneumoniae was present in 56.4% of severe cases versus 25% of mild cases; more than one-third of H1N1pdm NPS with S. pneumoniae were from subjects with severe disease (22 of 62 S. pneumoniae-positive NPS, p = 0.0004). In subjects 6 to 55 years of age, the adjusted odds ratio (OR) of severe disease in the presence of S. pneumoniae was 125.5 (95% confidence interval [CI], 16.95, 928.72; p<0.0001).The association of S. pneumoniae with morbidity and mortality is established in the current and previous influenza pandemics. However, this study is the first to demonstrate the prognostic significance of non-invasive antemortem diagnosis of S. pneumoniae infection and may provide insights into clinical management

Caracterización molecular de cepas de influenza A (H1N1) 2009 de casos leves y graves de la Argentina

Fil: Cisterna, Daniel. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Campos, Ana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Pontoriero, Andrea. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Alonio, Virginia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Molina, Viviana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Palacios, Gustavo. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Solovyov, Alexander. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Hui, Jeffrey. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Savji, Nazir. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Bussetti, Ana Valeria. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Jabado, Omar J. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Street, Craig. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Hirschberg, David L. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Rabadan, Raul. Columbia University. Department of Biomedical Informatics; Estados UnidosFil: Hutchison, Stephen. 454 Life Sciences; Estados UnidosFil: Egholm, Michael. 454 Life Sciences; Estados Unidos.Fil: Lipkin, W. Ian. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Baumeister, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; ArgentinaWhile worldwide pandemic influenza A(H1N1) pdm case fatality rate (CFR) was 0.4%, Argentina’s was 4.5%. A total of 34 strains from mild and severe cases were analyzed. A full genome sequencing was carried out on 26 of these, and a partial sequencing on the remaining eight. We observed no evidence that the high CFR can be attributed to direct virus changes. No evidence of re-assortment, mutations associated with resistance to antiviral drugs, or genetic drift that might contribute to virulence was observed. Although the mutation D225G associated with severity in the latest reports from the Ukraine and Norway is not observed among the Argentine strains, an amino acid change in the area (S206T) surrounding the HA receptor binding domain was observed, the same previously established worldwide. (ES) Mientras que la tasa de letalidad (CFR) para (H1N1)pdm en todo el mundo era del 0.4%, en la Argentina la mortalidad observada fue de 4.5%. La secuenciación del genoma completo de 26 cepas de virus argentinos de influenza A (H1N1)pdm de casos leves y graves y de 8 cepas secuenciadas parcialmente no mostró evidencia de que la elevada tasa de letalidad se pueda atribuir directamente a cambios en el virus. No se encontraron hallazgos de recombinación, de mutaciones asociadas con la resistencia a los medicamentos antivirales ni de variaciones genéticas que puedan contribuir a la virulencia observada. Si bien la mutación D225G asociada con la gravedad, comunicada en informes procedentes de Ucrania y Noruega, no se ha encontrado en las cepas argentinas estudiadas, se ha observado un cambio aminoacídico en la región (S206T) en torno al dominio del sitio de unión al receptor en la HA, el mismo hallado en cepas distribuidas alrededor del mundo

Caracterización molecular de cepas de influenza A (H1N1) 2009 de casos leves y graves de la Argentina

Fil: Cisterna, Daniel. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Campos, Ana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Pontoriero, Andrea. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Alonio, Virginia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Molina, Viviana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Palacios, Gustavo. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Solovyov, Alexander. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Hui, Jeffrey. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Savji, Nazir. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Bussetti, Ana Valeria. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Jabado, Omar J. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Street, Craig. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Hirschberg, David L. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Rabadan, Raul. Columbia University. Department of Biomedical Informatics; Estados UnidosFil: Hutchison, Stephen. 454 Life Sciences; Estados UnidosFil: Egholm, Michael. 454 Life Sciences; Estados Unidos.Fil: Lipkin, W. Ian. Columbia University. Center for Infection and Immunity; Estados Unidos.Fil: Baumeister, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; ArgentinaWhile worldwide pandemic influenza A(H1N1) pdm case fatality rate (CFR) was 0.4%, Argentina’s was 4.5%. A total of 34 strains from mild and severe cases were analyzed. A full genome sequencing was carried out on 26 of these, and a partial sequencing on the remaining eight. We observed no evidence that the high CFR can be attributed to direct virus changes. No evidence of re-assortment, mutations associated with resistance to antiviral drugs, or genetic drift that might contribute to virulence was observed. Although the mutation D225G associated with severity in the latest reports from the Ukraine and Norway is not observed among the Argentine strains, an amino acid change in the area (S206T) surrounding the HA receptor binding domain was observed, the same previously established worldwide. (ES) Mientras que la tasa de letalidad (CFR) para (H1N1)pdm en todo el mundo era del 0.4%, en la Argentina la mortalidad observada fue de 4.5%. La secuenciación del genoma completo de 26 cepas de virus argentinos de influenza A (H1N1)pdm de casos leves y graves y de 8 cepas secuenciadas parcialmente no mostró evidencia de que la elevada tasa de letalidad se pueda atribuir directamente a cambios en el virus. No se encontraron hallazgos de recombinación, de mutaciones asociadas con la resistencia a los medicamentos antivirales ni de variaciones genéticas que puedan contribuir a la virulencia observada. Si bien la mutación D225G asociada con la gravedad, comunicada en informes procedentes de Ucrania y Noruega, no se ha encontrado en las cepas argentinas estudiadas, se ha observado un cambio aminoacídico en la región (S206T) en torno al dominio del sitio de unión al receptor en la HA, el mismo hallado en cepas distribuidas alrededor del mundo

Characteristics of H1N1pdm influenza subjects.

*<p>Mann-Whitney U, <i>p</i> = ns.</p>**<p><i>p</i><0.0001.</p>§<p><i>p</i> = 0.09.</p>¶<p><i>p</i><0.0001.</p>#<p><i>p</i> = 0.0056.</p

Relationship of <i>S. pneumoniae</i> coinfection to H1N1 influenza disease severity, stratified by age risk category.

*<p>Restricted to subjects with age data.</p>§<p><i>p</i><0.0001.</p

Coinfection patterns in severe and mild H1N1pdm influenza.

*<p><i>p</i> = 0.0004; ** <i>p</i><0.0001; *** <i>p</i> = 0.0008; ^¶<i>p</i> = 0.0085; ^¶¶<i>p</i> = 0.0017.</p>‡<p>No evidence of other bacterial respiratory pathogens in any subjects, including: <i>C. pneumoniae</i>; <i>L. pneumophila</i>; <i>M. pneumoniae</i>; <i>M. tuberculosis</i>; <i>N. meningitides</i>; <i>C. albicans</i>; <i>Enterobacter spp</i>; <i>Enterococcus spp</i>.; <i>Pseudomonas spp</i>.; <i>S. pyogenes</i>.</p>‡‡<p>No evidence of other viral respiratory pathogens in any subjects, including: strains of FLUAV other than H1N1pdm, FLUBV, HPIV 1-4, HMPV, HEV, HAdV. The <i>A. baumannii</i>-positive case was also positive for <i>S. aureus</i>.</p