title: Streptococcus pneumoniae coinfection is correlated with the severity of H1N1 pandemic influenza.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USA. gp2050@columbia.edu
authors.forename: Gustavo
authors.initials: G
authors.lastname: Palacios
authors.forename: Mady
authors.initials: M
authors.lastname: Hornig
authors.forename: Daniel
authors.initials: D
authors.lastname: Cisterna
authors.forename: Nazir
authors.initials: N
authors.lastname: Savji
authors.forename: Ana Valeria
authors.initials: AV
authors.lastname: Bussetti
authors.forename: Vishal
authors.initials: V
authors.lastname: Kapoor
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hui
authors.forename: Rafal
authors.initials: R
authors.lastname: Tokarz
authors.forename: Thomas
authors.initials: T
authors.lastname: Briese
authors.forename: Elsa
authors.initials: E
authors.lastname: Baumeister
authors.forename: W Ian
authors.initials: WI
authors.lastname: Lipkin
mesh_terms: D000293:Adolescent; D000328:Adult; D001118:Argentina / Q000453:epidemiology; D012634:Bodily Secretions / Q000382:microbiology / Q000821:virology; D002648:Child; D004196:Disease Outbreaks; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000150:complications / Q000453:epidemiology / Q000382:microbiology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000150:complications* / Q000382:microbiology* / Q000821:virology; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D013296:Streptococcus pneumoniae / Q000502:physiology*; D055815:Young Adult