# 4204
Readers with long memories may remember that last July I reported in this blog that researchers from Columbia University’s Mailman School of Public Health were to travel to Argentina to investigate the perceived high CFR (Case Fatality Ratio) among H1N1 cases there.
Jason Gale and Eliana Raszewski, writing for Bloomberg news, described the project in a story entitled: Argentina Flu Death Mystery Sparks Probe for Virus Mutation.
Scientists from Columbia University and Argentina’s National Institute of Infectious Diseases now plan to decode the complete genomic sequences of at least 150 virus samples over the next 10 days to gauge the frequency of the changes and whether they are linked to more severe illness. Major changes in the pandemic virus could erode the effectiveness of vaccines being prepared to fight the scourge.
You’ll find further details on these deaths, and the planned investigation, in the following blogs.
Argentina Working To Release Viral Sequences
Follow Up On Yesterday’s Report On Argentina Sequences
Since that report in July, we’ve heard very little other than the fact that no unusual viral mutations had been discovered in Argentina that could account for the higher CFR.
That is, until November of last month, when two of the authors of the following PLoS One study appeared on Vincent Racaniello’s excellent podcast, TWiV (This week In Virology) to discuss their upcoming paper.
TWiV 59: Dog bites virus
by Vincent Racaniello on 22 November 2009
Hosts: Vincent Racaniello, Alan Dove, Rich Condit, Gustavo Palacios, and Mady Hornig
A TWiV panel of five considers the finding of Streptococcus pneumoniae in fatal H1N1 cases in Argentina, hysteria in the Ukraine over pandemic influenza, and human vaccinia infection after contact with a raccoon rabies vaccine bait.
TWiV is both entertaining and informative, and I highly recommend it to anyone with curiosity about the field of virology. While sometimes it can’t avoid being a bit technical, the panel does a great job making the information accessible and understandable to the general public.
In this episode, Gustavo Palacios, and Mady Hornig reveal that it was the presence of S. pneumoniae in those infected with H1N1 that often led to the heightened severity of their illness.
Excerpts from the PLoS One study are posted below.
In it, the authors suggest that testing for the presence of S. pneumoniae may accurately predict who will develop severe disease. They write:
In our study of Argentinean victims of H1N1pdm, the presence of S. pneumoniae in NPS predicts severe disease outcome. The risk associated with S. pneumoniae is particularly prominent in 6-to-55 year-old individuals.
Indeed, severity of disease in this low risk group can be predicted with 90.97% accuracy via a multivariable logistic regression model that considers the presence of S. pneumoniae together with viruses other than influenza and a risk-associated medical condition.
But before we go there, a reminder:
I have suggested on numerous occasions that people should consult with their health care provider about the advisability of taking the Pneumococcal polysaccharide vaccine (PPSV) – even if you aren’t sure you fall into a recommended category.
Along the way, a few of my blogs on the subject include:
CDC Promoting Better Uptake Of PPSV in Adults
An Appropriate Level Of Concern (Revisited)
Referral: Effect Measure On Pneumococcal Vaccines
CDC Issues Pneumococcal Vaccine Recommendations
The PPSV is designed to help protect against many (but not all) strains of S. pneumoniae.
Something to bear in mind as you read this report.
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.
Gustavo Palacios1#*, Mady Hornig1#, Daniel Cisterna2, Nazir Savji1, Ana Valeria Bussetti1, Vishal Kapoor1, Jeffrey Hui1, Rafal Tokarz1, Thomas Briese1, Elsa Baumeister2, W. Ian Lipkin1*
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