Wednesday, July 13, 2011

BMC Study: A Crowded Viral Field




# 5689



While it is a distinction often lost on the public, doctors know that during the height of every flu season the majority of patients reporting `flu-like symptoms’ likely have something other than influenza.


Even during the opening weeks and months of the H1N1 pandemic of 2009, a large percentage – perhaps even a majority – of people who either thought (or they were told) they had `swine flu’, had something else.


In October of 2009, during the height of the fall wave of the H1N1 pandemic, I posted the following graphic on my blog.


Of the more than 10,000 samples submitted for testing during the 1st week of October 2009, more than 72%almost 3/4ths –  came back negative for influenza.


ILIs or Influenza-Like Illnesses, like adenovirus, parainfluenza, rhinovirus and others are often indistinguishable from influenza without laboratory tests.


Most of the time, it doesn’t matter much.  


Unless there are serious complications – often exacerbated by pre-existing medical conditions - viral illnesses generally resolve themselves after a few days without medical intervention.


Which is why doctors don’t automatically run expensive and time consuming lab tests on every `flu’ patient that shows up a their door.


The odds are, the patient will have recovered before the results come back.


But during a pandemic, when rapid decisions must be made regarding patient isolation and the administration of antivirals, things become more complicated. 



We’ve a new study appearing in BMC Infectious Diseases that looks at laboratory testing on thousands of people clinically diagnosed with `H1N1 Swine Flu’ in Scotland during the opening months (April-July) of the 2009 outbreak.




It turns out that of the more than 16,000 patients tested for the H1N1 virus by the West of Scotland Specialist Virology Centre (WoSSVC) in Glasgow over a 4 month period, only 9% were actually positive for the Swine flu virus.


Using real time reverse transcriptase polymerase chain reaction (rtRT-PCR) assays, the laboratory was able to screen 3247 of these negative samples for a wide variety of respiratory pathogens;


  • Influenza A (generic & H1N1/2009 specific)
  • Influenza B and C
  • RSV
  • Rhinovirus
  • Parainfluenza 1-4
  • Human metapneumovirus
  • Coronavirus (229E, NL63, HKU1 & OC43)
  • Adenovirus
  • Mycoplasma pneumoniae


Despite the broad scope and sensitivity of these lab tests, more than 70% of those patients diagnosed with the swine flu tested negative for any of the above listed respiratory illnesses.


First a link to the study (open access), and then I’ll return with a little more.


During the summer 2009 outbreak of "swine flu" in Scotland what respiratory pathogens were diagnosed as H1N1/2009?

Rory N Gunson email and William F Carman email

BMC Infectious Diseases 2011, 11:192doi:10.1186/1471-2334-11-192


During the April-July 2009 outbreak of H1N1/2009 in scotland the West of Scotland Specialist Virology Centre (WoSSVC) in Glasgow tested >16 000 clinical samples for H1N1/2009. Most were from patients clinically diagnosed with H1N1/2009. Out of these, 9% were positive. This study sought to determine what respiratory pathogens were misdiagnosed as cases of H1N1/2009 during this time.


We examined the results from 3247 samples which were sent to the laboratory during April-July 2009. All were from patients clinically diagnosed as having H1N1/2009 (based on accepted criteria) and all were given a full respiratory screen using real time reverse transcriptase polymerase chain reaction (rtRT-PCR) assays.


In total, respiratory pathogens were detected in 27.9% (95% confidence interval, 26.3-29.5%) of the samples submitted. Numerous pathogens were detected, the most common of which were rhinovirus (8.9% (95% confidence interval, 7.9-9.9%)), parainfluenza 1 (1.9% (95% confidence interval, 1.4-2.4%)) and 3 (4.1% (95% confidence interval, 3.3-4.9%)), and adenovirus ((3.5% (95% confidence interval, 2.9-4.2%)).


This study highlights the problems of using a clinical algorithm to detect H1N1/2009. Clinicians frequently misdiagnosed common respiratory pathogens as H1N1/2009 during the spring/summer outbreak in Scotland. Many undesirable consequences would have resulted, relating to treatment, infection control, and public health surveillance.


The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.


You may be wondering about the 70% of these samples that tested negative for any respiratory pathogen. 


  • Some of these cases may have involved the `worried well’, people who – due the publicity given the outbreak – rushed to their doctors with imagined symptoms (see Pandemics And The `Worried Well’).


  • Samples taken included gargles, throat swabs, nasal
    swabs, nasopharyngeal aspirates, sputums, and endotracheal secretions – and collection techniques and transport issues, along with the timing of taking these samples - could have produced some false negatives.


  • Some of these samples (especially early on) may have come from asymptomatic patients who were exposed to a known or suspected H1N1 case (part of the Epidemiological Criteria for testing).


  • And while the list of pathogens tested for was extensive, it was by no means complete; Coronavirus HKU1, Boca Virus HBoV, and many viral and bacterial pathogens were not included in the screening panel.


Apart from giving us a better insight into the spectrum of non-flu viruses in circulation (even in the summer), this study highlights the need for rapid and reliable in-office flu tests during a pandemic.


Clinical diagnostic algorithms may be useful, are limited in their ability exclude non-pandemic viral illnesses.