Monday, March 17, 2014

Lancet: Community Burden & Severity Of Seasonal And Pandemic Influenza


Photo Credit CDC PHIL 

# 8379


Despite decades of research, a surprising number of seemingly basic questions about the influenza virus, and the host’s immune response to infection, remain less than fully answered.  Questions like:

  • How is the virus most commonly spread? (Aerosolized virus particles, Large Droplets, Fomites . . . )
  • How long are we infectious?
  • How effective are NPIs like masks, eye-protection, hand-washing, social distancing?
  • How common are asymptomatic infections?
  • Can (and do) asymptomatic carriers spread the virus to others?

As you might imagine, public policy decisions - such as when and how long we close schools, what protective gear we should require for health care workers, and how soon those who have been infected should be allowed to return to work - all hinge on having good answers to the above questions.


In recent years, research (see PLoS One: Influenza Viral Shedding & Asymptomatic Infections, Influenza Transmission, PPEs & `Super Emitters’ & Study: The Role Of Aerosols In The Spread Of Influenza) has shed considerable light on these issues, but the knowledge gained is incremental, and not always in complete agreement.


Today we’ve a major study appearing in The Lancet Respiratory Medicine, that uses  UCL’s FluWatch Study to compile perhaps the most comprehensive multi-year (2006-2011) serological analysis of community influenza we’ve seen to date.


The abstract from Cohort Profile: The Flu Watch Study describes the methodology, which involved 5,484 participants from 2,205 households in England.


Baseline data were collected on demographic, medical, social and behavioural risk factors and pre-season blood samples taken for immunological assays. Households were contacted weekly to report respiratory symptoms throughout the influenza season and asked to collect nasal swabs during respiratory illnesses for testing for a panel of respiratory viruses using PCR. Post-season blood samples, questionnaires and medical records checks were done.


While asymptomatic or sub-clinical infection with the influenza virus is already known to occur with some frequency, this study finds the rate of asymptomatic infection to be higher than commonly suspected.  As many as 75% of those who show serological evidence of infection reported no significant influenza symptoms.


First the Abstract, and link to the open access report (which is well worth reading in its entirety), after which I’ll be back with more.


Comparative community burden and severity of seasonal and pandemic influenza: results of the Flu Watch cohort study

Dr Andrew C Hayward MD a Corresponding AuthorEmail Address, Ellen B Fragaszy MSc a c, Alison Bermingham PhD d, Lili Wang PhD f, Andrew Copas PhD a, W John Edmunds PhD c, Neil Ferguson DPhil h, Nilu Goonetilleke PhD f g, Gabrielle Harvey MPH a, Jana Kovar PhD a, Megan S C Lim PhD a i, Andrew McMichael PhD f, Elizabeth R C Millett MSc a c, Jonathan S Nguyen-Van-Tam DM j, Irwin Nazareth PhD b, Richard Pebody MBChB e, Faiza Tabassum PhD a, John M Watson FRCP e, Fatima B Wurie BSc a, Prof Anne M Johnson MD a †, Maria Zambon PhD d †, on behalf of the Flu Watch Group



Assessment of the effect of influenza on populations, including risk of infection, illness if infected, illness severity, and consultation rates, is essential to inform future control and prevention. We aimed to compare the community burden and severity of seasonal and pandemic influenza across different age groups and study years and gain insight into the extent to which traditional surveillance underestimates this burden.


Using preseason and postseason serology, weekly illness reporting, and RT-PCR identification of influenza from nasal swabs, we tracked the course of seasonal and pandemic influenza over five successive cohorts (England 2006—11; 5448 person-seasons' follow-up). We compared burden and severity of seasonal and pandemic strains. We weighted analyses to the age and regional structure of England to give nationally representative estimates. We compared symptom profiles over the first week of illness for different strains of PCR-confirmed influenza and non-influenza viruses using ordinal logistic regression with symptom severity grade as the outcome variable.


Based on four-fold titre rises in strain-specific serology, on average influenza infected 18% (95% CI 16—22) of unvaccinated people each winter. Of those infected there were 69 respiratory illnesses per 100 person-influenza-seasons compared with 44 per 100 in those not infected with influenza. The age-adjusted attributable rate of illness if infected was 23 illnesses per 100 person-seasons (13—34), suggesting most influenza infections are asymptomatic. 25% (18—35) of all people with serologically confirmed infections had PCR-confirmed disease. 17% (10—26) of people with PCR-confirmed influenza had medically attended illness. These figures did not differ significantly when comparing pandemic with seasonal influenza. Of PCR-confirmed cases, people infected with the 2009 pandemic strain had markedly less severe symptoms than those infected with seasonal H3N2.


Seasonal influenza and the 2009 pandemic strain were characterised by similar high rates of mainly asymptomatic infection with most symptomatic cases self-managing without medical consultation. In the community the 2009 pandemic strain caused milder symptoms than seasonal H3N2.


Medical Research Council and the Wellcome Trust.

The bottom line is that during this five-year study period, just under 20% of the (unvaccinated) study cohort contracted the flu each year, but of those, roughly three-quarters did so without displaying classic influenza symptoms. 


There are limitations to this study, of course, including low participation rates, no data gathered from patients < 5 years of age, self-reporting of symptoms, and difficulty in obtaining a fully representative sample.


Still, the authors report that `Participants were generally highly diligent at completing weekly illness reports and submitting nasal swabs during illness (>85% completion)’.


In a related commentary (see Community studies of influenza: new knowledge, new questions),  Dr Peter William Horby  writes:


"In view of the undoubtedly high rates of subclinical influenza infection, an important unanswered question is the extent to which mild and asymptomatic influenza infections contribute to transmission…A large number of well individuals mixing widely in the community might, even if only mildly infectious, make a substantial contribution to onward transmission."


The question of asymptomatic transmission is an important one, and may well explain the lack of success in interdicting flu carriers at airports and border checkpoints during the 2009 pandemic (see Pathogens At the Gate).  While many nations are quick to set up thermal scanners at entry points, the evidence that they can forestall a virus from entering a country is seriously lacking (see Branswell: Limitations Of Airport Disease Screening).


Similarly, telling people who are sick to stay home during an epidemic (while excellent advice), isn’t a panacea to prevent community transmission if 75% of those infected are unaware of the fact they are infected. 


The good news in all of this is that 75% of people who get the flu don’t get sick enough to notice it.


The bad news is, influenza stealthily infects far more people each year than surveillance would suggest.  And that means that should a highly contagious (and pathogenic) novel virus emerge, controlling its spread may be more challenging than previously envisioned.


For more on the plans to mitigate the spread of influenza during a pandemic, you may wish to revisit:


Pandemic Preparedness: Taking Our Cue From The Experts
NPM13: Pandemic Planning Assumptions
CDC: Updated H7N9 Guidance Docs

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