Thursday, August 30, 2012

Pre-Symptomatic Transmission Of H1N1 Influenza In the Ferret Model


Not the only way to spread the Flu - Photo Credit PHIL


# 6524


There are a lot of things we think we know about influenza transmission, but for which we have limited physical proof. Sometimes, the evidence we do have is conflicting, or less than conclusive.


Which helps explains why we continue to see debate and controversy over the value of many protective measures, like hand washing, the wearing of masks, school closures, and screening airline passengers during a pandemic.


One of the assumptions has been that under certain circumstances it may be possible for an infected host to transmit the flu virus before their symptoms appear.


Last year in EID Journal: Pre-Symptomatic Influenza Transmission, we looked at research out of Japan which found evidence suggesting transmission of the 2009 H1N1 virus during a carrier’s presymptomatic phase.


If presymptomatic and asymptomatic carriers of a flu virus are capable of efficiently transmitting the illness on to others, then strategies that seek to identify and isolate symptomatic cases would have only limited success in containing a pandemic.


And we saw indications of these limitations during the 2009 pandemic when nations like Japan, India, and China attempted to identify and isolate those who might be carrying the H1N1 virus as they entered the country.


While their efforts may have slowed the introduction of the virus, they certainly didn’t stop it.  Earlier blogs on these attempts include:


Japan: Quarantine At Ports Ineffective Against Pandemic Flu
Experts: Extreme Measures Won’t Stop The Flu


The assumption is their failure was probably due to the large number of presymptomatic, and asymptomatic carriers of the virus that arrived without showing signs of illness.


All of which serves as prologue to a study, which appeared yesterday in PLoS One, that tests the hypothesis of presymptomatic transmission of the 2009 H1N1 virus using ferrets.


Transmission of a 2009 H1N1 Pandemic Influenza Virus Occurs before Fever Is Detected, in the Ferret Model

Kim L. Roberts, Holly Shelton, Peter Stilwell, Wendy S. Barclay

ABSTRACT (excerpt)

We found that pre-symptomatic influenza transmission occurred via both contact and respiratory droplet exposure before the earliest clinical sign, fever, developed.


Three of 3 animals exposed in direct contact between day 1 and 2 after infection of the donor animals became infected, and 2/3 of the animals exposed at this time period by the RD route acquired the infection, with the third animal becoming seropositive indicating either a low level infection or significant exposure.


Moreover, this efficient transmission did not temporally correlate with respiratory symptoms, such as coughs and sneezes, but rather with the peak viral titre in the nose. Indeed respiratory droplet transmission did not occur late in infection, even though this was when sneezing and coughing were most apparent.


None of the 3 animals exposed at this time by the RD route became infected and these animals remained seronegative at the end of the experiment. These data have important implications for pandemic planning strategies and suggest that successful containment is highly unlikely for a human-adapted influenza virus that transmits efficiently within a population.



Essentially, researchers inoculated ferrets with the 2009 H1N1 flu, and then placed them near uninfected ferrets (some in direct contact, others in adjacent cages) at different stages after infection.


They then tested the exposed ferrets to see when, and under what circumstances, they became infected. They found that ferrets became infectious just 24 hours after becoming infected, and nearly 24 hours before showing the earliest outward signs of infection (fever).


Since limited presymptomatic transmission of influenza has long been suspected, the big surprise here wasn’t confirming that it can occur, but rather, how robust this form of transmission turned out to be.


Influenza is believed to be transmitted via large droplets – usually expelled by coughing and sneezing - along with smaller aerosolized virus particles, plus contaminated surfaces (fomites) where airborne droplets may land or we may otherwise touch and contaminate.


Today’s study strongly suggests (with ferrets, anyway) that simply breathing in and out can shed sufficient flu virus into the air to spread to others, without the added `boost’ provided by coughs and sneezes.


Indeed, the only transmission these researchers observed occurred early in the infection, before the symptoms of coughing and sneezing appeared.


This suggests that those who may be symptomatic, but 5 or 6 days into their illness, may be far less likely to transmit the virus to others. 


The caveats with this research include that this study was conducted on ferrets, not humans, and with a single flu strain. Other experiments have shown variations in transmission traits depending on the strain tested.


As I wrote in They Walk Among Us, back during the pandemic in 2009:


Like it or not, there is no easy litmus test for infection (and viral shedding) when it comes to influenza.   The array of symptoms (or lack thereof) displayed by those infected with the H1N1 virus preclude any kind of 100% accurate `checklist for infection’.


Sure, we could lock up everyone who sneezes, coughs, or spikes a fever for 2-weeks.  But even that wouldn’t catch those who are shedding the virus before developing symptoms, or those who remain asymptomatic for the full course of their illness.


While the advice to `stay home if you are sick’ remains valid, the truth is, you don’t have to be visibly ill in order to pass the flu virus on to others.


These findings will likely fuel the debate over the need for Health Care Workers -- and others who have direct contact with vulnerable populations - to get the annual flu vaccination. 


If we can be infectious without knowing it, then we cannot simply say we will stay home or wear a mask when we are sick, in order to protect others.


For more on asymptomatic respiratory illnesses, you may wish to revisit:


The Very Common Cold
EID Journal: Airport Screening For Pandemic Flu In New Zealand
PLoS One: H1N1 Seroprevalence Study
ICEID: Asymptomatic H1N1 in HCWs

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