“Flu can be spread long before symptoms appear,” according to the Daily Mail.
The news reports followed a study aiming to investigate whether someone could pass the flu virus onto others before they themselves have developed any symptoms such as sneezing and a high temperature.
The researchers infected ferrets with a strain of the 2009 H1N1 (swine flu) virus and found that they were able to spread the virus to other ferrets before they developed symptoms. When the researchers housed these pre-symptomatic ferrets with three others, all three became infected. When they housed another three ferrets in neighbouring cages, two of these also became infected, suggesting the virus was spreading via respiratory droplets. The ferrets seemed to be most infectious and had the highest viral levels 24 hours after they had been infected, despite not developing symptoms until a day or so later.
This study has public health implications and is significant for those planning strategies to cope with future flu pandemics. During the previous swine flu pandemic, attempts were made to limit the spread of the virus by screening and then isolating people who appeared to have the symptoms of flu.
While this approach is still valid, the research suggests it may not be enough to stop the spread of any future flu pandemic.
If a more serious strain of flu did emerge, it may be necessary to develop more rapid diagnostic tests that could detect the presence of the virus before the symptoms of flu occurred.
Where did the story come from?
The study was carried out by researchers from Imperial College London and was funded by the Medical Research Council and a grant from the Imperial National Institute for Health Research (NIHR) Biomedical Research Centre.
The study was published in the peer-reviewed medical journal PLOS One.
The media reported this research fairly, although the Mail is incorrect in saying that the researchers called for widespread vaccination, as they did not.
What the lead researcher (Professor Wendy Barclay) did stress is the importance of healthcare workers making sure that their flu vaccinations were up to date. This is because they are more likely to come into close contact with people who are susceptible to developing serious complications if they catch flu, such as:
- the elderly
- pregnant women
- people with weakened immune systems
Implementation of a mass vaccination programme, as described by the Mail, would require extensive consideration of the evidence on the effectiveness, safety, cost-effectiveness and potential benefits.
What kind of research was this?
This was animal research which intended to investigate the infectivity of swine flu and to see when during the course of infection with flu infected animals are able to pass the flu virus onto others.
The researchers said that during the 2009 H1N1 (swine flu) pandemic, various control measures were introduced to try to contain the spread of the virus, such as isolation of individuals who had developed symptoms.
However, these control measures ultimately did not prevent the worldwide spread of the virus. As the researchers said, when devising methods to reduce the spread of a virus within a population it is vital to understand when an individual becomes infected, and how this corresponds with the onset of symptoms.
Animal research such as this is valuable in investigating how viruses can spread between mammals, as this could have significance for how viruses can also spread between humans.
The researchers used ferrets in this study because they are said to be the only animal that develops “human-like” flu-like symptoms after infection, such as fever, coughing and sneezing.
What did the research involve?
The researchers used a strain of the H1N1 virus. Prior to infection, they implanted (under general anaesthetic) a temperature monitor into the abdomen of three ferrets, allowing them to measure the ferrets’ baseline body temperature. They also observed the ferrets for 15-minute periods over the course of a few days to get a baseline idea of how often the ferrets coughed or sneezed. They then infected the ferrets with the flu virus via the nose.
They were interested in whether these ferrets could spread the virus by direct contact and via transmission of respiratory droplets (small droplets of infected mucus that can be spread when someone talks, coughs or sneezes). To investigate direct contact, they housed infected ferrets with non-infected ferrets 24 hours after the ferrets had been infected and before they were symptomatic. To investigate respiratory transmission, they housed other non-infected ferrets in cages adjacent to the infected ones (25mm between cages, allowing direct airflow between the two). To investigate transmission after symptoms had developed they repeated the housing experiments, housing a different set of uninfected ferrets either in the same cage or an adjacent cage to symptomatic ferrets.
The researchers then collected regular nasal washout samples from both the ferrets that they had directly infected with flu and the uninfected ferrets.
What were the basic results?
After the ferrets were infected, the researchers were able to measure flu virus in the nasal washout samples from the first to the sixth day. The peak viral levels were observed about 24 hours after infection. These infected ferrets developed their first symptom of fever about 38 to 40 hours after they were directly infected. Their first respiratory symptom of sneezing didn’t develop until slightly later, and was most pronounced from the fifth day onwards.
The infected ferrets were housed with three non-infected ferrets for a period of 30 hours – between 24 and 54 hours after they were directly infected. Despite the infected ferrets not having respiratory symptoms at the time, all three non-infected ferrets became infected through this direct contact, and their nasal samples became positive for the virus. Of the three ferrets housed adjacently, two of them also became infected, suggesting the virus could also be spread through respiratory droplets even before respiratory symptoms had developed.
When they repeated the tests after the ferrets had developed respiratory symptoms (120 to 150 hours after they had been infected), two of three ferrets housed with them became infected. Conversely none of three ferrets housed in adjacent cages to the symptomatic ferrets became infected.
How did the researchers interpret the results?
The researchers concluded that their findings “have important implications for pandemic planning strategies” and suggested that it would be difficult to contain successfully an influenza virus in humans that spreads efficiently between people before symptoms have developed.
The researchers demonstrated that infected ferrets can spread flu virus to uninfected ferrets both through direct contact and via the respiratory route (in other words, spreading the virus through sneezing or coughing).
They also found that levels of the virus (viral load) were highest during two days following infection, before symptoms had developed. This suggests that humans with the flu may be actually be most contagious before they develop any symptoms (although further research would be needed to confirm or disprove this).
Animal research such as this is valuable in investigating how viruses can spread between mammals, as this could have significance for how viruses can also spread between humans. Humans infected with influenza virus may demonstrate a similar level of infectivity, and this may explain the rapid global transmission of the flu pandemic, which seemed resistant to such containment strategies as isolation of infected individuals. However, as the researchers said, although the ferret model is the best that is currently available to study flu transmission, such a study is limited by small animal numbers and may not be fully representative of what happens in humans.
In particular, as the ferrets in this study had been directly inoculated with viral samples via the nose, this may not be comparable to the viral load or infectivity of humans who have caught flu via the normal airborne transmission of respiratory droplets. Furthermore, the researchers were only looking at the H1N1 (swine flu) strain of the flu virus, so the findings may not apply to other strains.
Nevertheless, this study has public health implications and is of importance for those planning strategies to cope with flu pandemics. During any pandemic, measures are usually taken to try to contain the spread of the virus but these measures may only have limited effectiveness if the virus is already being spread before people are symptomatic.
However, the study’s findings do not necessarily call for everyone to be vaccinated against flu, which the media implies. Currently, vaccination is only recommended for people in high-risk groups for complications, or people who are likely to come into close contact with high-risk groups (doctors, nurses and other healthcare or social-care workers).
Read more about who should get a flu vaccination.
- Roberts KL, Shelton H, Stillwell P, Barclay WS. Transmission of a 2009 H1N1 pandemic influenza virus occurs before fever is detected, in the ferret model. PLoS ONE. Published online August 29 2012