New bird flu strain ‘should not be underestimated’ – experts respond

A new strain of bird flu, avian influenza A H10N8, was responsible for the death of a 73-year-old woman in Nanchang, say Chinese scientists.

An analysis of the infection and virus, published today in the Lancet, notes the new strain is distinct from previously reported H10N8 viruses, and appears to be able to replicate efficiently in humans.

Although China has previously detected H10N8 in wild and domestic birds, this is the first ever report of H10N8 isolated from a patient.

The woman, from Nanchang City in China, presented to hospital with fever and severe pneumonia on November 30, 2013. Despite antibiotic and antiviral treatment she deteriorated rapidly, developed multiple organ failure, and died 9 days after illness onset.

In an accompanying media release, co-author Dr Mingbin Liu from Nanchang City Center for Disease Control and Prevention warns hat that the pandemic potential of this novel virus should not be underestimated, “A second case of H10N8 was identified in Jiangxi Province, China on January 26, 2014. This is of great concern because it reveals that the H10N8 virus has continued to circulate and may cause more human infections in future.”

The WHO is currently monitoring H10N8 developments.

Our colleagues at the UK SMC collected the following expert commentary.

Dr Jeremy Farrar, Director of the Wellcome Trust, said:

“We should always be worried when viruses cross the species barrier from birds or animals to humans as it is very unlikely that we will have prior immunity to protect us. We should be especially worried when those viruses show characteristics that suggest they have the capacity to replicate easily or to be virulent or resistant to drugs. This virus ticks several of these boxes and therefore is a cause for concern.

“We are now much better at surveillance and at sharing information on emerging infections. It is highly unlikely this event would even have been noticed or reported just a few years ago.  But we need to work out how we deal with this new information. There are still major questions about what works to mitigate the consequences of the emergence of a new infection whether through public health interventions, treatment or vaccines.  We also cannot say how common it was for a virus to jump the species barrier in the ‘pre-surveillance’ era, which makes it difficult to put this latest information in context and we do not understand what causes pathogens to cross into humans, cause disease and become transmissible.  As a result we cannot judge how worrying an individual event is and therefore have to worry about them all.”

Dr Ben Neuman, Virologist, University of Reading, said:

“This fatal case of the flu is a personal tragedy for the family and friends of the victim.  While the H10N8 virus bears watching, there is no cause for alarm at this time.  The patient will have had contact with tens or hundreds of friends, family, acquaintances and health care workers before the severity of the disease was apparent.  As yet there are no reports that the virus has spread to anyone else.  H10N8 fits the profile of an avian flu virus in that the disease is terrible, but the virus is not readily transmitted.

“H10N8 avian flu viruses exist in a very competitive world.  They battle the elements, the immune system, and even other flu viruses every day in order to survive.  The survivors are exquisitely adapted to their bird hosts, which usually means that they are not very well suited to growing in people.

“The new H10N8 is reported to have some mutations that have been linked to more severe disease in other flu viruses.  However, talking about mutations only makes sense if the context is right.  Imagine the virus is a car, and the mutation is a jet engine.  It sounds like combining the two should give you a really fast car, but in reality, if that engine is not bolted down, or is pointing in anything other than the perfect direction, you would end up with a fiery disaster instead of a jet-car.

“The flu virus is a complex biological machine, and it is difficult to predict how well all the gears will mesh, or what effect it will have on a host.”

Dr Linda Klavinskis, Senior Lecturer in Immunobiology at King’s College London, said:

“The available data does not indicate any evidence of human to human transmission of this H10N8 virus and it is not currently associated with any apparent disease in poultry. Based on this, the current H10N8 virus does not currently appear to be a major threat – the fatality was in a person who had many chronic illnesses and was immunocompromised, so it is possible it could be an accidental bird to human case.

“However, avian influenza A viruses can evolve which differ markedly in their surface structures (Hemagglutinin) that allows these viruses to adapt. This enables them to bind (latch onto) receptors on human cells (which may occur in association with other subtle mutations) and subsequently cause human infection. This emphasises the need to develop ‘universal’ influenza A vaccines that overcome the short comings of current vaccines that are only effective when exactly matched with the seasonal strain of influenza A that is circulating, but may be ineffective against newly emerging viruses. Vaccines that provide ‘universal’ and long-lasting immune responses against the internal components of the virus, common across current and future influenza A viruses, may be a game-changer in the future and something we are working towards.”

Dr John McCauley, Director of the WHO Collaborating Centre for Influenza, MRC National Institute for Medical Research (NIMR), said:

“The potential epidemiological significance of this zoonotic infection is not clear. Avian influenza viruses of the sub-type H10N8 are probably not particularly unusual. Whether there were complications in this case is unclear.

“This case reminds us to be aware of human infections from animal influenza viruses, like the H7N9 cases in China which increase daily. Previously we did not think that H7N9 infections might be so lethal. Now we also must consider H10N8 infections as well.”

“The risk of this virus spreading from the patient to nursing staff and other contacts seems low since the H10N8 virus is not expected to be transmitted well between humans.

“More human infections by avian H10N8 viruses cannot be ruled out. H10N8 viruses are of low pathogenicity in poultry and so infection in birds is not easy to detect. Whether humans are frequently exposed and infected is also not known. Human serological studies might well be able to determine this and are very likely to be ongoing in the region. It seems likely that the underlying conditions of the patient exacerbated the infection.”

Dr Steven Riley, Reader in Infectious Disease Ecology and Epidemiology, Imperial College London, said:

“Although many more people are tested for influenza now than before, this first case of H10N8 is still a significant event. Six of the 8 genes share a common recent history with the H7N9. Therefore it looks like these 6 genes are especially successful in poultry and able to swap out the other 2 genes. The concern is that the “internal” 6 may find a combination of the external two genes – the H and the N – that would allow efficient transmission in humans. However, it is virtually impossible to quantify that increased risk based on current evidence.”

Background information from Prof Wendy Barclay, Chair in Influenza Virology, Imperial College London:

Influenza viruses that infect and circulate in humans as seasonal flu viruses come in 4 ‘flavours’, as defined by the names of numbers given to their major antigens, the parts of the virus our immune system sees. If you catch flu this winter you could be infected by an H3N2 virus, an H1N1 strain, or either of two different influenza type B viruses. Because we can’t predict which one you will get, the vaccine we give to those people at risk from a bad outcome from seasonal flu is quadrivalent – in other words it’s a mixture of vaccines to protect you against all 4 of those possibilities.

Out there in nature in ducks, geese, domestic poultry and pigs, there are other flavours of influenza A virus that we don’t have vaccines against and which rarely infect people. These are numbered or grouped to indicate how related to each other are HA and the NA proteins such as H5N1, H7N9, or H10N8. Viruses with different HA numbers are completely unrelated and vaccination against or previous infection by one will not protect you against another. When we occasionally see humans being infected with these viruses, we get worried because we have no vaccines against them and the human population has no pre-existing immunity to them either, so everyone is highly susceptible. Luckily for us most of the time these zoonotic infections are dead ends because although the first exposed person gets ill, they do not pass on the virus to another human… transmission is too inefficient to sustain an outbreak or a new pandemic. Pandemics only occur if these viruses undergo mutations that allow them to interact better with human cells and survive longer in order to be transmitted through the air.

The most notorious of all the avian influenza viruses is the H5N1 bird flu because it is very widespread and numerous and since 2003 has infected more than 684 people often with very severe outcome or death. This virus has a particular type of HA protein with a multibasic cleavage site that allows it to replicate outside of the respiratory tract in birds and also in humans, conferring what is termed High Pathogenicity. In recent years it seems as if we hear about people being infected by avian influenza viruses more often but this may well be because of the heightened surveillance for these events that is a result of the worry that a virus like H5N1 could mutate to become transmissible between humans and spark a very severe pandemic.

In Spring 2013 another worrying avian influenza virus emerged in Shanghai and is now spread quite widely in China in chickens. Unlike the H5N1 virus, H7N9 does not have the multibasic cleavage site in its HA protein, so it does not kill chickens. This is actually quite a problem because it makes it difficult to know where the virus is. (But note! H7 viruses are the other influenza A virus subtype that can mutate and acquire this motif so H7N9 could in time become more pathogenic to chickens than it currently is.) Meanwhile the virus has infected more than 250 people and killed around 70 of them. Genetically speaking the virus has some changes that look like it’s a little more able to infect humans than the ‘typical’ avian influenza virus; for example the site on the HA protein that binds to the cell surface receptor has one of the two key mutations seen in human adapted viruses, although experiments have shown that the virus does not yet bind to cells like a human virus would.

The latest new comer to this stage is the H10N8 virus that has infected two people in China after they were exposed to infected chickens. The Lancet paper describes this new virus in detail and also reports the fatal outcome of the 73 year old woman who was infected. It is not clear how serious the virus would be in a young healthy person. The sequence details given in the paper are quite reassuring: there is no obvious clue that the virus is specially adapted to humans; one of the most important things to look at is the receptor binding specificity of the HA protein which is clearly reported as avian-virus like. There is a human adapting mutation present in the polymerase enzyme of the H10N8 virus, PB2 E627K, which has also been seen in many of the H7N9 and H5N1 bird flus that have infected people. The evidence in the Lancet paper suggests this mutation was selected for in the infected person as the virus tried to replicate in human cells. This mutation is probably required but not sufficient to transform these avian influenza viruses into pandemics.

It is worth noting that these three avian influenza viruses are not the only ones out there being picked up; an H6N1 virus infected a woman in Taiwan last year, and H9N2 viruses have occasionally also infected people in recent years.