The paper, published in the British Medical Journal, is a case study investigating the apparent transmission of the disease from a father to his daughter, both of whom have since died. It is the first case study of its kind.
“There is great cause for concern in that this is such a lethal form of influenza, we’ve hardly seen anything more lethal”
Peter Openshaw Director of the Centre for Respiratory Infection at Imperial College London, Director of the Centre for Respiratory Infection at Imperial College London.
Although the news will be met with concern in China, where 132 cases have been recorded on the mainland since its outbreak in March across 40 cities, resulting in 43 deaths, it is an incredibly rare instance. It has aways been suspected that other bird influenzas have been passed from human to human on rare occassions. However, as with this rare recorded and researched case, those instances tended to be among genetically related family members, suggesting that those involved have pre-disposed vulnerabilities.
The World Health Organisation issued warnings early this year to the effect that H7N9 is one of the most lethal forms of the bird flu virus, as it appeared to be transmitted far more easily than even the deadly H5N1 virus. “So far it’s been very reassuring not to have signs of human to human transmission, and this is the first well documented case. But we need to appreciate this was a transmission to a blood relative within a family.”
The first cases of H7N9 were reported in early March. Advanced cases present with symptoms including severe pneumonia and acute respiratory distress syndrome. It was not until the end of April, more than a month after the outbreak, and 23 deaths later, that the apparent cause of the disease was detected. It had been traced back to live poultry farms in the east, in particular hubs at Zhejiang along the coast.
The H7 was thought to have derived from domestic ducks in the province, and the N5 from wild birds in South Korea. It was after visiting a live poultry farm that the first patient in the new study fell ill in March this year. He had visited the markets regularly, and had also bought six quails that had already been slaughtered by a vendor a week before falling ill. By contrast, the 60-year-old’s daughter had not — as far as anyone involved in the study knows — had any contact with live poultry, aside from two black swans owned by an employee of her property’s management team. Those swans were swabbed, however, and no sign of the virus showed up in samples.
The daughter cared for her father on and off throughout his illness, which was initially not diagnosed as bird flu. In the early stages of his illness she cared for him at home, but also routinely visited him in hospital once admitted. The father, who had a history of hypertension, fell ill on 8 March and deteriortated rapidly from the 18 March. It was on 21 March that the daughter, who had no underlying health issues, fell ill. Multiple courses of antibiotics did not thwart the disease, and she died of multi-organ failure and cardiac arrest on 24 April 2013.
Although the study’s authors admit there’s no way of knowing whether the daughter did in fact have some other contact with poultry (both patients had died by the time the investigation began), they believe the genetic evidence is enough to confirm the transmission from father to daughter.
“Sequence analysis showed that both possessed high degrees of similarity between nucleotide (99.6 percent to 99.9 percent) and amino acid (99.0 percent and 100 percent) sequences,” write the authors. The only other person to provide beside care for the father was his son-in-law (who did not fall ill), along with the doctors and nurses that would have attended to him — further circumstantial evidence suggesting it’s the genetics that’s the key to the human to human transmission. In total 39 hospital workers came into contact with the pair, and none fell ill.
“We know that there are genetic factors that contribute to human to human transmission,” according to Openshaw. “Some people are much more susceptible to flu than others, and that’s the reason it’s such a devastating disease. It’s shared genetic factors that makes people vulnerable.”
Going forward, Openshaw says the public has to realise that although cases of human to human transmission are rare, we should be abiding by standard safety measures stringently, as though infection were a real possibility.
“In hospital when you know someone has it, all precautions are taken in order to protect staff, but actually it’s very rare among most strains for transmission to happen. It’s the reason Sars became so deadly — it transmitted very well to healthcare staff, and other patients.” Openshaw recommends never dropping any kind of safety measures. For instance, some healthcare workers will just wear a mask, and not gloves, or scrubs but not a mask. “Relatives will be caring for their sick and elderly and although absolute protection is very hard to guarantee, we should never drop any measures.”
Openshaw did commend China for managing to curb the spread of the disease quite effectively, after closing a series of poultry markets.
“The Chinese are really good at doing things properly in a way that’s hard to achieve in perhaps more liberal countries, and that should be admired. Whether it comes back again when the season returns is the question. People are holding their breath to see if it truly went away or it’s just a pause, because we know a lot of flu is quite seasonal.”
When it comes to protecting future generations from human to human transmission, Openshaw says we need to be doing more to identify the underlying genetic causes that make some people more vulnerable to infection than others.
“We need to show how much variations in the virus contribute, and how much variations in the human host contribute.” Openshaw is currently working with 45 research groups based in the UK and abroad to find the answer. Eight thousand samples have been gathered from patients hospitalised due to severe flu in London and Liverpool, and the team has just begun to trawl through that data to look for recurring patterns.
A past study published in Nature, of which Openshaw was an author, found that those with the gene IFITM3 and the protein used to encode it, were more likely to be hospitalised because of flu.
“It’s a major risk factor in our hospital study, and that finding has been replicated in Southeast Asia where it’s quite normal to see big variations in IFITM3 — among Han Chinese it’s about 25 percent, and among Japanese there is a variation of up to 40 percent.”
Openshaw says he and his team have a list of around 20 genes that appear to be associated with flu vulnerability, and he hopes to have the opportunity to further investigate samples from the father and daughter, who were not tested for IFITM3.