Why are some more vulnerable to bird flu than others?

New findings show why some groups in the population are at particular risk. Elizabeth Finkel reports.

A breeder in Zhejiang province in China despairs over a threatened cull of his chickens, which he insists are not infected with the H7N9 virus. – Reuters/William Hong

The next deadly flu pandemic is not a question of if, but when. We’ve already had a few close calls with killer bird flu and now an increase in cases in China is causing concerns ahead of Chinese New Year. One of the great puzzles, though, is the way it picks its victims. Rather than targeting the elderly and infirm as seasonal influenza does, the young have been most vulnerable. Alaskan and Aboriginal communities have fared particularly badly. Now thanks to research from an international collaboration, we stand a better chance of protecting those at risk when the big one comes.

In two papers published in the Proceedings of the National Academy of Science in December and January, researchers identify two genes that predict the severity of illness as a result of infection with a deadly new bird flu virus called H7N9. According to immunologist Katherine Kedzierska, leader of the University of Melbourne team, the same genes also predict vulnerability to other varieties of flu, including the swine flu virus (HIN1) responsible for 150, 000 to 500,000 deaths in the 2009 pandemic, in which 80% of its victims were younger than 65 – more than half them in Africa and Southeast Asia.

As the world braces for the next onslaught, “these new findings are very important in helping us tease out which groups in the population are at particular risk, and may be in need of tailored interventions”, says Jodie McVernon, an epidemiologist at the Melbourne School of Population and Global Health.

H7N9 was first detected in February 2013 in China’s Eastern provinces along the Yangtze River delta where migrating birds cluster. It was worrying. Its first victims were typically older men, retired husbands who went out shopping for their wives at the live bird markets, says immunologist and Nobel laureate Peter Doherty, a member of the University of Melbourne team. Mortality was very high at more than 30%. Patients died from pneumonia and haemorrhaging likely caused by a “cytokine storm”, a case of extreme collateral damage as the body releases these potent chemicals to fight the virus. The number of cases soared to 137 in the space of a few months with 45 deaths. The saving grace is that so far the virus has not mutated to a pandemic form – one which can transfer directly from human to human. But “it looks like it’s close”, says Doherty, basing his judgement on the analysis of the DNA sequence.

Testing for bird flu in Huaibei, China in April 2013. The problem is that some birds do not show much in the way of symptoms.

Authorities in Shanghai responded aggressively, culling sick birds but the problem is that some birds do not show much in the way of symptoms following H7N9 infection.

For all these reasons H7N9 set alarm bells ringing. It also galvanised a collaboration involving researchers in China, Australia, America, Singapore and the UK. A key goal was to try and understand why some people are able to fight the virus successfully while others cannot, crucial information in a pandemic where medications and hospital intensive care units run short. It could also lead to the design of new flu drugs.

The research has yielded two stunning findings.

The December report studied 18 patients in hospital who were seriously affected by the H7N9 virus. Those patients who suffered the worst cytokine storm were more likely to carry two defective copies of a gene called IFITM3. The working gene is known to help limit the multiplication of the virus.

Meanwhile research reported in January examined the pre-existing immunity people had to the virus. Mostly it came from their killer T-cells. Killer T-cells search out and destroy other cells that have been infected by the virus. To successfully do their job, they have to discriminate between infected and uninfected cells. And that relies on a “uniform” worn by every cell which displays bits of virus as if they were war medals. The uniform is made of HLA genes and some genes do a better job of displaying the virus to the killer T-cells than others. The researchers found that 57% of Caucasians and about 37% of Asian and Africans carried a protective set of HLA uniform genes. But among Alaskan natives and Australian aborigines, only 16% carried the protective uniform.

This helps explain why these communities are so susceptible to bird flu. In the 1918 pandemic, entire Alaskan villages were wiped out, while the mortality rate of Australian aboriginals was 20% higher than the European population. In the 2009 Swine flu epidemic (the virus H1N1 is actually a type of bird flu) members of aboriginal communities were also disproportionally affected, accounting for 16% of those admitted to hospital in Australia.

Kedzierska and Doherty speculate that knowing the gene profiles of patients could be extremely valuable for triaging patients in the event of the next bird flu pandemic. The new research comes not a moment too soon. While H7N9 appears to be gaining momentum once again in China, reports last week show that swine flu is also re-emerging in California, with the toll suddenly spiking to 45 confirmed deaths in adults under 65. For now authorities are recommending vaccination, frequent hand-washing and to stay away from people who are ill.

  1. http://www.fao.org/news/story/en/item/212599/icode/
  2. http://www.pnas.org/content/early/2013/12/17/1321748111.abstract
  3. http://www.pnas.org/content/early/2014/01/03/1322229111.abstract
  4. http://www.cdc.gov/flu/spotlights/pandemic-global-estimates.htm
  5. http://www.sfgate.com/health/article/Deaths-from-influenza-outbreak-shoot-up-in-5153695.php
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