Science – As flu season bears down, the world is warily eyeing China. A novel H7N9 avian flu strain emerged here in March, infecting at least 135 people and killing 45 before petering out in the summer. Now it is back, with four human cases in southern China in the past month. More cases are a certainty, and researchers, public health experts, and vaccinemakers are preparing for the remote but real possibility that H7N9 will explode into a pandemic.
For now, the signs are reassuring. Sustained human-to-human transmission would be needed for H7N9 to cause widespread illness. But so far, there have been only a handful of possible instances of people infecting each other. In 70% of cases, victims are believed to have picked up the virus directly from live poultry, says Masato Tashiro, head of a World Health Organization (WHO) flu collaborating center in Tokyo. H7N9 is “still looking for ways to adapt well to humans,” says George Gao, deputy director-general of the Chinese Center for Disease Control and Prevention (China CDC).
Disturbingly, however, the signatures of the H7N9 strains isolated from the four new cases show that the virus is evolving rapidly. Les Sims, an animal disease consultant in Palm Grove, Australia, says that H7N9 appears to be swapping genes with other avian flu strains in poultry, adding additional genetic variation to the naturally high mutation rate of any flu virus.
For researchers watching the virus’s genetic moves, Tashiro says, “the most important question” is which mutations would enable the virus to spread in people’s coughs and sneezes, like seasonal flu. Virologist Ron Fouchier at Erasmus MC in Rotterdam, the Netherlands, and others authored a letter that appeared online in Science on 7 August advocating a way to find out: gain-of-function studies that would give H7N9 the genetic wherewithal to spread through the air, in a secure facility. Many scientists oppose creation of such a strain, which might set off a pandemic if it were released. Fouchier says he has not embarked on an H7N9 gain-of-function study.
In the meantime, China is girding for an eventful winter. China CDC researchers have given staff members at nearly 1000 hospitals and labs a crash course in how to detect the virus in patients. Respiratory samples are collected daily from hospitals and tested for H7N9, says Shu Yuelong, director of the Chinese National Influenza Center here.
A far tougher task is tracing H7N9’s movements in the environment. “What has been lacking is an understanding of exactly where this virus is in the poultry sector,” says Malik Peiris, a virologist at the University of Hong Kong’s School of Public Health. The virus causes no discernible symptoms in poultry, making infections difficult to spot. Another puzzle is why so few birds test positive for the virus. China’s National Avian Influenza Reference Laboratory in Harbin had only a handful of positive hits in some 84,000 poultry samples it collected this spring (Science, 26 April, p. 414). “Biologically, that’s really difficult to explain,” Peiris says.
Scientists are divided on whether China should permanently shutter its live poultry markets. Doing so is clearly effective: In four cities that temporarily closed markets in spring—Shanghai, Hangzhou, Huzhou, and Nanjing—human H7N9 cases were effectively snuffed out, according to a report last month in The Lancet. But Chinese consumers generally shun packaged meat. In the absence of a pandemic, they would never accept permanent closure, Gao says: “You cannot change culture.” He favors closing markets a day or two a week for disinfection.
One intriguing possibility may not require China to kick its live poultry habit. H7N9 may be hiding out in a particular species kept in smaller numbers in the markets, such as quail. Six of H7N9’s eight gene segments—what Peiris calls its “genetic engine”—are derived from another family of bird flu viruses, H9N2. Some H9N2 strains that bind well to human receptors have been detected in quail, Fouchier says. He notes that so far, few quail from China’s poultry markets have been tested for H7N9. If H7N9 turns out to be a quail virus, it could be spreading from a small number of poultry holdings or a small area of China, offering hope that “the virus can still be eradicated at the original source,” Fouchier says.
If eradication fails and H7N9 does mutate into a pandemic strain, health officials hope a vaccine will be ready to ward off disaster. Labs in the WHO network now have six H7N9 seed stocks—a version of the virus that can be grown in large quantities as the basis for a vaccine. Chinese labs are awaiting approval for clinical trials; meanwhile, some Japanese drug manufacturers have begun clinical trials.
European and U.S. researchers are further along. Novartis, based in Switzerland, has announced that 85% of 400 adults enrolled in a clinical trial of an H7N9 vaccine candidate showed some protective immune response. In September, the U.S. National Institutes of Health launched clinical trials of another vaccine candidate. And earlier this month, Novavax, a Maryland-based company, published encouraging results from an H7N9 vaccine clinical trial online in The New England Journal of Medicine. “We don’t know if a vaccine will be necessary,” Tashiro says. Everyone would prefer that it isn’t.Source and Photo: Science, November 29, 2013 Labex Korea on Twitter and Facebook