H7N9 Human Infection of 'Public Health Significance'

Troy Brown

April 12, 2013

A novel avian-origin influenza A (H7N9) virus circulating in China appears to be more virulent than previously observed influenza A subtype H7 viruses, according to an analysis of clinical, epidemiologic, and virologic data from 3 patients who died in March after becoming infected with the H7N9 virus.

Rongbao Gao, MD, from the National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention in China and colleagues report their findings online April 11 in the New England Journal of Medicine .

As of today, the World Health Organization reports that H7N9 has been confirmed in 43 patients and 11 have died.

The Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, received a specimen of the H7N9 virus from China yesterday. On April 9, the CDC activated the Emergency Operation Center (EOC) at Level 2 (there are 3 levels, with 1 as the highest) to support the management of the emerging H7N9 situation, Sharon KD Hoskins, MPH, senior press officer at the CDC told Medscape Medical News in an email.

Researchers used real-time reverse-transcriptase-polymerase-chain-reaction assays, viral culturing, and sequence analyses to test the patients' respiratory specimens for influenza and other respiratory viruses.

Infection of poultry with influenza A subtype H7 viruses is widespread, but this subtype has not been observed in humans in Asia before now. Previously, most human infections with highly pathogenic avian influenza (HPAI) A (H7) viruses have resulted in mild illness. Transmission of H7 viruses to mammals is rare in Asia, and human infection with N9 subtype viruses has never been documented anywhere.

Fever and cough were the most common symptoms in the 3 patients, all of whom had acute respiratory distress syndrome. Their conditions deteriorated rapidly after the onset of symptoms.

One patient had no known exposure to birds in the 2 weeks before becoming ill, 1 patient worked in a market where live birds were sold but had no contact with birds (he was a butcher of pigs), and the third patient visited a chicken market 1 week before becoming ill.

Genetic sequence data indicate that the H7N9 virus may bind more easily to human receptors than avian receptors and that the virus may also be transmitted by air.

"Currently there is no vaccine available for these novel viruses, and it is not known whether the current candidate H7 vaccine viruses, of which three are North American viruses and the other three are avian viruses from 2000 in the Netherlands, may be effective," the authors write.

Diagnostic tests for the novel reassortant H7N9 viruses have been developed based on these data. The specific sequences can be found on the website of the World Health Organization (www.who.int/influenza/gisrs_laboratory/a_h7n9/en/).

'Public Health Significance'

In an accompanying perspective, Timothy M. Uyeki, MD, MPH, MPP, and Nancy J. Cox, PhD, from the Influenza Division, National Center for Immunization and Respiratory Diseases at the CDC, commented on the article, noting that this outbreak "is of major public health significance."

"The hemagglutinin (HA) sequence data suggest that these H7N9 viruses are a low-pathogenic avian influenza A virus and that infection of wild birds and domestic poultry would therefore result in asymptomatic or mild avian disease, potentially leading to a 'silent' widespread epizootic in China and neighboring countries," Drs. Uyeki and Cox write. The HPAI H5N1 virus usually causes rapid death in infected chickens.

Researchers believe the animal reservoir is birds, but many experts wonder whether the virus might also infect pigs, "another common reservoir for zoonotic infections," they write.

The viral sequence data also suggest antiviral resistance to the adamantanes and susceptibility to neuraminidase inhibitors, and continued surveillance is needed to determine if this is significant. Oral oseltamivir or inhaled zanamivir should be given to patients with suspected or confirmed H7N9 as soon as possible, Drs. Uyeki and Cox write.

Clinicians should be alert to the development of secondary bacterial infections and treat with antibiotics as appropriate, they write.

"The coming weeks will reveal whether the epidemiology reflects only a widespread zoonosis, whether an H7N9 pandemic is beginning, or something in between," Drs. Uyeki and Cox conclude.

The institutions of 15 authors (including Rongbao Gao) received grant funding from the National Basic Research Program (973) of China. One author's institution received a grant from the National Natural Science Foundation of China.

Dr. Uyeki and Dr. Cox have disclosed no relevant financial relationships.