H7N9 analyses hint at genetic mutations, drug resistance

In the latest H7N9 avian influenza developments, analysis of virus samples from China and Taiwan hint at mutations including resistance to the antiviral class of drugs known as neuraminidase inhibitors, and the World Health Organization (WHO) said today that the burgeoning number of cases this season now account for a third of all cases reported since the outbreak began in 2013.

Also, local officials reported three new cases in three Chinese provinces, signaling ongoing virus activity.

Scientists track pathogenicity, resistance mutations

Yesterday, Guangdong province's Center for Disease Control (Guangdong CDC) announced that two virus samples collected from humans show mutations that suggest H7N9 may be becoming more pathogenic in birds, according to an official statement translated and posted by Avian Flu Diary (AFD), an infectious disease news blog.

Authorities said an analysis of four samples from poultry in Guangdong province by agriculture colleagues had found similar changes in the virus and that the two groups would work together to monitor the virus.

H7N9 has been a low-pathogenic virus in poultry, which has made it difficult to track. Often, the virus isn't found in local poultry flocks until human illnesses in the area have been reported.

In a related development, Taiwan's CDC today, in an analysis of H7N9 from in imported case in January, found similar protein changes in the hemagglutinin (HA) protein that may make the virus more pathogenic in poultry, but it also said it found a mutation in the neuraminidase (NA) protein that may suggest resistance to antivirals such as oseltamivir (Tamiflu) and zanamivir (Relenza), which are neuraminidase inhibitors.

The statement from Taiwan CDC, also translated and posted by AFD, said the patient is a 69-year-old man from Guangdong province who is still hospitalized in critical condition. Officials said the mutation seen in an H7N9 sample from the man may have been a spontaneous mutation that occurred while he was undergoing treatment.

Hong Kong's Centre for Health Protection (CHP) in a statement today acknowledged the genetic findings announced by Guangdong CDC and said it will continue to monitor virus activity, but so far its analysis of viruses from its recent imported H7N9 cases from the mainland have not found any significant changes or any sign of resistance to oseltamivir.

A Feb 10 update from the WHO said an analysis of 83 H7N9 samples collected since Oct 1 from the current fifth wave of infections found no evidence of changes that would make the virus more virulent or more adapted to mammals. The group, however, noted three contained mutations in the NA protein that suggested reduced sensitivity to neuraminidase inhibitors.

The WHO added that testing is under way to assess in vitro susceptibility to the drugs.

WHO update notes two new clusters

In its update today, the WHO said China notified it of 304 more cases between Jan 19 and Feb 14, bringing the total during this wave to at least 418, similar to the total reported last week in the latest update from Hong Kong. Though similar sudden increases have been seen in past seasons, the recent surge exceeds those of previous years and now accounts for one third of all human cases since H7N9's first detection in humans in early 2013.

So far epidemiologic and virologic evidence doesn't suggest that H7N9 has acquired the ability to spread more easily in humans, but the situation needs close monitoring, the agency said. It warned that more human cases are expected, given ongoing detection in poultry and their environments, and that sporadic cases could continue in previously unaffected areas of China, because of the silent circulation of the low-pathogenic virus in birds.

The most recent cases reported to the WHO are from 18 of China's provinces. The most-affected ones are Jiangsu, Zhejiang, Guangdong, Anhui, Jiangxi, Hunan, Fujian, and Hubei. For patients with known clinical presentations, two had mild symptoms, 82 had pneumonia (48 classified as severe), and 36 died.

Of the 304 patients, 144 (47%) had been exposed to poultry or live-poultry markets. Eleven had no clear exposure, and investigations are still under way for 149.

The WHO noted two clusters among the cases: a 22-year-old mother who took care of her 3-year-old daughter while the child was sick (both had been exposed to poultry) and a 43-year-old woman who took care of her 45-year-old sister while she was sick. Both of the women had likewise been exposed to poultry.

"While common exposure to poultry is likely, human-to-human transmission cannot be ruled out," the WHO said of the clusters.

New cases in 3 provinces

The newest cases reported from China were noted in today's CHP update and include patients in three different provinces.

One is a 45-year-old individual from Guizhou in the southwest who is being treated in Qiandongnan. In addition, Guangxi province in southern China reported a fatal infection in a 41-year-old woman in Nanning who worked as a poultry seller in a live market before she became ill. The third patient is a 48-year-old woman in Shandong province in the east.

So far China has reported at least 422 cases in the fifth wave of H7N9 activity. Also, Hong Kong, Macao, and Taiwan have reported a spate of cases imported from the mainland. The WHO today said the global total based on reports received since 2013 is 1,222 lab-confirmed cases.

See also:

Feb 19 AFD post on Guangdong CDC statement

Feb 20 AFD post on Taiwan CDC statement

Feb 20 Hong Kong CHP report

Feb 10 WHO update

Feb 20 WHO update

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