Though no new novel H7N9 avian flu cases have been reported since the end of May, response and preparedness activities are under way, with the World Health Organization (WHO) updating its risk assessment and US officials issuing and tweaking guidance documents.

The most recent H7N9 case was reported on May 29 and had an illness onset of May 21, the WHO said in its latest update on flu at the human-animal interface. The patient appears to be a boy from Beijing whose infection was detected during surveillance activities. So far the global total stands at 132 infections, including 37 deaths.

In the WHO´s updated H7N9 risk assessment today, the first since May 10, the agency said it has not changed its assessment of the threat, but it added new information based on the latest developments and medical literature reports.

The WHO said evidence continues to build that the human infections are related to live poultry and their environments, though investigations are ongoing to answer questions about the main exposures and routes of infections. Also, other possible reservoirs such as wild birds or mammals have not been identified, the group said.

Four small human clusters have been reported in the outbreak suggesting limited human-to-human spread, but so far there is no evidence of sustained human-to-human transmission, the WHO said.

H7N9 infections have been severe in many patients, and so far there don´t appear to be large numbers of milder cases. Testing of more than 20,000 people in China for flulike illness in March and April detected only six H7N9 infections, the WHO said.

It´s unclear if H7N9 will show the warm-weather drop-off in activity seen with H5N1 cases. Sporadic infections are likely to occur in affected and possibly neighboring areas. So far there is no indication of international spread, but if the transmissibility of the H7N9 virus increased, the possibility of further geographic spread would also rise, according to the WHO.

Genetic changes seen among H7N9 viruses suggest adaptation to mammals, and further adaptation could occur, which the WHO said is concerning. It urged countries to continue surveillance and preparedness activities.

CDC documents
Meanwhile, the US Centers for Disease Control and Prevention (CDC) yesterday released an assessment for labs of the risk of working with the H7N9 virus as well as handling recommendations. Labs in the United States and other countries are conducting experiments with the virus to learn more about its features, such as pathogenicity, origin, and whether antivirals are useful for treating human infections.

The virulence and transmissibility of the virus are under investigation, the CDC said. The potential for H7N9 aerosol spread and its ability to remain viable for extended periods in dry and liquid forms suggest proper safeguards should be in place to protect lab workers and the environment, according the assessment.

So far H7 vaccines have shown to be poorly immunogenic, and there´s not enough information to gauge the effects of antivirals.

So far the US Department of Health and Human Services hasn´t determined if it will propose that the H7N9 virus be regulated as a select agent, and so far it is classified as a low-pathogenic avian influenza strain and isn´t subject to US Department of Agriculture (USDA) select agent requirements. However, labs must obtain USDA and CDC permits to import and ship the virus.

In vitro work with H7N9 should be conducted in biosafety level 3 (BSL-3) laboratories, and animal work with the virus should be done in an enhanced BSL-3 setting, the CDC said.

In related developments, the CDC today updated a guidance documents on case definitions for H7N9 investigations in the United States and issued its first interim guidance on specimen collection and processing samples for patients with suspected H7N9 infections.

Virus studies
Two new studies have identified mutations that could boost the infectivity of H7N9 and H5N1 viruses through improved binding to receptors in humans´ respiratory tracts. The studies were conducted by the same research teams at the Massachusetts Institute of Technology, and both were published yesterday in Cell.

The group´s investigation of the H7N9 virus structure found that its hemagglutinin (HA) protein shows a limited ability to bind to human receptors, but a single amino acid mutation—G228S—could allow a substantive change that would allow extensive binding in the upper airways, according to the study.

The investigators also found evolving HA mutations that indicate that current prepandemic H7 vaccines would not be effective against the new H7N9 virus.

When they did a similar analysis of the H5N1 virus structure, they found that the HAs from currently circulating clades needed as minor as only a single base pair mutation to switch binding to human receptors. The authors wrote that the mutations they found might be useful for monitoring the emergence of pandemic-potential strains.

See also:

Jun 7 WHO risk assessment

Jun 6 CDC H7N9 biosafety guidance

Jun 7 CDC updated H7N9 case definition

Jun 7 CDC interim guidance for specimen collection

Jun 6 Cell study on receptor binding of H7N9 HA abstract

Jun 6 Cell study on H5N1 receptor HA specificity abstract