Dossier H7N9: Bird Flu Has the Makings of a Pandemic Virus

Scientists in China have identified an influenza virus that they say has the potential to spread around the world, sickening and killing people whose immune systems have never faced a threat like it.

The H7N9 flu emerged in humans in eastern China in February 2013, sickening 133 people and killing about a third of them before winding down in May. It seemed that the outbreak was over, but it reemerged in October 2013 and has been spreading steadily since.

“H7N9 viruses should be considered as a major candidate to emerge as a pandemic strain in humans,” they wrote in a study published Wednesday by the journal Nature.

According to the World Health Organization, 571 people have had laboratory-confirmed H7N9 infections and 212 people have died. All but three cases were in China, Hong Kong and Taiwan. The others involved a Chinese traveler to Malaysia and two Canadians who had visited China.

The virus developed in birds before spreading to humans. Like the H5N1 bird flu and the H1N1 swine flu, it contains a combination of genes that are new to people.

All flu viruses are made of just eight genes. Two of those genes make the proteins that stud the surface of the virus. Hemagglutinin (H), helps invading flu particles latch on to cells. Once inside, the virus hijacks the host cell’s machinery to make hundreds of copies of itself. When those copies are ready to spread to other cells, the neurominidase (N) protein allows them to get out.

Scientists have identified 18 types of hemagglutinin proteins and 11 types of neurominidase proteins. All of them have infected birds, but only some of them have been documented in people.

So far, H7N9 is spreading primarily among chickens in live-poultry markets, according to the authors of the Nature study. Researchers tested market chickens in 15 cities in the Chinese provinces of Zhejiang, Guangdong, Jiangxi, Jiangsu and Shandong. Infected chickens were found in seven of those cities.

What’s more, each of those seven cities also had at least one case of human infection with H7N9, the study authors wrote.

To figure out how this virus managed to make a comeback, the research team sequenced the complete genomes of 438 samples of H7N9 found in poultry, as well as 19 samples taken from human hospital patients in Shenzhen. They also sequenced 263 related bird flu viruses.

The RNA sequences of the hemagglutinin genes confirmed that the H7N9 viruses now circulating are descendants of the viruses that appeared in the spring of 2013. The viruses probably hitched a ride around China inside chickens that were transported along trade routes. The current viruses can be grouped into three categories, or “clades.” All of them are descendants of the viruses that appeared in the spring of 2013.

One of the clades likely originated in the Yangtze River delta region and then spread to other provinces as chickens were transported to distant markets. Another clade was mainly limited to Jiangxi, though it somehow spread to two people in Taiwan.

A third clade has been found in only Guangdong, but it is responsible for more human infections than either of the other two. The proliferation of these viruses suggests it is prevalent in chickens there, according to the study.

When the researchers looked at the neuraminidase genes, they found evidence that multiple strains of H7N9 have been circulating in Guangdong. When two or more flu viruses infect the same body, they can mix and match their genetic material.

Overall, this second wave of H7N9 influenza viruses represents “a major increase in genetic diversity” compared with the viruses in the first wave, the study authors wrote. Unless live poultry markets are permanently closed, merchants stop transporting chickens from region to region, and other control measures are put in place, the virus will “persist and cause a substantial number of severe human infections.”

So far, most people were sickened by handling infected chickens; cases of the virus spreading directly from person to person have been limited. That might change if the virus mutates, as happened with the H1N1 swine flu pandemic that began 2009. Or it might not, like the H5N1 bird flu that emerged in 2003.

But as long as chickens are on the move, it’s a safe bet that H7N9 will spread too, the researchers warned.

“It is probable that the H7N9 virus is now present across most of China,” they wrote. “Given the current pattern of dissemination, it will only be a matter of time before poultry movement spreads this virus beyond China by cross-border trade.”


Dossier H7N9: AI Virus Transmission between Finches and Poultry

Finches, parakeets and sparrows are the ultimate source of H7N9 avian influenza, a new study concludes. More than 600 people have contracted H7N9 bird flu in China, and more than 200 have died. Most of the people probably caught it from infected chickens, but it hasn’t been clear where chickens pick up the virus.

In laboratory experiments, society finches spread H7N9 from their mouths into water when they drank, researchers report in the April Emerging Infectious Diseases.

Chickens and quail could then be infected by drinking that same water, the researchers found. The virus does not seem to spread between birds through the air. It is unclear how the H7N9 virus re-emerged and how it will develop further; potentially it may become a long-term threat to public health.

The H7N9 viruses have spread from eastern to southern China and become persistent in chickens, which has led to the establishment of multiple regionally distinct lineages with different reassortant genotypes. Repeated introductions of viruses from Zhejiang to other provinces and the presence of H7N9 viruses at live poultry markets have fuelled the recurrence of human infections.

This rapid expansion of the geographical distribution and genetic diversity of the H7N9 viruses poses a direct challenge to current disease control systems. It’s likely to suggest that H7N9 viruses have become enzootic in China and may spread beyond the region, following the pattern previously observed with H5N1 and H9N2 influenza viruses


Dossier AI transmission risks: Analysis of On-farm biosecurity measures and contact structure

Contacts between people, equipment and vehicles prior and during outbreak situations are critical to determine the possible source of infection of a farm. Hired laborers are known to play a big role in interconnecting farms. Once a farm is infected, culling entire flock is the only option to prevent further spreading with devastating consequences for the industry.

In this paper, based on the HPAI outbreak in Holland 2003, the researchers found that 32 farms hired external labor of which seven accessed other poultry on the same day.

However, they were not the only ‘connectors’ as some (twelve) farmers also reported themselves helping on other poultry farms. Furthermore, 27 farms had family members visiting poultry or poultry-related businesses of which nine entered poultry houses during those visits. The other enhancing factor of farm interconnections was the reported ownership of multiple locations for ten of the interviewed farms and the reported on-premises sale of farm products on one pullet and eight layer farms. Also worth mentioning is the practice of a multiple age system reported on eight of the interviewed farms as this may increase the risk of infecting remaining birds when off-premises poultry movements occur.

AI viruses may be introduced into poultry from reservoirs such as aquatic wild birds but the mechanisms of their subsequent spread are partially unclear. Transmission of the virus through movements of humans (visitors, servicemen and farm personnel), vectors (wild birds, rodents, insects), air- (and dust-) related routes and other fomites (e.g., delivery trucks, visitors’ clothes and farm equipment) have all been hypothesized.

It is therefore hypothesized that the risk of introducing the virus to a farm is determined by the farm’s neighborhood characteristics, contact structure and its biosecurity practices. On the one hand, neighborhood characteristics include factors such as the presence of water bodies (accessed by wild birds), the density of poultry farms (together with the number and type of birds on these farms) and poultry-related businesses and the road network. The use of manure in the farm’s vicinity is also deemed to be risky.

On the other hand, contact structure risk factors include the nature and frequency of farm visits. Therefore, a detailed analysis of the contact structure, including neighborhood risks, and biosecurity practices across different types of poultry farms and poultry-related businesses helps the improvement of intervention strategies, biosecurity protocols and adherence to these, as well as contact tracing protocols. Farmers’ perception of visitor- and neighborhood-associated risks of virus spread is also important due to its relevance to adherence with biosecurity protocols, to contact tracing and to communicating advice to them.

The between-farm virus transmission risks may be split into two categories:

1. Introduction
2. Onward-spread risks

The former entail the target farm’s exposure through incoming contacts (human and fomite), through inputs such as feed and egg trays and through neighborhood-related risks such as air-borne contamination.
The latter can be through farm outputs (waste and non-waste), outgoing contacts (human and fomite) and contamination of the neighborhood (e.g., through emissions from the farm). Therefore, all day-to-day farm activities involving people and/or materials and/or equipment going in or out of the farm were systematically analyzed.


High pathogen AI in the US: No surveillance – no outbreaks?

Although the US has reported three different isolates in two states, there have been no reports of outbreaks in commercial farms. Similarly, although Canada has reported H5N2 in 12 farms in British Columbia, there have been no reports of H5N8 anywhere, and no reports of any Fujian H5 in wild birds.

These absences raises serious concerns about the level of surveillance and the true distribution of H5N8 and H5N2 in North America.


Dossier investigation: identification of the agent

Influenza in birds is caused by infection with viruses of the family Orthomyxoviridae placed in the genus influenzavirus A. Influenza A viruses are the only orthomyxoviruses known to naturally affect birds. Many species of birds have been shown to be susceptible to infection with influenza A viruses; aquatic birds form a major reservoir of these viruses, and the overwhelming majority of isolates have been of low pathogenicity (low virulence) for chickens and turkeys. Influenza A viruses have antigenically related nucleocapsid and matrix proteins, but are classified into subtypes on the basis of their haemagglutinin (H) and neuraminidase (N) antigens (World Health Organization Expert Committee, 1980). At present, 16 H subtypes (H1–H16) and 9 N subtypes (N1–N9) are recognised with proposed new subtypes (H17, H18) for influenza A viruses from bats in Guatemala (Swayne et al., 2013; Tong et al., 2012; 2013). To date, naturally occurring highly pathogenic influenza A viruses that produce acute clinical disease in chickens, turkeys and other birds of economic importance have been associated only with the H5 and H7 subtypes. Most viruses of the H5 and H7 subtype isolated from birds have been of low pathogenicity for poultry. As there is the risk of a H5 or H7 virus of low pathogenicity (H5/H7 low pathogenicity avian influenza [LPAI]) becoming highly pathogenic by mutation, all H5/H7 LPAI viruses from poultry are notifiable to OIE. In addition, all high pathogenicity viruses from poultry and other birds, including wild birds, are notifiable to the OIE.


Basic information about avian influenza

Avian influenza is usually an inapparent or nonclinical viral infection of wild birds that is caused by a group of viruses known as type A influenzas. These viruses are maintained in wild birds by fecal-oral routes of transmission. This virus changes rapidly in nature by mixing of its genetic components to form slightly different virus subtypes. Avian influenza is caused by this collection of slightly different viruses rather than by a single virus type. The virus subtypes are identified and classified on the basis of two broad types of antigens, hemagglutinan (H) and neuraminidase (N); 15 H and 9 N antigens have been identified among all of the known type A influenzas.


Dossier Avian Influenza: the next pandemic?

Kathleen Harriman PhD, MPH, RN published an interesting presenation on the relationship between outbreaks of high pathogen Avian Influenza and the risks of the next human pandemics. Kathy has worked in the healthcare and public health fields for the past 35 years as a pediatric emergency room nurse, a hospital infection control practitioner, and as an infectious disease epidemiologist.

For the last two years, Kathy has been Chief of the Vaccine Preventable Disease Epidemiology Section in the Immunization Branch of the California Department of Public Health. Prior to joining CDPH, she worked for 15 years at the Minnesota Department of Health in a number of public health areas, including HIV/AIDS and the Emerging Infections Program.

During her last five years there she supervised the Infection Control Unit where she worked on community-associated MRSA and a variety of infectious disease issues, including many community and healthcare-associated outbreaks. Kathy has an MPH from the University of Sydney (Australia) and a PhD from the University of Minnesota.


Dossier Vaccination: what causes poultry vaccination to fail

This is the third presentation on vaccination, posted recently by Dr. Ossama Motawae, an Egyptian veterinarian. In this presentation, he explains what causes vaccination programs to fail. An interesting presentation for those who are not so familiar with the day-to-day practice of poultry vaccination.


Dossier Vaccination: The use of inactivated H5N2 vaccine in Hong Kong

This month, dr Ossama Motawae, an Egyptian veterinarian, published an interesting presentation on the use of inactivated H5N2 vaccine to reduce the H5N1 virus load and inhibit the further reemergence of H5N1 genotypes. His conclusion is that commercial inactivated oil-emulsion A/CK/Mexico/ 232/94 (H5N2) provides protection against challenge with low doses of A/CK/HK/86.3/02 (H5N1) virus but does not prevent virus shedding. When the severity of challenge was increased in the second experiment, 1 of 10 vaccinated birds died but not in the third experiment. However, virus shedding in vaccinates in the first experiment was sufficient to infect 50% of unvaccinated contact controls. Despite high levels of HI antibody, the heavily challenged birds were not fully protected, thus raising the question of lack of genetic similarity between the vaccine and challenge virus.


AVT session 1: The Principles of Outbreak Response

This is the first of a series of 6 presentations on the subject of Emergency Response to an outbreak of Avian Influenza.