1. What is avian influenza?

Avian influenza (such as H5N1, H9N2) is a type of influenza A. It was known previously to infect birds only, but 18 human cases caused by the H5N1 strain were documented in Hong Kong in 1997 and another two were documented in 2003.

2. What is the difference between viruses causing human influenza and those causing avian influenza?

Human influenza and avian influenza are both caused by influenza viruses. In Hong Kong, human influenza is commonly caused by influenza A (H3N2), influenza A (H1N1) and influenza B viruses, while avian influenza is commonly caused by influenza A (H5N1) and influenza A (H9N2) viruses.

3. What are the symptoms of avian influenza?

The initial symptoms of avian influenza are similar to those of other influenza viruses, including fever, headache, muscle pain, runny nose, cough and sore throat. However, it is more likely to result in high fever, chest infection, respiratory failure, multi-organ failure, and death.

4. How can I tell the difference between having avian influenza and SARS?

You cannot differentiate between avian influenza and SARS by symptoms alone. Confirmation of diagnosis will depend on laboratory tests on clinical samples from the patient.

Transmission

5. How is avian influenza transmitted?

Avian influenza is transmitted from infected live birds to humans. Human-to-human transmission is inefficient. Outbreaks of avian influenza in poultry have recently been reported in some Asian and European countries, and some cases of human infection have been reported. Hong Kong has an effective surveillance system for influenza in birds and humans. The Department of Health has been closely monitoring the situation and has adopted appropriate preventive measures to guard against the disease.

6. Why bother if the H5N1 virus does not usually infect humans?

Avian influenza is transmitted from infected live birds to humans. Although human-to-human transmission is inefficient, all influenza viruses have the ability to change genetically, and scientists are concerned that the H5N1 virus could one day be able to spread easily from one person to another. Because the virus does not commonly infect humans, there is little or no immune protection against it in the human population. If the H5N1 virus could spread easily from person to person, an influenza pandemic could occur. No one can predict when a pandemic might strike. However, experts from around the world are watching the H5N1 situation very closely and are preparing for the possibility that the virus may begin to spread more easily and widely from person to person.

7. Who is susceptible to contracting the disease?

People in close contact with poultry are more susceptible to contracting avian flu. The elderly, children and people with chronic illness have a higher risk of developing complications such as bronchitis and pneumonia.

Do you remember this?

Hong Kong health authorities closed down a poultry market here Saturday after excrement samples collected from hencoops at the marketplace were confirmed infected with the deadly strain of H5N1 avian influenza virus.

Dr. York Chow, Secretary for Food and Health, announced at a press conference here Saturday afternoon that the Po On Road Market in Kowloon an infected area of the H5N1 virus and ordered the immediate suspension of trading in the market.

Chow said after days of laboratory testings, five of the 20 excrement samples collected from three poultry stores on June 3 were confirmed H5N1 positive and an order was issued immediately to cull about 2,700 chickens in the market.

"We are still investigating on the source of the H5N1 virus infections," he said, adding other 64 poultry markets had reported no H5N1 cases.

Chow said there has been no report of human case of H5N1 infections but the department had decided to raise the response level from "vigilance" to "serious" in the city.

In response to the latest H5N1 virus find, Chow said, the Food and Health Department had suspended immediately the live poultry imports from the Chinese mainland and trading from local chicken farms will be suspended immediately

He said such suspension will last for as long as 21 days if necessary.

Chow said the Hong Kong Special Administrative Region government had noticed the Ministry of Agriculture and the General Administration of Quality Supervision, Inspection and Quarantine on the latest development of bird flu in Hong Kong.

Chow said there had been no unusual incidents reported in the registered chicken farm in the Chinese mainland and none abnormal death of poultry had been reported by store owners during the past days.

Thomas Tsang, Controller of the Center for Health Protection, said the center would conduct health checkups and prescribe anti- virus medicine for those people in close contact with live poultry.

Tsang also called on doctors in the city to quickly report suspected cases of H5N1 infection to the center once they diagnose those patients with a fever.

The Agriculture, Fisheries and Conservation Department said they would strengthen the testing of live poultry on the bird flu virus and disinfecting of poultry whole sale markets.

Scientists are looking at a novel strategy to prevent the spread of pandemic avian influenza. They have developed a vaccine that protects ducks, a known natural reservoir for the virus.

 

Waterfowl are considered to be the natural reservoir of influenza A viruses due to the isolation of all subtypes from these hosts. Current research indicates that influenza A viruses are continuously evolving within their natural environment and can be transmitted to a variety of animals, including humans. H5N1 avian influenza A viruses are now endemic in domestic poultry in many Asian countries and ducks are believed to be the primary source of infection. Reducing the spread of H5N1 in ducks could play a key role in minimizing the risk of a pandemic outbreak.

In the study researchers first identified dominant pathogenic strains of H5N1 influenza A viruses circulating in Asian poultry and found that four caused symptomatic illness in domestic ducks, but not all were lethal. In addition the researchers reversed the genetics of the viruses in domestic ducks to develop three different inactivated oil emulsion whole-virus H5 influenza vaccines. Following one round of inoculation with the vaccines ducks were completely protected when challenged with a lethal dose of the H5N1 virus.

"The vaccines provided complete protection against the lethal challenge of the homologous and heterologous H5N1 avian influenza A virus with no evidence of morbidity, mortality, or shedding of the challenge virus," say the researchers. "The complete protection offered by these vaccines will be useful for reducing the shedding of H5N1 avian influenza A viruses among vaccinated agricultural avian populations."

 

The concern is greatest in rural areas of affected countries, where traditional free-ranging ducks, chickens and wildlife mingle, frequently sharing the same source of water, according to a joint statement by the UN Food and Agriculture Organization (FAO), the World Health Organization (WHO) and the Office International des Epizooties (OIE).

Findings pointing to an altered role for domestic ducks join other recent evidence that the H5N1 virus circulating in parts of Asia has increased its virulence in chickens and mice (a laboratory model for mammals), and has expanded its host range to include mammals, such as certain members of the felidae family (e.g. cats and tigers), not previously considered susceptible to infection.

Influenza A viruses occur naturally in wild birds. Although these birds aren’t affected by the virus, domestic poultry such as chickens and turkeys are – and so are people.

H5N1 has become common among birds in Asia, who shed the virus in their saliva, nasal secretions and faeces. More than 90 per cent of birds who get H5N1 die, and mortality among humans is also high.

The H5N1 virus was first shown to have passed from birds to humans in 1997, during an outbreak of avian influenza among poultry in Hong Kong. The virus caused severe respiratory illness in 18 people, of whom six died.

New flu strains tend to emerge in Asia, Africa and the East, where people live in closer quarters with their animals, and different flu viruses may mix to cause new strains or pass between species. For example, domestic ducks may carry H5N1 without symptoms and release the virus for long periods, acting as what is known as a silent reservoir.

In rural areas, free-ranging ducks and chickens often mingle and share the same water supplies. The virus may then be passed from one animal to another and possibly even to humans.

More worryingly, recent research has shown that H5N1 has changed so that it’s even more deadly in chickens and mice, and can now infect cats too. H5N1 is also resistant to some of the drugs used to treat flu (such as amantadine).

Millions of chickens and ducks have been slaughtered across South East Asia in an effort to prevent the virus spreading from birds to humans. A vaccine against H5N1 has already been developed, and others are in development.

If H5N1 becomes able to pass from human to human then the situation will be even more serious as most people have little immunity to the strain and there will be rapid spread.

Flu viruses continually alter through small changes in their make-up called antigenic drift and occasional abrupt major changes called antigenic shift.

This means that although you may have fought and won a miserable battle against flu a year or two ago, the next time the virus appears your body won’t recognise it because the antibodies your body made against flu last time won’t work. This is why people need to be immunised against flu each year, using the most up-to-date strains of the virus.

There are three types of influenza viruses: A, B and C. Type C only causes mild problems in humans. Type B can cause more serious illness and seasonal epidemics, but as it only changes through the slower process of antigenic drift there is little risk of a pandemic, where millions of people are suddenly exposed to a new, dramatically different virus.

That threat is more likely to come from type A, which can undergo rapid shift

Overestimating Avian Flu

Would you estimate the percentage of movie fans in the world by polling at a cinema? Would you calculate the number of overweight Americans by taking a survey at Weight Watchers locations? Not if you were aiming for any sort of statistical accuracy; such methods would not give you samples at all representative of a larger population.

Regrettably, just this sort of sampling bias may have lead to huge errors in avian flu mortality numbers. While stony-faced newscasters somberly report that more than 50% of people infected with avian flu ultimately die, the death rate may be much lower.

A study published in the January 9th issue of Archives of Internal Medicine found that as many as 600 to 750 people in Vietnam may have come down with a mild variant of the avian flu—one that does not carry lethal consequences. This suggests that current mortality estimates, which are derived from only the most severely ill patients, are biased. We may be underestimating the virus’ transmission rate while overestimating the deadliness of avian flu.
Thorson’s work suggests that the WHO statistics do not account for all cases of H5N1 infection in humans, because many cases go unreported by patients who do not seek medical assistance for milder symptoms.

Christian Sandrock, a physician and an assistant professor at the University of California Davis Health System, as well as a specialist in public health issues, says Thorson’s study brings public attention to a hotly-debated question in the medical community: Is there a mild or asymptomatic version of avian flu?

Sandrock explains that, without serology studies to confirm a patient’s infection with H5N1, Thorson’s study does not fully answer that question.

"It is not at all conclusive," he said.

However, Sandrock thinks that the WHO’s 50% mortality figure will eventually be revised downward.

"There’s going to definitely be some people with the disease that were either asymptomatic or subclinical, that really didn’t come up on radar," Sandrock said. "I think 50% is going to be the high end. How much it’s going to drop, I don’t know. What we’d like to see is that it goes from 50% to 3%. But, I think what we may see is that it goes from 50% to 40%, or 50% to 30%, which is still a phenomenally high mortality."

H5N1 is a subtype of the species Influenza A virus of the Influenzavirus A genus of the Orthomyxoviridae family. Like all other influenza A subtypes, the H5N1 subtype is an RNA virus. It has a segmented genome of eight negative sense, single-strands of RNA, abbreviated as PB2, PB1, PA, HA, NP, NA, MP and NS.

HA codes for hemagglutinin, an antigenic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. NA codes for neuraminidase, an antigenic glycosylated enzyme found on the surface of the influenza viruses. It facilitates the release of progeny viruses from infected cells.[19] The hemagglutinin (HA) and neuraminidase (NA) RNA strands specify the structure of proteins that are most medically relevant as targets for antiviral drugs and antibodies. HA and NA are also used as the basis for the naming of the different subtypes of influenza A viruses. This is where the H and N come from in H5N1.

Influenza A viruses are significant for their potential for disease and death in humans and other animals. Influenza A virus subtypes that have been confirmed in humans, in order of the number of known human pandemic deaths that they have caused, include:

    * H1N1, which caused "Spanish flu" and currently causes seasonal human flu
    * H2N2, which caused "Asian flu"
    * H3N2, which caused "Hong Kong flu" and currently causes seasonal human flu
    * H5N1, the world’s major current pandemic threat
    * H7N7, which has unusual zoonotic potential and killed one person
    * H1N2, which is currently endemic in humans and pigs and causes seasonal human flu
    * H9N2, which has infected three people
    * H7N2, which has infected two people
    * H7N3, which has infected two people
    * H10N7, which has infected two people

Genetics of H5N1

The first known strain of HPAI A(H5N1) (called A/chicken/Scotland/59) killed two flocks of chickens in Scotland in 1959; but that strain was very different from the current highly pathogenic strain of H5N1. The dominant strain of HPAI A(H5N1) in 2004 evolved from 1999 to 2002 creating the Z genotype.[14] It has also been called "Asian lineage HPAI A(H5N1)".

Asian lineage HPAI A(H5N1) is divided into two antigenic clades. "Clade 1 includes human and bird isolates from Vietnam, Thailand, and Cambodia and bird isolates from Laos and Malaysia. Clade 2 viruses were first identified in bird isolates from China, Indonesia, Japan, and South Korea before spreading westward to the Middle East, Europe, and Africa. The clade 2 viruses have been primarily responsible for human H5N1 infections that have occurred during late 2005 and 2006, according to WHO. Genetic analysis has identified six subclades of clade 2, three of which have a distinct geographic distribution and have been implicated in human infections: Map

    * Subclade 1, Indonesia
    * Subclade 2, Europe, Middle East, and Africa (called EMA)
    * Subclade 3, China"[10][15][16]

A 2007 study focused on the EMA subclade has shed further light on the EMA mutations. "The 36 new isolates reported here greatly expand the amount of whole-genome sequence data available from recent avian influenza (H5N1) isolates. Before our project, GenBank contained only 5 other complete genomes from Europe for the 2004–2006 period, and it contained no whole genomes from the Middle East or northern Africa. Our analysis showed several new findings. First, all European, Middle Eastern, and African samples fall into a clade that is distinct from other contemporary Asian clades, all of which share common ancestry with the original 1997 Hong Kong strain. Phylogenetic trees built on each of the 8 segments show a consistent picture of 3 lineages, as illustrated by the HA tree shown in Figure 1. Two of the clades contain exclusively Vietnamese isolates; the smaller of these, with 5 isolates, we label V1; the larger clade, with 9 isolates, is V2. The remaining 22 isolates all fall into a third, clearly distinct clade, labeled EMA, which comprises samples from Europe, the Middle East, and Africa. Trees for the other 7 segments display a similar topology, with clades V1, V2, and EMA clearly separated in each case. Analyses of all available complete influenza (H5N1) genomes and of 589 HA sequences placed the EMA clade as distinct from the major clades circulating in People’s Republic of China, Indonesia, and Southeast Asia."[17]

H5N1, Influenza A virus subtype

Do you know what is H5N1?

Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species.[1] A bird-adapted strain of H5N1, called HPAI A(H5N1) for "highly pathogenic avian influenza virus of type A of subtype H5N1", is the causative agent of H5N1 flu, commonly known as "avian influenza" or "bird flu". It is enzootic in many bird populations, especially in Southeast Asia. One strain of HPAI A(H5N1) is spreading globally after first appearing in Asia. It is epizootic (an epidemic in nonhumans) and panzootic (affecting animals of many species, especially over a wide area), killing tens of millions of birds and spurring the culling of hundreds of millions of others to stem its spread. Most references to "bird flu" and H5N1 in the popular media refer to this strain.[2]

As of the July 25, 2008 FAO Avian Influenza Disease Emergency Situation Update, H5N1 pathogenicity is continuing to gradually rise in wild birds in endemic areas but the avian influenza disease situation in farmed birds is being held in check by vaccination. Eleven outbreaks of H5N1 were reported worldwide in June 2008 in five countries (China, Egypt, Indonesia, Pakistan and Vietnam) compared to 65 outbreaks in June 2006 and 55 in June 2007. The "global HPAI situation can be said to have improved markedly in the first half of 2008 [but] cases of HPAI are still underestimated and underreported in many countries because of limitations in country disease surveillance systems".[3]