View With Charts & Images


flu symptoms

Although there have been few human cases to
determine the exact incubation period of bird flu, it would be expected to be
from three to 10 days. The symptoms of bird flu in humans are similar to those
of regular influenza and include:

  • Fever
  • Sore
  • Cough
  • Headache
  • Aching

Complications Of Bird flu

Bird flu in humans can cause a range of serious and potentially fatal
complications, including:

  • Eye
  • Pneumonia,
    including viral pneumonia
  • Acute
    respiratory distress
  • Inflammation
    of the brain and heart.

Tell your doctor if you’ve
been to a country where there is bird flu


If you have recently returned from a country that had an outbreak of bird flu
and you get flu symptoms, see your doctor immediately. When making the
appointment, tell the clinic staff about your travel including any visits to
markets, farms or anywhere else where birds were present.

Influenza viruses can mutate

Influenza viruses that infect animal species can mutate and infect humans. The
human immune system may have no defences against viruses that previously only
infected animals. That’s why infection with these viruses can result in more
severe disease in people.

If the H5N1 bird flu virus were to mix with a human influenza virus, such a
‘combined’ virus could create a new human influenza virus that could spread

Health experts are concerned that the current bird flu affecting Asia could
become a worldwide pandemic if the virus does mutate. The worst influenza
pandemic in modern history was the Spanish flu, which occurred in 1918–19 and
killed up to 50 million people.

Measures to contain the spread of the current bird flu virus include
identifying and culling affected poultry flocks, research into tests and
vaccines, and rigorous quarantine practices.

Treatment options

Several antiviral medications used to treat human influenza are also effective
for bird flu. These could be used if a person developed symptoms after possible
exposure to bird flu, or to prevent illness in a person who was in close
contact with bird flu. Currently testing for bird flu vaccines is an ongoing


At the moment, there is no need for people living in USA, or people making
short visits to countries with cases of bird flu, to have antiviral
medications. Americans living long-term in countries affected by bird flu
should consider having a supply of antiviral medications in the home to use on
medical advice should the situation change while they are away from the US.

The Federal government is stockpiling Relenza and Tamiflu, two drugs that may
be used in the treatment of human cases of bird flu. In the case of an outbreak
in humans, these drugs would be used to maintain essential services, prevent
transmission and provide treatment for people who are already ill.

A vaccine against bird flu is in development, but is not currently available.
The current influenza vaccines will not protect humans against bird flu.
However, people who may be exposed to bird flu should consider being vaccinated
against human influenza viruses to reduce the risk of the viruses ‘mixing’ to
form a new flu strain.

Advice for travelers

Be aware of the risk of bird flu if you are travelling to a country where
outbreaks are occurring. Suggestions include:

  • Avoid
    contact with wild or domesticated birds such as chickens, ducks and geese.
    Don’t go to farms or market places, since these are the primary carriers
    of bird flu
  • Stop young
    children from putting contaminated objects or their own fingers into their
  • Eggshells
    may be contaminated with bird faeces. Wash eggs thoroughly before breaking
    and wash your hands thoroughly after handling eggs.
  • Avoid
    foods that contain uncooked egg, such as mayonnaise.
  • Wash
    hands, chopping boards and utensils thoroughly after handling raw poultry.
  • Cook
    poultry at high temperatures. Cooking temperatures of 80°C or higher
    destroy the bird flu virus in about 60 seconds.

Control of avian
influenza A(H5N1): public health concerns

10 February 2004

The current outbreaks of highly pathogenic H5N1
avian influenza in poultry in parts of Asia have had immediate and severe
consequences for the agricultural sector.1 Human cases, with a high
fatality, have been reported in two countries, Viet Nam and Thailand, with very
widespread outbreaks in poultry.

It can be anticipated that human cases will also
be detected in other countries where outbreaks in poultry are rapidly

The number of human cases presently detected is
very small compared with the large number of infected birds distributed over a
wide geographical area. This suggests that the H5N1 virus strain may not easily
infect humans.

To date, no human-to-human transmission is known
to have occurred. However, the continuing presence of infection in poultry may
also create opportunities for the emergence of a new influenza virus subtype
with a capacity to spread easily among humans, thus marking the start of an
influenza pandemic. Should this rare event occur (three pandemics occurred
during the previous century), it would immediately have serious consequences
for human health throughout the world.

For this reason, public health concerns about the
present H5N1 situation must be given the highest priority when weighing the
immediate and measurable economic losses in animals against possible yet
unpredictable consequences for humans.

Several other diseases in animals can be
transmitted to humans. Experience with such diseases, known as “zoonoses”, has
shown that strict measures on animal health, imposed by the need to protect
human health, helped rebuild consumer confidence.2

Recent experience has also shown that measures
for the control of zoonotic diseases, aimed at halting further spread in
animals and minimizing economic losses, need to be closely coordinated with
measures that minimize the longer-term risks to human health. In the present
situation, measures aimed at eliminating the disease in poultry will also
reduce the presence of the virus in the environment and thus reduce
opportunities for human exposures and infections. These measures must be
carried out urgently, giving highest priority to the protection of human
health. Previous outbreaks of highly pathogenic avian influenza associated with
human infections occurred in areas, such as Hong Kong and the Netherlands, with
industrial poultry production and well developed health and agricultural
infrastructures. Even so, elimination of infection in poultry was a complex,
difficult, and costly undertaking. Both outbreaks were eventually controlled
through immediate culling of infected flocks, quarantine and disinfection of
farms, strict biosecurity, restrictions on the movement of animals, and
compensation for farmers.

The present situation is different. Control of
outbreaks of highly pathogenic avian influenza is known to be especially
difficult in areas where poultry range freely. In several affected countries,
up to 80% of the total poultry population is raised in small backyard farms.
Most rural families keep a small free-range flock.

Given these features of the present situation
there is potential that the H5N1 virus could become established in bird
populations in this geographical region and possibly spread to other parts of
the world. This was one of several conclusions reached during a joint FAO/OIE/WHO
technical consultation
 on the control of avian influenza, held in Rome from
3–4 February.

No single blueprint for control in animals, and
thus reduction of risks for humans, is available. Over the past four decades,
only 18 outbreaks of highly pathogenic avian influenza, most caused by strains
other than H5N1, have occurred throughout the world. Existing evidence will not
suffice to provide universally applicable recommendations for a rapid and
effective response in affected countries.

Control measures must be tailored to each
country’s unique epidemiological situation and unique capacity, with health and
agricultural sectors working hand-in-hand. Agricultural authorities face the
immediate challenge of rapidly eliminating the H5N1 reservoir in poultry.
Authorities in all affected countries need to work together in a coordinated

Transparency in reporting of human and animal
disease is absolutely essential.

Despite the uncertainties, experts fully agree
that immediate culling of infected and exposed birds is the first line of
defence for both the protection of human health and the reduction of further
losses in the agricultural sector. Other measures, such as the vaccination of
healthy flocks, may play a supportive role in some cases when undertaken in
conjunction with measures for preventing further spread of infection. WHO has
repeatedly stressed the
need to ensure that culling
 is carried out in a way that does not fuel more
human cases. and that vaccination of poultry should not lead to the dropping of
vigilance or compromise other necessary control measures.

In responding to the situation, WHO emphasises
three strategic goals: to avert an influenza pandemic, to control the present
human outbreaks and prevent further spread, and to conduct the research needed
for better preparedness and response, including the immediate development of a
new vaccine for humans against H5N1. WHO has issued a series of technical
aimed at minimizing the risk of further human cases and
facilitating a coordinated international response.

1 Highly pathogenic avian influenza is
categorized by OIE as a “list A” disease. List A includes transmissible
diseases “which have the potential for very serious and rapid spread,
irrespective of national borders, which are of serious socio–economic or public
health consequence and which are of major importance in the international trade
of animals and animal products.”

2 One example is the spread of bovine spongiform
encephalopathy, or “mad cow disease”, in cattle, which led to the emergence of
a rare yet invariably fatal new disease in humans.

History of Avian Flu

The Avian Flu disease has captured considerable
international attention over the past year with serious epidemics of this
disease affecting Japan, South Korea, and areas of South-east Asia earlier this
year.  Now considered a pandemic, serious outbreaks of avian influenza had
also affected the Netherlands, Belgium, and Germany in 2003.  Avian flu had
also been reported in Australia, Pakistan, Italy, Chile, and Mexico.  The
impact of this serious disease has been disruptive to the poultry industries as
millions of chickens, geese, and turkeys were slaughtered to prevent further
transmission of this highly contagious disease.

Besides its devastating effect on domestic
poultry, Avian Flu has received unprecedented publicity because of what
occurred in Hong Kong in 1997.  Before this time, Avian flu was thought to
infect birds only, however, a different strain of Avian Flu virus was detected
in humans, marking the first time that Avian Flu was transmitted to
humans.  During this outbreak, 18 people were hospitalized and 6 of them
died.  To control the outbreak, authorities killed about 1.5 million
chickens to remove the source of the virus.

Earlier this year in January, a major outbreak of
Avian influenza surfaced again in Vietnam’s and Thailand’s poultry
industry.  Within a few short weeks, the disease had spread to ten
countries and regions in Asia, including Indonesia, South Korea, Japan and
China.  Over 50 million chickens, ducks, geese, and turkey were
slaughtered in an intensive effort to stop the disease from spreading any
further.  The outbreak was then contained in March.  Unfortunately,
this outbreak took a considerable toll on human lives.  There were 34
people infected with the Avian Flu in Vietnam and Thailand, of which 23 of them
tragically died.

Though scientists determined that the spread of
the Avian flu virus from birds to humans are rare occurrences, they were also
quick to express grave caution that this problem could become significantly
worse if the virus mutated into a more lethal form, or a form that could pass
easily from humans to humans.  The World Health Organization (WHO) is particularly
concerned about the Avian virus’ potential to swap genes with a common flu
virus, creating a lethal form of the virus that could spread around the globe
within months.

Avian Flu was first recorded in Italy more than
100 years ago in 1878.  As the cause of massive poultry epidemics, this
disease was then known as “Fowl Plague”.  This disease reared its ugly
head in the United States in 1924-25, and then again in 1929.  In 1955, it
was determined that the virus causing Fowl Plague was one of the influenza
viruses.  All influenza viruses affecting domestic animals (equine, swine,
avian) belong to Type A, and Type A influenza virus is the most common type
producing serious epidemics in humans. Types B and C do not affect domestic

There are two forms of Influenza A viruses
occurring worldwide – (i) highly pathogenic and (ii) mildly pathogenic.
The outbreaks in Hong Kong, and those that were found reported recently are
caused by the Highly Pathogenic Avian Influenza A virus (HPAI – subtypes H5 and
H7).  It is a form of this virus that has the ability to be transmitted to
humans.  Although our understanding of Avian Flu is relatively limited,
the recent outbreaks have stimulated research all around the world to further
our knowledge of this important disease and virus.

History of Avian Influenza

Confirmed instances of avian influenza viruses
infecting humans since 1997 include :

1997: In Hong Kong, avian influenza A (H5N1)
infected both chickens and humans. This was the first time an avian influenza
virus had ever been found to transmit directly from birds to humans. During
this outbreak, 18 people were hospitalized and 6 of them died.

1999: In Hong Kong, cases of avian influenza
A (H9N2) were confirmed in 2 children. Both patients recovered, and no
additional cases were confirmed. The evidence suggested that poultry was the
source of infection and the main mode of transmission was from bird to human.

2003: Two cases of avian influenza A (H5N1)
infection occurred among members of a Hong Kong family that had traveled to
China. One person recovered, the other died. How or where these 2 family
members were infected was not determined. Another family member died of a
respiratory illness in China, but no testing was done. No additional cases were

2003: Avian influenza A (H7N7) infections
among poultry workers and their families were confirmed in the Netherlands
during an outbreak of avian flu among poultry. More than 80 cases of H7N7
illness were reported (the symptoms were mostly confined to eye infections,
with some respiratory symptoms), and 1 patient died (in a veterinarian who had
visited an affected farm). There was evidence of some human-to-human

2003: H9N2 infection was confirmed in a child
in Hong Kong. The child was hospitalized but recovered.

of Avian Influenza

Taking a pharyngeal swab for the isolation of avian influenza virus

Clinical signs and post-mortal lesions may be
indicative of avian influenza infection. Virus isolation is needed for a
definitive diagnosis.

Laboratory Diagnosis


  1. Identification
    of the agent

    • Live
      birds – tracheal swabs and cloacal swabs or faeces
    • Dead
      birds – organs and faeces
  2. Serology
    • Clotted
      blood samples or
    • serum


Identification of the Agent

Inoculation of 9-11-day-old embryonated chicken
eggs followed by:

  1. Haemagglutination
    immunodiffusion test to confirm the presence of influenza A virus
  2. Subtype
    determination with monospecific antisera
  3. Strain virulence
    evaluation: evaluation of the intravenous pathogenicity index (IVPI) in
    4-8-week-old chickens




  • Detects
    antibodies to all AI virus, does not distinguish subtypes
  • Only
    suitable for testing chicken and turkey serum
  • Within 1
    week of infection, antibodies are detected in more than half the

AGID (Agar Gel Immunodiffusion

  • As for
    ELISA does not distinguish AI subtypes
  • Within 1
    week of infection, antibodies are detected in more than half the

HI (Haemagglutination Inhibition

  • Serotype
    specific test
  • Test
    available for each H subtype
  • HI titres
    are positive a few days later than ELISA or AGID, titres persist long
    after infection
  • Standard
    test for all avian species

IFT (Immunofluoresence test)

  • Able to
    detect antibodies to specific N-subtype
  • Can be
    used to detect infection in vaccinated birds if a heterologous vaccine is
    used. Read more in Monitoring.

RT-PCR (Reverse-transcriptase
polymerase chain reaction)

  • Able to
    detect influenza virus at very low levels
  • The
    presence of subtype H5 or H7 can be confirmed by using H5 or H7 specific

Transmission of
Influenza A Viruses Between Animals and People
Avian Flu: The Virus
& its Spread
Between Animal & People

A viruses have infected many different animals, including ducks, chickens,
pigs, whales, horses, and seals. However, certain subtypes of influenza A virus
are specific to certain species, except for birds, which are hosts to all known
subtypes of influenza A. Subtypes that have caused widespread illness in people
either in the past or currently are H3N2, H2N2, H1N1, and H1N2. H1N1 and H3N2
subtypes also have caused outbreaks in pigs, and H7N7 and H3N8 viruses have
caused outbreaks in horses.

A viruses normally seen in one species sometimes can cross over and cause
illness in another species. For example, until 1998, only H1N1 viruses
circulated widely in the U.S. pig population. However, in 1998, H3N2 viruses
from humans were introduced into the pig population and caused widespread
disease among pigs. Most recently, H3N8 viruses from horses have crossed over
and caused outbreaks in dogs.

influenza A viruses may be transmitted from animals to humans in two main ways:

  • Directly from birds or from avian
    virus-contaminated environments to people.
  • Through an intermediate host, such as
    a pig.

A viruses have eight separate gene segments. The segmented genome allows
influenza A viruses from different species to mix and create a new influenza A
virus if viruses from two different species infect the same person or animal.
For example, if a pig were infected with a human influenza A virus and an avian
influenza A virus at the same time, the new replicating viruses could mix
existing genetic information (reassortment) and produce a new virus that had
most of the genes from the human virus, but a hemagglutinin and/or
neuraminidase from the avian virus. The resulting new virus might then be able
to infect humans and spread from person to person, but it would have surface
proteins (hemagglutinin and/or neuraminidase) not previously seen in influenza
viruses that infect humans.

type of major change in the influenza A viruses is known as antigenic shift.
Antigenic shift results when a new influenza A subtype to which most people
have little or no immune protection infects humans. If this new virus causes
illness in people and can be transmitted easily from person to person, an influenza
pandemic can occur.

It is
possible that the process of genetic reassortment could occur in a human who is
co-infected with avian influenza A virus and a human strain of influenza A
virus. The genetic information in these viruses could reassort to create a new
virus with a hemagglutinin from the avian virus and other genes from the human
virus. Theoretically, influenza A viruses with a hemagglutinin against which
humans have little or no immunity that have reassorted with a human influenza
virus are more likely to result in sustained human-to-human transmission and
pandemic influenza. Therefore, careful evaluation of influenza viruses
recovered from humans who are infected with avian influenza is very important
to identify reassortment if it occurs.

it is unusual for people to get influenza virus infections directly from
animals, sporadic human infections and outbreaks caused by certain avian
influenza A viruses and pig influenza viruses have been reported. (For more
information see Avian
Influenza Infections in Humans 
.) These sporadic human infections and
outbreaks, however, rarely result in sustained transmission among humans.

Avian Influenza: Introduction

 (Fowl plague)

Avian influenza
(AI) viruses infect domestic poultry and wild birds. In domestic poultry, AI
viruses are typically of low pathogenicity (LP), causing subclinical
infections, respiratory disease, or drops in egg production. However, a few
AI viruses cause severe systemic infections with high mortality. This highly
pathogenic (HP) form of the disease has historically been called fowl plague.
In most wild birds, AI viral infections are subclinical.
influenza viruses are type A orthomyxoviruses characterized by
antigenically homologous nucleoprotein and matrix internal proteins, which
are identified by serology in agar gel immunodiffusion (AGID) tests. AI
viruses are further divided into 15 hemagglutinin (H1-15) and 9
neuraminidase (N1-9) subtypes based on hemagglutinin inhibition and
neuraminidase inhibition tests, respectively. Most AI viruses (H1-15
subtypes) are of LP, but some of the H5 and H7 AI viruses are HP for
chickens, turkeys, and related gallinaceous domestic poultry.

Epidemiology and

LP viruses are
distributed worldwide and are recovered frequently from clinically normal
shorebirds and migrating waterfowl. Occasionally, LP viruses are recovered
from imported pet birds and ratites. The viruses may be present in backyard
flocks and other birds sold through live-poultry markets, but most
commercially raised poultry in developed countries are free of AI viruses.
The HP viruses arise from mutation of some H5 and H7 LP viruses and cause
devastating epizootics. Depopulation and quarantine programs are used to
quickly eliminate the HP viruses.
The incubation
period is highly variable and ranges from a few days to 1 wk. Transmission
between individual birds is by ingestion or inhalation. Experimentally,
cats have been infected with 1 strain of H5N1 Asian HP AI following
respiratory exposure, ingestion of infected chickens, or contact with
infected cats. Potentially, domestic house cats could serve as a
transmission vector between farms, but the ability of other AI viruses,
including other H5N1 strains, to infect cats is unknown. Transmission
between farms is the result of breaches in biosecurity practices,
principally by movement of infected birds or contaminated feces and
respiratory secretions on fomites such as equipment or clothing. Airborne
dissemination may be important over limited distances.

Clinical Findings and

signs, severity of disease, and mortality rates vary depending on AI virus
strain and host species.


Low Pathogenicity AI Viruses:

These AI
viruses typically produce respiratory signs such as ocular and nasal
discharge and swollen infraorbital sinuses. Sinusitis is common in domestic
ducks, quail, and turkeys. Lesions in the respiratory tract typically
include congestion and inflammation of the trachea and lungs. In layers and
breeders, there may be decreased egg production or fertility, ova rupture
(evident as yolk in the abdominal cavity) or involution, or mucosal edema
and inflammatory exudates in the lumen of the oviduct. Some layer and
breeder chickens may have acute renal failure and visceral urate deposition
(visceral gout). The morbidity and mortality is usually low unless
accompanied by secondary bacterial or viral infections or aggravated by
environmental stress factors.


High Pathogenicity AI Viruses:

Even in the
absence of secondary pathogens, HP viruses cause severe, systemic disease
with high mortality in chickens, turkeys, and other gallinaceous birds. In
peracute cases, clinical signs or gross lesions may be lacking before
death. However, in acute cases, lesions may include cyanosis and edema of
the head, comb, and wattle; edema and discoloration of the shanks and feet
due to subcutaneous ecchymotic hemorrhages; petechial hemorrhages on
visceral organs and in muscles; and blood-tinged oral and nasal discharges.
In severely affectedbirds,
greenish diarrhea is common. Birds that survive the fulminating infection
may develop CNS involvement evident as torticollis, opisthotonos, or
incoordination. The location and severity of microscopic lesions are highly
variable and may consist of edema, hemorrhage, and necrosis in parenchymal
cells of multiple visceral organs, skin, and CNS.

Avian influenza, hemorrhagic skin, chicken
Avian influenza, hemorrhagic skin, chicken
Avian influenza, hemorrhagic skin, chicken
Avian influenza, hemorrhagic skin, chicken


AI viruses can
be readily isolated from tracheal and cloacal swabs. They grow well in the
allantoic sac of embryonating chicken eggs and agglutinate RBC. The
hemagglutination is not inhibited by Newcastle disease or other
paramyxoviral antiserum. AI viruses are identified by demonstrating the
presence of 1) influenza A matrix or nucleoprotein antigens using AGID or
other suitable immunoassays, or 2) viral RNA using an influenza A specific
RT-PCR tests.


LP AI must be
differentiated from other respiratory diseases or causes of decreased egg
production including: 1) acute to subacute viral diseases such as
infectious bronchitis, infectious laryngotracheitis, lentogenic Newcastle
disease, and infections by other paramyxoviruses; 2) bacterial diseases
such as mycoplasmosis, infectious coryza, ornithobacteriosis, turkey
coryza, and the respiratory form of fowl cholera; and 3) fungal diseases
such as aspergillosis. HP AI must be differentiated from other causes of
high mortality such as velogenic Newcastle disease, peracute septicemic
fowl cholera, heat exhaustion, and severe water deprivation.

Prevention and Treatment:

Vaccines can
prevent clinical signs and death. Furthermore, viral replication and
shedding from the respiratory and GI tracts may be reduced in vaccinated
birds. Specific protection is achieved through autogenous virus vaccines or
from vaccines prepared from AI virus of the same hemagglutinin subtype.
Antibodies to the viral neuraminidase antigens may provide some protection.
Currently, only inactivated whole AI virus and recombinant fowlpox-AI-H5
vaccines are licensed in the USA. The use of AI vaccine requires approval
of the state veterinarian. In addition, use of H5 and H7 AI vaccines in the
USA requires USDA approval. Treating LP-affected flocks with broad-spectrum
antibiotics to control secondary pathogens and increasing house
temperatures may reduce morbidity and mortality. Treatment with antiviral
compounds is not approved or recommended. Suspected outbreaks should be reported
to appropriate regulatory authorities.

Zoonotic Risk:

influenza viruses exhibit host adaptation and rarely infect humans, usually
as isolated individual cases without human-to-human transmission. In the
1997 Hong Kong outbreak, the risk factor for human infection was direct
contact with infected poultry, but not the handling, cooking, or
consumption of poultry meat. In 2004, HP AI of strain H5N1 infected poultry
and wild birds in 9 Asian countries. In Thailand and Vietnam, 37 human cases
were confirmed, with a case fatality rate of 68%.

Avian influenza is an infectious disease of birds caused by
type A strains of the influenza virus. The disease occurs worldwide. While all
birds are thought to be susceptible to infection with avian influenza viruses,
many wild bird species carry these viruses with no apparent signs of harm.

Other bird species, including domestic poultry, develop
disease when infected with avian influenza viruses. In poultry, the viruses
cause two distinctly different forms of disease – one common and mild, the
other rare and highly lethal. In the mild form, signs of illness may be
expressed only as ruffled feathers, reduced egg production, or mild effects on
the respiratory system. Outbreaks can be so mild they escape detection unless
regular testing for viruses is in place.

In contrast, the second and far less common highly
pathogenic form is difficult to miss. First identified in Italy in 1878, highly
pathogenic avian influenza is characterized by sudden onset of severe disease,
rapid contagion, and a mortality rate that can approach 100% within 48 hours.
In this form of the disease, the virus not only affects the respiratory tract,
as in the mild form, but also invades multiple organs and tissues. The
resulting massive internal haemorrhaging has earned it the lay name of “chicken

All 16 HA (haemagluttinin) and 9 NA (neuraminidase)
subtypes of influenza viruses are known to infect wild waterfowl, thus
providing an extensive reservoir of influenza viruses perpetually circulating
in bird populations. In wild birds, routine testing will nearly always find
some influenza viruses. The vast majority of these viruses cause no harm.

To date, all outbreaks of the highly pathogenic form of
avian influenza have been caused by viruses of the H5 and H7 subtypes. Highly
pathogenic viruses possess a tell-tale genetic “trade mark” or signature – a
distinctive set of basic amino acids in the cleavage site of the HA – that
distinguishes them from all other avian influenza viruses and is associated
with their exceptional virulence.

Not all virus strains of the H5 and H7 subtypes are highly
pathogenic, but most are thought to have the potential to become so. Recent
research has shown that H5 and H7 viruses of low pathogenicity can, after
circulation for sometimes short periods in a poultry population, mutate into
highly pathogenic viruses. Considerable circumstantial evidence has long
suggested that wild waterfowl introduce avian influenza viruses, in their low pathogenic
form, to poultry flocks, but do not carry or directly spread highly pathogenic
viruses. This role may, however, have changed very recently: at least some
species of migratory waterfowl are now thought to be carrying the H5N1 virus in
its highly pathogenic form and introducing it to new geographical areas located
along their flight routes.

Apart from being highly contagious among poultry, avian
influenza viruses are readily transmitted from farm to farm by the movement of
live birds, people (especially when shoes and other clothing are contaminated),
and contaminated vehicles, equipment, feed, and cages. Highly pathogenic
viruses can survive for long periods in the environment, especially when
temperatures are low. For example, the highly pathogenic H5N1 virus can survive
in bird faeces for at least 35 days at low temperature (4oC). At a much higher
temperature (37oC), H5N1 viruses have been shown to survive, in faecal samples,
for six days.

For highly pathogenic disease, the most important control measures
are rapid culling of all infected or exposed birds, proper disposal of
carcasses, the quarantining and rigorous disinfection of farms, and the
implementation of strict sanitary, or “biosecurity”, measures. Restrictions on
the movement of live poultry, both within and between countries, are another
important control measure. The logistics of recommended control measures are
most straightforward when applied to large commercial farms, where birds are
housed indoors, usually under strictly controlled sanitary conditions, in large
numbers. Control is far more difficult under poultry production systems in
which most birds are raised in small backyard flocks scattered throughout rural
or periurban areas.

When culling – the first line of defence for containing
outbreaks – fails or proves impracticable, vaccination of poultry in a
high-risk area can be used as a supplementary emergency measure, provided
quality-assured vaccines are used and recommendations from the World Organisation for Animal
Health (OIE)
 are strictly followed. The use of poor quality vaccines
or vaccines that poorly match the circulating virus strain may accelerate
mutation of the virus. Poor quality animal vaccines may also pose a risk for
human health, as they may allow infected birds to shed virus while still
appearing to be disease-free.

Apart from being difficult to control, outbreaks in
backyard flocks are associated with a heightened risk of human exposure and
infection. These birds usually roam freely as they scavenge for food and often
mingle with wild birds or share water sources with them. Such situations create
abundant opportunities for human exposure to the virus, especially when birds
enter households or are brought into households during adverse weather, or when
they share areas where children play or sleep. Poverty exacerbates the problem:
in situations where a prime source of food and income cannot be wasted,
households frequently consume poultry when deaths or signs of illness appear in
flocks. This practice carries a high risk of exposure to the virus during
slaughtering, defeathering, butchering, and preparation of poultry meat for
cooking, but has proved difficult to change. Moreover, as deaths of birds in
backyard flocks are common, especially under adverse weather conditions, owners
may not interpret deaths or signs of illness in a flock as a signal of avian
influenza and a reason to alert the authorities. This tendency may help explain
why outbreaks in some rural areas have smouldered undetected for months. The
frequent absence of compensation to farmers for destroyed birds further works
against the spontaneous reporting of outbreaks and may encourage owners to hide
their birds during culling operations.

During 2005, an additional and significant source of
international spread of the virus in birds became apparent for the first time,
but remains poorly understood. Scientists are increasingly convinced that at
least some migratory waterfowl are now carrying the H5N1 virus in its highly
pathogenic form, sometimes over long distances, and introducing the virus to
poultry flocks in areas that lie along their migratory routes. Should this new
role of migratory birds be scientifically confirmed, it will mark a change in a
long-standing stable relationship between the H5N1 virus and its natural
wild-bird reservoir.

Evidence supporting this altered role began to emerge in
mid-2005 and has since been strengthened. The die-off of more than 6000
migratory birds, infected with the highly pathogenic H5N1 virus, that began at
the Qinghai Lake nature reserve in central China in late April 2005, was highly
unusual and probably unprecedented. Prior to that event, wild bird deaths from
highly pathogenic avian influenza viruses were rare, usually occurring as
isolated cases found within the flight distance of a poultry outbreak.
Scientific studies comparing viruses from different outbreaks in birds have
found that viruses from the most recently affected countries, all of which lie
along migratory routes, are almost identical to viruses recovered from dead
migratory birds at Qinghai Lake. Viruses from Turkey’s first two human cases,
which were fatal, were also virtually identical to viruses from Qinghai Lake.

The outbreaks of highly pathogenic H5N1 avian influenza
that began in south-east Asia in mid-2003 and have now spread to a few parts of
Europe, are the largest and most severe on record. To date, nine Asian countries
have reported outbreaks (listed in order of reporting): the Republic of Korea,
Viet Nam, Japan, Thailand, Cambodia, the Lao People’s Democratic Republic,
Indonesia, China, and Malaysia. Of these, Japan, the Republic of Korea, and
Malaysia have controlled their outbreaks and are now considered free of the
disease. Elsewhere in Asia, the virus has become endemic in several of the
initially affected countries.

In late July 2005, the virus spread geographically beyond
its original focus in Asia to affect poultry and wild birds in the Russian
Federation and adjacent parts of Kazakhstan. Almost simultaneously, Mongolia
reported detection of the highly pathogenic virus in wild birds. In October
2005, the virus was reported in Turkey, Romania, and Croatia. In early December
2005, Ukraine reported its first outbreak in domestic birds. Most of these
newer outbreaks were detected and reported quickly. Further spread of the virus
along the migratory routes of wild waterfowl is, however, anticipated.
Moreover, bird migration is a recurring event. Countries that lie along the
flight pathways of birds migrating from central Asia may face a persistent risk
of introduction or re-introduction of the virus to domestic poultry flocks.

Prior to the present situation, outbreaks of highly
pathogenic avian influenza in poultry were considered rare. Excluding the
current outbreaks caused by the H5N1 virus, only 24 outbreaks of highly
pathogenic avian influenza have been recorded worldwide since 1959. Of these,
14 occurred in the past decade. The majority have shown limited geographical
spread, a few remained confined to a single farm or flock, and only one spread
internationally. All of the larger outbreaks were costly for the agricultural
sector and difficult to control.

Influenza viruses are normally highly species-specific, meaning that viruses
that infect an individual species (humans, certain species of birds, pigs,
horses, and seals) stay “true” to that species, and only rarely spill over to
cause infection in other species. Since 1959, instances of human infection with
an avian influenza virus have been documented on only 10 occasions. Of the
hundreds of strains of avian influenza A viruses, only four are known to have
caused human infections: H5N1, H7N3, H7N7, and H9N2. In general, human
infection with these viruses has resulted in mild symptoms and very little
severe illness, with one notable exception: the highly pathogenic H5N1 virus.

Of all influenza viruses that circulate in birds, the H5N1
virus is of greatest present concern for human health for two main reasons.
First, the H5N1 virus has caused by far the greatest number of human cases of
very severe disease and the greatest number of deaths. It has crossed the species
barrier to infect humans on at least three occasions in recent years: in Hong
Kong in 1997 (18 cases with six deaths), in Hong Kong in 2003 (two cases with
one death) and in the current outbreaks that began in December 2003 and were
first recognized in January 2004.

A second implication for human health, of far greater
concern, is the risk that the H5N1 virus – if given enough opportunities – will
develop the characteristics it needs to start another influenza pandemic. The
virus has met all prerequisites for the start of a pandemic save one: an
ability to spread efficiently and sustainably among humans. While H5N1 is
presently the virus of greatest concern, the possibility that other avian
influenza viruses, known to infect humans, might cause a pandemic cannot be
ruled out.

The virus can improve its transmissibility among humans via
two principal mechanisms. The first is a “reassortment” event, in which genetic
material is exchanged between human and avian viruses during co-infection of a
human or pig. Reassortment could result in a fully transmissible pandemic
virus, announced by a sudden surge of cases with explosive spread.

The second mechanism is a more gradual process of adaptive
mutation, whereby the capability of the virus to bind to human cells increases
during subsequent infections of humans. Adaptive mutation, expressed initially
as small clusters of human cases with some evidence of human-to-human
transmission, would probably give the world some time to take defensive action,
if detected sufficiently early.

During the first documented outbreak of human infections
with H5N1, which occurred in Hong Kong in 1997, the 18 human cases coincided
with an outbreak of highly pathogenic avian influenza, caused by a virtually
identical virus, in poultry farms and live markets. Extensive studies of the
human cases determined that direct contact with diseased poultry was the source
of infection. Studies carried out in family members and social contacts of
patients, health workers engaged in their care, and poultry cullers found very
limited, if any, evidence of spread of the virus from one person to another.
Human infections ceased following the rapid destruction – within three days –
of Hong Kong’s entire poultry population, estimated at around 1.5 million birds.
Some experts believe that that drastic action may have averted an influenza

All evidence to date indicates that close contact with dead
or sick birds is the principal source of human infection with the H5N1 virus.
Especially risky behaviours identified include the slaughtering, defeathering,
butchering and preparation for consumption of infected birds. In a few cases,
exposure to chicken faeces when children played in an area frequented by
free-ranging poultry is thought to have been the source of infection. Swimming
in water bodies where the carcasses of dead infected birds have been discarded
or which may have been contaminated by faeces from infected ducks or other
birds might be another source of exposure. In some cases, investigations have been
unable to identify a plausible exposure source, suggesting that some as yet
unknown environmental factor, involving contamination with the virus, may be
implicated in a small number of cases. Some explanations that have been put
forward include a possible role of peri-domestic birds, such as pigeons, or the
use of untreated bird faeces as fertilizer. At present, H5N1 avian influenza
remains largely a disease of birds. The species barrier is significant: the
virus does not easily cross from birds to infect humans. Despite the infection
of tens of millions of poultry over large geographical areas since mid-2003,
fewer than 200 human cases have been laboratory confirmed. For unknown reasons,
most cases have occurred in rural and periurban households where small flocks
of poultry are kept. Again for unknown reasons, very few cases have been
detected in presumed high-risk groups, such as commercial poultry workers,
workers at live poultry markets, cullers, veterinarians, and health staff
caring for patients without adequate protective equipment. Also lacking is an
explanation for the puzzling concentration of cases in previously healthy
children and young adults. Research is urgently needed to better define the
exposure circumstances, behaviours, and possible genetic or immunological
factors that might enhance the likelihood of human infection.

Investigations of all the most recently confirmed human cases, in China,
Indonesia, and Turkey, have identified direct contact with infected birds as
the most likely source of exposure. When assessing possible cases, the level of
clinical suspicion should be heightened for persons showing influenza-like
illness, especially with fever and symptoms in the lower respiratory tract, who
have a history of close contact with birds in an area where confirmed outbreaks
of highly pathogenic H5N1 avian influenza are occurring. Exposure to an
environment that may have been contaminated by faeces from infected birds is a
second, though less common, source of human infection. To date, not all human
cases have arisen from exposure to dead or visibly ill domestic birds. Research
published in 2005 has shown that domestic ducks can excrete large quantities of
highly pathogenic virus without showing signs of illness. A history of poultry
consumption in an affected country is not a risk factor, provided the food was
thoroughly cooked and the person was not involved in food preparation. As no
efficient human-to-human transmission of the virus is known to be occurring anywhere,
simply travelling to a country with ongoing outbreaks in poultry or sporadic
human cases does not place a traveller at enhanced risk of infection, provided
the person did not visit live or “wet” poultry markets, farms, or other
environments where exposure to diseased birds may have occurred.

In many patients, the disease caused by the H5N1 virus follows an unusually
aggressive clinical course, with rapid deterioration and high fatality. Like
most emerging disease, H5N1 influenza in humans is poorly understood. Clinical
data from cases in 1997 and the current outbreak are beginning to provide a
picture of the clinical features of disease, but much remains to be learned.
Moreover, the current picture could change given the propensity of this virus
to mutate rapidly and unpredictably.

The incubation period for H5N1 avian influenza may be
longer than that for normal seasonal influenza, which is around two to three
days. Current data for H5N1 infection indicate an incubation period ranging
from two to eight days and possibly as long as 17 days. However, the
possibility of multiple exposure to the virus makes it difficult to define the
incubation period precisely. WHO currently recommends that an incubation period
of seven days be used for field investigations and the monitoring of patient

Initial symptoms include a high fever, usually with a
temperature higher than 38oC, and influenza-like symptoms. Diarrhoea, vomiting,
abdominal pain, chest pain, and bleeding from the nose and gums have also been
reported as early symptoms in some patients. Watery diarrhoea without blood
appears to be more common in H5N1 avian influenza than in normal seasonal
influenza. The spectrum of clinical symptoms may, however, be broader, and not
all confirmed patients have presented with respiratory symptoms. In two
patients from southern Viet Nam, the clinical diagnosis was acute encephalitis;
neither patient had respiratory symptoms at presentation. In another case, from
Thailand, the patient presented with fever and diarrhoea, but no respiratory
symptoms. All three patients had a recent history of direct exposure to
infected poultry.

One feature seen in many patients is the development of
manifestations in the lower respiratory tract early in the illness. Many
patients have symptoms in the lower respiratory tract when they first seek
treatment. On present evidence, difficulty in breathing develops around five
days following the first symptoms. Respiratory distress, a hoarse voice, and a
crackling sound when inhaling are commonly seen. Sputum production is variable
and sometimes bloody. Most recently, blood-tinted respiratory secretions have
been observed in Turkey. Almost all patients develop pneumonia. During the Hong
Kong outbreak, all severely ill patients had primary viral pneumonia, which did
not respond to antibiotics. Limited data on patients in the current outbreak
indicate the presence of a primary viral pneumonia in H5N1, usually without
microbiological evidence of bacterial supra-infection at presentation. Turkish
clinicians have also reported pneumonia as a consistent feature in severe
cases; as elsewhere, these patients did not respond to treatment with

In patients infected with the H5N1 virus, clinical
deterioration is rapid. In Thailand, the time between onset of illness to the
development of acute respiratory distress was around six days, with a range of
four to 13 days. In severe cases in Turkey, clinicians have observed
respiratory failure three to five days after symptom onset. Another common
feature is multiorgan dysfunction. Common laboratory abnormalities, include
leukopenia (mainly lymphopenia), mild-to-moderate thrombocytopenia, elevated
aminotransferases, and with some instances of disseminated intravascular

Limited evidence suggests that some antiviral drugs,
notably oseltamivir (commercially known as Tamiflu), can reduce the duration of
viral replication and improve prospects of survival, provided they are
administered within 48 hours following symptom onset. However, prior to the
outbreak in Turkey, most patients have been detected and treated late in the
course of illness. For this reason, clinical data on the effectiveness of
oseltamivir are limited. Moreover, oseltamivir and other antiviral drugs were
developed for the treatment and prophylaxis of seasonal influenza, which is a
less severe disease associated with less prolonged viral replication.
Recommendations on the optimum dose and duration of treatment for H5N1 avian
influenza, also in children, need to undergo urgent review, and this is being
undertaken by WHO.

In suspected cases, oseltamivir should be prescribed as
soon as possible (ideally, within 48 hours following symptom onset) to maximize
its therapeutic benefits. However, given the significant mortality currently
associated with H5N1 infection and evidence of prolonged viral replication in
this disease, administration of the drug should also be considered in patients
presenting later in the course of illness.

Currently recommended doses of oseltamivir for the
treatment of influenza are contained in the product
 at the manufacturer’s web site. The recommended dose of
oseltamivir for the treatment of influenza, in adults and adolescents 13 years
of age and older, is 150 mg per day, given as 75 mg twice a day for five days.
Oseltamivir is not indicated for the treatment of children younger than one
year of age.

As the duration of viral replication may be prolonged in
cases of H5N1 infection, clinicians should consider increasing the duration of
treatment to seven to ten days in patients who are not showing a clinical
response. In cases of severe infection with the H5N1 virus, clinicians may need
to consider increasing the recommended daily dose or the duration of treatment,
keeping in mind that doses above 300 mg per day are associated with increased
side effects. For all treated patients, consideration should be given to taking
serial clinical samples for later assay to monitor changes in viral load, to
assess drug susceptibility, and to assess drug levels. These samples should be
taken only in the presence of appropriate measures for infection control.

In severely ill H5N1 patients or in H5N1 patients with
severe gastrointestinal symptoms, drug absorption may be impaired. This
possibility should be considered when managing these patients.

Avian influenza: methods
for the disease control

Avian influenza, also known as bird flu, is a
highly contagious viral disease affecting mainly chickens, turkeys, ducks and
other birds.

While avian influenza caused by highly pathogenic
virus strains have sometimes been shown to infect man, this disease should not
be confused with human influenza, a common human disease. However, avian influenza
under certain circumstances could pose a serious threat to humans.

The OIE, through its experts and its world
network of Reference Laboratories and Collaborating Centres remain at the
disposal of all Member Countries requesting assistance in the defintion of
policies on diagnosis, control and eradication of the disease in animals.

The following information is meant to help
Governments and the Veterinary Services of Member Countries which are affected
by or which want to protect the territories from the disease :

Background information

and recommendations: FAO/OIE/WHO Expert Consultation on Avian Influenza
Rome (Italy) 3-4 February 2004

Message from Dr Bernard Vallat, OIE Director General –
Meeting on Avian Infuenza in Thailand

addressed to the Honourable Prime Minister of Vietnam

use of vaccination as an option for the control of avian influenza
Capua & Stefano Marangon)

Report of the Ad hoc Group on Avian Influenza
 (non official – to be
submitted to OIE International Committee in May 2004)

Safety of International Trade

– Actual
Avian Influenza Chapter

– Actual Newcastle
Disease Chapter

– Proposed
Chapter on Avian Influenza
 (non official – to be submitted to OIE
International Committee in May 2004)

Vaccines and Diagnostic Methods

influenza chapter
 and Sampling

– List
of OIE Reference Laboratories and other experts on avian influenza

Methods of Humane Killing and Carcass

– Provisional
Report of the OIE Ad hoc Group on Humane Killing of animals

– Slaughter
of poultry for disease control purposes

– Provisional
Report of the OIE Ad hoc Group on the Slaughter of animals for human

– Provisional
Report of the OIE Ad hoc Group on Carcass Disposal

– Interim
Guidelines on protection of farmers and slaughterhouses workers

Food Safety

– Risks for

Description of the disease

– Disease card

Guidelines for Control of the Disease

– Conclusions
and recommendations: FAO/OIE/WHO Expert Consultation on Avian Influenza
Rome (Italy) 3-4 February 2004

– Extract
from IZSV Contingency Manual for Avian Influenza
 (Avian Influenza, Eds
Edizioni Tecnico Scientifiche, Bologna, Italy, 2000)