Avian influenza frequently
asked questions
revised 5 December 2005
What is avian
influenza?
Avian influenza, or “bird flu”, is a
contagious disease of animals caused by viruses
that normally infect only birds and, less
commonly, pigs. Avian influenza viruses are highly
species-specific, but have, on rare occasions,
crossed the species barrier to infect humans.
In domestic poultry, infection with avian
influenza viruses causes two main forms of
disease, distinguished by low and high extremes of
virulence. The so-called “low pathogenic” form
commonly causes only mild symptoms (ruffled
feathers, a drop in egg production) and may easily
go undetected. The highly pathogenic form is far
more dramatic. It spreads very rapidly through
poultry flocks, causes disease affecting multiple
internal organs, and has a mortality that can
approach 100%, often within 48 hours.
Which viruses cause
highly pathogenic disease?
Influenza A viruses1 have 16 H
subtypes and 9 N subtypes2. Only
viruses of the H5 and H7 subtypes are known to
cause the highly pathogenic form of the disease.
However, not all viruses of the H5 and H7 subtypes
are highly pathogenic and not all will cause
severe disease in poultry.
On present understanding, H5 and H7 viruses are
introduced to poultry flocks in their low
pathogenic form. When allowed to circulate in
poultry populations, the viruses can mutate,
usually within a few months, into the highly
pathogenic form. This is why the presence of an H5
or H7 virus in poultry is always cause for
concern, even when the initial signs of infection
are mild.
Do migratory
birds spread highly pathogenic avian influenza
viruses?
The role of migratory birds in the spread of
highly pathogenic avian influenza is not fully
understood. Wild waterfowl are considered the
natural reservoir of all influenza A viruses. They
have probably carried influenza viruses, with no
apparent harm, for centuries. They are known to
carry viruses of the H5 and H7 subtypes, but
usually in the low pathogenic form. Considerable
circumstantial evidence suggests that migratory
birds can introduce low pathogenic H5 and H7
viruses to poultry flocks, which then mutate to
the highly pathogenic form.
In the past, highly pathogenic viruses have
been isolated from migratory birds on very rare
occasions involving a few birds, usually found
dead within the flight range of a poultry
outbreak. This finding long suggested that wild
waterfowl are not agents for the onward
transmission of these viruses.
Recent events make it likely that some
migratory birds are now directly spreading the
H5N1 virus in its highly pathogenic form. Further
spread to new areas is expected.
What is special about
the current outbreaks in poultry?
The current outbreaks of highly pathogenic
avian influenza, which began in South-East Asia in
mid-2003, are the largest and most severe on
record. Never before in the history of this
disease have so many countries been simultaneously
affected, resulting in the loss of so many birds.
The causative agent, the H5N1 virus, has proved
to be especially tenacious. Despite the death or
destruction of an estimated 150 million birds, the
virus is now considered endemic in many parts of
Indonesia and Viet Nam and in some parts of
Cambodia, China, Thailand, and possibly also the
Lao People’s Democratic Republic. Control of the
disease in poultry is expected to take several
years.
The H5N1 virus is also of particular concern
for human health, as explained below.
Which countries have
been affected by outbreaks in poultry?
From mid-December 2003 through early February
2004, poultry outbreaks caused by the H5N1 virus
were reported in eight Asian nations (listed in
order of reporting): the Republic of Korea, Viet
Nam, Japan, Thailand, Cambodia, Lao People’s
Democratic Republic, Indonesia, and China. Most of
these countries had never before experienced an
outbreak of highly pathogenic avian influenza in
their histories.
In early August 2004, Malaysia reported its
first outbreak of H5N1 in poultry, becoming the
ninth Asian nation affected. Russia reported its
first H5N1 outbreak in poultry in late July 2005,
followed by reports of disease in adjacent parts
of Kazakhstan in early August. Deaths of wild
birds from highly pathogenic H5N1 were reported in
both countries. Almost simultaneously, Mongolia
reported the detection of H5N1 in dead migratory
birds. In October 2005, H5N1 was confirmed in
poultry in Turkey and Romania. Outbreaks in wild
and domestic birds are under investigation
elsewhere.
Japan, the Republic of Korea, and Malaysia have
announced control of their poultry outbreaks and
are now considered free of the disease. In the
other affected areas, outbreaks are continuing
with varying degrees of severity.
What are the
implications for human health?
The widespread persistence of H5N1 in poultry
populations poses two main risks for human health.
The first is the risk of direct infection when
the virus passes from poultry to humans, resulting
in very severe disease. Of the few avian influenza
viruses that have crossed the species barrier to
infect humans, H5N1 has caused the largest number
of cases of severe disease and death in humans.
Unlike normal seasonal influenza, where infection
causes only mild respiratory symptoms in most
people, the disease caused by H5N1 follows an
unusually aggressive clinical course, with rapid
deterioration and high fatality. Primary viral
pneumonia and multi-organ failure are common. In
the present outbreak, more than half of those
infected with the virus have died. Most cases have
occurred in previously healthy children and young
adults.
A second risk, of even greater concern, is that
the virus – if given enough opportunities –
will change into a form that is highly infectious
for humans and spreads easily from person to
person. Such a change could mark the start of a
global outbreak (a pandemic).
Where have human cases
occurred?
In the current outbreak, laboratory-confirmed
human cases have been reported in four countries:
Cambodia, Indonesia, Thailand, and Viet Nam.
Hong Kong has experienced two outbreaks in the
past. In 1997, in the first recorded instance of
human infection with H5N1, the virus infected 18
people and killed 6 of them. In early 2003, the
virus caused two infections, with one death, in a
Hong Kong family with a recent travel history to
southern China.
How do people become
infected?
Direct contact with infected poultry, or
surfaces and objects contaminated by their faeces,
is presently considered the main route of human
infection. To date, most human cases have occurred
in rural or periurban areas where many households
keep small poultry flocks, which often roam
freely, sometimes entering homes or sharing
outdoor areas where children play. As infected
birds shed large quantities of virus in their
faeces, opportunities for exposure to infected
droppings or to environments contaminated by the
virus are abundant under such conditions.
Moreover, because many households in Asia depend
on poultry for income and food, many families sell
or slaughter and consume birds when signs of
illness appear in a flock, and this practice has
proved difficult to change. Exposure is considered
most likely during slaughter, defeathering,
butchering, and preparation of poultry for
cooking.
Is it safe to eat
poultry and poultry products?
Yes, though certain precautions should be
followed in countries currently experiencing
outbreaks. In areas free of the disease, poultry
and poultry products can be prepared and consumed
as usual (following
good hygienic practices and proper cooking),
with no fear of acquiring infection with the H5N1
virus.
In areas experiencing outbreaks, poultry and
poultry products can also be safely consumed
provided these items are properly cooked and properly
handled during food preparation. The H5N1
virus is sensitive to heat. Normal temperatures
used for cooking (70oC in all parts of
the food) will kill the virus. Consumers need to
be sure that all parts of the poultry are fully
cooked (no “pink” parts) and that eggs, too,
are properly cooked (no “runny” yolks).
Consumers should also be aware of the risk of
cross-contamination. Juices from raw poultry and
poultry products should never be allowed, during
food preparation, to touch or mix with items eaten
raw. When handling raw poultry or raw poultry
products, persons involved in food preparation
should wash their hands thoroughly and clean and
disinfect surfaces in contact with the poultry
products Soap and hot water are sufficient for
this purpose.
In areas experiencing outbreaks in poultry, raw
eggs should not be used in foods that will not be
further heat-treated as, for example by cooking or
baking.
Avian influenza is not transmitted through
cooked food. To date, no evidence indicates that
anyone has become infected following the
consumption of properly cooked poultry or poultry
products, even when these foods were contaminated
with the H5N1 virus.
Does the virus
spread easily from birds to humans?
No. Though more than 100 human cases have
occurred in the current outbreak, this is a small
number compared with the huge number of birds
affected and the numerous associated opportunities
for human exposure, especially in areas where
backyard flocks are common. It is not presently
understood why some people, and not others, become
infected following similar exposures.
What about the pandemic
risk?
A pandemic can start when three conditions have
been met: a new influenza virus subtype emerges;
it infects humans, causing serious illness; and it
spreads easily and sustainably among humans. The
H5N1 virus amply meets the first two conditions:
it is a new virus for humans (H5N1 viruses have
never circulated widely among people), and it has
infected more than 100 humans, killing over half
of them. No one will have immunity should an
H5N1-like pandemic virus emerge.
All prerequisites for the start of a pandemic
have therefore been met save one: the
establishment of efficient and sustained
human-to-human transmission of the virus. The risk
that the H5N1 virus will acquire this ability will
persist as long as opportunities for human
infections occur. These opportunities, in turn,
will persist as long as the virus continues to
circulate in birds, and this situation could
endure for some years to come.
What changes are needed
for H5N1 to become a pandemic virus?
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.
What is the significance
of limited human-to-human transmission?
Though rare, instances of limited
human-to-human transmission of H5N1 and other
avian influenza viruses have occurred in
association with outbreaks in poultry and should
not be a cause for alarm. In no instance has the
virus spread beyond a first generation of close
contacts or caused illness in the general
community. Data from these incidents suggest that
transmission requires very close contact with an
ill person. Such incidents must be thoroughly
investigated but – provided the investigation
indicates that transmission from person to person
is very limited – such incidents will not change
the WHO overall assessment of the pandemic risk.
There have been a number of instances of avian
influenza infection occurring among close family
members. It is often impossible to determine if
human-to-human transmission has occurred since the
family members are exposed to the same animal and
environmental sources as well as to one another.
How serious is the
current pandemic risk?
The risk of pandemic influenza is serious. With
the H5N1 virus now firmly entrenched in large
parts of Asia, the risk that more human cases will
occur will persist. Each additional human case
gives the virus an opportunity to improve its
transmissibility in humans, and thus develop into
a pandemic strain. The recent spread of the virus
to poultry and wild birds in new areas further
broadens opportunities for human cases to occur.
While neither the timing nor the severity of the
next pandemic can be predicted, the probability
that a pandemic will occur has increased.
Are there any other
causes for concern?
Yes. Several.
• Domestic ducks can now excrete large
quantities of highly pathogenic virus without
showing signs of illness, and are now acting as a
“silent” reservoir of the virus, perpetuating
transmission to other birds. This adds yet another
layer of complexity to control efforts and removes
the warning signal for humans to avoid risky
behaviours.
• When compared with H5N1 viruses from 1997
and early 2004, H5N1 viruses now circulating are
more lethal to experimentally infected mice and to
ferrets (a mammalian model) and survive longer in
the environment.
• H5N1 appears to have expanded its host
range, infecting and killing mammalian species
previously considered resistant to infection with
avian influenza viruses.
• The behaviour of the virus in its natural
reservoir, wild waterfowl, may be changing. The
spring 2005 die-off of upwards of 6,000 migratory
birds at a nature reserve in central China, caused
by highly pathogenic H5N1, was highly unusual and
probably unprecedented. In the past, only two
large die-offs in migratory birds, caused by
highly pathogenic viruses, are known to have
occurred: in South Africa in 1961 (H5N3) and in
Hong Kong in the winter of 2002–2003 (H5N1).
Why are pandemics such
dreaded events?
Influenza pandemics are remarkable events that
can rapidly infect virtually all countries. Once
international spread begins, pandemics are
considered unstoppable, caused as they are by a
virus that spreads very rapidly by coughing or
sneezing. The fact that infected people can shed
virus before symptoms appear adds to the risk of
international spread via asymptomatic air
travellers.
The severity of disease and the number of
deaths caused by a pandemic virus vary greatly,
and cannot be known prior to the emergence of the
virus. During past pandemics, attack rates reached
25-35% of the total population. Under the best
circumstances, assuming that the new virus causes
mild disease, the world could still experience an
estimated 2 million to 7.4 million deaths
(projected from data obtained during the 1957
pandemic). Projections for a more virulent virus
are much higher. The 1918 pandemic, which was
exceptional, killed at least 40 million people. In
the USA, the mortality rate during that pandemic
was around 2.5%.
Pandemics can cause large surges in the numbers
of people requiring or seeking medical or hospital
treatment, temporarily overwhelming health
services. High rates of worker absenteeism can
also interrupt other essential services, such as
law enforcement, transportation, and
communications. Because populations will be fully
susceptible to an H5N1-like virus, rates of
illness could peak fairly rapidly within a given
community. This means that local social and
economic disruptions may be temporary. They may,
however, be amplified in today’s closely
interrelated and interdependent systems of trade
and commerce. Based on past experience, a second
wave of global spread should be anticipated within
a year.
As all countries are likely to experience
emergency conditions during a pandemic,
opportunities for inter-country assistance, as
seen during natural disasters or localized disease
outbreaks, may be curtailed once international
spread has begun and governments focus on
protecting domestic populations.
What are the most
important warning signals that a pandemic is about
to start?
The most important warning signal comes when
clusters of patients with clinical symptoms of
influenza, closely related in time and place, are
detected, as this suggests human-to-human
transmission is taking place. For similar reasons,
the detection of cases in health workers caring
for H5N1 patients would suggest human-to-human
transmission. Detection of such events should be
followed by immediate field investigation of every
possible case to confirm the diagnosis, identify
the source, and determine whether human-to-human
transmission is occurring.
Studies of viruses, conducted by specialized
WHO reference laboratories, can corroborate field
investigations by spotting genetic and other
changes in the virus indicative of an improved
ability to infect humans. This is why WHO
repeatedly asks affected countries to share
viruses with the international research community.
What is the status
of vaccine development and production?
Vaccines effective against a pandemic virus are
not yet available. Vaccines are produced each year
for seasonal influenza but will not protect
against pandemic influenza. Although a vaccine
against the H5N1 virus is under development in
several countries, no vaccine is ready for
commercial production and no vaccines are expected
to be widely available until several months after
the start of a pandemic.
Some clinical trials are now under way to test
whether experimental vaccines will be fully
protective and to determine whether different
formulations can economize on the amount of
antigen required, thus boosting production
capacity. Because the vaccine needs to closely
match the pandemic virus, large-scale commercial
production will not start until the new virus has
emerged and a pandemic has been declared. Current
global production capacity falls far short of the
demand expected during a pandemic.
What drugs are
available for treatment?
Two drugs (in the neuraminidase inhibitors
class), oseltamivir (commercially known as Tamiflu)
and zanamivir (commercially known as Relenza) can
reduce the severity and duration of illness caused
by seasonal influenza. The efficacy of the
neuraminidase inhibitors depends, among others, on
their early administration ( within 48 hours after
symptom onset). For cases of human infection with
H5N1, the drugs may improve prospects of survival,
if administered early, but clinical data are
limited. The H5N1 virus is expected to be
susceptible to the neuraminidase inhibitors.
Antiviral resistance to neuraminidase inhibitors
has been clinically negligible so far but is
likely to be detected during widespread use during
a pandemic.
An older class of antiviral drugs, the M2
inhibitors amantadine and rimantadine, could
potentially be used against pandemic influenza,
but resistance to these drugs can develop rapidly
and this could significantly limit their
effectiveness against pandemic influenza. Some
currently circulating H5N1 strains are fully
resistant to these the M2 inhibitors. However,
should a new virus emerge through reassortment,
the M2 inhibitors might be effective.
For the neuraminidase inhibitors, the main
constraints – which are substantial – involve
limited production capacity and a price that is
prohibitively high for many countries. At present
manufacturing capacity, which has recently
quadrupled, it will take a decade to produce
enough oseltamivir to treat 20% of the world’s
population. The manufacturing process for
oseltamivir is complex and time-consuming, and is
not easily transferred to other facilities.
So far, most fatal pneumonia seen in cases of
H5N1 infection has resulted from the effects of
the virus, and cannot be treated with antibiotics.
Nonetheless, since influenza is often complicated
by secondary bacterial infection of the lungs,
antibiotics could be life-saving in the case of
late-onset pneumonia. WHO regards it as prudent
for countries to ensure adequate supplies of
antibiotics in advance.
Can a
pandemic be prevented?
No one knows with certainty. The best way to
prevent a pandemic would be to eliminate the virus
from birds, but it has become increasingly
doubtful if this can be achieved within the near
future.
Following a donation by industry, WHO will have
a stockpile of antiviral medications, sufficient
for 3 million treatment courses, by early 2006.
Recent studies, based on mathematical modelling,
suggest that these drugs could be used
prophylactically near the start of a pandemic to
reduce the risk that a fully transmissible virus
will emerge or at least to delay its international
spread, thus gaining time to augment vaccine
supplies.
The success of this strategy, which has never
been tested, depends on several assumptions about
the early behaviour of a pandemic virus, which
cannot be known in advance. Success also depends
on excellent surveillance and logistics capacity
in the initially affected areas, combined with an
ability to enforce movement restrictions in and
out of the affected area. To increase the
likelihood that early intervention using the WHO
rapid-intervention stockpile of antiviral drugs
will be successful, surveillance in affected
countries needs to improve, particularly
concerning the capacity to detect clusters of
cases closely related in time and place.
What
strategic actions are recommended by WHO?
In August 2005, WHO sent all countries a
document outlining recommended
strategic actions for responding to the avian
influenza pandemic threat. Recommended actions aim
to strengthen national preparedness, reduce
opportunities for a pandemic virus to emerge,
improve the early warning system, delay initial
international spread, and accelerate vaccine
development.
Is the world
adequately prepared?
No. Despite an advance warning that has lasted
almost two years, the world is ill-prepared to
defend itself during a pandemic. WHO has urged all
countries to develop preparedness plans, but only
around 40 have done so. WHO has further urged
countries with adequate resources to stockpile
antiviral drugs nationally for use at the start of
a pandemic. Around 30 countries are purchasing
large quantities of these drugs, but the
manufacturer has no capacity to fill these orders
immediately. On present trends, most developing
countries will have no access to vaccines and
antiviral drugs throughout the duration of a
pandemic.
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1 Influenza viruses are grouped into
three types, designated A, B, and C. Influenza A
and B viruses are of concern for human health.
Only influenza A viruses can cause pandemics.
2 The H subtypes are epidemiologically
most important, as they govern the ability of the
virus to bind to and enter cells, where
multiplication of the virus then occurs. The N
subtypes govern the release of newly formed virus
from the cells
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