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...the official
Bird Flu Damper for Homeland Security
Bird Flu (Avian Influenza) FAQ's
Provided by the World Health
Organization (WHO)
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.
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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.
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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.
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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.
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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.
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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).
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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).
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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.
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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.
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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.
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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.
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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.
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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.
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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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