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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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