Avian
influenza (bird flu) frequently asked questions
updated 14 October 2005
· What is avian influenza?
· Which viruses cause highly pathogenic disease?
· Do migratory birds spread the disease?
· What is special about the current outbreaks in
poultry?
· Which countries have been affected by outbreaks in
poultry?
· What are the implications for human health?
· Where have human cases occurred?
· How do people become infected?
· Does the virus spread easily from birds to humans?
· What about the pandemic risk?
· What changes are needed for H5N1 to become a pandemic
virus?
· What is the significance of limited human-to-human
transmission?
· How serious is the current pandemic risk?
· Are there any other causes for concern?
· Why are pandemics such dreaded events?
· What are the most important warning signals that a
pandemic is about to start?
· What is the status of vaccine development and
production?
· What drugs are available for treatment?
· Can a pandemic be prevented?
· What strategic actions are recommended by WHO?
· Is the world adequately prepared?
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 Vietnam.
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. There is no evidence that
properly cooked poultry or eggs can be a source of infection.
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 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. 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 on their 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.
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.
--------------------------------------------------
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