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Avian Flu FAQs
Source: The World Health Organization, Feb.
2006
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.
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
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 Southeast 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
Vietnam and in some parts of Cambodia, China, Thailand, and 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 nine Asian nations (listed in
order of reporting): the Republic of Korea, Vietnam, Japan, Thailand,
Cambodia, Lao People’s Democratic Republic, Indonesia, China, and
Malaysia. 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 eleven countries: Cambodia, China, Egypt, Indonesia, Lao
People's Democratic Republic, Myanmar, Nigeria, Pakistan, Thailand,
Turkey, 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.
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 (70°C [158°F] 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?
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
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.
Information Please® Database, © 2007 Pearson Education,
Inc. All rights reserved.
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