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
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
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
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
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
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
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?
• 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
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
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
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
Can a pandemic be
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
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
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
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
Courtesy: World Health
Epidemic and Pandemic
Alert and Response (EPR)