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.
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.
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.
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.
Exposure is considered most likely during slaughter, defeathering,
butchering, and preparation of poultry for cooking.
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.
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.
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.
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.
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.
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
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.
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.
--------------------------------------------------
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
Redactie: info(at)rijskamp.com
Leeuwarden, december 2005
