Avian influenza (“bird flu”) and the significance of its
transmission to human
The disease in birds: impact and control measures
Avian influenza is an infectious disease of birds caused by
type A strains of the influenza virus. The disease, which was
first identified in Italy more than 100 years ago, occurs
worldwide.
All birds are thought to be susceptible to infection with
avian influenza, though some species are more resistant to
infection than others. Infection causes a wide spectrum of
symptoms in birds, ranging from mild illness to a highly
contagious and rapidly fatal disease resulting in severe
epidemics. The latter is known as “highly pathogenic avian
influenza”. This form is characterized by sudden onset, severe
illness, and rapid death, with a mortality that can approach
100%.
Fifteen subtypes of influenza virus are known to infect birds,
thus providing an extensive reservoir of influenza viruses
potentially circulating in bird populations. To date, all
outbreaks of the highly pathogenic form have been caused by
influenza A viruses of subtypes H5 and H7.
Migratory waterfowl – most notably wild ducks – are the
natural reservoir of avian influenza viruses, and these birds
are also the most resistant to infection. Domestic poultry,
including chickens and turkeys, are particularly susceptible
to epidemics of rapidly fatal influenza.
Direct or indirect contact of domestic flocks with wild
migratory waterfowl has been implicated as a frequent cause of
epidemics. Live bird markets have also played an important
role in the spread of epidemics.
Recent research has shown that viruses of low pathogenicity
can, after circulation for sometimes short periods in a
poultry population, mutate into highly pathogenic viruses.
During a 1983–1984 epidemic in the United States of America,
the H5N2 virus initially caused low mortality, but within six
months became highly pathogenic, with a mortality approaching
90%. Control of the outbreak required destruction of more than
17 million birds at a cost of nearly US$ 65 million. During a
1999–2001 epidemic in Italy, the H7N1 virus, initially of low
pathogenicity, mutated within 9 months to a highly pathogenic
form. More than 13 million birds died or were destroyed.
The quarantining of infected farms and destruction of infected
or potentially exposed flocks are standard control measures
aimed at preventing spread to other farms and eventual
establishment of the virus in a country’s poultry population.
Apart from being highly contagious, avian influenza viruses
are readily transmitted from farm to farm by mechanical means,
such as by contaminated equipment, vehicles, feed, cages, or
clothing. Highly pathogenic viruses can survive for long
periods in the environment, especially when temperatures are
low. Stringent sanitary measures on farms can, however, confer
some degree of protection.
In the absence of prompt control measures backed by good
surveillance, epidemics can last for years. For example, an
epidemic of H5N2 avian influenza, which began in Mexico in
1992, started with low pathogenicity, evolved to the highly
fatal form, and was not controlled until 1995.
A constantly mutating virus: two consequences
All type A influenza viruses, including those that regularly
cause seasonal epidemics of influenza in humans, are
genetically labile and well adapted to elude host defenses.
Influenza viruses lack mechanisms for the “proofreading” and
repair of errors that occur during replication. As a result of
these uncorrected errors, the genetic composition of the
viruses changes as they replicate in humans and animals, and
the existing strain is replaced with a new antigenic variant.
These constant, permanent and usually small changes in the
antigenic composition of influenza A viruses are known as
antigenic “drift”.
The tendency of influenza viruses to undergo frequent and
permanent antigenic changes necessitates constant monitoring
of the global influenza situation and annual adjustments in
the composition of influenza vaccines. Both activities have
been a cornerstone of the WHO Global Influenza Programme since
its inception in 1947.
Influenza viruses have a second characteristic of great public
health concern: influenza A viruses, including subtypes from
different species, can swap or “reassort” genetic materials
and merge. This reassortment process, known as antigenic
“shift”, results in a novel subtype different from both parent
viruses. As populations will have no immunity to the new
subtype, and as no existing vaccines can confer protection,
antigenic shift has historically resulted in highly lethal
pandemics. For this to happen, the novel subtype needs to have
genes from human influenza viruses that make it readily
transmissible from person to person for a sustainable period.
Conditions favourable for the emergence of antigenic shift
have long been thought to involve humans living in close
proximity to domestic poultry and pigs. Because pigs are
susceptible to infection with both avian and mammalian
viruses, including human strains, they can serve as a “mixing
vessel” for the scrambling of genetic material from human and
avian viruses, resulting in the emergence of a novel subtype.
Recent events, however, have identified a second possible
mechanism. Evidence is mounting that, for at least some of the
15 avian influenza virus subtypes circulating in bird
populations, humans themselves can serve as the “mixing
vessel”.
Human infection with avian influenza viruses: a timeline
Avian influenza viruses do not normally infect species other
than birds and pigs. The first documented infection of humans
with an avian influenza virus occurred in Hong Kong in 1997,
when the H5N1 strain caused severe respiratory disease in 18
humans, of whom 6 died. The infection of humans coincided with
an epidemic of highly pathogenic avian influenza, caused by
the same strain, in Hong Kong’s poultry population.
Extensive investigation of that outbreak determined that close
contact with live infected poultry was the source of human
infection. Studies at the genetic level further determined
that the virus had jumped directly from birds to humans.
Limited transmission to health care workers occurred, but did
not cause severe disease.
Rapid destruction – within three days – of Hong Kong’s entire
poultry population, estimated at around 1.5 million birds,
reduced opportunities for further direct transmission to
humans, and may have averted a pandemic.
That event alarmed public health authorities, as it marked the
first time that an avian influenza virus was transmitted
directly to humans and caused severe illness with high
mortality. Alarm mounted again in February 2003, when an
outbreak of H5N1 avian influenza in Hong Kong caused 2 cases
and 1 death in members of a family who had recently travelled
to southern China. Another child in the family died during
that visit, but the cause of death is not known.
Two other avian influenza viruses have recently caused illness
in humans. An outbreak of highly pathogenic H7N7 avian
influenza, which began in the Netherlands in February 2003,
caused the death of one veterinarian two months later, and
mild illness in 83 other humans. Mild cases of avian influenza
H9N2 in children occurred in Hong Kong in 1999 (two cases) and
in mid-December 2003 (one case). H9N2 is not highly pathogenic
in birds.
The most recent cause for alarm occurred in January 2004, when
laboratory tests confirmed the presence of H5N1 avian
influenza virus in human cases of severe respiratory disease
in the northern part of Viet Nam.
Why H5N1 is of particular concern
Of the 15 avian influenza virus subtypes, H5N1 is of
particular concern for several reasons. H5N1 mutates rapidly
and has a documented propensity to acquire genes from viruses
infecting other animal species. Its ability to cause severe
disease in humans has now been documented on two occasions. In
addition, laboratory studies have demonstrated that isolates
from this virus have a high pathogenicity and can cause severe
disease in humans. Birds that survive infection excrete virus
for at least 10 days, orally and in faeces, thus facilitating
further spread at live poultry markets and by migratory birds.
The epidemic of highly pathogenic avian influenza caused by
H5N1, which began in mid-December 2003 in the Republic of
Korea and is now being seen in other Asian countries, is
therefore of particular public health concern. H5N1 variants
demonstrated a capacity to directly infect humans in 1997, and
have done so again in Viet Nam in January 2004. The spread of
infection in birds increases the opportunities for direct
infection of humans. If more humans become infected over time,
the likelihood also increases that humans, if concurrently
infected with human and avian influenza strains, could serve
as the “mixing vessel” for the emergence of a novel subtype
with sufficient human genes to be easily transmitted from
person to person. Such an event would mark the start of an
influenza pandemic.
Influenza pandemics: can they be averted?
Based on historical patterns, influenza pandemics can be
expected to occur, on average, three to four times each
century when new virus subtypes emerge and are readily
transmitted from person to person. However, the occurrence of
influenza pandemics is unpredictable. In the 20th century, the
great influenza pandemic of 1918–1919, which caused an
estimated 40 to 50 million deaths worldwide, was followed by
pandemics in 1957–1958 and 1968–1969.
Experts agree that another influenza pandemic is inevitable
and possibly imminent.
Most influenza experts also agree that the prompt culling of
Hong Kong’s entire poultry population in 1997 probably averted
a pandemic.
Several measures can help minimize the global public health
risks that could arise from large outbreaks of highly
pathogenic H5N1 avian influenza in birds. An immediate
priority is to halt further spread of epidemics in poultry
populations. This strategy works to reduce opportunities for
human exposure to the virus. Vaccination of persons at high
risk of exposure to infected poultry, using existing vaccines
effective against currently circulating human influenza
strains, can reduce the likelihood of co-infection of humans
with avian and influenza strains, and thus reduce the risk
that genes will be exchanged. Workers involved in the culling
of poultry flocks must be protected, by proper clothing and
equipment, against infection. These workers should also
receive antiviral drugs as a prophylactic measure.
When cases of avian influenza in humans occur, information on
the extent of influenza infection in animals as well as humans
and on circulating influenza viruses is urgently needed to aid
the assessment of risks to public health and to guide the best
protective measures. Thorough investigation of each case is
also essential. While WHO and the members of its global
influenza network, together with other international agencies,
can assist with many of these activities, the successful
containment of public health risks also depends on the
epidemiological and laboratory capacity of affected countries
and the adequacy of surveillance systems already in place.
While all these activities can reduce the likelihood that a
pandemic strain will emerge, the question of whether another
influenza pandemic can be averted cannot be answered with
certainty.
Clinical course and treatment of human cases of H5N1 avian
influenza
Published information about the clinical course of human
infection with H5N1 avian influenza is limited to studies of
cases in the 1997 Hong Kong outbreak. In that outbreak,
patients developed symptoms of fever, sore throat, cough and,
in several of the fatal cases, severe respiratory distress
secondary to viral pneumonia. Previously healthy adults and
children, and some with chronic medical conditions, were
affected.
Tests for diagnosing all influenza strains of animals and
humans are rapid and reliable. Many laboratories in the WHO
global influenza network have the necessary high-security
facilities and reagents for performing these tests as well as
considerable experience. Rapid bedside tests for the diagnosis
of human influenza are also available, but do not have the
precision of the more extensive laboratory testing that is
currently needed to fully understand the most recent cases and
determine whether human infection is spreading, either
directly from birds or from person to person.
Antiviral drugs, some of which can be used for both treatment
and prevention, are clinically effective against influenza A
virus strains in otherwise healthy adults and children, but
have some limitations. Some of these drugs are also expensive
and supplies are limited.
Experience in the production of influenza vaccines is also
considerable, particularly as vaccine composition changes each
year to match changes in circulating virus due to antigenic
drift. However, at least four months would be needed to
produce a new vaccine, in significant quantities, capable of
conferring protection against a new virus subtype.
WHO
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