Back to Infectious Disease Articles
Thursday 27th July, 2006
If given enough opportunities, the H5N1 can change into a highly
infectious form that spreads easily from person to person.
The World Health Organization (WHO) has warned of a
substantial risk of an influenza epidemic in the near future, most
probably from the H5N1 type of avian influenza virus.
One of the primary concerns is that the virus could quickly
spread across countries as various birds follow their migration routes.
In response, countries have begun planning in anticipation of an
outbreak. While short-term strategies to deal with an outbreak focus on
limiting travel and culling and vaccinating poultry, long-term
strategies require substantial changes in the lifestyles of the most
WHO announced on November, 16, 2005 that an outbreak is
most likely to hit the Hong Kong Special Administrative issue by
mid-December of this year. "If it were to hit in a highly residential
area like Tin Hau, it would be sure to spread like wildfire." Dr. N
Column, Head of Epidemic Prevention announced.
The WHO divides a pandemic into six phases, ranging from
minimal risk of an outbreak to full scale pandemic. Most health
authorities categorize the situation as of 2005 at Phase 3, by which is
meant that human infections of a new sub-type has occurred but there is
little evidence of sustained human-to-human transmission.
Avian influenza (bird flu)
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. 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.
Influenza A viruses have 16 H subtypes and 9 N subtypes.
Only viruses of the H5 and H7 subtypes are known to cause the highly
pathogenic form of the disease. On present understanding, H5 and H7
viruses may circulate and infect poultry flocks in their low pathogenic
form. The viruses can then 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.
Risks posed to humans
The first risk that the virus poses to humans 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.
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
The second and greater risk, 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).
Are you a doctor or a nurse?
Do you want to join the Doctors Lounge online medical community?
Participate in editorial activities (publish, peer review, edit) and
give a helping hand to the largest online community of patients.
Click on the link below to see the requirements:
Doctors Lounge Membership
Mode of transmission
Human influenza is transmitted by inhalation of infectious
droplets and droplet nuclei, by direct contact, and perhaps, by indirect
(fomite) contact, with self-inoculation onto the upper respiratory tract
or conjunctival mucosa.
Currently, H5N1 does not spread easily among humans. 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
H5N1 can be transmitted to humans by several methods:
Animal to human
Environment to human
Human to human
1. Animal to human transmission
Most patients to date have had a history of direct contact
with poultry. Exposure to ill poultry and butchering of birds were
associated with seropositivity for influenza A (H5N1).
Direct contact with infected poultry is presently
considered the main route of human infection. Plucking and preparing of
diseased birds; handling fighting cocks; playing with poultry,
particularly asymptomatic infected ducks; and consumption of duck?s
blood or possibly undercooked poultry have all been implicated.
Transmission to felids has been observed by feeding raw
infected chickens to tigers and leopards in zoos in Thailand and to
domestic cats under experimental conditions.
It is considered safe to eat poultry and poultry products
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.
Normal temperatures used for cooking (70?C in all parts of
the food) will kill the virus in areas experiencing outbreaks. 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. 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).
Soap and hot water are sufficient to disinfect the surfaces
that come in contact with poultry products and for cleaning in persons
involved in handling raw poultry or in food preparation.
2. Environment to human transmission
Given the survival of influenza A (H5N1) in the
environment, several other modes of transmission are theoretically
possible. Oral ingestion of contaminated water during swimming and
direct intranasal or conjunctival inoculation during exposure to water
are other potential modes, as is contamination of hands from infected
fomites and subsequent self-inoculation. The widespread use of untreated
poultry feces as fertilizer is another possible risk factor.
3. Human to human transmission
Human-to-human transmission of influenza A (H5N1) has been
suggested in several household
clusters and in one case of apparent child-to-mother transmission.
Intimate contact without the use of precautions was implicated, and so
far no case of human-to-human transmission by small-particle aerosols
has been identified.
Recently, intensified surveillance of contacts of patients
by reverse-transcriptase?polymerase-chain-reaction (RT-PCR) assay has
led to the detection of mild cases, more infections in older adults, and
an increased number and duration of clusters in families in northern
Vietnam, findings suggesting that the local virus strains may be
adapting to humans.
However, epidemiologic and virologic studies are needed to
confirm these findings. To date, the risk of nosocomial transmission to
health care workers has been low, even when appropriate
isolation measures were not used. However, one case of severe illness
was reported in a nurse exposed to an infected patient in Vietnam.
The current outbreak
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
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. Other countries
have also reported poultry outbreaks caused by the H5N1 virus such as
the Republic of Korea, Japan, Malaysia, Russia, Kazakhstan, Mongolia;
and most recently Turkey and Romania. Most of these countries had never
before experienced an outbreak of highly pathogenic avian influenza in
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.
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 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 can then mutate to the highly pathogenic form. In
such cases migratory birds would be directly spreading the H5N1 virus in
its highly pathogenic form. Further spread to new areas would thus be
The risk of a pandemic
A pandemic can start when three conditions have been met:
A new influenza virus subtype emerges
It infects humans, causing serious illness
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
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.
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.
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
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.
If an influenza pandemic occurs the condition can rapidly
affect 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 travelers.
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
Pandemics can cause large surges in the numbers of people
requiring or seeking medical or hospital treatment, temporarily
overwhelming health services. The high rates of illness could also have
devastating effects on world commerce.
Other causes for concern
? 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
? 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.
? H5N1 appears to have expanded its host range, infecting
and killing mammalian species previously considered resistant to
infection with avian influenza viruses.
? The behavior 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).
The clinical spectrum of influenza A (H5N1) in humans is
based on descriptions of hospitalized patients.
The frequencies of milder illnesses, subclinical
infections, and atypical presentations (e.g., encephalopathy and
gastroenteritis) have not been determined, but case reports indicate
that each occurs. Most patients have been previously healthy young
children or adults.
The incubation period of avian influenza A (H5N1) may be
longer than for other known human influenzas with ranges of up to eight
days. The case-to-case intervals in household clusters have generally
been 2 to 5 days, but the upper limit has been 8 to 17 days, possibly
owing to unrecognized exposure to infected animals or environmental
Most patients have initial symptoms of high fever
(typically a temperature of more than 38?C) and an influenza-like
illness with lower respiratory tract symptoms. Upper respiratory tract
symptoms are present only sometimes. Diarrhea, vomiting, abdominal pain,
pleuritic pain, and bleeding from the nose and gums have also been
reported early in the course of illness in some patients.
Lower respiratory tract manifestations develop early in the
course of illness and are usually found at presentation. In one series,
dyspnea developed a median of 5 days after the onset of illness (range,
1 to 16). Respiratory distress, tachypnea, and inspiratory crackles are
common. Sputum production is variable and sometimes bloody. Almost all
patients have clinically apparent pneumonia; radiographic changes
include diffuse, multifocal, or patchy infiltrates; interstitial
infiltrates; and segmental or lobular consolidation with air
bronchograms. Radiographic abnormalities were present a median of 7 days
after the onset of fever in one study (range, 3 to 17). In Ho Chi Minh
City, Vietnam, multifocal consolidation involving at least two zones was
the most common abnormality among patients at the time of admission.
Pleural effusions are uncommon. Limited microbiologic data indicate that
this process is a primary viral pneumonia, usually without bacterial
suprainfection at the time of hospitalization.
Progression to respiratory failure has been associated with
diffuse, bilateral, ground-glass infiltrates and manifestations of the
acute respiratory distress syndrome (ARDS). In Thailand,
15 the median time from the onset of illness to ARDS was 6 days (range,
4 to 13). Multiorgan failure with signs of renal dysfunction and
sometimes cardiac compromise, including cardiac dilatation and
supraventricular tachyarrhythmias, has been common.
Recent avian influenza A (H5N1) infections have caused high
rates of death among infants and young children. The case fatality rate
was 89 percent among those younger than 15 years of age in Thailand.
Death has occurred an average of 9 or 10 days after the onset of illness
(range, 6 to 30), and most patients have died of progressive respiratory
Common laboratory findings have been leukopenia,
particularly lymphopenia; mild-to-moderate
thrombocytopenia; and slightly or moderately elevated aminotransferase
levels. Marked hyperglycemia, perhaps related to corticosteroid use, and
elevated creatinine levels also occur. In Thailand, an increased risk of
death was associated with decreased leukocyte, platelet, and
particularly, lymphocyte counts at the time of admission.
Antemortem diagnosis of influenza A (H5N1) has been
confirmed by viral isolation, the detection of H5-specific RNA, or both
methods. Although avian influenza virus in humans can be detected with
standard influenza virus tests, these tests have not always proved
Unlike human influenza A infection, avian influenza A
(H5N1) infection may be associated with a higher frequency of virus
detection and higher viral RNA levels in pharyngeal than in nasal
samples. In Vietnam, the interval from the onset of illness to the
detection of viral RNA in throat-swab samples ranged from 2 to 15 days
(median, 5.5), and the viral loads in pharyngeal swabs 4 to 8 days after
the onset of illness were at least 10 times as high among patients with
influenza A (H5N1).
Commercial rapid antigen tests are less sensitive in
detecting influenza A (H5N1) infections than are RT-PCR assays. In
Thailand, the results of rapid antigen testing were positive in only 4
of 11 patients with culture-positive influenza A (H5N1) (36 percent) 4
to 18 days after the onset of illness.
Microneutralization requires use of the live virus to
interact with antibodies from the patient's blood; because live virus is
required, for safety reasons the test can only be done in a level three
Antiviral drugs such as olestamivir (commercially known as
Tamiflu), zanamivir (commercially known as Relenza) and amantadine are
sometimes effective in both preventing and treating the infection.
Countries have been stockpiling olestamivir, but may shift towards
zanamivir due to a November 2005 issue of JAMA, which reported
olestamivir resistant strains of avian flu in Vietnam.
Further, as a result of widespread use of the antiviral
drug amantadine as a preventive or treatment for chickens in China
starting in the late 1990s, some strains of the avian flu virus in Asia
have developed drug resistance against amantadine.
Vaccines effective against a pandemic virus are not yet
available. Vaccines take at least four months to produce and must be
prepared for each subtype. 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.
developed by Glaxo SmithKline (GSK) has shown promising results in