Avian Influenza (Bird Flu):
Implications for Human Disease
Avian Influenza in Humans
The 2003-2005 Outbreak of H5N1 in Asia
Clinical and Treatment Considerations
WHO and CDC Travel Recommendations
Use of Seasonal Influenza Vaccine in Humans
at Risk for H5N1 Infection
Influenza Pandemic Considerations
Avian influenza is caused by influenza A virus.
More information about avian influenza in bird populations can be found
in the overview titled Avian Influenza (Bird Flu): Agricultural and Wildlife
- Family: Orthomyxoviridae
- Genus: Influenza
- Virions are 80 to 120 nm in diameter and may be
- Eight different segments of negative-stranded RNA
are present; this allows for genetic reassortments in single cells
infected with more than one virus and may result in multiple strains
that are different from the initial ones (see References:
- Type designation is based on the antigenic character
of the M protein located in the virus envelope and the nucleoprotein
within the virus particle. There are three types of influenza viruses
(A, B, and C).
- The virus envelope glycoproteins have hemagglutinin
(HA) and neuraminidase (NA) activity; these characteristics are
used to subtype the A, B, and C viruses.
- Type: Influenza A
- Influenza A viruses are the cause of avian influenza
and also are a major cause of influenza in humans.
- All past influenza pandemics in humans have been
caused by influenza A viruses.
- Influenza A also occurs in pigs, horses, and certain
marine mammals (whales and seals); recently H5N1 has been recognised
in tigers and cats. The H5N1 avian influenza virus circulating in
Asia has expanded its host range to include cats, tigers, and leopards,
which generally have not been considered susceptible to influenza
A (see References: Keawcharoen
2004, Kuiken 2004).
- There are 16 different HA antigens (H1 to H16) and
nine different NA antigens (N1 to N9) for influenza A. Until recently,
15 HA types had been recognised, but a new type (H16) was isolated
from black-headed gulls caught in Sweden and the Netherlands in
1999 and reported in the literature in 2005 (see References:
- Human disease historically has been caused by three
subtypes of HA (H1, H2, and H3) and two subtypes of NA (N1 and N2).
- All known subtypes of influenza A can be found in
birds, but only subtypes H5 and H7 have caused severe outbreaks
of disease in bird populations (known as highly pathogenic avian
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In the past several years, it has become clear that avian influenza
viruses can infect humans. Situations where avian influenza viruses have
been recognised in humans include the following:
No. of Cases
18 (6 deaths)
Cases were linked to an outbreak of H5N1 in
poultry. Sustained person-to-person transmission did not occur
and the outbreak stopped when all birds in the Hong Kong commercial
poultry industry (about 1.4 million) were slaughtered
2 (children ages 4 yr, 13 mo)
Both case-patients had been hospitalised with
influenza-like illness and both recovered uneventfully (see References:
Peiris 1999, Uyeki 2002). No additional cases of person-to-person
transmission occurred. Further investigation demonstrated that
H9N2 strains were circulating in poultry in Hong Kong and China,
although the viruses were not highly pathogenic for birds.
United States (Virginia)
Evidence of infection was found in one person
in Virginia following a poultry outbreak.
2 (1 death)
The 2 case-patients were family members who
had recently travelled to China (see References:
CDC: Basic information about avian influenza). A third family
member died while in China of an undiagnosed respiratory illness).
No direct link between these cases and H5N1infection in poultry
89 (1 death)
During an outbreak of H7N7 avian influenza
in poultry, infection spread to poultry workers and their families
in the area (see References:
Fouchier 2004; Koopmans 2004). Most patients had conjunctivitis
and several complained of influenza-like illness. The death occurred
in a 57-year-old veterinarian. Subsequent serologic testing demonstrated
that additional case-patients had symptomatic infection.
The source of exposure was not determined
(see References: NIAID:
Significant dates in influenza history).
114 (59 deaths), according to official WHO
Vietnam, Thailand, Cambodia, Indonesia
Human cases are associated with an ongoing
extensive outbreak of avian influenza in poultry (see References:
WHO: Cumulative number of confirmed human cases of avian influenza
A (H5N1) since 28 January 2004; WHO: Avian influenza: situation
in Viet Nam, Mar 7, 2005). To date, human-to-human transmission
has been limited. More information on this situation can be found
in the section below.
Canada (British Columbia)
Poultry workers became ill during an outbreak
of H7N3 avian influenza in poultry (see References:
Health Canada 2004).
The source of infection remains unknown (see
References: National Institute
of Allergy and Infectious Diseases: Focus on the Flu).
One childs father was a poultry merchant
(see References: NIAID:
Significant dates in influenza history).
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The 2003-2005 Outbreak of H5N1
An outbreak of HPAI caused by a strain of
H5N1 avian influenza started in Asia in the fall of 2003 and spread in
domestic poultry farms at an historically unprecedented rate. The outbreak
tapered off in spring 2004 but in summer re-emerged in several areas and
is still of great concern. The strain causing the outbreak is genetically
distinct from the one isolated from humans in Hong Kong in 2003.
Areas affected by H5N1 avian influenza in
- Hong Kong
- South Korea
WHO has officially
recognised 114 human cases of H5N1 influenza, 59 of them fatal, as of
September 19, 2005; cases have been reported from Vietnam, Thailand, Cambodia,
and Indonesia (see References:
WHO: Cumulative number of confirmed human cases of avian influenza A [H5N1];
WHO: Situation updates). Media reports put the number higher . A recent
report suggests that low perceived risk and high population exposures
to live chickens are factors that may contribute to the spread of H5N1
in Asia (see References: Fielding
2005). One case of encephalitis has been confirmed as H5N1 (see References:
de Jong 2005).
Guidelines have been issued from WHO and CDC
regarding reporting (see References:
WHO: Cumulative number of confirmed human cases of avian influenza A (H5N1)
since 28 January 2004; CDC: Outbreaks of avian influenza A (H5N1) in Asia
and interim recommendations for evaluation and reporting of suspected
cases United States, 2004).
Sustained person-to-person transmission has
not occurred to date, although a suspected person-to-person transmission
in a family cluster, thought to be an isolated event, occurred in Thailand
in fall 2004 (see References: Ungchusak 2005). In that
situation, an ill child apparently spread the virus to her mother and
aunt. Genetic analysis of the strain circulating indicates that no reassortment
with human genes has occurred.
The virus has, however, shown an ability to
jump species, infecting cats, pigs, tigers, and leopards in recent years.
A summer 2004 study showed that the virus was causing increasingly severe
disease when injected into laboratory mice (see References:
Chen 2004). In August 2005, H5N1 was confirmed in civets in Vietnam
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Clinical and Treatment
A recent report of avian influenza A (H5N1)
in 10 patients in Vietnam (see References:
Hien 2004) demonstrated the following clinical features of the illness:
- For eight of nine patients in whom a history of exposure
to infected birds could be ascertained, the median time of exposure
to onset of illness was 3 days (range, 2 to 4 days).
- All patients presented with fever, shortness of breath,
and cough; median time from onset of illness to hospitalisation was
5.9 days (range, 3 to 8 days).
- Five patients (50%) reported sputum production and
in three of these patients, the sputum was blood-tinged.
- Seven patients (70%) reported diarrhoea.
- None of the patients complained of sore throat, conjunctivitis,
rash, or a runny nose.
- All patients had abnormal chest radiographs at the
time of admission (including extensive bilateral infiltration, lobar
collapse, focal consolidation, and air bronchograms).
- All of the patients had lymphopenia at the time of
presentation; the median lymphocyte count was 700 per cubic millimetre
(range, 250 to 1,100 with the lower limit of normal being 1500).
- Nine of the patients also had thrombocytopenia; the
median platelet count was 75,500 per cubic millimetre (range, 45,000
to 174,000 with the lower limit of normal being 150,000).
- Eight patients (80%) died.
- All patients received broad-spectrum antibiotics and
five were treated with oseltamivir (four of whom died).
The 2004 H5N1 strain is resistant to amantadine
and rimantadine, complicating treatment and prophylaxis for human infections.
The neuraminidase inhibitors are generally effective against influenza
A and may be useful in treatment of and prophylaxis against H5N1 influenza,
although the clinical utility of neuraminidase inhibitors in treating
patients with H5N1 influenza is not yet known.
- Oseltamivir is approved for treatment of influenza
in persons aged 1 year and older and approved for prophylaxis of influenza
in persons aged 13 years and older.
- Zanamivir is approved for treatment of influenza in
persons 7 years and older but is not an approved form prophylaxis.
Another report involving 12 confirmed H5N1
influenza cases from Thailand showed similar findings (see References:
Chotpitayasunondh 2005). Laboratory tests on admission demonstrated leukopenia
in seven (58%), lymphopenia in seven (58%), and thrombocytopenia in four
(33%). Eight (67%) patients died. Acute respiratory distress syndrome
(ARDS) was associated with a fatal outcome, and leukopenia and thrombocytopenia
at time of admission were associated with development of ARDS. All 12
patients had abnormal chest radiographs by 7 days after onset of fever;
two patients had interstitial infiltrates and 10 had patchy lobar infiltrates
in a variety of patterns.
A recent case report of a 4-year-old Vietnamese
child with H5N1 avian influenza who presented in 2004 with encephalitis
demonstrated the following features (see References:
de Jong 2005):
- The child presented with a 2-day history of fever,
headache, vomiting, and severe diarrhoea. (approximately 10 episodes
per day). The stools were watery without blood or mucus.
- Laboratory tests on admission were unremarkable and
chest x-ray was normal.
- On the third day following initial presentation, the
child had a generalised convulsion and became comatose. He developed
respiratory failure and died on the fifth day after initial presentation.
Acute encephalitis of unknown origin was reported as the cause of
death; no autopsy was performed.
- H5N1 influenza A virus was isolated from cerebrospinal
fluid, fecal, throat, and serum specimens.
- The patients 9-year-old sister had died 2 weeks
earlier from a similar clinical syndrome.
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of concerns about the pandemic potential of H5N1, WHO has been working
with laboratories in the WHO influenza network to develop vaccines against
this subtype (see References: WHO: Development
of a vaccine effective against avian influenza H5N1).
- Candidate vaccines were developed during 2003 by network
laboratories in London and in Memphis, Tennessee, for protection against
the strain that was isolated from humans in Hong Kong in February
of that year. However, the 2004 strain is different from that strain.
- In April 2004, WHO made the prototype seed strain
for an H5N1 vaccine available to manufacturers (see References:
WHO: Avian flu: situation in Thailand; status of pandemic vaccine
- The National Institute of Allergy and Infectious Diseases
(NIAID) awarded two contracts to support the production and clinical
testing of an investigation vaccine based on the prototype seed strain
made available by WHO (see References:
NIAID: Press release, May 2004).
- The contracts were awarded to Aventis Pasteur (now
Sanofi Pasteur) of Swiftwater, Pennsylvania, and to Chiron Corporation
of Emeryville, California. Each manufacturer is using established
techniques in which the virus is grown in eggs and then inactivated
and further purified before being formulated into vaccines.
- Clinical trials of candidate H5N1 vaccines are currently
under way (see References: WHO: Avian
flu: situation in Thailand; status of pandemic vaccine development;
Mar 23, 2005. On August 6, 2005, NIAID announced that the Sanofi Pasteur
vaccine was meeting with positive results in the first wave of testing
in healthy adults. However, the amount of antigen needed was 180 mcg
versus the 15 mcg given in annual flu shots, which makes the problem
of adequate production far more acute. Further testing is ongoing,
including trials to determine effectiveness and safety in children
and the elderly (see August 8, 2005.
At this point, it is not clear if prototype
H5 vaccines will offer protection against an emergent pandemic strain.
Research in this area is a high priority because stockpiling prototype
vaccines may be worthwhile if protection against emergent strains can
be demonstrated (see References:
- One recent study demonstrated good cross-protection
against H5N1 in mice following vaccination with an H5 influenza vaccine
created through reverse genetics (see References:
Lipotov 2005). Protection was achieved despite antigenic differences
and incomplete matching between the vaccine strain and the challenge
virus. Although these findings are promising, it is not clear if similar
protection would occur for humans.
- A second study suggested that use of adjuvanted prototype
vaccines may induce antibody capable of neutralising a pandemic strain
until a well-matched vaccine can be made available. In the study,
14 human subjects vaccinated with an adjuvanted influenza A/duck/Singapore
97 (H5N3) vaccine demonstrated higher seroconversion rates to four
strains of H5N1 compared with 11 subjects who were vaccinated with
a nonadjuvanted vaccine (see References:
Stephenson 2005). For those who received the MF59-adjuvanted vaccine,
100% seroconverted to A/HongKong/156/97 and A/HongKong/213/03, 71%
to A/Thailand/16/04, and 43% to A/Vietnam/1203/04.
One way of protecting against all types of
influenza, including emerging pandemic strains, would be a universal flu
vaccine that would not have to be re-engineered each year. The British
company Acambis announced in early August 2005 that it is developing such
a vaccine and has had successful results in animal testing (see References:
Acambis 2005). The vaccine would focus on the M2 viral protein, which
does not change, rather than the surface hemagglutinin and neuraminidase
proteins targeted by traditional vaccines. The universal vaccine is made
through bacterial fermentation technology, which would greatly speed up
the rate of production over that possible with culture in chicken eggs,
plus the vaccine could be produced continuously, since its formulation
would not change. Still, such a vaccine is years away from full testing,
approval, and use. Other researchers are also working on a universal agent.
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WHO and CDC Travel Recommendations
As of Feb 11, 2004, WHO has released the following
advice to international travellers regarding H5N1 influenza (see References:
WHO: Advice to international travellers):
- No restrictions on travel to areas affected by H5N1
are currently recommended.
- Travellers to areas that are experiencing outbreaks
of H5N1 in poultry should avoid contact with live animal markets and
- Since influenza viruses are destroyed by heat, consumers
in areas affected by H5N1 should ensure that all foods from poultry
(including eggs) are thoroughly cooked. In addition, WHO has stressed
the importance of good hygiene practices during handling of poultry
products (eg, good handwashing, prevention of cross-contaminations,
and adequate cooking).
CDC issued a similar advisory to travellers
to Vietnam in March 2005 (last updated August 11 [see References:
CDC: Update: Notice to travellers about avian influenza A]). The advisory
is intended for travellers to Cambodia, China, Indonesia, Malaysia, and
Thailand, as well as Vietnam. CDC recommends the following:
Before You Leave
- Educate yourself and others who may be ravelling with
you about avian influenza A (H5N1).
- Be sure you are up-to-date with all your shots, and
see your doctor or healthcare provider at least 4 to 6 weeks before
travel to get any additional shots or information you may need.
- Assemble a travel health kit containing basic first-aid
and medical supplies. Be sure to include a thermometer and alcohol-based
hand rub for hand hygiene. Additional information is available from
CDC on putting together a kit (see References:
CDC: Travellerss Health Kit).
- Identify in-country healthcare resources in advance
of your trip.
- Check your health insurance plan or get additional
insurance that covers medical evacuation in case you become sick.
Information about medical evacuation services is provided on the US
Department of State website (see References:
US Department of State).
- Avoid places such as poultry farms and bird markets
where live poultry are raised or kept, and avoid contact with sick
or dead poultry.
- As with other infectious illnesses, one of the most
important preventive practices is careful and frequent handwashing.
Cleaning your hands often, using either soap and water or waterless
alcohol-based hand rubs, removes potentially infectious materials
from your skin and helps prevent disease transmission.
- Influenza viruses are destroyed by heat; therefore,
as a precaution, all foods from poultry, including eggs and poultry
blood, should be thoroughly cooked.
- If you become sick with symptoms such as a fever,
difficulty breathing, cough, or any illness that requires prompt medical
attention, a US consular officer can assist you in locating medical
services and informing your family or friends (see References:
Travellerss Health: Illness Abroad).
- It is advisable that you defer further travel until
you are free of symptoms.
After Your Return
- Monitor your health for 10 days.
- If you become ill with fever, difficulty breathing,
cough, or any illness during this period, consult a healthcare provider.
Before you visit a healthcare setting, tell the provider about your
symptoms and recent travel so that he or she can be aware you have
travelled to an area reporting avian influenza.
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Use of Seasonal Influenza
Vaccine in Humans at Risk for H5N1 Infections
On January 30, 2004, WHO released guidelines
for the use of seasonal influenza vaccine among persons at risk for H5N1
influenza (see References: WHO: Guidelines
for the use of seasonal influenza vaccine in humans at risk of H5N1 infection).
WHO is recommending targeted use of seasonal influenza vaccine to reduce
the potential for humans to be infected with H5N1 at the same time that
they are harbouring a human influenza strain. This will decrease the opportunity
for genetic reassortment of the avian H5N1 strain with genes from a human
(H1 or H3) strain and thereby reduce the likelihood that a novel pandemic
strain will emerge from the current situation in Asia.
Groups recommended for vaccination include:
- All persons who expected to be in contact with poultry
or poultry farms suspected or known to be affected with avian influenza
- Cullers involved in destruction of poultry
- People living and working on poultry farms where
H5N1 has been reported or is suspected or where culling takes place
- Healthcare workers involved in the daily care of known
or confirmed human cases of influenza H5N1
- Healthcare workers in emergency care facilities in
areas where there is confirmed occurrence of influenza H5N1 in birds
(provided that sufficient supplies of vaccine are available)
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According to current recommendations from
CDC (see References: CDC: Outbreaks
of avian influenza A (H5N1) in Asia and interim recommendations for evaluation
and reporting of suspected cases, United States, 2004), testing for H5N1
of patients hospitalised in the United States is indicated for patients
who have both of the following conditions:
- Radiographically confirmed pneumonia, acute respiratory
distress syndrome (ARDS), or other severe respiratory illness for
which an alternative diagnosis has not been established
- A history of travel within 10 days of symptom onset
to a country with documented H5N1 avian influenza infection in poultry
Testing for influenza A (H5N1) also should
be considered for patients with all of the following:
- Documented temperature of over 100.4:F (38:C)
- Cough, sore throat, or shortness of breath
- History of contact with poultry or domestic birds
(eg, visited a poultry farm, a household raising poultry, or a bird
market) or a known or suspected patient with influenza A (H5N1) in
an H5N1-affected country within 10 days of symptom onset)
The Centre's for Disease Control and Prevention
(CDC) recommends the following for laboratory testing of clinical specimens
from patients with suspected H5N1 influenza A:
- Virus isolation studies on respiratory specimens should
not be performed unless all biosafety level (BSL)-3+ laboratory conditions
- Clinical specimens can be tested by polymerase chain
reaction (PCR) assays by using standard BSL-2 work practices in a
Class II biological safety cabinet.
- Commercially available antigen-detection tests can
be used under BSL-2 levels to test for influenza.
- Specimens from suspected cases should be sent to CDC
if they test positive for influenza A either by PCR or antigen-detection
testing, or if PCR assays for influenza are not locally available.
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Past influenza pandemics occurring
during the 20th century apparently all arose from the Eurasian avian lineage
of viruses. These strains underwent genetic reassortment, most likely
in pigs, before spreading widely among humans. It is unclear whether reassortment
in another animal host is necessary or whether an avian strain could directly
cause a global pandemic in humans
Of the avian influenza subtypes, H5N1 is of
concern for the following reasons (see References:
WHO: Avian influenza: assessing the pandemic threat):
- The subtype mutates rapidly.
- It has shown a propensity to acquire genes from viruses
infecting other animal species.
- It causes severe disease in humans, with a high case-fatality
- The virus has spread rapidly throughout poultry flocks
in Asia, increasing the likelihood of infecting humans or pigs, where
genetic reassortment with human strains could occur, leading to a
new pandemic strain.
The current H5N1 strain circulating in Asia
appears to be highly pathogenic for humans, and immunity in the human
population is generally lacking. However, the strain has not been shown
to be easily transmitted between humans, and sustained person-to-person
transmission has not yet occurred. If the virus continues to circulate
widely among poultry, it has a greater potential to infect humans and
other animals (such as pigs), where genetic reassortment could take place
and create a new pandemic strain. A WHO consultation held May 6-7, 2005,
in Manila suggested that the pandemic potential of H5N1 is continuing
to evolve (see References: WHO:
Inter-country consultation on influenza A/H5N1 in humans in Asia). However,
WHO stated June 30, 2005, that a team of experts sent to Vietnam found
no laboratory evidence that the virus had changed appreciably (see References:
WHO: Situation updates: avian flu [click update 24]).
Recently, WHO developed guidelines on infection
control for management of patients with H5N1 avian influenza (see References:
WHO: Influenza A [H5N1]: WHO interim infection control guidelines for
health care facilities). The WHO infection control guidelines recommend
that the following precautions be implemented for patients with H5N1 influenza:
- Standard precautions
- Droplet precautions
- Contact precautions
- Airborne precautions (including use of high-efficiency
masks and negative-pressure rooms if available)
For adults and children over 12 years of age,
these precautions should be implemented at the time of admission and maintained
until 7 days after resolution of fever. For children 12 and under, precautions
should be continued until 21 days have lapsed from onset of illness.
The WHO guidelines also recommend that all
healthcare workers who may come into contact with the H5N1 virus or with
infected patients should be vaccinated with the current WHO-recommended
vaccine. Although this will not protect against H5N1 influenza A, it will
help avoid simultaneous infection with other influenza strains and may
thereby decrease the risk of genetic reassortment.
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Acambis. Acambis enters flu vaccine
arena with launch of flu vaccine development programme. Aug 4, 2005 [Full
CDC. Basic Information about avian
influenza (bird flu), Jan 29, 2004 [Web
CDC. Outbreaks of avian influenza A
(H5N1) in Asia and interim recommendations for evaluation and reporting
of suspected cases: United States, 2004. MMWR 2004 Feb 13;53(5):97-100
CDC. Travellerss health: Illness
CDC. Travellerss health: Travellerss
health kit [Web
CDC. Update: Notice to travellers about
avian influenza A (H5N1) [Full
Chen H, Deng G, Li Z, et al. The evaluation
of H5N1 influenza viruses in ducks in southern China. Proc Nat Acad Sci
2004 Jul 13;101(28):10452-7 [Full
Chotpitayasunondh T, Ungchusak K, Hanshaoworakul
W, et al. Human disease from influenza A (H5N1), Thailand, 2004. Emerg
Infect Dis 2005 Feb;11(2) [Full
De Jong MD, Van Cam B, Tu Qui P, et al.
Fatal avian influenza A (H5N1) in a child presenting with diarrhoea.
followed by coma. N Engl J Med 2005;352:686-91 [Abstract]
Fielding R, Lam WTW, Ho EYY, et al. Avian
influenza risk perception, Hong Kong. Emerg Infect Dis 2005 May;11(5):677-82
Fouchier RAM, Schneeberger PM, Rozendaal
FW, et al. Avian influenza A virus (H7N7) associated with human conjunctivitis
and a fatal case of acute respiratory distress syndrome. Proc Natl Acad
SCI 2004 Feb 3;101(5):1356-61 [Abstract]
Fouchier RAM, Munster V, Wallensten A,
et al. Characterization of a novel influenza A virus hemagglutinin
subtype (H16) obtained from black-headed gulls J Virol 2005 Mar;79(5):2814-22
Health Canada. Avian influenza: British
Columbia (update). Infectious Diseases News Briefs. Apr 8, 2004 [Full
Hien TT, Liem NT, Dung NT, et al. Avian
influenza A (H5N1) in 10 patients in Vietnam. N Engl J Med 2004 Mar 18;350(12):1179-88
Keawcharoen J, Oraveerakul K, Kuiken T,
et al. Avian influenza H5N1 in tigers and leopards. Emerg Infect Dis
2004 Dec;10(12) [Full
Koopmans M, Wilbrink B, Conyn M, et al.
Transmission of H7N7 avian influenza A virus to human beings during
a large outbreak in commercial poultry farms in the Netherlands. Lancet
2004 Feb 21;363(9409):587-93 [Abstract]
Kuiken T, Rimmelzwaan G, van Riel D, et
al. Avian H5N1 influenza in cats. Science 2004 Oct 8;306(5694):241
Lipotov AS, Webby RJ, Govorkova EA, et
al. Efficacy of H5 influenza vaccines produced by reverse genetics
in a lethal mouse model. J Infect Dis 2005 Apr 15;191:1216-20 [Abstract]
NIAID. Significant dates in influenza
history. Focus on the Flu (NIAID Web site) [Web
NIAID. NIAID announces contracts to
develop vaccine against H5N1 avian influenza. May 2004 [Press
Peiris M, Yuen KY, Leung CW, et al. Human
infection with influenza H9N2. Lancet 1999;354:916-7 [Abstract]
PHS (Poultry Health Services). Fowl
plague, avian influenzahighly pathogenic. PHS Avian Influenza Forum [Web
Schwartz B, Gellin B. Vaccination strategies
for an influenza pandemic. (Commentary) J Infect Dis 2005 Apr 15;191:1207-9
Snacken R, Kendal AP, Haaheim, et al. The
next influenza pandemic: lessons from Hong Kong, 1997. Emerg Infect Dis
1999 Mar-Apr;5(2):195-203 [Full
Stephenson I, Bugarini R, Nicholson KG,
et al. Cross-reactivity to highly pathogenic avian influenza H5N1
viruses after vaccination with nonadjuvanted and MF59-adjuvanted influenza
A/duck/Singapore/97 (H5N3) vaccine: a potential priming strategy. J Infect
Dis 2005 Apr 15;191:1210-5 [Abstract]
Ungchusak K, Auewarakul P, Dowell SF, et
al. Probable person-to-person transmission of avian influenza (H5N1).
N Engl J Med 2005 Jan 27;352(4): 323-4 [Full
Uyeki TM, Chong YH, Katz JM, et al.
Lack of evidence for human-to-human transmission of avian influenza A
(H9N2) viruses in Hong Kong, China, 1999. Emerg Infect Dis 2002 Feb;8(2):154-9
US Department of State. Medical information
for Americans traveling abroad [Web
Voyles BA. Orthomyxoviruses. In: The
biology of viruses. Ed 2. New York, NY: McGraw-Hill, 2002:147
Webster RG. Predictions for future
human influenza pandemics. J Infect Dis 1997 Aug;176(Suppl 1):S14-19 [Full
WHO. Advice to international travelers.
Feb 11, 2004 [Web
WHO. Avian influenza: assessing the
pandemic threat [Full
WHO. Avian influenza [Home
WHO. Avian influenza:
situation in Thailand; status of pandemic vaccine development. Oct
4, 2004 [Web page]
WHO. Avian influenza: situation in
Viet Nam. Mar 7, 2005 [Full
WHO. Cumulative number of confirmed
human cases of avian influenza A(H5N1) since 28 January 2004 [Web
page - open most recent report available]
WHO. Guidelines for the use of seasonal
influenza vaccine in humans at risk of H5N1 infection. Jan 30, 2004 [Web
WHO. Influenza A (H5N1): WHO interim
infection control guidelines for health care facilities. Mar 11, 2004
WHO. Inter-country consultation: influenza
A/H5N1 in humans in Asia. May 6-7, 2005; Manila, The Phillipines [Full
WHO. Situation updates: avian flu [Web
Yuen KY, Chan PKS, Peiris M, et al.
Clinical features and rapid viral diagnosis of human disease associated
with avian influenza A H5N1 virus. Lancet 1998;351(9101):467-71 [Abstract]
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