During December 2003–February 2004, outbreaks of highly pathogenic
avian influenza A (H5N1) among poultry were reported in Cambodia, China, Indonesia,
Japan, Laos, South Korea, Thailand, and Vietnam. As of February 9, 2004, a
total of 23 cases of laboratory-confirmed influenza A (H5N1) virus infections
in humans, resulting in 18 deaths, had been reported in Thailand and Vietnam.
In addition, approximately 100 suspected cases in humans are under investigation
by national health authorities in Thailand and Vietnam. CDC, the World Health
Organization (WHO), and national health authorities in Asian countries are
working to assess and monitor the situation, provide epidemiologic and laboratory
support, and assist with control efforts. This report summarizes information
about the human infections and avian outbreaks in Asia and provides recommendations
to guide influenza A (H5N1) surveillance, diagnosis, and testing in the United
On December 12, 2003, an outbreak of avian influenza A (H5N1) among
poultry in South Korea was reported. Subsequent influenza A (H5N1) outbreaks
among poultry were confirmed in Vietnam (January 8, 2004), on a single farm
in Japan (January 12), in Thailand (January 23), in Cambodia (January 24),
in China (January 27), in Laos (January 27), and in Indonesia (February 2).
On January 19, a single peregrine falcon found dead in Hong Kong also tested
positive for influenza A (H5N1) virus, but no poultry outbreak has been identified.
In Vietnam, as of February 9, a total of 18 human influenza A (H5N1)
infections had been reported, resulting in 13 deaths. Patients ranged in age
from 4 to 30 years; 10 patients were aged <18 years. The cases included
fatal infections in two sisters who were part of a cluster of four cases of
severe respiratory illness in a single family.
In Thailand, influenza A (H5N1) infection was confirmed in four males,
aged 6-7 years, and one female, aged 58 years. All five patients died.1 Other cases are under investigation.
Antigenic analysis and genetic sequencing distinguish between influenza
viruses that usually circulate among birds and those that usually circulate
among humans. Sequencing of the H5N1 viruses obtained from five persons in
Vietnam and Thailand, including one sister from the cluster in Vietnam, has
indicated that all of the genes of these viruses are of avian origin. No evidence
of genetic reassortment between avian and human influenza viruses has been
identified. If reassortment occurs, the likelihood that the H5N1 virus can
be transmitted more readily from person to person will increase. Although
all the genes are of avian origin, the current H5N1 viruses are antigenically
distinguishable from those isolated from humans in Hong Kong in 1997 and 2003.
Genetic sequencing of the five human H5N1 isolates from Thailand and
Vietnam also indicates that the viruses have genetic characteristics associated
with resistance to the influenza antiviral drugs amantadine and rimantadine.
Antiviral susceptibility testing confirms this finding. Testing for susceptibility
of the H5N1 isolates to the neuraminidase inhibitor oseltamivir has demonstrated
the sensitivity of these viruses to the drug; testing to determine susceptibility
to the neuraminidase inhibitor zanamavir is under way.
CDC recommends that state and local health departments, hospitals, and
clinicians enhance their efforts to identify patients who could be infected
by influenza A (H5N1) virus and take infection-control precautions when influenza
A (H5N1) is suspected (see sidebar). Testing of hospitalized patients for
influenza A (H5N1) infection is indicated when both of the following exist:
(1) radiographically confirmed pneumonia, acute respiratory distress syndrome
(ARDS), or other severe respiratory illness for which an alternative diagnosis
has not been established and (2) a history of travel within 10 days of symptom
onset to a country with documented H5N1 avian influenza infections in poultry
or humans. Ongoing listings of countries affected by avian influenza are available
from the World Organization for Animal Health.*
Testing for influenza A (H5N1) also should be considered on a case-by-case
basis in consultation with state and local health departments for hospitalized
or ambulatory patients with all of the following: (1) documented temperature
of >100.4°F (>38°C); (2) cough, sore throat, or shortness of breath;
and (3) history of contact with poultry or domestic birds (e.g., 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 highly pathogenic avian influenza A (H5N1) virus requires Biosafety
Level (BSL)-3 + laboratory conditions for certain procedures. CDC recommends
that virus isolation studies on respiratory specimens from patients who meet
the testing criteria should not be performed unless all BSL-3 + conditions
are met. However, 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. CDC has developed real-time PCR protocols† for various
respiratory pathogens, including SARS and influenza A and B viruses. In addition,
commercially available antigen-detection tests can be used under BSL-2 levels
to test for influenza. Although these rapid tests for human influenza also
can detect avian influenza A (H5N1) viruses, the sensitivity of these tests
is substantially lower than that of virus culture or PCR.2
Specimens from persons meeting clinical and epidemiologic indications
for testing 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
available locally. CDC also will accept, for follow-up testing, specimens
from persons meeting the clinical and epidemiologic indications but testing
negative on the rapid tests when PCR assay was not available. Requests for
testing by CDC should come through local and state health departments, which
should contact CDC's Emergency Operations Center, telephone 770-488-7100.
CDC/WHO Avian Influenza Response Team.
Since 1997, human infection with avian influenza viruses has been confirmed
on five occasions.‡ The ability of avian viruses to transmit from person
to person appears limited. Rare person-to-person infection was noted in the
A (H5N1) outbreak in Hong Kong in 19973,4 and
in the A (H7N7) outbreak in the Netherlands in 2003,5 but
these secondary cases did not result in sustained chains of transmission or
communitywide outbreaks. These previous experiences with avian influenza viruses
suggest that limited person-to-person transmission of the current H5N1 viruses
The majority of the human H5N1 cases are apparently associated with
direct exposure to infected birds or to surfaces contaminated with excretions
from infected birds. The family respiratory illness cluster in Vietnam suggests
the possibility of limited person-to-person transmission. However, other possibilities
(e.g., transmission through exposure to surfaces contaminated by H5N1-infected
poultry feces) cannot be ruled out. Although no evidence for sustained person-to-person
transmission of influenza A (H5N1) has been identified, influenza viruses
have the capacity to change quickly. Continued monitoring for new transmission
patterns is an important aspect of the current investigation.
In 1997, the influenza A (H5N1) outbreak among persons in Hong Kong
ended abruptly after the culling of poultry. However, the current outbreaks
present challenges because of the large geographic areas and numbers of affected
poultry. Asian poultry populations are maintained both on large commercial
farms and in backyard flocks. In addition, infections among wild bird populations
might be extensive, and the resources to address this problem are limited
in certain affected countries. Because of increasing evidence that avian influenza
viruses infect humans, persons involved in the slaughter of poultry potentially
infected with avian influenza viruses or their contaminated environments should
follow WHO recommendations for worker protection.§
Because the influenza A (H5N1) virus could develop the ability to maintain
sustained person-to-person transmission, WHO collaborating centers are working
to coordinate vaccine development. Efforts are under way in the United Kingdom
and the United States to develop influenza A (H5N1) reference viruses for
use in vaccine preparation. The minimum estimated time necessary to complete
reference virus development and safety testing is 3 months. Production by
vaccine manufacturers of pilot lots of vaccine for clinical testing can begin
only after reference virus development and safety testing have been completed.
Decisions on whether to proceed with vaccine manufacture will depend, in part,
on the evolution of the current outbreaks.
On February 4, CDC issued an order for an immediate ban∥ on the
import of all birds from Cambodia, China (including Hong Kong), Indonesia,
Japan, Laos, South Korea, Thailand, and Vietnam. Birds from these affected
countries potentially can infect humans with influenza A (H5N1). This order
complements a similar action taken by the U.S. Department of Agriculture (USDA).
CDC advises that travelers to countries in Asia with documented H5N1
outbreaks should avoid poultry farms, contact with animals in live food markets,
and any surfaces that appear to be contaminated with feces from poultry or
other animals. More information on travel is available from CDC at http://www.cdc.gov/travel. Additional information on influenza viruses and avian influenza is
available from CDC at http://www.cdc.gov/flu. Updated information
on human infections is available from WHO at http://www.who.int/en.
*Available at http://www.oie.int/eng/en_index.htm.
†These protocols are available to public health laboratories
and have been posted, under SARS (password required), by the Association of
Public Health Laboratories at http://www.aphl.org/members_only/index.cfm.
‡Influenza A (H5N1) in Hong Kong in 1997 and 2003, influenza
A (H9N2) in Hong Kong in 1999 and 2003, and influenza A (H7N7) in the Netherlands
§Available at http://www.wpro.who.int/avian/docs/recommendations.asp.
∥Additional information on the embargo is available at http://www.cdc.gov/flu/avian/embargo.htm.
Outbreaks of Avian Influenza A (H5N1) in Asia and Interim Recommendations for Evaluation and Reporting of Suspected Cases—United States, 2004. JAMA. 2004;291(10):1191-1193. doi:10.1001/jama.291.10.1191