CDC UPDATED INTERIM GUIDANCE FOR LABORATORY TESTING OF PERSONS WITH SUSPECTED INFECTIONS WITH AVIAN
INFLUENZA A (H5N1) VIRUS IN THE UNITED STATES
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This is an official
CDC Health Update
Distributed via Health Alert Network
June 07, 2006, 19:50 EDT (07:50 PM EDT)
Updated Interim Guidance for Laboratory Testing of Persons with
Suspected Infection with Avian Influenza A (H5N1) Virus in the United States
CDC Health Update
This update provides revised interim guidance for testing of suspected human cases of avian influenza A (H5N1) in the United States and
is based on the current state of knowledge regarding human infection with H5N1 viruses. The epidemiology of H5N1 human infections has not
changed significantly since February 2004. Therefore, CDC recommends that H5N1 surveillance in the United States remain at the enhanced
level first established at that time. However, this revised interim guidance provides an updated case definition of a suspected H5N1
human case for the purpose of determining when testing should be undertaken and also provides more detailed information on laboratory
testing. Effective surveillance will continue to rely on health care providers obtaining information regarding international travel and
other exposure risks from persons with specified respiratory symptoms as detailed in the recommendations below. This guidance will be
updated as the epidemiology of H5N1 changes. Note: CDC is revising its interim guidance for infection control precautions for avian
influenza A (H5N1). These will be issued as soon as they are available.
The avian influenza A (H5N1) epizootic (animal outbreak) in Asia has expanded to wild birds and/or poultry in parts of Europe, the Near
East and Africa. Sporadic human infections with H5N1 continue to be reported and have most recently occurred in China, Egypt, Indonesia,
Azerbaijan, Cambodia, and Djibouti. In addition, rare instances of probable human-to-human transmission associated with H5N1 viruses have
occurred, most recently in a family cluster in Indonesia. So far, however, the spread of H5N1 virus from person to person has been rare,
inefficient, and unsustained. The total number of confirmed human cases of H5N1 reported as of June 7, 2006 has reached 225. The case
fatality rate for these reported cases continues to be approximately 50 percent. As of this date, H5N1 has not been identified among
animals or humans in the United States.
The epizootic in Asia and parts of Europe, the Near East and Africa is not expected to diminish significantly in the short term and it is
likely that H5N1 infection among birds has become enzootic in certain areas. It is expected that human infections resulting from direct
contact with infected poultry will continue to occur in affected countries. Since no sustained human-to-human transmission of influenza
H5N1 has been documented anywhere in the world, the current phase of alert, based on the World Health Organization (WHO) global influenza
preparedness plan, remains at Phase 3 (Pandemic Alert).* In addition, no evidence for genetic reassortment between human and avian
influenza A virus genes has been found. Nevertheless, this expanding epizootic continues to pose an important and growing public health
threat. CDC is in communication with WHO and other national and international agencies and continues to monitor the situation closely.
Reporting and Testing Guidelines
CDC recommends maintaining the enhanced surveillance efforts practiced currently by state and local health departments, hospitals, and
clinicians to identify patients at increased risk for avian influenza A (H5N1). Guidance for enhanced surveillance was first described in
a HAN update issued on February 3, 2004 and most recently updated on February 4, 2005.
Testing for avian influenza A (H5N1) virus infection is recommended for:
A patient who has an illness that:
- requires hospitalization or is fatal; AND
- has or had a documented temperature of ≥ 38°C (≥ 100.4° F); AND
- has radiographically confirmed pneumonia, acute respiratory distress syndrome (ARDS), or other severe respiratory illness for which
an alternate diagnosis has not been established; AND
- has at least one of the following potential exposures within 10 days of symptom onset:
- History of travel to a country with influenza H5N1 documented in poultry, wild birds, and/or humans, † AND had at least one of
the following potential exposures during travel:
• direct contact with (e.g., touching) sick or dead domestic poultry;
• direct contact with surfaces contaminated with poultry feces;
• consumption of raw or incompletely cooked poultry or poultry products;
• direct contact with sick or dead wild birds suspected or confirmed to have influenza H5N1;
• close contact (approach within 1 meter [approx. 3 feet]) of a person who was hospitalized or died due to a severe unexplained
- Close contact (approach within 1 meter [approx. 3 feet]) of an ill patient who was confirmed or suspected to have H5N1;
- Worked with live influenza H5N1 virus in a laboratory.
Testing for avian influenza A (H5N1) virus infection can be considered on a case-by-case basis, in consultation with local and state
health departments, for:
- A patient with mild or atypical disease‡(hospitalized or ambulatory) who has one of the exposures listed above (criteria A, B,
or C); OR
- A patient with severe or fatal respiratory disease whose epidemiological information is uncertain, unavailable, or otherwise
suspicious but does not meet the criteria above (examples include: a returned traveler from an influenza H5N1-affected country whose
exposures are unclear or suspicious, a person who had contact with sick or well-appearing poultry, etc.)
Clinicians should contact their local or state health department as soon as possible to report any suspected human case of influenza H5N1
in the United States.
Specimen Collection and Testing Guidelines
- Oropharyngeal swab specimens and lower respiratory tract specimens (e.g., bronchoalveolar lavage or tracheal aspirates) are preferred
because they appear to contain the highest quantity of virus for influenza H5N1 detection, as determined on the basis of available data.
Nasal or nasopharyngeal swab specimens are acceptable, but may contain less virus and therefore not be optimal specimens for virus
- Detection of influenza H5N1 is more likely from specimens collected within the first 3 days of illness onset. If possible, serial
specimens should be obtained over several days from the same patient.
- Bronchoalveolar lavage is considered to be a high-risk aerosol-generating procedure. Therefore, infection control precautions should
include the use of gloves, gown, goggles or face shield, and a fit-tested respirator with an N-95 or higher rated filter. A loose-fitting
powered air-purifying respirator (PAPR) may be used if fit-testing is not possible (for example, if the person has a beard).
Detailed guidance on infection control precautions for health care workers caring for suspected influenza H5N1 patients is
- Swabs used for specimen collection should have a Dacron tip and an aluminum or plastic shaft. Swabs with calcium alginate or cotton
tips and wooden shafts are not recommended.§ Specimens should be placed at 4°C immediately after collection.
- For reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, nucleic acid extraction lysis buffer can be added to specimens
(for virus inactivation and RNA stabilization), after which specimens can be stored and shipped at 4°C. Otherwise, specimens should
be frozen at or below -70°C and shipped on dry ice. For viral isolation, specimens can be stored and shipped at 4°C. If specimens
are not expected to be inoculated into culture within 2 days, they should be frozen at or below -70°C and shipped on dry ice. Avoid
repeated freeze/thaw cycles.
- Influenza H5N1-specific RT-PCR testing conducted under Biosafety Level 2 conditions¶ is the preferred method for diagnosis. All
state public health laboratories, several local public health laboratories, and CDC are able to perform influenza H5N1 RT-PCR testing,
and are the recommended sites for initial diagnosis.
- Viral culture should NOT be attempted on specimens from patients suspected to have influenza H5N1, unless conducted under Biosafety
Level 3 conditions with enhancements.¶
- Commercial rapid influenza antigen testing in the evaluation of suspected influenza H5N1 cases should be interpreted with caution.
Clinicians should be aware that these tests have relatively low sensitivities, and a negative result would not exclude a diagnosis of
influenza H5N1. In addition, a positive result does not distinguish between seasonal and avian influenza A viruses.
- Serologic testing for influenza H5N1-specific antibody, using appropriately timed specimens, can be considered if other influenza
H5N1 diagnostic testing methods are unsuccessful (for example, due to delays in respiratory specimen collection). Paired serum specimens
from the same patient are required for influenza H5N1 diagnosis: one sample should be tested within the first week of illness, and a
second sample should be tested 2-4 weeks later. A demonstrated rise in the H5N1-specific antibody level is required for a diagnosis of
H5N1 infection. Currently, the microneutralization assay, which requires live virus, is the recommended test for measuring H5N1-specific
antibody. Any work with live wild-type highly pathogenic influenza H5N1 viruses must be conducted in a USDA-approved Biosafety Level 3
enhanced containment facility. Visit http://www.cdc.gov/flu/h2n2bsl3.htm for more information about procedures and facilities
recommended for manipulating highly pathogenic avian influenza viruses.
Laboratory testing results positive for influenza A (H5N1) in the United States should be confirmed at CDC, which has been designated as
a WHO H5 Reference Laboratory. Before sending specimens, state and local health departments should contact CDC’s on-call
epidemiologist at (404) 639-3747 or (404) 639-3591 (Monday – Friday, 8:30 AM - 5:00 PM) or (770) 488-7100 (all other times).
Travel Health Notice
CDC has not recommended that the general public avoid travel to any of the countries affected by H5N1. However, CDC does recommend that
travelers to these countries avoid poultry farms and bird markets or other places where live poultry are raised or kept. For details
about other ways to reduce the risk of infection, see http://www.cdc.gov/travel/other/avian_influenza_se_asia_2005.htm.
*For the current WHO Pandemic Phase, see http://www.who.int/csr/disease/avian_influenza/phase/en/index.html
† For a listing of influenza H5N1-affected countries,
‡ For example, a patient with respiratory illness and fever who does not require hospitalization, or a patient with significant
neurologic or gastrointestinal symptoms in the absence of respiratory disease.
|| Interim recommendations for infection control in health-care facilities caring for patients with known or suspected avian influenza
are available at http://www.cdc.gov/flu/avian/professional/infect-control.htm.
§ Specimens can be transported in viral transport media, Hanks balanced salt solution, cell culture medium, tryptose-phosphate
broth, veal infusion broth, or sucrose-phosphate buffer. Transport media should be supplemented with protein, such as bovine serum
albumin or gelatin, to a concentration of 0.5% to 1%.
¶ Information regarding Laboratory Biosafety Level Criteria can be found at http://www.cdc.gov/od/ohs/biosfty/bmbl4/bmbl4s3.htm.
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