Updated Interim Guidance
for Laboratory Testing of Persons with Suspected Infection with Avian Influenza
A (H5N1) Virus in the United States
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.
Current Situation:
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:
A)
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 respiratory illness;
B)
Close contact (approach within 1 meter [approx. 3 feet]) of an ill patient who
was confirmed or suspected to have H5N1;
C)
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.
§
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 available.||
§
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.
More Information:
Department of Health and Human Services at www.pandemicflu.gov
World Health Organization at
World Organization for Animal Health (OIE) at http://www.oie.int/eng/en_index.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, visit the CDC website at http://www.cdc.gov/flu/avian/outbreaks/current.htm; the OIE website at http://www.oie.int/eng/en_index.htm; and the WHO website at http://www.who.int/csr/disease/avian_influenza/en/.
‡ 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.