Clinical Features and Diagnostic Testing
Last updated December 16, 2010. At the current time, this content is considered historical and will not be updated until further notice.
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Clinical Features
Diagnostic Testing
Clinical Features
Incubation Period
The incubation period is generally 1.5 to 3 days but can extend to 7 days (Writing Committee of the WHO).
Most patients who presented for care during the primary pandemic period had typical influenza-like illness with fever, cough, sore throat, and rhinorrhea; however, gastrointestinal symptoms (including nausea, vomiting, and diarrhea) were reported more frequently among pH1N1 cases than among patients with seasonal influenza (Writing Committee of the WHO).
Observational studies have shown that pH1N1 2009 infection can cause a broad range of clinical syndromes, from afebrile upper respiratory illness to fulminate viral pneumonia.
Complications
Complications include the following (Writing Committee of the WHO):
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Diffuse viral pneumonitis (can be associated with severe hypoxia and acute respiratory distress syndrome [ARDS])
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Shock and renal failure among some patients with ARDS
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Prolonged exacerbation of chronic obstructive pulmonary disease (COPD)
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Secondary bacterial pneumonia
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Neurologic manifestations (eg, altered mental status, seizures, encephalopathy, encephalitis)
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Myocarditis
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Dehydration
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Death
Case-Fatality Rates
The overall case-fatality rate during the pandemic period was estimated to be somewhat less than 0.5% (Writing Committee of the WHO). Most deaths occurred in younger populations.
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Diagnostic Testing
Laboratory Testing for Influenza
A variety of tests are available for confirming influenza infection (CDC: Rapid diagnostic testing for influenza). These are outlined in the table below.
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Procedure
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Influenza Virus Types Detected
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Acceptable Specimens
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Test Time
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Viral culture
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A and B
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NP swab/aspirate, nasal swab/aspirate/wash, throat swab, bronchioalveolar lavage
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3-10 daysa
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Immunofluorescence (direct fluorescent antibody [DFA] or indirect fluorescent antibody [IFA] staining)
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A and B
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NP swab/aspirate, nasal swab/aspirate/wash, throat swab,
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2-4 hours
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RT-PCR
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A and B
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NP swab/aspirate, nasal swab/aspirate/wash, throat swab, bronchioalveolar lavage, sputum
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2-4 hours
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Serologyb
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A and B
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paired acute and convalescent serum samples
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2 weeks or more
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Enzyme immunoassay (EIA)
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A and B
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NP swab/aspirate, nasal swab/aspirate/wash, throat swab
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2 hours
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Rapid diagnostic tests
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Dependent on the specific test used
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Dependent on the specific test used
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10-15 minutes
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Viral RNA detection by conventional or real-time RT-PCR assay remains the best method for diagnosis of pH1N1 2009 influenza (Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic H1N1 2009 Influenza).
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Nasopharyngeal aspirates or swabs are recommended for patients who have typical influenza-like illness.
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For those with lower respiratory infection, endotracheal or bronchoscopic aspirates have higher yields.
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Negative results, however, do not rule out pH1N1 2009 infection.
Commercially available rapid influenza diagnostic tests (RIDTs) have poor clinical sensitivity (11% to 70%) for detection of pH1N1 2009 virus in clinical specimens; therefore, negative test results should not be used to make decisions regarding clinical management or appropriate infection control. Furthermore, RIDTs cannot distinguish between influenza A subtypes. Other points regarding use of RIDTs include the following:
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False-positive (and true-negative) results are more likely to occur when influenza is uncommon in the community, which is generally at the beginning and end of an outbreak.
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False-negative (and true-positive) results are more likely to occur when influenza is common in the community, which is typically at the height of an outbreak.
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Test sensitivity may vary depending on collection timing. Respiratory specimens for testing should be collected in the first 4 to 5 days after illness onset, when viral shedding is greatest.
Several studies suggest that direct fluorescent antibody (DFA) staining performs better than RIDTs for diagnosis of pH1N1 2009 influenza, particularly for patients who have high levels of virus replication (Pollock 2009). However, if DFA testing is negative, the diagnosis of pH1N1 influenza cannot be ruled out and RT-PCR testing should be considered if diagnostic confirmation is needed.
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Specimen Collection
Swabs
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Nasopharyngeal swab/aspirate or nasal wash/aspirates are the most appropriate for testing; if these specimens cannot be collected, a nasal swab or throat swab is acceptable.
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Ideally, swab specimens should be collected using swabs with a synthetic tip (eg, polyester or Dacron) and an aluminum or plastic shaft. Swabs with cotton tips or wooden shafts are not recommended. Specimens collected with swabs made of calcium alginate are not acceptable.
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The swab specimen collection vials should contain 1 to 3 mL of viral transport medium (eg, containing protein stabilizer, antibiotics to discourage bacterial and fungal growth, and buffer solution).
Storing Clinical Specimens
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All respiratory specimens should be kept at 4°C for no longer than 4 days.
Shipping Clinical Specimens
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Clinical specimens should be shipped on wet ice or cold packs in appropriate packaging.
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All specimens should be labeled clearly and include information requested by the appropriate state public health laboratory.
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