Respiratory illness caused by influenza virus, commonly known as the flu, is often difficult to distinguish from the diseases caused by other respiratory pathogens merely on the basis of signs and symptoms. Sole interpretation by a clinician is therefore not specific, and strict clinical definitions have also shown poor performance in some studies on older patients.
Proper treatment of patients with respiratory illness depends on precise and timely diagnosis. Several tests have been developed to detect influenza viruses which differ in regard to their sensitivity, specificity, availability, throughput, cost and other important factors. Early diagnosis of influenza can decrease the inappropriate use of antibiotics and provide the option of using antiviral therapy.
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Clinical presentation of influenza
Uncomplicated influenza illness is characterized by an average incubation period of 2 days, after which constitutional and respiratory signs and symptoms ensue – namely high fever, headache, myalgia, severe malaise (feeling unwell), dry cough, sore throat and rhinitis. Cough can be severe and last for two or more weeks.
Among children, otitis media (inflammation of the middle ear) with nausea and vomiting are also common symptoms of influenza. Young children are less likely to report most typical symptoms such as fever and cough, and initial symptoms can mimic bacterial sepsis. In studies conducted among children between 5 and 12 years of age, the positive predictive value of fever and cough together was between 71 and 83%, compared with 64% among children younger than 5 years of age.
The disease typically resolves after 3-7 days for the majority of patients, although there is a possibility of developing infectious complications. Influenza virus infections can thus result in primary influenza viral pneumonia, lead to secondary bacterial pneumonia or sinusitis, exacerbate underlying medical conditions (i.e. pulmonary or cardiac disease) or contribute to coinfections with other pathogens.
In adults, influenza virus is being shed one day before symptoms through 5-10 days after illness onset. However, there is a swift decrease in the amount of the virus and infectivity 3-5 days after onset in an experimental human infection model. Young children might shed virus several days before the onset of illness, whereas severely immunocompromised individuals are known to shed virus for weeks or even months.
Tools to detect a virus
There are a number of tests available that can aid in the diagnosis of influenza. Preferred samples for testing include nasopharyngeal or nasal swab, and nasal wash or aspirate, and should be collected within the first 4 days of illness. All the results are evaluated by health-care providers according to the clinical and epidemiologic context.
Although viral culture is laborious and time-consuming, it has been a mainstay for the detection of influenza virus for many years. Madin-Darby canine kidney (MDCK) cells, monkey kidney cells and A549 cells are used for detection of influenza viruses. Only culture can provide information about circulating strains and subtypes of influenza viruses, which is needed is needed in order to guide decisions regarding influenza vaccination, treatment and chemoprophylaxis.
Antibodies that are produced after the onset of influenza virus illness can be detected using serological diagnostic techniques like complement fixation technique, hemagglutination inhibition assay, enzyme immunoassay and neutralization tests. Routine serological testing for influenza requires paired acute and convalescent sera, and antibody titer usually peaks within 14 days of illness; thus they are recommended only for research and public health investigations.
The fast and specific rapid influenza diagnostic tests (also knowns as point of care tests) are simple, handy, cheap and easily interpretable. However, although they can detect influenza viruses within 15 minutes, they are not recommended due to their poor performance when compared to the culture methods.
For both quantitative and qualitative approaches to diagnosis, reverse transcription-polymerase chain reaction (RT-PCR) is regarded as the king of diagnosis due to its sensitivity and specificity. Direct fluorescence antibody assay (staining of cells followed by bioconjugation of antibodies to the fluorescent dye) provides fast and reliable results, although it is not as sensitive as the PCR test. More research is needed to validate the interpretation of influenza virus diagnostic methods.
- Nicholson KG, Webster RG, Hay AJ. Textbook of Influenza. Blackwell Science, Oxford, 1998.
- Lamb RA, Krug RM. Orthomyxoviridae: The viruses and their Replication. In: Fields Virology fourth edition, Knipe DM, Howley PM eds, Lippincott, Philadelphia 2001, pp 1487-1531.