Influenza occurs in outbreaks mainly from December to March in the northern hemisphere and between May and September in the southern hemisphere. Influenza seasonality is less well defined in tropical countries.[82]Tamerius J, Nelson MI, Zhou SZ, et al. Global influenza seasonality: reconciling patterns across temperate and tropical regions. Environ Health Perspect. 2011 Apr;119(4):439-45.
https://ehp.niehs.nih.gov/doi/10.1289/ehp.1002383
http://www.ncbi.nlm.nih.gov/pubmed/21097384?tool=bestpractice.com
[83]Caini S, Andrade W, Badur S, et al. Temporal patterns of influenza A and B in tropical and temperate countries: what are the lessons for influenza vaccination? PLoS One. 2016 Mar 31;11(3):e0152310.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152310
http://www.ncbi.nlm.nih.gov/pubmed/27031105?tool=bestpractice.com
Knowledge of local community disease activity is important when assessing the likelihood that a patient has influenza. The US Centers for Disease Control and Prevention (CDC) publishes a weekly influenza surveillance report for the US.
CDC: FluView - weekly influenza surveillance report
Opens in new window The World Health Organization also tracks and reports incidence rates of influenza.
WHO: influenza update
Opens in new window
Diagnosis is usually made clinically during an outbreak in the community. Patients at high risk of developing complications, including those with a history of chronic lung, heart, or renal disease, infants and young children, and older adults, require special attention.[16]Centers for Disease Control and Prevention. Influenza (flu). Feb 2024 [internet publication].
https://www.cdc.gov/flu/index.htm
Testing for influenza should be done if it will influence the decision to begin antiviral therapy, to order additional diagnostic tests, to institute infection control measures, and for community surveillance of influenza circulation.[84]Centers for Disease Control and Prevention. Information for clinicians on influenza virus testing. Dec 2023 [internet publication].
https://www.cdc.gov/flu/professionals/diagnosis/index.htm
In the US, the CDC has provided guidance on testing and treatment of influenza when influenza and SARS-CoV-2 viruses are co-circulating.[84]Centers for Disease Control and Prevention. Information for clinicians on influenza virus testing. Dec 2023 [internet publication].
https://www.cdc.gov/flu/professionals/diagnosis/index.htm
Recommendations on testing may vary in different locations and you should consult your local guidance.
History and examination
Influenza presents most commonly as an acute respiratory illness during the winter season (in tropical countries, influenza seasonal patterns are less well defined).[82]Tamerius J, Nelson MI, Zhou SZ, et al. Global influenza seasonality: reconciling patterns across temperate and tropical regions. Environ Health Perspect. 2011 Apr;119(4):439-45.
https://ehp.niehs.nih.gov/doi/10.1289/ehp.1002383
http://www.ncbi.nlm.nih.gov/pubmed/21097384?tool=bestpractice.com
[83]Caini S, Andrade W, Badur S, et al. Temporal patterns of influenza A and B in tropical and temperate countries: what are the lessons for influenza vaccination? PLoS One. 2016 Mar 31;11(3):e0152310.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152310
http://www.ncbi.nlm.nih.gov/pubmed/27031105?tool=bestpractice.com
After an incubation period of approximately 2 days, there is an abrupt onset of high fever, chills, headache, and myalgia. These systemic symptoms may be associated with upper and lower respiratory tract symptoms similar to a common cold, such as cough and sore throat.[85]Call SA, Vollenweider MA, Hornung CA, et al. Does this patient have influenza? JAMA. 2005 Feb 23;293(8):987-97.
http://www.ncbi.nlm.nih.gov/pubmed/15728170?tool=bestpractice.com
Viral shedding in influenza peaks within 48 hours of the illness, and most uncomplicated cases resolve within 1 week.[86]Hayden FG, Fritz R, Lobo MC, et al. Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense. J Clin Invest. 1998 Feb 1;101(3):643-9.
https://www.jci.org/articles/view/1355/pdf
http://www.ncbi.nlm.nih.gov/pubmed/9449698?tool=bestpractice.com
Influenza does not present commonly with primary gastrointestinal symptoms such as nausea and vomiting, except in the paediatric population. Diarrhoea is rare with influenza and would suggest a viral gastroenteritis. Despite not being caused by influenza, these illnesses are commonly referred to as stomach flu.
During a known influenza outbreak, any person with acute fever and respiratory symptoms should be considered to possibly have influenza. However, if the person has been exposed to influenza or a situation where influenza may spread quickly (e.g., international travel, cruise ships), the diagnosis of influenza should be considered at any time of the year.
Although there are no clear pathognomonic features of influenza, it affects the upper and lower respiratory tract in association with systemic symptoms. Fever, headache, myalgia, and fatigue are often associated with upper respiratory tract symptoms such as sore throat and lower respiratory symptoms of cough.[87]Monto AS, Gravenstein S, Elliott M, et al. Clinical signs and symptoms predicting influenza infection. Arch Intern Med. 2000 Nov 27;160(21):3243-7.
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/485554
http://www.ncbi.nlm.nih.gov/pubmed/11088084?tool=bestpractice.com
Not all patients with influenza exhibit these symptoms, and those that do may not always have influenza. Manifestations of influenza infection also depend on patient age and previous history of immunisation.[85]Call SA, Vollenweider MA, Hornung CA, et al. Does this patient have influenza? JAMA. 2005 Feb 23;293(8):987-97.
http://www.ncbi.nlm.nih.gov/pubmed/15728170?tool=bestpractice.com
[87]Monto AS, Gravenstein S, Elliott M, et al. Clinical signs and symptoms predicting influenza infection. Arch Intern Med. 2000 Nov 27;160(21):3243-7.
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/485554
http://www.ncbi.nlm.nih.gov/pubmed/11088084?tool=bestpractice.com
With sporadic cases of influenza, it may be difficult to differentiate influenza clinically from infections caused by other respiratory viruses. In this scenario, influenza virus infection may account for only a small number of such cases.
Clinical findings are helpful, but do not confirm or exclude the diagnosis of influenza.[85]Call SA, Vollenweider MA, Hornung CA, et al. Does this patient have influenza? JAMA. 2005 Feb 23;293(8):987-97.
http://www.ncbi.nlm.nih.gov/pubmed/15728170?tool=bestpractice.com
Examination may yield non-specific findings, since physical findings are generally few in cases of uncomplicated influenza. The patient may appear hot and flushed, and the oropharynx may demonstrate hyperaemia, with complaints of severe sore throat. Mild cervical lymphadenopathy may be present and is more frequent in younger patients.
Laboratory testing
Diagnostic testing is not usually required to confirm a clinical diagnosis of suspected influenza, especially when there is increased influenza activity in the local community. In the US, testing is recommended for all hospitalised patients with signs and symptoms suggestive of influenza and is recommended for outpatients if the results of the test would influence clinical management, for example, use of antiviral treatment or antibiotic treatment, need for further diagnostic tests, consideration for home care, or considerations for those at high-risk for influenza complications.[2]Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical practice guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenza. Clin Infect Dis. 2019 Mar 5;68(6):e1-47.
https://academic.oup.com/cid/article/68/6/e1/5251935
http://www.ncbi.nlm.nih.gov/pubmed/30566567?tool=bestpractice.com
[84]Centers for Disease Control and Prevention. Information for clinicians on influenza virus testing. Dec 2023 [internet publication].
https://www.cdc.gov/flu/professionals/diagnosis/index.htm
Diagnostic tests available for influenza include molecular assays (rapid molecular assays, reverse-transcription polymerase chain reaction [RT-PCR], other nucleic acid amplification tests [NAATs]), antigen detection tests (rapid influenza diagnostic tests, immunofluorescence assays), viral culture, and serology.[2]Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical practice guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenza. Clin Infect Dis. 2019 Mar 5;68(6):e1-47.
https://academic.oup.com/cid/article/68/6/e1/5251935
http://www.ncbi.nlm.nih.gov/pubmed/30566567?tool=bestpractice.com
[84]Centers for Disease Control and Prevention. Information for clinicians on influenza virus testing. Dec 2023 [internet publication].
https://www.cdc.gov/flu/professionals/diagnosis/index.htm
[88]Vesikari T, Beran J, Durviaux S, et al. Use of real-time polymerase chain reaction (rtPCR) as a diagnostic tool for influenza infection in a vaccine efficacy trial. J Clin Virol. 2012 Jan;53(1):22-8.
http://www.ncbi.nlm.nih.gov/pubmed/22079305?tool=bestpractice.com
[89]Egilmezer E, Walker GJ, Bakthavathsalam P, et al. Systematic review of the impact of point-of-care testing for influenza on the outcomes of patients with acute respiratory tract infection. Rev Med Virol. 2018 Sep;28(5):e1995.
http://www.ncbi.nlm.nih.gov/pubmed/30101552?tool=bestpractice.com
[90]Huang HS, Tsai CL, Chang J, et al. Multiplex PCR system for the rapid diagnosis of respiratory virus infection: systematic review and meta-analysis. Clin Microbiol Infect. 2017 Oct;24(10):1055-63.
https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(17)30649-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29208560?tool=bestpractice.com
Nasopharyngeal specimens are recommended for a respiratory specimen for viral isolation.[2]Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical practice guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenza. Clin Infect Dis. 2019 Mar 5;68(6):e1-47.
https://academic.oup.com/cid/article/68/6/e1/5251935
http://www.ncbi.nlm.nih.gov/pubmed/30566567?tool=bestpractice.com
They are more effective than throat swab specimens. The Infectious Diseases Society of America recommends using rapid molecular assays for detection of influenza viruses in respiratory specimens of outpatients and RT-PCR or other molecular assays for detection in respiratory specimens of hospitalised patients.[2]Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical practice guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenza. Clin Infect Dis. 2019 Mar 5;68(6):e1-47.
https://academic.oup.com/cid/article/68/6/e1/5251935
http://www.ncbi.nlm.nih.gov/pubmed/30566567?tool=bestpractice.com
NAATs are the preferred method for detection of influenza virus in clinical samples because of their superior diagnostic sensitivity compared to rapid antigen tests.[91]Miller JM, Binnicker MJ, Campbell S, et al. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2024 update by the Infectious Diseases Society of America and the American Society for Microbiology. Clin Infect Dis. 2024 Mar 5:ciae104.
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciae104/7619499
http://www.ncbi.nlm.nih.gov/pubmed/38442248?tool=bestpractice.com
Viral culture remains the definitive test, but is not used for initial clinical management as results may take 3 to 10 days. Rather, it is used for confirming screening tests and for public health surveillance. Culture isolates can provide specific information regarding circulating strains and subtypes of influenza viruses. Virus isolates may also provide information about the emergence of antiviral resistance and the development of novel influenza A subtypes that may potentially cause a pandemic. Some molecular assays can identify influenza virus types and specific influenza A virus subtypes.[2]Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical practice guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenza. Clin Infect Dis. 2019 Mar 5;68(6):e1-47.
https://academic.oup.com/cid/article/68/6/e1/5251935
http://www.ncbi.nlm.nih.gov/pubmed/30566567?tool=bestpractice.com
Rapid molecular assays are 66% to 99% sensitive and 55% to 99% specific, depending on virus type.[2]Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical practice guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenza. Clin Infect Dis. 2019 Mar 5;68(6):e1-47.
https://academic.oup.com/cid/article/68/6/e1/5251935
http://www.ncbi.nlm.nih.gov/pubmed/30566567?tool=bestpractice.com
Rapid influenza diagnostic tests (antigen detection) have poor sensitivity (50% to 75%), though specificity is high (90% to 99%).[2]Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical practice guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenza. Clin Infect Dis. 2019 Mar 5;68(6):e1-47.
https://academic.oup.com/cid/article/68/6/e1/5251935
http://www.ncbi.nlm.nih.gov/pubmed/30566567?tool=bestpractice.com
[91]Miller JM, Binnicker MJ, Campbell S, et al. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2024 update by the Infectious Diseases Society of America and the American Society for Microbiology. Clin Infect Dis. 2024 Mar 5:ciae104.
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciae104/7619499
http://www.ncbi.nlm.nih.gov/pubmed/38442248?tool=bestpractice.com
Routine serological testing for influenza requires paired acute and convalescent sera. It is not recommended for accurate clinical decision-making.[84]Centers for Disease Control and Prevention. Information for clinicians on influenza virus testing. Dec 2023 [internet publication].
https://www.cdc.gov/flu/professionals/diagnosis/index.htm
Pneumonia
If a patient has an underlying chronic medical condition or falls into a high-risk category, viral or bacterial pneumonia should be considered. These patients will experience persistence of their symptoms beyond the usual time frame for resolution of uncomplicated influenza. There may be high fever, cough, and dyspnoea. If there is an exacerbation of fever and cough with purulent sputum, a secondary bacterial pneumonia is most likely. A chest x-ray confirms infiltrates.
Diagnosis in children
Signs and symptoms of upper and/or lower respiratory tract involvement are common, but influenza may present more variably in children, depending on age and previous exposure.
The typical symptoms of uncomplicated influenza virus infection are still often present and include the abrupt onset of fever, headache, myalgia, and malaise associated with manifestations of respiratory tract illness, such as cough, sore throat, and rhinitis.
However, young children frequently struggle to vocalise such symptoms as myalgia and headache. Cough and fever may be less prominent symptoms in young children, or they may have higher fevers than adult patients, experience febrile seizures, and have more gastrointestinal complaints (e.g., nausea and vomiting, poor appetite).[92]Glezen WP, Taber LH, Frank AL, et al. Influenza virus infections in infants. Pediatr Infect Dis J. 1997 Nov;16(11):1065-8.
http://www.ncbi.nlm.nih.gov/pubmed/9384341?tool=bestpractice.com
[93]Peltola V, Ziegler T, Ruuskanen O. Influenza A and B virus infections in children. Clin Infect Dis. 2003 Feb 1;36(3):299-305.
http://www.ncbi.nlm.nih.gov/pubmed/12539071?tool=bestpractice.com
[94]Ohmit SE, Monto AS. Symptomatic predictors of influenza virus positivity in children during the influenza season. Clin Infect Dis. 2006 Sep 1;43(5):564-8.
https://academic.oup.com/cid/article/43/5/564/503835
http://www.ncbi.nlm.nih.gov/pubmed/16886147?tool=bestpractice.com
Respiratory symptoms may be less prominent in children at the onset of illness than in adolescents and adults.[92]Glezen WP, Taber LH, Frank AL, et al. Influenza virus infections in infants. Pediatr Infect Dis J. 1997 Nov;16(11):1065-8.
http://www.ncbi.nlm.nih.gov/pubmed/9384341?tool=bestpractice.com