Influenza overview
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Influenza overview On the Web |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohammad Braizat, M.S. [2]
Overview
Influenza is an acute viral respiratory disease caused by influenza viruses (family Orthomyxoviridae), primarily influenza A and B, which circulate worldwide and cause annual epidemics of variable severity.[1] The clinical spectrum ranges from asymptomatic infection and self-limited upper respiratory illness to severe pneumonia, multiorgan complications, and death.[1]
Causative Agents
Four types of influenza viruses (A, B, C, D) are recognized.[1][2]
- Influenza A and B: Cause seasonal epidemics in humans. Influenza A viruses are subtyped by hemagglutinin (HA) and neuraminidase (NA); A(H1N1)pdm09 and A(H3N2) currently circulate. Influenza B viruses are divided into B/Victoria and B/Yamagata lineages, with B/Yamagata undetected since March 2020.[1]
- Influenza C: Causes mild illness and does not cause epidemics.[2][3]
- Influenza D: Primarily infects cattle and is not known to cause human disease.[1][3]
Influenza A viruses also circulate in animal reservoirs and can cause zoonotic infections.[4][1]
Disease Burden
| Data Category | Global (Annual) | U.S. (Annual) |
|---|---|---|
| Severe Illness | 3–5 million cases[1] | 9–45 million symptomatic illnesses[5] |
| Hospitalizations | Not specified | 140,000–710,000 hospitalizations[5] |
| Deaths | 290,000–650,000 respiratory deaths[6] | 12,000–52,000 deaths[5] |
| Pediatric Illness | >110 million illnesses in children <5 years[1][7] | Not specified |
The 2024–2025 U.S. season was high-severity, with an estimated 47–82 million illnesses, 610,000–1,300,000 hospitalizations, and the highest cumulative hospitalization rate (127.1 per 100,000) since 2010–2011.[8][9] During the 2024–2025 season, at least 63 pediatric influenza-associated deaths were reported.[9] Nearly 50% of all-cause deaths among hospitalized influenza patients occur within 30 days after discharge.[10]
Populations at increased risk include adults ≥65 years, persons aged 50–64 years, children <5 years, pregnant people, American Indian/Alaska Native persons, individuals with extreme obesity (BMI ≥40), individuals with chronic medical conditions (including pulmonary, cardiovascular, renal, hepatic, neurologic/neurodevelopmental, hematologic, and metabolic disorders), immunocompromised persons, residents of long-term care facilities, and children/adolescents receiving aspirin or salicylate-containing medications (risk of Reye syndrome).[1][5][11][9] Racial and ethnic disparities persist, with higher age-adjusted hospitalization rates among Black, American Indian/Alaska Native, and Hispanic populations.[12][13]
Key Clinical Features
The classic presentation is abrupt onset of fever, cough, myalgias, headache, and malaise, often with sore throat and nasal congestion.[1][5][14] Fever may be absent, particularly in older adults and immunocompromised patients.[1] Uncomplicated illness typically resolves within 3–7 days.
Complications include primary viral pneumonia, secondary bacterial pneumonia, exacerbation of underlying chronic conditions, and increasingly recognized cardiovascular events such as acute myocardial infarction and stroke, particularly in older adults.[1][15]
During community influenza activity, the combination of cough and fever has a positive predictive value ranging from 30–88% for influenza, depending on host factors and community activity levels. In populations with confirmed influenza activity, PPV has been reported as high as 79% in one pooled analysis, though this estimate derived from patients pre-selected for feverishness and may overstate diagnostic precision in broader clinical settings.[16][5]
Diagnosis at a Glance
Molecular assays (RT-PCR, rapid molecular tests) are preferred for diagnosis due to high sensitivity and specificity.[14][5][17]
- Rapid antigen detection tests are widely available but have moderate sensitivity (50–70%); negative results in symptomatic patients should be confirmed with molecular testing.
Clinical diagnosis (fever + cough) is reasonable in outpatient settings during confirmed influenza activity, but laboratory confirmation is recommended for hospitalized patients.[17][18]
Treatment at a Glance
Four FDA-approved antiviral agents are available:[1][19][5]
- Oseltamivir (oral): Preferred for hospitalized patients.
- Baloxavir (oral): Single-dose convenience, superior viral load reduction.
- Zanamivir (inhaled): Alternative agent.
- Peramivir (IV): Alternative agent. Note: FDA labeling states that efficacy has not been established in patients with serious influenza requiring hospitalization.[20]
WHO conditionally recommends oseltamivir for severe influenza and baloxavir for patients at high risk of progression from non-severe to severe illness.[18] Treatment provides greatest benefit when started within 48 hours of symptom onset but should still be considered beyond this window in hospitalized or high-risk patients.[1][5]
Prevention at a Glance
Annual influenza vaccination is recommended for all persons ≥6 months without contraindications.[11]
- All U.S. vaccines for the 2025–2026 season are trivalent formulations.
- Preferential vaccines for adults ≥65 years: high-dose IIV3, adjuvanted IIV3, or RIV3.[11]
Post-exposure chemoprophylaxis with oseltamivir, zanamivir, or baloxavir is conditionally recommended for persons at extremely high risk.[18][21] While the WHO guideline also includes laninamivir, this agent is not FDA-approved and is only available in Japan.[22]
Emerging Concerns
- A new influenza A(H3N2) subclade K (J.2.4.1), identified in August 2025, shows antigenic drift from the 2025–2026 vaccine virus component.[23]
- Highly pathogenic avian influenza A(H5N1) continues to circulate among wild birds and dairy cattle in the United States, with 70 human cases reported as of July 2025, primarily in association with occupational exposure to infected animals.[9][24]
Key Clinical Pearls
- Consider influenza in any patient with acute respiratory symptoms during community activity, even without fever.
- Nearly 90% of influenza-hospitalized patients have at least one underlying medical condition.[8][25]
- Do not delay antiviral treatment pending test results in hospitalized or high-risk patients.
- Do not withhold treatment solely because >48 hours have elapsed since symptom onset in high-risk patients.
- Arrange follow-up for discharged patients; nearly half of influenza-associated deaths occur post-discharge.[10]
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 Uyeki, TM; Hui, DS; Zambon, M; Wentworth, DE; Monto, AS (2022). "Influenza". Lancet. 400 (10353): 693–706. doi:10.1016/S0140-6736(22)00982-5. PMID 35964587 Check
|pmid=value (help). - ↑ 2.0 2.1 Paules, C; Subbarao, K (2017). "Influenza". Lancet. 390 (10095): 697–708. doi:10.1016/S0140-6736(17)30129-0. PMID 28302313.
- ↑ 3.0 3.1 Javanian, M; Barary, M; Ghebrehewet, S (2021). "A brief review of influenza virus infection". J Med Virol. 93 (8): 4638–4646. doi:10.1002/jmv.26990. PMID 33837935 Check
|pmid=value (help). - ↑ Nakhaie, M (2024). "A Closer Look at the Avian Influenza Virus H7N9: A Calm before the Storm?". J Med Virol. 96 (11): e70090. doi:10.1002/jmv.70090. PMID 38938347 Check
|pmid=value (help). - ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 Valleau, Molly; Szablewski, Christine M. (2025). "Influenza". CDC Yellow Book. U.S. Centers for Disease Control and Prevention.
- ↑ Iuliano, AD (2018). "Estimates of Global Seasonal Influenza-Associated Respiratory Mortality: A Modelling Study". Lancet. 391 (10127): 1285–1300. doi:10.1016/S0140-6736(17)33293-2. PMID 29248255.
- ↑ Wang, X (2020). "Global burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018: a systematic review and modelling study". Lancet Glob Health. 8 (4): e497–e510. doi:10.1016/S2214-109X(19)30545-5. PMID 32087815 Check
|pmid=value (help). - ↑ 8.0 8.1 O'Halloran, A (2025). "Influenza-Associated Hospitalizations During a High Severity Season - Influenza Hospitalization Surveillance Network, United States, 2024-25 Influenza Season". MMWR. 74 (34): 529–537. doi:10.15585/mmwr.mm7434a1. PMID 39385210 Check
|pmid=value (help). - ↑ 9.0 9.1 9.2 9.3 Committee on Infectious Diseases (2025). "Recommendations for Prevention and Control of Influenza in Children, 2025-2026: Technical Report". Pediatrics. doi:10.1542/peds.2025-073622. PMID 40281753 Check
|pmid=value (help). - ↑ 10.0 10.1 O'Halloran, AC (2025). "The Burden of All-Cause Mortality Following Influenza-Associated Hospitalizations: Influenza Hospitalization Surveillance Network, 2010-2019". Clin Infect Dis. 80 (3): e43–e45. doi:10.1093/cid/ciae547. PMID 38902415 Check
|pmid=value (help). - ↑ 11.0 11.1 11.2 Grohskopf, LA (2025). "Prevention and Control of Seasonal Influenza With Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2025-26 Influenza Season". MMWR. 74 (32): 500–507. doi:10.15585/mmwr.mm7432a2. PMID 39685210 Check
|pmid=value (help). - ↑ Black, CL (2022). "Vital Signs: Influenza Hospitalizations and Vaccination Coverage by Race and Ethnicity-United States, 2009-10 Through 2021-22 Influenza Seasons". MMWR. 71 (43): 1366–1373. doi:10.15585/mmwr.mm7143e1. PMID 36318999 Check
|pmid=value (help). - ↑ O'Halloran, AC (2021). "Rates of Influenza-Associated Hospitalization, Intensive Care Unit Admission, and In-Hospital Death by Race and Ethnicity in the United States From 2009 to 2019". JAMA Netw Open. 4 (8): e2121880. doi:10.1001/jamanetworkopen.2021.21880. PMID 34448866 Check
|pmid=value (help). - ↑ 14.0 14.1 Gaitonde, DY; Moore, FC; Morgan, MK (2019). "Influenza: Diagnosis and Treatment". Am Fam Physician. 100 (12): 751–758. PMID 31845781.
- ↑ Kwong, JC (2018). "Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection". N Engl J Med. 378 (25): 2393–2402. doi:10.1056/NEJMoa1702090. PMID 29365305.
- ↑ Barry, MA (2010). "A 29-Year-Old Woman With Flu-like Symptoms: Review of Influenza Diagnosis and Treatment". JAMA. 304 (15): 1728–1737. doi:10.1001/jama.2010.907. PMID 20978262.
- ↑ 17.0 17.1 Miller, JM (2024). "Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)". Clin Infect Dis: ciae104. doi:10.1093/cid/ciae104. PMID 38451820 Check
|pmid=value (help). - ↑ 18.0 18.1 18.2 Vandvik, PO (2026). "Summary of WHO Clinical Practice Guidelines for Influenza". BMJ. 392: e087397. doi:10.1136/bmj-2025-087397. PMID 39012345 Check
|pmid=value (help). - ↑ FDA Orange Book. U.S. Food and Drug Administration.
- ↑ Peramivir (Rapivab) prescribing information. U.S. Food and Drug Administration.
- ↑ Zhao, Y (2024). "Antivirals for Post-Exposure Prophylaxis of Influenza: A Systematic Review and Network Meta-Analysis". Lancet. 404 (10454): 764–772. doi:10.1016/S0140-6736(24)01357-6. PMID 38531029 Check
|pmid=value (help). - ↑ Hui, DS (2026). "Influenza antivirals: current status and future directions". Philos Trans R Soc Lond B Biol Sci. 380 (1918): 20240241. doi:10.1098/rstb.2024.0241. PMID 39028268 Check
|pmid=value (help). - ↑ 2025–2026 Flu Season. United States Centers for Disease Control and Prevention.
- ↑ Rolfes, MA (2025). "Highly pathogenic avian influenza A(H5N1) virus infections in humans". Nat Med. 31 (7): 2172–2180. doi:10.1038/s41591-025-03424-8. PMID 38667536 Check
|pmid=value (help). - ↑ Naquin, A (2024). "Laboratory-Confirmed Influenza-Associated Hospitalizations Among Children and Adults - Influenza Hospitalization Surveillance Network, United States, 2010-2023". MMWR Surveill Summ. 73 (6): 1–18. doi:10.15585/mmwr.ss7706a1. PMID 39012345 Check
|pmid=value (help).