Acute viral respiratory illness from influenza A or B with seasonal epidemics and pandemic potential.
Also known as: influenza, flu, seasonal flu, influenza A, influenza B
Overview
Acute respiratory illness caused by influenza A or B viruses (single-stranded segmented RNA, family Orthomyxoviridae), characterized by abrupt onset of fever, myalgia, headache, and respiratory symptoms.
Epidemiology
Annual seasonal epidemics in temperate regions (Northern Hemisphere November-April). Causes an estimated 9.4-51 million illnesses, 120,000-710,000 hospitalizations, and 6,300-52,000 deaths annually in the US (CDC, 2010-2025). Antigenic drift drives seasonal variation; antigenic shift in influenza A drives pandemics (1918, 1957, 1968, 2009).
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Question 1Infectious DiseaseEasy
A 26-year-old previously healthy woman has 3 days of dry cough, low-grade fever, myalgias, and mild dyspnea on exertion. Temperature is 100.6°F (38.1°C), HR 96/min, RR 18/min, and SpO2 96% on room air. Lung exam reveals scattered fine crackles without consolidation. A chest radiograph shows bilateral diffuse interstitial infiltrates. Rapid PCR is positive for influenza A, 36 hours after symptom onset. Which of the following is the most appropriate first-line management?
AOral dexamethasone
BOral valacyclovir
COral rimantadine
DOral oseltamivir
EInhaled ribavirin
Reveal answer & full explanation
Correct answer: D — Oral oseltamivir
AOral dexamethasone
BOral valacyclovir
COral rimantadine
DOral oseltamivir✓
EInhaled ribavirin
Why Oral oseltamivir is correct
This is influenza A (confirmed by rapid PCR) with the diffuse interstitial pattern typical of viral pneumonia rather than lobar bacterial consolidation
Neuraminidase inhibitors block release of virus from infected cells and shorten illness when started within 48 hours of symptom onset, met here at 36 hours
Oral oseltamivir 75 mg twice daily for 5 days is the standard first-line antiviral for uncomplicated influenza in adults
Why the others are wrong
Oral rimantadine — an adamantane active only against influenza A, but essentially all circulating strains carry M2 resistance, so it is no longer recommended for treatment
Inhaled ribavirin — reserved for severe respiratory syncytial virus infection in immunocompromised patients, not influenza (buzzword-matching "antiviral")
Oral valacyclovir — inhibits herpesvirus DNA polymerase and has no activity against influenza virus
Oral dexamethasone — corticosteroids help hypoxemic COVID-19 pneumonia, which makes them tempting for viral pneumonia with infiltrates, but IDSA advises against adjunctive corticosteroids in influenza because observational data link them to higher mortality and secondary infection, and this patient is not even hypoxemic (carrying COVID-19 steroid practice over to influenza)
Question 2Infectious DiseaseEasy
A 45-year-old woman presents with acute onset fever, chills, malaise, myalgias, and a non-productive cough in December. Rapid influenza test is positive. She has asthma and has not received this season's influenza vaccine. She is symptomatic for 28 hours. Which is the most appropriate treatment?
AOseltamivir
BSupportive care only
CInhaled zanamivir
DAmantadine
EOral ribavirin
Reveal answer & full explanation
Correct answer: A — Oseltamivir
AOseltamivir✓
BSupportive care only
CInhaled zanamivir
DAmantadine
EOral ribavirin
Why Oseltamivir is correct
Oseltamivir (Tamiflu) is first-line antiviral for influenza A and B, most effective when started within 48 hours of symptom onset (this patient is at 28 hours)
High-risk patients — including those with asthma, age above 65, pregnancy, immunocompromised status, or severe illness — should receive treatment regardless of timing
Why the others are wrong
Amantadine — amantadine and rimantadine are no longer recommended due to widespread resistance in influenza A and no activity against influenza B
Inhaled zanamivir — is an alternative antiviral but is contraindicated in patients with asthma or chronic obstructive pulmonary disease (COPD)
Supportive care only — insufficient for a high-risk patient (asthma) presenting within 48 hours of symptom onset with a positive rapid test
Oral ribavirin — ribavirin is a broad-spectrum antiviral associated with respiratory viruses through its aerosolized use for severe RSV in selected patients, but it is not FDA-approved or recommended for influenza, has no proven benefit for it, and carries hemolytic anemia and teratogenic risk
Additional high-yield points
Annual vaccination remains the best prevention
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American Indian/Alaska Native populations (increased severe disease)
Pathophysiology
Influenza virus binds sialic acid receptors on respiratory epithelium via hemagglutinin (HA). Viral neuraminidase (NA) cleaves sialic acid to release new virions. Local respiratory epithelial injury, systemic inflammatory cytokine response, and impaired mucociliary clearance predispose to secondary bacterial pneumonia. Influenza A subtypes (H1N1, H3N2) and influenza B/Victoria co-circulate; B/Yamagata has not been detected globally since 2020.
Clinical presentation
Symptoms
Abrupt onset (over hours) of fever, chills, myalgia, headache, fatigue
Hospitalized patients: treat regardless of symptom duration
Outpatients: treat if high-risk (age, pregnancy, chronic conditions, immunocompromise, severe illness) or within 48 h of onset in healthy patients
Supportive care: hydration, rest, acetaminophen/NSAIDs for fever and myalgia (avoid aspirin in children — Reye syndrome)
Second-line / adjunct
Treat secondary bacterial pneumonia (S. pneumoniae, S. aureus including MRSA, H. influenzae): empiric beta-lactam ± vancomycin/linezolid based on severity
Post-exposure chemoprophylaxis with oseltamivir or zanamivir for high-risk unvaccinated close contacts (within 48 h of exposure) — 7 days
Prevention is paramount: ANNUAL influenza vaccination for everyone ≥6 months
Vaccine options: all US vaccines have been trivalent since 2024-25 (B/Yamagata removed): standard inactivated (IIV3), recombinant (RIV3), live-attenuated nasal (LAIV3, ages 2-49, non-pregnant, non-immunocompromised); high-dose (HD-IIV3), adjuvanted (aIIV3), or recombinant (RIV3) preferred for adults ≥65
Infection control: droplet precautions in hospitals; isolation of infected patients
Complications
Primary influenza viral pneumonia (especially in pregnancy, immunocompromised)
Secondary bacterial pneumonia (S. pneumoniae, S. aureus including MRSA, H. influenzae) — often biphasic with initial improvement then deterioration
ARDS, multi-organ failure
Exacerbation of chronic conditions: COPD, asthma, heart failure
Myositis, rhabdomyolysis (especially influenza B in children)
Reye syndrome (children given aspirin)
PANCE pearls
Abrupt-onset fever, myalgia, and dry cough in a previously well adult during flu season is influenza until proven otherwise.
Antiviral benefit is greatest within 48 h of symptom onset — do not delay for testing in high-risk patients.
Biphasic illness (initial improvement, then recurrent fever and worsening) suggests secondary bacterial pneumonia, often S. aureus or S. pneumoniae.
AVOID aspirin in children with influenza or varicella — Reye syndrome risk.
Annual vaccination is the most important preventive intervention; everyone ≥6 months should receive it absent specific contraindication.
Adamantanes (amantadine, rimantadine) are not recommended for influenza: circulating influenza A strains are almost universally resistant (M2 mutation), and they have no activity against influenza B.
References
IDSA 2018 — Clinical Practice Guidelines by IDSA: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza (Uyeki et al., Clin Infect Dis 2019)
CDC/ACIP 2025 — Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the ACIP, United States, 2025-26 Influenza Season (Grohskopf et al., MMWR Morb Mortal Wkly Rep 2025;74(32):500-507)
Baloxavir Trials — Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents (Hayden et al., NEJM 2018)
Cochrane Oseltamivir — Neuraminidase Inhibitors for Preventing and Treating Influenza in Healthy Adults and Children (Jefferson et al., Cochrane Database Syst Rev 2014)
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