Definition and epidemiology
Influenza is a contagious viral respiratory infection caused by influenza A or B viruses (influenza C and D cause minimal human disease). It occurs in annual epidemics during cooler months in temperate climates, with periodic pandemics caused by antigenically novel influenza A strains.
- Transmission is via respiratory droplets, aerosols, and contact with contaminated surfaces.
- Incubation period is typically 1-4 days.
- Attack rates vary by season; influenza causes substantial seasonal morbidity and hospitalization, with the very young, elderly, pregnant women, and those with chronic cardiopulmonary disease at highest risk for severe disease.
- Influenza A is subtyped by hemagglutinin (H) and neuraminidase (N) surface proteins (e.g., H1N1, H3N2); influenza B is divided into Victoria and Yamagata lineages.
- Abrupt onset of high fever and severe myalgia distinguishes influenza from the common cold.
- Antigenic drift causes seasonal epidemics; antigenic shift (reassortment) causes pandemics.
- Hemagglutinin mediates viral attachment; neuraminidase enables viral release from infected cells.
- Neuraminidase inhibitors (oseltamivir) work best when started within 48 hours of symptom onset.
- Secondary bacterial pneumonia (S. pneumoniae, S. aureus) is the most common serious complication.
- Avoid aspirin in children with influenza due to Reye syndrome risk.
- Annual vaccination is recommended for essentially everyone 6 months and older.
- Amantadine and rimantadine are no longer used due to resistance.
Etiology and risk factors
Influenza viruses are enveloped, segmented, single-stranded RNA viruses of the Orthomyxoviridae family.
- Antigenic drift: minor point mutations in H and N proteins, responsible for the need for annual vaccine reformulation.
- Antigenic shift: major reassortment of genetic segments (often involving animal reservoirs such as swine or avian hosts), capable of producing pandemic strains due to lack of pre-existing population immunity.
Risk factors for severe disease
- Age under 5 years (especially under 2) or over 65 years
- Pregnancy
- Chronic conditions: asthma, COPD, heart disease, diabetes, chronic kidney or liver disease
- Immunosuppression
- Residence in long-term care facilities
- Obesity (BMI 40 or higher)
Pathophysiology
The virus binds sialic acid receptors on respiratory epithelial cells via hemagglutinin, enters the cell, and replicates, causing direct cytopathic injury to ciliated columnar epithelium of the trachea and bronchi. Neuraminidase cleaves sialic acid residues, allowing release of new virions and further spread.
Epithelial destruction impairs mucociliary clearance, predisposing to secondary bacterial infection (classically Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae). Systemic symptoms (fever, myalgias, malaise) result from a robust innate immune response with release of interferons and proinflammatory cytokines, which also contributes to the abruptness and severity of symptom onset.
Clinical features
Classic presentation is abrupt onset of:
- High fever (often 38.5-40°C) with chills
- Severe myalgias and arthralgias
- Headache
- Dry cough
- Sore throat and nasal congestion
- Prominent fatigue and malaise, often out of proportion to upper respiratory symptoms
Symptoms typically peak within 2-3 days and resolve over 5-7 days, though cough and fatigue may persist longer. Children may additionally have vomiting, diarrhea, and febrile seizures. Elderly patients may present atypically with confusion or without fever.
Diagnosis
Diagnosis is often clinical during known community outbreaks but can be confirmed with laboratory testing, especially when results will change management.
| Test | Characteristics |
|---|---|
| Rapid antigen test | Fast, low-moderate sensitivity |
| Rapid molecular/PCR assay | High sensitivity and specificity, now widely used at point of care |
| Viral culture | Reference standard but slow, used mainly for surveillance |
| Serology | Research/epidemiologic use only |
- Nasopharyngeal swab is the preferred specimen.
- Multiplex PCR panels can simultaneously test for influenza A/B, RSV, and SARS-CoV-2.
- Chest imaging is reserved for suspected pneumonia or complications.
- Routine testing is not required in low-risk outpatients during a confirmed local outbreak but is recommended for hospitalized patients, high-risk patients, and those for whom antiviral therapy or infection control decisions depend on the result.
Differential diagnosis
- Common cold (rhinovirus): gradual onset, mild symptoms, low-grade or no fever
- COVID-19: overlapping symptoms; often more associated with anosmia/ageusia, requires specific testing to distinguish
- Respiratory syncytial virus (RSV): especially in infants and elderly, more bronchiolitis/wheeze predominant
- Streptococcal pharyngitis: sore throat predominant, exudate, tender adenopathy, no significant cough
- Community-acquired bacterial pneumonia: focal consolidation, productive cough, often follows or complicates influenza
- Acute HIV infection: consider if risk factors present and symptoms atypical or prolonged
Management
Most cases are managed with supportive care alone.
Supportive care
- Rest, oral hydration
- Antipyretics/analgesics (acetaminophen or NSAIDs) for fever and myalgia
- Avoid aspirin in children due to Reye syndrome risk
Antiviral therapy
Neuraminidase inhibitors (oseltamivir, zanamivir) or the cap-dependent endonuclease inhibitor baloxavir reduce symptom duration and may reduce complications when started early.
- Most beneficial when initiated within 48 hours of symptom onset, though hospitalized or severely ill patients may still benefit later.
- Recommended for patients who are hospitalized, severely ill, or at high risk for complications (per CDC and WHO guidance), regardless of symptom duration.
- May be considered in otherwise healthy outpatients at clinician discretion, though benefit is more modest.
- Amantadine/rimantadine are no longer recommended due to widespread resistance in circulating strains.
Prevention
- Annual inactivated or live-attenuated influenza vaccination is the cornerstone of prevention, recommended for essentially all persons 6 months and older without contraindication.
- Vaccine composition is updated yearly based on circulating strain surveillance.
- Chemoprophylaxis with antivirals can be considered for high-risk unvaccinated contacts after exposure.
- Infection control: droplet precautions, hand hygiene, isolation of symptomatic patients in healthcare settings.
Secondary bacterial infection
Suspect if fever recurs after initial improvement ('biphasic' illness) or if new focal pulmonary findings develop; treat with appropriate antibiotics covering S. pneumoniae, S. aureus (including MRSA coverage if indicated), and H. influenzae.
Complications and prognosis
Most healthy individuals recover fully within 1-2 weeks without specific therapy.
Complications
- Secondary bacterial pneumonia (most common serious complication)
- Primary viral pneumonia (more severe, can cause ARDS)
- Exacerbation of underlying cardiopulmonary disease
- Myocarditis, pericarditis
- Encephalopathy, encephalitis, febrile seizures (especially children)
- Reye syndrome (associated with aspirin use in children)
- Guillain-Barré syndrome (rare)
- Multiorgan failure in severe cases
Prognosis
Prognosis is excellent in healthy individuals. Mortality and severe morbidity are concentrated among the very young, elderly, pregnant women, and those with significant comorbidities, who account for the large majority of influenza-related hospitalizations and deaths each season.
FLU = Fever (abrupt), Lethargy/myaLgias, aqUte onset — contrast with the common cold's gradual, afebrile course.
Practice questions
1. A 34-year-old woman presents with abrupt onset of fever to 39.2°C, severe myalgias, headache, and dry cough that began 18 hours ago. She is otherwise healthy and not pregnant. Rapid influenza PCR is positive for influenza A. Which of the following is the most appropriate next step in management?
2. A 7-year-old boy with influenza B infection initially improves after 4 days but then develops recurrent fever, productive cough, and new right lower lobe crackles on day 6 of illness. Which pathogen is most likely responsible for this new presentation?
3. A mother asks why her 5-year-old son with suspected influenza should not be given aspirin for fever control. Which of the following best explains the rationale?
Frequently asked questions
What causes influenza?
Influenza is caused by influenza A or B RNA viruses that infect respiratory epithelial cells. Influenza A viruses are further classified by hemagglutinin and neuraminidase surface proteins and can undergo antigenic drift (minor mutations causing seasonal epidemics) or antigenic shift (major reassortment causing pandemics). Influenza B causes milder, more localized outbreaks and does not cause pandemics.
What are the first symptoms of influenza?
The first symptoms are usually abrupt fever, chills, severe muscle aches, and headache, often appearing within hours. A dry cough, sore throat, and nasal congestion typically follow. This sudden, systemic onset distinguishes influenza from the common cold, which develops gradually and causes milder symptoms without significant fever or body aches.
How is influenza diagnosed?
Influenza is often diagnosed clinically based on symptoms and known community circulation, but confirmation uses a nasopharyngeal swab tested by rapid antigen testing or, preferably, molecular PCR assay for higher accuracy. Testing is most important for hospitalized, high-risk, or severely ill patients where results guide antiviral therapy and infection control decisions.
Is influenza curable?
Influenza is self-limiting in most healthy people, resolving within 1-2 weeks without specific cure, as there is no treatment that eradicates the virus outright. Antivirals like oseltamivir can shorten illness duration and reduce complication risk if started early, but recovery mainly depends on the immune system clearing the infection naturally.
Influenza vs common cold — what is the difference?
Influenza has abrupt onset with high fever, severe myalgias, and marked fatigue, while the common cold develops gradually with mild symptoms, minimal or no fever, and prominent nasal congestion or sneezing. Influenza is also more likely to cause significant complications like pneumonia, whereas colds rarely cause serious illness in healthy people.
Key drugs
Related conditions and differentials
Sources and further reading
StatPearls (NCBI Bookshelf)MedlinePlusWHO ICD-10: J10
Educational content for medical students, prepared by the WhiteCoat Pro editorial team with AI assistance; every page is reviewed by a second AI model for factual errors. It is not medical advice and does not replace the product label, local guidelines or a clinician.