Influenza (Flu - Orthomyxoviruses)
Overview
Plain-Language Overview
Influenza (Flu) is a contagious respiratory illness caused by influenza viruses that primarily affect the nose, throat, and lungs. It spreads easily from person to person through coughing, sneezing, or close contact. The infection leads to symptoms like fever, cough, sore throat, body aches, and fatigue, which can range from mild to severe. In some cases, especially in the very young, elderly, or those with weakened immune systems, it can cause serious complications such as pneumonia. The flu season typically occurs in the colder months, and outbreaks can lead to widespread illness in communities.
Clinical Definition
Influenza (Flu) is an acute viral infection of the respiratory tract caused by Orthomyxoviridae family viruses, primarily types A and B. The virus infects epithelial cells of the upper and lower respiratory tract, leading to cell death and inflammation. Transmission occurs via respiratory droplets, and the virus exhibits antigenic drift and shift, enabling frequent epidemics and pandemics. Clinically, it presents with sudden onset of fever, myalgia, headache, malaise, nonproductive cough, and sore throat. The infection can cause complications such as viral or secondary bacterial pneumonia, exacerbation of chronic diseases, and rarely, myocarditis or encephalitis. Diagnosis and management are critical due to its high morbidity and mortality during seasonal outbreaks.
Inciting Event
Inhalation of respiratory droplets containing influenza virus from infected persons.
Contact with contaminated surfaces followed by touching the nose or mouth.
Exposure during seasonal influenza epidemics in community or healthcare settings.
Latency Period
Typical incubation period is 1 to 4 days after viral exposure.
Symptoms usually develop rapidly within 2 days of infection.
Diagnostic Delay
Early symptoms mimic common viral illnesses leading to misattribution as a common cold.
Lack of rapid testing availability or use delays confirmation by RT-PCR or rapid antigen tests.
Mild or atypical presentations in vaccinated or partially immune individuals obscure diagnosis.
Clinical Presentation
Signs & Symptoms
Abrupt onset of high fever, myalgia, and headache are hallmark symptoms.
Nonproductive cough and sore throat commonly accompany systemic symptoms.
Fatigue and malaise can be severe and prolonged.
Nasal congestion and rhinorrhea are frequent upper respiratory symptoms.
Gastrointestinal symptoms like nausea and vomiting may occur, especially in children.
History of Present Illness
Abrupt onset of high fever, chills, and myalgia within 1-2 days of exposure.
Prominent cough, sore throat, and nasal congestion develop shortly after systemic symptoms.
Patients often report fatigue and headache accompanying respiratory complaints.
Symptoms typically last 5 to 7 days, with cough and malaise sometimes persisting longer.
Past Medical History
History of chronic lung disease such as asthma or COPD increases risk of severe illness.
Previous influenza vaccination status affects disease severity and presentation.
Immunocompromising conditions like HIV infection or cancer chemotherapy alter clinical course.
Prior episodes of influenza or other respiratory infections may influence immunity.
Family History
No specific heritable syndromes are associated with influenza susceptibility.
Family members often share exposure risks during household outbreaks.
Genetic polymorphisms in immune response genes may modulate severity but are not routinely tested.
Physical Exam Findings
Fever and tachycardia are common during acute influenza infection.
Pharyngeal erythema without exudate is frequently observed.
Diffuse rhonchi or crackles may be present if lower respiratory tract involvement occurs.
Conjunctival injection can be seen in some cases.
Lymphadenopathy is generally absent or mild.
Diagnostic Workup
Diagnostic Criteria
Diagnosis of influenza is primarily clinical during peak season, based on acute onset of fever, cough, and systemic symptoms. Confirmation is achieved by detecting viral RNA or antigen using reverse transcription polymerase chain reaction (RT-PCR) or rapid antigen tests from nasopharyngeal swabs. Viral culture is less commonly used due to longer turnaround time. Chest imaging may be performed if pneumonia is suspected. Laboratory findings are nonspecific but may show leukopenia or mild lymphopenia.
Pathophysiology
Key Mechanisms
Infection with influenza virus, an enveloped negative-sense RNA virus of the Orthomyxoviridae family, leads to respiratory epithelial cell damage.
Viral hemagglutinin (HA) binds to sialic acid receptors on respiratory epithelial cells facilitating viral entry.
Neuraminidase (NA) cleaves sialic acid residues to promote viral release and spread to adjacent cells.
Host immune response causes inflammation and systemic symptoms through cytokine release, contributing to fever and malaise.
Epithelial damage impairs mucociliary clearance, increasing susceptibility to secondary bacterial pneumonia.
| Involvement | Details |
|---|---|
| Organs | Lungs are the primary organs affected, with viral pneumonia as a major complication. |
Nasal passages serve as the initial site of viral entry and replication. | |
Spleen participates in immune response by filtering blood and activating lymphocytes. | |
| Tissues | Respiratory mucosa is damaged by viral replication leading to inflammation and increased susceptibility to secondary infections. |
| Cells | Respiratory epithelial cells are the primary targets of influenza virus infection and replication. |
Cytotoxic T lymphocytes mediate clearance of infected cells through targeted killing. | |
Macrophages contribute to viral clearance and release proinflammatory cytokines driving symptoms. | |
| Chemical Mediators | Interferon-alpha is produced by infected cells and initiates antiviral responses. |
Tumor necrosis factor-alpha (TNF-α) promotes inflammation and systemic symptoms like fever. | |
Interleukin-6 (IL-6) contributes to acute phase response and fever during infection. |
Treatments
Pharmacological Treatments
Oseltamivir
- Mechanism:
Inhibits the neuraminidase enzyme, preventing viral release from infected cells.
- Side effects:
Nausea
Vomiting
Headache
- Clinical role:
First-line
Zanamivir
- Mechanism:
Blocks neuraminidase, reducing viral spread in the respiratory tract.
- Side effects:
Bronchospasm
Cough
Nasal irritation
- Clinical role:
First-line
Baloxavir marboxil
- Mechanism:
Inhibits the cap-dependent endonuclease activity of the viral polymerase, blocking viral mRNA synthesis.
- Side effects:
Diarrhea
Bronchitis
Headache
- Clinical role:
Second-line
Non-pharmacological Treatments
Supportive care with hydration and rest to aid recovery.
Use of antipyretics such as acetaminophen to reduce fever and myalgia.
Isolation and respiratory hygiene to prevent transmission.
Prevention
Pharmacological Prevention
Annual influenza vaccination with inactivated or live-attenuated vaccines is the primary prevention.
Neuraminidase inhibitors like oseltamivir can be used for post-exposure prophylaxis in high-risk individuals.
Baloxavir marboxil is an alternative antiviral for prophylaxis in certain cases.
Non-pharmacological Prevention
Hand hygiene with soap and water or alcohol-based sanitizers reduces transmission.
Respiratory etiquette including covering coughs and sneezes limits spread.
Avoidance of close contact with infected individuals during outbreaks is recommended.
Use of masks in crowded or healthcare settings helps prevent viral spread.
Isolation of infected patients reduces nosocomial transmission.
Outcome & Complications
Complications
Primary viral pneumonia causing respiratory failure is a severe complication.
Secondary bacterial pneumonia often due to Staphylococcus aureus or Streptococcus pneumoniae.
Exacerbation of chronic lung diseases such as asthma or COPD.
Myocarditis and pericarditis can occur rarely.
Reye syndrome is a rare but serious complication in children given aspirin.
| Short-term Sequelae | Long-term Sequelae |
|---|---|
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Differential Diagnoses
Influenza (Flu - Orthomyxoviruses) versus Common Cold (Rhinovirus Infection)
Influenza (Flu - Orthomyxoviruses) | Common Cold (Rhinovirus Infection) |
|---|---|
Abrupt onset with high fever and systemic symptoms lasting about 3-7 days | Gradual onset with mild symptoms lasting 7-10 days |
Leukopenia with relative lymphopenia commonly observed | Normal or mildly elevated white blood cell count without lymphopenia |
Exposure during influenza season or outbreaks with rapid spread | Exposure to individuals with mild upper respiratory symptoms, often in community settings |
Influenza (Flu - Orthomyxoviruses) versus Respiratory Syncytial Virus (RSV) Infection
Influenza (Flu - Orthomyxoviruses) | Respiratory Syncytial Virus (RSV) Infection |
|---|---|
Affects all age groups, with severe disease more common in elderly and immunocompromised | Primarily affects infants and young children |
Predominantly upper respiratory symptoms with systemic features like myalgia and high fever | Often causes bronchiolitis with wheezing and lower respiratory tract involvement |
Positive rapid antigen test or PCR for influenza virus | Positive rapid antigen test or PCR for RSV |
Influenza (Flu - Orthomyxoviruses) versus Bacterial Pneumonia
Influenza (Flu - Orthomyxoviruses) | Bacterial Pneumonia |
|---|---|
Acute onset with dry cough and diffuse systemic symptoms | Progressive symptoms with productive cough and localized chest findings |
Leukopenia or normal WBC count with relative lymphopenia | Leukocytosis with neutrophilia and elevated procalcitonin |
Diffuse or patchy infiltrates without lobar consolidation | Focal lobar consolidation on chest X-ray |
Influenza (Flu - Orthomyxoviruses) versus COVID-19 (SARS-CoV-2 Infection)
Influenza (Flu - Orthomyxoviruses) | COVID-19 (SARS-CoV-2 Infection) |
|---|---|
Exposure to influenza virus during seasonal outbreaks | Exposure to confirmed COVID-19 cases or high-risk settings during pandemic |
Short incubation with abrupt onset of fever, myalgia, and respiratory symptoms | Variable incubation period with symptoms ranging from mild to severe respiratory distress over days |
Positive influenza virus PCR or rapid antigen test | Positive SARS-CoV-2 PCR or antigen test |
Influenza (Flu - Orthomyxoviruses) versus Adenovirus Infection
Influenza (Flu - Orthomyxoviruses) | Adenovirus Infection |
|---|---|
Primarily respiratory symptoms with abrupt fever and systemic myalgia | Often causes pharyngitis, conjunctivitis, and gastroenteritis with prolonged fever |
Positive influenza virus PCR or rapid antigen test | Positive adenovirus PCR or culture |
Seasonal outbreaks in community settings during winter | Common in close-contact environments like military barracks or daycare centers |