Influenza for USMLE Step 1
Influenza for the USMLE Step 1 Exam
Etiology
- Influenza Virus:
- Influenza is caused by influenza viruses, which are enveloped, single-stranded RNA viruses from the Orthomyxoviridae family.
- Influenza A and Influenza B are the primary causes of seasonal epidemics, while Influenza C causes mild illness.
- Influenza A is further classified into subtypes based on its surface glycoproteins:
- Hemagglutinin (H): Mediates viral entry into host cells by binding to sialic acid receptors.
- Neuraminidase (N): Facilitates viral release from infected cells.
- The most common subtypes in humans are H1N1 and H3N2.
- Antigenic Drift vs. Antigenic Shift:
- Antigenic drift: Gradual point mutations in hemagglutinin and neuraminidase, leading to seasonal outbreaks.
- Antigenic shift: Abrupt reassortment of viral genome segments, causing pandemics. This occurs primarily in Influenza A.
Transmission
- Respiratory Droplets:
- Influenza spreads through respiratory droplets generated by coughing, sneezing, or talking. It can also spread by contact with contaminated surfaces followed by touching the face.
- Seasonality:
- Influenza is most prevalent during the winter months in temperate climates, causing seasonal epidemics.
Pathophysiology
- Viral Replication:
- The virus infects the respiratory epithelium, binding to sialic acid receptors through hemagglutinin. Viral replication causes damage to epithelial cells and desquamation of the respiratory tract lining, impairing mucociliary clearance.
- Immune Response:
- Infection triggers an immune response with the release of interferons and other cytokines (e.g., IL-6, TNF-α), causing systemic symptoms such as fever and myalgias.
- Complications:
- Influenza can predispose to secondary bacterial infections and can lead to direct viral pneumonia, particularly in immunocompromised or elderly patients.
Clinical Features
- Incubation Period:
- The incubation period for influenza is 1-4 days.
- Systemic Symptoms:
- Sudden onset of high fever, myalgias (especially in the back and legs), headache, and fatigue.
- Respiratory Symptoms:
- Dry cough, sore throat, and rhinorrhea. Respiratory symptoms often worsen as the disease progresses.
- Gastrointestinal Symptoms:
- In children, influenza may also cause nausea, vomiting, and diarrhea.
Complications
- Primary Viral Pneumonia:
- A severe form of pneumonia characterized by worsening dyspnea, high fever, and hypoxia during the acute phase of influenza. Chest X-ray shows diffuse bilateral infiltrates.
- Secondary Bacterial Pneumonia:
- Occurs after initial improvement of symptoms, with recurrence of fever and productive cough. Common pathogens include Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae.
- Other Complications:
- Exacerbation of chronic diseases (e.g., asthma, COPD), myocarditis, and rhabdomyolysis.
Diagnosis
- Clinical Diagnosis:
- During influenza season, diagnosis is often made clinically based on sudden onset of fever, myalgias, and respiratory symptoms.
- Laboratory Testing:
- Rapid influenza diagnostic tests (RIDTs): Detect viral antigens but have lower sensitivity.
- RT-PCR: The most accurate test, used to confirm infection and differentiate between influenza A and B.
Management
Antiviral Therapy
- Neuraminidase Inhibitors:
- Oseltamivir and zanamivir inhibit neuraminidase, preventing viral release from infected cells. They are effective against influenza A and B and should be initiated within 48 hours of symptom onset to reduce illness duration and severity.
- Baloxavir:
- A newer antiviral that inhibits cap-dependent endonuclease required for viral replication. Effective against both influenza A and B and requires only a single oral dose.
Supportive Care
- Symptomatic Treatment:
- Antipyretics (e.g., acetaminophen) for fever, hydration, and rest. Cough suppressants may be used for cough relief.
Prevention
- Vaccination:
- Annual influenza vaccination is recommended for all individuals ≥6 months. Vaccines are updated yearly to match circulating strains and include inactivated influenza vaccines (IIV) and live attenuated influenza vaccines (LAIV).
- Hand Hygiene:
- Regular handwashing and the use of alcohol-based hand sanitizers help reduce transmission.
Key Points
- Influenza is caused by Influenza A and B viruses, transmitted via respiratory droplets and presenting with sudden onset of fever, myalgias, and respiratory symptoms.
- Diagnosis is often clinical but can be confirmed by RT-PCR or RIDT.
- Complications include primary viral pneumonia, secondary bacterial pneumonia, and exacerbation of chronic diseases.
- Neuraminidase inhibitors (e.g., oseltamivir) and baloxavir are most effective when started within 48 hours of symptom onset.
- Annual vaccination is the cornerstone of prevention, recommended for all individuals ≥6 months.