• Acute onset (within hours)

• High fever with rigors

• Severe body ache — especially back and limbs

• Marked weakness and prostration (“can’t get out of bed”)

• Dry, persistent cough

• Sore throat and hoarseness

• Nasal symptoms:

– Rhinorrhea

– Nasal obstruction

• Chest burning or discomfort

• Anorexia, nausea, occasional vomiting

• Children:

– GI symptoms more common

– Febrile seizures possible

• Elderly:

– Minimal fever

– Confusion, lethargy

• Complicated influenza:

– Dyspnea

– Hypoxia

– Pleuritic chest pain

– Persistent high fever >3–4 days

• Primary influenza viral pneumonia

– Rapid hypoxia, diffuse bilateral infiltrates

– Occurs more in elderly, pregnant, immunocompromised

• Secondary bacterial pneumonia

– Classically after initial improvement

– Sudden high fever, productive cough

– Staph aureus causes severe necrotizing pneumonia

• Acute respiratory distress syndrome (ARDS)

• Exacerbation of chronic diseases

– COPD, asthma

– Heart failure worsening

• Myositis / Rhabdomyolysis

– Severe muscle pain, elevated CPK

• Otitis media (especially in children)

• Sinusitis

• Neurologic complications

– Encephalitis

– Acute necrotizing encephalopathy (rare)

– Guillain-Barré syndrome (rare)

• Cardiac complications

– Myocarditis

– Pericarditis

• Sepsis and multiorgan failure (severe cases)

• Dehydration (common in elderly & children)

• COVID-19

– Fever, myalgia, cough overlap

– Loss of smell/taste more suggestive

– RT-PCR differentiates

• Other Viral Respiratory Infections:

– Rhinovirus

– Adenovirus

– Parainfluenza

– RSV

– Human metapneumovirus

• Bacterial Pneumonia

– Higher fever, rigors

– Focal consolidation on auscultation or CXR

– Higher WBC count

• Mycoplasma / Atypical Pneumonia

– Dry cough, slow onset

– Extrapulmonary features possible

• Acute bronchitis

– Cough predominant, minimal systemic symptoms

• Sinusitis with post-nasal drip

– Facial pressure, localized sinus tenderness

• Allergic rhinitis / non-infective causes

– Itching, sneezing, no fever

• Early sepsis from other sources

– Depends on systemic signs and lab markers

• *Influenza A* infects humans, birds, pigs → responsible for epidemics & pandemics.

- Characterized by antigenic **shift** (reassortment) and **drift** (point mutations).

- Subtypes determined by *Hemagglutinin (H)* and *Neuraminidase (N)* genes (e.g., H1N1, H3N2).

• *Influenza B* infects humans only → limited outbreaks; undergoes **only antigenic drift**.

• *Influenza C* causes mild upper respiratory infections in children.

• Transmission: respiratory droplets, aerosols, and contaminated surfaces.

• CBC:

– Normal or low WBC

– Lymphopenia common

• CRP: usually mildly elevated

• Virological Tests:

– RT-PCR (gold standard)

– Detects Influenza A, B (and subtyping if needed)

– Highest yield within first 48–72 hours of illness

– Can be done from nasopharyngeal swab, throat swab, or aspirates

• Rapid Influenza Diagnostic Tests (RIDTs):

– Provide results in 10–20 minutes

– Sensitivity moderate; false negatives common

– Positive test useful; negative test does NOT rule out influenza

• Viral culture:

– Rarely used clinically

– Takes several days

• Chest Radiography:

– Usually normal in uncomplicated influenza

– If pneumonia suspected:

▪ Patchy infiltrates

▪ Bilateral involvement

▪ Lobar consolidation suggests bacterial superinfection

• Oxygen saturation (Pulse oximetry) for all moderate–severe cases

• Additional tests if complications suspected:

– ABG (respiratory distress)

– LFTs (Reye syndrome in children on aspirin)

– Troponin/EKG (myocarditis)

– CXR/CT (severe lower respiratory disease)

• **Why influenza spreads rapidly**

– High mutation rate (antigenic drift)

– Periodic emergence of new strains (antigenic shift → pandemics)

– Short incubation period (1–3 days)

– Peak viral shedding occurs **before symptoms fully appear**

• **Difference between Influenza A, B, and C**

– **A:** Most severe; infects humans + animals; causes pandemics

– **B:** Milder, mostly human; causes localized outbreaks

– **C:** Mild cold-like illness; rarely diagnosed clinically

• **Why symptoms are severe (pathophysiology pearl)**

– Many symptoms (fever, myalgia, malaise) are due to **cytokine storm** from interferons & inflammatory mediators

– Influenza primarily affects **upper airway epithelium**, but severe cases damage alveoli → viral pneumonitis

• **Complications occur due to two mechanisms**

– **Direct viral damage:** viral pneumonitis, ARDS

– **Secondary bacterial infection:** S. aureus, S. pneumoniae, H. influenzae

(Look for sudden worsening after initial improvement)

• **Red flags in influenza**

– Persistent high fever >3–4 days

– Dyspnea, hypoxia

– Altered sensorium

– Chest pain

– Rapid deterioration in pregnancy or elderly

• **Why antivirals help when started early**

– Viral replication peaks within 48 hours

– Oseltamivir works best if started **within 2 days** of symptom onset

– Benefit decreases once viral replication drops

• **Influenzas mimics many diseases**

– Dengue (fever, myalgia)

– COVID-19 (cough, GGO on CT)

– Pneumonia (fever + cough)

– Meningitis (in children → irritability)

• **Teaching pearl**

– “**Influenza causes interstitial pneumonia; consolidation means bacteria**.”

This is a key diagnostic distinction.

• **Important vaccination reminder**

– Annual flu vaccines are needed because **influenza viruses mutate every year**.

– Vaccine reduces severity, complications, and mortality even if infection occurs.

• Virus enters via inhalation → attaches using **Hemagglutinin (H)** to sialic-acid receptors.

• Viral replication occurs in respiratory epithelial cells → **cell necrosis & desquamation**.

• Loss of mucociliary clearance → increased risk of **bacterial superinfection**.

• Release of pro-inflammatory cytokines (IL-1, IL-6, TNF-α) causes:

– High fever

– Myalgia

– Fatigue

– Systemic toxicity

• Viremia is rare but may contribute to myocarditis or encephalopathy.

• Immune response:

– Innate (NK cells, interferons) controls early infection

– Adaptive immunity (IgA, IgG) prevents reinfection but wanes in months

– Virus infects ciliated columnar epithelium of nose, trachea & bronchi

– Causes *cell death, desquamation,* and loss of mucociliary clearance

– Interstitial infiltration with **lymphocytes, macrophages, plasma cells**

– Submucosal edema → airway narrowing

• **Diffuse alveolar damage (DAD) in severe cases**

– Hyaline membrane formation

– Alveolar collapse and impaired gas exchange

– Leads to ARDS in severe influenza A infections (especially H1N1)

• **Secondary bacterial infection predisposition**

– Damaged epithelium allows invasion by *Staph aureus, Strep pneumoniae, H. influenzae*

– This is a major cause of fatal influenza pneumonia

• **Airways changes**

– Plugging with necrotic debris and mucus

– Bronchiolitis with sloughing of epithelium

• **Lymphoid tissue involvement**

– Reactive hyperplasia in lymph nodes & spleen

– Mild necrosis in severe cases

• **Systemic pathology (rare but recognised)**

– Myositis & rhabdomyolysis (viral muscle invasion)

– Myocarditis (lymphocytic)

– Encephalitis (immune-mediated rather than direct viral)

Influenza pathology is mainly **epithelial destruction + interstitial inflammation**, creating conditions for **secondary bacterial pneumonia**, which is the primary cause of severe morbidity and mortality.

• Vaccination

– Recommended yearly for **all individuals ≥6 months**

– High-dose or adjuvanted vaccine for elderly (>65 yrs)

– Strongly recommended for pregnant women, healthcare workers, chronic disease patients

– Provides protection against Influenza A & B (not C, which is mild)

• Infection control

– Frequent hand washing

– Use masks in crowded settings during outbreaks

– Avoid close contact with symptomatic individuals

– Proper respiratory hygiene: cover coughs/sneezes

• Community-level prevention

– Early detection and isolation of infected persons

– School/workplace absentee policy during fever/illness

– Annual vaccination campaigns in hospitals, institutions

• Household prevention

– Isolate symptomatic members

– Clean commonly touched surfaces (phones, door handles, keyboards)

• Chemoprophylaxis (special situations)

– *Oseltamivir prophylaxis in high-risk exposed individuals*

– Used in nursing homes, immunocompromised patients, post-exposure situations

– Duration usually 7–10 days after last exposure

• Prevention of complications

– Good control of asthma/COPD

– Smoking cessation

– Adequate nutrition and hydration

• **Chest X-ray – Typical findings**

– Patchy or diffuse **bilateral interstitial infiltrates**

– Peribronchial cuffing

– Reticulonodular opacities

– Hyperinflated lungs (especially in children)

– Usually **no lobar consolidation** unless secondary bacterial infection

• **Chest X-ray – Severe/complicated influenza**

– Diffuse ground-glass appearance

– Patchy alveolar opacities

– Signs of **ARDS** in severe influenza A (H1N1):

· Bilateral hazy opacities

· Dependent consolidations

· Reduced lung volumes

• **CT Chest**

– **Ground-glass opacities (GGO)**, bilateral and peripheral

– Interlobular septal thickening

– Patchy consolidation (rare in pure viral pneumonia)

– Tree-in-bud is uncommon; if present → consider bacterial infection

– Areas of atelectasis in dependent lung regions

• **Features suggesting secondary bacterial pneumonia**

– Dense lobar consolidation

– Air bronchograms

– Pleural effusion

– Cavitation (Staph aureus)

• **Pleural effusion**

– Rare in influenza

– Presence suggests superadded bacterial infection

Radiology in influenza shows **interstitial viral pneumonitis**, while **lobar consolidation or effusion indicates secondary bacterial pneumonia**, which dramatically changes management.

• **Influenza A – multiple subtypes**

– Classified by **Hemagglutinin (H)** and **Neuraminidase (N)** surface proteins

– Examples: **H1N1**, **H3N2**, H5N1, H7N9

– Responsible for most epidemics & pandemics

– High mutation & reassortment ability

• **Influenza B – lineages, not subtypes**

– Two major lineages: **B/Yamagata** and **B/Victoria**

– Less antigenic variation than Type A

– Causes seasonal outbreaks

• **Influenza C – mild, no major subtypes**

– Limited human disease

– No significant antigenic drift/shift

– Not included in routine diagnostic panels

• Special points

– *Influenza A undergoes both antigenic drift and shift* → pandemics

– *Influenza B has only antigenic drift*

– Vaccines are updated yearly to match circulating A subtypes + B lineages

• Flushed face

• Warm, sweaty skin

• Conjunctival injection

• Pharyngeal erythema without exudate

• Tender cervical lymph nodes (mild)

• Dry cough with chest discomfort

• Auscultation:

– Usually clear early

– Occasional scattered rhonchi

• In children:

– Signs of otitis media

– Tachypnea

• In elderly:

– Hypoxia

– Confusion / altered mentation

• Severe cases:

– Signs of pneumonia

– Wheezes / crackles

– Respiratory distress

Influenza is an acute respiratory illness caused by Orthomyxoviridae viruses (Influenza A, B, and C).

Seasonal epidemics occur every winter; pandemics are due to Influenza A antigenic shifts.

• Headache — often frontal or retro-orbital

• Dry, painful cough

• Sore throat

• Nasal congestion / rhinorrhea

• Chills and rigors

• Loss of appetite

• Sweating

• Generalized weakness

• Children may have:

– Vomiting

– Abdominal pain

– Otitis media

• Elderly often show:

– Worsening of underlying COPD/asthma

– Confusion / delirium

• Antiviral therapy

– **Oseltamivir** 75 mg twice daily × 5 days (adults)

– **Zanamivir** inhaled (avoid in asthma/COPD)

– **Peramivir** IV (for hospitalized patients)

– Benefit even after 48 hours in severe/progressive disease

• Indications for antivirals (start immediately):

– Hospitalized patients

– Severe/progressive disease

– High-risk groups: >65 yrs, pregnancy, chronic diseases, immunocompromised, obesity, children <5 yrs

• Supportive care

– Adequate hydration

– Antipyretics (paracetamol)

– Avoid aspirin in children (risk of Reye syndrome)

• Oxygen therapy if hypoxic

• Treat secondary bacterial infections

– Start antibiotics if bacterial pneumonia suspected

– Staph aureus coverage if rapid worsening (e.g., cloxacillin/cephalosporin + macrolide)

• Management of complications

– ARDS: ICU care, ventilatory support

– Exacerbation of COPD/asthma: bronchodilators, steroids as per protocol

– Myositis/rhabdomyolysis: monitor CPK, aggressive fluids

• Isolation precautions

– Droplet precautions

– Sick people stay home until fever-free for 24 hours without antipyretics