VIRUSES ASSOCIATED WITH UPPER RESPIRATORY TRACT

Viruses commonly associated with upper respiratory tract infections (URTIs):

• Rhinoviruses: The most common cause of the common cold.
• Coronaviruses: Includes seasonal coronaviruses and SARS-CoV-2.
• Influenza viruses (A, B, and C): Responsible for seasonal flu epidemics.
• Parainfluenza viruses: Can cause croup in children.
• Respiratory syncytial virus (RSV): A major cause of bronchiolitis in infants but also affects the upper respiratory tract.
• Adenoviruses: Known for causing pharyngitis and conjunctivitis.
• Enteroviruses: Includes Coxsackieviruses, which can cause herpangina or hand-foot-and-mouth disease.

Significance in relation to antibiotic abuse: Antibiotics are ineffective against viral infections. However, due to misdiagnosis or patient demand, antibiotics are often prescribed unnecessarily for URTIs caused by viruses. This misuse contributes to:

1. Antibiotic resistance: Overuse leads to the development of resistant bacterial strains, making future bacterial infections harder to treat.
2. Adverse effects: Unnecessary antibiotic use can lead to side effects such as gastrointestinal disturbances or allergic reactions.
3. Healthcare costs: Misuse increases healthcare expenditures without improving patient outcomes.

Structure of the Influenza Virus and Its Evasiveness/Virulence

The influenza virus is an enveloped RNA virus belonging to the Orthomyxoviridae family. Its structure includes:

1. Envelope: Contains two glycoproteins:
   • Hemagglutinin (HA): Facilitates viral entry by binding to sialic acid receptors on host cells.
   • Neuraminidase (NA): Assists in viral release from infected cells by cleaving sialic acid residues.
2. Matrix proteins (M1 and M2): Provide structural integrity and mediate ion channel activity during replication.
3. Genome: Composed of segmented single-stranded negative-sense RNA, allowing genetic reassortment between different strains.
4. Nucleoprotein (NP) and Polymerase Complex (PB1, PB2, PA): Essential for replication and transcription.

Evasiveness and virulence mechanisms:

• Antigenic drift: Minor mutations in HA/NA genes allow the virus to evade pre-existing immunity.
• Antigenic shift: Reassortment of genome segments between different strains creates novel subtypes capable of causing pandemics.
• High mutation rate: Due to lack of proofreading by RNA polymerase, leading to rapid evolution.

Epidemiology in Birds, Animals, Humans; Pandemic Causes; Naming Methodology

Epidemiology

Influenza viruses infect a wide range of hosts:

1. Birds: Wild aquatic birds are natural reservoirs for influenza A viruses. These viruses often circulate asymptomatically but can spill over into domestic poultry, causing outbreaks.
2. Animals: Swine serve as “mixing vessels” where reassortment between avian, human, and swine influenza strains occurs.
3. Humans: Seasonal influenza epidemics occur annually due to antigenic drift. Pandemics arise when a novel strain emerges via antigenic shift.

Why it causes pandemics:

Pandemics occur when:

1. A new influenza A subtype emerges via antigenic shift.
2. The population lacks immunity to this novel strain.
3. The virus acquires efficient human-to-human transmissibility.

Examples include the 1918 H1N1 pandemic (“Spanish flu”) and the 2009 H1N1 pandemic (“swine flu”).

Naming methodology:

The World Health Organization (WHO) names influenza strains based on:

• Type (A/B/C)
• Host species (if non-human origin)
• Geographic location where first isolated
• Strain number
• Year of isolation
• For type A: Subtype based on HA/NA proteins (e.g., H5N1).

Example: A/Hong Kong/156/97(H5N1).

Genetics, Clinical Presentation, Pathogenesis, Immune Response; Reye’s Syndrome

Genetics

The segmented genome allows reassortment between strains during co-infection of a host cell—this is key for antigenic shift.

Clinical presentation

Symptoms range from mild to severe:

• Fever, cough, sore throat
• Myalgia, fatigue
• Severe cases may involve pneumonia or acute respiratory distress syndrome (ARDS).

Pathogenesis

After inhalation:

1. Virus binds sialic acid receptors via HA protein.
2. Enters epithelial cells; replicates using host machinery.
3. Cell death leads to inflammation and impaired mucociliary clearance.

Immune response

Innate immunity involves interferons that limit viral spread but contribute to symptoms like fever/fatigue. Adaptive immunity generates neutralizing antibodies targeting HA/NA proteins.

Reye’s syndrome

A rare complication seen in children recovering from viral infections like influenza or varicella when treated with aspirin:

• Causes encephalopathy and liver dysfunction due to mitochondrial damage.

Laboratory Diagnosis

Diagnostic methods include:

1. Reverse transcription-polymerase chain reaction (RT-PCR): Gold standard for detecting viral RNA with high sensitivity/specificity.
2. Rapid antigen tests: Quick but less sensitive than RT-PCR.
3. Viral culture: Slow but useful for research purposes.
4. Immunofluorescence assays: Detect viral antigens directly from respiratory samples.

Antiviral Drugs Used and Their Mechanisms

Common antivirals include:

1) Neuraminidase inhibitors

Examples: Oseltamivir (oral), Zanamivir (inhaled). Mechanism: Block NA activity—preventing release of progeny virions from infected cells.

2) Polymerase inhibitors

Examples: Baloxavir marboxil. Mechanism: Inhibits cap-dependent endonuclease activity required for viral mRNA synthesis.

3) Adamantanes

Examples: Amantadine/Rimantadine. Mechanism: Inhibit M2 ion channel function—preventing uncoating of the virus inside host cells. Note: Resistance limits their current use against most circulating strains.

Vaccination Significance; Target Groups; Frequency; Side Effects

Significance

Vaccination reduces morbidity/mortality by inducing protective immunity against circulating strains.

Target groups:

1. High-risk populations:
   • Elderly (>65 years)
   • Pregnant women
   • Individuals with chronic conditions like asthma or diabetes
2. Healthcare workers

4. Children aged 6 months–5 years
5. General population during pandemics

Frequency

Annual vaccination is recommended due to antigenic drift causing changes in circulating strains each year.

Side effects:

Most are mild/localized—soreness at injection site or low-grade fever—but severe allergic reactions are rare.