Influenza Virus and Its Impact

Influenza virus causes acute febrile illness with variable degrees of systemic symptoms, ranging from mild fatigue to respiratory failure and death.
The World Health Organization (WHO) estimates that 3-5 million cases of severe illness and about 250,000 to 500,000 deaths occur annually.

The 1918 Spanish Flu (H1N1) caused 20-40 million deaths.
The 1957 Asian Flu (H2N2) caused 1-4 million deaths.
The 1968 Hong Kong Flu (H3N2) caused 1-4 million deaths.
The 1977 H1N1 pandemic occurred.
The 2009 H1N1 pandemic (Swine Flu) caused thousands of deaths and was a hybrid of swine, avian, and human strains (Influenza A (H1N1)).

Influenza viruses are RNA-enveloped viruses.
They have RNA-dependent RNA polymerase, which is important for infectivity and has transcription errors (~1:10kb of the genome).
The RNA is single-stranded, negative sense, and approximately 8 segments (types A and B) or 7 segments (type C).

Haemagglutinin is a glycoprotein that allows the virus to adhere to endothelial cells in the respiratory tract by binding to sialic acid-containing receptors.
It is the main determinant of immunity and stimulates the production of neutralizing antibodies.
Haemagglutinin agglutinates certain species' erythrocytes.

Neuraminidase is an enzyme that allows the release of newly formed viruses within the host.
It is a determinant of disease severity.
There are 9 serotypes of Neuraminidase (not in type C).

Influenza viruses have two types of antigens: group-specific antigens and type-specific antigens.
Group-specific antigens are determined by Ribonucleoproteins and distinguish types A, B, and C.
Type-specific antigens are HA and NA, and are used for serotyping.

Antigenic shift occurs in type A and leads to pandemics.
Antigenic shift involves the reassortment/swapping of genetic RNA, leading to a major change and the appearance of new HA and NA.
Antigenic drift occurs in all types and leads to outbreaks/epidemics.
Antigenic drift involves the accumulation of mutations in HA and NA, making the immune response no longer fully protective.

Influenza viruses can survive in cold sea water for several weeks.
They can stay in dust for more than 2 weeks/1 week on the human body.
They are inactivated by heat, ether, phenol, ethanol, formaldehyde, soaps, and many others.
Type A has many hosts, type B infects humans only, and type C infects humans and pigs.

Influenza virus pathogenesis is multifactorial, involving host factors, viral factors, and environmental factors.
The mechanism involves:
- Structural and functional damage of respiratory cells
- Desquamation and affectation of respiratory clearance mechanism
- Stimulation of inflammatory response
- Direct tissue toxicity
- Increased susceptibility to bacterial infections (superinfection)

The initial control involves:
- Interferon production
- Rapid generation of natural killer cells
- Class I major histocompatibility complex (MHC)–restricted cytotoxic T cells
The host response then involves:
- Appearance of local and humoral antibody (inhibits spread)
- Evolving cellular immunity
Finally, tissue damage is repaired (2-10 weeks).

Mode of transmission: Respiratory droplets/airborne (more in winter, crowded areas)
Incubation period: 1-4 days (symptoms may last 3-7 days on average)
Main symptoms (mainly type A):
- Sudden onset: fever, chills, headache, myalgia, cough, anorexia, rhinitis, and ocular symptoms
- Note: type B is somewhat milder; type C is usually afebrile
Severity is more in:
- Extreme ages and immunocompromised
- Chronic lung and heart diseases
Pulmonary complications:
- Croup (young children)
- Primary influenza virus pneumonia
- Secondary bacterial infection (Streptococcus pneumoniae, Staphylococcus aureus, Hemophilus influenzae)
Non-pulmonary complications:
- Cardiac: myositis (rare, more in children, more with type B)
- Liver and CNS: Rey's syndrome (encephalopathy + liver degeneration, precipitated by aspirin)
- Peripheral nervous system: Guillian-Barré syndrome/Ascending paralysis (autoimmune disease)

Diagnosis involves culturing the virus from nasopharyngeal samples (takes 7 days) or serology to detect at least a 4-fold increase in antibody titer (needs 2 serum samples during the acute illness and 10-14 days later).