Virus Influenza

Zoonoses Associated with Agriculture

• Human-Livestock-Wildlife Interface: The interactions between humans, livestock, and wildlife destruction to clear land for agricultural use that can facilitate the transmission of zoonoses.

• Global Commerce in Livestock Products: The increasing trade of animal products, which can lead to zoonotic disease spread across borders.

• Increased Demand for Animal Protein: The growth in consumer preferences for animal protein, resulting in intensified animal farming.

• Loss of Wildlife Habitat and Ecosystem Degradation: The conversion of wildlife habitats into agricultural land, causing ecological imbalances.

• Increased Opportunity for Human-Animal Interaction: More frequent interactions between humans and animals due to agricultural practices.

Emerging and Re-emerging Zoonoses (1996-2002)

Pathogen-Disease-Transmission Overview

• The 1918 flu pandemic:

  • Duration: January 1918 – December 1920

  • Infected approximately 30% of the global population.

  • Caused upwards of 50 million deaths globally.

Influenza Virus Overview

• Family: Orthomyxoviridae (the name derived from "myxo" meaning mucus).

• Main Types:

  • Type A: Affects multiple species; associated with seasonal epidemics and pandemics.

  • Type B: Primarily affects humans; associated with seasonal epidemics.

  • Type C: Affects humans and swine, generally less significant.

  • Type D: Affects cattle and pigs.

• Genomic Structure: Consists of 7-8 RNA segments coding for 9-10 proteins.

1918 “Spanish” Influenza

• Strain Information: Avian-derived adaptation of the H1N1 strain.

  • Associated with animal and mini-outbreaks occurring in the year preceding the pandemic.

  • Spread significantly facilitated by troop movements during World War I.

  • Estimated total deaths: 40-100 million, exceeding those from the 1914-1918 war.

• Unusual infection demographics for Spanish flu

  • Typically infectious diseases kill young and old

  • Influenza shows a spike between 20 - 30

    • Healthier immune systems meant immune systems were more likely to enter over drive

Physical Features of Influenza A

• Genome Structure:

  • Negative-sense, single-stranded RNA (ssRNA).

  • Composed of 8 linear chromosomes, approximately 13,000 nucleotides in length.

• Gene and Protein Makeup:

  • Important proteins include Matrix Protein 1 (M1), Matrix Protein 2 (M2), Hemagglutinin (HA), and Neuraminidase (NA).

  • Hemagglutinin (HA): 18 subtypes

  • Neuraminidase (NA): 11 subtypes.

Glycoproteins in Influenza A

• Role: Facilitate entry and exit of viruses.

  • HA binds to sialic acid, assisting viral entry into host cells.

  • NA cleaves sialic acid, aiding in the release of new viral particles from infected cells.

• Pathogenicity: H5N1 is classified as a highly pathogenic avian influenza virus.

Aquatic Birds are natural hosts

• Wild birds may be heavily infected without apparent disease.

• Shed avian Influenza A viruses in their saliva, nasal secretions and faeces.

• Duck faeces may contain up to 1 x10^9.7 infectious doses per gram.

• Virus may persist for >100 days <17 ^oC and overwinter in ice.

• Other species may be infected, e.g. seals, mink, pigs, ferrets, horses, tigers.

Symptoms

• Incubation period: 3-14 days

• Birds found dead

• Drop in egg production

• Neurological signs

• Depression, anorexia, ruffled feathers

• Combs swollen, cyanotic

• Conjunctivitis and respiratory signs

Seasonal Influenza

• 6th largest cause of death in the USA

• Extremely contagious

• Highly efficient transmission by aerosol and with contaminated items

• 3 - 9 have asymptomatic patients

Clinical Features of Influenza

• Transmission: Highly contagious; primarily via aerosols or contaminated surfaces (fomites).

• Symptom Onset: Rapid

  • Fever (pyrexia), headache, muscle aches (myalgia), anorexia, malaise.

  • Incubation phase: 2-4 days

  • Acute phase: 3-7 days

• Complications:

  • Severe inflammatory responses leading to respiratory failure or hypoxia.

  • Secondary infections from pathogens such as Streptococcus and Staphylococcus, potentially leading to septic shock.

Pandemic Influenza Threats

• Public Health Concern: Pandemic influenza represents a major health risk due to lack of pre-existing immunity.

  • Known Issues: Some viral isolates display anti-viral resistance and vaccination gaps.

  • Potential Projected Pandemic Costs: 10-180 million deaths globally, with significant economic impacts (2-3.1% of global GDP, estimated > $2 trillion).

Historical Data on Influenza Pandemics

• Estimated Deaths:

  • 1918 Spanish Flu: 50+ million - H1N1

  • 1957 Asian flu: ~2.5 million - H2N2

  • 1968 Hong Kong flu: ~1 million - H3N2

  • 1977 Russian flu: ~0.5 million - H1N1

  • 2009 Swine/Mexican flu: >17,000 - H1N1

Antigenic Changes in Influenza A

• Antigenic Drift:

  • Viral replication is error-prone, leading to sequence variations in HA and NA that can produce escape mutants.

• Antigenic Shift:

  • Through reassortment, avian influenza A can shift greatly in human host adaptation.

Vaccination Against Influenza

• Strategies:

  • Inactivated Influenza Vaccines (IIV)

  • Live Attenuated Influenza Vaccines (LAIV)

  • Recombinant Influenza Vaccine (RIV): Involves HA gene incorporation into baculovirus, produced in insect cells.

• Current vaccines include both trivalent (3 strains) and quadrivalent (4 strains) formulas.

Future Considerations

• Current Situation of H5N1:

  • H5N1 continues to pose a risk with recent outbreaks in livestock across multiple states in the USA.

  • Potential for a pandemic due to H5N1 human adaptation or reassortment events leading to new strains capable of human transmission.