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Influenza: virus, disease, prevention & control, treatment Lecture presented by Dr Ghassan Awar 02 May 2009 Virus Influenza Virus Orthomyxovirus 3 The Virus Types of Influenza Virus Three types: A, B, C Influenza Type A can infect: People, birds, pigs, horses, seals, whales and others Influenza Type B: Human virus Not classified according to Subtype Cause human epidemics but not pandemics Influenza Type C cause mild illness in humans Not classified according to subtype Do not cause epidemics or pandemics Influenza Virus Types A and B Type A (Seasonal, avian, swine influenza) Type B (Seasonal influenza) Can cause significant disease Generally causes milder disease but may also cause severe disease Infects humans and other species (e.g., birds; H5N1) Limited to humans Can cause epidemics and pandemics (worldwide epidemics) Generally causes milder epidemics 6 Influenza A Virus Subtyping • Influenza A subtypes are determined by two surface glycoproteins: Hemagglutinin (HA) Neuraminidase (NA) 16 HA’s and 9 NA’s 7 Species Infected by Influenza A, HA and NA Subtypes H2 N1 N2 H3 H4 N3 N4 H5 H6 H7 H8 N5 N6 N7 N8 N9 H1 H9 H10 H11 H12 H13 H14 H15,16 8 Influenza Nomenclature Influenza type Year of isolation Hemagglutinin subtype A/Sydney/5/97 (H3N2) Geographic source Isolate number Neuraminidase subtype Antigenic Drift Point mutations in the hemagglutinin gene cause minor antigenic changes to HA Continuous process Immunity against one strain may be limited Antigenic drift produces new virus strains that may not be recognized by antibodies to earlier influenza strains One of the main reasons why people can get the flu more than one time (Seasonal epidemics). one or two of the three virus strains in the influenza vaccine are updated: 6-8 months process Targeted at high-risk (inactivated) Antigenic Shift new influenza virus that can infect humans and has (new HA subtype ± NA) through: Genetic reassortment (human and animal viruses) Direct animal (poultry) to human transmission if most people have little or no protection against the new virus: Spread easily from person to person Pandemic (worldwide spread) may occur How Do Influenza Viruses Become More Pathogenic? Antigenic Shift Strong selection pressure acting on mutations or changes in HA or NA Direct infection in humans Re-assortment Two different strains of influenza infect the same host “Reassorted” virus emerges Examples of Re-assortment and Direct Transmission Non-human virus Human virus RE-ASSORTMENT Reassortant virus Epidemiology Terms Endemic A disease that occurs at an expected constant level in a population “Background” level Red line: Expected deaths each year Cécile Viboud, et al. Emerg Infect Dis [serial on the Internet]. 2006 Apr. Available from http://www.cdc.gov/ncidod/EID/vol12no04/05-0695-G2.htm Epidemiology Terms Epidemic When the cases of a disease exceed what is normally expected Pandemic An epidemic that occurs over a large geographic area, or across the whole world Seasonal Epidemics vs. Pandemics Seasonal Influenza A public health problem each year Usually some immunity built up from previous exposures to the same subtype Infants and elderly most at risk Influenza Pandemics Appear in the human population rarely and unpredictably Human population lacks any immunity All age groups, including healthy young adults Seasonal Epidemics vs. Pandemics Seasonal Influenza A public health problem each year Usually some immunity built up from previous exposures to the same subtype Infants and elderly most at risk Influenza Pandemics Appear in the human population rarely and unpredictably Human population lacks any immunity All age groups, including healthy young adults Prerequisites for pandemic influenza A new influenza virus emerges to which the general population has little/no immunity The new virus must be able to replicate in humans and cause disease The new virus must be efficiently transmitted from one human to another Disease Chain of Infection + Quantity of pathogen Virulence Route of transmission Port Sensitive host Avian Influenza precautions Contact precautions Droplet precautions Airborne Precautions Transmission of Influenza Viruses Seasonal Influenza in Humans Droplet Yes Airborne Likely Contact Yes Routes of Transmission Droplet Large droplets within 1 meter transmit infection via: Coughing, sneezing, talking Medical procedures Routes of Transmission Airborne (droplet nuclei) Very small particles of evaporated droplets or dust with infectious agent may.. Remain in air for a long time Travel farther than droplets Become aerosolized during procedures General Information Human influenza Vulnerable Age Groups Time from exposure to illness All ages affected Highest rates in children < 5 years Most serious complications in elderly >60 years Mean 2 days Range: 1 – 5 days Signs and Symptoms Human Influenza Type of infection Upper and lower respiratory Fever Yes Headache Yes Cough Yes Respiratory symptoms Gastrointestinal symptoms Recovery Varies; sore throat to difficulty breathing Uncommon, except children, elderly 2-7 days Complications Seasonal Influenza Ear infection, sinusitis Bronchitis, bronchiolitis Pneumonia viral or secondary bacterial Exacerbation of chronic conditions Muscle inflammation Neurologic Disease Seizures Brain inflammation Reye’s syndrome Prevention and control Pharmaceutical interventions: Vaccination Chemoprophylaxis Non-pharmaceutical interventions NPI Seasonal Vaccine Primary means of preventing influenza Proven efficacy / effectiveness to prevent infection, severe illness (hospitalization) and death Cost effective in many target groups, Safe, Generally safe 350 million* doses produced annually (5% of 6.7 billion population) Production and consumption highly localized. >95% produced in 9 countries (>65% in Europe) 12% of population use 62% of vaccine Production dependent on eggs Very little surge capacity * 2006 estimate Influenza Vaccine Benefits Can match a seasonal vaccine with a circulating strain Can be highly effective for prevention of seasonal influenza Vaccination of rapid responders reduces the risk of infection and prevents viral reassortment Non-pharmaceutical Interventions 1. Delay disease transmission and outbreak peak 2. Decompress peak burden on healthcare infrastructure 3. Diminish overall cases and health impacts #1 Pandemic outbreak: No intervention #2 Daily Cases Pandemic outbreak: With intervention #3 Days since First Case Overview of NPI Individual level Isolation Quarantine Infection control Community level Quarantine of groups/sites Measures to increase social distance School closures Business and market closure Cancellation of events Movement restrictions Infection control Voluntary Isolation Separation and restricted movement of ill persons with contagious disease (often in a hospital setting and Primarily individual level) Isolate severe and mild cases Location of isolation (home, hospital) depends on several factors (severity of illness, the number of affected persons, the domestic setting) Do not wait for lab confirmation Plan for large number of severe cases Provide medical and social care Voluntary Quarantine Separation and restricted movement of well persons presumed exposed Identification of contacts Often at home, but may be designated residential facility or hospital Applied at the individual or community level Regular health monitoring is essential part of quarantine Self-health monitoring and reporting Infection Control Hand hygiene Cough etiquette Facemasks Hand Washing Method Wet hands with clean (not hot) water Apply soap Rub hands together for at least 20 seconds Rinse with clean water Dry with disposable towel or air dry Use towel to turn off faucet Alcohol-based Hand Rubs Effective if hands not visibly soiled More costly than soap & water Method Apply appropriate (3ml) amount to palms Rub hands together, covering all surfaces until dry Cough etiquette Respiratory etiquette Cover nose / mouth when coughing or sneezing Hand washing! Patients Cared for at Home Potential for transmission Must educate family caregivers Fever / symptom monitoring Infection control measures Hand washing Use of available material as mask … Treatment Case Management Antivirals Consider age group Supportive care Antibiotics Anti-viral Drugs: Classes of Influenza Specific Antivirals Neuraminidase inhibitors 1. Oseltamivir* (Tamiflu) Zanamivir (Relenza) Adamantanes 2. Amantadine Rimantadine *Primary drug for mass chemoprophylaxis and for treating human cases of avian influenza. Neuraminidase Inhibitor Two drugs available Oseltamivir and zanamivir Should be given as soon as possible Effective for treatment and prevention Used for seasonal, avian and swine influenza Oseltamivir Treatment in Seasonal Influenza (5 days) Adults: 75 mg twice a day for 5 days Children: <1 year, not studied adequately < 15 kg - 30 mg twice a day >15 kg to <23 kg - 45 mg twice a day >23 kg to <40 kg - 60 mg twice a day >40 kg - 75 mg twice a day Zanamivir Inhaled by mouth via special device May be used for > 5 years of age Unstudied in human H5N1 illness Treatment dosage 2 inhalations (10 mg), once in morning and night for 5 days Side effects Wheezing, and breathing problems