Conflict of Interest and Disclosures. Research funding from GSK, Biofire

Transcription

1 Pandemic Influenza Suchitra Rao, MBBS, Assistant Professor, Pediatric Infectious Diseases, Hospital Medicine and Epidemiology Global Health and Disasters Course, 2018

2 Conflict of Interest and Disclosures Research funding from GSK, Biofire

3 Objectives Describe the influenza virus types, subtypes and epidemiology Review clinical manifestations of influenza Discuss the implications of antigenic shift and drift Understand the historic perspective on influenza including lessons learned from past pandemics Outline how pandemics occur and tools for preparedness

4 Background

5 Influenza virus RNA viruses Orthomyxoviridae family 3 virus subtypeshumans

6 Influenza types Type A: potentially severe illness Epidemics and pandemics Rapidly changing Birds, swine, horses, seals, animals Type B: Usually less severe illness Epidemics More uniform Humans Type C: Usually mild or asymptomatic Minimal public health impact Humans rarely, swine

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8 Antigenic Shift and Drift Human strain Non-human strain

9 Why is all this important? Segmented RNA- enables gene re-assortment HA- novel subtypes contribute to pandemics, antibodies confer protection NA- target for antiviral drugs Antigenic drift- why we need to change flu vaccine each year and get annual vaccine Antigenic shift- responsible for pandemics

10 CLINICAL MANIFESTATIONS/ PATHOPHYSIOLOGY

11 Pathology of influenza infection Binding to sialic acid Entering cell Replication Release from cell

12 Epidemiology of influenza Small particle droplets, aerosols, or fom Attacks epithelial cells of upper & lowe tract Incubation period 1-3 days Shedding for 3-7 days

13 Epidemiology of influenza Planning length of isolation for cases, development of definition for contacts of cases, isolation/quarantine duration Short incubation period and viral shedding before symptoms of develop- harder to stop spread of influenza Aerosol-inducing procedures- highest risk of

14 Clinical manifestations

15 Influenza Season

16 Influenza Disease Burden in the US

17 Influenza Disease burden worldwide Annual epidemics are estimated to result in about 3 to 5 million cases of severe illness to deaths Industrialized countries, most deaths > 65 yrs of age Resource limited settings, children < 5 yrs Lancet, 391(10127), , 2017

18 IIV 3/4 LAIV 4 Vaccine types All individuals 6 months of age and older should receive influenza vaccination This season, either IIV or LAIV

19 Vaccine types IIV 3/4 LAIV 4 Standard dose Cell culture High dose Recombinant Intradermal Adjuvant

20 Oseltamivir- oral preparation, no issues with resistance currently Influenza treatment- Antiviral agents Zanamavir- 2 breath-activated inhalations Peramavir- intravenous medication now available Baloxavir single dose

21 Influenza epidemics More cases of disease than expected in a given area or among a specific group of people over a particular period of time Occur in winter months when cold, crowding of people Starts in Eastern or Southern Hemisphere countries, and later spread to Europe or North America More likely when a variant virus appears (drift) showing antigenic changes (low cross-reacting antibody)

22 Influenza pandemics Epidemic that has spread through human populations across a large region, for instance multiple continents, or even worldwide High percentage of individuals are infected resulting in increased mortality rates

23 How do pandemics occur? 1. Influenza A virus emerges from animal and merges with human virus 2. This subtype undergoes antigenic shift and infects humans 3. People do not have immunity to the virus 4. Contagious, spread among susceptible individuals 5. Younger people at risk as well as older people 6. Higher population, affected worldwide 7. Traditional season, but can occur at any time of year

24 PANDEMIC INFLUENZA- Historical context

25 A brief history of influenza 412 BC first mentioned by Hippocrates 1357 AD- term influenza coined sweating sickness : affects 100,000s in Britain first recorded influenza pandemic begins in Europe pandemics Spanish flu pandemic influenza A first isolated in the laboratory first vaccine developed influenza B first isolated

26 pandemic- the Spanish Flu One of the most dramatic events in medical history Estimated to have affected 50% of world s population million deaths worldwide Infections developed into pneumonia US soldiers brought it to the world during WW1 Preceded by a milder epidemic H1N1 strain

27 The Spanish Flu Both individuals and governments were gripped with fear and took extreme measures to try to stop the disease from spreading. Some cities closed down theaters and schools. Some communities shut down completely until the worst had passed. Families with small children were in serious trouble if the parents were stricken, because friends and family members were often too frightened to enter the household to assist and care for the little ones... Hoehling, Adolph A. The Great Epidemic. Boston: Little, Brown & Co., 1961: p. 4.

28 2009 H1N1 Pandemic First detected in North America Not a new subtype Infected children and adults, sparing over 65 years of age Relatively mild compared with 1918 flu But still significant mortality First in April-May, then peaked October-November 35 million cases - adults aged 18 to 64, 19 million in children, and 6 million in those older than 64.

29 Pandemicslessons learned Unpredictable, can occur at any time HA responsible for infectivity and lethality Obesity risk factor for severe flu Reinforced increased risk pregnant female Pandemic preparedness Value of early antiviral treatment Need for rapid, large scale influenza vaccine production

30 PANDEMIC PREPAREDNESS VACCINE TREATMENT NON- PHARMACO- LOGICAL

31 Effect of next pandemic Rapid spread- little time to implement measures Medical facilities struggling to cope with demand Shortages of personnel and products disruption of key infrastructure and services Delayed and limited availability for influenza vaccines, antivirals, antibiotics, other medical supplies Negative impact on social and economic activities that could have impact for years afterwards Global emergency limiting potential for international assistance

32 Novel influenza strains SOURCE OF THE NEXT PANDEMIC?

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34 H7N9 Since 5 th Avian May flu 23, epidemic 2017, 688 human infections with Avian H7N9 bird flu Largest epidemic of Avian H7N9 human infections in China since virus emerged Associated with exposure to poultry Human cases- serious illness, 40% mortality No sustained person-to-person spread Not detected in people or birds in the United States

35 H5N1 Disease outbreaks in poultry in China, Vietnam, Thailand, Indonesia, Egypt widespread reemergence in Devastating mortality in flocks it infects Over four hundred human cases Highly pathogenic; high mortality (70%) Direct contact or close exposure to infected poultry No human-human transmission Currently the most visible influenza virus with pandemic potential

36 Let s apply some principles

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38 Global Surveillance Systems Phase 1- animal flu, no human infection Phase 2 animal flu, infection in humans known to occur Phase 3 clusters of disease in people, no human-human transition Phase 4- human to human transmission has occurred Phase 5 community level outbreaks in two or more countries in same region Phase 6- sustained community level outbreaks in at least one other country in another region Post peak period- pandemic below peak levels Possible new wave Post-pandemic period returned to baseline levels

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40 Seasonal flu versus pandemic flu Seasonal flu Infection in all age groups Most deaths in the elderly and those with underlying medical conditions Number of people affected variable Occurs in winter

41 Seasonal flu versus pandemic flu Pandemic flu Infection in all age groups Tends to affect more young people and healthy people High number of people affected Can occur during other times, not just flu season

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43 Challenges- Pandemic Flu Seasonal Influenza vaccine not effective against pandemic flu strain May have issues with resistance to traditional antivirals Unpredictable season Highly contagious, no prior immunity

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45 NPIs/Community mitigation strategies

46 Pandemic preparedness, then and now 1919 Virus not yet discovered No vaccines No testing No treatment Isolation Quarantine Social distancing Public gathering bans School closures Mask wearing 2018 and beyond Rapid production pandemic vaccine Treatment Prophylaxis Molecular diagnostics Surveillance/seque ncing Community mitigation strategies

47 Take home points 2 subtypes infect humans- A and B Antigenic drift annual flu vaccines Antigenic shift- influenza A- pandemic potential Different challenges with pandemic flu versus seasonal flu Know why current avian flu pose concerns

48 Questions?

49 Additional slides

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51 Influenza vaccination

52 IIV 3/4 LAIV 4 Vaccine types RIV

53 Global Influenza vaccine recommendations Most developed countries had national policies on immunization against seasonal influenza. In contrast, 64 of the 138 (46%) Low and Middle Income Countries from the tropics and subtropics had a national vaccination policy against seasonal influenza. Notably, populous countries such as Bangladesh, China, India, Pakistan and Sri Lanka in Asia representing about 45% of the world s population did not have a national vaccination policy against influenza.