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Influenza (flu)

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Title: Influenza (flu)


1
Influenza (flu)
  • Highly contagious, potentially serious viral
    infection of the nose, throat, and lungs.
  • Spreads via aerosol particles from
    human-to-human, animal- to-human, and
    human-to-animal contact
  • Seasonal influenza affects more than 60 million
    individuals in the US every year.
  • In some cases severe complications like
    pneumonia.
  • In US annually, gt 200,000 individuals are
    hospitalized and between 3,000-49,000 die from
    influenza-related complications.

2
Geographic hot spots for influenza
  • Most seasonal influenza originates in Asia where
    there is high density of animals and humans in
    close proximity
  • Pigs, poultry are major reservoirs but also wild
    birds

3
Poultry markets in Asia
4
CAFOs (concentrated animal feed operations)
  • Crowding of pigs or poultry, especially when they
    are genetically homogenous, may increase the
    potential for influenza viruses to infect them

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Avian and swine flu can also jump from birds to
humans
7
Modes of transmission
  • Among birds and pigs
  • Birds and pigs to humans
  • Humans to birds and pigs
  • Human to human only when the influenza virus
    becomes capable of transmission from human to
    another human is it possible for it to rapidly
    progress through the human population

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  • Influenza can travel globally and evolve through
    molecular changes in a short amount of time

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How the flu virus works
  • Virus contains RNA
  • Virus enters epithelial cells in respiratory
    tract
  • RNA inserted into nucleus
  • Polymerases in nucleus used to make copies of
    viral RNA
  • These copies of RNA leave the epithelial cells to
    infect another person
  • Winter outbreaks
  • Closer contact among humans in winter
  • Drying of epithelial cells due from warm air in
    winter aids reproduction and release of virus
  • Vaccines can be designed for seasonal influenza

12
Types of influenza
  • Three types of influenza viruses A, B, and C.
  • Influenza B and C viruses are specific to humans
    only and spread via human-to-human transmission
  • Influenza A viruses can spillover from non-human
    hosts and infect humans
  • Can be highly pathogenic.
  • But does not necessarily have the potential to be
    spread from human to human.
  • Epidemics of seasonal influenza occur due to
    influenza A or B viruses.
  • Only A viruses are known to cause global pandemics

13
Naming influenza A viruses (H1N1, H3N2)
  • H and N refer to hemagglutinin and neuraminidase.
  • Two main proteins on the outside of the virus
  • Referred to as antigens because they are the
    structures to which our immune system responds.
  • Antigens are categorized according to antibodies
    that respond to them.
  • There are 18 known hemagglutinin subtypes for
    influenza A (H1 to H18) and 11 known
    neuraminidase subtypes (N1 to N11).

14
Vaccinations for influenza
  • Flu vaccination is a preventative stimulation of
    your body to produce antibodies to a particular
    combination of H and N subtypes predicted to be
    abundant during flu season

15
Antigenic drift
  • Slow small changes in the genes of an influenza
    virus due to mutations

16
Antigenic shift
  • Large and sudden change
  • New H and/or N subtypes
  • Corresponds to the emergence of a new virus
  • Humans have no prior acquired immunity
  • Type A viruses undergo shifts and drifts
  • Type B viruses undergo only drift
  • Both antigenic drift and antigenic shift alter
  • Infectiousness of virus
  • Pathogenicity

17
Influenza A
  • Has a high potential to evolve and become a
    pandemic
  • In a single host, viruses remain relatively
    unchanged, showing minimal evolution over
    extended periods.
  • After transfer to a new type of avian or
    mammalian host, influenza viruses can undergo
    antigenic shift as well as drift, and render
    vaccinations ineffective

18
Spanish Influenza of 1918
  • One third of Earths population infected
  • 50-100 million deaths worldwide
  • 675,000 deaths in the United States with
    unusually high death rate among healthy adults 15
    to 34 yrs

19
Spanish Influenza of 1918
  • Influenza A
  • First jumped from bird to human
  • Then acquired properties to allow it to be spread
    from human to human
  • Virus is related to a influenza A (H1N1) virus

20
Nurses outside of Miller Hall during 1918 Spanish
Influenza outbreak
21
Recovering patients, Buell Armory, UK Campus
22
A H1N1 2009
  • Became transmissible from human-to-human
  • Same virus type as Spanish Influenza
  • Much more pathogenic than typical seasonal flu
  • World Health Organization declared its first ever
    public health emergency of international concern
  • CDC stopped counting cases and declared the
    outbreak a pandemic.
  • Virus contained genes of swine influenza from two
    continents, as well as genes from strains of
    human and avian influenza viruses

23
A H1N1 2009
  • Began in Veracruz Mexico
  • After its first year, killed an estimated 280,000
    people and sickened about 1 in 5 people worldwide
    mostly in Africa and Southeast Asia

24
Avian influenza H5N1 (1997)
  • Outbreaks of H5N1 in birds and in humans have
    been confined to Asia

25
Avian influenza A H5N1
  • Migratory waterfowl were the main reservoir
  • H5N1 first discovered in 1997
  • Spillover to human populations
  • 50 60 human mortality rate
  • But no human-to-human transmission (although a
    few cases have been suggested)

26
Avian influenza A H5N1
  • Governments in China and Hong Kong had to kill
    millions of poultry through enforced culling.
  • Other large economic costs to
  • Vaccinate poultry
  • Vaccinate poultry workers
  • Increase market and farm hygiene

27
Migratory waterfowl likely distributed H5N1
globally
28
H5N1 and its evolution
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30
H5N2 is the influenza virus that had a very large
economic impact on the US in 2014-2015.
31
A H7N9 2013
  • Emergence of H7N9 virus led to closing of poultry
    markets and culling
  • Very pathogenic
  • Limited evidence of possible human-to-human
    transmission
  • Unlike H5N1, birds can be asymptomatic

32
Flu politics
  • China is under international pressure to
    identify, announce, and contain outbreaks
  • China criticized for taking 27 days to announce
    first H7N9 cases

33
Flu politics
  • H5N1 infected poultry die quickly so farmers want
    vaccination to limit losses
  • Because poultry with H7N9 can be asymptomatic,
    monitoring H7N9 difficult
  • Poultry farmers resist testing since a positive
    test forces them to destroy flocks they might
    have been able to sell

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Influenza in your future
  • A global pandemic is likely to occur again
  • Worst case scenario human infected by human B
    flu virus and an avian flu A virus
    simultaneously, allowing the pathogencity of
    avian flu to acquire the ability to be spread via
    human-to-human contacts instead of bird-to-human.

36
Influenza in your future
  • A global pandemic is likely to occur again
  • Worst case scenario human infected by human B
    flu virus and an avian flu A virus
    simultaneously, allowing the pathogencity of
    avian flu to acquire the ability to be spread via
    human-to-human contacts instead of bird-to-human.
  • Surprises inevitable, viral pathogens are hard to
    detect and constantly changing

37
Mosquito-borne diseases
  • Malaria, dengue, Chikungunya, Zika
  • Of the millions of insects, only a tiny fraction
    of them, less than 1, are pests.
  • A vast majority are beneficial to humans

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44
Temporal scale is relevant for understanding
influence of climate change on malaria (Gething
et al 2010)
45
Malaria
  • 198 million cases in 2013 600,000 deaths
  • 90 of deaths occur in Africa
  • Children lt 5 yrs account for 75 of deaths.

http//vimeo.com/9864081
46
Plasmodium falciparum malaria accounts for more
than 90 of all deaths.
47
Malaria
48
Plasmodium is endemic to humans yet has the
potential for new spillovers
  • Plasmodium jumped to mammals millions of years
    ago and from gorillas to humans 10,000 years ago
  • Plasmodium knowlesi primarily infect macaques but
    has recently made jump to humans and can now
    spread from human to humans
  • Plasmodium gaboni identified in chimpanzees but
    has not yet jumped to humans
  • Likely to see new types of malaria in the future

49
Overview of malaria control
  • 1955 1969 WHO (World Health Organization)
    Global Malaria Eradication Campaign
  • Malaria eliminated from much of Europe, North
    America, Caribbean and parts of Asia,
    South-Central America
  • Malaria persisted in sub-Saharan Africa
  • Drug resistance began to develop at the same time
    financial support of international effort
    collapsed
  • 1978 A child dies every six seconds from malaria
  • 2000 Second major WHO global initiative to
    reduce malaria
  • Targeted sub-Saharan Africa
  • 2016 Every minute a child dies
  • Areas exist where endemic transmission of malaria
    has been stopped due to public-private
    initiatives
  • Interventions
  • Indoor residual spraying (IRS)
  • Treatment of clinical malaria with
    artemisinin-based combination therapy (ACT)
  • Insecticide-treated bed nets (ITNs)

50
30 reduction in malaria in Africa since 2000
Last 15 years have seen international financing
for malaria control increase approximately
twentyfold the distribution of free bed nets
has been a large part of this reduction
51
Plasmodium falciparum parasite rate (Pf PR).
52
Indoor residual spraying
53
Quinine and chloroquine two older anti-malarial
drugs
54
Resistance to quinine-based drugs
  • First WHO war on malaria was based on
    drug-treatment
  • Resistance to quinine-based drugs developed

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Quinine medicines replaced by artemisinin-based
combination therapy
Youyou Tu
57
2016 Nobel Prize awarded to Youyou Tu of the
China Academy of Traditional Chinese Medicine in
Beijing
  • China was backing North Vietnamese in their war
    with US and South Vietnam
  • North Vietnamese troops were suffering due to
    Plasmodiums resistance to quinine and
    chloroquine
  • Chairman Mao of China had secret program to find
    new medicine and recruited scientists to examine
    herbs used in traditional Chinese medicine (TCM)
  • Sweet wormwood, (Artemisia annua) used in TCM to
    treat fevers
  • Tu was first to demonstrate utility of chemical
    from Artemisia to treat malaria

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Social origins of artemisinin resistance
  • Khymer Rouge, led by Pol Pot established Year
    Zero (1975) which was a genocidal restructuring
    of society
  • Collapse of medical infrastructure

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Biogeographical origins of artemisinin resistance
  • 19 species of mosquito (Anopheles genus)
  • Small isolated mosquito populations
  • In small populations, Plasmodium is able to pass
    on mutations that confer resistance easier and
    these can then spread to other populations

64
Strategies of deploying antimalarials
  • Mass drug administration
  • Now emphasized where there are high rates of
    infection
  • Treatment of the entire population with curative
    dose of antimalarial drug without first testing
    for infection
  • But difficult to fund and organize at large scale
    and may have only short term impact on
    transmission rates
  • Prophylatic seasonal chemoprevention
  • Given ahead of season to prevent infection
  • May enhance drug resistance

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Insecticide treated nets
  • In 2005, supported by the US Presidents Malaria
    Initiative, which reintroduced indoor residual
    spraying in 15 high-burden countries across
    Africa
  • Free bed nets to protect sleeping children

67
Overall use of nets has increased but rates of
availability and adoption variable from country
to country
68
Unintended uses and perceptions of mosquito nets
69
Non-local malaria
  • Malaria can be spread by human mobility and
    global travel non-local malaria thwarts its
    control.
  • This is malaria that comes from somewhere else
  • Even in places where malaria has been eliminated,
    an outbreak can start when a traveler is infected
    in a foreign country and then returns home and
    bitten by a mosquito
  • Malaria cases in US are non-local

70
How will climate change impact the distribution
of malaria?
  • Climate change is not just changes in
    temperature, but also changes in rainfall and
    humidity and how these variables coincide
    spatially and temporally
  • This complexity intersects with life cycle of the
    mosquito
  • Warmer more mosquitoes more malaria is
    simplistic

71
Predictions using temperature and rainfall as
climate factors (Rogers and Randolph 2000)
72
  • However, other mosquito-born diseases emerging
    dengue, chikungunya, Zika
  • These are all caused by viruses
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