Influenza (flu)

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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.

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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

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Poultry markets in Asia
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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
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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

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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

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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).

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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

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Antigenic drift

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

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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

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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

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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

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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

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Nurses outside of Miller Hall during 1918 Spanish
Influenza outbreak
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Recovering patients, Buell Armory, UK Campus
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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

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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

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Avian influenza H5N1 (1997)

• Outbreaks of H5N1 in birds and in humans have
  been confined to Asia

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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)

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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

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Migratory waterfowl likely distributed H5N1
globally
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H5N1 and its evolution
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H5N2 is the influenza virus that had a very large
economic impact on the US in 2014-2015.
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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

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Flu politics

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

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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.

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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.
• Surprises inevitable, viral pathogens are hard to
  detect and constantly changing

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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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Temporal scale is relevant for understanding
influence of climate change on malaria (Gething
et al 2010)
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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
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Plasmodium falciparum malaria accounts for more
than 90 of all deaths.
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Malaria
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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

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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)

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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
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Plasmodium falciparum parasite rate (Pf PR).
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Indoor residual spraying
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Quinine and chloroquine two older anti-malarial
drugs
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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
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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

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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

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Overall use of nets has increased but rates of
availability and adoption variable from country
to country
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Unintended uses and perceptions of mosquito nets
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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

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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

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