Ebola Virus - Lehigh Universityinbios21/PDF/Fall2015/Rice_11232015.pdf · Disease emergence: a case...
Transcript of Ebola Virus - Lehigh Universityinbios21/PDF/Fall2015/Rice_11232015.pdf · Disease emergence: a case...
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Emerging Diseases Biosciences in the 21st Century
Dr. Amber Rice November 23, 2015
Ebola Virus
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Outline
• Disease emergence: a case study • How do pathogens shift hosts? • Evolution within hosts: The evolution of
virulence • Treatments: the evolution of drug
resistance
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Disease emergence: a case study Ebola Virus • First identified in Zaire, 1976 • Outbreaks in mid-90s, early 2000s, mid 2000s,
2014 • Average 50% fatality rate
Gire et al. 2014, Science
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Outline
• Disease emergence: a case study • How do pathogens shift hosts? • Evolution within hosts: The evolution of
virulence • Treatments: the evolution of drug
resistance
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Reading a phylogenetic tree
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No currently existing species is ancestral to any other
There is no linear ancestor-descendent relationship! Humans did not evolve from cats or fish!
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Phylogeny of HIV
Three separate introductions from chimpanzees
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Back to our case study: Ebola’s natural reservoir
Ebola isolates from fruit bats
Ebola isolate from fruit bats
Leroy et al. 2005, Nature
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Shifting to another host species
• phi 6: virus that infects bacteria (bacteriophage)
• phi 6 only infects Pseudomonas syringae
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Shifting to another host species
Duffy et al. 2007
• Could phi 6 switch hosts? • Plated on 14 different Pseudomonas
species • A few viruses infected and survived • All had mutation in protein for attaching to
host
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• Once in a new host, must adapt quickly • Slow growth can lead to extinction
Shifting to another host species
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Outline
• Disease emergence: a case study • How do pathogens shift hosts? • Evolution within hosts: The evolution of
virulence • Treatments: the evolution of drug
resistance
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What is evolution? Evolution is a change in a population’s allele frequencies over time.
Generation t
AA
AA
AA
aa Aa
AA
Aa
AA
AA aa
70% A 30% a
Generation t+1
AA
AA
aa
aa Aa
AA
Aa
AA
Aa Aa
60% A 40% a
time
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Mechanisms of evolution: sources of variation
Mutation: a change in DNA sequence, gene order, or chromosome number
– Random – Increases genetic variation within populations – Types of mutations:
• Point mutations • Insertions • Deletions • Gene duplications • Chromosomal inversions • Polyploidy
Figure: Univ. of Calif. Mus. of Paleontology’s Understanding Evolution Site
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Mechanisms of evolution: sources of variation
Gene flow (or migration): movement of genes between populations
– Increases genetic variation within populations – Makes populations more similar to each other
Figure: Univ. of Calif. Mus. of Paleontology’s Understanding Evolution Site
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Mechanisms of evolution Natural selection: differential reproductive success
– Non-random – Not forward-looking, can only work with existing
variation – Only adaptive mechanism of evolution
Figure: Univ. of Calif. Mus. of Paleontology’s Understanding Evolution Site
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Evolution by natural selection
Ingredients needed for evolution by natural selection • Variation in traits • Inheritance • Differential reproduction
(natural selection)
End result: Traits that increase reproductive success increase in frequency in a population. Figure: Univ. of Calif. Mus. of Paleontology’s Understanding Evolution Site
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• Once in a new host, must adapt quickly • Slow growth can lead to extinction • Host switching leads to strong selection:
– Infection – Evade immune system and replicate
• What factors allow pathogens to evolve quickly?
Evolution within the host species
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Back to our case study: the transmission of Ebola, 2014-15
Carroll et al. 2015, Nature
262 patient samples Full Ebola genome sequences
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Evolution of virulence: a trade-off
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Mode of transmission affects virulence
Direct transmission, vectorborne, waterborne
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Mode of transmission affects virulence
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Evolution of virulence: implications for public health
Select for lower virulence by interfering with transmission • Improve hygiene • Wear masks • Provide clean water • Widespread vaccination
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Outline
• Disease emergence: a case study • How do pathogens shift hosts? • Evolution within hosts: The evolution of
virulence • Treatments: the evolution of drug
resistance
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• Once in a new host, must adapt quickly • Slow growth can lead to extinction • Host switching leads to strong selection:
– Infection – Evade immune system and replicate
• What’s another source of strong selection?
Evolution within the host species
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Time
+AZT
AZT-susceptible
Partially susceptible
AZT-resistant
The evolution of drug resistance by natural selection
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| Antimicrobial Resistance Global Report on Surveillance 2014
Estimates of Burden of Antibacterial Resistance European Union
population 500m
25,000 deaths per year
2.5m extra hospital days
Overall societal costs (€ 900 million, hosp. days)
Approx. €1.5 billion per year
United States population 300m
>23,000 deaths
>2.0m illnesses
Overall societal costs Up to $20 billion direct
Up to $35 billion indirect
Source: ECDC 2007 Source: US CDC 2013
Thailand population 70m
>38,000 deaths
>3.2m hospital days
Overall societal costs US$ 84.6–202.8 mill. direct
>US$1.3 billion indirect
Source: Pumart et al 2012
Global information is insufficient to show complete disease burden impact and costs
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Resistance to “last resort” antibiotics
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Avoiding more widespread resistance
1. Avoid contracting infections 2. Minimize transmission of resistant microbes
3. Improve use of antimicrobial drugs – Take only when appropriate (i.e., don’t take an
antibiotic for the flu!)
– Use antibacterial soaps/cleaners ONLY around people with weakened immune systems
– Avoid broad-spectrum antibiotics if possible. – Take ALL of the medication
– Reduce agricultural use of antibiotics
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• Resistant bacteria escape livestock, spread to humans
Why can reducing inappropriate use of antimicrobial drugs combat resistance?
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Current research aims • Can we predict which pathogens are more
likely to shift to humans? • What makes some strains so much more
deadly than others? • How can we develop effective new
vaccines and drugs? • What is the mechanism of resistance? • How can we develop better and faster
diagnostic tools?