Week 2/2-2/8

Lecture 2/3

Sylvatic - living in the wild or forests

Simian - relating to monkeys or apes

Bushmeat - meat huned from wild animals

P = probability of infection of a new host species/time

  • Decreases with high phylogenetic distance

  • Factors

    • More interactions

    • Proximity

    • Types of transmission

    • Type of animal

    • Relatedness

      • Related intrinsic properties of the pathogen

    • High encounters

  • Disease emergence causes

    • Access to healthcare

    • Religion

    • Access to water & better infrastructure

    • Air quality

    • Immune suppression, immunocompromised

Stages in Disease Emergence

  1. Pre-emergence

  2. Localized emergence

  3. Some spillover events lead to indefinitely sustained human-human outbreaks

Microbial Threats

  • Newly recognized agents

  • Mutation of zoonotic agents that cause human disease

  • Resurgence of endemic diseases

Factors contributing to emergence or re-emergence

  • Demographic change

  • Exposed to new environmental sources

    • Infectious agents

    • Insects

    • Animals

  • Breakdowns of sanitary and other public health measures in overcrowded cities

  • Economic development

  • Climate changes

  • Changing human behaviors

    • Child-care

    • Sexual and drug use behaviors

    • Patterns of outdoor recreation

  • Social inequality

  • Stages

    1. Agent only in animals → none

    2. Primary infection → only from animals

    3. Limited outbreak → from animals or humans

    4. Long outbreak → from animals or humans

    5. Exclusive human agent → only from humans

  • Resistance of the vectors of vector-borne infectious diseases to pesticides

Tropical vs. Temperate

  • Tropical

    • More diseases spread by insects

    • More animal reservoir diseases

    • More stage 2 or 3 diseases

  • Temperate

    • More long-term immunity

    • More stage 5 disease

Lecture 2/5

Co-evolution - reciprocal evolutionary change between species

Co-speciation - host and pathogen specialty together

Host jumping

Co-evolution

  • Evolution - change in the inherited traits of a population of organisms from one generation to the next

  • Co-evolution - reciprocal, adaptive genetic changes between interacting species

The Red Queen Hypothesis

  • “Evolutionary arms-race” - a lot of effort is required simply not to lose ground. Moving ahead is even more difficult.

  • Pathogen is constantly exerting selective pressure against host

  • Host immune system is exerting selective pressure against pathogen

  • “Co-evolutionary arms race” to keep in the same place

Co-evolution and human pathogens

Hunter gatherers → settled villages (intensified zoonoses, infection) → pre industrialized cities (endemic, beginnings of epidemics) → industrialized cities (endemic, epidemics, pandemics) → TODAY (age-related diseases, emerging diseases)

  • Sick Cell Anemia

    • Moon shaped red blood cells

    • Low O2 tension

    • Less Capillary blockage

    • Heme oxygenase-1 (HO-1) is induced

      • making carbon monoxide

      • confers protection against cerebral malaria

  • Sickle Cell Anemia & Malaria

    • Point mutation

    • SS, Ss ss

    • African and mediterranean groups

    • Anopheles gambiae mosquito

    • 150 mosquito bites per year

    • 100% infection rate in kids

    • 25% greater survivability = SS.

    • Humans have adapted to malaria in endemic areas

      • Human populations adapting to selective pressure

Koch’s Postulates

  1. The microorganism must be found in abundance of suffering organisms, but should not be found in healthy organisms

  2. The microorganism must be isolated from a diseased organism and grown in pure culture

  3. The cultured microorganism should cause disease → healthy organism

  4. The microorganism must be relsolated from the inoculated, diseased experimental host

How do we measure co-evolution?

  • Compare evolutionary history of organisms using observable characteristics:

    • Morphology

    • DNA sequences

    • Protein sequences

  • Look for similar patterns of speciation or co-speciation

  • Build phylogenetic trees

Different ways to scale branch lengths

  • Additive tree - genetic distance can be added up

  • Ultrametric tree - all terminal branches terminate in the present → used to express time as well as genetic distance → molecular clock

Viruses: fasted pathogens around

  • Pathogens tend to evolve faster than their hosts

  • Difference most extreme in viruses: often evolve many order of magnitude faster

  • Thus virus phylogenies can be used to look at ecological and evolutionary processes

Co-evolution

  • Reciprocal, adaptive genetic changes between interacting species

  • Can look for signature of co-evolution using shared phylogenetic histories

Co-evolution vs. co-speciation

  1. Cospeciation - joint speciation of two or more lineages

  2. Coevolution - reciprocal adaptation between associated species

Pathogen counter-strategies

  • Rapid proliferation

    • e.g. measles, small pox, common cold

  • Herpes simples virus hides in sensory neurons

  • Antigen-switching

    • Trypanosomes, gonorrhea

  • Attachment of host proteins or host mimicry

    • Coating with host proteins e.g. enveloped viruses (herpes, retroviruses, flaviviruses)

    • Molecular mimicry - pathogen proteins resembling the host

Why do pathogens tend to become less virulent over time? Herd immunity, vaccines, mutations no longer powerful

What is the best way for a pathogen to increase lifespan and fecundity (produce offspring) Kill the immune system and still be transmissible