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How do we compete with pathogens?

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Friend died of puerperal sepsis contracted during autopsy ... C. pneumoniae also found in autopsied brains of Alzheimer's patients (not in controls) ... – PowerPoint PPT presentation

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Title: How do we compete with pathogens?


1
How do we compete with pathogens?
  • Bacteria and viruses reproduce much more rapidly
  • Bacteria and viruses are very numerous
  • Bacteria and viruses tolerate vast fluctuations
    in population size
  • Recover so quickly
  • 1 of bacterial population is insignificant but
    1 of human population is a major proportion
  • Enormous genetic diversity with rapid evolution
  • Summary Pathogens have large populations that
    undergo rapid fluctuation, evolving at a much
    higher rate than their hosts.

2
  • Pathogens have a shared interest in our survival
    with few exceptions, a dead host inhibits the
    spread of the pathogen.

3
Evolutionary mechanisms include intraclonal
(within the cell) and interclonal (between
different cells) processes.
4
Intraclonal Processes
  • DNA Replication microbes are constantly exposed
    to chemical and physical mutagens, resulting in
    high variation of genomes
  • RNA Replication no repair mechanisms means a
    mutation rate so high that for many RNA viruses
    virtually every particle is genetically different
  • Haploid Organisms single copy genomes means no
    delay in expressing new genetic factors
  • Phase Variation many pathogens seem to have an
    archive of genetic material that may be silent
    under normal conditions but can become expressed
    and give the appearance of an adaptive change

5
Interclonal Processes
  • Genetic Exchange conjugation, transduction, and
    transformation increase the genetic, and often
    the phenotypic, diversity
  • Host-Parasite Coevolution hosts and parasites
    coadapt with parasites generally prolonging their
    survival by overcoming host defenses and
    mitigating their virulence
  • Symptoms symptoms may be a host defense or a
    virulence mechanism

6
The Germ Theory of Disease
  • (Revisited)

7
Foundations of Microbiology
  • Antoni van Leeuwenhoek first observed
    microorganisms
  • Louis Pasteur laid the foundation for modern
    microbiology
  • Robert Koch developed methods and concepts

8
Kochs Postulates
  • The disease-causing organism must be present in
    all diseased hosts and absent in healthy hosts.
  • The disease-causing organism must be isolated and
    grown in pure culture.
  • Inoculation of a healthy host with the
    disease-causing organism must result in the
    original disease.
  • The disease-causing organism must be re-isolated
    and shown to be the same as was inoculated.

9
Ignaz Semmelweis
  • Observed that mortality rate of new mothers was
    higher with physicians than with midwives
  • Suggested better hygiene to reduce mortality
  • Friend died of puerperal sepsis contracted during
    autopsy
  • Hypothesized invisible agents responsible for
    the spread of disease

10
The Germ Theory of Disease
  • Microbes are responsible for the spread of
    disease.

11
Leading Causes of Death in the U.S.
12
Darwinian MedicineThe influence of evolution on
disease.
  • How does a disease affect reproductive fitness?
  • An inherited disease with a severe fitness cost
    will be selected against.

When diseases have been present in human
populations for many generations and still have a
substantial negative impact on peoples fitness
they are likely to have an infectious
cause. ---- Paul Ewald
13
Darwinian Medicine and Microbiology
  • Evolutionary change occurs very rapidly in the
    microbial world
  • Evolutionary drive is to reproduce
  • Do reproductive and transmission strategies
    influence disease symptoms?
  • Are disease symptoms caused by the pathogen or
    the host?

14
Evolution of Infectious Disease
  • Too many copies of an infectious agent can kill
    or immobilize a host before it can spread
  • Pathogens transferred by a vector tend to be more
    virulent

15
Chronic Diseases
Diseases that could not fulfill Kochs Postulates
were attributed to heredity, environmental, or
multifactorial causes
16
Darwinian Medicine and Microbiology II
  • Some of the diseases attributed to genetic or
    environmental factors, including some forms of
    heart disease, cancer, and mental illness, are in
    many cases actually due to microbial infections.

17
Heart Disease
  • Clogged coronary arteries have been found full of
    Chlamydia pneumoniae
  • Some estimates that 80 of coronary heart disease
    is caused by C. pneumoniae
  • C. pneumoniae also found in autopsied brains of
    Alzheimers patients (not in controls)

18
HIV
  • High mutation rate
  • Preventative measures curb the spread of
    infection
  • Would transmission-prevention programs be more
    effective than the search for a vaccine?

19
Cancer
  • HTLV-1, a retrovirus endemic in parts of Asia,
    Africa, and the Caribbean, has been linked to
    some leukemias and lymphomas
  • Epstein-Barr Virus, the cause of mononucleosis,
    has been linked to some lymphomas and
    nasopharyngeal cancers
  • HPV has been shown to cause cervical cancer
  • Hepatitis B and C have been linked to liver
    cancer

20
Ulcers
  • Barry Marshall demonstrated that up to 75 of
    ulcers may be due to Helicobacter pylori
  • Over 90 of cases are cured with antibiotics
  • Infection by H. pylori causes a 6-fold greater
    risk of stomach cancer

21
Prediction from Ewald
  • Throughout history most people have died of
    infectious disease, and most people continue to
    die of infectious disease.
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