L24 emerging infections Flashcards
emerging pathogen definition
A. A previously unknown organism that causes disease
or
B. A previously identified organism that has recently acquired the capacity to cause disease
or
C. A previously identified pathogen that has recently acquired the capacity to resist antibiotic treatment *** most concerning
WHY ARE WE SEEING EMERGING PATHOGENS NOW?
- Human demographics and behavior sexual practices, longer life spans
- Technology and industry misuse of antibiotics in livestock
- Economic development and land use movement of populations, disruption of societies, poor sewage control
- International travel and commerce there are no longer any effective barriers to the movements of people or things
- Microbial adaptation and change bacteria have plastic genomes
- Breakdown of public health measures public health is
often not as high a priority as it needs to be. A low or nonexistent priority where it is needed the most
MECHANISMS OF RESISTANCE ACQUISITION
opportunity for resistance to arise is present when a patient is treated with antibiotics giving the resistant bacteria a selective advantage and increased ability to grow and divide
In a healthy host in the absence of drug, a resistant strain of a pathogen might not reach a particularly high titer, as it will not necessarily have any growth advantage over non-resistant strains or the normal flora, nor any increased virulence. In the presence of the drug, however, much of the normal bacterial flora will be suppressed allowing the resistant organism to flourish.
multi-drug efflux system
can non-specifically export drugs that penetrate one or both membrane layers
especially likely to arise when the organism encounters multiple drugs
correct drug therapy vs incorrect drug therapy
correct drug therapy uses a dose and duration that kills the pathogenic bacteria before they have a change to reproduce giving resistant bacteria an advantage.
Low dose of drug permits bacterial replication. The presence of drug provides modest levels of selection which result in evolution of drug resistance
things that increase the rate of resistance development
higher rates of mutation
Evolutionary medicine
or evolutionary epidemiology or virulence management
Involves using insights from the study of evolution to reduce pathogen virulence.
Lethality can compromise transmission.
Evolution balances lethality and transmission.
Transmission via an abioitc vector can permit greater virulence.
2 approaches to drug discovery
- reductionist approach
2. genomic approach
reductionist approach
- Identify molecular mechanisms of disease (i.e. virulence factors).
- Design drugs to target virulence factors identified by experiment
(rational drug design). [Also useful for vaccine target selection]
genomic approach
- Sequence the genome of the pathogen.
2. Design drugs to target all potential virulence factors. [Also useful for vaccine target selection]