BIO220H1 Lecture 9: Resistance

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6 Feb 2019
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Resistance
▪ The evolution of resistance
Malaria: resistance in a protozoan parasite and its mosquito vector
Antibiotics: resistance in a bacterial pathogen
HIV: resistance in a viral pathogen
Malaria
Caused by a protozoan parasite, Plasmodium sp.
Transmitted by mosquitoes
Fever, chills, anemia due to loss of red blood cells
~200 million cases
~ 500,000 deaths
Life cycle and methods of control
killing the parasite, i.e., drug treatments in humans
killing the vector, i.e., mosquito control / eradication (e.g. using chemical)
decreasing contact between humans and vector (e.g. bed net, inhibit transmission)
Drug treatment in humans leads to drug resistance in parasites
Why?
1. There is genetic variation in parasite sensitivity to drugs.
(malaria infection is diverse)
2. Under drug pressure, less sensitive (i.e., more resistant)
strains have two fitness advantages:
(1) They survive better.
(2) Their competitors have been removed. (other strains are killed)
Eradicating mosquitoes I:
(controlling vector at) The larval stage
Eradicating mosquitoes II:
(targeting) The adult stage
Indoor residual spraying, IRS Insecticide‐treated bednets, ITNs
Rapid killing action
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Reduce vector density and vector longevity
(reduce the contact, insecticide chemicalapplying selection pressure)
Evolution of insecticide resistance in mosquitoes
Treatment with an organophosphate insecticide started in 1968
Treatment ended in 1990
(switched to Bacillus sphaericus (BS) toxin)
Insecticide use began in 1968 and was stopped in 1990
By 1978, resistance allele was common near the sea (and spreading north)
After spraying was stopped, its frequency declined rapidly
Antibiotics and bacterial pathogens
The antibiotic penicillin was discovered in 1929 by Sir Alexander Fleming
Antibiotics kill bacteria by disrupting a variety of biochemical processes
They are a major life saver for humans
For bacteria, they are a major force of selection
susceptible genotypes are killed by antibiotics
resistant genotypes survive
Therefore antibiotic use amounts to a selection experiment
Antibiotic resistance evolves rapidly
Resistance increases with drug use
Resistance decreases with decreased drug use
Icelandic health officials campaign to reduce the use of penicillin,
because of increasing rates of resistance in Streptococcus pneumoniae
Antibiotic use among children was reduced by ~13% over this span.
The result was a decline in the frequency of resistant strains.
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