Methods of control of malaria
Vector Control: killing vector (mosquito control)
Drug: killing parasite
Decreasing contact between humans and vector
drug treatmetns in humans leads to
drug resistance in parasites
why is there drug resistance in parasites
- Genetic variation in parasite sensitivity to drugs
- Under drug pressure less sensitiv/more resistance strains survive better and remove competitiors
insecticide resistance
treatment with organophoshate between 1968-1990 because of resistance allele
why are antibiotics a major force of selection for bacteria
- susceptible genotypes killed by antibiotics
- resistant genotypes survive
Plasmids and Horizontal Gene Transfer
resistance genes can be transferred among bacterial cells via extra-chromosomal loops of DNA called plasmids
Life Cycle of HIV
- HIV is a dsRNA retrovirus
- infects hosts CD$ helper T cells
- Viral enzyme (reverse transcriptase) turns RNA into DNA
- Embeds genome into host DNA
- Viral Genes transcribed and translated by host machinary
- New virus buds out of host cells
AZT resistance in HIV
- AZT drug binds to and inactivates HIV enzyme
- new mutant enzyme arose with binding site that was resistant to AZT
why does HIC evolve so fast
- massive population size
- short generation time
- high mutation rate
solutions for drug resistance
- Higher dose
- earlier treatment
- combinations of drugs
virulence
- disease severity as assessed by reductions in host fitness due to infection
- interpeted as the additional mortaility rate that a pathogen imposes on an infected individual
Conventional Wisdom
not true
pathogens that harm their hosts therby harm themselves
conventional wisom predictions
- over time, the coevolution of pathogens and their host will lead to a mutualistic association
- evolution would eventully lead to avirulance
- instances of highly virulent pathogens are cases where host-pathogen relationship is recent**
** applies to ebola and bird flu
challenges to conventional wisdom
tuberculosis (has been around sincee 3000 BCE)
Myxoma: (rabbit disease) over time, it adapted to an intermediate vrulence which cannot be explained
- biggest challenge
tradeoff hypothesis
- level of virulence is consequence of pathogen replication in host => cost of replication
- Benefit: pathogen replication is required for transmission between hosts
- Replication rate of pathogen and virulence evolves to maximize overall tranmission and spread
Model of virulence evolution
(equation)
R0=T(r) x D(r)
T(r)= # of new infections/ day (transmission rate)
D(r)= # days infection lasts (duration)
increased r (replication rate) increases transmission rate but decreases duration
pathogen cannot increase infection without decreasing duration
optimizing virulence
most virulent=x, least virulent= y
most virulence= high transmission but kill host quickly
least virulent= long infections but transmit poorly
**Prediction: ** strains of intermediate virulence will increase in frequency
this prediction was upheld in myxoma
Modes of Disease transmission
direct host to host transmission
Vector transmission
direct host to host transmission
hosts must be mobile and functioning relatively well in order to transmit disease
prediciton low replication rate and low virulence
vector transmission
host do not need to be mobile to transmit
prediction high replication and high virulence
virulence evolution
- virulance is unvaoidable consequence of parasite transmission
- parasites need to exploit hosts to transit to new hosts
- increase in transmission due to replication = cost of increase in virulence
transmission is the benefit, virulence is cost
benefit-cost of parasites is maximized
at intermediate levels
at intermediate replication rate, marginal beneft = marginal cost
for single parasite
at low replication rates
at high replication rates
marginal benefit vs cost
marginal benefit > marginal cost (selection for increasing replication
marginal benefit < marginal cost (selection for decreasing replication)
for single parasite
Multiple infections
favour evolution of more virulent parasites
