20. Evolution and Ecology Part II

Question 1

Evolution of SARS-CoV-2 Delta variant:

Answer 1

-first detected in Dec 2020 in India
-UK first case in March 2021
*replaces alpha in March 2021=EVOLUTION
-odds of household transmission 70% higher than alpha
>less than 3% of people fully vaccinated

Question 2

Delta viral load over infection:

Answer 2

-higher viral loads over duration of infection compared to other variants

Question 3

R0 of Delta:

Answer 3

-R0=5-10 (compared to 1-3)
-more transmissible and more competitive than ancestral strains
>replaced them in a few months
*evolution by natural selection has produced a ‘fitter’ pathogen

Question 4

Widespread use of antimicrobials in food animals and human medicine:

Answer 4

-has caused bacteria to EVOLVE antimicrobial resistance (AMR)

Question 5

Evolution of AMR occurs through:

Answer 5

-natural selection

Question 6

Antibiotic resistance scenario:

Answer 6

-person infected with bacterial pathogen is treated with antibiotic drug
-drug kills most bacteria, but some mutants carry an AMR gene that protects them
-mutant reproduces and passes AMR gene on
-patient carries a drug-resistant population of bacteria: patient recovers
*AMR bacteria are transmitted to other patients in hospital (or animal herd)

Question 7

AMR evolution:

Answer 7

-happens very quickly
-percentage of Enterobacteriacea strains resistant to 10 antibiotics increased!
>Salmonella, E.coli, Klebsiella and Shingella

Question 8

Penicillin resistance vs. penicillin usage:

Answer 8

-penicillin tested on pneumococci cultured from human patients
-N. EU has strict regulations
-S. EU less strict
*resistance to pencillin in pneumococci is higher in S vs. N. EU

Question 9

AMR bacteria (‘superbugs’) in Europe kills:

Answer 9

-around 33,000 people across Europe each year
-variation in countries is mostly due to differences in population size

Question 10

AMR bacteria worldwide kill:

Answer 10

-700,000 people/year
-10million by 2050
*evolving faster than science is inventing new antibiotics

Question 11

Discovery of new antibiotics has stopped:

Answer 11

-no treatment options for some bacterial infections
-1987 was the last discovery of new marketable class
*bacterial infections are becoming harder to treat worldwide (DISCOVERY VOID)

Question 12

Antimicrobial use in Canada in 2016:

Answer 12

-Canada is a major food producer
-19x more domestic animals than humans
*4x more antibiotics for animals than humans

Question 13

Antimicrobial use in Canada in 2016 by sector:

Answer 13

-20% humans
-78% production animals (cattle, pigs, poultry)
-1% companion animals

Question 14

Health Canada’s 4 categories for antimicrobials of importance for human medicine:

Answer 14

1. Very high
2. High
3. Medium
4. Low

Question 15

Class 1 antimicrobial drugs:

Answer 15

-restricted to humans and domestic animals
Ex. cephalosporins, fluroquinolones

Question 16

Class 2 antimicrobial drugs:

Answer 16

-used in all 3 sectors
Ex. penicillin, lincosamides, marcolides

Question 17

Class 3 antimicrobial drugs:

Answer 17

-used in food animals
Ex. tetracycline
*food production might not be as responsible for AMR

Question 18

How does AMR spread from food animals to humans?

Answer 18

-farm workers have direct contact
-eating food products contaminated with AMR
-animal waster is used to fertilize crops and contaminates water supplies

Question 19

Evidence that evolution of AMR in agriculture influences human health:

Answer 19

-Ceftiofur, Salmonella, and broilers
-MRSA, pigs and people

Question 20

Ceftiofur:

Answer 20

-third-generation cephalosporin (class 1)
>approved for use in domestic animals in Canada
-used off label in poultry industry
-infected in eggs to control omphalitis in broiler chickens

Question 21

Healthy chickens and Salmonella Heidelberg:

Answer 21

-humans acquire Salmonella Heidelberg from poultry or eggs
-concern that use of ceftiofur could drive CROSS-RESISTANCE to other cephalosporins
>Ceftriaxone and cephamycins used to treat Salmonellosis in children and pregnant women

Question 22

Ceftiofur-resistant Salmonella in chickens and humans:

Answer 22

*links between annual prevalence in chicken samples and in humans cases

Question 23

Quebec hatcheries:

Answer 23

-used to have a high level of off-label use of ceftiofur (78%)
-voluntarily reduced their use

Question 24

Result of Quebec hatcheries using less Ceftiofur?

Answer 24

-decreased ceftiofur-resistant Salmonella H in retail chicken meat by 89% in 2 years
-decreased ceftiofur-resistant Salmonella H in humans by 78% in two years
*started using it again and the resistance re-emerged

Question 25

Staphylococcus aureus:

Answer 25

-causes disease in humans and livestock

Question 26

Methicillin:

Answer 26

-a narrow spectrum beta-lactam antibiotic of the penicillin class used to treat infection gram-positive bacteria
*methicillin-resistance (MRSA) vs. methicillin-sensitive (MSSA) S. aureus

Question 27

Multi-locus sequence typing (MLST):

Answer 27

-used to classify clones of S. aureus
-clonal complex 398 (CC398) contains MRSA and MSSA

Question 28

Phylogenetic tree of CC398:

Answer 28

-2 clades: human-associated (HA) and livestock-associated (LA)
>HA clade but not LA clade has genes associated with human adaptation
>LA clones: resistance genes to methicillin and tetracycline
*evidence that CC398 clones evolved AMR in farm animals rather than humans

Question 29

LA widespread on pig farms in Netherlands:

Answer 29

-CC398 accounted for 39% of all MRSA in humans patients in Netherlands
-those working on the farm >20hr/week are 5x more likely to carry LA-MRSA
*farm workers are transmitting LA-MRSA to larger community and medical hospitals

Question 30

Durations of antimalarials and antibiotics:

Answer 30

-only a few years (transient)
*effectiveness of vaccines is much longer

Question 31

Vaccines:

Answer 31

-small pox was vaccinated to extinction
-influenza vaccine must be changed to track viral evolution
-some infectious disease are vaccine escape mutants (Hep B, pertussis)

Question 32

Pathogens with high diversity of strains:

Answer 32

-over 90 strains of streptococcus pneumoniae world-wide
>each have distinct antigens that are recognized by host immune system=induce strain-specific antibody responses
*vaccine development is complicated for pathogens with high strain diversity

Question 33

Vaccine against S. pneumoniae:

Answer 33

-Prevenar7 (PCV7) and Prevenar13 (PCV13)
>target the most common serotypes: 7 and 13 (90 total)
*has reduced the incidence of IPD

Question 34

IPD:

Answer 34

-invasive pneumoccal disease from S. pneumoniae
-includes: bacteremia, sepsis, meningitis and pneumonia

Question 35

What are the consequences of vaccination with PCV13 for other serotypes?

Answer 35

-will result in strain replacement
-strain targeted by the vaccine will disappear
*strains not targeted will increase in frequency

Question 36

Changes in frequency from vaccination:

Answer 36

*evolution
>genetic composition is changing

Question 37

Leaky vaccines can:

Answer 37

-prevents symptoms but not infection and transmission
*select for deadly strains (highly virulent)
-RARE!

Question 38

Marek’s disease in chickens:

Answer 38

-highly contagious viral neoplastic disease
-“Marek’s disease virus” (MDV) (alphaherpesvirus)
*infected can shed for life

Question 39

Symptoms of Marek’s disease:

Answer 39

-T cell lymphoma
-infiltration of nerves and organs by lymphocytes

Question 40

Transmission of Marek’s disease:

Answer 40

-spread in dander from feather follicles
-transmitted by inhalation

Question 41

“leaky” vaccine for Marek’s disease:

Answer 41

-original strain: caused mild paralysis and low mortality
-current strain: 100% mortality rate in unvaccinated chickens

Question 42

Compared MDV shedding between vaccinated and unvaccinated chickens:

Answer 42

-strains of different virulence
*virulent strains have higher fitness in vaccinated hosts
>because non-vaccinated chickens die so quickly

Question 43

Summary of Marek’s disease vaccine:

Answer 43

-leaky vaccine selected for highly virulent strains of MDV
>100% lethal in unvaccinated chickens
*vaccination resulted in evolution of highly virulent strains
-globally all chickens must be vaccinated

Question 44

Vaccine vs. antimicrobials to prevent evolution of escape mutants?

Answer 44

-vaccines!