Lecture 20 - Ecology and Evolution Part 2_v05.pptx PDF

Final exam in Disease Ecology & Epidemiology Do final exam in Canvas rather than paper version. Bring laptop to final exam Today, quiz consisting of a single easy question with no marks Case fatality rate (CFR) is the proportion of infected individuals that die from the infection CFR = (infe...

Final exam in Disease Ecology & Epidemiology Do final exam in Canvas rather than paper version. Bring laptop to final exam Today, quiz consisting of a single easy question with no marks Case fatality rate (CFR) is the proportion of infected individuals that die from the infection CFR = (infected hosts that die over course of disease)/total number of hosts infected with the disease followed till recovery or death Example: 100 crows are experimentally infected with West Nile fever virus and 15 crows die while the rest recover. CFR is 15% (15/100) over course of the infection Question: Is the CFR an estimate of prevalence or incidence? Evolution and Ecology Part 2 Pathogen Evolution  Outline of Pathogen Evolution  Evolution of SARS-CoV-2 Delta variant in human populations  Bacteria have evolved antimicrobial resistance in response to human use of antimicrobials in food animals and medicine (human culture)  High levels of antimicrobial use in food animals results in evolution of antimicrobial resistance (AMR). Examples of how AMR bacteria in chickens and pigs ended up in humans  Pathogens evolve in response to vaccination (human culture). Vaccines can drive strain replacement (e.g., Streptococcus pneumoniae)  Leaky vaccines can select for more virulent pathogen strains, but this phenomenon is rare (e.g., Marek’s disease in chickens)  Duration of effectiveness of vaccines is longer than antibiotics, but vaccines can select for escape mutants Evolution of SARS-CoV-2 in human host  Evolution of SARS- CoV-2 Delta variant  SARS-CoV-2 variant B.1.617.2, classified by WHO as ‘Delta’ variant  First detected in India in Dec 2020. First case in UK detected in March 2021  Delta replaced Alpha (B.1.1.7) from April to June 2021  20 h/week (solid diamonds) or < 20 h/week (open diamonds)  Humans working on pig farms >20 h/week are 5x more likely to carry livestock-associated-MRSA compared to 90 strains exist world-wide. These strains have distinct antigens recognized by host immune system  Strains induce strain-specific antibody responses. Antibody-response against strain X is not protective against strains Y, and Z  Vaccine development is complicated for pathogens with high strain diversity and that induce strain- specific immunity  Vaccine against Streptococcus pneumoniae reduced incidence of invasive pneumococcal disease in children  Streptococcus pneumonia causes invasive pneumococcal disease (IPD), which includes bacteremia, sepsis, meningitis, and pneumonia  Pneumococcal conjugate vaccines (PCV) Prevenar 7 (PCV7) and Prevenar13 (PCV13) target the 7 and 13 most common serotypes of S. pneumoniae  Vaccination of children in Australia has reduced incidence of IPD. Vaccine works, but there are are 90 serotypes of S. pneumoniae  Question: What are the consequences of vaccination with PCV7 or PCV13 for other serotypes of S. pneumoniae? Mehr & Wood. 2012. Lancet 13: 258-264  Vaccination drives strain replacement of S. pneumoniae  Vaccines that target subset of pathogen strains will result in strain replacement  Strains targeted by vaccine will disappear; strains not targeted will increase in frequency  PCV7 was used in Australian children < 5 years old  Frequency of blue strains targeted by vaccine decreased after introduction of PCV7 in 2005. Frequency of red strains not included in vaccine increased over time  Changes in frequencies are evolution; genetic composition is changing Time = 10:10 AM Mehr & Wood. 2012. Lancet 13: 258-264  Leaky vaccines can select for virulent pathogen strains  Marek’s disease in chickens  Marek’s disease highly contagious viral neoplastic disease in chickens. Discovered in 1907 by veterinarian József Marek  Disease is caused by an alphaherpesvirus called Marek’s disease virus (MDV)  Disease is characterized by T cell lymphoma and infiltration of nerves and organs by lymphocytes  Infected birds shed MDV from feather follicles for life. Transmission occurs via inhalation of dander  Vaccine for Marek’s disease is leaky  First vaccine was introduced in 1970 and greatly reduced disease incidence  “Leaky” vaccine prevented disease but not infection and transmission  Vaccinated chickens selected for highly virulent strains of Marek’s disease virus  Original strain caused mild paralysis and low mortality in unvaccinated chickens  Current strains have mortality rates of 100% in unvaccinated chickens Kennedy & Read. 2018. PNAS 115(51): 12878–12886  Virulent MDV strains and vaccinated chickens  Compare chicken mortality and MDV shedding between vaccinated and unvaccinated chickens challenged with avirulent and virulent MDV strains  Vaccinate 1-day-old chicks with herpesvirus of turkeys (HVT) and unvaccinated controls  After vaccination, expose chicks to 1 of 5 different MDV strains that differ in their virulence  Top row: mortality rates due to MDV strain  Middle row: MDV shedding over time  Bottom row: cumulative shedding of MDV over the duration of infection  Avirulent strains have higher fitness in unvaccinated hosts. Virulent strains have higher fitness in vaccinated hosts! Read 2015 PLOS Biology 13(7): e1002198  Summary of Marek’s disease vaccine  Marek’s disease is problem in poultry  1970 vaccine reduced incidence of Marek’s disease in poultry flocks  Leaky vaccine selected for highly virulent strains of MDV. These new strains are 100% lethal in unvaccinated chickens  Virulent strains have higher lifetime transmission in vaccinated than unvaccinated chickens  Globally, all chickens must be vaccinated against Marek’s disease!  Vaccines that prevent disease but not transmission can select for and result in the evolution of highly virulent strains!  Vaccines last longer than antimicrobials  Duration of effectiveness of antimalarial, antibiotics, and vaccines  Effectiveness of antimalarials and antibiotics is transient (a few years)  Effectiveness of vaccines is much longer  Smallpox was vaccinated to extinction  Influenza vaccine must be changed to track viral evolution  For some infectious diseases (pertussis, pneumococcal disease, and Hepatitis B virus), there are vaccine escape mutants Kennedy & Read. 2018. PNAS 115(51): 12878–12886  Summary of Pathogen Evolution SARS-CoV-2 variants have evolved rapidly Bacteria have evolved antimicrobial resistance in response to human use of antibiotics (human culture) Pathogens have evolved in response to host immunity whether induced via natural infection or vaccination (human culture) Leaky vaccines can select for more virulent pathogen strains, but this phenomenon is rare (e.g., Marek’s disease) Vaccines are better than antimicrobials to prevent evolution of escape mutants End of lecture 20 Time = 10:20 AM