Lecture 30 Flashcards
(46 cards)
1
Q
What is an emerging virus?
A
Causative agent of a new or previously unrecognized infection (not new though obvi)
The term became popular in the 1990s however emerging viruses, new infectious agents have invaded human populations since the rise of agriculture 11,000 years ago
2
Q
What are some characteristics of emerging viruses?
A
- Expanded host range with an increase in disease not previously obvious
- zoonosis accounts for 60-80% of human emerging infectious diseases
- cross-species infection may establish a new virus in the population however often cross-species infection cannot be sustained (ebola and Marburg is from bats to humans) humans often dead ends not always though since some ebola outbreaks have indeed been human to human
3
Q
What is zoonosis?
A
- Transmission of a virus from a wild or domesticated animal to humans
4
Q
What are some factors influencing disease emergence?
A
- Globalization, rapid air travel, altered ecosystems, deforestation, environmental changes, ‘mega-cities’, poverty, expanding populations, microbial evolution
5
Q
How has evolution contributed to emerging diseases?
A
- leads to biodiversity of pathogens existing in nature
- adaptation to new hosts and environments through variation (due to error prone polymerases, recombination, reassortment) and selection
6
Q
What are the four interactions between hosts and viruses and what are the common paths of emerging infections?
A
Stable: maintain virus in ecosystem
Evolving: passage of virus to naive populations
Dead-End: one way to different species
Resistant: infection blocked
- From stable to evolving or stable to dead-end
7
Q
Define stable host-virus interactions?
A
- both participants survive and multiply
- some are effectively permanent (humans are the sole natural host for measles virus, herpes simplex, HCMV, smallpox
- May include infection of more than one species (influenza A virus which is also in birds, flaviviruses and rotaviruses which are in mammals and insects
8
Q
Define evolving host-virus interactions?
A
Hallmarks are instability and unpredictability
Outcome of infection from completely benign to death
- Introduction of smallpox and measles to natives of Americas by Old World colonists and slave traders
- Introduction of West Nile virus into the Western Hemisphere (New York)
- Introduction of a pox virus to rid Australia of rabbits
9
Q
What are dead-end host-virus interactions?
A
- frequent outcome of cross-species infection like for ebolavirus, humans, chimps and gorillas are dead end hosts
- new infected host may not transmit the infection to others of the same species (avian influenza H5N1)
- These kinds of interactions contribute little to the spread of a natural infection since it is a dead end
10
Q
What are resistant host-virus interactions?
A
- situation in which the host blocks infection of the virus completely
- Vast majority of human encounters with viruses are uneventful and are not able to initiate an infection like how we live and breathe in a cloud of viruses that do not cause infection soooo resistance
- Resistance can be characterized by very strong body defences and the fact that host cells are not susceptible
11
Q
What are the two things that need to happen for an emerging infection?
A
- Introduction into a population
- Establishment and dissemination
Successful encounters require access to susceptible and permissive cells
Population density and health are important factors
Virus populations will endure in nature only because of serial infections (a chain of transmission) which is why we quarantine and isolate
12
Q
What kinds of genera do viruses that infect humans belong to?
A
- 32% adapted pathogens (joined us when we diverged as Homo sapiens and remain stable)
- 37% are zoonotic pathogens
- 16% heirloom pathogens come from our ancestors but before speciation to Homo sapiens
- 6% heirloom pathogens come from our ancestors and given to us after speciation to Homo sapiens
13
Q
How do human find new ways to meet viruses?
A
- Dams and water impoundments
- Irrigation
- Massive deforestation
- Rerouting of wildlife migration patterns
- Wildlife parks
- Long distance transport of livestock and birds
- Air travel
- Uncontrolled urbanization
- Day care centers (stuff in most and touching everything)
- Hot tubs
- Air conditioning
- Millions of used tires (chikungunya to Americas)
- Blood transfusion (Hep C)
- Xenotransplantation
- Societal changes with regard to drug abuse and sex
14
Q
What are the determinants of disease emergence and persistence?
A
- Infectious agent (genetic instability of viruses like error prone polymerases and quasispecies, cell/tissue tropism, immune evasion like the strategies used by virus)
- Host (individuals and population level, tissue/cell tropism, immune response by the host)
- Environment (human activities is a key determinant of disease emergence)
15
Q
What’s an example of humans changing their behaviour and influencing virus behaviour?
A
- Poliomyelitis from poliovirus had been a stable host for over 4000 years but then BAM emergence in the 20th century with large outbreaks yet no change in the viral genome
- what caused the emergence? human behaviour so rural communities had poor sanitation and children were infected at an early age (protected by maternal ABs) then improved sanitation delayed transmissions so in this case human behaviour aline caused emergence and influenced disease outbreaks
16
Q
Hantavirus 1st appearance and clinical presentation?
A
1st noted in Four Corners, New Mexico in 1993
- First named Four Corners virus, but people didn’t like it so they called it Huerto canyon virus cuz isolated near Huerto canyon town, but Nawrrrr so Sin nombre virus
- Hantavirus pulmonary syndrome: flu-like symptoms, pulmonary disorders (fluid accumulation in lungs), death in 1/3
- Hemorrhagic fever with renal syndrome (HFRS)
17
Q
Hantavirus epidemiology, where it came from?
A
- Sin nombre virus (Bunyaviridae) (-) ssRNA viruses
- Endemic in the deer mouse (30% of them are virus positive)
- Transmitted to humans through rodent urine, saliva and feces
- Large spike in piñon or pine nuts due to unseasonably high rainfall that year, so spike in rodents including deer mice who found more ways to interact with humans since the population was so large
18
Q
How hantavirus became emergent?
A
- 1992-1993, abundant rainfall produced a large crop of piñon or pine nuts
- facilitated by climate change
- Mouse population rose and contact with humans increased (in cottages, in cars and lots of areas more contact with mice or contaminated surfaces by mouse feces or dust leading to human infections
- humans are not the natural host, so human disease is rare however hantavirus really affects other places in the world like South America (Chile) big hantavirus problem
19
Q
Hendra virus discovery and clinical features?
A
- Discovered in Hendra, Australia, Sep 1994
- Henipavirus from family paramyxoviridae (beyond mucus viruses)
- Severe respiratory and neurological diseases in horses and humans
- > 70% mortality in horses and around 57% in humans
- Around 39 outbreaks since 1994
20
Q
Zoonosis and epidemiology of Hendra virus?
A
Both Hendra and nippah virus outbreaks located to the same region where flying foxes are usually found (hint of zoonosis with flying foxes which are bats)
21
Q
How does Hendra virus spread and what is a form of treatment?
A
- Spread from flying foxes (fruit bats) to horses, then to humans
- Horses continue to acquire the infections as an intermediate host between bats and humans
- Equivac (R) HeV vaccine (2012), only veterinary vaccine to prevent infection and prevent the intermediate host from passing to humans in that way
22
Q
Emergence of Nipah virus?
A
- 1st outbreak in Nipah, Malaysia, 1998
- its a Henipavirus from the family paramyxoviridae
- outbreak of neurological and respiratory disease on pig farms
- then 105 human deaths, so 1 million pigs culled to stop spread of infection
- subsequent outbreaks have occurred in Bangladesh and India, presenting as acute respiratory syndrome and encephalitis
- 74.5% case mortality in humans
23
Q
Zoonosis and epidemiology of Nipah virus?
A
- It was common to plant mango trees near pig farms and fruit bats, which are the reservoir, love mangoes near the pig farms, so the pigs become the intermediate hosts as fruit bats excrete virus in urine and saliva on partially eaten fruits, so they’re sick and then they spread the infection to humans
- Subsequently, fruit trees were no longer permitted above pig pens
24
Q
So how do humans get infected with Nipah virus and how is it spreading now?
A
- Humans infected by consuming date palm sap contaminated by bats (India and Bangladesh) because bats drink, defecate or drown in the sap
- 30 outbreaks in Bangladesh since 2001, subsequently human to human interactions has occurred so infections do continue
25
Why did people get infected in spite of the don't drink sap campaign?
Despite the large campaign in Bangladesh to prevent infection, 14 cases recorded in 2015 (8 deaths) because people liked to use the sap to ferment it into Tari to make palm wine (around 5-8% alcohol content). Alcohol consumption is restricted and highly stigmatized in Bangladesh so people weren't willing to admit that they had been consuming this type of wine. Reminiscent of salmonella outbreak in USA from contaminated marijuana so once again hard to figure out because people didn't want to admit to using a banned substance.
26
When were Marburg and Ebola viruses identified as emerging viruses and how were they spread? (think index patients)
- 1967: Marburg, germany, identification of Marburg virus in an animal facility
- 1976: simultaneous outbreaks in DRC (democratic republic of Congo) and Sudan
Sudan index case: cotton factory workers, spread by the use of contaminated needles among family members, named after a small river in northwestern DRC ebola virus
27
What was the worst outbreak of ebolavirus?
The worst outbreak on record was the 2013-2016 ebola outbreak which led to 28, 637 infections with 11,315 deaths.
28
How did Ebolavirus even emerge in Guinea 2013?
Index case was 2 year old cared by mum and grandma. Latter went to see healer, healer died, very well known so many people attended the funeral. This seeded that outbreak
- Spread by contact with infected blood or body fluids (urine, saliva, sweat, feces, vomit, breast milk, semen) or contaminated objects like syringes or needles
- Rnot = 2 (inefficient, close contact is required since spread through contact with bodily fluids)
29
What are the clinical feature of Ebola/Marburg?
- Incubation 2-21 days (not contagious)
- early symptoms: fever, headache, muscle pain, diarrhea, vomiting, stomach pain
- peak illness: rash, hemorrhage, convulsions, severe metabolic disturbances, diffuse coagulopathy
- multi-system involvement: systemic, gastrointestinal, respiratory, vascular, neurological
30
Describe the pathogenesis of ebola?
- Bored cell tropism: monocytes, macrophages, dendritic cells, endothelial cells, fibroblasts, hepatocytes, adrenal cortical cells, epithelial cells
- extensive necrosis in parenchymal cells of many organs (liver, spleen, kidney, gonads)
- elevation in liver enzymes, shock (adrenal)
- massive lymphocyte death (yet these cells are not infected) but there is a cytokine storm, impairment of vascular and coagulation sytems
31
Is ebola really acute?
- hard to understand and determine long term effects of ebola since not many people survived at all during the outbreaks
- Can be persistence of ebola in ocular fluid even 9 weeks after clearance of viremia, many ebola survivors have catarrh and require surgical intervention and doctors were scared to perform surgery because of the evidence of ebola in the ocular fluid, so now they have safe ways to treat, it can also persist in breast mil and semen (49% of men tested months after onset)
- they are immunologically privileged sites (eyes, testes) where body doesn't want inflammation because can cause eye loss or sterility, so different kinds of immune responses at these sites which may explain why viruses are able to persist there
32
Well, where did filoviruses come from?
- Marburg virus was isolated from a cave-dwelling fruit bat (probs reservoir host)
- Zaire ebolavirus RNA, antibodies found in 3 tree-roosting bats but no full infectious virus was actually isolated from these bats
33
Explain how Ebola adapted to human infection in the 2014 outbreak
- A82V mutation in EBOV envelope glycoprotein which facilitates binding to EBOV receptor NPC1 (From March 2014 where most contained A to May 2015 where most contained V at this position)
- Increased viral entry in human cells (at least in cell cultures)
- Simultaneously decreasing viral entry into bat cells
- Reminiscent to COVID (delta/omicron) variants adapted to receptor
34
Describe the emergence of SARS-CoV-2 (bestie)?
- 1st human cases of COVID-19 were reported in Wuhan city (china) in dec 2019
- Environmental samples were taken in a food market in Wuhan were positive for the virus (the stalls in a wet market)
- concentrated in an are where wild and farmed animal trade was present (spillover from an intermediate animal host?)
- market - origin of virus or at least played a role as an amplifying setting for the initial spread
35
What are the clinical features of COVID-19?
- Transmission: primarily droplets and aerosols as well as fomites
- Tropism: upper respiratory tract/lung (and nasal passages), early studies suggest GI tract infection (fecal-oral transmission maybe)
- No age distinction/discrimination but can be more serious in the elderly
- Symptoms include fever, cough, fatigue, shortness of breath, muscle/joint pain, sore throat, headache, chills, nausea/vomiting, nasal congestion, diarrhea, hemoptysis, conjunctival congestion
- Shedding is often at the peak of symptom onset but there can be pre-symptomatic transmission
36
What is the world situation on covid 19?
630 million confirmed cases, probs underestimation because Canada doesn't do widespread testing and lots of vaccine doses administered to date. Early cases mostly imported through air travel and quickly became local transmission (Canada). 4.36 million cases in Canada and 1.23 million in Quebec alone. Wastewater surveillance is a good early indicator. Important to expand this early warning system.
37
What differs SARS-CoV-2 from other respiratory viruses?
Flu: Rnot 1.3, incubation 1-4 days, hospitalization rate 2%, fatality rate 0.05-0.1%, annual infection rate, 1 billion
COVID19: Rnot 1.38-5 probably overestimating because only testing symptomatic and in hospital also because sometimes would base on cell culture which is obviously not the same as human to human transmission, incubation 4-14 days longer period for virus transmission, hospitalization rate 19%, 5.5%, fatality rate 2.5% global 1.1% Canada, over 387 million
SARS: Rnot 3, incubation 2-7 days, hospitalization most cases, fatality rate 9.6-11%, 8098 in 2003
MERS: Rnot 0.3-0.8, 6 day incubation, most cases hospitalization, fatality rate 34.4%, annual 420
38
Where did SARS-CoV-2 come from?
Early reports suggested pangolins but identity only 91%, bat coronaviruses are 96% identity so probably bats possibly with another intermediate host, 32kb so like 1200 nucleotide difference, RATG13 96% virus identity
39
How can viruses make the species jump like how corona HOWWWW?
either directly bat to human or bat to intermediate host to human
- subtle changes like in the spike protein can alter tissues that can be infected, host range and disease manifestation
40
What is the molecular basis of host switching?
- Steep or shallow fitness valleys between donor and recipient species, when steep, a lot of changes must be made for host switching, when shallow, not a lot of changes needed, these adaptational Barriers need to be crossed, greater donor-host (species) similarities facilitate switching (requires fewer adaptational mutations)
- Pathogen opportunity: given enough opportunities, even a relatively unfit virus can adapt
41
Give examples of viruses whose reservoir is bats?
- Nipah, MERS, SARS, Ebola, Hendra, Rabies, marburg
42
What makes bats so good as reservoir host for emerging viruses?
- Account for 25% of all mammalian species, there are microbats (insects) and megabits (fruit)
- Long evolutionary history (52.5 million years old) which provides a long period for host-virus co-evolution
- Huge diversity of bat species since they account for 25% of mammals on earth
- Flight = hollow bones (little bone marrow and different immune response)
- Constitutive expression of IFNalpha, so any virus in a bat learns to live with IFNalpha and there is no inflammation from expression of interferon
- Hibernation (reduced body temperature and metabolic rate so harder to clear viruses) - suppresses immune response and delays viral clearance
- Social: live in close proximity to one another which facilitates viral transmission (stable circulation in a population)
- Echolocation (microbats) - vibration of the larynx which can perfectly create aerosols (transmission)
- Worldwide distribution (except Antarctica) so everywhere that humans are and we have plenty of opportunities to interact with bats and other mammals do too
- Only mammals that can fly - carry viruses to distant areas like air travel
- Eating behaviours - cannot ingest a lot of food because must be light to fly, tend to chew food, get nutrient and spit it out, don't want to swallow to not be heavy so they can fly and partially digested fruits can come in contact with other animals and transmit
- Longevity - average lifespan of 10-40 years some even as old as 70 years old, long period for transmission to humans and other mammals
43
How does the host range expand and how common is it?
- can be expanded by mutation, recombination and reassortment
- host range jumps that actually produce sustaining transmission are quite rare since most are dead ends
incredibly hard to predict but we can know what is out there and react #preparedness
44
What new technology can help for viral discovery?
- emerging viruses often come from unknown agents
- Today we can use RNA seq to facilitate viral discovery, detect and characterize with relative ease (rapid identification in different species)
- Like for SARS-CoV-1/2)
- Correlation os not causation, people thought XMRV was related to prostate cancer, just because a virus is seen with disease does not mean it caused disease so proceed with caution
45
How can we manage and surveil emerging infections?
- R&D in academia and industry (facilitate understanding of high-risk pathogen groups to make vaccines and develop antivirals, understand mechanism of transmission for PPE and measures like social distancing)
- New diagnostic tools made for early detection and identification
- get a database of all viral genomes in the ecosystem to better understand the major reservoir of bat viruses but also where other viruses are coming from
- first responder actions combined with rapid communication (!!!) like Vietnam doc in vietnam
- Public health actions (vaccines, drug/ppe stockpiles, quarantines, social distancing, travel restrictions) and widespread compliance
- surveillance and cooperation by governmental and international agencies
46
What is a quote to think about when it comes to emerging viruses?
- We remain at risk for the foreseeable future
- Covid19 and other emerging viruses should force us to think in earnest and collectively about living in more thoughtful and creative harmony with nature, even as we plan for nature's inevitable , and always unexpected, surprises
