Bio412 - Exam 3 (special topics)

What is an emerging infectious disease

an infectious disease that has either

• newly appeared in population\

• been known for some time but is rapidly increasing in incidence and/or geographic range

Three primary types of emerging infectious diseases

Zoonotic infections (novel infections that now infect humans and are transmitted from other animals)

Infections that have evolved into new strains/emerge following control

• primarily through selection for drug resistance and immune escape (MRSA)

Infections that spread into new geographic areas

• known infections that spread into areas not previously recorded (Dengue, Zika)

Spillover vs jump

Host spillover is when the the pathogen invades a novel host (a host whose species hasnt seen the infection yet)

Host jump is when the virus establishes itself into another host species 

Ex: HPAI began in fowl and is now in cows 

Reservoir host

a host that harbors a pathogen and serves as a source of infection. Resovir hosts may or may not show symptoms

Spillback

this is when the pathogen returns from the novel host back into the original host

Species jump in humans, humansa being the novel host

humans have not seen the infection. Now, this zoonotic disease ia able to inefct us and we are able to spread it to toehr people. Causes widespread infection

Spill-over in humans

this is also known as primary infection

humans have become infected with a zoonotic disease can they are susceptbiel to but are rarely exposed. Often dosent sustain via human-human transmission

Secondaty infetion/onward transmission

humans were once the novel host, now they are a host and can spread it to other poeple (we see human to human transmission)

How many deaths worldwide are a direct result in infectious disease

about 25% (15 million)

EID distribution

in US: we use aggressive drug treatments, but may see antimicrobial resistance. this means that we do see re-emerging diseases that were once bad, then we helped a lot, and then now bad again. they evolved. We also see newly emerging diseases too

In SE Asia: we see that they have high biodiversity (many potential hosts) and increasingly antropogenic change (human development). also high contact rate human-human but also animals and people, both directly and through the food that they eat. They eat a lot fo wildlife.

Are EIDs ioncreasing

we believe so, but cant tell for sure

EIDs origin

many EIDs originate in wildlife, about 58%. THerefore, many EIDs are zoonotic

HIV

Old world monkeys have naturally occuring simian immunodeficiency viruses, and those SIVs crossed the barrier to large apes and humans. We not got HIV :( 

Do all EIDs cause outbreaks? (what are the stages)

no, different EIDs reach different stages

1) Have resovior species that hold the pathogen

2) that infection doesnt have replication in people (people cannot transmit it). Ro=0

3) INfection has an Ro lower than 1, meaning it can die out

4) INfection has Ro larger than 1, danger zone because growing

5) infection is now exclusive to humans

What happens if the antive host has an Ro > 1, but we have an Ro < 1

the disease is circulating in the resovior species, and can infection people, but wont establish and maintain in humans.

• why? maybe infection period too short to transmit, maybe pop is not dense enough to transmit to new susceptibles, maybe its so virulent that it kills the host quickly without a chance to reproduce

Barriers to spillover

spillover is only possible under certain circumstances. The diseases must be able to persevere, and thats depending on factors like res host distribution, res host density, how intense the disease is, how the pathogen is released from res host, how the pathogen is spread/how lijely is it to survive out of host, Exposure to humans, immune resp, and then the virus must replicate. Once all of those conditions are right, then the infection can spillover

What factos allow an ifnectious disease to emerge?

Ecological factors:

• Promximity of donor and recepient populations

• SIze/density of those pops

• climate and ecosystem disruption (can alter how parasite is tolerated in host, their life cycles, their reproduction, habitat shifts, and how fast they grow and distribute)

- overall, the host and the recip must come into contact. contact can increase via

• ag and land use changes

• increase in vector pop

• increase in animal movements

• increase in human traveling

Genetic Factors: the pathogen must adapt to novel host

• High mutation rate is favored, like ebola, hendra, corona

• small genome size

• Recominate fast to quicker mutate

• infections that are in very selective environments are favored

  • nosocomial infections (gotten in hosp) are favored because that person is likely recieving medicine that the virus can adapt for

Ebola in West Africa, 2014-2016 agent, res species, course of infection, and transmission

agent: RNA filovirus

Course of infection: virus targets macrophages (WBC) which leads to immune systems issuesand causes massive internal bleeding. 50-90% mortality

Transmitted via direct contact and bodily fluids

Spatial patterns of Ebola

a two year old died in an isolated area, where it reamined isolated, then a health care worker brought it to a larger town. Not long after, public health officials notified

Why did West Africa get a bad Ebola outbreak

late ID

lack of public knowledge

densely population/high transmission

Lack of infrastructure, many people in crappy houses and even treatment palces are bad

Types of vectors

Biological: arthropods that the virus may or may not replicate in. most important group

Mechanical: pathogen transmitted without replication, just a means of carrying it. Example, flies carry salmonella to meals. mosq qith myxoma

Fomites: inanimate bjects transmissting pathogen, like farm vehices

Classes of vectors

Insecta with fleas, lice, mosq

Arachnida wit ticks and mites

What diseases do vectors cause

Causes them in both wildlife and people, people often being a spillover. Some vectors are specific to one pathogen, some can do many

70% emerging diseases are curtesy of vectors, and majority are zoonotic

Examples of type of diseases vectors can passage

viral like dengue

Helminthic

Bacterial like lyme

protozoan like malaria

Heterogeneities that matter when looking at vectors spreading disease

Vector behavior: daily biting habits

Host exposure and sus: sometimes sex determines how sus you are, dengue has much worse second infection

interactions between host, vector, and environment: lyme disease has distinct seaosnality, malaria depends on climate

Mosq biting patterns

some species feed constantly while others only in early evening, etc. Also depends on people. If everyone wears spray and a bednet and stuff, then obviously they wont bite as often. Dependent on species and also our habits

Mosquito traits with Ro (their success as vectors)

based on species, Ro varies. Ro depends on biting rate, fecundity, life span, and more. Hard to calcuate. Most prominent factor often times is temperature. Mosq need very specific range, which varies on species. Not lineaar, more bell-shapes (cant be too hot or cold)

Host heterogeneities in vectors: exposure and susceptibility

Host heterogenies do not affect vector heterogeneities

host heterogeneities can be home range size, behavior, density of hosts, immunity, stress and hormones, sex and body mass

ENvironmental drivers in vectors: how does environment relate to vector success

seasonality in vectors are found in temperate areas, which casues seasonality in infection. In tropical areas, the vectors persist with development, so infection persists. Good example is ticks and Lyme (late spring, summer, and early fall are prime tick season because temps are good, so it’s also lyme tyme). Ticks dont develop when cold, kind of hibernate.

Seasonlity in Malaria

Malaria transmits with rain because more rain means more mosq. 

Trend in Malaria

still huge number of cases, but gradually going down

nearly exclusive in Africa

E Med is seeing rates go up actually which is sad

Malaria agent

Anopheles mosq and Plasmodium

• Plasmodium falciparium (most severe) - in africa

• P. vviax - not in Africa

Mortality of Malaria

Anemia because parasites destroy RBC

Cerebral malaria because brain is damaged alongside other vital organs. Severe consequences. 

Anopholes biting pattern

many Anopholes are specific to their host (only bit lizards, mammals, etc)

Changing global pattern of Malaria

We are seeing a reduction in land affected by malaria due to human efforts, but the popultion exposed is going up. This is ebcause we cannot control reprpduction/introduction of new sus, especially in urban areas.

Temperaute for malaria transmission

always thought it was high. now we know its lower (around 25C compared to 35 we thought). this means that most palces can get malaria

Climate change and malaria

increased avg temp causes mosq survival and hungier skeeters, so more bites. also promites pathogen development

We are seeing more hospitalizations from malaria. Why?

better reporting and survillence, not just number of cases. also better at taking care of people (more available beds)

Vegetative cover and malaria

more habitat for mosq = more mosq, so increased malaria

Urban areas and malaria

urban areas are increasing in density and population, so increases susceptibles for malaria. causes increase in malaria incidence

Ways to prevent malaria

Reduce mosq population

• Remove habitat

• use insecticide to kill them

Reduce biting rate of mosq

• bednets, with and wihtout insecticide

Target P.

• drugs to treat those already affected

• vaccines

What methods can we use to reduce mosq population

Reduce habitat via biological controls like fungi, fish, etc that could change the habitat enough to make it no longer suitable.

Use insecticides, but risky because Anopheles are assholes that have developed resistance

Reducing mosq bite rates moethods

Bednets are very effective and cheap, can use insecticide but could backfire big time

reduce infant death rate by 20%

Drugs targeting Plasmodium

these drugs attack P. during its asexual vulnerable ohase (wont reproduce)

can be Erythrocytic where is works when P. is in RBC

can be Exoerythrocitic when P. is outside RBC

overall, seeing P. develop resistance

Vaccine targeting P.

There is a virus that’s about 75% effective. Recommended for children by WHO.

Dengue facts

single strand RNA with 4 serotypes

2.1 million infections per year.

Ades mosq

deaths = 21000, mostly Asia

Severity of Dengue

DENV asymptomatic

DF: self-limiting febrile rash

DHF: Hemmoragic

DSS: shock syndrome - most severe

• DHF and DSS more common in second infection

Why is the second infection more likely to be wrose in Dengue?

Unsure, 4 hypothesis

• differences in genetic susceptibility

• maybe the second is just a hyper virulent strain

• overactive t-cell response like anaphyl

• MOST USED: Antibody dependent enhancement. Antibodies created for first infection’s serotype is used to help second serotype into cells

History of Dengue

Was in several areas, then went mostly inactive. Re-emerged

• SE Asia and WW2 caused ecological disruptions that made mosq habitat optimal

• Urbanization increased, and now soldiers and stuff from overseas. Overall man new sus

• WIldlife contact?

  • Likely that Dengue became endemic in tropics

Genetic Diversity of Dengue

Once, there were only some strains in certain areas (like 1 and 2 in US, all 4 in Asia, 1 and 2 in Africa

Now, we see all 4 serotypes endemic in many locations. This is called hyper-endemicity

Original Dengue ecology (Native host)

Sylvatic cycle, meaning that the wildlife and their environment circulated Dengue. Then it moved to humans in rural communities, still needed wildlife aspect (spillover). Go to now, humans maintain it without help of wildlife. Cycles are now entirely separate. Host jump. 

Dengue Prevention

Can use bednets, can be insecticide treated but can be problematic because of resistance

can reduce vectors (ex: Wolbachia bact reduced mosq)

antivirals: more for treatment, not good for prevention

vaccine: difficult because wiuold need to work with all 4 seros, otherwise could see ADE.

Influenza facts

segmented RNA virus

often confused with Rhinocirus, not the same thing!

Aerosol, saliva, fecces, blood

lives about one week in the human body, can be inactivated by detergents nd disinfectants,

flu dynamics - general

the flu is has seaosnal spidemics with dramatic pandemics, generally causes thousands of death each year, infects millions

Orthomyxoviridae

this is the family of viruses that includes influenza

3 major species on Ortho/flu

A: common with yearly epidemics, higher mortality and higher antigenic evol

B: less common, less fatal, less antigenic evol

C: less common, lower mortality, low antigenic evolution

Influenza A subtypes

the subtypes are categorized based of the surface proteins (Haemagglutin and Neuraminidase)

18 known H serotypes, 11 known A serotypes

Host range of flu

began in water fowl and other wild birds

moved to domesticated birds like chickens

Humans can get it and spread it to one another but cant spread it to any other species, pigs can give it to us, cows can get and spread it, cats can get it

Avian Influenza in wild birds

isolated from 105 wild bird species

mostly wild aquatic birdsccsuch as waterofowl and shorebirds

AIV prevelence varies depeinging on species, behavior, ecology

AIV infects intestines and is shed out via fecal matter, so oral-fecal route

Why do we get the flu more than once?

1) our acquired immunity is not permanent. after we recover from one antigenic variant, someone will usually be susceptible to a new variant in a few years. This is because the virus naturally evolved gradually over time, so we will become susceptible to that evolved strain.

2) Antigenic variation: virus alters the surface proteins to evade the host’s immune response. this amy take place on a larger scale throughout population, or it may take place even within the host. This is especally important for pathogens that want to

• target long lived hosts because theyll have an immune system most likely, and wihtout being able to adapt, their immune system will eventually overcome the virus and kill it

• repeatedly infect the same host

• are easily transmitted, so can better match this new hosts immune response. need to be adaptable if easily transmiteed.

Flu A evolution (two ways)

1) Antigenic Drift: this is seen in epidemics. this is a season to season evol in HA and NA surface proteins, they literally change shape

2) Antigenic shift: this is responsible for pandemics. this is when we see reassortment of surface proteins to produce a new strain that no one would be immune to

Studying antigenic Drift

epidemics and changes shape

we usually work on the HA because those are the surface proteins that we base the vaccie off of

research showed that flu does have antigenic drift, and that the viral lineages with more mutations in positive AA are shown to be progenitors of the future seasonal strain

overall, our immune response triggers the antigenic drift (evolution)

Seasonality of flu A

the virus circualtes in NH and SH, and is more constant in the tropics which ends up providing a source for the NH and SH

in NH, it is in winter months

in SH, its there for the summer months

We are not entirely sure as to why this seasonality happens. Hypothesis:

• change in host-host transmission

• humidifty and temperature directly affect transmission

• social pattersns change, such as school and more time spent indoors

• there is a higher viral production in winter

• novel strains from the tropics are introduced

Seasonal flu vaccine

There are two types

1) Injectable: this is killed and inactive virus. because it is killed, it is good for people who may be immunocompromised

2) Nasal Spray: this is weakened but alive. because of this, not recommended for people who are immunocompromised and/or pregnant

We made these vaccines annually due to the rapid evol of the flu. We try to predict the flu based on global survillence and estimates of SP patterns

Immune response in people begins about 2 weeks after vaccination

Pandemics of the flu occur when and prime examples

Pandemics often happen when there is a novel strain of the flu (we haven’t seen it before, therefore we are all susceptible unless vaccinated and its correct). Often this is because it was in a different animal species, and now we get it :(

Antigenic shift causes this because shift reassorts SP, which creates something new. Drift doesnt really create something totally new to the world, maybe just that area or even person

Spanish flu and Asian flu

Spanish Flu

this is very virulent - H1N1 and spread everywhere, even remote areas

50-100million dead, 500mill infected (3-6% of the world is dead)

Partially killed via cytokine storm (immune overreaction)

2 major descendent lineages and 2 additional reassortment lineages currently persist

• Human H1N1

• H1N1 in Swine (swine flu)

• H3N2 in humans, which led to

• porcine H3H2

Originated from AIV

Spanish Flu in US vs UK

In US, saw that children, elderly, and even healthy young adults were targeted to resemble a W curve with 3 peaks. 

In UK, saw that there were 3 waves of the virus, and the last two were worse than the first

What three things made antigenic drift

mutation + immune selection + recombination

Asian Flu

followed AIV in China

wild duck strain mutated with human strain to make h2n2

1-4 million deaths, even 69800 in US

Hong Kong Flu

genes from multiple subtypes reassorted to make new H3N2

1 million global deaths, 33800 in US

2009 h1n1 pandemic in Mexico City

Virus was circulating without people knowing. In a silent epidemic. Then 2 US children were infected. got attention

within days of recognition, MC shut down and ubsuccessfully suggested to close borders

firsts flu outbreak in 21st century decalred by WHO, but never got to serious outbreak

comprised of 4 known strains (one was endemic in ppl, 2 in pigs, and 1 in birds)

HPAI H5N1

highly pathogenic, currently native host is wild birds, poultry, and now cattle. many countries saying they also see in mammals. We see spillover into mammals as other countries do, such as cats and even humans. 50% fatality in people, but humans cannot transmit yet.

CDC says that it is probably not a risk for public health. Problematic in other ways

• economy

• food security

• what is the future? will we become the next species jump victim?

• can become pandemic potentially and wreck havoc all over the world

2009 Swine Flu

Did research to see how to vaccinate

• Use homologous vaccine (same vaccine for both regimens) and with no delay in 70% of kids

What is the classic view of how a pathogen evolves

pathogen evolves towards mutualism where they will become benign with their host

Flaws based on classic view

theoretically, the parasite would become benign after a while in its host. Why? Is it the pathogen evolving this way, or the host’s immune response kicking in?

This would mean that the parasite would want to maximize transmission and minimize virulence to create commensalism or even mutualism

However, doesn’t fit with the fact that higher virulence corresponds to high transmission (positive correlation). If you want to transmit, you must reproduce, which would hurt your host. Overall, this higher transmission desire leads to higher virulence via reproduction/replication

Ro

Ro = rate of infection or transmission / parasite induced host mort*natural death*recovery

Trade off Theory

This is the idea that there is a balance of virulence and transmission. Natural selection favors for the pathogen to replicate without causing too much harm too host. Intermediate level, not really low or really high virulence

Rabbit-Myxoma background

European rabbits were introduced in Aus in 1800s and became invasive species. Tried Myxoma as biological control

Myxoma

biological control for the European rabbits. from south america

in native hosts, usually quite survivable and easy to recover from. In European rabbits, we see nearly 100% mortality.

First Myxoma introduction failed. Tried a second time and took several months to really take off, but there was a massive spread when it did take off. Specifically, released in August and took off in December

Timeline of Myxoma

In December (warm in Aust), we see mosq coming back from cold summer months. THis means that the mosq transmit the virus very well, its warm but also a ton of these rabbits. High virulence does well here - very few survivors, but still some

In May, low mosq populations, few and isolated bunny populations. rabbits breed. virus needs to adapt to change for new situation, cant be relaly virulent any longer because too few individuals, can risk killing them. Lower density means higher selection pressure for virus

In Dec, most come back. second epidemic. we see more rabbits proportionately survive this time, and we see higher rates of seropositivity. See grade 2 and 3 virus

In May, we have teh second bottleneck so higher selection pressure. lower transmission. see baby bunnies

Dec: third epidemic, even higher raatio of rabbits survive. attenuated virus does well because its just trying to be there and not die out, high selection pressure

Overall, transmission bottlenecks kept the virus from staying too virulent because it cared a lot about transmission and had to adapt to the rabbit population’s sharp decline (lack of hosts)

Grades of Myxoma

1 is the most virulent, then 2, then 3, then 3A, then 3B, then 4, then 5 being the least virulent that keeps them alive the most

In Aus, we see that they started with 1, then had all, and then finished with 3 being selected. see similar findings in a UK study. So, virus doesnt want to be too weak, but also doesnt want to just kill everyone due to the low density of rabbits. this is an example of trade off hypothesis! DIdnt want to be too strong toherwise all hosts would die and wouldnt transmit, but if left too attenuated, theimmune response would kill the virus. Need to keep them impaired, not healthy and not dead.

When looking at a phenology tree for Myxoma, we see a lot of grade 3 selected. Still see some 1 though at the end, like the virus evolved into grade 1. Why would it do this?

Maybe the rabbits have extremely strong immune systems in some areas so that Grade 3 in that area would be like a grade 5 in Aus. May need to be more virulent to not be controlled by immune response. 

What is intereting about Myxoma as a replicator?

Myxoma is a large DNA virus, but replicates fast like a one-stranded RNA. this is quite uncommon

What makes Myxoma virulent?

Not just one gene, but 12. Just 1 wont do it

SPE in native host

SPE is when we move the pathogen for it, elimating the need for the virus to account for transmission bottleneck

In native hosts, we see virulence increase with each passage. WHen viruses dont need to worry about transmission, they become more virulent in antive host

SPE in non-native host

IN non-native hosts, virulence decreases with passages. The virus wants to establish itself, so it rapidly evolves to not be virulent. Not really worried about transmitting, more worried about maintaining.

SPE in media without host

We see that virulence decreases with each passage. No immune response to combat with, so doesnt need to keep getting stronger/more virulent. Also, no competiton from other infections, so doesnt need to overpower those via increased virulence.