Video 5.3: The Pathogen: Evolution

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From the course by The University of Hong Kong

Epidemics

33 ratings

The University of Hong Kong

Epidemics

33 ratings

“If history is our guide, we can assume that the battle between the intellect and will of the human species and the extraordinary adaptability of microbes will be never-ending.” (1) Despite all the remarkable technological breakthroughs that we have made over the past few decades, the threat from infectious diseases has significantly accelerated. In this course, we will learn why this is the case by looking at the fundamental scientific principles underlying epidemics and the public health actions behind their prevention and control in the 21st century. This course covers the following four topics: 1. Origins of novel pathogens; 2. Analysis of the spread of infectious diseases; 3. Medical and public health countermeasures to prevent and control epidemics; 4. Panel discussions involving leading public health experts with deep frontline experiences to share their views on risk communication, crisis management, ethics and public trust in the context of infectious disease control. In addition to the original introductory sessions on epidemics, we revamped the course by adding: - new panel discussions with world-leading experts; and - supplementary modules on next generation informatics for combating epidemics. -------------------------------------------------------- (1) Fauci AS, Touchette NA, Folkers GK. Emerging Infectious Diseases: a 10-Year Perspective from the National Institute of Allergy and Infectious Diseases. Emerg Infect Dis 2005 Apr; 11(4):519-25. What you'll learn - Demonstrate knowledge of the origins, spread and control of infectious disease epidemics - Demonstrate understanding of the importance of effective communication about epidemics - Demonstrate understanding of key contemporary issues relating to epidemics from a global perspective

From the lesson

Theme Two: Spread (Epidemiological triangle)

Theme One descriptions

Week 5 Introduction0:51

Video 5.1: Epidemiologic Triangle1:08

Video 5.2: The Pathogen: The effects of dose and pathogen genetics5:13

Video 5.3: The Pathogen: Evolution9:29

Video 5.4: The Host: Overview5:00

Video 5.5: The Host: Age7:33

Video 5.6: The Host: Sexual mixing4:45

Video 5.7: The Environment7:54

Meet the Instructors

Gabriel M. Leung (HKU)
Dean
Li Ka Shing Faculty of Medicine
Joseph T. Wu (HKU)
Associate Professor
Li Ka Shing Faculty of Medicine
Kwok-Yung Yuen (HKU)
Professor
Li Ka Shing Faculty of Medicine
Tommy Lam (HKU)
Assistant Professor
Li Ka Shing Faculty of Medicine
Maria Huachen Zhu (HKU)
Associate Professor
Li Ka Shing Faculty of Medicine
Guan Yi (HKU)
Chair Professor
Li Ka Shing Faculty of Medicine
Benjamin Cowling (HKU)
Professor
Li Ka Shing Faculty of Medicine
Thomas Abraham (HKU)
Associate Professor
Journalism and Media Studies Centre
Mark Jit (LSHTM)
Professor
Department of Infectious Disease Epidemiology
Malik Peiris (HKU)
Chair Professor
Li Ka Shing Faculty of Medicine
Marc Lipsitch (Harvard)
Professor
Department of Epidemiology

Previously, we learned that the dose

and genetic properties of a pathogen

one is exposed to can affect the risk

and severity of disease.

But these genetic properties

which proteins a pathogen expresses,

and even the dose that is available for transmission

are shaped by evolution.

In this session, we will discuss

several examples of pathogen evolution,

that is, changes in pathogen populations over time

that arise due to the action of natural selection.

For evolution by natural selection to occur,

two things are required:

the organisms must have genetic variation

and there must be differential reproductive success

of different genetic types.

In the case of pathogens,

both conditions are very often met.

Bacteria and viruses reproduce

in a matter of hours to a few days,

and every round of reproduction results

in genetic mutations that provide ample genetic variation.

Bacteria have evolved many mechanisms

that enhance this genetic variation,

by allowing transfer of DNA between

even distantly related species,

such as plasmid transfer and DNA transformation.

Viruses don’t have these mechanisms,

as far as we know,

but they do often have very high mutation rates,

leading to the generation of highly diverse

populations of virus even during one infection.

Natural selection on microbes takes many forms as well.

Any property that makes a pathogen

reproduce faster within a host

and outrun the immune system will be favored,

though there is some limit to this,

because growing too fast may kill the host,

leading to the end of the infection.

Sometimes, it’s useful to think of the pathogen

as racing to reproduce faster than the host‘s

immune response can ramp up.

But it’s a race where winning too decisively

can be harmful in the long run,

as dead hosts don’t usually transmit infection.

Let’s see two examples of this kind of evolution.

Myxoma virus is a virus that infects European rabbits,

causing a disease called myxomatosis.

In the 1950s, myxoma virus was imported to Australia,

where rabbits were crop pests,

in the hopes of using it as a bio-control agent

to kill off rabbit populations.

Frank Fenner, who is famous for his role

in eradicating smallpox, was a young scientist then

and realized that this was a grand evolutionary experiment.

At the start, he put aside some stocks of the virus

so he could have some virus that had not had a chance

to evolve in the Australian rabbits.

He also gathered some wild rabbits

and kept them in captivity,

where they would not be exposed to myxomatosis.

In this way, he had some unevolved rabbits

that could be used as a test

for evolutionary changes in the myxoma virus,

and unevolved virus that could be used

to test for changes in the rabbits.

Evolution in both rabbits and virus happened very fast.

When the virus was first introduced,

almost all strains killed over 99 percent

of the rabbits infected.

Over time, the lethality declined, though not to zero.

Why?

It‘s believed that strains that

kept their hosts alive longer

produced more secondary cases

than those that killed off their hosts too quickly.

But some virulence was necessary

to the perpetuation of the virus,

which was spread by direct contact

with lesions on the skin of a rabbit,

or by biting insects.

A strain that was too unaggressive

would be unable to reach high enough levels in the rabbit

and get to the surface for transmission

before being cleared by the immune system.

Thus it seems that an intermediate level of virulence

was optimal for the transmission success of this virus.

The host, too, evolved.

After all, rabbits reproduce rapidly,

so natural selection can work fast on them, too.

The most susceptible rabbits were killed off

before they could reproduce,

so they left few or no offspring.

Rabbits with more genetic resistance did better,

leaving more descendants who inherited

the genetic resistance from their parents.

Over time, the lethality of the unevolved virus

declined as the host evolved resistance.

Another example comes from

human immunodeficiency virus, or HIV.

As we saw in a previous session,

the virus transmits more efficiently

from an infected to a susceptible person

when the amount of virus in the blood,

and correspondingly in genital secretions, is high.

Studies have shown that the viral load

in an infected person is determined in part

by genetic properties of the HIV virus that infects them.

Different strains tend to produce higher or lower

viral loads in each of the people they infect.

If all else were equal,

selection would favor viral loads to be

as high as possible,

and viral load would evolve upward indefinitely

until some limit was reached

where it could not be higher.

But, in fact, all else is not equal.

Higher viral load is associated

with faster progression of the infected person

towards AIDS and death.

These data show the survival curves

of persons with different HIV viral loads.

Those with the highest viral loads

died several years earlier on average

than those with lower viral loads.

Thus, like myxoma, HIV faces a tradeoff.

Strains that are too aggressive

maintain high viral loads and are more transmissible,

but kill the host faster,

while those that are less aggressive

keep the host alive longer,

but have a lower chance of transmitting

each month, or in each sexual act.

Evolutionary theory predicts

that the average viral load under these conditions

will evolve toward a level that balances these,

producing the largest number of secondary cases over time.

Quantitatively, the predicted mean steady state

viral load, depending on some details of the assumptions,

is between 10,000 and 100,000.

This is consistent with what we observe

in modern HIV cases.

Growing quickly to outrun the immune system

is not the only trait that is selected for in pathogens.

Our immune systems respond to specific components

of each infectious agent called antigens.

Therefore, strains that can change or shed

the major antigens can gain an advantage,

as long as the change doesn't have too much of an impact

on their ability to infect the host.

This is particularly apparent when we use a vaccine

that selectively targets certain strains of a pathogen

but not others.

Mass administration of such vaccines

can create very strong selective pressures

in the population as a whole.

One such vaccine is a vaccine against

Streptococcus pneumoniae, or pneumococcus,

and is called the pneumococcal conjugate vaccine.

The first such vaccine licensed, PCV7,

included seven of the over 90 serotypes

of pneumococcus.

As this graph shows, declines in disease

in small kids in the United States,

from the serotypes included in the vaccine,

were partially offset by increases in disease

from other types, most notably 19A.

Since 2010, the U.S. has been using PCV13,

an updated vaccine that includes serotype 19A.

The population of pneumococci continues to evolve,

with the most recent studies showing a rise

of those serotypes not included in PCV13.

Fortunately, those remaining sereotypes

tend to have a low propensity to cause disease,

so although they are present

in children's respiratory tracts,

they are less of a public health concern

than the ones they replaced.

I've saved for last perhaps the best-known example

of how pathogens evolve in response to selection.

That is antimicrobial resistance,

which is caused largely by the use

of antimicrobial drugs for treatment of infections,

and also by their overuse and misuse,

for example, to treat viral infections

for which they are not effective.

This graph shows the relationship between

penicillin use in different European countries,

and the prevalence of penicillin resistance

in Streptococcus pneumoniae in those countries.

It is striking that France uses

about four times as much penicillin per capita

as the Netherlands just next door.

The more intense selection pressure in France in 2000

was reflected in much higher rates

of penicillin resistance.

In this segment, we have considered some of the ways

that pathogen populations change genetically

in response to selection pressure.

This is evolution in action,

a process we can observe,

because microbes reproduce so quickly,

going through many generations

in the periods in which we observe them.

Whether the selection comes from

the pressure to grow and transmit,

or to escape our immune responses,

or to escape antimicrobial treatment,

pathogens usually evolve quickly in response.

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