Concepts of virulence and infectivity Flashcards
ILOs
- Understand the difference between disease and infection
- Understand what constitutes an infection
- Be able to discuss the concept of virulence and virulence factors
- Have an appreciation of polymicrobial diseases
What do we mean by disease?
The term “disease” refers to conditions that impair
normal tissue function
Cystic fibrosis, atherosclerosis, and measles are all
considered diseases.
Cystic fibrosis (CF) is due to a specific genotype that
results in impaired transport of chloride ions across
cell membranes – genetic or metabolic disease
Atherosclerosis, may be considered a disease of
aging, because it typically becomes a problem later
in life after plaques of cholesterol have built up and
partially blocked arteries
Measles is an infectious disease because it occurs
when an individual contracts an outside agent
Disease and infection are not synonymous
An infection results when a pathogen invades and
begins growing within a host. Disease results only if and
when, as a consequence of the invasion and growth of a
pathogen, tissue function is impaired
Pathogens
What is a pathogen?
A true pathogen is an infectious agent that causes disease in virtually any susceptible host. Opportunistic pathogens are potentially infectious agents that rarely cause disease in individuals with healthy immune systems
Pathogenicity
Pathogenicity is defined by the capacity of a microbe to
cause damage in a (susceptible) host.
Pathogenicity is a discontinuous variable, that is, there is
or is not pathogenicity.
Pathogenicity is a microbial variable that can only be
expressed in a susceptible host, underscoring that it is
dependent on host variables.
There is no difference between an opportunistic pathogen and any other kind of pathogen. Both are microbes and both have the potential to cause damage/disease in a host
Pathogenicity contd.
One view is that there are only microbes and hosts and the outcomes of their interactions, which include commensalism, colonisation, latency and disease
Pathogenicity is defined by the capacity of a microbe to
cause damage in a (susceptible) host.
It is the damage that separates pathogens from non pathogens:
Encounter - Entry - Multiplication - Spread - Damage
Damage – What is it?
Tissue Pathology
Loss of organ function
Growth in normally sterile sites
Virulence
Virulence is one of a number of possible outcomes of
host-microbe interaction.
Virulence is a continuous variable, that is, it is defined
by the amount of damage or disease that is manifest
How is virulence measured?
LD50 or ID50 - percent infected against dose
Virulence question 1
Two bacterial pathogens were used to infect mice separately at the indicated dosages and the resulting morbidity and mortality was scored (see tables below). What are the approximate ID50 and LD50 values for both pathogens?
Pathogen A
Dose (CFU) 10-1 10-2 10-3 10-4 10-5
% Morbidity 10 100 100 100 100
% Mortality 0 0 10 40 100
Pathogen B
Dose (CFU) 10-1 10-2 10-3 10-4 10-5
% Morbidity 0 1 15 60 100
% Mortality 0 0 10 40 100
Virulence question 2
Provide a hypothesis explaining why the patterns of
morbidity and mortality differ between these two pathogens
Virulence question 3
What could influence the ID50 and LD50 values of a pathogen?
- route of infection - e.g. cutaneous anthrax vs. inhalation anthrax (latter is systemic - ‘cardinal’s cap’)
- host immune status
- genetic makeup of host
What is a virulence factor?
The word “virulence” is traditionally used to describe a
microbial characteristic
The concept that virulence is an intrinsic microbial
property that distinguishes pathogenic from nonpathogenic microbes is difficult to apply in the face of increasing evidence that host factors are critical determinants of the outcome of host-microbe interactions
Nevertheless, there is a school of thought that provides a
testable hypothesis for virulence factors based on Koch’s
postulates
Koch’s molecular postulates
- “The gene under investigation should be associated with pathogenic members of a genus or pathogenic strains of a species.” Additionally, the gene in question should be found in all pathogenic strains of the genus or species but be absent from non-pathogenic strains
- “The gene, which causes virulence, must be expressed during infection.“
- “Specific inactivation of the gene(s) associated with the suspected virulence trait should lead to a measurable loss in pathogenicity or virulence.” Virulence of the microorganism with the inactivated gene must be less than that of the unaltered microorganism in an appropriate animal model.
4.”Reversion or allelic replacement of the mutated gene should lead to restoration of pathogenicity.”
In other words, reintroduction of the gene into the microbe should restore virulence in the animal model
Classic virulence factors
Toxins - e.g. Anthrax. Toxins encoded on a plasmid. Removal of plasmid results in attenuation
Limitations of the virulence factor concept!
The view that pathogenicity is conferred by virulence factors is difficult to apply to many microbes whose pathogenicity is limited mostly to immunocompromised hosts, such as C. albicans and Aspergillus fumigatus
Biofilms and polymicrobial infections
Planktonic bacteria are vulnerable to several
anti microbial phenomena
In a biofilm, the physical nature of this entity protects the
bacteria
