Pathogenicity, Virulence, And Infection Disease

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Microbe-Human Interactions

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Normal Flora: microorganisms usually found at given anatomical sites in a healthy body without causing infection or disease

- help by preventing more serious infections

from establishing

- do not penetrate sterile tissues or fluids

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Microbe-Human Interactions

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Infection occurs if NORMAL FLORA exists anywhere other than:

- skin

- eyes (conjuctiva)

- upper respiratory tract

- mouth (upperGI tract)

- lower digestive tract

- urogenital tracts (male and female)

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Microbe-Human Interactions

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Categories:

Resident flora: remains part of the normal flora throughout a person’s lifespan

Transient flora: can be found in the same locations as resident flora, but resides in the body for a brief period of time

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Microbe-Human Interactions

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Pathogens: an infections agent capable of causing disease

- able to penetrate the host defenses
- invade sterile tissues and multiply, resulting in infection

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Definitions

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Disease: any deviation from or disruption of the normal structure or function of any tissue, organ, or organ system

- characterized by signs and symptoms

Pathology: the study of the nature of disease, its causes, development and outcome

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Definitions

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Etiology: the study of the cause of disease

Pathogenesis: the cellular events, reactions and other pathologic mechanisms occurring in the
development of disease

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Definitions

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Prognosis:

- a forecast as to the probable outcome of a disease

- based on signs/symptoms

- based on severity of findings

- based on clinicians experience

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Signs and Symptoms

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Signs: any abnormality uncovered upon physical
examination that indicates the presence of
disease (objective)

Symptoms: the subjective evidence of infection and disease as perceived by the patient

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Syndromes and Sequelae

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Syndrome: the collection of signs and symptoms that, taken together, equal a disease

Sequela: a morbid complication that follows a disease

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Pathogenicity vs. Virulence

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Pathogenicity: the ability of a pathogen to produce infectious disease in another organism

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Pathogenicity vs. Virulence

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Virulence: the capacity of a pathogen to infect and harm host cells

- the extent of pathogenicity

Virulence Factor: a microbial structure or product promotes infection or harm to the host

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Developing an Infection

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- portal of entry

- adhesion

- invasion

- multiplication

- infection of target (tissue, organ, etc.)

- portal of exit

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Portals of Entry

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- conjunctiva

- respiratory tract

- GI tract

- skin

- pregnancy and birth

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Bacterial Virulence Factors

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- virulence factors allow for bacterial survival against host defenses through

- adhesion

- colonization

- invasion

- evasion of host defenses

- toxins and enzymes

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Bacterial Virulence Factors: Adhesion

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First step in establishing infection

Allows organism to avoid removal via:

- ciliary motion

- sneezing/coughing

- swallowing

- urine flow

- intestinal peristalsis

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Bacterial Virulence Factors: Adhesion

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Presence of a Capsule

- polysaccharide fibres aid in adherence

- prevent phagocytosis by host cell’s leukocytes

- in macrophages, capsule protects organism from digestion and allows it to grow (immune response)

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Bacterial Virulence Factors: Adhesion

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Presence of a Fimbriae

- also anti-phagocytic → slows ingestion

- allows organisms to attach to each other

- surface molecules called adhesins
- enhance ability of pathogen to attach to host (key in lock mechanism)

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Bacterial Virulence Factors: Adhesion

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Other Adhesion Mechanisms

- Dextrans in slime layer of oral streptococci helps organisms adhere to tooth surfaces

- M protein and lipoteichoic acid on surface of Streptococcus pyogenes binds receptors on respiratory mucosa

- Viral spikes allow virus particles to attach

to specific host cells

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Bacterial Virulence Factors: Colonization

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- human pathogens colonize tissues in contact with external environment

- establishment of pathogen at portal of entry

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Bacterial Virulence Factors: Invasion

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- ability to penetrate the epithelial surface of the host

Production of enzymes and toxins – invasins – which lyse cells or break down material between cells

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Bacterial Virulence Factors: Evasion of Host Defenses

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1. avoid contact with phagocytes

2. inhibit engulfment by phagocytes

3. survive inside the phagocytes

4. create products that damage/kill phagocytes

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Bacterial Virulence Factors: Toxins and Enzymes

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Production of Toxins

- organisms that produce toxins = toxigenic

- 2 types of toxins produced:

- exotoxins (gram positive)

- endotoxins (gram negative)

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Bacterial Virulence Factors: Toxins and Enzymes

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Site of Toxic Action

- neurotoxin = nervous system

- cytotoxin = cell

- enterotoxin = GI tract

- hepatotoxin = liver

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Bacterial Virulence Factors: Toxins and Enzymes

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Exotoxins

- secreted by bacterial cells during exponential growth phase

- product of genes carried on bacterial plasmids or bacteriophages

- highly specific targets

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Bacterial Virulence Factors: Toxins and Enzymes

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Exotoxins

- highly immunogenic

- can be converted to toxoids for

immunization

- stimulate production of antitoxins

(antibodies)

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Bacterial Virulence Factors: Toxins and Enzymes

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Exotoxins

- leukocidins and leukostatin affect neutrophils and macrophages and interfere with phagocytosis (neutralize pathogens)

- leukocidins: kill WBC

- leukostatin: inhibit WBC functions

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Bacterial Virulence Factors: Toxins and Enzymes

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Endotoxins

- bacterial intracellular toxin

- made of lipopolysaccharide (gram negative)

- endotoxins released when bacterial cell lyses

- only when cell bursts

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Bacterial Virulence Factors: Toxins and Enzymes

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Endotoxins

- weakly immunogenic; not strong enough for vac
- not converted to toxoids

- less potent than exotoxins; effects are more generalized (more systematic)

- toxins can act on remote sites

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Bacterial Virulence Factors: Toxins and Enzymes

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Hemolysins
- both enzyme and toxin

- can increase virulence of some organisms

- release iron from RBCs for microbial metabolism

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Bacterial Virulence Factors: Toxins and Enzymes

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Hyaluronidase
- “spreading factor”

- allows pathogens to invade surrounding tissues

- destroys hyaluronic acid between cells on connective tissue

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Bacterial Virulence Factors: Toxins and Enzymes

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Coagulase
- “cementing factor”

- converts fibrinogen into fibrin (= fibrin clots)

- produces protective barrier aroundorganisms

- exposed to antibiotics and build response

to make them useless

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Bacterial Virulence Factors: Toxins and Enzymes

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Kinase

- converts plasminogen to plasmin

- streptokinase, staphylokinase

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Bacterial Virulence Factors: Toxins and Enzymes

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Mucinase

- digests protective coating on mucous

membranes

- help organisms invade

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Bacterial Virulence Factors: Toxins and Enzymes

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Keratinase

- digests the principle component of skin and hair (useful if organism wants to infect the skin)

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Bacterial Virulence Factors: Toxins and Enzymes

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Collagenase

- digests the principal fibre of connective tissue

- breaks down collagen

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Infection vs. Infectious Disease

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Infection: the entry, establishment and

multiplication of pathogenic organisms within a host

Infectious disease: the state of damage or toxicity in the body caused by an infectious agent

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Stages of Infection

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Contamination
- presence of microbes in or on the body

- NB: not all contacts result in colonization and infection!!

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Infectious Disease Classifications

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Acute
- sudden onset, short duration

- signs and symptoms severe

- ex: influenza

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Infectious Disease Classifications

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Chronic
- gradual onset, longer persistence

- signs and symptoms generally milder

- may experience acute episodes

- ex: asthema, COPD

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Infectious Disease Classifications

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Sub-acute
- intermediate status

- lies between acute and chronic diseases

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Infectious Disease Classifications

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Clinical
- symptomatic, obvious infection

- clinical diagnosis made based on S & S

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Infectious Disease Classifications

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Subclinical
- asymptomatic

- diagnosis made through testing

- ex: blood tests, cultures, diagnostic imaging

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Patterns of Infection

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Local

- infection confined to one area of body

- microbe enters and infects a specific
tissue/target

- ex: absess after dental surgery

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Patterns of Infection

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Systemic
- disease spreads throughout the body via the
circulatory system; often a secondary infection

- septicemia (umbrella term - use when don't know what is causing infection)

- emia = circulatory system

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Patterns of Infection

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Focal
- disease starts in one part of the body then
spreads to another specific site via blood or
lymph (not a generalized spread)

- not widespread

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Patterns of Infection

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Superinfection
- an infection occurring during antimicrobial
therapy that is caused by an overgrowth of
drug-resistant microorganisms

- involves washing out of normal flora

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Patterns of Infection

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Primary

- only gain word primary when there is subsequent infection

- an initial infection, followed by complcations due to another microbe

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Patterns of Infection

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Secondary
- follows a primary infection

- caused by a different microbe

- opportunistic normal flora (normal flora that causes infection)

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Persistent Infections

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Persistent
- organism stays in the body for an extended
period of time (ex: chicken pox)

- often used to describe viral infections

- can be described as latent, chronic or slow

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Persistent Infections

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Latent
- period of inactivity following a disease episode
where no S & S present

- pathogen not multiplying

- recurrence of disease later

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Persistent Infections

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Chronic

- gradual onset, mild course, long duration

- ex: HIV infection (until transitions to AIDS)

Slow

- long uncubation period before disease episode(before S & S are visible)

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Opportunistic Infections

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True Pathogens
- capable of causing disease in healthy persons
with normal immune defenses

- ex: influenza virus, malarial protozoan

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Opportunistic Infections

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Opportunistic Pathogens
- organisms that do not cause disease in an
immune-competent individual

- ex: Pseudomonas sp & Candida albicans

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Mixed Infections

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Polymicrobial
- caused by more than one organism at the
site of infection

- on their own, may not cause infection but together can cause infection

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Factors that Weaken Host Defenses

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- extremes of age

- immune deficiencies

- surgery and organ transplantation

- organic disease

- cancer, liver dysfunction, diabetes

- chemotherapy/immunosuppressive drugs

- physical and mental stress- other infections

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Process of Infection and Disease

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4 Stages of Clinical Infections

- incubation period

- prodromal stage (may or may not see)

- period of invasion

- convalescent period

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Clinical Infections: Incubation Period

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- time from initial contact with the infection agent to the appearance of first symptoms

- not enough to have visible damage, just lots of multiplication

- duration - several hours to several years

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Clinical Infections: Prodromal Stage

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- vague feelings of discomfort

- signs and symptoms are nonspecific

- not all diseases demonstrate this stage

- some infections don’t progress past the
prodromal stage

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Clinical Infections: Period of Invasion/Illness

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- multiplies at high levels, becomes well established; more specific S & S

- acute phase: patient is most ill, specific S & S, most likely to die in acute phase

- decline phase: patient starting to get better, S & S becoming more mild

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Clinical Infections: Convalescent Period

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- a person begins to respond to the infection (immune response), symptoms decline

- varies by patient (initially healthier patient will recover faster than unhealthy patient)

- fatigue persists, patient vulnerable to a secondary infection

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Portals of Exit

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- coughing, sneezing

- skin cells (open lesions)

- insect bite

- urine

- feces

- removal of blood

- other secretions/excretions