BIOL 2421 Microbiology
Lecture Notes: Principles of Disease Infection & Epidemiology
Dr. Weis
Definitions:
Infection: invasion or colonization of the body by a pathogenic organism
Disease: any change in the body’s state of homeostasis
Pathogenesis: method or manner in which a disease develops
Symbiosis: living together in close association between two (+) different organisms
Can be ectosymbiants: one organism remains outside another
Or endosymbiants: one organism is present within another
Mutualism: type of symbiosis which is beneficial to both
Commensalism: type of symbiosis, which benefits one, but does not harm the other.
Parasitic: type of symbiosis where one benefits at the expense of another.
Ectoparasite: lives on the surface of its host
Endoparasite: lives internally
Final (Definitive) Host: where parasite reaches maturity and reproduces
Intermediate host: temporary residence for parasite, necessary part of life cycle
Transfer host: not necessary for parasite life cycle, used as vehicle to reach final host.
Opportunistic: commensalistic organism now can cause harm to the other (host).
Normal Microbiota:
Also known as normal flora, a population of organisms that colonizes the body systems and do not cause disease under normal circumstances. Derived through various methods of contact. Once established, the normal microbiota prevent overgrowth of harmful microorganisms by competing for nutritional sources, a phenomenon called microbial antagonism. Resident flora remain on the host for longer periods. Transients only for a few hours as they are unable to multiply.
Normal Flora:
A. Digestive System
Mouth and Throat
Streptococci
Diptheroids
Lactobacillus
Actinomyces
Anaerobes
Staphylococcus epidermidis
Spirochetes
Corynebacterium
Stomach
Staphylococcus
Streptococcus
Lactobacillus
Peptostreptococcus
Small Intestine
Lactobacilli
Gram negative anaerobes
Enterococci
Enterobacteriaceae
Large Intestine
Lactobacilli
Enterococci
Enterobacteriaceae
Proteus
Shigella
Bacteroides
E. coli
Klebsiella
Clostridia
B. Upper respiratory
Nose, nasopharynx, and sinuses
Staphylococcus (epidermidis, aureus)
Streptococcus ( pyogenes, pneumoniae)
Diptheriods
Haemophilus
Neisseria
C. Skin
Staphylococcus (epidermidis, aureus)
Diptheroids (Corynebacterium, Propionbacterium)
Candidia [fungus]
Eye: Staph, Strep, Haemophilus
Ear: Staph, Diptheriods, Pseudomonas
D. Urogenital Tract
Staphylococcus
Streptococcus
Lactobacillus
Pseudomonas
Klebsiella
Proteus
Bacteriodes
Clostridium
Etiology of Infectious Disease
Etiology is the cause of the disease. Koch’s postulates are used as a starting point.
Pathogenicity is the progression of the disease based on several factors.
Symptoms: subjective changes in the body’s structure and function.
Signs: objective changes (observed and measures) in the body’s structure and function
Syndrome: a specific group of symptoms and
signs that accompany a particular disease
Pathogenicity:
Invasiveness: ability of an organism to spread from one tissue to adjacent tissues
Infectivity: ability of an organism to establish a focal point of infection
Pathogenic potential: degree that the pathogen causes morbid symptoms
Virulence: degree or intensity of the pathogenicity. Measured one of two ways
LD 50 : Lethal Dose that will kill 50% of the infected hosts / time
ID 50: Infectious dose that will infect 50% of the hosts/ time
Determinants of Infectious Disease: To introduce an infectious disease, a pathogen must
1) Initially be transported to the host via contact, vehicles, or vectors
2) Adhere to, colonize, or invade the host via adhesions [portal of entry]
Portal of Entry => mucous membrane, skin, parental
Numbers of Invading Microbes – ID50 [infectious dose]
Adherence via surface molecules (usually glycoproteins or lipoproteins) called adhesions or ligands that bind to receptors on host tissues. Adhesins may be located on the glycocalyx, fimbria, flagella, pili and can also form a biofilm. Host tissue receptors are usually sugars, such as mannose.
3) Multiply and complete its life cycle on or in the host
invade epithelial cells
via host cytoskeleton (primarily actin)
microbe surface proteins called invasions to rearrange the actin
filaments at one end of the bacteria to help propel them
through the cell.
disseminate through body
Microbes can also make glycoproteins called cadherin, which helps bridge membrane junctions and allow the bacteria to move from cell to cell.
produce virulence factors: toxins, enzymes
Toxins: a metabolite that damages the host
Exotoxins: G(+) bacteria, released to environment
e.g. Staph (aureus), Clostridia, Salmonella, Shigella
Plasmid or prophage mediated genes
Very lethal, even in small amounts
Named for system, bacteria, disease
system affects: neurotoxin, Enterotoxins, cytotoxins,
cardiotoxins, hepatoxins, leukotoxins
bacteria: botulinum toxin, vibrio toxin
disease: diphtheria toxin, tetanus toxin
Toxins cause antitoxin production by immune system
Can be inactivated by chemicals to form toxoids
Three principle types of Exotoxins:
A-B; Membrane Disrupting, & Superantigens
A-B Toxins (also called type III toxins)
Usually contain two subunits (A-B)
B for binding to host receptor cells, nontoxic
A for toxic activity within the host.
~ inhibit protein synthesis
~ damage plasma membrane
~ disrupt membrane transport
~ overstimulating the immune system
~ affecting synapse function
~ stimulate cAMP over production
e.g. botulinum toxin, vibrio toxin, tetanus toxin
Membrane Disrupting Toxins (also called type II toxins)
Cause lysis of host plasma membranes
~ form protein channels [Staph, Strep]
* hemolysins
* leukocidins
~ disrupt phospholipid portion of membrane
[Clostridia perfringes]
Superantigens (also called type I toxins)
Bacterial proteins that provoke a very intense immune
Response by stimulating the proliferation of T-cells, which then release cytokines
Overabundance of cytokines cause 2nd effects [V/D/F]
e.g. Staph toxins that cause food poisoning, toxic shock
Endotoxins: G(-) bacteria, part of outer cell membrane: LPS
(Lipopolysaccharide) called Lipid A
Released only upon disintegration of bacteria or
During bacterial multiplication
Work by activating intrinsic clotting pathway and
The complement pathways
Stimulate macrophages to release cytokines, if in high levels can cause toxic signs [V/D/Fever/Shock]
Il-1 and Tumor Necrosis Factor are secreted
Enzymes
Used to help avoid or penetrate host’s defenses
Coagulase : forms clot around bacteria
Streptokinase: dissolves clots for tissue invasion
Hyaluronidase: destroys part of basement membrane
Leukoccidins: destroy phagocytes via their own lysosomes
Hemolysins: destroy RBCs
Streptolysin – O à Beta hemolysis
Streptolysin – S à Alpha hemolysis
Collagenase: breaks down collagen (CT & Muscles)
IgA proteases: destroy IgA antibodies
4) Initially evade host’s defense mechanisms
* capsules impair phagocytosis, antibodies can be produced
* M protein of the cell wall that aids in heat and acid resistance
* waxes in cell wall of Mycobacteria help resist phagocytosis
* exoenzymes [see above]
* Antigenic
variation: alter surface antigen (genes for coding)
5) Possess ability to damage the host via mechanical, chemical, or molecular
* using host’s nutrients (primarily iron)
* direct damage in the vicinity of the invasion (cells ruptured)
* toxin production and transport via blood, lymph [see above]
* induce
hypersensitivity reactions
6) Maintain a portal of exit: via
urine, feces, respiratory secretions, blood, vector uptake, open wounds
Most common are through respiratory and gastrointestinal tract.
Viral Mechanisms:
Evading Host: attach and enter host cell
Cytopathic effects vary:
* stop cellular synthesis of macromolecules
* cause host cell to release lysosomal enzymes, cytocidal
* form inclusion bodies [viral parts- NA, proteins]
* cause adjacent cells to fuse and form a multinucleate syncytium
* change cell function with no visible change
* induce production of interferons to help protect
* antigenic changes on surface of infected cells
* chromosomal damage, breakage
* activate oncogenes of host
I. Classification of a Disease
a) Communicable: spreads from one host to the other, direct or indirectly
b) Contagious: easily spread
c) Noncommunicable:
not spread from one host to the other
II. Occurrence of a Disease
Based on incidence (number of people with disease) and prevalence (number of people with disease from the start, indicates how serious and how long a disease affects a population).
Various classifications can be made based on incidence and prevalence:
a) Sporadic Disease: occurs occasionally in limited populations
b) Endemic Disease: constantly present in a certain population
c) Epidemic Disease: many people with disease in a short period of time
d) Pandemic Disease:
world wide spread of disease
III. Severity or Duration of a Disease
a) Acute: develops rapidly, short duration of time
b) Chronic: develops more slowly, continual or recurrent for long periods
c) Subacute: between acute and chronic
d) Latent: inactive
for some then active to cause signs and symptoms of disease.
IV. Host Involvement
a) Local infection: limited to a small area of the body
b) Systemic infection: generalized infection, spread throughout the body
c) Focal infection: infections that spread, but are then confined to one area
When an organism spreads throughout the body via blood, can be referred to as
* bacteremia; if bacteria multiply in the blood = sepsis
* viremia
* parasitemia
* fungemia
* toxemia ( if the organism product is spreading, such as a toxin)
Host resistance also has an effect on the extent of the infection
~ Primary infection: acute infection that causes the primary illness
~ Secondary infection: caused by opportunistic pathogens once immune
system defenses have been weakened
~ Subclinical infection: unapparent, does not cause any noticeable illness
Patterns of Disease
I. Predisposing Factors
Makes the body more susceptible to disease and may alter the outcome
* Gender
* Genetics
* Environment: climate, weather, region of country/world
* Nutrition
* Age
* Occupation
* Previous illness
* Habits, Lifestyle
* Stress
* Sleep, Fatigue
* Previous
treatments (chemotherapeutic agents)
II. Development of Disease
Once a microorganism overcomes the host defenses, disease progression begins in a certain sequence. Disease can still be spread to others during many of these stages.
a. Incubation Period: time interval between initial infection and signs
time depends on microorganism, virulence factors, number of
infecting organism, host defenses
b. Prodromal Period: generalized, mild symptoms of disease
c. Acme Period: period of illness at the acute stage of disease shows specific symptoms for that disease. Immune response necessaryto overcome infection.
d. Decline Period: signs and symptoms subside. Still vulnerable to secondary infections.
e. Convalescence
Period: recovery from disease, return to normal
III. Spread of Infection
A. Reservoirs of Infection: provides housing, nutrition, and opportunity to be transmitted. Can be living or nonliving.
Carriers can be casual / acute / transient if harbored for a short time or chronic if they harbor the pathogen for longer periods.
* Human Reservoirs: carriers or latent infection
Carriers have inapparent infections for which no sign or symptoms exist.
Latent carry disease symptom free @ incubation or convalescence period of infection.
* Animal Reservoirs: wild and domestic animals can carry microorganisms that are infectious to humans = Zoonoses
* Nonliving Reservoirs: soil and water
can be associated with animal (human also) feces as source
of contamination
IV. Transmission of Disease
Disease causing agents can be spread from reservoir to host one of three ways
Contact, vehicles, vectors
A. Contact: via direct, indirect, or droplet
Direct contact = person to person physical contact
Indirect contact = spread by nonliving object called a fomite
Droplet transmission = mucous droplets that travel a short distance
B. Vehicle Transmission via food, water, air, other media
Waterborne: water contamination or untreated sewage
Food borne: incompletely cooked, poorly refrigerated or prepared
Airborne: droplet nuclei that travel longer distances
Other media: blood, body fluids, IV fluids, drugs
C. Vector Transmission: animals that carry pathogens from one host to the other. Arthropods are a predominate vector.
Two types of vector transmission: Mechanical and Biological
Mechanical: passive transfer of pathogens on a body part such as Insect’s feet.
Biological:
pathogen’s may reproduce or have part of it’s life cycle in a vector, which
then can be transmitted via bite, feces, or regurgitation
into a wound created by the vector.
V. Nosocomial Infections
Infection acquired as the result of a hospital stay due to
* Microorganisms in the hospital
opportunistic infections
antimicrobial resistance
secondary infections with resistant strains
* Compromised Host
Mechanical barrier broken
burns, surgery, trauma, catheters, injection sites
invasive procedures, ventilators
Suppressed immune system
T and B cell counts down due to:
Drugs, radiation, steroid therapy, DM, burns, stress,
Kidney disease, leukemia, malnutrition
* Chain of Transmission
Hospital personnel in direct contact with patient
Fomite spread (catheters, needles, respiratory aids)
Control of Nosocomial Infections
* aseptic techniques
* proper disposal of contaminated materials
* Hand washing
* isolation rooms
* disinfection of room
Epidemiology: the science that studies disease occurrence and transmission (where, when, how). Procedures include: collecting data, analyzing, testing, and reporting. Major governmental agency = CDC [Center for Disease Control]. Give morbidity (incidence of disease) and mortality (number of deaths caused by a disease) reports on a weekly basis.
Herd Immunity: resistance of the population to infection and pathogen spread due to the immunity of a large percentage of the population.
Pathogens can change that immune individuals become susceptible again.
* Antigenic Shift: a major genetically determined change in the antigenic character
of a pathogen so that it is no longer recognized by the host’s immune system.
Due to mutation, hybridization (between animal and human),
Intermingling between serovars.
* Antigenic Drift: smaller antigenic changes that enable the pathogen to avoid the
host’s immune mechanisms.
Immergence of New Diseases:
~ Rapid transportation
~ Large populations and overcrowding
~ International Commerce (movement of animals and plant materials)
~ Disruption of ecosystems (natural or man made)
Control Steps: Quarantine/ Isolate, Destroy, Treat contamination, Therapy for Individuals