Define the 5 steps involved in a successful microbial infection.
Identify the ways in which infectious diseases are transmitted.
Define the role of the compromised host in the spread of infection.
Define the basic principles of epidemiology in the classification, transmission, and prevention of infectious diseases.
Requirements for a Successful Infection
Entry: Getting in.
Establishment: Staying in.
Defeat host defenses.
Damage the host.
Exit the host to be transmitted to another host.
Portals of Entry
Any point at which a pathogen enters.
Examples:
Eye
Ear
Nose
Mouth
Broken skin
Mammary glands
Placenta
Vagina
Urethra
Anus
Main routes:
Mucous membranes
Skin
Parenteral route
Mucous Membranes
Are in direct contact with the external environment.
Pathogens can cross and gain access to the interior of the body.
Found in:
Respiratory tract
Gastrointestinal tract
Genitourinary tract
Respiratory Tract
Number one portal of entry.
Includes:
Nose
Mouth
Bronchi
Epiglottis
Trachea
Potential pathogens:
Staphylococcus
Streptococcus
Haemophilus
Veillonella
Candida
Most Common Respiratory Pathogens
Adenoviruses
Streptococcus pneumoniae
Staphylococcus aureus
Mycobacterium tuberculosis
Bordetella pertussis
Influenza
Rubella
Varicella-zoster
Gastrointestinal Tract
Second most common portal of entry.
Includes:
Mouth
Epiglottis
Esophagus
Liver
Gall bladder
Pancreas
Stomach
Small intestine
Colon
Rectum
Most Common Gastrointestinal Pathogens
Escherichia coli
Helicobacter pylori
Clostridium botulinum
Candida
Enterococcus faecalis
Poliovirus
Shigella spp
Rotavirus
Salmonella
Norovirus
Genitourinary Tract
Includes sexually transmitted infections.
Urinary tract infections more common in women than men due to:
Shorter urethra
Proximity to anus
Most Common Genitourinary Pathogens
Mycobacterium smegmatis
Chlamydia trachomatis
Neisseria gonorrheae
Trichomonas vaginalis
Herpesviruses
Human Immunodeficiency Virus
Escherichia coli
Candida
Skin
Largest organ of the body.
Many microorganisms reside on the skin (normal flora).
Impermeable barrier unless broken.
Parenteral Route
Refers to breaks in skin that allow passage of microbes.
Normal flora causing infection: Opportunistic pathogens.
Depends on cuts, abrasions, injections, wounds, surgical incisions, or insect bites.
Establishment
After entering the body, pathogens must find a way of staying in.
Pathogens use virulence structures such as capsules or fimbriae to attach to the surface of cells or tissues.
Pathogens may also use adhesins to attach to tissue.
Plaque on teeth is an example of an adhesion beginning a process resulting in an accumulation of bacteria. This is called a biofilm.
Life activities of the bacteria plus their presence results in the formation of plaque.
Spirochetes corkscrew into tissues, which is a very lengthy process.
Increasing the Numbers
Some pathogens can double their numbers every 20 minutes.
An organism that doubles every 20 minutes = 2^{72} (4.72 X 10^{21}) in just 24 hours.
Bacteria reproduce by binary fission.
One cell splits in 2; 2 become 4; 4 becomes 8; 8 becomes 16; 16 becomes 32; 32 becomes 64…
Defeating the Host
Passive defense: using intrinsic features of the pathogen.
Active defense: attacking the host defenses.
Pathogens must avoid, evade, or compromise these defenses in order to survive.
Passive Defense
The inherent ability to protect themselves via intrinsic factors (e.g., cell walls, lipopolysaccharide membranes) or extrinsic factors produced from existing resources at the expense of the host (e.g., capsules, M protein).
Bacterial Cell Walls
Peptidoglycans
Cell Walls Gram+
Very thick
M proteins:
Streptococcus spp.
Increases adhesion to host tissue
Inhibits phagocytosis
Cell Walls Gram-
Very thin
Compensate by having an outer lipopolysaccharide membrane = endotoxin
Endotoxin: Lipid A which elicits a very powerful immune response
Cell Walls - Mycolic Acid
Acid-Fast Organisms
Mycobacterium spp.
tuberculosis
leprae
Inhibits phagocytosis
Inhibits antibiotics
Capsules
Protect against phagocytosis
Active Defense
Produced by microbes solely for "attack," e.g., toxins and enzymes.
Hiding from Host Defenses
Pathogens hide inside host cells as a way to defeat the host.
Protection from host immune response.
Viruses are obligate intracellular parasites.
Bacteria use cell microtubules and microfilaments as transportation system.
Damaging the Host
Two types of damage to the host:
That which occurs because pathogens are present and active (e.g., pus).
That which occurs because of host defense mechanisms (e.g., diarrhea, vomiting, sneezing).
Pathogen Damage to the Host
Direct damage:
Is obvious
Includes destruction of host cells and tissues
Controlled by host immune response
Indirect damage:
Involves systemic infection as a result of toxin production by the pathogen
Active Defense
Involve the production of extracellular enzymes.
Increase protection against host defenses
Enable the spread of infection by attacking and killing host defensive cells
Bacterial Enzymes
Leukocidins: destroy WBCs
Hemolysins: attack both RBCs and WBCs
Coagulase: formation of fibrin clots
Kinase: breaks down fibrin and destroys clots
Hyaluronidase: breaks down connective tissue
Collagenase: breaks down collagen
Coagulase and Kinase
Coagulase causes formation of a clot.
Kinase causes breakdown of a clot.
Hyaluronidase
Hyaluronidase allows pathogens to invade deeper tissues.
Bacterial Toxins
There are 2 types
Exotoxins
Endotoxins
Very poisonous
Soluble in aqueous solutions
Easily diffusible into blood and lymph, causing distal pathology
Bacterial Toxins
Can produce fatal outcomes in patients.
Common signs and symptoms of bacterial toxicity:
Fever
Shock
Diarrhea
Cardiac and neurological trauma
Destruction of blood vessels
Bacterial Exotoxins
Produced by and exported from certain pathogens and then enter host cells.
Some of the most lethal substances known.
Usually an enzymatic protein soluble in blood and lymph.
Rapidly diffuse into tissues where they inhibit metabolic function.
Genes coding for toxin production: PLASMIDS
Bacterial Exotoxins
There are 3 types of exotoxins:
Cytotoxins: kill cells
Neurotoxins: interfere with neurological signaling
Enterotoxins: affect the lining of the digestive tract
Cytotoxins
Bacillus anthracis
Gram+ spore-forming bacillus
Increases vascular permeability in host tissues
Corynebacterium diphtheriae
Gram+ bacillus
Inhibits protein synthesis
A single molecule can kill a host cell
Neurotoxins
Etiologic agents:
Clostridium tetani
Clostridium botulinum
Produce exotoxins with affinity for CNS tissue.
Antibiotic therapy ineffective once exotoxin has been produced.
Neurotoxins - Clostridium tetani
Gram+ spore-forming bacillus
Produces toxin “tetanospasm”
Prevents muscle relaxation
Uncontrollable convulsive muscle contractions
“Lockjaw”
Opisthotonus
Tetanus
Tetanus spores require low oxygen levels
Area of necrosis surrounding injury
Spores germinate
Bacteria do not cause damage to the tissue but produce toxin
Toxin enters presynaptic terminals of lower motor neurons
Travels to CNS
Outcomes of Tetanus
Factors affecting mortality:
Location of lesion
Incubation period
Age
Highest in infants and elderly
Death results from exhaustion and respiratory failure
Neurotoxins - Clostridium botulinum
Gram+ spore-forming bacillus
Inhibits release of acetylcholine
Flaccid (limp) paralysis of skeletal muscle
"Botox"
Pathogenesis of Botulism
Begins with cranial nerve palsy
Develops into a descending symmetrical motor paralysis
May involve diaphragm
No fever or inflammation
No obvious sign of infection
Progression of Botulism
Symmetrical paralysis
Most serious complication: complete respiratory paralysis
Limp or flaccid paralysis
Mortality rates: 10-20%
Nervous system dysfunction
Ocular (blurred vision, REM)
Laryngeal
Diaphragm
Trunk
Extremities
Categories of Botulism
Food poisoning
Infant botulism
Wound contamination
Foodborne Botulism
Classified as an INTOXICATION
Starts 12-36 post-ingestion of the toxin
Nausea, dry mouth, and occ. diarrhea
Toxin is absorbed directly through the intestinal tract
Reaches a neuromuscular junction via the bloodstream
Infected host is a very important part of the disease process
Host’s ability to mount a defense is IMMUNOCOMPETENCE
Damaged host defenses = disease potential
Considered as vulnerable or immunocompromised people:
HIV-AIDS
Genetic immunodeficiency diseases
Chemotherapy
Broad-spectrum antibiotics
Premature and neonates
Health care workers
Elderly
Koch’s Postulates
Robert Koch studied disease transmission and found the following conditions must be met in order to “communicate” disease
Same pathogen must be present in every case of the disease
Pathogen must be isolated from the sick host and purified
Pure pathogen must cause the same disease when given to infected hosts
Pathogen must be re-isolated from newly infected hosts
Development of Disease
Incubation period: No signs or symptoms
Prodromal period: Mild symptoms
Period of illness: Major signs and symptoms (immune response is strongest)
Period of decline: Signs and symptoms wane but highest chance of secondary infection
Period of convalescence: Recovery
Epidemiology
Study of the factors and mechanisms involved in the frequency and spread of diseases or other health-related problems
Used to study disease and also a way to design methods for control and prevention
Prevalence
Definition: Total number of people infected within a population at any given time
Used to measure strength and length of a particular disease
“Streaming video”
Incidence
Definition: The number of new cases contracted within a set population in a specific period
Provides a reliable indication of the spread of a disease
“Snapshot”
Rates
MORBIDITY
Number of individuals affected by the disease during a set period divided by the total population
MORTALITY
Number of deaths due to a specific disease during a specific period divided by the total population
Disease Occurrence
Endemic
Epidemic
Pandemic
Endemic Disease
Diseases that are found constantly within a population
Epidemic Disease
Incidence of disease suddenly higher than expected in a specific region
Common-source
Propagated
Epidemic Disease
COMMON SOURCE EPIDEMIC
Arises from contact with contaminated substances
Fecal contamination of water
Improperly prepared or stored food
Affect large numbers of people but once source is identified quickly subside
PROPAGATED EPIDEMIC
Amplification of the number of infected individuals as person-to-person contact occurs
Stay in the population for long periods
More difficult to control
“Patient Zero”
Pandemic
Diseases that occur in epidemic proportions throughout the world
Types of Epidemiological Studies
DESCRIPTIVE
Concerned with the physical aspects of patients and the spread of disease
Traces the outbreak and identifies the first case
ANALYTICAL
Focus is on correlation “cause and effect hypothesis”
Always uses a control group
Observational Study (Descriptive)
The investigator observes the occurrence of the condition/disease in population groups that have assigned themselves to a certain exposure.
Often most practical and feasible to conduct.
Carried out in more natural settings – representative of the target population.
Often, there is little control over the study situation – results are susceptible to distorting influences.
Cohort Study (Analytical)
Are a type of medical research used to investigate the causes of disease, establishing links between risk factors and health outcomes.
In a prospective cohort study, researchers first raise a research question, forming a hypothesis about the potential causes of a disease. The researchers then observe a group of people, the cohort, over a period of time (often several years), collecting data that may be relevant to the disease. This allows the researchers to detect any changes in health in relation to the potential risk factors they have identified.
Disease Reporting
Health departments of local and state governments require reports of certain diseases
Some diseases are referred to as “nationally notifiable” meaning that they must be reported to the Centers for Disease Control and Prevention
Nationally Notifiable Diseases
Anthrax
Cholera
Diphtheria
Dysentery (amoebic or bacillary)
Encephalitis, acute
Food poisoning
Haemorrhagic fever (viral)
Hepatitis, viral
Leprosy
Leptospirosis
Malaria
Measles
Meningitis
Meningococcal septicaemia (without meningitis)
Mumps
Ophthalmia neonatorum
Paratyphoid fever
Plague
Poliomyelitis, acute
Rabies
Relapsing fever
Rubella
Scarlet fever
Smallpox
Tetanus
Tuberculosis
Typhoid fever
Typhus
Whooping cough
Yellow fever
Disease Reporting Pathway
Healthcare Providers, Others, Institutions -> County/Local Health Departments -> State Health Department -> CDC -> Labs
Nosocomial Infections
Acquired in a hospital or medical facility within 48 hours of visit