Principles of Disease and Epidemiology 14 Principles of Disease and Epidemiology

State of balance of a complex system Homeostasis State of balance of a complex system Maintenance of homeostasis is an indicator of good health Unable to maintain homeostasis- disease

Infection- colonization of the body by pathogenic microorganisms Definitions Infection- colonization of the body by pathogenic microorganisms also when a particular organism is found where it shouldn’t be. Ex. E.coli in urinary tract. Infectious disease- due to pathogenic microorganisms or their products

Pathology- study of disease Pathogenesis- way that disease develops Definitions Pathology- study of disease Pathogenesis- way that disease develops Etiology- cause or agent of disease Genetic - cystic fibrosis Infectious – diptheria. Corynebacterium diphtheriae

Normal Microbiota or (Flora) Permanent, colonizing microbes 1013 body cells vs 1014 bacterial cells Protection by microbial antagonism Competition Antibiotics Maintain environmental conditions

Figure 14.1 Representative normal microbiota for different regions of the body.

Opportunistic Microorganisms Potentially pathogenic Take advantage of weakened host Ex. E. coli Pneumocystis jirovecii Neisseria meningitidis 10% of adults are carriers.

Etiology- the cause B. anthracis – Koch Postulates.

Classification of Infectious Diseases Alterations to homeostasis Signs – objective changes; observable by physician Symptoms – subjective changes like pain and malaise Syndrome – group of signs and symptoms Type of transmission Communicable - chickenpox, non-communicable - tetanus Ex tetanus – lock jaw. Ex influenza – headaches, stomach ache – not apparent to an observer. Ex malaria –

Classification of Infectious Diseases Frequency Sporadic – typhoid, Endemic – common cold or malaria epidemic – AIDS, influenza Pandemic – AIDS, influenza (involves the whole world) Herd immunity – when many immune people exist.

Classification of Infectious Diseases Severity and duration Acute – rapid but short ex. influenza Chronic – slow to develop, lasts long period ex. mono, tuberculosis, hepatitis B Latent causative agent remains inactive and the becomes active ex. Shingles, caused by varicella virus (chicken pox).

Classification of Infectious Diseases Affect on host Localized - abcess Systemic – spread throughout the body by blood or lymph, measles Focal – disease is spread and then localizes, ex. Teeth then biofilm localizes on artificial heart valve.

Extent of Host Involvement Sepsis: toxic inflammatory condition arising from the spread of microbes, especially bacteria or their toxins, from a focus of infection Bacteremia: bacteria in the blood Septicemia: also known as blood poisoning; growth of bacteria in the blood

Classification of Infectious Diseases State of host Primary (smallpox) Secondary infection, (AIDS) Subclinical – disease does not display signs or symptoms ex. Typhoid Mary, polio.

Patterns of Disease Development

Reservoirs of Infection Humans – carriers ex. AIDS, diptheria, typhoid, hepatitis, ebola, flu Animals – zoonoses ex. Rabies (wild animals), lyme disease (ticks), ebola (bats) Non-living – soil, water ex. Clostridium, Salmonella, Vibrio, anthrax

Mechanisms of Transmission Contact – direct (touching, kissing, sex), indirect (fomite – utensils, toys, bedding), droplets Vehicle – water, food, air, blood, drugs, needles, fluids. Vectors Biological (bites – like malaria) and mechanical (microbes carried on insect’s foot)

Specific for most pathogens Respiratory and GI tracts most common Portals of Exit Specific for most pathogens Respiratory and GI tracts most common

Nosocomial Infections – 8th leading cause of death in US. Presence of microbes Compromised host Chain of transmission

Table 14.4 Microorganisms Involved in Healthcare-Associated Infections

Microbial Mechanisms of Pathogenicity 15 Microbial Mechanisms of Pathogenicity

Microbial Pathogenicity

Ability of a microbe to cause disease Pathogenicity Ability of a microbe to cause disease Virulence is a measure of pathogenicity

Steps of Pathogenicity To cause disease a pathogen must: Gain entry Adhere or penetrate Evade host defenses Damage tissue

The routes of infection Portals of Entry The routes of infection Mucous membranes Skin Injection or puncture Parenteral – punctures, wounds, splitting of the skin surgery, bites, cuts etc.

Entry is Only the First Step Preferred portals of entry Minimum dose- number of organisms required to cause disease (a threshold) ID50 – infectious dose for 50% of populuation LD50 – lethal dose of toxin for 50% of populuation

Numbers of Invading Microbes Bacillus anthracis Portal of Entry ID50 Skin 10–50 endospores Inhalation 10,000–20,000 endospores Ingestion 250,000–1,000,000 endospores

Adherence Adhesins and ligands- surface molecules bind specifically to host cell surfaces

Invasive factors aid in penetration and evasion of host defenses Virulence Factors Invasive factors aid in penetration and evasion of host defenses Toxigenic factors are toxins that directly damage host tissues

Capsules Glycocalyx around the cell wall Impair phagocytosis Streptococcus pneumoniae—pneumonia Haemophilus influenzae—pneumonia and meningitis Bacillus anthracis—anthrax Yersinia pestis—plague Waxy lipid (mycolic acid) resists digestion Mycobacterium tuberculosis

Enzymes Coagulases: coagulate fibrinogen Kinases: digest fibrin clots Ex. Staphs. Kinases: digest fibrin clots Hyaluronidase: digests polysaccharides that hold cells together Collagenase: breaks down collagen Ex. Clostridium helps spread gas gangrene IgA proteases: destroy IgA antibodies Ex. Neisseria meningitidis.

S. pyogenes - streptokinase Applications of Microbiology 15.1b S. pyogenes - streptokinase

Antigenic Variation Pathogens alter their surface antigens (and antibodies are rendered ineffective) Example – Influenza ---avoids secondary immune response (Memory cells) because it mutates every year. -HIV highly mutable within the host – avoids antibodies and T-mediated responses.

Poisonous products transported by blood and/or lymph Toxins Poisonous products transported by blood and/or lymph Local or systemic damage Two primary types Exotoxins and endotoxins

Products of normal metabolism Gram positive or gram negative bacteria Exotoxins Proteins Products of normal metabolism Gram positive or gram negative bacteria

Cytotoxins- kill or impair cells Exotoxins Cytotoxins- kill or impair cells Neurotoxins- disrupt nerve impulse transmission Enterotoxins- cause GI disorders Hemolysins – membrane disrupting erthrocytes

Power of toxins Toxins LD50 Botulinum 0.03 ng/kg Shiga toxin 250 ng/kg Staphylococcal enterotoxin 1350 ng/kg LD50 – lethal dose of toxin for 50% of populuation

Gram negative cell walls Released on lysis of cells Endotoxin (within) Lipid A portion of LPS (endotoxins are lipolysaccharides, exotoxins are proteins) Gram negative cell walls Released on lysis of cells Systemic signs (fever, chills, shock, and sometimes death)

Septic shock – decrease in blood pressure caused by bacteria - endotoxins cause macrophages to release cytokines like TNF. TNF changes permeability in capillaries. Loose fluid, blood pressure plummets.

Washwater containing Pseudomonas was sterilized and used to wash cardiac catheters. Three patients developed fever, chills, and hypotension following cardiac catheterization. The water and catheters were sterile. Why did the patients show these reactions? How should the water have been tested?

Mitosis cell stops (cytocidal) Viral Pathogenicity Cytopathic effects- the characteristic changes to host cells resulting from viral infection Mitosis cell stops (cytocidal) Host cells are made to release their enzymes (cytocidal) Inclusion bodies (used to detect rabies)

Fungi lack defined virulence factors. Fungal Pathogenicity Fungi lack defined virulence factors. Candida albicans releases proteases to help attachment to cell membranes. Some allergic responses and a few toxins (mycotoxin phallodin aka deathcap)

Protozoa and Helminths Invasive and toxigenic and long lasting ex. Plasmodium invades hosts cells, reproduce in cells and release toxins (waste products) ex. Trypanosoma – uses antigenic variations, changes its antigens every two weeks.