Microbiology: Infectious Disease, Pathogenicity, and Epidemiology

General Microbiology: Infectious Disease, Pathogenicity, and Epidemiology

Symbiotic Relationships Between Microbes and Their Hosts

• Symbiosis: "to live together"
• Types of Symbiosis:
  • Mutualism: mutual benefit
  • Commensalism: benefits one, the other is not affected
  • Amensalism: one is not affected, the other is harmed
  • Parasitism: benefits one, harms the other
• Pathogen: Any parasite that causes disease.
• Primary Pathogens: Cause disease in a host regardless of the host’s resident microbiota or immune system.
• Opportunistic Pathogens: Can only cause disease in situations that compromise the host’s defenses.

How Normal Microbiota Become Opportunistic Pathogens

• Conditions Providing Opportunities:
  • Introduction of normal microbiota into an unusual site in the body
  • Immune suppression (e.g., chemotherapy, immunosuppressive drugs)
  • Changes in the relative abundance of normal microbiota
  • Absence of microbial antagonism (competition)
  • Stressful conditions

Reservoirs of Infectious Diseases of Humans

• Reservoirs of infection: Sites where pathogens are maintained as a source of infection.
• Three Types of Reservoirs:
  • Animal reservoir
  • Human carriers
  • Nonliving reservoir

Animal Reservoirs

• Zoonoses: Diseases naturally spread from animal host to humans (over 200 identified so far).
• Acquisition Routes:
  • Direct contact with the animal or its waste
  • Eating animals
  • Bloodsucking arthropods (e.g., mosquitos)
• Humans are usually a dead-end host for zoonotic pathogens.
• Difficult to eradicate.
• Examples of Zoonoses:
  • Helminthic: Tapeworm infestation (Dogs), Fasciola infestation (Sheep, cattle)
  • Protozoan: Malaria (Monkeys), Toxoplasmosis (Cats and other animals)
  • Fungal: Ringworm (Domestic animals)
  • Bacterial: Anthrax (Domestic livestock), Bubonic plague (Rodents), Lyme disease (Deer), Salmonellosis (Birds, rodents, reptiles), Typhus (Rodents)
  • Viral: Rabies (Bats, skunks, foxes, dogs), Hantavirus pulmonary syndrome (Deer mice), Yellow fever (Monkeys)

Human Carriers

• Active Carriers: Infected individuals who can transmit the disease to others.
  • May or may not exhibit signs or symptoms of infection.
  • Asymptomatic infected individuals can be infective but do not exhibit signs or symptoms.
  • Some develop the disease (e.g., tuberculosis, syphilis, AIDS), while others never get sick.
• Passive Carriers: Contaminated with the pathogen and can mechanically transmit it to another host; however, a passive carrier is not infected.
• Healthy carriers may have defensive systems that protect them.

Nonliving Reservoirs

• Soil, water, and food can be reservoirs of infection.
• Presence of microorganisms often due to contamination by feces or urine.

The Invasion and Establishment of Microbes in Hosts: Stages of Pathogenesis

• Exposure to Microbes:
  • Contamination: The mere presence of microbes in or on the body.
  • Infection: When an organism evades the body's external defenses, multiplies, and becomes established in the body.
    • May or may not result in disease.

Stages of Pathogenesis

• Four Stages:
  1. Exposure (contact)
  2. Adhesion (colonization)
  3. Invasion
  4. Infection
• Requirements for Pathogens:
  1. Gain entry to the host
  2. Travel to the location where it can establish an infection
  3. Evade or overcome the host’s immune response (spread)
  4. Cause damage resulting in disease to the host.
• Cycle Completion: Pathogen exits the host and is transmitted to a new host.

Stages of Pathogenesis: Step 1 - Exposure (Contact)

• Portals of Entry: Sites through which pathogens enter the body.
• Major Pathways:
  • Skin
  • Mucous membranes
  • Placenta
  • Parenteral route: Circumvents the usual portals of entry

Portals of Entry: Skin

• Outer layer of dead skin cells acts as a physical barrier to pathogens.
• Parenteral route:
  • Some pathogens can enter through openings or cuts.
  • Others enter by burrowing into or digesting outer layers of skin.

Portals of Entry: Mucous Membranes

• Line the body cavities that are open to the environment.
• Provide a moist and warm environment hospitable to pathogens.
• Respiratory tract is the most common site of entry.
  • Entry is through the nose, mouth, or eyes.
  • Many viruses enter via the eyes (conjunctiva).
• Gastrointestinal tract may be route of entry.
  • Must survive the acidic pH of the stomach ($HCl$).

Portals of Entry: Placenta

• Typically forms an effective barrier to pathogens.
• Pathogens may cross the placenta and infect the embryo or fetus (~2% of pregnancies).
• Can cause spontaneous abortion, birth defects, and premature birth.
• Examples of Pathogens Capable of Crossing the Placental Barrier:
  • Protozoan: Toxoplasma gondii (Toxoplasmosis)
  • Bacterium: Treponema pallidum (Syphilis)
  • Virus: Varicella-zoster virus (Chickenpox), Hepatitis B virus (Hepatitis B), Retrovirus (HIV), Parvovirus B19 (Fifth disease), Togavirus (Rubella), Human herpesvirus 5 (Cytomegalovirus), Herpes simplex viruses (Herpes)

Portals of Entry: Parenteral Route

• Not a true portal of entry.
• Means by which portals of entry can be circumvented.
• Pathogens deposited directly into tissues beneath the skin or mucous membranes (e.g., cuts, punctures).

The Role of Adhesion in Infection

• Process by which microorganisms attach themselves to cells or tissues.
• Required to successfully establish colonies within the host.
• Uses adhesion factors:
  • Specialized structures
  • Attachment molecules
• Ligands (adhesion factors) help in adhesion
  • Found on viruses and many bacteria
  • Viral or bacterial ligands bind host cell receptors
  • Interaction can determine host cell specificity

Example of Adhesion

• $E. coli$ using ligands to adhere to the Mucous membrane of the intestine.

Biofilm Formation

• Some bacterial pathogens attach to each other to form a biofilm (not all directly attached to the host).

Invasion

• Invasion involves the dissemination (spread) of a pathogen throughout local tissues or the body.
• Pathogens may produce exoenzymes or toxins, which serve as virulence factors that allow them to colonize and damage host tissues as they spread deeper into the body.
• Pathogens may also produce virulence factors that protect them against immune system defenses.
• A pathogen’s specific virulence factors determine the degree of tissue damage that occurs.

Infection

• Multiplication of the pathogen leads to infection.
• Infections can be described as local, focal, or systemic, depending on the extent of the infection.
  • A local infection is confined to a small area of the body, typically near the portal of entry.
  • A focal infection, a localized pathogen, or the toxins it produces, can spread to a secondary location.
  • A systemic infection becomes disseminated throughout the body.

The Nature of Infectious Disease

• Infection: The invasion of the host and establishment by a pathogen.
• Disease: Results if the invading pathogen alters normal body functions (adversely affects the body).
• Disease is also referred to as morbidity (change in state of health).
• Every disease alters the body's structures and functions in particular ways.

Manifestations of Disease: Symptoms, Signs, and Syndromes

• Symptoms: Subjective characteristics of disease felt only by the patient.
• Signs: Objective manifestations of disease observed or measured by others.
• Syndrome: Symptoms and signs that characterize a disease or abnormal condition.
• Asymptomatic (subclinical) infections lack symptoms but may still have signs of infection.

Disease Terminology Prefixes/Suffixes

• carcino-: Cancer

• col-, colo-: Colon

• dermato-: Skin

• -emia: Pertaining to the blood

• endo-: Inside

• -gen, gen-: Give rise to

• hepat-: Liver

• idio-: Unknown

• -itis: Inflammation of a structure

• -oma: Tumor or swelling

• -osis: Condition of

• -patho, patho-: Abnormal

• septi-: Rotting; refers to presence of pathogens

• terato-: Defects

• tox-: Poison
  Examples for the terminology:

• Carcinogenic: giving rise to cancer

• Colitis: inflammation of the colon

• Dermatitis: inflammation of the skin

• Viremia: viruses in the blood

• Endocarditis: inflammation of lining of heart

• Pathogen: giving rise to disease

• Hepatitis: inflammation of the liver

• Idiopathic: pertaining to a disease of unknown cause

• Meningitis: inflammation of the meninges (covering of the brain)

• Papilloma: wart

• Toxoplasmosis: being infected with Toxoplasma

• Pathology: study of disease

• Septicemia: pathogens in the blood

• Teratogenic: causing birth defects

• Toxin: harmful compound

Disease Categories

• Hereditary: Caused by errors in the genetic code received from parents.
• Congenital: Anatomical and physiological defects present at birth.
• Degenerative: Result from aging.
• Nutritional: Result from a lack of essential nutrients.
• Endocrine: Due to excesses or deficiencies of hormones.
• Mental: Emotional or psychosomatic.
• Immunological: Hyperactive or hypoactive immunity.
• Neoplastic: Abnormal cell growth.
• Infectious: Caused by an infectious agent.
• Iatrogenic: Caused by medical treatment or procedures.
• Idiopathic: Unknown cause.
• Healthcare-associated (nosocomial): Disease acquired in a health care setting.

Using Koch's Postulates

• Germ theory of disease: Infections by pathogenic microorganisms cause disease
• Robert Koch developed a set of postulates one must satisfy to show a particular pathogen causes a particular disease
• Koch was the first to show that a specific infectious disease is caused by a specific microorganism that can be isolated and cultured on artificial media.

Koch’s Postulates

1. The same pathogen must be present in every case of the disease
2. The pathogen must be isolated from the diseased host and grown in pure culture
3. The pathogen from the pure culture must cause the disease when it is inoculated into a healthy, susceptible lab animal
4. The same pathogen must be reisolated from the inoculated animal and must be shown to be the original pathogen

Exceptions to Koch's Postulates

• Some pathogens can't be cultured in the laboratory.
• Diseases caused by a combination of pathogens and other cofactors.
• Ethical considerations prevent applying Koch's postulates to pathogens that require a human host (e.g., HIV causing AIDS).
• Difficulties in satisfying Koch's postulates:
  • Diseases can be caused by more than one pathogen.
  • Pathogens that are ignored as potential causes of disease (e.g., majority of ulcers caused by Helicobacter pylori).

Pathogenicity and Virulence

• Pathogenicity: Ability of a microorganism to cause disease (not severity).
• Virulence: Degree of pathogenicity.
• Virulence Factors of Infectious Agents:
  • Adhesion factors
  • Biofilms
  • Extracellular enzymes
  • Toxins
  • Antiphagocytic factors (e.g., capsules)

Relative Virulence of Some Microbial Pathogens (Less to More)

• Lactobacilli, diphtheroids
• Candida albicans (vaginitis, thrush)
• Clostridium difficile (antibiotic-induced colitis)
• Pseudomonas aeruginosa (infections of burns)
• Bordetella pertussis (whooping cough)
• Yersinia pestis (plague)
• Francisella tularensis (rabbit fever)

Virulence Factors of Infectious Agents: Adhesion

• Adhesion factors are found on bacterial, viral, fungal, and protozoan pathogens.
• Some Bacterial Adhesins and Their Host Attachment Sites:
  • Streptococcus pyogenes adhesion Protein F to Respiratory epithelial cells (Strep throat)
  • Streptococcus mutans adhesion Adhesin P1 to Teeth (Dental caries)
  • Neisseria gonorrhoeae adhesion Type IV pili to Urethral epithelial cells(Gonorrhea)
  • Enterotoxigenic E. coli (ETEC) adhesion Type 1 fimbriae to Intestinal epithelial cells (Traveler’s diarrhea)
  • Vibrio cholerae adhesion N-methylphenylalanine pili to Intestinal epithelial cells (Cholera)

Virulence Factors of Infectious Agents: Extracellular Enzymes

• Extracellular enzymes are secreted by the pathogen
• Hyaluronidase and collagenase: Invasive bacteria reach epithelial surface, Bacteria invade deeper tissues.
• Coagulase and kinase: Bacteria produce coagulase, Clot forms, Bacteria later produce kinase dissolving the clot and releasing bacteria
• Dissolve structural chemicals in the body
• Help pathogens invade, maintain infection, and avoid body defenses.
• Important to virulence of the pathogen
• Mutant species that do not secrete the extracellular enzymes are often avirulent

Virulence Factors of Infectious Agents: Toxins

• Chemicals that harm tissues or trigger host immune responses that cause damage.
• Toxemia refers to the presence of toxins in the bloodstream.
• Two types:
  • Exotoxins: Secreted from the microbe (e.g., cytotoxins, neurotoxins, and enterotoxins).
    • Protective antibodies (antitoxins) can neutralize.
  • Endotoxin: Lipid A (in LPS) of Gram-negative bacteria.
• Lipopolysaccharide contains lipid A (endotoxin) that promotes inflammation and fever.

Comparison of Endotoxin and Exotoxins Produced by Bacteria

Virulence Factors of Infectious Agents: Immune Evasion

• Antiphagocytic Factors: Factors prevent phagocytosis by the host's phagocytic cells
• Capsule around bacterium: Allow pathogens to remain in a host for a longer time.
  • Composed of chemicals not recognized as foreign
  • Large and slippery, making it difficult for phagocytes to engulf
• Antiphagocytic chemicals:
  • Prevent fusion of lysosome and phagocytic vesicles
  • Leukocidins directly destroy phagocytic white blood cells

The Stages of Infectious Disease

• Incubation period: no signs or symptoms
• Prodromal period: vague, general symptoms
• Illness: most severe signs and symptoms
• Decline: declining signs and symptoms
• Convalescence: no signs or symptoms

The Movement of Pathogens Out of Hosts: Portals of Exit

• Pathogens leave the host through portals of exit
• Many portals of exit are the same as portals of entry
• Pathogens often leave hosts in materials the body secretes/excretes or bodily fluids

Modes of Infectious Disease Transmission

• Transmission is from a reservoir or a portal of exit to another host's portal of entry
• 3 groups of transmission:
  • Contact transmission
  • Vehicle transmission
  • Vector transmission

Contact Transmission

• Direct contact transmission: Usually involves body contact between hosts, Transmission within a single individual can also occur
• Indirect contact transmission: Pathogens are spread from host to host by fomites (non-living object)
• Droplet transmission: Spread of pathogens in droplets of mucus by exhaling, coughing, and sneezing (short distance)

Vehicle Transmission

• Airborne transmission: When pathogens travel more than 1 meter (long distance) via an aerosol
  • Aerosols can occur from various activities, e.g., Sneezing, coughing, air-conditioning systems, and sweeping
• Waterborne transmission: Important in the spread of many gastrointestinal diseases, Includes fecal-oral infection (e.g., water contaminated by feces)
• Foodborne transmission: Spread of pathogens in and on foods, e.g., Inadequately processed, cooked, or refrigerated foods, Foods may become contaminated with feces (fecal-oral infection)
• Bodily fluid transmission: Bodily fluids such as blood, urine, saliva can carry pathogens, Prevent contact with conjunctiva or breaks in the skin or mucous membranes

Vector Transmission

• Biological vectors: Transmit pathogens and serve as host for some stage of the pathogen's life cycle biting arthropods transmit many diseases to humans (e.g., mosquitos, ticks, and fleas)
• Mechanical vectors: Passively transmit pathogens present on their body to new hosts (not a host for the pathogen)

Arthropod Vectors Examples

• Houseflies and Cockroaches: Mechanical Vector of Foodborne infections (Shigella spp., Salmonella spp., Escherichia coli)

• Black fly: Biological Vector of Onchocerciasis (Onchocerca volvulus)

• Flea: Biological Vector of Plague (Yersinia pestis) and Murine typhus (Rickettsia typhi)

• Louse: Biological Vector of Relapsing fever (Borrelia recurrentis) and Typhus (Rickettsia prowazekii)

• Mosquito: Biological Vector of Malaria (Plasmodium falciparum) and Yellow fever (Yellow fever virus)

• Tick: Biological Vector of Lyme disease (Borrelia spp.) and Rocky Mountain spotted fever (Rickettsia rickettsii)

Summary of Modes of Disease Transmission

Classification of Infectious Diseases

• Diseases can be classified in several ways:
  • The body system they affect
  • Taxonomic categories
  • Their longevity and severity
  • How they are spread to their host
  • The effects they have on populations

Terms Used to Classify Infectious Diseases

Epidemiology of Infectious Diseases

• Frequency of Disease:
  • Incidence: Number of new cases of a disease in a given area during a given period of time
  • Prevalence: Number of total cases of a disease in a given area during a given period of time
• Occurrence also evaluated in terms of frequency and geographic distribution

Different Terms for the Occurrence of Disease

• Endemic: Disease is constantly present
• Sporadic: Disease seen occasionally
• Epidemic: Larger than expected disease occurrence in a geographical location
• Pandemic: Epidemic that occurs on a global scale

Morbidity and Mortality Weekly Report (MMWR)

• The CDC publishes the Morbidity and Mortality Weekly Report (MMWR)
• Provides updates on public health issues and the latest data pertaining to notifiable diseases.

National Notifiable Diseases Surveillance System (NNDSS)

• The NNDSS monitors diseases considered to be of public health importance on a national scale.
• Such diseases are called notifiable diseases or reportable diseases because all cases must be reported to the CDC.
• A physician treating a patient with a notifiable disease is legally required to submit a report on the case.

Epidemiological Studies

• Descriptive Epidemiology: Careful tabulation of retrospective data concerning a disease to Record location and time of the cases of disease, Collect patient information, and Identify the index case of the disease (patient zero)
• Analytical Epidemiology: Seeks to determine the probable cause, mode of transmission, and methods of prevention, Useful in situations when Koch's postulates can't be applied, Often retrospective, Investigation occurs after an outbreak has occurred
• Experimental Epidemiology: Test a hypothesis concerning the cause of a disease, Application of Koch's postulates, Often involve Prospective Studies to Follow individuals and monitor their disease state during the course of the study

Hospital Epidemiology: Healthcare-Associated (Nosocomial) Infections

• Types of healthcare-associated infections (HAIs):
  • Exogenous: Pathogen acquired from the health care environment
  • Endogenous: Pathogen arises from normal flora within the patient
  • Iatrogenic: Results from modern medical procedures
  • Superinfections: Use of antimicrobial drugs inhibits some resident flora, allowing other microbes to thrive

Control of HAIs

• Requires aggressive control measures
• Handwashing is the most effective (degerming) way to reduce healthcare-associated infections

Epidemiology and Public Health

• The Sharing of Data Among Public Health Organizations between Agencies at the local, state, national, and global level.
• The United States Public Health Service and National public health agency.
• World Health Organization (WHO): Coordinates public health efforts worldwide.

The Role of Public Health Agencies in Interrupting Disease Transmission

• Public health agencies work to limit disease transmission
• Enforce cleanliness of water (EPA) and food supplies (USDA & FDA)
• Work to reduce disease vectors and reservoirs
• Establish and enforce immunization schedules
• Locate and treat individuals exposed to contagious pathogens
• Establish isolation and quarantine measures

Public Health Education

• Diseases transmitted sexually and through the air are difficult to control
• Public health agencies campaign to educate the public on healthful choices to limit disease