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Requirements for Infection Notes

Requirements for Infection

Learning Objectives

  • 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
    • Binds and inhibits the release of acetylcholine
    • Causes muscular paralysis

Infant Botulism

  • Occurs between 3 weeks to 8 months
  • Organism introduced upon weaning or RAW HONEY
  • S&S: constipation, poor muscle tone, lethargy, feeding problems, vision problems and paralysis

Wound Botulism

  • Very rare
  • Seen in IV drug users
  • Begins with weakness in extremities used as injection sites

Enterotoxins - Vibrio cholerae

  • Gram – vibrio (bacillus)
  • Causes release of large amount of electrolytes
    • Lethal diarrhea
    • “Rice Water Stools”
    • Vomiting

Enterotoxins - Staphylococcus aureus

  • Gram+ coccus
  • Toxic Shock Syndrome
    • Excessive loss of electrolyte fluids
    • Hypotensive shock
    • Common food poisoning

Bacterial Endotoxins

  • Intrinsic part of Gram- bacterial cell wall
  • Released upon death of bacterium
  • Released in the form of Lipid A
  • Endotoxins cause
    • Chills
    • Fever
    • Aches
    • Muscle weakness
    • Disseminated intravascular clotting

Viral Pathogenic Effects

  • Viral host cell damage: cytopathogenic effect (CPE)
  • Occurs in 3 ways:
    • Viral overload
    • Cytocidal effects (killing of host cells)
    • Non-cytocidal effects (damage caused by host defenses)

Exiting the Host

  • Transmission is dependent upon the organism and the system it is infecting

Principles of Transmission

  • Where are pathogens found?
  • What are the mechanisms of transmission?
  • How can the chain of transmission be broken?

Factors Affecting Transmission

  • Reservoirs of infection: Places where pathogens grow and accumulate
  • Mechanisms of transmission: Various ways pathogens move from place to place

Pathogen Reservoirs

  • Three potential reservoirs of pathogens:
    • Human
    • Animals
    • Non-living

Human Reservoirs

  • Sick people: Easy to identify
  • Carriers: Those who are infectious but never show signs or symptoms

Animal Reservoirs

  • Zoonotic diseases:
    • Those infections that may be transmitted from animals to humans
      • Anthrax
      • Brucellosis
      • Cat scratch fever
      • Lyme
      • Plague
      • Tuberculosis
      • Ringworm
      • Rocky Mountain Spotted Fever

Non-living Reservoirs

  • Include water, food, and soil
  • Fecal-oral transmission
  • Food spoilage
  • Soil dwelling bacteria may be transmitted through human activity or animal husbandry

Mechanisms of Transmission

  • Three mechanisms of pathogen transmission
    • Contact
    • Vehicle
    • Vector

Contact Transmission

  • Occurs when an uninfected person is exposed to a pathogen via touching or proximity with an infected individual, animal, or object
  • There are 3 types of contact transmission:
    • Direct
    • Indirect
    • Droplet

Direct Contact Transmission

  • There is no intermediary between the infected person/animal and the uninfected person
  • Example: rabies

Indirect Contact Transmission

  • Occurs through intermediates that are not alive (FOMITES) such as tissues, handkerchiefs, towels, bedding, and contaminated needles

Droplet Transmission

  • Spread through aerosolized saliva, mucous, and sputum
  • Spread by talking, laughing, and sneezing

Vehicle Transmission

  • Pathogens "ride" on:
    • Water
    • Food
    • Air
      • Including dust particles

Vector Transmission

  • Pathogens are transmitted to a healthy person by a carrier known to be associated with a certain disease
  • Most common vector: Arthropods
    • Fleas
    • Ticks
    • Body lice
    • Mosquitoes
    • Flies

Vector Transmission

  • Biological (pathogen lives within the vector)
    • plague (flea), malaria (mosquito), yellow fever (mosquito)
  • Mechanical (pathogen is physically carried by the vector)
    • Rocky Mountain spotted fever (tick), Lyme disease (tick)
    • E. coli diarrhea, salmonellosis

Factors Affecting Disease Transmission

  • Age
  • Gender
  • Lifestyle
  • Occupation
  • Geography
  • General health

The Compromised Host

  • 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
  • Affect patients and health care workers

Most Common Organisms in Nosocomial Infections

  • Staphylococcus aureus
  • Escherichia coli
  • Streptococcus
  • Pseudomonas
  • Klebsiella
  • Enterobacter
  • Candida
  • Staphylococcus epidermidis
  • Serratia

Nosocomial Infections

  • Propagation of antibiotic-resistant organisms
  • Very poor patient prognosis
  • Clostridium difficile (C. diff)
  • Neisseria gonorrhoeae
  • Carbapenem-resistant Enterobacteraciae (CRE)
  • Vancomycin-resistant Enterococcus (VRE)
  • Vancomycin-resistant Staphylococcus aureus (VRSA)
  • Multi-drug resistant TB (MDRTB/XDRTB)