Mechanisms of Infectious Diseases Flashcards

Objectives

• Define key terms: host, infectious disease, colonization, microflora, virulence, pathogen, and saprophyte.
• Describe host–microorganism interactions: commensalism, mutualism, and parasitic relationships.
• List different types of pathogens and compare their similarities and differences.
• Describe the stages of an infectious disease after pathogen entry.
• List systemic manifestations of an infectious disease.
• Explain differences between culture, serology, and antigen/metabolite/molecular detection methods for diagnosing infectious diseases.
• Cite three general intervention methods for treating infectious illnesses.
• List infectious agents posing the highest bioterrorism threat.
• State an important concept in containing infections due to bioterrorism and global travel.

Case Study

• A 32-year-old laborer, Jason, fell ill after working on a job digging up old water pipes, involving exposure to stagnant water.
• Ten days later, Jason developed a fever, aching muscles, nausea, vomiting, and diarrhea.
• His advanced practice provider suspected West Nile fever and ordered serological testing.
• Jason recovered by the end of the week.

Terminology Involved in the Study of Infectious Disease

• Host: Any organism capable of supporting the nutritional and physical growth requirements of another organism.
• Microflora: Bacteria inhabiting exposed surfaces of the body.
• Colonization:
  • The presence and multiplication of a living organism on or within the host.
  • Does not cause harm to the host.
  • Colonization DOES NOT equal infection.
• Infection: The presence and multiplication of another living organism within a host.
• Infectious disease: The disease state brought about by the interaction with another organism that causes harm to the host.

Terminology (cont.)

• Virulence: The disease-inducing potential.
• Pathogens: Microorganisms so virulent that they are rarely found in the absence of disease.
• Saprophytes:
  • Free-living organisms obtaining their growth from dead or decaying organic material from the environment.
  • Humans are not usually affected by saprophytes.
• Opportunistic pathogens: Microorganisms capable of producing infectious disease when the host's health and immunity have been severely weakened.

Relationships Between Microorganisms and Hosts

• Mutualism:
  • An interaction in which both the microorganism and the host benefit.
  • Example: Bacteria in the gut that produce Vitamin K; the bacteria are supported by the body and the body gets the benefit of not bleeding to death.
• Commensalism:
  • An interaction in which colonizing organisms acquire nutritional needs and shelter, but the host body is not affected.
• Parasitic relationship:
  • Only the infecting organism benefits from the relationship; the host sustains injury or pathologic damage, resulting in infectious disease.

Common Pathogens

• Prion
  • Structural Characteristics: The protein (PrP) is found throughout the body; however, the Prpsc in infectious materials is misfolded.
  • Functional Characteristics: Protein found in infected animals
  • Treatment: Current research for effective treatment
  • Common Diseases: Creutzfeldt-Jakob disease (associated with other neurodegenerative conditions)
• Viruses
  • Structural Characteristics: DNA/RNA and protein coat
  • Functional Characteristics: Cannot reproduce outside of cells
  • Treatment: Antivirals, which slow viral replication
  • Common Diseases: Influenza, the common cold, measles, HIV/AIDS
• Bacteria
  • Structural Characteristics: Microscopic cell without nucleus
  • Functional Characteristics: Common on keyboards, water fountains, toilets, etc.
  • Treatment: Antibiotics, which slow bacterial reproduction
  • Common Diseases: Strep throat, some sinus and lung infections, some food poisoning
• Fungi
  • Structural Characteristics: Microscopic, unicellular (yeasts) or multicellular (molds)
  • Functional Characteristics: Usually infect body surfaces and openings
  • Treatment: Antifungals, which destroy the cell walls
  • Common Diseases: Athlete's foot, yeast infections
• Protozoa
  • Structural Characteristics: Microscopic, unicellular
  • Functional Characteristics: Common in water supplies of developing countries
  • Treatment: Antiprotozoan drugs, which interfere with protozoan metabolism
  • Common Diseases: Malaria, sleeping sickness
• Worms (Helminths)
  • Structural Characteristics: Multicellular
  • Functional Characteristics: Prefer to live within body spaces and cells
  • Treatment: Antihelminthics, which interfere with the worm's metabolism
  • Common Diseases: Roundworms, tapeworms

Agents of Infectious Disease

• Refer to Table 10.2 in Norris (11th ed.), p. 255, for a comparison of the characteristics of human microbial pathogens.
• Consider differences and similarities in cellular organization (nucleus/no nucleus), genomic material (DNA/RNA), size, motility, and whether they are intracellular, extracellular, or both.

Prions (Objective 2)

• Protein particles that lack any demonstrable genome and are able to transmit infection.
• Cause slow progression, non-inflammatory neuronal degeneration.
• Symptoms include ataxia, dementia, and death over months to years.
• Associated with transmissible neurodegenerative diseases such as Creutzfeldt-Jacob disease and kuru.
• Resistant to antibiotics, as they lack reproductive and metabolic functions.

Viruses

• Smallest obligate intracellular pathogens.
• Have no organized cellular structure.
• Incapable of replication outside of a living cell.
• Consist of a protein coat (capsid) surrounding a nucleic acid core (genome) of DNA or RNA (but never both).
• Can be single-stranded or double-stranded.
• Categorized by size, physical characteristics, mechanisms of replication, mode of transmission, and type of disease produced.
• Examples: Epstein-Barr Virus (EBV), Herpes Simplex Virus (HSV), Varicella Zoster (chickenpox), Hepatitis B, Human Immunodeficiency Virus (HIV).

Figure 10.2 The basic structure of a virus

• Virion
• Capsid
• Nucleic acid genome (DNA or RNA)
• Envelope

Figure 10.3 Schematic representation of the many possible consequences of viral infection of host cells, including cell lysis (poliovirus), continuous release of budding viral particles, or latency (herpesviruses) and oncogenesis (papovaviruses).

• Absorption
• Penetration
• Uncoating
• Viral replication
• Protein coat synthesis
• Viral maturation
• Host cell lysis
• Malignancy
• Latency
• Oncogenesis

Case Study Question 1

• West Nile virus has a single-stranded RNA genome. How does this virus replicate?
• In general terms, what are the various effects viruses can have on host cells?
• Specifically, what is required for the virus to replicate?
• Review slide 11 and note the many manifestations that can occur because of viral infections.

Microorganisms (aka “bugs”) (Objective 2)

• Prokaryotes (Bacteria)
  • Lack an organized nucleus.
  • Primitive.
  • Contain both DNA and RNA.
  • Plasmids (circular pieces of DNA).
  • Contain both cytoplasmic (cell) membranes and rigid cell walls.
• Eukaryotes (Fungi)
  • Contain a membrane-bound (organized) nucleus.
  • Yeasts
    • Single celled.
    • Reproduce by budding.
  • Molds
    • Produce long, hollow, branching filaments called hyphae.
  • Dimorphic fungi: Yeast at one temperature, molds at another temperature.
    • Examples:
      • Blastomycosis.
      • Histoplasmosis.
      • Coccidioidomycosis.

Classification of Bacteria

• According to the microscopic appearance
  • bacilli (rods), cocci (spherical), spirilla (helical)
• According to staining of the cell
  • Gram-positive organisms: stain PURPLE by a primary basic dye (usually crystal violet) (remember “P” for positive and purple)
  • Gram-negative organisms: do not stain PURPLE but are counterstained RED by a second dye (safranin)

Parasites

• Types
  • Protozoa—single celled animals with well defined nucleus and organelles
  • Helminths—worms, also animals: roundworms, tapeworms, flukes
  • Arthropods— insects also animals, mosquitoes, biting flies, etc.
• Method of Infecting
  • These members of the animal kingdom infect and cause diseases in humans or other animals either directly or indirectly.
  • Infected animals may then transmit disease to humans.

Rickettsiaceae, Anaplasmataceae, Chlamydiaceae, Coxiella

• Organisms that combine the characteristics of viral and bacterial agents to produce disease in humans
• Are obligate intracellular pathogens (like viruses)
• Produce a rigid peptidoglycan cell wall (like bacteria)
• Reproduce asexually by cellular division (like bacteria)
• Contain RNA and DNA (like bacteria and viruses)

Rickettsiaceae, Anaplasmataceae, Chlamydiaceae, Coxiella Organisms of significance:

• Rickettsiaceae—Tick born: Rocky Mountain Spotted Fever; possibly Lyme disease
• Chlamydiaceae—Directly transmitted: Chlamydophila trachomatis (C. trachomatis), an STI
• Other examples of diseases:
  • Anaplasmataceae—Probably tick born: sennetsu fever seen in Japan
  • Coxiella—Q fever, a nonspecific febrile illness with muscle aches and fever

Question

• Which of the following pathogens does not fit the typical description of an organism?
  • A. Viruses
  • B. Bacteria
  • C. Rickettsiaceae
  • D. Chlamydiaceae
  • E. Fungi
  • F. Parasites
• Think “structure and organization”

Answer

• A. Viruses
• Rationale: Viruses have no organized cellular structure and cannot live outside another “organism.”

Epidemiology (Terminology review) (Objective 3, 4)

• Epidemiology: the study of factors, events, and circumstances that influence the transmission of infectious diseases among humans
• Why is epidemiology important regarding infectious diseases?
• Incidence: The rate at which a certain event occurs (e.g., the number of new cases of a specific disease during a particular period of time in a population at risk)
• How would this help you in your clinical practice? If you are a pediatric NP, you understand what happens during cold and flu season!
• Prevalence: The number of new and old cases of a disease that is present in a population at a given time, or occurrences of an event during a particular period of time.
• How would knowing this help you in your clinical practice? If you practice as a family NP in south Florida, this may help you with your understanding of mosquito born illnesses.

Epidemiology (Terminology)

• Endemic disease: Found in a particular geographic region
  • The incidence and prevalence are expected and relatively stable. (Remember prevalence and incidence from Chapter 1, or perhaps more recently in the previous slide?)
• Epidemic: Abrupt and unexpected increase in the incidence of disease over endemic rates (influenza; yellow fever; polio (yes it still exixts)
• Pandemic: Spread of disease beyond continental boundaries (Ebola, Covid-19, cholera)

Classification of Infectious Disease

• Incidence—Why is this important? If it is mentioned twice, it is probably important to know!
• Portal of entry—How does the “bug” get in?
• Source—Where did it come from?
• Symptoms—How does it affect the host?
• Disease course—What happens once the “bug” gets to the party?
• Site of infection—What is affected?
• Virulence factors—Things that make the “bug” more harmful

Portals of Entry

• Penetration—what factors would make penetration easier? (No, alcohol is not involved! What were you thinking?)
  • burns, abrasions, penetrating wounds, surgery, catheterization, surface infections that disrupt the skin, IV drug use
• Direct contact—think “STI’s” as an example
  • direct—from infected mucosa to intact mucosa—gonorrhea, syphilis, chlamydia, genital herpes
  • vertical transmission—mother to child such as with breast feeding
  • congenital—acquired during gestation
• Ingestion—”My, what a lovely potato salad! How long did you say it has been sitting on the picnic table?”
  • oral cavity and GI tract—ingestion of contaminated food and water
  • infections agent must be able to survive the acidity of the stomach
  • infections agent must be large enough to establish infection  infectious dose
• Inhalation—what factors might make this portal an easier access?
  • smoking, decreased mucocilliary function, impaired respiratory function (cystic fibrosis, emphysema)

Source of an Infectious Disease: Who, What, Where or When

• Location
  • Nosocomial: develop in hospitalized patients
    • Example: hospital acquired UTI from an indwelling catheter
  • Community acquired: acquired outside of health care facilities
    • Most common colds are community acquired
    • Consider the difference between community acquired pneumonia and hospital acquired pneumonia
• Host
  • An object or substance from which the infectious agent was acquired
  • Endogenous—from the host’s own microflora
  • Exogenous—water, food, air, soil, animals
  • Fomites: inanimate objects that carry disease
    • Handkerchiefs, toys, unwashed hands, that glass you share in the bathroom to rinse out your mouth

Symptomatology

• Specific: reflects the site of infection (e.g., diarrhea, rash, convulsions, hemorrhage, pneumonia)
• Nonspecific: can be shared by a number of diverse infectious diseases (e.g., symptoms such as fever, myalgia, headache)
• Obvious: predictable patterns (e.g., chickenpox and measles)
• Covert: may require laboratory testing to detect (e.g.,hepatitis or increased white blood cell count)

Disease Course in Infection

• ACUTE
  • FULMINANT ILLNESS—abrupt onset with little or no prodrome
  • INSIDIOUS—prodromal phase is prolonged
• Incubation period
  • pathogens begin active replication without symptoms » time frame is variable: salmonellosis (6-12 hours), hepatitis B (50-180 days), HIV (months to years)
• Prodromal stage
  • initial appearance of symptoms » vague: malaise, mild fever, myalgia, headache, fatigue

Disease Course in Infection

• Acute stage
  • host experiences maximum impact of the disease process
  • rapid proliferation and dissemination of the pathogen
  • toxic by-products may result in cell lysis, immune response, damage to host tissue, inflammation
  • usually more specific and may be pathogen and site specific
• Convalescent stage
  • containment of infection, progressive elimination of the pathogen, repair of damaged tissue, resolution of associated symptoms
• Resolution stage
  • total elimination of the pathogen without residual signs or symptoms of disease
• Subacute (Subclinical)
  • protracted and irregular course without clinically apparent symptoms

Stages of Primary Infectious Diseases Related to Severity of Symptoms, Figure 10.7 Stages of a primary infectious disease as they appear in relation to the severity of symptoms and numbers of infectious agents. The clinical threshold corresponds with recognizable symptoms, whereas the critical threshold represents the peak of disease intensity.

Case Study Question 2

• When Jason was feeling at his worst, he had extreme malaise, vomiting, and diarrhea. What stage of the illness was he experiencing at that time?
• What are the physiological mechanisms that give rise to the signs and symptoms of infectious illness?
• Hint: See the previous slide!

Factors Influencing the Site of an Infectious Disease

• Type of pathogen
  • Site specific
    • M. pneumonia—tuberculosis  lungs
    • N. gonorrhoeae (typically)—gonorrhea  genital tract, oral pharynx
    • H. pylori—gastric ulcers  stomach
  • Systemic
    • N. meningitides—meningitis  brain, vascular system (meningococcemia), and other organs
    • S. typhi—typhoid fever  vascular, gastrointestinal
• Portal of entry
  • Oral
  • Skin (penetration)
  • Vascular (IV drug use with dirty needles [although this could be a subset of penetration])
• Competence of the host’s immunologic defense system
  • Normal
  • Compromised—chemotherapy, concurrent diseases such as HIV infection, starvation

Categories of Virulence Factors

• Toxins: Substances that alter or destroy the normal function of the host or host’s cells
  • Exotoxins
    • proteins released from bacteria during cell growth
    • may cause many different types of symptoms
    • may produce nausea, vomiting  enterotoxins
  • Endotoxins
    • found in Gram negative bacteria
• Adhesion factors
  • allows the pathogen to attach and colonize
  • this is a passive process
  • site specific, cell specific or nonspecific

Categories of Virulence Factors

• Evasive factors
  • mechanisms which allow pathogens to avoid the host’s defenses
  • capsules, slime, surface proteins, mucous layers
• Invasive factors
  • facilitates the penetration of anatomic barriers
  • enzymes; any combination of factors that may cause tissue damage to facilitate penetration

Question

• Is the following statement true or false?
• The symptoms of an infection are always obvious and apparent.

Answer

• False
• Rationale: Symptoms may be covert or nonspecific in presentation.

Criteria for Diagnosis of an Infectious Disease

• The recovery of a probable pathogen or evidence of its presence from the infected sites of a diseased host
• AND
• Accurate documentation of clinical signs and symptoms (symptomatology) compatible with an infectious process

Techniques for Laboratory Diagnosis of an Infectious Agent

• Culture—the propagation of a microorganism outside of the body usually on or in artificial growth media such as agar plates or in broth.
  • bacteria: identification based on microscopic appearance, Gram stain reaction, shape, texture and color of the colonies or biochemical reactions
  • pathogens such as Chlamydiaceae, Rickettsiaceae, and all human viruses are obligate intracellular organisms and require cell culture
• Serology or detection of characteristic antigens
  • Helpful for organisms that are difficult to culture
  • M. leprae (leprosy) and T. pallidum (syphilis) do not grow in culture—identified by serology
  • Labeled antibodies are useful to identify specific antigens
• Genomic sequences or metabolites produced by the pathogen
  • DNA or RNA sequences may be unique to a single agent
  • DNA probe hybridization
  • polymerase chain reaction
  • real-time PCR includes a fluorescence-labeled probe that specifically binds a target DNA

Case Study Question 3

• Jason’s nurse practitioner ordered serological tests.
• How would antibody titers assist the him in confirming his diagnosis?

Types of Antimicrobial Agents

• Anticipate what each of these do:
  • Antibacterial agents
  • Antiviral agents
  • Antifungal agents
  • Antiparasitic agents
• How do they work?

Antibiotic Mechanisms

• Interference with a specific step in bacterial cell wall synthesis
  • ex: penicillin
• Inhibition of bacterial protein synthesis
  • ex: vancomycin
• Interruption of bacterial nucleic acid synthesis
  • ex: ciprofloxin
• Interference with normal bacterial metabolism
  • ex: sulfaziazine
• These should not be new concepts!!!

Classification of Antibiotic Action (Objective 6)

• Bactericidal
  • causes irreversible and lethal damage to the bacterial pathogen
  • -cide  to kill
• Bacteriostatic
  • inhibitory effects on bacterial growth are reversed when the agent is eliminated; depends on other assistance such as phagocytosis to kill bacteria
  • Competent immune system is required
  • -static  still
• These should not be new concepts!!!

Classification and Target Site of Antibacterial Agents

• Cell Wall
  • Penicillins
  • Cephalosporins
  • Monobactams
• Ribosomes
  • Aminoglycosides
  • Tetracyclines
  • Macrolides
  • Glycopeptides
• DNA Synthesis
  • Quinolones
• Folic Acid Synthesis
  • Sulfonamides

Drug Resistance

• Bacterial resistance mechanisms
  • Inactivate antibiotics
  • Genetically alter antibiotic binding sites
  • Bypass antibiotic activity
  • Changes in the bacterial cell wall
• Antiviral resistance mechanisms
  • Nucleoside analogs
  • Protease inhibitors
• Need for combination or alternating therapy with multiple antiretroviral agents

Intravenous Immunoglobulin and Cytokine Therapy

• Supplementing or stimulating the host’s immune response so that the spread of a pathogen is limited or reversed
• Pathogen-specific antibodies given to the patient as an infusion to facilitate neutralization, phagocytosis, and clearance of infectious agents above and beyond the capabilities of the diseased host

Nonpharmacological Intervention

• Surgical interventions
  • Providing access to an infected site by antimicrobial agents (incision and drainage of an abscess)
  • Cleaning of the site (debridement)
  • Removing infected organs or tissue (e.g., appendectomy).

Question

• Is the following statement true or false?
• Surgical therapy is used in tandem with antibiotic treatment in some cases of severe infection.

Answer

• True

BIOTERRORISM

• First known outbreak: October 2001 (after 9/11/2001 attack)
• Contaminated envelopes delivered by US Postal Service
• Bacillus anthracis  Anthrax
• Pathogens categorized in three levels based risk of use, transmissibility, invasiveness and mortality rate
• Aided by ease of international travel
• Examples of diseases of recent concern (not necessarily bioterrorism threats)
  • Sever Acute Respiratory Syndrome (SARS)
  • West Nile Virus (WNV)
  • Ebola

Weapons of Bioterrorism – How could these be spread?

• Category A Agents
  • Plague
  • Tularemia
  • Smallpox
  • Hemorrhagic fever viruses
• Category B Agents
  • Agents of food-borne and water-borne diseases
  • Agents of zoonotic infections
  • Viral encephalitides
  • Toxins from castor bean (Ricin—remember the final episode of Breaking Bad?)
• Category C Agents
  • Mycobacterium tuberculosis
  • Nipah virus and hantavirus
  • Tick-borne and Yellow fever viruses
  • Cryptosporidium parvum

Age Related Issues

• Geriatrics
  • Aging increases the effects of exposure to human papillomavirus (HPV), hepatitie B (HepB), and Epstein-Barr virus (EBV).
• Children
  • Increased risk due to immaturity of immune system
  • VACCINES reduce illness
  • Rashes are common – helpful in diagnosis of certain illness
  • Fever common with illness
  • Neonates may not have fever or may by hypothermic (Remember Module 01?)

Case Study Answers

• 1.West Nile virus has a single-stranded RNA genome. How does this virus replicate? In general terms, what are the various effects viruses can have on host cells? Viruses have either a single DNA or RNA strand. In order to replicate, they require the genetic material of a host and cannot replicate outside of a living cell. Once in the host cell, they may replicate and migrate from the cell.
• 2. When Jason was feeling at his worst, he had extreme malaise, vomiting, and diarrhea. What stage of the illness was he experiencing at that time? What are the physiological mechanisms that give rise to the signs and symptoms of infectious illness? When Jason was feeling at his worst, he was experiencing the acute phase of the illness. At this time, there is rapid proliferation and spread of the pathogen within the body. Toxic by-products of microbial metabolism and cell lysis contribute to the specific signs and symptoms of the invading pathogen. The host’s immune response generates inflammation and tissue damage, further adding to the clinical presentation.
• 3. Jason’s nurse practitioner ordered serological tests. How would antibody titers assist him in confirming his diagnosis? Antibody titers (or levels) indicate the presence of infection. Certain titers are elevated during the acute phase of a specific illness and tend to decline during convalescence.