INTRODUCTION TO INFECTIOUS DISEASES

INTRODUCTION TO INFECTIOUS DISEASES
PAUL A. GULIG, PH.D.

April 2, 8:30, 9:30 AM
Office - R1-250, 392-0050
Lab R1-144, 392-0682
email: [email protected]
1. Randall, a first year IDP student, went on a picnic at Crescent Beach. Before leaving for the beach he made chicken salad sandwiches, which sat in the hot car for five hours before being eaten. The next afternoon he had nausea, diarrhea, and mild fever, which persisted for three days, just long enough to ruin the condo rental! Symptoms resolved by the time he returned to school.
Diagnosis

Treatment

Keys
1. Randall, a first year IDP student, went on a picnic at Crescent Beach. Before leaving for the beach he made chicken salad sandwiches, which sat in the hot car for five hours before being eaten. The next afternoon he had nausea, diarrhea, and mild fever, which persisted for three days, just long enough to ruin the condo rental! Symptoms resolved by the time he returned to school.
Diagnosis – Salmonella gastroenteritis

Treatment - Symptomatic

Keys – Poor food preparation, bacterial invasion, intercellular communication
2. Marsha, another IDP student, went on a picnic at Manatee Springs. She ate some potato salad that had sat in on the picnic table while she was snorkeling. Five hours later, she had severe, profuse vomiting, followed by some diarrhea. It resolved in a day.
Diagnosis

Treatment

Keys
2. Marsha, another IDP student, went on a picnic at Manatee Springs. She ate some potato salad that had sat in on the picnic table while she was snorkeling. Five hours later, she had severe, profuse vomiting, followed by some diarrhea. It resolved in a day.
Diagnosis – Staphylococcal food poisoning (intoxication)

Treatment - Symptomatic

Keys – Poor food preparation, toxin-mediated damage
3. Ann, a single 35 year old woman from Miami met a guy at a bar in South Beach. After having a few drinks, they engaged in wild sex. She experienced mild, flu-like symptoms a couple of weeks afterward. One year later on giving blood, she was informed she was HIV-positive. Despite treatment with newest combination HAART therapy, she developed protracted, watery diarrhea that could not be treated. The diagnosis was made by observing oocysts in her stool. She ultimately succumbed to her intestinal ailments. None of here friends had ever experienced, nor ever would, her intestinal disease, although they encountered the agent frequently.
Diagnosis

Treatment

Keys
3. Ann, a single 35 year old woman from Miami met a guy at a bar in South Beach. After having a few drinks, they engaged in wild sex. One year later on giving blood, she was informed she was HIV-positive. Despite treatment with newest combination HAART therapy, she developed protracted, watery diarrhea that could not be treated. The diagnosis was made by observing oocysts in her stool. She ultimately succumbed to her intestinal ailments. None of here friends had ever experienced, nor ever would, her intestinal disease, although they encountered the agent frequently.
Diagnosis – AIDS + Cryptosporidium parvum diarrhea

Treatment – HAART, no cure for Crypto

Keys – Viral mediated immunodeficiency, opportunistic infection
4. Alice another graduate student from the IDP traveled up North to visit her family in Rochester, NY for spring break. It was still very cold. The first day home, she went to a movie. The person sitting next to her had a “cold” and was sneezing, coughing, and blowing her nose. Two days later, Alice had high fever, sore throat, respiratory congestion, aches, pains, and chills. It lasted for the rest of break. When Alice returned to class, with some residual sneezing and coughing, she gave the disease to all of her friends in class.
Diagnosis

Treatment

Keys
4. Alice another graduate student from the IDP traveled up North to visit her family in Rochester, NY for spring break. It was still very cold. The first day home, she went to a movie. The person sitting next to her had a “cold” and was sneezing, coughing, and blowing her nose. Two days later, Alice had high fever, sore throat, respiratory congestion, aches, pains, and chills. It lasted for the rest of break. When Alice returned to class, with some residual sneezing and coughing, she gave the disease to all of her friends in class.
Diagnosis - Influenza

Treatment – Amantidine (early), Symptomatic

Keys – Viral respiratory infection, Host-host spreading
5. Brad, a 35 year old investment banker went hiking in the Rocky Mountains of Colorado. During his hiking trip he experienced severe watery diarrhea with gas and pain. He just drank extra fluid to make up for the fluid loss from diarrhea. The diarrhea did not resolve for more than two weeks after returning to New York City.
Diagnosis

Treatment

Keys
5. Brad, a 35 year old investment banker went hiking in the Rocky Mountains of Colorado. During his hiking trip he experienced severe watery diarrhea with gas and pain. He just drank extra fluid to make up for the fluid loss from diarrhea. The diarrhea did not resolve for more than two weeks after returning to New York City.
Diagnosis – Giardia lamblia diarrhea

Treatment – Anti-protozoals, symptomatic

Keys – Protozoal, zoonotic infection
6. Mary, an undergraduate student at U.F., had a bad cold. She went to the student clinic demanding antibiotics. After some resistance, they gave in to get rid of her. Three days later she experienced very severe irritation of the genital tract with redness, white plaque-like material, itching, and inflammation.
Diagnosis

Treatment

Keys
6. Mary, an undergraduate student at U.F., had a bad cold. She went to the student clinic demanding antibiotics. After some resistance, they gave in to get rid of her. Three days later she experienced very severe irritation of the genital tract with redness, white plaque-like material, itching, and inflammation.
Diagnosis – Candida albicans (yeast) infection

Treatment – Anti-fungals

Keys – Post antibiotic infection, normal flora, host response/inflammation
INTRODUCTION TO INFECTIOUS DISEASES
I. Wide variety of diseases with infectious causes
A. Severity: self-limiting vs. lethal

B. Time course: acute vs. chronic vs. latent
C. Where: any organ system

D. From: the environment or people or animals

E. Highly contagious vs. non-transmissible

F. Relationship with the infectious agent: infection vs. non-infection (toxin only)
II. Wide variety of microorganisms that can cause infectious disease in humans

A. viruses - parasitic nucleic acid
1. RNA vs. DNA genomes
2. enveloped vs. non-enveloped

II. Wide variety of microorganisms that can cause infectious disease in humans

B. bacteria - prokaryotic
1. cell wall: gram-positive vs. gram- negative vs. acid-fast
2. physiology: aerobes vs. anaerobes

II. Wide variety of microorganisms that can cause infectious disease in humans

C. fungi - eukaryotic
- yeasts vs. molds
II. Wide variety of microorganisms that can cause infectious disease in humans

D. protozoans- eukaryotic
- unicellular organisms with complex life cycles
II. Wide variety of microorganisms that can cause infectious disease in humans

E. worms - animals
- large organisms with complex life cycles
III. Microbial Pathogenesis

Infectious disease usually constitutes a cycle of biological interactions.

Intervention + preventing ≠ physician.

Understanding pathogenesis  intervention + prevention other than antibiotics or vaccines.
A. Definitions and concepts

1. Disease - damage caused by presence of microorganisms or their products

2. Pathogen - any organism that has the potential to cause disease

a. overt pathogens - a high probability of causing disease in an otherwise healthy host

b. opportunistic pathogens have a low probability and usually require a debilitated or compromised host
A. Definitions and concepts

3. Normal flora - organisms that are found in a significant portion of the healthy population; may still have the potential to cause disease (i.e., some pathogens are normal flora)

4. Infection - presence of bacteria in or on the body (note that some use this term synonymously with disease)

5. Colonization - presence of microorganisms at a site (some infer no damage)
B. Functions/stages of pathogens/disease

1. Encounter

a. Exogenous vs. endogenous infection and normal flora

i. Exogenous - disease initiated shortly after encounter, no stable interaction

ii. Endogenous - disease initiated after long-term stable relationship
B. Functions/stages of pathogens/disease

b. sources: food, water, air, body fluids, insects, animals, fomites (things)

c. Is there a reservoir in other animals or in the environment?

d. Can we eliminate the source or reservoir?
2. Entry - where in/on the body do we initially contact the microbes

a. surface of skin

b. mucosal membrane open to outside
i. ingestion
ii. inhalation
iii. sex

c. direct inoculation (trauma, bite, injection, surgery)
2. Entry - where in/on the body do we initially contact the microbes

d. virulence function – adherence

i. to infect a mucosal surface or tract bathed with moving fluid, microbes must stick or be washed away

ii. specific ligand-receptor interactions - not glue
3. Spread - movement from surface through tissues and body

a. not all microbes spread to cause disease

b. microbes cannot penetrate intact skin, require macro or microlesions

c. mucosal surface is usually first barrier


3. Spread - virulence functions
i. cellular invasion - invading into host cells to become intracellular

professional phagocytes (macrophages and PMN) by phagocytosis

non-professional phagocytes (epithelial cells, endothelial cells, hepatocytes, etc.) by microbial mediated endocytosis

some microbes escape the phagosome into the cytoplasm
Spread

ii. tissue invasion - through tissues, either through cells or between cells
- degrade extracellular matrix
- disrupt tight junctions

e. use of host cells as vehicles to move through blood or lymph (intracellular pathogens)
4. Multiplication
a. inoculum is not sufficient, need increase

b. nutritional environments in the body
i. intestinal lumen, blood, urine
ii. intracellular bacteria- cytoplasm vs. phagolysosome

c. incubation period
how long it takes the inoculum to result in clinical damage
5. Evasion of host defenses (later lecture)

*consider where the microbes are and which defenses they will encounter

a. Complement -beyond mucosal surface
b. Phagocytes - beyond mucosal surface
EXTRACELLULAR vs. INTRACELLULAR c. Antibodies
d. Cell-mediated immunity
e. Latency
i. dormant in host
ii. many viruses (e.g., Herpes)
6. Damage

a. cytotoxicity (kill host cells)
i. from outside - toxins
ii. from inside - intracellular growth

b. pharmacology/physiology (alter host cell function) - toxins
6. Damage

c. host immune/inflammatory response (host causes damage to itself)

i. nonspecific: inflammation, abscess, prostaglandins, cytokines

ii. specific immune response: antibodies, cell-mediated
d. TOXINS

i. Endotoxin vs. Exotoxin

d. TOXINS
ii. Endotoxin (LPS) from gram-negative bacteria only

- damage - macrophages producing cytokines (TNF-α, IL-1, IL-6)
d. TOXINS

iii. Exotoxins (proteins)

several have A-B motif

A=active portion
B=binding portion
iii. Exotoxins (proteins)

lytic (pores or lipase activity)







cytotoxic (kill host cells by altering functions, e.g., protein synthesis)
iii. Exotoxins (proteins)

pharmacological (alter host cell function, e.g., cAMP levels)

extracellular enzymes (degrade extracellular matrix, e.g., protease, DNase, hyaluronidase)
iii. Exotoxins (proteins)

superantigens (stimulate host immune response in antigen-independent manner resulting in cytokine cascade - similar to endotoxin)
7. Spread to new host

a. completes the cycle to lead to new encounter virulence step 1

b. not all pathogens spread to new human host (e.g., Legionella pneumophila)

c. not all pathogens are contagious - humans may be dead end hosts
7. Spread to new host

d. most bacterial pathogens are contagious - some examples of how:
i. fecal-oral
ii. sexually transmitted
iii. droplet spread (respiration)
iv. skin-skin
v. fomites
vi. vertical - in utero, at birth