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INFECTIOUS DISEASE PATHOLOGY

Lecture 3

Prepared and presented by
Marc Imhotep Cray, M.D.

Scanning electron micrograph of Staphylococcus aureus bound to the surface of a human neutrophil. “Granulocytic Phagocytes,” by Frank R. DeLeo and William M. Nauseef.
Key Concepts
 These organisms are infrequent causes of human diseases in developed
countries
 Diseases occur more frequently in developing countries
 Some of these bacteria are highly pathogenic

Summary of Virulence Factors of Aerobic Gram-positive Rods
Organism Virulence Factor
Bacillus anthracis Capsule of D-glutamic acid
2 exotoxins:
protective antigen (PA) + edema factor (EF) = edema toxin (ET)
PA + lethal factor (LF) = lethal toxin (LT)
Bacillus cereus Heat labile enterotoxin, Heat stable emetic toxin
Corynebacterium diphtheriae Diphtheria toxin
Listeria monocytogenes Listeriolysin O , Internalin
Marc Imhotep Cray, M.D.
Case 1
A 35-year-old rancher presents with complaints of an ulcerated lesion on
the back of his hand that has turned black and necrotic. Although the
lesion does not hurt, his hand has swelled and he has recently developed
a fever and headache. Questioning reveals that several of the patient’s
cattle have died recently from unknown causes.

Marc Imhotep Cray, M.D.
Cutaneous Anthrax
 Organism: Bacillus anthracis
 Physical Char: Gram-positive rod, end-to-end chains, forms endospores
 Disease: Anthrax
 Etio. and Epidem: Transmitted through contact with spores
 Primarily a disease of animals, human infection (zoonoses) can occur following
contact with infected animals or animal products (eg, hides)
 Spores may remain viable for years in environment
 Clinical Manifestations: Three forms of anthrax are recognized based on
site of inoculation
1. Cutaneous anthrax, most common form, causes a localized inflammatory black
necrotic lesion (eschar)
2. Inhalation anthrax is highly fatal and characterized by rapid and massive edema in
chest followed by cardiovascular shock
3. Gastrointestinal anthrax resulting from ingestion of spores is rare but also highly
fatal

Marc Imhotep Cray, M.D.
Cutaneous Anthrax cont.
Pathogenesis: Major virulence factors are edema toxin (EF + PA), lethal
toxin (LF + PA), and a capsule of D-glutamic acid
 PA binds anthrax toxin receptor on surface of host cells and facilitates translocation of
EF and LF into cell
 EF is an adenylate cyclase that increases intracellular cAMP, stimulating an efflux of
fluids and ions that results in edema
 LF is a mitogen-activated protein kinase kinase (MAPKK) protease that disrupts cell
signaling causing cell death and tissue necrosis
Treatment and Prevention Antibiotics such as ciprofloxacin, doxycycline,
and rifampin have been used for treatment
 Suspected exposures are often treated with a long course (60 days) of antibiotics
 A variety of antitoxin strategies are currently in development
 Vaccination with anthrax vaccine adsorbed (AVA) vaccine targets PA toxin subunit and is
given as 6 shots over 18 months with yearly boosters

Marc Imhotep Cray, M.D.
Case 2
One hour after dinning on sweet and sour pork and pork fried rice at a local
Chinese restaurant, an 18-year-old college freshman exhibits abdominal
discomfort and nausea and then begins vomiting. Her roommate suspects that it
is something she ate, and helps bring her to the campus health center. After
determining that the symptoms were not alcohol induced, she is treated
symptomatically.

Marc Imhotep Cray, M.D.
Food Poisoning
Organism: Bacillus cereus
Physical Char: Gram-positive rod, forms endospores.
 Disease: Food poisoning, eye infections, intravenous catheter
infections
Etio and Epidem: Food poisoning is by “intoxication” Spores
survive usual cooking temperatures and germinate when food is
left at room temperature
 bacteria produce two different toxins:
1. heat-labile enterotoxin
 associated with contaminated meats and vegetables
2. heat-stable emetic toxin
 heat-stable toxin is associated with fried rice
Marc Imhotep Cray, M.D.
Food Poisoning cont.
Clinical Findings: Food poisoning symptoms include watery diarrhea—which
can occur 6 to 24 hours after ingestion of contaminated meats, poultry, or
vegetables—and vomiting, which may occur 1 to 6 hours after ingestion of
contaminated fried rice
 Opportunistic manifestations include traumatic eye and intravenous
catheter-related infections
Pathogenesis:
 heat-labile toxin stimulates cellular adenylate cyclase, leading to an elevation of cAMP
and watery diarrhea
 heat-stable toxin stimulates vomiting through an unknown mechanism
Treatment and Prevention: Food poisoning is treated with fluid replacement
 Blood and eye infections often require vancomycin because of resistance to multiple
antibiotics
 Food poisoning can be prevented through proper food handling such as refrigeration
and heating foods above 56°C before eating (heat-labile toxin)
Marc Imhotep Cray, M.D.
Case 3
A 3-year-old boy is brought to the hospital with a sore throat, fever,
malaise, and difficulty breathing. Physical examination reveals the presence
of a gray membrane covering the pharynx. Questioning of the mother
reveals that the boy had not received any vaccinations.

Marc Imhotep Cray, M.D.
Diphtheria
Organism Corynebacterium diphtheriae
 Physical Characteristics: Gram-positive rod, pleomorphic
Disease: Diphtheria
 Etio and Epidem: Humans are natural host Transmission is by respiratory droplets
 Clinical Findings: A prominent feature of nasopharyngeal diphtheria is presence of a
pseudomembrane comprised of necrotic cells, fibrin, and bacteria pseudomembrane
serves as a platform for bacterial growth and toxin production Death can result from
mechanical obstruction of airway or by toxemia-induced myocardial and neurologic
damage
 Pathogenesis: major virulence factor is an exotoxin called diphtheria toxin diphtheria
toxin is an A-B toxin that ADP ribosylates translation elongation factor 2 (EF2) resulting
in shutdown of protein synthesis and cell death
 Treatment and Prevention Tx includes a combination of antitoxin administration and
antibiotics such as penicillin or erythromycin
 Diphtheria is effectively controlled by immunization with an inactivated toxin
(diphtheria toxoid)

Marc Imhotep Cray, M.D.
Case 4
A 45-year-old man presents to his oncologist with fever, headache, and stiff
neck. He has been undergoing chemotherapy for the last 4 months for
advanced-stage colon cancer. A lumbar puncture reveals numerous
neutrophils and gram-positive rods. He is admitted to the hospital and
started on IV ampicillin and gentamicin.

Marc Imhotep Cray, M.D.
Meningitis
 Organism: Listeria monocytogenes
 Phys. Char: Gram-positive rod, tumbling motility, growth at low temperatures.
 Disease: Listeriosis
 Etio and Epidem: Transmission is from ingestion of contaminated foods and through
person-to-person spread
 Food contamination is accentuated by organism’s ability of grow at refrigerator
temperatures
 Sources of infection include contaminated meats, cheese, milk, poultry, and seafood
 Person-to-person spread can occur through in utero infections, colonization of birth
canal, and nosocomial transmission by hospital workers
 Clinical Findings: There are three categories of listeriosis:
1. Perinatal listeriosis can manifest as meningitis, pneumonia, or septicemia, with severe cases
resulting in stillborn births, spontaneous abortion, or an overwhelming disease called
granulomatosis infantiseptica
2. Asymptomatic infections can occur in immune-competent adults including pregnant women
3. Adult bacterial meningitis caused by Listeria is rare in healthy adults but common in
individuals who are immunocompromised from cancer chemotherapy, transplants, or HIV
infection
Marc Imhotep Cray, M.D.
Meningitis (2)
 Pathogenesis: major pathogenic mechanism involves host cell invasion
 facilitated by two virulence factors, Internalin and listeriolysin O
o Internalin binds to host cells and promotes endocytosis
o Listeriolysin O is a pore forming toxin that allows organisms to escape from
endosome
 L monocytogenes replicates in cytoplasm and spreads to adjacent cells, thus escaping
humoral immune response
 Transplacental spread is mediated by invasion of placental endothelial cells from a
bacteremia in an asymptomatic pregnant woman
 Immunity is primarily cell-mediated
 Treatment and Prevention Listeria infections can be treated with a variety of
antibiotics including aminoglycosides, trimethoprim- sulfamethoxazole, and
ampicillin
 Infection control involves elimination of animal reservoirs, care in handling infants, and
early diagnosis and treatment of infected pregnant women

Marc Imhotep Cray, M.D.
THE END

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Sources and further study:
eLearning (IVMS Cloud)
 Infectious Disease
 Microbial biology & Immune System
 Rural Medicine Global Health (Focus on Ethiopia)

Textbooks:
 Ryan KJ and Ray CG Eds. Sherris Medical Microbiology, 5th Ed. New York: McGraw-Hill, 2010
 Carroll KC etal. Jawetz, Melnick, & Adelberg’s Medical Microbiology 27th Ed. New York:
McGraw-Hill, 2016

Marc Imhotep Cray, M.D. 15