Describe the clinical picture of Diphtheria
Describe Corynebacterium diphtheriae, its morphologic, cultural characteristics and their normal habitat and life cycle..
Who are the susceptible hosts for
Corynebacterium diphtheriae The answer How does Corynebacterium diphtheriae get exposed to humans? The answer
Who are the susceptible hosts for Corynebacterium diphtheriae
How does Corynebacterium diphtheriae get exposed to humans?
How does Corynebacterium diphtheriae invade and spread in humans? Describe the pathogenic mechanisms. How do these organisms able to overcome human defenses?
Disease is caused by exotoxin which inhibits protein synthesis of eukaryotic cells
The exotoxin is absorbed into the blood stream and distributed, resulting in systemic complications
The diphtheria toxin also causes local destruction at the site of membrane formation.
The toxin contains a toxic A subunit (active toxin) and the receptor binding B subunit.
Fragment B attaches to cellular receptors and grants fragment A entrance into the cell, where it inhibits protein synthesis.
The B subunit (fragment) facilitates translocation of the A subunit from the phagosome to the cytosol, followed by separation, allowing full activity of the A subunit on its target protein elongation factor-2. EF-2 transfers polypeptidyl-transfer RNA from acceptor to donor sites on the ribosome of the host cell.
The A subunit catalyzes transfer of adenine ribose phosphate from NAD to EF-2 (ADP ribosylation), inactivating EF-2, and turning off protein synthesis, C. diphtheria toxin is able to inhibit protein synthesis of all eukaryotic cells.
Fragment A has the enzymatic activity
Describe the toxin gene of Corynebacterium diphtheriae
Gene for the diphtheria toxin is carried in genome of a bacteriophage.
C. diphtheria strains must contain a bacteriophage (beta-phage), acquired by transduction from other C. diphtheria strains, in order to express the toxin.
The phage must be Iysogenized following transduction.
The toxin expression (fox gene) is regulated by a chromosomally encoded repressor protein (DtxR) when iron is limited.
Incubation period is 2-5 days
Diphtheria is the result of local and systemic effects of diphtheria toxin.
Diphtheria toxin can circulate in blood and affect heart and CNS systems.
Myocarditis, with cardiac enlargement, circulatory collapse, heart failure, AV blocks and dysrhythmias.
What is the natural history of untreated infection with Corynebacterium diphtheriae?
How can we diagnose diphtheria?
Initial diagnosis is clinical
No rapid lab test
Gram stain of throat not helpful
Organism can be cultured to confirm diagnosis.
Missed on routine cultures.
Notify the lab of possible diagnosis
Toxin production of cultured strains can be performed by immunodiffusion.
Serum for antibodies to diphtheria toxin
Other useful evaluations
EKG and Cardiac enzymes to detect myocarditis
CXR: Hyperinflation, subglottic narrowing
C. diphtheriae antitoxin is given promptly to neutralize free toxin.
Contact CDC for antitoxin and instructions on use.
Do not wait for culture confirmation.
Antibodies produced against the toxin in natural infection.
Treat with toxin to neutralize free toxin before it binds to cells.
The organism itself can be treated with penicillin, cephalosporins, and erythromycin.
Notify the health department
Clinical diphtheria does not confer immunity, hence active immunization with diphtheria toxoid should be provided during convalescence.
Bronchodilators if needed.
Watch for respiratory obstruction and take necessary steps.
Watch for myocarditis and mange appropriately
What are the clinical infections of other species of Corynebacterium?
Describe the clinical picture of gas gangrene.
Usually a complication of a crushing injury
Incubation period is fewer than 3 days with rapid onset of symptoms
Infectious disease emergency
Rapid onset of myonecrosis
Mortality in traumatic gas gangrene is >25%
Progression of toxemia and shock is rapid.
Describe clostridium welchii, its morphologic, cultural characteristics and their normal habitat and life cycle..
Normally found in soil and GI tract and widely distributed in the environment
Large gram positive bacilli, pleomorphic
Spore forming bacilli
Exotoxin producing Clostridial species
Thrives in the absence of oxygen
Breed in damaged tissue
Who are the susceptible hosts for gas gangrene?
Traumatic or post Surgical gas gangrene (Clostridium perfringens)
Contamination may also occur from patient's faecal flora
Immune compromised host
Spontaneous gas gangrene (Clostridium septicum)
Associated with hematological and GI malignancies
Drug abuse is a risk factor
How does clostridium welchii gain access to humans?
Direct inoculation into a open wounds due to trauma, bullet wounds, and multiply along with facultative co infecting or colonizing organisms.
Gas gangrene is usually a mixed infection aerobic and anaerobic.
Condition consisting of low oxidation reduction potential are necessary for C. perfringens sporulation, followed by rapid division.
Presumably, the other facultative organisms assist in reducing the oxidative-reductive potential.
How does clostridium welchii invades and spreads in humans? How do these organisms able to overcome human defenses?
Exotoxin, not bacterial proliferation, is responsible for rapid spread of infection. Exotoxin causes muscle destruction and creates an anaerobic environment conducive to further bacilli growth.
alpha toxin is produced by the growing C. perfringens, which kill muscle cells and inflammatory cells, alpha toxin's biologic activity is a lecithinase, causing necrosis, and hemolysis.
Beta and epsilon toxins are also necrotizing, and considered major toxins. Subsequently, new necrotic areas will foster growth and spread of the organisms.
Carbohydrate fermentation by C. perfringens is responsible for the gas production (crepitus).
Secondary toxicity. Products of tissue breakdown cause secondary toxicity
What are the human defenses for clostridium welchii infection?
WBC's try to attack these organisms.
We have no defense against toxins
What is the end result of this battle between organisms and humans. Describe the pathological consequences of this battle? What are the local manifestations of gas gangrene?
Fowl-smelling serosanguinous discharge
Ischemic appearing muscle tissue
Gas in soft tissue within fascial planes
What are the systemic manifestations of gas gangrene?
Death occurs within about two days if the condition is not treated. Often have shock, jaundice, hemolysis and renal failure along with local findings.
Systemic secondary to toxins
Fever or hypothermia.
hypothermia, or just absence of fever can predominate the clinical course.
frequently out of proportion to elevation of temperature
Altered level of consciousness
Coagulopathy and thrombocytopenia
Myoglobinemia and Myoglobinuria
What is the natural history of untreated gas gangrene?
Death occurs within about two days if the condition is not treated.
Often have shock, jaundice, hemolysis and renal failure along with local findings.
How do we diagnose gas gangrne?
Rapid diagnosis is by
Gram stain of bullae fluid or muscle tissue:
Paucity of WBC with gram positive bacilli.
Inflammatory cells are killed along with muscle cells by alpha toxin.
Pathologic demonstration of myonecrosis :
Radiographs showing gas within fascial planes
CBC: Anemia hemolytic secondary to toxins
LFT: Liver dysfunction
Renal panel: Kidney dysfunction
ABG: Metabolic acidosis
Coagulation panel: Coagulopathy and thrombocytopenia
What is the therapeutic strategy for gas gangrene?
Emergency Surgical consult.
Treatment may include fasciotomy, debridement, or amputation.
Surgical debridement is the definitive treatment:
Hyperbaric oxygen: may be helpful.
Aggressive volume expansion
Treat mixed infection with Penicillin Sodium and Amino glycosides or Vancomycin.
How can you prevent occurrence of gas gangrene? How can you prevent it from spreading to others? How can you prevent its recurrence?
Appropriate wound care at the time of injury
removal of dead tissue
Prophylactic antibiotics: Benzyl penicillin
The organism is not contagious and does not spread from person to person.
No anti toxin
What are the other body sites where infections of clostridium welchii have been repotted?
Gall bladder with abdominal wall muscle involvement following surgery,
What are the other clinical infections of associated clostridium species?
Food poisoning: Botulism
.Describe Listeria monocytogene, its morphologic, cultural characteristics and their normal habitat and life cycle..
Describe succinctly the disease caused by Listeria monocytogene. What are the other clinical infections with these organisms?
What kinds of hosts are susceptible to infection
with Listeria monocytogene?
How does Listeria monocytogene gain access to
How does Listeria monocytogene invade and spread
What defenses humans have against Listeria
How does Listeria monocytogene able to overcome human defenses? What is the end result of this battle between organisms and humans. Describe the pathological consequences of this battle?
Listeria is able to manipulate host cell action (actin) to propel it into pseudopods that extend to adjacent host cells.
Thus, listeria can spread from cell to cell with minimal contact with the host immune system.
How do you diagnose infection with Listeria monocytogene?Diagnosis
Other useful evaluations
What will be your therapeutic strategy for
infections due to Listeria monocytogene?
How can you prevent its occurrence of Listeria monocytogene infections? How can you prevent it from spreading to others? How can you prevent its recurrence?The answer
What are the other clinical infections with Listeria monocytogene?
Describe the source and morphology of Neisseria meningitides
Gram negative diplococci with flattened sides "kidney bean shaped", polysaccharide capsule present, not readily seen, but serves as the basis for serotyping.
Capsules and pili
Describe the cultural characteristics Neisseria meningitides
Fastidious species require enriched media (chocolate agar)
Meningococcus grows as a transparent, non-pigmented, non-hemolytic colony under conditions of moisture and 5-10% C02. Mediums include blood agar, trypticase soy agar, supplemented chocolate agar, and Mueller Hinton agar.
Growth enhanced in CO2
Describe the structural characteristics Neisseria meningitides
Endotoxic lipopolysaccharide complexed with protein in outer membrane
9 serogroups. A,B,C,Y,W-135 most important
immunogenic except Group B
Describe the meningitis caused by Neisseria meningitides
What are the consequences of invasion of meninges by Neisseria meningitides. Describe the pathological consequences?
This invasion of meninges by this organism results in
Increased permeability of the blood brain barrier
Exudates form extending throughout the CSF, particularly to basal cisterns
Damaging cranial nerves
Obliterating CSF pathways (obstructive hydrocephalus)
Impair cerebral blood flow:
Change of mental status and decreasing alertness.
Intracranial pressure increases
Brain edema progresses
What are the symptoms from meningitis?
What are the physical findings of meningitis?
What kinds of hosts are susceptible to infection with Neisseria meningitides?
How does Neisseria meningitides gain access to humans?The answer
Nasopharynx (of a carrier or the one with disease) is a common source
Respiratory droplets requiring close contact and susceptibility (lack of antibody).
The majority of persons exposed do not contract the disease, likely due to the limited time exposure.
The virulence of the strain, host defense and their interactions determine whether the disease is going to follow.
How does Neisseria meningitides invade and spread in humans? What is the end result of this battle between Neisseria meningitides and humans.
pilus mediated attachment- microvilli of nonciliated nasopharyngeal cells
Transverse cell in vesicle to submucosa
Damage ciliated cells
Blood stream survival enhanced by antiphagocytic polysaccharide capsule
Meningeal seeding follows bacteremia.
Bacterial cell wall components initiate a cascade of complement and cytokine mediated events.
CNS inflammation generated by cell wall peptidoglycan
LPS, other bacterial products and its mediated by IL-1 and TNF (host response)
Once in CSF, the paucity of antibodies, complement components, and white blood cells allow the bacterial infection to flourish.
Endotoxin mediated activation of complement leading to shock and hemorrhage
What defenses humans have against Neisseria meningitides?
How does Neisseria meningitides able to overcome human defenses?
Polysaccharide capsule resists neutrophil phagocytosis as well as complement mediated bactericidal activity.
How do you diagnose infection with Neisseria meningitides?
What will be your therapeutic strategy for Neisseria meningitides?
How can you prevent its occurrence of Neisseria meningitides? How can you prevent it from spreading to others? How can you prevent its recurrence?Prevention
What are the endotoxin mediated events of Neisseria meningitides?
Fulminant meningococcal disease, manifested by endotoxin from the N. meningitides cell wall are
DIC (disseminated intravascular coagulation)
Bilateral hemorrhagic destruction of the adrenal glands (Waterhouse-Friderichsen syndrome) may occur.