Flashcards in toxigenic bacteria Deck (34):
compare Corynebacterium diphtheriae and Bordetella pertussis
In both cases, the primary site of infection is the upper respiratory tract, but the major manifestations of the infections are the result of the production of potent exotoxins that have similar enzymatic mechanisms of action at the molecular level. These toxins are components of extremely important vaccines.
Lab Diagnosis of C. diphtheria
Requires demonstration of toxin production by the isolate. Immunoprecipitation and PCR detection of tox gene. Cultures are obtained from the throat and/or any skin lesions in the case of cutaneous diphtheria. Can take at least 5 days
pleomorphic (occurring in various distinct forms), gram-positive bacilli. often appear as rods clubbed at one or both ends.
Clinical diagnosis of C. diphtheria
diagnosis is usually made on clinical grounds. Treatment (antitoxin and antibiotics) is administered before a final laboratory diagnosis is made bcause antibodies cannot reverse the effects of the toxin once it is bound to the eukaryotic cell receptor of the toxin, so the sooner the unbound toxin is neutralized the less likely it is to cause damage.
which form of diphtheria is more contagious
B. pertussis structure
Gram-negative coccobacillus grows very slowly (small colonies in 3-5 days)
B. pertussis diagnosis
A nasopharyngeal (NP) aspirate (saline flush) or a nasopharyngeal swab is collected. The organism is most frequently recovered in the catarrhal or very early paroxysmal stages. The organism is extremely difficult to recover past the catarrhal stage. Culture is the Gold standard (100% specificity)- tkes 3-4 days. NO testing for toxin. Presently, a PCR based test is increasingly being used for diagnosis
During what time is pertussis best diagnosed
PCR should be tested from NP specimens taken at 0-3 weeks following cough onset, but may provide accurate results for up to 4 weeks of cough in infants or unvaccinated persons. After the fourth week of cough, the amount of bacterial DNA rapidly diminishes, which increases the risk of obtaining false-negative results.
Diphtheria toxin MOA
Cleaved by trypsin-like enzymes > releases active fragment A > Fragment B and hydrophobic domain help deliver fragment A to epidermal growth factor precursor then cytoplasm > Fragment A ADP-ribosylates Elongation factor-2 (EF-2) >EF-2 cant function in chain elongation so protein synthesis stops. Targt cells die (cardiac), kidney and peripheral nerves are damaged, heart stops
Pertussis toxin MOA
The A toxin ADP-ribosylates the inhibitory subunit of adenylyl cyclase of eukaryotic cell > adenylyl cyclase is turned on > increased cAMP. Pertussis toxin does NOT kill cell like diphtheria, but the full MOA is unknown
virulence factors for diphtheria
diphtheria toxin is only virulence factor
virulence factors for pertussis
1. pertussis toxin. 2. tracheal cytotoxin- part of the peptidoglycan, destroys ciliated epithelial cells in upper respiratory tract. 3. Adenylyl cylase toxin- affects macrophage trafficking. 4. Filametous hemagglutinin (FHA)- attachment to ciliated respiratory epithelial cells
regulation of diphteria toxin
regulated by iron. , increased amounts of iron in the environment (>10µM) will shut off toxin synthesis while <1µM will lead to increased expression. a dead eukaryotic cell gives up its iron more readily than a live cell, which is required for bacterial growth. Also requires tox gene from bacteriophage
regulation of pertussis toxin
VIR gene regulates most of the pertussis virulence factors.
membranous nasopharyngitis and/or obstructive laryngotracheitis plus low-grade fever and gradual onset of manifestation during 1 to 2 days. Bull neck. Cutaneous diphtheria common in temperate climates. Toxin production affects heart, peripheral nerves and kidneys.
Organisms that cuase Cutaneous Diphtheria and Diphtheria-like infections
toxigenic Corynebacterium ulcerans carried by domestic and wild animals. Some of these strains carry a bacteriophage, which has the gene encoding diphtheria toxin. Treated like diphtheria
Who gets whooping cough
Mainly affects infants but adults can be asymptomatic carriers or, they may have mild disease that is unrecognized as Whooping Cough.You are NOT immune for life if you received the pertussis vaccine, but the disease is generally milder in persons who were immunized during their childhood
stages of whooping cough
(i) Catarrhal stage - inflammation of mucous membrane with a free discharge - resembles minor respiratory illness, highly communicable, dry cough. (ii) Paroxysmal stage - 1-6 weeks - sudden recurrence or intensification of symptoms, spasms or seizures & whoop. NOTE: in infants (less than 6 mo) adolescents and adults, the whoop or cough paroxysm will likely be considerably diminished or absent. (iii) Convalescent stage - 7-10 days, or up to several months. decreasing symptoms (cough) but, they may last for months.
Pertussis secondary complications
secondary viral and bacterial infections occur. Possible complications also include seizures and neurological damage from hypoxia that occurs during coughing seizures. cerebral hemorrhage. Also, in contrast to C. diphtheriae, Bordetella pertussis is known to produce invasive infection, particularly in the lung. Many infants with pertussis ultimately die of pneumonia.
Where does pertussis infect
has a predilection for ciliated epithelial cells. Tracheal epithelial cells are heavily colonized.
Which age range is the largest growing group for pertussis infections
adolescents and adults
Natural immunity wanes after 15 years. Immunity after immunization also wanes
Equine antitoxin for all, and used immediately ( do not wait for labs). Erythromycin is added to prevent spread (not a substitute for antitoxin). Penicillin can also be used. Close contacts should be vaccinated (toxoid) and given antibiotics.
how do you get diphtheria antitoxin
Call State Department of Health & CDC
NO antitoxin therapy available. Antimicrobials (erythromycin) given early in the catarrhal stage may mitigate the symptoms of this disease. After paroxysms are established, antimicrobials have no effect on the course of illness and are given to limit spread of the organisms to others. This fact illustrates the toxin-mediated nature of the disease.
Why are antibiotics used for diphtheria and pertussis
while these agents have no direct effect on the toxins, Antibiotics: (i) can eliminate carriage and subsequent transmission of these organism (ii) reduce the bacterial load that is producing the toxins, thereby they may reduce the severity of the disease and (iii) are critical to prophylactic treatment of persons who have been in contact with someone who has the disease.
List the antigens for diphtheria and pertussis that elicit immune responses
Diphtheria: the toxin. Pertussis: toxin plus other antigens like adenylyl cyclase, FHA,
describe the DPT vaccine
The vaccine formerly used to protect against Diphtheria, Whooping Cough and tetanus. Trivalent: Diphtheria toxoid (non-toxic derivative of toxin), tetanus toxoid, and Merthiolate, heat, or formalin-killed cells from fully virulent (phase I) B. pertussis
Describe the tetramune vaccine
DPaT plus H. flu type B
efficacy/safety of DPT vaccine
The diphtheria toxoid and the tetanus toxoid portion part of the vaccine are perfect. The pertussis component was not. it was made of Merthiolate (which contains mercury) killed virulent B. pertussis (whole cell). This method worked, but side effects are observed. A new acellular pertussis vaccine was created with less adverse events, containing purified antigenic pertussis.
describe the DTaP vaccines
contain Diphtheria toxoid (non-toxic derivative of toxin), tetanus toxoid, and accelular pertussis. ACEL-IMUNE® and Tripedia® ---have now been licensed for the past 8-10 years for children 6 weeks- 6 years. Tripedia is licensed for the initial 4 doses and ACEL-IMUNE® for all 5 doses. Infanrix is also licensed for first four doses.
Tdap vaccination during pregnancy
The CDC now strongly recommends that pregnant women be vaccinated with Tdap during their third trimester even if they have been previously vaccinated. Also, cocooning (vaccinating those around the new infant) is recommended
List the available vaccines with pertussis component
• DTaP: Diphtheria-Tetanus-acellular Pertussis vaccine (commercial name Daptacel®)
• DTaP in combination with Haemophilus influenzae type b (Hib) vaccine
• DTaP in combination with hepatitis B and inactivated polio vaccines
• Tdap: Diphtheria-Tetanus-acellular Pertussis vaccine (commercial name Adacel®)