1. Corynebacterium C. diphtheriae: causes diphtheria.
Other corynebacteria (coryneform) may cause opportunistic infections.
Gram-positive, irregularly-shaped rod. "Club shaped".
In stained smears, individual rods tend to lie parallel or at acute angles to one another (pallisades). Metachromatic granules (often near the poles) give the rod a beaded appearance.
Grow aerobically on most media.
Corynebacteria grow on Löffler's serum medium more readily than other respiratory pathogens, and show typical morphology in smears.
Non-motile; noncapsulate.

2. C. diphtheriae Pathogenesis and Immunity
C. diphtheriae occurs in the respiratory tract, in wounds, or on the skin of infected persons or normal carriers. It is spread by droplets or by direct contact.
Portal of entry: respiratory tract or skin abrasions.
Diphtheria bacilli colonize and grow on mucous membranes, and start to produce toxin, which is then absorbed into the mucous membranes, and even spread by the bloodstream.
Local toxigenic effects: elicit inflammatory response and necrosis of the faucial mucosa cells-- formation of "pseudo-membrane“ (composed of bacteria, lymphocytes, plasma cells, fibrin, and dead cells), causing respiratory obstruction.
Systemic toxigenic effects: necrosis in heart muscle, liver, kidneys and adrenals. Also produces neural damage.

3. C. diphtheriae Clinical Diseases Respiratory diphtheria
Incubation period: 2-6 days.
Inflammation begins in the respiratory tract, causing sore throat, exudative pharyngitis that develops into pseudomembrane, and low grade fever. Prostration and dyspnea soon follow, which may lead to suffocation if not promptly relieved by intubation or tracheotomy.
Damage to the heart causes irregular cardiac rhythm.
Visual disturbance, difficulty in swallowing and paralysis of the arms and legs also occur but usually resolve spontaneously.
Death may be due to asphyxia or heart failure.
Cutaneous diphtheria: mild (papule ulcer with grayish membrane) with little toxigenic effects. Stimulates antitoxin production.

4. C. diphtheriae Laboratory Diagnosis
Specific treatment should be given before the lab reports if the clinical picture strongly suggests diphtheria.
Specimens: swabs from the nose, throat or suspected lesions.
Gram's stain: beaded rods in typical arrangement (unreliable).
Culture: inoculate specimen onto a blood plate, a Löffler slant, and a tellurite plate. Identification: biochemical tests.
Toxigenicity test:
1. in vivo test: inject the culture into antitoxin-protected and unprotected guinea pigs subcutaneously.
2. Tissue culture neutralization assay.
3. in vitro test: immunodiffusion assay (Elek test ).
4. Detection of toxin gene by PCR.

5. C. diphtheriae Treatment
Treatment of diphtheria rests on prompt administration of antibiotics (penicillin, erythromycin) and diphtheria antitoxin.
Maintenance of an open airway.
Treatment of bacteremia or endocarditis must be guided by antibiotic susceptibility tests.

6. C. diphtheriae Prevention and Control
Humans are the only known reservoir of C. diphtheriae.
Diphtheria was mainly a disease of small children.
This organism is maintained in the oroparynx or skin of asymptomatic carriers.
The bacteria are spread directly from person to person.
To limit contact with diphtheria bacilli to a minimum, patients with diphtheria should be isolated.
Prophylactic antibiotic treatment to unimmunized contacts.

7. C. diphtheriae Prevention and Control
Active immunization in childhood with diphtheria toxoid yields antitoxin levels adequate until adulthood. All children must receive an initial course of immunizations and boosters.
Regular booster with Td (tetanus and diphtheria) toxoids are particularly important for adults who travel to developing countries.
Schick test can be used to test susceptibility of a person to diphtheria.
Toxoids for delayed absorption: Fluid toxoid absorbed onto aluminum hydroxide or aluminum phosphate. Usually combined with tetanus toxoid and/or pertussis vaccine (DPT vaccine).

8. Other Corynebacterium Species
They are ubiquitous in plants and animals. Many are found as part of human normal flora and may cause opportunistic infections, such as pneumonia, endocarditis, and soft tissue and bone infections, in immunocompromised patients.
C. jeikeium: sepsis, endocarditis, wound infections, foreign body infections.
C. urealyticum causes UT infections. It is a strong urease producer, infection of UT may lead to formation of stones.
C. ulcerans is closely related to C. diphtheriae. May cause diphtheria-like disease.
Resistant to many antibiotics. Treatment of bacteremia or endocarditis must be guided by antibiotic susceptibility tests.

9. Listeria and Erysipelothrix
L. monocytogenes: meningitis and bacteremia
E. rhusiopathiae: erysipeloid
Structure and Physiology
Small gram-positive coccobacilli, facultative anaerobic.
Motile at room temperature but not at 37 oC.
Grow on most conventional media in a wide pH range and cold temperatures.

10. L. monocytogenes Pathogenesis and Immunity
Widely distributed in nature (soil, water, vegetation, and the intestines of a variety of animals). Fecal carriage in healthy people: 1%-5%.
Human disease is restricted to neonates and the elderly, pregnant women, and immunocompromised patients (particularly those with defective cell-mediated immunity, such as AIDS patients).
Facultative intracellular pathogen. The intracellular survival and spread of the bacteria are critically important in pathogenesis and, therefore, cellular immunity is more important than humoral immunity in host defense against this organism.

11. L. monocytogenes Clinical Diseases Adults Neonates Healthy
Asymptomatic or mild influenza-like illness.
Gastrointestinal symptoms in some patients.
Immunocompromised
Meningitis (high risk: organ transplant patients, cancer patients, pregnant women)
Primary bacteremia: chills and fever; high fever and hypotension in severe cases. Maybe fatal.
Neonates
Early onset disease (acquired transplacentally in utero): granulomatosis infantiseptica, with disseminated abscesses and granulomas in multiple organs.
Late onset disease (acquired at or soon after birth): meningitis or meningoencephalitis with septicemia, similar to that caused by group B streptococci.

12. L. monocytogenes Laboratory Diagnosis Specimen: CSF and blood.
Gram stain: CSF typically show no Listeria because of the low bacterial concentration.
Culture
Listeria grows on most conventional media.
Selective media and cold enrichment are used for specimens contaminated with rapidly growing bacteria.
Hemolysis (b-) and motility in liquid or semisolid medium are useful for preliminary identification.
Identification
Biochemical and serological tests.

13. L. monocytogenes Treatment, Prevention, and Control
L. monocytogenes is resistant to multiple antibiotics (e.g., cephalosporin and tetracycline). Currently, penicillin or ampicillin, either alone or with gentamicin, is the treatment of choice.
Outbreaks have been associated with the consumption of contaminated milk, soft cheese, undercooked meat, unwashed raw vegetables, and cabbage. Refrigeration of contaminated food products permits the slow multiplication of the organisms to an infectious dose.
Because Listeria organisms are ubiquitous and most infections are sporadic, prevention and control are difficult. High risk people should avoid eating raw or partially cooked foods.

14. Erysipelothrix (Hair of red disease)
E. rhusiopathiae
Slender gram-positive, microaerophilic, with a tendency to form filaments. Form small, grayish a-hemolytic colonies after 2 to 3 days incubation.
Widely distributed in wild and domestic animals. Animal disease (particularly in swine) is widely recognized, but human disease is uncommon.
Causes zoonotic infections through an abrasion or wound:
Localized skin infection (erysipeloid): 1-4 day incubation; painful and pruritic, slowly spreading inflammatory skin lesions on the fingers or hands, violaceous with raised edge. Suppuration is uncommon.
Generalized (diffuse) cutaneous infection: rare and often associated with systemic manifestation.
Septicemia: uncommon and frequently associated with endocarditis.

15. Erysipelothrix Penicillin is the antibiotic of choice.
Specimen: full-thickness biopsy specimens or deep aspirates (because the bacteria locate only on deep tissues).
Culture: grow on most conventional media in the presence of 5%-10% CO2.
Identification
Motility- and catalase-negative.
Biochemical tests.
People at occupational risk (butchers, meat processors, farmers, poultry workers, fish handlers, and veterinarians) are prevented by use of gloves and other coverings on exposed skin.
Vaccination is used to control disease in swine.

17. Diphtheria toxin is an A-B toxin expressed from a temperate phage (b-phage) in the presence of low iron concentrations.
This toxin binds to receptors on the surface of many eukaryotic cells, particularly heart and nerve cells, and results in inhibition of polypeptide chain elongation by ribosylation of the elongation factor EF-2.
It can induce protective antibodies (antitoxin).
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18. Bull-neck appearance
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20. Internalins
Listeriolysin O
ActA
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21. 細菌名稱 診斷？ 疾病？症狀？ 如何造成疾病？（致病機制） 治療？ 預防？ A菌 B菌 型態 生長特性 生化反應 血清學反應
細菌本身：侵襲性（毒力因素？ ）；產毒力（毒素？ ）
宿主因素：抵抗力？ 易感因素？
如何感染：途徑？ 媒介？
抗生素？ （抗藥性？ ） ；抗毒素？ ；症狀治療？
環境及個人衛生？ 疫苗？ A菌 B菌