Corynebacterium

Corynebacterium diphtheriae

Epidemiology

• In immunized individuals, the rate is low: < 5 per 100,000.
• Remains endemic in certain parts of the world (Brazil, Nigeria, India, certain parts of the former Soviet Union)
• No racial or sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria predilection
• Can affect children and adults

Transmission

• Humans are the only known reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli.
• Airborne droplets Droplets Varicella-Zoster Virus/Chickenpox
• Direct contact with respiratory secretions
• Contact with skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions
• Can be transmitted by immunized and asymptomatic carriers Carriers The Cell: Cell Membrane

Virulence Virulence The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its virulence factors. Proteus factors

• Not an invasive organism
• Pathogenicity is based on diphtheria Diphtheria Diphtheria is an infectious disease caused by Corynebacterium diphtheriae that most often results in respiratory disease with membranous inflammation of the pharynx, sore throat, fever, swollen glands, and weakness. The hallmark sign is a sheet of thick, gray material covering the back of the throat. Diphtheria toxin (exotoxin):
  • Only produced if lysogenized by a β-bacteriophage
  • Has 2 subunits:
    • A—active
    • B—binding
  • B binds to the cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane and A enters the cell.
  • Ribosylation of elongation Elongation Polymerase Chain Reaction (PCR) factor (EF-2)
  • Inhibits protein synthesis Synthesis Polymerase Chain Reaction (PCR)
  • Causes cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death

Clinical presentation

Diphtheria Diphtheria Diphtheria is an infectious disease caused by Corynebacterium diphtheriae that most often results in respiratory disease with membranous inflammation of the pharynx, sore throat, fever, swollen glands, and weakness. The hallmark sign is a sheet of thick, gray material covering the back of the throat. Diphtheria (respiratory):

• Sore throat Throat The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx: Anatomy, malaise Malaise Tick-borne Encephalitis Virus, cervical lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy, low-grade fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
• Pharyngeal erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion with spots of white and gray exudate Exudate Exudates are fluids, cells, or other cellular substances that are slowly discharged from blood vessels usually from inflamed tissues. Pleural Effusion
• Can also have nasal, laryngeal, and tracheobronchial forms
• Pseudomembranes Pseudomembranes Raised yellow or off-white plaques up to 2 cm in diameter that form as a result of mucosal ulceration Pseudomembranous Colitis:
  • Form in ⅓ of cases
  • Composed of fibrin Fibrin A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. Rapidly Progressive Glomerulonephritis, necrotic debris, inflammatory cells, and organisms
  • Tightly adherent to underlying tissue; bleeds with scraping
  • Can spread to any portion of the respiratory tract
• “Malignant diphtheria Diphtheria Diphtheria is an infectious disease caused by Corynebacterium diphtheriae that most often results in respiratory disease with membranous inflammation of the pharynx, sore throat, fever, swollen glands, and weakness. The hallmark sign is a sheet of thick, gray material covering the back of the throat. Diphtheria”:
  • Associated with extensive pseudomembranes Pseudomembranes Raised yellow or off-white plaques up to 2 cm in diameter that form as a result of mucosal ulceration Pseudomembranous Colitis (“pseudomembranous pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis”)
  • Severe “bull’s neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess” lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy
  • Severe swelling Swelling Inflammation of tonsils Tonsils Tonsillitis and uvula Uvula A fleshy extension at the back of the soft palate that hangs above the opening of the throat. Peritonsillar Abscess
  • Can result in airway obstruction Airway obstruction Airway obstruction is a partial or complete blockage of the airways that impedes airflow. An airway obstruction can be classified as upper, central, or lower depending on location. Lower airway obstruction (LAO) is usually a manifestation of chronic disease, such as asthma or chronic obstructive pulmonary disease (COPD). Airway Obstruction, respiratory stridor Stridor Laryngomalacia and Tracheomalacia, and eventual death
• Exam tip: A common question stem may include an immigrant with a sore throat Throat The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx: Anatomy; physical exam reveals tonsils Tonsils Tonsillitis with grayish exudate Exudate Exudates are fluids, cells, or other cellular substances that are slowly discharged from blood vessels usually from inflamed tissues. Pleural Effusion.

Complications/systemic toxemia:

• Cardiac:
  • Myocarditis Myocarditis Myocarditis is an inflammatory disease of the myocardium, which may occur alone or in association with a systemic process. There are numerous etiologies of myocarditis, but all lead to inflammation and myocyte injury, most often leading to signs and symptoms of heart failure. Myocarditis
  • Arrhythmias
• Neurologic:
  • Local neuropathies Neuropathies Chédiak-Higashi Syndrome
  • Cranial neuropathies Neuropathies Chédiak-Higashi Syndrome
  • Peripheral neuritis
• Renal: renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome from hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension or direct exotoxin effects

Cutaneous (wound) diphtheria Diphtheria Diphtheria is an infectious disease caused by Corynebacterium diphtheriae that most often results in respiratory disease with membranous inflammation of the pharynx, sore throat, fever, swollen glands, and weakness. The hallmark sign is a sheet of thick, gray material covering the back of the throat. Diphtheria:

• Initial papule Papule Elevated lesion < 1 cm in diameter Generalized and Localized Rashes that becomes a chronic, non-healing ulcer
• Ulcer is usually covered with a grey membrane.
• May be caused by toxin or non-toxin-producing strains
• In the United States, most common among alcoholic Alcoholic Persons who have a history of physical or psychological dependence on ethanol. Mallory-Weiss Syndrome (Mallory-Weiss Tear) homeless men or drug users

Identification Identification Defense Mechanisms

• Cultures:
  • Should be obtained from throat Throat The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx: Anatomy or nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose and Nasal Cavity: Anatomy, including a portion of membrane
  • Cultured on Loeffler’s Loeffler’s Diphtheria or tellurite Tellurite Diphtheria media
• Toxin detection:
  • Elek’s test: isolates toxin-producing bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology from the pseudomembrane Pseudomembrane Candida/Candidiasis
  • Enzyme immunoassay Enzyme immunoassay HIV Infection and AIDS ( EIA EIA HIV Infection and AIDS)

Prevention

• Toxoid Toxoid Preparations of pathogenic organisms or their derivatives made nontoxic and intended for active immunologic prophylaxis. They include deactivated toxins. Anatoxin toxoids are distinct from anatoxins that are tropanes found in cyanobacteria. Vaccination vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination
• Infants are protected by maternal antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions.

Management

• Passive immunization Passive immunization Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (adoptive transfer). Vaccination or anti-toxin: 1st line
• Antibiotics: Erythromycin Erythromycin A bacteriostatic antibiotic macrolide produced by streptomyces erythreus. Erythromycin a is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50s ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. Macrolides and Ketolides or penicillin Penicillin Rheumatic Fever are the 1st choices for 14 days.
• Supportive management: 
  • Airway Airway ABCDE Assessment protection
  • Bedrest

Mnemonic

“ABCDEFGs of Corynebacterium diphtheriae Corynebacterium diphtheriae Diphtheria is an infectious disease caused by corynebacterium diphtheriae that most often results in respiratory disease with membranous inflammation of the pharynx, sore throat, fever, swollen glands, and weakness. The hallmark sign is a sheet of thick, gray material covering the back of the throat. Diphtheria”:

• ADP-ribosylation
• β-bacteriophage
• Corynebacterium
• Diphtheriae
• Elongation Factor 2 (EF-2)
• Granules