WBR0291

Author	[[PageAuthor::Ogheneochuko Ajari, MB.BS, MS [1] (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Microbiology, MainCategory::Pathophysiology
Sub Category	SubCategory::General Principles, SubCategory::Infectious Disease
Prompt	[[Prompt::A 4-year-old boy is brought to the emergency department (ED) with fever, sore throat, and malaise. His mother states that the patient has no significant past medical history. She denies any known allergies to medications or drugs. The family immigrated to the United States from Africa only 2 days ago. His temperature is 38.3 °C (101 °F), blood pressure is 136/86 mmHg, and heart rate is 100/min. Physical examination is remarkable for cervical lymphadenopathy, pharyngeal erythema, and presence of grey-white exudative membrane that bleeds when scraped in the pharynx. The patient is isolated and is managed promptly. Two days later, a club-shaped, gram-positive rod that contains metachromatic granules grows on Loffler's media. What is the mechanism of virulence that characterizes the organism responsible for this patient's condition?]]
Answer A	AnswerA::It binds to MHC II and T-cell receptor, resulting in polyclonal T-cell activation
Answer A Explanation	AnswerAExp::
Answer B	AnswerB::It acts via antibodies to M proteins to enhance the host defenses
Answer B Explanation	AnswerBExp::
Answer C	AnswerC::It inhibits protein synthesis via ADP ribosylation of EF-2
Answer C Explanation	AnswerCExp::
Answer D	AnswerD::It blocks GABA and glycine release from cells in the spinal cord
Answer D Explanation	AnswerDExp::
Answer E	AnswerE::It produces catalase to degrade hydrogen peroxide
Answer E Explanation	AnswerEExp::
Right Answer	RightAnswer::C
Explanation	[[Explanation::Diphtheria is an acute infectious disease caused by Corynebacterium diphtheriae. C. diphtheriae is an exon-producing, club-shaped, urease-negative, catalase-positive, gram-positive bacteria that is usually transmitted by direct contract or by aerosol. The most common manifestations of C. diphtheriae infection include an upper respiratory tract infection that often includes the posterior oral and the proximal pharyngeal regions, resulting in significant edema and formation of "pseudomembranes" following coalescence of the bacteria on the mucosal membranes and the outpouring of fibrinosuppurative exudates. The "pseudomembrane" is often described as dirty-looking with firm attachment to the mucosa; it is usually white-grey early in the disease and becomes necrotic green-black when left untreated. The bacteria's exotoxin acts by inhibiting the cellular protein synthesis by stimulation of adenosine diphosphate (ADP) ribosylation and inactivation of protein synthesis elongation factor 2. The toxigenicity of C. diphtheriae is derived from 3 tox gene, which are structural genes in lysogenic corynebacteriophages that are inserted into the genome. The bacteria regulates the expression of these genes in an iron-dependent manner (increased toxin production in low iron concentrations). Following excretion from the bacteria, the toxins undergo cleavage into 2 chains (A and B) that are held by a disulfide bond. Systemic manifestations of C. diphtheriae infection may occur due to the absorption of exotoxin into the blood. Cervical lymph nodes may become enlarged and hemorrhagic with a "bull neck" appearance. Other complications include myocarditis and neuropathy. Cardiac failure develops due to myocardial distortions, granular degeneration with loss of striations, and cardiac conduction abnormalities. Patients with diphtheria and cardiac complications may eventually die of myocardiosclerosis within 1-2 weeks of disease progression. On autopsy, hearts will appear dilated and pale with a "streaky" appearance. Neuropathy first manifests with food regurgitation through the nose due to paralysis of the soft palate and the posterior pharyngeal wall. Other cranial and peripheral motor and sensory neuropathies develop at later stage during disease progression. The diagnosis of diphtheria should be considered upon high clinical suspicion among young patients with consistent manifestations (sore throat and fever) and findings on physical examination (cervical lymphadenopathy, pharyngeal edema, and pseudomembranes that bleed when scraped in the palate and the pharynx). Suspicion is confirmed with gram stain and culture from the throat, nose, secretions of the respiratory tract, or parts of the pseudomembrane. Gram stain may rapidly aid in the diagnosis, often demonstrating gram-positive rods with a "Chinese character" distribution. Metachromatic granules are observed on Loffler's media, and black colonies with halos are observed on Tindale's media. Once suspected, management includes early isolation, administration of anti-toxin and intravenous antibiotics (erythromycin or penicillin G), and careful monitoring for respiratroy, cardiac, or neurological complications. The optimal choice of antibiotic regimen is then based on the antibiogram results. With the introduction of vaccines against C. diphtheriae infection, the incidence of diphtheria has greatly been reduced; and diphtheria respiratory infection noawadays is rarely described in developed countries. However, cutaneous diphtheria is still a common source of wound and umbilical infections, often showing single/multiple, curved, punched-out ulcers with elevated margins. Educational Objective: References: ]]
Approved	Approved::Yes
Keyword
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::