A 34-year-old man comes to the office due to severe fatigue. The patient was diagnosed with paroxysmal nocturnal hemoglobinuria 3 years ago, and he has required several blood transfusions due to anemia. Treatment is initiated with a monoclonal antibody that prevents formation of the protein complex leading to hemolysis in this patient. Prophylactic pharmacotherapy will be required to prevent infection by which of the following organisms?

Question

A 34-year-old man comes to the office due to severe fatigue.  The patient was diagnosed with paroxysmal nocturnal hemoglobinuria 3 years ago, and he has required several blood transfusions due to anemia.  Treatment is initiated with a monoclonal antibody that prevents formation of the protein complex leading to hemolysis in this patient.  Prophylactic pharmacotherapy will be required to prevent infection by which of the following organisms?

Quizplus · Accepted Answer

11ec160b_37d5_c394_9249_85d8ca131a1e_MD0001_00 Paroxysmal nocturnal hemoglobinuria (PNH) is caused by a mutation in hematologic stem cells that eliminates production of an anchoring protein that attaches surface molecules to the cell membrane. Loss of this membrane anchor prevents erythrocytes from expressing the complement-inactivating surface proteins CD55 and CD59. Without these surface proteins, autoactivated components of the alternative complement cascade cannot be disabled. This leads to spontaneous complement amplification, the generation of membrane attack complexes (MACs) on the red cell membrane, and subsequent complement-mediated hemolysis. Treatment with a monoclonal antibody (eg, eculizumab) that targets C5, the first complement protein that contributes to the formation of MACs, can drastically reduce hemolysis and improve symptoms (eg, fatigue) in patients with PNH. However, the generation of MACs is crucial for defense against encapsulated organisms (eg, Neisseria meningitidis, Streptococcus pneumoniae) because these pathogens are resistant to other host defense mechanisms (eg, immunoglobulin binding, phagocytosis). Patients receiving anti-C5 therapy require vaccination against encapsulated pathogens (N meningitidis, S pneumoniae) and appropriate antibiotic prophylaxis (eg, penicillin) to prevent fulminant infection. (Choice A) Nontypable strains of Haemophilus influenzae are not encapsulated; therefore, these strains are susceptible to phagocytosis and immunoglobulin-mediated opsonization. Control is not primarily mediated by the formation of MACs. (Choice B) Host defense to Mycobacterium tuberculosis depends more on T-cell and antigen-presenting cells than on complement activation and MAC formation. (Choices D and E) Staphylococcus aureus and Streptococcus pyogenes often secrete factors that disable the complement cascade. Therefore, they are primarily countered by other components of the immune system (eg, neutrophils, humoral immunity). Educational objective: Paroxysmal nocturnal hemoglobinuria leads to the formation of membrane attack complexes on erythrocytes. Treatment with monoclonal antibody against C5, the first component of the membrane attack complex, can improve symptoms. However, it also increases risk for encapsulated bacterial infection. Therefore, patients require vaccination and antibiotic prophylaxis against Neisseria meningitidis and Streptococcus pneumoniae.

A 34-Year-Old Man Comes to the Office Due to Severe