A 3-year-old boy who recently immigrated to the United States is brought to the emergency department with fever, malaise, and a painful, swollen right knee. He is hypotensive and tachycardic. Medical history is significant for a recent episode of acute otitis media and several vaccinations that are not up to date. Arthrocentesis of the right knee shows cloudy synovial fluid. Gram stain of the aspirate reveals pleomorphic, gram-negative coccobacilli. Cultures performed on a blood agar plate supplemented with a disk containing hematin and nicotinamide adenine dinucleotide (NAD⁺) grow colonies only near the disk. The organism responsible for this patient's condition most likely produces which of the following virulence factors?

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11ec160b_38a2_b0a6_9249_f5955f9d102b_MD0001_00 This patient's arthrocentesis findings are diagnostic for septic arthritis due to Haemophilus influenzae. H influenzae is a small, pleomorphic, gram-negative coccobacillus that requires both X factor (hematin) and V factor (NAD⁺) to grow. Because these factors are found within erythrocytes, optimal concentrations are present only in lysed blood agar (chocolate agar). Growth on regular blood agar requires exogenous supplementation of X and V factors, which are typically provided by an impregnated disk. Localized infections (eg, acute otitis media, sinusitis) are caused predominantly by unencapsulated (nontypeable) strains of H influenzae, although H influenzae type b (Hib) can also cause these infections in undervaccinated patients. Type b strains have a polyribosylribitol phosphate polysaccharide capsule that prevents phagocytosis. This allows the organism to invade the vasculature and spread hematogenously to distant sites, predisposing to invasive disease (eg, septic arthritis, meningitis, bacteremia). In vaccinated patients, antibodies against the type b capsule provide immunity by promoting complement fixation and opsonization. Therefore, invasive Hib infections have been rare since the advent of the Hib immunization. (Choice B) Cytotoxic exotoxins are secreted by certain bacteria (Clostridium botulinum, Clostridium tetani, Corynebacterium diphtheriae) to promote host cell death. No strains of H influenzae produce an exotoxin. (Choice C) Fimbriae are proteinaceous projections from bacterial cells that attach to target tissues during the initial stages of an infectious process. Fimbriae on H influenzae enable attachment to endothelial cells during colonization of the respiratory tract but are not the major virulence factor contributing to invasive disease. (Choice D) Staphylococcus aureus produces alpha-hemolysin, which causes infection by destroying the cell membrane of red and white blood cells. Hemolysins are not secreted by H influenzae. (Choice E) Hyaluronidase is an enzyme used by bacteria (eg, S aureus, Streptococcus pyogenes, Clostridium perfringens) to digest extracellular ground substance and enhance their ability to spread. Hyaluronidase is not produced by H influenzae. Educational objective: Haemophilus influenzae is a gram-negative coccobacillus that requires both X factor (hematin) and V factor (NAD⁺) to grow. H influenzae type b has an antiphagocytic polysaccharide capsule, which allows it to spread hematogenously and cause invasive disease such as septic arthritis and meningitis. __________ References: Etiology of septic arthritis in children: an update for the new millennium. (http://www.ncbi.nlm.nih.gov/pubmed/20674219) Economic evaluations of Haemophilus influenzae type b (Hib) vaccine: a systematic review. (http://www.ncbi.nlm.nih.gov/pubmed/28737468)

A 3-Year-Old Boy Who Recently Immigrated to the United States