A 16-year-old girl is brought to the emergency department after she became unresponsive. Temperature is 39.7 C (103.5 F), blood pressure is 70/40 mm Hg, and pulse is 130/min and thready. There is a diffuse petechial and ecchymotic skin rash. Laboratory testing reveals leukocytosis with left shift and evidence of disseminated intravascular coagulation and multiorgan failure. Despite aggressive interventions, the patient dies several hours after admission. Autopsy reveals hemorrhagic necrosis of many internal organs, including the bilateral adrenal glands. Which of the following microbial components is directly responsible for the severity of disease in this patient?

Question

A 16-year-old girl is brought to the emergency department after she became unresponsive.  Temperature is 39.7 C (103.5 F), blood pressure is 70/40 mm Hg, and pulse is 130/min and thready.  There is a diffuse petechial and ecchymotic skin rash.  Laboratory testing reveals leukocytosis with left shift and evidence of disseminated intravascular coagulation and multiorgan failure.  Despite aggressive interventions, the patient dies several hours after admission.  Autopsy reveals hemorrhagic necrosis of many internal organs, including the bilateral adrenal glands.  Which of the following microbial components is directly responsible for the severity of disease in this patient?

Quizplus · Accepted Answer

Neisseria meningitidis is a common cause of rapid-onset sepsis and circulatory collapse in otherwise healthy young individuals. Infections usually start suddenly with myalgias, high fever, headache, and altered level of consciousness and quickly progress to hypotension, organ failure, and death. Many patients also develop a petechial/ecchymotic rash due to underlying disseminated intravascular coagulation. N meningitidis has an outer cell membrane virulence factor called lipo-oligosaccharide (LOS), which is primarily responsible for the severity of meningococcal disease. LOS, and its close analogue lipopolysaccharide (found in gram-negative enteric rods), are endotoxins that cause toxicity when released into the plasma via shedding of the outer membrane ("blebbing") or bacterial lysis. Endotoxins bind to Toll-like receptor 4 on monocytic and dendritic cells and trigger the release of inflammatory cytokines (eg, IL-1, IL-6, TNF-alpha), which leads to endothelial damage, capillary leakage, and hemorrhagic necrosis. (Choices A and B) The capsular polysaccharide of N meningitidis is an important virulence factor that helps the bacteria resist phagocytosis and complement activation. N meningitidis also releases IgA protease, which aids in nasopharyngeal epithelial colonization. However, these virulence factors are not the direct cause of meningococcal septic shock. (Choice D) Lipoteichoic acid is a major component of the cell wall of most gram-positive bacteria and acts as a regulator of autolytic cell wall enzymes. Although lipoteichoic acid can stimulate the complement cascade, it is not a major cause of septic shock and hemorrhagic inflammation in patients with meningococcemia (a gram-negative organism). (Choice E) Toxic shock syndrome is due to Staphylococcus aureus exotoxins, which act as superantigens and result in the wide-spread activation of T-cells (with massive inflammatory cytokine release). Patients usually present with circulatory collapse, organ failure, and erythroderma (a diffuse macular rash that looks like a sunburn). Petechiae and ecchymosis would be atypical. Educational objective: Neisseria meningitidis can cause sepsis and circulatory collapse in previously healthy young individuals. Lipooligosaccharide, a virulence factor in the pathogens outer membrane, is the major underlying cause of disease severity. __________ References: Neisseria meningitidis: biology, microbiology, and epidemiology. (http://www.ncbi.nlm.nih.gov/pubmed/21993636)

A 16-Year-Old Girl Is Brought to the Emergency Department After