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1
Question:

A 7-year-old boy is evaluated for a foot wound.  He sustained a splinter injury to his left foot while playing in the yard several days ago and has continued to have purulent drainage from the wound.  The patient has no significant medical history and is up to date with all recommended vaccinations.  Wound examination reveals a small retained foreign body with surrounding necrotic tissue and pus.  Anaerobic culture of the wound swab grows thin, gram-positive rods with terminal spore, which is biochemically identified as Clostridium tetani.  Which of the following most likely protected this patient from developing neurological symptoms of the infection?

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Explanation:

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Clostridium tetani is a thin, gram-positive rod with a round terminal spore that grows in strict anaerobic conditions.  It is found in the gastrointestinal tract of many mammals and in soil worldwide.  Transmission to humans typically occurs when C tetani spores are inoculated into a skin wound.  In the anaerobic microenvironment, the spores germinate into a vegetative rod and replicate locally.

Growing C tetani bacteria produce a neurotoxic exotoxin called tetanospasmin (tetanus toxin) that travels by retrograde axonal transport through the lower motor neurons to the central nervous system.  There, it acts at the level of the anterior horn cells, blocking inhibitory neurotransmission, which results in the clinical syndrome of tetanus.  Manifestations include increased muscle tone (eg, opisthotonos, lockjaw), painful spasms, and autonomic instability.

In the United States, the tetanus toxoid vaccine (formaldehyde-inactivated tetanus toxin) is part of routine childhood vaccinations.  This vaccine stimulates a humoral antibody response against tetanus toxin that prevents the toxin from causing neurological damage.  Tetanus is very rare in those who have been vaccinated; almost all cases occur in unvaccinated individuals or those who have not received appropriate booster vaccines.

(Choice A)  Activated macrophages engulf and digest foreign microbes and are the principal cell type responsible for granuloma formation.  Although macrophages help clear bacteria locally from the wound, they would not be able to neutralize the tetanus toxin secreted by Clostridium tetani.

(Choice B)  Circulating antibodies bind to extracellular pathogens and promote complement fixation and phagocytosis.  Complement can opsonize and help eliminate extracellular bacteria, but it would not impair the activity of tetanus toxin.

(Choice D)  Neutrophils are responsible for phagocytosis of foreign organisms and are part of the initial response against extracellular pathogens.  These cells are important for controlling bacterial infections, but play no role in neutralizing tetanus toxin molecules.

(Choice E)  Cytotoxic CD8 lymphocytes play an important role in host defense against viral infections.  They are also capable of destroying tumor cells and contribute to rejection reactions.

Educational objective:
Clostridium tetani produces the neurotoxin tetanospasmin, which blocks inhibitory neurotransmission in the spinal cord and leads to tonic muscular contraction.  Tetanus is prevented by immunization with an inactivated toxoid that triggers the production of antitoxin antibodies (active immunity).