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Natural Clostridioides difficile Toxin Immunization in Colonized Infants

Larry K Kociolek1,2, Robyn O Espinosa2, Dale N Gerding3,4

  • 1Department of Pediatrics, Northwestern University Feinberg School of Medicine.

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
|June 30, 2019
PubMed

Insights

Infant colonization with toxigenic Clostridioides difficile (TCD) triggers an immune response, increasing antibodies against TCD toxins A and B. This natural exposure may offer future protection against C. difficile infection (CDI).

Area of Science:

  • Microbiology
  • Immunology
  • Pediatrics

Background:

  • Infant colonization with Clostridioides (Clostridium) difficile is common.
  • The serological consequences of infant C. difficile colonization are not well understood.

Purpose of the Study:

  • To investigate the serological sequelae of toxigenic C. difficile (TCD) colonization in infants.
  • To assess the development of antibodies against TCD toxins and their neutralizing capacity.

Main Methods:

  • Prospective cohort study of healthy infants from 1-12 months.
  • Serial stool sample testing for TCD, followed by whole-genome sequencing of isolates.
  • Measurement of serum IgA, IgG, IgM against TCD toxins A and B, and neutralizing antibody (NAb) titers against toxin B at 9-12 months.
  • Comparison with serum from unrelated mothers (cord blood).

Main Results:

  • 50% of infants were colonized with TCD; transmission occurred within households and clinics.
  • Infants colonized with TCD >1 month prior showed significantly higher serum antitoxin IgA and IgG against toxins A and B.
  • 42% of colonized infants developed detectable NAb titers against toxin B, compared to none in non-colonized infants.
  • Breastfeeding did not influence serological measurements.

Conclusions:

  • TCD colonization in infants is associated with a robust humoral immune response, including antibody production against toxins A and B.
  • Evidence suggests in vitro neutralization of toxin B by antibodies developed post-colonization.
  • Further research is needed to determine the long-term protective effects against C. difficile infection (CDI) from natural C. difficile immunization events.
Abstract

Keywords:
C difficileimmunitypediatricpreventiontoxin

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