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Natural Clostridioides difficile toxin immunization in colonized infants.

Kociolek LK, et al. Clin Infect Dis. 2019.


BACKGROUND: Clostridioides (Clostridium) difficile colonization is very common among infants. The serological sequelae of infant C. difficile colonization are poorly understood.

METHODS: In this prospective cohort study of healthy infants, stools serially collected between 1-2 months and 9-12 months old were tested for non-toxigenic and toxigenic C. difficile (TCD). Cultured isolates underwent whole genome sequencing. Serum collected at 9-12 months old underwent measurement of IgA, IgG, and IgM against TCD toxins A and B and neutralizing antibody (NAb) titers against toxin B. For comparison, anti-toxin IgG and NAb were measured in cord blood from 50 mothers unrelated to study infants.

RESULTS: Among 32 infants, 16 (50%) were colonized with TCD; 12 were first colonized >1 month prior to serology measurements. A variety of sequence types were identified, and there was evidence of putative in-home (enrolled siblings) and outpatient clinic transmission. Infants first colonized with TCD >1 month prior had significantly greater serum anti-toxin IgA and IgG against toxins A (p=0.02 for both) and B (p=0.009, p=0.008, respectively) compared to non-TCD-colonized infants, and greater IgG compared to unrelated cord blood (p=0.005). Five of 12 (42%) colonized infants had detectable NAb titers compared to zero non-TCD-colonized infants (p=0.02). Breastfeeding was not associated with differences in serological measurements.

CONCLUSIONS: TCD colonization is associated with a humoral immune response against toxins A and B, with evidence of toxin B neutralization in vitro. The extent and duration of protection against CDI later in life afforded by natural C. difficile immunization events requires further investigation.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail:


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