Infants who are colonized with toxigenic Clostridioides difficile may develop an antitoxin humoral immune response against toxins A and B and may neutralize toxin B activity, according to research published in Clinical Infectious Diseases.

In a prospective cohort study, a team of researchers aimed to determine the association between infant C difficile colonization and antitoxin seropositivity. The hypothesis was that infants who were naturally colonized with toxigenic strains of C difficile would develop a humoral immune response against C difficile toxins. The investigators also studied the frequency and molecular epidemiology of C difficile colonization in infants.

Infant stool samples were collected between ages 1 and 2 months and 9 and 12 months and tested for toxigenicity. Serum was collected from ages 9 to 12 months for measures of immunoglobulin A (IgA), IgG, and IgM concentrations against toxigenic C difficile toxins A and B and neutralizing antibody titers against toxin B.

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Of the 32 infants included in the analysis, 16 were colonized with toxigenic C difficile and 12 were colonized with nontoxigenic C difficile; 5 were colonized with both strains of C difficile. Toxin A and B enzyme immunoassay results were positive for at least 1 toxin in 56% of the infants who were colonized with toxigenic C difficile; 75% of these infants were colonized at least 1 month before serologic measures were obtained.

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Results suggested that IgG and IgA against toxins A and B were significantly higher for infants colonized with toxigenic C difficile (with colonization occurring >1 month earlier) compared with infants colonized with nontoxigenic C difficile. Results were similar for detectable toxin B neutralizing antibody titers: 42% vs 0% in toxigenic vs nontoxigenic C difficile, respectively. No associations were reported between breastfeeding and serologic measures. 

“While these data suggest that this humoral response in [toxigenic C difficile]-colonized infants is associated with toxin B neutralization in vitro, additional studies are required to determine the extent and duration of protection against [C difficile infection] afforded by this natural C difficile immunization event during childhood,” the investigators noted. “This additional knowledge would guide our understanding of the potential public health value of identifying children as a priority population for C difficile vaccine clinical trials.”


Kociolek LK, Espinosa RO, Gerding DN, et al. Natural Clostridioides difficile toxin immunization in colonized infants [published June 29, 2019]. Clin Infect Dis. doi:10.1093/cid/ciz582