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Natural Clostridioides difficile Toxin Immunization in Colonized Infants.


ABSTRACT:

Background

Clostridioides (Clostridium) difficile colonization is common among infants. Serological sequelae of infant C. difficile colonization are poorly understood.

Methods

In this prospective cohort study of healthy infants, stools serially collected between ages 1-2 and 9-12 months were tested for non-toxigenic and toxigenic C. difficile (TCD). Cultured isolates underwent whole-genome sequencing. Serum collected at 9-12 months underwent measurement of IgA, IgG, and IgM against TCD toxins A and B and neutralizing antibody (NAb) titers against toxin B. For comparison, antitoxin 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 before 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 antitoxin IgA and IgG against toxins A (P = .02 for both) and B (P = .009 and .008, respectively) compared with non-TCD-colonized infants, and greater IgG compared with unrelated cord blood (P = .005). Five of 12 (42%) colonized infants had detectable NAb titers compared with zero non-TCD-colonized infants (P = .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 require further investigation.

SUBMITTER: Kociolek LK 

PROVIDER: S-EPMC7201415 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Natural Clostridioides difficile Toxin Immunization in Colonized Infants.

Kociolek Larry K LK   Espinosa Robyn O RO   Gerding Dale N DN   Hauser Alan R AR   Ozer Egon A EA   Budz Maria M   Balaji Aakash A   Chen Xinhua X   Tanz Robert R RR   Yalcinkaya Nazli N   Conner Margaret E ME   Savidge Tor T   Kelly Ciaran P CP  

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20200501 10


<h4>Background</h4>Clostridioides (Clostridium) difficile colonization is common among infants. Serological sequelae of infant C. difficile colonization are poorly understood.<h4>Methods</h4>In this prospective cohort study of healthy infants, stools serially collected between ages 1-2 and 9-12 months were tested for non-toxigenic and toxigenic C. difficile (TCD). Cultured isolates underwent whole-genome sequencing. Serum collected at 9-12 months underwent measurement of IgA, IgG, and IgM agains  ...[more]

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