Larry K Kociolek1,2, Robyn O Espinosa2, Dale N Gerding3,4, Alan R Hauser5,6, Egon A Ozer5, Maria Budz7, Aakash Balaji1, Xinhua Chen8, Robert R Tanz1,9, Nazli Yalcinkaya10, Margaret E Conner11, Tor Savidge10, Ciaran P Kelly8. 1. Department of Pediatrics, Northwestern University Feinberg School of Medicine. 2. Division of Infectious Diseases, Ann & Robert H. Lurie Children's Hospital of Chicago. 3. Department of Medicine, Loyola University Chicago Stritch School of Medicine, Hines. 4. Department of Medicine, Edward Hines Jr Veterans Administration Hospital, Research Service, Hines. 5. Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago. 6. Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago. 7. Special Infectious Diseases Laboratory, Ann & Robert H. Lurie Children's Hospital of Chicago, Illinois. 8. Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. 9. Division of Academic General Pediatrics and Primary Care, Ann & Robert H. Lurie Children's Hospital of Chicago, Illinois. 10. Department of Pathology and Immunology, Baylor College of Medicine and Texas Children's Hospital, Houston. 11. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas.
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.
BACKGROUND:Clostridioides (Clostridium) difficile colonization is common among infants. Serological sequelae of infantC. 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.
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