In the JournalsPerspective

Infants ‘naturally immunized’ against toxigenic C. difficile

Photo of Larry Kociolek
Larry K. Kociolek

Findings from a prospective cohort study of healthy infants suggested that colonization with toxigenic Clostridioides difficile, or TCD, triggers an immune response against the toxins, providing “natural immunization.”

Larry K. Kociolek, MD, MSCI, assistant professor of pediatrics at the Northwestern University Feinberg School of Medicine, told Infectious Diseases in Children that C. difficile infection (CDI) is much more common in adults compared with children. However, the prevalence of infection is increasing among children.

“Interestingly, and for reasons that are unknown, children have a much lower frequency of severe complications compared with adults,” he said. “Infants in particular are a unique population regarding CDI. Our research suggests that despite not developing symptoms of CDI, infants exposed to C. difficile toxins in infancy develop an immune response against these toxins.”

Kociolek and colleagues collected stool samples from 32 infants aged 1 to 2 months and 9 to 12 months and tested them for both nontoxigenic and toxigenic C. difficile. The researchers also collected serum samples from infants aged 9 to 12 months to measure immunoglobulin A, immunoglobulin G and immunoglobulin M 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 collected from 50 mothers of infants who were not included in the study.

According to the researches, half the infants (n = 16) were colonized with TCD, and most of these infants (n = 12) were colonized with the bacterium more than 1 month before the serum samples were collected. The researchers found evidence of C. difficile transmission to siblings at home and in an outpatient setting.

Infants who were colonized with TCD more than 1 month before testing had higher anti-toxin IgA and IgG against TCD toxin A (P = .02) compared with infants who were not colonized with TCD. Additionally, those infants also had higher anti-toxin IgA (P = .009) and IgG (P = .008) against TCD toxin B and higher levels of IgG compared with cord blood (P = .005).

Five of the colonized infants (42%) had detectable NAb titers, whereas zero noncolonized infants had detectable titers (P = .02).

Breastfeeding had no impact on the findings, the researchers wrote.

“Our next steps include understanding the clinical implications of this anti-toxin immune response that develops during infancy,” Kociolek said. “We would like to better understand if this immune response provides protection against CDI and its implications later in childhood, and if so, how long this protection lasts. With recent clinical development of C. difficile vaccines, understanding the prevalence and natural history of anti-toxin immunity will identify priority populations for C. difficile vaccination.” – by Katherine Bortz

Disclosures: Kociolek has numerous ties to industry. Please see the study for all other authors’ relevant financial disclosures.

Photo of Larry Kociolek
Larry K. Kociolek

Findings from a prospective cohort study of healthy infants suggested that colonization with toxigenic Clostridioides difficile, or TCD, triggers an immune response against the toxins, providing “natural immunization.”

Larry K. Kociolek, MD, MSCI, assistant professor of pediatrics at the Northwestern University Feinberg School of Medicine, told Infectious Diseases in Children that C. difficile infection (CDI) is much more common in adults compared with children. However, the prevalence of infection is increasing among children.

“Interestingly, and for reasons that are unknown, children have a much lower frequency of severe complications compared with adults,” he said. “Infants in particular are a unique population regarding CDI. Our research suggests that despite not developing symptoms of CDI, infants exposed to C. difficile toxins in infancy develop an immune response against these toxins.”

Kociolek and colleagues collected stool samples from 32 infants aged 1 to 2 months and 9 to 12 months and tested them for both nontoxigenic and toxigenic C. difficile. The researchers also collected serum samples from infants aged 9 to 12 months to measure immunoglobulin A, immunoglobulin G and immunoglobulin M 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 collected from 50 mothers of infants who were not included in the study.

According to the researches, half the infants (n = 16) were colonized with TCD, and most of these infants (n = 12) were colonized with the bacterium more than 1 month before the serum samples were collected. The researchers found evidence of C. difficile transmission to siblings at home and in an outpatient setting.

Infants who were colonized with TCD more than 1 month before testing had higher anti-toxin IgA and IgG against TCD toxin A (P = .02) compared with infants who were not colonized with TCD. Additionally, those infants also had higher anti-toxin IgA (P = .009) and IgG (P = .008) against TCD toxin B and higher levels of IgG compared with cord blood (P = .005).

Five of the colonized infants (42%) had detectable NAb titers, whereas zero noncolonized infants had detectable titers (P = .02).

Breastfeeding had no impact on the findings, the researchers wrote.

“Our next steps include understanding the clinical implications of this anti-toxin immune response that develops during infancy,” Kociolek said. “We would like to better understand if this immune response provides protection against CDI and its implications later in childhood, and if so, how long this protection lasts. With recent clinical development of C. difficile vaccines, understanding the prevalence and natural history of anti-toxin immunity will identify priority populations for C. difficile vaccination.” – by Katherine Bortz

Disclosures: Kociolek has numerous ties to industry. Please see the study for all other authors’ relevant financial disclosures.

    Perspective

    Since its discovery in 1935 in the stool of healthy newborns, we’ve known that C. difficile can colonize the intestinal tract of infants. Yet, we have a limited understanding of the infant’s immune response to colonization.

    In the study by Kociolek and colleagues, infants colonized with toxigenic C. difficile, compared with noncolonized infants, had higher levels of anti-toxin IgG and IgA and higher titers of neutralizing antibodies against toxin B. The results suggest that infant colonization may induce a “natural immunization event.”

    These findings take on added significance given studies have found that adults with anti-toxin antibodies have a lower risk for symptomatic CDI. Based on their findings, the authors hypothesized that the infant’s immune response to colonization may protect against subsequent CDI. This excellent study increases our understanding of the host response to C. difficile during infancy.

    • Jonathan Crews, MD, MS
    • Assistant professor of pediatrics
      Baylor College of Medicine
      The Children’s Hospital of San Antonio