Infants Gain C. Difficile Immunity Early in Life

Larry Kociolek, MD

New research suggests infants naturally exposed to the C. difficile infections gain an immunity that protects them later in life.

A team from the Ann & Robert H. Lurie Children’s Hospital of Chicago found that when naturally exposed to C. diff in the environment, infants become colonized with the bacteria with antibodies in their blood, neutralizing the toxins that cause infections and preventing harmful effects to cells exposed to the toxins.

"We found an immune response in infants colonized with C. difficile, which might be beneficial as they get older, although we are still studying the extent and duration of this natural immunization," lead author Larry Kociolek, MD, MSCI, from Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago, said in a statement. "We are optimistic because we know from previous studies that adults with anti-toxin antibodies have a lower risk for illness from C. difficile infection."

The investigators serially collected and tested stool from 32 healthy infants between 1-2 months and 9-12 months old for non-toxigenic and toxigenic C. difficile (TCD).

They also whole genome sequencing on cultured isolates and collected and measured serum at 9-12 months old of IgA, IgG, and IgM against TCD toxins A and B, and neutralizing antibody (NAb) titers against toxin B.

The team measured anti-toxin IgG and Nab in cord blood from 50 mothers unrelated to the infants in the study for comparisons sake.

Of the 32 infants, the investigators found half were colonized with TCD and 12 were first colonized more than 1 month prior to serology measurements. They identified a variety of sequence types, with evidence of putative in-home and outpatient clinic transmission.

The infants first colonized with TCD more than 1 month prior had significantly greater serum anti-toxin IgA and IgG against toxins A (P= .02 for both) and B (P= .009, P= .008 respectfully) compared to non-TCD-colonized infants. They also had greater IgG compared to unrelated cord blood (P= .005).

Also, 5 of the 12 colonized infants had detectable Nab titers, while none of the non-TCD-colonized infants (P= .02) had detectable Nab titers.

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

C. diff frequently causes community and healthcare-associated infections in both adults and children. While approximately half of all infants are exposed to the disease, the majority do not actually get sick from the bacteria.

"Given our results, we suspect that young children who get sick from C. difficile were probably not exposed as infants and so did not develop immunity," Kociolek said. "In adolescents, immunity might be waning. If with more research we can show that this is true, then there might be a role for vaccinating susceptible children and teens against C. difficile."

Recent studies suggest the cost associated with hospital-acquired Clostridioides difficile infections (HA-CDI) is significant.

In a study, which took place in acute-care facilities in Alberta, Canada, the mean attributable cost of HA-CDI was $14,190 and the average extra length of hospital stays was 5.6 days per HA-CDI case.

The study, “Natural Clostridioides difficile toxin immunization in colonized infants,” was published online in Clinical Infectious Diseases.