Sudden unexpected infant death (SUID), including Sudden Infant Death Syndrome (SIDS), results in about 3,400 deaths each year in the United States. By state law, almost all of these deaths require an autopsy in an effort to find cause of death.
If the coroner’s office and/or law enforcement rule the death scene out—i.e., no obvious safety impediments like blankets or strings—and the medical examiner finds no other cause, the death is typically attributed to SIDS.
But SIDS is unlike most other causes of death medical examiners identify. For one, there is still not a common set of diagnostic features that indicate SIDS. Even at autopsy, there are no pathognomonic markers of the fatal event.
Part of this hails from the fact that, despite decades of research, the root cause of SIDS is still unknown.
Now, researchers at Rockefeller University are exploring the hypothesis that SIDS may be triggered by exposure to Clostridium perfringens enterotoxin. Clostridium perfringens is a gram-positive bacillus that is based on production of one (or more) of four toxins. Each of these “toxintypes” is also capable of carrying the gene for C. perfringens enterotoxin (CPE)—a toxin that causes gastrointestinal issues, like food poisoning and diarrhea, gangrene, and is suspected to play a role in multiple sclerosis. It’s this enterotoxin that SIDS researchers are especially interested in.
Collaborating with the Office of the Chief Medical Examiner of New York City, the Rockefeller scientists collected and analyzed fecal samples from 74 infants who died suddenly. Of those, 26 (35%) tested positive for C. perfringens. Further, 16 of those 26 (62%) strains tested positive for CPE.
“C. perfringens strains typically carry the CPE gene at a frequency of less than 15%,” the researchers explain. “[This] four-fold CPE gene enrichment in SUID cases strongly implicates CPE-producing C. pefringens strains in the pathogenesis of sudden infant death syndrome.”
Additionally, when comparing CPE gene carriage to the designated cause of death, 12 of 16 (75%) were associated with SIDS. However, there were 25 of 74 cases (34%) identified as SIDS or death “undetermined” for which no CPE carriage could be identified.
While the results of this study are meaningful in a lab-scale diagnostic sense, the researchers said their current assay is neither sensitive nor specific enough to be utilized for criminal justice determinations.
“Harvesting a CPE-positive strain from a victim should not be used as exculpatory evidence for wrong-doing, as the literature suggests that as many as 15% of healthy individuals can carry CPE-producing C. perfringens bacteria,” the authors conclude. “Furthermore, the inability to register a CPE signal should not imply that SIDS has not occurred. In our study, there were 25 instances where SIDS cases were negative for CPE. Such a high
false negative rate should discourage using the assay, in its current form, for criminal justice purposes.”
Still, the insight from the study, as well as further research from the team, could eventually provide a mechanism for how enterotoxin might cause the brain damage commonly found in SIDS victims upon autopsy—ultimately paving the way to a SIDS-specific pathognomonic marker.
“Beyond the present study, we envision extending our fecal culture experiments to healthy infants as well as live controls so as to determine CPE-carriage rates for healthy infants under our unique experimental conditions,” said Vincent Fischetti, head of Rockefeller University’s Laboratory of Bacterial Pathogenesis.
Photo: This photomicrograph reveals Clostridium perfringens grown in Schaedler’s broth using Gram-stain. Credit: CDC