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Descriptive Epidemiology of Infant Botulism in California: The First 40 Years. OBJECTIVE: To ascertain the descriptive epidemiology of infant botulism, the flaccid paralysis that results when neurotoxigenic Clostridium species produce botulinum toxin (BoNT) in the infant colon, in its first 40 years following initial recognition in California in 1976. STUDY DESIGN: Cases were defined by laboratory identification of BoNT and/or neurotoxigenic Clostridium species in patients' feces. Parents were interviewed using a structured questionnaire. Descriptive epidemiologic characteristics were compared between 1976-1996 and 1997-2016. RESULTS: From 1976-2016, 1345 cases of infant botulism occurred in 45 of 58 California counties (6.5 cases/100 000 live-births/year) caused by BoNT types A, B, Ba, Bf, and F; 88% of cases were ≤6 months of age and 51% were female. Cases were white (84.2%), Asian (8.9%), other races (3.8%), and African American (2.8%); 29.4% of cases were Hispanic. More than 99% of cases were hospitalized. Case occurrence peaked in summer-fall. Of 8 designated geographic regions, the Central Coast counties had 3 times the statewide incidence in both 20-year time periods. Breast-fed patients (83%) were more than twice as old at onset as formula-fed patients (median, 4.4 vs 1.7 months, respectively; P < .001). BoNT/A cases were older at onset than BoNT/B cases (median, 3.8 vs 2.9 months, respectively; P < .001). CONCLUSIONS: Comprehensive continuous surveillance of infant botulism for 40 years in a large, diversely populated state identified fundamental epidemiologic characteristics of this uncommon illness. Unusual features included greater than 99% case hospitalization, absence of male preponderance, and a distinctive age distribution.