Objectives Evidence of surgical transmission of sporadic Creutzfeldt–Jakob disease (sCJD) remains debatable in part due to misclassification of exposure levels. In a registry-based case–control study, the authors applied a risk-based classification of surgical interventions to determine the association between a history of surgery and sCJD.

Design Case–control study, allowing for detailed analysis according to time since exposure.

Setting National populations of Denmark and Sweden.

Participants From national registries of Denmark and Sweden, the authors included 167 definite and probable sCJD cases with onset during the period 1987–2003, 835 age-, sex- and residence-matched controls and 2224 unmatched. Surgical procedures were categorised by anatomical structure and presumed risk of transmission level. The authors used logistic regression to determine the odds ratio (OR) for sCJD by surgical interventions in specified time-windows before disease-onset.

Results From comparisons with matched controls, procedures involving retina and optic nerve were associated with an increased risk at a latency of ≥1 year OR (95% CI) 5.53 (1.08 to 28.0). At latencies of 10 to 19 years, interventions on peripheral nerves 4.41 (1.17 to 16.6) and skeletal muscle 1.58 (1.01 to 2.48) were directly associated. Interventions on blood vessels 4.54 (1.01 to 20.0), peritoneum 2.38 (1.14 to 4.96) and skeletal muscle 2.04 (1.06 to 3.92), interventions conducted by vaginal approach 2.26 (1.14 to 4.47) and a pooled category of lower-risk procedures 2.81 (1.62 to 4.88) had an increased risk after ≥20 years. Similar results were found when comparing with unmatched controls.

Interpretation This observation is in concordance with animal models of prion neuroinvasion and is likely to represent a causal relation of surgery with a non-negligible proportion of sCJD cases.