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Background: Parkinson's disease (PD) is a neurodegenerative disorder that progressively damages the autonomic and central nervous systems, leading to hallmark symptoms such as resting tremor, bradykinesia, and rigidity. Despite extensive research, the underlying cause of PD remains unclear, and current treatments are unable to halt the progression of the disease. In this retrospective study, based on historical electronic health records (EHR) from a national health provider covering the period from 2003 to 2023, we investigated the impact of vaccination and medication purchases on PD occurrence and severity. Methods: Using a case-control design, we compared the vaccination histories of 1446 PD patients with 7230 matched controls to assess the association between vaccination and PD onset. Additionally, we explored statistical associations between vaccination, medication purchases, and PD severity over an average of 9 years of follow-up, utilizing a machine learning algorithm to quantify disease severity based on annual antiparkinsonian medication purchases. Results: Our analysis revealed a significant reduction in PD occurrence following tetanus-diphtheria (Td) vaccination, with an adjusted odds ratio of 0.17 (95% CI [0.04, 0.70]) for PD onset within 5 years post-vaccination. Furthermore, a time-dependent relationship was identified between the duration since vaccination and both the rate of PD onset and disease progression. Notably, we observed that antimicrobial treatments significantly influenced disease severity, consistent with the antibiotic sensitivity profile of Clostridium tetani. Conclusions: These findings support the hypothesis that tetanus vaccination and/or C. tetani eradication may reduce PD occurrence and slow its progression, suggesting promising directions for future research in PD prevention and treatment.
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