Dengue Virus Infection and Risk of Parkinson’s Disease: A Nationwide Longitudinal Study

Article type: Research Article

Authors: Hsu, Tien-Wei^a | Chu, Che-Sheng^{a; b; c; d} | Tsai, Shih-Jen^{e; f} | Cheng, Chih-Ming^{e; f} | Su, Tung-Ping^{e; f; g} | Chen, Tzeng-Ji^{h; i} | Bai, Ya-Mei^{e; f} | Liang, Chih-Sung^{j; k; *; 1} | Chen, Mu-Hong^{e; f; *; 1}

Affiliations: [a] Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan | [b] Center for Geriatric and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan | [c] Non-invasive Neuromodulation Consortium for Mental Disorders, Society of Psychophysiology, Taipei, Taiwan | [d] Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan | [e] Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan | [f] Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan | [g] Department of Psychiatry, General Cheng Hsin Hospital, Taipei, Taiwan | [h] Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan | [i] Institute of Hospital and Health Care Administration, National Yang Ming Chiao Tung University, Taipei, Taiwan | [j] Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, Taipei, Taiwan | [k] Department of Psychiatry, National Defense Medical Center, Taipei, Taiwan

Correspondence: [*] Correspondence to: Chih-Sung Liang, MD, Department of Psychiatry, No. 60, Xinmin Road, Beitou District, Taipei, Taiwan 11243. Tel.: +886 2 2895 9808; Fax: +886 222895 7633; E-mail: [email protected]; ORCID: 0000-0003-1138-5586 and Mu-Hong Chen, MD, PhD, Department of Psychiatry, No. 201, Sec. 2, Shihpai Road, Beitou District, Taipei, Taiwan 11217. Tel.: +886 2 28344012; Fax: +886 2 28344012; E-mail: [email protected]; ORCID: 0000-0001-6516-1073.

Note: [1] These authors contributed equally to this work as corresponding authors.

Abstract: Background:Increasing evidence suggests a potential relationship between viral infection and Parkinson’s disease (PD). Objective:Herein, we explore the association between infection by dengue virus and PD. Methods:Between 1997 and 2012, we recruited 1,422 patients with dengue fever and 14,220 matched controls (age, sex, time of enrollment, and medical and mental comorbidities) from the Taiwan National Health Insurance Research Database. We identified new onset of PD to the end of 2013. The Kaplan-Meier method was used to estimate the incidence rate of PD. Cox-regression analysis was applied to calculate the hazard ratios (HRs) with 95% confidence intervals (CIs) after adjustment for confounders. Results:During the follow up period, the dengue group had higher incidence of PD than the control group (1.2% vs. 0.4% , p = 0.001). Patients with dengue fever had a significantly higher risk of developing PD [HR, 2.59; 95% CI, 1.51–4.44] compared with the controls, after adjustments for demographic data, PD-related comorbidities, and all-cause clinical visits. The subgroup analysis, stratified by age and sex, found that higher risk for PD was statistically significant for male (HR, 3.51; 95% CI, 1.76–7.00) and patients aged >60 years (HR, 2.96; 95% CI, 1.62–5.41). Conclusion:The risk of PD was 2.59-fold higher in patients with dengue fever than in non-infected controls during the follow-up period. Clinicians need to monitor signs of PD during patient recovery from dengue fever. Additional studies are needed to confirm our results and investigate the mechanisms linking PD and dengue virus infection.

Keywords: Dengue, Parkinson’s disease, virus infection, neurological sequelae, Taiwan

DOI: 10.3233/JPD-212938

Journal: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 679-687, 2022