Seroprevalence of Lyme Disease in Asian Human Populations: A Systematic Review and Meta-Analysis.

Background: Lyme disease (LD, also known as Lyme borreliosis) is the most frequent tick-transmitted disease caused by the spirochete Borrelia in Europe and the United States. LD is distributed in the Northern Hemisphere, but the seroprevalence of LD in Asian human populations is unclear. Objectives: To investigate the seroprevalence of LD in Asian human populations. Data Sources: PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and other sources were searched for relevant studies with MeSH terms from their inception up to 20 June 2022. Study Eligibility Criteria: Cross-sectional studies with no language restrictions. Participants: Healthy people, at-risk people, and patients with suspected LD. Moreover, the seroprevalence of LD was diagnosed by laboratory diagnosis (nzyme-linked immunosorbent assays (ELISA)/Immunofluorescence assays (IFA) or/and two-tier testing) in human populations. Assessment of Risk of Bias: Risk of bias was rated using the Joanna Briggs Institute (JBI) standardized critical appraisal instrument for prevalence studies (Critical Appraisal Checklist for Analytical Cross-Sectional Studies). Methods of Data Synthesis: Seroprevalence and proportion of LD in human populations in Asia were obtained from the included studies. Two authors independently screened and selected studies according to our predefined criteria (PROSPERO CRD42022362029) and assessed their risk of bias. A third author was available for arbitrating discrepancies. A random-effects model meta-analysis was conducted to determine the proportions of LD and related information, and further subgroup analyses of some studies were conducted, such as methods for diagnosing LD, gender, and human populations with and without tick bites. Results: There are 18 studies included after full-text screening and 11,498 people in the meta-analysis. These studies encompassed countries such as China, Japan, Korea, Türkiye, Singapore, and Indonesia. Regarding the risk of bias and the JBI checklist, 2 studies scored 7 points and 16 studies scored 8 points. All studies were rated as high quality (≥5 points). In the meta-analysis, the seroprevalences of LD were 12.1% (95% confidence interval [CI] 0.081-0.168) by ELISA/IFA and 5.7% (95% CI 0.034-0.085) for two-tier seropositivity testing in Asia. In subgroup analyses, the proportion of those diagnosed with LD by ELISA/IFA (14.7%, 95% CI 0.094-0.208) was significantly higher than the proportion diagnosed by two-tier testing (5.9%, 95% CI 0.032-0.095) (p < 0.01). The proportion of LD (two-tier testing) was slightly higher in women (7.4%, 95% CI 0.036-0.123) than in men (6.2%, 95% CI 0.026-0.111), but the difference was not significant (p = 0.70). In the study population, 47% (95% CI 0.159-0.795) were bitten by ticks (people with confirmed tick bites). The difference in the proportion of LD (two-tier testing) in people who suffered tick bites (7.9%, 95% CI 0.019-0.166) and those who did not (people not found to have confirmed tick bites) (2.7%, 95% CI 0.013-0.089) was not significant (p = 0.09). Conclusions: The meta-analysis reveals a high seroprevalence of LD in Asia, indicating that it has become a significant public health concern in the region. Relevant government departments and health organizations in Asia should enhance their surveillance and education efforts regarding LD. This study highlights the importance of a reliable and accurate standard serological diagnostic procedure for confirming a diagnosis of LD. The strict implementation of two-tier testing is especially crucial in diagnosing LD. If only ELISA/IFA is used, it may cause false positive results. Its findings on the prevalence of LD can serve as a foundation for future research on surveillance and the prevalence of LD in the region. In addition, these findings may be useful for clinicians in their work.