Prevalence and clinical manifestation of Borrelia miyamotoi in Ixodes ticks and humans in the northern hemisphere: a systematic review and meta-analysis

Background: Various studies have evaluated the infection of Ixodes ticks and humans with the relapsing fever spirochaete Borrelia miyamotoi. However, to our knowledge, the prevalence of infection and disease has not been assessed systematically. We aimed to examine the prevalence of B miyamotoi in Ixodes ticks and humans, and the disease it can cause, in the northern hemisphere. Methods: For this systematic review and meta-analysis, we searched PubMed and Web of Science up to March 1, 2021. Studies assessing Ixodes tick infection published since Jan 1, 2011 were eligible, whereas no time limitation was placed on reports of human infection and disease. We extracted B miyamotoi test positivity ratios and used a random-effects model to calculate estimated proportions of infected ticks, infected humans, and human disease with 95% CI. This study was registered with PROSPERO, CRD42021268996. Findings: We identified 730 studies through database searches and 316 additional studies that referenced two seminal articles on B miyamotoi. Of these 1046 studies, 157 were included in the review, reporting on 165 637 questing ticks, 45 608 unique individuals, and 504 well described cases of B miyamotoi disease in humans. In ticks, the highest prevalence of B miyamotoi was observed in Ixodes persulcatus (2·8%, 95% CI 2·4–3·1) and the lowest in Ixodes pacificus (0·7%, 0·6–0·8). The overall seroprevalence in humans was 4·4% (2·8–6·3), with significantly (p<0·0001) higher seroprevalences in the high-risk group (4·6%, 2·6–7·1), participants with confirmed or suspected Lyme borreliosis (4·8%, 1·8–8·8), and individuals suspected of having a different tick-borne disease (11·9%, 5·6–19·9) than in healthy controls (1·3%, 0·4–2·8). Participants suspected of having a different tick-borne disease tested positive for B miyamotoi by PCR significantly more often than did the high-risk group (p=0·025), with individuals in Asia more likely to test positive than those in the USA (odds ratio 14·63 [95% CI 2·80–76·41]). Interpretation: B miyamotoi disease should be considered an emerging infectious disease, especially in North America and Asia. Prospective studies and increased awareness are required to obtain further insights into the burden of disease. Funding: ZonMW and the European Regional Development Fund (Interreg).