Global prevalence of Borrelia burgdorferi and Anaplasma phagocytophilum coinfection in wild and domesticated animals: A systematic review and meta-analysis.

Background: Both Borrelia burgdorferi (Bb) and Anaplasma phagocytophilum (Ap) can infect humans and animals through tick-borne transmission, resulting in zoonosis. Under certain conditions, human infection can lead to Lyme disease (LD) and human granulocytosis (HGA), whereas infection in animals can cause various acute and non-specific symptoms. The combination of Bb and Ap has been reported to increase the disease severity in infected animals. In this systematic review and meta-analysis, we investigated the global diversity of Bb and Ap coinfection in animals and their prevalence and distribution regarding spatial and species ecoepidemiology.

Methods: We queried PubMed, Web of Science, Embase, and the Cochrane Library for original studies on Bb and Ap coinfection. We assessed the rate of Bb and Ap in all included articles by single-group meta-analysis and subgroup analyses. We evaluated publication bias using a combination of funnel plots, Egger's tests, and Begg's tests, and conducted risk of bias assessment using the SYRCLE tool.

Results: Our search retrieved 40 articles, with eight involving 8419 infected animals meeting our inclusion criteria. The SYRCLE bias risk assessment indicated that most of the included studies were of high quality. Forest maps showed that the combined Bb and Ap infection rate in animals worldwide was 5.5% (95% confidence interval (CI) = 2.4-9.6). Subgroup analysis of forest maps showed that the coinfection rates were 8.2% (95% CI = 2.2-17.2) in North American, 0.2% (95% CI = 0.1-0.7) in European, and 1.2% (95% CI = 0.8-1.8) in Asian animals. Coinfection rates were 6.7% (95% CI = 2.7-12.2) in domestic and 0.0% (95% CI = 0.0-0.4) in wild animals. The coinfection rates were 9% (95% CI = 5.7-12.8) in domestic horses and 6% (95% CI = 1.9-12.2) in domestic dogs, whereas 7.5% (95% CI = 3-17.9) in wild squirrels and 0.2% (95% CI = 0.1-0.7) in wild mice. Funnel diagrams, Egger's tests, and Begg's tests showed no significant publication bias in the included studies.

Conclusions: Spatial epidemiology showed that coinfection with Bb and Ap in animals worldwide was most prevalent in the southwestern region of North America, whereas species epidemiology showed that coinfection was most prevalent in domesticated horses, followed by wild squirrels and domesticated dogs, but was less common in wild mice. These data on the epidemiological status of Bb and Ap coinfection in animals may help guide the prevention and treatment of zoonosis.