BACKGROUND Lyme borreliosis (LB) diagnosis currently relies mainly on serological tests and sometimes PCR or culture. However, other biological assays are being developed to try to improve Borrelia-infection diagnosis and/or monitoring. OBJECTIVES To analyse available data on these unconventional LB diagnostic assays through a systematic literature review. METHODS We searched PubMed and Cochrane Library databases according to the PRISMA-DTA method and the Cochrane Handbook for Systematic Reviews of Interventions. We analysed controlled and uncontrolled studies (published 1983-2018) on biological tests for adults to diagnose LB according to the European Study Group for Lyme Borreliosis or the Infectious Diseases Society of America definitions, or identify strongly suspected LB. Two independent readers evaluated study eligibility and extracted data from relevant study reports; a third reader analysed full texts of papers to resolve disagreements. The quality of each included study was assessed with the QUADAS-2 evaluation scale. RESULTS Forty studies were included: two meta-analyses, 25 prospective controlled studies, five prospective uncontrolled studies, six retrospective controlled studies and two case reports. These biological tests assessed can be classified as: (i) proven to be effective at diagnosing LB and already in use (CXCL-13 for neuroborreliosis), but not enough to be standardized; (ii) not yet used routinely, requiring further clinical evaluation (CCL-19, OspA and interferon-α); (iii) uncertain LB diagnostic efficacy because of controversial results and/or poor methodological quality of studies evaluating them (lymphocyte transformation test, interferon-γ, ELISPOT); (iv) unacceptably low sensitivity and/or specificity (CD57+ natural killer cells and rapid diagnostic tests); and (v) possible only for research purposes (microscopy and xenodiagnoses). DISCUSSION QUADAS-2 quality assessment demonstrated high risk of bias in 25/40 studies and uncertainty regarding applicability for 32/40, showing that in addition to PCR and serology, several other LB diagnostic assays have been developed but their sensitivities and specificities are heterogeneous and/or under-evaluated or unassessed. More studies are warranted to evaluate their performance parameters. The development of active infection biomarkers would greatly advance LB diagnosis and monitoring.

中文翻译：

---

莱姆病的非常规诊断测试：系统评价。

背景技术目前，莱姆病（LB）诊断主要依靠血清学检测，有时还需要PCR或培养。然而，正在开发其他生物学测定法以尝试改善博氏疏螺旋体感染的诊断和/或监测。目的通过系统的文献综述来分析这些非常规LB诊断方法的可用数据。方法我们根据PRISMA-DTA方法和Cochrane手册对干预进行系统评价，检索了PubMed和Cochrane图书馆数据库。我们根据欧洲莱姆疏螺旋体病研究小组或美国传染病学会的定义，分析了针对成年人的生物学测试的对照和非对照研究（于1983-2018年发表），以诊断LB，或鉴定出高度怀疑的LB. 两名独立读者评估了研究资格，并从相关研究报告中提取了数据；第三位读者分析了全文，以解决分歧。使用QUADAS-2评估量表评估每个纳入研究的质量。结果共纳入40项研究：两项荟萃分析，25项前瞻性对照研究，5项前瞻性非对照研究，6项回顾性对照研究和2例病例报告。评估的这些生物学测试可以归类为：（i）已被证明对LB诊断有效并且已经在使用（对于神经性硼中毒则使用CXCL-13），但还不足以进行标准化；（ii）尚未常规使用，需要进一步的临床评估（CCL-19，OspA和干扰素-α）；（iii）由于有争议的结果和/或评估研究结果的方法学质量较差（淋巴细胞转化试验，γ-干扰素，ELISPOT），LB诊断功效不确定；（iv）不可接受的低灵敏度和/或特异性（CD57 +自然杀伤细胞和快速诊断测试）；（v）仅可能用于研究目的（显微镜和异种诊断）。讨论QUADAS-2质量评估显示25/40研究存在偏倚的高风险以及32/40适用性的不确定性，表明除PCR和血清学外，还开发了其他几种LB诊断测定法，但它们的敏感性和特异性是异质的， /或被低估或未评估。有必要进行更多的研究来评估其性能参数。