Unconventional diagnostic tests for Lyme borreliosis: a systematic review.

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.

Ticks and tick-borne diseases.

Ticks are a major group of arthropod vectors, characterized by the diversity of pathogens they transmit, by their impact on human and animal health, and by their socioeconomic implication especially in countries of the Southern Hemisphere. In Europe, Ixodes is the most important tick due to its wide distribution in the ecosystems and the variety of transmitted pathogens, in particular Borrelia (responsible for Lyme borreliosis), but also the tick-borne encephalitis virus. Their increased presence in the environment since the beginning of the 20th century is undeniable, because of major modifications in the biodiversity caused by humans. Increasing the awareness of health professionals and the general population is required to achieve better control of these infections. Thus, "a better understanding of these tick-borne diseases for a better control" is a simple but effective approach, considering their ubiquity in the environment and their particular mode of pathogen transmission (long-lasting blood meal for hard ticks and delayed transmission for bacteria and parasites). Finally, these ectoparasites are problematic due to the potential allergic reactions and other damages caused by their saliva, in humans and animals.