Effects of Borrelia on host immune system: Possible consequences for diagnostics

Borreliosis, Lyme disease, is the fastest growing tick borne infection in the world. Annually 300,000 (0.094%) people are diagnosed in the USA. Objective: To clarify and aid in the understanding of the indirect diagnostics of Borreliosis in the light of immune dysfunction. Diagnosis is difficult not only due to multi-systemic and nonspecific nature of symptoms but also due to the indirect diagnostics assuming immuno-competence in all three stages of Borreliosis. Indirect diagnostics are the most common method of testing for Borreliosis as they are cheap and convenient. However due to wide variation in antigenicity of genospecies, the sensitivity and specificity of diagnostics can be questioned. Evidence is accumulating which suggests that immune dysregulation induced by Borrelia (and other tick borne infections) can impact the indirect diagnostics, especially in Stage 3. The direct detection of Borrelia using nucleotide amplification method is possible but wider usage of this method is difficult as it has high specificity and narrow sensitivity. In vitro culturing is ideal but difficult as Borrelia has fastidious growth requirements. The immune status of the borreliosis patient needs to be considered, especially in Stage 3 in conjunction with clinical symptoms in the diagnosis. Borrelia has the ability to manipulate both the innate and active immunity and alter the cytokines secreted hence alter the path of the immune response. Immune parameters such as IFN-gamma/IL-10, lymphocyte markers, complement C3a, C4a, and total immunoglobulin levels may help to discriminate between stages and monitor treatment outcomes. The level of immune dysfunction in Stage 3 may depend on the number of co-infections delivered by a tick bite, such as Babesia, and Rickettsia, the genospecies of Borrelia, other pathogens, the patients' biome and immunogenetics. (C) 2014 Elsevier Ltd. All rights reserved.