The Chronic Manifestation Knot (CMK) model : a holistic and unified approach to facilitate graphical data visualization and statistical predictive modelling for diseases at the microorganism level

Abstract

Borrelia species are predominantly responsible for the most common form of Tick-borne diseases (TBD) which is Lyme borreliosis (LB). Episodes of Lyme arthritis (LA) is a hallmark symptom of LB patients. LA is an atypical form of reactive arthritis (ReA) that is a sub-type of Spondyloarthritis (SpA). Coinfections such as Ehrlichia chaffeensis accompany primary Borrelia species during the later stages of LB infection to induce severe symptoms. Currently, there is no holistic approach that would unify different TBD pathogens into independent and multiple TBD infection (MTBDI) combination categories to facilitate graphical and statistical analysis between any two patients groups. The chronic manifestation knot (CMK) model with its eight categories is a holistic and unified approach that facilitates data visualization and predictive statistical modelling (binary logistic regression) between two patients groups (LB and SpA patient groups). The CMK model helps to discover and clinically understand different developmental aspects of a disease at the microorganism(s) level. In order to validate the newly proposed CMK model, immune response frequencies of LB and SpA patient groups were statistically moulded to clinically understand relevant MTBDI combination(s) that may play an imperative in inducing chronic conditions. The immune response frequencies by LB and SpA patient groups (n = 54) to Borrelia burgdorferi, Borrelia burgdorferi RB, Borrelia afzelii, Borrelia garinii, and Ehrlichia chaffeensis were obtained from two independent studies that emphasized on recording the immune responses on the enzyme-linked Immunosorbent assay (ELISA) platform. The raw optical density (OD) values from both the studies were converted into the optical density index (ODI), and finally transformed into binary codes for establishing the eight CMK categories. Graphically, immune responses by both patient groups to the CMK categories revealed that the outer surface membrane proteins across both Borrelia morphologies are different. Statistically, the results revealed that Borrelia’s pleomorphic ability may play a crucial role for Borrelia spirochete to progress through the early to late stages of LB, to induce chronic conditions like arthritis together with coinfections. From statistical and experimental standpoints, the inclusion of Borrelia RB for diagnostic purposes should strongly be considered to improve the detection efficiency of the ongoing diagnostic tools.