Antibodies against tick-borne pathogens: Diagnostics and epidemiology

Abstract

Climate change has expanded tick habitats, leading to greater human exposure to ticks and the pathogens they carry, especially in areas where nature-preserving activities like reforestation and urban greenspaces create overlapping habitats. In Northern Europe, Ixodes ricinus is the most prevalent tick species, known for transmitting Borrelia burgdorferi s.l., the causative agent of Lyme borreliosis (LB). In the Netherlands, LB is the most common vector-borne disease, with its incidence quadrupling since the 1990s. Other known I. ricinus-borne pathogens, including Anaplasma phagocytophilum, Babesia species, and Rickettsia helvetica, are emerging. Little is known about their epidemiology, which requires further study. The dissertation has two main objectives: (i) evaluating the performance of commercially available antibody assays and test strategies for LB diagnosis and their clinical interpretation, and (ii) assessing the prevalence of human antibodies against tick-borne pathogens and associated risk factors in various populations. The main conclusions of part I of this dissertation were that commercially available assays and test strategies perform comparably well. While IgG or combined IgM/IgG assays and strategies showed high sensitivity and acceptable specificity, the added value of IgM testing is debatable. Despite advancements in serological testing, a reliable marker for active LB is still lacking, emphasizing the importance of interpreting laboratory results in the context of clinical history. A survey among medical microbiologists in the Netherlands revealed challenges in diagnosing active disease for low-incidence Lyme manifestations, suggesting the need for continued education. Artificial intelligence-guided algorithms and a case register could aid clinical decision-making, resulting in optimized diagnostic accuracy and increased patient trust. In part II, a study of 2016/2017 data found a 4.4% prevalence of B. burgdorferi s.l.-specific antibodies in the general population, with higher rates in men, older individuals, and those with frequent tick bites. Comparisons with 1995/1996 data showed a significant increase in seroprevalence over time, particularly among those over 50, possibly due to increased outdoor activities. A cohort of nature management workers showed higher seropositivity rates for B. burgdorferi s.l. and demonstrated exposure to non-borrelial pathogens, indicating occupational exposure risks. Future research should focus on identifying reliable markers for active LB and developing state-of-the-art diagnostics for rare pathogens. Continued surveillance and diagnostic development are crucial for understanding the epidemiology and pathology of tick-borne diseases, ultimately aiding in disease prevention and burden reduction.