Rodino, Kyle G.

ABSTRACT Recent decades have seen a rise in the incidence of tick-borne diseases in the US, along with an increased number of pathogens transmitted by ticks, and geographic expansion of tick populations. A variety of laboratory testing methodologies are available for the diagnosis of tick-borne diseases, including serology, microscopy, and molecular-based methods. The preferred approach varies by the specific disease, locally available test options, and the stage of illness at patient presentation. This mini-review focuses on updates in our understanding of the epidemiology of tick-borne diseases in the US and advances in the field of laboratory diagnostics.

Abstract Objectives Recent work has demonstrated that automated fluorescence flow cytometry (FLC) is a potential alternative for the detection and quantification of Plasmodium parasites. The objective of this study was to apply this novel FLC method to detect and quantify Babesia parasites in venous blood and compare results to light microscopy and polymerase chain reaction methods. Methods An automated hematology/malaria analyzer (XN-31; Sysmex) was used to detect and quantify B microti–infected red blood cells from residual venous blood samples (n = 250: Babesia positive, n = 170; Babesia negative, n = 80). As no instrument software currently exists for Babesia, qualitative and quantitative machine learning (ML) algorithms were developed to facilitate analysis. Results Performance of the ML models was verified against the XN-31 software using P falciparum–infected samples. When applied to Babesia-infected samples, the qualitative ML model demonstrated an area under the curve (AUC) of 0.956 (sensitivity, 95.9%; specificity, 83.3%) relative to polymerase chain reaction. For valid scattergrams, the qualitive model achieved an AUC of 1.0 (sensitivity and specificity, 100%), while the quantitative model demonstrated an AUC of 0.986 (sensitivity, 94.4%; specificity, 100%). Conclusions This investigation demonstrates that Babesia parasites can be detected and quantified directly from venous blood using FLC. Although promising, opportunities remain to improve the general applicability of the method.

Abstract Background Tick populations have expanded in many parts of the globe, bringing with them an enhanced appreciation and discovery of novel tickborne pathogens, as well an increased in reported human cases of tickborne disease. Targeted and unbiased (shotgun) clinical metagenomic sequencing tests are increasingly used for detection of known and emerging infectious agents and have recently been employed for detection of tickborne pathogens. Content This review describes the types of metagenomic sequencing assays used for detection of emerging tickborne pathogens and reviews the recent literature on this topic. Important diagnostic and interpretative challenges are also covered. Summary Metagenomic analysis has emerged as a powerful tool for detection, discovery, characterization, and classification of tickborne pathogens. Shotgun metagenomics is especially promising because it allows for detection of all tickborne bacteria, viruses, and parasites in a single specimen. Despite the potential advantages, there are several important challenges, including high cost, complexity of testing and interpretation, and slow turnaround time. No doubt, these challenges will diminish with increased use and advances in the field.

Reported cases of tick-borne diseases have steadily increased for more than a decade. In the United States, a majority of tick-borne infections are caused by bacteria.

Shotgun metagenomic sequencing can detect nucleic acids from bacteria, fungi, viruses, and/or parasites in clinical specimens; however, little data exist to guide its optimal application to clinical practice. We retrospectively reviewed results of shotgun metagenomic sequencing testing requested on cerebrospinal fluid samples submitted to an outside reference laboratory from December 2017 through December 2019. Of the 53 samples from Mayo Clinic patients, 47 were requested by neurologists, with infectious diseases consultation in 23 cases.

Abstract Background Tick-borne diseases are an important cause of human morbidity and mortality in the United States. The past several decades have witnessed an increase in both the number of recognized tick-borne pathogens and the number of tick-borne disease cases, whereas tick surveys have revealed substantial geographic expansions of tick populations throughout the country. Multiple laboratory testing options exist for diagnosis of tick-borne diseases, including serology, microscopy, and molecular-based methods. The preferred approach varies by the specific disease, locally available test options, and the stage of illness at patient presentation. Accurate and timely detection of tick-borne illness is of utmost importance, as prompt treatment is strongly linked to better outcomes. Content This review covers the clinical manifestations and preferred diagnostic approaches for important bacterial, viral, and parasitic tick-borne diseases in the United States, including Lyme disease, tick-borne relapsing fever, anaplasmosis, ehrlichiosis, spotted fever rickettsioses, and babesiosis. Infection with emerging pathogens such as Borrelia miyamotoi, Powassan virus, Heartland virus, Colorado tick fever virus, and Bourbon virus are also covered. Summary Our understanding of tick-borne diseases in the United States continues to improve with the detection of novel pathogens and development of new diagnostic modalities. While conventional diagnostic methods, including serology and microscopy, will play an ongoing role in the diagnosis of tick-borne diseases, implementation of advanced molecular diagnostics will further broaden our understanding of these diseases by facilitating detection of emerging pathogens and providing more accurate and timely diagnosis.