In Pursuit of a Stealth Pathogen: Laboratory Diagnosis of Bartonellosis

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Abstract

Members of the genus Bartonella cause illnesses in humans and animals. Bartonella spp. are gram-negative, fastidious, facultative, intracellular pathogens transmitted by the bites of certain arthropods or by bites and scratches from infected animals. While some of the illnesses are acute and self-limiting, others are chronic, debilitating, and difficult to diagnose. Bartonella spp. are able to invade host cells and modulate the host immune response, contributing to their success as stealth pathogens. This article provides an overview of diseases caused by members of the genus Bartonella and the mechanisms of pathogenesis. The laboratory diagnosis of bartonellosis relies on three primary methods. This article examines the evolution of culture techniques, serology, and nucleic acid amplification tests used to detect Bartonella spp. in clinical specimens and suggests areas for future research to improve laboratory diagnostics. In this way, a better understanding of the epidemiology of bartonellosis can be achieved.

Section snippets

Background

Members of the genus Bartonella have excelled as stealth pathogens, causing a variety of acute and chronic disease manifestations that vary not only with the infecting species, but also with the host species that becomes infected. Although bacteremia, which can be relapsing in nature and persistent in character, typifies the ecological behavior of Bartonella spp. within the host, the sites of bacterial localization, as well as the distribution of disease pathology, can vary substantially, even

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      This is due to the fastidious nature of the bacteria (exhibit a doubling time between 21 and 24 h), their complex growth requirements (i.e., requirement of growth factors such as hemoglobin or heme groups), and the relapsing, low-level bacteremia associated with Bartonella spp. infection (resulting in very low to undetectable levels of bacteria within blood, tissues, and body fluids). In addition, Bartonella spp. can invade several cell types, evade the host's immune system (often leading to long delays in seroconversion and negative serology test results) and subvert cellular functions leading to vasoproliferative or chronic (granulomatous) inflammatory disorders (Andersson and Kempf, 2004; Franz and Kempf, 2011; Arvand et al., 2001; Il'ina and Bashkirov, 2008; Pulliainen and Dehio, 2009; Pulliainen and Dehio, 2012; Resto-Ruiz et al., 2003; Chomel et al., 2009; Maggi et al., 2005; Hong et al., 2017; Wolf, 2014; Harms and Dehio, 2012). The current diagnostic gold standard for documentation of Bartonella spp. infection (the Bartonella species ePCR® platform) includes Bartonella DNA amplification from blood (or alternatively, cerebrospinal fluid, joint fluid and pathological effusions) before and after sample enrichment in a specialized formulated liquid broth, such as BAPGM (Bartonella Alpha Proteobacteria Growth Medium) (Andersson and Kempf, 2004; Franz and Kempf, 2011; Lynch et al., 2011; Riess et al., 2008; Weeden et al., 2017).

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