Review An update on the treatment of canine monocytic ehrlichiosis (Ehrlichia canis) Mathios E. Mylonakis a, *, Shimon Harrus b , Edward B. Breitschwerdt c a Companion Animal Clinic, School of Veterinary Medicine, Aristotle University of Thessaloniki, 11 Stavrou Voutyra st., Thessaloniki 54627, Greece b Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100, Israel c Intracellular Pathogens Research Laboratory, Comparative Medicine Institute, College of Veterinary Medicine, North Carolina State University (NCSU- CVM),1060 William Moore Drive, Raleigh, NC 27607 USA A R T I C L E I N F O Article history: Accepted 30 January 2019 Keywords: Aplastic pancytopenia Canine monocytic ehrlichiosis Dog Ehrlichia canis Treatment A B S T R A C T Canine monocytic ehrlichiosis (CME), caused by Ehrlichia canis, a gram-negative, obligate intracellular bacterium, is a tick-borne disease of worldwide distribution. Experimentally, the course of E. canis infection can be sequentially divided into acute, subclinical and chronic phases, although distinction of these phases is challenging in the clinical setting. Spontaneous clinical recovery of acutely infected dogs is common; however, dogs at this stage require medical treatment in order to hasten their clinical recovery, and to prevent clinical exacerbation or death. An unpredictable proportion of subclinically infected dogs will eventually develop the chronic, severe form of ehrlichiosis, characterized by aplastic pancytopenia and high mortality. The aims of antimicrobial treatment in CME include the achievement of clinical remission, resolution of the clinicopathologic abnormalities, and eradication of the infection, although the latter is not always feasible or diagnostically confirmable. Treatment of dogs with aplastic pancytopenia should be undertaken with the clear understanding that medical management will require long-term care, will be expensive, and may eventually prove ineffective. This manuscript reviews the current state of knowledge regarding treatment of ehrlichiosis, caused by E. canis infection in dogs, provides expert opinion guidelines for the management of the CME-associated aplastic pancytopenia, and outlines methods for evaluation of treatment outcomes. © 2019 Elsevier Ltd. All rights reserved. Introduction Ehrlichia canis is recognized as the principal cause of canine monocytic ehrlichiosis (CME) (Neer et al., 2002; Sainz et al., 2015). The disease is endemic in every continent except Australia (Sykes, 2014). In North America, and other less well characterized regions of the world, dogs can be infected with other Ehrlichia species, particularly Ehrlichia chaffeensis (Neer et al., 2002). E. canis bacteria are transmitted transstadially and intrastadially by the brown dog tick (Rhipicephalus sanguineous) (Bremer et al., 2005). Experimen- tal transmission has also been accomplished with Dermacentor variabilis ticks (Johnson et al., 1998), but the biological role of this vector in nature is obscure. In the experimental setting, after an incubation period of 8–20 days following blood transfusion or tick attachment, the course of E. canis infection can be sequentially divided into acute (2–4 weeks duration), subclinical (months to years) and chronic phases, although the distinction among these phases is not straightforward in dogs with naturally-occurring disease (Harrus et al., 2012). Fever (or hypothermia in profoundly pancytopenic dogs), depression or lethargy, anorexia, generalized lymphadeno- megaly, splenomegaly, mucosal pallor, bleeding tendency and ocular abnormalities (e.g. anterior or posterior uveitis) are typical clinical manifestations in naturally-occurring CME. Dogs with acute disease are likely to be infested with ticks. Ulcerative stomatitis and necrotic glossitis, hind limb and/or scrotal edema, and central nervous system signs such as seizures, ataxia, vestibular dysfunction and cervical pain, have been more frequently reported in the chronic disease. Bleeding diathesis may occur in both the acute and chronic phases of CME, but is more common and severe in the chronic phase, and is manifested as cutaneous and mucosal petechiae and ecchymoses, epistaxis, hematuria, melena and prolonged bleeding from venipuncture sites. In the subclinical phase of CME, clinical manifestations and/ or hematological abnormalities may be absent, or mild (e.g. splenomegaly, intermittent fever, thrombocytopenia, anemia) (Codner and Farris-Smith, 1986; Waner et al., 1997; Harrus et al., 1997: Harrus et al., 1998a; Mylonakis et al., 2011; Harrus & Waner, * Corresponding author. E-mail address: mmylonak@vet.auth.gr (M.E. Mylonakis). https://doi.org/10.1016/j.tvjl.2019.01.015 1090-0233/© 2019 Elsevier Ltd. All rights reserved. The Veterinary Journal 246 (2019) 45–53 Contents lists available at ScienceDirect The Veterinary Journal journal homepage: www.else vie r.com/locate /t vjl