Efficacy of a Doxycycline Treatment Regimen Initiated during Three Different Phases of Experimental Ehrlichiosis

Abstract

Doxycycline is the treatment of choice for canine monocytic ehrlichiosis (CME), a well-characterized disease and valuable model for tick-borne zoonoses. Conflicting reports of clearance of Ehrlichia canis after treatment with doxycycline suggested that the disease phase during which treatment is initiated influences outcomes of these treatments. The purpose of this study was to evaluate the efficacy of a 28-day doxycycline regimen for clearance of experimental E. canis infections from dogs treated during three phases of the disease. Ten dogs were inoculated with blood from E. canis carriers and treated with doxycycline during acute, subclinical, or chronic phases of CME. Daily rectal temperatures and semiweekly blood samples were monitored from each dog, and Rhipicephalus sanguineus ticks were acquisition fed on each dog for xenodiagnosis. Blood collected from dogs treated during acute or subclinical CME became PCR negative for E. canis as clinical parameters improved, but blood samples collected from dogs treated during chronic CME remained intermittently PCR positive. R. sanguineus ticks fed on dogs after doxycycline treatments became PCR positive for E. canis, regardless of when treatment was initiated. However, fewer ticks became PCR positive after feeding on two persistently infected dogs treated with doxycycline followed by rifampin, suggesting that antibiotic therapy can reduce tick acquisition of E. canis.

Farmacocinética y efectos adversos de la doxiciclina en el tratamiento de la Ehrlichiosis: fundamentos teóricos para ensayos clínicos en caninos

“…Sin embargo se reportó en un estudio que comprendió el uso de doxiciclina en ejemplares caninos clasificados en las 3 fases de la EMC (aguda, subclínica y crónica) a una dosis de 10 mg/Kg al día por 28 días. A 8 perros en fase aguda y subclínica de EMC no les fueron amplificados segmentos de genes para Ehrlichia canis por PCR, sin embargo hubo persistencia intermitente de bandas en la electroforesis en dos ejemplares con Ehrlichiosis crónica y en garrapatas que fueron alimentadas con estos de manera experimental (51). En otro estudio se evaluó la persistencia de Ehrlichia canis en 5 perros tratados con doxiciclina durante 7 días a una dosis de 10 mg/kg al día, y se pudo determinar la amplificación de segmentos de DNA de la bacteria en sangre, riñón, nódulos linfáticos, hígado y bazo en 3 ejemplares de los 5 perros estudiados, sin embargo en esta investigación en un grupo de 8 perros tratados por 14 días no se observaron resultados positivos a Ehrlichia canis por PCR (49).…”

“…Los resultados de estas investigaciones confirman la eficacia de la doxiciclina para contrarrestar la EMC en fase aguda y subclínica de la enfermedad. Diversos estudios indican que Ehrlichia canis puede persistir en perros clínicamente normales, incluso después de un amplio régimen de tratamiento con doxiciclina (49,51).…”

“…However, a study that included the use of doxycycline in canine specimens classified in the 3 phases of CME (acute, subclinical and chronic) at a dose of 10 mg/kg per day for 28 days, reported 8 dogs in the acute and subclinical phase of CME that did not show amplified gene segments for Ehrlichia canis by PCR. However there was an intermittent persistence of bands in the electrophoresis of two individuals with chronic Ehrlichiosis and in ticks that were experimentally fed (51). Another study evaluated the persistence of Ehrlichia canis in 5 dogs treated with doxycycline for 7 days at a dose of 10 mg/kg per day, and the amplification of DNA segments of the bacteria in blood, kidney, lymph nodes, liver and spleen in 3 specimens of the 5 dogs studied was determined.…”

In silico characterization of three two-component systems of Ehrlichia canis and evaluation of a natural plant-derived inhibitor

“…It provides the best results for the clinical improvement of treated animals. Nevertheless, although a series of reports confirm the elimination of E. canis in treated animals, others raise the possibility that total elimination varies with the stage of the disease (McClure et al, 2010). Therefore, new treatment regimens using new drugs, alone or in conjunction with doxycycline, are relevant for the treatment of CME and possibly other rickettsial diseases.…”

Bacterial canine vector-borne zoonotic diseases in “One Health” concept

“…For CME, the treatment of choice is based in daily administration of doxycycline for 1 month. This treatment will lead to a complete response in most clinical cases [27].…”