IDCases 14 (2018) xxx–xxx Contents lists available at ScienceDirect IDCases journal homepage: www.elsevier.com/locate/idcr Case report Anaplasmosis: An emerging tick-borne disease of importance in Canada a, b,c d,e e,f Kelsey Uminski *, Kamran Kadkhoda , Brett L. Houston , Alison Lopez , g,h i c c Lauren J. MacKenzie , Robbin Lindsay , Andrew Walkty , John Embil , d,e Ryan Zarychanski a Rady Faculty of Health Sciences, Max Rady College of Medicine, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada b Cadham Provincial Laboratory, Government of Manitoba, Winnipeg, MB, Canada c Rady Faculty of Health Sciences, Max Rady College of Medicine, Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada d Rady Faculty of Health Sciences, Max Rady College of Medicine, Department of Internal Medicine, Section of Medical Oncology and Hematology, University of Manitoba, Winnipeg, MB, Canada e CancerCare Manitoba, Department of Medical Oncology and Hematology, Winnipeg, MB, Canada f Rady Faculty of Health Sciences, Max Rady College of Medicine, Department of Pediatrics and Child Health, Section of Infectious Diseases, Winnipeg, MB, Canada g Rady Faculty of Health Sciences, Max Rady College of Medicine, Department of Internal Medicine, Section of Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada h Rady Faculty of Health Sciences, Max Rady College of Medicine, Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada i Public Health Agency of Canada, National Microbiology Laboratory, Zoonotic Diseases and Special Pathogens, Winnipeg, MB, Canada A R T I C L E I N F O A B S T R A C T Article history: Human Granulocytic Anaplasmosis (HGA) is an infection caused by the intracellular bacterium Received 11 September 2018 Anaplasma phagocytophilum. As a tick-borne disease, the public health impact of HGA continues to Received in revised form 21 November 2018 increase with range expansion of the disease vector. The clinical presentation of HGA is often a non- Accepted 22 November 2018 specific febrile illness. The presence of leukopenia, thrombocytopenia, and mild hepatic injury are frequently noted on laboratory investigations, which can be important diagnostic clues in attaining an Keywords: appropriate diagnosis. Herein we present three cases of HGA, highlighting the spectrum of disease by Anaplasma phagocytophilum which HGA can manifest. Although each case has their unique features, we outline important shared Human granulocytic anaplasmosis clinical elements to facilitate an empiric diagnosis while definitive laboratory investigations are pending. HGA Our case series further serves to highlight the critical importance of prompt antimicrobial treatment to Tick-borne illness Zoonosis reduce morbidity and potential mortality. Canada © 2018 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). Introduction the expanding geographic range of the disease vector [4]. Since Manitoba became the first and only province in Canada to Human Granulocytic Anaplasmosis (HGA) is a rickettsial provincially mandate HGA reporting in 2015, the number of infection of granulocytes caused by the intracellular bacterium confirmed HGA cases, in addition to A. phagocytophilum prevalence Anaplasma phagocytophilum [1]. As a tick-borne disease, its among field-collected blacklegged ticks continues to rise [5]. transmission results in human illness through bites of the Despite this, recent human seroprevalence data suggest the true blacklegged tick (Ixodes scapularis) [2]. This same vector is incidence and prevalence of HGA remains underestimated, with implicated in the transmission of other known pathogens possible subclinical presentation of illness or missed clinical including Borrelia burgdorferi and Babesia microti, the etiologic opportunities of disease recognition [6]. agents of Lyme disease and Babesiosis, respectively [3]. The public The clinical presentation of HGA is often non-specific, with health impact of HGA continues to increase, largely attributed to most patients presenting with fever, chills, myalgias, arthralgias, headache and gastrointestinal symptoms [4]. Tick-exposure, if known, usually precedes symptom development by one to two weeks. In contrast to some other tick-borne diseases, the presence * Corresponding author at: Department of Internal Medicine, Rady Faculty of of rash is uncommon. Although complications, such as sepsis, heart Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, R3A 1R9, Canada. failure, renal failure, neurologic disease and rhabdomyolysis E-mail address: [email protected] (K. Uminski). remain infrequent [4], almost half of patients with HGA require https://doi.org/10.1016/j.idcr.2018.e00472 2214-2509/© 2018 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 2 K. Uminski et al. / IDCases 14 (2018) e00472 9 hospital admission [7]. Severe clinical presentations, although less 18 Â 10 /L) and hepatocellular injury (AST 118; ALT 71). Additional common, can be life threatening and require critical care support, findings included an elevated serum triglyceride level (2.3 [normal particularly amongst the elderly and immunocompromised or <1.7] mmol/L), hyperferritinemia (ferritin 13 806 [normal 20–200] those with significant comorbidities [7]. With B. burgdorferi co- ug/L), and splenomegaly. PCR testing of whole blood and infection rates with HGA ranging from 2.3 to 10% [8], consideration cerebrospinal fluid for A. phagocytophilum DNA confirmed the of concurrent infectious processes in the appropriate clinical diagnosis of HGA. Initial serologic testing for B. burgdorferi co- context must be given. Clinical overlap with features of thrombo- infection was negative. Oral doxycycline was empirically initiated cytopenia, elevated hepatic enzymes and anemia may be observed prior to receipt of confirmatory testing. The patient rapidly in Babesiosis; however, in many cases, the presence of the improved with complete resolution of neurologic symptoms over pathonogmonic “Maltese cross” formation of the parasite on three days, followed by normalization of all hematologic and peripheral blood smear is observed with marked gastrointestinal laboratory aberrations. Repeat serologic testing one month later symptoms [9]. Leukocytosis and thrombocytopenia are uncom- for IgG antibodies to A. phagocytophilum demonstrated serocon- mon with Lyme disease [9]. version. Herein we present three cases of HGA, presenting to an urban Case 3: A 72-year old male presented with generalized tertiary care center, highlighting the spectrum of disease by which weakness resulting in a fall. He endorsed a two week history of HGA can manifest. Although each case has unique features, we fevers and chills, with findings of progressive confusion and outline important shared clinical elements to facilitate an empiric respiratory distress noted at the time of initial assessment. On diagnosis. Our case series further highlights the critical importance collateral history, an unengorged tick had been removed from his of prompt recognition and antimicrobial treatment to reduce body one week prior to illness. Laboratory investigations 9 morbidity and potential mortality. demonstrated thrombocytopenia (platelet count 39 Â 10 /L), anemia (hemoglobin 98 [normal 130–170] g/L), hepatocellular Cases injury (AST 110 U//L; ALT 59 U/L), elevated serum triglycerides (2 mmol/L) and hyperferritinemia (4740 mg/L). Given the suspicion Case 1: A 68-year old previously well male farmer, presented of a tick-borne infection, doxycycline 100 mg orally twice daily was with complaints of fatigue, myalgias and confusion. He reported a initiated empirically. Given concern for evolving acquired hemo- tick bite two weeks prior to symptom onset. Fever was noted, with phagocytic lymphohistiocytosis (HLH) [10,11 ], intravenous immu- an otherwise unremarkable physical examination. Laboratory noglobulin and dexamethasone were concurrently administered. investigations revealed lymphopenia (lymphocyte count 0.40 Review of peripheral blood smear demonstrated neutrophils 9 [normal 1.3–3.2] Â10 /L), thrombocytopenia (platelet count 16 containing morulae. Subsequent, whole blood A. phagocytophilum 9 [normal 140–440] Â 10 /L), hepatocellular injury (AST 840 [normal PCR confirmed a diagnosis of HGA. With appropriate antimicrobial 10–32] U/L; ALT 189 [normal 0–25] U/L), rhabdomyolysis (creatine therapy following receipt of confirmatory testing, the patient’s kinase 57,624 [normal 20–215] U/L) and acute kidney injury condition quickly improved. (creatinine 3.77 [normal 0.40–1.10] mg/dL). Polymerase chain reaction (PCR) testing on whole blood for A. phagocytophilum DNA Discussion was positive. A peripheral blood smear demonstrated a neutrophil containing intracytoplasmic inclusions (morulae) suspicious for A. HGA is an emerging infectious disease of public health concern phagocytophilum (Fig. 1). The patient was promptly started on in Canada. With demonstrated geographic range expansion of the empiric oral doxycycline 100 mg twice daily prior to receipt of disease vector, the incidence of HGA disease has followed in confirmatory testing, with complete resolution of symptoms and parallel. In Manitoba, the number of confirmed HGA cases has normalization of laboratory aberrations, without complications.