Human granulocytic anaplasmosis: First reported case in Canada

Canadian ticks. Herein we present a case of HGA acquired in an urban Alberta centre. Canadian physicians must be aware of the possibility of tick-borne rickettsial diseases as etiology of fever in individuals presenting with leukopenia/lymphopenia, thrombocytopenia and elevated transaminases during periods of tick activity. Prompt recognition and treatment are important in minimizing resultant morbidity and mortality.

Human granulocytic anaplasmosis (HGA) is a tick-borne rickettsial infection of peripheral blood neutrophils caused by Anaplasma phagocytophilum.While this infection is increasingly recognized as endemic throughout much of the United States, no Canadian cases have been previously described, despite the agent being identified in Canadian ticks.Herein we present a case of HGA acquired in an urban Alberta centre.Canadian physicians must be aware of the possibility of tickborne rickettsial diseases as etiology of fever in individuals presenting with leukopenia/lymphopenia, thrombocytopenia and elevated transaminases during periods of tick activity.Prompt recognition and treatment are important in minimizing resultant morbidity and mortality.

Discussion
There are a number of medically important ticks capable of transmitting zoonoses to humans found in North America (Table 1 HGA is a tick-borne rickettsial infection of neutrophils caused by A phagocytophilum.While HGA has previously been described in many parts of the United States (northeastern, mid-Atlantic, upper-midwest and Pacific northwest states), Europe and Asia, it has not been described in Canada (although the agent has been found in Canadian ticks) (4).A reportable condition in the United States, documented infections tripled from 2000 to 2005.In 2005, there were 700 cases reported to the Center for Disease Control and Prevention (5).The true burden of infection may be much higher because seroprevalence studies in populations living in areas of high endemicity show 0.6% to 14.9% of individuals have reactive antibodies.However, prospective studies do not show this same burden of disease; therefore, it is unknown if this relates to mild or subacute infection or rather to cross-reacting antibodies to other agents.
Human infection occurs as a result of a bite from a tick infected with A phagocytophilum.Patients often present with febrile illness associated with headache, fever and myalgias (4-6).Rash is not a common manifestation of disease.Most patients report tick exposure one to two weeks before the onset of infection.Laboratory findings often include thrombocytopenia, leukopenia/lymphopenia and elevated hepatic transaminases.Approximately 50% of patients with documented HGA require hospital admission and 7% require intensive care support.Unlike Rocky Mountain spotted fever and human monocytic ehrlichiosis, death is uncommon and occurs in only 0.5% of documented infections.Complications are uncommon but include sepsis-like syndromes, acute respiratory distress syndrome, heart failure, acute renal failure, rhabdomyolysis and  (7).Anaplasma species are uniformly susceptible to tetracyclines (4,5).Because of favourable pharmacokinetics, treatment with doxycycline 100 mg by mouth twice daily for five to 14 days is recommended in patients for whom the drug is not contraindicated.For those with history of allergy, pregnancy or young age, rifampin serves as alternate therapy.Patients typically exhibit full recovery within 24 h to 48 h of therapy.
The majority of I scapularis ticks are not infected with infectious disease agents that are transmissible to humans.Rates of infection vary greatly depending on region where ticks were collected but Canadian data suggests A phagocytophilum affects 0.4% of I scapularis (United States rates are much higher, at 4.7%) (3,8).Other common infections transmitted by I scapularis ticks include Lyme disease (caused by Borrelia burgdorferi), rickettsial species and babesiosis (caused by Babesia microti), although the later two have not been described as endemic to Canada.There has, however, been one case of transfusionassociated babesiosis acquired in Canada where the blood donor had travelled to endemic zones in the United States (9).Multiply infected ticks are occasionally found, predominately in the eastern and mid-eastern parts of the United States, leading to coinfections with more than one individual tick-borne pathogen (5).There is increasing concern that through environmental changes, including global warming, there will be an associated expansion of tick populations to many other areas of Canada and with them, potentially tick-borne illnesses (10).High-density populations of suitable rodent/white tail deer populations exist in many parts of Canada, which could readily support their expansion.
While HGA has not previously been described in Canada, there have been occasions in which anaplasmosis has been described in animals.Most recently, three separate cases of canine anaplasmosis were described in Saskatchewan dogs presenting with fever, lethargy, vomiting and diarrhea (11).Furthermore, A phagocytophilum-infected I scapularis ticks have been infrequently identified from migratory birds in eastern Canada (3).Neither HGA nor any other tick-borne disease is currently a mandatory reportable illness in Canada.
In the case described herein, it is apparent that A phagocytophilum from a tick acquired in Canada has resulted in the first case of locally transmitted HGA.Locally reproducing populations of I scapularis are not known to exist in the province of Alberta and as such this likely represents an adventitiously introduced tick.The fact that the adherent tick was negative for A phagocytophilum when screened at the National Microbiology Laboratory should not be surprising, given that normal time from tick acquisition to disease is seven to 14 days (4,5), much longer then tick adherence.As such, it is likely that this gentleman unknowingly had repeated recent tick exposures and a previous tick was responsible for disease transmission.
The present case illustrates that Canadians are at risk for tick-borne illnesses not previously thought to occur in Canada.There is an urgent need for Canadian-specific data regarding the epidemiology of ticks and tick-borne agents in Canada.Patients presenting during times of tick activity (May to September) with fever, leukopenia/lymphopenia, thrombocytopenia and increased serum transaminases should have rickettsial diseases such as HGA included in the differential diagnosis.Lack of historical or epidemiological features for tick exposure should not exclude the diagnosis when the clinical features are present, as illustrated by the present case.
DiscLosure: All authors are free of potential conflicts.The patient described herein has provided written consent for the publication of this case report.

TAble 1 Tick-borne diseases endemic in North America that are transmissible to humans
Risk factors for adverse outcomes include advanced age and host immune-suppression.Recently, secondary cases of human to human nosocomial transmission of HGA were documented in China, associated with large volume exposure to the index patient's blood and respiratory secretion