An apparent, locally acquired case of rickettsialpox (Rickettsia akari) in Ontario, Canada

Abstract

Rickettsialpox, caused by Rickettsia akari, is a spotted fever group rickettsiae transmitted to humans through the bite of the house mouse mite (Liponyssoides sanguineus). Worldwide, rickettsialpox is most commonly associated with exposure to rodents in urban environments. Here, we present the case of a 47-year-old woman from Brantford, Ontario, with fever, eschar on the right leg, expanding erythema, and right groin lymphadenopathy. Early in infection, R. akari serology was negative (IgG <1:64), but convalescent titre increased to 1:1,024. The patient did not travel outside of Ontario in the previous year. She denied any rodent or arthropod exposures in her home, but recently visited a friend’s home infested with bats and mice. The patient was afebrile after treatment with doxycycline, with resolution of most clinical and laboratory findings in 5 days. This is the first rickettsialpox case reported in Canada and highlights the importance of obtaining convalescent serology to assist in the diagnosis of rickettsial infection.

Case Presentation

A 47-year-old woman living in Brantford, Ontario (population ca. 134,000 for metropolitan area), presented to a local hospital in November 2018 with a 4-day history of abrupt onset of fevers, abdominal distention/pain, right groin pain, hematuria and mild shortness of breath with associated pleuritic chest discomfort. Her medical history was notable only for isolated Raynaud’s for over 10 years, and she was not on any long-term prescribed or over-the-counter medications. There was no family history of connective tissue diseases or other notable illness. Early in her admission, a progressive erythema developed over the right leg. A detailed physical examination revealed normal blood pressure and oxygen saturations, but a resting heart rate of 105 bpm and elevated temperatures reaching a high of 38.2°C. Her abdomen was grossly distended with diffuse tenderness consistent with peritonitis. A cardiac exam was unremarkable, but for the presence of anasarca. Mild crackles were heard at the lung base. There was tender lymphadenopathy at the right groin, and a small eschar was present over the right popliteal fossa (Figure 1). A progressive erythema tracked from the eschar up the thigh, onto the right flank/torso (Figure 2).

Figure 1:

Eschar over right popliteal fossa

Figure 2:

Diffuse truncal rash originating from the eschar, spanning over the right leg and onto torso. Abdominal distention in this otherwise thin woman is evident

She had not left Ontario for over a year, and in the preceding month had not travelled any significant distance away from her home. Her home is near a wooded park where she often walks her dog. She denied any rodent exposures in her home or tick exposure but had spent an hour visiting a friend’s home infested with bats and mice in the preceding 2–3 weeks.

A complete blood count revealed peripheral leukocytosis of 16.7 × 10⁹ cells/L (normal 4 to 11 × 10⁹ cells/L); her hemoglobin was 100 g/L (normal 120 to 160 g/L), MCV was 86 (normal 76 to 96 fL), and platelet count was 148 × 10⁹ cells/L (normal 140 to 440 × 10⁹ cells/L). Creatinine on admission was elevated at 191 µmol/L (normal 47 to 97 µmol/L) and normalized within 2 days. A liver profile revealed elevated C-reactive protein of 342 (normal <10 mg/L), with slightly elevated aspartate aminotransferase (AST) at 71 U/L (normal <34 U/L). Her direct bilirubin was normal at 7 µmol/L (normal 0–20 µmol/L), alanine aminotransferase (ALT) was 64 U/L (normal 10 to 49 U/L), alkaline phosphatase (ALP) was 61 U/L (normal 45 to 129 U/L), and albumin was 28 g/L (normal 32 to 48 g/L). A non-contrast computed tomography (CT) scan of the abdomen and pelvis revealed marked inflammatory change in the right retroperitoneal fascial planes (Figure 3). Inflammation was seen around the right psoas, and a small amount of fluid was noted in the perirectal space (Figure 4). Small effusions were evident in the pericardium and left pleural space. Her liver and spleen appeared normal.

Figure 3:

Non-contrast computed tomography scan showing retroperitoneal inflammatory change (white arrow)

Figure 4:

Non-contrast computed tomography scan revealing inflammatory change over psoas muscle (white arrow) and a small perirectal fluid collection (grey arrow)

Serial blood and urine cultures were negative, and stool testing for pathogenic bacteria and parasites was also negative. A routine bacterial swab of the eschar prior to initiation of doxycycline showed no growth. Rheumatologic testing in the form of antinuclear antibodies, antineutrophil cytoplasmic antibodies, anticyclic citrullinated peptide antibodies, and C3 and C4 complement levels were negative. A rheumatoid factor was 18 IU/mL. Serologies performed 7 days into her illness were negative for Francisella tularensis, Treponema pallidum, Borrelia burgdorferi, Coxiella burnetii, Bartonella, Leptospira, Histoplasma, hepatitis B/C viruses, and spotted fever group (SFGR) and typhus fever group (TFGR) rickettsiae.

She was initially treated with ceftriaxone, but showed no improvement after 3 days. Ceftriaxone was discontinued in favour of piperacillin-tazobactam, and upon identification of her rash and eschar the same day, empiric doxycycline was added. Her clinical and laboratory findings subsequently resolved over the next 5 days, though mild right groin and left pleuritic pain persisted for over 6 weeks.

We performed convalescent serology 4 weeks after initial testing through the Public Health Ontario Laboratory; results showed an SFGR titre >1:256. We subsequently forwarded the patient’s serologic samples to the United States Centers for Disease Control and Prevention (Atlanta, Georgia, USA) for Rickettsia species-specific serology. Titres for Rickettsia akari demonstrated the most marked change, with IgG titres on acute serum <1:64, increasing to 1:1,024 on convalescent serum (five-fold increase in IgG titres). Paired-sera titres for other Rickettsia species showed less pronounced elevations (i.e., SFGR: R. rickettsii <32 to 128, R. parkeri 128 to 256; TFGR: R. typhi <32 to 32, R. prowazekii 256 to 512).

Discussion

Rickettsia are obligate, gram-negative, intracellular bacteria that infect endothelial cells, causing vascular permeability and rash (1). Typically, Rickettsia are transmitted to humans through the bite of an arthropod vector, such as a tick or mite. Individuals develop a myriad of symptoms from mild to severe disease, with different SFGR and TFGR showing varying proclivity to cause an eschar, rash and lymphadenopathy. Human cases of rickettsioses are not common in Canada despite frequent reports in the United States (2–4). Historically, locally acquired cases of Rocky Mountain spotted fever (R. rickettsii) in Canada are known primarily from Alberta (1935–1950), with a single case reported from Ontario (1978) (5,6). Imported rickettsial infections are known from Ontario, such as African tick-bite fever (R. africae) (7). To our knowledge, the 1978 Rocky Mountain spotted fever case in Ontario is the sole report of a locally acquired rickettsial infection in the province.

We believe this is the first reported locally acquired R. akari infection in Canada. Though direct molecular testing was not possible due to a lack of appropriate samples, the greater than four-fold increase in the convalescent R. akari IgG titre indicated a recent infection and supported a diagnosis of rickettsialpox (8,9). Rickettsialpox is self-limited, and typically causes eschar formation and regional lymphadenopathy; a rash is almost universally present and is classically vesicular (10,11). The incubation period for R. akari is not well established and assumed 6–15 days, approximating the patient’s potential exposure 2–3 weeks prior to her symptom onset (12,13). During a study of rickettsialpox in New York, NY, an estimate of the incubation period ranged from 9 to 24 days, and an ensuing eschar can appear 1–7 days post-mite bite (14). In our case, her cellulitis-like rash is atypical, though variations of the rickettsialpox rash are known from the literature (14–17). In the closely related R. rickettsii, the development of the rash can be delayed or even absent in some cases (18,19). As well, the classic vesicular rash in rickettsialpox can occur between 4 to 14 days following the eschar formation (16,17,20). Accordingly, it is possible that the initiation of doxycycline could have aborted the classic rash from occurring, which is known to occur in Rocky Mountain spotted fever (19). Her prominent abdominal symptoms and findings of fascial involvement are also unusual. However, the patient’s significant clinical improvement after treatment with doxycycline is also further evidence of a rickettsial infection as doxycycline is the antibiotic of choice for rickettsial diseases. Piperacillin-tazobactam was initiated at the same time; however, given the clinical context and similarities in the spectrum of activity from ceftriaxone, it is unlikely that this portion of her therapy would have contributed to her rapid improvement, particularly when considering the multiple negative cultures.

R. akari is transmitted by the painless bite of the house mouse mite (Liponyssoides sanguineus) and was first described in an outbreak in New York City, NY, in 1946 (14). During this outbreak, skin lesions on patients resembled chickenpox, leading to its moniker rickettsialpox. Subsequent outbreaks and sporadic cases have been identified globally, including Costa Rica, Croatia, France, Italy, Mexico, Korea, Russia, South Africa, Turkey, and Ukraine (9,11,21,22). The best-known focus of rickettsialpox in North America is New York, NY, where approximately 10 cases per year (range 5–15) were reported from 2012 through 2017 (23). In addition, rickettsialpox cases in the United States are widespread and known from Arizona, Connecticut, Maryland, Massachusetts, North Carolina, Ohio, Pennsylvania, and Utah (10,21,24). Due to underreporting, the distribution of R. akari is likely much wider than the literature suggests (20). In addition, there is growing evidence that R. akari is not restricted to the house mouse (Mus musculus), as serological studies have demonstrated exposure in sylvatic rodents in California and domestic dogs in New York (25,26). In urban settings, there is a relatively high R. akari seroprevalence among the homeless and those who inject drugs; however, population-level seroprevalence studies are lacking (27,28). The Rickettsia species associated with rodents and their ectoparasites in Ontario are unknown, presenting an opportunity for detailed field and epidemiological studies.

Conclusion

The ultimate source of this patient’s exposure is unclear. She is not from a marginalized population, and so there may have been exposure to a biting arthropod in her home, her friend’s home, while walking her dog in the wooded area nearby, or from an unknown source. Rickettsial infections are not reportable in Ontario, and so it is possible that the lack of reporting of other cases will be on that basis, or perhaps due to mild clinical disease. Nonetheless, the finding is important to clinicians in considering rickettsial infections in the right clinical context and exposure history. Given the scarce literature on the clinical presentation of rickettsialpox and the ecology of R. akari, a diagnosis of rickettsialpox should not be excluded based on an atypical clinical presentation, denial of arthropod exposure, or geography. This case highlights the importance of obtaining convalescent serology to assist in diagnosis, but ideally, molecular testing from a skin biopsy of the eschar or whole blood would allow more reliable confirmation and speciation.

Competing Interests:

The authors have no conflicts of interest to declare related to this work.

Ethics Approval:

N/A

Informed Consent:

Written informed consent for the case to be published was obtained from the patient, including accompanying images and medical history.

Registry and the Registration No. of the Study/Trial:

N/A

Animal Studies:

N/A

Funding:

No funding was received for this work.

Peer Review:

This article has been peer reviewed.