Pathogen Safety Data Sheet: Infectious Substances – Rickettsia japonica

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Section I: Infectious agent

Name: Rickettsia japonica
Agent type: Bacteria


Family: Rickettsiaceae
Genus: Rickettsia
Species: japonica

Synonym or cross reference: Japanese spotted feverFootnote 1, also known as Oriental spotted feverFootnote 2,Footnote 3.


Brief Description: R. japonica are Gram negative, non-motile bacilli measuring 0.5 μm by 0.8-1.5 μmFootnote 1. These obligate intracellular bacteria can be cultured in vitro using Vero cellsFootnote 1. In animal models and humans, Rickettsia spp. primarily target endothelial cells that line small blood vesselsFootnote 4.

Properties: Spotted fever group Rickettsiae, such as R. japonica, adhere to host cell receptors using OmpA and OmpBFootnote 1. R. japonica enter host cells via induced phagocytosis. Once inside the host cell, bacteria escape from the phagosome, invade the cytosol, and replicate by binary fission. R. japonica use host cell machinery to activate apoptosis for release from host cellsFootnote 1.

Section II: Hazard identification

Pathogenicity/toxicity: R. japonica is the causative agent of Japanese spotted fever, which was recognized as a new disease in 1984Footnote 5.  Symptoms usually include fever, headache, and rashFootnote 1Footnote 2. An eschar, a localized and inflammatory necrotic skin lesion, at the site of the tick bite may also be present. Eschars generally persist for 1 to 2 weeksFootnote 3. Erythema on the palms and soles are strongly associated with Japanese spotted feverFootnote 3,Footnote 6.

The mortality rate of Japanese spotted fever is approximately 1%Footnote 3. Nervous system (e.g., meningoencephalitis)Footnote 7,Footnote 8, cardiacFootnote 9, disseminated intravascular coagulationFootnote 3, respiratory failureFootnote 10, and multiple organ failureFootnote 8,Footnote 11 complications have been documented.

R. japonica-infected dogs can develop clinical symptoms including feverFootnote 12, but there have been no reported cases of natural animal infection for R. japonica.Footnote 13

Predisposing factors: Renal dysfunction is associated with the development of complications, such as disseminated intravascular coagulation and prolonged disease courseFootnote 14.

Communicability: Inoculation of R. japonica into a host via a tick vector is the most common mode of transmission. Tick-borne rickettsia are transmitted to humans by tick-salivary excretions, but Rickettsia in general are not transmittable from person to personFootnote 15. Transmission by inhalation is considered likely given that aerosolized forms of other Rickettsia spp. have caused disease in laboratory workers and can cause infection in monkeys and guinea pigsFootnote 16,Footnote 17,Footnote 18,Footnote 19.

Epidemiology: Japan and KoreaFootnote 2,Footnote 20. The incidence rate of Japanese spotted fever is approximately 0.38 per 1,000,000 people per yearFootnote 21. There were 241 and 175 reported cases in Japan in 2014 and 2013 respectivelyFootnote 22. Incidence rates of Japanese spotted fever are significantly higher in some prefectures of Japan (e.g., Shimane, Kochi, Kagoshima, Tokushima, Miyazaki, Wakayama, and Ehime) compared to the national averageFootnote 21. Japanese spotted fever is associated with old age and residing in wooded areasFootnote 6. Cases of Japanese spotted fever typically occur between April and OctoberFootnote 6.

Host range

Natural Host(s): Humans, dogs and cats.Footnote 13

Other Host(s): Guinea pigs can be experimentally infected with spotted fever group RickettsiaeFootnote 1,Footnote 23.

Infectious dose: Unknown for R. japonica; Rickettsiae are considered infectious at low doses in aerosolized formFootnote 19.

Incubation period: 2 to 10 days after a tick biteFootnote 3.

Incubation period: Unknown.

Section III: Dissemination

Reservoir: TicksFootnote 3, rodentsFootnote 24, catsFootnote 25, dogsFootnote 25,Footnote 26, small carnivores such as feral raccoonsFootnote 27,Footnote 28, cattle and deerFootnote 29.

Zoonosis/reverse zoonosis: None.

Vectors: R. japonica are inoculated into host skin by an infected tick during feeding via salivary excretions.Footnote 1,Footnote 30.  R. japonica have been detected in various tick species including Amblyomma testudinarium, Ixodes monospinosus, Ixodes ovatus, Ixodes persulcatus, Dermacentor taiwanensis, Haemaphysalis flava, Haemaphysalis hystricis, Haemaphysalis longicornis, Haemaphysalis megaspinosa, Haemaphysalis cornigera, Haemaphysalis formosensis Footnote 2,Footnote 3,Footnote 31,Footnote 32.

Section IV: Stability and viability

Drug susceptibility: Tetracyclines (e.g., doxycycline), chloramphenicolFootnote 33, fluoroquinolones (e.g., ciprofloxacin, ofloxacin, pefloxacin), and some macrolides, such as josamycin and leucomycinFootnote 33,Footnote 34 are effective against R. japonica.

Drug resistance: R. japonica are resistant to erythromycinFootnote 34.

Susceptibility to disinfectants: Rickettsiae are susceptible to 1% sodium hypochlorite, 70% ethanol, 2% glutaraldehyde, formaldehyde, and quaternary ammonium compoundsFootnote 35.

Physical inactivation: Moist heat (121°C for 15 min) and dry heat (170°C for 1 hour) are effective against bacteria such as R. japonicaFootnote 36.

Survival outside host: Rickettsiae are usually unable to survive for long periods when they are separated from host cell componentsFootnote 1. Generally, bacterial persistence on inanimate surfaces also depends on environmental conditions, such as relative humidity, temperature, biofilm, and surface typeFootnote 37.

Section V: First aid and medical

Surveillance: Diagnosis is accomplished through the monitoring of clinical symptoms, patient history, and laboratory testsFootnote 2. Serological tests (e.g., indirect immunofluorescence assay, ELISA) can be used to detect spotted fever group Rickettsiae but lack the specificity to distinguish individual speciesFootnote 38,Footnote 39. Paired blood samples are required (acute and convalescent phase) and seroconversion is usually detected 7 to 15 days after disease onset, which limits the utility of these tests for making timely clinical decisionsFootnote 2. PCR analysis of bloodFootnote 11,Footnote 40,Footnote 41 and skin samples taken from the eschar or lesionsFootnote 40,Footnote 42 can be used to rapidly detect R. japonica.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook (CBH).

First aid/treatment: Japanese spotted fever can be treated with appropriate antibiotics. Tetracycline (e.g., doxycycline, minocycline), alone or in combination with a fluoroquinolone (e.g., ciprofloxacin), is commonly administeredFootnote 3,Footnote 43.
Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the CBH.

Immunization:  No vaccine currently available.

Note: More information on the medical surveillance program can be found in the CBH, and by consulting the Canadian Immunization Guide.

Prophylaxis: None.
Note: More information on prophylaxis as part of the medical surveillance program can be found in the CBH.

Section VI: Laboratory hazards

Laboratory-acquired infections: None reported to date. However, R. rickettsia, which is closely related to R. japonica, has been known to infect laboratory personnel via aerosolized bacteriaFootnote 17.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements and guidelines for reporting exposure incidents.

Sources/Specimens: Blood, skin biopsyFootnote 42.

Primary hazards: Inhalation of infectious aerosols, exposure of mucous membranes, accidental inoculation or bites from infected ticks.

Special hazards: None.

Section VII: Exposure controls and personal protection

Risk group classification: R. japonica is a Risk Group 3 human pathogen and Risk Group 1 animal pathogenFootnote 44.

Containment requirements: Containment Level 3 facilities, equipment, and operational practices outlined in the CBS for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing: The applicable Containment Level 3 requirements for personal protective equipment and clothing outlined in the CBS should be followed. Full coverage PPE, including eye protection and respiratory protection, should be considered

Other precautions: All activities involving open vessels of infectious material or toxins should be performed in a certified BSC or other appropriate primary containment deviceFootnote 45. Additional precautions should be considered when handling infected arthropods. Procedures for arthropod containment, handling, immobilization, monitoring, and recovery of escaped arthropods should be implemented. Refer to the applicable arthropod requirements of the Containment Standards for Facilities Handling Plant PestsFootnote 46.

Section VIII: Handling and storage

Allow aerosols to settle. Wearing protective clothing, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean upFootnote 47.

All materials/substances that have come in contact with the infectious agent should be completely decontaminated before they are removed from the containment zone.  This can be achieved by using a decontamination method that has been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontaminationFootnote 47.

The applicable Containment Level 3 requirements for storage outlined in the CBSshould be followed.  Containers of infectious material or toxins stored outside the containment zone should be labelled, leakproof, impact resistant, and kept in locked storage equipment and within an area with limited accessFootnote 47.

Section IX: Regulatory and other information

Regulatory information: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.

Canadian Regulatory Context: At the time of publication of this PSDS, this pathogen is subject to official control. The following is a non-exhaustive list of applicable designations, regulation, or legislation:

Updated: September, 2019

Prepared by: Centre for Biosecurity, Public Health Agency of Canada.

Although the information, opinions, and recommendations contained in this Pathogen Safety Data Sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.

Copyright © Public Health Agency of Canada, 2019, Canada         



Footnote 1

Yu, X. J., and D. H. Walker. 2005. Genus I. Rickettsia, p. 96. In G. M. Garrity, D. J. Brenner, N. R. Krieg, and J. T. Staley (eds.), Bergey's Manual of Systematic Bacteriology, Second Edition. Volume Two: The Proteobacteria (Part C). Springer, USA.

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Footnote 2

Parola, P., C. D. Paddock, C. Socolovschi, M. B. Labruna, O. Mediannikov, T. Kernif, M. Y. Abdad, J. Stenos, I. Bitam, P. -. Fournier, and D. Raoult. 2013. Update on Tick-Borne Rickettsioses around the World: a Geographic Approach. Clinical Microbiology Reviews. 26(4):657-702.

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Footnote 3

Mahara, F. 2006. Rickettsioses in Japan and the far East. Ann. N. Y. Acad. Sci. 1078:60-73.

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Footnote 4

Sahni, S. K., and E. Rydkina. 2009. Host-cell interactions with pathogenic Rickettsia species. Future Microbiol. 4:323-339.

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Footnote 5

 Kawamura, A.,Jr, and H. Tanaka. 1988. Rickettsiosis in Japan. Jpn. J. Exp. Med. 58:169-184.

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Footnote 6

Sando, E., M. Suzuki, M. Yaegashi, M. Taira, T. Ogawa, and K. Ariyoshi. 2017. Clinical and Epidemiological Characteristics of Japanese Spotted Fever and Scrub Typhus in Central Japan, 2004–2015. Open Forum. Infect. Dis. 4:S119.

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Footnote 7

Araki, M., K. Takatsuka, J. Kawamura, and Y. Kanno. 2002. Japanese Spotted Fever Involving the Central Nervous System: Two Case Reports and a Literature Review. J. Clin. Microbiol. 40:3874-3876.

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Footnote 8

Nakata, R., M. Motomura, M. Tokuda, H. Nakajima, T. Masuda, T. Fukuda, A. Tsujino, T. Yoshimura, and A. Kawakami. 2012. A case of Japanese spotted fever complicated with central nervous system involvement and multiple organ failure. Intern. Med. 51:783-786.

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Footnote 9

Fukuta, Y., F. Mahara, T. Nakatsu, T. Yoshida, and M. Nishimura. 2007. A case of Japanese spotted fever complicated with acute myocarditis. Jpn. J. Infect. Dis. 60:59-61.

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Footnote 10

Takiguchi, J., K. Okimura, M. Ishii, K. Okamura, H. Sakamoto, S. Inamoto, and S. Ando. 2016. Severe Japanese Spotted Fever Complicated by Acute Respiratory Failure in Kobe City. Kansenshogaku Zasshi. 90:120-124.

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Footnote 11

Kodama, K., T. Senba, H. Yamauchi, Y. Chikahira, T. Katayama, Y. Furuya, H. Fujita, and S. Yamamoto. 2002. Fulminant Japanese spotted fever definitively diagnosed by the polymerase chain reaction method. J. Infect. Chemother. 8:266-268.

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Footnote 12

Inokuma, H., H. Matsuda, L. Sakamoto, M. Tagawa, and K. Matsumoto. 2011. Evaluation of Rickettsia japonica Pathogenesis and Reservoir Potential in Dogs by Experimental Inoculation and Epidemiologic Survey. Clin. Vaccine Immunol. 18:161-166.

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Footnote 13

Tabuchi, M., Jilintai, Y. Sakata, N. Miyazaki, and H. Inokuma. 2007. Serological Survey of Rickettsia japonica Infection in Dogs and Cats in Japan. Clin Vaccine Immunol. 14:1526-1528.

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Footnote 14

Nakamura, T., K. Takagaki, Y. Matsubara, and K. Kikuchi. 2011. Predictive values of clinical parameters for severe Japanese spotted fever. J. Infect. Chemother. 17:246-253.

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Footnote 15

Azad, A. F., and C. B. Beard. 1998. Rickettsial pathogens and their arthropod vectors. Emerg. Infect. Dis. 4:179-186.

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Footnote 16

Kenyon, R. H., R. A. Kishimoto, and W. C. Hall. 1979. Exposure of guinea pigs to Rickettsia rickettsii by aerosol, nasal, gastric, and subcutaneous routes and protection afforded by an experimental vaccine. Infection and Immunity. 25(2):580-582.

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Footnote 17

Oster, C. N., D. S. Burke, R. H. Kenyon, M. S. Ascher, P. Harber, and C. E. Pedersen. 1977. Laboratory-acquired Rocky Mountain spotted fever.  The hazard of aerosol transmission. The New England Journal of Medicine. 297(16):859-863.

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Footnote 18

Saslaw, S., and H. N. Carlisle. 1966. Aerosol infection of monkeys with Rickettsia rickettsii. Bacteriological Reviews. 30(3):636-645.

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Footnote 19

Walker, D. H. 2003. Principles of the malicious use of infectious agents to create terror: reasons for concern for organisms of the genus Rickettsia. Ann. N. Y. Acad. Sci. 990:739-742.

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Footnote 20

Chung, M. H., S. H. Lee, M. J. Kim, J. H. Lee, E. S. Kim, M. K. Kim, M. Y. Park, and J. S. Kang. 2006. Japanese spotted fever, South Korea. Emerg. Infect. Dis. 12:1122-1124.

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Footnote 21

Hashimoto, S., M. Kawado, Y. Murakami, M. Izumida, A. Ohta, Y. Tada, M. Shigematsu, Y. Yasui, K. Taniguchi, and M. Nagai. 2007. Epidemics of Vector-borne Diseases Observed in Infectious Disease Surveillance in Japan, 2000-2005. J. Epidemiol. 17:S48-55.

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Footnote 22

Japan Ministry of Health, Labour and Welfare. Handbook of Health Welfare and Statistics 2016. 2018.

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Footnote 23

Bechah, Y., C. Capo, J. L. Mege, and D. Raoult. 2008. Rickettsial diseases: from Rickettsia-arthropod relationships to pathophysiology and animal models. Future Microbiol. 3:223-236.

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Footnote 24

Yamamoto, S., C. Morita, and K. Tsuchiya. 1992. Isolation of spotted fever group rickettsia from Apodemus speciosus in an endemic area in Japan. Jpn. J. Med. Sci. Biol. 45:81-86.

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Footnote 25

Tabuchi, M., Jilintai, Y. Sakata, N. Miyazaki, and H. Inokuma. 2007. Serological Survey of Rickettsia japonica Infection in Dogs and Cats in Japan. Clin. Vaccine Immunol. 14:1526-1528.

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Footnote 26

Inokuma, H., S. Yamamoto, and C. Morita. 1998. Survey of tick-borne diseases in dogs infested with Rhipicephalus sanguineus at a kennel in Okayama Prefecture, Japan. J. Vet. Med. Sci. 60:761-763.

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Footnote 27

Inoue, K., H. Kabeya, H. Fujita, T. Makino, M. Asano, S. Inoue, H. Inokuma, S. Nogami, and S. Maruyama. 2011. Serological survey of five zoonoses, scrub typhus, Japanese spotted fever, tularemia, Lyme disease, and Q fever, in feral raccoons (Procyon lotor) in Japan. Vector Borne Zoonotic Dis. 11:15-19.

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Footnote 28

Sashika, M., G. Abe, K. Matsumoto, and H. Inokuma. 2010. Molecular survey of rickettsial agents in feral raccoons (Procyon lotor) in Hokkaido, Japan. Jpn. J. Infect. Dis. 63:353-354.

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Footnote 29

Hoshina, K., H. Itogawa, A. Itagaki, M. Gomyoda, and T. Uchida. 1995. Serosurvey for spotted fever group rickettsial infection in vertebrates in Shimane Prefecture. Kansenshogaku Zasshi. 69:524-531.

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Footnote 30

Levin, M. L., L. F. Killmaster, and G. E. Zemtsova. 2012. Domestic dogs (Canis familiaris) as reservoir hosts for Rickettsia conorii. Vector Borne Zoonotic Dis. 12:28-33.

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Footnote 31

Ando, S., and H. Fujita. 2013. Diversity between spotted fever group rickettsia and ticks as vector. Med. Entomol. Zool. 64:5-7.

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Footnote 32

Fournier, P. E., H. Fujita, N. Takada, and D. Raoult. 2002. Genetic Identification of Rickettsiae Isolated from Ticks in Japan. J. Clin. Microbiol. 40:2176-2181.

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Footnote 33

Miyamura, S., and T. Ohta. 1991. In vitro susceptibility of Rickettsial strains from patients with Japanese spotted fever to quinolones, penicillins and other selected chemotherapeutic agents. Chemotherapy. 39:258-260.

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Footnote 34

Rolain, J. M., M. Maurin, G. Vestris, and D. Raoult. 1998. In vitro susceptibilities of 27 rickettsiae to 13 antimicrobials. Antimicrob. Agents Chemother. 42:1537-1541.

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Footnote 35

Narang, R. 2016. Biology of Orientia tsutsugamushi, p. 385. In S. Thomas (ed.), Rickettsiales: Biology, Molecular Biology, Epidemiology, and Vaccine Development. Springer, Cham, Switzerland.

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Footnote 36

Hancock, C. O. 2013. Heat Sterilization, p. 277-293. In A. P. Fraise, P. A. Lambert, and J. Y. Maillard (eds.), Russell, Hugo & Ayliffe's: Principles and Practice of Disinfection, Preservation and Sterilization, Fifth Edition. Wiley-Blackwell.

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Footnote 37

Kramer, A., and O. Assadian. 2014. Survival of microorganisms on inanimate surfaces, p. 7. In G. Borkow (ed.), Use of Biocidal Surfaces for Reduction of Healthcare Acquired Infections. Springer.

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Footnote 38

Amano, K., H. Hatakeyama, M. Okuta, T. Suto, and F. Mahara. 1992. Serological studies of antigenic similarity between Japanese spotted fever rickettsiae and Weil-Felix test antigens. J. Clin. Microbiol. 30:2441-2446.

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Footnote 39

Wu, J. J., D. B. Huang, K. R. Pang, and S. K. Tyring. 2005. Rickettsial infections around the world, part 1: pathophysiology and the spotted fever group. J. Cutan. Med. Surg. 9:54-62. 

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Footnote 40

Kondo, M., S. Akachi, M. Kawano, K. Yamanaka, A. Yamagiwa, E. C. Gabazza, K. Ando, and H. Mizutani. 2015. Improvement in early diagnosis of Japanese spotted fever by using a novel Rick PCR system. J. Dermatol. 42:1066-1071.

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Footnote 41

Hanaoka, N., M. Matsutani, H. Kawabata, S. Yamamoto, H. Fujita, A. Sakata, Y. Azuma, M. Ogawa, A. Takano, H. Watanabe, T. Kishimoto, M. Shirai, I. Kurane, and S. Ando. 2009. Diagnostic Assay for Rickettsia japonica. Emerg. Infect. Dis. 15:1994-1997.

Footnote 42

 Kurokawa, I., M. Kondo, and S. Akachi. 2013. Early diagnosis of Japan spotted fever by PCR using skin samples. J. Infect. Chemother. 19:628-632.

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Footnote 43

Botelho-Nevers, E., C. Socolovschi, D. Raoult, and P. Parola. 2012. Treatment of Rickettsia spp. infections: a review. Expert Rev. Anti Infect. Ther. 10:1425-1437.

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Footnote 44

Public Health Agency of Canada. 2015. Human Pathogens and Toxins Act (HPTA).

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Footnote 45

Government of Canada. 2015. Canadian Biosafety Standard. , Ottawa, Canada.

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Footnote 46

Canadian Food Inspection Agency. 2014. Containment Standards for facilities Handling Plant Pests, First Edition.

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Footnote 47

Government of Canada. 2016. Canadian Biosafety Handbook, 2nd edition. , Ottawa, Canada.

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