Pathogen Safety Data Sheet: Infectious Substances – Rickettsia japonica

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• Section I: Infectious agent
• Section II: Hazard identification
• Section III: Dissemination
• Section IV: Stability and viability
• Section V: First aid and medical
• Section VI: Laboratory hazards
• Section VII: Exposure controls and personal protection
• Section VIII: Handling and storage
• Section IX: Regulatory and other information
• References

Section I: Infectious agent

Name: Rickettsia japonica
Agent type: Bacteria

Taxonomy

Family: Rickettsiaceae
Genus: Rickettsia
Species: japonica

Synonym or cross reference: Japanese spotted fever^{Footnote 1}, also known as Oriental spotted fever^{Footnote 2,Footnote 3}.

Characteristics

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

Properties: Spotted fever group Rickettsiae, such as R. japonica, adhere to host cell receptors using OmpA and OmpB^{Footnote 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 cells^{Footnote 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 1984^{Footnote 5}.  Symptoms usually include fever, headache, and rash^{Footnote 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 weeks^{Footnote 3}. Erythema on the palms and soles are strongly associated with Japanese spotted fever^{Footnote 3,Footnote 6}.

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

R. japonica-infected dogs can develop clinical symptoms including fever^{Footnote 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 course^{Footnote 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 person^{Footnote 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 pigs^{Footnote 16,Footnote 17,Footnote 18,Footnote 19}.

Epidemiology: Japan and Korea^{Footnote 2,Footnote 20}. The incidence rate of Japanese spotted fever is approximately 0.38 per 1,000,000 people per year^{Footnote 21}. There were 241 and 175 reported cases in Japan in 2014 and 2013 respectively^{Footnote 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 average^{Footnote 21}. Japanese spotted fever is associated with old age and residing in wooded areas^{Footnote 6}. Cases of Japanese spotted fever typically occur between April and October^{Footnote 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 Rickettsiae^{Footnote 1,Footnote 23}.

Infectious dose: Unknown for R. japonica; Rickettsiae are considered infectious at low doses in aerosolized form^{Footnote 19}.

Incubation period: 2 to 10 days after a tick bite^{Footnote 3}.

Incubation period: Unknown.

Section III: Dissemination

Reservoir: Ticks^{Footnote 3}, rodents^{Footnote 24}, cats^{Footnote 25}, dogs^{Footnote 25,Footnote 26}, small carnivores such as feral raccoons^{Footnote 27,Footnote 28}, cattle and deer^{Footnote 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), chloramphenicol^{Footnote 33}, fluoroquinolones (e.g., ciprofloxacin, ofloxacin, pefloxacin), and some macrolides, such as josamycin and leucomycin^{Footnote 33,Footnote 34} are effective against R. japonica.

Drug resistance: R. japonica are resistant to erythromycin^{Footnote 34}.

Susceptibility to disinfectants: Rickettsiae are susceptible to 1% sodium hypochlorite, 70% ethanol, 2% glutaraldehyde, formaldehyde, and quaternary ammonium compounds^{Footnote 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. japonica^{Footnote 36}.

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

Section V: First aid and medical

Surveillance: Diagnosis is accomplished through the monitoring of clinical symptoms, patient history, and laboratory tests^{Footnote 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 species^{Footnote 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 decisions^{Footnote 2}. PCR analysis of blood^{Footnote 11,Footnote 40,Footnote 41} and skin samples taken from the eschar or lesions^{Footnote 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 administered^{Footnote 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 bacteria^{Footnote 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 biopsy^{Footnote 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 pathogen^{Footnote 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 device^{Footnote 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 Pests^{Footnote 46}.

Section VIII: Handling and storage

Spills:
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 up^{Footnote 47}.

Disposal:
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 decontamination^{Footnote 47}.

Storage:
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 access^{Footnote 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:

• Human Pathogen and Toxins Act and Regulations
• Transportation of Dangerous Goods Regulations 

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         

References