Rickettsia conorii: Infectious substances pathogen safety data sheet 

Section I - Infectious agent

Name

Rickettsia conorii

Agent type

Bacteria

Taxonomy

Family

Rickettsiaceae

Genus

Rickettsia

Species

conorii

Synonym or cross-reference

Spotted fever; Mediterranean spotted fever, also known as boutonneuse fever, Marseilles fever, or Kenya tick typhus (R. conorii subsp. conorii or Malish strain); Astrakhan fever (R. conorii subsp. caspia); Indian tick typhus (R. conorii subsp. indica); and Israeli spotted fever (R. conorii subsp. israelensis)^{Footnote 1Footnote 2Footnote 3Footnote 4}.

Characteristics

Brief description

R. conorii are Gram negative, non-motile bacilli, measuring 0.5 μm by 0.8-2.0 μm^{Footnote 2}. The genome of all subspecies is around 1.3 Mbp long, with a GC content of 32-33%^{Footnote 3}. These obligate intracellular bacteria can be grown in vitro using chicken embryos or tissue culture (e.g., Vero, L-929, MRC5, BHK-21, HEL cells)^{Footnote 2}.

Properties

In animal models and humans, Rickettsia species primarily target vascular endothelial cells^{Footnote 5}. Spotted fever group Rickettsia, such as R. conorii, adhere to host cell receptors using OmpA and OmpB^{Footnote 2}. R. conorii 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. conorii use host cell machinery to move and replicate intracellularly and to activate apoptosis for release from host cells to invade adjacent cells^{Footnote 2Footnote 6}. The infection results in activation of oxidative mechanisms and TNF-α and IFN-γ production, leading to increased vascular permeability, inflammatory responses, edema, and oxidant-mediated endothelial cell injury^{Footnote 6Footnote 7}. R. conorii has the ability to evade host immune defenses by infecting macrophages and changing their gene expressions to promote its intracellular survival^{Footnote 6}.

Section II - Hazard identification

Pathogenicity and toxicity

R. conorii is an etiological agent of spotted fever. Symptoms include fever, flu-like symptoms, and muscle pain. Most individuals develop a maculopapular rash on their palms and soles^{Footnote 3Footnote 6}. An eschar, a localized and inflammatory necrotic skin lesion, may also be present, usually on the trunk or limbs in adults and head or neck in children^{Footnote 6}. The frequency of an eschar at the tick inoculation site depends on the subspecies of the causative agent of infection, for instance, an eschar rarely appears in subsp . caspia and indica^{Footnote 1Footnote 3}. Hepato-splenomegaly has been reported as a clinical manifestation at higher rates in children^{Footnote 8}. Nausea and vomiting are frequent symptoms for Israeli spotted fever^{Footnote 3}. Pathogenicity and virulence vary among R. conorii subspecies^{Footnote 9}. Symptoms are often self-limiting, persisting for 12-20 days^{Footnote 10}, however, hospitalization may be required^{Footnote 6}.

Mediterranean spotted fever is the most common rickettsial disease in Europe^{Footnote 11}. The mortality rate of Mediterranean spotted fever is estimated at 1-18%^{Footnote 1Footnote 2Footnote 12Footnote 13}, although the mortality rate was as high as 32% in Portugal in 1997^{Footnote 1}. Similarly, the mortality rate of Israeli spotted fever is estimated at <3.5%^{Footnote 1}, but higher mortality rates (21-30%) have been reported for some strains^{Footnote 9Footnote 10}. Fatal forms of Astrakhan spotted fever and Indian tick typhus have not been reported^{Footnote 1}.

Rickettsia can cause vascular dysfunction and damage, with complications occurring in approximately 6-10% of Mediterranean spotted fever cases^{Footnote 14Footnote 15}. Renal^{Footnote 16}, neurologic^{Footnote 17Footnote 18}, cardiac^{Footnote 19Footnote 20}, and ocular complications^{Footnote 21Footnote 22}have been reported.

Dogs can experience acute, febrile illness involving anorexia and lethargy. Other animals do not usually show signs of clinical disease^{Footnote 23}.

Epidemiology

Geographical distribution primarily includes European countries bordering the Mediterranean Sea, Africa, and Asia^{Footnote 2Footnote 3}. Incidence rates of spotted fevers caused by R. conorii subspecies vary geographically and temporally^{Footnote 10}. R. conorii subsp. conorii and israelensis are distributed in Europe, Africa, and Asia, while R. conorii subsp. caspia is distributed in Europe and Africa, and subsp. indica is distributed in Europe and Asia^{Footnote 3}. There are approximately 1 to 10 reported cases per 100,000 people per year^{Footnote 24Footnote 25}. Most cases occur during the summer; climatic factors, including warm weather, affect the tendency of ticks to bite humans^{Footnote 10Footnote 26}.

Patients with cardiac disease, diabetes, alcoholism, glucose-6-phosphate dehydrogenase deficiency, immunodeficiency, delayed treatment, and the elderly, present with more severe symptoms, and complications are generally more common^{Footnote 11Footnote 27Footnote 28Footnote 29}.

Host range

Natural host(s)

Humans, cattle, sheep, dogs, rodents and other small mammals, ticks^{Footnote 30}. Humans are dead-end hosts^{Footnote 3}.

Other host(s)

Guinea pigs can be experimentally infected with spotted fever group Rickettsia ^{Footnote 2Footnote 31}. Mice have been infected with R. conorii subsp. conorii^{Footnote 32}. Captive baboons, rhesus monkeys, and cynomolgus monkeys have been infected with R. conorii subsp. israelensis^{Footnote 33Footnote 34}.

Infectious dose

Unknown for R. conorii; Rickettsia are considered infectious at low doses in aerosolized forms^{Footnote 35}.

Incubation period

Approximately 6 days after the bite of an infected tick but can range from 1-16 days^{Footnote 3Footnote 6}.

Communicability

Inoculation of R. conorii 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 35Footnote 36}. 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 34Footnote 35Footnote 37Footnote 38}.

Section III - Dissemination

Reservoir

Dogs^{Footnote 39}, ticks^{Footnote 40}, other mammals^{Footnote 6}.

Zoonosis

None.

Vectors

R. conorii are inoculated into host skin by an infected tick during feeding via salivary excretions^{Footnote 2Footnote 39}. Rhipicephalus sanguineus or "brown dog tick" is the most common vector; other ticks capable of transmitting R. conorii include Boophilus microplus, Haemaphysalis leachi, Rh. pumilio, Rh. bursa, Rh. simus, Rh. mushamae, D. reticulatus, D. marginatus, and I. ricinus^{Footnote 3Footnote 41Footnote 42}. Ticks can transmit R. conorii to larvae via infected ova^{Footnote 6}.

Section IV - Stability and viability

Drug susceptibility/resistance

Tetracyclines (e.g., doxycycline)^{Footnote 43Footnote 44Footnote 45}, chloramphenicol, rifampicin, fluoroquinolones (e.g., pefloxacin, ofloxacin, ciprofloxacin)^{Footnote 43Footnote 44}, telithromycin^{Footnote 46}, and some macrolides (e.g., josamycin, azithromycin, clarithromycin)^{Footnote 43Footnote 45Footnote 47} are generally effective against R. conorii. Aminoglycosides, beta-lactams, and co-trimoxazole are not effective against R. conorii^{Footnote 43}.

Susceptibility to disinfectants

Rickettsia are susceptible to 1% sodium hypochlorite, 70% ethanol, 2% glutaraldehyde, 0.1% formalin, antiviral lysozyme (AVL) buffer, 0.125% β-propiolactone, and quaternary ammonium compounds^{Footnote 48Footnote 49}.

Physical inactivation

Heat at 56^oC for 5 minutes is effective against Rickettsia^{Footnote 49}.

Survival outside host

Rickettsia are usually unable to survive for long periods when they are separated from host cell components^{Footnote 2}. Generally, bacterial persistence on inanimate surfaces depends on environmental conditions such as relative humidity, temperature, presence of a biofilm, and surface type^{Footnote 50}.

Section V - First aid/medical

Surveillance

Diagnosis is accomplished through the monitoring of clinical symptoms, patient history, and laboratory tests^{Footnote 3Footnote 51}. Serological tests (e.g., indirect immunofluorescence assay, ELISA) can be used to detect spotted fever group Rickettsia infection but lack the specificity to distinguish individual species. Immunostaining methods are also used to detect Rickettsia in infected cells under microscope, however this method also lacks the specificity to distinguish between species^{Footnote 52}.

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 3}. PCR analysis of eschar swabs and biopsy samples can be used to rapidly detect R. conorii^{Footnote 3Footnote 53Footnote 54}.

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.

First aid/treatment

Spotted fevers caused by R. conorii can be treated with appropriate antibiotics. Doxycycline is commonly prescribed (100 mg twice daily for 5-7 days minimum)^{Footnote 1Footnote 6Footnote 43}; however, doxycycline has contraindications including pregnancy. Other treatments, including azithromycin, clarithromycin, and josamycin are also effective^{Footnote 6}. Timely diagnosis and treatment tend to improve patient outcomes.

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 Canadian Biosafety Handbook.

Immunization

No vaccine currently available.

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

Prophylaxis

Post-exposure administration of one-dose azithromycin has been used with promising results^{Footnote 55}.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the Canadian Biosafety Handbook.

Section VI - Laboratory hazard

Laboratory-acquired infections

None reported to date. However, R. rickettsia, which is closely related to R. conorii, has infected laboratory personnel working with aerosolized bacteria, and accidental inoculation with needles has been reported pre-1970^{Footnote 31Footnote 56}.

Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents.

Sources/specimens

Blood, skin biopsy, body fluids, and eschar samples^{Footnote 6}.

Primary hazards

Inhalation of infectious aerosols, exposure of mucous membranes to infectious material, and accidental inoculation or bites from infected ticks are primary hazards associated with exposure to R. conorii.

Special hazards

None.

Section VII - Exposure controls/personal protection

Risk group classification

R. conorii is a Risk Group 2 Human Pathogen and Risk Group 2 Animal Pathogen^{Footnote 57}.

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the Canadian Biosafety Standard for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

The applicable Containment Level 2 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard are to be followed. The personal protective equipment could include the use of a labcoat and dedicated footwear (e.g., boots, shoes) or additional protective footwear (e.g., boot or shoe covers) where floors may be contaminated (e.g., animal cubicles, PM rooms), gloves when direct skin contact with infected materials or animals is unavoidable, and eye protection where there is a known or potential risk of exposure to splashes.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone and work activities must be documented.

Other precautions

The low infectious dose of aerosolized forms of R. conorii justifies the use of a BSC or other primary containment device for activities with open vessels; centrifugation to be carried out in sealed safety cups or rotors that are unloaded using a mechanism that prevents their release. Respiratory protection to be considered when a BSC or other primary containment device cannot be used; inward airflow is required for work involving large animals or large scale activities.

Use of needles and syringes are to be strictly limited. Bending, shearing, re-capping, or removing needles from syringes to be avoided, and if necessary, performed only as specified in standard operating procedures (SOPs). Additional precautions are required for work involving animals or large-scale activities.

Proper precautions should be considered when working with infected arthropods. These may include implementing a program to prevent escape and monitoring any escaped arthropods, as well as using suitable personal protective equipment (PPE), among other measures^{Footnote 58Footnote 59}.

For diagnostic laboratories handling primary specimens that may contain R. conorii, the following resources may be consulted:

• Human Diagnostic Activities Biosafety Guideline
• Local Risk Assessment Biosafety Guideline

Section VIII - Handling and storage

Spills

Allow aerosols to settle. While wearing personal protective equipment, 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 (Canadian Biosafety Handbook).

Disposal

All materials/substances that have come in contact with the regulated materials to be completely decontaminated before they are removed from the containment zone or standard operating procedures (SOPs) to be in place to safely and securely move or transport waste out of the containment zone to a designated decontamination area or third party. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (Canadian Biosafety Handbook).

Storage

The applicable Containment Level 2 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Primary containers of regulated materials removed from the containment zone to be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.

Section IX - Regulatory and other information

Canadian regulatory information

Controlled activities with R. conorii require a Pathogen and Toxin licence issued by the Public Health Agency of Canada (PHAC). R. conorii is a non-indigenous terrestrial animal pathogen in Canada; therefore, importation of R. conorii requires an import permit under the authority of the Health of Animals Regulations (HAR), issued by the Canadian Food Inspection Agency.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• Transportation of Dangerous Goods Act and Transportation of Dangerous Goods Regulations

Last file update

October, 2023

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

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