Rickettsia typhi: Infectious substances pathogen safety data sheet
Section I – Infectious agent
Name
Rickettsia typhi
Agent type
Bacteria
Taxonomy
Family
Rickettsiaceae
Genus
Rickettsia
Species
typhi
Synonym or cross-reference
Also known as Rickettsia mooseriFootnote 1, Murine typhus, endemic typhus, or fleaborne typhusFootnote 2.
Characteristics
Brief description
Rickettsia typhi (R. typhi) are Gram negative, non-motile bacilli measuring 0.5 μm by 0.8-2.0 μm. The single circular genome is 1.1 Mbp long with an average GC content of 28.9%Footnote 3. These obligate intracellular bacteria can be grown in vitro using chicken embryos or in tissue culture cells (e.g., L-929, Vero, MRC5, BHK-21, HEL cells)Footnote 1. In humans and in animal models, Rickettsia species preferentially target vascular endothelial cellsFootnote 4.
Properties
In flea vectors, R. typhi grows in the midgut epithelial cells and are excreted in fecesFootnote 5. R. typhi is transmitted between vectors through a reservoir (usually rats), or through transovarial transmission to their offspringFootnote 5. In the host, R. typhi targets endothelial cellsFootnote 5Footnote 6. R. typhi adhere to host cells using a rOmpB protein that form intermolecular disulphide only present in Typhus rickettsiaeFootnote 1Footnote 7. R. typhi 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. typhi are released from lysed host cells shortly after host cell invasionFootnote 1Footnote 5. Infection stimulates activation of oxidative mechanisms and other immune responses that lead to symptomsFootnote 6.
Section II – Hazard identification
Pathogenicity and toxicity
R. typhi is the causative agent of murine typhusFootnote 6. Symptoms include abrupt onset of fever with headache, myalgia and malaiseFootnote 8. Macular or maculopapular rash on the trunk and limbs is present in approximately 50% of casesFootnote 8. Anorexia, nausea, vomiting and abdominal pain are often present. The case-fatality rate of murine typhus is less than 4%, and is even lower with appropriate treatmentFootnote 1Footnote 2Footnote 8Footnote 9Footnote 10Footnote 11. Hospitalization occurs in more than 50% of cases and complications occur in approximately 25% of casesFootnote 8Footnote 12Footnote 13. Pulmonary, renal, gastrointestinal, and neurologic complications have been reportedFootnote 8Footnote 13Footnote 14Footnote 15Footnote 16. Rare complications include disseminated intravascular coagulation, splenic rupture, ocular complications, and multi-organ failureFootnote 8Footnote 17. Fever typically resolves 3 days after treatment but can last up to 22 days without treatmentFootnote 8Footnote 13Footnote 18.
Animals do not typically experience clinical signs of disease when infected by R. typhi, as determined by seroprevalence studies in otherwise healthy animalsFootnote 2Footnote 11Footnote 19Footnote 20Footnote 21Footnote 22.
Epidemiology
R. typhi infection occurs worldwide at endemic levelsFootnote 23. Murine typhus is prevalent in tropical and subtropical regions, particularly in dense, urban environmentsFootnote 2. Murine typhus tends to be less severe in childrenFootnote 8Footnote 18Footnote 24. Most cases occur during summer and fall, but seasonal variation is not observed in some regionsFootnote 8. In the United States, cases are likely present along coastal areas with ports where it is maintained among rat reservoirs, with most cases occurring in suburban areas in HawaiiFootnote 25, TexasFootnote 26, and CaliforniaFootnote 2Footnote 18. In these states, less than 100 cases are reported annually, but murine typhus is often underreported due to misdiagnosisFootnote 11Footnote 22. An outbreak of murine typhus occurred in 1982 in Texas with a cluster of five cases reportedFootnote 27.
Disease severity is associated with older age, renal dysfunction, eukocytosis, hypoalbuminemia, nutritional status, quality of supportive care, or the previous usage of sulfa antibioticsFootnote 10Footnote 13Footnote 28.
Host range
Natural host(s)
HumansFootnote 2, dogsFootnote 29.
Other host(s)
R. typhi experimentally introduced in guinea pigs, C3H/HeN mice, and opossums, produces clinical signs of diseaseFootnote 30Footnote 31.
Infectious dose
ID50 in rats is approximately 1 organismFootnote 32.
Incubation period
Can range from 8 to 16 days, averaging 11 daysFootnote 33.
Communicability
R. typhi is transmitted by injection through bites of flea vectors into a host, or contact with flea feces to disrupted skin or mucous membranesFootnote 19. Bacteria are also present in the flea's reproductive organs, enabling transovarial infection to the vector's offspringFootnote 2. Transmission by inhalation is considered likely given that aerosolized forms of R typhi and other Rickettsia spp. have caused disease in laboratory workers and can cause infection in monkeys and guinea pigsFootnote 34Footnote 35Footnote 36Footnote 37Footnote 38.
Section III – Dissemination
Reservoir
Rats are the primary reservoirs in the "urban" transmission cycleFootnote 1. Opossums, cats, and dogs are reservoirs in the "suburban" transmission cycleFootnote 2Footnote 21Footnote 22.
Zoonosis
None.
Vectors
Rat louse "Polyplax spinulosus", rat flea "Xenopsylla cheopis", human flea Pulex irritans, cat flea Ctenocephalides felis, and Leptopsylla segnisFootnote 1Footnote 2Footnote 39.
Section IV – Stability and viability
Drug susceptibility/resistance
Tetracyclines (e.g., doxycycline, minocycline)Footnote 40Footnote 41; macrolides such as josamycin, azithromycin and clarithromycinFootnote 40Footnote 42; rifampinFootnote 40; telithromycinFootnote 43; chloramphenicolFootnote 44; thiamphenicolFootnote 40; fluoroquinolones (ciprofloxacin, ofloxacin, pefloxacin)Footnote 40 and erythromycinFootnote 40 are effective against R. typhi.
Rifampin resistant isolates have been reportedFootnote 45. Some groups of antibiotics, including β-lactams, aminoglycosides and co-trimoxazole are not effective at all for treatment of RickettsiaeFootnote 5.
Susceptibility to disinfectants
Rickettsiae are susceptible to 1% sodium hypochlorite, 70% ethanol, 2% glutaraldehyde, 0.1% formalin, AVL buffer, 0.125% β-propiolactone, and quaternary ammonium compoundsFootnote 46Footnote 47.
Physical inactivation
Moist heat (121°C for 15 minutes) and dry heat (170°C for 1 hour) are effective against bacteria such as R. typhiFootnote 46Footnote 48. Heat at 56oC for 5 minutes is effective against RickettsiaeFootnote 47.
Survival outside host
Rickettsiae rely on host cells for survival and replication, therefore they are unable to survive for a long period of time outside the hostFootnote 49. However, R. typhi in dried flea feces can survive for up to 40 days at room temperatureFootnote 50.
Section V – First aid/medical
Surveillance
Diagnosis is accomplished through the monitoring of clinical symptoms. Serological tests (e.g., indirect immunofluorescence assay, indirect immunoperoxidase assay, latex agglutination, ELISA) can be used to detect typhus group RickettsiaeFootnote 51Footnote 52Footnote 53Footnote 54. Indirect immunofluorescence assay is the gold standardFootnote 2Footnote 18. Serological tests lack the specificity to distinguish individual Rickettsia species. 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 18. PCR analysis of blood samples and tissue biopsies has been used to detect R. typhi by amplifying genes specific to R. typhiFootnote 55Footnote 56Footnote 57. Immunostaining methods are also used to detect Rickettsiae in infected cells under microscope, however, this method also lacks the specificity to distinguish between speciesFootnote 58.
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
Murine typhus can be treated with appropriate antibiotics. Doxycycline alone (200 mg daily) or in combination with a fluoroquinolone antibiotic is commonly administeredFootnote 2Footnote 8Footnote 41Footnote 44. Timely diagnosis and treatment tend to improve patient outcomesFootnote 10. The usual duration of treatment is 3-7 daysFootnote 2Footnote 41. However, doxycycline is not recommended for pregnant women. Chloramphenicol has been used as a treatment during pregnancy, however there is risk of aplastic anemiaFootnote 2Footnote 59. Other treatments including macrolides (i.e. azithromycin) are safer alternatives, however, is less efficacious than doxycyclineFootnote 60.
Dogs who clinically present with R. typhi infection are treated with doxycyclineFootnote 29.
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 hazard
Laboratory-acquired infections
Sixty-eight cases of murine typhus associated with laboratory exposures were reported prior to 1974Footnote 61. From 1979 to 2004, there were 12 reported laboratory-acquired infections associated with typhus group RickettsiaeFootnote 62. One case of murine typhus occurred after a solution containing R. typhi splashed into a laboratory worker's eye and lipsFootnote 63. Multiple cases are suspected to be transmitted by aerosolsFootnote 38.
Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.
Sources/specimens
Blood, tissue, and vector specimensFootnote 2.
Primary hazards
Accidental autoinoculation with infectious material, inhalation of infectious aerosols and exposure of mucous membranes are primary hazards associated with exposure to R. typhiFootnote 2Footnote 38.
Special hazards
None.
Section VII – Exposure controls/personal protection
Risk group classification
R. typhi is considered to be a Risk Group 3 Human Pathogen and a Risk Group 3 Animal PathogenFootnote 64.
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 are to be followed. At minimum, use of full body coverage dedicated protective clothing, dedicated protective footwear and/or additional protective footwear, gloves when handling infectious materials or animals, face protection when there is a known or potential risk of exposure to splashes or flying objects, respirators when there is a risk of exposure to infectious aerosols, and an additional layer of protective clothing prior to work with infectious materials or animals.
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 must be documented.
Other precautions
All activities involving open vessels of pathogens are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. The use of needles, syringes, and other sharp objects to be strictly limited. Additional precautions must be considered with work involving animals or large scale activities.
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 with the disinfectant before clean up (CBH).
Disposal
Regulated materials, as well as all items and waste to be decontaminated at the containment barrier prior to removal from the containment zone, animal room, animal cubicle, or post mortem room. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).
Storage
The applicable Containment Level 3 requirements for storage outlined in the CBS are to be followed. Primary containers of regulated materials removed from the containment zone to be stored in a labelled, leak-proof, impact-resistant secondary container, and kept either in locked storage equipment or within an area with limited access.
An inventory of RG3 pathogens to be maintained and to include:
- specific identification of the regulated materials
- a mechanism that allows for the detection of a missing or stolen sample in a timely manner
Section IX – Regulatory and other information
Canadian regulatory information
Controlled activities with R. typhi require a Human Pathogens and Toxins licence issued by the Public Health Agency of Canada (PHAC). R. typhi is a terrestrial animal pathogen in Canada; therefore, importation of R. typhi requires an import permit under the authority of the Health of Animals Regulations (HAR). The PHAC issues a "Pathogen and Toxin Licence document" for both a Human Pathogens and Toxins Act Licence and HAR importation permit.
The following is a non-exhaustive list of applicable designations, regulations, or legislations:
- Human Pathogen and Toxins Act and Human Pathogens and Toxins Regulations
- Health of Animals Act and Health of Animals Regulations
- 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.
Copyright © Public Health Agency of Canada, 2023, Canada
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