Pathogen Safety Data Sheets: Infectious Substances – Rickettsia rickettsii
PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES
SECTION I - INFECTIOUS AGENT
NAME: Rickettsia rickettsii
SYNONYM OR CROSS REFERENCE: Rocky Mountain Spotted Fever (RMSF), Brazilian Spotted Fever, Tobia Fever, fiebre maculosa, fiebre manchada, New World Spotted Fever, Tick- borne typhus fever, Sao Paulo Fever
CHARACTERISTICS: Rickettsia rickettsii is an obligate intracellular alpha proteobacteria that belongs to the Rickettsiacae familyFootnote 1Footnote 2Footnote 3. It is a small (0.2-0.5 µm by 0.2-0.3 µm) pleomorphic, gram-negative coccobacillus which multiplies by binary fission and has both DNA and RNAFootnote 1Footnote 2Footnote 3.
SECTION II – HAZARD IDENTIFICATION
PATHOGENICITY/TOXICITY: RMSF is a potentially fatal tick-borne disease normally causing moderate to severe illnessFootnote 1. It can appear as an abrupt onset of fever (typically higher than 38.9 ºC), malaise, headache, anorexia, nausea, vomiting, abdominal pain, photophobia, diarrhoea and neck stiffnessFootnote 1Footnote 3. The characteristic maculopapular rash usually appears 2-5 days after the other symptoms, starting on wrists and ankles before progressing to the rest of the bodyFootnote 1. 95% of children and 80% of adults have the rash; however, absence of the rash is more common in fatal cases and cases involving the elderly or African-AmericansFootnote 1. The rash is due to the infection of host vascular endothelial cells and is a multisystem vasculitis that can lead to necrotic or gangrenous lesions in severe casesFootnote 1Footnote 3. Mucosal ulcers, postinflammatory hyperpigmentation, jaundice, cough, pneumonia, acute renal failure, lymphadenopathy, hepatomegaly, splenomegaly, conjunctivitis, peripheral, periorbal and optic disk oedema, arterial occlusion, retinal vein engorgement, retinal haemorrhage and retinal sheathing are some of the complications that can be caused by RMSFFootnote 1Footnote 3. After the skin, the CNS is the most affected system and people over 15 are at higher risk of developing CNS complicationsFootnote 3. 40% of all patients reported neurological abnormalities such as meningismus, seizures, altered mental states, temporary deafness, lethargy and amnesiaFootnote 1Footnote 3. The symptoms can last 2 weeks although some patients have neurological sequelae lasting up to one year after disease onset. 20% of untreated cases are fatal compared to 5% of treated casesFootnote 1. Mortality rates are higher for patients over the age of 60Footnote 1. The symptoms of RMSF can be confused with meningococcemia, various viral infections and other tick-borne diseasesFootnote 1Footnote 3.
EPIDEMIOLOGY: The disease is restricted to the Americas where it is common in the United States of America, Western Canada, Mexico, Panama, Costa Rica, Argentina, Brazil, Colombia and BoliviaFootnote 1Footnote 2Footnote 3. It is the most common tick-borne disease in the USA where 250-1200 cases are reported each yearFootnote 1. 90-93% of the cases reported in the USA occurred between April and October with most of them occurring in rural and suburban areasFootnote 1Footnote 3. The highest infection rates were among children between 5-9, Caucasians and menFootnote 3. Infections are more common in tick-infested areasFootnote 1.
INFECTIOUS DOSE: The precise infectious dose for R.rickettsii is unknown; however rickettsiales generally have a very low infectious dose. The bite of a single tick is sufficient to cause RMSF in humansFootnote 1Footnote 3. Dogs that were innoculated with approximately 3000 vero cells infected with RMSF or infected with 10 ticks all developed clinical symptoms of the diseaseFootnote 5.
MODE OF TRANSMISSION: RMSF is usually spread by the bite of an infectious tick where the bacterium changes from a dormant avirulent state to a pathogenic stateFootnote 1. The tick normally needs to be attached for a 4-6 hour period in order to transmit the disease to humansFootnote 1. Rickettsia rickettsii can also be spread through contact with the tick's infected saliva, blood, bodily fluids or fecesFootnote 1Footnote 2Footnote 6. Human-to-human transmission has not been confirmed but aerosols are a potential source of infectionFootnote 4Footnote 7.
SECTION III - DISSEMINATION
RESERVOIR: The disease in maintained by transovarial and transstadial passages in ticks where it is then spread to humans, dogs, rodents and other mammalsFootnote 1Footnote 2. Small mammals can serve as amplifying hosts by maintaining the bacteria in their blood (they are infective for a maximum of 8 days) and then passing it to a tick during a blood mealFootnote 8.
ZOONOSIS: The disease is spread from ticks to humans through the bite, or contact with tick feces or internal contentsFootnote 1Footnote 2. Mammals (such as dogs) can also spread the ticks to humans, thus spreading the RMSF infectionFootnote 2Footnote 4.
VECTORS: Several tick species are responsible for the spread of this diseaseFootnote 1. Dermacentor variabilis is most prevalent in the United States of America, Demacentor andersoni in the Rocky Mountains and in Canada, Rhipicephalus sanguineus in Mexico, Amblyomma cajennense in Central and South America and Amblyomma aureolatum in BrazilFootnote 1.
SECTION IV – STABILITY AND VIABILITY
DRUG SUSCEPTIBILITY: Tetracyclines and chloramphenicol are the only drugs that are confirmed as being effective against an infection by Rickettsia rickettsiiFootnote 1. The most effective and recognized antibiotic used to treat RMSF is doxycyclineFootnote 1Footnote 3.
SUSCEPTIBILITY TO DISINFECTANTS: Gram-negative bacteria are susceptible to 1% sodium hypochlorite, 4% formaldehyde, 2% glutaraldehyde, 70% ethanol, 2% peracetic acid, 3- 6% hydrogen peroxide and 0.16% iodineFootnote 4.
PHYSICAL INACTIVATION: Rickettsia rickettsii is susceptible to moist heat (121 ºC for at least 15 minutes) and dry heat (170 ºC for at least 1 hour)Footnote 9.
SECTION V – FIRST AID / MEDICAL
SURVEILLANCE: Monitor for symptoms. The presence of the pathogen can be confirmed using a variety of laboratory techniquesFootnote 11. Immunofluorescent assays (IFAs) and ELISAs can be used to identify antibodies to the bacteria; however, sera must be tested at least 7 days after the appearance of symptoms in order to detect seroconversion because IgG antibodies do not appear until a minimum of 7 days after the onset of the diseaseFootnote 3. A four-fold increase in titres of paired samples or a convalescent titre greater 1/64 is considered diagnosticFootnote 1. The bacteria can be visualized using Giemsa and Gimenez staining methods. Immunohistochemical staining of skin biopsies can be useful in patients presenting with rashFootnote 1Footnote 2Footnote 3. Immunohistochemical staining is the most useful method to diagnose RMSF in severe casesFootnote 12. PCR of blood, biopsy tissues and ticks is possible although this technique is not sensitive enough to be commonly used to diagnose RMSF and most diagnoses of the disease are retrospectiveFootnote 1Footnote 3.
Note: All diagnostic methods are not necessarily available in all countries.
FIRST AID/TREATMENT: Appropriate antibiotic therapy (i.e. doxycycline) should be initiated at the onset of RMSF-like symptoms without waiting for laboratory confirmation of the diagnosisFootnote 11Footnote 13. 100 mg of doxycycline should be taken twice a day for 5-7 days and until the patient is afebrile for at least 2-3 daysFootnote 1Footnote 3. For children weighing less than 45 kg, a 2.2 mg/ kg twice daily dose of doxycycline is recommended for 5 to 7 daysFootnote 1Footnote 3.
IMMUNIZATION: NoneFootnote 11
PROPHYLAXIS: The administration of the appropriate antibiotic treatment before any signs of clinical illness is not recommendedFootnote 2.
SECTION VI - LABORATORY HAZARDS
LABORATORY-ACQUIRED INFECTIONS: 63 laboratory-acquired infections have been reported as of date with 11 deathsFootnote 11. The 11 fatal cases were associated with manipulating infected eggs, tissue cultures or ticks, and the respiratory route, mucous membrane contact, needle puncture wounds or cuts were involvedFootnote 13. 9 cases were reported in the same lab over a 6 year period, all caused by infectious aerosolsFootnote 7.
SOURCES/SPECIMENS: Tissues and blood from ticks or infected animalsFootnote 1.
PRIMARY HAZARDS: Accidental parenteral inoculation and exposure to infectious aerosols are the primary hazards when working with RMSFFootnote 11. Infected mammals and arthropods are also a riskFootnote 11.
SPECIAL HAZARDS: None
SECTION VII – EXPOSURE CONTROLS / PERSONAL PROTECTION
RISK GROUP CLASSIFICATION: Risk group 3Footnote 14.
CONTAINMENT REQUIREMENTS: Containment Level 3 facilities, equipment, and operational practices for work involving infected or potentially infected material, including necropsy of infected animals, arthropods, inoculation, incubation and harvesting of embryonated eggs or tissue cultures.
PROTECTIVE CLOTHING: Personnel entering the laboratory should remove street clothing and jewellery, and change into dedicated laboratory clothing and shoes, or don full coverage protective clothing (i.e., completely covering all street clothing). Additional protection may be worn over laboratory clothing when infectious materials are directly handled, such as solid-front gowns with tight fitting wrists, gloves, and respiratory protection. Eye protection must be used where there is a known or potential risk of exposure to splashesFootnote 15.
OTHER PRECAUTIONS: All activities with infectious material should be conducted in a biological safety cabinet (BSC) or other appropriate primary containment device in combination with personal protective equipment. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are loaded or unloaded in a biological safety cabinet. The use of needles, syringes, and other sharp objects should be strictly limited. Open wounds, cuts, scratches, and grazes should be covered with waterproof dressings. Additional precautions should be considered with work involving animals or large scale activitiesFootnote 15.
SECTION VIII - HANDLING AND STORAGE
SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply appropriate disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (30 min)Footnote 15.
DISPOSAL: Decontaminate all wastes before disposal by incineration or steam sterilizationFootnote 15.
STORAGE: The infectious agent should be stored in a sealed and identified container in a level 3 containment laboratoryFootnote 15.
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 Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.
UPDATED: July 2010
PREPARED BY: Pathogen Regulation Directorate, 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.
Public Health Agency of Canada, 2010
- Footnote 1
Dantas-Torres, F. (2007). Rocky Mountain spotted fever. The Lancet Infectious Diseases, 7(11), 724-732. doi:10.1016/S1473-3099(07)70261-X
- Footnote 2
Chen, L. F., & Sexton, D. J. (2008). What's new in Rocky Mountain spotted fever? Infectious Disease Clinics of North America, 22 (3), 415-32, vii-viii. doi:10.1016/j.idc.2008.03.008
- Footnote 3
Minniear, T. D., & Buckingham, S. C. (2009). Managing Rocky Mountain spotted fever. Expert Review of Anti-Infective Therapy, 7 (9), 1131-1137. doi:10.1586/eri.09.94
- Footnote 4
Collins, C. H., & Kennedy, D. A. (1999). Laboratory acquired infections. Laboratory acquired infections: History, incidence, causes and prevention (4th ed., pp. 1-37). Woburn, MA: BH.
- Footnote 5
Piranda, E. M., Faccini, J. L., Pinter, A., Saito, T. B., Pacheco, R. C., Hagiwara, M. K., & Labruna, M. B. (2008). Experimental infection of dogs with a Brazilian strain of Rickettsia rickettsii: clinical and laboratory findings. Memorias do Instituto Oswaldo Cruz, 103 (7), 696-701.
- Footnote 6
Brock, T. D., Madigan, M. T., Martinko, J. M., & Parker, J. (2000). Biology of Microorganisms (9th ed.). New Jersey, USA: Prentice-Hall, Inc.
- Footnote 7
Fleming, D. O., Richardson, J. H., Tulis, J. J., & Vesley, D. (Eds.). (1995). Laboratory Safety Principles and Practices (2nd ed.). Washington: American Society for Microbiology.
- Footnote 8
Goodman, J. L., Dennis, D. T., & Sonenshine, D. E. (Eds.). (2005). Tick-Borne Diseases of Humans
- Footnote 9
Joslyn, L. J. (2001). Sterilization by Heat. In S. S. Block (Ed.), Disinfection, Sterilization, and Preservation (5th ed., pp. 695). Philadelphia: Lippincott Williams & Wilkins.
- Footnote 10
La Scola, B., & Raoult, D. (1997). Laboratory diagnosis of rickettsioses: current approaches to diagnosis of old and new rickettsial diseases. Journal of Clinical Microbiology, 35 (11), 2715-2727.
- Footnote 11
Richmond, J. Y., & McKinney, R. W. (Eds.). (2007). Biosafety in Microbiological and Biomedical Laboratories (BMBL) (5th ed.). Washington, D.C.: Centers for Disease Control and Prevention.
- Footnote 12
Murray, P. R., Baron, E. J., Jorgensen, J. H., Landry, M. L., & Pfaller, M. A. (Eds.). (2007). Manual of Clinical Microbiology (9th ed.). Washington: ASM Press.
- Footnote 13
Fleming D & Hunt D (Ed.). (2006). Biological Safety Principles and Practices (4th ed.). Washington: ASM Press.
- Footnote 14
Human pathogens and toxins act. S.C. 2009, c. 24, Second Session, Fortieth Parliament, 57- 58 Elizabeth II, 2009. (2009).
- Footnote 15
Public Health Agency of Canada. (2004). In Best M., Graham M. L., Leitner R., Ouellette M. and Ugwu K. (Eds.), Laboratory Biosafety Guidelines (3rd ed.). Canada: Public Health Agency of Canada.
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