COXIELLA BURNETII

PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Coxiella burnetii

SYNONYM OR CROSS REFERENCE: Q fever ^{Footnote 1, Footnote 2}, Query fever ^{Footnote 1, Footnote 3}, previously known as Rickettsia burnetii ^{Footnote 1, Footnote 3}.

CHARACTERISTICS: Coxiella burnetii belongs to the γ subdivision of the class Proteobacteria ^{Footnote 4}. It is a pleomorphic, Gram-negative, spore-forming coccobacillus ^{Footnote 1, Footnote 4, Footnote 5}. It is an obligate intracellular pathogen, and completes its development cycle in the phagolysosome ^{Footnote 3}. It exists in two different forms: 1) a small-cell variant, consisting of an electron-dense center of condensed nucleoid filaments; and 2) a large cell variant, which is less electron-dense and is the metabolically active intracellular form ^{Footnote 1}.

SECTION II - HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: Coxiella burnetii is the causative agent of Q fever ^{Footnote 4}. Infections are asymptomatic in as many as 60% of cases ^{Footnote 6}. Manifestations of Q fever can be affected by age, strain, route of transmission, gender, and inoculum size, and vary from country to country ^{Footnote 1, Footnote 4, Footnote 5}.

Acute Q fever: The clinical presentation of acute Q fever varies considerably. The most common manifestations of acute Q fever are self-limited flu-like illness, atypical pneumonia and hepatitis. One of the most common manifestations is acute, self-limiting febrile illness, characterized by severe headaches (51%), cough (34%), myalgia (37%), arthralgia (27%), pericarditis (1%), chills, weakness, malaise, severe sweats, and rarely a rash ^{Footnote 1, Footnote 4, Footnote 6, Footnote 7}. In most cases the primary infection resolves completely following generation of the host’s immune response against the bacteria ^{Footnote 4}. Acute Q fever is rarely fatal ^{Footnote 5}.

Pneumonia: Pneumonia, caused by inhalation of aerosols, is the main manifestation of the infection in Canada, Switzerland, the United Kingdom, and Spain ^{Footnote 4, Footnote 5}. The main symptoms are nonproductive cough and fever associated with minimal auscultatory abnormalities on exam. Abnormal chest X rays can be found in 27% of the patients ^{Footnote 1, Footnote 4}. The duration of symptoms varies from 10 to 90 days. The mortality rate of this presentation ranges from 0.5 to 1.5% ^{Footnote 1}.

Hepatitis: Hepatitis is a common manifestation of acute Q fever in France, Australia, and southern Spain ^{Footnote 4, Footnote 5}. Hepatitis may occur in 3 major forms: an infectious hepatitis-like form with hepatomegaly, clinically asymptomatic hepatitis, and granulomatous hepatitis ^{Footnote 1}. The main symptoms of hepatitis include fever, abdominal pain, nausea, vomiting, anorexia, and diarrhea ^{Footnote 1}.

Other rarer manifestations of acute Q fever include neurological presentations such as meningitis, cardiac presentations such as myocarditis, acute acalculous cholecystitis, and isolated lymphadenitis ^{Footnote 4}.

Chronic Q fever: In immunocompromised individuals, chronic infection (lasting longer than 6 months) may develop as a result of the inability of the immune response to control the infection ^{Footnote 4, Footnote 5}. Although chronic infections can affect any organ system, the main manifestation is often endocarditis, characterized by fever, hepatitis, weight loss, stroke, or heart failure ^{Footnote 1, Footnote 4}. Patients with acute Q fever, who have cardiac valve lesions, are at highest risk of developing endocarditis ^{Footnote 4, Footnote 5}. Other manifestations of chronic disease include osteomyelitis, chronic hepatitis, pseudotumor of the spleen or lung, infection of the ventriculo-peritoneal drain, vasculitis, and pulmonary amyloidosis ^{Footnote 1, Footnote 4}. Chronic infection is associated with a high mortality rate.

EPIDEMIOLOGY: Q fever was first described in 1935 as an outbreak among abattoir workers in Brisbane, Australia ^{Footnote 1}. Currently, Q fever is a public health problem in many countries, including, France, the United Kingdom, the Netherlands, Italy, Spain, Germany, Israel, Greece, and Canada^{Footnote 1} and is endemic throughout the world. Q fever outbreaks have been reported in virtually every country in the world but New Zealand ^{Footnote 1}. 18 outbreaks involving 2 to 289 people were reported from 12 different countries between the years 1999 to 2004 ^{Footnote 1}. The largest outbreak documented to date has occurred in The Netherlands with 3523 cases reported between 2007 and 2009 ^{Footnote 8}. Most outbreaks involve exposure to infected pets, wild, or domestic animals ^{Footnote 1}. Direct or indirect contact with parturient cats has been responsible for outbreaks in North America ^{Footnote 1}. Epidemics also occur in stockyards, meat packing facilities, and medical labs ^{Footnote 7}. Outbreaks are common among abattoir workers, farmers, veterinary surgeons, hide handlers, and butchers ^{Footnote 7}.

HOST RANGE: Humans and many different wild and domestic animals, including cattle, sheep, goats, cats, and dogs ^{Footnote 1, Footnote 7, Footnote 9}.

INFECTIOUS DOSE: Approximately 1-10 organisms are required to cause infection ^{Footnote 5, Footnote 10}.

MODE OF TRANSMISSION: Transmission occurs mainly via inhalation of contaminated aerosols from amniotic fluid, placenta, or contaminated wool from farm animals (airborne organism may be carried miles downwind) ^{Footnote 2, Footnote 4}. Transmission can also occur through direct or indirect contact with infected animals and their dried excreta, contaminated hides, straw and wool, fertilizer, and laundry of exposed persons ^{Footnote 1, Footnote 7, Footnote 11}. Ingestion of raw milk products has been associated with disease in some cases ^{Footnote 2, Footnote 4}. Ticks are also capable of transmitting this agent to animals, including humans, although transmission to humans via tick bites is rare.

INCUBATION PERIOD: 13-28 days if acquired through respiratory route ^{Footnote 9, Footnote 11, Footnote 12}. Symptoms can appear in 24-48 hours in people who have accidently inoculated themselves with the pathogen ^{Footnote 12}.

COMMUNICABILITY: Person-to-person transmission is rare ^{Footnote 1}. Transmission of Q fever has been reported among hospital staff and autopsy attendants ^{Footnote 1}.

SECTION III - DISSEMINATION

RESERVOIR: Farm animals such as cattle, goats, and sheep; pets such as cats, rabbits, and dogs ^{Footnote 1}; more than 40 species of ticks ^{Footnote 11}. Many wild animals, including coyotes, mice, and birds ^{Footnote 7}.

ZOONOSIS: Yes. Transmission to humans occurs mainly from sheep, goat and cattle, but can also occur from other animals ^{Footnote 2, Footnote 3}.

VECTOR: Q fever is mainly transmitted through inhalation of aerosols generated by infected animals. Arthropods such as ticks can transmit the disease between animals, but are not believed to play a significant role in the transmission of infection to humans ^{Footnote 1, Footnote 4, Footnote 5, Footnote 11}.

SECTION IV – STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY: In vitro assays in HEL cells demonstrated that cotrimoxazole, rifampin, doxycycline, minocycline, tetracycline, clarithromycin, sparfloxacin, and quinolones are bacteriostatic for C. burnetii. These assays also demonstrated that amikacin and amoxicillin are not effective against these bacteria ^{Footnote 1, Footnote 4}. It has been shown that use of chloroquine along with doxycycline and pefloxacin, makes these antibiotics bactericidal ^{Footnote 1}.

DRUG RESISTANCE: Strains resistant to doxycycline, tetracycline, fluoroquinolones, and rifampin have been reported ^{Footnote 1}.

SUSCEPTIBILITY TO DISINFECTANTS: C. burnetii is more resistant to chemical disinfectants than vegetative bacteria and rickettsiae ^{Footnote 10}. Liquid suspensions of the bacteria have been shown to be inactivated completely by 70% ethyl alcohol, 5% chloroform, or 5% Enviro-Chem within 30 minutes, but not by 0.5% sodium hypochlorite, 5% Lysol, 5% formalin, or 2% Rocca even after 24 hours ^{Footnote 10}. Overnight exposure to formaldehyde or ethylene gas can inactivate C. burnetii within a small, sealed humidified chamber, but not in a large (5600 cubic feet) room without humidity control ^{Footnote 10}.

PHYSICAL INACTIVATION/RESISTANCE TO PHYSICAL AGENTS: More resistant to physical agents than any rickettsiae ^{Footnote 3}. It is resistant to osmotic stress, elevated temperatures, desiccation, osmotic shock, ultraviolet light and mechanical agitation ^{Footnote 3, Footnote 10}. It can be inactivated by gamma irradiation ^{Footnote 10, Footnote 13}.

SURVIVAL OUTSIDE HOST: C. burnetii can withstand harsh environmental conditions ^{Footnote 2, Footnote 4}. It can survive at 15-20°C for 10 months, on meat in cold storage for more than 1 month, in skim milk at room temperature for more than 40 months ^{Footnote 4}. It can also survive in soil, contaminated buildings, food and fomites for years ^{Footnote 2, Footnote 3}.

SECTION V – FIRST AID / MEDICAL

SURVEILLANCE: Diagnosis can consist of: 1) Presence of clinical symptoms ^{Footnote 11}; 2) direct detection of antigen in the valvular tissues with immunofluorescence, electron microscopy or immunohistology in case of Q fever endocarditis ^{Footnote 1, Footnote 4, Footnote 5}; 3) Serological tests such as microagglutination, ELISA, CF (Complement fixation) test, or indirect immunofluorescent antibody (IFA) test to demonstrate high titer of antibody against the C. burnetii antigen ^{Footnote 1, Footnote 2, Footnote 4, Footnote 5, Footnote 11}; 4) PCR-based diagnostic assays of IS1111 ^{Footnote 1}; 5) Isolation of the bacteria from clinical samples can be performed on HEL cells using the shell vial centrifugation technique ^{Footnote 1}. The bacteria can be propagated in 5-7 days when monolayers of inoculated HEL cells are incubated at 37°C at 5% CO^{2 Footnote 1, Footnote 5}. Following cell culture, the bacteria can be microscopically identified using Gimenez staining or by indirect immunofluorescence using polyclonal/monoclonal anti-C. burnetii antibodies ^{Footnote 1, Footnote 5}.

Note: All diagnostic methods are not necessarily available in all countries.

FIRST AID/TREATMENT: Antibiotic therapy is useful, especially when initiated within the first 3 days of illness ^{Footnote 5}.

Acute Q fever: Treated with doxycycline ^{Footnote 1, Footnote 5, Footnote 11}. Other drugs that can be used include: floroquinolones, rifampin, pefloxacin, chloramphenicol, and co-trimoxazole ^{Footnote 1, Footnote 5}. Doxycycline can be used for infection in children; trimethoprim or sulfamethoxazole can be used for pregnant women ^{Footnote 1}.

Chronic Q fever: Treated with doxycycline in combination with hydroxychloroquine ^{Footnote 5, Footnote 11}. Other combinations effective in treating chronic Q fever consist of doxycycline in combination with ofloxacin ^{Footnote 1, Footnote 11}. Trimethoprim and sulfamethoxazole can be used for treating chronic Q fever in children ^{Footnote 1}.

IMMUNIZATION: Q-vax vaccine (whole-cell formalin-inactivated vaccine) is used in Australia for immunization of high risk individuals ^{Footnote 1, Footnote 11}. It provides protection for up to 5 years ^{Footnote 11}.

PROPHYLAXIS: None.

SECTION VI - LABORATORY HAZARDS

LABORATORY-ACQUIRED INFECTIONS: C. burnetii accounted for the highest number of rickettsial laboratory infections, and second highest number of all laboratory infections up to 1976, with outbreaks involving 15 or more persons recorded in several institutions ^{Footnote 14, Footnote 15}. In total, 278 cases of C. burnetii were reported up to 1976 with 1 death ^{Footnote 14}.

SOURCE/SPECIMENS: Infected arthropods, blood, urine, feces, milk, yolk sac suspensions, contaminated laundry and clothing, naturally or experimentally infected animals, and tissues of humans or other hosts ^{Footnote 1, Footnote 4, Footnote 9, Footnote 15}.

PRIMARY HAZARDS: Exposure to infectious aerosols, ingestion, or accidental parenteral inoculation ^{Footnote 1, Footnote 9, Footnote 15}.

SPECIAL HAZARDS: Exposure to naturally infected and often asymptomatic sheep and to their birth products is a documented hazard to personnel, as is exposure to experimentally infected guinea pigs ^{Footnote 9, Footnote 15}.

SECTION VII – EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 3 ^{Footnote 16}.

CONTAINMENT REQUIREMENTS: Containment Level 3 facilities, equipment, and operational practices for work involving infectious or potentially infectious material, animals, or cultures ^{Footnote 17}.

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 to splashes ^{Footnote 17}.

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 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 activities ^{Footnote 17}.

SECTION VIII – HANDLING AND STORAGE

SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply an appropriate disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up ^{Footnote 17}.

DISPOSAL: All infectious material must be decontaminated before disposal using autoclave, chemical disinfection, gaseous decontamination, irradiation, incineration, or other appropriate method ^{Footnote 17}.

STORAGE: In properly labeled locked, leak proof containers that are secured in appropriate containment level facilities ^{Footnote 17}.

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: November 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.

Copyright ©
Public Health Agency of Canada, 2010
Canada

REFERENCES:

Footnote 1

Angelakis, E., & Raoult, D. (2010). Q Fever. Veterinary Microbiology, 140(3-4), 297-309.

Footnote 2

Drew, W. L. (2004). Rickettsia, Coxiella, Ehrlichia and Bartonella. In K. J. Ryan, & C. G. Ray (Eds.), Sherris medical microbiology: An introduction to infectious diseases (4th ed., pp. 471-479). USA: McGraw Hill.

Footnote 3

McCaul, T. F. (1991). The development cycle of Coxiella burnetii. In J. C. Williams, & H. A. Thompson (Eds.), Q fever: The biology of Coxiella burnetii (pp. 223-258). Florida: CRC Press.

Footnote 4

Brouqui, P., Marrie, T., & and Raoult, D. (2007). Coxiella. In P. R. Murray (Ed.), Manual of Clinical Microbiology (9th ed., pp. 1062-1069). Washington, D.C.: ASM Press.

Footnote 5

Olson, J. G., Jones, F. R., & Blair, P. J. (2006). Coxiella burnetii. In S. H. Gillespie, & P. M. Hawkey (Eds.), Principles and practice of clinical bacteriology (2nd ed., pp. 457-462). England: John Wiley & Sons.

Footnote 6

Anonymous. (2006). Q Fever. Guide to Surveillance, Reporting and Control,

Footnote 7

Marrie, T. J. (2009). Q fever. Bacterial Infections of Humans, , 643-660.

Footnote 8

Roest, H. I., Tilburg, J. J., VAN DER Hoek, W., Vellema, P., VAN Zijderveld, F. G., Klaassen, C. H., & Raoult, D. (2010). The Q fever epidemic in The Netherlands: history, onset, response and reflection. Epidemiology and Infection, , 1-12. doi:10.1017/S0950268810002268

Footnote 9

Kaufmann, A. F., & Boyce, J. M. (1995). Transmission of bacterial and rickettsial zoonoses in the laboratory. In D. O. Fleming, J. H. Richardson, J. J. Tulis & D. Vesley (Eds.), Laboratory Safety: Principles and Practices (2nd ed., pp. 93-104). Washington, D.C.: ASM Press.

Footnote 10

Scott, G. H., & Williams, J. C. (1990). Susceptibility of Coxiella burnetii to chemical disinfectants. Annals of the New York Academy of Sciences, 590, 291-296.

Footnote 11

Krauss, H., Weber, A., Appel, M., Enders, B., Isenberg, H. D., Schiefer, H. G., Slenczka, W., von Graevenitz, A., & Zahner, H. (2003). Bacterial Zoonoses. Zoonoses: Infectious Diseases Transmissible from Animals to Humans. (3rd ed., pp. 173-252). Washington, DC.: ASM press.

Footnote 12

Coggin, J. H. (2006). Bacterial pathogens. In D. O. Fleming, & D. L. Hunt (Eds.), Biological safety: principles and practices (4th ed., pp. 93-114). Washington, D.C.: ASM Press.

Footnote 13

Scott, G. H., McCaul, T. F., & Williams, J. C. (1989). Inactivation of Coxiella burnetii by gamma irradiation. Journal of General Microbiology, 135(12), 3263-3270.

Footnote 14

Pike, R. M. (1976). Laboratory associated infections: summary and analysis of 3921 cases. Health Laboratory Science, 13(2), 105-114.

Footnote 15

Rickettsial Agents. (1999). In J. Y. Richmond, & R. W. Mckinney (Eds.), Biosafety in microbiological and biomedical laboratories (4th ed., pp. 148-152). Washington D.C.: CDC & NIH.

Footnote 16

Human Pathogens and Toxins Act. S.C. 2009, c. 24. Government of Canada, Second Session, Fortieth Parliament, 57-58 Elizabeth II, 2009, (2009).

Footnote 17

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.