Table of Contents:

• Taxonomy Information
• Lifecycle Information
• Genome Information
• Biosafety Information
• Culturing Information
• Epidemiology Information
• Diagnostic Tests Information
• Infected Hosts Information
• Phinet: Pathogen-Host Interaction Network
• Lab Animal Pathobiology & Management
• References
• Data Provenance and Curators

1. Species:
   1. Coxiella burnetii (Website 6):
      1. GenBank Taxonomy No.: 777
      2. Description: Coxiella burnetii, the causative agent of Q fever, is an obligate intracellular gram-negative bacterium classified in the Rickettsiaceae family and belonging to the gamma subdivision of Proteobacteria(Maurin and Raoult, 1999). Although Coxiella was historically considered "Rickettsia-like," 16S rRNA gene sequence analysis and genome analysis (based on shared proteins across genomes and phylogenetic analysis of a set of 20 highly conserved proteins) indicate that it is a gamma proteobacteria (order Legionellales) and thus is distant from the gamma proteobacterial Rickettsia group. Coxiella is also distant from any other lineage within the subgroup, its closest relationship is with Legionella pneumophila, a facultative intracellular human pathogen, and Rickettsiella grylli, an intracellular arthropod pathogen(Seshadri et al., 2003). C. burnetii is very resistant to killing in nature and is further able to survive in the acidic environment of phagolysosomes(Maurin and Raoult, 1999).
      3. Variant(s):
         • Coxiella burnetii Group I (Maurin and Raoult, 1999):
           • Parents: Coxiella burnetii
           • Description: DNA from 38 Coxiella burnetii isolates was examined by restriction fragment length polymorphism (RFLP) analysis, resulting in the description of six genomic groups (I to VI). Genomic Group I is associated with animal, tick, or acute Q fever isolates (referred to as acute strains) and contains the plasmid QpH1(Maurin and Raoult, 1999).
         • Coxiella burnetii Group II (Maurin and Raoult, 1999):
           • Parents: Coxiella burnetii
           • Description: DNA from 38 Coxiella burnetii isolates was examined by restriction fragment length polymorphism (RFLP) analysis, resulting in the description of six genomic groups (I to VI). Genomic Group II is associated with animal, tick, or acute Q fever isolates (referred to as acute strains) and contains the plasmid QpH1(Maurin and Raoult, 1999).
         • Coxiella burnetii Group III (Maurin and Raoult, 1999):
           • Parents: Coxiella burnetii
           • Description: DNA from 38 Coxiella burnetii isolates was examined by restriction fragment length polymorphism (RFLP) analysis, resulting in the description of six genomic groups (I to VI). Genomic Group III is associated with animal, tick, or acute Q fever isolates (referred to as acute strains) and contains the plasmid QpH1(Maurin and Raoult, 1999).
         • Coxiella burnetii Group IV (Maurin and Raoult, 1999):
           • Parents: Coxiella burnetii
           • Description: DNA from 38 Coxiella burnetii isolates was examined by restriction fragment length polymorphism (RFLP) analysis, resulting in the description of six genomic groups (I to VI). Genomic Group IV is associated with human Q fever endocarditis isolates (referred to as chronic strains) and contains the plasmid QpRS(Maurin and Raoult, 1999).
         • Coxiella burnetii Group V (Maurin and Raoult, 1999):
           • Parents: Coxiella burnetii
           • Description: DNA from 38 Coxiella burnetii isolates was examined by restriction fragment length polymorphism (RFLP) analysis, resulting in the description of six genomic groups (I to VI). Genomic Group V is associated with human Q fever endocarditis isolates (referred to as chronic strains) and is plasmidless. However, Group V isolates were found to contain chromosome-integrated DNA sequences with homology to the QpRS plasmid(Maurin and Raoult, 1999).
         • Coxiella burnetii Group VI (Maurin and Raoult, 1999):
           • Parents: Coxiella burnetii
           • Description: DNA from 38 Coxiella burnetii isolates was examined by restriction fragment length polymorphism (RFLP) analysis, resulting in the description of six genomic groups (I to VI). Genomic Group VI isolates (obtained from feral rodents) are of unknown pathogenicity and contain the plasmid QpDG(Maurin and Raoult, 1999).
         • Coxiella burnetii Nine Mile Strain (Maurin and Raoult, 1999):
           • Parents: Coxiella burnetii
           • Description: Strain of Coxiella burnetii that was originally isolated in the 1930s from ticks in Nine Mile, Montana(Maurin and Raoult, 1999). The Nine Mile strain contains plasmid QpH1(Willems et al., 1998).
         • Coxiella burnetii French Strain (Maurin and Raoult, 1999):
           • Parents: Coxiella burnetii
           • Description: Plasmid QpDV is found in a French strain isolated from an endocarditis patient(Maurin and Raoult, 1999).
         • Coxiella burnetii Small-Cell Variants (Maurin and Raoult, 1999):
           • Parents: Coxiella burnetii
           • Description: Small-cell variants (SCVs) are metabolically inactive and resistant to osmotic pressure and correspond to the extracellular form of Coxiella burnetti. SCVs attach to the eukaryotic cell membrane to enter phagocytic cells. After phagolysosomal fusion, acid activation of the metabolism of SCVs may lead to the formation of large-cell variants (LCVs). SCVs have a typical eubacterial gram-negative cell wall with two membranes separated by a periplasmic space. A dense material fills the periplasmic space in SCVs and corresponds to proteins and peptidoglycan. This material may explain the increased resistance of SCVs to environmental conditions(Maurin and Raoult, 1999).
         • Coxiella burnetii Small-dense-cell Variants (Heinzen et al., 1999):
           • Parents: Coxiella burnetii Small-Cell Variants
           • Description: The small-dense-cell (SDC) variant is a sub-population of the small-cell variant and displays extreme tolerance to rupture under high pressure (approximately 1400 kg / cm)(Heinzen et al., 1999).
         • Coxiella burnetii Large-Cell Variants (Maurin and Raoult, 1999):
           • Parents: Coxiella burnetii
           • Description: Large-cell variants (LCVs) correspond to the metabolically active intracellular form of Coxiella burnetii. A sporogenic differentiation has been characterized in LCVs, leading to the formation of resistant, spore-like forms of bacteria. The endogenous spore-like forms undergo further development to become the metabolically inactive small-cell variants (SCVs), which are then released from the infected host cell either by cell lysis or possibly by exocytosis(Maurin and Raoult, 1999).
         • Coxiella burnetii Phase I (Maurin and Raoult, 1999):
           • Parents: Coxiella burnetii
           • Description: Coxiella burnetii displays antigenic variations similar to the smooth-rough variation in the family Enterobacteriaceae. Phase variation is related mainly to mutational variation in the lipopolysaccharide (LPS). Phase I is the highly infectious, natural phase of Coxiella burnetii corresponding to smooth lipopolysaccharide (LPS). Phase I is found in infected animals, arthropods, or humans(Maurin and Raoult, 1999). This antigenic variation is extremely valuable for the serological differentiation between acute and chronic Q fever as the presence of anti-phase I antibodies is indicative of chronic Q fever(Maurin and Raoult, 1999, Fournier et al., 1998).
         • Coxiella burnetii Phase II (Maurin and Raoult, 1999):
           • Common Name: Phase II
           • Parents: Coxiella burnetii
           • Description: Coxiella burnetii displays antigenic variations similar to the smooth-rough variation in the family Enterobacteriaceae. Phase variation is related mainly to mutational variation in the lipopolysaccharide (LPS). Phase II is the "not very infectious" phase of Coxiella burnetii obtained only after serial passages in cultures. It corresponds to rough lipopolysaccharide (LPS). Compared to phase I, phase II displays a truncated LPS and lacks some protein cell surface determinants(Maurin and Raoult, 1999). This antigenic variation is extremely valuable for the serological differentiation between acute and chronic Q fever as the presence of anti-phase II antibodies is indicative of acute Q fever(Maurin and Raoult, 1999, Fournier et al., 1998).
         • Coxiella burnetii large cell variants (Madariaga et al., 2003):
           • Common Name: Coxiella burnetii large cell variants
           • Parents: Coxiella burnetii
           • Description: Electron microscopy suggests that coxiella has two morphological forms (large and small), a phenomenon different from the phase variation phenomenon and the developmental stages of the organism. Coxiella is ingested as a small variant form by the host cell. Fusion of the primary lysosome and the phagosome containing the organism occurs. The acid pH of the phagolysosome activates the enzymes of C. burnetii and leads to development of the large cell variant, which in turn may produce highly resistant spores. Six strain types have been described: Hamilton, Bacca, Rasche, Biothere, Corazon and Dod(Madariaga et al., 2003).

1. 1. Stage Information:
      1. Vegetative Cell:
         • Size: Small, 0.2 to 0.4 microns wide, 0.4 to 1 microns long (Maurin and Raoult, 1999). The small-cell variants: 0.2 to 0.5 microns; Length can exceed 1.0 micron for large-cell variants
         • Shape: Pleomorphic rod. Rod-like, compact. Large-cell variants are more pleomorphic than the small-cell variants.

1. Genome of Coxiella burnetii Nine Mile Strain
   1. Description: The 1,995,275-bp genome of Coxiella burnetii, Nine Mile phase I RSA493, a highly virulent zoonotic pathogen and category B bioterrorism agent, was sequenced by the random shotgun method(Seshadri et al., 2003). However, the genome size is highly variable among different C. burnetii strains, ranging from 1.5 to 2.4 Mb(Maurin and Raoult, 1999). Although previously suspected to be linear, genome sequencing and analysis suggest a circular topology for the chromosome. The genome is predicted to encode 2,134 CDSs, of which 719 (33.7%) are hypothetical, i.e., have no significant matches to other sequenced genes, which is a high proportion given the large number of gamma proteobacterial genome sequences currently available. Genome analysis identified 83 "pseudogenes" (genes disrupted by one or more authentic frameshifts and/or point mutations or, in some cases, truncations) suggesting that some genome reduction is underway(Seshadri et al., 2003). Genomic sequence data indicate that 21 genes encoding products that are similar to components of the Legionella pneumophila Dot/Icm type IV secretion system are located on a contiguous 35 kb region of the Coxiella chromosome(Zamboni et al., 2003).
   2. Chromosome(Website 8)
      1. GenBank Accession Number: NC_002971
      2. Size: 2.1 Mb(Willems et al., 1998, Maurin and Raoult, 1999).
      3. Description: The chromosome shape is probably linear(Willems et al., 1998, Maurin and Raoult, 1999).
   3. Plasmid QpH1(Website 9)
      1. GenBank Accession Number: NC_002118
      2. Size: 37 kb(Website 9).
      3. Description: Plasmid QpH1 is found in genomic groups I, II, and III and is thus associated with acute Coxiella burnetii strains(Maurin and Raoult, 1999).
   4. Plasmid QpRS
      1. Size: 39 kb(Maurin and Raoult, 1999).
      2. Description: Plasmid QpRS is a 39-kb plasmid found in genomic group IV. This plasmid was found in Coxiella burnetii Priscilla, obtained from an aborted goat fetus. The QpRS plasmid was also found in human Q fever endocarditis isolates(Maurin and Raoult, 1999).
   5. Plasmid QpDG
      1. Size: 42 kb(Maurin and Raoult, 1999).
      2. Description: Plasmid QpDG is a 42 kb plasmid found in genomic group VI isolates (obtained from feral rodents)(Maurin and Raoult, 1999).
   6. Plasmid QpDV(Website 10)
      1. GenBank Accession Number: NC_002131
      2. Size: 33 kb(Maurin and Raoult, 1999).
      3. Description: Plasmid QpDV is a 33-kb plasmid that has been found in a French strain isolated from an endocarditis patient(Maurin and Raoult, 1999).
   7. Plasmid pQpH1(Website 18)
      1. GenBank Accession Number: NC_004704
      2. Size: 37 kb(Website 18).
      3. Description: Plasmid pQpH1 is found in Coxiella burnetii strain RSA 493(Website 18).

1. Biosafety information for Coxiella burnetii
   1. Level: Depending on the work being done, practices associated with biosafety level 2 or 3 are recommended (C. burnetii: MSDS; Rickettsial agents - Coxiella).
   2. Precautions: Biosafety level 2 practices and containment for nonpropagative laboratory procedures including serological examinations and staining of impression smears. Biosafety level 3 practices and containment for activities involving the inoculation, incubation, and harvesting of embryonated eggs or tissue cultures, the necropsy of infected animals, and the manipulation of infected tissues(Website 1, Website 13, Bernard et al., 1982, Spinelli et al., 1981). Protective clothing including laboratory coats, gloves, and gown (tight wrists and fastened back) should always be worn when working with this organism. Masks may also be used(Website 1). Since infected guinea pigs and other rodents may shed the organisms in urine or feces, experimentally infected rodents should be maintained under Animal Biosafety Level 3. Recommended precautions for facilities using sheep as experimental animals are described in Bernard et al. (1982) and Spinelli et al. (1981). An investigational new Phase I Q fever vaccine (IND) is available from the Special Immunizations Program, U.S. Army Medical Research Institute for Infectious Diseases (USAMRIID), Fort Detrick, Maryland. The use of this vaccine should be limited to those at high risk of exposure and who have no demonstrated sensitivity to Q fever antigen. Individuals with valvular heart disease should not work with Coxiella burnetii(Website 13, Bernard et al., 1982, Spinelli et al., 1981).
   3. Disposal: Decontaminate all wastes before disposal: incineration (animal wastes), steam sterilization(Website 1).

1. Culturing Overview :
   1. Description: Since Coxiella burnetii is a strict intracellular bacterium, culturing is not possible in axenic medium. Although it has been successfully isolated in guinea pigs, mice, and embryonated eggs, such techniques have been abandoned because they are more hazardous than in vitro cell cultures(Maurin and Raoult, 1999). In vitro, C. burnetii replicates within a wide variety of epithelial, fibroblast, and macrophage-like cell lines(Heinzen et al., 1999). including; human embryonic lung fibroblasts (HEL cells), which are highly susceptible to C. burnetii infection,(Maurin and Raoult, 1999, Raoult et al., 1990). murine macrophage-like cell lines P388D1, J774, and PU-5-IR;(Maurin and Raoult, 1999, Baca et al., 1981). mouse L929 fibroblasts;(Capo et al., 1999). and Buffalo green monkey kidney cells (BGM cell line)(Macellaro et al., 1998).
2. Culture of Coxiella burnetii in HEL cells :
   1. Description: A system for isolation and routine in vitro culture of Coxiella burnetii in human embryonic lung fibroblasts (HEL cells) was developed by Raoult et al(Maurin and Raoult, 1999, Raoult et al., 1990). HEL cell monolayers were grown in a shell vial until confluent and a sample containing Coxiella burnetii was added to it. To increase the attachment and penetration of the bacteria into the cells, the vial was centrifuged at 700 x g for 1 hour at 22 degrees celcius(Raoult et al., 1990). Following the spin, the inoculum was removed, the shell vial was washed with phosphate-buffered saline, medium was added, and the vial was incubated for 6 days at 37 degrees Celsius. The bacteria were visible in cells of the monolayer when Gimenez or immunofluorescent staining was performed(Maurin and Raoult, 1999). Subculturing: samples from shell vials were harvested and inoculated into 25-cm squared flasks containing HEL cell monolayers. The medium was changed every 3 days. When cells were determined to be heavily infected following examination by Gimenez staining, they were harvested and inoculated into 150-cm squared flasks(Raoult et al., 1990).
   2. Medium: Eagle's minimal essential medium (MEM) with 10% fetal calf serum and 1% glutamine(Raoult et al., 1990).
   3. Optimal Temperature: 37 degrees Celsius(Raoult et al., 1990).
3. Culture of Phase I and Phase II Coxiella burnetii in murine macrophage-like cell lines :
   1. Description: Phase I Coxiella burnetii is the highly infectious, natural phase of the bacterium corresponding to smooth lipopolysaccharide (LPS). Phase I is found in infected animals, arthropods, or humans(Maurin and Raoult, 1999). Phase I Coxiella burnetii was found to proliferate in the murine macrophage-like tumor cell lines P388D1, J774, and PU-5-IR(Maurin and Raoult, 1999, Baca et al., 1981). Phase II is the "not very infectious" phase of Coxiella burnetii obtained only after serial passages in cultures. It corresponds to rough lipopolysaccharide (LPS)(Maurin and Raoult, 1999). Phase II C. burnetii proliferated in P388D1, J774, and PU-5-IR cell lines plus WEHI-3 and WEHI-274(Baca et al., 1981). Before exposure to the bacteria, cell lines were washed and suspended to appropriate concentrations in antibiotic-free medium. Following infection, the cells were kept at 37 degrees Celsius in a 4% CO2 atmosphere and passaged every 3 days. Cell-associated bacteria were visualized using Gimenez staining, (see protocol for Gimenez staining in "light microscopy, diagnostic test")(Baca et al., 1981).
   2. Medium: Dulbecco's modified Eagle's medium (DME) with 5-10% fetal calf serum with nonessential amino acids included for the PU-5 line only(Baca et al., 1981).
   3. Optimal Temperature: 37 degrees Celsius(Baca et al., 1981).
4. Culture of Coxiella burnetii in BGM cells :
   1. Description: Coxiella burnetii was grown in Buffalo green monkey cells (BGM, Flow Laboratories). Confluent cell layers were infected with the bacteria and incubated at 37 degrees Celsius. Fresh medium was added after 20-24 hours. C. burnetii could be collected from the media of actively growing cultures after 7-8 days using differential centrifugation (8 minutes/4,000 x g/4 degrees Celsius to remove cell debris and 20 minutes/25,000 x g/4 degrees Celsius to collect the bacteria)(Macellaro et al., 1998).
   2. Medium: Eagle's minimal essential medium (MEM), supplemented with Earle's salts, 2 mM L-glutamine, 0.2% NaHCO3, 5% calf serum, and 1% nonessential amino acids(Macellaro et al., 1998).
   3. Optimal Temperature: 37 degrees Celsius(Macellaro et al., 1998).
5. Culture of Coxiella burnetii in L929 mouse fibroblasts :
   1. Description: Coxiella burnetii was cultured in L929 mouse fibroblasts. After 1 week, L929 cells were sonicated and bacteria could be collected(Capo et al., 1999).
   2. Medium: Antibiotic-free minimal essential medium (MEM) supplemented with 4% fetal calf serum and 2 mM L-glutamine(Capo et al., 1999).

1. Outbreak Locations:
   1. Q fever (caused by Coxiella burnetii) has been described in almost every country, with New Zealand remaining an exception(Maurin and Raoult, 1999). Explosive epidemics occur in stockyards, meat packing plants, and medical labs using sheep for research(Website 1).
2. Transmission Information:
   1. From: Domestic animals , To: Domestic animals (Marrie and Raoult, 1997)
      Mechanism: Dairy cows are important in the spread of Q fever while beef cows are rarely infected. Once Coxiella burnetii is introduced into a herd, rapid spread occurs so that 80% of cows are positive within a few months. Infected wildlife may be important in infecting cattle since in a large portion of newly infected herds, a source of infection is not found(Marrie and Raoult, 1997).
   2. From: Ticks , To: Domestic animals , With Destination:Homo sapiens (Maurin and Raoult, 1999, Website 1)
      Mechanism: Ticks infect domestic and wild animals by expelling heavy loads of the organism with their feces onto the animal's skin at the time of feeding, however ticks are not considered essential in the natural cycle of Coxiella burnetti infection in livestock(Maurin and Raoult, 1999). Infected ticks have been found on rabbits, goats, cattle, sheep, and many other animals(Marrie and Raoult, 1997). Cattle, goats, and sheep are considered the primary reservoirs from which human contamination occurs most often by inhalation of infected fomites(Maurin and Raoult, 1999, Marrie and Raoult, 1997).
   3. From: Domestic animals , To: Homo sapiens (Maurin and Raoult, 1999, Norlander, 2000, Website 1)
      Mechanism: The aerosol route (inhalation of infected fomites) is the primary mode of human contamination with Coxiella burnetii(Maurin and Raoult, 1999). This can occur following contact with infected animals and their birth products, with wool from infected sheep, with infected straw or fertilizer, or with the laundry of a person exposed to the infected animal(Maurin and Raoult, 1999, Norlander, 2000, Website 1). The mode of spread results in the following persons being at risk for infection: abattoir workers, farmers, and veterinarians(Marrie, 1990). The largest outbreak of acute Q fever in the United Kingdom occurred in 1989. The most likely route of infection for the 147 diagnosed cases was assumed to be the windborne spread from farmland to an urban area(Norlander, 2000).
   4. From: Milk , To: Homo sapiens (Maurin and Raoult, 1999, Marrie and Raoult, 1997)
      Mechanism: There is a suggestion from epidemiological studies that ingestion of contaminated milk is a risk factor for Q fever infection. However, evidence from experiments where contaminated milk was fed to volunteers is contradictory, making this mode of infection controversial(Maurin and Raoult, 1999, Marrie and Raoult, 1997).
   5. From: Infected tick, intradermal inoculation, blood transfusion. , To: Homo sapiens (Marrie, 1990, Marrie and Raoult, 1997)
      Mechanism: There has been a report that a human became infected with Coxiella burnetii after crushing a tick between his fingers, developing Q fever 16 days later. However, aerosol exposure in this case could not be ruled out. In addition, a study in which volunteers were intradermally infected with C. burnetii all developed clinical signs of Q fever. There has also been one report of transmission of Q fever via a blood transfusion(Marrie, 1990, Marrie and Raoult, 1997).
   6. From: Homo sapiens , To: Homo sapiens (Milazzo et al., 2001)
      Mechanism: There have only been a few cases of documented person to person transmission of Q fever. There are two reports of transmission of Q fever to attendants during human autopsies, and one report of transmission of infection from a patient to hospital staff(Marrie and Raoult, 1997). Sexual Transmission: Although rare, sexual transmission of Q fever in humans has been documented. In a 1996 report, sheep shearers that acquired Q fever from sheep subsequently infected their wives via sexual intercourse. Another report in 2001 described sexually transmitted Q fever from a man (infected via the aerosol route) to his wife. This report demonstrated the presence of Coxiella burnetii in the man's semen, however, sexual intercourse may also involve the exchange of fluids such as saliva, blood, or urine, which may actually be the vehicle of infection(Milazzo et al., 2001). From Placenta to Fetus: Because Coxiella burnetii has been isolated from human placentas, it has been suggested that there may be a reactivation of infection at the time of pregnancy in women previously infected with the organism. This has rarely been documented however, and the overall importance of vertical transmission is thought to be unimportant in the overall epidemiology of Q fever in man(Marrie, 1990, Marrie and Raoult, 1997).
3. Environmental Reservoir:
   1. Wild animals(Maurin and Raoult, 1999, Norlander, 2000):
      1. Description: Many species of wildlife including rats, mice, rabbits, water buffalo, bandicoots, hedgehogs, camels, baboons, ducks, geese, pigeons, and bats can be infected with Coxiella burnetti(Maurin and Raoult, 1999, Website 1, Norlander, 2000, Marrie and Raoult, 1997).
   2. Domestic animals(Maurin and Raoult, 1999, Norlander, 2000):
      1. Description: Cattle, sheep and goats are considered to be the main reservoirs of the agent responsible for infection of humans(Norlander, 2000). Cats and dogs may also represent reservoirs of Coxiella burnetii. The possibility of human Q fever acquired from infected dogs has been reported and human Q fever cases were described in Nova Scotia after contact with parturient cats(Maurin and Raoult, 1999). 44 (14.2%) of 310 pet cats in Japan were seropositive, as were 15 (41.7%) of 36 stray cats in Japan and 10 (8.6%) of 116 pet cats in Korea. The positivity among stray cats was significantly higher than among pet cats in both countries (P<0.01), but there was no significant difference in the positivity rate between Japan and Korea. Only 4 (1.3%) of pet cats in Japan were PCR-positive(Komiya et al., 2003).
   3. Ticks(Maurin and Raoult, 1999, Norlander, 2000):
      1. Description: Over 40 tick species are naturally infected with Coxiella burnetii and they expel heavy loads of C. burnetii with their feces onto the skin of the animal host at the time of feeding. Ticks are considered to be the natural primary reservoirs of C. burnetii responsible for the spread of the infection in wild animals and for transmission of C. burnetii from wild to domestic animals (Norlander, 2000). The possibility of C. burnetii being transmitted to humans via a tick bite has seldom been reported. Human Q fever, as opposed to other rickettsial diseases, is rarely, an arthropod-borne disease(Maurin and Raoult, 1999, Norlander, 2000).
   4. Dried sputum(Website 1):
      1. Description: dried sputum(Website 1).
      2. Survival: C. burnetii can survive for 30 days in dried sputum(Website 1).
   5. Soil(Website 1):
      1. Description: soil(Website 1).
      2. Survival: C. burnetii can survive for years within soil(Website 1).
   6. Dust(Website 1):
      1. Description: dust(Website 1).
      2. Survival: C. burnetii can survive for 120 days in dust(Website 1).
   7. Dried Urine(Website 1):
      1. Description: dried urine(Website 1).
      2. Survival: C. burnetii can survive for 49 days in the dried guinea pig urine(Website 1).
   8. Tick Feces(Website 1):
      1. Survival: C. burnetii can survive for 586 days in tick feces(Website 1).
   9. Milk(Website 1):
      1. Description: milk(Website 1).
      2. Survival: C. burnetii can survive for 42 months in milk stored at 4-6 degrees Celcius(Website 1).
   10. Wool(Website 1):
       1. Description: wool(Website 1).
       2. Survival: C. burnetii can survive for 12-16 months in wool kept at a temperature of 4-6 degrees Celcius(Website 1).
   11. Extracellular Environment(Heinzen et al., 1999):
       1. Description: extracellular environment(Heinzen et al., 1999).
       2. Survival: Coxiella burnetii can survive heating at 63 degrees Celcius for 30 minutes, exposure to a 10% salt solution for 180 days at room temperature, or exposure to 0.5% formalin for 24 hours(Heinzen et al., 1999).
4. Intentional Releases:
   1. Intentional Release Information:
      1. Description: Q fever is deemed a category B biological terrorist agent, since, although it has potential for large-scale dissemination, it lacks capacity for the massive fatalities potentially caused by category A agents (smallpox, anthrax, plague, botulism, tularaemia, and viral haemorrhagic fevers). However, compared with category A agents, Q fever might be more suitable for use as a biological weapon because of its widespread availability, natural potential for aerosolised use, environmental stability, and the possibility of producing large quantities of infectious material(Website 4). Humans acquire Q fever by inhaling Coxiella burnetii(Website 4). Ease of aerosol dissemination, environmental persistence, and high infectivity (ID50 = 1-10) make C. burnetii a serious threat for military personnel and civilians. This agent has already been weaponized and mass-produced under various biological warfare programs(Seshadri et al., 2003). As an agent of biological warfare, Q fever is an incapacitating agent and would not be expected to cause significant fatalities(Website 4).
      2. Emergency Contact: In 1999, Q fever became a notifiable disease in the United States, thus health care providers are required to report to State or local public health officials (Q fever)(Website 3).
      3. Delivery Mechanism: If Coxiella burnetii was intentionally released, it would likely be distributed as a cloud of C. burnetii-infected particles that would be inhaled(Website 4). If used against troops, loss of manpower can range from 23% to 77%, and operational efficiency can be severely impaired. If used as a biological weapon in a civilian population, the degree of infectivity may rival that of anthrax, and although associated mortality will be low, Q fever can cause extensive acute and chronic morbidity(Madariaga et al., 2003).
      4. Containment: Coxiella burnetii is highly infectious via the aerosol route and very stable in the environment, but it is possible to disinfect contaminated articles by using a 0.5% hypochlorite solution, 1% Lysol, or 5% hydrogen peroxide(Website 2, Website 4, Marrie et al., 2000).

1. Organism Detection Test:
   1. Gimenez staining :
      1. Description: The organism appears as a short rod which is not stained by Gram staining but which is visible after Giemsa or Gimenez staining(Fournier et al., 1998). After Gimenez staining, macrophages containing large vacuoles full of the organism can be identified at 400x magnification (see Fig. 6, Maurin and Raoult, 1999). Protocol for Gimenez staining (Gimenez, 1964): Reagents:1. Prepare a stock solution of carbol basic fuschin by mixing 100 ml of 10% (w/v) basic fuschin in 95% ethanol, 250 ml of 4% (v/v) aqueous phenol, and 650 ml of distilled water. Keep the stock solution at 37 degrees C for 48 hours before use (stock solution is stable for at least 10 months). 2. A 0.1M sodium phosphate buffer solution at pH 7.45 is made by mixing 3.5 ml of 0.2 M NaH2PO4, 15.5 ml of 0.2 M Na2HPO4, and 19 ml of distilled water.3. The working solution of carbol basic fuschin is prepared by mixing 4 ml of stock solution with 10 ml of pH 7.45 buffer. This is immediately filtered, and filtered again before every stain.4. Other solutions: 0.8% malachite green oxalate, 4% aqueous Fe(NO3)3/9H₂O, and 5% aqueous fast green FCF.Procedure: 1. Prepare the sample for staining. If necessary, make a very thin smear. 2. After air drying (with or without fixing by passing through a flame) the preparation is covered with carbol basic fushcin (working solution) and let stand 1 to 2 minutes. 3. Wash thoroughly with water and cover the preparation with the malachite green solution for 6-9 seconds. 4. Repeat step 3 by again washing and covering the preparation with the malachite green solution for 6-9 seconds.5. Wash thoroughly with water and dry the preparation with absorbent paper(Maurin and Raoult, 1999, Gimenez, 1964).
   2. Indirect immunofluorescence staining :
      1. Description: Indirect immunofluorescence staining was used by Muhlemann et al. (1995) to demonstrate the presence of Coxiella burnetii in heart valves of patients treated for Q fever endocarditis. The method used, involved the isolation of C. burnetii from heart valve tissue and inoculation of the bacteria into human fetal lung fibroblasts (MCR-5). MCR-5 cell monolayers were examined by indirect immunofluorescence using high titer anti-Coxiella burnetii human serum followed by sheep anti-human Ig and Evan's blue counterstaining(Muhlemann et al., 1995).
   3. Immunohistologic/Immunoperoxidase Staining (Fournier et al., 1998, Brouqui et al., 1994, Raoult et al., 1994):
      1. Time to Perform: 1-hour-to-1-day
      2. Description: The detection of Coxiella burnetii in tissues is especially informative in patients who are undergoing treatment for chronic Q fever (Fournier et al., 1998). Brouqui et al. (1994) examined the valves of 17 patients with Q fever endocarditis using a monoclonal antibody (Raoult, 1994) and immunohistochemical methods. The organisms were clustered as a single intracytoplasmic mass within mononuclear cells and usually occupied the entire cytoplasm(Fournier et al., 1998).
2. Immunoassay Test:
   1. A monoclonal antibody-based capture ELISA/ELIFA :
      1. Time to Perform: 1-to-2-days
      2. Description: A monoclonal antibody-based capture ELISA/ELIFA for detection of Coxiella burnetii in clinical specimens was developed in 1992 by Thiele and coworkers. The assay used a monoclonal antibody (4/11) as capture and detection antibody. The system recognized a minimum dose of 2500 Coxiella burnetii particles, demonstrated broad reactivity with both phase I and phase II Coxiella burnetii, and did not cross-react with 20 other strains of bacteria(Thiele et al., 1992).
   2. PANBIO Coxiella burnetii (Q fever) IgM ELISA test :
      1. Time to Perform: 1-hour-to-1-day
      2. Description: Serum antibodies of the IgM class, when present, combine with C. burnetii antigen attached to the polystyrene surface of the microwell test strips. Residual serum is removed by washing and peroxidase conjugated anti-human IgM added. The microwells are washed and a colourless substrate system, tetramethylbenzidine/hydrogen peroxide (TMB/H₂O2) is added. The substrate is hydrolysed by the enzyme and the chromogen changes to a blue color. After stopping the reaction with acid, the TMB becomes yellow. The color intensity is directly related to the concentration of the C. burnetii IgM antibodies in the test sample (Coxiella burnetti IgM). During acute Q fever, seroconversion is usually detected from 7 to 15 days after the onset of clinical symptoms and antibodies are detected by the third week in about 90% of cases(Maurin and Raoult, 1999, Website 14). A comparison of the IgM ELISA to indirect fluorescent antibody test (IFAT) and the complement fixation test (CFT) was performed by Field et al., 2000. The ELISA demonstrated 92% agreement with the reference method (IFAT), and gave a sensitivity of 99% (69 of 70 samples) and a specificity of 88% (106 of 121). Specificity can be increased with confirmation by IFAT. CFT was found to have a specificity of 90% (107 of 119), although it was lacking in sensitivity (73%; 51 of 70). No cross-reactivity was observed in the ELISA with serum samples from patients with mycoplasma (n = 6), chlamydia (n = 5), or legionella (n = 4) infections, although 2 of 5 patients with leptospirosis and 1 of 4 samples containing rheumatoid factor (RF) demonstrated positive results in the ELISA. Results indicate that the performance of the PANBIO C. burnetii (Q fever) IgM ELISA (F = 187) is superior to that of CFT (F = 163), and consequently the ELISA should be a useful aid in the diagnosis of acute Q fever(Field et al., 2000, Website 14).
   3. PANBIO Coxiella burnetii (Q fever) IgG ELISA test :
      1. Time to Perform: 1-hour-to-1-day
      2. Description: Serum antibodies of the IgG class, when present, combine with C. burnetii antigen attached to the polystyrene surface of the microwell test strips. Residual serum is removed by washing and peroxidase conjugated anti-human IgG added. The microwells are washed and a colourless substrate system, tetramethylbenzidine/hydrogen peroxide (TMB/H₂O2) is added. The substrate is hydrolysed by the enzyme and the chromogen changes to a blue color. After stopping the reaction with acid, the TMB becomes yellow. The color intensity is directly related to the concentration of the C. burnetii IgG antibodies in the test sample. In Q fever infection, IgG antibodies reach peak levels within six weeks and slowly decline to lower levels which persist indefinitely. A significant rise in specific IgG antibody suggests a recent infection(Field et al., 2002). In a study (Field et al., 2002), the PANBIO IgG ELISA was compared to the complement fixation test (CFT), and the indirect fluorescent-antibody test (IFAT) was used to resolve discrepant results between the other two tests. A total of 214 serum samples were tested. The ELISA demonstrated a specificity of 96% (46 of 48 samples) and a sensitivity of 71% (95 of 134 samples). Of the six serum pairs showing CFT seroconversion, three pairs showed a corresponding ELISA seroconversion. No cross-reactivity was observed in the ELISA with serum samples from patients with mycoplasma, brucella, and chlamydia infections. One of the 13 patients with leptospirosis demonstrated a positive result in the ELISA but not in the CFT or the IFAT, and Legionella pneumophila serogroup 4 antibody was found in one of the two sera that were false-positive by ELISA. The results presented in this study suggest that the PANBIO Q fever IgG ELISA is a specific alternative method for prevaccination testing and an aid for the diagnosis of Q fever. This test is suitable for use as a screening assay, with CFT and/or IFAT used to confirm negative results(Field et al., 2002).
   4. IFA, microimmunofluorescence test :
      1. Description: The IFA remains the reference technique for Q fever diagnosis. The microimmunofluorescence test has the advantage of requiring only small amounts of antigen. In order to prepare antigens for this test, phase II C. burnetii Nine Mile reference strain is grown in confluent layers of L929 mouse fibroblasts, while phase I antigens are obtained from the spleens of mice inoculated with phase II organisms. This method of preparation has been demonstrated to yield antigens with the highest sensitivity for C. burnetii antibody detection. Sera are diluted in phosphate-buffered saline with 3% nonfat powdered milk to avoid the nonspecific fixation of antibodies. This method can be used to determine antibodies to phases I and II in the IgG, IgM, and IgA fractions. However, test results can be confounded by the presence of a rheumatoid factor. Thus, a rheumatoid factor absorbant is used in order to remove IgG before the determination of IgM and IgA. The choice of a negative cutoff titer depends upon the source and purity of the antigen and the amount of background antigen stimulation in the population to be studied. Screening is performed with anti-phase II anti-immunoglobulins with a 1:50 dilution for the tested sera. Positive sera are then serially diluted and tested for the presence of anti-phase I and II IgG, IgM, and IgA. Seroconversion to IgM is usually detected 7 to 15 days after the onset of clinical symptoms. About 90% of patients have detectable antibodies by the third week(Fournier et al., 1998).
   5. PANBIO Coxiella burnetii (Q fever) IFA slides :
      1. Time to Perform: 1-hour-to-1-day
      2. Description: The PANBIO Coxiella burnetii IFA slides contain both Phase I and Phase II purified organisms as well as a normal yolk sac (NYS) control. All three are represented on each well of the slides as distinct microdots. Dilutions of the patient's serum are placed in wells on the slide, permitting the antibody to bind specifically to the organisms. Bound antibodies are tagged with a fluorescein labeled anti-human conjugate and observed using a fluorescence microscope. In this format, organisms are readily identified as small coccobacilli. Fluorescent coxiellae are bright yellow against a dull red background (counterstain) (Coxiella burnetti IFA)(Website 16). During acute Q fever, seroconversion is usually detected from 7 to 15 days after the onset of clinical symptoms and antibodies are detected by the third week in about 90% of cases(Maurin and Raoult, 1999).
   6. PANBIO DIP-S-TICKS :
      1. Time to Perform: minutes-to-1-hour
      2. Description: The PANBIO Q Fever Dip-S-Ticks assay utilizes an enzyme-linked immunoassay (EIA) dot technique for thedetection of antibodies to Coxiella burnetii. The antigens are dispensed as discrete dots onto a solid membrane. After adding specimen to a reaction vessel, an assay strip is inserted, allowing patient antibodies reactive with the test antigen to bind to the strip's solid support membrane. In the second stage, the reaction is enhanced by removal of non-specifically bound materials. During the third stage, alkaline phosphatase-conjugated anti-human antibodies are allowed to react with bound patient antibodies. Finally, the strip is transferred to enzyme substrate reagent, which reacts with bound alkaline phosphate to produce an easily seen, distinct spot. Cultivation of the Q fever organism, C. burnetii, produces two distinct antigens: Phase I and Phase II. Antibodies to Phase II antigen are produced early in acute infections. Later, Phase I antibodies can be detected but may be in reduced concentration with respect to Phase II. Patients having chronic infections exhibit high antibody levels to both Phase I and Phase II antigens. PANBIO Q fever Dip-S-Ticks have dots for both Phase I and Phase II antigens. Three dots are for Phase II (acute infection) determination and one is for Phase I (chronic infection) determination(Website 17).
3. Nucleic Acid Detection Test:
   1. Restriction fragment length polymorphism (RFLP) - pulsed field gel electrophoresis (PFGE) :
      1. Time to Perform: 2-to-7-days
      2. Description: Restriction fragment length polymorphism (RFLP) combined with pulsed field gel electrophoresis (PFGE) was performed on 80 Coxiella burnetii isolates from animals and humans in Europe, USA, Africa, and Asia. After NotI restriction of total C. burnetii DNA and PFGE, 20 different restriction patterns were discovered, including 4 distinguished patterns from reference isolates and 16 new "restriction groups"(Jager et al., 1998).

1. Human
   1. Taxonomy Information:
      1. Species:
         1. Homo sapiens (Website 6):
            • Common Name: Homo sapiens
            • GenBank Taxonomy No.: 9606
            • Description: Humans are usually infected by contaminated aerosols from domestic animals, particularly after contact with parturient females and their birth products. Although often asymptomatic, Q fever may manifest in humans as an acute disease (mainly as a self-limited febrile illness, pneumonia, or hepatitis) or as a chronic disease (mainly endocarditis), especially in patients with previous valvulopathy and to a lesser extent in immunocompromised hosts and in pregnant women(Maurin and Raoult, 1999).
   2. Infection Process:
      1. Infectious Dose: Estimates of infectivity for humans range from 1 to 10 bacteria(Norlander, 2000), Estimates of infectivity for humans range from 1 to 10 bacteria(Norlander, 2000),
      2. Description: Humans are primarily infected through the inhalation of fomites contaminated with Coxiella burnetii(Maurin and Raoult, 1999), The lungs not only serve as a portal of entry of the pathogen into the human body, but also as an area of primary infectious focus where C. burnetii proliferates in alveolar macrophages(Norlander, 2000, Heinzen et al., 1999), Possibly in part due to the mobility of the lung macrophages, C. burnetti subsequently spreads hematogenously to the liver, bone marrow, and spleen(Norlander, 2000, Heinzen et al., 1999, Website 11), Once phagocytosed by monocytes and macrophages, C. burnetii resides within a moderately acidic parasitophorous vacuole that has characteristics of a secondary lysosome(Heinzen et al., 1999), Results of a study indicate that C. burnetii is not simply a passive bystander in the development of its large and spacious, replicative parasitophorous vacuole (PV). The PV also acidifies to a pH of approximately 4.8 which activates the metabolism of C. burnetii. Coxiella burnetii undergoes luxurious growth within this environment despite the presence of lysosomal constituents normally considered bactericidal. Observations suggest that continuous C. burnetii protein synthesis is necessary to maintain the fusogenic properties and structural integrity of the replicative PV. Development of the large and spacious PV does not require Coxiella replication(Howe et al., 2003), The organism replicates to high numbers at a doubling time of 8-12 hours, despite the presence of toxic host factors(Maurin and Raoult, 1999, Norlander, 2000, Heinzen et al., 1999, Website 11, Zamboni et al., 2003, Howe et al., 2003), Genomic sequence data indicate that 21 genes encoding products that are similar to components of the Legionella pneumophila Dot/Icm type IV secretion system are located on a contiguous 35 kb region of the Coxiella chromosome. It was found that several dot/icm genes were expressed by Coxiella during host cell infection and that dot/icm gene expression preceded the formation of large replicative vacuoles. Studies suggest that a dot/icm-related secretion system could play an important role in creating the specialized vacuole that supports Coxiella replication(Howe et al., 2003),
   3. Disease Information:
      1. Acute Q fever :
         1. Incubation: The incubation period for Q fever depends on the size of the infectious dose. It is usually 2-3 weeks,(Maurin and Raoult, 1999), but incubation periods as long as 39 days are reported(Fournier et al., 1998), In one study, human volunteers who inhaled one infectious dose had an incubation period of 16 days, whereas those who were exposed to 1500 infectious doses had an incubation period of 10 days(Marrie and Raoult, 1997),
         2. Prognosis:
            Coxiella burnetii infection may present with acute or chronic clinical manifestations. However, almost 60% of Q fever cases are asymptomatic. Among the 40% of patients who are symptomatic, the majority (38% of the 40%) will experience a mild disease without the need for hospitalization. Hospitalized patients represent only 2% of infected individuals, whereas 1/10 of them (0.2%) suffer from chronic Q fever(Maurin and Raoult, 1999), Acute Q fever, if properly diagnosed and treated, has very low morbidity and mortality. Death results in only 1-2% of all cases(Website 5),
         3. Symptom Information :
            • Syndrome -- Acute Q fever as self-limited febrile illness :
              • Description: In symptomatic patients, the most frequent clinical manifestation of acute Q fever is probably a self-limited febrile illness associated with severe headaches(Maurin and Raoult, 1999, Marrie et al., 2000).
              • Symptom -- Fever :
                • Description: Fever: In acute Q fever patients, the fever may reach from 39 to 40 degrees celcius (102 to 104 degrees fahrenheit), usually remaining elevated all day. Fever typically increases to a plateau within 2 to 4 days, and then after 5 to 14 days the temperature returns rapidly to normal(Maurin and Raoult, 1999).
                • Observed:
                  88-100%(Maurin and Raoult, 1999),
              • Symptom -- Fatigue :
                • Description: Fatigue: 97-100% of patients with acute Q fever report fatigue(Maurin and Raoult, 1999). Additionally, a link between chronic fatigue syndrome and Coxiella burnetii infection has been suggested, but this remains to be confirmed(Raoult, 2002).
                • Observed:
                  97-100%(Maurin and Raoult, 1999),
              • Symptom -- Headache :
                • Description: Headache: The fever is usually accompanied by severe headaches(Maurin and Raoult, 1999).
                • Observed:
                  68-98%(Maurin and Raoult, 1999),
            • Syndrome -- Pneumonia associated with acute Q fever :
              • Description: There are three presentations of this form of the disease: atypical pneumonia, rapidly progressive pneumonia, and pneumonia as an incidental finding in a patient with febrile illness(Marrie et al., 2000). The disease is usually mild, as is typical for viral atypical pneumonia. Clinical signs are often lacking on physical examination. The most frequent finding is inspiratory crackles. Radiographic findings may include single or multiple opacities of rounded configuration, increased reticular markings, atelectasis, and pleural effusion(Maurin and Raoult, 1999).
              • Symptom -- Fever :
                • Description: Fever: Almost all patients suffering from acute Q fever pneumonia present with a fever(Maurin and Raoult, 1999, Marrie et al., 2000). The fever may reach from 39 to 40 degrees celcius (102.2 to 104 degrees fahrenheit), usually remaining elevated all day. Fever typically increases to a plateau within 2 to 4 days, and then after 5 to 14 days the temperature returns rapidly to normal. However, in untreated patients, fever may last from 5 to 57 days. Thus, acute Q fever is a cause of prolonged fever of unknown etiology. One-quarter of acute Q fever patients experience a biphasic fever. The first phase is as described above. The second phase corresponds to the reappearance of fever, usually to lower levels and intermittently, and lasts from 1 to 19 days. Fever has been reported to be of longer duration in older patients, lasting for over 14 days in 60% of patients older than 40 years and in only 29% of patients younger than 40 years(Maurin and Raoult, 1999).
                • Observed:
                  88-100%(Maurin and Raoult, 1999),
              • Symptom -- Headache :
                • Description: Headache: Acute Q fever is usually accompanied by severe headaches(Maurin and Raoult, 1999, Marrie et al., 2000).
                • Observed:
                  68-98%(Maurin and Raoult, 1999),
              • Symptom -- Chills :
                • Description: Chills(Maurin and Raoult, 1999).
                • Observed:
                  68-88%(Maurin and Raoult, 1999),
              • Symptom -- Myalgia :
                • Description: Myalgia(Maurin and Raoult, 1999).
                • Observed:
                  47-69%(Maurin and Raoult, 1999),
              • Symptom -- Sweats :
                • Description: Sweats(Maurin and Raoult, 1999).
                • Observed:
                  31-98%(Maurin and Raoult, 1999),
              • Symptom -- Cough :
                • Description: Cough(Maurin and Raoult, 1999).
                • Observed:
                  24-90%(Maurin and Raoult, 1999),
              • Symptom -- Nausea :
                • Description: Nausea(Maurin and Raoult, 1999).
                • Observed:
                  22-49%(Maurin and Raoult, 1999),
              • Symptom -- Vomiting :
                • Description: Vomiting(Maurin and Raoult, 1999).
                • Observed:
                  13-42%(Maurin and Raoult, 1999),
              • Symptom -- Chest pain :
                • Description: Chest Pain(Maurin and Raoult, 1999).
                • Observed:
                  10-45%(Maurin and Raoult, 1999),
              • Symptom -- Diarrhea :
                • Description: Diarrhea(Maurin and Raoult, 1999).
                • Observed:
                  5-22%(Maurin and Raoult, 1999),
              • Symptom -- Splemomegaly :
                • Description: Splenomegaly(Maurin and Raoult, 1999).
                • Observed:
                  5%(Maurin and Raoult, 1999),
            • Syndrome -- Q fever hepatitis :
              • Description: There are three presentations of Q fever hepatitis: (1) An infectious hepatitis-like picture, (2) Fever of unknown origin with characteristic granulomas on liver biopsy, (3) As an incidental finding in a patient with acute Q fever pneumonia(Marrie et al., 2000). Q fever hepatitis is usually only revealed by an increase in hepatic enzyme levels. Alkaline phosphatase, AST, and ALT levels are usually mildly elevated to two to three times the normal level. Q fever hepatitis is usually accompanied clinically by fever and less frequently by abdominal pain (especially in the right hypochondrium), anorexia, nausea, vomiting, and diarrhea. Progressive jaundice and palpation of a mass in the right hypochondrium have also been reported. Extensive destruction of liver tissue leading to hepatic coma and death have occasionally been reported. If liver biopsy is performed, histology typically reveals a granulomatous hepatitis, even in asymptomatic patients. Frequently, patients with hepatitis exhibit autoantibodies, including antibodies directed to smooth muscle, anticardiolipin antibodies, antiphospholipid antibodies, circulating anticoagulant, and antinuclear antibodies. The presence of circulating antibodies should be checked before a hepatic biopsy is performed, because of the risk of hemorrhage(Maurin and Raoult, 1999).
            • Syndrome -- Skin Rash associated with Q fever :
              • Description: Although Coxiella burnetii was first considered to be a rickettsial pathogen, Q fever was differentiated clinically from spotted-fever-group rickettsiosis (including Rocky Mountain spotted fever) or typhus group rickettsiosis because of the lack of cutaneous eruption. More recent clinical descriptions have emphasized the possibility of skin rash in Q fever disease, whereas spotted-fever-group rickettsiosis occasionally presents as spotless fever. The Q fever rash is nonspecific and may correspond to pink macular lesions or purpuric red papules of the trunk(Maurin and Raoult, 1999).
              • Observed:
                5-21%(Maurin and Raoult, 1999),
            • Syndrome -- Myocarditis associated with acute Q fever :
              • Description: Myocarditis is a rare but life-threatening clinical manifestation of acute Q fever. In most patients, myocarditis is revealed only by abnormalities on the electrocardiogram. Thus, it is probable that myocarditis is an underestimated clinical manifestation of Q fever disease. The most frequent electrocardiogram abnormality is T-wave change. Myocarditis may also be revealed clinically through tachycardia, hypoxemia requiring ventilatory support, and cardiac failure, which may lead to death(Maurin and Raoult, 1999).
              • Observed:
                0.5-1%(Maurin and Raoult, 1999),
            • Syndrome -- Pericarditis associated with acute Q fever :
              • Description: Pericarditis has been infrequently reported in Q fever patients, and most cases have been recorded in Spain. Since chest pain is often noted in patients suffering from Q fever, it is possible that Q fever pericarditis is underdiagnosed. Pericarditis usually occurs as a clinical manifestation of acute Q fever and may be associated with concomitant myocarditis or pleuritis. Clinical manifestations of Q fever pericarditis are not specific and most often correspond to a fever with thoracic pain. An electrocardiogram may reveal abnormalities, especially on T wave, whereas an echocardiogram may show the presence of pericardial effusion(Maurin and Raoult, 1999).
              • Observed:
                1%(Maurin and Raoult, 1999),
            • Syndrome -- Meningoencephalitis associated with acute Q fever :
              • Description: A few cases of encephalitis, meningoencephalitis, and encephalomyelitis have been reported to occur late in the course of acute Q fever. Cerebrospinal fluid examination may reveal the presence of leukocytes, composed mainly of mononuclear cells, increased protein concentration, and usually normal glucose concentration. Such clinical manifestations, however, should be differentiated from embolic manifestations in Q fever endocarditis patients. The most common residual disorder of Q fever meningitis is disturbance of vision(Maurin and Raoult, 1999).
              • Observed:
                1%(Maurin and Raoult, 1999),
         4. Treatment Information:
            • Doxycycline : Doxycycline is the preferred antibiotic in the treatment of acute Q fever(Maurin and Raoult, 1999). The starting of treatment within 3 days of illness is thought necessary for treatment to be most effective. The treatment of choice for acute Q fever is tetracycline or doxycycline for 7 to 14 days, or continued for at least 3 days after remission of fever(Madariaga et al., 2003). Doxycycline therapy is now recommended instead of tetracycline due to its improved pharmacokinetic properties and less frequent gastric intolerance. Adult dose: 200 mg, orally, twice daily for 14 days(Maurin and Raoult, 1999). Children greater than 8 years of age: 3 mg/kg/day, orally, twice daily, not to exceed 200 mg/day(Website 5).
              • Contraindicator: Doxycycline cannot be used in: children less than 8 years of age, patients with documented hypersensitivity, patients with severe hepatic dysfunction; or in pregnant women(Maurin and Raoult, 1999, Website 5).
              • Success Rate: In one study, fever duration was reduced from 3.3 days in untreated patients to 1.7 days in those receiving 100 mg of doxycycline twice a day(Maurin and Raoult, 1999).
              • Drug Resistance: In a cell culture model to mimic an acute Q fever, doxycycline was effective against 13 tested strains of Coxiella burnetii(Didier, 1993).
            • Tetracycline : A randomized study was carried out with tetracycline alone compared to placebo. Although tetracycline administered at 500 mg four times a day (q.i.d.) reduced the duration of fever by 50%, antibiotic treatment had to be started during the first 3 days of the illness to be effective. In a nonrandomized comparison of acute Q fever treatments, the mean duration of fever was 3.3 days in untreated patients, 2 days in patients treated with tetracycline at 500 mg q.i.d., and 1.7 days in patients receiving doxycycline at 100 mg twice a day (b.i.d.). Doxycycline therapy is now recommended instead of tetracycline due to its improved pharmacokinetic properties and less frequent gastric intolerance(Maurin and Raoult, 1999).
              • Complication: Gastric intolerance may be experienced with use of tetracycline(Maurin and Raoult, 1999).
              • Success Rate: In one study, a 50% reduction in fever duration was achieved(Maurin and Raoult, 1999).
              • Drug Resistance: In a cell culture model to mimic an acute Q fever, tetracycline was effective against 13 tested strains of Coxiella burnetii(Didier, 1993).
            • Fluoroquinolones : Fluoroquinolones, such as ofloxacin 200 mg three times a day or pefloxacin 400 mg twice a day for 2 to 3 weeks. Fluoroquinolones are considered to be a reliable alternative to doxycycline and have been advocated for patients with Q fever meningoencephalitis, because they penetrate the cerebrospinal fluid(Maurin and Raoult, 1999).
              • Contraindicator: All of the fluoroquinolones have been shown to cause cartilage damage in immature animals; none are FDA-approved for use in children less than 18 years of age or in pregnant or nursing women(Website 12).
              • Drug Resistance: In a cell culture model to mimic an acute Q fever, ofloxacin was effective against 12 of 13 tested strains of Coxiella burnetii(Didier, 1993).
            • Erythromycin : Erythromycin (500 mg q.i.d.) has been used successfully to treat Q fever pneumonia cases. Patients made a rapid clinical improvement and were apyretic by day 4 of antibiotic treatment. However, it is reported that erythromycin was ineffective in the treatment of severe cases of Q fever pneumonia, even with daily intravenous dosage of 4 g. Although erythromycin is currently recommended for the antibiotic treatment of atypical pneumonia, it is still unclear if such a regimen is adequate for Q fever pneumonia. Erythromycin susceptibility varies among different Coxiella burnetii strains in vitro, and such antibiotic susceptibility may correlate with discrepancies in the clinical efficiency of this drug to treat acute Q fever cases. In most patients, lack of isolation of the infecting C. burnetii strain precludes the assessment of its susceptibility to erythromycin. Thus, erythromycin should not be considered a reliable alternative for Q fever treatment. In vitro experiments have shown that clarithromycin and roxithromycin are more effective than erythromycin, but clinical trials with these newer macrolides are lacking(Maurin and Raoult, 1999).
              • Drug Resistance: In a cell culture model to mimic an acute Q fever, 7 of 13 Coxiella burnetii strains were of intermediate susceptibility to erythromycin, while the other 6 strains were resistant(Didier, 1993).
            • Doxycycline and Hydroxychloroquine : The recommended treatment for Q fever endocarditis is a combination of doxycycline and hydroxychloroquine. Rolain et al., (2003) found a correlation between serum doxycycline concentrations and decreases in levels of phase 1 Coxiella burnetii antibodies, in 24 patients with Q fever endocarditis. Patients who had a > 2-fold decrease in levels of phase 1 antibodies had serum doxycycline concentrations higher than those of the other patients (mean +/- SD, 5.29 +/- 1.75 vs. 3.14 +/- 1.40 g/mL; P = 0.003). They recommend adjusting the posology of doxycycline to achieve a serum concentration of at least 5 g/mL.The MICs found for doxycycline against C. burnetii may vary from 1 to 4 g/mL, and, thus, failures or relapses in these patients may be explained by an inappropriate serum doxycycline concentration. Thus, treatment and monitoring of patients with Q fever endocarditis should include evaluation of the antibiotic susceptibility of the isolate, when available, and measurement of serum doxycycline concentrations.Because a difference in serum doxycycline concentration can be observed after 3 months, measuring the serum doxycycline concentration after 3 months of therapy and adjusting the dosage to achieve a serum concentration of 5 g/mL it is recommended. Considering the low and erratic levels produced by the usual 200-mg dose of doxycycline, it is possible that higher doses (400 mg) may be justified in the treatment of some cases of Q fever endocarditis, especially for patients who are infected with strains with higher MICs against doxycycline(Rolain et al., 2003).
              • Contraindicator: Doxycycline cannot be used in: children less than 8 years of age, patients with documented hypersensitivity, patients with severe hepatic dysfunction; or in pregnant women(Maurin and Raoult, 1999, Website 5).
              • Success Rate: In one study, fever duration was reduced from 3.3 days in untreated patients to 1.7 days in those receiving 100 mg of doxycycline twice a day(Maurin and Raoult, 1999).
              • Drug Resistance: In a cell culture model to mimic an acute Q fever, doxycycline was effective against 13 tested strains of Coxiella burnetii(Didier, 1993).
            • Other antibiotics (Maurin and Raoult, 1999): Anecdotal reports and in vitro experiments indicate that lincomycin, cotrimoxazole, chloramphenicol, clarithromycin, and roxithromycin may be effective in the treatment of acute Q fever pneumonia(Maurin and Raoult, 1999).
      2. Chronic Q Fever :
         1. Prognosis:
            Coxiella burnetii infection may present with acute or chronic clinical manifestations. However, almost 60% of Q fever cases are asymptomatic. Among the 40% of patients who are symptomatic, the majority (38% of the 40%) will experience a mild disease without the need for hospitalization. Hospitalized patients represent only 2% of infected individuals, whereas 1/10 of them (0.2%) suffer from chronic Q fever(Maurin and Raoult, 1999), Acute Q fever, if properly diagnosed and treated, has very low morbidity and mortality. Chronic Q fever endocarditis can be very serious,(Didier, 1993), and requires long-term antibiotic therapy combined with close follow-up care by an infectious disease specialist(Maurin and Raoult, 1999, Website 5),
         2. Symptom Information :
            • Syndrome -- Chronic Q fever endocarditis :
              • Description: Endocarditis is the major clinical presentation of chronic Q fever. It accounts for 60 to 70% of all chronic Q fever cases. Q fever endocarditis represents 3% of all cases of endocarditis diagnosed in England and Wales and at least 5% in France. Although it can be spontaneously fatal when untreated, mortality from Q fever endocarditis is less than 10% when appropriate antibiotic therapy is administered. However, most clinical studies have shown relapse rates of over 50% after antibiotic therapy is withdrawn. Q fever endocarditis supervenes almost exclusively in patients with previous cardiac valve defects (over 90% of Q fever endocarditis patients). The underlying heart disease may be congenital, rheumatic, degenerative, or syphilitic. The aortic and mitral valves are mostly involved. Q fever prosthetic valve endocarditis has been increasingly reported over recent years. The male/female ratio is 75%, and most patients are older than 40 years. Immunosuppression such as is observed in organ transplant recipients, patients with cancer, lymphoma, or chronic renal insufficiency, and AIDS patients is also associated, although less frequently, with the evolution of Q fever to chronicity. This may be related, in part, to valvular damages due to chronic inflammation and cardiotoxic drug administration in this population(Maurin and Raoult, 1999). Q fever endocarditis patients usually present with symptoms suggestive of cardiac involvement including heart failure or cardiac valve dysfunction. They may also present with a less specific general disease characterized by a low-grade fever (present at the beginning of the disease in 68% of patients), often remittent and well tolerated, which may be associated with malaise, weakness, fatigue, weight loss, chills, anorexia, and night sweats. Cardiac symptoms are related to heart failure in 67% of infected patients with previous valvulopathy, dyspnea, acute pulmonary edema, angina, and palpitations. A heart valve murmur may be present but often corresponds to a previously diagnosed valvulopathy. A chest X ray may show cardiomegaly. Electrocardiography may reveal arrhythmia and ventricular hypertrophy. Cardiac vegetation is visible on the echocardiogram in only 12% of patients and is often small. Transesophageal echography is superior to transthoracic echography. Worsening valvular dysfunction is the most frequently observed abnormality(Maurin and Raoult, 1999). Peripheral manifestations of endocarditis are common. These include digital clubbing (in 37% of patients) and a purpuric rash (in 19% of patients), usually on the extremities and mucosa, which corresponds to immune complex vasculitis. Splenomegaly and hepatomegaly are frequent, especially in patients with long-term evolution of the disease. Renal involvement with microscopic haematuria is frequent and corresponds to immune complex glomerulonephritis, which may evolve to renal insufficiency. Embolic manifestations are observed in about 20% of patients and may involve the brain (with stroke) and arm or leg vessels. Whereas diagnosis of Q fever endocarditis may be missed in the early stage of the disease, symptoms progressively complement one another after several months and evolve into the more evident clinical presentation including considerable hepatomegaly, renal insufficiency, purpuric rash, and embolic manifestations, which may result in death(Maurin and Raoult, 1999).
              • Symptom -- Endocarditis-aortic valve vegetations :
                • Description: Endocarditis-aortic valve vegetations(Maurin and Raoult, 1999).
                • Observed:
                  33%(Maurin and Raoult, 1999),
              • Symptom -- Endocarditis-mitral valve vegetations :
                • Description: Endocarditis-mitral valve vegetations(Maurin and Raoult, 1999).
                • Observed:
                  50%(Maurin and Raoult, 1999),
              • Symptom -- Endocarditis-aortic and mitral valve vegetations :
                • Description: Endocarditis-aortic and mitral valve vegetations(Maurin and Raoult, 1999).
                • Observed:
                  17%(Maurin and Raoult, 1999),
              • Symptom -- Fever :
                • Description: Fever(Maurin and Raoult, 1999).
                • Observed:
                  68%(Maurin and Raoult, 1999),
              • Symptom -- Cardiac failure :
                • Description: Cardiac failure(Maurin and Raoult, 1999).
                • Observed:
                  67%(Maurin and Raoult, 1999),
              • Symptom -- Hepatomegaly :
                • Description: Hepatomegaly(Maurin and Raoult, 1999).
                • Observed:
                  56%(Maurin and Raoult, 1999),
              • Symptom -- Splenomegaly :
                • Description: Splenomegaly(Maurin and Raoult, 1999).
                • Observed:
                  55%(Maurin and Raoult, 1999),
              • Symptom -- Clubbing of digits :
                • Description: Clubbing of digits(Maurin and Raoult, 1999).
                • Observed:
                  37%(Maurin and Raoult, 1999, Marrie, 1990),
              • Symptom -- Purpuric rash :
                • Description: Purpuric rash(Maurin and Raoult, 1999).
                • Observed:
                  19%(Maurin and Raoult, 1999),
              • Symptom -- Arterial embolism :
                • Description: Arterial embolism(Maurin and Raoult, 1999).
                • Observed:
                  21%(Maurin and Raoult, 1999),
            • Syndrome -- Chronic Q fever - vascular infections :
              • Description: Coxiella burnetii vascular infection is a rare but life-threatening condition. There are 13 cases of C. burnetii vascular infection reported in the literature. Almost all patients presented with a severe inflammatory syndrome, including a highly elevated erythrocyte sedimentation rate and high levels of C-reactive protein and fibrinogen in serum. A total of 70% were febrile at presentation. Weight loss and abdominal pain were frequently reported. In contrast, hyperleukocytosis, thrombocytopenia, and elevated hepatic enzyme levels were less frequently observed than in Q fever endocarditis patients. No specific symptoms of vascular involvement were found. Since the clinical manifestations of C. burnetii vascular infection are nonspecific, the disease may be recognized by physicians only if C. burnetii serology is performed systematically, especially in patients with aneurysm or vascular graft with unexplained fever, abdominal pain, or weight loss(Maurin and Raoult, 1999).
            • Syndrome -- Chronic Q fever - osteoarticular infections :
              • Description: Three types of Coxiella burnetii osteoarticular infections, including osteomyelitis, osteoarthritis, and aortic graft infection with contiguous spinal osteomyelitis, have been reported. C. burnetii infection of bones has been found more frequently in children suffering from coxitis or spondylodiskitis and is not associated with specific host factors in this population. Bone infections have also been reported in adults who are immunocompromised or have a joint prosthesis(Maurin and Raoult, 1999).
            • Syndrome -- Chronic Q fever - hepatitis :
              • Description: Although chronic Q fever involvement of the liver is frequently associated with endocarditis, a few cases of chronic hepatitis without Q fever endocarditis have been described(Maurin and Raoult, 1999).
            • Syndrome -- Chronic Q fever - pulmonary infections :
              • Description: Chronic lung involvement is rare and may correspond to pulmonary fibrosis or pseudotumors. Pneumonic fibrosis has been reported as a complication of chronic Q fever in the former USSR(Maurin and Raoult, 1999).
            • Syndrome -- Chronic fatigue syndrome :
              • Description: Chronic fatigue syndrome has been reported infrequently as a possible clinical manifestation following acute Q fever(Maurin and Raoult, 1999, Raoult, 2002). One report found that in a follow-up of patients with Q fever, fatigue and idiopathic chronic fatigue were found in nearly 65% of patients, twice as frequently as in controls. Whether this fatigue is psychological or directly caused by the bacterium remains to be determined(Raoult, 2002).
         3. Treatment Information:
            • Doxycycline-chloroquine : A doxycycline-chloroquine combination consisting of doxycycline 100 mg twice a day and chloroquine 200 mg three times a day for at least 18 months is a currently recommended therapy to treat Q fever endocarditis(Maurin and Raoult, 1999). Chloroquine increases the intracellular pH level from about 4.8 to 5.7, which increases the activity of doxycycline to bactericidal(Kagawa et al., 2003). Relapse upon withdrawal of antibiotic therapy is very problematic in the treatment of Q fever endocarditis, thus necessitating the need for extended treatment periods(Maurin and Raoult, 1999, Didier, 1993). Clinical and biological evaluation should be performed on a monthly basis during antibiotic therapy, including blood cell numeration, measurement of hepatic enzyme levels in serum and creatinine levels in serum, and Q fever serology. Lymphocyte typing may also be useful because as inversion of the T4/T8 lymphocytic ratio was shown to be an indicator of relapse. Upregulation of IL-10 gene transcription by PBMC from Q fever endocarditis patients has been demonstrated, and the presence of IL-10 in PBMC supernatants has also been proposed as a marker of disease relapse. An echocardiogram should be performed every 3 months. Chloroquine levels in serum should be monitored to ensure that they are maintained at of 1 +/- 0.2 mg/liter. The chloroquine dose often has to be adjusted because of intolerance. In most patients, chloroquine was administered at 200 mg three times a day for the first 3 to 6 months and then decreased to 200 mg twice a day or even once a day(Maurin and Raoult, 1999).
              • Contraindicator: Doxycycline cannot be used in: children less than 8 years of age, patients with documented hypersensitivity, patients with severe hepatic dysfunction; or in pregnant women(Maurin and Raoult, 1999, Website 5).
              • Complication: Disease relapse is possible following cessation of doxycycline-chloroquine therapy. However, treatment for 18 months was shown to prevent most relapses. Chloroquine used at therapeutic dosages may have some deleterious effects, including the risk of retinopathy, necessitating a regular ophthalmologic examination. Chloroquine levels in serum should be monitored to ensure that they are maintained at a concentration of 1 +/- 0.2 mg/liter(Maurin and Raoult, 1999).
              • Success Rate: In one study, the use of doxycycline-chloroquine to treat chronic Q fever endocarditis decreased the death rate to less than 5%. In addition, only 14.3% of the patients experienced disease relapse, a significantly lower value that the relapse occurrences associated with other treatments(Maurin and Raoult, 1999).
            • Doxycycline-ofloxacin : A doxycycline-fluoroquinolone combination consisting of doxycycline 100 mg twice a day and ofloxacin 200 mg three times a day for at least three years is recommended for patients that cannot receive the doxycycline-chloroquine combination(Maurin and Raoult, 1999). Relapse upon withdrawal of antibiotic therapy is very problematic in the treatment of Q fever endocarditis, thus necessitating the need for extended treatment periods(Maurin and Raoult, 1999, Didier, 1993). Clinical and biological evaluation should be performed on a monthly basis during antibiotic therapy, including blood cell numeration, measurement of hepatic enzyme levels in serum and creatinine levels in serum, and Q fever serology. Lymphocyte typing may also be useful because as inversion of the T4/T8 lymphocytic ratio was shown to be an indicator of relapse. Upregulation of IL-10 gene transcription by PBMC from Q fever endocarditis patients has been demonstrated, and the presence of IL-10 in PBMC supernatants has also been proposed as a marker of disease relapse. An echocardiogram should be performed every 3 months(Maurin and Raoult, 1999).
              • Contraindicator: Doxycycline cannot be used in: children less than 8 years of age, patients with documented hypersensitivity, patients with severe hepatic dysfunction; or in pregnant women(Maurin and Raoult, 1999, Website 5). All of the fluoroquinolones have been shown to cause cartilage damage in immature animals; none are FDA-approved for use in children less than 18 years of age or in pregnant or nursing women(Website 12).
              • Complication: Use of doxycycline can lead to hypersensitivity reactions and/or severe hepatic dysfunction. It can also be associated with gastric intolerance(Maurin and Raoult, 1999, Website 5).
              • Success Rate: In one study, the use of the doxycycline-fluoroquinolone combination therapy for the treatment of chronic Q fever endocarditis reduced the mortality rate to 6%. However, studies have shown disease relapse in 50-64.3% of treated patients following cessation of treatment(Maurin and Raoult, 1999).
            • Cardiac valve replacement : Valve replacement has been proposed in addition to antibiotic treatment in Q fever endocarditis. Cardiac surgery was proposed mainly as a result of hemodynamic failure. In such cases, the presence of Coxiella burnetii in removed cardiac tissue should be systematically assessed by both culture and PCR. Since Q fever endocarditis is a disseminated disease, surgery should be reserved for patients with hemodynamic complications and should be combined with an antibiotic therapy to prevent relapse. In patients undergoing valve replacement, antibiotics are also needed, because of the risk of infection of the prosthetic valve from a dormant site, including from the other cardiac valves. The increasing use of cardiac surgery for valve replacement over recent years has led to an increase in the number of prosthetic valve endocarditis cases reported worldwide, especially endocarditis due to Staphylococcus species. Q fever prosthetic valve endocarditis has also been increasingly reported(Maurin and Raoult, 1999).
              • Contraindicator: Since Q fever endocarditis is a disseminated disease, surgery should be reserved for patients with hemodynamic complications(Maurin and Raoult, 1999).
              • Complication: Following cardiac valve replacement, there is a risk of infection of the prosthetic valve from a dormant site, including from the other cardiac valves. Antibiotic therapy should therefore be used prior to and concurrent with surgery. In addition, although surgery may be necessary to resolve hemodynamic complication, it does not necessarily mean a complete cure. Q fever prosthetic valve endocarditis has been increasingly reported(Maurin and Raoult, 1999).
   4. Prevention:
      1. Q-Vax
         • Description: Q-Vax is a vaccine consisting of formalin inactivated suspension of phase I Henzerling strain Coxiella burnetii which contains LPS-protein complex antigens(Maurin and Raoult, 1999, Waag et al., 2002), It was licensed for use in Australia in March 1989, but is not available in the United States(Maurin and Raoult, 1999, Website 3, Waag et al., 2002), The vaccine is generally administered as a single subcutaneous 30 microgram dose(Waag et al., 2002, Ackland et al., 1994),
         • Efficacy:
           • Rate: A retrospective cohort survey of all employees at three South Australian abattoirs was conducted to determine the incidence of Q fever among Q-Vax vaccinated and unvaccinated employees during the period 1985 to 1990. There were two cases of Q fever among 2555 vaccinated employees of the three abattoirs, compared with 55 cases among 1365 unvaccinated employees. The two Q fever cases in vaccinated employees were within a few days of vaccination, before immunity had developed, and represented a coincidence of natural infection and vaccination. Protective efficacy was 100%, even with a batch of Q-Vax containing 20 micrograms/dose rather than the standard dose of 30 micrograms/dose(Ackland et al., 1994).
           • Duration: In the Southern Australia study, the duration of Q-Vax protection was found to be over 5 years(Waag et al., 2002, Ackland et al., 1994).
         • Contraindicator: To prevent severe postvaccination reactions (including local erythema, induration, granulomas, sterile abscesses, and systemic reactions) Q-Vax should not be used in individuals previously exposed to Coxiella burnetii. Ideally, both cellular and humoral immune responses to C. burnetii should be assessed prior to vaccination. Skin and lymphocyte proliferation tests have been reported to be more predictive of postvaccination adverse effects than is serology(Maurin and Raoult, 1999),
         • Complication: Severe post-vaccination reactions are possible if Q-Vax is given to individuals with prior exposure to Coxiella burnetii. A skin test and a lymphocyte proliferation test should be performed prior to vaccination to assess humoral and cellular immune responses. Additionally, decreased lymphocyte responsiveness to mitogens, immunopathological changes including hepatosplenomegaly, and death have been reported in mice receiving this vaccine(Maurin and Raoult, 1999),
      1. CMR Vaccine(Maurin and Raoult, 1999, Waag et al., 2002)
         • Description: A chloroform:methanol residue (CMR) Q fever vaccine was developed at the Rocky Mountain Laboratories in the late 1970s. However, this vaccine has not been extensively tested in humans. A 2002 study involving cynomolgus monkeys (as well as other studies in non-primate animals) showed that CMR is immunogenic and gave protection against Q fever equivalent Q-Vax(Waag et al., 2002),
      1. Chemovaccine(Maurin and Raoult, 1999)
         • Description: A Q fever chemovaccine (trichloroacetic acid-extracted antigen from phase I C. burnetii Nine Mile strain) was evaluated in agricultural workers in Central Slovakia between 1977 and 1978 and in laboratory personnel (State Veterinary Institute) in East Slovakia and workers of a cotton-processing plant in Moravia in 1980. The immunogenicity of the vaccine was shown by seroconversion 5 weeks after vaccination in 393 of 714 patients (55%) receiving a single dose of vaccine and even more frequently (74.4%) in those receiving two doses. The protective effect of the vaccine was not evaluated(Maurin and Raoult, 1999),
         • Complication: Local reactions of minor severity and systemic reactions (flu-like symptoms) occurred in 39.6 and 4.3% of 714 vaccinated persons, respectively, although reactogenicity was more frequent in previously infected individuals(Maurin and Raoult, 1999),
      1. Preventative measures
         • Description: Educate the public on sources of infection; appropriately dispose of placentas, birth products, fetal membranes, and aborted fetuses at facilities housing sheep and goats; restrict access to barns and laboratories used in housing potentially infected animals; use only pasteurized milk and milk products; use appropriate procedures for bagging, autoclaving, and washing of laboratory clothing; quarantine imported animals; ensure that holding facilities for sheep are located away from populated animals and routinely test the animals for antibodies to Coxiella burnetii; counsel persons at highest risk for developing chronic Q fever, especially persons with pre-existing cardiac valve disease or individuals with vascular grafts(Website 3),

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1. Lab Biosafety Containment:
   
2. Environmental Stability:
   
3. Methods of Enviromental Disinfection:
   
4. Use in Rodent Research:
   
5. Comparison between Human & Lab Animal:
   1. Infectious Dose:
      
   2. Excretion & Transmission:
      
6. Documented Human Laboratory Exposures:
   
7. Considerations with Animal Housing, Handling, and Disposals:
   1. Animal Housing and Handling
      
   2. Tissue and Carcass Disposal
      

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Bernard et al., 1982: Bernard KW, Parham GL, Winkler WG, Helmick CG. Q fever control measures: recommendations for research facilities using sheep. Infection Control. 1982; 3(6); 461-465. [PubMed: 6924645].

Brouqui et al., 1994: Brouqui P, Dumler JS, Raoult D. Immunohistologic demonstration of Coxiella burnetii in the valves of patients with Q fever endocarditis. The American Journal of Medicine. 1994; 97; 451-458. [PubMed: 7977434].

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Komiya et al., 2003: Komiya T, Sadamasu K, Kang MI, Tsuboshima S, Fukushi H, Hirai K. Seroprevalence of Coxiella burnetii infections among cats in different living environments. Journal of Veterinary Medical Science. 2003; 65(9); 1047-1048. [PubMed: 14532705].

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Seshadri et al., 2003: Seshadri R, Paulsen IT, Eisen JA, Read TD, Nelson KE, Nelson WC, Ward NL, Tettelin H, Davidsen TM, Beanan MJ, Deboy RT, Daugherty SC, Brinkac LM, Madupu R, Dodson RJ, Khouri HM, Lee KH, Carty HA, Scanlan D, Heinzen RA, Thompson HA, Samuel JE, Fraser CM, Heidelberg JF. Complete genome sequence of the Q-fever pathogen Coxiella burnetii. Proc Natl Acad Sci (U S A).. 2003; 100(9); 5455-5460. [PubMed: 12704232].

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Website 1: Coxiella burnetii: Material Safety Data Sheet (MSDS)

Website 10: Coxiella burnetii plasmid QpDV, complete sequence

Website 11: Rickettsiae

Website 12: Topics in drug therapy; Sept. 2002

Website 13: Rickettsial agents - Coxiella burnetii

Website 14: COXIELLA BURNETII (Q FEVER) IgM ELISA TEST

Website 16: COXIELLA BURNETII (Q FEVER) IFA SLIDES

Website 17: DIP-S-TICKS Q FEVER (Coxiella burnetii)

Website 18: Coxiella burnetii RSA 493 plasmid pQpH1, complete sequence

Website 2: Coxiella burnetii as a Bioterrorist Agent

Website 3: Q Fever

Website 4: Biological Warfare Defense Information Sheet: Q Fever

Website 5: Q fever

Website 6: Coxiella burnetii, NCBI Taxonomy Browser

Website 8: NCBI Coxiella burnetii genome

Website 9: Coxiella burnetii plasmid QpH1, complete sequence

Willems et al., 1998: Willems H, Jager C, Baljer G. Physical and genetic map of the obligate intracellular bacterium Coxiella burnetii. Journal of Bacteriology. 1998; 180(15); 3816-3822. [PubMed: 9683477].

Zamboni et al., 2003: Zamboni DS, McGrath S, Rabinovitch M, Roy CR. Coxiella burnetii express type IV secretion system proteins that function similarly to components of the Legionella pneumophila Dot/Icm system. Molecular Microbiology. 2003; 49(4); 965-976. [PubMed: 12890021].

 

PathInfo: Randy Vines, Krista Morris

HazARD: Rachel Liepman (for the section of Lab Animal Pathobiology & Management)

PHIDIAS: Yongqun "Oliver" He

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