APPENDIX 2

Coxiella burnetii Common Human Exposure Routes: • Inhalation of aerosols or contaminated dusts con- Disease Agent: taining air-borne bacteria derived from infected • Coxiella burnetii ruminants or their products. A single inhaled organ- ism may produce clinical illness. Disease Agent Characteristics: • Bacteria are shed in milk, urine, and feces of infected animals. High numbers of organisms in the amniotic • Small, Gram-negative, pleomorphic coccoba- fluids and placenta during birthing (e.g., 109 cillus; obligate intracellular bacterium that lives in bacteria/g placenta) macrophages • Contact with contaminated wool • Order: Rickettsiales; Family: Rickettsiaceae • Ingestion of unpasteurized contaminated milk or • Size: 0.5-0.8 mm ¥ 1.2-3 mm meat • Nucleic acid: Rickettsial genomes are among the • Ideal for aerosol dissemination smallest of bacteria. Coxiella is approximately 1600 kb. Likelihood of Secondary Transmission: • Physicochemical properties: Resistant to heat, low or high pH, 0.5% sodium hypochlorite, UV irradiation, • Extremely rare and environmental conditions, such as desiccation, • Has been described in only a few cases involving drying, and sunlight, because of the presence of a patients with pneumonia spore stage. It can survive for 7-10 months on wool at 15-20°C, for more than 1 month on fresh meat in cold At-Risk Populations: storage, and for 40 months in skim milk at room tem- • Farmers, veterinarians, or those who handle poten- perature. It can be isolated from infected tissues stored tially infected livestock, especially animals giving in formaldehyde. birth • The microorganism exists in two antigenic forms: • A threat as a bioterrorist weapon for susceptible phase I and phase II. Phase I is highly infectious, populations whereas phase II is sporelike, metabolically dormant, and avirulent. Vector and Reservoir Involved:

Disease Name: • Greater than 40 tick species are involved in transmis- sion among domestic animals and are considered to • Q fever be the organism’s primary vector; tick bites are rarely involved in transmission to humans. Priority Level: • Reservoirs for human infection include domesticated ruminants, primarily cattle, sheep, and goats. • Scientific/Epidemiologic evidence regarding blood safety: Very low Blood Phase: • Public perception and/or regulatory concern regard- • Bacteremia documented during both acute and ing blood safety: Absent chronic infections, with and without symptoms. • Public concern regarding disease agent: Absent • The organism replicates in macrophages. This could result in eventual cell lysis and the dissemination of Background: free bacteria in plasma.

• Described in 1935 by E. H. Derrick in abattoir workers Survival/Persistence in Blood Products: in Australia as a disease of unknown origin and, there- fore, termed “query fever.” • No information on storage stability under blood bank • Isolated in 1937 by Burnet and Freeman who identi- conditions fied the organism as a Rickettsia species. Transmission by Blood Transfusion: • Cox and Davis isolated the pathogen from ticks in Montana in 1938 and described its transmission. The • A single case of transmission from blood transfusion agent was then officially named Coxiella burnetii the has been described. The donor and the recipient both same year. showed serological evidence of C. burnetti infection, • No longer regarded as closely related to Rickettsia and the clinical symptoms and their time courses species were compatible with the diagnosis of Q fever. • Classified (Category B) as bioterrorism agent by the • Also reported to have been transmitted by bone CDC. marrow transplantation

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• Increased antibody prevalence in drug users, HIV- Agent-Specific Screening Question(s): infected and dialysis patients further supports the • No specific question is in use. possibility of transmission by blood. • Not indicated because transfusion transmission is Cases/Frequency in Population: very infrequent, and incidence of infection in the population is very low. • Fewer than 30 cases reported annually from 1978- • No sensitive or specific question is feasible. 1986 • Under circumstances of a bioterrorism threat, the • Worldwide distribution except Antarctica and New need for and potential effectiveness of specific donor- Zealand screening questions would need to be addressed.

Incubation Period: Laboratory Test(s) Available:

• 20 days (range: 14-39 days) • No FDA-licensed blood donor screening test exists. • Available tests include antibody testing (IgM/IgG) by Likelihood of Clinical Disease: complement fixation, indirect immunofluorescence, • 60% of initial infections are asymptomatic. and EIA. Indirect immunofluorescence is sensitive and specific and is the method of choice. Primary Disease Symptoms: ᭺ The antibody titer is higher to phase II antigen than to phase I antigen in acute disease, whereas • Humans are the only species that exhibit illness as a the reverse occurs in chronic disease. result of infection. • NAT and immunohistochemical staining are addi- • Acute disease is characterized by high fever (usually tional diagnostic tools. >40°C) and headache (usually retro-orbital). The fever lasts approximately 7-14 days. Other signs and symp- Currently Recommended Donor Deferral Period: toms include hallucinations, diarrhea, weight loss, • No FDA Guidance or AABB Standard exists. facial pain, and speech impairment. A rash is rarely • Prudent practice would be to defer donor until signs observed in Q fever, in contrast to other rickettsial and symptoms are gone and a course of treatment is infections. completed. • Pneumonia or hepatitis in 30-50% of infections, depending on route of exposure (i.e., inhalation or Impact on Blood Availability: ingestion) • Infrequently causes endocarditis, pericarditis, myo- • Agent-specific screening question(s): Not applicable; carditis, or meningoencephalitis in response to a bioterrorism threat, impact of a local deferral would be significant. Severity of Clinical Disease: • Laboratory test(s) available: Not applicable

• May progress to chronicity in approximately 1% of Impact on Blood Safety: those infected if untreated, in which case mortality • Agent-specific screening question(s): Not applicable; increases. Chronic disease is defined as Q fever lasting unknown impact in response to a bioterrorism threat >6 months. • Laboratory test(s) available: Not applicable • Predominantly occurs in individuals with underlying valvular heart disease, vascular aneurysms, or vascu- Leukoreduction Efficacy: lar grafts manifesting primarily as culture-negative endocarditis • May have efficacy because organism is an obligate intracellular bacterium in monocytes/macrophages Mortality: Pathogen Reduction Efficacy for Plasma Derivatives: • 1-2% in acute infection • Unknown, but the bacterium is highly resistant to • Approximately 65% in untreated chronic infection heat and chemical/physical disinfection. Chronic Carriage: Other Prevention Measures: • Approximately 1% • Vaccine is available in some parts of the world Treatment Available/Efficacious: (formalin-inactivated phase I organisms), and its use is recommended for exposed or high-risk individuals • Doxycycline (acute) and doxycycline and hydroxy- (livestock handlers, abattoir workers, veterinarians, chloroquine (chronic illness) and laboratory workers) who do not have immunity.

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• Adverse effects when vaccine administered in previ- 4. Centers for Disease Control and Prevention. Q fever— ously infected individuals California, Georgia, Pennsylvania, and Tennessee, • In the US, investigational vaccines are available. 2000-2001. Morb Mortal Wkly Rep MMWR 2002;51: 924-7. Suggested Reading: 5. Centers for Disease Control and Prevention. Q fever— 1. Anonymous. 1977. Comment on Q fever transmitted California. Morb Mortal Wkly Rep MMWR 1977;26: by blood transfusion—Can Dis Weekly Rep 3:210 86-7. (Editorial). 6. Christie AB. Q fever. In: Christie AB. Infectious dis- 2. Bossi P, Tegnell A, Baka A, Van Loock F, Hendriks J, eases, epidemiology and clinical practice. Edinburgh: Werner A, Maidhof H, Gouvras G; Task Force on Bio- Churchill Livingstone; 1974. p. 876-91. logical and Chemical Agent Threats, Public Health 7. Maurin M, Raoult D. Q Fever. Clin Microbiol Rev 1999; Directorate, European Commission, Luxembourg. 12:518-53. Bichat Guidelines for the clinical management of Q 8. Musso D, Raoult D. Coxiella burnetii blood cultures fever and bioterrorism-related Q fever. Euro Surveill from acute and chronic Q fever patients. J Clin Micro- 2004; 9:1-5. [cited 2009 May]. Available from: http:// biol. 1995;33:3129-32. www.eurosurveillance.org/ViewArticle.aspx? 9. Walker DH, Raoult D, Dumler JS, Marrie T. Rickettsial ArticleId=499 diseases. In. Kasper DL, Fauci AS, Longo DL, Braun- 3. Byrne, WR. Q Fever. In: Sidell FR, Takafugi ET, Franz wald E, Hauser SL, Jameson JL, editors, Harrison’s DR, editors. Medical aspects of chemical and bio- principles of internal medicine, 16th ed. New York: logical warfare, Chapter 26. Washington DC: TMM McGraw Hill; 2005. p. 999-1008. Publications; 1997. p. 523-37.

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