APPENDIX 2

Brucella Species percutaneous needle stick) or splash (mucous mem- branes or conjunctiva) Disease Agent: Likelihood of Secondary Transmission: • abortus () • Human-to-human transmission is extremely rare. • B. melitensis () Sexual, transplacental, and breast-feeding transmis- • B. canis () sions have been described. A few transfusion- • B. suis (swine) transmitted infections and one case of transmission Disease Agent Characteristics: by transplantation have been reported.

• Gram-negative coccobacillus, aerobic, nonmotile, At-Risk Populations: nonspore-forming, facultatively intracellular bacte- • Individuals who live in countries that do not have rium effective public health and animal control measures • Order: Rhizobiales; Family: or those who travel to or import unpasteurized dairy • Species known to cause human disease: B. abortus, products from these areas B. melitensis, B. canis, and B. suis • Occupational risk for farmers, , abattoir • Size: 0.6-1.5 mm ¥ 0.5-0.7 mm workers, and laboratory personnel • Nucleic acid: The genomes of Brucella species • A threat as a bioterrorist weapon for susceptible range from 3100-3300 kb of DNA in two circular populations chromosomes. Vector and Reservoir Involved: Disease Name:

• • Reservoir is infected animals.

Priority Level: Blood Phase:

• Scientific/Epidemiologic evidence regarding blood • Bacteremia develops within 1-3 weeks of exposure if safety: Very low in North America and low in endemic the host immune system cannot control the infection. areas • Hematogenous dissemination is followed by localiza- • Public perception and/or regulatory concern regard- tion of the in the , , and bone ing blood safety: Absent marrow where granulomas develop. Intermittent or • Public concern regarding disease agent: Low persistent bacteremia is seen in clinical cases.

Background: Survival/Persistence in Blood Products:

• In 1887, a British Army physician, David Bruce, iso- • Unknown based on the lack of studies lated the organism from the of five patients • Likely to be some survival, based on cases of probable with fatal cases on Malta. The organism bears his transfusion-transmitted brucellosis: however, dura- name. tion is unknown • The disease gets its colloquial names from both its Transmission by Blood Transfusion: course (undulant fever) and location (Malta fever, Crimean fever). • A few probable cases of transmission by blood trans- • B. melitensis is thought to be the most virulent and fusion have been reported worldwide. causes the most severe and acute cases of brucellosis. • A case report from Turkey strongly suggests transmis- This species is also the most prevalent worldwide. sion of brucellosis by bone marrow transplantation. • Classified (Category B) as bioterrorism agent by the Cases/Frequency in Population: CDC. • The incidence in the US is approximately 200 Common Human Exposure Routes: reported cases per year. In Texas and California, the • Gastrointestinal tract: Usually by ingestion of unpas- epidemiology has changed from disease associated teurized dairy products (meat products have a low with exposure to cattle to one linked to consumption bacterial load) of unpasteurized milk products imported from • Respiratory tract: Inhalation of infectious aerosols Mexico. (e.g., abattoir personnel, farmers) • Brucellosis is the most common zoonotic infection • Direct contact with infected animals or their secre- worldwide. Endemic areas include the Mediterranean tions (milk, urine, blood, carcasses, products of Basin (Portugal, Spain, Southern France, Italy, Greece, conception, etc.) through breaks in the skin (e.g., Turkey, North Africa), South and Central America,

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Eastern Europe, Asia, Africa, the Caribbean, and the Laboratory Test(s) Available: Middle East. • No FDA-licensed blood donor screening test exists. Incubation Period: • Direct detection: Brucella species are recovered from • Usually 2-4 weeks (range: 1-8 weeks and sometimes blood, bone marrow, or other tissues. Isolation rate even longer) from bone marrow is higher than from blood. • NAT assays may be useful. Likelihood of Clinical Disease: • Serology: Serum agglutination test (SAT), which tests for anti-O-polysaccharide antibody, is widely used. • Infection without clinical disease is possible. B. This is complicated by antigenic cross-reactivity with melitensis family studies suggest the clinical attack other Gram-negative bacteria, such as Yersinia rate is around 50%. enterocolitica. Primary Disease Symptoms: • EIAs for the detection of IgG and IgM antibodies have also been used. • Nonspecific symptoms, such as fever, malaise, sweats • Other symptoms: arthralgias, anorexia, headache, Currently Recommended Donor Deferral Period: and back pain. An “undulant” fever pattern may be observed. Mild lymphadenopathy, splenomegaly, or • No FDA Guidance or AABB Standard exists. hepatomegaly may also be observed. • The Council of Europe guidelines recommend defer- • Brucellosis is a systemic infection in which any organ ral for at least 2 years following full recovery. However, or system of the body can be involved. the deferral period may be waived when the donation is used exclusively for plasma fractionation. Severity of Clinical Disease: Impact on Blood Availability: • More severe cases involve the central nervous system (e.g., meningitis, encephalitis) and the cardiovascular • Agent-specific screening question(s): Not applicable system (e.g., endocarditis, pericarditis). Abscess for- in low incidence areas. In response to a bioterrorism mation can occur in the brain, liver, spleen, or threat, impact of a local deferral would be significant. elsewhere. • Laboratory test(s): Not applicable in low-incidence Mortality: areas.

• Low mortality rate. Endocarditis accounts for the Impact on Blood Safety: majority of deaths. • Agent-specific screening question(s): Not applicable Chronic Carriage: in low-incidence areas; unknown impact in response • Chronic infection (>12 months) may occur but it is to a bioterrorism threat rare. It consists of persistent deep foci of infection, • Laboratory test(s): Not applicable in low-incidence such as suppurative lesions in the bone, joints, liver, areas. spleen, or kidneys. This form is also characterized by Leukoreduction Efficacy: persistently high titers of IgG antibodies in the serum. • Relapses are not uncommon (may occur in 10% of • Unknown the cases) within 3-6 months after discontinuing treatment. Pathogen Reduction Efficacy for Plasma Derivatives:

Treatment Available/Efficacious: • Specific data indicate that the multiple steps in the fractionation process are robust and capable of inac- • A combination antibiotic therapy (e.g., tivating and/or removing bacteria at concentrations and rifampin or an aminoglycoside) is recommended that may be present in plasma. to treat and prevent relapse of infection. • Complications, such as meningitis and endocarditis, Other Prevention Measures: are treated with longer courses of doxycycline in com- bination with other drugs. • Endemic regions: education of high-risk population and implementation of animal control measures Agent-Specific Screening Question(s): • Effective attenuated live bacterial vaccines exist for B. • No specific question is in use. abortus and B. melitensis for nonhuman use. No safe • Not indicated in countries with a low incidence of effective vaccine has been developed to immunize disease humans against brucellosis.

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Suggested Reading: transfusion. [Case Reports, Letter]. J Hosp Infect 2001; 49:151-2. 1. Akcakus M, Esel D, Cetin N, Kisaarslan AP,Kurtog˘lu S. 6. Economidou J, Kalafatas P,Vatopoulou T., Brucellosis in blood cultures of two newborns in two thalassemic patients infected from the same due to exchange transfusion. Turk J Pediatr 2005; donor. Acta Haematol 1976;55:244-9. 47:272-4. 7. Ertem M, Kurekci AE, Aysev D, Unal E, Ikinciog˘ullari 2. Al-Kharfy TM, Neonatal brucellosis and blood A. Brucellosis transmitted by bone marrow transplan- transfusion: case report and review of the literature. tation. Bone Marrow Transplant 2000;26:225-6. Ann Trop Paediatr 2001;21:349-52. 8. European Directorate for the Quality of Medicine and 3. Centers for Disease Control and Prevention. Brucel- HealthCare (EDQM). Guide to the preparation, use losis. In: Case definitions for infectious conditions and quality assurance of blood components, 14th ed. under public health surveillance. Morb Mortal Wkly Council of Europe Publishing; 2008. Rep MMWR 1997;46(RR10):8-9. 9. Pappas G, Papadimitriou P, Akritidis N, Christou L, 4. Centers for Disease Control and Prevention. Sus- Tsianos EV.The new global map of human brucellosis. pected brucellosis case prompts investigation of pos- Lancet Infect Dis 2006;6:91-9. sible bioterrorism related activity—New Hampshire 10. Young E., Brucella Species. In Mandell G, Bennett J, and Massachusetts, 1999. Morb Mortal Wkly Rep Dolin R, editors. Principles and practice of infectious MMWR 2000;49;509-12. diseases, 6th ed. Philadelphia: Elsevier-Churchill 5. Doganay M, Aygen B, Esel D. Brucellosis due to blood Livingstone; 2005. p. 2386-93.

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