Bartonella Species • These Organisms Cause Intraerythrocytic Bacteremia, That Can Be Chronic Or Relapsing, So Concerns Have Been Raised About Transfusion Transmission

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Bartonella Species • These organisms cause intraerythrocytic bacteremia, that can be chronic or relapsing, so concerns have been raised about transfusion transmission. Disease Agents:  Infections with B. bacilliformis and B. quintana occur • Bartonella henselae in populations unlikely to be qualifed blood donors. • Bartonella quintana The former is geographically restricted to the Andes • Bartonella bacilliformis mountains and is associated with signifcant acute and chronic morbidity, while infections with the latter Disease Agent Characteristics: occur primarily in conditions of poor sanitation and • Gram-negative bacillus or coccobacillus, aerobic, nonmo- hygiene, especially among the homeless, and immune tile, nonspore-forming, facultative intracellular bacterium compromised persons. • Order: Rhizobiales; Family: Bartonellaceae  In contrast, B. henselae is a common human pa- • Size: 0.3-0.6 × 0.3-1.0 mm thogen. • Nucleic acid: Approximately 1.6-2 × 106 base pairs of DNA Common Human Exposure Routes: Disease Names: • B. henselae is commonly transmitted to humans by the bite Bartonella henselae or saliva-contaminated scratch of cats that are the natural reservoir for the bacteria. • Cat scratch disease in normal hosts • B. bacilliformis and B. quintana are vector-borne. Their non- • Bacillary angiomatosis in immune compromised hosts and human reservoirs are not yet identifed. bacillary peliosis are vasculo-proliferative manifestations of infection in immune compromised hosts Likelihood of Secondary Transmission:

Bartonella quintana • Unlikely

• Trench fever under conditions of poor sanitation and hy- At-Risk Populations: giene • Bacillary angiomatosis in immune compromised hosts • Persons of all ages are at risk from B. henselae, but recog- nized infections primarily occur in children following rough Bartonella bacilliformis play with cats. • Oroya fever • Immunocompromised persons are more likely to have • Verruca peruana complications. • Carrion‘s disease Vector and Reservoir Involved: Priority Level: • Chronically infected cats are the reservoir for B. henselae. • Scientific/Epidemiologic evidence regarding blood safety:  Recent evidence suggests exposure to infected fleas Theoretical and ticks may also play a role in transmission to • Public perception and/or regulatory concern regarding humans, but is controversial. The cat fea is the primary blood safety: Absent vector for cat-to-cat transmission. • Public concern regarding disease agent: Very low  Ixodes ticks may serve as B. henselae vectors, based on amplifcation of DNA from ticks, but replication of the Background: organism and actual transmission by fleas or ticks to • In 1909, A L Barton described organisms that adhered to humans has not been proven. RBCs. • B. bacilliformis and B. quintana are vector-borne by sand • The name Bartonella bacilliformis was used for the only fies and body lice respectively. Their non-human reservoirs member of the group identified before 1993. are not yet identifed. • Several other species of Bartonella, most importantly hense- Blood Phase: lae and quintana, commonly infect humans, and at present, B. henselae represents by far the most common infecting • Intraerthrocytic bartonellae can be identifed by a variety of agent in the US and is of greatest concern. methods in natural infections. • They are primarily infections of non-human animals, with • B. henselae is found in endothelial cells and RBCs. Infected humans as incidental hosts. CD34+ hematopoietic progenitor cells give rise to infected • A variety of bartonellae from other species have been RBCs in vitro and this, rather than attachment and invasion described infecting humans at the individual case report of mature RBCs, may be the source of intraerythrocytic level. bacteria. • Stable in the population • Occult bacteremia sometimes occurs.

February 2012: update to TRANSFUSION 2009;49(Suppl):192-93S 1 Survival/Persistence in Blood Products: with macrolide antibiotics (erythromycin, azithromycin, or clarithromycin) or doxycycline. • A spiking study suggests that B. henselae added to RBCs can be recovered on solid media through 35 days of storage Agent-Specific Screening Question(s): at 4°C. • No specific question is in use. Transmission by Blood Transfusion: • Not indicated because transfusion transmission has not been demonstrated • Theoretical • No sensitive or specific question is feasible. • Survival in stored RBCs and unconfrmed transmission by organ transplantation have been cited to raise concerns Laboratory Test(s) Available: about transfusion transmission. • No FDA-licensed blood donor screening test exists. Cases/Frequency in Population: • Unlicensed IFA and PCR available • In immunocompetent at-risk persons, diagnosis of the agent • 22,000 cases of cat scratch disease per year estimated in is enhanced by combining PCR with pre-enrichment culture. the US • 2-6% seroprevalence of B. henselae in US blood donors Currently Recommended Donor Deferral Period: • Cumulative seroprevalence of 7.1% to B. henselae and B. • No FDA Guidance or AABB Standard exists. quintana in US veterinary professionals • Prudent practice would be to defer donor until signs Incubation Period: and symptoms are gone and any course of treatment is complete. • 3-10 days to appearance of papule at B. henselae inoculation site; regional adenopathy may follow after a few weeks Impact on Blood Availability:

Likelihood of Clinical Disease: • Agent-speciﬁc screening question(s): Not applicable • Laboratory test(s) available: Not applicable • Cat scratch disease in normal hosts is relatively benign and self-limiting, lasting 6-12 weeks in the absence of antibiotic Impact on Blood Safety: therapy. • Agent-speciﬁc screening question(s): Not applicable Primary Disease Symptoms: • Laboratory test(s) available: Not applicable

• B. henselae generally causes a mild infection at point of Leukoreduction Efficacy: injury and lymphadenopathy involving the draining nodes, • Unknown, unlikely to affect intraerythrocytic organisms generally of the head, neck, and upper torso  Fever, headache, fatigue, nausea and vomiting, sore Pathogen Reduction Efficacy for Plasma Derivatives: throat, conjunctivitis (Parinaud’s oculoglandular syn- • Specific data indicate that the multiple steps in the fraction- drome) and poor appetite also occur. ation process are robust and capable of inactivating and/or  Symptoms may be intermittent or chronic with a removing bacteria at concentrations that may be present waxing and waning course. in plasma.

Severity of Clinical Disease: Other Prevention Measures:

• More severe manifestations from B. henselae, bacillary angi- • None omatosis or peliosis, and endocarditis, can occur in immune compromised hosts and are particularly well described Suggested Reading: complicating HIV infection. 1. Breitschwerdt EB, Kordick DL. Bartonella infection in Mortality: animals: carriership, reservoir potential, pathogenicity, and zoonotic potential for human infection. Clin Microbiol Rev • Unknown, but probably low 2000;13:428-38. 2. Breitschwerdt ER, Maggi RG, Duncan AW, Nicholson WL, Chronic Carriage: Hegarty BC, Woods CW. Bartonella species in blood of • Limited data to suggest the possibility of persistence in immunocompetent persons with animal and arthropod humans contact. Emerg Infect Dis 2007;13:938-41. • Persists in many animals, including cats 3. Chomel BB, Abbott RC, Kasten RW, Floyd-Hawkins KA, Kass PH, Glaser CA, Pederson NC, Kochler JE. Bartonella henselae Treatment Available/Efﬁcacious: prevalence in domestic cats in California: risk factors and • Immunocompetent patients usually do not require treat- association between bacteremia and antibody titers. J Clin ment, but immunocompromised patients should be treated Microbiol 1995;33:2445-50.

2 4. Chomel BB, Kasten RW, Sykes JE, Boulouis HJ, Breitschwerdt G. Bartonella spp. seroprevalence in healthy Swedish blood EB. Clinical impact of persistent Bartonella bacteremia in donors. Scand J Infect Dis 2005;37:723-30. humans and animals. Ann NY Acad Sci 2003;990:267-78. 10. Rolain JM, La Scola B, Liang Z, Davoust B, Raoult D. 5. Harms A, Dehio C. Intruders below the radar: molecular Immunoﬂuorescent detection of intraerythrocytic Barton- pathogenesis of Bartonella spp. Clin Microbol Rev 2012;25: ella henselae in naturally infected cats. J Clin Microbiol 42-78. 2001;39:2978-80. 6. Koehler JE, Duncan LM. Case records of the Massachusetts 11. Schulein R, Seubert A, Gille C, Lanz C, Hansmann Y, Piémont General Hospital. Case 30-2005. A 56-year old man with fever Y, Dehio C. Invasion and persistent intracellular colonization and axillary lymphadenopathy. N Engl J Med 2005;353:1387- of erythrocytes: a unique parasitic strategy of the emerging 94. pathogen Bartonella. J Exp Med 2001;193:1077-86. 7. Magalhães RF, Pitassi LH, Salvadego M, de Moraes AM, Bar- 12. Scolfaro C, Mignone F, Gennari F, Alfarano A, Veltri A, Rom- jas-Castro ML, Velho PE. Bartonella henselae survives after agnoli R, and Salizzoni M. Possible donor-recipient barton- the storage period of red blood cell units: is it transmissible ellosis transmission in a pediatric liver transplant. Transpl by transfusion? Trans Med 2008;18:287-91. Infect Dis 2008;10:431-3. 8. Mandle T, Einsele H, Schaller M, Neumann D, Vogel W, 13. Velho PE. Blood transfusion as an alternative bartonellosis Autenrieth IB, Kempf VA. Infection of human CD34+ transmission in a pediatric liver transplant. Transpl Inf Dis progenitor cells with Bartonella henselae results in 2009;11:474. intraerythrocytic presence of B. henselae. Blood 2005; 14. Zangwill KM, Hamilton DH, Perkins BA, Regnery RL, Plikay- 106L1215-22. tis BD, Hadler JL, Cartter ML, Wenger JD. Cat scratch disease 9. McGill S, Wesslen L, Hjelm E, Holmberg M, Auvinen MK, in Connecticut: epidemiology, risk factors and evaluation of Berggren K, Grandin-Jarl B, Johnson U, Wikström S, Friman a new diagnostic test. N Engl J Med 1993;329:8-13.