Skip to main content

Brucella: Potential Biothreat Agent

  • Chapter
  • First Online:
Defense Against Biological Attacks

Abstract

Brucellosis is an ancient disease caused by brucellae, which are small, facultative, intracellular, gram-negative coccobacilli. Ten species of Brucella have been identified as the causative agents of brucellosis in mammalian hosts. Natural infections with Brucellae occur globally among humans and animals, resulting in significant economic losses. Research in recent years has focused on appropriate methods for environmental sampling, early detection techniques, decontamination procedures, and the development of new therapeutics and vaccines. Despite this research focus, there is still no human vaccine available. This is of particular concern as Brucellae are highly infectious via the aerosol route; therefore, they have the potential to be misused as agents of biological warfare. The global biological terrorist risk is increasing yearly due to a number of factors including increased migration, escalating numbers of displaced people, the speed and scale of global travel, and technological advances which have enhanced our ability to manipulate pathogens. Presented are a review of the recent developments in brucellosis research and an evaluation of the risks associated with the use of brucellae in deliberate biological attacks.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Corbel MJ, Alton GG, Ariza J et al. Brucellosis in humans and animals. World Health Organization, Geneva; 2006.

    Google Scholar 

  2. Pappas G, Papadimitriou P, Akritidis N, et al. The new global map of human brucellosis. Lancet Infect Dis. 2006;6:91–9.

    Article  PubMed  Google Scholar 

  3. Cirincione J, Wolfsthal JB, Rajkumar M. Deadly Arsenal: nuclear, biological and chemical threat. 2nd ed. Washington: Carnegie Endowment for International Peace; 2005.

    Google Scholar 

  4. Pappas G, Panagopoulou P, Christou L, Akritidis N. Brucella as a biological weapon. Cell Mol Life Sci. 2006;63:2229–36.

    Article  CAS  PubMed  Google Scholar 

  5. Robinson JPP, Cosivi O, Davey BJ, et al. Public health response to biological and chemical weapons; WHO guidance. Geneva: World Health Organization; 2004.

    Google Scholar 

  6. Doganay M, Demiraslan H. Refugees of the Syrian Civil War: impact on reemerging infections, health services, and biosecurity in Turkey. Health Secur. 2016;14:220–5.

    Article  PubMed  Google Scholar 

  7. Rosman Y, Eisenkraft A, Milk N, et al. Lessons learned from the Syrian sarin attack: evaluation of a clinical syndrome through social media. Ann Intern Med. 2014;160:644–8.

    Article  PubMed  Google Scholar 

  8. Bossi P, Tegnell A, Baka A, et al. Bichat guidelines for the clinical management of brucellosis and bioterrorism-related brucellosis. Euro Surveill. 2004;9(12):1–5.

    Article  Google Scholar 

  9. Dinler-Doganay G, Doganay M. Brucella as a potential agent of bioterrorism. Recent Pat Antiinfect Drug Discov. 2013;8:27–33.

    Article  Google Scholar 

  10. Gyles C. Agroterrorism. Can Vet J. 2010;51:347–8.

    PubMed  PubMed Central  Google Scholar 

  11. Araj GE. Brucella. In: Jorgensen JH, Pfaller MA, Carroll KC, et al., editors. Manual of clinical microbiology. 11th ed. Washington, DC: ASM Press; 2015. p. 863–72.

    Chapter  Google Scholar 

  12. Atluri VL, Xavier MN, Maarten FJ, et al. Interactions of the human pathogenic Brucella species with their hosts. Annu Rev Microbiol. 2011;65:523–41.

    Article  CAS  PubMed  Google Scholar 

  13. Falenski A, Mayer-Scholl A, Filter M, et al. Survival of Brucella spp. in mineral water, milk and yogurt. Int J Food Microbiol. 2011;145:326–30.

    Article  PubMed  Google Scholar 

  14. Godfroid J, Scholz HC, Barbier T, et al. Brucellosis at the animal/ecosystem/human interface at the beginning of 21st century. Prev Vet Med. 2011;102:118–31.

    Article  CAS  PubMed  Google Scholar 

  15. Bosilkovski M. Microbiology, epidemiology, and pathogenesis of Brucella, 2017. Accessed September 13, 2017. https://www.uptodate.com/contents/microbiology-epidemiology-and-pathogenesis-of-brucella?source=search_result&search=brucellosis&selectedTitle=2~102

  16. Doganay M, Aygen B. Human brucellosis: an overview. Int J Infect Dis. 2003;7:173–82.

    Article  Google Scholar 

  17. Morse AM. Historical perspective of microbial bioterrorism. In: Anderson B, Friedman H, Bendinelli M, editors. Microorganism and bioterrorism. Florida: Springer; 2006. p. 15–29.

    Chapter  Google Scholar 

  18. Christopher GW, Cieslak TJ, Pavlin JA, et al. Biological warfare: A historical perspective. JAMA. 1997;278(5):412–7.

    Article  CAS  PubMed  Google Scholar 

  19. Kaufmann AF, Meltzer MI, Schmid GP. The economic impact of a bioterrorist attack: are prevention and postattack intervention programs justifiable? Emerg Infect Dis. 1997;3:83–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dalziel GR. Food defence incidents 1950–2008: a chronology and analysis of incidents involving the malicious contamination of the food supply chain. Singapore: Nanyang Technological University; 2009.

    Google Scholar 

  21. Agriculture related CBW activity. Chronology of chemical and biological incidents targeting the food industry 1946–2006. Accessed January 2012. http://cns.miis.edu/cbw/foodchron.htm

  22. Seleem MN, Boyle SM, Sriranganathan N. Brucellosis: a re-emerging zoonoses. Vet Microbiol. 2010;140:392–8.

    Article  PubMed  Google Scholar 

  23. Noviella S, Gallo R, Kelly M, et al. Laboratory-acquired brucellosis. Emerg Infect Dis. 2004;10:1848–50.

    Article  Google Scholar 

  24. Yagupsky P, Peled N, Riesenberg K, Banai M. Exposure of hospital personnel to Brucella melitensis and occurrence of laboratory-acquired disease in an endemic area. Scand J Infect Dis. 2000;32:31–5.

    Article  CAS  PubMed  Google Scholar 

  25. Doganay M, Aygen B, Esel D, et al. Brucellosis due to blood transfusion. J Hosp Infect. 2001;49:151–2.

    Article  CAS  PubMed  Google Scholar 

  26. Kato Y, Masuda G, Itoda I, et al. Brucellosis in a returned traveler and his wife: probable person-to-person transmission of Brucella melitensis. J Travel Med. 2007;14:343–5.

    Article  PubMed  Google Scholar 

  27. Franco MP, Mulder M, Gilman RH, Smits HL. Human brucellosis. Lancet Infect Dis. 2007;7(12):775–86.

    Article  CAS  PubMed  Google Scholar 

  28. Andriopoulos P, Tsironi M, Deftereos S, et al. Acute brucellosis: presentation, diagnosis, and treatment of 144 cases. Int J Infect Dis. 2007;11:52–7.

    Article  PubMed  Google Scholar 

  29. Aygen B, Doganay M, Sumerkan B, et al. Clinical manifestations, complications and treatment of brucellosis: a retrospective evaluation of 480 patients. Med Mal Infect. 2002;32:485–93.

    Article  Google Scholar 

  30. Bosilkovski M, Krteva L, Dimzova M, et al. Human brucellosis in Macedonia – 10 years of clinical experience in endemic region. Croat Med J. 2010;51(4):327–36.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Buzgan T, Karahocagil MK, Irmak H, et al. Clinical manifestations and complications in 1028 cases of brucellosis: a retrospective evaluation and review of the literature. Int J Infect Dis. 2010;14(6):e469–78.

    Article  PubMed  Google Scholar 

  32. Demiroglu YZ, Turunc T, Aliskan H, et al. Brucellosis: retrospective evaluation of the clinical, laboratory and epidemiological features of 151 cases. Mikrobiyol Bul. 2007;41:517–27.

    PubMed  Google Scholar 

  33. Memish Z, Mah MW, Al Mahmoud S, et al. Brucella bacteraemia: clinical and laboratory observations in 160 patients. J Infect. 2000;40:59–63.

    Article  CAS  PubMed  Google Scholar 

  34. Pourbagher MA, Pourbagher A, Savas L, et al. Clinical pattern and abdominal sonographic findings in 251 cases of brucellosis in southern Turkey. AJR Am J Roentgenol. 2006;187:W191–4.

    Article  PubMed  Google Scholar 

  35. Tasbakan MI, Yamazhan T, Gökengin D, et al. Brucellosis: a retrospective evaluation. Trop Dr. 2003;33:151–3.

    Google Scholar 

  36. Solera J. Update on brucellosis: therapeutic challenges. Int J Antimicrob Agents. 2010;36(Suppl 1):S18–20.

    Article  CAS  PubMed  Google Scholar 

  37. Ariza J, Corredoira J, Pallares R, et al. Characteristics of and risk factors for relapse of brucellosis in humans. Clin Infect Dis. 1995;20(5):1241–9.

    Article  CAS  PubMed  Google Scholar 

  38. Maves RC, Castillo R, Guillen A, et al. Antimicrobial susceptibility of Brucella melitensis isolates in Peru. Antimicrob Agents Chemother. 2011;55(3):1279–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Herrick JA, Lederman RJ, Sullivan B, et al. Brucella arteritis: clinical manifestations, treatment, and prognosis. Lancet Infect Dis. 2014;14(6):520–6.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Dean AS, Crump L, Greter H, et al. Clinical manifestations of human brucellosis: a systematic review and meta-analysis. PLoS Negl Trop Dis. 2012;6(12):e1929.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Ulu-Kilic A, Sayar MS, Tütüncü E, et al. Complicated brucellar spondylodiscitis: experience from an endemic area. Rheumatol Int. 2013;33(11):2909–12.

    Article  CAS  PubMed  Google Scholar 

  42. Araj GF. Update on laboratory diagnosis of human brucellosis. Int J Antimicrob Agents. 2010;36(Suppl 1):S12–7.

    Article  CAS  PubMed  Google Scholar 

  43. La Spada E, Micalizzi A, La Spada M, et al. Abnormal liver function in brucellosis. Infez Med. 2008;16(3):148–53.

    PubMed  Google Scholar 

  44. Bourantas LK, Pappas G, Kapsali E, et al. Brucellosis-induced autoimmune hemolytic anemia treated with rituximab. Ann Pharmacother. 2010;44(10):1677–80.

    Article  PubMed  Google Scholar 

  45. Kaygusuz TO, Kaygusuz I, Kilic SS, et al. Investigation of hearing loss in patients with acute brucellosis by standard and high-frequency audiometry. Clin Microbiol Infect. 2005;11(7):559–63.

    Article  PubMed  Google Scholar 

  46. Karaali Z, Baysal B, Poturoglu S, Kendir M. Cutaneous manifestations in brucellosis. Indian J Dermatol. 2011;56(3):339–40.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Sasmazel A, Baysal A, Fedakar A, et al. Treatment of Brucella endocarditis: 15 years of clinical and surgical experience. Ann Thorac Surg. 2010;89(5):1432–6.

    Article  PubMed  Google Scholar 

  48. Sagi M, Nesher L, Yagupsky P. The Bactec FX blood culture system detects Brucella melitensis bacteremia in adult patients within the routine 1-week incubation period. J Clin Microbiol. 2017;55(3):942–6.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Mohamed Zahidi J, Bee Yong T, Hashim R, et al. Identification of Brucella spp. isolated from human brucellosis in Malaysia using high-resolution melt (HRM) analysis. Diagn Microbiol Infect Dis. 2015;81(4):227–33.

    Article  CAS  PubMed  Google Scholar 

  50. Al Dahouk S, Nöckler K. Implications of laboratory diagnosis on brucellosis therapy. Expert Rev Anti-Infect Ther. 2011;9(7):833–45.

    Article  PubMed  Google Scholar 

  51. Osoba AO, Balkhy H, Memish Z, et al. Diagnostic value of Brucella ELISA IgG and IgM in bacteremic and non-bacteremic patients with brucellosis. J Chemother. 2001;13(Suppl 1):54–9.

    Article  PubMed  Google Scholar 

  52. Mantur B, Parande A, Amarnath S, et al. ELISA versus conventional methods of diagnosing endemic brucellosis. Am J Trop Med Hyg. 2010;83(2):314–8.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Memish ZA, Almuneef M, Mah MW, et al. Comparison of the Brucella standard agglutination test with the ELISA IgG and IgM in patients with Brucella bacteremia. Diagn Microbiol Infect Dis. 2002;44(2):129–32.

    Article  CAS  PubMed  Google Scholar 

  54. Gómez MC, Nieto JA, Rosa C, et al. Evaluation of seven tests for diagnosis of human brucellosis in an area where the disease is endemic. Clin Vaccine Immunol. 2008;15(6):1031–3.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Orduña A, Almaraz A, Prado A, Gutierrez MP, et al. Evaluation of an immunocapture-agglutination test (Brucellacapt) for serodiagnosis of human brucellosis. J Clin Microbiol. 2000;38(11):4000–5.

    PubMed  PubMed Central  Google Scholar 

  56. Yu WL, Nielsen K. Review of detection of Brucella spp. by polymerase chain reaction. Croat Med J. 2010;51:306–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Solís García del Pozo J, Solera J. Systematic review and meta-analysis of randomized clinical trials in the treatment of human brucellosis. PLoS One. 2012;7(2):e32090.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Alavi SM, Alavi L. Treatment of brucellosis: a systematic review of studies in recent twenty years. Caspian J Intern Med. 2013;4(2):636–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Keles C, Bozbuga N, Sismanoglu M, et al. Surgical treatment of Brucella endocarditis. Ann Thorac Surg. 2001;71(4):1160–3.

    Article  CAS  PubMed  Google Scholar 

  60. Ulu-Kilic A, Karakas A, Erdem H, et al. Update on treatment options for spinal brucellosis. Clin Microbiol Infect. 2014;20(2):O75–82.

    Article  CAS  PubMed  Google Scholar 

  61. Erdem H, Ulu-Kilic A, Kilic S, et al. Efficacy and tolerability of antibiotic combinations in neurobrucellosis: results of the Istanbul study. Antimicrob Agents Chemother. 2012;56(3):1523–8. https://doi.org/10.1128/AAC.05974-11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Tanyel E, Coban AY, Koruk ST, et al. Actual antibiotic resistance pattern of Brucella melitensis in central Anatolia. An update from an endemic region. Saudi Med J. 2007;28(8):1239–42.

    PubMed  Google Scholar 

  63. Cannons A, Amuso P, Anderson B. Biotechnology and the public health response to bioterrorism. In: Anderson B, Friedman H, Bendinelli M, editors. Microorganisms and bioterrorism. Infectious agents and pathogenesis. Boston, MA: Springer; 2006.

    Google Scholar 

  64. Jernigan DB, Raghunathan PL, Bell BP, the National Anthrax Epidemiologic Investigation Team, et al. Investigation of Bioterrorism-Related Anthrax, United States, 2001: epidemiologic findings. Emerg Infect Dis. 2002;8(10):1019–28.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Refai M. Application of biotechnology in the diagnosis and control of brucellosis in the Near East Region. World J Microbiol Biotechnol. 2003;19:443–9.

    Article  Google Scholar 

  66. Hinic V, Brodard I, Thomann A, et al. Novel identification and differentiation of Brucella melitensis, B. abortus, B. suis, B. ovis, B. canis and N. neotomae suitable for both conventional and real-time PCR systems. J Microbiol Methods. 2008;75:375–8.

    Article  CAS  PubMed  Google Scholar 

  67. Vizcaino N, Cloeckaert A, Verger J, et al. DNA polymorphism in the genus Brucella. Microbes Infect. 2000;2:1089–100.

    Article  CAS  PubMed  Google Scholar 

  68. Rahi A, Sattarahmady N, Heli H. An ultrasensitive electrochemical genosensor for Brucella based on palladium nanoparticles. Anal Biochem. 2016;510:11–7.

    Article  CAS  PubMed  Google Scholar 

  69. Sattarahmady N, Tondro GH, Gholchin M, Heli H. Gold nanoparticles biosensor of Brucella spp. genomic DNA: visual and spectrophotometric detections. Biochem Eng J. 2015;97:1–7.

    Article  CAS  Google Scholar 

  70. Sikarwar B, Singh VV, Sharma PK, et al. DNA-probe-target interaction based detection of Brucella melitensis by using surface plasmon resonance. Biosens Bioelectron. 2017;87:964–9. https://doi.org/10.1016/j.bios.2016.09.063.

    Article  CAS  PubMed  Google Scholar 

  71. Abbady AQ, Al-Mariri A, Zarkawi M. Expression and purification of Brucella-specific nanobodies. Iran J Biotechnol. 2013;11(2):80–8.

    Article  CAS  Google Scholar 

  72. Yagupsky P, Baron EJ. laboratory exposure to Brucellae and implications for bioterrorism. Emerg Infect Dis. 2005;11:1180–5.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Perkins SD, Smither SJ, Atkins HS. Towards a Brucella vaccine for humans. FEMS Microbiol. 2010;34:379–94.

    Article  CAS  Google Scholar 

  74. Avila-Calderon ED, Lopez-Merino A, Sriranganathan N, et al. A history of the development of Brucella vaccines. Biomed Res Int. 2013;2013:743509. https://doi.org/10.1155/2013/743509.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mehmet Doganay .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Doganay, M., Dinler-Doganay, G., Ulu-Kilic, A., Ingram, R.J. (2019). Brucella: Potential Biothreat Agent. In: Singh, S., Kuhn, J. (eds) Defense Against Biological Attacks. Springer, Cham. https://doi.org/10.1007/978-3-030-03071-1_6

Download citation

Publish with us

Policies and ethics