Brucellar Arthritis

  • Eduardo Gotuzzo Herencia
  • Karen Isabel Vega-Villanueva


Brucellosis has a long-standing history being first described by Hippocrates, and despite of its ancient history, it has not been possible to control or eradicate it, and it remains endemic in many parts of the world. Fever, low back pain, and arthralgias/arthritis are the classic triad that we will find in florid cases of the disease, although we cannot ignore that it could also be a cause of fever of unknown origin (FUO). Being a systemic disease, one of its main complications is osteoarticular involvement, more specifically brucellar arthritis.

Great progress has occurred in its diagnosis in which ELISA or a molecular technique such as PCR facilitates its rapid detection, and imaging techniques such as nuclear magnetic resonance have become very important for an early diagnosis as well as in patient follow-up. Therapies, however, have not evolved much from the antibiotics developed in the 1950s, and at present, antibiotic regimens used to treat both new cases and relapses in brucellosis are similar.


Brucella sp. Arthritis Spondylitis Sacroiliitis Brucella in children Agglutination titers Culture PCR MRI Doxycycline Streptomycin Rifampicin 


Conflicts of Interest

EMM: None. KVV: None.


  1. 1.
    Bruce D. Note on discovery of a micrococcus in Malta fever. Practitioner. 1887;39:161–2.Google Scholar
  2. 2.
    De Figuereido P, Ficht TA, Rice-Ficht A, Rosetti CA, Adams G. Pathogenesis and immunobiology of brucellosis. Review of Brucella-Host interactions. Am J Pathol. 2015;185:1505–17.CrossRefGoogle Scholar
  3. 3.
    Young EJ. Brucella spp. principles and practice of clinical bacteriology. 2nd ed. West Sussex: John Wiley&SonsLtd; 2006. p. 265–72.CrossRefGoogle Scholar
  4. 4.
    Kulowski J, Vinke T. Undulant (Malta) fever spondylitis: report of a case, due to Brucella melitensis, bovine variety, surgically treated. JAMA. 1932;99:1656–9.CrossRefGoogle Scholar
  5. 5.
    De Anquin C. Espondilitis bruselósica. II Jornadas Argentinas de Ortopedia. 1951:176–83.Google Scholar
  6. 6.
    Mandell GL, Bennett JE, Dolin R. Principles and practices of infectious disease, vol. 2. 5th ed. Filadelfia: Churchill Livingstone; 2000. p. 2386–93.Google Scholar
  7. 7.
    Pappas G, Papadimitriou P, Akritidis N, et al. The new global map of human brucellosis. Lancet Infect Dis. 2006;6:91–9.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Beeching NJ, Madkour MM. Chapter 28: brucellosis. In: Farrar J, editor. Manson’s tropical diseases. 23rd ed. United Kingdom: Elsevier; 2014.Google Scholar
  9. 9.
    Elzein FE, Sherbeeni N. Brucella septic arthritis: case reports and review of the literature. Case Rep Infect Dis. 2016;2016:4687840.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Gotuzzo E, Carrillo C, Seas C, et al. Características epidemiológicas y clínicas de la brucelosis en 39 grupos familiares. RevEspInternInfectMicrobiolClin. 1989;7:519.Google Scholar
  11. 11.
    Goossens H, Marcelis L, Dekeyser P, et al. Brucella melitensis: person-to-person transmission? Lancet. 1983;1:773.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Gotuzzo E, Carrillo C, Seas C, et al. Caracteristicasepidemiólogicas y clinicas de la brucelosis en 50 grupos familiares. RevMedHered. 1990;1:8.Google Scholar
  13. 13.
    Gotuzzo E, Seas C, Guerra J, et al. Brucellar arthritis – study of 39 Peruvian families. Ann Rheum Dis. 1987;46:506.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Ulloa V, Rojas J, Gotuzzo E. Púrpura trombocitopénica asociada a brucelosis. Rev Med Hered. 1992;3:87.Google Scholar
  15. 15.
    Gotuzzo E, Pappas G. Chapter 40.Brucellosis. In: Guerrant RL, editor. Tropical infectious diseases. 3rd ed. Spain: Saunders- Elsevier; 2011.CrossRefGoogle Scholar
  16. 16.
    Mousa ARM, Elhag KM, Hkogall M, et al. The nature of human brucellosis in Kuwait, study of 379 cases. J Infect Dis. 1988;10:211.Google Scholar
  17. 17.
    Al-Tawfiq JA, AbuKhamsin A. A 24-year study of the epidemiology of human brucellosis in a health-care system in Eastern Saudi Arabia. J Infect Public Health. 2009;2(2):81–5.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Wang D, Zhang S. Advances in treatment of acute brucellosis. ZhongGuoGan Ran Kong ZhiZaZhi. 2001;16:94–5.(In Chinese).Google Scholar
  19. 19.
    Shang DQ. Research advances in brucellosis disease. ZhongGuoGan Ran Kong ZhiZaZhi. 2004;19:204–12.(In Chinese).Google Scholar
  20. 20.
    World Health Organization in collaboration with Food and Agriculture Organization and World Organization for Animal Health. Brucellosis in humans and animals. Geneva: WHO; 2006.Google Scholar
  21. 21.
    Pappas G. The changing. Int J Antimicrob Agents. 2010;36:S8–S11.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Momjian R, George M. Atypical imaging features of tuberculous spondylitis: case report with literature review. J Radiol Case Rep. 2014;8(11):1–14.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Moreno E, Stackebrandt E, Dorsch M, et al. Brucella abortus 16S rRNA and lipid A reveal a phylogenetic relationship with members of the alpha-2 subdivision of the class Proteobacteria. J Bacteriol. 1990;172:3569.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    DeLay J, Mannheim W, Segers P, et al. Ribosomal ribonucleic acid cistron similarities and taxonomic neighborhood of Brucella and CDC group Vd. Int J SystBacteriol. 1987;37:35.CrossRefGoogle Scholar
  25. 25.
    Verger JM, Grimont F, Grimont PAD, et al. Brucella, a monospecific genus as shown by deoxyribonucleic acid hybridization. Int J SystBacteriol. 1985;35:292–5.CrossRefGoogle Scholar
  26. 26.
    Corbel MJ. International Committee on Systemic Bacteriology Subcommittee on the Taxonomy of Brucella. Int J SystBacteriol. 1988;38:450.CrossRefGoogle Scholar
  27. 27.
    Foster G, Osterman BS, Godfroid J, et al. Brucella ceti sp. nov. and Brucella pinnipedialis sp. nov. for Brucella strains with cetaceans and seals as their preferred hosts. Int JSystEvolMicrobiol. 2007;57:2688.Google Scholar
  28. 28.
    Sohn AH, Probert WS, Glaser CA, et al. Human neurobrucellosis with intracerebral granuloma caused by a marine mammal. Emerg Infect Dis. 2003;9:485.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Scholz HC, Hubalek Z, Sedlacek I, et al. Brucella microti sp. nov., isolated from the common vole Microtus arvalis. Int J SystEvolMicrobiol. 2008;58:375.Google Scholar
  30. 30.
    Madkour MM. Brucellosis: overview. In: Madkour MM, editor. Madkour’s brucellosis. 2nd ed. Berlin: Springer; 2001. p. 1–14.CrossRefGoogle Scholar
  31. 31.
    Naparsteck E, Block CS, Slavin S. Transmission of brucellosis in bone marrow transplantation. Lancet. 1982;1:574.CrossRefGoogle Scholar
  32. 32.
    Al Dahouk S, Tomaso H, Prenger-Berninghoff E, et al. Identification of Brucella species and biotypes using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Crit Rev Microbiol. 2005;31:191–6.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Al Dahouk S, Nöckler K. Implications of laboratory diagnosis on brucellosis therapy. Expert Rev Anti-Infect Ther. 2011;9:833–45.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Von Bargen K, Gorvel JP, Salcedo SP. Internal affairs: investigating the. FEMS Microbiol Rev. 2012;36:533–62.CrossRefGoogle Scholar
  35. 35.
    Castañeda-Roldán EI, Avelino-Flores F, Dall’Agnol M, Freer E, Cedillo L, Dornand J, Girón JA. Adherence of Brucella to human epithelial cells and macrophages is mediated by sialic acid residues. Cell Microbiol. 2004;6:435–45.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Rossetti CA, Drake KL, Adams LG. Transcriptome analysis of HeLa cells response to Brucella melitensis infection: a molecular approach to understand the role of the mucosal epithelium in the onset of the Brucella pathogenesis. Microbes Infect. 2012;14:756–67.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Qin QM, Pei J, Ancona V, Shaw BD, Ficht TA, de Figueiredo P. RNAi screen of endoplasmic reticulum-associated host factors reveals a role for IRE1alpha in supporting Brucella replication. PLoSPathog. 2008;4:e1000110.Google Scholar
  38. 38.
    Kohler S, Foulongne V, Ouahrani-Bettache S, Bourg G, Teyssier J, Ramuz M, Liautard JP. The analysis of the intramacrophagicvirulome of Brucella suis deciphers the environment encountered by the pathogen inside the macrophage host cell. Proc Natl AcadSci U S A. 2002;99:15711–6.CrossRefGoogle Scholar
  39. 39.
    Roux CM, Rolan HG, Santos RL, Beremand PD, Thomas TL, Adams LG, Tsolis RM. Brucella requires a functional Type IV secretion system to elicit innate immune responses in mice. Cell Microbiol. 2007;9:1851–69.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Lamontagne J, Forest A, Marazzo E, Denis F, Butler H, Michaud JF, Boucher L, Pedro I, Villeneuve A, Sitnikov D, Trudel K, Nassif N, Boudjelti D, Tomaki F, Chaves-Olarte E, Guzman-Verri C, Brunet S, Cote-Martin A, Hunter J, Moreno E, Paramithiotis E. Intracellular adaptation of Brucella abortus. J Proteome Res. 2009;8:1594–609.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Rambow-Larsen AA, Rajashekara G, Petersoen E, Splitter G. Putative quorum-sensing regulator BlxR of Brucella melitensis regulates virulence factors including the Type IV secretion system and flagella. J Bacteriol. 2008;190:3274–82.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Weeks JN, Galindo CL, Drake KL, Adams GL, Garner HR, Ficht TA. Brucella melitensisVjbR and C12-HSL regulons: contributions of the N-dodecanoylhomoserine lactone signaling molecule and LuxR homologue VjbR to gene expression. BMC Microbiol. 2010;10:167.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Billard E, Dornand J, Gross A. Brucella suis prevents human dendritic cell maturation and antigen presentation through regulation of tumor necrosis factor alpha secretion. Infect Immun. 2007;75:4980–9.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Young EJ, HasanjaniRoushan MR, Shafae S, Genta RM, Taylor SL. Liver histology of acute brucellosis caused by Brucella melitensis. Hum Pathol. 2014;45:2023–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Fernandes DM, Benson R, Baldwin CL. Lack of a role for natural killer cells in early control of Brucella abortus 2308 infections in mice. Infect Immun. 1995;63:4029–33.PubMedPubMedCentralGoogle Scholar
  46. 46.
    De Figueiredo P, Ficht TA, Rice-Ficht A, Rossetti CA, Adams LG. Pathogenesis and immunobiology of brucellosis: review of Brucella–Host interactions. Am J Pathol. 2015;185(6):1505–17.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Salcedo SP, Marchesini MI, Lelouard H, Fugier E, Jolly G, Balor S, Muller A, Lapaque N, Demaria O, Alexopoulou L, Comerci DJ, Ugalde RA, Pierre P, Gorvel JP. Brucella control of dendritic cell maturation is dependent on the TIR-containing protein Btp1. PLoS Pathog. 2008;4:e21.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Smith JA, Khan M, Magnani DD, Harms JS, Durward M, Radhakrishnan GK, Liu YP, Splitter GA. Brucella induces an unfolded protein response via TcpB that supports intracellular replication in macrophages. PLoS Pathog. 2013;9:e1003785.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Ministerio de Salud del Perú. Norma técnica de diagnóstico y tratamiento de brucelosis humana: N.T. No. 002-MINSA/DGSP-V.01/Ministerio de Salud. Dirección General de Salud de las Personas. Dirección Ejecutiva de Atención Integral de Salud – Lima: Ministerio de Salud;2005. 23 p.Google Scholar
  50. 50.
    Ruiz-Castañeda M, Tovar R, Velez R. Studies on brucellosis in Mexico. Comparative study of various diagnostic tests and classification of the isolate bacteria. J Infect Dis. 1942;70:97.CrossRefGoogle Scholar
  51. 51.
    Williams E. Brucellosis. Practitioner. 1982;226:1507.PubMedGoogle Scholar
  52. 52.
    Ruiz-Mesa JD, Sanchez-Gonzalez J, Reguera JM, Martin L, Lopez-Palmero S, Colmenero JD. Rose Bengal test: diagnostic yield and use for the rapid diagnosis of human brucellosis in emergency departments in endemic areas. ClinMicrobiol Infect. 2005;11(3):221–5.CrossRefGoogle Scholar
  53. 53.
    Christopher S, Umapathy BL, Ravikumar KL. Brucellosis: review on the recent trends in pathogenicity and laboratory diagnosis. J Lab Physicians. 2010;2(2):55–60.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Perry MB, Bundle DR. Lipopolysaccharide antigens and carbohydrates of Brucella. In: Adams LG, editor. Advances in brucellosis research. Austin: Texas A and M University; 1990. p. 76–88.Google Scholar
  55. 55.
    Almuneef M, Memish ZA. Persistence of Brucella antibodies after successful treatment of acute brucellosis in an area of endemicity. JClinMicrobiol. 2002;40(6):2313.Google Scholar
  56. 56.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Zourbas J, Masse L, Roussey A, David C, Maurin J, Torte J. Sampling survey on brucellosis among farmers and their families in IIIe-et-Vilaine (Brittany). Int J Epidemiol. 1977;6:335–43.PubMedCrossRefGoogle Scholar
  58. 58.
    Gilbert GL, Beaton CP, Forsyth JR, Bell CO. An epidemiological survey of human brucellosis in three Victorian abattoirs. Med J Aust. 1980;1:482–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Daz R, Maravi-Poma E, Rivero A. Comparison of counterimmuno-electrophoresis with other serological tests in the diagnosis of human brucellosis. Bull World Health Organ. 1976;53:417–24.PubMedGoogle Scholar
  60. 60.
    Monir MM, Dennis LK. Brucellosis. In: Braunwald F, Kasper H, Lango J, editors. Harrison’s principles of internal medicine. 15th ed. New York: McGraw-Hill Education; 2001. p. 986–90.Google Scholar
  61. 61.
    Serra J, Vinas M. Laboratory diagnosis of brucellosis in a ruralendemic area in northeastern Spain. Int Microbiol. 2004;7(1):53–8.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Young EJ. An overview of human brucellosis. Clin Infect Dis. 1995;21(2):283–9.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Araj GF, Kaufmann AF. Determination by enzyme-linked immunosorbent assay of immunoglobulin G (IgG), IgM, and IgA to Brucella melitensis major outer membrane proteins and whole cell heat-killed antigens in sera of patients with brucellosis. J Clin Microbiol. 1989;27(8):1909–12.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Osoba AO, Balkhy H, Memish Z, Khan MY, Al-Thagafi A, Al Shareef B, 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.PubMedCrossRefGoogle Scholar
  65. 65.
    Kostoula A, Bobogianni H, Virioni G, Tabatabai LB. Detection of Brucella IgG, IgM and IgA antibodies with ELISA method in patients with brucellosis. Clin Microbiol Infect. 2001;7(1):108.Google Scholar
  66. 66.
    Agasthya AS, Isloor S, Krishnamsetty P. Seroprevalence study of human brucellosis by conventional tests and indigenous indirect enzyme-linked immunosorbent assay. Sci World J. 2012;2012:104239.CrossRefGoogle Scholar
  67. 67.
    Gad El-Rab MO, Kambal AM. Evaluation of a Brucella enzyme immunoassay test (ELISA) in comparison with bacteriological culture and agglutination. J Infect. 1998;36:197–201.PubMedCrossRefGoogle Scholar
  68. 68.
    Ariza J, Pellicer T, Pallares R, Foz A, Gudiol F. Specific antibody profile in human brucellosis. ClinInfectDis. 1992;14:131–40.Google Scholar
  69. 69.
    Gazapo E, Gonzalez Lahoz J, Subiza JL, Baquero M, Gil J, de la Concha EG. Changes in IgM and IgG antibody concentrations in brucellosis over time: importance for diagnosis and follow-up. J Infect Dis. 1989;159:219–25.PubMedCrossRefGoogle Scholar
  70. 70.
    Reddin JL, Anderson RK, Jenness R, Spink WW. Significance of 7S and macroglobulin Brucella agglutinins in human brucellosis. N Engl J Med. 1965;272:1263–8.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Roushan MR, Amin MJ, Abdoel TH, Smits HL. Application of a user-friendly Brucella-specific IgM and IgG antibody assay for the rapid confirmation of Rose Bengal-positive patients in a hospital in Iran. Trans R Soc Trop Med Hyg. 2005;99(10):744–50.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Pabuccuoglu O, Ecemis T, El S, Coskun A, Akcali S, Sanlidag T. Evaluation of serological tests for diagnosis of brucellosis. Jpn J Infect Dis. 2011;64(4):272–6.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Ministerio de Salud del Perú. Norma técnica de salud para la atención integral de la persona afectada con brucelosis. NTS N° -MINSA/DGSP-V.01 Ministerio de Salud.Dirección General de Salud de las Personas. Dirección Ejecutiva de Atención Integral de Salud – Lima: Ministerio de Salud;2009.Google Scholar
  74. 74.
    Mitka S, Anetakis C, Souliou E, Diza E, Kansouzidou A. Evaluation of different PCR assays for early detection of acute and relapsing brucellosis in humans in comparison with conventional methods. J ClinMicrobiol. 2007;45(4):1211–8.Google Scholar
  75. 75.
    Al Ajlan HH, Ibrahim AS, Al Salamah AA. Comparison of different PCR methods for detection of Brucella spp. in human blood samples. Pol J Microbiol. 2011;60(1):27–33.Google Scholar
  76. 76.
    Wang, et al. Polymerase chain reaction–based assays for the diagnosis of human brucellosis. Ann Clin Microbiol Antimicrob. 2014;13:31.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Morata P, Queipo-Ortuño MI, Reguera JM, García-Ordoñez MA, Pichardo C, Colmenero JD. Posttreatment follow-up of brucellosis by PCR assay. J ClinMicrobiol. 1999;37(12):4163–6.Google Scholar
  78. 78.
    Elfaki MG, Al-Hokail AA, Nakeeb SM, Al-Rabiah FA. Evaluation of culture, tube agglutination, and PCR methods for the diagnosis of brucellosis in humans. Med SciMonit. 2005;11(11):MT69–74.Google Scholar
  79. 79.
    Briones Lara E, del C Palacios Saucedo G, Martínez Vázquez IO, Morales Loredo A, del PilarBilbao Chávez L. Response to the treatment of brucellosis among children. Evaluation with Huddleson reaction and PCR. Rev Med Inst Mex SeguroSoc. 2007;45(6):615–22.Google Scholar
  80. 80.
    Baddour MM, Alkhalifa DH. Evaluation of three polymerase chain reaction techniques for detection of Brucella DNA in peripheral human blood. Can J Microbiol. 2008;54(5):352–7.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Navarro E, Escribano J, Fernández J, Solera J. Comparison of three different PCR methods for detection of Brucella spp. in human blood samples. FEMS Immunol Med Microbiol. 2002;34(2):147–51.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Morata P, Queipo-Ortuño MI, de Dios CJ. Strategy for optimizing DNA amplification in a peripheral blood PCR assay used for diagnosis of human brucellosis. J ClinMicrobiol. 1998;36(9):2443–6.Google Scholar
  83. 83.
    Ginzinger DG. Gene quantification using real-time quantitative PCR: an emerging technology hits the mainstream. ExpHematol. 2002;30(6):503–12.Google Scholar
  84. 84.
    Queipo-Ortuño MI, Colmenero JD, Reguera JM, García-Ordoñez MA, Pachón ME, Gonzalez M, Morata P. Rapid diagnosis of human brucellosis by SYBR Green I-based real-time PCR assay and melting curve analysis in serum samples. ClinMicrobiol Infect. 2005;11(9):713–8.CrossRefGoogle Scholar
  85. 85.
    Surucuoglu S, El S, Ural S, Gazi H, Kurutepe S, Taskiran P, Yurtsever SG. Evaluation of real-time PCR method for rapid diagnosis of brucellosis with different clinical manifestations. Pol J Microbiol. 2009;58(1):15–9.PubMedPubMedCentralGoogle Scholar
  86. 86.
    Alsayed Y, Monen F. Brucellosis laboratory tests in Syria: what are their diagnostic efficacies in different clinical manifestations? J Infect Dev Ctries. 2012;6(6):495–500.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Huber B, Scholz HC, Lucero N, Busse HJ. Development of a PCR assay for typing and subtyping of Brucella species. Int J Med Microbiol. 2009;299(8):563–73.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Queipo-Ortuño MI, Colmenero JD, Bermudez P, Bravo MJ, Morata P. Rapid differential diagnosis between extrapulmonary tuberculosis and focal complications of brucellosis using a multiplex real-time PCR assay. PLoS One. 2009;4(2):e4526.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Colmenero JD, Morata P, Ruiz Mesa JD, Bautista D, Bermúdez P, Bravo MJ, Queipo-Ortuño MI. Multiplex real-time polymerase chain reaction: a practical approach for rapid diagnosis of tuberculous and brucellar vertebral osteomyelitis. Spine (Phila Pa 1976). 2010;35(24):E1392–6.CrossRefGoogle Scholar
  90. 90.
    Sanjuan Jimenez R, Colmenero JD, Bermúdez P, Alonso A, Morata P. Amplicon DNA melting analysis for the simultaneous detection of Brucella spp. and Mycobacterium tuberculosis complex. Potential use in rapid differential diagnosis between extra-pulmonary tuberculosis and focal complications of brucellosis. PLoS One. 2013;8(3):e58353.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Yagupsky P. Detection of Brucellae in blood cultures. J Clin Microbiol. 1999;37(11):3437–42.PubMedPubMedCentralGoogle Scholar
  92. 92.
    Araj GF, Lulu AR, Mustafa MY, Khateeb MI. Evaluation of ELISA in the diagnosis of acute and chronic brucellosis in human beings. J Hyg (Lond). 1986;97(3):457–69.CrossRefGoogle Scholar
  93. 93.
    Corbel MJ. Brucellosis: an overview. Emerg Infect Dis. 1997;3(2):213–21.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Mantur BG, Mangalgi SS. Evaluation of conventional castaneda and lysis centrifugation blood culture techniques for diagnosis of human brucellosis. J Clin Microbiol. 2004;42(9):4327–8.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Cetin ES, Kaya S, Demirci M, Aridogan BC. Comparison of the BACTEC blood culture system versus conventional methods for culture of normally sterile body fluids. AdvTher. 2007;24(6):1271–7.Google Scholar
  96. 96.
    Gaviria-Ruiz MM, Cardona-Castro NM. Evaluation and comparison of different blood culture techniques for bacteriological isolation of Salmonella typhi and Brucella abortus. J Clin Microbiol. 1995;33(4):868–71.PubMedPubMedCentralGoogle Scholar
  97. 97.
    Gotuzzo E, Carrillo C, Guerra J, et al. Evaluation of diagnostic methods for brucellosis. Value of bone marrow culture. J Infect Dis. 1986;153:122.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Diaz R, Moriyon I. Laboratory techniques in the diagnosis of human brucellosis. In: Young EJ, Corbel MK, editors. Brucellosis: clinical and laboratory aspects. Boca Raton: CRC Press; 1989. p. 73.Google Scholar
  99. 99.
    Ozkurt Z, Erol S, Tasyaran MA, Kaya A. Detection of Brucella melitensis by the BacT/Alert automated system and Brucella broth culture. Clin Microbiol Infect. 2002;8(11):749–52.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Apa H, Devrim I, Memur S, Gunay I, Gulfidan G, Celegen M, et al. Factors affecting Brucella spp. blood cultures positivity in children. Vector Borne Zoonotic Dis. 2013;13(3):176–80.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Deepak S, Bronson SG, Joseph W, Thomas M, Sibi. Brucella isolated from bone marrow. J Assoc Physicians India. 2003;51:717–8.PubMedPubMedCentralGoogle Scholar
  102. 102.
    Assadi M, et al. Brucellosis in Iran: a literature review. J Am Sci. 2013;9(3):203–8.Google Scholar
  103. 103.
    Yang B, Hu H, Chen J, He X, Li H. The evaluation of the clinical, laboratory, and radiological findings of 16 cases of Brucellar Spondylitis. Biomed Res Int. 2016;2016:8903635.PubMedPubMedCentralGoogle Scholar
  104. 104.
    Farid Z, Trabolsi B, Yassin W, et al. Acute brucellosis presenting as fever of unknown origin (FUO). Trans R SocTropMedHyg. 1980;74:402.Google Scholar
  105. 105.
    Dean AS, Crump L, Greter H, Hattendorf J, Schelling E, Zinsstag J. Clinical manifestations of human brucellosis: a systematic review and meta-analysis. Carabin H, ed. PLoS Negl Trop Dis. 2012;6(12):e1929.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Gotuzzo E, Alarcón G, Bocanegra T, et al. Articular involvement in human brucellosis: a retrospective analysis of 304cases. Semin Arthritis Rheum. 1982;12:245–55.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Madkour MM. Madkour’s brucellosis. Berlin: Springer; 2001.CrossRefGoogle Scholar
  108. 108.
    Kennedy JC. Notes on a case of chronic synovitis on bursitis due to tge organism of Mediterranean fever. J Roy Army Med Corps. 1904;2:178–80.Google Scholar
  109. 109.
    Bocanegra T, Gotuzzo E, Alarcón G, et al. Circulating immune complexes in acute fever and brucellosis. Clin Res. 1981;29:381.Google Scholar
  110. 110.
    Gottesman G, Vanunu D, Maayan MC, et al. Childhood brucellosis in Israel. Pediatr Infect Dis J. 1996;15:610.PubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Alarcón GS, Bocanegra T, Gotuzzo E, et al. Reactive arthritis associated with brucellosis: HLA studies. J Rheumatol. 1981;8:621.PubMedPubMedCentralGoogle Scholar
  112. 112.
    Bocanegra T, Gotuzzo E, Castañeda O, et al. Rheumatic manifestations of brucellosis. Ann RheumDis. 1986;45:526.CrossRefGoogle Scholar
  113. 113.
    Brito M, Gonzales-Dias J, Marques J, et al. Brucellosis osteoarticular. RevEspReumatolEnfermOsteoarthritis (Barcelona). 1972;15:219.Google Scholar
  114. 114.
    Sany P. Una polyarthrite pseudo-rhumatoide. Rhumatologia. 1975;27:411.Google Scholar
  115. 115.
    Hizel K, Guzel O, Dizbay M, et al. Age and duration of disease as factors affectingclinical findings and sacroiliitis in brucellosis. Infection. 2007;35:434–7.PubMedCrossRefPubMedCentralGoogle Scholar
  116. 116.
    Gheita TA, Sayed S, Azkalany GS, et al. Subclinical sacroiliitis in brucellosis. Clinical presentation and MRI findings. Z Rheumatol. 2015;74(3):240–5.PubMedCrossRefPubMedCentralGoogle Scholar
  117. 117.
    Gotuzzo E, Carrillo C. In: Espinoza L, Goldberg D, Arnett F, editors. Infections in the rheumatic disease. Orlando: Grune& Stratton; 1988. p. 31.Google Scholar
  118. 118.
    Norton WL. Brucellosis and rheumatic syndromes in Saudi Arabia. J Rheumatol. 1984;43:810–5.Google Scholar
  119. 119.
    Rotes-Querol J. Manifestaciones osteoarticulares de la Brucelosis. Barcelona, Spain: Barcelona JIMS Editorial; 1959.Google Scholar
  120. 120.
    Feldman JL, Menkes CJ, Weil B, et al. Les sacro-ileitesinfecticuses. Etude multicentriqe sue 214 observations. Rev Rhum Med Osteartic. 1981;48:83–91.Google Scholar
  121. 121.
    Momjian R, George M. Atypical imaging features of tuberculous spondylitis: case report with literature review. JRadiolCaseRep. 2014;8(11):1–14.Google Scholar
  122. 122.
    Ariza J, Gudiol F, Valverde J, et al. Brucellar spondylitis: a detailed analysis based on current findings. Rev Infect Dis. 1985;7:656.PubMedCrossRefPubMedCentralGoogle Scholar
  123. 123.
    Spink WW. The nature of brucellosis. Minneapolis: University of Minnesota Press; 1956.Google Scholar
  124. 124.
    Munoz E. Brucellosis in Kumate J and Gutierrez G: manual de Infectología- Mexico. Edic del Hospital Infantil de Mexico. 1977:32–8.Google Scholar
  125. 125.
    Young EJ. Human brucellosis. Rev Infect Dis. 1983;5:821–42.PubMedCrossRefPubMedCentralGoogle Scholar
  126. 126.
    Ibero I, Vela P, Pascual E. Arthritis of shoulder and spinal cord compression due to. Br J Rheumatol. 1997;36:377.PubMedCrossRefPubMedCentralGoogle Scholar
  127. 127.
    Pons P. Spondylitis melitoccocita. Ann Med. 1929;5:227.Google Scholar
  128. 128.
    Roux H, Peloux Y, Gaborit P, et al. Les manifestations ostéo-articulaires de la brucellose. EncMedChir Paris. 1983;14:1.Google Scholar
  129. 129.
    Turgut M, Turgut A, Koşar U. Spinal brucellosis: Turkish experience based on 452 cases published during the last century. Actaneurochirurgica. 2006;148(10):1033–44.Google Scholar
  130. 130.
    Bozgeyik Z, Ozdemir H, Demirdag K, Ozden M, Sonmezgoz F, Ozgocmen S. Clinical and MRI findings of brucellar spondylodiscitis. Eur J Radiol. 2008;67(1):153–8.PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    Tekkok IH, Berker M, Ozcan OE, et al. Brucellosis of the spine. Neurosurgery. 1993;33:838–44.PubMedGoogle Scholar
  132. 132.
    Iqbal QM, Khan O. Brucellosis of the spine. J R CollSurgEdinb. 1990;35:395–7.Google Scholar
  133. 133.
    Tu L, Liu X, Gu W, et al. Imaging-assisted diagnosis and characteristics of suspected spinal brucellosis: aretrospective study of 72 cases. Med Sci Monit. 2018;24:2647–54.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Arslan F, Karagoz E, Arslan BY, et al. Spinal brucellosis diagnosed with positron emission tomography combined with computed tomography (PET/CT). Spine J. 2016;16:e381–2.PubMedCrossRefGoogle Scholar
  135. 135.
    Lim K-B, Kwak Y-G, Kim D-Y, Kim Y-S, Kim J-A. Back pain secondary to Brucella spondylitis in the lumbar region. Ann Rehabil Med. 2012;36(2):282–6.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Cobbaert K, Pieters A, Devinck A, Devos M, Goethals I, Mielants H. Brucellarspondylodiscitis: case report. Acta Clin Belg. 2007;62(5):304–7.PubMedCrossRefGoogle Scholar
  137. 137.
    Lynch EC, McKechnie JC, Alfrey CP. Brucellosis with pancytopenia. Ann Intern Med. 1968;69:319.PubMedCrossRefGoogle Scholar
  138. 138.
    Uluğ M, Yaman Y, Yapici F, et al. Clinical and laboratory features complications and treatment outcome of brucellosis in childhood and review of the literature. Turk J Pediatr. 2011;53(4):413–24.PubMedGoogle Scholar
  139. 139.
    Eser B, Altuntas F, Soyuer I, et al. Acute lymphoblastic leukemia associated with brucellosis in two patients with fever and pancytopenia. YonseiMed J. 2006;47(5):741–4.CrossRefGoogle Scholar
  140. 140.
    Navarro-Martínez A, Solera J, Corredoira J, et al. Epididymoorchitisdueto. ClinInfectDis. 2001;33:2017.Google Scholar
  141. 141.
    Al Deeb SM, Yaqub BS, Sharif HS, et al. Neurobrucellosis: clinical characteristics, diagnosis and outcome. Neurology. 1989;39:498.PubMedCrossRefGoogle Scholar
  142. 142.
    Bashir R, Al-Kawl Z, Harder EJ, et al. Nervous system brucellosis: diagnosis and treatment. Neurology. 1985;35:1576.PubMedCrossRefPubMedCentralGoogle Scholar
  143. 143.
    Bouza E, de la Torre MG, Parras F, et al. Brucellar meningitis. RevInfectDis. 1987;9:810.Google Scholar
  144. 144.
    Karaoglan I, Namiduru M, Akcali A, Cansel N. Different manifestations of nervous system involvement by neurobrucellosis. Neurosciences. 2008;13:283–7.PubMedPubMedCentralGoogle Scholar
  145. 145.
    Elberg SS. A guide to the diagnosis, treatment and prevention of brucellosis. Bull WHO. 1981;81:31.Google Scholar
  146. 146.
    Bruguera M, Cervantes F. Hepatic granulomas in brucellosis. Ann Intern Med. 1980;92:571.PubMedCrossRefPubMedCentralGoogle Scholar
  147. 147.
    Spink WW, Hoffbauer FW, Walker WW, et al. Histopathology of the liver in human brucellosis. J Lab Clin Med. 1949;34:40.PubMedPubMedCentralGoogle Scholar
  148. 148.
    Arias Stella J. Brucellosis. Contribución al conocimiento patológico. Ann FacMed (Peru). 1951;34:429.Google Scholar
  149. 149.
    El-Koumi MA, Afify M, Al-Zahrani SH. A prospective study of brucellosis in children: relative frequency of pancytopenia. Iran J Pediatr. 2014;24(2):155–60.Google Scholar
  150. 150.
    Al-Anazi KA, Al-Jasser AM. Brucella bacteremia in patients with acute leukemia: a case series. J Med Case Rep. 2007;1:144.PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Mantur BG, Amarnath SK, Shinde RS, et al. Review of clinical and laboratory features of human brucellosis. Indian J MedMicrobiol. 2007;25(3):188–202.CrossRefGoogle Scholar
  152. 152.
    Al Hashan GM, el-Fetoh NMA, Nasser IA, et al. Pattern of childhood brucellosis in Najran, south Saudi Arabia in 2013–2017. Electron Physician. 2017;9(12):5902–7. Scholar
  153. 153.
    Sari I, Altuntas F, Hacioglu S, et al. A multicenter retrospective study defining the clinical and hematological manifestations of brucellosis and pancytopenia in a large series: hematological malignancies, the unusual cause of pancytopenia in patients with brucellosis. Am J Hematol. 2008;83(4):334–9.PubMedCrossRefPubMedCentralGoogle Scholar
  154. 154.
    Serpa JA, Knights S, Farmakiotis D, Campbell J. Brucellosis in adults and children: a 10-year case series at two large Academic Hospitals in Houston, Texas. SouthMed J. 2018;111(6):324–7.CrossRefGoogle Scholar
  155. 155.
    Solera J, Martinez-Alfaro E, Espinosa A. Recognition and optimum treatment of brucellosis. Drugs. 1997;53:245–56.PubMedCrossRefPubMedCentralGoogle Scholar
  156. 156.
    Salvana EMT, Salata RA. Brucellosis. In: Goldman L, Schafer AI, editors. Goldman-Cecil medicine. Philadelphia: Elsevier-Saunders; 2016.Google Scholar
  157. 157.
    Spink WW, Braude AI, Castaneda MR, et al. Aureomycin therapy in human brucellosis due to Brucella melitensis. JAMA. 1948;138:1145–8.CrossRefGoogle Scholar
  158. 158.
    Baykam N, Esener H, Egonul O, Eren S, Celikbas AK, Dokuzoguz B. In vitro antimicrobial susceptibility of Brucella species. Int J Antimicrob Agents. 2004;23:405–7.PubMedCrossRefPubMedCentralGoogle Scholar
  159. 159.
    Dimitrov TS, Panigrahi D, Emara M, Awni F, Passadilla R. Seropidemiological and microbiological study of brucellosis in Kuwait. Med PrincPract. 2004;13:215–9.Google Scholar
  160. 160.
    Ariza J, Gudiol F, Pallares R, et al. Comparative trial of rifampicin/doxycycline versus tetracycline/streptomycin in the therapy of human brucellosis. Antimicrob Agents Chemother. 1985;28:548–51.PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    Llorens-Terol J, Busquets RM. Brucellosis treated with rifampin. Arch Dis Child. 1980;55:486–8.PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Acocella G, Bertrand A, Beytout J, et al. Comparison of the three different regimens in the treatment of acute brucellosis: a multicenter study. J AntimicrobChemother. 1989;23:433–9.Google Scholar
  163. 163.
    Waitz JA, Weinstein MJ. Recent antimicrobiological studies with gentamicin. J InfectDis. 1969;119:355–60.CrossRefGoogle Scholar
  164. 164.
    Joint FAO/WHO expert committee on brucellosis. World Health Organ Tech Rep Ser. 1986;740:1–132.Google Scholar
  165. 165.
    Ariza J, Bosilwowski M, Cascio A, Colmenero JD, Corbel MJ, Falagas ME, et al. Perspectives for the treatment of brucellosis in the 21st century: the Ioannina recommendations. PLoSMed. 2007;4:1872–8.Google Scholar
  166. 166.
    Solera J, Martinez-Alfaro E, Saez L. Meta-analysis of the efficacy of the combination of rifampicin and doxycycline in the treatment of human brucellosis. Med Clin (Barc). 1994;102:731–8.Google Scholar
  167. 167.
    Colmenero Castillo JD, HernandezMarquez S, Reguera Iglesias JM, Cabrera Franquelo F, RiusDiaz F, et al. Comparative trial of doxycycline plus streptomycin versus doxycycline plus rifampin for the therapy of human brucellosis. Chemotherapy. 1989;35:146–52.PubMedCrossRefGoogle Scholar
  168. 168.
    Cisneros JM, Viciana P, Colmenero J, Pachon J, Martinez C, et al. Multicenter prospective study of treatment of Brucella melitensis brucellosis with doxycycline for 6 weeks plus streptomycin for 2 weeks. Antimicrob Agents Chemother. 1990;34:881–3.PubMedPubMedCentralCrossRefGoogle Scholar
  169. 169.
    Ariza J, Gudiol F, Pallares R, Viladrich PF, Rufi G, et al. Treatment of human brucellosis with doxycycline plus rifampin or doxycycline plus streptomycin. A randomized, double-blind study. Ann Intern Med. 1992;117:25–30.PubMedCrossRefGoogle Scholar
  170. 170.
    Solera J, Rodríguez-Zapata M, Geijo P, et al. Doxycycline-rifampin versus doxycycline-streptomycin in treatment of human brucellosis. AntimicrobAgentsChemother. 1995;39:2061–7.Google Scholar
  171. 171.
    Colmenero JD, Fernandez-Gallardo LC, Agundez JA, Sedeno J, Benitez J, et al. Possible implications of doxycycline-rifampin interaction for treatment of brucellosis. Antimicrob AgentsChemother. 1994;38:2798–802.CrossRefGoogle Scholar
  172. 172.
    Garraffo R, Dellamonica P, Fournier JP, Lapalus P, Bernard E, et al. Effects of rifampicin on the pharmacodynamics of doxycycline. PatholBiol (Paris). 1987;35:746–9.Google Scholar
  173. 173.
    Marianelli C, Ciuchini F, Tarantino M, Pasquali P, Adone R. Genetic bases of the rifampin resistance phenotype in Brucella spp. J ClinMicrobiol. 2004;42:5439–43.Google Scholar
  174. 174.
    Pappas G, Siozopoulou V, Akritidis N, Falagas ME. Doxycycline-rifampicin: Physicians’ inferior choice in brucellosis or how convenience reigns over science. J Infect. 2007;54:459–46.PubMedCrossRefPubMedCentralGoogle Scholar
  175. 175.
    Pappas G, Siozopoulou V, Saplaoura K, Vasiliou A, Christou L, et al. Health literacy in the field of infectious diseases: the paradigm of brucellosis. J Infect. 2007;54:40–5.PubMedCrossRefPubMedCentralGoogle Scholar
  176. 176.
    World Health Organization. Brucellosis in humans and animals. Geneva: WHO; 2006. WHO/CDS/EPR/2006.7.Google Scholar
  177. 177.
    Akova M, Uzun O, Akalin HE, Hayran M, Unal S, Gur D. Quinolones in treatment of human brucellosis: comparative trial of ofloxacin- rifampin versus doxycycline-rifampin. Antimicrob Agents Chemother. 1993;37:1831–4.PubMedPubMedCentralCrossRefGoogle Scholar
  178. 178.
    Karabay O, Sencan I, Kayas D, Sahin I. Ofloxacin plus rifampicin versus doxycycline plus rifampicin in the treatment of brucellosis: a randomized clinical trial. BMC Infect Dis. 2004;4:18.PubMedPubMedCentralCrossRefGoogle Scholar
  179. 179.
    Saltoglu N, Tasova Y, Inal AS, Seki T, Aksu HS. Efficacy of rifampicin plus doxycycline versus rifampicin plus quinolone in the treatment of brucellosis. Saudi Med J. 2002;23:921–4.PubMedPubMedCentralGoogle Scholar
  180. 180.
    Kalo T, Novi S, Nushi A, Dedja S. Ciprofloxacin plus doxycycline versus rifampicin plus doxycycline in the treatment of acute brucellosis. Med Mal Infect. 1996;26:587–9.CrossRefGoogle Scholar
  181. 181.
    Agalar C, Usubutun S, Turkyilmaz R. Ciprofloxacin and rifampicin versus doxycycline and rifampicin in the treatment of brucellosis. Eur J ClinMicrobiol Infect Dis. 1999;18:535–8.CrossRefGoogle Scholar
  182. 182.
    Skalsky K, Yahav D, Bishara J, Pitlik S, Leibovici L, Paul M. Treatment of human brucellosis: systematic review and meta-analysis of randomized controlled trials. BMJ. 2008;336:701–4.PubMedPubMedCentralCrossRefGoogle Scholar
  183. 183.
    Hashemi SH, Gachkar L, Keramat F, Mamani M, et al. Comparison of doxycycline- streptomycin, doxycycline-rifampin, and ofloxacin-rifampin in the treatment of brucellosis: a randomized clinical trial. Int J Infect Dis. 2012;16:e247–51.PubMedCrossRefPubMedCentralGoogle Scholar
  184. 184.
    Pappas G, Christou I, Akritidis N, Tsianos EV. Quinolones for brucellosis: treating old diseases with new drugs. ClinMicrobiol Infect. 2006;12:823–5.CrossRefGoogle Scholar
  185. 185.
    Hasanain A, Mahdy R, Mohamed A, Mostafa A. A randomized, comparative study of dual therapy (doxycycline- rifampin) versus triple therapy (doxycycline- rifampin- levofloxacin) for treating acute/subacute brucellosis. Braz J Infect Dis. 2016;20(3):250–4.PubMedCrossRefPubMedCentralGoogle Scholar
  186. 186.
    Solera J, Martinez-Alfaro E, Espinoza A, Castillejos MI, Geijo P, Rodríguez-Zapata M. Multivariate model for predicting relapses in human brucellosis. J Infect. 1998;36:85–92.PubMedCrossRefPubMedCentralGoogle Scholar
  187. 187.
    Raoult D, Houpikian P, TissotDupont H, Riss JM, Arditi-Djiane J, Brouqui P. Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine. Arch Intern Med. 1999;159:167–73.PubMedCrossRefPubMedCentralGoogle Scholar
  188. 188.
    Majzoobi MM, Hashemi SH, Mamani M, Keramat F, Poorolajal J, Basir HRG. Effect of hydroxychloroquine on treatment and recurrence of acute brucellosis: a single-blind randomized clinical trial. Int J Antimicrob Agents. 2018;51(3):365–9.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Eduardo Gotuzzo Herencia
    • 1
  • Karen Isabel Vega-Villanueva
    • 2
  1. 1.Department of Infectious, tropical and dermatological diseasesCayetano Heredia National HospitalLimaPeru
  2. 2.Department of Medicine – Section of RheumatologyCayetano Heredia National HospitalLimaPeru

Personalised recommendations