Francisella and Brucella*

Jeannine M. Petersen; Martin E. Schriefer; George F. Araj

doi:10.1128/9781555816728.ch44

Chapter 44 : Francisella and Brucella *

Authors: Jeannine M. Petersen, Martin E. Schriefer, George F. Araj

Content Type: Reference

Publication Year: 2011

Category: Clinical Microbiology

Book DOI: 10.1128/9781555816728

Chapter DOI: 10.1128/9781555816728.ch44

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:

Francisella and Brucella * , Page 1 of 2

< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555816728/9781555814632_Chap44-1.gif /docserver/preview/fulltext/10.1128/9781555816728/9781555814632_Chap44-2.gif

Abstract:

The family Francisellaceae, a member of the gamma subclass of proteobacteria, consists of the single genus Francisella. Francisella tularensis, Francisella novicida, Francisella philomiragia, and Francisella noatunensis as well as unclassified Francisella spp. comprise the genus. Characterization data indicate that these Francisella spp. are distinct from F. tularensis, F. novicida, and F. philomiragia. The genus Francisella comprises tiny gram-negative coccobacilli that can be distinguished from similar genera by several features. A few key differences separate species of the Francisella genus. Under microscopic examination of Gram-stained specimens, Francisella cells (single and pleomorphic) appear tiny and counterstain so faintly with safranin that they can easily be missed. It is important to consider that many F. tularensis PCR assays cross-react with F. novicida. All Francisella isolates examined to date are β-lactamase positive, so penicillins and cephalosporins are not effective and should not be used to treat tularemia. Antimicrobial susceptibility testing of F. tularensis is not usually performed in clinical microbiology laboratories because of safety concerns in working with this organism. Currently, the most effective treatment regimen and optimal duration of treatment remain unclear. Interpretation of serologic test results in relation to exposure, diagnosis, and prognosis of the disease necessitates an accurate assessment of the clinical history and current status of patients and understanding the usefulness and pitfalls of the laboratory tests. Positive cutoff titers in the Brucella agglutination test for diagnosis have generally been considered to be greater than equal to 160 in symptomatic patients.

Citation: Petersen J, Schriefer M, Araj G. 2011. Francisella and Brucella * , p 751-769. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch44

Key Concept Ranking

Central Nervous System Diseases: 0.5689908
Tumor Necrosis Factor alpha: 0.43443614
TaqMan Real-Time PCR Assay: 0.40483078

0.5689908

Highlighted Text: Show | Hide

Full text loading...

Figures

Francisella and Brucella*

[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555816728.chap44-1,webId=/content/author/10.1128/9781555816728.chap44-1,properties={foaf_givenname=Jeannine M., foaf_name=Jeannine M. Petersen, foaf_surname=Petersen}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555816728.chap44-2,webId=/content/author/10.1128/9781555816728.chap44-2,properties={foaf_givenname=Martin E., foaf_name=Martin E. Schriefer, foaf_surname=Schriefer}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555816728.chap44-3,webId=/content/author/10.1128/9781555816728.chap44-3,properties={foaf_givenname=George F., foaf_name=George F. Araj, foaf_surname=Araj}]]

/content/10.1128/9781555816728.chap44.fig44-1

FIGURE 1

F. tularensis on CA (A) and CHAB (B) after 48 hours of growth; B. melitensis on blood agar (C) and Mueller-Hinton broth (D) after 48 hours of growth.

10.1128/9781555816728/fig44-1_thmb.gif

10.1128/9781555816728/fig44-1.gif

FIGURE 1

F. tularensis on CA (A) and CHAB (B) after 48 hours of growth; B. melitensis on blood agar (C) and Mueller-Hinton broth (D) after 48 hours of growth.

/content/10.1128/9781555816728.chap44.fig44-2

FIGURE 2

Gram stain of F. tularensis (A) and B. melitensis (B). Magnification, ~ ×810.

10.1128/9781555816728/fig44-2_thmb.gif

10.1128/9781555816728/fig44-2.gif

FIGURE 2

Gram stain of F. tularensis (A) and B. melitensis (B). Magnification, ~ ×810.

/content/10.1128/9781555816728.chap44.fig44-3

FIGURE 3

DFA staining of a culture of F. tularensis. Magnification, ˜ ×490.

10.1128/9781555816728/fig44-3_thmb.gif

10.1128/9781555816728/fig44-3.gif

FIGURE 3

DFA staining of a culture of F. tularensis. Magnification, ˜ ×490.

References

/content/book/10.1128/9781555816728.chap44

1. Ahmed, K.,, K. A. Al-Matrouk,, G. Martinez,, K. Oishi,, V. O. Rotimi,, and T. Nagatake. 1999. Increased serum levels of interferon-gamma and interleukin-12 during human brucellosis. Am. J. Trop. Med. Hyg. 61: 425– 427.

2. Akova, M.,, D. Gür,, D. M. Livermore,, T. Kocagöz,, and H. E. Akalin. 1999. In vitro activities of antibiotics alone and in combination against Brucella melitensis at neutral and acidic pHs. Antimicrob. Agents Chemother. 43: 1298– 1300.

3. Al-Dahouk, S.,, P. Le Flèche,, K. Nöckler,, I. Jacques,, M. Grayon,, H. C. Scholz,, H. Tomaso,, G. Vergnaud,, and H. Neubauer. 2007. Evaluation of Brucella MLVA typing for human brucellosis. J. Microbiol. Methods 69: 137– 145.

4. Alton, G. G.,, L. M. Jones,, R. D. Angus,, and J. M. Verger. 1988. Techniques for the Brucellosis Laboratory. Institut National de la Recherche Agronomique, Paris, France.

5. Anda, P.,, J. S. del Pozo,, J. M. D. Garcia,, R. Escudero,, F. J. G. Peña,, M. C. L. Velasco,, R. E. Sellek,, M. R. J. Chillarón,, L. P. S. Serrano,, and J. F. M. Navarro. 2001. Waterborne outbreak of tularemia associated with crayfish fishing. Emerg. Infect. Dis. 7: 575– 582.

6. Araj, G. F. 1988. Profiles of brucella specific immunoglobulin G subclass in serum of patients with acute and chronic brucellosis. Serodiag. Immunother. Infect. Dis. 2: 401– 410.

7. Araj, G. F. 1999. Human brucellosis: a classical infectious disease with persistent diagnostic challenges. Clin. Lab. Sci. 12: 207– 212.

8. Araj, G. F. 2000. Human brucellosis revisited: a persistent saga in the Middle East. BMJ (Middle East) 7: 6– 15.

9. Araj, G. F.,, A. R. Lulu,, M. A. Saadah,, A. M. Mousa,, I. L. Strannegard,, and R. A. Shakir. 1986. Rapid diagnosis of central nervous system brucellosis by ELISA. J. Neuroimmunol. 12: 73– 82.

9a. Araj, G. F.,, and M. M. Kattar. 2003. Rapid diagnosis of human brucellosis using the Bact/Alert continuous culture monitoring system. Abstr. 103rd Annu. Meet. Am. Soc. Microbiol., abstract C-002.

10. Araj, G. F.,, A. R. Lulu,, M. Y. Mustafa,, and M. I. Khateeb. 1986. Evaluation of ELISA in the diagnosis of acute and chronic brucellosis in human beings. J. Hyg. Lond. 97: 457– 469.

11. Araj, G. F.,, G. M. Brown,, M. M. Haj,, and N. V. Madhavan. 1988. Assessment of Brucellosis Card Test in screening patients for brucellosis. Epidemiol. Infect. (London) 100: 389– 398.

12. Araj, G. F.,, A. R. Lulu,, M. I. Khateeb,, M. A. Saadah,, and R. A. Shakir. 1988. ELISA versus routine tests in the diagnosis of patients with systemic and neurobrucellosis. Acta Pathlol. Microbiol. Scand. 96: 171– 176.

13. Araj, G. F.,, and A. F. Kaufman. 1989. 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. 27: 1909– 1912.

14. Araj, G. F.,, R. Dhar,, J. L. Lastimoza,, and M. Haj. 1990. Indirect fluorescent-antibody test versus enzyme-linked immunosorbent assay and agglutination tests in the serodiagnosis of patients with brucellosis. Serodiag. Immunother. Infect. Dis. 4: 1– 8.

15. Araj, G. F.,, A. R. Lulu,, M. I. Khateeb,, and M. M. Haj. 1990. Specific IgE response in patients with brucellosis. Epidemiol. Infect. (London) 105: 571– 577.

16. Araj, G. F.,, and R. A. Azzam. 1996. Seroprevalence of brucella antibodies among persons in high-risk occupation in Lebanon. Epidemiol. Infect. 117: 281– 288.

17. Araj, G. F.,, M. Kattar,, L. G. Fattouh,, O. K. Bajakian,, and S. A. Kobeissi. 2005. Evaluation of the PANBIO Brucella immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays for diagnosis of human brucellosis. Clin. Diagn. Lab. Immunol. 12: 1334– 1335.

18. Ariza, J.,, T. Pellicer,, R. Pallares,, Z. Fox,, and F. Gudiol. 1992. Specific antibody profile in human brucellosis. Clin. Infect. Dis. 14: 131– 140.

19. Ariza, J.,, J. Corredoira,, R. Pallares,, P. F. Viladrich,, G. Rufi,, M. Pujol,, and F. Gudiol. 1995. Characteristics of and risk factors for relapse of brucellosis in humans. Clin. Infect. Dis. 20: 1241– 1249.

20. Ariza, J.,, M. Bosilkovski,, A. Cascio,, J. D. Colmenero,, M. J. Corbel,, M. E. Falagas,, Z. A., Memish,, M. R. Roushan,, E. Rubinstein,, N. V. Sipsas,, J. Solera,, E. J. Young,, and G. Pappas. 2007. Perspectives for the treatment of brucellosis in the 21st century: the Ioannina recommendations. PLoS Med. 4: e317.

21. Baldi, P.C.,, S. E. Miguel,, C. A. Fossati,, and J. C. Wallach. 1996. Serologic follow-up of human brucellosis by measuring IgG antibodies to LPS and cytoplasmic proteins of Brucella species. Clin. Infect. Dis. 22: 446– 455.

22. Barns, S. M.,, C. C. Grow,, R. T. Okinaka,, P. Keim,, and C. R. Kuske. 2005. Detection of diverse new Francisella-like bacteria in environmental samples. Appl. Environ. Microbiol. 71: 5494– 5500.

23. Behan, K. A.,, and G. C. Klein. 1982. Reduction of Brucella species and Francisella tularensis cross-reacting agglutinins by dithiothreitol. J. Clin. Microbiol. 16: 756– 757.

24. Bell, J. F., 1980. Tularemia, p. 161– 193. In J. H. Steele (ed.), CRC Handbook Series in Zoonoses. CRC Press, Boca Raton, FL.

25. Bevanger, L.,, J. A. Maeland,, and A. I. Kvam. 1994. Comparative analysis of antibodies to Francisella tularensis antigens during the acute phase of tularemia and eight years later. Clin. Diagn. Lab. Immunol. 1: 238– 240.

26. Birdsell, D. N.,, T. Stewart,, A. J. Vogler,, E. Lawaczeck,, A. Diggs,, T. L. Sylvester,, J. L. Buchhagen,, R. K. Auerbach,, P. Keim,, and D. M. Wagner. 2009. Francisella tularensis subsp. novicida isolated from a human in Arizona. BMC Res. Notes 2: 223.

27. Birkbeck, T. H.,, M. Bordevik,, M. K. Frøystad,, and A. Baklien. 2007. Identification of Francisella sp. from Atlantic salmon, Salmo salar L., in Chile. J. Fish Dis. 30: 505– 507.

28. Brew, S. D.,, L. L. Perrett,, J. A. Stack,, and A. P. MacMillan. 1999. Human exposure to Brucella recovered from a sea mammal. Vet. Res. 24: 483.

29. Brown, S. L.,, F. T. McKinney,, G. C. Klein,, and W. L. Jones. 1980. Evaluation of a safranin-O-stained antigen microagglutination test for Francisella tularensis antibodies. J. Clin. Microbiol. 11: 146– 148.

30. Celebi, G.,, F. Baruönü,, F. Ayoğlu,, F. Cinar,, A. Karadenizli,, M. B. Uğur,, and S. Gedikoğlu. 2006. Tularemia, a reemerging disease in northwest Turkey: epidemiological investigation and evaluation of treatment responses. Jpn. J. Infect. Dis. 59: 229– 234.

31. Centers for Disease Control and Prevention. 2002. Tularemia—United States, 1990-2000. MMWR Morb. Mortal. Wkly. Rep. 51: 182– 184.

32. Centers for Disease Control and Prevention. 2008. Update: potential exposures to attenuated vaccine strain Brucella abortus RB51 during a laboratory proficiency test—United States and Canada. MMWR Morb. Mortal. Wkly. Rep. 57: 36– 39.

33. Centers for Disease Control and Prevention. 2008. Laboratory-acquired brucellosis—Indiana and Minnesota, 2006. MMWR Morb. Mortal. Wkly. Rep. 57: 39– 42.

34. Centers for Disease Control and Prevention. 2008. Public health consequences of a false-positive laboratory test result for Brucella—Florida, Georgia, and Michigan. MMWR Morb. Mortal. Wkly. Rep. 57: 603– 605.

35. Clarridge, J. E., III,, T. J. Raich,, A. Sjöstedt,, G. Sandström,, R. O. Darouiche,, R. M. Shawar,, P. R. Georghiou,, C. Osting,, and L. Vo. 1996. Characterization of two unusual clinically significant Francisella strains. J. Clin. Microbiol. 34: 1995– 2000.

36. Clinical and Laboratory Standards Institute. 2006. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard—seventh edition. CLSI document M7-A7. Clinical and Laboratory Standards Institute, Wayne, PA.

37. Clinical and Laboratory Standards Institute. 2009. Performance standards for antimicrobial susceptibility testing; ninteeth informational supplement. M100-S19. Clinical and Laboratory Standards Institute, Wayne, PA.

38. Cloeckaert, A.,, J. Verger,, M. Grayon,, J. Paquet,, B. Garin-Bastuji,, G. Foster,, and J. Godfroid. 2001. Classification of Brucella spp. isolated from marine mammals by DNA polymorphism at the omp2 locus. Microbes Infect. 3: 729– 738.

39. Colmenero, J. D.,, J. M. Reguera,, F. Martos,, D. Sanchez-De-Mora,, M. Delgado,, M. Causse,, A. Martin-Farafan,, and C. Juarez. 1996. Complications associated with Brucella melitensis infection: a study of 530 cases. Medicine (Baltimore) 75: 195– 211.

40. Colmenero, J. D.,, N. L. Muñoz-Roca,, P. Bermudez,, A. Plata,, A. Villalobos,, and J. M. Reguera. 2007. Clinical findings, diagnostic approach, and outcome of Brucella melitensis epididymo-orchitis. Diagn. Microbiol. Infect. Dis. 57: 367– 372.

41. Corbel, M. J. 1997. Brucellosis: an overview. Emerg. Infect. Dis. 3: 213– 221.

42. Corbel, M. J.,, and N. J. Beeching,. 2005. Brucellosis, p. 914– 917. In D. L. Kasper,, E. Braunwald,, A. S. Fauci,, S. L. Hauser,, D. L. Longo,, and J. L. Jameson (ed.), Harrison’s Principles of Internal Medicine, 16th ed., vol. 1. McGraw-Hill, New York, NY.

43. DeBeaumont, C.,, P. A. Falconnet,, and M. Maurin. 2005. Real-time PCR for detection of Brucella spp. DNA in serum samples. Eur. J. Clin. Microbiol. Infect. Dis. 24: 842– 845.

44. Department of Health and Human Services, Centers for Disease Control and Prevention and National Institutes of Health. 2007. Biosafety in Microbiological and Biomedical Laboratories, 5th ed. Department of Health and Human Services, Centers for Disease Control and Prevention and National Institutes of Health, Washington, DC. http://www.cdc.gov/od/ohs/biosfty/bmbl5/bmbl5toc.htm.

45. Drancourt, M.,, P. Brouqui,, and D. Raoult. 1997. Afipia clevelandensis antibodies and cross-reactivity with Brucella spp. and Yersinia enterocolitica O:9. Clin. Diagn. Lab. Immunol. 4: 748– 752.

46. Eliasson, H.,, J. Lindbäck,, J. P. Nuorti,, M. Arneborn,, J. Giesecke,, and A. Tegnell. 2002. The 2000 tularemia outbreak: a case-control study of risk factors in disease-endemic and emergent areas, Sweden. Emerg. Infect. Dis. 8: 956– 960.

47. Eliasson, H.,, P. Olcén,, A. Sjöstedt,, M. Jurstrand,, E. Bäck,, and S. Andersson. 2008. Kinetics of the immune response associated with tularemia: comparison of an enzyme-linked immunosorbent assay, a tube agglutination test, and a novel whole-blood lymphocyte stimulation test. Clin. Vaccine Immunol. 15: 1238– 1243.

48. Ellis, J.,, P. C. Oyston,, M. Green,, and R. W. Titball. 2002. Tularemia. Clin. Microbiol. Rev. 15: 631– 646.

49. Ericsson, M.,, G. Sandström,, A. Sjöstedt,, and A. Tärnvik. 1994. Persistence of cell-mediated immunity and decline of humoral immunity to the intracellular bacterium Francisella tularensis. J. Infect. Dis. 170: 110– 114.

50. Escudero, R.,, M. Elía,, J. A. Sáez-Nieto,, V. Menéndez,, A. Toledo,, G. Royo,, M. Rodríguez-Vargas,, M. J. Whipp,, H. Gil,, I. Jado,, and P. Anda. 25 August 2009. A possible novel Francisella genomic species isolated from blood and urine of a patient with severe illness. Clin. Microbiol. Infect. [Epub ahead of print.] doi:10.1111/j.1469-0691.2009.03029.x.

51. Estevao, M. H.,, L. M. Baverosa,, L. M. Matos,, A. A. Barrosa,, and H. C. da Mota. 1995. Neurobrucellosis in children. Eur. J. Pediatr. 154: 120– 122.

52. Evans, M. E.,, D. W. Gregory,, W. Schaffner,, and Z. A. McGee. 1985. Tularemia: a 30-year experience with 88 cases. Medicine (Baltimore) 64: 251– 269.

53. Feldman, K. A., 2003. Tularemia. J. Am. Vet. Med. Assoc. 222: 725– 730.

54. Feldman, K. A.,, R. Enscore,, S. Lathrop,, B. Matyas,, M. McGuill,, M. Schriefer,, D. Stiles-Enos,, D. Dennis,, and E. Hayes. 2001. Outbreak of primary pneumonic tularemia on Martha’s Vineyard. N. Engl. J. Med. 345: 1601– 1606.

55. Fernandez-Prada, C. M.,, E. B. Zelazowska,, M. Nikolich,, T. L. Hadfield,, R. M. Roop,, G. L. Robertson,, and D. L. Hoover. 2003. Interaction between Brucella melitensis and human phagocytes: bacterial surface O-polysaccharide inhibits phagocytosis, bacterial killing, and subsequent host cell apoptosis. Infect. Immun. 71: 2110– 2119.

56. Forsman, M.,, G. Sandström,, and B. Jaurin. 1990. Identification of Francisella species and discrimination of type A and type B strains of F. tularensis by 16S rRNA analysis. Appl. Environ. Microbiol. 56: 949– 955.

57. Forsman, M.,, G. Sandström,, and A. Sjöstedt. 1994. Analysis of 16S ribosomal DNA sequences of Francisella strains and utilization for determination of the phylogeny of the genus and for identification of strains by PCR. Int. J. Syst. Bacteriol. 44: 38– 46.

58. Foster, G.,, B. S. Osterman,, J. Godfroid,, I. Jacques,, and A. Cloeckaert. 2007. Brucella ceti sp. nov., and Brucella pinnipedialis sp. nov for Brucella strains with cetaceans and seals as their preferred hosts. Int. J. Syst. Evol. Microbiol. 57: 2688– 2693.

59. Franco, M. P.,, M. Mulder,, R. H. Gilman,, and H. L. Smits. 2007. Human brucellosis. Lancet Infect. Dis. 7: 775– 786.

60. Friis-Møller, A.,, L. E. Lemming,, N. H. Valerius,, and B. Bruun. 2004. Problems in identification of Francisella philomiragia associated with fatal bacteremia in a patient with chronic granulomatous disease. J. Clin. Microbiol. 42: 1840– 1842.

61. Garrity, G. M.,, and J. G. Holt,. 2001. Taxonomic outline of the Archaea and Bacteria, p. 155– 166. In D. R. Boone, and R. C. Castenholz (ed.), Bergey’s Manual of Systematic Bacteriology, 2nd ed., vol. 1. Springer-Verlag, New York, NY.

62. Gazapo E.,, J. Gonzalez Lahoz,, J. L. Subiza,, M. Banquero,, J. Jil,, and E. G. de la Concha. 1989. Changes in IgM and IgG antibody concentration in brucellosis over time: importance for diagnosis and follow-up. J. Infect. Dis. 159: 219– 225.

63. Gilligan, P. H.,, and M. K. York. 2002. Basic Protocols for Level A Laboratories for the Presumptive Identification of Brucella Species. American Society for Microbiology, Washington, DC.

64. Godfroid, J.,, A. Cloeckaert,, J. Liautard,, S. Kohler,, D. Fretin,, K. Walravens,, B. Garin-Bastuji,, and J. Letesson. 2005. From the discovery of the Malta fever’s agent to the discovery of a marine mammal reservoir, brucellosis has continuously been a re-emerging zoonosis. Vet. Res. 36: 313– 326.

65. Goethert, H. K.,, I. Shani,, and S. R. Telford. 2004. Genotypic diversity of Francisella tularensis infecting Dermacentor variabilis ticks on Martha’s Vineyard, Massachusetts. J. Clin. Microbiol. 42: 4968– 4973.

66. Goldbaum, F. A.,, J. Leoni,, J. C. Wallach,, and C. A. Fossati. 1993. Characterization of an 18-kilodalton Brucella cytoplasmic protein which appears to be a serological marker of active infection of both human and bovine brucellosis. J. Clin. Microbiol. 31: 2141– 2145.

67. Golding, B.,, D. E. Scott,, O. Scharf,, L. Y. Huang,, M. Zaitseva,, C. Lapham,, N. Eller,, and H. Golding. 2001. Immunity and protection against Brucella abortus. Microbes Infect. 3: 43– 48.

68. Gómez, M. C.,, J. A. Nieto,, C. Rosa,, P. Geijo,, M. A. Escribano,, A. Muñoz,, and C. López. 2008. Evaluation of seven tests for diagnosis of human brucellosis in an area where the disease is endemic. Clin. Vaccine Immunol. 15: 1031– 1033.

69. Gorvel, J. P. 2008. Brucella: a Mr “Hide” converted into Dr Jekyll. Microbes Infect. 10: 1010– 1013.

70. Greenfield, R. A.,, D. A. Drevets,, L. J. Machado,, G. W. Voskuhl,, P. Cornea,, and M. S. Bronze. 2002. Bacterial pathogens as biological weapons and agents of bioterrorism. Am. J. Med. Sci. 323: 299– 315.

71. Guarner, J.,, P. R. Breer,, J. C. Bartlett,, M. C. Chu,, W. J. Shieh,, and S. R. Zaki. 1999. Immunohistochemical detection of Francisella tularensis in formalin-fixed paraffin-embedded tissue. Appl. Immunohistochem. Mol. Morphol. 7: 122– 126.

72. Gür, D.,, S. Kocagöz,, M. Akova,, and S. Unal. 1999. Comparison of E test to microdilution for determining in vitro activities of antibiotics against Brucella melitensis. Antimicrob. Agents Chemother. 43: 2337.

73. Halling, S. M.,, B. D. Peterson-Burch,, B. J. Bricker,, R. L. Zuerner,, Z. Qing,, L. Li,, V. Kapur,, D. P. Alt,, and S. C. Olsen. 2005. Completion of the genome sequence of Brucella abortus and comparison to the highly similar genomes of Brucella melitensis and Brucella suis. J. Bacteriol. 187: 2715– 2726.

74. Hollis, D. G.,, R. E. Weaver,, A. G. Steigerwalt,, J. D. Wenger,, C. W. Moss,, and D. J. Brenner. 1989. Francisella philomiragia comb. nov. (formerly Yersinia philomiragia) and Francisella tularensis biogroup novicida (formerly Francisella novicida) associated with human disease. J. Clin. Microbiol. 27: 1601– 1608.

75. Hopla, C. E.,, and A. K. Hopla,. 1994. Tularemia, p. 113– 126. In G. W. Beran, and J. H. Steele (ed.), Handbook of Zoonoses, 2nd ed. CRC Press, Boca Raton, FL.

76. Ibrahim, A. I. A.,, R. Awad,, S. D. Shetty,, M. Saad,, and N. E. Bilal. 1988. Genito-urinary complications of brucellosis. Br. J. Urol. 61: 294– 298.

77. Ikäheimo, I.,, H. Syrjälä,, J. Karhukorpi,, R. Schildt,, and M. Koskela. 2000. In vitro antibiotic susceptibility of Francisella tularensis isolated from humans and animals. J. Antimicrob. Chemother. 46: 287– 290.

78. Jantzen, E.,, B. P. Berdal,, and T. Omland. 1979. Cellular fatty acid composition of Francisella tularensis. J. Clin. Microbiol. 10: 928– 930.

79. Jellison, W. L. 1974. Tularemia in North America, 1930-1974, p. 1– 276. University of Montana, Missoula, MT.

80. Jellison, W. L.,, C. R. Owen,, J. F. Bell,, and G. M. Kohls. 1961. Tularemia and animal populations: ecology and epizootiology. Wildl. Dis. 17: 1– 15.

81. Jensen, W. I.,, C. R. Owen,, and W. L. Jellison. 1969. Yersinia philomiragia sp. n ., a new member of the Pasteurella group of bacteria, naturally pathogenic for the muskrat (Ondatra zibethica). J. Bacteriol. 100: 1237– 1241.

82. Johansson, A.,, L. Berglund,, U. Eriksson,, I. Göransson,, R. Wollin,, M. Forsman,, A. Tärnvik,, and A. Sjöstedt. 2000. Comparative analysis of PCR versus culture for diagnosis of ulceroglandular tularemia. J. Clin. Microbiol. 38: 22– 26.

83. Johansson, A.,, J. Farlow,, P. Larsson,, M. Dukerich,, E. Chambers,, M. Byström,, J. Fox,, M. Chu,, M. Forsman,, A. Sjöstedt,, and P. Keim. 2004. Worldwide genetic relationships among Francisella tularensis isolates determined by multiple-locus variable-number tandem repeat analysis. J. Bacteriol. 186: 5808– 5818.

84. Joint FAO/WHO Expert Committee on Brucellosis. 1986. Sixth report. World Health Organization Technical Report Series no. 740. World Health Organization, Geneva, Switzerland.

85. Kattar, M. M.,, P. A. Zallou,, G. F. Araj,, J. Samaha-Kfoury,, H. Shbaklo,, S. K. Kanj,, S. Khalife,, and M. Deeb. 2007. Development and evaluation of real-time polymerase chain reaction assays on whole blood and paraffin-embedded tissues for rapid diagnosis of human brucellosis. Diagn. Microbiol. Infect. Dis. 59: 23– 32.

86. Kattar, M. M.,, R. F. Jaafar,, G. F. Araj,, P. Le Flèche,, G. M. Matar,, R. Abi Rached,, S. Khalife,, and G. Vergnaud. 2008. Evaluation of a multilocus variable-number tandem-repeat analysis scheme for typing human Brucella isolates in a region of brucellosis endemicity. J. Clin. Microbiol. 46: 3935– 3940.

87. Kerr, W. R.,, W. J. McCaughey,, J. D. Coghlan,, D. J. H. Payn,, R. A. Quaife,, L. Robertson,, and I. D. Farell. 1968. Techniques and interpretation in the serological diagnosis of brucellosis in man. J. Med. Microbiol. 1: 181– 193.

88. Khatun, M.,, A. Islam,, B. K. Baek,, and S. I. Lee. 2009. Characteristics of the immune response during acute brucellosis in Sprague-Dawley rats. J. Infect. Dev. Ctries. 3: 392– 397.

89. Kugeler, K. J.,, N. Gurfield,, J. G. Creek,, K. S. Mahoney,, J. L. Versage,, and J. M. Petersen. 2005. Discrimination between Francisella tularensis and Francisella-like endosymbionts when screening ticks by PCR. Appl. Environ. Microbiol. 71: 7594– 7597.

90. Kugeler, K. J.,, P. S. Mead,, K. L. McGowan,, J. M. Burnham,, M. D. Hogarty,, E. Ruchelli,, K. Pollard,, B. Husband,, C. Conley,, T. Rivera,, T. Kelesidis,, W. M. Lee,, W. Mabey,, J. M. Winchell,, H. L. Stang,, J. E. Staples,, L. J. Chalcraft,, and J. M. Petersen. 2008. Isolation and characterization of a novel Francisella sp. from human cerebrospinal fluid and blood. J. Clin. Microbiol. 46: 2428– 2431.

91. Kugeler, K. J.,, P. S. Mead,, A. M. Janusz,, J. E. Staples,, K. A. Kubota,, L. G. Chalcraft,, and J. M. Petersen. 2009. Molecular epidemiology of Francisella tularensis in the United States. Clin. Infect. Dis. 48: 863– 870.

92. Larson, C. L.,, W. Wicht,, and W. L. Jellison. 1955. A new organism resembling P. tularensis isolated from water. Public Health Rep. 70: 253– 258.

93. Larsson, P.,, D. K. Elfsmark,, K. Svensson,, P. Wikström,, M. Forsman,, T. Brettin,, P. Keim,, and A. Johansson. 2009. Molecular evolutionary consequences of niche restriction in Francisella tularensis, a facultative intracellular pathogen. PLoS Pathog. 5: e1000472.

94. Leelaporn, A.,, S. Yongyod,, S. Limsrivanichakorn,, T. Yungyuen,, and P. Kiratisin. 2008. Francisella novicida bacteremia, Thailand. Emerg. Infect. Dis. 14: 1935– 1937.

95. Lindquist, D.,, M. C. Chu,, and W. S. Probert,. 2007. Francisella and Brucella, p. 815– 834. In P. R. Murray,, E. J. Baron,, J. H. Jorgensen,, M. L. Landry,, and M. A. Pfaller (ed.), Manual of Clinical Microbiology, 9th ed. ASM Press, Washington, DC.

96. Lista, F.,, G. Faggioni,, S. Valjevac,, A. Ciammaruconi,, J. Vaissaire,, C. Le Doujet,, O. Gorgé,, R. De Santis,, A. Carattoli,, A. Ciervo,, A. Fasanella,, F. Orsini,, R. D’Amelio,, C. Pourcel,, A. Cassone,, and G. Vergnaud. 2006. Genotyping of Bacillus anthracis strains based on automated capillary 25-loci multiple locus variable-number tandem repeats analysis. BMC Microbiol. 6: 33.

97. Lubani, M. M.,, K. Dudin,, G. F. Araj,, D. S. Manaudhar,, and F. Y. Rachid. 1989. Neurobrucellosis in children. Pediatr. Infect. Dis. J. 8: 79– 82.

98. Lubani, M. M.,, K. I. Dudin,, D. C. Sharda,, D. S. Manadhar,, G. F. Araj,, A. H. Hafez,, Q. A. Al Saleh,, I. Helin,, and M. M. Salhi. 1989. A multicenter therapeutic study of 1100 children with brucellosis. Pediatr. Infect. Dis. J. 8: 75– 78.

99. Lubani, M. M.,, K. I. Dudin,, D. C. Sharda,, N. M. Abu Sinna,, T. Al-Shab,, A. A. Al-Refe’ai,, S. M. Labani,, and A. Nasrallah. 1998. Neonatal brucellosis. Eur. J. Pediatr. 147: 520– 522.

100. Lulu, A. R.,, G. F. Araj,, M. I. Khateeb,, M. Y. Mustafa,, A. R. Yusuf,, and F. F. Fenech. 1988. Human brucellosis in Kuwait: a prospective study of 400 cases. Q. J. Med. 66: 39– 54.

101. Lulu, A. R.,, and G. F. Araj,. 1991. Pulmonary complications of brucellosis, p. 157– 176. In O. P. Sharma (ed.), Lung Disease in the Tropics. Marcel Dekker Inc., New York, NY.

102. Madkour, M. M., 1989. Overview, p. 71– 89. In M. M. Madkour (ed.), Brucellosis. Butterworths, University Press, Cambridge, United Kingdom.

103. Makhseed, M.,, A. Harouny,, G. F. Araj,, M. A. Mousa,, and P. Sharma. 1998. Obstetric and gynecologic implication of brucellosis in Kuwait. J. Perinatol. 8: 196– 199.

104. Makis, A. C.,, E. Galanakis,, E. C. Hazmichael,, Z. L. Papadopoulou,, A. Simopoulou,, and K. L. Bourantas. 2005. Serum levels of soluble interleukin-2 receptor alpha (sIL-2Ralpha) as a predictor of outcome in brucellosis. J. Infect. 51: 206– 210.

105. Mantecon, M. A.,, P. Gutierrez,, M. del Pilar Zarzosa,, A. I. Duenas,, J. Solera,, L. Fernández-Lago,, N. Vizcaíno,, A. Almaraz,, M. A. Bratos,, A. Rodríguez Torres,, and A. Orduña-Domingo. 2006. Utility of an immunocapture-agglutination test and an enzyme-linked immunosorbent assay test against cytosolic proteins from Brucella melitensis B115 in the diagnosis and follow-up of human acute brucellosis. Diagn. Microbiol. Infect. Dis. 55: 27– 35.

106. Mantur, B. G.,, S. K. Amarnath,, and R. S. Shinde. 2007. Review of clinical and laboratory features of human brucellosis. Ind. J. Med. Microbiol. 25: 188– 202.

107. Marianelli, C.,, C. Graziani,, C. Santangelo,, M. T. Xibilia,, A. Imbriani,, R. Amato,, D. Neri,, M. Cuccia,, S. Rinnone,, V. Di Marco,, and F. Ciuchini. 2007. Molecular epidemiological and antibiotic susceptibility characterization of Brucella isolates from humans in Sicily, Italy. J. Clin. Microbiol. 45: 2923– 2928.

108. Martín, C. M.,, T. Gallardo,, L. Mateos,, E. Vián,, M. J. García,, J. Ramos,, A. C. Berjón,, M. del CarmenViña,, M. P. García,, J. Yáñez,, L. C. González,, T. Muñoz,, M. Allue,, C. Andrés,, C. Ruiz,, and J. Castrodeza. 2007. Outbreak of tularaemia in Castilla y León, Spain. Euro Surveill. 12: E071108.1

109. Matyas, B. T.,, H. S. Nieder,, and S. R. Telford III. 2007. Pneumonic tularemia on Martha’s Vineyard: clinical, epidemiologic, and ecological characteristics. Ann. N. Y. Acad. Sci. 1105: 351– 377.

110. Mayefield, J. E.,, B. J. Bricker,, H. Godfrey,, R. M. Crosby,, D. J. Knight,, S. M. Halling,, D. Balinsky,, and L. B. Tabatabai. 1988. The cloning, expression and nucleotide sequence of a gene (BCS P31) coding for an immunogenic B. abortus protein (31 KDa). Gene 63: 1– 9.

111. McDonald, W. L.,, R. Jamaludin,, G. Mackereth,, M. Hansen,, S. Humphrey,, and P. Short. 2006. Characterization of a Brucella sp. strain as a marine-mammal type despite isolation from a patient with spinal osteomyelitis in New Zealand. J. Clin. Microbiol. 44: 4363– 4370.

112. Memish, Z. A.,, and H. H. Balkhy. 2004. Brucellosis and international travel. J. Travel Med. 11: 49– 55.

113. Mercier, E.,, E. Jumas-Bilak,, A. Allardet-Servent,, D. O’Callaghan,, K. F. Meyer,, and E. B. Shaw. 1996. A comparison of the morphologic, culture and biochemical characteristics of B. abortus and B. melitensis: studies on the genus Brucella nov. gen. I. J. Infect. Dis. 27: 173– 184.

114. Mikalsen, J.,, A. B. Olsen,, T. Tengs,, and D. J. Colquhoun. 2007. Francisella philomiragia subsp. noatunensis subsp. nov., isolated from farmed Atlantic cod (Gadus morhua L.). Int. J. Syst. Evol. Microbiol. 57: 1960– 1965.

115. Mitka, S.,, C. Anetakis,, E. Souliou,, E. Diza,, and A. Kansouzidou. 2007. Evaluation of different PCR assays for the early detection of acute and relapsing human brucellosis in comparison with conventional methods. J. Clin. Microbiol. 45: 1211– 1218.

116. Molins, C. R.,, J. K. Carlson,, J. Coombs,, and J. M. Petersen. 2009. Identification of Francisella tularensis subsp. tularensis A1 and A2 infections by real-time polymerase chain reaction. Diagn. Microbiol. Infect. Dis. 64: 6– 12.

117. Molins, C. R.,, and J. M. Petersen. 2010. Subpopulations of F. tularensis subspecies tularensis and holarctica: identification and associated epidemiology. Future Microbiol. 5: 649– 661.

118. Molins, C. R.,, M. Delorey,, B. M. Yockey,, J. W. Young,, S. W. Sheldon,, S. M. Reese,, M. E. Schriefer,, and J. M. Petersen. 2010. Virulence comparison among Francisella tularensis subsp. tularensis clades in mice. PLoS One 5( 4): e10205.

119. Morata, P.,, M. I. Quiepo-Ortuno,, J. M. Reguera,, F. Miralles,, J. J. Lopez-Gonzalez,, and J. D. Colmenero. 2001. Diagnostic yield of a PCR assay in focal complications of brucellosis. J. Clin. Microbiol. 39: 3743– 3746.

120. Moriyon, I.,, and I. Lopez-Goni. 1998. Structure and properties of the outer membranes of Brucella abortus and Brucella melitensis. Int. Microbiol. 1: 19– 26.

121. Naparstek, E.,, C. S. Block,, and S. Slavin. 1982. Transmission of brucellosis by bone marrow transplantation. Lancet i: 574– 575.

122. Navarro, E.,, J. C. Segura,, M. J. Castaño,, and J. Solera. 2006. Use of real-time quantitative polymerase chain reaction to monitor the evolution of Brucella melitensis DNA load during therapy and post-therapy follow-up in patients with brucellosis. Clin. Infect. Dis. 42: 1266– 1273.

123. Navarro-Martinez, A.,, E. Navarro,, M. J. Castano,, and J. Solera. 2008. Rapid diagnosis of human brucellosis by quantitative real-time PCR: a case report of brucellar spondylitis. J. Clin. Microbiol. 46: 385– 387.

124. Noviello, S.,, R. Gallo,, M. Kelly,, R. J. Limberger,, K. De Angelis,, L. Cain,, B. Wallace,, and N. Dumas. 2004. Laboratory-acquired brucellosis. Emerg. Infect. Dis. 10: 1848– 1850.

125. Ohara, S.,, T. Sato,, and M. Homma. 1974. Serological studies on Francisella tularensis, Francisella novicida, Yersinia philomiragia, and Brucella abortus. Int. J. Syst. Bacteriol. 24: 191– 196.

126. Oliveira, S.,, and G. A. Splitter. 1996. Immunization of mice with recombinant L7/L12 ribosomal protein confers protection against Brucella abortus infection . Vaccine 14: 959– 962.

127. Olsufiev, N. G.,, O. S. Emelyanova,, and T. N. Dunaeva. 1959. Comparative study of strains of B. tularense in the old and new world and their taxonomy. J. Hyg. Epidemiol. Microbiol. Immunol. 3: 138– 149.

128. Olsufjev, N. G.,, and I. S. Meshcheryakova. 1982. Infraspecific taxonomy of tularemia agent Francisella tularensis McCoy et Chapin. J. Hyg. Epidemiol. Microbiol. Immunol. 3: 291– 299.

129. Orduña, A.,, A. Almarza,, A. Prado,, M. P. Gutierrez,, A. Garcia-Pascual,, A. Duenas,, M. Cuervo,, R. Abad,, B. Hernandez,, B. Lorenzo,, M. A. Bratos,, and A. R. Torres. 2000. Evaluation of an immunocapture-agglutination test (Brucellacapt) for serodiagnosis of human brucellosis. J. Clin. Microbiol. 38: 4000– 4005.

130. Orhan, G.,, A. Bayram,, Y. Zer,, and I. Balci. 2005. Synergy tests by E test and checkerboard methods of antimicrobial combinations against Brucella melitensis. J. Clin. Microbiol. 43: 140– 143.

131. Ottem, K. F.,, A. Nylund,, E. Karlsbakk,, A. Friis-Møller,, and T. Kamaishi. 2009. Elevation of Francisella philomiragia subsp. noatunensis Mikalsen et al. (2007) to Francisella noatunensis comb. nov. [syn. Francisella piscicida Ottem et al. ( 2008 ) syn. nov.] and characterization of Francisella noatunensis subsp. orientalis subsp. nov., two important fish pathogens. J. Appl. Microbiol. 106: 1231– 1243.

132. Overholt, E. I.,, W. D. Tigertt,, P. J. Kadull,, M. K. Ward,, N. D. Charkes,, R. M. Rene,, T. E. Salzman,, and M. Stephens. 1961. An analysis of forty-two cases of laboratory-acquired tularemia. Am. J. Med. 30: 785– 806.

133. Owen, C. R.,, E. O. Buker,, W. L. Jellison,, D. B. Lackman,, and J. F. Bell. 1964. Comparative studies of Francisella tularensis and Francisella novicida. J. Bacteriol. 87: 676– 683.

134. Palanduz, A.,, S. Palanduz,, K. Guler,, and N. Guler. 2000. Brucellosis in a mother and her young infant: probable transmission by breast milk. Int. J. Infect. Dis. 4: 55– 56.

135. Pappas, G.,, N. Akritidis,, M. Bosilkovski,, and E. Tsianos. 2005. Brucellosis. New Engl. J. Med. 35: 2325– 2336.

136. Pappas, G.,, P. Pangopoulou,, L. Christou,, and N. Akritidis. 2006. Category B potential bioterrorism agents: bacteria, viruses, toxins, and foodborne and waterborne pathogens. Infect. Dis. Clin. N. Am. 20: 395– 421.

137. Pappas, G.,, P. Papadimitriou,, N. Akritidis,, L. Christou,, and E. Tsianos. 2006. The new global map of human brucellosis. Lancet Infect. Dis. 6: 91– 99.

138. Paton, N. I.,, N. W. Teu,, C. F. Vu,, and T. P. Teo. 2001. Brucellosis due to blood transfusion. Clin. Infect. Dis. 32: 1248.

139. Payne, L.,, M. Arneborn,, A. Tegnell,, and J. Giesecke. 2005. Endemic tularemia, Sweden, 2003. Emerg. Infect. Dis. 11: 1440– 1442.

140. Pellicer, T.,, J. Ariza,, Z. Fox,, R. Pallares,, and F. Gudiol. 1988. Specific antibodies during relapse of human brucellosis. J. Infect. Dis. 157: 918– 924.

141. Petersen, J. M.,, M. E. Schriefer,, K. L. Gage,, J. A. Montenieri,, L. G. Carter,, M. Stanley,, and M. C. Chu. 2004. Methods for enhanced culture recovery of Francisella tularensis. Appl. Environ. Microbiol. 70: 3733– 3735.

142. Petersen, J. M.,, J. K. Carlson,, G. Dietrich,, R. J. Eisen,, J. Coombs,, A. M. Janusz,, J. Summers,, C. B. Beard,, and P. S. Mead. 2008. Multiple Francisella tularensis subspecies and clades, tularemia outbreak, Utah. Emerg. Infect. Dis. 14: 1928– 1930.

143. Petersen, J. M.,, J. Carlson,, B. Yockey,, S. Pillai,, C. Kuske,, G. Garbalena,, S. Pottumarthy,, and L. Chalcraft. 2009. Direct isolation of Francisella spp. from environmental samples. 48: 663– 667.

144. Petersen, J. M.,, P. S. Mead,, and M. E. Schriefer. 2009. Francisella tularensis: an arthropod-borne pathogen. Vet. Res. 40: 07.

145. Pike, R. M. 1976. Laboratory-associated infections: summary and analysis of 3921 cases. Health Lab. Sci. 13: 105– 114.

146. Porsch-Özcürümez, M.,, N. Kischel,, H. Priebe,, W. Splettstösser,, E. J. Finke,, and R. Grunow. 2004. Comparison of enzyme-linked immunosorbent assay, Western blotting, microagglutination, indirect immuno-fluorescence assay, and flow cytometric serological diagnosis of tularemia. Clin. Diagn. Lab. Immunol. 11: 1008– 1015.

147. Probert, W. S.,, K. N. Schrader,, N. Y. Khuong,, S. L. Bystrom,, and M. H. Graves. 2004. Real-time multiplex PCR assay for detection of Brucella spp., B. abortus, and B. melitensis. J. Clin. Microbiol. 42: 1290– 1293.

148. Quipo-Ortuño, M. I.,, J. D. Colmenero,, M. J. Bravo,, M. A. García-Ordoñez,, and P. Morata. 2008. Usefulness of a quantitative real-time PCR assay using serum samples to discriminate between inactive, serologically positive and active human brucellosis. Clin. Microbiol. Infect. 14: 1128– 1134.

149. Quipo-Ortuño, M. I.,, F. Tena,, J. D. Colmenero,, and P. Morata. 2008. Comparison of seven commercial DNA extraction kits for the recovery of Brucella DNA from spiked human serum samples using real-time PCR. Eur. J. Clin. Microbiol. Infect. Dis. 27: 109– 114.

150. Reintjes, R.,, I. Dedushaj,, A. Gjini,, T. R. Jorgensen,, B. Cotter,, A. Lieftucht,, F. D’Ancona,, D. T. Dennis,, M. A. Kosoy,, G. Mulliqi-Osmani,, R. Grunow,, A. Kalaveshi,, L. Gashi,, and I. Humolli. 2002. Tularemia outbreak investigation in Kosovo: case control and environmental studies. Emerg. Infect. Dis. 8: 69– 73.

151. Rossetti, O. L.,, A. I. Arese,, M. L. Boschiroli,, and S. L. Cravero. 1996. Cloning of B. abortus gene and characterization of expressed 26-kilodalton periplasmic protein: potential use for diagnosis. J. Clin. Microbiol. 34: 165– 169.

152. Rotz, L. D.,, A. S. Kahn,, S. R. Lillibridge,, S. M. Ostroff,, and J. M. Hughes. 2002. Public health assessment of potential biological terrorism agents. Emerg. Infect. Dis. 8: 225– 230.

153. Ruben, B.,, J. D. Band,, P. Wong,, and J. Colvelli. 1991. Person-to-person transmission of Brucella melitensis. Lancet i: 14– 15.

154. Ruiz-Mesa, J. D.,, J. Sánchez-Gonzalez,, J. M. Reguera,, L. Martin,, S. Lopez-Palmero,, and J. D. Colmenero. 2005. Rose Bengal test: diagnostic yield and use for the rapid diagnosis of human brucellosis in emergency departments in endemic areas. Clin. Microbiol. Infect. 11: 221– 225.

155. Rusnak, J. M.,, M. G. Kortepeter,, R. J. Hawley,, A. O. Anderson,, E. Boudreau,, and E. Eitzen. 2004. Risk of occupationally acquired illnesses from biological threat agents in unvaccinated laboratory workers. Biosecur. Bioterror. 2: 281– 293.

156. Samra, Y.,, Y. Shaked,, M. Hertz,, and G. Altman. 1983. Brucellosis: difficulties in diagnosis and a report on 38 cases. Infection 11: 310– 312.

157. Sandström, G.,, A. Sjöstedt,, M. Forsman,, N. V. Pavlovich,, and B. N. Mishankin. 1992. Characterization and classification of strains of Francisella tularensis isolated in the Central Asian focus of the Soviet Union, and in Japan. J. Clin. Microbiol. 30: 172– 175.

158. Sangari, F. J.,, A. Seoane,, M. C. Rodriguez,, J. Aguero,, and M. Garcia Lobo. 2007. Characterization of the urease operon of Brucella abortus and assessment of its role in virulence of the bacterium. Infect. Immun. 75: 774– 780.

159. Schmitt, P.,, W. Splettstosser,, M. Porsch-Özcürümez,, E. J. Finke,, and R. Grunow. 2005. A novel screening ELISA and a confirmatory Western blot useful for diagnosis and epidemiological studies of tularemia. Epidemiol. Infect. 133: 759– 766.

160. Scoles, G. A. 2004. Phylogenetic analysis of the Francisella-like endosymbionts of Dermacentor ticks. J. Med. Entomol. 41: 277– 286.

161. Shakir, R. A.,, A. S. N. Al-Din,, G. F. Araj,, A. R. Lulu,, A. R. Mousa,, and M. A. Saadah. 1987. Clinical categories of neurobrucellosis: a report on 19 cases. Brain 110: 213– 223.

162. Shapiro, D. S.,, and D. R. Schwartz. 2002. Exposure of laboratory workers to Francisella tularensis despite a bioterrorism procedure. J. Clin. Microbiol. 40: 2278– 2281.

163. Sharda, D. C.,, and M. M. Lubani. 1986. A study of brucellosis in childhood. Clin. Pediatr. 25: 492– 495.

164. Sicherer, S. H.,, E. J. Asturias,, J. A. Winkelstein,, J. D. Dick,, and R. E. Willoughby. 1997. Francisella philomiragia sepsis in chronic granulomatous disease. Pediatr. Infect. Dis. J. 16: 420– 422.

165. Sjöstedt, A., 2005. Francisella, p. 200– 210. In D. J. Brenner,, N. R. Krieg,, J. T. Staley,, and G. M. Garrity (ed.), Bergey’s Manual of Systematic Bacteriology, 2nd ed., vol. 2. The Proteobacteria. Springer-Verlag, New York, NY.

166. Sjöstedt, A. 2007. Tularemia: history, epidemiology, pathogen physiology, and clinical manifestations. Ann. N. Y. Acad. Sci. 1105: 1– 29.

167. Sjöstedt, A.,, U. Eriksson,, L. Berglund,, and A. Tärnvik. 1997. Detection of Francisella tularensis in ulcers of patients with tularemia by PCR. J. Clin. Microbiol. 35: 1045– 1048.

168. Skalsky, K.,, D. Yahav,, J. Bishara,, S. Pitlik,, L. Leibovici,, and M. Paul. 2008. Treatment of human brucellosis: systematic review and meta-analysis of randomised controlled trials. BMJ 336: 701– 704.

169. Smits, H. L.,, T. H. Abdoel,, J. Solera,, E. Clavijo,, and R. Dial. 2003. Immunochromatographic Brucella-specific immunoglobulin M and G lateral flow assays for rapid serodiagnosis of human brucellosis. Clin. Diagn. Lab. Immunol. 10: 1141– 1146.

170. Sohn, A. H.,, W. S. Probert,, C. A. Glaser,, N. Gupta,, A. W. Bollen,, J. D. Wong,, E. M. Grace,, and W. C. McDonald. 2003. Human neurobrucellosis with intra-cerebral granuloma caused by a marine mammal Brucella spp. Emerg. Infect. Dis. 9: 485– 488.

171. Solera, J.,, E. Martinez-Alfaro,, A. Espinosa,, M. L. Castillejos,, P. Geijo,, and M. Rodriguez-Zapata. 1998. Multivariate model for predicting relapse in human brucellosis. J. Infect. 36: 85– 92.

172. Spink, W. W. 1956. The Nature of Brucellosis. University of Minnesota Press, Minneapolis.

173. Sréter-Lancz, Z.,, Z. Széll,, T. Sréter,, and K. Márialigeti. 2008. Detection of a novel Francisella in Dermacentor reticulatus: a need for careful evaluation of PCR-based identification of Francisella tularensis in Eurasian ticks. Vector Borne Zoonotic Dis. 9: 123– 126.

174. Staples, J. E.,, K. A. Kubota,, L. G. Chalcraft,, P. S. Mead,, and J. M. Petersen. 2006. Epidemiologic and molecular analysis of human tularemia, United States, 1964-2004. Emerg. Infect. Dis. 12: 1113– 1118.

175. Surcel, H. M.,, J. Ilonen,, K. Poikonen,, and E. Herva. 1989. Francisella tularensis-specific T-cell clones are human leukocyte antigen class II restricted, secrete interleukin-2 and gamma interferon, and induce immunoglobulin production. Infect. Immun. 57: 2906– 2908.

176. Surcel, H. M.,, M. Sarvas,, I. M. Helander,, and E. Herva. 1989. Membrane proteins of Francisella tularensis LVS differ in ability to induce proliferation of lymphocytes from tularemia-vaccinated individuals. Microb. Pathog. 7: 411– 419.

177. Syrjälä, H.,, R. Schildt,, and S. Räisäinen. 1991. In vitro susceptibility of Francisella tularensis to fluoroquinolones and treatment of tularemia with norfloxacin and ciprofloxacin. Eur. J. Clin. Microbiol. Infect. Dis. 10: 68– 70.

178. Tärnvik, A. 1989. Nature of protective immunity to Francisella tularensis. Rev. Infect. Dis. 11: 440– 451.

179. Tärnvik, A.,, and M. C. Chu. 2007. New approaches to diagnosis and therapy of tularemia. Ann. N. Y. Acad. Sci. 1105: 378– 404.

180. Thalhammer, F.,, G. Eberl,, and U. Kopetzki-Kogler. 1998. Unusual route of transmission for Brucella abortus. Clin. Infect. Dis. 26: 763– 764.

181. Tomaso, H.,, S. Al Dahouk,, E. Hofer,, W. D. Splettstoesser,, T. M. Treu,, M. P. Dierich,, and H. Neubauer. 2005. Antimicrobial susceptibilities of Austrian Francisella tularensis holarctica biovar II strains. Int. J. Antimicrob. Agents 26: 279– 284.

182. Urich, S. K.,, and J. M. Petersen. 2008. In vitro susceptibility of isolates of Francisella tularensis types A and B from North America. Antimicrob. Agents Chemother. 52: 2276– 2278.

183. Uwaydah, M.,, A. Khalil,, N. Shamsuddine,, F. Matar,, and G. F. Araj. 1998. Brucella-ovarian dermoid cyst causing initial treatment failure in a patient with acute brucellosis. Infection 26: 131– 132.

184. Valade, E.,, J. Vaissaire,, A. Mérens,, E. Hernandez,, C. Gros,, C. Le Doujet,, J. C. Paucod,, F. M. Thibault,, B. Durand,, M. Lapalus,, I. Dupuis,, A. Caclard,, D. R. Vidal,, and J. D. Cavallo. 2008. Susceptibility of 71 French isolates of Francisella tularensis subsp. holarctica to eight antibiotics and accuracy of the Etest method. J. Antimicrob. Chemother. 62: 208– 210.

185. Vanderca, B. 1990. Isolation of Brucella melitensis from human sperm. Eur. J. Clin. Microbiol. Infect. Dis. 9: 303– 304.

186. Versage, J. L.,, D. D. Severin,, M. C. Chu,, and J. M. Petersen. 2003. Development of a multitarget real-time TaqMan PCR assay for enhanced detection of Francisella tularensis in complex specimens. J. Clin. Microbiol. 41: 5492– 5499.

187. Viljanen, M. K.,, T. Nurmi,, and A. Salminen. 1983. Enzyme-linked immunosorbent assay (ELISA) with bacterial sonicate antigen for IgM, IgA, and IgG antibodies to Francisella tularensis: comparison with bacterial agglutination test and ELISA with lipopolysaccharide antigen. J. Infect. Dis. 148: 715– 720.

188. Vogler, A. J.,, D. Birdsell,, L. B. Price,, J. R. Bowers,, S. M. Beckstrom-Sternberg,, R. K. Auerbach,, J. S. Beckstrom-Sternberg,, A. Johansson,, A. Clare,, J. L. Buchhagen,, J. M. Petersen,, T. Pearson,, J. Vaissaire,, M. P. Dempsey,, P. Foxall,, D. M. Engelthaler,, D. M. Wagner,, and P. Keim. 2009. Phylogeography of Francisella tularensis: global expansion of a highly fit clone. J. Bacteriol. 191: 2474– 2484.

189. Vrioni, G.,, C. Gartzonika,, A. Kostoula,, C. Boboyiami,, C. Papadopoulou,, and S. Levidiotou. 2004. Application of a polymerase chain reaction enzyme immunoassay in peripheral whole blood and serum specimens for diagnosis of acute human brucellosis. Eur. J. Clin. Microbiol. Infect. Dis. 23: 194– 199.

190. Waag, D. M.,, K. T. McKee, Jr.,, G. Sandström,, L. L. K. Pratt,, C. R. Bolt,, M. J. England,, G. O. Nelson,, and J. C. Williams. 1995. Cell-mediated and humoral immune responses after vaccination of human volunteers with the live vaccine strain of Francisella tularensis. Clin. Diagn. Lab. Immunol. 2: 143– 148.

191. Wenger, J. D.,, D. G. Hollis,, R. E. Weaver,, C. N. Baker,, G. R. Brown,, D. J. Brenner,, and C. V. Broome. 1989. Infection caused by Francisella philomiragia (formerly Yersinia philomiragia): a newly recognized human pathogen. Ann. Intern. Med. 110: 888– 892.

192. Weyant, R. S.,, C. W. Moss,, R. E. Weaver,, D. G. Hollis,, J. G. Jordan,, E. C. Cook,, and M. I. Daneshvar. 1996. Identification of Unusual Pathogenic Gram-Negative Aerobic and Facultatively Anaerobic Bacteria, 2nd ed. The Williams & Wilkins Co., Baltimore, MD.

193. Whatmore, A. M. 2009. Current understanding of the genetics diversity of Brucella, an expanding genus of zoonotic pathogens. Infect. Genet. Evol. 9: 1168– 1184.

194. Whipp, M. J.,, J. M. Davis,, G. Lum,, J. de Boer,, Y. Zhou,, S. W. Bearden,, J. M. Petersen,, M. C. Chu,, and G. Hogg. 2003. Characterization of a novicida-like subspecies of Francisella tularensis in Australia. J. Med. Microbiol. 52: 839– 842.

195. Willke, A.,, M. Meric,, R. Grunow,, M. Sayan,, E. J. Finke,, W. Splettstösser,, E. Seibold,, S. Erdogan,, O. Ergonul,, Z. Yumuk,, and S. Gedikoglu. 2009. An outbreak of oropharyngeal tularaemia linked to natural spring water. J. Med. Microbiol. 58: 112– 116.

196. World Health Organization. 2006. Brucellosis in humans and animals, p. 36– 41. WHO/CDS/EPR/2006.7. World Health Organization, Geneva, Switzerland.

197. World Health Organization. 2007. WHO guidelines on tularemia. World Health Organization, Geneva, Switzerland. http://www.cdc.gov/tularemia/resources/whotularemiamanual.pdf.

198. Wyatt, H. V. 2000. Sir Themistocles Zammit: his honours and an annotated bibliography of his medical work. Maltese Med. J. 12: 27– 30.

199. Yagupsky, P. 1999. Detection of brucellae in blood cultures. J. Clin. Microbiol. 37: 3437– 3442.

200. Yagupsky, P.,, and E. J. Baron. 2005. Laboratory exposures to brucellae and implications for bioterrorism . Emerg. Infect. Dis. 11: 1180– 1185.

201. Yingst, S.,, and D. L. Hoover. 2003. T cell immunity to brucellosis. Crit. Rev. Microbiol. 29: 313– 331.

202. Young, E. J., 2009. Brucella species, p. 2921– 2925. In G. L. Mandell,, J. E. Bennett,, and R. Dolin (ed.), Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 7th ed. Elsevier Inc., Philadelphia, PA.

203. Zhang, F.,, W. Liu,, X. M. Wu,, Z. T. Xin,, Q. M. Zhao,, H. Yang,, and W. C. Cao. 2008. Detection of Francisella tularensis in ticks and identification of their genotypes using multiple-locus variable-number tandem repeat analysis. BMC Microbiol. 8: 152.

204. Zinsstag, J.,, E. Schelling,, F. Roth,, B. Bonfoh,, D. de Savigny,, and M. Tanner. 2007. Human benefits of animal interventions for zoonoses control. Emerg. Infect. Dis. 13: 527– 531.

Tables

Francisella and Brucella*

/content/10.1128/9781555816728.chap44.tab44-1

TABLE 1

Presumptive differentiation of Francisella and Brucella from similar gram-negative genera a

a +, greater than or equal to 90% positive; –, less than or equal to 10% positive; V, variable (11 to 89% positive); ccb, coccobacilli. Data are from reference 169.

b Does not include Bartonella bacilliformis, which is the only motile species.

c Formerly Moraxella phenylpyruvica.

d Haemophilus spp. requiring X and V factors or V factor only.

e While not required, X factor (hemin) enhances growth for many strains.

f May be difficult to demonstrate.

g The number before the colon indicates the number of carbons; the number after the colon is the number of double bonds, vindicates the location of the double bond counting from the hydrocarbon end of the carbon chain, OH indicates a hydroxy group at the 2 or 3 position from the carboxyl end, c indicates the cis isomer, and cyc indicates a cyclopropane ring structure. Hydroxy acids listed are at least 2% of the total cellular fatty acid (CFA) composition; all others are at least 10%.

h B. canis lacks 19:0cyc. Cellular fatty acid data for marine mammal strains are not available.

10.1128/9781555816728/tab44-1_thmb.gif

10.1128/9781555816728/tab44-1.gif

TABLE 1

Presumptive differentiation of Francisella and Brucella from similar gram-negative genera a

a +, greater than or equal to 90% positive; –, less than or equal to 10% positive; V, variable (11 to 89% positive); ccb, coccobacilli. Data are from reference 169.

b Does not include Bartonella bacilliformis, which is the only motile species.

c Formerly Moraxella phenylpyruvica.

d Haemophilus spp. requiring X and V factors or V factor only.

e While not required, X factor (hemin) enhances growth for many strains.

f May be difficult to demonstrate.

h B. canis lacks 19:0cyc. Cellular fatty acid data for marine mammal strains are not available.

/content/10.1128/9781555816728.chap44.tab44-2

TABLE 2

Characteristics of Francisella spp.

a Standard bacteriological media: blood, Trypticase soy, and brain heart infusion.

b Delayed or variable reaction. F. tularensis subsp. mediasiatica does not ferment glucose ( 165 ).

c V, variable or slow reaction.

d NT, not tested.

10.1128/9781555816728/tab44-2_thmb.gif

10.1128/9781555816728/tab44-2.gif

TABLE 2

Characteristics of Francisella spp.

a Standard bacteriological media: blood, Trypticase soy, and brain heart infusion.

b Delayed or variable reaction. F. tularensis subsp. mediasiatica does not ferment glucose ( 165 ).

c V, variable or slow reaction.

d NT, not tested.

/content/10.1128/9781555816728.chap44.tab44-3

TABLE 3

Epidemiology of Francisella spp. affecting humans

10.1128/9781555816728/tab44-3_thmb.gif

10.1128/9781555816728/tab44-3.gif

TABLE 3

Epidemiology of Francisella spp. affecting humans

/content/10.1128/9781555816728.chap44.tab44-4

TABLE 4

Tests commonly used in laboratory diagnosis of brucellosis

10.1128/9781555816728/tab44-4_thmb.gif

10.1128/9781555816728/tab44-4.gif

TABLE 4

Tests commonly used in laboratory diagnosis of brucellosis

/content/10.1128/9781555816728.chap44.tab44-5

TABLE 5

Interpretation of commonly used serologic tests based on the immunoglobulin type detected and usefulness in the diagnosis of different disease categories/stages of human brucellosis

10.1128/9781555816728/tab44-5_thmb.gif

10.1128/9781555816728/tab44-5.gif

TABLE 5

Interpretation of commonly used serologic tests based on the immunoglobulin type detected and usefulness in the diagnosis of different disease categories/stages of human brucellosis