Chapter 1 : Clinical Disease: Current Treatment and New Challenges

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

Preview this chapter:
Zoom in

Clinical Disease: Current Treatment and New Challenges, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817336/9781555816773_Chap01-1.gif /docserver/preview/fulltext/10.1128/9781555817336/9781555816773_Chap01-2.gif


This chapter reviews and discusses (i) the human disease manifestations for major pathogenic groups, with some attention to detail on how these differ between genera and species within a single genus; (ii) the evolution of treatment for rickettsial infections; (iii) the existing challenges for treatment and management in human infections; and (iv) corroborated or suspected treatment failures or persistent clinical complaints. The underlying theme for disease manifestations in the is systemic infection of endothelial cells, leading to increased vascular permeability. Once diagnosed, rickettsioses, ehrlichiosis, and anaplasmosis are primarily managed with specific antimicrobial agent therapy. The major advantage of doxycycline is its twice-daily oral dosing, as opposed to three or four doses daily for tetracycline. In general, tetracycline antibiotics are considered rickettsiastatic, not rickettsiacidal. This concept has led to several specific recommendations regarding treatment in rickettsial disease. First, treatment should be provided for long enough that immune recognition and clearance of active infection can proceed to eliminate viable although nonreplicating rickettsia surviving within intracellular niches. Second, since proper immune induction is in part dependent on rickettsial antigen mass, early therapy can sometimes simply suppress growth in the absence of waxing immunity, leading to relapse after apparent appropriate treatment doses and intervals. The identification of innate resistance owing to naturally occurring genetic mutations that confer resistance to currently useful antibiotics underscores the degree of genetic diversity observed in genome projects.

Citation: Dumler J. 2012. Clinical Disease: Current Treatment and New Challenges, p 1-39. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch1
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


1. Abbott, K. C.,, S. J. Vukelja,, C. E. Smith,, C. K. McAllister,, K. A. Konkol,, T. J. O’Rourke,, C. J. Holland,, and M. Ristic. 1991. Hemophagocytic syndrome: a cause of pancytopenia in human ehrlichiosis. Am. J. Hematol. 38: 230 234.PubMed
2. Abramson, J. S.,, and L. B. Givner. 1990. Should tetracycline be contraindicated for therapy of presumed Rocky Mountain spotted fever in children less than 9 years of age? Pediatrics 86: 123 124.PubMed
3. Ackley, A. M.,, and W. J. Peter. 1981. Indigenous acquisition of epidemic typhus in the eastern United States. South. Med. J. 74: 245 247.PubMed
4. Aguero-Rosenfeld, M. E.,, L. Donnarumma,, L. Zentmaier,, J. Jacob,, M. Frey,, R. Noto,, C. A. Carbonaro,, and G. P. Wormser. 2002. Seroprevalence of antibodies that react with Anaplasma phagocytophila, the agent of human granulocytic ehrlichiosis, in different populations in Westchester County, New York. J. Clin. Microbiol. 40: 2612 2615.PubMed CrossRef
5. Aguero-Rosenfeld, M. E.,, H. W. Horowitz,, G. P. Wormser,, D. F. McKenna,, J. Nowakowski,, J. Muñoz,, and J. S. Dumler. 1996. Human granulocytic ehrlichiosis: a case series from a medical center in New York State. Ann. Intern. Med. 125: 904 908.PubMed
6. Apperson, C. S.,, B. Engber,, W. L. Nicholson,, D. G. Mead,, J. Engel,, M. J. Yabsley,, K. Dail,, J. Johnson,, and D. W. Watson. 2008. Tick-borne diseases in North Carolina: is “ Rickettsia amblyommii” a possible cause of rickettsiosis reported as Rocky Mountain spotted fever? Vector Borne Zoonotic Dis. 8: 597 606.PubMed CrossRef
7. Archibald, L. K.,, and D. J. Sexton. 1995. Long-term sequelae of Rocky Mountain spotted fever. Clin. Infect. Dis. 20: 1122 1125.
8. Azad, A. F. 1990. Epidemiology of murine typhus. Annu. Rev. Entomol. 35: 553 569.PubMed CrossRef
9. Azad, A. F.,, S. Radulovic,, J. A. Higgins,, B. H. Noden,, and J. M. Troyer. 1997. Flea-borne rickettsioses: ecologic considerations. Emerg. Infect. Dis. 3: 319 327.PubMed CrossRef
10. Bacellar, F.,, L. Beati,, A. Franca,, J. Pocas,, R. Regnery,, and A. Filipe. 1999. Israeli spotted fever rickettsia ( Rickettsia conorii complex) associated with human disease in Portugal. Emerg. Infect. Dis. 5: 835 836.PubMed CrossRef
11. Bakken, J. S.,, and J. S. Dumler,. 2002. Ehrlichia and Anaplasma species (ehrlichioses), p. 875 882. In V. L. Yu,, R. Weber,, and D. Raoult (ed.), Antimicrobial Therapy and Vaccines. Apple Trees Production, LLC, New York, NY.
12. Bakken, J. S.,, J. S. Dumler,, S. M. Chen,, M. R. Eckman,, L. L. Van Etta,, and D. H. Walker. 1994. Human granulocytic ehrlichiosis in the upper Midwest United States. A new species emerging? JAMA 272: 212 218.PubMed
13. Bakken, J. S.,, and S. Dumler. 2008. Human granulocytic anaplasmosis. Infect. Dis. Clin. North. Am. 22: 433 448, viii.
14. Bakken, J. S.,, P. Goellner,, M. Van Etten,, D. Z. Boyle,, O. L. Swonger,, S. Mattson,, J. Krueth,, R. L. Tilden,, K. Asanovich,, J. Walls,, and J. S. Dumler. 1998. Seroprevalence of human granulocytic ehrlichiosis among permanent residents of northwestern Wisconsin. Clin. Infect. Dis. 27: 1491 1496.PubMed CrossRef
15. Bakken, J. S.,, J. Krueth,, R. L. Tilden,, J. S. Dumler,, and B. E. Kristiansen. 1996a. Serological evidence of human granulocytic ehrlichiosis in Norway. Eur. J. Clin. Microbiol. Infect. Dis. 15: 829 832.PubMed
16. Bakken, J. S.,, J. Krueth,, C. Wilson-Nordskog,, R. L. Tilden,, K. Asanovich,, and J. S. Dumler. 1996b. Clinical and laboratory characteristics of human granulocytic ehrlichiosis. JAMA 275: 199 205.PubMed
17. Barker, L. F. 1968. Determination of antibiotic susceptibility of Rickettsiae and Chlamydiae in BS-C-1 cell cultures. Antimicrob. Agents Chemother. 8: 425 428.PubMed
18. Basrai, D.,, C. Pox,, and W. Schmiegel. 2007. Fever of intermediate duration after return from the Canary Islands. Internist (Berl.) 48: 413 419. (In German.)PubMed CrossRef
19. Bechah, Y.,, C. Capo,, J. L. Mege,, and D. Raoult. 2008. Epidemic typhus. Lancet Infect. Dis. 8: 417 426.PubMed CrossRef
20. Bella, F.,, E. Espejo,, S. Uriz,, J. A. Serrano,, M. D. Alegre,, and J. Tort. 1991. Randomized trial of 5-day rifampin versus 1-day doxycycline therapy for Mediterranean spotted fever. J. Infect. Dis. 164: 433 434.PubMed CrossRef
21. Bella, F.,, B. Font,, S. Uriz,, T. Muñoz,, E. Espejo,, J. Traveria,, J. A. Serrano,, and F. Segura. 1990. Randomized trial of doxycycline versus josamycin for Mediterranean spotted fever. Antimicrob. Agents Chemother. 34: 937 938.PubMed CrossRef
22. Bella-Cueto, F.,, B. Font-Creus,, F. Segura-Porta,, E. Espejo-Arenas,, P. López-Parés,, and T. Muñoz-Espin. 1987. Comparative, randomized trial of one-day doxycycline versus 10-day tetracycline therapy for Mediterranean spotted fever. J. Infect. Dis. 155: 1056 1058.PubMed CrossRef
23. Belongia, E. A. 2002. Epidemiology and impact of coinfections acquired from Ixodes ticks. Vector Borne Zoonotic Dis. 2: 265 273.PubMed CrossRef
24. Bernabeu-Wittel, M.,, J. Pachon,, A. Alarcon,, L. F. Lopez-Cortes,, P. Viciana,, M. E. Jimenez-Mejias,, J. L. Villanueva,, R. Torronteras,, and F. J. Caballero-Granado. 1999. Murine typhus as a common cause of fever of intermediate duration: a 17-year study in the south of Spain. Arch. Intern. Med. 159: 872 876.PubMed CrossRef
25. Bernabeu-Wittel, M.,, J. L. Villanueva-Marcos,, A. de Alarcon-Gonzalez,, and J. Pachon. 1998. Septic shock and multiorganic failure in murine typhus. Eur. J. Clin. Microbiol. Infect. Dis. 17: 131 132.PubMed CrossRef
26. Billings, A. N.,, J. A. Rawlings,, and D. H. Walker. 1998. Tick-borne diseases in Texas: a 10-year retrospective examination of cases. Tex. Med. 94: 66 76.PubMed
27. Biswas, S.,, D. Raoult,, and J. M. Rolain. 2008. A bioinformatic approach to understanding antibiotic resistance in intracellular bacteria through whole genome analysis. Int. J. Antimicrob. Agents 32: 207 220.PubMed CrossRef
28. Biswas, S.,, D. Raoult,, and J. M. Rolain. 2009. Molecular mechanism of gentamicin resistance in Bartonella henselae. Clin. Microbiol. Infect. 15( Suppl. 2): 98 99.PubMed CrossRef
29. Bitsori, M.,, E. Galanakis,, A. Gikas,, E. Scoulica,, and S. Sbyrakis. 2002. Rickettsia typhi infection in childhood. Acta Paediatr. 91: 59 61.PubMed CrossRef
30. Boostrom, A.,, M. S. Beier,, J. A. Macaluso,, K. R. Macaluso,, D. Sprenger,, J. Hayes,, S. Radulovic,, and A. F. Azad. 2002. Geographic association of Rickettsia felis-infected opossums with human murine typhus, Texas. Emerg. Infect. Dis. 8: 549 554.PubMed CrossRef
31. Botelho-Nevers, E.,, C. Rovery,, H. Richet,, and D. Raoult. 2011. Analysis of risk factors for malignant Mediterranean spotted fever indicates that fluoroquinolone treatment has a deleterious effect. J. Antimicrob. Chemother. 66: 1821 1830.PubMed CrossRef
32. Branger, S.,, J. M. Rolain,, and D. Raoult. 2004. Evaluation of antibiotic susceptibilities of Ehrlichia canis, Ehrlichia chaffeensis, and Anaplasma phagocytophilum by real-time PCR. Antimicrob. Agents Chemother. 48: 4822 4828.PubMed CrossRef
33. Brouqui, P.,, P. Parola,, P. E. Fournier,, and D. Raoult. 2007. Spotted fever rickettsioses in southern and eastern Europe. FEMS Immunol. Med. Microbiol. 49: 2 12.PubMed CrossRef
34. Brouqui, P.,, and D. Raoult. 1990. In vitro susceptibility of Ehrlichia sennetsu to antibiotics. Antimicrob. Agents Chemother. 34: 1593 1596.PubMed CrossRef
35. Brouqui, P.,, and D. Raoult. 1992. In vitro antibiotic susceptibility of the newly recognized agent of ehrlichiosis in humans, Ehrlichia chaffeensis. Antimicrob. Agents Chemother. 36: 2799 2803.PubMed CrossRef
36. Brouqui, P.,, Y. O. Sanogo,, G. Caruso,, F. Merola,, and D. Raoult. 2003. Candidatus Ehrlichia walkerii: a new Ehrlichia detected in Ixodes ricinus tick collected from asymptomatic humans in Northern Italy. Ann. N. Y. Acad. Sci. 990: 134 140.PubMed CrossRef
37. Brown, G. W.,, J. P. Saunders,, S. Singh,, D. L. Huxsoll,, and A. Shirai. 1978. Single dose doxycycline therapy for scrub typhus. Trans. R. Soc. Trop. Med. Hyg. 72: 412 416.PubMed CrossRef
38. Browning, M. D.,, J. W. Garyu,, J. S. Dumler,, and D. G. Scorpio. 2006. Role of reactive nitrogen species in development of hepatic injury in a C57BL/6 mouse model of human granulocytic anaplasmosis. Comp. Med. 56: 55 62.PubMed
39. Buitrago, M. I.,, J. W. IJdo,, P. Rinaudo,, H. Simon,, J. Copel,, J. Gadbaw,, R. Heimer,, E. Fikrig,, and F. J. Bia. 1998. Human granulocytic ehrlichiosis during pregnancy treated successfully with rifampin. Clin. Infect. Dis. 27: 213 215.PubMed CrossRef
40. Buller, R. S.,, M. Arens,, S. P. Hmiel,, C. D. Paddock,, J. W. Sumner,, Y. Rikhisa,, A. Unver,, M. Gaudreault-Keener,, F. A. Manian,, A. M. Liddell,, N. Schmulewitz,, and G. A. Storch. 1999. Ehrlichia ewingii, a newly recognized agent of human ehrlichiosis. N. Engl. J. Med. 341: 148 155.PubMed CrossRef
41. Bunnell, J. E.,, E. R. Trigiani,, S. R. Srinivas,, and J. S. Dumler. 1999. Development and distribution of pathologic lesions are related to immune status and tissue deposition of human granulocytic ehrlichiosis agent-infected cells in a murine model system. J. Infect. Dis. 180: 546 550.PubMed CrossRef
42. Cao, W. C.,, L. Zhan,, J. He,, J. E. Foley,, S. J. de Vlas,, X. M. Wu,, H. Yang,, J. H. Richardus,, and J. D. Habbema. 2006. Natural Anaplasma phagocytophilum infection of ticks and rodents from a forest area of Jilin Province, China. Am. J. Trop. Med. Hyg. 75: 664 668.PubMed
43. Carlyon, J. A.,, and E. Fikrig. 2006. Mechanisms of evasion of neutrophil killing by Anaplasma phagocytophilum. Curr. Opin. Hematol. 13: 28 33.PubMed
44. Carpenter, C. F.,, T. K. Gandhi,, L. K. Kong,, G. R. Corey,, S. M. Chen,, D. H. Walker,, J. S. Dumler,, E. Breitschwerdt,, B. Hegarty,, and D. J. Sexton. 1999. The incidence of ehrlichial and rickettsial infection in patients with unexplained fever and recent history of tick bite in central North Carolina. J. Infect. Dis. 180: 900 903.PubMed CrossRef
45. Cascio, A.,, and C. Colomba. 2002. Macrolides in the treatment of children with Mediterranean spotted fever. Infez. Med. 10: 145 150. (In Italian.)PubMed
46. Cascio, A.,, C. Colomba,, S. Antinori,, D. L. Paterson,, and L. Titone. 2002. Clarithromycin versus azithromycin in the treatment of Mediterranean spotted fever in children: a randomized controlled trial. Clin. Infect. Dis. 34: 154 158.PubMed CrossRef
47. Cascio, A.,, C. Colomba,, D. Di Rosa,, L. Salsa,, L. di Martino,, and L. Titone. 2001. Efficacy and safety of clarithromycin as treatment for Mediterranean spotted fever in children: a randomized controlled trial. Clin. Infect. Dis. 33: 409 411.PubMed CrossRef
48. Centers for Disease Control. 1984. Epidemic typhus—Georgia. MMWR Morb. Mortal. Wkly. Rep. 33: 618619.PubMed
49. Centers for Disease Control and Prevention. 2003. Murine typhus—Hawaii, 2002. MMWR Morb. Mortal. Wkly. Rep. 52: 12241226. PubMed
50. Chapman, A. S.,, J. S. Bakken,, S. M. Folk,, C. D. Paddock,, K. C. Bloch,, A. Krusell,, D. J. Sexton,, S. C. Buckingham,, G. S. Marshall,, G. A. Storch,, G. A. Dasch,, J. H. McQuiston,, D. L. Swerdlow,, S. J. Dumler,, W. L. Nicholson,, D. H. Walker,, M. E. Eremeeva,, and C. A. Ohl. 2006. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis—United States: a practical guide for physicians and other health-care and public health professionals. MMWR Recomm. Rep. 55: 1 27.PubMed
51. Chen, S. M.,, J. S. Dumler,, J. S. Bakken,, and D. H. Walker. 1994. Identification of a granulocytotropic Ehrlichia species as the etiologic agent of human disease. J. Clin. Microbiol. 32: 589 595.PubMed
52. Childs, J. E.,, and C. D. Paddock. 2003. The ascendancy of Amblyomma americanum as a vector of pathogens affecting humans in the United States. Annu. Rev. Entomol. 48: 307 337.PubMed CrossRef
53. Choi, K. S.,, J. Garyu,, J. Park,, and J. S. Dumler. 2003. Diminished adhesion of Anaplasma phagocytophilum-infected neutrophils to endothelial cells is associated with reduced expression of leukocyte surface selectin. Infect. Immun. 71: 4586 4594.PubMed
54. Choi, K. S.,, J. T. Park,, and J. S. Dumler. 2005. Anaplasma phagocytophilum delay of neutrophil apoptosis through the p38 mitogen-activated protein kinase signal pathway. Infect. Immun. 73: 8209 8218.PubMed CrossRef
55. Choi, K. S.,, D. G. Scorpio,, and J. S. Dumler. 2004. Anaplasma phagocytophilum ligation to Toll-like receptor (TLR) 2, but not to TLR4, activates macrophages for nuclear factor-κB nuclear translocation. J. Infect. Dis. 189: 1921 1925.PubMed CrossRef
56. Christova, I.,, L. Schouls,, I. van De Pol,, J. Park,, S. Panayotov,, V. Lefterova,, T. Kantardjiev,, and J. S. Dumler. 2001. High prevalence of granulocytic ehrlichiae and Borrelia burgdorferi sensu lato in Ixodes ricinus ticks from Bulgaria. J. Clin. Microbiol. 39: 4172 4174.PubMed CrossRef
57. Cohen, J.,, Y. Lasri,, and Z. Landau. 1999. Mediterranean spotted fever in pregnancy. Scand. J. Infect. Dis. 31: 202 203.PubMed
58. Colomba, C.,, L. Saporito,, V. F. Polara,, R. Rubino,, and L. Titone. 2006. Mediterranean spotted fever: clinical and laboratory characteristics of 415 Sicilian children. BMC Infect. Dis. 6: 60.PubMed CrossRef
59. Dahlgren, F. S.,, E. J. Mandel,, J. W. Krebs,, R. F. Massung,, and J. H. McQuiston. 2011. Increasing incidence of Ehrlichia chaffeensis and Anaplasma phagocytophilum in the United States, 2000-2007. Am. J. Trop. Med. Hyg. 85: 124 131.PubMed CrossRef
60. Dalton, M. J.,, M. J. Clarke,, R. C. Holman,, J. W. Krebs,, D. B. Fishbein,, J. G. Olson,, and J. E. Childs. 1995. National surveillance for Rocky Mountain spotted fever, 1981-1992: epidemiologic summary and evaluation of risk factors for fatal outcome. Am. J. Trop. Med. Hyg. 52: 405 413.PubMed
61. de la Fuente, J.,, A. Torina,, V. Naranjo,, S. Nicosia,, A. Alongi,, F. La Mantia,, and K. M. Kocan. 2006. Molecular characterization of Anaplasma platys strains from dogs in Sicily, Italy. BMC Vet. Res. 2: 24.PubMed CrossRef
62. De Martino, S. J.,, J. A. Carlyon,, and E. Fikrig. 2001. Coinfection with Borrelia burgdorferi and the agent of human granulocytic ehrlichiosis. N. Engl. J. Med. 345: 150 151.PubMed CrossRef
63. Demma, L. J.,, R. C. Holman,, J. H. McQuiston,, J. W. Krebs,, and D. L. Swerdlow. 2005. Epidemiology of human ehrlichiosis and anaplasmosis in the United States, 2001-2002. Am. J. Trop. Med. Hyg. 73: 400 409.PubMed
64. de Sousa, R.,, N. Ismail,, S. Doria-Nobrega,, P. Costa,, T. Abreu,, A. Franca,, M. Amaro,, P. Proenca,, P. Brito,, J. Pocas,, T. Ramos,, G. Cristina,, G. Pombo,, L. Vitorino,, J. Torgal,, F. Bacellar,, and D. Walker. 2005. The presence of eschars, but not greater severity, in Portuguese patients infected with Israeli spotted fever. Ann. N. Y. Acad. Sci. 1063: 197 202.PubMed CrossRef
65. Dierberg, K. L.,, and J. S. Dumler. 2006. Lymph node hemophagocytosis in rickettsial diseases: a pathogenetic role for CD8 T lymphocytes in human monocytic ehrlichiosis (HME)? BMC Infect. Dis. 6: 121.PubMed CrossRef
66. Duffy, P. E.,, H. Le Guillouzic,, R. F. Gass,, and B. L. Innis. 1990. Murine typhus identified as a major cause of febrile illness in a camp for displaced Khmers in Thailand. Am. J. Trop. Med. Hyg. 43: 520 526.PubMed
67. Dumler, J. S. 2005. Anaplasma and Ehrlichia infection. Ann. N. Y. Acad. Sci. 1063: 361 373.PubMed CrossRef
68. Dumler, J. S. 2010. Fitness and freezing: vector biology and human health. J. Clin. Invest. 120: 3087 3090.PubMed CrossRef
69. Dumler, J. S.,, N. C. Barat,, C. E. Barat,, and J. S. Bakken. 2007a. Human granulocytic anaplasmosis and macrophage activation. Clin. Infect. Dis. 45: 199 204.PubMed CrossRef
70. Dumler, J. S.,, A. F. Barbet,, C. P. Bekker,, G. A. Dasch,, G. H. Palmer,, S. C. Ray,, Y. Rikihisa,, and F. R. Rurangirwa. 2001. Reorganization of genera in the families Rickettsiaceae and Anaplasmataceae in the order Rickettsiales: unification of some species of Ehrlichia with Anaplasma, Cowdria with Ehrlichia and Ehrlichia with Neorickettsia, descriptions of six new species combinations and designation of Ehrlichia equi and ‘HGE agent’ as subjective synonyms of Ehrlichia phagocytophila. Int. J. Syst. Evol. Microbiol. 51: 2145 2165.PubMed CrossRef
71. Dumler, J. S.,, K. S. Choi,, J. C. Garcia-Garcia,, N. S. Barat,, D. G. Scorpio,, J. W. Garyu,, D. J. Grab,, and J. S. Bakken. 2005. Human granulocytic anaplasmosis and Anaplasma phagocytophilum. Emerg. Infect. Dis. 11: 1828 1834.PubMed CrossRef
72. Dumler, J. S.,, J. E. Madigan,, N. Pusterla,, and J. S. Bakken. 2007b. Ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment. Clin. Infect. Dis. 45( Suppl. 1): S45 S51.PubMed CrossRef
73. Dumler, J. S.,, W. L. Sutker,, and D. H. Walker. 1993. Persistent infection with Ehrlichia chaffeensis. Clin. Infect. Dis. 17: 903 905.PubMed CrossRef
74. Dumler, J. S.,, J. P. Taylor,, and D. H. Walker. 1991. Clinical and laboratory features of murine typhus in south Texas, 1980 through 1987. JAMA 266: 1365 1370.PubMed
75. Dumler, J. S.,, and D. H. Walker,. 2005a. Order II. Rickettsiales, p. 96 145. In G. M. Garrity,, D. J. Brenner,, N. R. Krieg,, and J. T. Staley (ed.), Bergey’s Manual of Systematic Bacteriology, 2nd ed., vol. 2. Springer-Verlag, New York, NY.
76. Dumler, J. S.,, and D. H. Walker. 2005b. Rocky Mountain spotted fever—changing ecology and persisting virulence. N. Engl. J. Med. 353: 551 553.PubMed CrossRef
77. Dunning Hotopp, J. C.,, M. Lin,, R. Madupu,, J. Crabtree,, S. V. Angiuoli,, J. Eisen,, R. Seshadri,, Q. Ren,, M. Wu,, T. R. Utterback,, S. Smith,, M. Lewis,, H. Khouri,, C. Zhang,, H. Niu,, Q. Lin,, N. Ohashi,, N. Zhi,, W. Nelson,, L. M. Brinkac,, R. J. Dodson,, M. J. Rosovitz,, J. Sundaram,, S. C. Daugherty,, T. Davidsen,, A. S. Durkin,, M. Gwinn,, D. H. Haft,, J. D. Selengut,, S. A. Sullivan,, N. Zafar,, L. Zhou,, F. Benahmed,, H. Forberger,, R. Halpin,, S. Mulligan,, J. Robinson,, O. White,, Y. Rikihisa,, and H. Tettelin. 2006. Comparative genomics of emerging human ehrlichiosis agents. PLoS Genet. 2: e21.PubMed CrossRef
78. Dzelalija, B.,, M. Petrovec,, T. Avsic-Zupanc,, J. Strugar,, and T. A. Milic. 2002. Randomized trial of azithromycin in the prophylaxis of Mediterranean spotted fever. Acta Med. Croatica 56: 45 47.PubMed
79. Eremeeva, M. E.,, A. Oliveira,, J. B. Robinson,, N. Ribakova,, N. K. Tokarevich,, and G. A. Dasch. 2006. Prevalence of bacterial agents in Ixodes persulcatus ticks from the Vologda Province of Russia. Ann. N. Y. Acad. Sci. 1078: 291 298.PubMed CrossRef
80. Esperanza, L.,, D. A. Holt,, J. T. T. Sinnott,, M. R. Cancio,, E. A. Bradley,, and M. Deutsch. 1992. Murine typhus: forgotten but not gone. South. Med. J. 85: 754 755.PubMed CrossRef
81. Fang, R.,, N. Ismail,, L. Soong,, V. L. Popov,, T. Whitworth,, D. H. Bouyer,, and D. H. Walker. 2007. Differential interaction of dendritic cells with Rickettsia conorii: impact on host susceptibility to murine spotted fever rickettsiosis. Infect. Immun. 75: 3112 3123.PubMed CrossRef
82. Fehr, J. S.,, G. V. Bloemberg,, C. Ritter,, M. Hombach,, T. F. Luscher,, R. Weber,, and P. M. Keller. 2010. Septicemia caused by tick-borne bacterial pathogen Candidatus Neoehrlichia mikurensis. Emerg. Infect. Dis. 16: 1127 1129.PubMed CrossRef
83. Fergie, J. E.,, K. Purcell,, and D. Wanat. 2000. Murine typhus in South Texas children. Pediatr. Infect. Dis. J. 19: 535 538.PubMed CrossRef
84. Fishbein, D. B.,, J. E. Dawson,, and L. E. Robinson. 1994. Human ehrlichiosis in the United States, 1985 to 1990. Ann. Intern. Med. 120: 736 743.PubMed
85. Fishbein, D. B.,, L. A. Sawyer,, C. J. Holland,, E. B. Hayes,, W. Okoroanyanwu,, D. Williams,, K. Sikes,, M. Ristic,, and J. E. McDade. 1987. Unexplained febrile illnesses after exposure to ticks. Infection with an Ehrlichia? JAMA 257: 3100 3104.PubMed CrossRef
86. Font-Creus, B.,, F. Bella-Cueto,, E. Espejo-Arenas,, R. Vidal-Sanahuja,, T. Muñoz-Espin,, M. Nolla-Salas,, A. Casagran-Borrell,, J. Mercade-Cuesta,, and F. Segura-Porta. 1985. Mediterranean spotted fever: a cooperative study of 227 cases. Rev. Infect. Dis. 7: 635 642.PubMed
87. Fournier, P. E.,, M. Drancourt,, and D. Raoult. 2007. Bacterial genome sequencing and its use in infectious diseases. Lancet Infect. Dis. 7: 711 723.PubMed CrossRef
88. Fournier, P. E.,, J. S. Dumler,, G. Greub,, J. Zhang,, Y. Wu,, and D. Raoult. 2003a. Gene sequence-based criteria for identification of new Rickettsia isolates and description of Rickettsia heilongjiangensis sp. nov. J. Clin. Microbiol. 41: 5456 5465.PubMed
89. Fournier, P. E.,, J. P. Durand,, J. M. Rolain,, J. L. Camicas,, H. Tolou,, and D. Raoult. 2003b. Detection of Astrakhan fever rickettsia from ticks in Kosovo. Ann. N .Y. Acad. Sci. 990: 158 161.PubMed CrossRef
90. Fournier, P. E.,, K. El Karkouri,, Q. Leroy,, C. Robert,, B. Giumelli,, P. Renesto,, C. Socolovschi,, P. Parola,, S. Audic,, and D. Raoult. 2009. Analysis of the Rickettsia africae genome reveals that virulence acquisition in Rickettsia species may be explained by genome reduction. BMC Genomics 10: 166.PubMed CrossRef
91. Fournier, P. E.,, F. Gouriet,, P. Brouqui,, F. Lucht,, and D. Raoult. 2005. Lymphangitis-associated rickettsiosis, a new rickettsiosis caused by Rickettsia sibirica mongolotimonae: seven new cases and review of the literature. Clin. Infect. Dis. 40: 1435 1444.PubMed CrossRef
92. Fournier, P. E.,, and D. Raoult. 2009. Current knowledge on phylogeny and taxonomy of Rickettsia spp. Ann. N. Y. Acad. Sci. 1166: 1 11.PubMed CrossRef
93. Fournier, P. E.,, S. Siritantikorn,, J. M. Rolain,, Y. Suputtamongkol,, S. Hoontrakul,, S. Charoenwat,, K. Losuwanaluk,, P. Parola,, and D. Raoult. 2008. Detection of new genotypes of Orientia tsutsugamushi infecting humans in Thailand. Clin. Microbiol. Infect. 14: 168 173.PubMed CrossRef
94. Fournier, P. E.,, B. Xeridat,, and D. Raoult. 2003c. Isolation of a rickettsia related to Astrakhan fever rickettsia from a patient in Chad. Ann. N. Y. Acad. Sci. 990: 152 157.PubMed CrossRef
95. Fournier, P. E.,, Y. Zhu,, X. Yu,, and D. Raoult. 2006. Proposal to create subspecies of Rickettsia sibirica and an emended description of Rickettsia sibirica. Ann. N. Y. Acad. Sci. 1078: 597 606.PubMed CrossRef
96. Garcia-Garcia, J. C.,, N. C. Barat,, S. J. Trembley,, and J. S. Dumler. 2009a. Epigenetic silencing of host cell defense genes enhances intracellular survival of the rickettsial pathogen Anaplasma phagocytophilum. PLoS Pathog. 5: e1000488.PubMed CrossRef
97. Garcia-Garcia, J. C.,, K. E. Rennoll-Bankert,, S. Pelly,, A. M. Milstone,, and J. S. Dumler. 2009b. Silencing of host cell CYBB gene expression by the nuclear effector AnkA of the intracellular pathogen Anaplasma phagocytophilum. Infect. Immun. 77: 2385 2391.PubMed CrossRef
98. Gaywee, J.,, J. B. Sacci, Jr.,, S. Radulovic,, M. S. Beier,, and A. F. Azad. 2003. Subcellular localization of rickettsial invasion protein, InvA. Am. J. Trop. Med. Hyg. 68: 92 96.PubMed
99. Ge, Y.,, and Y. Rikihisa. 2006. Anaplasma phagocytophilum delays spontaneous human neutrophil apoptosis by modulation of multiple apoptotic pathways. Cell. Microbiol. 8: 1406 1416.PubMed CrossRef
100. Georgiades, K.,, V. Merhej,, K. El Karkouri,, D. Raoult,, and P. Pontarotti. 2011. Gene gain and loss events in Rickettsia and Orientia species. Biol. Direct 6: 6.PubMed CrossRef
101. Gikas, A.,, S. Doukakis,, J. Pediaditis,, S. Kastanakis,, A. Manios,, and Y. Tselentis. 2004. Comparison of the effectiveness of five different antibiotic regimens on infection with Rickettsia typhi: therapeutic data from 87 cases. Am. J. Trop. Med. Hyg. 70: 576 579.PubMed
102. Gikas, A.,, S. Doukakis,, J. Pediaditis,, S. Kastanakis,, A. Psaroulaki,, and Y. Tselentis. 2002. Murine typhus in Greece: epidemiological, clinical, and therapeutic data from 83 cases. Trans. R. Soc. Trop. Med. Hyg. 96: 250 253.PubMed CrossRef
103. Gillespie, J. J.,, M. S. Beier,, M. S. Rahman,, N. C. Ammerman,, J. M. Shallom,, A. Purkayastha,, B. S. Sobral,, and A. F. Azad. 2007. Plasmids and rickettsial evolution: insight from Rickettsia felis. PLoS One 2: e266.PubMed CrossRef
104. Gillespie, J. J.,, K. Williams,, M. Shukla,, E. E. Snyder,, E. K. Nordberg,, S. M. Ceraul,, C. Dharmanolla,, D. Rainey,, J. Soneja,, J. M. Shallom,, N. D. Vishnubhat,, R. Wattam,, A. Purkayastha,, M. Czar,, O. Crasta,, J. C. Setubal,, A. F. Azad,, and B. S. Sobral. 2008. Rickettsia phylogenomics: unwinding the intricacies of obligate intracellular life. PLoS One 3: e2018.PubMed CrossRef
105. Giroud, P.,, P. Le Gac,, M. Rouby,, J. Lagarde,, and J. A. Gaillard. 1951. Contribution to the study of rickettsial diseases in Oubangui-Chari following brush fire; 4 new cases in Bangui; clinical cases, serological behavior, isolation of strains; spectacular results of antibiotics. Bull. Soc. Pathol. Exot. Filiales 44: 871 879. (In French.)PubMed
106. Gómez, J.,, M. Molina Boix,, V. Baños,, and M. Sempere. 1992. Murine typhus. Efficacy of treatment with ciprofloxacin. Enferm. Infecc. Microbiol. Clin. 10: 377. (In Spanish.)PubMed
107. Goodman, J. L.,, C. Nelson,, B. Vitale,, J. E. Madigan,, J. S. Dumler,, T. J. Kurtti,, and U. G. Munderloh. 1996. Direct cultivation of the causative agent of human granulocytic ehrlichiosis. N. Engl. J. Med. 334: 209 215.PubMed CrossRef
108. Grab, D. J.,, E. Nyarko,, N. C. Barat,, O. V. Nikolskaia,, and J. S. Dumler. 2007. Anaplasma phagocytophilum-Borrelia burgdorferi coinfection enhances chemokine, cytokine, and matrix metalloprotease expression by human brain microvascular endothelial cells. Clin. Vaccine Immunol. 14: 1420 1424.PubMed CrossRef
109. Granquist, E. G.,, M. Aleksandersen,, K. Bergström,, S. J. Dumler,, W. O. Torsteinbø,, and S. Stuen. 2010. A morphological and molecular study of Anaplasma phagocytophilum transmission events at the time of Ixodes ricinus tick bite. Acta Vet. Scand. 52: 43.PubMed CrossRef
110. Graves, S. R.,, J. Banks,, B. Dwyer,, and G. K. King. 1992. A case of murine typhus in Queensland. Med. J. Aust. 156: 650 651.PubMed
111. Gray, E.,, P. Atatoa-Carr,, A. Bell,, S. Roberts,, D. Al Mudallal,, and G. D. Mills. 2007. Murine typhus: a newly recognised problem in the Waikato region of New Zealand. N. Z. Med. J. 120: U2661.PubMed
112. Gross, E. M.,, and P. Yagupsky. 1987. Israeli rickettsial spotted fever in children. A review of 54 cases. Acta Trop. 44: 91 96.PubMed
113. Gudiol, F.,, R. Pallares,, J. Carratala,, F. Bolao,, J. Ariza,, G. Rufi,, and P. F. Viladrich. 1989. Randomized double-blind evaluation of ciprofloxacin and doxycycline for Mediterranean spotted fever. Antimicrob. Agents Chemother. 33: 987 988.PubMed CrossRef
114. Hamburg, B. J.,, G. A. Storch,, S. T. Micek,, and M. H. Kollef. 2008. The importance of early treatment with doxycycline in human ehrlichiosis. Medicine (Baltimore) 87: 53 60.PubMed CrossRef
115. Hassan, I. S.,, and E. L. Ong. 1995. Fever in the returned traveller. Remember murine typhus! J. Infect. Dis. 31: 173 174.PubMed
116. Helmick, C. G.,, K. W. Bernard,, and L. J. D’Angelo. 1984. Rocky Mountain spotted fever: clinical, laboratory, and epidemiological features of 262 cases. J. Infect. Dis. 150: 480 488.PubMed CrossRef
117. Hernandez Cabrera, M.,, A. Angel-Moreno,, E. Santana,, M. Bolanos,, A. Frances,, M. S. Martin-Sanchez,, and J. L. Perez-Arellano. 2004. Murine typhus with renal involvement in Canary Islands, Spain. Emerg. Infect. Dis. 10: 740 743.PubMed CrossRef
118. Holden, K.,, E. Hodzic,, S. Feng,, K. J. Freet,, R. B. Lefebvre,, and S. W. Barthold. 2005. Coinfection with Anaplasma phagocytophilum alters Borrelia burgdorferi population distribution in C3H/HeN mice. Infect. Immun. 73: 3440 3444.PubMed CrossRef
119. Horowitz, H. W.,, T. C. Hsieh,, M. E. Aguero-Rosenfeld,, F. Kalantarpour,, I. Chowdhury,, G. P. Wormser,, and J. M. Wu. 2001. Antimicrobial susceptibility of Ehrlichia phagocytophila. Antimicrob. Agents Chemother. 45: 786 788.PubMed CrossRef
120. Horowitz, H. W.,, E. Kilchevsky,, S. Haber,, M. Aguero-Rosenfeld,, R. Kranwinkel,, E. K. James,, S. J. Wong,, F. Chu,, D. Liveris,, and I. Schwartz. 1998. Perinatal transmission of the agent of human granulocytic ehrlichiosis. N. Engl. J. Med. 339: 375 378.PubMed CrossRef
121. Hove, M. G.,, and D. H. Walker. 1995. Persistence of rickettsiae in the partially viable gangrenous margins of amputated extremities 5 to 7 weeks after onset of Rocky Mountain spotted fever. Arch. Pathol. Lab. Med. 119: 429 431.PubMed
122. Hudson, H. L.,, A. B. Thach,, and P. F. Lopez. 1997. Retinal manifestations of acute murine typhus. Int. Ophthalmol. 21: 121 126.PubMed CrossRef
123. Hulinska, D.,, J. Votypka,, J. Plch,, E. Vlcek,, M. Valesova,, M. Bojar,, V. Hulinsky,, and K. Smetana. 2002. Molecular and microscopical evidence of Ehrlichia spp. and Borrelia burgdorferi sensu lato in patients, animals and ticks in the Czech Republic. New Microbiol. 25: 437 448.PubMed
124. Huys, J.,, P. Freyens,, J. Kayihigi,, and G. Van den Berghe. 1973a. Treatment of epidemic typhus. A comparative study of chloramphenicol, trimethoprim-sulphamethoxazole and doxycycline. Trans. R. Soc. Trop. Med. Hyg. 67: 718 721.PubMed CrossRef
125. Huys, J.,, J. Kayhigi,, P. Freyens,, and G. Van den Berghe. 1973b. Single-dose treatment of epidemic typhus with doxycyline. Chemotherapy 18: 314 317.PubMed CrossRef
126. IJdo, J. W.,, A. C. Carlson,, and E. L. Kennedy. 2007. Anaplasma phagocytophilum AnkA is tyrosine-phosphorylated at EPIYA motifs and recruits SHP-1 during early infection. Cell. Microbiol. 9: 1284 1296.PubMed CrossRef
127. IJdo, J. W.,, and A. C. Mueller. 2004. Neutrophil NADPH oxidase is reduced at the Anaplasma phagocytophilum phagosome. Infect. Immun. 72: 5392 5401.PubMed CrossRef
128. IJdo, J. W.,, C. Wu,, L. A. Magnarelli,, and E. Fikrig. 1999. Serodiagnosis of human granulocytic ehrlichiosis by a recombinant HGE-44-based enzyme-linked immunosorbent assay. J. Clin. Microbiol. 37: 3540 3544.PubMed
129. Ismail, N.,, E. C. Crossley,, H. L. Stevenson,, and D. H. Walker. 2007. Relative importance of T-cell subsets in monocytotropic ehrlichiosis: a novel effector mechanism involved in Ehrlichia-induced immunopathology in murine ehrlichiosis. Infect. Immun. 75: 4608 4620.PubMed CrossRef
130. Ismail, N.,, H. L. Stevenson,, and D. H. Walker. 2006. Role of tumor necrosis factor alpha (TNF-α) and interleukin-10 in the pathogenesis of severe murine monocytotropic ehrlichiosis: increased resistance of TNF receptor p55- and p75-deficient mice to fatal ehrlichial infection. Infect. Immun. 74: 1846 1856.PubMed CrossRef
131. Ismail, N.,, and D. H. Walker. 2005. Balancing protective immunity and immunopathology: a unifying model of monocytotropic ehrlichiosis. Ann. N. Y. Acad. Sci. 1063: 383 394.PubMed CrossRef
132. Jensenius, M.,, P. E. Fournier,, P. Kelly,, B. Myrvang,, and D. Raoult. 2003. African tick bite fever. Lancet Infect. Dis. 3: 557 564.PubMed CrossRef
133. Jensenius, M.,, A. Maeland,, and S. Vene. 1997. Endemic typhus imported to Norway. Tidsskr. Nor. Laegeforen. 117: 2447 2449. (In Norwegian.)PubMed
134. Jones, S. L.,, E. Athan,, D. O’Brien,, S. R. Graves,, C. Nguyen,, and J. Stenos. 2004. Murine typhus: the first reported case from Victoria. Med. J. Aust. 180: 482.PubMed
135. Kao, G. F.,, C. D. Evancho,, O. Ioffe,, M. H. Lowitt,, and J. S. Dumler. 1997. Cutaneous histopathology of Rocky Mountain spotted fever. J. Cutan. Pathol. 24: 604 610.PubMed CrossRef
136. Kaplowitz, L. G.,, J. V. Lange,, J. J. Fischer,, and D. H. Walker. 1983. Correlation of rickettsial titers, circulating endotoxin, and clinical features in Rocky Mountain spotted fever. Arch. Intern. Med. 143: 1149 1151.PubMed CrossRef
137. Kawahara, M.,, Y. Rikihisa,, E. Isogai,, M. Takahashi,, H. Misumi,, C. Suto,, S. Shibata,, C. Zhang,, and M. Tsuji. 2004. Ultrastructure and phylogenetic analysis of ‘ Candidatus Neoehrlichia mikurensis’ in the family Anaplasmataceae, isolated from wild rats and found in Ixodes ovatus ticks. Int. J. Syst. Evol. Microbiol. 54: 1837 1843.PubMed CrossRef
138. Kelly, D. J.,, P. A. Fuerst,, W. M. Ching,, and A. L. Richards. 2009. Scrub typhus: the geographic distribution of phenotypic and genotypic variants of Orientia tsutsugamushi. Clin. Infect. Dis. 48( Suppl. 3): S203 S230.PubMed CrossRef
139. Kenyon, R. H.,, R. G. Williams,, C. N. Oster,, and C. E. Pedersen, Jr. 1978. Prophylactic treatment of Rocky Mountain spotted fever. J. Clin. Microbiol. 8: 102 104.PubMed
140. Kim, C. M.,, M. S. Kim,, M. S. Park,, J. H. Park,, and J. S. Chae. 2003. Identification of Ehrlichia chaffeensis, Anaplasma phagocytophilum, and A. bovis in Haemaphysalis longicornis and Ixodes persulcatus ticks from Korea. Vector Borne Zoonotic Dis. 3: 17 26.PubMed CrossRef
141. Kim, C. M.,, Y. H. Yi,, D. H. Yu,, M. J. Lee,, M. R. Cho,, A. R. Desai,, S. Shringi,, T. A. Klein,, H. C. Kim,, J. W. Song,, L. J. Baek,, S. T. Chong,, M. L. O’Guinn,, J. S. Lee,, I. Y. Lee,, J. H. Park,, J. Foley,, and J. S. Chae. 2006. Tick-borne rickettsial pathogens in ticks and small mammals in Korea. Appl. Environ. Microbiol. 72: 5766 5776.PubMed CrossRef
142. Kim, D. M.,, K. D. Yu,, J. H. Lee,, H. K. Kim,, and S. H. Lee. 2007. Controlled trial of a 5-day course of telithromycin versus doxycycline for treatment of mild to moderate scrub typhus. Antimicrob. Agents Chemother. 51: 2011 2015.PubMed CrossRef
143. Kim, Y. S.,, H. J. Yun,, S. K. Shim,, S. H. Koo,, S. Y. Kim,, and S. Kim. 2004. A comparative trial of a single dose of azithromycin versus doxycycline for the treatment of mild scrub typhus. Clin. Infect. Dis. 39: 1329 1335.PubMed CrossRef
144. Kirkland, K. B.,, P. K. Marcom,, D. J. Sexton,, J. S. Dumler,, and D. H. Walker. 1993. Rocky Mountain spotted fever complicated by gangrene: report of six cases and review. Clin. Infect. Dis. 16: 629 634.PubMed CrossRef
145. Klein, M. B.,, S. Hu,, C. C. Chao,, and J. L. Goodman. 2000. The agent of human granulocytic ehrlichiosis induces the production of myelosuppressing chemokines without induction of proinflammatory cytokines. J. Infect. Dis. 182: 200 205.PubMed CrossRef
146. Klein, M. B.,, C. M. Nelson,, and J. L. Goodman. 1997. Antibiotic susceptibility of the newly cultivated agent of human granulocytic ehrlichiosis: promising activity of quinolones and rifamycins. Antimicrob. Agents Chemother. 41: 76 79.PubMed
147. Kocan, K. M.,, J. de la Fuente,, E. F. Blouin,, J. F. Coetzee,, and S. A. Ewing. 2010. The natural history of Anaplasma marginale. Vet. Parasitol. 167: 95 107. PubMed CrossRef
148. Koliou, M.,, C. Christoforou,, and E. S. Soteriades. 2007a. Murine typhus in pregnancy: a case report from Cyprus. Scand. J. Infect. Dis. 39: 625 628.PubMed CrossRef
149. Koliou, M.,, A. Psaroulaki,, C. Georgiou,, I. Ioannou,, Y. Tselentis,, and A. Gikas. 2007b. Murine typhus in Cyprus: 21 paediatric cases. Eur. J. Clin. Microbiol. Infect. Dis. 26: 491 493.PubMed CrossRef
150. Koutaro, M.,, A. S. Santos,, J. S. Dumler,, and P. Brouqui. 2005. Distribution of ‘ Ehrlichia walkeri’ in Ixodes ricinus ( Acari: Ixodidae) from the northern part of Italy. J. Med. Entomol. 42: 82 85.PubMed CrossRef
151. Krause, D. W.,, P. L. Perine,, J. E. McDade,, and S. Awoke. 1975. Treatment of louse-borne typhus fever with chloramphenicol, tetracycline or doxycycline. East. Afr. Med. J. 52: 421 427.PubMed
152. Krause, P. J.,, C. L. Corrow,, and J. S. Bakken. 2003. Successful treatment of human granulocytic ehrlichiosis in children using rifampin. Pediatrics 112: e252 e253.PubMed
153. Krause, P. J.,, K. McKay,, C. A. Thompson,, V. K. Sikand,, R. Lentz,, T. Lepore,, L. Closter,, D. Christianson,, S. R. Telford,, D. Persing,, J. D. Radolf,, and A. Spielman. 2002. Disease-specific diagnosis of coinfecting tickborne zoonoses: babesiosis, human granulocytic ehrlichiosis, and Lyme disease. Clin. Infect. Dis. 34: 1184 1191.PubMed CrossRef
154. Laferl, H.,, P. E. Fournier,, G. Seiberl,, H. Pichler,, and D. Raoult. 2002. Murine typhus poorly responsive to ciprofloxacin: a case report. J. Travel Med. 9: 103 104.PubMed CrossRef
155. Lane, R. S.,, J. E. Foley,, L. Eisen,, E. T. Lennette,, and M. A. Peot. 2001. Acarologic risk of exposure to emerging tick-borne bacterial pathogens in a semirural community in northern California. Vector Borne Zoonotic Dis. 1: 197 210.PubMed CrossRef
156. Lee, H. C.,, and J. L. Goodman. 2006. Anaplasma phagocytophilum causes global induction of antiapoptosis in human neutrophils. Genomics 88: 496 503.PubMed CrossRef
157. Leiby, D. A.,, and J. E. Gill. 2004. Transfusion-transmitted tick-borne infections: a cornucopia of threats. Transfus. Med. Rev. 18: 293 306.PubMed CrossRef
158. Letaief, A. O.,, N. Kaabia,, M. Chakroun,, M. Khalifa,, N. Bouzouaia,, and L. Jemni. 2005. Clinical and laboratory features of murine typhus in central Tunisia: a report of seven cases. Int. J. Infect. Dis. 9: 331 334.PubMed CrossRef
159. Levin, M. L.,, and D. Fish. 2000. Acquisition of coinfection and simultaneous transmission of Borrelia burgdorferi and Ehrlichia phagocytophila by Ixodes scapularis ticks. Infect. Immun. 68: 2183 2186.PubMed CrossRef
160. Lewin, M. R.,, D. H. Bouyer,, D. H. Walker,, and D. M. Musher. 2003. Rickettsia sibirica infection in members of scientific expeditions to northern Asia. Lancet 362: 1201 1202.PubMed CrossRef
161. Li, W.,, G. Ortiz,, P. E. Fournier,, G. Gimenez,, D. L. Reed,, B. Pittendrigh,, and D. Raoult. 2010. Genotyping of human lice suggests multiple emergencies of body lice from local head louse populations. PLoS Negl. Trop. Dis. 4: e641.PubMed CrossRef
162. Li, W.,, D. Raoult,, and P. E. Fournier. 2009. Bacterial strain typing in the genomic era. FEMS Microbiol. Rev. 33: 892 916.PubMed CrossRef
163. Liddell, A. M.,, S. L. Stockham,, M. A. Scott,, J. W. Sumner,, C. D. Paddock,, M. Gaudreault-Keener,, M. Q. Arens,, and G. A. Storch. 2003. Predominance of Ehrlichia ewingii in Missouri dogs. J. Clin. Microbiol. 41: 4617 4622.PubMed CrossRef
164. Lin, M.,, A. den Dulk-Ras,, P. J. Hooykaas,, and Y. Rikihisa. 2007. Anaplasma phagocytophilum AnkA secreted by type IV secretion system is tyrosine phosphorylated by Abl-1 to facilitate infection. Cell. Microbiol. 9: 2644 2657.PubMed CrossRef
165. Little, S. E. 2010. Ehrlichiosis and anaplasmosis in dogs and cats. Vet. Clin. North Am. Small Anim. Pract. 40: 1121 1140.PubMed CrossRef
166. Long, S. W.,, X. Zhang,, J. Zhang,, R. P. Ruble,, P. Teel,, and X. J. Yu. 2003. Evaluation of transovarial transmission and transmissibility of Ehrlichia chaffeensis ( Rickettsiales: Anaplasmataceae) in Amblyomma americanum ( Acari: Ixodidae). J. Med. Entomol. 40: 1000 1004.PubMed
167. Maeda, K.,, N. Markowitz,, R. C. Hawley,, M. Ristic,, D. Cox,, and J. E. McDade. 1987. Human infection with Ehrlichia canis, a leukocytic rickettsia. N. Engl. J. Med. 316: 853 856.PubMed CrossRef
168. Marshall, G. S.,, G. G. Stout,, R. F. Jacobs,, G. E. Schutze,, H. Paxton,, S. C. Buckingham,, J. P. DeVincenzo,, M. A. Jackson,, V. H. San Joaquin,, S. M. Standaert,, and C. R. Woods. 2003. Antibodies reactive to Rickettsia rickettsii among children living in the southeast and south central regions of the United States. Arch. Pediatr. Adolesc. Med. 157: 443 448.PubMed CrossRef
169. Martinez, J. J.,, S. Seveau,, E. Veiga,, S. Matsuyama,, and P. Cossart. 2005. Ku70, a component of DNA-dependent protein kinase, is a mammalian receptor for Rickettsia conorii. Cell 123: 1013 1023.PubMed CrossRef
170. Marty, A. M.,, J. S. Dumler,, G. Imes,, H. P. Brusman,, L. L. Smrkovski,, and D. M. Frisman. 1995. Ehrlichiosis mimicking thrombotic thrombocytopenic purpura. Case report and pathological correlation. Hum. Pathol. 26: 920 925.PubMed CrossRef
171. Massung, R. F.,, L. E. Davis,, K. Slater,, D. B. McKechnie,, and M. Puerzer. 2001. Epidemic typhus meningitis in the southwestern United States. Clin. Infect. Dis. 32: 979 982.PubMed CrossRef
172. Mathai, E.,, J. M. Rolain,, L. Verghese,, M. Mathai,, P. Jasper,, G. Verghese,, and D. Raoult. 2003. Case reports: scrub typhus during pregnancy in India. Trans. R. Soc. Trop. Med. Hyg. 97: 570 572.PubMed CrossRef
173. Maurin, M.,, C. Abergel,, and D. Raoult. 2001. DNA gyrase-mediated natural resistance to fluoroquinolones in Ehrlichia spp. Antimicrob. Agents Chemother. 45: 2098 2105.PubMed CrossRef
174. Maurin, M.,, J. S. Bakken,, and J. S. Dumler. 2003. Antibiotic susceptibilities of Anaplasma ( Ehrlichia) phagocytophilum strains from various geographic areas in the United States. Antimicrob. Agents Chemother. 47: 413 415.PubMed CrossRef
175. McDade, J. E. 1969. Determination of antibiotic susceptibility of Rickettsia by the plaque assay technique. Appl. Microbiol. 18: 133 135.PubMed
176. McKechnie, D. B.,, K. S. Slater,, J. E. Childs,, R. F. Massung,, and C. D. Paddock. 2000. Survival of Ehrlichia chaffeensis in refrigerated, ADSOL-treated RBCs. Transfusion 40: 1041 1047.PubMed CrossRef
177. McLeod, M. P.,, X. Qin,, S. E. Karpathy,, J. Gioia,, S. K. Highlander,, G. E. Fox,, T. Z. McNeill,, H. Jiang,, D. Muzny,, L. S. Jacob,, A. C. Hawes,, E. Sodergren,, R. Gill,, J. Hume,, M. Morgan,, G. Fan,, A. G. Amin,, R. A. Gibbs,, C. Hong,, X. J. Yu,, D. H. Walker,, and G. M. Weinstock. 2004. Complete genome sequence of Rickettsia typhi and comparison with sequences of other rickettsiae. J. Bacteriol. 186: 5842 5855.PubMed CrossRef
178. Meloni, G.,, and T. Meloni. 1996. Azithromycin vs. doxycycline for Mediterranean spotted fever. Pediatr. Infect. Dis. J. 15: 1042 1044.PubMed CrossRef
179. Miah, M. T.,, S. Rahman,, C. N. Sarker,, G. K. Khan,, and T. K. Barman. 2007. Study on 40 cases of rickettsia. Mymensingh Med. J. 16: 85 88.PubMed CrossRef
180. Mitchell, P. D.,, K. D. Reed,, and J. M. Hofkes. 1996. Immunoserologic evidence of coinfection with Borrelia burgdorferi, Babesia microti, and human granulocytic Ehrlichia species in residents of Wisconsin and Minnesota. J. Clin. Microbiol. 34: 724 727.PubMed
181. Miyamura, S.,, T. Ohta,, and A. Tamura. 1989. Comparison of in vitro susceptibilities of Rickettsia prowazekii, R. rickettsii, R. sibirica and R. tsutsugamushi to antimicrobial agents. Nihon Saikingaku Zasshi 44: 717 721. (In Japanese.)PubMed CrossRef
182. Moron, C. G.,, V. L. Popov,, H. M. Feng,, D. Wear,, and D. H. Walker. 2001. Identification of the target cells of Orientia tsutsugamushi in human cases of scrub typhus. Mod. Pathol. 14: 752 759.PubMed CrossRef
183. Moss, W. J.,, and J. S. Dumler. 2003. Simultaneous infection with Borrelia burgdorferi and human granulocytic ehrlichiosis. Pediatr. Infect. Dis. J. 22: 91 92.PubMed CrossRef
184. Munderloh, U. G.,, M. J. Lynch,, M. J. Herron,, A. T. Palmer,, T. J. Kurtti,, R. D. Nelson,, and J. L. Goodman. 2004. Infection of endothelial cells with Anaplasma marginale and A. phagocytophilum. Vet. Microbiol. 101: 53 64.PubMed CrossRef
185. Muñoz-Espin, T.,, P. López-Parés,, E. Espejo-Arenas,, B. Font-Creus,, I. Martinez-Vila,, J. Travería-Casanova,, F. Segura-Porta,, and F. Bella-Cueto. 1986. Erythromycin versus tetracycline for treatment of Mediterranean spotted fever. Arch. Dis. Child. 61: 1027 1029.PubMed
186. Murphy, J. R.,, C. L. Wisseman, Jr.,, and P. Fiset. 1978. Mechanisms of immunity in typhus infection: some characteristics of Rickettsia mooseri infection of guinea pigs. Infect. Immun. 21: 417 424.PubMed
187. Naitou, H.,, D. Kawaguchi,, Y. Nishimura,, M. Inayoshi,, F. Kawamori,, T. Masuzawa,, M. Hiroi,, H. Kurashige,, H. Kawabata,, H. Fujita,, and N. Ohashi. 2006. Molecular identification of Ehrlichia species and ‘ Candidatus Neoehrlichia mikurensis’ from ticks and wild rodents in Shizuoka and Nagano Prefectures, Japan. Microbiol. Immunol. 50: 45 51.PubMed
188. Ndip, L. M.,, R. N. Ndip,, V. E. Ndive,, J. A. Awuh,, D. H. Walker,, and J. W. McBride. 2007. Ehrlichia species in Rhipicephalus sanguineus ticks in Cameroon. Vector Borne Zoonotic Dis. 7: 221 227.PubMed CrossRef
189. Newton, P. N.,, J. M. Rolain,, B. Rasachak,, M. Mayxay,, K. Vathanatham,, P. Seng,, R. Phetsouvanh,, T. Thammavong,, J. Zahidi,, Y. Suputtamongkol,, B. Syhavong,, and D. Raoult. 2009. Sennetsu neorickettsiosis: a probable fish-borne cause of fever rediscovered in Laos. Am. J. Trop. Med. Hyg. 81: 190 194.PubMed
190. Niang, M.,, P. Brouqui,, and D. Raoult. 1999. Epidemic typhus imported from Algeria. Emerg. Infect. Dis. 5: 716 718.PubMed CrossRef
191. Niebylski, M. L.,, M. E. Schrumpf,, W. Burgdorfer,, E. R. Fischer,, K. L. Gage,, and T. G. Schwan. 1997. Rickettsia peacockii sp. nov., a new species infecting wood ticks, Dermacentor andersoni, in western Montana. Int. J. Syst. Bacteriol. 47: 446 452.PubMed CrossRef
192. Nogueira Angerami, R.,, E. M. Nunes,, E. M. M. Nascimento,, A. Ribas Freitas,, B. Kemp,, A. F. C. Feltrin,, M. R. Pacola,, G. E. C. Perecin,, V. Sinkoc,, M. Ribeiro Resende,, G. Katz,, and L. Jacintho da Silva. 2009. Clusters of Brazilian spotted fever in São Paulo State, southeastern Brazil. A review of official reports and the scientific literature. Clin. Microbiol. Infect. 15: 202 204.PubMed CrossRef
193. Norazah, A.,, A. Mazlah,, Y. M. Cheong,, and A. G. Kamel. 1995. Laboratory acquired murine typhus—a case report. Med. J. Malaysia 50: 177 179.PubMed CrossRef
194. Nyarko, E.,, D. J. Grab,, and J. S. Dumler. 2006. Anaplasma phagocytophilum-infected neutrophils enhance transmigration of Borrelia burgdorferi across the human blood brain barrier in vitro. Int. J. Parasitol. 36: 601 605.PubMed CrossRef
195. Ohashi, N.,, M. Inayoshi,, K. Kitamura,, F. Kawamori,, D. Kawaguchi,, Y. Nishimura,, H. Naitou,, M. Hiroi,, and T. Masuzawa. 2005. Anaplasma phagocytophilum-infected ticks, Japan. Emerg. Infect. Dis. 11: 1780 1783.PubMed CrossRef
196. Older, J. J. 1970. The epidemiology of murine typhus in Texas, 1969. JAMA 214: 2011 2017.PubMed CrossRef
197. Openshaw, J. J.,, D. L. Swerdlow,, J. W. Krebs,, R. C. Holman,, E. Mandel,, A. Harvey,, D. Haberling,, R. F. Massung,, and J. H. McQuiston. 2010. Rocky Mountain spotted fever in the United States, 2000-2007: interpreting contemporary increases in incidence. Am. J. Trop. Med. Hyg. 83: 174 182.PubMed CrossRef
198. O’Reilly, M.,, C. Paddock,, B. Elchos,, J. Goddard,, J. Childs,, and M. Currie. 2003. Physician knowledge of the diagnosis and management of Rocky Mountain spotted fever: Mississippi, 2002. Ann. N. Y. Acad. Sci. 990: 295 301.PubMed CrossRef
199. Padbidri, V. S.,, J. J. Rodrigues,, P. S. Shetty,, M. V. Joshi,, B. L. Rao,, and R. N. Shukla. 1984. Tick-borne rickettsioses in Pune district, Maharashtra, India. Int. J. Zoonoses 11: 45 52.PubMed
200. Paddock, C. D. 2005. Rickettsia parkeri as a paradigm for multiple causes of tick-borne spotted fever in the Western Hemisphere. Ann. N. Y. Acad. Sci. 1063: 315 326.PubMed CrossRef
201. Paddock, C. D.,, and J. E. Childs. 2003. Ehrlichia chaffeensis: a prototypical emerging pathogen. Clin. Microbiol. Rev. 16: 37 64.PubMed CrossRef
202. Paddock, C. D.,, R. W. Finley,, C. S. Wright,, H. N. Robinson,, B. J. Schrodt,, C. C. Lane,, O. Ekenna,, M. A. Blass,, C. L. Tamminga,, C. A. Ohl,, S. L. McLellan,, J. Goddard,, R. C. Holman,, J. J. Openshaw,, J. W. Sumner,, S. R. Zaki,, and M. E. Eremeeva. 2008. Rickettsia parkeri rickettsiosis and its clinical distinction from Rocky Mountain spotted fever. Clin. Infect. Dis. 47: 1188 1196.PubMed CrossRef
203. Paddock, C. D.,, S. M. Folk,, G. M. Shore,, L. J. Machado,, M. M. Huycke,, L. N. Slater,, A. M. Liddell,, R. S. Buller,, G. A. Storch,, T. P. Monson,, D. Rimland,, J. W. Sumner,, J. Singleton,, K. C. Bloch,, Y. W. Tang,, S. M. Standaert,, and J. E. Childs. 2001. Infections with Ehrlichia chaffeensis and Ehrlichia ewingii in persons coinfected with human immunodeficiency virus. Clin. Infect. Dis. 33: 1586 1594.PubMed CrossRef
204. Paddock, C. D.,, P. W. Greer,, T. L. Ferebee,, J. Singleton, Jr.,, D. B. McKechnie,, T. A. Treadwell,, J. W. Krebs,, M. J. Clarke,, R. C. Holman,, J. G. Olson,, J. E. Childs,, and S. R. Zaki. 1999. Hidden mortality attributable to Rocky Mountain spotted fever: immunohistochemical detection of fatal, serologically unconfirmed disease. J. Infect. Dis. 179: 1469 1476.PubMed CrossRef