eMedicine Specialties > Infectious Diseases > Bacterial Infections

Relapsing Fever: Differential Diagnoses & Workup

Author: Kauser Akhter, MD, Clinical Assistant Professor, Internal Medicine, Florida State University College of Medicine; Infectious Diseases Faculty Practice, Orlando Health
Coauthor(s): Pierre A Dorsainvil, MD, Medical Director, HIV Specialist, Palm Beach County Main Detention Center; Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Lake Ida Medical Center; Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Contributor Information and Disclosures

Updated: Apr 9, 2009

Differential Diagnoses

Ascending cholangitis
Lymphocytic Choriomeningitis
Babesiosis
Malaria
Brucellosis
Meningococcemia
Colorado tick fever
Rat bite fever
Dengue Fever
Rickettsioses
Echoviruses
Trench Fever
Ehrlichiosis
Viral hemorrhagic fever
Hepatitis, Viral
Yellow Fever
Leptospirosis

Other Problems to Be Considered

Depending on the history findings, influenza, typhoid fever, and tularemia may also need to be considered.13

Workup

Laboratory Studies

  • Peripheral blood smears
    • Tick-borne relapsing fever (TBRF) is definitively confirmed in the laboratory with direct observation of spirochetes in peripheral blood smears during episodes of fever. A thin smear or thick drop of blood is deposited on a microscope slide, which is then stained with either Wright or Giemsa, and examined under oil immersion. On average, 5 organisms are visible per oil immersion field.

      Peripheral blood smear in relapsing fever. (Image...

      Peripheral blood smear in relapsing fever. (Image originally printed in Blevins SM, Greenfield RA, Bronze MS. Blood smear analysis in babesiosis, ehrlichiosis, relapsing fever, malaria, and Chagas disease. Cleve Clin J Med. Jul 2008;75(7):521-30. Reprinted with permission from the Cleveland Clinic.)

      [ CLOSE WINDOW ]
      Peripheral blood smear in relapsing fever. (Image...

      Peripheral blood smear in relapsing fever. (Image originally printed in Blevins SM, Greenfield RA, Bronze MS. Blood smear analysis in babesiosis, ehrlichiosis, relapsing fever, malaria, and Chagas disease. Cleve Clin J Med. Jul 2008;75(7):521-30. Reprinted with permission from the Cleveland Clinic.)

    • Peripheral blood smears yield a sensitivity of 70%,19 and the technique is more sensitive in TBRF than in louse-borne relapsing fever (LBRF).
    • Smears performed between relapses do not demonstrate the organism and should be repeated when the fever reappears. Inexperience in reading smears or a low index of suspicion for the infection may also result in false-negative blood smear results.2
  • Direct or immunofluorescence staining: These techniques may also be used to visualize spirochetes using a fluorescence microscope.
  • Dark-field microscopy: This may show spirochetes in the blood.
  • Peripheral blood wet mounts: This may show red cells colliding with spirochetes.2
  • Nonspecific laboratory findings: These include normal to mildly increased leukocyte counts, anemia, thrombocytopenia, increased liver enzyme levels, and prolonged coagulation parameters.
  • Cerebrospinal fluid (CSF) studies: In patients with neurologic involvement, CSF studies show mononuclear pleocytosis and a mildly elevated protein level.4

Imaging Studies

  • No special imaging is required in relapsing fever. Imaging would be performed only to evaluate suspected intracranial hemorrhage or other complications.
  • Chest radiography may reveal pulmonary edema.

Other Tests

  • Quantitative buffy coat is 100 times more sensitive than thick films in vitro and may be useful in diagnosis of relapsing fever. However, it requires special equipment.20
  • The organism can be grown in culture using a specific liquid medium developed by Kelly.21 In this technique, a couple of drops of blood are added to the medium, which is incubated at 30-37°C and kept for 2-6 weeks. Dark-field microscopy is used to periodically check for spirochetes.
  • In the research setting, the patient’s blood can be inoculated into mice and the spirochetes amplified in murine blood.5
  • Monoclonal antibodies can be used to diagnose B hermsii infection.22
  • Polymerase chain reaction (PCR) amplification has been developed for identification of most Borrelia species.23 A real-time PCR assay for B recurrentis was described in 2003, and it does not cross-react with other Borrelia species.24
  • Serologies: Antibodies to Borrelia species can be detected with enzyme immunoassays. With this technique, TBRF is confirmed with (1) a 4-fold rise in titers between acute and convalescent samples or (2) a single reactive sample. However, few laboratories perform these assays, and the sensitivity needs to be improved. Enzyme-linked immunosorbent assay (ELISA) is most commonly performed using B hermsii as the antigen. False-positive ELISA results have been noted in patients infected with other Borrelia species. In addition, false-positive results for syphilis and Lyme disease have been described.25,26
  • An immunoreactive protein termed glycerophosphoryl diester phosphodiesterase (G1pQ) has been identified in spirochetes that cause relapsing fever. It recognizes antibodies produced during relapsing fever but, unlike serological testing, does not recognize the antibodies made in Lyme disease or syphilis.2

Histologic Findings

Spirochetes may be detected in tissue using silver stains (eg, Warthin-Starry or modified Dieterle). Alternatively, they may be visualized with immunofluorescence using antibodies.6

On gross pathology, endothelial cell edema, microvascular leakage, perivascular mononuclear infiltrates, microabscesses, and hemorrhage may be seen. In fatal LBRF, myocarditis with histiocytic infiltrates and microhemorrhages may be observed. In the liver and spleen, focal necrotic areas may be noted.16

More on Relapsing Fever

Overview: Relapsing Fever
Differential Diagnoses & Workup: Relapsing Fever
Treatment & Medication: Relapsing Fever
Follow-up: Relapsing Fever
Multimedia: Relapsing Fever
References
[ CLOSE WINDOW ]

References

  1. Barbour AG, Hayes SF. Biology of Borrelia species. Microbiol Rev. Dec 1986;50(4):381-400. [Medline].

  2. Dworkin MS, Schwan TG, Anderson DE Jr, Borchardt SM. Tick-borne relapsing fever. Infect Dis Clin North Am. Sep 2008;22(3):449-68, viii. [Medline].

  3. Wynns HL. The epidemiology of relapsing fever. In: Moulton FR. A Symposium on Relapsing Fever in the Americas. American Association for the Advancement of Science. Washington, DC: 1942:100-5.

  4. Blevins SM, Greenfield RA, Bronze MS. Blood smear analysis in babesiosis, ehrlichiosis, relapsing fever, malaria, and Chagas disease. Cleve Clin J Med. Jul 2008;75(7):521-30. [Medline].

  5. Moursund WH. Historical introduction to the symposium on relapsing fever. In: Moulton FR. A Symposium on Relapsing Fever in the Americas. American Association for the Advancement of Science. Washington, DC: 1942:1-6.

  6. Barbour AG. Microbiology, pathogenesis, and epidemiology of relapsing fever. UpToDate. Available at http://www.uptodate.com/online/content/topic.do?topicKey=tickflea/11713&selectedTitle=2~15&source=search_result#references. Accessed November 25, 2008.

  7. Fuchs PC, Oyama AA. Neonatal relapsing fever due to transplacental transmission of Borrelia. JAMA. Apr 28 1969;208(4):690-2. [Medline].

  8. Thein M, Bunikis I, Denker K, Larsson C, Cutler S, Drancourt M, et al. Oms38 is the first identified pore-forming protein in the outer membrane of relapsing fever spirochetes. J Bacteriol. Nov 2008;190(21):7035-42. [Medline].

  9. Gelderblom H, Schmidt J, Londoño D, Bai Y, Quandt J, Hornung R, et al. Role of interleukin 10 during persistent infection with the relapsing fever Spirochete Borrelia turicatae. Am J Pathol. Jan 2007;170(1):251-62. [Medline].

  10. Londoño D, Marques A, Hornung RL, Cadavid D. Relapsing fever borreliosis in interleukin-10-deficient mice. Infect Immun. Dec 2008;76(12):5508-13. [Medline].

  11. Centers for Disease Control and Prevention (CDC). Acute respiratory distress syndrome in persons with tickborne relapsing fever--three states, 2004-2005. MMWR Morb Mortal Wkly Rep. Oct 19 2007;56(41):1073-6. [Medline].

  12. Brouqui P, Stein A, Dupont HT, Gallian P, Badiaga S, Rolain JM, et al. Ectoparasitism and vector-borne diseases in 930 homeless people from Marseilles. Medicine (Baltimore). Jan 2005;84(1):61-8. [Medline].

  13. Barbour AG. Clinical features and management of relapsing fever. UpToDate. Available at http://www.uptodate.com/online/content/topic.do?topicKey=tickflea/11413#1. Accessed November 25, 2008.

  14. Rhee KY, Johnson WD Jr. Borrelia species (relapsing fever). In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Vol 2. 6th ed. Philadelphia, PA: Churchill Livingstone; 2005:2795-8.

  15. Goubau PF. Relapsing fevers. A review. Ann Soc Belg Med Trop. 1984;64(4):335-64. [Medline].

  16. Southern PM, Sanford JP. Relapsing fever: a clinical and microbiological review. Medicine. 1969;48:129-49.

  17. Perine PL, Parry EH, Vukotich D, Warrell DA, Bryceson AD. Bleeding in louse-borne relapsing fever. I. Clinical studies in 37 patients. Trans R Soc Trop Med Hyg. 1971;65(6):776-81. [Medline].

  18. Dennis DT, Awoke S, Doberstyn EB, Fresh JW. Bleeding in louse-borne relapsing fever in Ethiopia; clinical and laboratory features in 29 patients. East Afr Med J. Apr 1976;53(4):220-5. [Medline].

  19. Parola P, Raoult D. Ticks and tickborne bacterial diseases in humans: an emerging infectious threat. Clin Infect Dis. Mar 15 2001;32(6):897-928. [Medline].

  20. van Dam AP, van Gool T, Wetsteyn JC. Tick-borne relapsing fever imported from West Africa: diagnosis by quantitative buffy coat analysis and in vitro culture of Borrelia crocidurae. J Clin Microbiol. Jun 1999;37(6):2027-30. [Medline].

  21. Kelly R. Cultivation of Borrelia hermsi. Science. Jul 30 1971;173(995):443-4. [Medline].

  22. Schwan TG, Gage KL, Karstens RH, Schrumpf ME, Hayes SF, Barbour AG. Identification of the tick-borne relapsing fever spirochete Borrelia hermsii by using a species-specific monoclonal antibody. J Clin Microbiol. Apr 1992;30(4):790-5. [Medline].

  23. Fukunaga M, Okada K, Nakao M, Konishi T, Sato Y. Phylogenetic analysis of Borrelia species based on flagellin gene sequences and its application for molecular typing of Lyme disease borreliae. Int J Syst Bacteriol. Oct 1996;46(4):898-905. [Medline].

  24. Jiang J, Temenak JJ, Richards AL. Real-time PCR duplex assay for Rickettsia prowazekii and Borrelia recurrentis. Ann N Y Acad Sci. Jun 2003;990:302-10. [Medline].

  25. Magnarelli LA, Anderson JF, Johnson RC. Cross-reactivity in serological tests for Lyme disease and other spirochetal infections. J Infect Dis. Jul 1987;156(1):183-8. [Medline].

  26. Magnarelli LA, Meegan JM, Anderson JF, Chappell WA. Comparison of an indirect fluorescent-antibody test with an enzyme-linked immunosorbent assay for serological studies of Lyme disease. J Clin Microbiol. Aug 1984;20(2):181-4. [Medline].

  27. [Best Evidence] Hasin T, Davidovitch N, Cohen R, Dagan T, Romem A, Orr N, et al. Postexposure treatment with doxycycline for the prevention of tick-borne relapsing fever. N Engl J Med. Jul 13 2006;355(2):148-55. [Medline].

  28. Dworkin MS, Anderson DE Jr, Schwan TG. Tick-borne relapsing fever in the northwestern United States and southwestern Canada. Clin Infect Dis. Jan 1998;26(1):122-31. [Medline].

  29. Scott R. Neurological complications of relapsing fever. Lancet. 1944;247:436-8.

  30. Cadavid D, Barbour AG. Neuroborreliosis during relapsing fever: review of the clinical manifestations, pathology, and treatment of infections in humans and experimental animals. Clin Infect Dis. Jan 1998;26(1):151-64. [Medline].

  31. Wengrower D, Knobler H, Gillis S, Chajek-Shaul T. Myocarditis in tick-borne relapsing fever. J Infect Dis. Jun 1984;149(6):1033. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

relapsing fever, louse-borne relapsing fever, LBRF, tick-borne relapsing fever, TBRF, human body louse, Pediculus humanus, soft-bodied ticks, Ornithodoros species, species, Borrelia recurrentis, Borrelia turicatae, Borrelia hermsii, Borrelia parkeri, Borrelia duttonii, B recurrentis, B turicatae, B hermsii, B parkeri, B duttonii

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Kauser Akhter, MD, Clinical Assistant Professor, Internal Medicine, Florida State University College of Medicine; Infectious Diseases Faculty Practice, Orlando Health
Disclosure: Nothing to disclose.

Coauthor(s)

Pierre A Dorsainvil, MD, Medical Director, HIV Specialist, Palm Beach County Main Detention Center; Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Lake Ida Medical Center
Disclosure: Nothing to disclose.

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

John M Leedom, MD, Professor of Medicine, Keck School of Medicine, University of Southern California; Chief, Division of Infectious Diseases, Department of Internal Medicine, Los Angeles County, University of Southern California Medical Center
John M Leedom, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Joseph F John Jr, MD, FACP, FIDSA, FSHEA, Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center
Disclosure: BioMerieux Honoraria Review panel membership; Cubist Honoraria Review panel membership; Pfizer Honoraria Speaking and teaching; Merck Stock dividends stock holdings

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center
Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Association of Professors of Medicine, Association of Program Directors in Internal Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.