eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Rickettsial Infection: Differential Diagnoses & Workup

Author: Mobeen H Rathore, MD, CPE, FAAP, FIDSA, Chief of Division of Pediatric Infectious Diseases/Immunology, Associate Chairman of Department of Pediatrics, University of Florida College of Medicine at Jacksonville; Hospital Epidemiologist and Section Chief of Infectious Disease and Immunology, Wolfson Children's Hospital; Director of University of Florida Center for HIV/AIDS Research, Education and Service (UF CARES)
Coauthor(s): Nizar F Maraqa, MD, Assistant Professor of Pediatrics, Pediatric Infectious Diseases, University of Florida at Jacksonville
Contributor Information and Disclosures

Updated: May 11, 2009

Differential Diagnoses

Dengue
Streptococcal Infection, Group A
Kawasaki Disease
Syphilis
Leptospirosis
Toxic Shock Syndrome
Malaria
Vasculitis and Thrombophlebitis
Measles
Meningococcal Infections
Rubella

Other Problems to Be Considered

  • Typhoid fever
  • Infectious mononucleosis
  • Enteroviral infections
  • Idiopathic thrombocytopenic purpura
  • Drug reaction
  • Chronic granulomatous bone lesions: These could be caused by Mycobacteria, Bartonella, Francisella, Brucella, and Nocardia species. These should be considered in the differential diagnosis for chronic recurrent multifocal osteomyelitis, in addition to chronic Q fever infection.

Workup

Laboratory Studies

  • Rickettsiae are not evident on blood smear findings and do not stain with most conventional stains.3,4
  • No rapid laboratory tests are available to diagnose rickettsial diseases early in the course of illness.
    • Serologic assays that demonstrate antibodies to rickettsial antigens (eg, indirect immunofluorescence, complement fixation, indirect hemagglutination, latex fixation, enzyme immunoassay, microagglutination) are preferable to the nonspecific and insensitive Weil-Felix test based on the cross-reactive antigens of Proteus vulgaris strains. Serologic findings usually take 10-12 days to become positive. The value of testing 2 sequential serum or plasma samples together to show a rising antibody level is considerably more important in confirming acute infection with rickettsial agents because antibody titers may persist in some patients for years after the original exposure.
    • Immunofluorescence assay (IFA) is currently considered to be the reference serological method. However, it cannot determine the causative agent to the species level.
    • Polymerase chain reaction (PCR) to detect rickettsiae in blood or tissue provides promise for early diagnosis. PCR testing and immunohistochemical staining of skin specimen obtained by performing a biopsy may help confirm the clinical diagnosis in patients with rash (high expertise is usually needed to interpret the biopsy result). However, serology remains the mainstay of diagnosis because these other tests are expensive and less available to clinicians.
    • Rickettsial isolation in culture is unnecessary, laborious, and hazardous to laboratory personnel.
  • Rocky Mountain spotted fever (RMSF)
    • Serology is the mainstay to confirm diagnosis.
    • Another approach to RMSF diagnostics is immunostaining whereby a skin biopsy of the rash from an infected patient is tested prior to therapy or within the first 48 hours after antibiotic therapy has been started. This test's use remains highly operator-dependent.
    • Other tests, such as PCR, are rather expensive and not readily available.
    • Nonspecific laboratory findings, such as thrombocytopenia, leukopenia, and mild hyponatremia, may give helpful clues to the treating physician.
    • If cerebrospinal fluid is examined, pleocytosis (generally <100 cells/μ L) is typically observed with polymorphonuclear or lymphocyte predominance, moderately elevated protein levels (100-200 mg/dL), and normal glucose levels.
  • Rickettsialpox
    • As with other rickettsial infections, diagnosis is clinical and may be confirmed by serology.
    • The Weil-Felix test is not useful because R akari does not produce Weil-Felix agglutinins.
    • R akari has a soluble antigen that cross-reacts with R rickettsii (the cause of RMSF) and other spotted fever groups of rickettsiae.
  • Boutonneuse fever
    • Serologic laboratory confirmation (complement fixation, microagglutination, western blot, indirect immunofluorescent tests) usually provides support for the diagnosis made on clinical and epidemiologic grounds. Additionally, a latex agglutination test for detection of antibodies to R conorii that is both specific and sensitive now can be performed in specialized laboratories.
    • R conorii has been detected from the tache noire by restriction fragment length polymorphism (RFLP) and by PCR.8
  • Louse-borne (epidemic) typhus
    • Serologic laboratory confirmatory tests are available as in RMSF. Patients initially have an IgM response followed by production of immunoglobulin G (IgG) antibodies.
    • However, a significant antigenic crossing is noted between this rickettsial organism and those of the spotted fever group.
    • PCR promises to be a rapid diagnostic test but is expensive and not yet widely available.
  • Brill-Zinsser disease (ie, relapsing louse-borne typhus): Laboratory studies are similar to those for primary louse-borne epidemic typhus. However, patients develop an anamnestic immune response whereby only IgG is produced.
  • Murine (endemic or flea-borne) typhus
    • Laboratory studies are analogous to those mentioned for epidemic louse-borne typhus.
    • Additionally, a mild-to-moderate elevation of serum aspartate aminotransferase (AST) level is present in approximately 90% of patients. Other indices of hepatocellular injury (alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase) are often also elevated.
  • Tsutsugamushi disease (ie, scrub typhus)
    • Serologic testing using specific methods (eg, immunofluorescence antibody test, indirect immunoperoxidase test, enzyme immunoassay) is superior to the Weil-Felix reaction.
    • However, these tests are cumbersome and only available in a few special laboratories.
  • Q fever
    • Laboratory findings in acute Q fever infection may include thrombocytopenia in approximately 25% of cases and elevated hepatic transaminases. In prolonged infections, autoantibodies (eg, anti-smooth muscle antibodies) may be found.5
    • In addition to clinical and epidemiologic features, serology (eg, microimmunofluorescence, complement fixation, enzyme immunoassay) remains the mainstay of diagnosis in acute and chronic illnesses.
    • As with other rickettsiae, attempts to isolate the organism are biohazardous and unnecessary.
    • PCR may be used; however, it remains less available and more expensive than serology.
    • Chronic Q fever endocarditis is diagnosed by demonstration of high antibody (IgG and IgA) titers against C burnetii in patients with signs of endocarditis whose blood cultures contain no organisms (ie, culture-negative endocarditis). These patients may have elevated erythrocyte sedimentation rate, anemia, thrombocytopenia, and hematuria.17,5

Imaging Studies

  • Chest radiography may be required in patients with severe illness or pulmonary manifestations, especially in patients with RMSF and Q fever.
  • Other imaging studies may be necessary, depending on the severity of organ involvement and development of complications.

Procedures

  • A lumbar puncture and other procedures may be needed to exclude other possible etiologies.

Histologic Findings

  • Evidence of vasculitis, angiitis, and perivascular mononuclear cell infiltration may be evident in involved organs.
  • Chronic Q fever infection of the skeletal system causes the formation of granulomatous lesions.

More on Rickettsial Infection

Overview: Rickettsial Infection
Differential Diagnoses & Workup: Rickettsial Infection
Treatment & Medication: Rickettsial Infection
Follow-up: Rickettsial Infection
Multimedia: Rickettsial Infection
References
Further Reading
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References

  1. Walker DH. Rickettsiae and rickettsial infections: the current state of knowledge. Clin Infect Dis. Jul 15 2007;45 Suppl 1:S39-44. [Medline].

  2. Jensenius M, Fournier P, Raoult D. Rickettsioses and the international traveler. Clin Infect Dis. 2004;34(10):1493-9. [Medline].

  3. Center of Disease Control and Prevention (CDC). Rickettsial Diseases. Infectious Disease Information. Available at http://www.cdc.gov/ncidod/dvrd/branch/vrzb.htm.

  4. Edwards MS, Feigin RD. Rickettsial diseases. In: Feigin RD, Cherry JD, Demmler GJ, Kaplan SL, eds. Textbook of Pediatric Infectious Diseases. 5th ed. WB Saunders Co; 2004:2497-2515/Chapter 195.

  5. Tissot-Dupont H, Raoult D. Q Fever. Infect Dis Clin N Am. Sept 2008;22:505-514. [Medline].

  6. Walker DH. Rickettsiae. In: Baron S, ed. Medical Microbiology. 4th ed. University of Texas Medical Branch; 1996:[Full Text].

  7. Azad AF. Pathogenic Rickettsiae as Bioterrorism Agents. Clin Infect Dis. Jul 15 2007;45 Suppl 1:S52-55. [Medline].

  8. Rovery C, Raoult D. Meditteranean Spotted Fever. Infect Dis Clin N Am. Sept 2008;22:515-530. [Medline].

  9. Dumler JS, Walker DH. Rocky Mountain spotted fever--changing ecology and persisting virulence. N Engl J Med. Aug 11 2005;353(6):551-3. [Medline].

  10. Graf PC, Chertien JP, Ung L, et al. Prevalence of serpositivity to spotted fever group rickettsiae and Anaplasma phagocytophilum in a large, dempgraphically diverse US sample. Clin Infect Dis. Jan 2008;46 (1):70-77. [Medline].

  11. Cowan G. Rickettsial diseases: the typhus group of fevers--a review. Postgrad Med J. May 2000;76(895):269-72. [Medline].

  12. Marshall GS. Rickettsia typhi seroprevalence among children in the Southeast United States. Tick-Borne Infections in Children Study (TICKS) Group. Pediatr Infect Dis J. Nov 2000;19(11):1103-4. [Medline].

  13. Fergie JE, Purcell K, Wanat D. Murine Typhus in South Texas children. Pediatr Infect Dis J. 2000;19(6):535-38. [Medline].

  14. Walker DH, Dumler JS. Emerging and reemerging rickettsial diseases. N Engl J Med. Dec 15 1994;331(24):1651-2. [Medline].

  15. Abramson JS, Givner LB. Rocky Mountain spotted fever. Pediatr Infect Dis J. Jun 1999;18(6):539-40. [Medline].

  16. Parola P, Davoust B, Raoult D. Tick- and flea-borne rickettsial emerging zoonoses. Vet Res. May-Jun 2005;36:469-492. [Medline].

  17. Ruiz-Contreras J, Gonzalez Montero R, Ramos Amador JT, et al. Q fever in children. Am J Dis Child. Mar 1993;147(3):300-2. [Medline].

  18. Nourse C, Allworth A, Jones A, et al. Three cases of Q fever osteomyelitis in children and a review of the literature. Clin Infect Dis. Oct 1 2004;39(7):e61-6. [Medline].

  19. Sexton DJ, Corey GR. Rocky Mountain "spotless" and "almost spotless" fever: a wolf in sheep's clothing. Clin Infect Dis. Sep 1992;15(3):439-48. [Medline].

  20. Demma LJ, Traeger MS, Nicholson et al. Rocky Mountain spotted fever from an unexpected tick vector in Arizona. N Engl J Med. Aug 11 2005;353(6):587-94. [Medline].

  21. Raoult D, Paddock CD. Rickettsia parkeri infection and other spotted fevers in the United States. N Eng J Med. 2005;353:626-7. [Medline].

  22. Raoult D, Drancourt M. Antimicrobial therapy of rickettsial diseases. Antimicrob Agents Chemother. Dec 1991;35(12):2457-62. [Medline].

  23. Purvis JJ, Edwards MS. Doxycycline use for rickettsial disease in pediatric patients. Pediatr Infect Dis J. Sep 2000;19(9):871-4. [Medline].

  24. Richards AL. Rickettsial Vaccines: the old and the new. Expert Rev Vaccines. October 2004;3:541-555. [Medline].

  25. Chapman AS, Bakken JS, Folk SM, et al. 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. Mar 31 2006;55(RR-4):1-27. [Medline].

  26. Fournier PE, Gouriet F, Brouqui P. Lymphangitis-associated rickettsiosis, a new rickettsiosis caused by Rickettsia sibirica mongolotimonae: seven new cases and review of the literature. Clin Infect Dis. May 15 2005;40(10):1435-44. [Medline].

  27. Jensenius M, Fournier P, Kelly P. African tick bite fever. Lancet Infect Dis. 2003;3(9):557-64. [Medline].

  28. Spach DH, Liles WC, Campbell GL, et al. Tick-borne diseases in the United States. N Engl J Med. Sep 23 1993;329(13):936-47. [Medline].

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Further Reading

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Keywords

Rocky Mountain spotted fever, RMSF, rickettsialpox, boutonneuse fever, Mediterranean spotted fever, Kenya tick-bite fever, African tick typhus, India tick typhus, Israeli spotted fever, Marseille fever, epidemic louse-borne typhus, endemic murine typhus, Tsutsugamushi disease, scrub typhus, Q fever, Brill-Zinsser disease, relapsing louse-borne typhus, rickettsial infection, Rickettsiae, Rickettsia, rickettsialpox, catscratch disease, trench fever, hypoalbuminemia, osteomyelitis, chronic hepatitis, chronic vascular infection, endocarditis, pericarditis, myocarditis, treatment, diagnosis, atelectasis, pulmonary edema

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Contributor Information and Disclosures

Author

Mobeen H Rathore, MD, CPE, FAAP, FIDSA, Chief of Division of Pediatric Infectious Diseases/Immunology, Associate Chairman of Department of Pediatrics, University of Florida College of Medicine at Jacksonville; Hospital Epidemiologist and Section Chief of Infectious Disease and Immunology, Wolfson Children's Hospital; Director of University of Florida Center for HIV/AIDS Research, Education and Service (UF CARES)
Mobeen H Rathore, MD, CPE, FAAP, FIDSA is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, European Society for Paediatric Infectious Diseases, Florida Medical Association, Florida Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Society for Healthcare Epidemiology of America, Society for Pediatric Research, Southern Medical Association, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

Coauthor(s)

Nizar F Maraqa, MD, Assistant Professor of Pediatrics, Pediatric Infectious Diseases, University of Florida at Jacksonville
Nizar F Maraqa, MD is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Medical Editor

José Rafael Romero, MD, Director of Pediatric Infectious Diseases Fellowship Program, Associate Professor, Department of Pediatrics, Combined Division of Pediatric Infectious Diseases, Creighton University/University of Nebraska Medical Center
José Rafael Romero, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, New York Academy of Sciences, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus
Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

CME Editor

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; sanofi pasteur Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

 
 
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