Mediterranean Spotted Fever 

  • Author: Jason F Okulicz, MD; Chief Editor: Michael Stuart Bronze, MD   more...
 
Updated: Nov 22, 2011
 

Background

Mediterranean spotted fever, also known as boutonneuse fever, is transmitted by the dog tick Rhipicephalus sanguineus. The tick bite causes a characteristic rash and a distinct mark, ie, a tache noire (black spot) at the site of the bite.

The etiologic agent that causes Mediterranean spotted fever is Rickettsia conorii, which is also associated with Marseilles fever, Kenya tick typhus, South African tick bite fever, Indian tick typhus, and Israeli tick typhus. Persons with Israeli spotted fever seldom, if ever, develop the tache noire at the site of the tick bite.

Rickettsiae are obligate, intracellular gram-negative coccobacilli that measure 1 µm X 0.3 µm and are found within the cytoplasm and occasionally the nucleus of eukaryotic cells.

Mediterranean spotted fever and African tick bite fever are separate illnesses in the same geographic area. In contrast to Mediterranean spotted fever, African tick bite fever causes local adenopathy and multiple eschars.

The frequency of travel-associated Mediterranean spotted fever has increased worldwide because of increased travel to endemic areas, including ecotourism.

Life-threatening complications or permanent disabilities may result from a delayed diagnosis of Mediterranean spotted fever and the common practice of prescribing beta-lactam antibiotics as empiric therapy.

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Pathophysiology

The pathophysiologic hallmark of R conorii infection is the invasion of vascular endothelial cells by the organism, causing endothelial injury and tissue necrosis, which is illustrated by the tache noire or eschar at the tick bite site. Thrombosis is not an important pathogenic mechanism in this infection, but deep venous thrombosis can occur late in the course of illness.

In a study of the reemergence of the disease in Bulgaria, Botelho-Nevers et al found that that spotted fever is characterized by a Th1 cytokine profile. The patient's immune system responds by proinflammatory and immunoregulatory cytokine production that accompanies the rickettsial vasculitis and contributes to the healing process. The latter is probably not fully achieved in the early convalescent period, according to data concerning some proinflammatory cytokine elevation at this period.[1]

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Epidemiology

Frequency

United States

Mediterranean spotted fever is uncommon in the United States. A similar disease, Rocky Mountain spotted fever, is found in the United States. Rocky Mountain spotted fever is caused by Rickettsia rickettsii, for which the ixodid tick is the vector.

International

Mediterranean spotted fever, caused by R conorii, is prevalent in southern Europe, Africa, and central Asia, including India.

Mortality/Morbidity

Until recently, Mediterranean spotted fever was characterized as a benign rickettsiosis; however, Guillain-Barré syndrome,[2] polyneuropathy,[2] altered mental status, hepatomegaly, acute renal failure, thrombocytopenia, hypoxemia, and death have been reported. Factors associated with more severe disease include older age, alcoholism, and glucose-6-phosphatase dehydrogenase (G-6-PD) deficiency. Mediterranean spotted fever carries an overall mortality rate of approximately 2%.

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Contributor Information and Disclosures
Author

Jason F Okulicz, MD  Assistant Professor of Medicine, Uniformed Services University of the Health Sciences; Staff, Infectious Disease Service, Brooke Army Medical Center

Jason F Okulicz, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)

Mark S Rasnake, MD, FACP  Assistant Professor of Medicine, Program Director, Internal Medicine Residency, University of Tennessee Graduate School of Medicine; Consulting Staff, Department of Infectious Diseases, University of Tennessee Medical Center at Knoxville

Mark S Rasnake, MD, FACP is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

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.

Specialty Editor Board

Joseph Richard Masci, MD  Professor of Medicine, Professor of Preventive Medicine, Mount Sinai School of Medicine; Director of Medicine, Elmhurst Hospital Center

Joseph Richard Masci, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, Association of Professors of Medicine, and Royal Society of Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Thomas M Kerkering, MD  Chief of Infectious Diseases, Virginia Tech Carilion School of Medicine

Thomas M Kerkering, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Medical Society of Virginia, and Wilderness Medical Society

Disclosure: Nothing to disclose.

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 Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

References

  1. Popivanova NI, Murdjeva MA, Baltadzhiev IG, Haydushka IA. Dynamics in serum cytokine responses during acute and convalescent stages of Mediterranean spotted fever. Folia Med (Plovdiv). Apr-Jun 2011;53(2):36-43. [Medline].

  2. Popivanova N, Hristova D, Hadjipetrova E. Guillain-Barré polyneuropathy associated with mediterranean spotted fever: case report. Clin Infect Dis. Dec 1998;27(6):1549. [Medline].

  3. Leone S, De Marco M, Ghirga P, et al. Retinopathy in Rickettsia conorii Infection: Case Report in an Immunocompetent Host. Infection. Aug 2008;36(4):384-6. [Medline].

  4. Tsiachris D, Deutsch M, Vassilopoulos D, et al. Sensorineural hearing loss complicating severe rickettsial diseases: report of two cases. J Infect. Jan 2008;56(1):74-6. [Medline].

  5. Giulieri S, Jaton K, Cometta A, Trellu LT, Greub G. Development of a duplex real-time PCR for the detection of Rickettsia spp. and typhus group rickettsia in clinical samples. FEMS Immunol Med Microbiol. Nov 21 2011;[Medline].

  6. Botelho-Nevers E, Rovery C, Richet H, Raoult D. Analysis of risk factors for malignant Mediterranean spotted fever indicates that fluoroquinolone treatment has a deleterious effect. J Antimicrob Chemother. Aug 2011;66(8):1821-30. [Medline].

  7. Aharonowitz G, Koton S, Segal S, et al. Epidemiological characteristics of spotted fever in Israel over 26 years. Clin Infect Dis. Nov 1999;29(5):1321-2. [Medline].

  8. Anton E, Font B, Munoz T, et al. Clinical and laboratory characteristics of 144 patients with mediterranean spotted fever. Eur J Clin Microbiol Infect Dis. Feb 2003;22(2):126-8. [Medline].

  9. Burgert SJ. Clinical manifestations of African tick-bite fever in the returning traveler. Infect Dis Clin Pract. 2000;9:137-8.

  10. Cascio A, Colomba C, Antinori S, et al. Clarithromycin versus azithromycin in the treatment of Mediterranean spotted fever in children: a randomized controlled trial. Clin Infect Dis. Jan 15 2002;34(2):154-8. [Medline].

  11. Elghetany MT, Walker DH. Hemostatic changes in Rocky Mountain spotted fever and Mediterranean spotted fever. Am J Clin Pathol. Aug 1999;112(2):159-68. [Medline].

  12. Jenkins DR, Rees JC, Pollitt C, et al. Mediterranean spotted fever mimicking Kawasaki disease. BMJ. Mar 1 1997;314(7081):655-6. [Medline].

  13. Jensenius M, Fournier PE, Raoult D. Tick-borne rickettsioses in international travellers. Int J Infect Dis. May 2004;8(3):139-46. [Medline].

  14. La Scola B, Raoult D. Diagnosis of Mediterranean spotted fever by cultivation of Rickettsia conorii from blood and skin samples using the centrifugation-shell vial technique and by detection of R. conorii in circulating endothelial cells: a 6-year follow-up. J Clin Microbiol. Nov 1996;34(11):2722-7. [Medline].

  15. Raoult D, Soulayrol L, Toga B, et al. Babesiosis, pentamidine, and cotrimoxazole. Ann Intern Med. Dec 1987;107(6):944. [Medline].

  16. Rolain JM, Jensenius M, Raoult D. Rickettsial infections--a threat to travellers?. Curr Opin Infect Dis. Oct 2004;17(5):433-7. [Medline].

  17. Shazberg G, Moise J, Terespolsky N, et al. Family outbreak of Rickettsia conorii infection. Emerg Infect Dis. Sep-Oct 1999;5(5):723-4. [Medline].

 
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