Rickettsia africae: Risks. . .But for Which Travelers?
Abstract & Commentary
Synopsis: African tick bite fever is an emerging infectious disease affecting travelers to parts of Africa and possibly other areas of the world. The risks of infection and means for prevention should be discussed with travelers and game hunters visiting high-risk areas, especially rural sub-Saharan Africa.
Source: Jensenius M, et al. African tick bite fever in travelers to rural sub-equatorial Africa. Clin Infect Dis. 2003;36:1411-1417.
The norwegian african tick bite fever study group prospectively assessed travelers to rural sub-equatorial Africa for the incidence, risk factors, and clinical presentations of African tick bite fever (ATBF). The study enrolled travelers at 9 travel clinics in Norway, from Jan. 1, 1999, through Dec. 31, 2000, who were planning to visit rural sub-equatorial Africa. Oral and written information on the disease was distributed to the travelers. Travelers were asked to complete a questionnaire after return to Norway. Only those who completed the questionnaire and had traveled to rural areas were included in the study (n = 940). The study group’s infectious disease specialists evaluated travelers who developed flu-like illnesses within 10 days of departure from rural areas. Physical findings, serology, and PCR for rickettsiae were specifically obtained, and suspected ATBF cases were followed up further.
Microbiological diagnosis was established on the basis of a positive "suicide" PCR (a PCR in which the primer is used only once) and the presence of serum antibodies to R africae by microimmunofluorescence (MIF), Western blot (WB), and cross-adsorption assay of serum test samples.
Among the 940 travelers in the study, 143 (15.2%) experienced flu-like illnesses, and 83 of the symptomatic travelers presented for medical evaluation. Thirty-eight travelers (4% of the total and 26.6% of those with flu-like symptoms) were diagnosed with ATBF (27 confirmed and 11 probable). An additional 12 travelers were diagnosed as having a nonspecific spotted fever group (SFG) rickettsiosis. Overall incidence of SFG rickettsiosis in the study was 5.3%, or 0.25 cases per person-travel-month.
The incidence of ATBF was highest in the group of hunters (25.3%), when compared to business travelers (2.8%), visitors to friends and relatives (2.6%), leisure travelers (2.1%), and backpackers (1.4%). Clustering of infections was observed in 56% of confirmed cases. Ticks and/or tick bites were noted by 48% of patients with ATBF. Three risk factors were associated with ATBF: hunting as the reason for travel, travel to southern Africa, and travel during the summer.
Clinical presentation of patients with ATBF included myalgia (87%), headache (83%), fever (81%), eschars (53%, and 21% of all ATBF cases had multiple eschars), regional lymphadenitis (50%), maculopapular rash (26%), vesicular rash (16%), and aphthous stomatitis (11%). A total of 39% of the patients received antirickettsial therapy, consisting of either doxycycline or ciprofloxacin.
Comment by Lin H. Chen, MD
The causative agent of ATBF is Rickettsia africae, a Gram-negative obligate intracellular bacterium that is a member of the SFG rickettsiae. Other species of the SFG rickettsiae that cause human disease include R rickettsii (Rocky Mountain spotted fever), R conorii (Mediterranean spotted fever or boutonneuse fever), R australis (Queensland tick typhus fever), R sibirica (Siberian tick typhus fever), R japonica (Japanese tick typhus), R honei (Flinders Island spotted fever), R akari (rickettsialpox; see TMA Update 2002;12[4]:30-32 for a recent review), R felis (California flea rickettsiosis), and R mongolotimonae.1,2 Rickettsiae of the SFG are transmitted to humans by insect vectors. While R akari is mite-borne, most other SFG rickettsiae are tick-borne. Amblyomma ticks, in particular A hebraeum, are the vectors of R africae.1 Although the name implies epidemiologic association with Africa, R africae infection has also been identified in Guadaloupe.3 A survey using a PCR assay for SFG rickettsiae in Amblyomma variegatum from St. Kitts and Nevis found that 41% of the ticks tested positive, and results were consistent with R africae.4
SFG rickettsiae attach to and enter endothelial cells, causing cell injury followed by vascular damage and immunologic responses.1 Symptoms develop after an incubation period of 4-7 days.5-8 Clinical manifestations can involve multiple organ systems and may include rash, abdominal pain, nausea, vomiting, cough, pulmonary edema, renal failure, headache, confusion, seizures, and arrhythmias.1 Nonspecific symptoms such as fever, headache, or myalgias are very common. Skin rash is frequently associated with infections caused by R conorii, R rickettsii, and R australis. However, R africae infections are associated with skin manifestations in only 50% of documented cases.5,9 Recent studies in travelers diagnosed with ATBF have typically found eschars or taches noire (single or multiple), regional adenopathy, and sometimes a maculopapular or vesicular rash.5-9 ATBF can be associated with abnormal laboratory findings such as thrombocytopenia or renal insufficiency.1
Diagnosis of ATBF can be established by microimmunofluorescent antibody determinations, serum cross-adsorption, Western blotting, rickettsial cultures, or PCR assay.9 Specific testing for R africae is only available in specialized laboratories (Unite des Rickettsias, Faculte de Medecine, Universite de la Mediterranee, Marseilles, France). However, serologic tests of R conorii and R rickettsii cross-react with R africae, and the diagnosis of ATBF can be established on the basis of positive rickettsial serologies given the right clinical and epidemiologic background. Treatment of ATBF is similar in other SFG rickettsioses: tetracycline, chloramphenicol, or ciprofloxacin are effective.1 Doxycycline 100 mg b.i.d. for 7-14 days is a convenient and frequently prescribed course; however, chloramphenicol has been the drug of choice for treatment of pregnant women.1 Ciprofloxacin has shown in vitro activity against SFG rickettsiae.10
ATBF has emerged as an important vector-borne disease that affects travelers to southern Africa, yet many travelers are not aware of their risk of ATBF. The incidences of ATBF and SFG rickettsial infection in the Jensenius study, 4.0% and 5.3%, respectively, suggests that ATBF is a significant imported tropical infection in travelers. The highest risk appears to be participants in game hunting and travel during the summer (November to April). Because the disease can affect short-term safari visitors, travel medicine specialists should discuss the risk of ATBF if the itinerary includes visits to endemic areas, especially South Africa, Swaziland, Lesotho, Namibia, and Botswana. Prevention is accomplished by wearing long sleeves and long pants, applying repellents containing DEET (N, N- diethyl-m-toluamide) to skin, and/or treating clothing with the insecticide, permethrin. Finally, only about 50% of affected patients presented with skin manifestations. Therefore, ATBF should be considered in the differential diagnosis of febrile returning travelers with possible exposure history, even in the absence of skin lesions.
Dr. Chen is Clinical Instructor, Harvard Medical School, Director, Travel Resource Center, Mt. Auburn Hospital, Cambridge, Mass.
References
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2. Raoult D, Roux V. Rickettsioses as paradigms of new or emerging infectious diseases. Clin Micro Rev. 1997; 10:694-719.
3. Parola P, et al. Tick-borne infection caused by Rickettsia africae in the West Indies. N Engl J Med. 1998; 338:1391-1392.
4. Kelly PJ, et al. A survey for spotted fever group rickettsiae and ehrlichiae in Amblyomma variegatum from St. Kitts and Nevis. Am J Trop Med Hyg. 2003; 69(1):58-59.
5. Fournier P-E, et al. Outbreak of Rickettsia africae infections in participants of an adventure race in South Africa. Clin Infect Dis. 1998;27:316-323.
6. CDC. African tick-bite fever among international travelers—Oregon, 1998. MMWR Morb Mortal Wkly Rep. 1998;47(44):950-952.
7. Sexton DJ, et al. Imported African tick bite fever: A case report. Am J Trop Med Hyg. 1999;60(5):865-867.
8. Brouqui P, et al. African tick-bite fever. Arch Intern Med. 1997;157:119-124.
9. Raoult D, et al. Rickettsia africae, a tick-borne pathogen in travelers to sub-Saharan Africa. N Engl J Med. 2001;344:1504-1510.
10. Rolain JM, et al. In vitro susceptibilities of 27 rickettsiae to 13 antimicrobials. Antimicrob Agents Chemo. 1998;42:1537-1541.
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