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Abstract & Commentary
Synopsis: Travelers returning from Africa are at risk for having acquired spotted fever rickettsiosis. Diagnosis requires antibody assays for IgG in paired acute and convalescent sera against Rickettsia antigens or immunohistochemical stains on skin biopsy specimens. The diagnosis can be missed if convalescent sera are obtained too early; therefore, convalescent specimens should be obtained at least 28 days after the onset of illness.
Source: McQuiston JH, et al. Imported spotted fever rickettsioses in United States travelers returning from Africa: A summary of cases confirmed by laboratory testing at the Centers for Disease Control and Prevention, 1999-2002. Am J Trop Med Hyg. 2004;70(1):98-101.
A review was performed in an attempt to correlate laboratory diagnosis of spotted fever group rickettsiosis (SFGR) with clinical and epidemiologic data. From 1999 to 2002, 31 cases of SFGR were confirmed in travelers returning from Africa by laboratory testing at the Centers for Disease Control and Prevention.
Diagnostic tests included immunofluorescent antibody assays for IgG against Rickettsia conorii, R rickettsii, and R akari antigens and immunohistochemical (IHC) stains on eschar or rash biopsy specimens. Eighteen cases of SFGR were confirmed, while 13 cases were classified as probable. Diagnoses were confirmed by a 4-fold or greater change in antibody titers (13), a 4-fold change in titer and IHC staining on biopsy specimen (3), IHC staining and a single positive antibody titer (1), and IHC staining alone (1). Twelve patients had an initial nonreactive acute-phase serum sample obtained on the third day of illness and were confirmed by testing a second convalescent-phase serum sample obtained a median of 32 days after illness onset. Nineteen patients with suspected SFGR had nonreactive sera obtained within 28 days after the onset of illness.
The most common destinations visited by these patients were South Africa (19), Zimbabwe (2), Rwanda (1), South Africa and Mozambique (1), Zambia and Tanzania (1), and 7 did not specify a country within Africa. Among patients who reported the month of illness onset, 48% reported their onset during March or April. A total of 77% of patients noted tick or other insect exposure. The most commonly reported symptoms were fever (74%) and eschar (55%). Rash was reported by only 26% of the patients. Group exposure was suggested by similarities in dates of illness, travel destinations, and surnames.
Comment by Lin H. Chen, MD
SFGR are zoonoses caused by obligate intracellular Gram-negative coccobacilli within the genus Rickettsia. The etiologic agent of scrub typhus, formerly R tsutsugamushi, has been renamed Orientia tsutsugamushi. Numerous human pathogens in the SFGR have been identified in recent years, as shown in the Table,1-5 including R parkeri which was recognized in a human in Virginia.5 Ticks are the usual vectors for SFGR, with the exception of R akari and R felis, which are transmitted by mites and fleas, respectively. Among the SFGR, R aeschlimannii R africae, R conorii, and R mongolotimori have been associated with human disease in Africa.1-4
Additional epidemiologic information has emerged regarding SFGR. A seroepidemiologic study of acutely febrile patients in Cameroon showed that 32% contained IgM antibodies to R africae.6 R africae has been identified in a traveler returning to France from Guadaloupe.7 SFGR have also emerged along the Thai-Myanmar border, where sera from patients have reacted to R helvetica, R conorii, and R felis.8 Another serologic survey has identified SFGR along with scrub typhus and murine typhus in Sri Lanka.9
R africae is the most common SFGR found in southern Africa, and it is likely the most frequently encountered SFGR in the cohort studied. Although the serologic tests used in the current study did not specifically identify R africae, antibodies to the SFGR cross-react with each other. An incubation period of 4-7 days usually follows a tick bite. Patients may then develop fever, rash, myalgia, abdominal pain, nausea, vomiting, and headache; additional symptoms include cough, pulmonary edema, renal failure, confusion, seizures, and arrhythmias.10 Skin manifestations occur in about 50% of the cases and include eschars and maculopapular or vesicular rash.11-13
A study on Norwegian travelers to Africa found serologic evidence for SFGR in 5.3% of the travelers, including 4.0% for R africae.11 Activities such as game hunting and photo safaris are associated with an increased risk. Travel during the summer (November to April) is associated with SFGR,11 and McQuiston et al found a similar prevalence in March and April.
A previous study reviewed 52 cases of imported SFGR in US travelers returning from Africa over a 10-year period from 1977 through 1986.14 The study by McQuiston et al collected 31 cases in a 4-year period. These figures take into account only specimens tested by the CDC and not tests performed by commercial laboratories. However, the rise in the number of cases suggests an increase in the incidence of SFGR, an increase in the volume of travelers, an increase in adventure travel, an increase in physician awareness of the disease, or a combination of all these factors. Travel medicine specialists should counsel travelers visiting endemic areas, especially if the itinerary includes rural exposure. In addition to wearing long sleeves, long pants, and tucking pants into socks, the use of DEET (N, N-diethyl-m-toluamide) on skin and application of permethrin on clothing are effective preventive strategies. The diagnosis of rickettsial infections should be considered in returning travelers with an acute febrile illness.
Diagnostic tests for SFGR include assaying paired acute and convalescent sera for antibodies to Rickettsia, IHC staining of skin biopsy specimens, and PCR (available in research laboratories). This report illustrates the use of IHC staining of skin biopsy specimens during early infection to confirm a diagnosis of SFGR in returning travelers. Given the negative serologies occurring during early infection, it is important to obtain convalescent-phase serum specimens at least 28 days after illness onset in order to establish a diagnosis.
Dr. Chen, Clinical Instructor, Harvard Medical School Director, Travel Resource Center, Mt. Auburn Hospital, Cambridge, Mass., is Associate Editor of Travel Medicine Advisor.
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