Rickettsia parkeri Infection and Other Spotted Fevers in the United States
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《新英格兰医药杂志》
To the Editor: Extensive cross-reactivity exists among antigens of various spotted-fever–group rickettsiae, and routine serologic assays are generally insufficient to identify conclusively the specific rickettsial agent responsible for the infection. Since 1989 one of us (Dr. Raoult) has investigated the reactivity of serum specimens from patients with various rickettsioses to define the serologic criteria for several of these infections in the Eastern Hemisphere.1,2 Rickettsia parkeri, a spotted-fever–group rickettsia first identified in 1939 in Gulf Coast ticks (Amblyomma maculatum) collected from Texas, has only recently been shown to be a cause of the disease in the United States.3 Herein we describe the use of Western blot techniques to show that additional human cases of infection with R. parkeri, or possibly other unrecognized spotted-fever–group rickettsiae, may have occurred in the United States.
Serum specimens from patients in the United States with rickettsioses are routinely submitted to the Centers for Disease Control and Prevention for diagnostic testing. Aliquots of 15 specimens with antibodies reactive with R. rickettsii, the agent of Rocky Mountain spotted fever, were evaluated at the Unité des Rickettsies, in Marseille, France, with the use of microimmunofluorescence and Western blot assays that compare the responses of antibodies against antigens of R. rickettsii and R. parkeri. Microimmunofluorescence assays showed that four patients had higher titers (by at least two dilutions) of IgG and IgM antibody to R. rickettsii, and five patients had higher titers of antibody to R. parkeri, and in six patients no difference between titers was observed. Four serum specimens with titers of antibody to R. parkeri that were greater than or equal to those to R. rickettsii on microimmunofluorescence assay were available in sufficient quantity to evaluate with the use of Western blot analysis, and each reacted with a 120-kD protein of R. parkeri (Figure 1), a finding suggestive of infection with this agent.
Figure 1. Results of Western Blot Assay of Serum from Four Patients in the United States with Various Confirmed or Suspected Spotted-Fever Rickettsioses.
The assays reacted with antigens of R. rickettsii, R. parkeri, or R. akari. Rocky Mountain spotted fever was suspected in Patient 1 (lanes 1 and 2). Patient 2 (lanes 3, 4, and 5) had polymerase-chain-reaction (PCR)–proved and culture-proved R. parkeri rickettsiosis. The results of the assay from Patient 3, who had PCR-proved Rocky Mountain spotted fever, are shown before (lanes 6, 7, and 8) and after (lanes 9, 10, and 11) adsorption with R. parkeri antigen. Patient 4 had PCR- and culture-proved rickettsialpox (lanes 12, 13, and 14). Reactivity with a 120-kD protein of R. parkeri is seen in the specimens from Patient 1 (arrow, lane 2) and from Patient 2 (arrow, lane 5). Reactivity with high-molecular-weight proteins of R. rickettsii and R. parkeri is seen in the specimen from Patient 3 (lanes 6 and 8); after adsorption with R. parkeri antigen, only reactivity with R. rickettsii remains (arrow, lane 9). No reactivity with R. rickettsii or R. parkeri was present after adsorption with R. rickettsii antigen (data not shown). Reactivity with a 90-kD protein of R. akari is seen only in the serum of Patient 4, who was infected with R. akari (arrow, lane 13).
These preliminary data are limited by the lack of accompanying clinical or epidemiologic correlates; however, the findings suggest that some infections with R. parkeri were previously classified as Rocky Mountain spotted fever. Recognized or potential arthropod-borne spotted-fever–group rickettsial pathogens in the United States, other than R. rickettsii, include R. akari, R. felis, R. parkeri, R. amblyommii, R. rhipicephali, and various unnamed serotypes (e.g., Tillamook and 364-D).4,5 Further molecular and culture-based studies will be needed to differentiate definitively the serologic responses of patients to these various agents. Nonetheless, the coexistence of several rickettsioses caused by distinct spotted-fever–group rickettsiae, increasingly recognized in Europe, Africa, and Asia, may also occur in the Western Hemisphere, and it is possible that several species of rickettsia, including R. parkeri, are responsible for cases of tick-borne rickettsiosis that have been described in the United States during the past century.
Didier Raoult, M.D., Ph.D.
Centre National de la Recherche Scientifique
13385 Marseille, France
didier.raoult@medecine.univ-mrs.fr
Christopher D. Paddock, M.D., M.P.H.T.M.
Centers for Disease Control and Prevention
Atlanta, GA 30333
References
Raoult D, Fournier PE, Fenollar F, et al. Rickettsia africae, a tick-borne pathogen in travelers to sub-Saharan Africa. N Engl J Med 2001;344:1504-1510.
Rolain JM, Shpynov S, Raoult D. Spotted-fever-group rickettsioses in north Asia. Lancet 2003;362:1939-1939.
Paddock CD, Sumner JW, Comer JA, et al. Rickettsia parkeri: a newly recognized cause of spotted fever rickettsiosis in the United States. Clin Infect Dis 2004;38:805-811.
Philip RN, Casper EA, Burgdorfer W, Gerloff RK, Hughes LE, Bell EJ. Serologic typing of rickettsiae of the spotted fever group by microimmunofluorescence. J Immunol 1978;121:1961-1968.
Raoult D, Roux V. Rickettsioses as paradigms of new or emerging infectious diseases. Clin Microbiol Rev 1997;10:694-719.
Serum specimens from patients in the United States with rickettsioses are routinely submitted to the Centers for Disease Control and Prevention for diagnostic testing. Aliquots of 15 specimens with antibodies reactive with R. rickettsii, the agent of Rocky Mountain spotted fever, were evaluated at the Unité des Rickettsies, in Marseille, France, with the use of microimmunofluorescence and Western blot assays that compare the responses of antibodies against antigens of R. rickettsii and R. parkeri. Microimmunofluorescence assays showed that four patients had higher titers (by at least two dilutions) of IgG and IgM antibody to R. rickettsii, and five patients had higher titers of antibody to R. parkeri, and in six patients no difference between titers was observed. Four serum specimens with titers of antibody to R. parkeri that were greater than or equal to those to R. rickettsii on microimmunofluorescence assay were available in sufficient quantity to evaluate with the use of Western blot analysis, and each reacted with a 120-kD protein of R. parkeri (Figure 1), a finding suggestive of infection with this agent.
Figure 1. Results of Western Blot Assay of Serum from Four Patients in the United States with Various Confirmed or Suspected Spotted-Fever Rickettsioses.
The assays reacted with antigens of R. rickettsii, R. parkeri, or R. akari. Rocky Mountain spotted fever was suspected in Patient 1 (lanes 1 and 2). Patient 2 (lanes 3, 4, and 5) had polymerase-chain-reaction (PCR)–proved and culture-proved R. parkeri rickettsiosis. The results of the assay from Patient 3, who had PCR-proved Rocky Mountain spotted fever, are shown before (lanes 6, 7, and 8) and after (lanes 9, 10, and 11) adsorption with R. parkeri antigen. Patient 4 had PCR- and culture-proved rickettsialpox (lanes 12, 13, and 14). Reactivity with a 120-kD protein of R. parkeri is seen in the specimens from Patient 1 (arrow, lane 2) and from Patient 2 (arrow, lane 5). Reactivity with high-molecular-weight proteins of R. rickettsii and R. parkeri is seen in the specimen from Patient 3 (lanes 6 and 8); after adsorption with R. parkeri antigen, only reactivity with R. rickettsii remains (arrow, lane 9). No reactivity with R. rickettsii or R. parkeri was present after adsorption with R. rickettsii antigen (data not shown). Reactivity with a 90-kD protein of R. akari is seen only in the serum of Patient 4, who was infected with R. akari (arrow, lane 13).
These preliminary data are limited by the lack of accompanying clinical or epidemiologic correlates; however, the findings suggest that some infections with R. parkeri were previously classified as Rocky Mountain spotted fever. Recognized or potential arthropod-borne spotted-fever–group rickettsial pathogens in the United States, other than R. rickettsii, include R. akari, R. felis, R. parkeri, R. amblyommii, R. rhipicephali, and various unnamed serotypes (e.g., Tillamook and 364-D).4,5 Further molecular and culture-based studies will be needed to differentiate definitively the serologic responses of patients to these various agents. Nonetheless, the coexistence of several rickettsioses caused by distinct spotted-fever–group rickettsiae, increasingly recognized in Europe, Africa, and Asia, may also occur in the Western Hemisphere, and it is possible that several species of rickettsia, including R. parkeri, are responsible for cases of tick-borne rickettsiosis that have been described in the United States during the past century.
Didier Raoult, M.D., Ph.D.
Centre National de la Recherche Scientifique
13385 Marseille, France
didier.raoult@medecine.univ-mrs.fr
Christopher D. Paddock, M.D., M.P.H.T.M.
Centers for Disease Control and Prevention
Atlanta, GA 30333
References
Raoult D, Fournier PE, Fenollar F, et al. Rickettsia africae, a tick-borne pathogen in travelers to sub-Saharan Africa. N Engl J Med 2001;344:1504-1510.
Rolain JM, Shpynov S, Raoult D. Spotted-fever-group rickettsioses in north Asia. Lancet 2003;362:1939-1939.
Paddock CD, Sumner JW, Comer JA, et al. Rickettsia parkeri: a newly recognized cause of spotted fever rickettsiosis in the United States. Clin Infect Dis 2004;38:805-811.
Philip RN, Casper EA, Burgdorfer W, Gerloff RK, Hughes LE, Bell EJ. Serologic typing of rickettsiae of the spotted fever group by microimmunofluorescence. J Immunol 1978;121:1961-1968.
Raoult D, Roux V. Rickettsioses as paradigms of new or emerging infectious diseases. Clin Microbiol Rev 1997;10:694-719.