Serologic Evidence for Infection of Humans By Multiple Spotted Fever Group (SFG) Rickettsiae in Tennessee

BACKGROUND:  Rocky Mountain Spotted Fever (RMSF) is the most common tick-borne disease reported in the state of Tennessee and is caused by R. rickettsii. It belongs to the Spotted Fever Group (SFG) rickettsiae that includes numerous other species such as R. montanensis, R. parkeri, and R. amblyommii. However, serologic cross-reactivity is common within the SFG rickettsiae and R. rickettsii has rarely been isolated from endemic ticks, suggesting SFG rickettsioses in Tennessee may be caused by other Rickettsial species. This study aims to investigate exposure to four Rickettsia species in sera from humans tested for RMSF to better understand the etiology of SFG rickettsioses in Tennessee.

METHODS:  A total of 45 human serum samples that tested positive for Rickettsia were obtained from diagnostic labs in 2010 and 2011 and from the Tennessee Unexplained Encephalitis Study (T.U.E.S.). Clinical signs and symptoms were identified from review of medical records and case report forms. Using an indirect immunoflourescent-antibody assay (IFA), reactivity of the sera to R. rickettsii, R. montanensis, R. parkeri and R. amblyommii were tested and a comparison of endpoint titers was used to determine the probable antigen that stimulated the antibody response. For samples whose endpoint titers were less than 4-fold different between species, cross-absorptions with the Rickettsia antigens were performed and the supernatants were retained for IFA and Western blotting.   

RESULTS:  In the initial IFA, 4 (9%) samples had a highest endpoint titer to R. amblyommii and 2 (4%) samples had a highest endpoint titer to R. parkeri. The rest of the samples (n=39) had titers with less than 4-fold difference between species. Among the latter set of samples, 26 (58%) had similar titers for all four species, 6 (13%) for R. montanensis, R. parkeri and R. amblyommii, 2 (4%) for R. rickettsii, R. parkeri and R. amblyommii, and 5 (11%) for R. parkeri and R. amblyommii. Cross-absorption of some samples with similar titers resulted in 3 samples positive for R. amblyommii and 1 was indeterminate.

CONCLUSIONS:  Significant serologic cross-reactivity was observed in the majority of the samples with higher titers to R. amblyommii and R. parkeri compared to R. montanensis and R. rickettsii. To our knowledge, this is the first time R. amblyommii and R. parkeri have been reported as possible causative agents of rickettsioses in Tennessee. Further investigation is needed to determine if the differences in titers correlate with clinical characteristics or severity of illness.