Researchers Identify Biomarker for Spotted Fever Rickettsial

Researchers recently discovered a sensitive and specific biomarker that may enable early diagnosis, treatment, and public notification of spotted fever rickettsial infections, including Mediterranean spotted fever (MSF), according to a study published in the American Journal of Pathology.

“Mediterranean spotted fever is a reemerging acute tick-borne infection produced by the α-proteobacterium, Rickettsia conorii,” authors said. “Rickettsia conorii infects vascular endothelial cells producing disseminated plasma leakage, manifesting as nonspecific fever, headache, and maculopapular rash. Because there are no available tests of early infection, Mediterranean spotted fever is often undiagnosed and untreated, resulting in significant mortality.”

The research involved use of a quantitative proteomics pipeline to identify a biomarker for the rickettsial infection in order to diagnose MSF. Researchers identified the rickettsial protein, RC0497, from a culture medium of primary human umbilical vein endothelial cells infected with Rickettsia conorri. They then developed assays for detecting RC0497 in blood. Researchers used a mouse model of Rickettsia conorii and serum samples from humans with acute rickettsioses.

Results suggested that RC0497 can significantly differentiate infected individuals from healthy controls and that different levels of RC0497 are proportional to the severity of the infection.

“The detection of RC0497 has the potential to diagnosis a wide variety of rickettsial spotted fever infections, including Rocky Mountain spotted fever,” co-lead investigator Yingxin Zhao, PhD, said in a statement.

Co-author, David H. Walker, MD, explained that the results may assist in developing a point-of-care diagnostic test that could revolutionize the diagnosis of spotted fever rickettsioses. However, a larger cohort study is needed in order to validate the results.

"The rickettsioses represent an important unmet need in human and veterinary medicine. Rickettsioses are a spectrum of potentially lethal diseases whose diagnosis and definitive treatment require a high index of suspicion," the researchers concluded.

Reference:

Zhao Y, Fang R, Zhang J, et al. Quantitative proteomics of the endothelial secretome identifies RC0497 as diagnostic of acute rickettsial spotted fever infections [published online January 16, 2020]. Am J Pathol. doi: 10.1016/j.ajpath.2019.10.007.