Hidden mortality attributable to rocky mountain spotted fever: Immunohistochemical detection of fatal, serologically unconfirmed disease

Rocky Mountain spotted fever (RMSF) is the most severe tickborne infection in the United States and is a nationally notifiable disease. Since 1981, th e annual case-fatality ratio for RMSF has been determined from laboratory-c onfirmed cases reported to the Centers for Disease Control and Prevention ( CDC), Herein, a description is given of patients with fatal, serologically unconfirmed RMSF for whom a diagnosis of RMSF was established by immunohist ochemical (IHC) staining of tissues obtained at autopsy. During 1996-1997, acute-phase serum and tissue samples from patients with fatal disease compa tible with RMSF were tested at the CDC. As determined by indirect immunoflu orescence assay, no patient serum demonstrated IgG or IgM antibodies reacti ve with Rickettsia rickettsii at a diagnostic titer (i.e,, greater than or equal to 64); however, IHC staining confirmed diagnosis of RMSF in all pati ents. Polymerase chain reaction validated the IHC findings for 2 patients f or whom appropriate samples were available for testing. These findings sugg est that dependence on serologic assays and limited use of IHC staining for confirmation of fatal RMSF results in underestimates of mortality and of c ase-fatality ratios for this disease.