title: Hidden mortality attributable to Rocky Mountain spotted fever: immunohistochemical detection of fatal, serologically unconfirmed disease.
abstract: Rocky Mountain spotted fever (RMSF) is the most severe tickborne infection in the United States and is a nationally notifiable disease. Since 1981, the annual case-fatality ratio for RMSF has been determined from laboratory-confirmed 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 immunohistochemical (IHC) staining of tissues obtained at autopsy. During 1996-1997, acute-phase serum and tissue samples from patients with fatal disease compatible with RMSF were tested at the CDC. As determined by indirect immunofluorescence assay, no patient serum demonstrated IgG or IgM antibodies reactive with Rickettsia rickettsii at a diagnostic titer (i.e., >/=64); however, IHC staining confirmed diagnosis of RMSF in all patients. Polymerase chain reaction validated the IHC findings for 2 patients for whom appropriate samples were available for testing. These findings suggest that dependence on serologic assays and limited use of IHC staining for confirmation of fatal RMSF results in underestimates of mortality and of case-fatality ratios for this disease.
authors.affiliation: Viral and Rickettsial Zoonoses Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Paddock
authors.forename: P W
authors.initials: PW
authors.lastname: Greer
authors.forename: T L
authors.initials: TL
authors.lastname: Ferebee
authors.forename: J
authors.initials: J
authors.lastname: Singleton
authors.forename: D B
authors.initials: DB
authors.lastname: McKechnie
authors.forename: T A
authors.initials: TA
authors.lastname: Treadwell
authors.forename: J W
authors.initials: JW
authors.lastname: Krebs
authors.forename: M J
authors.initials: MJ
authors.lastname: Clarke
authors.forename: R C
authors.initials: RC
authors.lastname: Holman
authors.forename: J G
authors.initials: JG
authors.lastname: Olson
authors.forename: J E
authors.initials: JE
authors.lastname: Childs
authors.forename: S R
authors.initials: SR
authors.lastname: Zaki
mesh_terms: D000328:Adult; D000368:Aged; D002487:Centers for Disease Control and Prevention, U.S.; D002675:Child, Preschool; D018563:Disease Notification; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D012284:Rickettsia rickettsii / Q000302:isolation & purification; D012373:Rocky Mountain Spotted Fever / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000401:mortality*; D014481:United States