Inadequacy of IgM Antibody Tests for Diagnosis of Rocky Mountain Spotted Fever

BACKGROUND: Tennessee is a Rocky Mountain spotted fever (RMSF) endemic area. Increasing incidence and high case fatality rates with untreated RMSF are of great concern. High incidence rates and spatial clustering of severe outcomes have been described in the western part of Tennessee. We enhanced surveillance efforts in partnership with local healthcare providers in four west Tennessee counties, which allowed for appropriately timed diagnostic testing and extended follow-up of antibody titers in clinically identified patients with suspected RMSF.

METHODS: Patients meeting the study criteria were identified by participating providers. Enrolled patients were tested for IgM and IgG antibodies to RMSF at 0 to 2 weeks after onset of illness, 2 to 4 weeks after onset, 4 to 8 weeks after onset, and approximately 1 year after onset. Cases of RMSF were classified according to the National Surveillance case definition (positive IgG or IgM result of > 1:64 between the 0 to 8 weeks after onset, fever, and one or more of the following symptoms: headache, myalgia, rash/eschar, anemia, thrombocytopenia, or elevated hepatic transaminases).

RESULTS: Thirteen patients with suspected Rocky Mountain spotted fever (RMSF) were identified during the study period and antibodies to R. rickettsii antigen were observed among 10 (77%) patients. IgM antibodies to R. rickettsii antigen were observed in 6/13 patients (46%) without a corresponding development of IgG antibodies; IgM antibodies were also present in samples from 3/10 patients (30%) with sera collected one year post-onset. Nine of 13 patients met the National Surveillance case definition of a probable case, but no patients met the criteria of a confirmed case, despite timely and clinically appropriate testing. One study patient had a four-fold drop in titer recorded over the study period, but did not have a fever at the time of diagnosis.

CONCLUSIONS: Recent infection with RMSF or another Spotted Fever Group Rickettsia (SFGR) could not be diagnostically confirmed for any patient, based on lack of rising antibody titers in properly timed acute and convalescent serologic specimens and negative findings by polymerase chain reaction (PCR) testing. Detected IgM antibodies were not often accompanied by rises in IgG antibodies, suggesting that the SFGR case definitions used in national surveillance programs lack specificity and may misclassify cases that do not represent current rickettsial infections. Use of IgM antibodies should be reconsidered as a basis for diagnosis and public health reporting of RMSF and other SFGR in the United States. Improved clinical diagnostic strategies are needed.