Antibody Titers Reactive With Rickettsia rickettsii in Blood Donors and Implications for Surveillance of Spotted Fever Rickettsiosis in the United States

Abstract

Background Since 2000, the reported prevalence of tick-borne spotted fever rickettsiosis has increased considerably. We compared the level of antibody reactivity among healthy blood donors from 2 widely separated regions of the United States and evaluated the impact of antibody prevalence on public health surveillance in one of these regions. Methods Donor serum samples were evaluated by indirect immunofluorescence antibody assay to identify immunoglobulin G (IgG) antibodies reactive with Rickettsia rickettsii. The Georgia Department of Public Health (GDPH) analyzed characteristics of cases from 2016 surveillance data to evaluate the utility of laboratory surveillance for case assessment. Results Of the Georgia donors (n = 1493), 11.1% demonstrated antibody titers reactive with R. rickettsii at titers ≥64, whereas 6.3% of donors from Oregon and Washington (n = 1511) were seropositive. Most seropositive donors had a titer of 64; only 3.1% (n = 93) of all donors had titers ≥128. During 2016, GDPH interviewed 243 seropositive case patients; only 28% (n = 69) met inclusion criteria in the national case definition for spotted fever rickettsiosis. Conclusions These findings suggest that a single IgG antibody titer is an unreliable measure of diagnosis and could inaccurately affect surveillance estimates that define magnitude and clinical characteristics of Rocky Mountain spotted fever and other spotted fever rickettsioses.

Assessing human exposure to spotted fever and typhus group rickettsiae in Ontario, Canada (2013–2018): a retrospective, cross-sectional study

“…As with other tick-borne serology tests, rickettsial serology is often negative in early infection; therefore, we would expect to miss infections in Ontario patients tested in the first week of illness. In contrast, we have likely overestimated rickettsial exposure, since we used sensitive case definitions for possible and previous rickettsial infection cases relying on single elevated IgG titers (≥ 1: 64), with or with clinical evidence of infection respectively [32]. It was difficult to document 4-fold increases in IgG titers in our study since our endpoint titer was relatively low at 1:256, meaning we likely underestimated confirmed cases.…”

“…A previous rickettsial infection case demonstrated a single elevated IgG titer (≥ 1:64), without evidence of the combination of fever plus any other sign or symptom. While single IgG titers ≥1:64 likely overestimate rickettsial infection, for this study we felt sensitivity was more important in our surveillance case definitions than specificity [32]. We did not assess IgM serological results for laboratory diagnoses, since, unlike for other infectious diseases, IgM is not useful in identifying current or recent rickettsial infections [3,33,34].…”

Rocky Mountain Spotted Fever in a Large Metropolitan Center, Mexico–United States Border, 2009–2019

“…PCR-positive patients are more likely to have severe manifestations, which could bias comparisons between groups confirmed by molecular and serologic methods. In addition, the molecular assay used to confirm cases of RMSF in Mexicali is specific only for the genus Rickettsia ( 17 ); because other pathogenic Rickettsia species, including R. massiliae , R. parkeri , and R. typhi , are endemic to northern Mexico ( 29 – 33 ), some PCR-positive patients identified in this series might have represented cases of rickettsial diseases other than RMSF. However, the overall severity of illnesses, coupled with extensive and consistent epidemiologic and environmental evidence implicating brown dog ticks as the principal vector perpetuating this outbreak ( 8 – 10 , 12 ), suggest strongly that most, if not all, PCR-confirmed cases were indeed infections caused by R. rickettsii .…”

“…Although IFA methods are used widely for epidemiologic evaluations of RMSF, the use of a single IgG titer can reflect past exposure to an SFGR at an undetermined time and can inaccurately reflect surveillance estimates that define the magnitude and clinical characteristics of RMSF ( 29 ). Because IgG titers are reflective of the host immune response to R. rickettsii , these titers are not expected to be elevated in the first several days of illness, when most patients seek medical attention.…”

The expanding spectrum of disease caused by the Lone Star Tick, Amblyomma americanum

“…R. amblyommatis elicits an immune response that can cause reactivity with the antigens used commercially to diagnose other SFGR such as Rocky Mountain Spotted Fever (RMSF). Moreover, other non-rickettsial pathogens such as BRBV and HRTV could be misdiagnosed with an infection caused by a SFGR if the individual has preexistent antibodies to R. amblyommatis [63,64]. The diagnosis of both HRTV and BRBV is restricted to a few research laboratories and CDC.…”