Follow-up investigation of antibody titers and diagnostic antibody cutoff values in patients with scrub typhus in South Korea

Abstract

Background: Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi. Few follow-up studies have assessed antibody titers using serologic tests from various commercial laboratories and the Korea Centers for Disease Control and Prevention (KCDC).

Methods: A prospective study to assess the antibody titers in patients with scrub typhus and seroprevalence in individuals undergoing health checkups was conducted using results of immunofluorescence antibody assays (IFAs) and serologic tests, used by the KCDC and commercial laboratories, respectively. The following tests were performed simultaneously: (i) indirect IFA used by the KCDC to detect immunoglobulin (Ig) M and IgG, (ii) IFA used by a commercial laboratory to detect total Ig, and (iii) antibody tests using two commercially available kits.

Results: When the IgM and IgG cutoff values (≥1:16 and ≥1:256, respectively) used in the IFA and the total IgG cutoff values (≥1:40) were used in prospective follow-up investigations, the antibody positivity rates of 102 patients with scrub typhus were 44.1, 35.3, and 57.6%, respectively, within 5 days of symptom onset. Among 91 individuals who recovered from scrub typhus, the follow-up IgM, IgG, and total Ig positivity rates for 13 years were 37.4% (34/91), 22.0% (20/91), and 76.9% (70/91), respectively. Among 216 individuals undergoing health checkups, the seroprevalence of IgM was 4.2% (9/216); no seroprevalence of IgG was observed.

Conclusions: IFAs used by the KCDC and the commercial laboratory and rapid commercial kits could not distinguish between patients who had recovered from scrub typhus and those who are currently infected with O. tsutsugamushi. In South Korea and other countries, where low antibody cutoff values are used, upward adjustments of cutoff values may be necessary.

Keywords: Fluorescent antibody technique; Orientia tsutsugamushi; Scrub typhus.

Fig. 1

Prospective follow-up of antibody titers in patients diagnosed with scrub typhus. The antibody titers were measured by an immunofluorescence assay (IFA). a. Mean (± standard deviation) antibody titers. b. Median (± interquartile range) antibody titers. Data show total immunoglobulin (Ig) levels measured by company A, which is a commercial laboratory, and IgM/G titers measured by the IFA used by the KCDC. Cf>IFA IgM and IgG were checked in 34 serum samples, but total Ig was checked in 33 serum samples at 0 weeks.

Fig. 2

Overview of prospective and retrospective follow-up antibody titers determined by the following tests: (i) IFA used by KCDC to detect IgM and IgG, (ii) IFA used by company A to detect total Ig, and (iii) antibody tests using two commercially available kits from companies C and D