Background: The rickettsial diseases Japanese spotted fever (JSF) and scrub typhus (ST) are caused by Rickettsia japonica and Orientia tsutsugamushi, respectively. The diseases share clinical symptoms, such as fever, rash, and eschar. However, there are no systematical investigations of the serological cross-reactivity between R. japonica and O. tsutsugamushi. Also, it has still been unclear the serological cross-reactivity among O. tsutsugamushi serotypes.
Methods: We analyzed 1,406 cases tested by indirect immunoperoxidase assay (IP) using 7 rickettsial antigensone R. japonica and 6 O. tsutsugamushi serotypes (Kato, Karp, Gilliam, Irie/Kawasaki, Hirano/Kuroki, and Shimokoshi)between 2003 and 2016 at 2 reference centers in Japan. Patient sera were 2-fold diluted from 1:40 to 1:40,960, and the titer was expressed as the reciprocal values. We defined the serology diagnosis as positive when a ≥ 4-fold increase in the IP IgM/IgG titer against R. japonica or O. tsutsugamushi was observed in the paired samples or if the IP IgM titer was ≥ 320.
Results: Of the 1,406 cases, 154 JSF and 138 ST cases were diagnosed by paired samples, and 13 JSF and 52 ST cases were diagnosed by a single sample. Figure 1a shows the serology results of 154 JSF cases6 cases showed an IgG titer of ≥ 40 against O. tsutsugamushi without any significant elevation and 4 cases showed a non-significant IgM elevation of < 320, which had none/few cross-reactions with other O. tsutsugamushi serotypes. Figure 1b shows the serology results of 138 ST cases, none showing any rise in the IgM/IgG titer against R. japonica except for one with an IgG titer of 80 only in the acute phase sample. We observed a massive degree of cross-reactivity between O. tsutsugamushi serotypes. When the correlation was further analyzed, cross-reactivity was significant among Karp, Hirano/Kuroki, and Kato types and between Gilliam and Irie/Kawasaki types in IgM. In contrast, the Shimokoshi type was less cross-reactive than the others (Figure 2).
Conclusion: There is no serological cross-reaction or no recall reaction between R. japonica and O. tsutsugamushi. The cross-reactivity among O. tsutsugamushi vary.
H. Fujita, None