BACKGROUND: Japanese spotted fever (JSF) mainly occurs in Japan; however, it has been increasingly reported in China. JSF is typically characterized by fever, rash, and eschar, in addition to non-specific symptoms. Yet, reports on the pulmonary indicators in JSF are limited. Herein, we report an unusual case of JSF associated with pleural effusion and pneumonia, in which the pathogen was identified via blood next-generation sequencing (NGS).
METHODS: We report a case of a 33-year-old woman who presented with fever for five days, rash for two days, and myalgia, fatigue, and edema for one day. She had recently been on vacation when an unknown insect bit her. The doctors at the local primary hospital considered a bacterial infection and administered dexamethasone, ceftriaxone, indomethacin, and anti-allergy agents, but the symptoms persisted. A rash without pruritus or pain developed gradually over the entire body and face. We considered rickettsial infection and administered doxycycline and levofloxacin. Metagenomic NGS from blood confirmed the presence of Rickettsia japonica (R. japonica). Abdominal computed tomography revealed bilateral pleural effusion with two atelectasis; patchy shadows with blurred edges, and uniform enhancement in both lower lungs. After several days of treatment, the symptoms and laboratory results improved. A literature review of the epidemiology of R. japonica and JSF in China, characteristics of JSF, and related pulmonary changes, and technology to diagnose JSF is provided.
CONCLUSIONS: JSF has a variety of symptoms and is becoming increasingly popular in China. Clinical doctors need to identify it carefully.

A 71-year-old male had disseminated multiple organ dysfunction syndrome (MODS). Following treatment with cefotaxime and piperacillin-tazobactam, his symptoms have worsened instead. Multiple organ failure caused by Japanese Spotted Fever (JSF) was diagnosed based on metagenomic next-generation sequencing (mNGS), we rapidly treated the patient with doxycycline. Thereafter, his symptoms gradually improved. In this report, we emphasized the importance of rapid microbial diagnostic tools and the early use of tetracyclines for the treatment of JSF.

To elucidate the epidemiology of murine typhus, which is infrequently reported in Japan, we conducted a cross-sectional study involving 2,382 residents of rickettsiosis-endemic areas in Honshu Island during August-November 2020. Rickettsia typhi seroprevalence rate was higher than that of Orientia tsutsugamushi, indicating that murine typhus is a neglected disease.

UNASSIGNED: Japanese spotted fever (JSF) is a tick-borne bacterial febrile disease caused by Rickettsia japonica characterized by fever, rash, and occasional death. The number of patients in Japan and the Tottori Prefecture has been increasing over the past 20 years. Most cases were found in Eastern Tottori; however, the distribution of patients has expanded to the Central and Western regions. Ticks carried by wild animals may be the cause, but the prevalence of R. japonica in ticks has not yet been analyzed.
UNASSIGNED: Ticks were collected by flagging-dragging from 16 sites in Tottori, Japan. The ticks were morphologically classified and DNA was extracted. The 17-kDa antigen gene was amplified using nested PCR. PCR amplicons from ticks and JSF patients were sequenced and phylogenetically compared.
UNASSIGNED: In total, 177 ticks were collected and identified as Haemahysalis, Ixodes, Amblyomma, and Dermcentor. The Spotted Fever Group Rickettsia (SFGR) was detected in Haemahysalis and Amblyomma spp. using PCR, with positivity rates of 36.8% and 33.3%, respectively. DNA sequencing and phylogenetic analysis revealed that positive ticks harbored R. japonica, P. raoultii, and other Rickettsiae species; however, the patient\'s samples were restricted to R. japonica. Similar to the incidence of JSF, the rate of R. japonica-positive ticks was higher in the Eastern region; however, R. japonica-positive ticks were also detected in the Western region.
UNASSIGNED: R. japonica sequences had been found in ticks collected in Tottori Prefecture. Ticks harboring R. japonica were found in the Eastern and Western parts of Tottori Prefecture and the sequences were identical to the human cases. Only the R. japonica sequence has been detected in patients with spotted fever symptoms, even though ticks were harboring various SFGRs.

OBJECTIVE: We examined the frequency of cross-reactions to Rickettsia typhi in patients with Japanese spotted fever (JSF) and evaluated the differences between two rickettsiae using antibody endpoint titers.
METHODS: Patients\' immunoglobulin (Ig)M and IgG titers against Rickettsia japonica and Rickettsia typhi in two phases were measured using an indirect immunoperoxidase assay at two reference centers for rickettsiosis in Japan. Cross-reaction was defined as a higher titer against R. typhi in convalescent sera than in acute sera among patients fulfilling the criteria for JSF diagnosis. The frequencies of IgM and IgG were also evaluated.
RESULTS: Approximately 20% of cases showed positive cross-reactions. A comparison of antibody titers revealed the difficulty in identifying some positive cases.
CONCLUSIONS: Cross-reactions of 20% in serodiagnosis may lead to the misclassification of rickettsial diseases. However, with the exception of some cases, we were able to successfully differentiate JSF from murine typhus using each endpoint titer.

We report a case-series study of 5 patients with Japanese spotted fever from the Three Gorges Area in China, including 1 fatal case. Seroprevalence of Rickettsia japonica was ≈21% among the local population. Our report highlights the emerging potential threat to human health of Japanese spotted fever in the area.

Severe fever with thrombocytopenia syndrome was diagnosed in a febrile woman in Japan after a tick bite. However, Rickettsia japonica DNA was retrospectively detected in the eschar specimen, suggesting co-infection from the bite. Establishment of the severe fever with thrombocytopenia syndrome virus infection might have overpowered the R. japonica infection.

(1) Background. Rickettsia japonica (R. japonica) infection induces severe inflammation, and the disappearance of eosinophil in the acute stage is one of the phenomena. (2) Materials and Methods. In the current study, we measured the serum concentrations of Th1, Th2, and Th17 cytokines in the acute and recovery stages. (3) Results. In the acute phase, IL-6 and IFN-γ levels were elevated and we speculated that they played a role as a defense mechanism against R. japonica. The high concentration of IFN-γ suppressed the differentiation of eosinophil and induced apoptosis of eosinophil, leading to the disappearance of eosinophil. On day 7, IL-6 and IFN-γ concentrations were decreased, and Th2 cytokines such as IL-5 and IL-9 were slightly increased. On day 14, eosinophil count recovered to the normal level. The transition of serum cytokine concentration in R. japonica infection was presented. (4) Conclusions. IL-6 and IFN-γ seem to be critical cytokines as defense mechanism against R. japonica in the acute phase, and this may deeply connect to the decrease of eosinophil.

Rickettsia heilongjiangensis is the causative agent of Far-Eastern spotted fever (FESF). In Japan, a human case of FESF was identified in Sendai in Miyagi Prefecture in 2008, and R. heilongjiangensis bacteria were isolated from Haemaphysalis concinna ticks collected in the suspected geographical area of infection. Although the intraspecies genome diversity of Rickettsia has been poorly investigated, our recent analysis revealed extremely low genomic diversity of R. japonica, the agent of Japanese spotted fever, which is a close relative of R. heilongjiangensis. In this study, to investigate the genomic diversity of R. heilongjiangensis and understand the genetic relationship between Japanese and Chinese isolates, we sequenced three isolates from H. concinna ticks collected in Sendai and one isolate from a H. concinna tick collected in Inner Mongolia, China, and performed genomic comparisons between these isolates and strain 054, the type strain isolated from a Dermacentor silvarum tick in Heilongjiang Province, China. Although the three Japanese strains were isolated in 2008, 2009, and 2012, their genome sequences were identical, indicating that H. concinna ticks carrying a single R. heilongjiangensis clone have been distributed in Sendai, Japan. Among the five R. heilongjiangensis isolates, only 81 SNPs and 13 insertion/deletion sites were identified, despite the significant differences in these isolates both geographically and temporally. A significant portion of the 81 SNPs (16/81) were found to be recombinogenic. These results indicate low genomic diversity of R. heilongjiangensis, as observed in R. japonica. We further performed a detailed genomic comparison of R. heilongjiangensis and R. japonica to accurately define conserved and species-specific genes. This analysis revealed that although notable variations were found in the genomic loci encoding RelA/SpoT family proteins and tandem repeats in major surface proteins, there was only a small difference in the gene repertoire between the two species, suggesting that SNPs and small InDels are responsible for the functional or physiological differences between the two species, if present. Through this analysis, several species-specific genomic regions that can serve as ideal PCR targets for distinguishing R. heilongjiangensis and R. japonica were also identified.

During 2014-2017, we screened for Rickettsia japonica infection in Xinyang, China, and identified 20 cases. The major clinical manifestations of monoinfection were fever, asthenia, myalgia, rash, and anorexia; laboratory findings included thrombocytopenia and elevated hepatic aminotransferase concentrations. Physicians in China should consider R. japonica infection in at-risk patients.