BACKGROUND: The geographic spread of Japanese spotted fever (JSF) in China is gradually expanding, particularly in regions where severe fever with thrombocytopenia syndrome (SFTS) is highly prevalent, with both diseases sharing similarities in epidemiology and clinical presentation. The microbiological diagnosis of JSF is challenging, compounded by low awareness among healthcare professionals in newly affected areas. Moreover, primary healthcare facilities without polymerase chain reaction (PCR) testing capabilities for SFTS often misdiagnose JSF as SFTS.
METHODS: All 3 patients had a history of working in the fields, with cold like symptoms in the early fever stages, but the fever did not improve after a few days. The accompanying symptoms were also very different. Physical examination revealed enlarged lymph nodes, different forms of rash, with or without eschar. Laboratory tests showed thrombocytopenia, eosinophilia, elevated lactate dehydrogenase, and transaminase, with 1 patient experiencing renal damage. It is worth noting that these 3 patients reside in an area where SFTS is endemic, and there have been no prior reports of JSF. They exhibited clinical symptoms and laboratory test results closely resembling those of SFTS. Therefore, they were initially misdiagnosed with SFTS in their local hospitals.
METHODS: The 3 patients who arrived at our hospital 7 days after symptom onset and were subsequently diagnosed with JSF by metagenomic next-generation sequencing (mNGS).
METHODS: Doxycycline treatment for 1 week.
RESULTS: The patients\' symptoms quickly improved with no side effects, and the results of laboratory tests went back to normal.
CONCLUSIONS: By comparing the clinical characteristics of JSF patients and SFTS patients comprehensively, we found that APTT and procalcitonin levels may be valuable in assisting in the identification of SFTS and JSF. In all areas where tick-borne diseases are endemic, include SFTS-epidemic areas, we recommend using the Weil-Felix test to screen for potential rickettsiosis in patients presenting with fever and thrombocytopenia with or without rash in primary healthcare settings, as well as simultaneous testing for the SFTS virus and spotted fever group rickettsioses sequence. Additionally, mNGS sequencing should be used to confirm the diagnosis and provide information for epidemiological investigations in patients who are suspected of having spotted fever group rickettsiosis.

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.

Central China has been reported to be one of the most important endemic areas of zoonotic infection by spotted fever group rickettsiae (SFGR), severe fever with thrombocytopenia syndrome virus (SFTSV) and hantaan virus (HTNV). Due to similar clinical symptoms, it is challenging to make a definite diagnosis rapidly and accurately in the absence of microbiological tests. In the present study, an all-in-one real-time PCR assay was developed for the simultaneous detection of nucleic acids from SFGR, SFTSV and HTNV. Three linear standard curves for determining SFGR-ompA, SFTSV-L and HTNV-L were obtained within the range of 101-106 copies/μL, with the PCR amplification efficiencies ranging from 93.46% to 96.88% and the regression coefficients R2 of >0.99. The detection limit was 1.108 copies/μL for SFGR-ompA, 1.075 copies/μL for SFTSV-L and 1.006 copies/μL for HTNV-L, respectively. Both the within-run and within-laboratory coefficients of variation on the cycle threshold (Ct) values were within the range of 0.53%-2.15%. It was also found there was no statistical difference in the Ct values between single template and multiple templates (PSFGR-ompA = 0.186, PSFTSV-L = 0.612, PHTNV-L = 0.298). The sensitivity, specificity, positive and negative predictive value were all 100% for determining SFGR-ompA and SFTSV-L, 97%, 100%, 100% and 99.6% for HTNV-L, respectively. Therefore, the all-in-one real-time PCR assay appears to be a reliable, sensitive, rapid, high-throughput and low cost-effective method to diagnose the zoonotic infection by SFGR, SFTSV and HTNV.

Spotted fever group rickettsiae (SFGR) are obligate intracellular bacteria that cause spotted fever. The limitations of gene manipulation pose great challenges to studying the infection mechanisms of Rickettsia. By combining bioorthogonal metabolism and click chemistry, we developed a method to label R. heilongjiangensis via azide moieties and achieved rapid pathogen localization without complex procedures. Moreover, we constructed a C57BL/6 mice infection model by simulating tick bites and discovered that the stomach is the target organ of R. heilongjiangensis infection through in vivo imaging systems, which explained the occurrence of gastrointestinal symptoms following R. heilongjiangensis infection in some cases. This study offers a unique perspective for subsequent investigations into the pathogenic mechanisms of SFGR and identifies a potential target organ for R. heilongjiangensis.

暂无摘要。

OBJECTIVE: Tetracyclines are the standard treatment for rickettsiosis, including Japanese spotted fever (JSF), a tick-borne rickettsiosis caused by Rickettsia japonica. While some specialists in Japan advocate combining fluoroquinolones with tetracyclines for treating JSF, the negative aspects of combination therapy have not been thoroughly evaluated. Whether fluoroquinolones should be combined with tetracyclines for JSF treatment is controversial. The study aimed to evaluate the disadvantages of fluoroquinolones combined with tetracyclines for JSF treatment.
METHODS: This retrospective cohort study was conducted using a Japanese database comprising claims data from April 2008 to December 2020. The combination therapy group (tetracyclines and fluoroquinolones) was compared with the monotherapy group (tetracycline only) regarding mortality and the incidence of complications.
RESULTS: A total of 797 patients were enrolled: 525 received combination therapy, and 272 received monotherapy. The adjusted odds ratio (OR) for mortality was 2.30 [95% confidence interval (CI): 0.28-18.77] in the combination therapy group with respect to the monotherapy group. According to the subgroup analysis, patients undergoing combination therapy with ciprofloxacin experienced higher mortality rates compared with those receiving monotherapy (adjusted OR = 25.98, 95% CI = 1.71-393.75). Additionally, 27.7% of the combination therapy group received NSAIDs concurrently with fluoroquinolones. The combination therapy with NSAIDs group was significantly more likely to experience convulsions than the monotherapy without NSAIDs group (adjusted OR: 5.44, 95% CI: 1.13-26.30).
CONCLUSIONS: This study found no evidence that combination therapy improves mortality outcomes and instead uncovered its deleterious effects. These findings facilitate a fair assessment of combination therapy that includes consideration of its disadvantages.

The incidence of spotted fever group (SFG) rickettsioses in the United States has tripled since 2010. Rocky Mountain spotted fever, the most severe SFG rickettsiosis, is caused by Rickettsia rickettsii. The lack of species-specific confirmatory testing obfuscates the relative contribution of R. rickettsii and other SFG Rickettsia to this increase. We report a newly recognized rickettsial pathogen, Rickettsia sp. CA6269, as the cause of severe Rocky Mountain spotted fever-like illness in 2 case-patients residing in northern California. Multilocus sequence typing supported the recognition of this pathogen as a novel Rickettsia genotype most closely related to R. rickettsii. Cross-reactivity observed for an established molecular diagnostic test indicated that Rickettsia sp. CA6269 might be misidentified as R. rickettsii. We developed a Rickettsia sp. CA6269-specific real-time PCR to help resolve this diagnostic challenge and better characterize the spectrum of clinical disease and ecologic epidemiology of this pathogen.

暂无摘要。

Japanese spotted fever (JSF) is caused by Rickettsia japonica, mainly vectored by hard ticks. However, whether R. japonica can be transmitted by other arthropods remains unknown. Moreover, it is of interest to investigate whether other Rickettsia species cause spotted fever in endemic areas. In this study, a survey of Rickettsia species was performed in hematophagous arthropods (mosquitoes, tabanids, and ticks) from endemic areas for JSF in Hubei Province, central China. The results showed that the diversity and prevalence of Rickettsia species in mosquitoes are low, suggesting that mosquitoes may not be the vector of zoonotic Rickettsia species. A novel Rickettsia species showed a high prevalence (16.31%, 23/141) in tabanids and was named \"Candidatus Rickettsia tabanidii.\" It is closely related to Rickettsia from fleas and mosquitoes; however, its pathogenicity in humans needs further investigation. Five Rickettsia species were identified in ticks. Rickettsia japonica, the agent of JSF, was detected only in Haemaphysalis longicornis and Haemaphysalis hystricis, suggesting that they may be the major vectors of R. japonica. Notably, two novel species were identified in H. hystricis ticks, one belonging to the spotted fever group and the other potentially belonging to the ancestral group. The latter one named \"Candidatus Rickettsia hubeiensis\" may provide valuable insight into the evolutionary history of Rickettsia.

Tick-borne disease burdens are increasing globally, impacting mostly rural and vulnerable communities. Among the most important emerging tick-borne pathogens are the Rickettsia species within the spotted fever group (SFGR) because of their genetic diversity and high lethality rate. Colombia is highly affected by SFGR despite not being reportable diseases; thus, research and clinical management are neglected. Although some departments have demonstrated high seroprevalence rates, in others, such as Boyacá Department, seroprevalence is unknown. Rickettsioses have not been described in Boyacá since 1943, and conversations with local physicians raised suspicions of recent undiagnosed disease compatible with rickettsiosis in some rural areas of the department, warranting epidemiological investigation. Using biobanked human and canine samples from a previous 2021 vector-borne disease study in Miraflores municipality, Boyacá, we had an opportunity to unearth SFGR\'s exposure in the region. Samples were evaluated using IgG indirect fluorescent assays against SFGR and complemented by survey questionnaires evaluating associated factors. Findings yielded first-time SFGR serological evidence in Boyacá with a 26.5% seroprevalence among dogs and a 20.4% among humans. Human and dog seroprevalences were positively associated, suggesting the presence of domestic transmission. Owning a greater number of domestic animals (prevalence ratio adjusted for all measured factors [aPR], 1.52) and living near crop fields (aPR, 7.77) were associated with an increased likelihood of household seropositivity. Our findings are consistent with the literature in Colombia, uncovering a suspected region where the disease is endemic. Future studies are warranted to continue defining high-risk areas to determine public health intervention plans.