Japanese spotted fever complicated by acute sensorineural hearing loss.

Japanese spotted fever is an emerging rickettsiosis caused by Rickettsia japonica and is characterized by high fever, rash, and eschar formation. Other symptoms are often vague and nonspecific and include headaches, nausea, vomiting, and myalgia. We present a case of a 46-year-old woman with Japanese spotted fever, complicated by transient bilateral sensorineural hearing loss and presenting cutaneous IgM/IgG immune complex vasculitis. The patient was admitted with a history of several days of high fever, generalized skin erythema, and hearing impairment. Laboratory findings revealed thrombocytopenia and elevated liver enzyme and C-reactive protein levels. Pure-tone audiometry revealed bilateral sensorineural hearing loss, and a skin biopsy revealed leukocytoclastic vasculitis with deposition of C3 and IgM on the vessel walls. Under the tentative diagnosis of rickettsiosis, scrub typhus, or Japanese spotted fever, the patient was treated with minocycline, and her symptoms improved within approximately 10 days. A definitive diagnosis was made on the basis of a serological test showing increased antibody levels against Rickettsia japonica. Japanese spotted fever can cause transient sensorineural hearing loss, a rare complication that presents with cutaneous IgM/IgG immune complex vasculitis.

Clinical Forms of Japanese Spotted Fever from Case-Series Study, Zigui County, Hubei Province, China, 2021.

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.

Nonnegligible Seroprevalence and Predictors of Murine Typhus, Japan.

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.

Co-infection with Severe Fever with Thrombocytopenia Syndrome Virus and Rickettsia japonica after Tick Bite, Japan.

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.

Rickettsia japonica Infection after Land Leech Bite, Japan.

We report a case of Rickettsia japonica infection in an 81-year-old man in central Japan. The patient had fever, rash, and an eschar but no evidence of a tick bite. His symptoms began 8 days after a land leech bite. The land leech is a potential vector of R. japonica.

Rickettsia japonica Infections in Humans, Xinyang, China, 2014-2017.

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.

In vitro evaluation of minimum inhibitory concentration of several antibacterial agents against Rickettsia japonica using a plaque reduction assay system.

The study was conducted to determine the minimum inhibitory concentrations (MICs) of several antibacterial agents against Rickettsia japonica, which causes Japanese spotted fever. A plaque reduction assay as an in vitro culture method was conducted to determine the MICs of antibacterial agents (4 types of tetracyclines: tetracycline, doxycycline, minocycline, and tigecycline; 3 types of quinolones: ciprofloxacin, ofloxacin, and levofloxacin; and 2 types of macrolides: azithromycin and clarythromycin) against R. japonica. R. japonica was sensitive to the antibacterial agents tested with MICs similar to those against other spotted fever rickettsia determined in previously described plaque reduction assays.

Distinguishing Japanese Spotted Fever and Scrub Typhus, Central Japan, 2004- 2015.

Japanese spotted fever (JSF) and scrub typhus (ST) are endemic to Japan and share similar clinical features. To document the clinical and epidemiologic characteristics that distinguish these 2 rickettsial diseases, during 2004-2015 we recruited 31 JSF patients, 188 ST patients, and 97 nonrickettsial disease patients from the southern Boso Peninsula of Japan. JSF occurred during April-October and ST during November-December. Patients with JSF and ST were significantly older and more likely to reside in wooded areas than were patients with nonrickettsial diseases. Spatial analyses revealed that JSF and ST clusters rarely overlapped. Clinical findings more frequently observed in JSF than in ST patients were purpura, palmar/plantar rash, hyponatremia, organ damage, and delayed defervescence after treatment. Although their clinical features are similar, JSF and ST differ in seasonality, geographic distribution, physical signs, and severity. Because a considerable percentage of patients did not notice rash and eschar, many rickettsial diseases might be underdiagnosed in Japan.

Rickettsia japonica Infections in Humans, Zhejiang Province, China, 2015.

We investigated 16 Japanese spotted fever cases that occurred in southeastern China during September-October 2015. Patients had fever, rash, eschar, and lymphadenopathy. We confirmed 9 diagnoses and obtained 2 isolates with high identity to Rickettsia japonica strain YH. R. japonica infection should be considered for febrile patients in China.

Japanese Spotted Fever in Eastern China, 2013.

We isolated Rickettsia japonica from a febrile patient in Lu'an City, China, in 2013. Subsequently, we found an R. japonica seroprevalence of 54.8% (494/902) in the rural population of Anhui Province and an R. japonica prevalence in Haemaphysalis longicornis ticks of 0.5% (5/935). R. japonica and its tick vector exist in China.

A Japanese Boy With Spotted Fever and Overlapping Symptoms of Kawasaki Disease: A Case Report.

Japanese spotted fever (JSF) is a tick-transmitted infection caused by Rickettsia japonica (R. japonica), which is indigenous to Japan. Patients with JSF typically present with fever and spotted erythema on the palms and/or soles, and most of them have site(s) of tick bites. The prognosis is good, but some cases have a fatal course. Kawasaki disease (KD) is a systemic vasculitis with an unknown cause that is characterized by symptoms such as fever, conjunctival injection, oral findings, amorphous rash, rigid edema, and nonsuppurative cervical lymphadenopathy. Although the symptoms of JSF are partially similar to those of KD, case reports of JSF overlapping KD have never been internationally published. Herein, we report a boy with JSF and KD symptoms. A five-year-old boy presented with fever and rash after he had been on a mountain inhabited by R. japonica. On the fifth day, erythema was spotted mainly on his bilateral palms, bilateral cervical lymphadenopathy, rigid edema of his lower feet, and mild conjunctival injection appeared. Intravenous immunoglobulin (IVIG) therapy was performed because these symptoms satisfied five out of the six diagnostic criteria for KD. However, on the sixth day, the fever persisted, and then we readministered IVIG in addition to tosufloxacin and azithromycin since we found a tick-bite eschar, which suggested a complication of JSF. His symptoms resolved soon after this treatment. Coronary artery lesions were never observed. This case indicates that the R. japonica infection overlaps clinically with KD. Tosufloxacin and azithromycin should be considered to avoid the use of minocycline in younger patients with JSF.

Atypical Rickettsia japonica Infection Involving Critical Illness Diagnosed by Metagenomic Next-Generation Sequencing: A Case Report.

Background: Rickettsia japonica infection is a rare disease, it is rare to report critical and severe case caused by this disease in Zhejiang Province, China. Patient Concerns: We report a patient who initially sought medical attention due to fever and developed coma and convulsions during treatment. The patient did not develop typical eschar and rash. Eventually, the patient needed to be treated in the intensive care unit due to acute respiratory failure. Diagnoses: The patient was diagnosed with Rickettsia japonica bloodstream infection by metagenomic next-generation sequencing (mNGS). Outcomes: Due to the critical illness, the patient was transferred to the intensive care unit, received doxycycline and other treatments, and rapidly recovered and discharged. Conclusion: The patient developed a critical illness after being infected with Rickettsia, when the medical history is unclear and clinical symptoms and signs are atypical, it is necessary to use mNGS examination for diagnosis.

Case report: Multiple organ failure caused by Japanese spotted fever.

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.

Japanese spotted fever complicated with pleural effusion in Zhejiang province, China: a case report and literature review.

INTRODUCTION: 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). CASE PRESENTATION: 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.

Prompt diagnosis and appropriate treatment of Japanese spotted fever: A report of three cases.

Background: Japanese Spotted Fever (JSF) is a Spotted Fever Group (SFG) rickettsiosis caused by Rickettsia japonica. More than 300 cases are diagnosed annually in Japan, and the number of reported cases has been increasing. Correct diagnoses depend on the triad of symptoms and signs, including fever, rash, and eschar, which can be seen at the site of vector bites. JSF is not life-threatening if treated appropriately without diagnostic delay but there are some fatal cases every year. This negligence leads to disseminated intravascular coagulation (DIC) and multiple organ failure (MOF), and poor prognoses, consequently. Prompt diagnosis of JSF is difficult when the aforementioned triad of signs and symptoms is not initially present. Case report: This report describes three JSF cases: an 87-year-old woman with fever, shock, pancytopenia, DIC, and MOF; a 79-year-old man with fever and difficulty in movement; and a 78-year-old man with fever, general fatigue, and appetite loss. All patients had a rash and eschar, which led to prompt diagnosis and appropriate treatment immediately. All patients were treated without any complications. Why should an emergency physician be aware of this?: As mentioned above, JFS can be fatal with delayed diagnoses and treatment initiations. The key for a prompt diagnosis is to recognize the triad of symptoms and signs, which are not often present initially, and it makes JSF diagnosis challenging. Repeated comprehensive physical examinations are essential for prompt diagnosis and improve prognosis of JSF.

Phylogenetic Analysis of Spotted Fever Group Rickettsia Gene from Ticks and Human Patients in Tottori Prefecture, Japan.

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Serological cross-reactivity between spotted fever and typhus groups of rickettsia infection in Japan.

OBJECTIVES: 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. CONCLUSION: 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.

A Case of Critical Japanese Spotted Fever in Zhejiang, China.

Background: Japanese spotted fever (JSF) is a rare disease, caused by Rickettsia japonica; no case has been reported in Zhejiang Province, China. Case Presentation: An elderly woman presented to the hospital with abdominal pain and fever. Her condition rapidly worsened with severe complications, such as multiple organ failure and central nervous system damage. The presence of R. japonica was quickly detected by metagenomic next-generation sequencing. On the basis of combined clinical manifestations and laboratory results, critical JSF was diagnosed and treated with doxycycline. The patient showed good prognosis. Typical symptoms (eschar and rash) were not observed in the early stage, consequently increasing the difficulty of clinical diagnosis. Conclusion: The delay of treatment caused by non-specific symptoms is an important factor affecting the progression of JSF. As an emerging pathogen detection method, mNGS has been successfully applied for disease diagnosis and treatment, and can be an important complement for the diagnosis of this disease.

Fatal Rickettsia Japonica Infection Complicating Disseminated Intravascular Coagulation in Yichang, China.

Background: Severe complications may cause a fatal or disabling outcome in patients with Rickettsia japonica infection but are poorly understood. Methods: We identified 11 patients with only Rickettsia japonica infection with metagenomics next generation sequencing (mNGS) during April to November 2021 at Yichang Central People's Hospital, China. Clinical data were obtained through review of medical records. Results: Most patients realized that they had symptoms about one or two days after being bitten. Fever (91%), pulmonary effusion (91%), rash or erythema (100%), abnormal urine (100%), neutropenia (100%), lymphopenia (100%), and thrombocytopenia (100%) were the most common clinical signs. Six severely ill patients were admitted to the intensive care unit and five had mild symptoms. Systemic manifestations such as vomiting (83%), neurological manifestations (100%), and disseminated intravascular coagulation (100%) were more frequently observed in the severe cases, 33.3% of whom developed purpura fulminans requiring amputation or skin graft, and 16.6% died two days after admission. Some patients experienced sequelae. Conclusion: Our study found that patients with critical Rickettsia japonica infection complicating disseminated intravascular coagulation had high risk of poor outcome.

The presence of Tularemia infection in patients with Japanese spotted fever.

In our previous study, by measuring serum cytokine levels in the acute and recovery stage of Japanese spotted fever (JSF), IFN-ɤ and IL-6 were proved to be the critical immunological cytokines against Rickettsia japonica (R. japonica) infection. Tularemia is an infectious disorder caused by tick biting or contact with infected animals, and is also known as rabbit fever. There have been no confirmed cases in the recent two decades in Japan. We measured serum anti Francisella tularensis (F. tularensis) IgG titer using indirect enzyme-linked immunosorbent assay (ELISA) kit in the acute and recovery stage of three patients with JSF. The result of the IgG titer was compared with the cytokine concentrations of IFN-ɤ, IL-6, IL-4, IL-5, IL-9, and IL-33, eosinophil count, and CRP quoted from our previous report. Two of three cases have anti F. tularensis IgG, and the IgG levels between acute and recovery stage were unchanged. These two cases showed low IFN-ɤ concentration and CRP, but IL-4, IL-5, IL-9, IL-33 levels and eosinophils were high compared to those in the F. tularensis IgG-negative patient. IL-6 concentration was unchanged between the three patients. Residents living in the endemic area of JSF in Mie prefecture, Japan, may have antibodies against F. tularensis, although tularemia has never been reported. The cases of having the F. tularensis antibody showed a mild inflammatory response of JSF and might skew to type 2 immunological condition even in the acute phase of JSF.