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. 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. Approximately 20% of cases showed positive cross-reactions. A comparison of antibody titers revealed the difficulty in identifying some positive cases. 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.

Severe fever with thrombocytopenia syndrome (SFTS) and Japanese spotted fever (JSF; a spotted fever group rickettsiosis) are tick-borne zoonoses that are becoming a significant public health threat in Japan and East Asia. Strategies for treatment and infection control differ between the two; therefore, initial differential diagnosis is important. We aimed to compare the clinical characteristics of SFTS and JSF based on symptomology, physical examination, laboratory data, and radiography findings at admission. This retrospective study included patients with SFTS and JSF treated at five hospitals in Nagasaki Prefecture, western Japan, between 2013 and 2020. Data from 23 patients with SFTS and 38 patients with JSF were examined for differentiating factors and were divided by 7:3 into a training cohort and a validation cohort. Decision tree analysis revealed leukopenia (white blood cell [WBC] < 4000/μL) and altered mental status as the best differentiating factors (AUC 1.000) with 100% sensitivity and 100% specificity. Using only physical examination factors, absence of skin rash and altered mental status resulted in the best differentiating factors with AUC 0.871, 71.4% sensitivity, and 90.0% specificity. When treating patients with suspected tick-borne infection, WBC < 4000/µL, absence of skin rash, and altered mental status are very useful to differentiate SFTS from JSF.

Background: Eosinophilic meningitis (EM) is a rare clinical syndrome caused by both infectious and noninfectious diseases. In tropical pacific countries, Angiostrongylus cantonensis is the most common cause. However, the EM definition varies in the literature, and its relation to parasitic meningitis (PM) remains unclear. Methodology/Principal findings: Adult and adolescent patients of 13 years old or above with suspected central nervous system (CNS) infections with abnormal CSF findings were prospectively enrolled at a tertiary referral hospital in Hanoi, Vietnam from June 2012 to May 2014. Patients with EM or suspected PM (EM/PM) were defined by the presence of either ≥10% eosinophils or an absolute eosinophil cell counts of ≥10/mm³ in the CSF or blood eosinophilia (>16% of WBCs) without CSF eosinophils. In total 679 patients were enrolled: 7 (1.03%) had ≥10% CSF eosinophilia, 20 (2.95%) had ≥10/mm³ CSF eosinophilia, and 7 (1.03%) had >16% blood eosinophilia. The patients with ≥10% CSF eosinophilia were significantly younger (p = 0.017), had a lower body temperature (p = 0.036) than patients with ≥10/mm³ CSF eosinophilia among whom bacterial pathogens were detected in 72.2% (13/18) of those who were tested by culture and/or PCR. In contrast, the characteristics of the patients with >16% blood eosinophilia resembled those of patients with ≥10% CSF eosinophilia. We further conducted serological tests and real-time PCR to identify A. cantonensis. Serology or real-time PCR was positive in 3 (42.8%) patients with ≥10% CSF eosinophilia and 6 (85.7%) patients with >16% blood eosinophilia without CSF eosinophils but none of patients with ≥10/mm³ CSF eosinophilia. Conclusions: The etiology of PM in northern Vietnam is A. cantonensis. The eosinophil percentage is a more reliable predictor of parasitic EM than absolute eosinophil count in the CSF. Patients with PM may present with a high percentage of eosinophils in the peripheral blood but not in the CSF.

Autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) are rare complications of coronavirus disease 2019 (COVID-19). Herein, we report the case of a 28-year-old Japanese man who showed severe AIHA exacerbation associated with PRCA after COVID-19. AIHA was diagnosed and maintained for 5 years. Approximately 4 weeks after COVID-19, the patient developed severe anemia (hemoglobin level, 3.4 g/dL). Laboratory test results confirmed hemolytic exacerbation of IgG-mediated warm-type AIHA. Despite the hemolysis phase, the bone marrow revealed extreme hypoplasia of erythroblasts with a decreased reticulocyte count, similar to that observed in patients with PRCA. During oral prednisolone treatment, the patient recovered from anemia and showed increased reticulocyte count and reduced hypoplasia of marrow erythroblasts. Exacerbation of AIHA and PRCA was triggered by COVID-19 because other causes were ruled out. Although this case report highlights that COVID-19 could lead to hematological complications such as AIHA and PRCA, the exact mechanisms remain unclear.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus. It involves multiple organ systems, including the lungs. However, the significance of the lung involvement in SFTS remains unclear. In the present study, we aimed to investigate the relationship between the clinical findings and abnormalities noted in the chest computed tomography (CT) of patients with SFTS. The medical records of 22 confirmed SFTS patients hospitalized in five hospitals in Nagasaki, Japan, between April 2013 and September 2019, were reviewed retrospectively. Interstitial septal thickening and ground-glass opacity (GGO) were the most common findings in 15 (68.1%) and 12 (54.5%) patients, respectively, and lung GGOs were associated with fatalities. The SFTS patients with a GGO pattern were elderly, had a disturbance of the conscious and tachycardia, and had higher c-reactive protein levels at admission (p = 0.009, 0.006, 0.002, and 0.038, respectively). These results suggested that the GGO pattern in patients with SFTS displayed disseminated inflammation in multiple organs and that cardiac stress was linked to higher mortality. Chest CT evaluations may be useful for hospitalized patients with SFTS to predict their severity and as early triage for the need of intensive care.