Severe Fever with Thrombocytopenia Syndrome Accompanied by Invasive Pulmonary Aspergillosis: An Autopsy Case

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tickborne infectious disease in China, Korea, and Japan caused by the SFTS virus (SFTSV). SFTS has a high mortality rate due to multiorgan failure. Recently, there are several reports on SFTS patients with mycosis. Here, we report a middle-aged Japanese SFTS patient with invasive pulmonary aspergillosis (IPA) revealed by an autopsy. A 61-year-old man with hypertension working in forestry was bitten by a tick and developed fever, diarrhea, and anorexia in 2 days. On day 4, consciousness disorder was appearing, and the patient was transferred to the University of Miyazaki Hospital. A blood test showed leukocytopenia, thrombocytopenia, as well as elevated levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase. The SFTSV gene was detected in serum using a reverse-transcription polymerase chain reaction. On day 5, respiratory failure appeared and progressed rapidly, and on day 7, the patient died. An autopsy was performed that revealed hemophagocytosis in the bone marrow and bleeding of several organs. IPA was observed in lung specimens. SFTSV infection may be a risk factor for developing IPA. Early diagnosis and treatment of IPA may be important in patients with SFTS.

Clinical Presentation and Mortality of Severe Fever with Thrombocytopenia Syndrome in Japan: A Systematic Review of Case Reports

“…A survey by the Ministry of the Environment reported that the habitat area of Japanese deer and wild boars was mainly West Japan, although the area had been spreading northward every year [ 17 , 18 , 19 , 20 ]. A previous study concluded that wildlife habitat area changes also accelerated the spread of infection of Japanese spotted fever and scrub typhus, both of which are related to ticks [ 21 , 22 , 23 ]. The spread of the habitat area of the wild animals may also be associated with the distribution of the ticks carrying the SFTS virus and the differences between regions in terms of case prevalence; therefore, the spread of infection should be studied in the future.…”

The Endless Wars: Severe Fever With Thrombocytopenia Syndrome Virus, Host Immune and Genetic Factors

“…Of note, 35% patients with SFTS had bleeding symptoms ( Li H. et al., 2018 ) and severe cases were generally expired from systemic bleeding caused by disseminated intravascular coagulation ( Gai Z. T. et al., 2012 ). Gross pathological findings in patients with fatal SFTSV reported the subcutaneous hemorrhage in multiple sites, including anterior chest, neck, elbow, groin area, abdomen, and limbs ( Hiraki et al., 2014 ; Uehara et al., 2016 ; Kaneko et al., 2018 ; Iwao et al., 2021 ), also reported hemorrhage in the gastrointestinal tract and lungs ( Hiraki et al., 2014 ; Uehara et al., 2016 ; Kaneko et al., 2018 ; Iwao et al., 2021 ), as well as bilateral kidney swelling with subepithelial hemorrhage in the renal pelvis ( Takahashi et al., 2014 ). Coagulation dysfunction caused by platelet depletion was a risk factor for bleeding.…”

“…Similarly, the significantly increased serum IP-10 levels were also found in patients with pneumonia at the acute phase of SFTSV infection when compared with those of patients with SFTS ( Deng et al., 2012 ), thus allowing for the speculation that IP-10 might play a role in the pathogenesis of SFTS-related lung injury. Furthermore, the autopsy studies of SFTS cases reported increased lung weight, alveolar hemorrhage, pulmonary edema, and diffuse alveolar injury ( Hiraki et al., 2014 ; Uehara et al., 2016 ; Kaneko et al., 2018 ; Iwao et al., 2021 ), indicating acute lung injury. SFTSV nucleoprotein antigen-positive atypical lymphoid cells were also detected in the lung ( Hiraki et al., 2014 ; Li S. et al., 2018 ).…”

“…Combined with the abovementioned findings (see the section of “Host immune response–Cytokines–Acute phase–Correlation between cytokines and clinical courses/outcomes of SFTSV infection” for details), it is speculated that the increased secretion of cytokines and chemokines induced by SFTSV and the infiltration of inflammatory cells may together mediate the immunopathological injury of the lung during SFTSV infection. One point worthy of noting was the fact that invasive fungal infections were detected in lung tissue, trachea and bronchus of a minority of patients with SFTS ( Hiraki et al., 2014 ; Uehara et al., 2016 ; Iwao et al., 2021 ), which might be related to the inhibition of host immune response by SFTSV through several different mechanisms as follow. First, SFTSV induced the production of anti-inflammatory cytokine IL-10, which suppressed the host immune system ( Choi et al., 2019 ), and the elevated IL-10 level in patients with SFTS was confirmed to be correlated strongly with the fatal outcomes ( Yoo et al., 2021 ).…”

Identification of severe fever with thrombocytopenia syndrome virus genotypes in patients and ticks in Liaoning Province, China

“…The general population is susceptible; therefore, its epidemic area tends to expand following initial infection [ 5 ]. Thousands of incidents of SFTS have been reported in more than 16 provinces and cities in China [ 9 ] as well as in the Republic of Korea [ 10 ], Japan [ 11 ] and the USA [ 12 ].…”