Severe Fever with Thrombocytopenia Syndrome, a Viral Hemorrhagic Fever, Endemic to Japan: Achievements in and Directions for Medical Research

Abstract

Severe fever with thrombocytopenia syndrome (SFTS), a novel infectious disease caused by a novel bunyavirus and with a high case fatality rate (CFR), was reported by Chinese scientists in 2011. The causative virus, Dabie bandavirus also known as the SFTS virus (SFTSV), belongs to the genus Bandavirus (formerly named Phlebovirus) of the family Phenuiviridae (formerly named Bunyaviridae). SFTS was also reported to be endemic in South Korea and Japan in 2013. SFTSV circulates between some species of ticks and animals in nature. Humans are infected with SFTSV through bites from ticks such as Haemaphysalis longicornis and Amblyomma testidinarium. Domesticated animals, such as cats and dogs, are also infected with SFTSV and shown SFTS-like symptoms with a high CFR, likely having been infected through tick bites in the living environment. Furthermore, there have been cases of patients with SFTS who were infected with SFTSV through close contact with sick cats or dogs. The CFR in patients with SFTS is approximately 30% in Japan. There is always a risk of SFTSV infection in human populations living in endemic areas. Therefore, the development of specific therapies and vaccines is urgently needed to reduce the number of fatal SFTS cases.

Elucidation of prognostic factors in the acute phase of feline severe fever with thrombocytopenia syndrome virus infection

“…Although the presence of acute viral myositis associated with SFTS viral infection in cats is unknown, it was significantly elevated in more severe (fatal) cases in our study. Jaundice or hyperbilirubinemia is frequently observed in cats with SFTS [19,20,22] , however, the specific mechanism of hyperbilirubinemia in feline SFTS has not been clarified in previous pathological reports [19,21,23].…”

“…Although the presence of acute viral myositis associated with SFTS viral infection in cats is unknown, it was significantly elevated in more severe (fatal) cases in our study. Jaundice or hyperbilirubinemia is frequently observed in cats with SFTS [ 19 , 20 , 22 ], however, the specific mechanism of hyperbilirubinemia in feline SFTS has not been clarified in previous pathological reports [ 19 , 21 , 23 ]. T-Bil was the only liver-related parameter associated with a fatal outcome in cats in our study; however, fatal human SFTS is characterized by liver damage secondary to shock, hypercytokinemia, or hemophagocytosis, and progressively elevated ALT and AST level until death [ 7 ].…”

“…SFTSV reached Japan in 2013 [ 27 ] and is now endemic to the west of the country. The virus is known to circulate in and between ticks and humans and a range of domestic and wild animal species in endemic area [ 23 ]. Among these affected species, humans have inevitably received the most attention.…”

“…Among these affected species, humans have inevitably received the most attention. Patients exhibit clinical signs including fever, thrombocytopenia, leukocytopenia, gastrointestinal dysfunction, muscular and neurological abnormalities, and coagulopathy [ 28 ], and the reported case fatality rate in Japan is 27–30% [ 12 , 23 ].…”