Clinical and Pathological Findings in Fatal Cases of Severe Fever With Thrombocytopenia Syndrome With High Viremia in Cats

Matsuu, Aya; Hatai, Hitoshi; Hifumi, Tatsuro; Hamakubo, Emu; Take, Maho; Tanaka, Tetsuya; Momoi, Yasuyuki; Endo, Yasuyuki; Koyoshi, Ai; Kamikubo, Yuka; Kamatsuki, Raye; Kurusu, Natsuki; Tabata, Haruna; Matsuyama, Hiroshi; Yanaidani, Mei; Kawabata, Michiyo; Kawabata, T.

doi:10.1016/j.tcam.2022.100756

Cited by 4 publications

(5 citation statements)

References 39 publications

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“…Analysis of these models demonstrated the pivotal contributions of IL-12, TNF-α, and IFN-γ to germinal centre suppression (Ryg-Cornejo et al, 2016;Elsner and Shlomchik, 2019). The cats experimentally infected with SFTSV showed a prominent increase in IL-12 levels from 1 dpi to 7 dpi, while the elevation of TNF-α, and IFN-γ varies even in fatal cases (Park et al, 2019;Matsuu et al, 2023). However, the difference between high Ab responders and low Ab responders were unclear in this observation.…”

Section: Discussionmentioning

confidence: 75%

Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats

Sakai,

Mura,

Kuwabara

et al. 2024

Front. Microbiol.

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IntroductionSevere fever with thrombocytopenia syndrome (SFTS) is a fatal viral disease characterized by high fever, thrombocytopenia, leukopenia, and multi-organ haemorrhage. Disruption of the humoral immune response and decreased lymphocyte numbers are thought to contribute to the disease severity. These findings have been obtained through the analysis of peripheral blood leukocytes in human patients, whereas analysis of lymph nodes has been limited. Thus, in this study, we characterized the germinal centre response and apoptosis in the lymph nodes of cats with fatal SFTS, because SFTS in cats well mimics the pathology of human SFTS.MethodsLymph node tissue sections collected during necropsy from seven fatal SFTS patients and five non-SFTS cases were used for histopathological analysis. Additionally, lymph node tissue sections collected from cats with experimental infection of SFTS virus (SFTSV) were also analysed.ResultsIn the lymphoid follicles of cats with SFTS, a drastic decrease in Bcl6- and Ki67-positive germinal centre B cells was observed. Together, the number of T cells in the follicles was also decreased in SFTS cases. In the paracortex, a marked increase in cleaved-caspase3 positivity was observed in T cells. These changes were independent of the number of local SFTS virus-positive cell. Furthermore, the analysis of cats with experimental SFTSV infection revealed that the intrafollicular Bcl6- and CD3-positive cell numbers in cats with low anti-SFTSV antibody production were significantly lower than those in cats with high anti-SFTSV antibody production.DiscussionThese results suggest that dysfunction of the humoral response in severe SFTS was caused by the loss of germinal centre formation and massive apoptosis of T cells in the lymph nodes due to systemically circulating viruses.

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Section: Discussionmentioning

confidence: 75%

Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats

Sakai,

Mura,

Kuwabara

et al. 2024

Front. Microbiol.

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Section: Discussionmentioning

confidence: 95%

“…Interestingly, two of the three cytokines that were investigated appeared to be associated to acute death (high IL-6 and TNF-α; IL-1β was not associated). These findings provide useful evidence for considering the role of cytokine storms,—in which a protective inflammatory response is converted into a detrimental response characterized by vascular permeability, tissue destruction, and organ dysfunction [ 20 ] — in fatal feline SFTS. Cytokine storms may occur in fatal human SFTS [ 26 ], where IL-6, IL-1β and TNF-α are three of the 17 elevated cytokines or chemokines that appear to predict a fatal outcome [ 3 , 13 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…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 ].…”

Section: Discussionmentioning

confidence: 99%

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

MATSUURA,

HAMAKUBO,

NISHIGUCHI

et al. 2024

The Journal of Veterinary Medical Science

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Severe fever with thrombocytopenia syndrome (SFTS) is a potentially fatal tick-borne zoonotic disease, endemic to Asian regions, including western Japan. Cats appear to suffer a particularly severe form of the disease; however, feline SFTS is not clinically well characterized.Accordingly, in this study, we investigated the associations of, demographic, hematological and biochemical, immunological, and virological parameters with clinical outcome (fatal cases vs. survivors) in SFTSV-positive cats. Viral genomic analysis was also performed. Viral load in blood, total bilirubin, creatine phosphokinase, serum amyloid A, interleukin-6, tumor necrotic factor-α, and virus-specific IgM and IgG differed significantly between survivors and fatal cases, and thus may have utility as prognosticators. Furthermore, survivor profiling revealed high-level of viremia with multiple parameters (white blood cells, platelet, total bilirubin, glucose, and serum amyloid A) beyond the reference range in the 7-day acute phase, and signs of clinical recovery in the post-acute phase (parameters returning to, or tending toward, the reference range). However, SFTSV was still detectable from some survived cats even 14 days after onset of disease, indicating the risk of infection posed by close-contact exposure may persist through the post-acute phase. This study provides useful information for prognostic assessments of acute feline SFTS, and may contribute to early treatment plans for cats with SFTS. Our findings also alert pet owners and animal health professionals to the need for prolonged vigilance against animal-to-human transmission when handling cats that have been diagnosed with SFTS.

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“…Although the infection with thrombocytopenia syndrome virus (SFTSV), a tick-borne virus (Matsuno et al 2018;Matsuu et al 2023), is accompanied by severe fever in Felidae, no studies have examined tick-borne viruses on Iriomote Island. Additionally, A. testudinarium, H. hystricis, and H. longicornis, found on Iriomote Island, are potential vectors of SFTSV (Sato et al 2021).…”

Section: List Of Identified Tick-borne Bacteria and Protozoanmentioning

confidence: 99%

The hard tick fauna (Acari: Ixodida) of the Iriomote cat (<I>Prionailurus bengalensis iriomotensis</I>) in Iriomote Island, Okinawa Prefecture, Japan: a literature review with emphasis on need for surveillance of tick-borne pathogens

Matsuyama

2023

Acta Arachnol.

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Understanding the hard tick (Acari: Ixodida) fauna of the Iriomote cat (Prionailurus bengalensis iriomotensis Imaizumi 1967), an endangered species, is important for ecosystem conservation. However, there are no comprehensive reports on this topic. In this study, literature on the composition of tick species infesting Iriomote cats between 1975 and 2012 were compared. This study also reviewed on tick-borne pathogens found on Iriomote Island. Ticks Amblyomma testudinarium Koch 1844, Haemaphysalis hystricis Supino 1897, Haemaphysalis longicornis Neumann 1901, and Asiatic blue ticks (Rhipicephalus [Boophilus] microplus Canestrini 1888) were identified from Iriomote cats. Asiatic blue ticks were identified in 1975 and 1983-1985, whereas H. longicornis was identified from Iriomote cats for the first time in 2011-2012. Amblyomma testudinarium and H. hystricis were identified from Iriomote cats throughout the study period. Gene fragments of

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Clinical and Pathological Findings in Fatal Cases of Severe Fever With Thrombocytopenia Syndrome With High Viremia in Cats

Cited by 4 publications

References 39 publications

Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats

Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats

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

The hard tick fauna (Acari: Ixodida) of the Iriomote cat (<I>Prionailurus bengalensis iriomotensis</I>) in Iriomote Island, Okinawa Prefecture, Japan: a literature review with emphasis on need for surveillance of tick-borne pathogens

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