Severe rhabdomyolysis associated with severe fever with thrombocytopenia syndrome in a married couple: a case report.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infection that has recently emerged. This infectious disease is due to the transfer of SFTS virus (SFTSV) from the infected blood of animals to humans. Approximately 30% of patients who are infected with SFTS die from multiorgan failure associated with severe infection, systemic inflammatory response syndrome, or disseminated intravascular coagulation. We treated an elderly Japanese couple (husband and wife) who had genetically identical SFTSV infections and who both developed severe rhabdomyolysis. CASE PRESENTATION: An 80-year-old man presented to the clinic with a fever; his 74-year-old wife presented with a fever 9 days later. Their laboratory results at diagnosis showed severe rhabdomyolysis with significantly elevated creatinine kinase (detected levels: husband, 9546 U/L; wife, 15,933 U/L). The creatinine kinase isozyme was 100% MM type in both patients. In both the husband and wife, SFTSV was identified with real-time polymerase chain reaction analysis. The detected SFTSVs in both the husband and wife were identical according to the genome sequence analysis. The husband's bone marrow indicated macrophage activation syndrome, but he responded to supportive therapy. He was discharged after being hospitalized for 32 days. The wife was admitted to our hospital in critical condition 2 days after SFTS symptom onset. She died of multiorgan failure 8 days after onset, despite being cared for in an intensive care unit. Both of the patients presented with rhabdomyolysis following SFTS symptom onset. The patients' clinical outcomes were different from each other; i.e., the husband survived, and the wife died. CONCLUSIONS: SFTSV infection-associated rhabdomyolysis has been reported in one patient, and simultaneous onset in two related patients has not been described previously. Our findings suggest that similar biological responses occurred, but they resulted in different clinical outcomes in the patients infected by the identical SFTSV isolates. Notably, a patient's clinical outcome depends on their own immune response. We suggest that one component of viral rhabdomyolysis involves immune-mediated responses. Severe immunological responses may adversely affect the treatment outcome, as demonstrated by the wife's clinical course. Our findings demonstrate that a patient's immune response contributes to their prognosis following SFTSV infection.

Case report: detection of the identical virus in a patient presenting with severe fever with thrombocytopenia syndrome encephalopathy and the tick that bit her.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease. Haemophysalis longicornis ticks have been considered the vector of severe fever with thrombocytopenia syndrome virus (SFTSV). However, clear data on the transmission of SFTS from ticks to humans are limited. CASE PRESENTATION: We report an 84-year-old woman who presented with fever and altered mentality, which was confirmed as SFTS with encephalopathy by reverse-transcription polymerase chain reaction in blood and cerebrospinal fluid. The SFTSV was also identified in the tick that bit her, H. longicornis. Phylogenetic analyses indicated that the SFTSV from the patient and the tick was identical. The patient gradually recovered with treatments of corticosteroids and immunoglobulin. CONCLUSION: These findings provide further evidence of SFTS viral transmission from H. longicornis to human.

Two confirmed cases of severe fever with thrombocytopenia syndrome with pneumonia: implication for a family cluster in East China.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) was first reported in China in 2011. Human-to-human transmission of the virus occurred occasionally in family clusters. However, pneumonia as an onset syndrome was not common in most SFTS cases. Our aim is to report a family cluster of SFTS with clinical manifestation of pneumonia in Shanghai. METHODS: Epidemiologic investigations were conducted when a family cluster of severe fever with thrombocytopenia syndrome virus (SFTSV) infection was identified in Shanghai in June 2016. Samples were collected from two secondary cases and two close contacts with fever. SFTSV was detected by Real-Time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: There were two confirmed STFS cases and one potential index case. The potential index case became ill on 21 May and died on 31 May. Case A had onset from 4 to 23 June and case B from 8 June to 25 June. All the three cases experienced pneumonia at the early stage of SFTSV infection. Three (3) out of thirty two (32) close contacts had symptoms of fever or cough but were detected STFSV negative by real-time RT-PCR. According to epidemiologic investigations, the potential index case had outdoor activities on a nearby hill. A tick bite could have been the reason for the SFTSV infection in the potential index case as ticks were found both in grassland or shrubs on the hill and also found on mice caught in her house. Both cases A and B had provided bedside care for the potential index case without any protection and had contacted with blood and other body fluids. CONCLUSION: It was a family cluster of SFTSV infection imported from Jiangsu province located in the east of China. We suggested to become alert to atypical SFTSV infected cases.

Seroprevalence of severe fever with thrombocytopenia syndrome virus in southeastern China and analysis of risk factors.

Severe fever with thrombocytopenia syndrome virus (SFTSV) has been prevalent for some time in China and it was first identified in 2010. However, the seroprevalence of SFTSV in the general population in southeastern China and risk factors associated with the infection are currently unclear. Blood samples were collected from seven counties across Zhejiang province and tested for the presence of SFTSV-specific IgG antibodies by ELISA. A total of 1380 blood samples were collected of which 5·51% were seropositive for SFTSV with seroprevalence varying significantly between sites. Seroprevalence of SFTSV in people who were family members of the patient, lived in the same village as the patient, or lived in a different village than the patient varied significantly. There was significant difference in seroprevalence between participants who bred domestic animals and participants who did not. Domestic animals are probably potential reservoir hosts and contact with domestic animals may be a transmission route of SFTSV.

Epidemiology, molecular virology and diagnostics of Schmallenberg virus, an emerging orthobunyavirus in Europe.

After the unexpected emergence of Bluetongue virus serotype 8 (BTV-8) in northern Europe in 2006, another arbovirus, Schmallenberg virus (SBV), emerged in Europe in 2011 causing a new economically important disease in ruminants. The virus, belonging to the Orthobunyavirus genus in the Bunyaviridae family, was first detected in Germany, in The Netherlands and in Belgium in 2011 and soon after in the United Kingdom, France, Italy, Luxembourg, Spain, Denmark and Switzerland. This review describes the current knowledge on the emergence, epidemiology, clinical signs, molecular virology and diagnosis of SBV infection.

Person-to-person transmission of severe fever with thrombocytopenia syndrome virus.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a newly discovered bunyavirus, SFTS virus (SFTSV), and causes high fatality (12% on average and as high as 30%). The objective of this study was to determine whether SFTSV could be transmitted from person to person. We analyzed sera of 13 patients from two clusters of unknown infectious diseases that occurred between September and November of 2006 in Anhui Province of China for SFTSV antibody by indirect immunofluorescence assay and for SFTSV RNA by RT-PCR. We found that all patients (n=14) had typical clinical symptoms of SFTS including fever, thrombocytopenia, and leukopenia and all secondary patients in both clusters got sick at 6-13 days after contacting or exposing to blood of index patients. We demonstrated that all patients in cluster 1 including the index patient and nine secondary patients and all three secondary patients in cluster 2 had seroconversion or fourfold increases in antibody titer to SFTSV and/or by RT-PCR amplification of SFTSV RNA from the acute serum. The index patient in cluster 2 was not analyzed because of lack of serum. No person who contacted the index patient during the same period, but were not exposed to the index patient blood, had got illness. We concluded that SFTSV can be transmitted from person to person through contacting patient's blood.

Pathogenesis of Dugbe virus infection in wild-type and interferon-deficient mice.

In 129 mice, infection with the nairovirus Dugbe virus (DUGV) was lethal following intracerebral but not intraperitoneal inoculation. Following both routes of inoculation, immunostaining of tissue sections demonstrated virus-positive cells in the brain, indicating that DUGV is neuroinvasive in mice. Many brain areas were affected and neurones were the main cell type infected. Infected cells showed punctate accumulations of viral nucleoprotein in the cytoplasm, indicative of virus replication sites. Immunostaining for activated caspase 3 demonstrated no evidence of apoptosis. The type I interferon (IFN) system plays a significant role in defence against DUGV, as 129 IFN-alpha/beta R(-/-) mice died rapidly following both intraperitoneal and intracerebral inoculations. Studies were undertaken to determine whether the IFN-inducible proteins, protein kinase R (PKR) and MxA, were important for protection; neither PKR nor constitutively expressed human MxA played significant roles.

Attenuation of bunyavirus replication by rearrangement of viral coding and noncoding sequences.

Bunyamwera virus (BUN) is the prototype virus of the family Bunyaviridae. BUN has a tripartite negative-sense RNA genome comprising small (S), medium (M), and large (L) segments. Partially complementary untranslated regions (UTRs) flank the coding region of each segment. The terminal 11 nucleotides of these UTRs are conserved between the three segments, while the internal regions are unique. The UTRs direct replication and transcription of viral RNA and are sufficient to allow encapsidation of viral RNA into ribonucleoprotein complexes. To investigate the segment-specific functions of the UTRs, we have used reverse genetics to recover a recombinant virus (called BUN MLM) in which the L segment open reading frame (ORF) is flanked by the M segment UTRs. Compared to wild-type virus, BUN MLM virus shows growth attenuation in cultured mammalian cells and a slower disease progression in mice, produces small plaques, expresses reduced levels of L mRNA and L (RNA polymerase) protein, synthesizes less L genomic and antigenomic RNA, and has an increased particle-to-PFU ratio. Our data suggest that the packaging of BUN RNAs is not segment specific. In addition, the phenotype of BUN MLM virus supports the finding that BUN UTRs differ in their regulation of RNA synthesis but suggests that the interplay between each segment UTR and its cognate ORF may contribute to that regulation. Since BUN MLM virus is attenuated due to an essentially irreversible mutation, the rearrangement of UTRs is a feasible strategy for vaccine design for the more pathogenic members of the Bunyaviridae.

Emerging infectious diseases in the United States, 1993.

Three outbreaks of disease in the United States in 1993 caused by Escherichia coli O157:H7, Cryptosporidium organisms, and a previously unrecognized hantavirus clearly illustrate the increasing challenges posed by emerging infectious diseases. The largest US outbreak of E. coli O157:H7 infection reported occurred as a result of contaminated hamburgers served at a fast-food restaurant chain. The largest recorded waterborne disease outbreak in US history was due to contamination of a municipal water supply with cryptosporidia. In the southwestern United States, hantavirus was first recognized as the cause of a pulmonary syndrome with a mortality rate exceeding 50%. The detection of and response to these outbreaks document the need for a strong partnership between the clinical and public health sectors to prevent and control diseases. Health care reform in the United States provides an opportunity to address critical needs, such as improved surveillance and diagnosis, to ensure timely detection of and rapid response to newly emerging infectious diseases.

Hantavirus pulmonary syndrome--United States, 1993.

In June 1993, a newly recognized hantavirus was identified as the etiologic agent of an outbreak of severe respiratory illness (hantavirus pulmonary syndrome [HPS]) in the southwestern United States. Since this problem was recognized, sporadic cases have been identified from a wide geographic area in the western United States. This report summarizes the epidemiologic characteristics of HPS cases reported to CDC from May 1 through December 31, 1993.

Puumala virus infection without signs of renal involvement.

Five cases of Puumala virus infection without renal involvement are described. The main signs were fever, headache, chills and thirst. Pulmonary involvement was also common. Neither increased levels of serum creatinine nor abnormal urinalyses were detected. We suggest that Hantavirus infection is included in the differential diagnosis of any febrile condition when exposure to aerosols from infectious secretions or secretions from rodents is suspected.

Pathogenesis of a phleboviral infection (Punta Toro virus) in golden Syrian hamsters.

The hamster, Mesocricetus auratus, was examined as a possible model for investigating the poorly defined pathogenesis of the family Bunyaviridae, genus Phlebovirus. Punta Toro virus (PTV) isolates from Eastern Panama were highly virulent for two outbred and five inbred hamster strains, while isolates from western Panama were of low virulence. The Adames strain (eastern Panama) of PTV (LD50 approximately 1 PFU, sc) caused an acute fatal disease (average survival time, 3.8 days) in 10-week-old Lak: LVG (SYR) hamsters. Severe necrosis of the liver, spleen, and small intestine was associated with extensive expression of viral antigen in these organs. The Balliet strain (western Panama) of PTV (LD50 greater than 6 log10 PFU, subcutaneously) caused a mild hepatocellular infection with peak viral liver titers of 3-4 log10 PFU/g compared to 8-9 log10 PFU/g for the Adames strain. We observed histological lesions in the red pulp of the spleen or the lamina propria of the small intestine with the Adames strain. Lesions in the hamsters had characteristics of disseminated intravascular coagulation (DIC). The PTV-hamster model shares similarities to Rift Valley fever (phleboviral disease), which causes fatal disease in man and domesticated ruminants.

[Virus transmission to man from Phlebotomus flies: role of the Tuscany virus (Bunyaviridae, Phlebovirus) in the etiology of infections of the central nervous system]. / Virus trasmessi all'uomo da flebotomi: ruolo del virus Toscana (Bunyaviridae, Phlebovirus) nell'eziologia di infezioni del sistema nervoso centrale.

During field studies on the ecology of arboviruses in Italy, strains of a new virus were isolated from sand flies, mostly females, of a pure colony of Phlebotomus perniciosus collected in a central Italian region (Tuscany). The prototype was named Toscana (TOS) virus, assigned to the Phlebotomus fever serogroup of arboviruses (family Bunyaviridae, genus Phlebovirus) and registered in 1980 in the International Catalogue of Arboviruses. Neutralizing antibodies to TOS virus were detected in human sera. Serologic surveys were carried out to estimate the natural distribution of TOS virus in Italy and it was shown that antibodies to this virus could be detected in humans mainly of the Tuscany region. In particular, a high infection rate (24.8%) was observed among residents of the province of Florence. Furthermore, several patients with a diagnosis of aseptic meningitis presented a serologic response which reflected a recent infection with TOS virus in the Tuscany and Marche regions. Consequently, between 1980 and 1986 studies were conducted at selected sites of the Tuscany region to determine the possible occurrence of vectors and presence of foci of TOS virus and to assess its public health importance. As a result of these investigations, several virus strains were isolated from pools of wild caught Ph. perniciosus and Ph. perfiliewi. Of the virus isolates obtained, 37 were identified as TOS virus and 47 as a new serotype, member of the Phlebotomus fever group. For this virus we suggested the name of Arbia (ARB) virus, Arbia being the river flowing across both Florence and Siena provinces from which the isolates originated.(ABSTRACT TRUNCATED AT 250 WORDS)

Punta Toro virus infection of C57BL/6J mice: a model for phlebovirus-induced disease.

Punta Toro virus infections of inbred strains of mice have been characterized and evaluated as a model in which to study various aspects of the host response to phlebovirus infections and the requirements for protective immunity. The Adames strain of Punta Toro virus was found to be strongly hepatotropic and lymphotropic and the outcome of infection was largely a function of age. C57BL/6J mice of less than 5 weeks of age uniformly developed fulminant hepatocellular necrosis with mean survival times of 4.2 days. Resistance to lethal infection increased with age such that greater than 95% of 8-week-old mice survived challenge. The kinetics of viremia, antibody production, and hematological changes in 4- and 8-week animals indicated that the survival of the older animals is related to their ability to delay virus replication and the development of hepatic lesions during the initial 48 h of infection and their ability to terminate virus replication and clear virus from the circulation 4 to 5 days after infection. The mechanisms responsible for this resistance were studied using anti-interferon serum, immunosuppression, and passive immunization.