Background. Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV), a novel bunyavirus reported to be endemic in central and northeastern China. This article describes the first identified patient with SFTS and a retrospective study on SFTS in Japan.

Methods. Virologic and pathologic examinations were performed on the patient's samples. Laboratory diagnosis of SFTS was made by isolation/genome amplification and/or the detection of anti-SFTSV immunoglobulin G antibody in sera. Physicians were alerted to the initial diagnosis and asked whether they had previously treated patients with symptoms similar to those of SFTS.

Results. A female patient who died in 2012 received a diagnosis of SFTS. Ten additional patients with SFTS were then retrospectively identified. All patients were aged ≥50 years and lived in western Japan. Six cases were fatal. The ratio of males to females was 8:3. SFTSV was isolated from 8 patients. Phylogenetic analyses indicated that all of the Japanese SFTSV isolates formed a genotype independent to those from China. Most patients showed symptoms due to hemorrhage, possibly because of disseminated intravascular coagulation and/or hemophagocytosis.

Conclusions. SFTS has been endemic to Japan, and SFTSV has been circulating naturally within the country.

The first identification and retrospective study of severe fever with thrombocytopenia syndrome in Japan

Two men from northwestern Missouri independently presented to a medical facility with fever, fatigue, diarrhea, thrombocytopenia, and leukopenia, and both had been bitten by ticks 5 to 7 days before the onset of illness. Ehrlichia chaffeensis was suspected as the causal agent but was not found on serologic analysis, polymerase-chain-reaction (PCR) assay, or cell culture. Electron microscopy revealed viruses consistent with members of the Bunyaviridae family. Next-generation sequencing and phylogenetic analysis identified the viruses as novel members of the phlebovirus genus. Although Koch's postulates have not been completely fulfilled, we believe that this phlebovirus, which is novel in the Americas, is the cause of this clinical syndrome.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1203378

A New Phlebovirus Associated with Severe Febrile Illness in Missouri

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging haemorrhagic fever that was first described in rural areas of China. The causative agent, SFTS virus (SFTSV), is a novel phlebovirus in the Bunyaviridae family. Since the first report in 2010, SFTS has been found in 11 provinces of China, with about 2500 reported cases, and an average case-fatality rate of 7·3%. The disease was also reported in Japan and Korea in 2012; Heartland virus, another phlebovirus genetically closely related to SFTSV, was isolated from two patients in the USA. The disease has become a substantial risk to public health, not only in China, but also in other parts of the world. The virus could undergo rapid evolution by gene mutation, reassortment, and homologous recombination in tick vectors and vertebrate reservoir hosts. No specific treatment of SFTS is available, and avoiding tick bites is an important measure to prevent the infection and transmission of SFTSV. This Review provides information on the molecular characteristics and ecology of this emerging tick-borne virus and describes the epidemiology, clinical signs, pathogenesis, diagnosis, treatment, and prevention of human infection with SFTSV.

https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(14)70718-2.pdf

Severe fever with thrombocytopenia syndrome, an emerging tick-borne zoonosis

Since the beginning of the 1980s, 33 emerging tick-borne agents have been identified in mainland China, including eight species of spotted fever group rickettsiae, seven species in the family Anaplasmataceae, six genospecies in the complex Borrelia burgdorferi sensu lato, 11 species of Babesia, and the virus causing severe fever with thrombocytopenia syndrome. In this Review we have mapped the geographical distributions of human cases of infection. 15 of the 33 emerging tick-borne agents have been reported to cause human disease, and their clinical characteristics have been described. The non-specific clinical manifestations caused by tick-borne pathogens present a major diagnostic challenge and most physicians are unfamiliar with the many tick-borne diseases that present with non-specific symptoms in the early stages of the illness. Advances in and application of modern molecular techniques should help with identification of emerging tick-borne pathogens and improve laboratory diagnosis of human infections. We expect that more novel tick-borne infections in ticks and animals will be identified and additional emerging tick-borne diseases in human beings will be discovered.

https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(15)00177-2.pdf

Emerging tick-borne infections in mainland China: an increasing public health threat

Most humans are in contact with animals in a way or another. A zoonotic disease is a disease or infection that can be transmitted naturally from vertebrate animals to humans or from humans to vertebrate animals. More than 60% of human pathogens are zoonotic in origin. This includes a wide variety of bacteria, viruses, fungi, protozoa, parasites, and other pathogens. Factors such as climate change, urbanization, animal migration and trade, travel and tourism, vector biology, anthropogenic factors, and natural factors have greatly influenced the emergence, re-emergence, distribution, and patterns of zoonoses. As time goes on, there are more emerging and re-emerging zoonotic diseases. In this review, we reviewed the etiology of major zoonotic diseases, their impact on human health, and control measures for better management. We also highlighted COVID-19, a newly emerging zoonotic disease of likely bat origin that has affected millions of humans along with devastating global consequences. The implementation of One Health measures is highly recommended for the effective prevention and control of possible zoonosis.

/pdf/zoonotic-diseases-etiology-impact-and-control-3f9bm52mdq.pdf

Zoonotic diseases: etiology, impact, and control

Background Seven persons in one family living in eastern China developed fever and thrombocytopenia during May 2007, but the initial investigation failed to identify an infectious etiology. In December 2009, a novel bunyavirus (designated severe fever with thrombocytopenia syndrome bunyavirus [SFTSV]) was identified as the cause of illness in patients with similar clinical manifestations in China. We reexamined this family cluster for SFTSV infection. Methods We analyzed epidemiological and clinical data for the index patient and 6 secondary patients. We tested stored blood specimens from the 6 secondary patients using real time reverse transcription polymerase chain reaction (RT-PCR), viral culture, genetic sequencing, micro-neutralization assay (MNA), and indirect immunofluorescence assay (IFA). Results An 80-year-old woman with fever, leucopenia, and thrombocytopenia died on 27 April 2007. Between 3 and 7 May 2007, another 6 patients from her family were admitted to a local county hospital with fever and other similar symptoms. Serum specimens collected in 2007 from these 6 patients were positive for SFTS viral RNA through RT-PCR and for antibody to SFTSV through MNA and IFA. SFTSV was isolated from 1 preserved serum specimen. The only shared characteristic between secondary patients was personal contact with the index patient; none reported exposure to suspected animals or vectors. Conclusions Clinical and laboratory evidence confirmed that the patients of fever and thrombocytopenia occurring in a family cluster in eastern China in 2007 were caused by a newly recognized bunyavirus, SFTSV. Epidemiological investigation strongly suggests that infection of secondary patients was transmitted to family members by personal contact.

/pdf/a-family-cluster-of-infections-by-a-newly-recognized-3bm4t96gu4.pdf

A Family Cluster of Infections by a Newly Recognized Bunyavirus in Eastern China, 2007: Further Evidence of Person-to-Person Transmission

Severe fever with thrombocytopenia syndrome virus (SFTSV), a newly discovered member of the Bunyaviridae family, is the causative agent of an emerging hemorrhagic fever, SFTS, in China. Currently, there are no vaccines or effective therapies against SFTS. In this study, a combinatorial human antibody library was constructed from the peripheral lymphocytes of 5 patients who had recovered from SFTS. The library was screened against purified virions for the production of single-chain variable-region fragments (ScFv). Of the 6 positive clones, one clone (monoclonal antibody [MAb] 4-5) showed neutralizing activity against SFTSV infection in Vero cells. MAb 4-5 was found to effectively neutralize all of the clinical isolates of SFTSV tested, which were isolated from patients in China from 2010 to 2012. MAb 4-5 was found to bind a linear epitope in the ectodomain of glycoprotein Gn. Its neutralizing activity is attributed to blockage of the interactions between the Gn protein and the cellular receptor, indicating that inhibition of virus-cell attachment is its main mechanism. These data suggest that MAb 4-5 can be used as a promising candidate molecule for immunotherapy against SFTSV infection.

Human Antibody Neutralizes Severe Fever with Thrombocytopenia Syndrome Virus, an Emerging Hemorrhagic Fever Virus

The invention relates to a liquid phase chip for detecting pathogeny of diseases, also relates to a preparation method of the liquid phase chip and applications thereof, belonging to the technical field of medical detection. The principle of the invention is as follows: by combining the liquid phase chip technology, 5' end is added with C12 molecular arm and a specificity detection probe which ismodified by amine and contains pathogenic characteristic information, and is coupled with and fluorescent beads to prepare the liquid phase chip; hybridization is carried out to the liquid phase chipand PCR amplified products of a sample to be detected; the obtained hybridization reaction products react with SA-PE; the purpose of fast and accurately detecting pathogeny is achieved by detection ofa liquid phase chip detector, wherein the pathogenic characteristic information is reverse primer marked with biotin. The liquid phase chip has the beneficial effects of: not only overcoming the limitation of common PCR and fluorescent quantitative PCR in multiple detecting aspects, simultaneously overcoming the defects that the solid phase chip has low sensitivity and poor repeatability for detecting results, having characteristics of various detecting types, short reaction time, high sensitivity, strong specificity and accurate detection and having wide application prospect.

Xian Li

Papers

A Family Cluster of Infections by a Newly Recognized Bunyavirus in Eastern China, 2007: Further Evidence of Person-to-Person Transmission

Human Antibody Neutralizes Severe Fever with Thrombocytopenia Syndrome Virus, an Emerging Hemorrhagic Fever Virus

Liquid phase chip for detecting pathogeny of hand foot and mouth disease, preparation method and applications thereof