Fever with thrombocytopenia syndrome (SFTS), an emerging hemorrhagic fever whose first cases were seen in rural China, is caused by SFTS virus (SFTSV), a new genus of virus in the family Bunyaviridae, the white lacewing viruses. Since it was first reported in 2010, approximately 2,500 cases of the disease have been identified in 11 provinces in China, with an average mortality rate of 7.3%. Jie Shenghua, Department of Infection, Wuhan Union Medical College Hospital
Heartland virus, a genetically similar virus of the genus Bunyavirus of the family Bunyaviridae, which was isolated from 2 patients in the United States, was also reported in Japan and Korea in 2012.
SFTS is a huge threat to public health not only in China but also elsewhere in the world. SFTS viruses can evolve rapidly through genetic mutation, recombination and homologous recombination within tick vectors and vertebrate hosts. There is no specific treatment for SFTS, and the most important measure to prevent SFTS virus infection and transmission is to prevent tick bites.
On May 16, 2014, Lancetinfectdisease published online a review on fever with thrombocytopenia syndrome by Dr. QuanLiu et al. from China. The review aims to provide information on the molecular characteristics and ecology of emerging tick-borne viruses and to describe the epidemiology, clinical symptoms, pathogenesis, diagnosis, treatment, and prevention of SFTSV infection. The full text is compiled below.
I. Overview
In May 2007, three patients with high fever, gastrointestinal bleeding, abdominal pain, abdominal distension, nausea, vomiting and elevated transaminases were diagnosed with acute gastritis by a local hospital in Xinyang, Henan Province, China. The relatives of one of the patients reported the disease to the Henan Provincial Center for Disease Control and Prevention (CDC).
A special investigation conducted by Henan CDC found that the clinical features of the disease were: acute onset, main symptoms including fever, reduced white blood cell and platelet count, elevated glutaminase, glutamic acid transaminase and proteinuria.
Based on these clinical features, Henan CDC ruled out the possibility of gastrointestinal disease and started to search for similar cases, and found that there were 79 cases of the disease in Henan in 2007, of which 10 died (12.7% mortality rate).
At that time, there was an outbreak of scrub typhus (jungle typhus) caused by Orientia tsutsugamushi in Henan Province, and an infection with human granulocytic anaplasmosis caused by phagocytic anaplasmosis in Anhui Province, a province near Henan Province. These diseases have similar clinical features. Therefore, rickettsial diseases (e.g., human granulocytic anaplasmosis, scrub typhus) and human monocytic ehrlichiosis caused by Ehrlichia chaffeensis were considered as possible causes of this disease outbreak in Henan.
However, only 6 of 206 suspected cases (3%) were finally diagnosed as granulocytic agranulocytic infection, and no pathogens were isolated for 3 years after 2007. Cases of SFTS have also been reported in Shandong, Jiangsu, Hubei, Anhui, and Liaoning.
In 2010, a novel virus known as SFTS virus or Bunyavirus was isolated from SFTS patients. This virus is thought to be the causative agent of fever with thrombocytopenia-associated fatal disease in China.
The disease was also reported in Japan and Korea in 2012. Another white lacewing virus, Heartland virus, was also reported in Missouri, USA, where another white lacewing virus, Heartland virus, was isolated from two patients with febrile thrombocytopenia and is genetically closely related to SFTS virus. The disease was traced back to the United States in 2009 and Japan and Korea in the summer of 2012, but there was no evidence that these patients had traveled to China.
These viruses may have different origins, but they can cause similar or even identical symptoms and clinical prognosis. The emerging SFTS virus did originate in China 50-150 years ago. Perhaps this pathogen was also present for a long time in Japan and Korea, and Heartland virus was also present in the United States.
In this review, the authors discuss the molecular characteristics and ecological information of SFTS viruses and describe the epidemiology, clinical signs, pathogenesis, diagnosis, treatment, and prevention of SFTS virus infections.
II. Pathogens
1.Classification
SFTS viruses belong to the genus Bunyaviridae (white lacewing viruses). The family Bunyaviridae has the largest proportion of RNA viruses, which includes more than 350 viruses and can be divided into the following five genera: Bunyaviridae, Hantavirus, Nairovirus, Whitefly virus and Tomato spotted wilt virus. All Bunyaviridae viruses are transmitted by arthropod vectors, except for Hantavirus, which is transmitted by rodents.
Viruses of the Bunyaviridae family can infect different species of animals and plants, and many viruses of this family can cause febrile infections in humans, including encephalitis and hemorrhagic fever. Due to the increased incidence of bunyaviruses in human hosts and geographic distribution, they are considered to be important emerging pathogens that threaten public health.
Viruses of the genus Leptospira contain about 70 serotypes with different antigenicity and are divided into two groups: the Leptospira fever group and the Ukunimi group of viruses. The viruses of the Lacewing fever group are transmitted by lacewings or mosquitoes, and the viruses of the Ukunimi group are transmitted by ticks.
Genetically, the SFTS virus should be classified into the genus Whitefly virus, but it differs from the other two known groups of viruses within the genus Whitefly virus, so it may be a third group of viruses within the genus Whitefly virus.
Although SFTS and Heartland viruses have limited sequence similarity to other members of the Ukunimivirus group, they are still classified in the Ukunimivirus group because they lack the nonstructural small protein in the M segment, but they have specific serological features and both use ticks as a common arthropod vector.
Matsuno and colleagues have identified a new group of viruses within the genus Bhanja, which includes Bhanja, Forecariah and Palma viruses. SFTS and Heartland viruses are more closely related to the Bhanja group than to the Ukunimi group.
2. Genes and structure
SFTS viral particles are spherical in shape, about 80-100 nm in diameter, with a lipid envelope and 5-10 nm long polypeptide spines on the surface.SFTS viral genome consists of three small, medium and large negative-stranded RNA fragments.
The small RNA fragment has 1744 nucleotides and encodes nuclear and non-structural proteins in a bidirectional manner. the untranslated regions at the 3′ and 5′ ends are highly conserved and form a pot-handle-like structure. Nucleoproteins package genomic RNA to the ribonucleoprotein complex to protect it from degradation by exogenous nucleases or the host cell immune system.
Although the nucleoprotein functions are similar, the crystal structure of the SFTS virus nucleoprotein can be processed into a stable hexameric ring structure to assist in the encapsulation of viral RNA, a critical step in viral replication.
The four residues in the small RNA fragment, A8, F11, A25 and L28, are essential for viral oligomerization and are very different from other members of the Bunyaviridae family. In addition, nuclear proteins have activating effects on RNA transcription, replication and viral assembly. both nuclear and nonstructural proteins of SFTS viruses inhibit the antiviral immune response of host cells by suppressing the activation of interferon β and nuclear factor κB signaling pathways.
The 3378 nucleotides of the medium RNA fragment, which contains a single open reading frame encoding 1073 amino acids of the glycoprotein precursor, are critical for viral assembly, viral particle formation, and adhesion to new target cells. Glycoprotein winding onto the non-myosin heavy chain IIA of cell surface proteins has a role in the efficiency of early SFTSV infection.
The large RNA fragment has 6368 nucleotides and encodes a large protein-viral RNA-dependent RNA polymerase of 2084 amino acids; this enzyme promotes replication and transcription of viral RNA. Its N-terminal influenza-like nucleic acid endonuclease region has an important role in viral guanosine cap-dependent transcription.
3. Genetic diversity
Disregarding the wide geographical distribution of SFTS viruses, SFTS viruses can be divided into five sublineages from A to E, despite the fact that more than 90% of the isolated SFTS viruses have similar sequences. The isolates from animals (dogs, cats, sheep, buffalo and domestic cattle) were sublineage A, which did not show geographic clustering, unlike other rabies viruses and zoonotic viruses such as hantavirus. Among the Bhanja group viruses Heartland virus and SFTSV share a common viral ancestor.
The molecular mechanisms underlying the genetic diversity of SFTSV have not been fully elucidated, but several studies have suggested that viruses can acquire rapid evolution through genetic mutations, natural recombination and homologous recombination. SFTSV has a high mutation rate during replication (~10-4 substitutions per site per year) due to the RNA-dependent RNA polymerase without proofreading function, which is the basis of its genetic diversity.
Recombination is a very efficient evolutionary force in segmented genomic viruses and is associated with high viral pathogenicity and vector-to-host transmission, which can even lead to new disease outbreaks. Evidence for the genetic evolution of natural recombination has been previously reported in members of the genus Whitefly virus, such as Rift Valley fever virus and Candiru virus.
Ding et al. have identified two SFTSV strains with recombination in small fragments, suggesting that recombination is the force driving rapid changes in SFTSV. Although homologous recombination is rare in negative-stranded RNA viruses, it has been found in mid-fragments of SFTSV and other negative-stranded RNA viruses such as influenza virus, Ebola virus, and hantavirus, suggesting a role for intergenic recombination in rapid viral evolution.
The tick-borne vector of SFTSV, the longhorned tick, and the vertebrate reservoir host could provide a location for homologous recombination of viruses and co-infection by natural recombination.
4. epidemiology
SFTS was first reported in July 2009 in rural areas of Henan and Hubei provinces in China. In fact, the first case occurred in September 2006 in Dingyuan County, Chuzhou City, Anhui Province. 171 patients were diagnosed with SFTS virus infection in Henan, Hubei, Shandong, Liaoning, Anhui and Jiangsu Provinces from June 2009 to September 2010. by the end of 2012, the disease had been identified in the following 11 provinces: Henan, Hubei, Anhui, Shandong, Jiangsu, Zhejiang, Jiangxi, Guangxi, Yunnan, Shaanxi and Liaoning. Guangxi, Yunnan, Shaanxi, and Liaoning.
From 2011-2012, there were 2047 SFTSV infections in China (including 129 deaths), with infections mainly in 206 counties in eastern and central China. Henan, Hubei, and Shandong had the highest number of cases, accounting for 48%, 22%, and 16% of the total, respectively.
The incidence of SFTS ranged from 0.03 per 1,000 in Hubei to 0.05 per 1,000 in Shandong.
The first case outside of China appeared in North Korea in 2009, a fatal case was diagnosed in South Korea in 2012, and six cases of the disease were reported in 2013, with four deaths. Japan reported 11 cases of the disease in April 2013, including 7 deaths, and its apparent increase in the number of cases appears to be limited to the local area rather than spread from China.
The disease was first noted in the United States in 2009 when two farmers in northwestern Missouri were hospitalized with high fever, fatigue, diarrhea, and thrombocytopenia; both farmers had been bitten by ticks 5-7 days prior to the onset of the disease.
The overall mortality rate of SFTS virus infection in China was approximately 7.3% (2391 cases, 174 deaths), compared with 6.3%-30.0% in other studies. Farmers in disease-endemic areas are the main risk group, with 97% of SFTS patients in China being farmers living in forest and hilly areas or working in farmland, and many having been bitten by ticks 7-9 days prior to the onset of disease.
The incubation period of the disease is generally 7-14 days, with an average of 9 days. cases of SFTS are mainly found in tick-exposed populations aged 35-80 years. In Henan Province SFTS occurs mainly in April and May during the tea picking season. Wilderness activities, such as camping and hiking, are also potential risk factors for exposure to ticks.
SFTS cases occur in a sporadic increase mainly in spring and summer. Direct contact with infected blood or bloody secretions can cause infection, and small groups of infections have been reported previously, suggesting a human-to-human mode of transmission of SFTS disease. Hospital nursing staff, relatives of patients, and accompanying persons are the second major susceptible group, and they become infected primarily through contact with bloody secretions from patients.
Although there is no evidence that the virus can cause infection in animals, blood from animals infected with subclinical viruses may be a source of infection. Therefore, veterinarians and slaughterhouse workers are also at risk of infection.
5.Life habits
(1) Vector of transmission
As a newly discovered white-wing virus, researchers believe that SFTS virus is an arthropod-borne virus, which means that the virus can be transmitted through different kinds of vectors. In China, SFTS virus has been found on the long-horned blood tick (prevalence 2.1-5.4%), which was collected from domesticated animals in areas where SFTS patients live. The RNA sequences of the viruses isolated from the ticks were closely related to the SFTSV sequences isolated from the patients.
SFTS virus has also been found on microscopic ticks in both endemic and non-endemic areas, but the prevalence of SFTS virus carriage on microscopic ticks was lower than on longhorned ticks (0.6% vs. 4.9%). The higher carriage rate of SFTS virus on T. longicornis in endemic areas compared to non-endemic areas suggests that T. longicornis is a major vector of SFTS virus transmission. Longhorned blood ticks and cattle spleens are widely distributed in China and other countries, so testing for SFTS virus on ticks in these areas is warranted.
SFTS virus has also been found on leatherback and chigger mites collected from blackline mice and goats in endemic areas, so both are also potential vectors. heartland virus has been found and isolated from larvae of the American blunt-eyed tick, which were obtained from a patient’s farm and a nearby farming reserve.
These findings suggest that the virus is transmitted to humans through the feeding tick larvae of the virus’ hosts and through the larvae seeking hosts in the spring and summer. Thus, the American blunt-eyed tick is also thought to be a vector for Heartland virus. SFTS virus and Heartland virus are still not found in mosquitoes, and white-wing virus has not yet been studied.
(2) Vertebrate reservoir hosts
Studies have suggested that SFTS viruses circulate in the endemic tick-vertebrate-tick chain. Although there is no evidence that SFTS viruses cause disease in animals, investigations based on a nucleoprotein double antigen sandwich ELISA for SFTSV seropositive screening have been conducted in domesticated animals.
In Shandong Province, the seropositivity rate was 75-95% in sheep, 57% in domestic cattle, 52% in dogs and 36% in domestic chickens. In Jiangsu Province, the seropositivity rate was 1% in domestic chickens, 5% in pigs, 6% in dogs, 32% in domestic cattle, and 57% in sheep.
In Hubei province, the seropositivity rate was 55% in dogs, 67% in sheep, and 80% in domestic cattle. Viral RNA, especially at low levels, was detected in only a small proportion of the animals investigated (1.7%-5.3%). These findings suggest that domesticated animals are the primary hosts for expanded SFTS virus transmission and that SFTS virus transmission can be expanded by feeding ticks to domesticated animals.
In addition to domesticated animals, many wild animals, such as deer, hedgehogs, skunks, brush-tailed opossums, and some birds, are regular hosts of ticks. SFTS virus infections have also been found on rodents, with infection rates ranging from 7% in the kiwi rat to 8% in the small house mouse and brown house mouse.
In Minnesota, USA, antibody positivity for SFTS virus nucleoproteins was 11% in goats, 13% in sheep, 16% in domestic cattle, 12% in white-tailed deer, and 18% in elk. Thus, all domesticated and captive farm animals in this region were exposed to SFTS virus or Heartland virus.
III. Clinical features
SFTS begins acutely with fever and respiratory or gastrointestinal signs, followed by progressive decreases in platelet and white blood cell counts. A typical SFTSV infection is divided into four phases: the incubation phase, the febrile phase, the multi-organ failure phase, and the recovery phase.
The incubation period is 5-14 days after the tick bite. The length of the incubation period can be influenced by a number of factors, including viral dose and route of infection. The average number of days between exposure or exposure to blood or bloody secretions of the patient and onset of illness is approximately 10 days (7-12 days).
The febrile phase is characterized by flu-like symptoms such as sudden onset of high fever (38-41°C) that persists for 5-11 days, headache, fatigue, myalgia, and gastrointestinal symptoms such as poor appetite, nausea, vomiting, and diarrhea, accompanied by thrombocytopenia and leukopenia, and enlarged lymph nodes. High viral load can be detected during this period, which is an important marker for clinical diagnosis.
The stage of multi-organ failure is characterized by progressive decline in multi-organ function in critically ill patients or self-limiting recovery in survivors. Multiorgan failure progresses rapidly, first involving the liver and heart, then the lungs and kidneys. The multi-organ failure phase may overlap with the febrile phase, with most cases entering the multi-organ failure phase 5 days after onset and lasting 7-14 days.
During the multi-organ failure phase, serum viral load decreases gradually in survivors, but remains high in deceased patients. During organ failure, levels of important biomarkers (e.g., glutamate transaminase, creatine kinase, lactate dehydrogenase, and CK-MB) were significantly higher in the deceased patients than in the survivors.
Clinical signs such as hemorrhage, neurological symptoms, DIC, multiorgan failure and persistent platelet count drop suggest severe disease and high risk of death. The multi-organ failure phase is important because patients who survive this phase eventually recover.
The average time from onset to death is 9 days. Most patients (85%) have a good prognosis, but those with previous underlying disease, presenting psychiatric symptoms, bleeding tendencies, hyponatremia or being elderly have a poor clinical prognosis.
The recovery period for survivors begins 11-19 days after the onset of the disease. At this time, clinical symptoms begin to subside and laboratory tests gradually return to normal. Thrombocytopenia (<100×109/L) and leukopenia (<4.0×109/L) appear to be consistent features of SFTSV infection, which may be due to peripheral organ damage or increasing platelet damage by circulating antibodies.
Patients with SFTS also present with elevated glutathione, glutamic oxalacetic transaminase, lactate dehydrogenase, and creatine kinase. Coagulation disorders are also observed in all patients, which lead to DIC and eventually to multi-organ failure. Survivors return to normal biochemical tests within 3-4 weeks.
Viral replication and host immune response can influence the severity and clinical prognosis of SFTS.
Indicators of close relationship between laboratory tests and death in critically ill and non-critically ill patients include: blood RNA viral load equal to or higher than 105 copies/ml, prothrombin time equal to or longer than 65.1 s, activated partial thromboplastin time equal to or longer than 62.6 s, and ghrelin equal to or higher than 288 U/L. Phospholipase A, fibrinogen, hepatic antimicrobial polypeptide, IL- 6, IL-10, interferon gamma, and chemokine IL-8 were significantly higher in acute temporal phase protein levels than in survivors.
Lu et al. found that elderly patients, decreased level of consciousness, elevated lactate dehydrogenase and elevated creatine kinase were positive predictors of high risk of death in patients who should be treated with more caution.
IV. Pathogenesis
The pathogenesis of SFTS is not fully understood. The common pathogenic features of Bunyaviridae viruses are the ability to suppress the host immune response and are characterized by rapid viral replication and multi-organ failure.
The immune function of SFTS patients was analyzed by Sun et al. found that the number of CD3+ T cells and CD4+ T cells in SFTS patients was significantly lower than normal, while the proportion of NK cells was elevated, especially in the acute phase of severe SFTSV infection. The suppression of immune function can worsen the physical condition of patients and increase the risk of secondary infection.
NK cells perform immunomodulatory functions by producing cytokines such as interferon gamma, tumor necrosis factor (TNF) alpha, IL-10 and granulocyte colony-stimulating factor (G-CSF). The levels of these cytokines correlate with the severity of the disease.
Production of interferon beta is a defense mechanism of the host’s intrinsic immune system against viral infection. However, interferon β is barely detectable in the blood of SFTS patients. in SFTS virus-infected monocytes, transcription factors associated with interferon β are appropriately upregulated, but the levels of TNF receptor-related factors 3 and 6 and mitochondrial antiviral signaling proteins, which are downstream molecules, are not altered or downregulated, thus inhibiting the induction of interferon β.
In addition, SFTS viruses encode proteins such as nuclear and nonstructural proteins that inhibit the activation of the interferon β promoter and nuclear factor κB signaling. These inhibitory effects can also be found on other Bunyaviruses.
Inflammatory factors play an important role in the pathogenesis of virus-induced disease. When the initial immune response fails to inhibit viral replication, the virus can induce the release of excessive cytokines from target cells, leading to pathological damage. Several pro-inflammatory cytokines are aberrantly expressed in the form of cytokine storms, which correlate with the severity of SFTS.
There are three distinct patterns of unbalanced cytokine expression. IL-1 receptor antagonists, IL-6, IL10, G-CSF, interferon gamma-inducible protein, and monocyte chemotactic protein 1 are increased in SFTS and are more commonly found in critically ill patients than in non-critically ill patients. In contrast, levels of platelet-derived growth factors and RANTES (factors that regulate the expression of activated and normal T cells) were decreased. These cytokines return to normal levels during the patient’s recovery period.
IL-1β, IL-8 and macrophage inflammatory proteins 1α and 1β expression was increased only in patients with severe SFTS, but these factors were also increased in survivors during the recovery period. These cytokines were associated with serum viral load and various clinical features.
For example, monocyte chemotactic protein 1 and IL-8 are important in progressive kidney injury, IL-1 receptor antagonists and IL-6 are associated with epidemic nephropathy, monocyte chemotactic protein 1 and interferon gamma-inducible protein cause liver inflammation and fibrosis, and IL-8 increases vascular permeability.
Low expression of RANTES is associated with the severity of virus-induced disease. low expression of RANTES and platelet-derived growth factors in SFTS patients may be due to a decrease in the number of circulating platelets, which are the main source of both cytokines in the peripheral circulation.
Hemorrhagic fever symptoms in SFTS are also associated with increased TNFα. TNFα acts on endothelial cells, induces vasodilator production and stimulates carbon monoxide synthesis, which increases capillary endothelial cell permeability.
SFTS virus adheres to platelets, which can be recognized and phagocytosed by splenic macrophages, resulting in thrombocytopenia, a common clinical manifestation of SFTS. SFTSV can replicate in a variety of cell types, but its primary target is reticulocytes. Infected monocytes are nearly intact and non-apoptotic, and they are able to maintain continuous viral replication due to their dissemination into the blood circulation via lymphatic vessels, causing initial viremia.
Although SFTS virus can hijack macrophages for viral replication, macrophages inhibit viral growth and eventually clear them in a mouse model. Thus, SFTS virus can be cleared in immunocompetent patients, but in immunosuppressed patients the virus can effectively proliferate and cause multi-organ dysfunction or patient death.
V. Diagnosis
Early diagnosis of SFTS virus infection plays a key role in patient survival and prevention of virus transmission. Currently, SFTS is diagnosed based on epidemiological features such as epidemic season, geographical distribution, history of tick bite, clinical manifestations and laboratory tests (thrombocytopenia and leukopenia). Because the clinical manifestations of SFTS are not specific, laboratory tests are necessary.
The differential diagnosis includes hemorrhagic fever with nephrotic syndrome, dengue fever, platelet purpura, typhoid fever, leptospirosis, and human borderworm disease.
SFTS virus isolation should be performed in a biosafety level III laboratory. SFTS virus can infect a variety of cell lines, including Vero, VeroE6, L929, and DH82, but it causes cytopathic lesions only in DH82 and VeroE6 cells.
Isolation of the virus from cultured cells is simple and rapid (2-5 days), but the virus may not yet induce cytopathic lesions or only a little lesion, so confirmation of viral pathogenesis by electron microscopy and molecular or serological methods is necessary.
RT-PCR is a highly specific, sensitive and rapid laboratory method for confirming SFTS virus infection. The advent of fully automated real-time PCR methods has allowed SFTS virus detection with lower contamination rates, higher sensitivity and specificity, and faster detection than traditional RT-PCR assays.
Currently multiplex real-time RT-PCR can simultaneously detect four hemorrhagic fever pathogens-SFTSV, hantavirus, Seoul virus, and dengue virus. Isothermal amplification techniques can also be used to detect SFTS virus RNA, including RT loop-mediated isothermal amplification and RT cross-primer amplification. All of these methods are highly specific and sensitive.
Although SFTS virus infection can produce high titer viremia, facilitating viral isolation and molecular detection, the duration is short, typically 1-6 days after onset. Specific antibodies to SFTS virus can be detected in the blood approximately 7 days after onset.
Specific IgG is still detectable 5 years after infection, but IgM is undetectable 4 months after infection. Recent SFTS virus infections can be diagnosed by testing for IgM antibodies, seroconversion of IgG antibodies, or a minimum 4-fold increase in antibody titers.
Several serologic methods are also available for detecting antibodies to the virus, including serum neutralization tests, indirect immunofluorescence assays, and ELISA.
The serum neutralization test is the gold standard, but it is laborious, expensive and requires live virus to perform. Therefore, serum neutralization tests can only be performed in special laboratories with high-level biosafety equipment.
ELISA is inexpensive, less time-consuming, and a recombinant, nucleoprotein-based, dual-antigen sandwich ELISA has been developed for the detection of SFTS virus antibodies in humans and animals. This method is more sensitive than the serum neutralization test, and it has no cross-reactivity in SFTS virus and dengue or hantavirus.
VI. Treatment
Since there is no specific treatment for SFTS, symptomatic and supportive treatment should be started for SFTS patients as early as possible. Bed rest, liquid or semi-liquid diet, and adequate hydration. If the patient is unable to eat or is in critical condition, energy and hydration are necessary to ensure the patient’s water-electrolyte balance, especially in patients with hyponatremia.
Patients with fever should be given physical cooling and, if necessary, antipyretics. Platelet and plasma transfusions are recommended for patients with significant bleeding or very low platelet counts (<30×109/L). If the patient has a severely reduced neutrophil count, G-CSF should be given. patients with combined bacterial or fungal secondary infections should be given appropriate antibiotics or antifungal agents. Psychological interventions can help patients recover.
Ribavirin is currently approved for the treatment of several viral infections, including Bunyaviruses of the genus Rift Valley fever virus and Crimean Congo fever virus. Although ribavirin inhibited viral activity in in vitro tests, it had no significant effect on platelet counts or viral load during hospitalization in critically ill or non-critically ill patients, so ribavirin has little role in the treatment of SFTS viral infections.
Antibodies have an important role in the treatment of diseases caused by a variety of viruses, such as hantavirus, cytomegalovirus, and rabies virus. The mechanisms of action include neutralization, activation of complement, antibody-dependent cytotoxicity, and modulation. Administration of neutralizing antibodies to patients may reduce viral load and prevent viral transmission, while potentially reducing the risk of poor prognosis.
Human monoclonal antibodies isolated from phage antibody libraries4-5 have been shown to neutralize SFTS viruses in in vitro assays and may be used to prevent viral infection in populations at high risk of human-to-human transmission such as hospital workers and relatives of patients.
The successful treatment of two patients with rapidly progressing SFTS by plasma exchange and ribavirin suggests that plasma exchange and ribavirin could be a potential life-saving therapy for the treatment of patients with severe SFTS.
VII. Prevention
There is no vaccine for the SFTS virus, so residents living in areas where the disease is endemic should focus on the following preventive measures: avoiding tick bites, including avoiding forests and bushes with heavy grass and leaf litter, especially during the active tick season when ticks are abundant; examining human or animal skin surfaces for ticks; and using insect repellents such as DEET or bemethrin.
Insect repellents containing 20 percent or more of DEET applied to exposed skin can protect for several hours, and bacitracin-treated items such as clothing, boots and tents can remain protected for more than 70 washes. Incidence.
SFTS patients should be isolated until the virus is no longer detected in the blood, and everyone in contact with these patients should be monitored for fever until the end of the incubation period.
SFTS viruses are sensitive to acid, heat, ether, sodium deoxycholate and other common disinfectants and UV radiation and can be rapidly inactivated by these substances. Surfaces of objects contaminated with patient blood, secretions, and excretions should be disinfected.
For people at high risk of infection, such as those directly exposed to the blood of SFTS patients through contact or needle-stick injuries, oral or subcutaneous administration of human monoclonal antibodies to ribavirin may be administered for prophylaxis.
VIII. Future research directions
The dynamics of the environment and transmission chain of SFTS virus and Heartland virus in endemic areas should be further elucidated. The role of climatic factors, storage hosts and vectors should be described in detail, and the seroconversion of SFTS virus infection in wildlife also needs further study. Comparative studies of viruses isolated from China, Japan, Korea, and the United States should elucidate the origin and diversity of these viruses.
In the meantime, effective measures including vaccines, antiviral drugs, therapeutic antibodies or immune sera should be taken to prevent and control viral infections. New information about viral replication may facilitate research on new drugs.
Further research on the pathogenesis of viral hemorrhagic fever will point the way to the pathogenesis of DIC and multi-organ failure. Understanding new mechanisms of SFTS viral infections or other viral hemorrhagic fevers will facilitate the study of new therapeutic molecules.
SFTS is difficult to control and prevent because of the complex chain of transmission, with its vertebrate hosts and vector ticks in a constantly changing environment. We should focus on the role of the one-person health-is-all-health approach in this emerging tick-borne zoonotic disease.