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BACKGROUND: Rabies is an incessant public health threat in China. The Ministry of Health implemented the Central Payment for Rabies Prevention and Control Project to assist with rabies prevention and control in a few representative provinces in 2006. METHODS: Data on human rabies cases reported by the National Infectious Disease Reporting Information Management System and national surveillance sites from 2006 to 2022 were collected, and statistical and multivariate analyses were then used to assess the effectiveness of current prevention and control efforts. RESULTS: During 2006-2022, a total of 2025 human rabies cases were collected by the national surveillance sites, with incidence rates far above the national average, but the incidence rate was consistent with the national trend. Human rabies cases demonstrated a dual peak distribution in terms of exposure and onset dates, with the peak exposure dates falling mostly in the spring and summer and the peak onset dates occurring mostly in the summer and autumn. Three danger categories are shown by the geographical distribution: high, medium and low. Dogs had a high infection rate (86.93%), with own domesticated dogs accounting for the majority of infections. The rates of post-exposure prophylaxis are not constant. The median incubation period was 71 days. CONCLUSIONS: Various measures and policies implemented by the government have played a key role in reducing the incidence of rabies. To effectively prevent and control the resurgence of epidemics and halt the spread of the virus among host animals, it is imperative to prioritize and implement a robust dog management system, accelerate research and development of animal vaccines and improve the level of post-exposure prophylaxis.
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Rabia , Rabia/epidemiología , Rabia/prevención & control , Rabia/veterinaria , China/epidemiología , Humanos , Animales , Perros , Incidencia , Masculino , Femenino , Adolescente , Niño , Adulto , Persona de Mediana Edad , Estaciones del Año , Preescolar , Adulto Joven , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/virología , Enfermedades de los Perros/prevención & control , Lactante , Anciano , Profilaxis Posexposición , Vacunas Antirrábicas/administración & dosificaciónRESUMEN
Rabies is a fatal neurological infectious disease caused by rabies virus (RABV), which invades the central nervous system (CNS). RABV with varying virulence regulates chemokine expression, and the mechanisms of signaling pathway activation remains to be elucidated. The relationship between Toll-like receptors (TLRs) and immune response induced by RABV has not been fully clarified. Here, we investigated the role of TLR7 in the immune response induced by RABV, and one-way analysis of variance (ANOVA) was employed to evaluate the data. We found that different RABV strains (SC16, HN10, CVS-11) significantly increased CCL2, CXCL10 and IL-6 production. Blocking assays indicated that the TLR7 inhibitor reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). The activation of the Myd88 pathway in BV-2 cells stimulated by RABV was TLR7-dependent, whereas the inhibition of Myd88 activity reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). Meanwhile, the RABV stimulation of BV-2 cells resulted in TRL7-mediated activation of NF-κB and induced the nuclear translocation of NF-κB p65. CCL2, CXCL10 and IL-6 release was attenuated by the specific NF-κB inhibitor used (p < 0.01). The findings above demonstrate that RABV-induced expression of CCL2, CXCL10 and IL-6 involves Myd88 and NF-κB pathways via the TLR7 signal.
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Factor 88 de Diferenciación Mieloide , FN-kappa B , Virus de la Rabia , Transducción de Señal , Receptor Toll-Like 7 , Receptor Toll-Like 7/metabolismo , Animales , Factor 88 de Diferenciación Mieloide/metabolismo , Factor 88 de Diferenciación Mieloide/genética , Virus de la Rabia/patogenicidad , Virus de la Rabia/inmunología , Ratones , FN-kappa B/metabolismo , Línea Celular , Interleucina-6/metabolismo , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Quimiocina CXCL10/metabolismo , Quimiocina CXCL10/genética , Rabia/virología , Rabia/metabolismo , Rabia/inmunología , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Inflamación/metabolismoRESUMEN
Rabies, caused by the rabies virus (RABV), is the most fatal zoonotic disease. It is a neglected tropical disease which remains a major public health problem, causing approximately 59,000 deaths worldwide annually. Despite the existence of effective vaccines, the high incidence of human rabies is mainly linked to tedious vaccine immunisation procedures and the overall high cost of post-exposure prophylaxis. Therefore, it is necessary to develop an effective vaccine that has a simple procedure and is affordable to prevent rabies infection in humans. RABV belongs to the genus Lyssavirus and family Rhabdoviridae. Previous phylogenetic analyses have identified seven major clades of RABV in China (China I-VII), confirmed by analysing nucleotide sequences from both the G and N proteins. This study evaluated the immunogenicity and protective capacity of SYS6008, an mRNA rabies vaccine expressing rabies virus glycoprotein, in mice and cynomolgus macaques. We demonstrated that SYS6008 induced sufficient levels of rabies neutralising antibody (RVNA) in mice. In addition, SYS6008 elicited strong and durable RVNA responses in vaccinated cynomolgus macaques. In the pre-exposure prophylaxis murine model, one or two injections of SYS6008 at 1/10 or 1/30 of dosage provided protection against a challenge with a 30-fold LD50 of rabies virus (China I and II clades). We also demonstrated that in the post-exposure prophylaxis murine model, which was exposed to lethal rabies virus (China I-VII clades) before vaccination, one or two injections of SYS6008 at both 1/10 and 1/30 dosages provided better protection against rabies virus challenge than the immunization by five injections of commercial vaccines at the same dosage. In addition, we proved that SYS6008-induced RVNAs could neutralise RABV from the China I-VII clades. Finally, 1/10 of the dosage of SYS6008 was able to stimulate significant RABV-G specificity in the T cell response. Furthermore, we found that SYS6008 induced high cellular immunity, including RABV-G-specific T cell responses and memory B cells. Our results imply that the SYS6008 rabies vaccine, with a much simpler vaccination procedure, better immunogenicity, and enhanced protective capacity, could be a candidate vaccine for post-exposure prophylaxis of rabies infections.
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Vacunas Antirrábicas , Virus de la Rabia , Rabia , Humanos , Animales , Ratones , Rabia/prevención & control , Vacunas Antirrábicas/genética , Virus de la Rabia/genética , Profilaxis Posexposición/métodos , Modelos Animales de Enfermedad , Filogenia , Anticuerpos Antivirales , MacacaRESUMEN
Rabies is a highly fatal disease, and it is vital to find effective ways to manage and control infection. There is a need for new effective antiviral drugs that are particularly effective treatments for rabies. Deoxynivalenol (DON) is known mainly for its toxicity, but at the molecular level, it can inhibit RNA and DNA replication, and there is increasing evidence that different doses of DON have a positive effect on inhibiting virus replication. Based on this, we evaluated the effect of DON on inhibiting the rabies virus in vitro. The inhibitory effect of DON on rabies virus activity was dose- and time-dependent, and 0.25 µg/mL of DON could inhibit 99% of rabies virus activity within 24 h. Furthermore, DON could inhibit the adsorption, entry, replication, and release of rabies virus but could not inactivate the virus. The inhibitory effect of DON on rabies virus may be achieved by promoting apoptosis. Our study provides a new perspective for the study of anti-rabies virus and expands the direction of action of mycotoxins.
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Micotoxinas , Virus de la Rabia , Tricotecenos , Micotoxinas/farmacología , Tricotecenos/toxicidad , Replicación ViralRESUMEN
Since the 1980s, a comprehensive field and laboratory investigation has been conducted throughout China, and a total of 29 virus species belonging to 7 families and 13 genera were identified through virological, morphological, and immunological methods, as well as whole-genome sequencing and molecular genetic analyses. Most of the virus isolates belong to 9 genera in the families Flaviviridae, Bunyaviridae, Togaviridae, and Reoviridae. Among them, 4 genera (Orthobunyavirus, Bunyavirus, Phlebovirus, and Nairovirus) belong to the family Bunyaviridae and 3 genera (Seadonavirus, Orbivirus, and Cypovirus) belong to the family Reoviridae. Analyses of the relationships between viruses and human/animal diseases indicated that Japanese encephalitis virus, dengue virus, severe fever with thrombocytopenia syndrome virus, tick-borne encephalitis virus, Crimean-Congo hemorrhagic fever virus, West Nile virus, and Tahyna virus can cause human and animal infections and disease epidemics in China. This review systematically introduces the current status of the diversity and geographical distribution of arboviruses and vectors in China. In addition, our results provide strong technical support for the prevention and control of arboviral diseases, the treatment of epidemics, and the early warning and prediction of diseases, and so they are significant for the control and prevention of arboviral diseases in Asia and around the world.
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Infecciones por Arbovirus/epidemiología , Infecciones por Arbovirus/virología , Arbovirus , Animales , Infecciones por Arbovirus/diagnóstico , Infecciones por Arbovirus/transmisión , Arbovirus/clasificación , Arbovirus/genética , Arbovirus/aislamiento & purificación , China/epidemiología , Vectores de Enfermedades , Geografía Médica , Humanos , Incidencia , FilogeniaRESUMEN
BACKGROUND: Rabies is a fatal disease that is preventable when post exposure prophylaxis (PEP) is administered in a timely fashion. CpG oligodeoxynucleotides (ODNs) can trigger cells that express Toll-like receptor 9, and their immunopotentiation activity in an inactivated aluminum-adjuvanted rabies vaccine for dogs has been identified using mouse and dog models. METHODS: A human diploid cell rabies vaccine (HDCV) of humans and a CpG ODNs with cross-immunostimulatory activity in humans and mice were used to evaluate the immunogenicity and protective efficacy of CpG ODN in a mouse model that simulates human PEP. RESULTS: HDCV combined with CpG ODN (HDCV-CpG) stimulated mice to produce rabies virus-specific neutralizing antibody (RVNA) earlier and increased the seroconversion rate. Compared with HDCV alone, either HDCV-1.25 µg CpG or HDCV-5 µg CpG increased the levels of RVNA. In particular, 5 µg CpG ODN per mouse significantly boosted the levels of RVNA compared with HDCV alone. IFN-γ producing splenocytes generated in the HDCV-5 µg CpG group were significantly increased compared to the group treated with HDCV alone. When the immunization regimen was reduced to three injections or the dose was reduced to half of the recommended HDCV combined with CpG ODN, the RVNA titers were still higher than those induced by HDCV alone. After viral challenge, 50% of mice immunized with a half-dose HDCV-CpG survived, while the survival rate of mice immunized with HDCV alone was 30%. CONCLUSIONS: The immunopotentiation activity of CpG ODNs for a commercially available human rabies vaccine was first evaluated in a mouse model on the basis of the Essen regimen. Our results suggest that the CpG ODN used in this study is a potential adjuvant to rabies vaccines for human use.
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Adyuvantes Inmunológicos/administración & dosificación , Oligodesoxirribonucleótidos/inmunología , Profilaxis Posexposición , Vacunas Antirrábicas/inmunología , Virus de la Rabia/inmunología , Rabia/inmunología , Animales , Anticuerpos Antivirales/sangre , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunogenicidad Vacunal , Ratones , Ratones Endogámicos BALB C , Oligodesoxirribonucleótidos/administración & dosificación , Rabia/prevención & control , Vacunas Antirrábicas/administración & dosificación , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/inmunologíaRESUMEN
To determine the role of systemic injection of rabies immunoglobulin (RIG) in rabies vaccination, we analyzed the level of antibody against rabies virus in the serum of mice that received various doses of RIG combined with rabies vaccine. Our results indicate that systemic injection of RIG does not contribute detectably to passive or adaptive immunization, suggesting that the main function of RIG in individuals with category III exposure is to neutralize rabies virus via immediate local infiltration of the wound.
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Anticuerpos Antivirales/administración & dosificación , Inmunoglobulina G/administración & dosificación , Vacunas Antirrábicas/administración & dosificación , Virus de la Rabia/inmunología , Rabia/inmunología , Inmunidad Adaptativa , Animales , Anticuerpos Antivirales/inmunología , Femenino , Humanos , Inmunización Pasiva , Inmunoglobulina G/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Rabia/tratamiento farmacológico , Rabia/virología , Vacunas Antirrábicas/inmunología , Virus de la Rabia/fisiología , VacunaciónRESUMEN
During July 2015, physicians at a hospital in Beijing, China, diagnosed rabies in 2 patients who had each received a kidney from a common organ donor who had died from acute progressive encephalitis of unknown cause. The patients had rabies incubation periods of 42 and 48 days. Altered mental status developed in both patients and progressively worsened to deep coma within 80 days after transplantation; both patients died. Two other transplant recipients received corneas but remained well after receiving timely rabies prophylaxis. An effective regulatory system for testing donors should be implemented to decrease the occurrence of donor-derived infectious diseases. In addition, health education should be improved to enhance public awareness of transplant-associated infectious diseases. Transplant recipients and other persons with exposure to organs or tissues from donors with rabies must be provided consistent health monitoring and follow-up, including rabies postexposure prophylaxis; any remaining organs and tissues must be quarantined and not transplanted.
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Trasplante de Riñón/efectos adversos , Rabia/transmisión , Adulto , Niño , Trasplante de Córnea , Humanos , Periodo de Incubación de Enfermedades Infecciosas , Masculino , Persona de Mediana Edad , Rabia/virología , Virus de la Rabia , Donantes de TejidosRESUMEN
Rabies, primarily transmitted to humans by dogs (accounting for 99% of cases). Once rabies occurs, its mortality rate is approximately 100%. Post-exposure prophylaxis (PEP) is critical for preventing the onset of rabies after exposure to rabid animals, and vaccination is a pivotal element of PEP. However, high costs and complex immunization protocols have led to poor adherence to rabies vaccinations. Consequently, there is an urgent need to develop new rabies vaccines that are safe, highly immunogenic, and cost-effective to improve compliance and effectively prevent rabies. In recent years, mRNA vaccines have made significant progress in the structural modification and optimization of delivery systems. Various mRNA vaccines are currently undergoing clinical trials, positioning them as viable alternatives to the traditional rabies vaccines. In this article, we discuss a novel mRNA rabies vaccine currently undergoing clinical and preclinical testing, and evaluate its potential to replace existing vaccines.
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Profilaxis Posexposición , Vacunas Antirrábicas , Rabia , Vacunas de ARNm , Vacunas Antirrábicas/inmunología , Vacunas Antirrábicas/administración & dosificación , Vacunas Antirrábicas/genética , Rabia/prevención & control , Animales , Humanos , Profilaxis Posexposición/métodos , Virus de la Rabia/inmunología , Virus de la Rabia/genética , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Desarrollo de Vacunas , Perros , Ensayos Clínicos como Asunto , ARN Mensajero/genética , ARN Mensajero/inmunologíaRESUMEN
Studies have shown that frailty increases cardiovascular disease (CVD) incidence in older patients and is associated with poor patient prognosis. However, the relationship between medication deviation (MD) and frailty remains unclear. This study aimed to explore the influence of frailty on MD during the hospital-family transition period among older patients with CVD. Between February 2022 and February 2023, 231 older people CVD patients were selected from a class III hospital in Nantong City using a multi-stage sampling method. A general information questionnaire was used to collect the socio-demographic characteristics of the participants prior to discharge, the frailty assessment scale was used to assess the participants frailty, and a medication deviation instrument was used to assess the participants MD on the 10th day after discharge. Propensity score matching was used to examine the effect of frailty on MD in older patients with CVD during the hospital-family transition period. The incidences of frailty and MD were 32.9% (76/231) and 75.8% (175/231), respectively. After propensity score matching, the risk of MD in frail patients with CVD was 4.978 times higher than that in non-frail patients with CVD (95% CI: [1.616, 15.340]; Pâ =â .005). Incidences of frailty and MD during the hospital-family transition period are high in older patients with CVD, and frailty has an impact on MD. Medical staff in the ward should comprehensively examine older patients with CVD for frailty and actively promote quality medication management during the hospital-family transition period to reduce MD occurrence and delay disease progression.
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Enfermedades Cardiovasculares , Fragilidad , Humanos , Anciano , Fragilidad/epidemiología , Enfermedades Cardiovasculares/epidemiología , Anciano Frágil , Factores de Riesgo , HospitalesRESUMEN
Rabies is a highly lethal infectious disease with no existing treatment available, thus investigating effective antiviral compounds to control rabies virus (RABV) infection is of utmost importance. Resveratrol is a natural phenolic compound that, as a phytoalexin, exhibits several biological activities, including antiviral activity. In this study, we evaluated the inhibitory effect of resveratrol on RABV infection and investigated its molecular antiviral mechanism. We found that resveratrol significantly inhibited RABV infection, including the phases of adsorption, replication, and release, and also directly inactivated RABV and inhibited its infectivity. However, resveratrol had no significant effect on RABV internalization. Resveratrol also reduced RABV-induced oxidative stress, specifically reactive oxygen species and malondialdehyde levels. Western blotting analysis revealed that resveratrol enhanced antioxidant signaling via the SIRT1/Nrf2/HO-1 pathway and inhibited viral replication. Viral infection was enhanced after SIRT1 knockdown, which inhibited the SIRT1/Nrf2/HO-1 antioxidant signaling pathway, suggesting that this pathway plays an important role in RABV replication. Overall, resveratrol prevented the adsorption, replication, and release of RABV and directly inactivated RABV, but failed to inhibit RABV internalization. Furthermore, resveratrol activated the SIRT1/Nrf2/HO-1 pathway to inhibit RABV replication and suppressed RABV-induced oxidative stress. These findings highlight the therapeutic potential of resveratrol for fighting RABV infections.
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Rabies is a lethal disease caused by the rabies virus (RABV), which causes acute neurological infections in mammals, including human beings. We previously reported that an mRNA vaccine (LVRNA001) encoding the rabies virus's glycoprotein induced strong protective immune responses to rabies in mice and dogs. Here, we further evaluate the safety of LVRNA001. First, we performed a confirmative efficacy study in dogs, which showed that LVRNA001 fully protected the animals from the virus, both pre- and post-infection. Moreover, using pre- and post-exposure prophylaxis murine models, we showed that LVRNA001, built from the CTN-1 strain, was able to protect against various representative RABV strains from the China I-VII clades. To evaluate the safety of the vaccine, chronic and reproductive toxicity studies were performed with cynomolgus macaques and rats, respectively. In a repeated-dose chronic toxicity study, vaccinated monkeys displayed no significant alterations in body weight, temperature, or hematological and biochemical markers. Lymphocyte subset measurement and histopathological examination showed that no toxicity was associated with the vaccine. The immunogenicity study in cynomolgus macaques demonstrated that LVRNA001 promoted the generation of neutralizing antibodies and Th1-biased immune response. Evaluation of reproductive toxicity in rats revealed that administration of LVRNA001 had no significant effects on fertility, maternal performance, reproductive processes, and postnatal outcomes. In conclusion, LVRNA001 can provide efficient protection against rabies virus infection in dogs and mice, and toxicity studies showed no significant vaccine-related adverse effects, suggesting that LVRNA001 is a promising and safe vaccine candidate for rabies prophylaxis and therapy.
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A replication-defective, recombinant Sindbis virus vector was utilized in a novel immunization strategy to induce humoral and cellular responses against hepatitis C virus (HCV). The recombinant vector, pVaXJ-E1E2, expressing the gene for HCV glycoproteins E2 and E1, was constructed by inserting the E1E2 gene into the replicon pVaXJ, a DNA vector derived from Sindbis-like virus XJ-160. The defective replicon particles, XJ-E1E2, were produced by transfecting BHK-21(E+Capsid) cells, the packaging cell lines for the vector from XJ-160 virus, with pVaXJ-E1E2. Both glycoproteins, E2 and E1, were stably expressed, as indicated by immunofluorescence assay (IFA) and Western blotting. Mice were vaccinated using a prime-boost strategy with XJ-E1E2 particles combined with Freund's incomplete adjuvant via intramuscular injection at 0 and 2 weeks. HCV-specific IgG antibody levels and cellular immune responses were evaluated by IFA and IFN-γ ELISPOT, respectively. The results showed that the defective XJ-E1E2 particles in combination with Freund's incomplete adjuvant induced effective humoral and cellular immune responses against HCV glycoprotein E1 or E2, suggesting that a defective Sindbis particle vaccine is capable of eliciting an effective immune response. These findings have important implications for the development of HCV vaccine candidates.
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Portadores de Fármacos , Vectores Genéticos , Hepacivirus/inmunología , Virus Sindbis/genética , Proteínas del Envoltorio Viral/inmunología , Vacunas Virales/inmunología , Animales , Femenino , Adyuvante de Freund/administración & dosificación , Hepacivirus/genética , Anticuerpos contra la Hepatitis C/sangre , Inmunidad Celular , Inmunoglobulina G/sangre , Inyecciones Intramusculares , Leucocitos Mononucleares/inmunología , Ratones , Ratones Endogámicos BALB C , Vacunación/métodos , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología , Proteínas del Envoltorio Viral/genética , Vacunas Virales/administración & dosificación , Vacunas Virales/genéticaRESUMEN
Rabies is a fatal zoonotic disease caused by the rabies virus. Despite existing vaccines, failures still persist. Complete protection relies on improving vaccination for delayed antibody response and weak cellular immunity. A more effective and secure vaccine is necessary for rabies prevention. For this purpose, we employed the use of PIKA adjuvant, a stabilized double-stranded RNA that interacts with TLR3, as an enhancer for the rabies immunization. Testing on mice infected with seven rabies strains prevalent in China showed over 80% protective efficacy without immunoglobulin. In contrast, the PIKA rabies vaccine exhibited a more significant enhancement in neutralizing antibody levels just 5 days post-vaccination, surpassing the immune response induced by licensed rabies vaccines. Furthermore, the administration of the PIKA rabies vaccine resulted in a significant augmentation in the population of T cells that produce IFN-γ in response to the antigen. Additionally, elevated levels of IL-1ß, IL-6, CCL-2, and TNF-α were observed at the injection site. Furthermore, an increase in the levels of chemotactic proteins and pro-inflammatory molecules in the serum was observed following administration of the PIKA rabies vaccine. Confirmation of the mechanism of action of PIKA was further established by testing it on TLR3-knockout mice, proving that its adjuvant function is dependent on the TLR3 pathway. Taken together, these results indicate that the PIKA vaccine for rabies shows potential as a highly efficacious approach, resulting in a significant enhancement of the efficacy of rabies vaccines.
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BACKGROUND: There are no local or international guidelines or consensus on the use of mAbs against the rabies virus. RESEARCH DESIGN AND METHODS: An expert group in the field of rabies prevention and control formulated the consensus presented in this paper. RESULTS: Class III exposed persons to rabies for the first time; Identify type II exposed persons with immune deficiency; those who are first exposed to Class II and re-exposed to Class III within 7 days. They can use ormutivimab injection after completing the PEP wound treatment. In the case of injection restrictions or a wound that is difficult to detect, it is recommended that the entire Ormutivimab dose be infiltrated close to the wound. For severe multi-wound bites, the recommended dosage of ormutivimab is 20 IU/kg. If the recommended dose cannot meet all of the wound infiltration requirements, appropriate dilution can be conducted at a dilution ratio of 3 ~ 5 times. If the requirements for infiltration cannot be met after dilution, it is recommended that the dosage be increased with caution (maximum dosage, 40 IU/kg). The use of Ormutivimab is safe and effective without any contraindications by all age groups. CONCLUSIONS: This consensus standardizes clinical use of Ormutivimab, improves post-exposure prophylaxis of rabies in China, reduces infection rate.
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To investigate the necessity and potential application of structural genes for expressing heterogenous genes from Sindbis virus-derived vector, the DNA-based expression vector pVaXJ was constructed by placing the recombinant genome of sindbis-like virus XJ-160 under the control of the human cytomegalovirus (CMV) promoter of the plasmid pVAX1, in which viral structural genes were replaced by a polylinker cassette to allow for insertion of heterologous genes. The defect helper plasmids pVaE or pVaC were developed by cloning the gene of glycoprotein E3E26KE1 or capsid protein of XJ-160 virus into pVAX1, respectively. The report gene cassette pVaXJ-EGFP or pV-Gluc expressing enhanced green fluorescence protein (EGFP) or Gaussia luciferase (G.luc) were constructed by cloning EGFP or G.luc gene into pVaXJ. EGFP or G.luc was expressed in the BHK-21 cells co-transfected with report gene cassettes and pVaE at levels that were comparable to those produced by report gene cassettes, pVaC and pVaE and were much higher than the levels produced by report gene cassette and pVaC, suggesting that glycoprotein is enough for Sindbis virus-derived DNA vector to express heterogenous genes in host cells. The method of gene expression from Sindbis virus-based DNA vector only co-transfected with envelop E gene increase the conveniency and the utility of alphavirus-based vector systems in general.
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Ingeniería Genética/métodos , Vectores Genéticos , Glicoproteínas/metabolismo , Virus Sindbis/crecimiento & desarrollo , Virus Sindbis/genética , Proteínas Virales/metabolismo , Genes Reporteros , Glicoproteínas/genética , Humanos , Regiones Promotoras Genéticas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Virales/genéticaRESUMEN
Heparan sulfate (HS) is ubiquitously expressed on the surfaces and in the extracellular matrix of virtually all cell types, making it an ideal receptor for viral infection. Compared with wild-type viruses, cell culture-adapted laboratory strains exhibit more efficient binding to cellular HS receptors. HS-binding viruses are typically cleared faster from the circulation and cause lower viremia than their non-HS-binding counterparts, suggesting that the HS-binding phenotype is a tissue culture adaptation that lowers virus fitness in vivo. However, when inoculated intracranially, efficient cell attachment through HS binding can contribute to viral neurovirulence. The primary aim of this review is to discuss the roles of HS binding in viral pathogenicity, including peripheral virulence and neurovirulence. Understanding how heparan sulfate functions during virus infection in vivo may prove critical for elucidating the molecular mechanism of viral pathogenesis, and may contribute to the development of therapeutics targeting HS.
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Heparitina Sulfato/fisiología , Virus/patogenicidad , Humanos , Receptores Virales/fisiología , VirulenciaRESUMEN
INTRODUCTION: The epidemiological characteristics of human rabies in China in 2016-2020 were analyzed in order to provide the scientific basis for the formulation of the prevention and control policy of rabies at next stage. METHODS: The data of China's National Notifiable Disease Reporting System (NNDRS) from 2016 to 2020 were collected and analyzed by using a descriptive epidemiology method. RESULTS: A total of 2,074 cases of human rabies were reported from 2016-2020 in China, there were year over year decreases in total number of cases. Human rabies appeared throughout the year, among which the highest in incidence happened from August to October, while March and December months were months in which the epidemic was weakest. CONCLUSION: Though decreases were observed for human rabies in China, further steps should be taken to maintain these results. Management should be strengthened and the immunity of dogs should be prioritized to control this situation from the source. In addition, all reported cases should be monitored and reported to achieve the accurate prevention and control.
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BACKGROUND: The mortality of humans due to rabies in China has been declining in recent years, but it is still a significant public health problem. According to the global framework, China strives to achieve the goal of eliminating human rabies before 2030. METHODS: We reviewed the epidemiology of human deaths from rabies in mainland China from 2004 to 2018. We identified high risk regions, age and occupational groups, and used a continuous deterministic susceptibility-exposure-infection-recovery (SEIR) model with periodic transmission rate to explore seasonal rabies prevalence in different human populations. The SEIR model was used to simulate the data of human deaths from rabies reported by the Chinese Center for Disease Control and Prevention (China CDC). We calculated the relative transmission intensity of rabies from canines to different human groups, and they provided a reliable epidemiological basis for further control and prevention of human rabies. RESULTS: Results showed that human deaths from rabies exhibited regional differences and seasonal characteristics in mainland China. The annual human death from rabies in different regions, age groups and occupational groups decreased steadily across time. Nevertheless, the decreasing rates and the calculated R0s of canines of various human groups were different. The transmission intensity of rabies from canines to human populations was the highest in the central regions of China, in people over 45 years old, and in farmers. CONCLUSIONS: Although the annual cases of human deaths from rabies have decreased steadily since 2007, the proportion of human deaths from rabies varies with region, age, gender, and occupation. Further enhancement of public awareness and immunization status in high-risk population groups and blocking the transmission routes of rabies from canines to humans are necessary. The concept of One Health should be abided and human, animal, and environmental health should be considered simultaneously to achieve the goal of eradicating human rabies before 2030.
Asunto(s)
Enfermedades de los Perros/virología , Rabia/transmisión , Rabia/veterinaria , Zoonosis Virales/transmisión , Adolescente , Adulto , Anciano , Animales , Niño , Preescolar , China/epidemiología , Simulación por Computador , Enfermedades de los Perros/epidemiología , Perros , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Teóricos , Prevalencia , Rabia/epidemiología , Rabia/virología , Factores de Riesgo , Zoonosis Virales/epidemiología , Zoonosis Virales/mortalidad , Zoonosis Virales/virología , Adulto JovenRESUMEN
Bats are well-recognized reservoirs of zoonotic viruses. Several spillover events from bats to humans have been reported, causing severe epidemic or endemic diseases including severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), SARS-CoV, Middle East respiratory syndrome-CoV (MERS-CoV), henipaviruses, and filoviruses. In this study, a novel rhabdovirus species, provisionally named Rhinolophus rhabdovirus DPuer (DPRV), was identified from the horseshoe bat (Rhinolophus affinis) in Yunnan province, China, using next-generation sequencing. DPRV shedding in the spleen, liver, lung, and intestinal contents of wild bats with high viral loads was detected by real-time quantitative PCR, indicating that DPRV has tropism for multiple host tissues. Furthermore, DPRV can replicate in vitro in multiple mammalian cell lines, including BHK-21, A549, and MA104 cells, with the highest efficiency in hamster kidney cell line BHK-21, suggesting infectivity of DPRV in these cell line-derived hosts. Ultrastructure analysis revealed a characteristic bullet-shaped morphology and tightly clustered distribution of DPRV particles in the intracellular space. DPRV replicated efficiently in suckling mouse brains and caused death of suckling mice; death rates increased with passaging of DPRV in suckling mice. Moreover, 421 serum samples were collected from individuals who lived near the bat collection site and had fever symptoms within 1 year. DPRV-specific antibodies were detected in 20 (4.75%) human serum samples by indirect immunofluorescence assay. Furthermore, 10 (2.38%) serum samples were DPRV positive according to plaque reduction neutralization assay, which revealed potential transmission of DPRV from bats to humans and highlighted the potential public health risk. Potential vector association with DPRV was not found with negative viral RNA in bloodsucking arthropods. IMPORTANCE We identified a novel rhabdovirus from the horseshoe bat (Rhinolophus thomasi) in China with probable infectivity in humans. DPRV was isolated in vitro from several mammalian cell lines, indicating wide host tropism, excluding bats, of DPRV. DPRV replicated in the brains of suckling mice, and the death rate of suckling mice increased with passaging of DPRV in vivo. Serological tests indicated the possible infectivity of DPRV in humans and the potential transmission to humans. The present findings provide preliminary evidence for the potential risk of DPRV to public health. Additional studies with active surveillance are needed to address interspecies transmission and determine the pathogenicity of DPRV in humans.