Oral immunization is an alternative or supplementary approach that can significantly improve dog vaccination coverage,especially for free-roaming dogs.Safe and effective oral rabies vaccines for dogs are still being s...Oral immunization is an alternative or supplementary approach that can significantly improve dog vaccination coverage,especially for free-roaming dogs.Safe and effective oral rabies vaccines for dogs are still being sought.In our previous studies,we generated a genetically modified rabies virus(RABV) ERA strain,rERAG_(333E),containing a mutation from arginine(Arg,R) to glutamic acid(Glu,E) at residue 333 of the G protein(G_(333E)).Our previous results demonstrated that rERAG_(333E) was safe for adult mice and dogs,and oral vaccination with rERAG_(333E) induced a strong and long-lasting protective immune response in dogs.Here,we further investigated the safety and immunogenicity of rERAG_(333E) in nontarget species,including suckling mice,rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.Suckling mice studies demonstrated that the G_(333E) mutation significantly reduced the virulence of the ERA strain.All of the suckling mice aged 10 days and above survived and showed no apparent signs of disease after intracerebral inoculation with rERAG_(333E).Animal studies demonstrated that rERAG_(333E) was safe in rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.None of those animals inoculated orally with 10 times the intended field dose of rERAG_(333E) showed abnormal clinical signs before and after the booster immunization with Rabvac 3,an inactivated rabies vaccine.Meanwhile,oral inoculation with rERAG_(333E) induced strong neutralizing antibody(NA) responses to RABV in rhesus monkeys,foxes,raccoon dogs,and piglets.These results demonstrated that rERAG_(333E) has the potential to serve as a safe oral rabies vaccine for dogs.展开更多
Rabies is a zoonotic disease with an estimated global mortality of 59,000 people annually and a burden of more than 3.7 million disability-adjusted life years(DALYs)that is caused by a neurotropic lyssavirus[1].Dogs a...Rabies is a zoonotic disease with an estimated global mortality of 59,000 people annually and a burden of more than 3.7 million disability-adjusted life years(DALYs)that is caused by a neurotropic lyssavirus[1].Dogs are the primary source of human rabies,as more than 95%of human cases can be traced to dogs[2,3].China faces a substantial burden of rabies,having endured three major human rabies epidemics,which occurred in the 1950s,1981,and 2007[4].Implementation of various prevention and control measures has decreased the number of human rabies cases from 3,300 in 2007 to 167 in 2024.In China.展开更多
Background: Rabies is endemic in India and every half an hour a person dies of this dreaded disease. Stray roaming dogs, mostly unvaccinated, are most dangerous host in spread of rabies in India and in our state of Hi...Background: Rabies is endemic in India and every half an hour a person dies of this dreaded disease. Stray roaming dogs, mostly unvaccinated, are most dangerous host in spread of rabies in India and in our state of Himachal Pradesh. Timely prophylaxis is the only method to save animal bite victims, including that of rabid dog bite patients. Objectives: Objective of this study was to investigate an impending outbreak of rabies in Shimla town in the absence of life saving rabies immunoglobulins (RIGs) in the market, and to know the source of infection by using one health approach and using epidemiological tools. Methods: On April 7, 2015, there was a sudden surge in cases of suspected rabid dog bites. Impending rabies outbreak was suspected as there were no RIGs available in the market. A rapid Response Team (RRT) consisting of the author, veterinary doctor, dog squad of Municipal Corporation (MC) Shimla along with the vehicles to impound rabid dogs was constituted to investigate the terror spread by two rabid dogs on biting spree in the Shimla Municipality. Results: A total of 18 people were bitten by suspected rabid dogs within three days period. A black bitch and a brown dog, on the identity of affected people, were captured by the dog squad of Municipality next day on April 8, 2015 and taken to Dog Sterilization Centre, Animal Birth Control (ABC) programme, MC Shimla for observation. The most furious Black bitch died of clinically confirmed symptoms of furious rabies after three days. The second rabid dog, brown in color, died after a month of observation due to paralytic dumb rabies. The brain of the brown dog was extracted for Fluorescent Antibody Testing (FAT) at central research Institute (CRI) Kasauli and was found to be positive for FAT. Follow up of patients was 100% by house to house visit and over telephone and no casualty was reported. Conclusion: While we were working on hypothesis of rabid dogs getting the infection from nearby forest about 8 - 10 KM away but on follow up of the patients, they reported that both the dog and bitch used to stay in the compound of their colony since the bitch was pregnant and there was no history of the bitch moving for away to forests neither any outside dog which was seen near them in the compound. This led us to think of other causes of what must had happened to the bitch that caused her to be rabid as for the past 9 years we had observed bitches becoming rabid after litter birth (Whelping) and making their pups rabid due to licking. Since the carrier state for rabies virus in bitches/dogs is known and a state of immunosuppression after whelping/parturition is also known, therefore there is a possibility of latent rabies virus getting activated due to immunosuppression after litter birth and it is thought to be as one of the probable causes of black bitch getting rabid and inflicting the infection to accompanying brown dog. We need to do further studies to ascertain this phenomenon before coming to a definite conclusion and suspect such a possibility in case a dam suddenly becomes rabid among a pack of stray dogs in rabies endemic countries like ours.展开更多
Background:This study investigated the relationship between meteorological factors and daily outpatient visits to rabies post-exposure prophylaxis clinics to inform animal injury prevention strategies.Methods:Daily ou...Background:This study investigated the relationship between meteorological factors and daily outpatient visits to rabies post-exposure prophylaxis clinics to inform animal injury prevention strategies.Methods:Daily outpatient visit data from rabies post-exposure prophylaxis clinics in Jinan and corresponding meteorological data were collected from January 1,2020,to December 31,2022.A generalized additive model was used to quantitatively assess the relationship between these factors.A total of 202,010 patients visited these clinics during this period.Results:Daily mean,maximum,and minimum temperatures,and relative humidity were positively associated with outpatient visits.A 1°C increase in mean,maximum,and minimum temperatures corresponded to increases in daily visits of 1.65%(95%Confidence Interval(CI):1.55–1.76),1.59%(95%CI:1.50–1.69),and 1.27%(95%CI:1.17–1.36)respectively.Each 1%increase in relative humidity was associated with a 0.18%(95%CI:0.15–0.20)increase in visits.Mean pressure was negatively associated with outpatient visits,the outpatient visits decreased by 0.91%(95%CI:−1.71 to−0.11)for every 1 kPa increased in mean pressure.Conclusion:The change of meteorological factors will lead to the increase of outpatient visits in rabies exposure treatment clinic.展开更多
Minks are highly susceptible to SARS-CoV-2,and have transmitted SARS-CoV-2 to humans.Oral immunization is one of the most promising strategies to prevent SARS-CoV-2 infection and transmission in minks.Here,we generate...Minks are highly susceptible to SARS-CoV-2,and have transmitted SARS-CoV-2 to humans.Oral immunization is one of the most promising strategies to prevent SARS-CoV-2 infection and transmission in minks.Here,we generated 3 recombinant rabies viruses(RABV),rERAG_(333E)/S6P,rERAG_(333E)/DS6P and rERAG_(333E)/BA2S6P,expressing the prefusion-stabilized SARS-CoV-2 spike protein of wild-type(S6P),δ(DS6P)or BA.2(BA2S6P)strain based on an oral rabies vaccine candidate(rERAG_(333E)).Oral or inactivated immunization of the 3 RABVs monovalent or trivalent were safe,and induced robust RABV neutralizing antibody and cross-antibody responses against the three SARS-CoV-2 in mice and minks.The challenge tests showed that 2 doses of rERAG_(333E)-S6P as an oral or inactivated vaccine completely protected mice against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts,and largely prevented viral replication and lung damage caused by wild-type SARS-CoV-2infection in minks.Notably,we also confirmed that 2 doses of rERAG_(333E)-S6P as an oral or inactivated vaccine can largely protect minks against wild-type SARS-CoV-2 transmission via respiratory droplets.Our findings suggest that rERAG_(333E)-based COVID-19 vaccines appear to be suitable oral candidates to protect minks from SARS-CoV-2infection and transmission,and may serve as inactivated vaccines for further investigation in humans.展开更多
BACKGROUND Rabies is a zoonotic viral disease affecting the central nervous system,caused by the rabies virus,with a case-fatality rate of 100%once symptoms appear.AIM To analyze high-risk factors associated with ment...BACKGROUND Rabies is a zoonotic viral disease affecting the central nervous system,caused by the rabies virus,with a case-fatality rate of 100%once symptoms appear.AIM To analyze high-risk factors associated with mental disorders induced by rabies vaccination and to construct a risk prediction model to inform strategies for improving patients’mental health.METHODS Patients who received rabies vaccinations at the Department of Infusion Yiwu Central Hospital between August 2024 and July 2025 were included,totaling 384 cases.Data were collected from medical records and included demographic characteristics(age,gender,occupation),lifestyle habits,and details regarding vaccine type,dosage,and injection site.The incidence of psychiatric disorders following vaccination was assessed using standardized anxiety and depression rating scales.Patients were categorized into two groups based on the presence or absence of anxiety and depression symptoms:The psychiatric disorder group and the non-psychiatric disorder group.Differences between the two groups were compared,and high-risk factors were identified using multivariate logistic regression analysis.A predictive model was then developed based on these factors to evaluate its predictive performance.RESULTS Among the 384 patients who received rabies vaccinations,36 cases(9.38%)were diagnosed with anxiety,52 cases(13.54%)with depression,and 88 cases(22.92%)with either condition.Logistic regression analysis identified the following signi ficant risk factors for psychiatric disorders:Education level of primary school or below,exposure site at the head and neck,exposure classified as grade III,family status of divorced/widowed/unmarried/living alone,number of wounds greater than one,and low awareness of rabies prevention and control(P<0.05).The risk prediction model demonstrated good performance,with an area under the receiver operating characteristic curve of 0.859,a specificity of 74.42%,and a sensitivity of 93.02%.CONCLUSION In real-world settings,psychiatric disorders following rabies vaccination are relatively common and are associated with factors such as lower education level,higher exposure severity,vulnerable family status,and limited awareness of rabies prevention and control.The developed risk prediction model may aid in early identification of high-risk individuals and support timely clinical intervention.展开更多
Objective Preliminary assessment of rabies virus neutralizing activity,safety and immunogenicity of a recombinant human rabies antibody(NM57)compared with human rabies immunoglobulin(HRIG)in Chinese healthy adults.Met...Objective Preliminary assessment of rabies virus neutralizing activity,safety and immunogenicity of a recombinant human rabies antibody(NM57)compared with human rabies immunoglobulin(HRIG)in Chinese healthy adults.Methods Subjects were randomly(1:1:1)allocated to Groups A(20 IU/kg NM57),B(40 IU/kg NM57),or C(20 IU/kg HRIG).One injection was given on the day of enrollment.Blood samples were collected on days-7 to 0(pre-injection),3,7,14,28,and 42.Adverse events(AEs)and serious AEs(SAEs)were recorded over a period of 42 days after injection.Results All 60 subjects developed detectable rabies virus neutralizing antibodies(RVNAs)(>0.05 IU/mL)on days 3,7,14,28,and 42.The RVNA levels peaked on day 3 in all three groups,with a geometric mean concentration(GMC)of 0.2139 IU/mL in Group A,0.3660 IU/mL in Group B,and0.1994 IU/mL in Group C.At each follow-up point,the GMC in Group B was significantly higher than that in Groups A and C.The areas under the antibody concentration curve over 0-14 days and 0-42 days in Group B were significantly larger than those in Groups A and C.Fifteen AEs were reported.Except for one grade 2 myalgia in Group C,the other 14 were all grade 1.No SAEs were observed.Conclusion The rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG,and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar.Safety was comparable between NM57 and HRIG.展开更多
Abstract The number of human rabies cases acquired from dog bites constitutes a high proportion of the total rabies cases in China, although the number of human rabies cases has gradually decreased in recent years. Th...Abstract The number of human rabies cases acquired from dog bites constitutes a high proportion of the total rabies cases in China, although the number of human rabies cases has gradually decreased in recent years. The pivotal role of dogs in the spread of rabies indicates that controlling and preventing canine rabies could be a key step in eradicating human rabies in China. The primary aims of this review are to discuss the properties and pathogenesis of the rabies virus, the clinical signs and diagnosis of canine rabies, threshold host density and vaccination of dogs, and the prevention and control of canine rabies in China.展开更多
Background:Rabies is a zoonosis transmitted via the bites of various mammals,primarily dogs and bats.Known since antiquity,this disease may have the deadliest human fatality rates and is responsible for approximately ...Background:Rabies is a zoonosis transmitted via the bites of various mammals,primarily dogs and bats.Known since antiquity,this disease may have the deadliest human fatality rates and is responsible for approximately 65,000 deaths worldwide per year.Case presentation:We report the case details of a 13-year-old boy from India belonging to a South Asian ethnicity,who presented with altered sensorium one month following a dog bite.He did not receive the active rabies immunization and was managed with supportive therapy.The patient had extensive T_2 weighted(T_2W)/fluid attenuation and inversion recovery(FLAIR) hyper intensities involving the deep gray matter of the cerebral hemispheres,hippocampus,brainstem,and cerebellum.The diagnosis was confirmed by the demonstration of the rabies antigen from a nuchal skin biopsy and a corneal smear.The patient had a slow but significant recovery over four months and was discharged from the hospital in stable condition with severe neurological sequelae.Conclusion:We report a unique case of survival after infection with a universally fatal disease.展开更多
Background: Rabies is a zoonotic disease and many vulnerable sections like rag pickers and municipality workers neglect animal bites due to ignorance of their potential deadly outcomes. Stray dogs abound in garbage pi...Background: Rabies is a zoonotic disease and many vulnerable sections like rag pickers and municipality workers neglect animal bites due to ignorance of their potential deadly outcomes. Stray dogs abound in garbage pits and this population is exposed to their attacks. It should be a mandate for municipalities to help protect their sanitary workforce, especially rag pickers, from deadly infectious diseases such as Rabies, Hepatitis-B, HIV, Tetanus etc. Objectives: Objective of this study was to study methods to provide pre-exposure Rabies vaccination for such highly exposed populations by engaging them and understanding their perception of this disease through a constant dialogue with them. Methods: We started by engaging with the rag pickers to know how best to entice them to get themselves immunized. We then attempted to search literature for the most practical methods likely to succeed in reducing risk of rabies deaths in this population. Results: WHO approved 3 injections of 0.1 ml tissue culture vaccine on days 0, 7 and 21 were tried but were shown to result in many dropouts among rag pickers for repeat injections. We then followed a method where 0.1 ml of rabies vaccine was injected at 4 different anatomical sited in one setting. This proved acceptable and relatively inexpensive. A small number of subjects were studied by determination of neutralizing antibody by RFFIT, which proved immunogenic having anamnestic response on boosters given single IM or at 4 sites ID subsequently, implying that short schedule rabies pre-exposure vaccination can be done in high risk groups and may save lives if applied to the poorest that are highly exposed.展开更多
Rabies is an acute encephalitis caused by a lyssavirus. It is primarily transmitted through bites of infected dogs which results in the worldwide death of an estimated 59000 humans every year. The disease is preventab...Rabies is an acute encephalitis caused by a lyssavirus. It is primarily transmitted through bites of infected dogs which results in the worldwide death of an estimated 59000 humans every year. The disease is preventable through the application of post-exposure prophylaxis (PEP) and its elimination has been demonstrated in many countries by applying multiple interventions simultaneously. Nonetheless, rabies is still widespread in many developing countries, primarily due to the poor implementation of intervention strategies that include inadequate dog-bite wound management practices, unavailability/unaffordability of PEP by the communities, failure to control the disease in free-roaming dogs and wildlife, improper dog population management, weak surveillance and diagnostic facilities and a lack of a One Health approach to the disease. In this review, strategies to control dog-mediated rabies through a One Health approach were discussed. We recommend applying multiple interventions against the disease by involving all the concerned stakeholders in selected urban and rural areas of the countries where rabies is endemic. An empirical demonstration of disease freedom in the selected areas through a One Health approach is needed to convince policymakers to invest in rabies prevention and control on the national level. This multifaceted One Health control model will enhance the likelihood of achieving the goal of global rabies eradication by 2030.展开更多
Rationale:Rabies is a zoonotic disease with a high mortality,primarily transmitted through the bite of infected mammals,particularly dogs and cats.Despite being a well-known disease since ancient times,it continues to...Rationale:Rabies is a zoonotic disease with a high mortality,primarily transmitted through the bite of infected mammals,particularly dogs and cats.Despite being a well-known disease since ancient times,it continues to cause a significant number of human deaths worldwide,with approximately 65000 fatalities reported annually.Patient concerns:We present two fatal cases of rabies in a 12-year-old immigrant boy and a 7-year-old boy.The first case was subject to a 24-hour delay in receiving appropriate medical attention and rabies preventive measures due to the lack of awareness among emergency hospital staff,leading to the administration of wound dressing only.The second case received timely rabies immunoglobulin administration;however,there was a 4-day delay in administering the fourth dose of the rabies vaccine,despite presenting evident symptoms of rabies.Diagnosis:Postmortem examination of brain samples from both patients confirmed the presence of rabies virus.Interventions:Post-exposure prophylaxis for rabies.Outcomes:Both patients were admitted to the hospital after the manifestation of rabies-related symptoms,with the 12-year-old child seeking medical care 47 days after the animal bite and the 7-year-old child seeking medical care 58 days after the exposure.Finally,the first patient died after 27 days and the second patient died after 40 days of hospitalization.Lessons:There is an urgent need for heightened awareness and education among both healthcare professionals and the public regarding the urgency of seeking immediate medical attention after potential rabies exposure.Timely recognition and initiation of post-exposure prophylaxis are pivotal in preventing the progression of the disease.Strengthening surveillance and reporting systems,coupled with continuous training for healthcare professionals,can contribute to early detection and management of rabies cases.展开更多
Background: In India every year an estimated 20,000 patients die of Rabies. Major reason for poor compliance to anti-rabies prophylaxis is the high cost of anti-rabies vaccine being prescribed intramuscularly (IM) as ...Background: In India every year an estimated 20,000 patients die of Rabies. Major reason for poor compliance to anti-rabies prophylaxis is the high cost of anti-rabies vaccine being prescribed intramuscularly (IM) as a routine i.e. 44.5 USD per course of five injections. In 1992 WHO recommended low cost intra-dermal rabies vaccination (IDRV), which costs only 7.5 USD or less per animal bite course. Methods: Interviews with doctors revealed that they were not prescribing intra-dermal anti rabies vaccination as they were either not aware or were not confident of this route of rabies vaccination. Also the vaccine vial did not have the label for “intra-dermal use”. These barriers were removed by advocacy efforts with policy makers & drug companies, credit sharing & team building, which led to starting of first intra dermal anti-rabies clinic of North India on 2nd August 2008. Results: Within a month of start of intra-dermal rabies vaccination clinic, i.e. by 2nd September, 2008, there was an increase in the hospital patient load by 2.8 times, and poor patients load by 3.2 times. In just less than two-year time, 200,000 USD of poor patients were saved and 5769 patients vaccinated. Each patient was asked to bring one vial on first visit & rest of doses were given “free” by pooling strategy. Pooling strategy involved distribution of one vial of vaccine among four persons and keep the three vials for use one by one by all the four patients on subsequent three visits. Another offshoot of the strategy was to prevent wasting of even few drops of vaccine that used to remain in each vial of 1 ml after distribution among four patients (0.2 mL or less). Out of more than 5000 vials utilised, every time we would transfer the left out drops of vaccine to the next new vial and use it immediately on a new pool of patients waiting for vaccination. We would, however, discard the unused vaccine after eight hours of reconstitution at the end of the day. The vaccine so saved turned to be a stock of more than 100 vials in less than two years that we were able to give free to more than 225 rag pickers, garbage collectors and newspaper hawkers on World Rabies Day, Sep 28, 2010. Conclusions: With intra-dermal clinic, we were able to successfully introduce the new cost effective intra-dermal method of rabies vaccination despite all odds & vested interests of companies & old mindset of doctors that had blocked this technique till now. This will go a long way in reducing the burden of disease & death due to rabies from India.展开更多
In recent years (2007 to 2011), although the overall number of rabies cases in China has decreased, there is evidence of emerging or re-emerging cases in regions without previous rabies cases or with low incidence of ...In recent years (2007 to 2011), although the overall number of rabies cases in China has decreased, there is evidence of emerging or re-emerging cases in regions without previous rabies cases or with low incidence of rabies. To investigate the origin and the factors affecting the spread of rabies in China, specimens were collected from 2007 to 2011 from provinces with emerging and re-emerging cases and tested for the presence of the rabies virus. Positive specimens were combined with sequences from GenBank to perform comparisons of homology and functional sites, and to carry out phylogenetic analyses. Out of these regions, five provinces had 9 positive specimens from canine and cattle, and 34 canine or human specimens were obtained from previously high-incidence provinces. Complete sequences of G gene were obtained for these samples. Homology of the sequences of these 43 specimens was 87%-100% at the nucleotide level and 93.7% -100% at the amino acid level. These G gene sequences were combined with reference sequence from GenBank and used to construct a phylogenetic tree. The results showed that 43 specimens were all assigned to China clade I and clade II, with all specimens from emerging and re-emerging areas placed within clade I. Specimens isolated from Shanxi and Inner Mongolia in 2011 were distinct from previously-isolated local strains and had closer homology to strains from Hebei, Beijing and Tianjin whereas new isolates from Shanghai were tightly clustered with strains isolated in the 1990s. Finally, Shaanxi isolates were clustered with strains from adjacent Sichuan. Our results suggest that the rabies cases in emerging and re-emerging areas in China in the last 5 years are a consequence of the epidemic spreading from of neighboring provinces and regions experiencing a serious epidemic of rabies.展开更多
To analyze features of the rabies epidemic in China between 2007 and 2011, identify factors influencing the epidemic and to provide a scientific basis for further control and prevention of rabies, Descriptive epidemio...To analyze features of the rabies epidemic in China between 2007 and 2011, identify factors influencing the epidemic and to provide a scientific basis for further control and prevention of rabies, Descriptive epidemiological methods and statistical analysis was used on data collected from the National Disease Reporting Information System between 2007 to 2011 and the National Active Surveillance System between 2007 and 2010. Our analysis shows that while the number of human rabies cases decreased year by year, the number of districts reporting cases did not show significant change. The situations in Guangdong, Guangxi, Guizhou and Hunan provinces clearly improved over the period but they remain provinces with high-incidence, and consequently influence the epidemic situation of surrounding provinces and possibly the whole country. Summer and autumn were high-incidence seasons. Farmers, students and pre-school children represent the high-risk populations, and rates of cases in farmers increased, those for students decreased, and pre-school children remained unchanged. Provinces with active surveillance programs reported a total of 2346 individual cases, of which 88.53% were associated with canines. Postexposure prophylaxis （PEP） of rabies cases was not significantly improved, whereas PEP in post-exposure population was good. In rural regions of China, canine density was reduced somewhat, and the immunization rate increased slightly. Finally we show that while the epidemic decreased 2007 to 2011 in China, cases continued to be diffused in certain regions. Lack of standardization of PEP on rabies eases was the main reason of morbidity. The high density and low immunization of dog in rural areas and the defective situation of PEP are still continuous occurrences in China and remain a cause for concern.展开更多
The World Health Organization (WHO) standard assay for determining levels of the rabies virus neutralization antibody (RVNA) is the rapid fluorescent focus inhibition test (RFFIT), which is used to evaluate the immuni...The World Health Organization (WHO) standard assay for determining levels of the rabies virus neutralization antibody (RVNA) is the rapid fluorescent focus inhibition test (RFFIT), which is used to evaluate the immunity effect after vaccination against rabies. For RFFIT, CVS-11 was used as the challenge virus, BSR cells as the adapted cells, and WHO rabies immunoglobulin (WHO STD) as the reference serum in this study. With reference to WHO and Pasteur RFFIT procedures, a micro-RFFIT procedure adapted to our laboratory was produced, and its specificity and reproducibility were tested. We tested levels of RVNA in human serum samples after immunization with different human rabies vaccines (domestic purified Vero cell rabies vaccine (PVRV) and imported purified chick embryo cell vaccine (PCECV)) using different regimens (Zagreb regimen and Essen regimen). We analyzed the levels of RVNA, and compared the immune efficacy of domestic PVRV and imported PCECV using different immunization regimens. The results showed that the immune efficacy of domestic PVRV using the Zagreb regimen was as good as that of the imported PCECV, but virus antibodies were generated more rapidly with the Zagreb regimen than with the Essen regimen. The RFFIT procedure established in our laboratory will enhance the comprehensive detection ability of institutions involved in rabies surveillance in China.展开更多
The epidemic of rabies has rapidly increased and expanded in Yunnan province in recent years. In order to further analyze and understand the etiological reasons for the rapid expansion of rabies in Yunnan, a strain of...The epidemic of rabies has rapidly increased and expanded in Yunnan province in recent years. In order to further analyze and understand the etiological reasons for the rapid expansion of rabies in Yunnan, a strain of rabies virus CYN1009D in Yunnan was isolated, and the complete genomic sequencing was carried out, and the bioimfomative analysis on genes/encoded proteins and phylogeny with reference to sequences in GenBank was performed. The complete genome of CYN1009D was 11923 nt in length and belonged to genotype I. The genes encoding different structural proteins were all conserved in their lengths, in comparison to other strains in China. The amino acid sequence was conserved at different antigen sites of NP, but the variation was detected at the secondary phosphorylation site of position 375; variations were also detected in the phosphorylation sites at positions 63-63 and 162 of PP; the sites playing important roles in virus synthesis, budding and viral morphology in MP were conserved; two glycosylation sites were detected at Asn37 and Ash319 in GP, the neutralizing antigen sites in GP were conserved; the initial amino acid of LP （ML） was different from that of most of the strains in China （MM）; the variations in G-L region in the intergenic region were significant. The phylogenic tree showed that CYN1009D has a closer genetic relationship to the strains in Southeast Asia, indicating that prevention and control on rabies in borderland areas should be reinforced meanwhile efforts are made to control rabies in China.展开更多
A simple method was established for the determination of β-propiolactone(BPL) in human inactivated rabies vaccine by gas chromatography-mass spectrometry(GC-MS). The determination was performed on an Agilent HP-INNOW...A simple method was established for the determination of β-propiolactone(BPL) in human inactivated rabies vaccine by gas chromatography-mass spectrometry(GC-MS). The determination was performed on an Agilent HP-INNOWAX(30 m ? 0.32 mm i.d., 0.25 mm) capillary column at the temperature of 80 °C.Electrospray ionization(ESI) was used by selective ion detection at m/z 42. The temperature for ESI source and inlet was set at 230 °C and 200 °C, respectively. Helium was used as the carrier gas at a flow rate of 25.1 m L/min. The total run time was 8 min. Acetonitrile and other components in the sample did not interfere with the determination of BPL. The results showed good linearity of BPL in the range of0.50–10.01 μg/mL, with the limit of detection and the limit of quantification of 0.015 μg/mL and0.050 μg/mL, respectively. Satisfactory precision was achieved for the current developed method. The method was applied to detect 6 batches of vaccine samples, and the results indicated that the target analyte BPL was present in three batches of unpurified samples, but was not detected in the purified samples, indicating the test samples were qualified. The established method was proved to be simple,versatile and sensitive, which can meet the requirements of quality control of BPL in human inactivated rabies vaccine.展开更多
Exosomes are cell-derived vesicles that are secreted by many eukaryotic cells. It has recently attracted attention as vehicles of intercellular communication. Virus-infected cells release exosomes, which contain viral...Exosomes are cell-derived vesicles that are secreted by many eukaryotic cells. It has recently attracted attention as vehicles of intercellular communication. Virus-infected cells release exosomes, which contain viral proteins, RNA, and pathogenic molecules. However, the role of exosomes in virus infection process remains unclear and needs to be further investigated.In this study, we aimed to evaluate the effects of exosomes on rabies virus infection. OptiPrep^(TM) density gradient centrifugation was used to isolate exosomes from rabies virus-infected cell culture supernatants. A rabies virus G protein enzyme-linked immunosorbent assay and acetylcholinesterase activity assays were performed to verify the centrifugation fractions. Exosomes were then characterized using transmission electron microscopy and Western blotting. Our results showed that rabies virus infection increased the release of exosomes. Treatment with GW4869 and si-Rab27 a, two exosomal secretion inhibitors, inhibited exosome release. Furthermore, the inhibitors reduced the levels of extracellular and intracellular viral RNA. These data indicated that exosomes may participate in the viral infection process. Moreover, our results establish a basis for future research into the roles of exosomes in rabies virus infection and as potential targets for developing new antiviral strategies.展开更多
Rabies remains a public health threat that kills approximately 59,000 people worldwide each year,most of which are from the developing countries of Africa and Asia where dog rabies are endemic.Therefore, developing an...Rabies remains a public health threat that kills approximately 59,000 people worldwide each year,most of which are from the developing countries of Africa and Asia where dog rabies are endemic.Therefore, developing an affordable and efficacious vaccine is crucial for rabies control in these countries. Interleukin(IL)-15, an immunoregulatory cytokine, is a pluripotent molecule with therapeutic potential, which targets many cell types and links the innate and adaptive immune system. In this study, IL-15 gene was cloned and inserted into the genome of a recombinant rabies virus(RABV) strain LBNSE(designated as LBNSE-IL15), and the effect of over-expression of IL-15 on the immunogenicity of RABV was investigated. It was found that mice vaccinated with LBNSEIL15 could induce significantly higher level of virus-neutralizing antibody(VNA) than those immunized with LBNSE, resulting in the higher protection after challenge. Further investigation was performed to find out the possible role of IL-15 plays in the process of antibody induction, and it was found that LBNSE-IL15 could enhance the maturation of dendritic cells(DCs) in immunized mice. Furthermore, the mice immunized with LBNSE-IL15 could promote the T_(FH) cells differentiation and the generation of germinal center B cells and plasma cells. Together, these data indicated that IL-15 could be a potential adjuvant in enhancing the immunogenicity of RABV, contributing to the development of more-efficacious rabies vaccines.展开更多
基金supported by the Natural Science Foundation of Heilongjiang Province,China (YQ2022C040)。
文摘Oral immunization is an alternative or supplementary approach that can significantly improve dog vaccination coverage,especially for free-roaming dogs.Safe and effective oral rabies vaccines for dogs are still being sought.In our previous studies,we generated a genetically modified rabies virus(RABV) ERA strain,rERAG_(333E),containing a mutation from arginine(Arg,R) to glutamic acid(Glu,E) at residue 333 of the G protein(G_(333E)).Our previous results demonstrated that rERAG_(333E) was safe for adult mice and dogs,and oral vaccination with rERAG_(333E) induced a strong and long-lasting protective immune response in dogs.Here,we further investigated the safety and immunogenicity of rERAG_(333E) in nontarget species,including suckling mice,rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.Suckling mice studies demonstrated that the G_(333E) mutation significantly reduced the virulence of the ERA strain.All of the suckling mice aged 10 days and above survived and showed no apparent signs of disease after intracerebral inoculation with rERAG_(333E).Animal studies demonstrated that rERAG_(333E) was safe in rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.None of those animals inoculated orally with 10 times the intended field dose of rERAG_(333E) showed abnormal clinical signs before and after the booster immunization with Rabvac 3,an inactivated rabies vaccine.Meanwhile,oral inoculation with rERAG_(333E) induced strong neutralizing antibody(NA) responses to RABV in rhesus monkeys,foxes,raccoon dogs,and piglets.These results demonstrated that rERAG_(333E) has the potential to serve as a safe oral rabies vaccine for dogs.
文摘Rabies is a zoonotic disease with an estimated global mortality of 59,000 people annually and a burden of more than 3.7 million disability-adjusted life years(DALYs)that is caused by a neurotropic lyssavirus[1].Dogs are the primary source of human rabies,as more than 95%of human cases can be traced to dogs[2,3].China faces a substantial burden of rabies,having endured three major human rabies epidemics,which occurred in the 1950s,1981,and 2007[4].Implementation of various prevention and control measures has decreased the number of human rabies cases from 3,300 in 2007 to 167 in 2024.In China.
文摘Background: Rabies is endemic in India and every half an hour a person dies of this dreaded disease. Stray roaming dogs, mostly unvaccinated, are most dangerous host in spread of rabies in India and in our state of Himachal Pradesh. Timely prophylaxis is the only method to save animal bite victims, including that of rabid dog bite patients. Objectives: Objective of this study was to investigate an impending outbreak of rabies in Shimla town in the absence of life saving rabies immunoglobulins (RIGs) in the market, and to know the source of infection by using one health approach and using epidemiological tools. Methods: On April 7, 2015, there was a sudden surge in cases of suspected rabid dog bites. Impending rabies outbreak was suspected as there were no RIGs available in the market. A rapid Response Team (RRT) consisting of the author, veterinary doctor, dog squad of Municipal Corporation (MC) Shimla along with the vehicles to impound rabid dogs was constituted to investigate the terror spread by two rabid dogs on biting spree in the Shimla Municipality. Results: A total of 18 people were bitten by suspected rabid dogs within three days period. A black bitch and a brown dog, on the identity of affected people, were captured by the dog squad of Municipality next day on April 8, 2015 and taken to Dog Sterilization Centre, Animal Birth Control (ABC) programme, MC Shimla for observation. The most furious Black bitch died of clinically confirmed symptoms of furious rabies after three days. The second rabid dog, brown in color, died after a month of observation due to paralytic dumb rabies. The brain of the brown dog was extracted for Fluorescent Antibody Testing (FAT) at central research Institute (CRI) Kasauli and was found to be positive for FAT. Follow up of patients was 100% by house to house visit and over telephone and no casualty was reported. Conclusion: While we were working on hypothesis of rabid dogs getting the infection from nearby forest about 8 - 10 KM away but on follow up of the patients, they reported that both the dog and bitch used to stay in the compound of their colony since the bitch was pregnant and there was no history of the bitch moving for away to forests neither any outside dog which was seen near them in the compound. This led us to think of other causes of what must had happened to the bitch that caused her to be rabid as for the past 9 years we had observed bitches becoming rabid after litter birth (Whelping) and making their pups rabid due to licking. Since the carrier state for rabies virus in bitches/dogs is known and a state of immunosuppression after whelping/parturition is also known, therefore there is a possibility of latent rabies virus getting activated due to immunosuppression after litter birth and it is thought to be as one of the probable causes of black bitch getting rabid and inflicting the infection to accompanying brown dog. We need to do further studies to ascertain this phenomenon before coming to a definite conclusion and suspect such a possibility in case a dam suddenly becomes rabid among a pack of stray dogs in rabies endemic countries like ours.
基金supported by Chinese Association of Preventive Medicine-Vaccine and Immunization Youth Talent Support Project(CPMAQT-YM0314)Shandong medical and health science and technology development plan project(202012050267)Shandong Center for Disease Control and Prevention-Youth Innovation Fund Project(QC-202301).
文摘Background:This study investigated the relationship between meteorological factors and daily outpatient visits to rabies post-exposure prophylaxis clinics to inform animal injury prevention strategies.Methods:Daily outpatient visit data from rabies post-exposure prophylaxis clinics in Jinan and corresponding meteorological data were collected from January 1,2020,to December 31,2022.A generalized additive model was used to quantitatively assess the relationship between these factors.A total of 202,010 patients visited these clinics during this period.Results:Daily mean,maximum,and minimum temperatures,and relative humidity were positively associated with outpatient visits.A 1°C increase in mean,maximum,and minimum temperatures corresponded to increases in daily visits of 1.65%(95%Confidence Interval(CI):1.55–1.76),1.59%(95%CI:1.50–1.69),and 1.27%(95%CI:1.17–1.36)respectively.Each 1%increase in relative humidity was associated with a 0.18%(95%CI:0.15–0.20)increase in visits.Mean pressure was negatively associated with outpatient visits,the outpatient visits decreased by 0.91%(95%CI:−1.71 to−0.11)for every 1 kPa increased in mean pressure.Conclusion:The change of meteorological factors will lead to the increase of outpatient visits in rabies exposure treatment clinic.
基金supported by the National Key Research and Development Program of China(2021YFC2301700)the Natural Science Foundation of Heilongjiang Province,China(YQ2022C040)。
文摘Minks are highly susceptible to SARS-CoV-2,and have transmitted SARS-CoV-2 to humans.Oral immunization is one of the most promising strategies to prevent SARS-CoV-2 infection and transmission in minks.Here,we generated 3 recombinant rabies viruses(RABV),rERAG_(333E)/S6P,rERAG_(333E)/DS6P and rERAG_(333E)/BA2S6P,expressing the prefusion-stabilized SARS-CoV-2 spike protein of wild-type(S6P),δ(DS6P)or BA.2(BA2S6P)strain based on an oral rabies vaccine candidate(rERAG_(333E)).Oral or inactivated immunization of the 3 RABVs monovalent or trivalent were safe,and induced robust RABV neutralizing antibody and cross-antibody responses against the three SARS-CoV-2 in mice and minks.The challenge tests showed that 2 doses of rERAG_(333E)-S6P as an oral or inactivated vaccine completely protected mice against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts,and largely prevented viral replication and lung damage caused by wild-type SARS-CoV-2infection in minks.Notably,we also confirmed that 2 doses of rERAG_(333E)-S6P as an oral or inactivated vaccine can largely protect minks against wild-type SARS-CoV-2 transmission via respiratory droplets.Our findings suggest that rERAG_(333E)-based COVID-19 vaccines appear to be suitable oral candidates to protect minks from SARS-CoV-2infection and transmission,and may serve as inactivated vaccines for further investigation in humans.
基金Supported by the 2024 Yiwu City Research Plan Project,No.24-3-102.
文摘BACKGROUND Rabies is a zoonotic viral disease affecting the central nervous system,caused by the rabies virus,with a case-fatality rate of 100%once symptoms appear.AIM To analyze high-risk factors associated with mental disorders induced by rabies vaccination and to construct a risk prediction model to inform strategies for improving patients’mental health.METHODS Patients who received rabies vaccinations at the Department of Infusion Yiwu Central Hospital between August 2024 and July 2025 were included,totaling 384 cases.Data were collected from medical records and included demographic characteristics(age,gender,occupation),lifestyle habits,and details regarding vaccine type,dosage,and injection site.The incidence of psychiatric disorders following vaccination was assessed using standardized anxiety and depression rating scales.Patients were categorized into two groups based on the presence or absence of anxiety and depression symptoms:The psychiatric disorder group and the non-psychiatric disorder group.Differences between the two groups were compared,and high-risk factors were identified using multivariate logistic regression analysis.A predictive model was then developed based on these factors to evaluate its predictive performance.RESULTS Among the 384 patients who received rabies vaccinations,36 cases(9.38%)were diagnosed with anxiety,52 cases(13.54%)with depression,and 88 cases(22.92%)with either condition.Logistic regression analysis identified the following signi ficant risk factors for psychiatric disorders:Education level of primary school or below,exposure site at the head and neck,exposure classified as grade III,family status of divorced/widowed/unmarried/living alone,number of wounds greater than one,and low awareness of rabies prevention and control(P<0.05).The risk prediction model demonstrated good performance,with an area under the receiver operating characteristic curve of 0.859,a specificity of 74.42%,and a sensitivity of 93.02%.CONCLUSION In real-world settings,psychiatric disorders following rabies vaccination are relatively common and are associated with factors such as lower education level,higher exposure severity,vulnerable family status,and limited awareness of rabies prevention and control.The developed risk prediction model may aid in early identification of high-risk individuals and support timely clinical intervention.
基金supported by 2021 Beijing Key Specialty Program for Major Epidemic Prevention and Control。
文摘Objective Preliminary assessment of rabies virus neutralizing activity,safety and immunogenicity of a recombinant human rabies antibody(NM57)compared with human rabies immunoglobulin(HRIG)in Chinese healthy adults.Methods Subjects were randomly(1:1:1)allocated to Groups A(20 IU/kg NM57),B(40 IU/kg NM57),or C(20 IU/kg HRIG).One injection was given on the day of enrollment.Blood samples were collected on days-7 to 0(pre-injection),3,7,14,28,and 42.Adverse events(AEs)and serious AEs(SAEs)were recorded over a period of 42 days after injection.Results All 60 subjects developed detectable rabies virus neutralizing antibodies(RVNAs)(>0.05 IU/mL)on days 3,7,14,28,and 42.The RVNA levels peaked on day 3 in all three groups,with a geometric mean concentration(GMC)of 0.2139 IU/mL in Group A,0.3660 IU/mL in Group B,and0.1994 IU/mL in Group C.At each follow-up point,the GMC in Group B was significantly higher than that in Groups A and C.The areas under the antibody concentration curve over 0-14 days and 0-42 days in Group B were significantly larger than those in Groups A and C.Fifteen AEs were reported.Except for one grade 2 myalgia in Group C,the other 14 were all grade 1.No SAEs were observed.Conclusion The rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG,and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar.Safety was comparable between NM57 and HRIG.
基金supported by grants from the National Natural Science Foundation of China(No.3097016081160353)+1 种基金China Mega-Project for Infectious Disease(2011ZX10004-001)the Development Grant of the State Key Laboratory for Infectious Disease Prevention and Control(2011SKLID705)
文摘Abstract The number of human rabies cases acquired from dog bites constitutes a high proportion of the total rabies cases in China, although the number of human rabies cases has gradually decreased in recent years. The pivotal role of dogs in the spread of rabies indicates that controlling and preventing canine rabies could be a key step in eradicating human rabies in China. The primary aims of this review are to discuss the properties and pathogenesis of the rabies virus, the clinical signs and diagnosis of canine rabies, threshold host density and vaccination of dogs, and the prevention and control of canine rabies in China.
文摘Background:Rabies is a zoonosis transmitted via the bites of various mammals,primarily dogs and bats.Known since antiquity,this disease may have the deadliest human fatality rates and is responsible for approximately 65,000 deaths worldwide per year.Case presentation:We report the case details of a 13-year-old boy from India belonging to a South Asian ethnicity,who presented with altered sensorium one month following a dog bite.He did not receive the active rabies immunization and was managed with supportive therapy.The patient had extensive T_2 weighted(T_2W)/fluid attenuation and inversion recovery(FLAIR) hyper intensities involving the deep gray matter of the cerebral hemispheres,hippocampus,brainstem,and cerebellum.The diagnosis was confirmed by the demonstration of the rabies antigen from a nuchal skin biopsy and a corneal smear.The patient had a slow but significant recovery over four months and was discharged from the hospital in stable condition with severe neurological sequelae.Conclusion:We report a unique case of survival after infection with a universally fatal disease.
文摘Background: Rabies is a zoonotic disease and many vulnerable sections like rag pickers and municipality workers neglect animal bites due to ignorance of their potential deadly outcomes. Stray dogs abound in garbage pits and this population is exposed to their attacks. It should be a mandate for municipalities to help protect their sanitary workforce, especially rag pickers, from deadly infectious diseases such as Rabies, Hepatitis-B, HIV, Tetanus etc. Objectives: Objective of this study was to study methods to provide pre-exposure Rabies vaccination for such highly exposed populations by engaging them and understanding their perception of this disease through a constant dialogue with them. Methods: We started by engaging with the rag pickers to know how best to entice them to get themselves immunized. We then attempted to search literature for the most practical methods likely to succeed in reducing risk of rabies deaths in this population. Results: WHO approved 3 injections of 0.1 ml tissue culture vaccine on days 0, 7 and 21 were tried but were shown to result in many dropouts among rag pickers for repeat injections. We then followed a method where 0.1 ml of rabies vaccine was injected at 4 different anatomical sited in one setting. This proved acceptable and relatively inexpensive. A small number of subjects were studied by determination of neutralizing antibody by RFFIT, which proved immunogenic having anamnestic response on boosters given single IM or at 4 sites ID subsequently, implying that short schedule rabies pre-exposure vaccination can be done in high risk groups and may save lives if applied to the poorest that are highly exposed.
文摘Rabies is an acute encephalitis caused by a lyssavirus. It is primarily transmitted through bites of infected dogs which results in the worldwide death of an estimated 59000 humans every year. The disease is preventable through the application of post-exposure prophylaxis (PEP) and its elimination has been demonstrated in many countries by applying multiple interventions simultaneously. Nonetheless, rabies is still widespread in many developing countries, primarily due to the poor implementation of intervention strategies that include inadequate dog-bite wound management practices, unavailability/unaffordability of PEP by the communities, failure to control the disease in free-roaming dogs and wildlife, improper dog population management, weak surveillance and diagnostic facilities and a lack of a One Health approach to the disease. In this review, strategies to control dog-mediated rabies through a One Health approach were discussed. We recommend applying multiple interventions against the disease by involving all the concerned stakeholders in selected urban and rural areas of the countries where rabies is endemic. An empirical demonstration of disease freedom in the selected areas through a One Health approach is needed to convince policymakers to invest in rabies prevention and control on the national level. This multifaceted One Health control model will enhance the likelihood of achieving the goal of global rabies eradication by 2030.
文摘Rationale:Rabies is a zoonotic disease with a high mortality,primarily transmitted through the bite of infected mammals,particularly dogs and cats.Despite being a well-known disease since ancient times,it continues to cause a significant number of human deaths worldwide,with approximately 65000 fatalities reported annually.Patient concerns:We present two fatal cases of rabies in a 12-year-old immigrant boy and a 7-year-old boy.The first case was subject to a 24-hour delay in receiving appropriate medical attention and rabies preventive measures due to the lack of awareness among emergency hospital staff,leading to the administration of wound dressing only.The second case received timely rabies immunoglobulin administration;however,there was a 4-day delay in administering the fourth dose of the rabies vaccine,despite presenting evident symptoms of rabies.Diagnosis:Postmortem examination of brain samples from both patients confirmed the presence of rabies virus.Interventions:Post-exposure prophylaxis for rabies.Outcomes:Both patients were admitted to the hospital after the manifestation of rabies-related symptoms,with the 12-year-old child seeking medical care 47 days after the animal bite and the 7-year-old child seeking medical care 58 days after the exposure.Finally,the first patient died after 27 days and the second patient died after 40 days of hospitalization.Lessons:There is an urgent need for heightened awareness and education among both healthcare professionals and the public regarding the urgency of seeking immediate medical attention after potential rabies exposure.Timely recognition and initiation of post-exposure prophylaxis are pivotal in preventing the progression of the disease.Strengthening surveillance and reporting systems,coupled with continuous training for healthcare professionals,can contribute to early detection and management of rabies cases.
文摘Background: In India every year an estimated 20,000 patients die of Rabies. Major reason for poor compliance to anti-rabies prophylaxis is the high cost of anti-rabies vaccine being prescribed intramuscularly (IM) as a routine i.e. 44.5 USD per course of five injections. In 1992 WHO recommended low cost intra-dermal rabies vaccination (IDRV), which costs only 7.5 USD or less per animal bite course. Methods: Interviews with doctors revealed that they were not prescribing intra-dermal anti rabies vaccination as they were either not aware or were not confident of this route of rabies vaccination. Also the vaccine vial did not have the label for “intra-dermal use”. These barriers were removed by advocacy efforts with policy makers & drug companies, credit sharing & team building, which led to starting of first intra dermal anti-rabies clinic of North India on 2nd August 2008. Results: Within a month of start of intra-dermal rabies vaccination clinic, i.e. by 2nd September, 2008, there was an increase in the hospital patient load by 2.8 times, and poor patients load by 3.2 times. In just less than two-year time, 200,000 USD of poor patients were saved and 5769 patients vaccinated. Each patient was asked to bring one vial on first visit & rest of doses were given “free” by pooling strategy. Pooling strategy involved distribution of one vial of vaccine among four persons and keep the three vials for use one by one by all the four patients on subsequent three visits. Another offshoot of the strategy was to prevent wasting of even few drops of vaccine that used to remain in each vial of 1 ml after distribution among four patients (0.2 mL or less). Out of more than 5000 vials utilised, every time we would transfer the left out drops of vaccine to the next new vial and use it immediately on a new pool of patients waiting for vaccination. We would, however, discard the unused vaccine after eight hours of reconstitution at the end of the day. The vaccine so saved turned to be a stock of more than 100 vials in less than two years that we were able to give free to more than 225 rag pickers, garbage collectors and newspaper hawkers on World Rabies Day, Sep 28, 2010. Conclusions: With intra-dermal clinic, we were able to successfully introduce the new cost effective intra-dermal method of rabies vaccination despite all odds & vested interests of companies & old mindset of doctors that had blocked this technique till now. This will go a long way in reducing the burden of disease & death due to rabies from India.
基金National Department Public Benefit Research Foundation (201103032)Pathogens Network Monitoring Technology Research (2008ZX10004-008)
文摘In recent years (2007 to 2011), although the overall number of rabies cases in China has decreased, there is evidence of emerging or re-emerging cases in regions without previous rabies cases or with low incidence of rabies. To investigate the origin and the factors affecting the spread of rabies in China, specimens were collected from 2007 to 2011 from provinces with emerging and re-emerging cases and tested for the presence of the rabies virus. Positive specimens were combined with sequences from GenBank to perform comparisons of homology and functional sites, and to carry out phylogenetic analyses. Out of these regions, five provinces had 9 positive specimens from canine and cattle, and 34 canine or human specimens were obtained from previously high-incidence provinces. Complete sequences of G gene were obtained for these samples. Homology of the sequences of these 43 specimens was 87%-100% at the nucleotide level and 93.7% -100% at the amino acid level. These G gene sequences were combined with reference sequence from GenBank and used to construct a phylogenetic tree. The results showed that 43 specimens were all assigned to China clade I and clade II, with all specimens from emerging and re-emerging areas placed within clade I. Specimens isolated from Shanxi and Inner Mongolia in 2011 were distinct from previously-isolated local strains and had closer homology to strains from Hebei, Beijing and Tianjin whereas new isolates from Shanghai were tightly clustered with strains isolated in the 1990s. Finally, Shaanxi isolates were clustered with strains from adjacent Sichuan. Our results suggest that the rabies cases in emerging and re-emerging areas in China in the last 5 years are a consequence of the epidemic spreading from of neighboring provinces and regions experiencing a serious epidemic of rabies.
基金National Department Public Benefit Research Foundation(201103032)the Pathogens Network Monitoring Technology Research(2008ZX10004-008)
文摘To analyze features of the rabies epidemic in China between 2007 and 2011, identify factors influencing the epidemic and to provide a scientific basis for further control and prevention of rabies, Descriptive epidemiological methods and statistical analysis was used on data collected from the National Disease Reporting Information System between 2007 to 2011 and the National Active Surveillance System between 2007 and 2010. Our analysis shows that while the number of human rabies cases decreased year by year, the number of districts reporting cases did not show significant change. The situations in Guangdong, Guangxi, Guizhou and Hunan provinces clearly improved over the period but they remain provinces with high-incidence, and consequently influence the epidemic situation of surrounding provinces and possibly the whole country. Summer and autumn were high-incidence seasons. Farmers, students and pre-school children represent the high-risk populations, and rates of cases in farmers increased, those for students decreased, and pre-school children remained unchanged. Provinces with active surveillance programs reported a total of 2346 individual cases, of which 88.53% were associated with canines. Postexposure prophylaxis （PEP） of rabies cases was not significantly improved, whereas PEP in post-exposure population was good. In rural regions of China, canine density was reduced somewhat, and the immunization rate increased slightly. Finally we show that while the epidemic decreased 2007 to 2011 in China, cases continued to be diffused in certain regions. Lack of standardization of PEP on rabies eases was the main reason of morbidity. The high density and low immunization of dog in rural areas and the defective situation of PEP are still continuous occurrences in China and remain a cause for concern.
基金National Department Public Benefit Research Foundation (201103032)
文摘The World Health Organization (WHO) standard assay for determining levels of the rabies virus neutralization antibody (RVNA) is the rapid fluorescent focus inhibition test (RFFIT), which is used to evaluate the immunity effect after vaccination against rabies. For RFFIT, CVS-11 was used as the challenge virus, BSR cells as the adapted cells, and WHO rabies immunoglobulin (WHO STD) as the reference serum in this study. With reference to WHO and Pasteur RFFIT procedures, a micro-RFFIT procedure adapted to our laboratory was produced, and its specificity and reproducibility were tested. We tested levels of RVNA in human serum samples after immunization with different human rabies vaccines (domestic purified Vero cell rabies vaccine (PVRV) and imported purified chick embryo cell vaccine (PCECV)) using different regimens (Zagreb regimen and Essen regimen). We analyzed the levels of RVNA, and compared the immune efficacy of domestic PVRV and imported PCECV using different immunization regimens. The results showed that the immune efficacy of domestic PVRV using the Zagreb regimen was as good as that of the imported PCECV, but virus antibodies were generated more rapidly with the Zagreb regimen than with the Essen regimen. The RFFIT procedure established in our laboratory will enhance the comprehensive detection ability of institutions involved in rabies surveillance in China.
基金National Department Public Benefit Research Foundation (201103032)Pathogens Network Monitoring Technology Research (2008ZX10004-008)
文摘The epidemic of rabies has rapidly increased and expanded in Yunnan province in recent years. In order to further analyze and understand the etiological reasons for the rapid expansion of rabies in Yunnan, a strain of rabies virus CYN1009D in Yunnan was isolated, and the complete genomic sequencing was carried out, and the bioimfomative analysis on genes/encoded proteins and phylogeny with reference to sequences in GenBank was performed. The complete genome of CYN1009D was 11923 nt in length and belonged to genotype I. The genes encoding different structural proteins were all conserved in their lengths, in comparison to other strains in China. The amino acid sequence was conserved at different antigen sites of NP, but the variation was detected at the secondary phosphorylation site of position 375; variations were also detected in the phosphorylation sites at positions 63-63 and 162 of PP; the sites playing important roles in virus synthesis, budding and viral morphology in MP were conserved; two glycosylation sites were detected at Asn37 and Ash319 in GP, the neutralizing antigen sites in GP were conserved; the initial amino acid of LP （ML） was different from that of most of the strains in China （MM）; the variations in G-L region in the intergenic region were significant. The phylogenic tree showed that CYN1009D has a closer genetic relationship to the strains in Southeast Asia, indicating that prevention and control on rabies in borderland areas should be reinforced meanwhile efforts are made to control rabies in China.
文摘A simple method was established for the determination of β-propiolactone(BPL) in human inactivated rabies vaccine by gas chromatography-mass spectrometry(GC-MS). The determination was performed on an Agilent HP-INNOWAX(30 m ? 0.32 mm i.d., 0.25 mm) capillary column at the temperature of 80 °C.Electrospray ionization(ESI) was used by selective ion detection at m/z 42. The temperature for ESI source and inlet was set at 230 °C and 200 °C, respectively. Helium was used as the carrier gas at a flow rate of 25.1 m L/min. The total run time was 8 min. Acetonitrile and other components in the sample did not interfere with the determination of BPL. The results showed good linearity of BPL in the range of0.50–10.01 μg/mL, with the limit of detection and the limit of quantification of 0.015 μg/mL and0.050 μg/mL, respectively. Satisfactory precision was achieved for the current developed method. The method was applied to detect 6 batches of vaccine samples, and the results indicated that the target analyte BPL was present in three batches of unpurified samples, but was not detected in the purified samples, indicating the test samples were qualified. The established method was proved to be simple,versatile and sensitive, which can meet the requirements of quality control of BPL in human inactivated rabies vaccine.
基金supported by the National Natural Science Foundation of China (Grant No. 31770184)Construction Project of Provincial-School of Jilin Province (No. 440050316A28)
文摘Exosomes are cell-derived vesicles that are secreted by many eukaryotic cells. It has recently attracted attention as vehicles of intercellular communication. Virus-infected cells release exosomes, which contain viral proteins, RNA, and pathogenic molecules. However, the role of exosomes in virus infection process remains unclear and needs to be further investigated.In this study, we aimed to evaluate the effects of exosomes on rabies virus infection. OptiPrep^(TM) density gradient centrifugation was used to isolate exosomes from rabies virus-infected cell culture supernatants. A rabies virus G protein enzyme-linked immunosorbent assay and acetylcholinesterase activity assays were performed to verify the centrifugation fractions. Exosomes were then characterized using transmission electron microscopy and Western blotting. Our results showed that rabies virus infection increased the release of exosomes. Treatment with GW4869 and si-Rab27 a, two exosomal secretion inhibitors, inhibited exosome release. Furthermore, the inhibitors reduced the levels of extracellular and intracellular viral RNA. These data indicated that exosomes may participate in the viral infection process. Moreover, our results establish a basis for future research into the roles of exosomes in rabies virus infection and as potential targets for developing new antiviral strategies.
基金partially supported by the National Natural Science Foundation of China(31402176,31372419,31522057)the National Program on Key Research Project of China(2016YFD0500400)+2 种基金the Fundamental Research Funds for the Central Universities(2662016 QD036,to MZ)the Ministry of Science and Technology of China(863 program,number 2011AA10A212)the Ministry of Agriculture of China(special fund for Agro-scientific research in the Public Interest,2013 03042,to ZFF)
文摘Rabies remains a public health threat that kills approximately 59,000 people worldwide each year,most of which are from the developing countries of Africa and Asia where dog rabies are endemic.Therefore, developing an affordable and efficacious vaccine is crucial for rabies control in these countries. Interleukin(IL)-15, an immunoregulatory cytokine, is a pluripotent molecule with therapeutic potential, which targets many cell types and links the innate and adaptive immune system. In this study, IL-15 gene was cloned and inserted into the genome of a recombinant rabies virus(RABV) strain LBNSE(designated as LBNSE-IL15), and the effect of over-expression of IL-15 on the immunogenicity of RABV was investigated. It was found that mice vaccinated with LBNSEIL15 could induce significantly higher level of virus-neutralizing antibody(VNA) than those immunized with LBNSE, resulting in the higher protection after challenge. Further investigation was performed to find out the possible role of IL-15 plays in the process of antibody induction, and it was found that LBNSE-IL15 could enhance the maturation of dendritic cells(DCs) in immunized mice. Furthermore, the mice immunized with LBNSE-IL15 could promote the T_(FH) cells differentiation and the generation of germinal center B cells and plasma cells. Together, these data indicated that IL-15 could be a potential adjuvant in enhancing the immunogenicity of RABV, contributing to the development of more-efficacious rabies vaccines.
