Fatal cases in pediatric patients after post-exposure prophylaxis for rabies:A report of two cases

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.

Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China

Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and protection.Methods Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120after the first immunization.Additionally,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death status.In a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28and 42 after the first immunization.Results A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P<0.05).The groups 0-3-7-14,0-3-7-21,and 0-3-7-28 showed no statistically significant difference(P>0.05)in RVNAs levels at any time point.The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05).Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14–28 d)on the immunization potential.

Eco-Epidemiological Characteristics of Human Rabies in Côte d’Ivoire, 2012-2017

Introduction: Human rabies is a major public health problem in many African countries, including Côte d’Ivoire. The present work aims at describing the eco-epidemiological characteristics of human rabies cases recorded in Côte d’Ivoire. Methods: This was a retrospective and prospective cross-sectional descriptive study based on epidemiological surveillance data that ran from september 2014 to december 2017. The clinical data were extracted from the database of the human rabies epidemiological surveillance management service of the National Institute of Public Hygiene’s rabies centre. These data cover the period from 1 January 2012 to 31 December 2017. Results: Human rabies is endemic in Côte d’Ivoire, with most people exposed in the south and especially in the west of the country. There was no association between any of the climatological parameters (temperature, humidity, rainfall) and the occurrence of human rabies during the months of exposure to rabies infection. Conclusion: Ultimately, effective prevention and control of human rabies requires a thorough understanding of the links between climatological parameters and rabies. Health authorities must take ownership of these results if we are to achieve our goal of eliminating rabies by 2030.

Study of Factors Associated with Knowledge, Attitudes and Practices Regarding Rabies in the Commune of Niakhéne in Senegal, in 2022

Introduction: Rabies is a serious disease, as it is always fatal, but it can be prevented by sero-vaccination. It is a neglected tropical disease endemic in Asia and Africa. The aim of this study was to assess knowledge, attitudes and practices regarding rabies and to determine the factors associated with them among people aged 18 and over in the commune of Niakhène. Methods: This was a cross-sectional, descriptive and analytical survey of subjects aged 18 and over living in the commune of Niakhène. A sample of 300 individuals was drawn from a two-stage cluster survey stratified by age and sex. Bivariate analysis was performed using association tests. Results: The mean age of respondents was 35.3 ± 16.9 years. It was noted that 67% (201) of respondents had a good knowledge of rabies. The results showed that 7.3% (22) of respondents owned a dog. Of the 278 people who did not own a dog, 78.4% (218) said they would have vaccinated their dog if they had had one. It should be noted that 83.7% (251) of respondents said they would go to a health facility if an animal bit them. None of the dog owners had vaccinated their dogs against rabies. Of the 41 people exposed to rabies, 39% went to a health facility. The age and education of the respondents had statistically significant associations with knowledge of rabies. Respondents’ age and education were statistically significantly related to whether they had vaccinated a domestic dog. The age, education and economic well-being quintile of respondents’ households had statistically significant associations with the use of a health facility in the event of being bitten or scratched by an animal vector. The education of respondents who had been bitten by an animal vector was statistically significantly associated with the use of a health facility. Conclusion: It would be imperative for human and animal health authorities to collaborate in a “One Health” approach in order to increase knowledge and promote the adoption of good practices in rabies prevention.

Spontaneous Rabies in a Stray Bitch after Parturition Induced Immunosuppression —Investigating an Impending Outbreak of Rabies with One Health Approach

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.

Brain-wide N2cG compensation permits glycoprotein-deleted rabies virus to trace neural circuits across multiple synapses

Rabies-viruses-based retrograde tracers can spread across multiple synapses in a retrograde direction in the nervous system of rodents and primates,making them powerful tools for determining the structure and function of the complicated neural circuits of the brain.However,they have some limitations,such as posing high risks to human health and the inability to retrograde trans-synaptic label inputs from genetically-de¯ned starter neurons.Here,we established a new retrograde trans-multi-synaptic tracing method through brain-wide rabies virus glycoprotein(RVG)compensation,followed by glycoprotein-deleted rabies virus(RV-△G)infection in specific brain regions.Furthermore,in combination with the avian tumor virus receptor A(TVA)controlled by a cell-type-specific promoter,we found that EnvA-pseudotyped RV-△G can mediate e±cient retrograde trans-multi-synaptic transduction from cell-type-specific starter neurons.This study provides new alternative methods for neuroscience researchers to analyze the input neural networks of rodents and nonhuman primates.

A rabies virus-based toolkit for efficient retrograde labeling and monosynaptic tracing

Analyzing the structure and function of the brain's neural network is critical for identifying the working principles of the brain and the mechanisms of brain diseases.Recombinant rabies viral vectors allow for the retrograde labeling of projection neurons and cell type-specific trans-monosynaptic tracing,making these vectors powerful candidates for the dissection of synaptic inputs.Although several attenuated rabies viral vectors have been developed,their application in studies of functional networks is hindered by the long preparation cycle and low yield of these vectors.To overcome these limitations,we developed an improved production system for the rapid rescue and preparation of a high-titer CVS-N2c-ΔG virus.Our results showed that the new CVS-N2c-ΔG-based toolkit performed remarkably:(1)N2cG-coated CVS-N2c-ΔG allowed for efficient retrograde access to projection neurons that were unaddressed by rAAV9-Retro,and the efficiency was six times higher than that of rAAV9-Retro;(2)the trans-monosynaptic efficiency of oG-mediated CVS-N2c-ΔG was 2–3 times higher than that of oG-mediated SAD-B19-ΔG;(3)CVS-N2c-ΔG could delivery modified genes for neural activity monitoring,and the time window during which this was maintained was 3 weeks;and(4)CVS-N2c-ΔG could express sufficient recombinases for efficient transgene recombination.These findings demonstrate that new CVS-N2c-ΔG-based toolkit may serve as a versatile tool for structural and functional studies of neural circuits.

Molecular epidemiological study of animal rabies in Kazakhstan

Rabies is a serious public health issue in Kazakhstan, with high economic impact and social burden. As part of a routine surveillance, 31 rabies-positive brain specimens taken from livestock(cattle) and carnivores(dogs, foxes, and cats)during 2013–2021 were subject to viral sequencing. Phylogenetic and Bayesian analysis were performed using obtained rabies virus(RABV) sequences. All 31 strains of RABV candidate belonged to the Cosmopolitan clade, of which 30strains belonged to steppe-type subclade, and 1 dog strain belonged to Other subclade. The 31 strains did not diverge from RABV strains in Kazakhstan and neighboring countries, including Russia, Mongolia, and China, suggesting that animal rabies has close relationship and transmission between borders. Fox-originated strains and cattle strains shared similar sequence signature, and some animal rabies cases had space–time intersection, showing that infected foxes were a major transmission source of cattle rabies in different Kazakhstan regions. Besides, free-roaming dogs played a pivotal role in rabies epizootics of cattle in Kazakhstan. The recent spread of animal rabies presents an increasing threat to public health, and provides updated information for improving current control and prevention strategies at the source for Kazakhstan and neighboring countries.

基于两量子比特Rabi模型暗态解的Bell态制备

Bell态在量子光学和量子信息中具有重要的应用价值.该文基于两量子比特Rabi模型的特殊暗态制备单光子源的方案,重点探究了Bell态的同时确定性制备,并研究了有无单光子释放的情况下,环境对制备Bell态保真度的影响.数值结果表明,所提出的方案可以制备确定性的Bell态,并且在耗散环境下能保持高保真度.

One Health for Rabies Elimination:China Rabies Annual Conference in 2023

The China Rabies Annual Conference in 2023 was held in Taiyuan,Shanxi Province,from May 12 to 13.With the theme of"One Health for Rabies Elimination",the conference was hosted by the Chinese Preventive Medicine Association(CMPA),the Chinese Association of Animal Science and Veterinary Medicine,and the China Working Dog Management Association.

Rabies in a postpandemic world:resilient reservoirs,redoubtable riposte,recurrent roadblocks,and resolute recidivism

Rabies is an ancient disease.Two centuries since Pasteur,fundamental progress occurred in virology,vaccinology,and diagnostics—and an understanding of pathobiology and epizootiology of rabies in testament to One Health—before common terminological coinage.Prevention,control,selective elimination,and even the unthinkable—occasional treatment—of this zoonosis dawned by the twenty-first century.However,in contrast to smallpox and rinderpest,eradication is a wishful misnomer applied to rabies,particularly post-COVID-19 pandemic.Reasons are minion.Polyhostality encompasses bats and mesocarnivores,but other mammals represent a diverse spectrum of potential hosts.While rabies virus is the classical member of the genus,other species of lyssaviruses also cause the disease.Some reservoirs remain cryptic.Although global,this viral encephalitis is untreatable and often ignored.As with other neglected diseases,laboratory-based surveillance falls short of the notifiable ideal,especially in lower-and middleincome countries.Calculation of actual burden defaults to a flux within broad health economic models.Competing priorities,lack of defined,long-term international donors,and shrinking local champions challenge human prophylaxis and mass dog vaccination toward targets of 2030 for even canine rabies impacts.For prevention,all licensed vaccines are delivered to the individual,whether parenteral or oral–essentially‘one and done’.Exploiting mammalian social behaviors,future‘spreadable vaccines’might increase the proportion of immunized hosts per unit effort.However,the release of replication-competent,genetically modified organisms selectively engineered to spread intentionally throughout a population raises significant biological,ethical,and regulatory issues in need of broader,transdisciplinary discourse.How this rather curious idea will evolve toward actual unconventional prevention,control,or elimination in the near term remains debatable.In the interim,more precise terminology and realistic expectations serve as the norm for diverse,collective constituents to maintain progress in the field.

Ground-state phase diagram,symmetries,excitation spectra and finite-frequency scaling of the two-mode quantum Rabi model

We investigate the two-mode quantum Rabi model(QRM)describing the interaction between a two-level atom and a two-mode cavity field.The quantum phase transitions are found when the ratioηof transition frequency of atom to frequency of cavity field approaches infinity.We apply the Schrieffer–Wolff(SW)transformation to derive the low-energy effective Hamiltonian of the two-mode QRM,thus yielding the critical point and rich phase diagram of quantum phase transitions.The phase diagram consists of four regions:a normal phase,an electric superradiant phase,a magnetic superradiant phase and an electromagnetic superradiant phase.The quantum phase transition between the normal phase and the electric(magnetic)superradiant phase is of second order and associates with the breaking of the discrete Z_(2) symmetry.On the other hand,the phase transition between the electric superradiant phase and the magnetic superradiant phase is of first order and relates to the breaking of the continuous U(1)symmetry.Several important physical quantities,for example the excitation energy and average photon number in the four phases,are derived.We find that the excitation spectra exhibit the Nambu–Goldstone mode.We calculate analytically the higher-order correction and finite-frequency exponents of relevant quantities.To confirm the validity of the low-energy effective Hamiltonians analytically derived by us,the finite-frequency scaling relation of the averaged photon numbers is calculated by numerically diagonalizing the two-mode quantum Rabi Hamiltonian.

Epidemiological Facies of Human Rabies Deaths in Côte d’Ivoire from 2016 to 2022

Introduction: Rabies is a highly fatal viral disease outside the post-exposure prophylaxis (PEP). Data from previous studies and reports from the rabies center show that cases of death from human rabies are regularly reported, despite training measures for health workers, awareness-raising and communities, and the availability of vaccines. Objectives: The aim of this study was to analyse the determinants of human rabies deaths in Côte d’Ivoire from 2016 to 2022. Method: A retrospective cross-sectional qualitative study was carried out from January to August 2023 on all the records of patients who died of human rabies at the Treichville Rabies Center from 2016 to 2022. An analysis of the rabies center’s annual activity reports from 2016 to 2022 was also carried out in order to complete the information gathered from the files. Results: The socio-demographic characteristics showed that out of 148 deaths, children accounted for 47.97% (71) and 66.22% (98) of rabies deaths were male, with an M/F sex ratio of 1.96. In terms of clinical characteristics, in 97.30% (144) of cases, the deceased had presented with furious rabies, and analysis by the Pasteur Institute of Côte d’Ivoire laboratory confirmed 101 cases (92.66%) of human rabies. Geographical distribution showed that cases of human rabies were recorded in 56 health district, and 64% (94) of the deceased lived in rural areas. The main causes of the occurrence of rabies were essentially non-use of post-exposure prophylaxis (PEP) and missed vaccination due to ignorance. Conclusion: In view of these results, control strategies and interventions need to be adapted to the epidemiological characteristics of the disease, using a community-based approach with a view to eliminating dog-transmitted rabies by 2030.

Analysis of Epidemiological Investigations and Responses to Human Rabies Deaths in Côte d’Ivoire, 2021

Rabies is an infectious disease that almost always leads to death as soon as the first signs appear, and is still endemic in several regions, including Côte d’Ivoire. Epidemiological investigations are carried out and response measures implemented in the event of any death from human rabies. However, the quality of these investigations does not always allow the adoption of response measures. The aim of this work was to evaluate the reports of epidemiological investigations and response actions carried out during the occurrence of human rabies deaths from 2016 to 2018. This was a cross-sectional study that took place from April to September 2021 at the National Institute of Public Hygiene and focused on human rabies deaths notified from 206 to 2018. Of sixty-one (61) human rabies deaths recorded, sixty (60) were investigated, among which fifty-nine (59) deaths had been subject to response. Most deaths occurred in rural areas (75%), and the main vector was the dog (98%). Several shortcomings were noted: response actions were not carried out promptly;joint interventions bringing together human and animal health professionals were rare, there was little communication about rabies to communities (36%), and very little vaccination of the vector, the source of the disease (12%);an almost total absence of capacity-building for local players (7%);the health districts of Abobo-Ouest, Bondoukou, Divo and Fresco, which had regularly recorded human rabies deaths, had not benefited from dog vaccination, which is supposed to break the circulation of the virus. The persistence of rabies deaths in the health districts could probably be linked to these shortcomings. Faced with these realities, it is essential to strengthen the epidemiological investigation capacities of the players involved, in order to improve the quality of investigations and ensure an effective response.

Analysis of Epidemiological Investigations and Responses to Human Rabies Deaths in Côte d’Ivoire, 2021

Rabies is an infectious disease that almost always leads to death as soon as the first signs appear, and is still endemic in several regions, including Côte d’Ivoire. Epidemiological investigations are carried out and response measures implemented in the event of any death from human rabies. However, the quality of these investigations does not always allow the adoption of response measures. The aim of this work was to evaluate the reports of epidemiological investigations and response actions carried out during the occurrence of human rabies deaths from 2016 to 2018. This was a cross-sectional study that took place from April to September 2021 at the National Institute of Public Hygiene and focused on human rabies deaths notified from 206 to 2018. Of sixty-one (61) human rabies deaths recorded, sixty (60) were investigated, among which fifty-nine (59) deaths had been subject to response. Most deaths occurred in rural areas (75%), and the main vector was the dog (98%). Several shortcomings were noted: response actions were not carried out promptly;joint interventions bringing together human and animal health professionals were rare, there was little communication about rabies to communities (36%), and very little vaccination of the vector, the source of the disease (12%);an almost total absence of capacity-building for local players (7%);the health districts of Abobo-Ouest, Bondoukou, Divo and Fresco, which had regularly recorded human rabies deaths, had not benefited from dog vaccination, which is supposed to break the circulation of the virus. The persistence of rabies deaths in the health districts could probably be linked to these shortcomings. Faced with these realities, it is essential to strengthen the epidemiological investigation capacities of the players involved, in order to improve the quality of investigations and ensure an effective response.

Rabies Virus Neutralizing Activity,Safety,and Immunogenicity of Recombinant Human Rabies Antibody Compared with Human Rabies Immunoglobulin in Healthy Adults

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.

半导体量子点Rabi振荡品质因子及其退相干机制

采用光致发光方法和纳米光谱成像技术,研究了单个半导体量子点中激发态激子的Rabi振荡。观测了在两个延时位相可控的!/2脉冲激发下,激发态激子数随其量子比特位相旋转而振荡的特性。由实验观测结果分析得知此单个半导体量子点量子比特的自由旋转品质因子约为9.8×104,动力旋转品质因子约为18。讨论了激子从浸润层到量子点的俘获过程对Rabi振荡衰减退相干的影响。简要分析了量子点的激子自旋操控和单光子发射统计特性。

量子Rabi模型中的Berry相的解析解

利用光子Fock态,给出量子Rabi模型的数值严格解,其结果比推广的转动波近似有很大改进.截取两个Fock态,可以给出简单明了的解析结果,在很大的耦合区间里,非常接近严格解,包含了主要的非旋波效应.我们获得Berr相的简明解析结果,与数值严格解在很大区间内吻合.

Recovery from rabies,a universally fatal disease

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.

Rabi分裂的位相相关性质

本文讨论了一个两能级原子在真空态和单光子Fock态的相干叠加场中的发射谱,发现原子发射谱中的两个Rabi分裂峰的幅度非常敏感地依赖于原子和场之间的相对位相,当相对位相在适当的范围内变化时,其中一个Rabi峰的幅度受到抑制,而另一个Rabi峰的幅度却得到加强,并且当相对位相确定后,对适当的相干叠加场,可以使其中一个Rabi分裂峰完全消失。