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Viruses May 2022Rabies is a devastating disease and affects millions of people globally, yet it is preventable with appropriate and timely postexposure prophylaxis (PEP). The current... (Review)
Review
Rabies is a devastating disease and affects millions of people globally, yet it is preventable with appropriate and timely postexposure prophylaxis (PEP). The current WHO exposure categories (Categories I, II, and III) need revision, with a special Category IV for severe exposures. Rare cases of PEP failure have occurred in severe bites to the head and neck. Multiple factors, including route, wound severity, depth, contamination, viral dose, proximity to highly innervated areas and the CNS, and the number of lesions, remain unconsidered. Injuries in areas of high neural density are the most significant considering lyssavirus pathophysiology. Current recommendations do not account for these factors. A Category IV designation would acknowledge the severity and the increased risk of progression. Subsequently, patient management would be optimized with wound care and the appropriate administration of rabies-immune globulin/monoclonal antibodies (RIG/MAbs). All Category IV exposures would be infiltrated with the full dose of intact RIG (i.e., human RIG or MAbs) if the patient was previously unvaccinated. More concentrated RIG/MAb formulations would be preferred. As a world rabies community, we cannot tolerate PEP failures. A fourth WHO categorization will improve the care of these high-risk patients and highlight the global health urgency of this neglected disease.
Topics: Antibodies, Monoclonal; Humans; Post-Exposure Prophylaxis; Rabies; Rabies virus; World Health Organization
PubMed: 35632852
DOI: 10.3390/v14051111 -
PLoS Neglected Tropical Diseases May 2021Human fatalities caused by rabies are rarely reported in Jordan; however, domestic animals are more likely to fall victim to rabies compared to wild animals, at least...
Human fatalities caused by rabies are rarely reported in Jordan; however, domestic animals are more likely to fall victim to rabies compared to wild animals, at least this is the case in Jordan due to the presence of canine rabies. In this study, twelve brain samples from domestic and wild animals suspected of being infected with rabies virus from different regions of Jordan were collected during 2019. Seven of them tested positive using the fluorescent antibody test and real-time SYBR RT-PCR assay. Five specimens were from stray dogs and two from foxes. The whole genome sequences were obtained from the positive samples. Sequence analysis showed that one dog virus from Al Quwaysimah city located in Amman governorate, was closely related to an Israeli strain belonging to a Cosmopolitan ME1a clade. The genomes of the remaining six viruses (four from dogs and two from foxes) collected from different areas of Jordan were genetically-related to each other and clustered together with sequences from Iran and Turkey; all belong to Cosmopolitan ME2 clade. These sequences were analyzed with six other Jordanian rabies virus nucleoprotein (N) gene sequences available in the public database, five of them belong to ME1a clade and one belongs to ME1b clade. Rabies virus whole genome data is scarce across the Middle East. This study provides a better understanding of the molecular epidemiology of rabies virus in the region.
Topics: Animals; Brain; Dog Diseases; Dogs; Foxes; Jordan; Molecular Epidemiology; Phylogeny; Rabies; Rabies virus; Whole Genome Sequencing
PubMed: 34014930
DOI: 10.1371/journal.pntd.0009431 -
Viruses Jul 2023Rabies, caused by the rabies virus (RABV), remains a significant public health issue in the Philippines despite efforts to control it. To eliminate rabies by 2030,...
Rabies, caused by the rabies virus (RABV), remains a significant public health issue in the Philippines despite efforts to control it. To eliminate rabies by 2030, effective surveillance strategies are crucial. In this study, we examined RABV evolution and phylodynamics in the Davao Region using genome sequences from Davao City and nearby provinces. We adapted the RABV ARTIC Protocol for Oxford Nanopore High-Throughput Sequencing to optimize workflow efficiency under limited resources. Comparing new virus samples collected from June 2019 to June 2021 ( = 38) with baseline samples from June 2018 to May 2019 ( = 49), new sub-clades were observed in the phylogenetic tree, suggesting divergence from older variants that were previously undetected. Most of the new viruses belonged to the Asian SEA4_A1.1.1 lineage, but new (SEA4_B1 and SEA4_B1.1) and emerging (SEA4_B1.1_E1) lineages that have never been reported in the Philippines were also identified. The baseline study reported phylogeographic clustering of RABV isolates from the same areas. However, this pattern was disrupted in the current biosurveillance, with variants detected in areas outside the original cluster. Furthermore, our findings revealed significant transmission routes between Davao City and neighboring provinces, contrasting with the predominantly intra-city transmission observed in the baseline study. These results underscore the need for ongoing and timely genomic surveillance to monitor genetic diversity changes and the emergence of novel strains, as well as to track alterations in transmission pathways. Implementing cost-effective next-generation sequencing workflows will facilitate the integration of genomic surveillance into rabies control programs, particularly in resource-limited settings. Collaborations between different sectors can empower local laboratories and experts in genomic technologies and analysis.
Topics: Humans; Rabies virus; Rabies; Philippines; Phylogeny; Genomics
PubMed: 37632001
DOI: 10.3390/v15081658 -
Cell Stress & Chaperones Jul 2023The endoplasmic reticulum (ER) response mechanism to cellular stress is mediated by the unfolded protein response/ER-associated degradation (UPR/ERAD) pathway. A viral...
The endoplasmic reticulum (ER) response mechanism to cellular stress is mediated by the unfolded protein response/ER-associated degradation (UPR/ERAD) pathway. A viral infection can trigger ER stress and engage some transcription factors, depending on the host cell and virus type, activating or inhibiting autophagy. The relationship between ER response and autophagy in rabies has not been investigated yet. In the present study, the mouse brain was infected with street rabies virus (SRABV). Total RNA was extracted from the brains of animals, and cDNA was synthesized. Next, real-time PCR assay was performed using specific primers. The expression of hypoxanthine-guanine phosphoribosyltransferase (Hprt), CCAAT/enhancer binding protein homologous protein (CHOP), apoptosis signal-regulating kinase 1 (ASK1), activating transcription factor 6 (ATF6), and caspase 3 (CASP3) genes was also investigated. Based on the results, SRABV caused significant changes in the mRNA expression of ATF6, CHOP, and ASK1 genes in the brains of infected mice in the control group (group V). Treatment of infected cells with the pIRES-EGFP-Beclin-1 vector and rapamycin caused changes in nearly most of the parameters. However, alterations in CASP3 gene expression were only observed when the vector and the virus were simultaneously injected into the cells. Overall, protection and autophagy against cell death induced by SRABV infection can be achieved by activating the ER stress pathway, followed by a marked increase in the expression of ATF6, CHOP, ASK1, and CASP3 genes.
Topics: Mice; Animals; Rabies virus; Apoptosis; Caspase 3; Unfolded Protein Response; Endoplasmic Reticulum Stress; Autophagy
PubMed: 37133695
DOI: 10.1007/s12192-023-01335-y -
Viruses Nov 2021The environment of the central nervous system (CNS) represents a double-edged sword in the context of viral infections. On the one hand, the infectious route for viral... (Review)
Review
The environment of the central nervous system (CNS) represents a double-edged sword in the context of viral infections. On the one hand, the infectious route for viral pathogens is restricted via neuroprotective barriers; on the other hand, viruses benefit from the immunologically quiescent neural environment after CNS entry. Both the herpes simplex virus (HSV) and the rabies virus (RABV) bypass the neuroprotective blood-brain barrier (BBB) and successfully enter the CNS parenchyma via nerve endings. Despite the differences in the molecular nature of both viruses, each virus uses retrograde transport along peripheral nerves to reach the human CNS. Once inside the CNS parenchyma, HSV infection results in severe acute inflammation, necrosis, and hemorrhaging, while RABV preserves the intact neuronal network by inhibiting apoptosis and limiting inflammation. During RABV neuroinvasion, surveilling glial cells fail to generate a sufficient type I interferon (IFN) response, enabling RABV to replicate undetected, ultimately leading to its fatal outcome. To date, we do not fully understand the molecular mechanisms underlying the activation or suppression of the host inflammatory responses of surveilling glial cells, which present important pathways shaping viral pathogenesis and clinical outcome in viral encephalitis. Here, we compare the innate immune responses of glial cells in RABV- and HSV-infected CNS, highlighting different viral strategies of neuroprotection or Neuroinflamm. in the context of viral encephalitis.
Topics: Animals; Astrocytes; Blood-Brain Barrier; Central Nervous System; Encephalitis, Viral; Herpes Simplex; Humans; Immunity, Innate; Inflammation; Microglia; Neuroglia; Rabies; Rabies virus; Signal Transduction; Simplexvirus
PubMed: 34960633
DOI: 10.3390/v13122364 -
ENeuro Jun 2021The Xenopus laevis experimental system has provided significant insight into the development and plasticity of neural circuits. Xenopus neuroscience research would be...
The Xenopus laevis experimental system has provided significant insight into the development and plasticity of neural circuits. Xenopus neuroscience research would be enhanced by additional tools to study neural circuit structure and function. Rabies viruses are powerful tools to label and manipulate neural circuits and have been widely used to study mesoscale connectomics. Whether rabies virus can be used to transduce neurons and express transgenes in Xenopus has not been systematically investigated. Glycoprotein-deleted rabies virus transduces neurons at the axon terminal and retrogradely labels their cell bodies. We show that glycoprotein-deleted rabies virus infects local and projection neurons in the Xenopus tadpole when directly injected into brain tissue. Pseudotyping glycoprotein-deleted rabies with EnvA restricts infection to cells with exogenous expression of the EnvA receptor, TVA. EnvA pseudotyped virus specifically infects tadpole neurons with promoter-driven expression of TVA, demonstrating its utility to label targeted neuronal populations. Neuronal cell types are defined by a combination of features including anatomical location, expression of genetic markers, axon projection sites, morphology, and physiological properties. We show that driving TVA expression in one hemisphere and injecting EnvA pseudotyped virus into the contralateral hemisphere, retrogradely labels neurons defined by cell body location and axon projection site. Using this approach, rabies can be used to identify cell types in Xenopus brain and simultaneously to express transgenes which enable monitoring or manipulation of neuronal activity. This makes rabies a valuable tool to study the structure and function of neural circuits in Xenopus.Studies in Xenopus have contributed a great deal to our understanding of brain circuit development and plasticity, regeneration, and hormonal regulation of behavior and metamorphosis. Here, we show that recombinant rabies virus transduces neurons in the Xenopus tadpole, enlarging the toolbox that can be applied to studying Xenopus brain. Rabies can be used for retrograde labeling and expression of a broad range of transgenes including fluorescent proteins for anatomical tracing and studying neuronal morphology, voltage or calcium indicators to visualize neuronal activity, and photo- or chemosensitive channels to control neuronal activity. The versatility of these tools enables diverse experiments to analyze and manipulate Xenopus brain structure and function, including mesoscale connectivity.
PubMed: 34099488
DOI: 10.1523/ENEURO.0477-20.2021 -
Clinical Infectious Diseases : An... Sep 2023All World Health Organization (WHO) pre-qualified rabies vaccines for humans are inactivated tissue culture rabies virus formulations produced for intramuscular (IM)...
Side-by-side Comparative Study of the Immunogenicity of the Intramuscular and Intradermal Rabies Post-exposure Prophylaxis Regimens in a Cohort of Suspected Rabies Virus Exposed Individuals.
All World Health Organization (WHO) pre-qualified rabies vaccines for humans are inactivated tissue culture rabies virus formulations produced for intramuscular (IM) administration. Due to costs and vaccine shortage, dose-saving intradermal (ID) administration of rabies post-exposure prophylaxis (PEP) is encouraged by WHO. This study compared the immunogenicity of the ID 2-site, 3-visit Institut Pasteur Cambodge (IPC) PEP regimen to the IM 1-site, 4-visit 4-dose Essen regimen using Verorab vaccine (Sanofi). The development of neutralizing antibodies (nAbs) and T cell response was assessed in 210 patients with a category II or III animal exposure in a rabies-endemic country. At day 28, all participants developed nAbs (≥0.5 IU/mL), irrespective of PEP scheme, age, or administration of rabies immunoglobulin. T cell response and nAb titers were similar for both PEP schemes. This study demonstrated that the 1-week ID IPC regimen is as effective as the 2-week IM 4-dose Essen regimen in inducing an anti-rabies immune response under real-life PEP.
Topics: Animals; Humans; Rabies Vaccines; Rabies virus; Post-Exposure Prophylaxis; Injections, Intramuscular; Rabies; Antibodies, Neutralizing; Injections, Intradermal; Antibodies, Viral
PubMed: 37337899
DOI: 10.1093/cid/ciad304 -
One Health (Amsterdam, Netherlands) Dec 2021Rabies is transmitted to humans mainly by dogs but also by other animal species. Reliable data on the incidence of Rabies virus (RABV) in humans, dogs, and other animal... (Review)
Review
Rabies is transmitted to humans mainly by dogs but also by other animal species. Reliable data on the incidence of Rabies virus (RABV) in humans, dogs, and other animal species in Africa, could be essential in the implementation of a global strategic plan to eliminate the RABV by 2030 as adopted by the WHO, OIE, and FAO. We searched the Pubmed, Embase, Scopus, African Journal Online, and African Index Medicus databases for relevant studies that report data on the incidence of RABV in Africa up to February 17, 2020. Information on active and past RABV exposures in various categories of dogs, humans and other animal species were extracted. Incidence and seroprevalence estimates were pooled using a random-effect meta-analysis. We included 73 articles which provided 142 RABV incidence and seroprevalence records in 21 African countries. The estimated incidence of RABV in 222 humans, 15,600 dogs, and 12,865 other animal species was 83.4% (95% CI = 64.6-96.5), 44.1% (95% CI = 35.1-53.4), and 41.4% (95% CI = 29.6-53.8), respectively. The estimated seroprevalence of RABV in 420 humans, 3577 dogs, and 8,55 other animal species was 33.8% (95% CI = 21.9-46.8), 19.8% (95% CI = 13.3-27.3), and 3.6% (95% CI = 0.3-9.2), respectively. The incidence of RABV in general was higher in suspected rabid dogs, other animal species of the Orders Perissodactyla, Artiodactyla and Carnivora. The incidence of RABV was higher for humans in regions of West and East Africa, for dogs in urban areas and in regions of Central and South Africa, and for animals of the order Perissodactyla in urban areas. This meta-analysis demonstrated a high incidence of RABV in Africa. Itis necessary to improve surveillance system to provide reliable data on RABV in Africa, essential for the implementation of an effective control strategy.
PubMed: 34258372
DOI: 10.1016/j.onehlt.2021.100285 -
Journal of the American Veterinary... Jan 2020To evaluate species identification and rabies virus (RABV) characterization among samples from bats submitted for rabies testing in the United States and assess whether...
OBJECTIVE
To evaluate species identification and rabies virus (RABV) characterization among samples from bats submitted for rabies testing in the United States and assess whether a standardized approach to specimen selection for RABV characterization could enhance detection of a sentinel event in virus dissemination among bats.
SAMPLE
United States public health rabies surveillance system data collected in January 2010 through December 2015.
PROCEDURES
The number of rabies-tested bats for which species was reported and the number of RABV-positive samples for which virus characterization would likely provide information regarding introduction of novel RABV variants and translocation and host-shift events were calculated. These specimens were designated as specimens of epizootiological importance (SEIs). Additionally, the estimated test load that public health laboratories could expect if all SEIs underwent RABV characterization was determined.
RESULTS
Species was reported for 74,928 of 160,017 (47%) bats submitted for rabies testing. Identified SEIs were grouped in 3 subcategories, namely nonindigenous bats; bats in southern border states, Florida, Puerto Rico, and the US Virgin Islands; and bats of species that are not commonly found to be inflected with RABV. Annually, 692 (95% CI, 600 to 784) SEIs were identified, of which only 295 (95% CI, 148 to 442) underwent virus characterization. Virus characterization of all SEIs would be expected to increase public health laboratories' overall test load by 397 (95% CI, 287 to 506) samples each year.
CONCLUSIONS AND CLINICAL RELEVANCE
Species identification and RABV characterization may aid detection of a sentinel event in bat RABV dissemination. With additional resources, RABV characterization of all SEIs as a standardized approach to testing could contribute to knowledge of circulating bat RABV variants.
Topics: Animals; Chiroptera; Florida; Puerto Rico; Rabies; Rabies virus; United States
PubMed: 31841089
DOI: 10.2460/javma.256.1.77 -
PloS One 2021Rabies is a viral disease of animals and people causing fatal encephalomyelitis if left untreated. Although effective pre- and post-exposure vaccines exist, they are not...
BACKGROUND
Rabies is a viral disease of animals and people causing fatal encephalomyelitis if left untreated. Although effective pre- and post-exposure vaccines exist, they are not widely available in many endemic countries within Africa. Since many individuals in these countries remain at risk of infection, post-exposure healthcare-seeking behaviors are crucial in preventing infection and warrant examination.
METHODOLOGY
A rabies knowledge, attitudes, and practices survey was conducted at 24 geographically diverse sites in Uganda during 2013 to capture information on knowledge concerning the disease, response to potential exposure events, and vaccination practices. Characteristics of the surveyed population and of the canine-bite victim sub-population were described. Post-exposure healthcare-seeking behaviors of canine-bite victims were examined and compared to the related healthcare-seeking attitudes of non-bite victim respondents. Wealth scores were calculated for each household, rabies knowledge was scored for each non-bitten survey respondent, and rabies exposure risk was scored for each bite victim. Logistic regression was used to determine the independent associations between different variables and healthcare-seeking behaviors among canine-bite victims as well as attitudes of non-bitten study respondents.
RESULTS
A total of 798 households were interviewed, capturing 100 canine-bite victims and a bite incidence of 2.3 per 100 person-years. Over half of bite victims actively sought medical treatment (56%), though very few received rabies post-exposure prophylaxis (3%). Bite victims who did not know or report the closest location where PEP could be received were less likely to seek medical care (p = 0.05). Respondents who did not report having been bitten by a dog with higher knowledge scores were more likely to respond that they would both seek medical care (p = 0.00) and receive PEP (p = 0.06) after a potential rabies exposure event.
CONCLUSIONS
There was varying discordance between what respondents who did not report having been bitten by a dog said they would do if bitten by a dog when compared to the behaviors exhibited by canine-bite victims captured in the KAP survey. Bite victims seldom elected to wash their wound or receive PEP. Having lower rabies knowledge was a barrier to theoretically seeking care and receiving PEP among not bitten respondents, indicating a need for effective and robust educational programs in the country.
Topics: Adult; Animals; Bites and Stings; Cross-Sectional Studies; Dogs; Female; Health Facilities; Health Knowledge, Attitudes, Practice; Humans; Incidence; Male; Patient Acceptance of Health Care; Post-Exposure Prophylaxis; Rabies; Rabies Vaccines; Rabies virus; Surveys and Questionnaires; Uganda
PubMed: 34077427
DOI: 10.1371/journal.pone.0251702