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BMC Infectious Diseases Mar 2020Rabies is a deadly preventable viral disease that affects all warm-blooded animals and widespread in many regions including Africa. The disease remains of major public...
BACKGROUND
Rabies is a deadly preventable viral disease that affects all warm-blooded animals and widespread in many regions including Africa. The disease remains of major public health importance in Uganda. The purpose of this study was to establish Knowledge, Attitude, Practice (KAP) of Rabies in Moyo and Ntoroko districts and to characterize Rabies virus (RABV) strains from seven districts of Uganda with consistent prevalence of rabies.
METHODS
KAP survey data were collected based on animal biting history by interviewing the head of the veterinary departments, the medical centers and selected households from the study sites. Data were obtained from 84 households in Ntoroko and Moyo districts. Thirty-five (35) brain samples were collected from bovine, dogs, goats, foxes, jackals ad sheep between 2011 and 2013. Samples were tested using fluorescent antibody test (FAT), One step RT-PCR (following RNA extraction) and partial RABV N gene was sequenced by Sanger method before phylogenetic and phylogeographic analyses of sequences.
RESULTS
Scarcity of post-exposure prophylaxis services in the health centers was noted. Poor attitude of wound washing and deficiency of knowledge on how to handle wounds related to dog bites and the significance among household participants lacked. There is a high risk of rabies infection due to a limited dog's vaccination. Dog biting episodes in humans were of 75.00 and 62.50% in Moyo and Ntoroko districts respectively. Twenty-seven (27) samples tested positive for rabies by FAT and PCR. Ugandan sequences were closely related (97% nucleotide id) to the rabies virus sequences from Tanzania, Rwanda, Burundi, Nigeria, Central African Republic and Sudan with both the "Africa 1A" and "Africa 1B" RABV clades represented. A putative new clade 1D was also detected.
CONCLUSIONS
Rabies remains a public health hazard in Uganda. There is urgent need to establish advocacy programs in both schools and communities to curtail the spread of rabies. Increasing the knowledge regarding wound washing, post-exposure prophylaxis and dogs vaccination would enhance prevention of rabies. A strong collaboration between medical and veterinary sectors under a one health platform is required to ensure sufficient preventative services to the communities.
Topics: Adolescent; Adult; Animals; Bites and Stings; Brain; Child; Dog Diseases; Dogs; Female; Health Knowledge, Attitudes, Practice; Humans; Male; Phylogeny; Phylogeography; Post-Exposure Prophylaxis; RNA, Viral; Rabies; Rabies virus; Uganda; Young Adult
PubMed: 32143593
DOI: 10.1186/s12879-020-4934-y -
PLoS Neglected Tropical Diseases Jan 2022Globally, traditional medicine is widely used to treat a variety of injuries and illnesses, including dog bites, and exposures that are risky for rabies. However,... (Review)
Review
INTRODUCTION
Globally, traditional medicine is widely used to treat a variety of injuries and illnesses, including dog bites, and exposures that are risky for rabies. However, efficacy of most traditional remedies used for rabies prevention or treatment has not been demonstrated in controlled trials or proven in community-based surveys.
METHODS
Six databases were searched including the terms rabies, traditional treatment, traditional remedy, traditional therapy, traditional medicine, and medicinal treatment to review traditional remedies used in the prevention and treatment of rabies. In addition, published literature of rabies transmission dynamics was used to estimate statistical likelihood of dog bite victims developing rabies to provide clarity as to why traditional healers have a high apparent success rate when preventing death from rabies in victims bitten by suspected rabid dogs.
RESULTS
Literature review yielded 50 articles, including three controlled experiments, that described use of traditional remedies for rabies prevention and treatment. Traditional remedies for rabies ranged from plant- or animal-based products to spiritual rituals; however, only a few controlled mice trials were conducted, and none of these trials demonstrated efficacy in preventing or treating rabies. Risk of dying from rabies after a bite from a dog with unknown rabies status is low, 1.90% (0.05%-29.60%). Therefore, traditional healers had a 98.10% (70.40%-99.95%) apparent success rate in preventing death from suspected rabid dog bites despite inefficaciousness of herbal remedies.
CONCLUSION
There was no universal plant species or route of administration that was consistently used for rabies prevention or treatment across countries. No traditional remedy was efficacious in the prevention or treatment of rabies in randomized controlled experiments. Understanding the cultural context under which traditional remedies are used may facilitate collaboration of traditional healers with the modern medical system to ensure timely and appropriate use of proven therapies for prevention and clinical management of rabies.
Topics: Animals; Dog Diseases; Dogs; Medicine, Traditional; Phytotherapy; Post-Exposure Prophylaxis; Rabies; Rabies virus
PubMed: 35051178
DOI: 10.1371/journal.pntd.0010087 -
Viruses Jul 2021Rabies virus is a highly neurophilic negative-strand RNA virus with high lethality and remains a huge public health problem in developing countries to date. The...
Rabies virus is a highly neurophilic negative-strand RNA virus with high lethality and remains a huge public health problem in developing countries to date. The double-stranded RNA-binding protein Staufen1 (STAU1) has multiple functions in RNA virus replication, transcription, and translation. However, its function in RABV infection and its mechanism of action are not clear. In this study, we investigated the role of host factor STAU1 in RABV infection of SH-SY-5Y cells. Immunofluorescence, TCID titers, confocal microscopy, quantitative real-time PCR and Western blotting were carried out to determine the molecular function and subcellular distribution of STAU1 in these cell lines. Expression of STAU1 in SH-SY-5Y cells was down-regulated by RNA interference or up-regulated by transfection of eukaryotic expression vectors. The results showed that N proficiently colocalized with STAU1 in SH-SY-5Y at 36 h post-infection, and the expression level of STAU1 was also proportional to the time of infection. Down-regulation of STAU1 expression increased the number of Negri body-like structures, enhanced viral replication, and a caused 10-fold increase in viral titers. Meanwhile, N protein and G protein mRNA levels also accumulated gradually with increasing infection time, which implied that STAU1 inhibited rabies virus infection of SH-SY-5Y cells in vitro. In conclusion, our results provide important clues for the detailed replication mechanism of rabies virus and the discovery of therapeutic targets.
Topics: Cell Line, Tumor; Cytoskeletal Proteins; Host-Pathogen Interactions; Humans; Inclusion Bodies, Viral; Nucleocapsid Proteins; RNA Interference; RNA-Binding Proteins; Rabies virus; Viral Envelope Proteins; Virus Replication
PubMed: 34452292
DOI: 10.3390/v13081426 -
Viruses Aug 2022The Pennsylvania Department of Health Bureau of Laboratories (PABOL) tested 6855 animal samples for rabies using both the direct fluorescent antibody test (DFA) and LN34...
The Pennsylvania Department of Health Bureau of Laboratories (PABOL) tested 6855 animal samples for rabies using both the direct fluorescent antibody test (DFA) and LN34 pan-lyssavirus reverse transcriptase quantitative PCR (RT-qPCR) during 2017-2019. Only two samples (0.03%) were initially DFA negative but positive by LN34 RT-qPCR. Both cases were confirmed positive upon re-testing at PABOL and confirmatory testing at the Centers for Disease Control and Prevention by LN34 RT-qPCR and DFA. Rabies virus sequences from one sample were distinct from all positive samples processed at PABOL within two weeks, ruling out cross-contamination. Levels of rabies virus antigen and RNA were low in all brain structures tested, but were higher in brain stem and rostral spinal cord than in cerebellum, hippocampus or cortex. Taken together, the low level of rabies virus combined with higher abundance in more caudal brain structures suggest early infection. These cases highlight the increased sensitivity and ease of interpretation of LN34 RT-qPCR for low positive cases.
Topics: Animals; Lyssavirus; Pennsylvania; RNA, Viral; RNA-Directed DNA Polymerase; Rabies; Rabies virus; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 36146650
DOI: 10.3390/v14091845 -
Current Opinion in Virology Oct 2014Despite its ability to infect all mammals, Rabies virus persists in numerous species-specific cycles that rarely sustain transmission in alternative species. The... (Review)
Review
Despite its ability to infect all mammals, Rabies virus persists in numerous species-specific cycles that rarely sustain transmission in alternative species. The determinants of these species-associations and the adaptive significance of genetic divergence between host-associated viruses are poorly understood. One explanation is that epidemiological separation between reservoirs causes neutral genetic differentiation. Indeed, recent studies attributed host shifts to ecological factors and selection of 'preadapted' viral variants from the existing viral community. However, phenotypic differences between isolates and broad scale comparative and molecular evolutionary analyses indicate multiple barriers that Rabies virus must overcome through adaptation. This review assesses various lines of evidence and proposes a synthetic hypothesis for the respective roles of ecology and evolution in Rabies virus host shifts.
Topics: Adaptation, Biological; Animals; Biological Evolution; Host Specificity; Host-Pathogen Interactions; Mammals; Rabies; Rabies virus
PubMed: 25064563
DOI: 10.1016/j.coviro.2014.07.004 -
Journal of Veterinary Science Jul 2021Fluorescent antibody virus neutralization (FAVN) test is a standard assay for quantifying rabies virus-neutralizing antibody (VNA) in serum. However, a safer rabies...
BACKGROUND
Fluorescent antibody virus neutralization (FAVN) test is a standard assay for quantifying rabies virus-neutralizing antibody (VNA) in serum. However, a safer rabies virus (RABV) should be used in the FAVN assay. There is a need for a new method that is economical and time-saving by eliminating the immunostaining step.
OBJECTIVES
We aimed to improve the traditional FAVN method by rescuing and characterizing a new recombinant RABV expressing green fluorescent protein (GFP).
METHODS
A new recombinant RABV expressing GFP designated as ERAGS-GFP was rescued using a reverse genetic system. Immuno-fluorescence assay, peroxidase-linked assay, electron microscopy and reverse transcription polymerase chain reaction were performed to confirm the recombinant ERAGS-GFP virus as a RABV expressing the GFP gene. The safety of ERAGS-GFP was evaluated in 4-week-old mice. The rabies VNA titers were measured and compared with conventional FAVN and FAVN-GFP tests using VERO cells.
RESULTS
The virus propagated in VERO cells was confirmed as RABV expressing GFP. The ERAGS-GFP showed the highest titer (10 TCID/mL) in VERO cells at 5 days post-inoculation, and GFP expression persisted until passage 30. The body weight of 4-week-old mice inoculated intracranially with ERAGS-GFP continued to increase and the survival rate was 100%. In 62 dog sera, the FAVN-GFP result was significantly correlated with that of conventional FAVN ( = 0.95).
CONCLUSIONS
We constructed ERAGS-GFP, which could replace the challenge virus standard-11 strain used in FAVN test.
Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Cell Line; Chlorocebus aethiops; Cricetinae; Gene Expression Regulation, Viral; Green Fluorescent Proteins; Rabies virus; Viral Proteins
PubMed: 34313041
DOI: 10.4142/jvs.2021.22.e56 -
Acta Tropica Apr 2021Despite declaration as a national priority disease, dog rabies remains endemic in Liberia, with surveillance systems and disease control activities still developing. The...
Despite declaration as a national priority disease, dog rabies remains endemic in Liberia, with surveillance systems and disease control activities still developing. The objective of these initial efforts was to establish animal rabies diagnostics, foster collaboration between all rabies control stakeholders, and develop a short-term action plan with estimated costs for rabies control and elimination in Liberia. Four rabies diagnostic tests, the direct fluorescent antibody (DFA) test, the direct immunohistochemical test (dRIT), the reverse transcriptase polymerase chain reaction (RT-PCR) assay and the rapid immunochromatographic diagnostic test (RIDT), were implemented at the Central Veterinary Laboratory (CVL) in Monrovia between July 2017 and February 2018. Seven samples (n=7) out of eight suspected animals were confirmed positive for rabies lyssavirus, and molecular analyses revealed that all isolates belonged to the Africa 2 lineage, subgroup H. During a comprehensive in-country One Health rabies stakeholder meeting in 2018, a practical workplan, a short-term action plan and an accurately costed mass dog vaccination strategy were developed. Liberia is currently at stage 1.5/5 of the Stepwise Approach towards Rabies Elimination (SARE) tool, which corresponds with countries that are scaling up local-level interventions (e.g. dog vaccination campaigns) to the national level. Overall an estimated 5.3 - 8 million USD invested over 13 years is needed to eliminate rabies in Liberia by 2030. Liberia still has a long road to become free from dog-rabies. However, the dialogue between all relevant stakeholders took place, and disease surveillance considerably improved through implementing rabies diagnosis at the CVL. The joint efforts of diverse national and international stakeholders laid important foundations to achieve the goal of zero dog-mediated human rabies deaths by 2030.
Topics: Animals; DNA, Viral; Diagnostic Tests, Routine; Dog Diseases; Dogs; Female; Humans; Liberia; Male; Mass Vaccination; Molecular Diagnostic Techniques; Phylogeny; Polymerase Chain Reaction; Rabies; Rabies Vaccines; Rabies virus
PubMed: 33385361
DOI: 10.1016/j.actatropica.2020.105787 -
Emerging Microbes & Infections Dec 2023Marburg virus disease (MVD) is a lethal viral haemorrhagic fever caused by Marburg virus (MARV) with a case fatality rate as high as 88%. There is currently no vaccine...
Marburg virus disease (MVD) is a lethal viral haemorrhagic fever caused by Marburg virus (MARV) with a case fatality rate as high as 88%. There is currently no vaccine or antiviral therapy approved for MVD. Due to high variation among MARV isolates, vaccines developed against one strain fail to protect against other strains. Here we report that three recombinant rabies virus (RABV) vector vaccines encoding two copies of GPs covering both MARV lineages induced pseudovirus neutralizing antibodies in BALB/c mice. Furthermore, high-affinity human neutralizing antibodies were isolated from a humanized mouse model. The three vaccines produced a Th1-biased serological response similar to that of human patients. Adequate sequential immunization enhanced the production of neutralizing antibodies. Virtual docking suggested that neutralizing antibodies induced by the Angola strain seemed to be able to hydrogen bond to the receptor-binding site (RBS) in the GP of the Ravn strain through hypervariable regions 2 (CDR2) and CDR3 of the VH region. These findings demonstrate that three inactivated vaccines are promising candidates against different strains of MARV, and a novel fully humanized neutralizing antibody against MARV was isolated.
Topics: Humans; Animals; Mice; Marburgvirus; Antibodies, Neutralizing; Rabies virus; Antibodies, Viral; Glycoproteins; Marburg Virus Disease; Viral Vaccines
PubMed: 36453198
DOI: 10.1080/22221751.2022.2149351 -
Neurotherapeutics : the Journal of the... Jul 2016Rabies viral encephalitis, though one of the oldest recognized infectious disease of humans, remains an incurable, fatal encephalomyelitis, despite advances in... (Review)
Review
Rabies viral encephalitis, though one of the oldest recognized infectious disease of humans, remains an incurable, fatal encephalomyelitis, despite advances in understanding of its pathobiology. Advances in science have led us on the trail of the virus in the host, but the sanctuaries in which the virus remains hidden for its survival are unknown. Insights into host-pathogen interactions have facilitated evolving immunologic therapeutic strategies, though we are far from a cure. Most of the present-day knowledge has evolved from in vitro studies using fixed (attenuated) laboratory strains that may not be applicable in the clinical setting. Much remains to be unraveled about this elusive virus. This review attempts to re-examine the current advances in understanding of the pathobiology of the rabies virus that modulate the diagnosis, treatment, and prevention of this fatal disease.
Topics: Animals; Encephalitis, Viral; Humans; Post-Exposure Prophylaxis; Pre-Exposure Prophylaxis; Rabies; Rabies virus
PubMed: 27324391
DOI: 10.1007/s13311-016-0452-4 -
Molecular Brain Jan 2022Retrograde tracers based on viral vectors are powerful tools for the imaging and manipulation of upstream neural networks projecting to a specific brain region, and they...
Retrograde tracers based on viral vectors are powerful tools for the imaging and manipulation of upstream neural networks projecting to a specific brain region, and they play important roles in structural and functional studies of neural circuits. However, currently reported retrograde viral tracers have many limitations, such as brain area selectivity or the inability to retrograde label genetically defined brain-wide projection neurons. To overcome these limitations, a new retrograde tracing method, AAV-PHP.eB assisted retrograde tracing systems (PARTS) based on rabies virus, was established through brain-wide TVA-dependent targeting using an AAV-PHP.eB that efficiently crosses the blood-brain barrier in C57BL/6 J mice, and complementation of EnvA-pseudotyped defective rabies virus that specifically recognizes the TVA receptor. Furthermore, combined with Cre transgenic mice, cell-type-specific PARTS (cPARTS) was developed, which can retrograde label genetically defined brain-wide projection neurons. Our research provides new tools and technical support for the analysis of neural circuits.
Topics: Animals; Brain; Genetic Vectors; Interneurons; Mice; Mice, Inbred C57BL; Mice, Transgenic; Rabies virus
PubMed: 35093138
DOI: 10.1186/s13041-022-00898-8