Postmortem confirmation of human rabies source.
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ABSTRACT:
SUBMITTER: Oliveira R
PROVIDER: S-EPMC3374424 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND: The frequent occurrence of ferret badger-associated human rabies cases in southeast China highlights the lack of laboratory-based surveillance and urges revisiting the potential importance of this animal in rabies transmission. To determine if the ferret badgers actually contribute to human and dog rabies cases, and the possible origin of the ferret badger-associated rabies in the region, an active rabies survey was conducted to determine the frequency of rabies infection and seroprevalence in dogs and ferret badgers. METHODS: A retrospective survey on rabies epidemics was performed in Zhejiang, Jiangxi and Anhui provinces in southeast China. The brain tissues from ferret badgers and dogs were assayed by fluorescent antibody test. Rabies virus was isolated and sequenced for phylogenetic analysis. The sera from ferret badgers and dogs were titrated using rabies virus neutralizing antibodies (VNA) test. RESULTS: The ferret badgers presented a higher percentage of rabies seroconversion than dogs did in the endemic region, reaching a maximum of 95% in the collected samples. Nine ferret badger-associated rabies viruses were isolated, sequenced, and were phylogenetically clustered as a separate group. Nucleotide sequence revealed 99.4-99.8% homology within the ferret badger isolates, and 83-89% homology to the dog isolates in the nucleoprotein and glycoprotein genes in the same rabies endemic regions. CONCLUSIONS: Our data suggest ferret badger-associated rabies has likely formed as an independent enzootic originating from dogs during the long-term rabies infestation in southeast China. The eventual role of FB rabies in public health remains unclear. However, management of ferret badger bites, rabies awareness and control in the related regions should be an immediate need.
| S-EPMC2927599 | biostudies-other
Project description:The direct fluorescent antibody test (dFAT) using brain sample after opening the skull is the standard rabies diagnostic test in animal rabies. However, it is not feasible in many resource-limited settings. Lateral flow devices (LFD) combined with a simple sampling methodology is quicker, simpler, and less hazardous than the standard test and can be a useful tool. We conducted a prospective on-site study to evaluate the diagnostic accuracy of the LFD with the straw sampling method compared with that of the dFAT with the skull opening procedure for post-mortem canine rabies diagnosis. We collected 97 rabies-suspected animals between December 1, 2020 and March 31, 2021. Among the 97 samples, 53 and 50 cases were positive tests for dFAT and LFD, respectively. The sensitivity and specificity of LFD with straw sampling method were 94.3% (95% confidence interval [CI], 84.3-98.8%) and 100% (95% CI, 92.0-100%), respectively. The performance of LFD by the straw sampling method showed relatively high sensitivity and 100% specificity compared with that of dFAT performed on samples collected after opening the skull. This methodology can be beneficial and is a strong tool to overcome limited animal surveillance in remote areas. However, because of our limited sample size, more data using fresh samples on-site and the optimizations are urgently needed for the further implementation in endemic areas.
| S-EPMC8659307 | biostudies-literature
Project description:Hydrophobia is a clinical sign characteristic of human rabies. This sign occurs following paroxysmal contractions of pharynx responsible for hydrophobic spasms.
| S-EPMC6293146 | biostudies-literature
Project description:Postmortem human microbiome Raw sequence reads
| PRJNA925138 | ENA
Project description:In Côte d'Ivoire, rabies is endemic and remains largely uncontrolled. The numbers of human exposures and rabies cases are unknown and are probably much higher than reported. Data on human rabies cases are collected by the National Institute of Public Health (NIPH) Anti-rabies Center in Abidjan through a network of 28 NIPH local units, which cover the population of the entire country. During 2014, the NIPH initiated a program to reinforce the human rabies surveillance system in those 28 NIPH local units, with specific goals of improving the infrastructure, training, communication, and government involvement. Here, we report the progress and findings during 2014-2016. The reinforced system recorded 50 cases of human rabies (15-18 cases/year; annual incidence = 0.06-0.08 per 100,000) and more than 30,000 animal exposures (annual incidence = 41.8-48.0 per 100,000). Almost one-half of the human rabies cases were in children ?15 years old. All were fatal and dog bites were the most common route by which rabies virus was transmitted. In the 32 cases where samples of sufficient quality for analysis were available, rabies was confirmed by reverse transcription-polymerase chain reaction RT-PCR. Post-exposure prophylaxis with rabies vaccine was administered to all animal exposure victims presenting at the NIPH local units, although only about 57% completed the full immunization schedule. All available reports were provided by the NIPH local units, indicating effective communication between them and the NIPH Anti-rabies Center. These findings indicate that the reinforcements resulted in highly specific detection of human rabies, provided detailed epidemiological data about these cases, and improved estimates of animal exposure numbers. These represent substantial advances, but further improvements to the surveillance system are needed to increase disease awareness and capture cases that are currently missed by the system. In the future, better communication between local health centers and the NIPH units, surveillance at the local health center level, and increased veterinarian engagement will help provide a more complete picture of the rabies burden in Côte d'Ivoire.
| S-EPMC6126804 | biostudies-literature
Project description:Rabies diagnosis is mainly made on fresh brain tissue postmortem by means of the direct immunofluorescence test. However, in some cases, it is not possible to use this technique, given that the affected nervous tissue goes through a postmortem degradation process, due to problems in the handling and transport of the samples. For this reason, the preservation in time of the rabies virus inclusions was assessed, as well as the immunoreactivity and the ultrastructure of viral particles in tissue with postmortem degradation. Brains of mice inoculated with rabies virus and control mice were processed for conventional histology, immunohistochemistry, electron microscopy, and immunoelectron microscopy in different postmortem times. In the processed tissues for hematoxylin and eosin, the presence of eosinophilic inclusions was not observed beyond 12 h postmortem. Surprisingly, the immunoreactivity of the viral antigens increased with time, at least until 30 h postmortem. It was possible to easily recognize the viral particles by means of conventional electron microscopy until 12 h postmortem. Immunoelectron microscopy allowed us to identify the presence of viral antigens disseminated in the neuronal cytoplasm until 30 h postmortem, but immunoreactive viral particles were not observed. The rabies infection did not cause histological or ultrastructural alterations different from those in the control group as a result of the postmortem degradation. In conclusion, the immunohistochemistry is a reliable test for rabies diagnosis in samples with postmortem degradation and that have been fixed with aldehydes.
| S-EPMC7552013 | biostudies-literature
Project description:BACKGROUND: With microarray technology the expression of thousands of genes can be measured simultaneously. It is well known that the expression levels of genes of interacting proteins are correlated significantly more strongly in Saccharomyces cerevisiae than those of proteins that are not interacting. The objective of this work is to investigate whether this observation extends to the human genome. RESULTS: We investigated the quantitative relationship between expression levels of genes encoding interacting proteins and genes encoding random protein pairs. Therefore we studied 1369 interacting human protein pairs and human gene expression levels of 155 arrays. We were able to establish a statistically significantly higher correlation between the expression levels of genes whose proteins interact compared to random protein pairs. Additionally we were able to provide evidence that genes encoding proteins belonging to the same GO-class show correlated expression levels. CONCLUSION: This finding is concurrent with the naive hypothesis that the scales of production of interacting proteins are linked because an efficient interaction demands that involved proteins are available to some degree. The goal of further research in this field will be to understand the biological mechanisms behind this observation.
| S-EPMC1127109 | biostudies-literature
Project description:The distribution of postmortem damage in mitochondrial DNA retrieved from 37 ancient human DNA samples was analyzed by cloning and was compared with a selection of published animal data. A relative rate of damage (rho(v)) was calculated for nucleotide positions within the human hypervariable region 1 (HVR1) and cytochrome oxidase subunit III genes. A comparison of damaged sites within and between the regions reveals that damage hotspots exist and that, in the HVR1, these correlate with sites known to have high in vivo mutation rates. Conversely, HVR1 subregions with known structural function, such as MT5, have lower in vivo mutation rates and lower postmortem-damage rates. The postmortem data also identify a possible functional subregion of the HVR1, termed "low-diversity 1," through the lack of sequence damage. The amount of postmortem damage observed in mitochondrial coding regions was significantly lower than in the HVR1, and, although hotspots were noted, these did not correlate with codon position. Finally, a simple method for the identification of incorrect archaeological haplogroup designations is introduced, on the basis of the observed spectrum of postmortem damage.
| S-EPMC420011 | biostudies-literature
Project description:DNA double-strand breaks (DSBs) are highly toxic DNA lesions that can lead to chromosomal instability, loss of genes and cancer. The MRE11/RAD50/NBN (MRN) complex is keystone involved in signaling processes inducing the repair of DSB by, for example, in activating pathways leading to homologous recombination repair and nonhomologous end joining. Additionally, the MRN complex also plays an important role in the maintenance of telomeres and can act as a stabilizer at replication forks. Mutations in NBN and MRE11 are associated with Nijmegen breakage syndrome (NBS) and ataxia telangiectasia (AT)-like disorder, respectively. So far, only one single patient with biallelic loss of function variants in RAD50 has been reported presenting with features classified as NBS-like disorder. Here, we report a long-term follow-up of an unrelated patient with facial dysmorphisms, microcephaly, skeletal features, and short stature who is homozygous for a novel variant in RAD50. We could show that this variant, c.2524G > A in exon 15 of the RAD50 gene, induces aberrant splicing of RAD50 mRNA mainly leading to premature protein truncation and thereby, most likely, to loss of RAD50 function. Using patient-derived primary fibroblasts, we could show abnormal radioresistant DNA synthesis confirming pathogenicity of the identified variant. Immunoblotting experiments showed strongly reduced protein levels of RAD50 in the patient-derived fibroblasts and provided evidence for a markedly reduced radiation-induced AT-mutated signaling. Comparison with the previously reported case and with patients presenting with NBS confirms that RAD50 mutations lead to a similar, but distinctive phenotype.
| S-EPMC7318339 | biostudies-literature
Project description:Sixty cases of human rabies in international travelers were reviewed from 1990-2012. A significant proportion of the cases were observed in migrants or their descendants when emigrating from their country of origin or after a trip to visit friends and relatives or for other reasons (43.3%). The cases were not necessarily associated with long-term travel or expatriation to endemic countries; moreover, cases were observed in travelers after short trips of two weeks or less. A predominance of male patients was observed (75.0%). The proportion of children was low (11.7%). Cases from India and Philippines were frequent (16 cases/60). In a significant proportion of cases (51.1%), diagnosis was challenging, with multiple missed diagnoses and transfers from ward to ward before the final diagnosis of rabies. Among the 28 patients whose confirmed diagnosis was obtained ante-mortem, the mean time between hospitalization and diagnosis was 7.7 days (median time: 6.0 days, range 2-30) including four cases with a diagnosis delayed by 15 or more days. In five cases, a patient traveled through one or more countries before ultimately being hospitalized. Three factors played a role in delaying the diagnosis of rabies in a number of cases: (i) a low index of suspicion for rabies in countries where the disease has been eradicated for a long time or is now rare, (ii) a negative history of animal bites or exposure to rabies, and (iii) atypical clinical presentation of the disease. Clinical symptomatology of rabies is complex and commonly confuses physicians. Furthermore, failure in diagnosing imported cases in more developed countries is most likely related to the lack of medical familiarity with even the typical clinical features of the disease.
| S-EPMC3642086 | biostudies-literature