scholarly journals Autoclave treatment of the classical scrapie agent US No. 13-7 and experimental inoculation to susceptible VRQ/ARQ sheep via the oral route results in decreased transmission efficiency

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243009
Author(s):  
Eric D. Cassmann ◽  
Najiba Mammadova ◽  
Justin J. Greenlee
Keyword(s):  
Incubation Period ◽  
Brain Homogenate ◽  
Transmission Efficiency ◽  
Oral Route ◽  
Classical Scrapie ◽  
Time Interval ◽  
Post Inoculation ◽  
Autoclave Treatment ◽  
Scrapie Strain ◽  
Rectal Biopsies

Scrapie, a prion disease of sheep, is highly resistant to conventional deactivation. Numerous methods to deactivate scrapie have been tested in laboratory animal models, and adequate autoclave treatment can reduce or remove the infectivity of some classical scrapie strains depending on the heating parameters used. In this study, we autoclaved brain homogenate from a sheep with US scrapie strain 13–7 for 30 minutes at 121°C. Genetically susceptible VRQ/ARQ sheep were orally inoculated with 3 grams of the autoclaved brain homogenate. For comparison, a second group of sheep was inoculated with a non-autoclaved brain homogenate. Rectal biopsies were used to assess antemortem scrapie disease progression throughout the study. Five out of ten (5/10) sheep that received autoclaved inoculum ultimately developed scrapie after an experimental endpoint of 72 months. These sheep had a mean incubation period of 26.99 months. Two out of five (2/5) positive sheep had detectable PrPSc in antemortem rectal biopsies, and two (2/5) other sheep had PrPSc in postmortem rectal tissue. A single sheep (1/5) was positive for scrapie in the CNS, small intestine, and retropharyngeal lymph node but had negative rectal tissue. All of the sheep (10/10) that received non-autoclaved inoculum developed scrapie with a mean incubation period of 20.2 months and had positive rectal biopsies at the earliest timepoint (14.7 months post-inoculation). These results demonstrate that sheep are orally susceptible to US derived classical scrapie strain 13–7 after autoclave treatment at 121°C for 30 minutes. Differences in incubation periods and time interval to first positive rectal biopsies indicate a partial reduction in infectivity titers for the autoclaved inoculum group.

Second passage of chronic wasting disease of mule deer to sheep by intracranial inoculation compared to classical scrapie

2021 ◽  
pp. 104063872110176
Author(s):  
Eric D. Cassmann ◽  
Rylie D. Frese ◽  
Justin J. Greenlee
Keyword(s):  
Chronic Wasting Disease ◽  
Mule Deer ◽  
Brain Homogenate ◽  
Classical Scrapie ◽  
Species Barrier ◽  
Wasting Disease ◽  
Detection Techniques ◽  
Scrapie Strain ◽  
Scrapie Strains ◽  
Current Detection

The origin of chronic wasting disease (CWD) in cervids is unclear. One hypothesis suggests that CWD originated from scrapie in sheep. We compared the disease phenotype of sheep-adapted CWD to classical scrapie in sheep. We inoculated sheep intracranially with brain homogenate from first-passage mule deer CWD in sheep (sCWDmd). The attack rate in second-passage sheep was 100% (12 of 12). Sheep had prominent lymphoid accumulations of PrPSc reminiscent of classical scrapie. The pattern and distribution of PrPSc in the brains of sheep with CWDmd was similar to scrapie strain 13-7 but different from scrapie strain x124. The western blot glycoprofiles of sCWDmd were indistinguishable from scrapie strain 13-7; however, independent of sheep genotype, glycoprofiles of sCWDmd were different than x124. When sheep genotypes were evaluated individually, there was considerable overlap in the glycoprofiles that precluded significant discrimination between sheep CWD and scrapie strains. Our data suggest that the phenotype of CWD in sheep is indistinguishable from some strains of scrapie in sheep. Given our results, current detection techniques would be unlikely to distinguish CWD in sheep from scrapie in sheep if cross-species transmission occurred naturally. It is unknown if sheep are naturally vulnerable to CWD; however, the susceptibility of sheep after intracranial inoculation and lymphoid accumulation indicates that the species barrier is not absolute.

Susceptibility of Common Family Anatidae Bird Species to Clade 2.3.4.4e H5N6 High Pathogenicity Avian Influenza Virus: An Experimental Infection Study

2021 ◽  
Author(s):  
Kosuke Soda ◽  
Yukiko Tomioka ◽  
Chiharu Hidaka ◽  
Mayu Matsushita ◽  
Tatsufumi Usui ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Late Phase ◽  
Clinical Signs ◽  
Bird Species ◽  
Oral Route ◽  
Post Inoculation ◽  
Infectious Dose ◽  
Epidemic Season ◽  
Source Of Infection ◽  
High Pathogenicity

Abstract Background: There were large outbreaks of high pathogenicity avian influenza (HPAI) caused by clade 2.3.4.4e H5N6 viruses in the winter of 2016–2017 in Japan, which caused large numbers of deaths among several endangered bird species including cranes, raptors, and birds in Family Anatidae. In this study, susceptibility of common Anatidae to a clade 2.3.4.4e H5N6 HPAI virus was assessed to evaluate their potential to be a source of infection for other birds. Eurasian wigeons (Mareca penelope), mallards (Anas platyrhynchos), and Northern pintails (Anas acuta) were intranasally inoculated with 106, 104, or 102 50% egg infectious dose (EID50) of clade 2.3.4.4e A/teal/Tottori/1/2016 (H5N6). Results: All birds survived for 10 days without showing any clinical signs of infection. Most ducks inoculated with ≥104 EID50 of virus seroconverted within 10 days post-inoculation (dpi). Virus was mainly shed via the oral route for a maximum of 10 days, followed by cloacal route in late phase of infection. Virus remained in the pancreas of some ducks at 10 dpi. Viremia was observed in some ducks euthanized at 3 dpi, and ≤106.3 EID50 of virus was recovered from systemic tissues and swab samples including eyeballs and conjunctival swabs. Conclusions: These results indicate that the subject duck species have a potential to be a source of infection of clade 2.3.4.4e HPAI virus to the environment and other birds sharing their habitats. Captive ducks should be reared under isolated or separated circumstances during the HPAI epidemic season to prevent infection and further viral dissemination.

scholarly journals Application of artificial neural networks to predict the COVID-19 outbreak

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Hamid Reza Niazkar ◽  
Majid Niazkar
Keyword(s):  
Neural Networks ◽  
Artificial Neural Networks ◽  
Incubation Period ◽  
Prediction Models ◽  
Time Interval ◽  
Policy Makers ◽  
Ann Models ◽  
Artificial Neural ◽  
Relative Errors ◽  
Mean Square Errors

Abstract Background Millions of people have been infected worldwide in the COVID-19 pandemic. In this study, we aim to propose fourteen prediction models based on artificial neural networks (ANN) to predict the COVID-19 outbreak for policy makers. Methods The ANN-based models were utilized to estimate the confirmed cases of COVID-19 in China, Japan, Singapore, Iran, Italy, South Africa and United States of America. These models exploit historical records of confirmed cases, while their main difference is the number of days that they assume to have impact on the estimation process. The COVID-19 data were divided into a train part and a test part. The former was used to train the ANN models, while the latter was utilized to compare the purposes. The data analysis shows not only significant fluctuations in the daily confirmed cases but also different ranges of total confirmed cases observed in the time interval considered. Results Based on the obtained results, the ANN-based model that takes into account the previous 14 days outperforms the other ones. This comparison reveals the importance of considering the maximum incubation period in predicting the COVID-19 outbreak. Comparing the ranges of determination coefficients indicates that the estimated results for Italy are the best one. Moreover, the predicted results for Iran achieved the ranges of [0.09, 0.15] and [0.21, 0.36] for the mean absolute relative errors and normalized root mean square errors, respectively, which were the best ranges obtained for these criteria among different countries. Conclusion Based on the achieved results, the ANN-based model that takes into account the previous fourteen days for prediction is suggested to predict daily confirmed cases, particularly in countries that have experienced the first peak of the COVID-19 outbreak. This study has not only proved the applicability of ANN-based model for prediction of the COVID-19 outbreak, but also showed that considering incubation period of SARS-COV-2 in prediction models may generate more accurate estimations.

scholarly journals Animal Model To Study Klebsiella pneumoniae Gastrointestinal Colonization and Host-to-Host Transmission

2020 ◽  
Vol 88 (11) ◽  
Author(s):  
Taylor M. Young ◽  
Andrew S. Bray ◽  
Ravinder K. Nagpal ◽  
David L. Caudell ◽  
Hariom Yadav ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Close Contact ◽  
Epidemiological Studies ◽  
Multidrug Resistant ◽  
Transmission Efficiency ◽  
Oral Route ◽  
Human Infection ◽  
Gi Tract ◽  
Content Type ◽  
Immunocompetent Mice

ABSTRACT An important yet poorly understood facet of the life cycle of a successful pathogen is host-to-host transmission. Hospital-acquired infections (HAI) resulting from the transmission of drug-resistant pathogens affect hundreds of millions of patients worldwide. Klebsiella pneumoniae, a Gram-negative bacterium, is notorious for causing HAI, with many of these infections difficult to treat, as K. pneumoniae has become multidrug resistant. Epidemiological studies suggest that K. pneumoniae host-to-host transmission requires close contact and generally occurs through the fecal-oral route. Here, we describe a murine model that can be utilized to study mucosal (oropharynx and gastrointestinal [GI]) colonization, shedding within feces, and transmission of K. pneumoniae through the fecal-oral route. Using an oral route of inoculation, and fecal shedding as a marker for GI colonization, we showed that K. pneumoniae can asymptomatically colonize the GI tract in immunocompetent mice and modifies the host GI microbiota. Colonization density within the GI tract and levels of shedding in the feces differed among the clinical isolates tested. A hypervirulent K. pneumoniae isolate was able to translocate from the GI tract and cause hepatic infection that mimicked the route of human infection. Expression of the capsule was required for colonization and, in turn, robust shedding. Furthermore, K. pneumoniae carrier mice were able to transmit to uninfected cohabitating mice. Lastly, treatment with antibiotics led to changes in the host microbiota and development of a transient supershedder phenotype, which enhanced transmission efficiency. Thus, this model can be used to determine the contribution of host and bacterial factors toward K. pneumoniae dissemination.

scholarly journals An Animal Model to Study Klebsiella pneumoniae Gastro-Intestinal Colonization and Host-to-Host Transmission

2020 ◽  
Author(s):  
Taylor M. Young ◽  
Andrew S. Bray ◽  
Ravinder K. Nagpal ◽  
David L. Caudell ◽  
Hariom Yadav ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Close Contact ◽  
Epidemiological Studies ◽  
Transmission Efficiency ◽  
Oral Route ◽  
Human Infection ◽  
Drug Resistant ◽  
Gi Tract ◽  
Fecal Shedding ◽  
Immunocompetent Mice

AbstractAn important yet poorly understood facet in the life cycle of a successful pathogen is the host-to-host transmission. Hospital-acquired infections (HAI) resulting from the transmission of drug-resistant pathogens affect hundreds of millions of patients worldwide. Klebsiella pneumoniae (Kpn), a gram-negative bacterium, is notorious for causing HAI, with many of these infections difficult to treat as Kpn has become multi-drug resistant. Epidemiological studies suggest that Kpn host-to-host transmission requires close contact and generally occurs through the fecal-oral route. Herein, we describe a murine model that can be utilized to study mucosal (oropharynx and gastrointestinal [GI]) colonization, shedding within feces, and transmission of Kpn through the fecal-oral route. Using an oral route of inoculation, and fecal shedding as a marker for GI colonization, we show that Kpn can asymptomatically colonize the GI tract of immunocompetent mice, and modifies the host GI microbiota. Colonization density within the GI tract and levels of shedding in the feces differed among the clinical isolates tested. A hypervirulent Kpn isolate was able to translocate from the GI tract and cause hepatic infection that mimicked the route of human infection. Expression of the capsule was required for colonization and, in turn, robust shedding. Furthermore, Kpn carrier mice were able to transmit to uninfected cohabitating mice. Lastly, treatment with antibiotics led to changes in the host microbiota and development of a transient super-shedder phenotype, which enhanced transmission efficiency. Thus, this model can be used to determine the contribution of host and bacterial factors towards Kpn dissemination.

scholarly journals PrP(d) accumulation in organs of ARQ/ARQ sheep experimentally infected with BSE by peripheral routes.

2006 ◽  
Vol 53 (2) ◽  
pp. 399-405 ◽  
Author(s):  
Stéphane Lezmi ◽  
Frédéric Ronzon ◽  
Anna Bencsik ◽  
Alexandre Bedin ◽  
Didier Calavas ◽  
...  
Keyword(s):  
Prion Protein ◽  
Peripheral Nerves ◽  
Clinical Symptoms ◽  
Prion Diseases ◽  
Small Ruminants ◽  
Brain Homogenate ◽  
Spongiform Encephalopathy ◽  
Post Inoculation ◽  
Muscle Types ◽  
Immunohistochemical Methods

To study the pathogenesis of bovine spongiform encephalopathy infection in small ruminants, two Lacaune sheep with the AA136RR154QQ171 and one with the AA136RR154RR171 genotype for the prion protein, were inoculated with a brain homogenate from a French cattle BSE case by peripheral routes. Sheep with the ARQ/ARQ genotype are considered as susceptible to prion diseases contrary to those with the ARR/ARR genotype. The accumulation of disease-associated prion protein (PrP(d)) was analysed by biochemical and immunohistochemical methods. No PrP(d) accumulation was detected in samples from the ARR/ARR sheep 2 years post inoculation. In the two ARQ/ARQ sheep that had scrapie-like clinical symptoms, PrP(d) was found in the central, sympathetic and enteric nervous systems and in lymphoid organs. Remarkably, PrP(d) was also detected in some muscle types as well as in all peripheral nerves that had not been reported previously thus revealing a widespread distribution of BSE-associated PrP(d) in sheep tissues.

Influence of Temperature on the Pathogenesis and Gene Expression of Rhizoctonia solani Causing Web Blight/Wet Root Rot Disease in Mungbean

2020 ◽  
Author(s):  
Bishnu Maya Bashyal ◽  
Bhupendra Singh Kharayat ◽  
Pooja Parmar ◽  
Ashish Kumar Gupta ◽  
S. C. Dubey ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Rhizoctonia Solani ◽  
Root Rot ◽  
Time Interval ◽  
Post Inoculation ◽  
Root Rot Disease ◽  
Different Temperatures ◽  
Rot Disease ◽  
Blight Disease ◽  
Web Blight

Background: Mungbean (Vigna radiata L. Wilzeck) is one of the most important pulse crops and grown in almost all parts of the India. Web blight/wet root rot disease of mungbean is caused by Rhizoctonia solani Kühn. Crop environmental factors plays a vital role in the development of web blight disease caused by R. solani. An understanding of the role of environmental factors on the infection and survival of the pathogen is necessary to develop disease management practices. Methods: The effect of different temperatures (4oC, 20oC, 25oC, 30oC and 35oC) on mycelial growth of seven different R. solani isolates belonging to different anastomosis group were evaluated under in vitro conditions. Effect of different temperatures on the development of root rot/web blight disease of mungbean was also evaluated under phytotron conditions at various temperatures with constant relative humidity (85%) and illumination (alternate dark and light period of 12 h). Effect of temperatures on the expression of selected pathogenicity related genes was evaluated through real time PCR. Result: Maximum radial growth in R. solani isolates was observed at 25 and 30oC after 48 hrs of incubation. Maximum disease incidence was observed with R. solani isolate RUPU-18 (73.11%) followed by R-17 (68.75%), RDLM-1 (63.45%) at 25oC on mungbean genotype Pusa Vishal. Expression of genes like ABC transporter was observed only at 35oC, while other genes like 1, 3 glucan hydrolase expressed maximum at 25oC after 24, 48 and 72 hrs post inoculation. Present study suggested that the expression of pathogenicity related genes in mungbean-R. solani system is dependent on the temperature and time interval post pathogen inoculation.

Inoculation of the attenuated Coxsackievirus B3 Sabin3-like strain induces a protection against virulent CVB3 Nancy and CVB4 E2 strains in Swiss mice by both oral and intraperitoneal routes

Biologia ◽  
2014 ◽  
Vol 69 (1) ◽  
Author(s):  
Nadia Jrad-Battikh ◽  
Amira Souii ◽  
Rym Hadhri ◽  
Mahjoub Aouni ◽  
Jawhar Gharbi ◽  
...  
Keyword(s):  
Coxsackievirus B3 ◽  
Oral Route ◽  
Post Inoculation ◽  
Translation Efficiency ◽  
Post Challenge ◽  
Genomic Context ◽  
Swiss Mice ◽  
Cvb3 Infection ◽  
Wild Strains

AbstractWe have previously addressed the question of whether the attenuating mutations of domain V of the Poliovirus IRES were specific for a given genomic context or whether they could be extrapolated to a genomic related virus, the Coxsackievirus B3 (CVB3). Accordingly, we have described that Sabin3-like mutation (U473→C) introduced in the CVB3 genome led to a defective mutant with a serious reduction in translation efficiency. In this study, we assessed the protection provided by the Sabin3-like mutant against CVB3 infection. For this purpose, we analyzed, in vivo, the Sabin3-like phenotype in Swiss mice inoculated with CVB3 and CVB4 E2 prototype strains either by oral or intraperitoneal (i.p) routes and explored the capacity of this mutant to act as a vaccine vector after the challenge. The Sabin3-like RNA was detected by semi-nested PCR in different organs: heart, pancreas and intestine at 10 days post-inoculation with both oral and i.p routes. Additionally, we did not observe any histological alterations in heart and intestine tissues. RNA was detected in the different organs of all mice immunized with the Sabin3-like strain and challenged with either CVB3 or CVB4 E2 by oral route at 7 days post-challenge. In contrast, no histological alteration of heart or pancreas tissues was observed after challenge with both wild-strains. Interestingly, the detection of viral RNA in heart, pancreas and intestine of mice immunized by i.p route was negative at 7 days post-challenge with CVB3 and CVB4 E2, and mice were protected from myocarditis and pancreatitis.

scholarly journals Relevance of oral experimental challenge with classical scrapie in sheep

2010 ◽  
Vol 91 (8) ◽  
pp. 2139-2144 ◽  
Author(s):  
Guillaume Tabouret ◽  
Caroline Lacroux ◽  
Séverine Lugan ◽  
Pierrette Costes ◽  
Fabien Corbière ◽  
...  
Keyword(s):  
Incubation Period ◽  
Prion Protein ◽  
Transmissible Spongiform Encephalopathy ◽  
Classical Scrapie ◽  
Spongiform Encephalopathy ◽  
Lymphoid Tissues ◽  
Relevant Model ◽  
Experimental Conditions ◽  
Oral Inoculation ◽  
Experimental Challenge

Oral inoculation is currently considered as the best approach to mimic natural TSE contamination in ruminants. In this study, we compared the timing of abnormal prion protein (PrPSc) dissemination and accumulation in the organism of susceptible sheep either orally inoculated or naturally infected with classical scrapie. Both animal groups shared a similar PrPSc dissemination scheme and accumulation dynamics in lymphoid tissues. However, orally challenged animals displayed an earlier neuro-invasion and a dramatically shorter incubation period than naturally exposed sheep. No differences were observed between the groups with regards to the neuro-invasion route. These results unambiguously indicate that oral inoculation can have an impact on both the earliness of neuro-invasion and the incubation period. They also support the statement that oral inoculation is a relevant model for investigating transmissible spongiform encephalopathy pathogenesis. Nevertheless, data obtained under such experimental conditions should be used with some caution.

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