We present an approach to computing the probability of epidemic "burnout," i.e., the probability that a newly emergent pathogen will go extinct after a major epidemic. Our analysis is based on the ...standard stochastic formulation of the Susceptible-Infectious-Removed (SIR) epidemic model including host demography (births and deaths) and corresponds to the standard SIR ordinary differential equations (ODEs) in the infinite population limit. Exploiting a boundary layer approximation to the ODEs and a birth-death process approximation to the stochastic dynamics within the boundary layer, we derive convenient, fully analytical approximations for the burnout probability. We demonstrate-by comparing with computationally demanding individual-based stochastic simulations and with semi-analytical approximations derived previously-that our fully analytical approximations are highly accurate for biologically plausible parameters. We show that the probability of burnout always decreases with increased mean infectious period. However, for typical biological parameters, there is a relevant local minimum in the probability of persistence as a function of the basic reproduction number Formula: see text. For the shortest infectious periods, persistence is least likely if Formula: see text; for longer infectious periods, the minimum point decreases to Formula: see text. For typical acute immunizing infections in human populations of realistic size, our analysis of the SIR model shows that burnout is almost certain in a well-mixed population, implying that susceptible recruitment through births is insufficient on its own to explain disease persistence.
The development of a rapid, specific, and sensitive SYBR Green I-based duplex real-time quantitative PCR assay is described for the simultaneous detection of porcine epidemic diarrhea virus (PEDV) ...and porcine circovirus type 3 (PCV3). The assay specifically detected PEDV and PCV3, with no fluorescence detected for other non-targeted pig pathogens. The assay showed a good linear relationship, and the limits of detection for this assay were 34.6 copies/μL and 61.2 copies/μL for PEDV and PCV3, respectively. The assay exhibited high repeatability and reproducibility, with intra-assay and inter-assay variation coefficients less than 2.0%. A clinical evaluation using intestinal tissue and fecal samples from piglets suffering from diarrhea at different pig farms in China revealed that the singular infection rates of PEDV and PCV3 were 43.94% (29/66) and 16.67% (11/66), respectively, while the co-infection rate of PCV3 with PEDV was 27.27% (18/66). The results indicate this assay is a rapid and reliable diagnostic tool for PEDV and PCV3 monitoring and surveillance in the field, and provides technical support for the quantitative detection of clinical samples infected or co-infected with PEDV and PCV3.
•PED outbreaks have been resulted in a huge economic loss in the pig farming industry.•PCV3 is a novel virus and has been detected in piglets affected with diarrhea.•A duplex qPCR assay was developed for the simultaneous detection of PEDV and PCV3.•The LOD for this assay were 34.6 copies/μL and 61.2 copies/μL for PEDV and PCV3, respectively.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To capture the impact of spatial heterogeneity of environment and movement of individuals on the persistence and extinction of a disease, Allen et al. in L.J.S. Allen, B.M. Bolker, Y. Lou, A.L. ...Nevai, Asymptotic profiles of the steady states for an SIS epidemic reaction–diffusion model, Discrete Contin. Dyn. Syst. Ser. A 21 (1) (2008) 1–20 proposed a spatial SIS (susceptible-infected-susceptible) reaction–diffusion model, and studied the existence, uniqueness and particularly the asymptotic behavior of the endemic equilibrium as the diffusion rate of the susceptible individuals goes to zero in the case where a so-called low-risk subhabitat is created. In this work, we shall provide further understanding of the impacts of large and small diffusion rates of the susceptible and infected population on the persistence and extinction of the disease, which leads us to determine the asymptotic behaviors of the endemic equilibrium when the diffusion rate of either the susceptible or infected population approaches to infinity or zero in the remaining cases. Consequently, our results reveal that, in order to eliminate the infected population at least in low-risk area, it is necessary that one will have to create a low-risk subhabitat and reduce at least one of the diffusion rates to zero. In this case, our results also show that different strategies of controlling the diffusion rates of individuals may lead to very different spatial distributions of the population; moreover, once the spatial environment is modified to include a low-risk subhabitat, the optimal strategy of eradicating the epidemic disease is to restrict the diffusion rate of the susceptible individuals rather than that of the infected ones.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Menstrual blood-derived MSC transplantation lower mortality of H7N9-induced ARDS.•Prospective and systematic study of H7N9-induced pneumonia to assess health status.•MSC transplantation has not ...harmful effect in human body with long-term follow-up.•MSC-based therapy is an alternative way to treat COVID-19 in severe ARDS patient.
H7N9 viruses quickly spread between mammalian hosts and carry the risk of human-to-human transmission, as shown by the 2013 outbreak. Acute respiratory distress syndrome (ARDS), lung failure, and acute pneumonia are major lung diseases in H7N9 patients. Transplantation of mesenchymal stem cells (MSCs) is a promising choice for treating virus-induced pneumonia, and was used to treat H7N9-induced ARDS in 2013. The transplant of MSCs into patients with H7N9-induced ARDS was conducted at a single center through an open-label clinical trial. Based on the principles of voluntariness and informed consent, 44 patients with H7N9-induced ARDS were included as a control group, while 17 patients with H7N9-induced ARDS acted as an experimental group with allogeneic menstrual-blood-derived MSCs. It was notable that MSC transplantation significantly lowered the mortality of the experimental group, compared with the control group (17.6% died in the experimental group while 54.5% died in the control group). Furthermore, MSC transplantation did not result in harmful effects in the bodies of four of the patients who were part of the five-year follow-up period. Collectively, these results suggest that MSCs significantly improve the survival rate of H7N9-induced ARDS and provide a theoretical basis for the treatment of H7N9-induced ARDS in both preclinical research and clinical studies. Because H7N9 and the coronavirus disease 2019 (COVID-19) share similar complications (e.g., ARDS and lung failure) and corresponding multi-organ dysfunction, MSC-based therapy could be a possible alternative for treating COVID-19.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Porcine epidemic diarrhea virus
(PEDV) is the causative agent of porcine epidemic diarrhea, which can cause death in suckling piglets. Vaccines confer only partial protection against new mutant ...strains, whereas antibodies targeting virus-encoded proteins may be effective prophylactics. In this study, we constructed a recombinant single chain variable fragment (scFv) library from the spleens of two pigs immunized with a recombinant PEDV nucleocapsid (N) protein. Among the positive clones directed against PEDV N protein isolated from the library, four scFvs that showed higher affinity for N were functionally analyzed. These scFvs specifically bound to the PEDV N protein, but not to the
transmissible gastroenteritis virus
(TGEV) N protein. Their framework regions were highly conserved, whereas their complementarity-determining regions displayed clear diversity. An immunofluorescence assay showed the co-localization of the four scFvs with PEDV N protein in cells. They significantly suppressed PEDV replication, detected with reverse transcription (RT)-quantitative PCR (qPCR;
P
< 0.01). Two of them significantly reduced the viral titer at 48 hpi and 72 hpi (
P
< 0.05). In addition, they observably suppressed the production of viral protein at 72 hpi. The expression of interferons, interferon regulatory factor 3 (IRF3), and IRF7 was assessed with RT-qPCR, which indicated that PEDV dramatically suppressed the transcription of interferon-λ1 and IRF7 and that the scFvs significantly upregulated their expression (
P
< 0.05). These findings facilitated the investigation of the mechanism by which PEDV evaded the host immune response and suggested that these porcine scFvs were potential candidate agents for the prevention and treatment of porcine diarrhea caused by PEDV.
Key points
• Four scFvs targeting PEDV N protein were generated from porcine spleens
• These scFvs co-localized with PEDV N protein and suppressed PEDV replication
• These scFvs significantly upregulated IFN-λ1 expression
Graphical abstract
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CEKLJ, DOBA, EMUNI, FZAB, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Porcine epidemic diarrhea virus (PEDV) causes high mortality in neonatal piglets. The PEDV spike (S) protein contains two intracellular sorting motifs, YxxΦ (tyrosine-based motif YEVF or YEAF) and ...KVHVQ at the cytoplasmic tail, yet their functions have not been fully elucidated. Some Vero cell-adapted and/or attenuated PEDV variants contain ablations in these two motifs. We hypothesized that these motifs contribute to viral pathogenicity. By transiently expressing PEDV S proteins with mutations in the motifs, we confirmed that the motif KVHVQ is involved in retention of the S proteins in the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC). In addition, we showed that the YxxΦ motif triggers endocytosis of S proteins. These two motifs synergistically regulate the level of S expressed on the cell surface. To investigate their role in viral pathogenicity, we generated three recombinant PEDVs by introducing deletions or a mutation in the two motifs of the infectious clone of PEDV PC22A strain (icPC22A): (i) icΔ10aa (ΔYxxΦEKVHVQ), (ii) icΔ5aa (ΔKVHVQ), and (iii) icYA (Y1378A, to an inactivated motif, AEVF). Infection of Vero cells with icΔ10aa resulted in larger syncytia and more virions, with reduced numbers of S protein projections on the surface compared with icPC22A. Furthermore, we orally inoculated five groups of 5-day-old gnotobiotic piglets with the three mutants, icPC22A, or a mock treatment. Mutant icΔ10aa caused less severe diarrhea rate and significantly milder intestinal lesions than icPC22A, icΔ5aa, and icYA. These data suggest that the deletion of both motifs can reduce the virulence of PEDV in piglets.
Many coronaviruses (CoVs) possess conserved motifs YxxΦ and/or KxHxx/KKxx in the cytoplasmic tail of the S protein. The KxHxx/KKxx motif has been identified as the ER retrieval signal, but the function of the YxxΦ motif in the intracellular sorting of CoV S proteins remains controversial. In this study, we showed that the YxxΦ of PEDV S protein is an endocytosis signal. Furthermore, using reverse genetics technology, we evaluated its role in PEDV pathogenicity in neonatal piglets. Our results explain one attenuation mechanism of Vero cell-adapted PEDV variants lacking functional YxxΦ and KVHVQ motifs. Knowledge from this study may aid in the design of efficacious live attenuated vaccines against PEDV, as well as other CoVs bearing the same motif in their S protein.
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The disease was first detected in Wuhan, the capital of China's Hubei province, ...in December 2019 and has since spread globally, especially to Europe and North America, resulting in the ongoing global coronavirus pandemic disaster of 2019-2020. Although most cases have mild symptoms, there is some progression to viral pneumonia and multi-organ failure and death. More than 4.6 million cases have been registered across 216 countries and territories as of 19 April 2020, resulting in more than 311,000 deaths. Risk to communities with continued widespread disease transmission depends on characteristics of the virus, including how well it spreads between people; the severity of resulting illness; and the medical or other measures available to control the impact of the virus (for example, vaccines or medications that can treat the illness) and the relative success of these. In the absence of vaccines or medications, non-pharmaceutical interventions were the most important response strategy based on community interventions such as person-to-person distancing, mask-wearing, isolation and good personal hygiene (hand-washing)-all of which have been demonstrated can reduce the impact of this seemingly unstoppable globally spreading natural disaster. This paper presents the results of quantitative research regarding the level of citizen preparedness for disasters caused by coronavirus disease (COVID-19) in Serbia. The survey was conducted using a questionnaire that was requested and then collected online among 975 respondents during disaster in April 2020. The questionnaire examined citizens' basic socio-economic and demographic characteristics, their knowledge, preparedness, risk perception and preventive measures taken individually and as a community to prevent the death and widespread transmission of novel coronavirus disease 2019 in the Republic of Serbia. Based on the findings that there are major differences in the public's perception of risks posed by communicable disease threats such as presented by COVID-19, emergency management agencies should use these differences to develop targeted strategies to enhance community and national preparedness by promoting behavioral change and improving risk management decision-making.
Porcine epidemic diarrhea virus (PEDV) is the predominant cause of severe entero-pathogenic diarrhea in swine. The lack of effective therapeutical treatment underlines the importance of research for ...new antivirals. In this study, we identified Q7R, which actively inhibited PEDV replication with a 50% inhibitory concentration (IC
50) of 0.014
μg/mL. The 50% cytotoxicity concentration (CC
50) of Q7R was over 100
μg/mL and the derived therapeutic index was 7142. Several structural analogues of Q7R, quercetin, apigenin, luteolin and catechin, also showed moderate anti-PEDV activity. Antiviral drugs and natural compounds revealed ribavirin, interferon-α, coumarin and tannic acid have relative weaker efficacy compared to Q7R. Q7R did not directly interact with or inactivate PEDV particles and affect the initial stage of PEDV infection by interfering of PEDV replication. Also, the effectiveness of Q7R against the other two viruses (TGEV, PRCV) was lower compared to PEDV. Q7R could be considered as a lead compound for development of anti-PEDV drugs to may be used to during the early stage of PEDV replication and the structure-activity data of Q7R may usefully guideline to design other related antiviral agents.
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