niryuu/sni-each-converted huggingface dataset:
Infectious diseases pose a great danger to public health internationally. The outbreak of SARS has exposed China's fragile public health system and its limited ability to detect and respond to emergencies in a timely and effective manner. In order to strengthen its capability of responding to future public health emergencies, China is developing a public health emergency response information system (PHERIS) to facilitate disease surveillance, detection, reporting, and response. The purpose of this study is to investigate the ongoing development of China's PHERIS. This paper analyzes the problems of China's existing public health system and describes the design and functionalities of PHERIS from both technical and managerial aspects.
Output: Investigating public health emergency response information system initiatives in China
Small-animal models have been developed for several Filoviridae species; however, serial adaptation was required to produce lethal infection. These adapted viruses have sequence changes in several genes, including those that modulate the host immune response. Nonhuman primate models do not require adaptation of filoviruses. Here, we describe lethal models of disease for Bundibugyo, Sudan, and Zaire species of Ebolavirus in the domestic ferret, using wild-type nonadapted viruses. Pathologic features were consistent with disease in primates. Of particular importance, this is the only known small-animal model developed for Bundibugyo and the only uniformly lethal animal model for Bundibugyo.
Output: The Journal of Infectious Diseases The Domestic Ferret (Mustela putorius furo) as a Lethal Infection Model for 3 Species of Ebolavirus
Contact patterns among hosts are considered as one of the most critical factors contributing to unequal pathogen transmission. Consequently, networks have been widely applied in infectious disease modeling. However most studies assume static network structure due to lack of accurate observation and appropriate analytic tools. In this study we used high temporal and spatial resolution animal position data to construct a high-resolution contact network relevant to infectious disease transmission. The animal contact network aggregated at hourly level was highly variable and dynamic within and between days, for both network structure (network degree distribution) and individual rank of degree distribution in the network (degree order). We integrated network degree distribution and degree order heterogeneities with a commonly used contact-based, directly transmitted disease model to quantify the effect of these two sources of heterogeneity on the infectious disease dynamics. Four conditions were simulated based on the combination of these two heterogeneities. Simulation results indicated that disease dynamics and individual contribution to new infections varied substantially among these four conditions under both parameter settings. Changes in the contact network had a greater effect on disease dynamics for pathogens with smaller basic reproduction number (i.e. R 0 , 2).
Output: Highly dynamic animal contact network and implications on disease transmission
The interferon (IFN)-inducing capacities of intact NDV virions, /3-propiolactone-inactivated particles and several structural components were compared, using human PBML as the IFN producing cells. Intact and inactivated virions as well as the nucleocapsid fraction did not differ significantly in their IFN-inducing capacity. In contrast, genomic RNA as well as M protein fraction and envelopes induced IFN titres to a level of about 10% of those achieved with virions. NDV-induced IFN production could be blocked specifically by incubation with polyclonal anti-NDV-monoclonal antibodies (mAbs) and with two of three anti-HN-mAbs, but not with anti-NDV-mAbs directed against the F, M or NP protein. In addition, IFN induction by fixed MDBK cells, expressing NDV surface proteins after infection with NDV Ulster, was inhibited by one of two anti-F-mAbs. The results suggest that the induction of IFN synthesis in human PBML is a complex process involving not only the HN protein but also the uncleaved F protein precursor, a component of the M protein fraction and -once having entered the cell -the genomic RNA.
Output: More than one component of the Newcastle disease virus particle is capable of interferon induction
BACKGROUND: Study of human coronavirus and other virus-associated respiratory illnesses is needed to describe their clinical effects on chronically ill, older adults. METHODS: A prospective study during 2009 to 2013 clinically assessed acute respiratory illnesses soon after onset and 3 to 4 weeks later in patients aged !60 years with chronic lung and heart diseases (group 1, 100 subjects) and healthy adults aged 18 to 40 years (group 2, 101 subjects). Respiratory secretions were tested for nucleic acids of a panel of respiratory viruses. An increase in antibody titer was assessed for 4 coronavirus strains. : Virus-associated illnesses (29 [39.1%] of 74 illnesses in group 1 and 59 [48.7%] of 121 illnesses in group 2) occurred in all calendar quarters, most commonly in the first and fourth quarters. Coronaviruses (group 1: 14 [18.9%] illnesses; group 2: 26 [21.5%] illnesses) and enteroviruses/rhinoviruses (group 1: 14 [18.9%] illnesses; group 2: 37 [30.6%] illnesses) were most common. Virus co-infections occurred in 10 illnesses. Illnesses with 9 to 11 symptoms were more common in group 1 (17 [23.0%]) than in group 2 (15 [12.4%]) (P < .05). Compared with group 2, more group 1 subjects reported dyspnea, more severe disease of longer duration, and treatment for acute illness with prednisone and antibiotics. Coronavirusassociated illnesses (percent of illnesses, group 1 vs group 2) were characterized by myalgias (21% vs 68%, P < .01), chills (50% vs 52%), dyspnea (71% vs 24%, P < .01), headache (64% vs 72%), malaise (64% vs 84%), cough (86% vs 68%), sputum production (86% vs 60%), sore throat (64% vs 80%), and nasal congestion (93% vs 96%). CONCLUSIONS: Respiratory illnesses were commonly associated with coronaviruses and enteroviruses/ rhinoviruses affecting chronically ill, older patients more than healthy, young adults. Published by Elsevier Inc.
Output: Coronavirus and Other Respiratory Illnesses Comparing Older with Young Adults
Background. Pneumonia, the leading infectious cause of child mortality globally, mainly afflicts developing countries. This prospective observational study aimed to assess the microorganisms associated with pneumonia in children aged <5 years in developing and emerging countries. Methods. A multicenter, case-control study by the GABRIEL (Global Approach to Biological Research, Infectious diseases and Epidemics in Low-income countries) network was conducted between 2010 and 2014 in Cambodia, China, Haiti, India (2 sites), Madagascar, Mali, Mongolia, and Paraguay. Cases were hospitalized children with radiologically confirmed pneumonia; controls were children from the same setting without any features suggestive of pneumonia. Nasopharyngeal swabs were collected from all subjects; 19 viruses and 5 bacteria were identified by reverse-transcription polymerase chain reaction. Associations between microorganisms and pneumonia were quantified by calculating the adjusted population attributable fraction (aPAF) after multivariate logistic regression analysis adjusted for sex, age, time period, other pathogens, and site. Results. Overall, 888 cases and 870 controls were analyzed; ≥1 microorganism was detected in respiratory samples in 93.0% of cases and 74.4% of controls (P < .001). Streptococcus pneumoniae, Mycoplasma pneumoniae, human metapneumovirus, rhinovirus, respiratory syncytial virus (RSV), parainfluenza virus 1, 3, and 4, and influenza virus A and B were independently associated with pneumonia; aPAF was 42.2% (95% confidence interval [CI], 35.5%-48.2%) for S. pneumoniae, 18.2% (95% CI, 17.4%-19.0%) for RSV, and 11.2% (95% CI, 7.5%-14.7%) for rhinovirus. Conclusions. Streptococcus pneumoniae, RSV, and rhinovirus may be the major microorganisms associated with pneumonia infections in children <5 years of age from developing and emerging countries. Increasing S. pneumoniae vaccination coverage may substantially reduce the burden of pneumonia among children in developing countries.
Output: Clinical Infectious Diseases Clinical Infectious Diseases ® 2017;65(4):604-12 Microorganisms Associated With Pneumonia in Children <5 Years of Age in Developing and Emerging Countries: The GABRIEL Pneumonia Multicenter, Prospective, Case-Control Study
The dynamics of coronavirus disease 2019 (COVID-19) transmissibility after symptom onset remains unknown. We conducted a prospective case-ascertained study on laboratory-confirmed COVID-19 cases and their contacts. Secondary clinical attack rate (considering symptomatic cases only) was analyzed for different exposure windows after symptom onset of index cases and for different exposure settings. Thirty-two confirmed patients were enrolled and 12 paired data (index-secondary cases) were identified among the 1,043 contacts. The secondary clinical attack rate was 0.9% (95% CI 0.5-1.7%). The attack rate was higher among those whose exposure to index cases started within five days of symptom onset (2.4%, 95% CI 1.1-4.5%) than those who were exposed later (zero case from 605 close contacts, 95% CI 0-0.61%). The attack rate was also higher among household contacts (13.6%, 95% CI 4.7-29.5%) and nonhousehold family contacts (8.5%, 95% CI 2.4-20.3%) than that in healthcare or other settings. The higher secondary clinical attack rate for contacts near symptom onset remained when the analysis was restricted to household and family contacts. There was a trend of increasing attack rate with the age of contacts (p for trend < 0.001). High transmissibility of COVID-19 near symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to contain the epidemic, and more generalized social distancing measures are required. Rapid reduction of transmissibility over time implies that prolonged hospitalization of mild cases might not be necessary in large epidemics.
Output: High transmissibility of COVID-19 near symptom onset
ORF la of lactate dehydrogenase-elevating virus, strain P (LDV-P), encodes a protein of 2206 amino acids. Eisenberg hydrophobic moment analysis of the protein predicted the presence of eleven transmembrane segments in the C-terminal half of the molecule (amino acids 980-1852) that flank the serine protease domain, cDNAs encoding ORF la protein segments encompassing transmembrane segments 5 to 11 and its amphipathic C-terminal end as well as the N-terminal 80 amino acids of the downstream ORF lb protein were transcribed and the transcripts in vitro translated in the absence and presence of microsomal membranes. The synthesis of the protein products with putative transmembrane segments was enhanced by the presence of the microsomal membranes and the proteins became membrane associated. When synthesized in the absence of membranes they were recovered in the supernatant upon ultracentrifugation of the translation reaction mixtures, whereas they were recovered in the membrane pellet when synthesized in the presence of membranes. Furthermore, the latter proteins were not released from the membranes by disruption of the membrane vesicles in carbonate buffer, pH 11.5, and large portions of the proteins were resistant to digestion by trypsin, chymotrypsin and proteinase K. No N-glycosylation was observed and only little, if any, processing of the protein by the putative serine protease. The results indicate that the C-terminal half of the ORF la protein represents a non-glycosylated integral membrane protein. Potential modes of synthesis and function of the protein are discussed. In addition, the results showed that the synthesis of the ORF la protein was generally terminated at its termination codon, but that read-through into the ORF lb gene occurred with low frequency.
Output: Membrane association of the C-terminal half of the open reading frame la protein of lactate dehydrogenase-elevating virus Brief Report
Many plants contain polyhydroxyalkaloids which are potent inhibitors of glucosidases, enzymes involved in oligosaccharide trimming. These are important in determining the final configuration of specific glycoproteins. Human cytomegalovirus (CMV) encodes a number of glycoproteins, some of which ultimately reside in the outer envelope of the mature virion and are important for virus infectivity. Treatment with three polyhydroxyalkaloids, castanospermine (CAST), deoxynojirimycin (DNJ) and 2R,5R-dihydroxymethyl-3R,4R-dihydroxypyrrolidine (DMDP) blocked the growth of infectious virus, as determined by yield reduction and plaque reduction assays. However, in the presence of CAST, CMV infected cells continued to shed virions into the extracellular medium, as determined by electron microscopy. Envelope glycoproteins of virions produced after treatment with CAST (2.5 mM) were immunoprecipitated with a monoclonal antibody (F5) specific for the gcI family of glycoproteins. Analysis by PAGE-SDS showed an absence of gcI complex 2 (gp52 disulphide-linked to gp130) with a proportional increase in gcI complex 1 (gp52 disulphide-linked to gp95). The results indicated that gpl30 alone, or linked to gp52, was important for CMV infectivity. As well as being potential targets for antiviral agents against CMV, inhibitors of glycoprotein trimming reactions may define components of the virion surface important for infectivity.
Output: Loss of cytomegalovirus infectivity after treatment with castanospermine or related plant alkaloids correlates with aberrant glycoprotein synthesis
A member of the family of coronaviruses has previously been identified as the cause of the severe acute respiratory syndrome (SARS). In this study, several monoclonal antibodies against the nucleocapsid protein have been generated to examine distribution of the nucleocapsid in virus-infected cells and to study antigenic regions of the protein. Confocal microscopic analysis identified nucleocapsids packaged in vesicles in the perinuclear area indicating viral synthesis at the endoplasmic reticulum and Golgi apparatus. The monoclonal antibodies bound to the central and carboxyterminal half of the nucleocapsid protein indicating prominent exposure and immunogenicity of this part of the protein. Antibodies recognised both linear and conformational epitopes. Predictions of antigenicity using mathematical modelling based on hydrophobicity analysis of SARS nucleoprotein could not be confirmed fully. Antibody binding to discontinuous peptides provides evidence that amino acids 274-283 and 373-382 assemble to a structural unit particularly rich in basic amino acids. In addition, amino acids 286-295, 316-325 and 361-367 that represent the epitope recognised by monoclonal antibody 6D11C1 converge indicating a well-structured C-terminal region of the SARS virus nucleocapsid protein and functional relationship of the peptide regions involved. Alternatively, dimerisation of the nucleocapsid protein may result in juxtaposition of the amino acid sequences 316-325 and 361-367 on one nucleoprotein molecule to amino acid 286-295 on the second peptide. The monoclonal antibodies will be available to assess antigenicity and immunological variabilities between different SARS CoV strains.
Output: Antigenic and cellular localisation analysis of the severe acute respiratory syndrome coronavirus nucleocapsid protein using monoclonal antibodies
The discovery of a novel coronavirus (CoV) as the causative agent of severe acute respiratory syndrome (SARS) has highlighted the need for a better understanding of CoV replication. The replication of SARS-CoV is highly dependent on host cell factors. However, relatively little is known about the cellular proteome changes that occur during SARS-CoV replication. Recently, we developed a cell line expressing a SARS-CoV subgenomic replicon and used it to screen inhibitors of SARS-CoV replication. To identify host proteins important for SARS-CoV RNA replication, the protein profiles of the SARS-CoV replicon cells and parental BHK21 cells were compared using a quantitative proteomic strategy termed "stable-isotope labeling by amino acids in cell culture-mass spectrometry" (SILAC-MS). Our results revealed that, among the 1,081 host proteins quantified in both forward and reverse SILAC measurements, 74 had significantly altered levels of expression. Of these, significantly upregulated BCL2-associated athanogene 3 (BAG3) was selected for further functional studies. BAG3 is involved in a wide variety of cellular processes, including cell survival, cellular stress response, proliferation, migration, and apoptosis. Our results show that inhibition of BAG3 expression by RNA interference led to significant suppression of SARS-CoV replication, suggesting the possibility that upregulation of BAG3 may be part of the machinery that SARS-CoV relies on for replication. By correlating the proteomic data with these functional studies, the findings of this study provide important information for understanding SARS-CoV replication.
Output: Quantitative Proteomics Analysis Reveals BAG3 as a Potential Target To Suppress Severe Acute Respiratory Syndrome Coronavirus Replication ᰔ
In the wake of dynamic economic and political transitions worldwide, the Institute of Medicine recently released its report advocating investments in global health from the United States (US). The expert panel reinforces the 'transnational and interdisciplinary' nature of global health research and practice as an endeavor 'to improve health and achieve greater equity for all people worldwide.' This report was judiciously timed given the growing recognition of global health, and is also acknowledged for incorporating themes that are particularly pertinent to the twenty-first century. New paradigms are introduced, denouncing the dichotomous distinction between rich and poor countries with the rapidly transitioning countries emerging as global powers, and affirming the need for models of respectful partnership and wider translation of science into practice. Cultivating sustainable partnerships and investing in the understanding and combat of diseases worldwide will become increasingly important for the US to maintain its global competitiveness, and may offer lessons in innovation, efficiency, and organization of institutions and human resources.
Output: The United States and global health: inseparable and synergistic? The Institute of Medicine's report on global health
The nucleoprotein-encoding gene (N) of murine hepatitis virus type 3 (MHV 3), from the Mill Hilt strain, was cloned and sequenced. It was compared to gene N from other routine coronaviruses and was found to share more similarities with N sequences from MHV 1 and MHV JHM strains than with the published MHV3 N sequence which is almost identical to MHVA59. We suggest that the evolution of some MHV N sequences resulted from a double recombination phenomenon between two ancestors. Furthermore, comparison of protein N from avian and mammalian coronaviruses leads to the hypothesis that horizontal transfer events of the virus from one host species to another have occurred.
Output: The gene encoding the nucleocapsid protein: sequence analysis in murine hepatitis virus type 3 and evolution in Coronaviridae
The immune system is an awe-inspiring control structure that maintains a delicate and constantly changing balance between pro-immune functions that fight infection and cancer, regulatory or suppressive functions involved in immune tolerance, and homeostatic resting states. These activities are determined by integrating signals in space and time; thus, improving control over the densities, combinations, and durations with which immune signals are delivered is a central goal to better combat infectious disease, cancer, and autoimmunity. Self-assembly presents a unique opportunity to synthesize materials with well-defined compositions and controlled physical arrangement of molecular building blocks. This review highlights strategies exploiting these capabilities to improve the understanding of how precisely-displayed cues interact with immune cells and tissues. We present work centered on fundamental properties that regulate the nature and magnitude of immune response, highlight pre-clinical and clinical applications of self-assembled technologies in vaccines, cancer, and autoimmunity, and describe some of the key manufacturing and regulatory hurdles facing these areas.
Output: Engineering self-assembled materials to study and direct immune function ☆-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Transmissible gastroenteritis (TGE) is a contagious and infectious disease that is characterized by severe vomiting and diarrhea of swine , especially piglet, and caused by transmissible gastroenteritis coronavirus (TGEV) . TGEV infection provokes mitochondrial damage of porcine intestinal epthelial cell (IPEC), which is responsible for inflammation and cell death. In our previous study, we have demonstrated that circular RNA circEZH2 was down-regulated during TGEV infection and promoted the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) via targeting miR-22 in porcine intestinal epithelial cell line (IPEC-J2). Activation of NF-κB is an important factor for mitochondrial damage. Mitochondrial permeability transition pore (mPTP) opening is a key reason for mitochondrial damage. So, we speculate that circEZH2 may regulate TGEV-induced mPTP opening via NF-kB pathway. In the present study, we found that mPTP opening of IPEC-J2 was occured during TGEV infection and suppressed by circEZH2 via attaching miR-22. Hexokinase 2 (HK2) and interleukin 6 (IL-6) were identified as the targets of miR-22. Silencing HK2 enhanced TGEV-induced mPTP opening, while no effect on NF-κB pathway. Silencing IL-6 promoted TGEV-induced mPTP opening and inhibited NF-κB pathway. Inhibitor of NF-κB increased TGEV-induced mPTP opening. The data revealed that TGEV-induced mPTP opening was regulated via two pathways: circEZH2/miR-22/HK2 axis and circEZH2/miR-22/IL-6/NF-κB axis.
Output: Circular RNA CircEZH2 Suppresses Transmissible Gastroenteritis Coronavirus-induced Opening of Mitochondrial Permeability Transition Pore via Targeting MiR-22 in IPEC-J2
Globalization describes how nations, peoples, and economies are becoming increasingly interconnected and interdependent. Globalization has contributed to health improvements through diffusion of new health knowledge, low-cost health technologies, and human rights. Economic globalization based upon a neoliberal model of liberalized trade and investment and minimal government regulation, however, has brought many health risks. This article outlines the health risks of neoliberal globalization from structural adjustment of the 1980s, through economic financialization of the 1990s and the 2000s, to the financial crisis and global recession of 2008 and subsequent 'austerity agenda' of state retrenchment. It concludes with a discussion of high-level public policies that would ensure that globalization works for 'health for all'.
Output: Globalization and Health
The SNP rs12252-C allele alters the function of interferon-induced transmembrane protein-3 increasing the disease severity of influenza virus infection in Caucasians, but the allele is rare. However, rs12252-C is much more common in Han Chinese. Here we report that the CC genotype is found in 69% of Chinese patients with severe pandemic influenza A H1N1/09 virus infection compared with 25% in those with mild infection. Specifically, the CC genotype was estimated to confer a sixfold greater risk for severe infection than the CT and TT genotypes. More importantly, because the risk genotype occurs with such a high frequency, its effect translates to a large population-attributable risk of 54.3% for severe infection in the Chinese population studied compared with 5.4% in Northern Europeans. Interferon-induced transmembrane protein-3 genetic variants could, therefore, have a strong effect of the epidemiology of influenza in China and in people of Chinese descent.
Output: ARTICLE Interferon-induced transmembrane protein-3 genetic variant rs12252-C is associated with severe influenza in Chinese individuals
The acute phase reaction (APR) is a response to potentially pathogenic stimuli. It begins with the release of interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-a from inflammatory cells. These cytokines induce fever, leucocytosis and release of serum acute phase proteins (APPs). In this review, the characteristics of the feline APR are described. In cats with inflammatory conditions, fever is a common finding, with leucocytosis due to the release of cells from the marginal pool, followed by activation of myelopoiesis. Because excitement frequently causes leucocytosis in cats, a diagnosis of inflammation should therefore be supported by additional findings such as the presence of toxic neutrophils. The major APPs are serum amyloid A and a 1 -acid glycoprotein (AGP), which both increase a few hours after the inflammatory stimulus and remain elevated for as long as the inflammation persists. AGP plays an important role in the diagnosis of feline infectious peritonitis (FIP) and may also be useful also in studies of FIP pathogenesis.
Output: The feline acute phase reaction
Each year, outbreaks of viral infections cause illness, disability, death, and economic loss. As learned from past incidents, the detrimental impact grows exponentially without effective quarantine. Therefore, rapid on-site detection and analysis are highly desired. In addition, for high-risk areas of viral contamination, close monitoring should be provided during the potential disease incubation period. As the epidemic progresses, a response protocol needs tobe rapidly implemented and the virus evolution fully tracked. For these scenarios, point-of-care microdevices can provide sensitive, accurate, rapid and low-cost analysis for a large population, especially in handling complex patient samples, such as blood, urine and saliva. Blood plasma can be considered as a mine of information containing sources and clues of biomarkers, including nucleic acids, immunoglobulin and other proteins, as well as pathogens for clinical diagnosis. However, blood plasma is also the most complicated body fluid. For targeted plasma biomarker detection or untargeted plasma biomarker discovery, the challenges can be as difficult as identifying a needle in a haystack. A useful platform must not only pursue single performance characteristics, but also excel at multiple performance parameters, such as speed, accuracy, sensitivity, selectivity, cost, portability, reliability, and user friendliness. Throughout the decades, tremendous progress has been made in point-ofcare microdevices for viral infectious diseases. In this paper, we review fully integrated lab-on-chip systems for blood analysis of viral infectious disease.
Output: Point-of-Care Microdevices for Blood Plasma Analysis in Viral Infectious Diseases
Background. Molecular methods of pathogen discovery have recently led to the description of several new respiratory viruses. Human bocavirus (HBoV), a proposed member of the family Parvoviridae, is one of the most recently described respiratory viruses. Initial reports indicate that HBoV is a common cause of respiratory tract infection in children. A total of 1474 nasal scraping specimens collected over a 20-month period were screened by polymerase chain reaction for the presence of HBoV nucleic acid. Positive results were confirmed with a second polymerase chain reaction assay from a different genomic region. The medical records of patients with positive results were reviewed for demographic and clinical data. Results. HBoV DNA was identified in 82 samples (5.6%). The peak rate of HBoV infection occurred during the period of March through May in both 2004 and 2005. Sixty-three percent of infected patients were !12 months of age. The most common symptoms were cough, rhinorrhea, and fever. Other symptoms of interest included diarrhea and a "paroxysmal" cough that was clinically suspected to be caused by Bordetella pertussis. Conclusions. HBoV DNA is commonly present in children with upper and lower respiratory tract infections. The presence of a pertussis-like cough and diarrhea in association with HBoV infection merits further investigation.
Output: Human Bocavirus: Prevalence and Clinical Spectrum at a Children's Hospital
Background: Household studies provide opportunities to understand influenza-like-illness (ILI) transmission, but data from (sub)tropical developing countries are scarce. Objective: To determine the viral etiology and epidemiology of ILI in households. Study design: ILI was detected by active case finding amongst a cohort of 263 northern Vietnam households between 2008 and 2013. Health workers collected nose and throat swabs for virus detection by multiplex real-time RT-PCR. Results: ILI was detected at least once in 219 (23.7%) of 945 household members. 271 (62.3%) of 435 nose/throat swabs were positive for at least one of the 15 viruses tested. Six viruses predominated amongst positive swabs: Rhinovirus (28%), Influenza virus (17%), Coronavirus (8%), Enterovirus (5%), Respiratory syncytial virus (3%), Metapneumovirus virus (2.5%) and Parainfluenza virus 3 (1.8%). There was no clear seasonality, but 78% of episodes occurred in Winter/Spring for Influenza compared to 32% for Rhinovirus. Participants, on average, suffered 0.49 ILI, and 0.29 virus-positive ILI episodes, with no significant effects of gender, age, or household size. In contrast to US and Australian community studies, the frequency of ILI decreased as the number of household members aged below 5 years increased (p = 0.006). Conclusion: The findings indicate the need for tailored ILI control strategies, and for better understanding of how local childcare practices and seasonality may influence transmission and the role of children.
Output: Epidemiology and etiology of influenza-like-illness in households in Vietnam; it's not all about the kids!
• SIS epidemic dynamics is studied in metapopulation networks. • NIR and PIR heterogeneous infection regimes are proposed. • The two regimes both increase the threshold when only infected individuals move. • NIR increases and PIR decreases the threshold if two types of individuals both move. • We also explore the impact of the two regimes on the temporal behavior of epidemic. In this paper, we study epidemic spreading in metapopulation networks wherein each node represents a subpopulation symbolizing a city or an urban area and links connecting nodes correspond to the human traveling routes among cities. Differently from previous studies, we introduce a heterogeneous infection rate to characterize the effect of nodes' local properties, such as population density, individual health habits, and social conditions, on epidemic infectivity. By means of a mean-field approach and Monte Carlo simulations, we explore how the heterogeneity of the infection rate affects the epidemic dynamics, and find that large fluctuations of the infection rate have a profound impact on the epidemic threshold as well as the temporal behavior of the prevalence above the epidemic threshold. This work can refine our understanding of epidemic spreading in metapopulation networks with the effect of nodes' local properties.
Output: Physica A Epidemic spreading in metapopulation networks with heterogeneous infection rates
Human sera were examined by immuno-blotting for antibodies to the reverse transcriptase of human hepatitis B virus (HBV) believed to be encoded in the P open reading frame (P-ORF). Sera from patients with self-limited (n = 58), acute (n = 23), and chronic (n = 8) hepatitis were analysed. One of the sera with markers of a prior infection and two sera of chronically infected patients reacted with a protein synthesized in E. coli that contains the middle part of the predicted polymerase. Other E. coli fusion proteins containing overlapping or different regions of P-ORF were used to localize antigenic domains. Antibody binding to two different domains representing the middle and the C-terminal region of P-ORF was obtained in the sera of chronically infected patients. Our findings are indirect evidence for the in vivo expression of the complete HBV polymerase reading frame.
Output: Abstracts of Papers Presented at the Session of the Virology Section of the Deutsche Gesellschaft fiir Hygiene und Mikrobiologie
Zaire ebolavirus (ZEBOV) infections are associated with high lethality in primates. ZEBOV primarily targets mononuclear phagocytes, which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis. The characterization of the responses of target cells to ZEBOV infection may therefore not only further understanding of pathogenesis but also suggest possible points of therapeutic intervention. Gene expression profiles of primary human macrophages exposed to ZEBOV were determined using DNA microarrays and quantitative PCR to gain insight into the cellular response immediately after cell entry. Significant changes in mRNA concentrations encoding for 88 cellular proteins were observed. Most of these proteins have not yet been implicated in ZEBOV infection. Some, however, are inflammatory mediators known to be elevated during the acute phase of disease in the blood of ZEBOV-infected humans. Interestingly, the cellular response occurred within the first hour of Ebola virion exposure, i.e. prior to virus gene expression. This observation supports the hypothesis that virion binding or entry mediated by the spike glycoprotein (GP 1,2 ) is the primary stimulus for an initial response. Indeed, ZEBOV virions, LPS, and virus-like particles consisting of only the ZEBOV matrix protein VP40 and GP 1,2 (VLP VP40-GP ) triggered comparable responses in macrophages, including pro-inflammatory and proapoptotic signals. In contrast, VLP VP40 (particles lacking GP 1,2 ) caused an aberrant response. This suggests that GP 1,2 binding to macrophages plays an important role in the immediate cellular response.
Output: Ebola Virion Attachment and Entry into Human Macrophages Profoundly Effects Early Cellular Gene Expression
Biological factors that influence the host range and spillover of Ebola virus (EBOV) and other filoviruses remain enigmatic. While filoviruses infect diverse mammalian cell lines, we report that cells from African straw-colored fruit bats (Eidolon helvum) are refractory to EBOV infection. This could be explained by a single amino acid change in the filovirus receptor, NPC1, which greatly reduces the affinity of EBOV-NPC1 interaction. We found signatures of positive selection in bat NPC1 concentrated at the virus-receptor interface, with the strongest signal at the same residue that controls EBOV infection in Eidolon helvum cells. Our work identifies NPC1 as a genetic determinant of filovirus susceptibility in bats, and suggests that some NPC1 variations reflect host adaptations to reduce filovirus replication and virulence. A single viral mutation afforded escape from receptor control, revealing a pathway for compensatory viral evolution and a potential avenue for expansion of filovirus host range in nature.
Output: Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats
Viral infection constitutes an unwanted intrusion that needs to be eradicated by host cells. On one hand, one of the first protective barriers set up to prevent viral replication, spread or persistence involves the induction of apoptotic cell death that aims to limit the availability of the cellular components for viral amplification. On the other hand, while they completely depend on the host molecular machinery, viruses also need to evade the cellular responses that are meant to destroy them. The existence of numerous antiapoptotic products within the viral kingdom proves that apoptosis constitutes a major threat that should better be bypassed. Among the different strategies developed to deal with apoptosis, one is based on what viruses do best: backfiring the cell on itself. Several unrelated viruses have been described to take advantage of apoptosis induction by expressing proteins targeted by caspases, the key effectors of apoptotic cell death. Caspase cleavage of these proteins results in various consequences, from logical apoptosis inhibition to more surprising enhancement or attenuation of viral replication. The present review aims at discussing the characterization and relevance of this post-translational modification that adds a new complexity in the already intricate host-apoptosis-virus triangle.
Output: Caspase cleavage of viral proteins, another way for viruses to make the best of apoptosis
In this paper, we propose and discuss a stochastic SIRS epidemic model with non-monotone incidence rate under regime-switching. First of all, we show that there is a unique positive solution, which is a prerequisite for analyzing the long-term behavior of the stochastic model. Then, a threshold dynamic determined by the basic reproduction number R s 0 is established: the disease can be eradicated almost surely if R s 0 < 1 and under mild extra conditions, whereas if R s 0 > 1 , the densities of the distributions of the solution can converge in L 1 to an invariant density by using the Markov semigroups theory. Finally, based on realistic parameters obtained from previous literatures, numerical simulations have been performed to verify our analytical results.
Output: A stochastic SIRS epidemic model with non-monotone incidence rate under regime-switching
Diarrhoea and pneumonia are the leading infectious causes of childhood morbidity and mortality. We comprehensively reviewed the epidemiology of childhood diarrhoea and pneumonia in 2010-11 to inform the planning of integrated control programmes for both illnesses. We estimated that, in 2010, there were 1·731 billion episodes of diarrhoea (36 million of which progressed to severe episodes) and 120 million episodes of pneumonia (14 million of which progressed to severe episodes) in children younger than 5 years. We estimated that, in 2011, 700 000 episodes of diarrhoea and 1·3 million of pneumonia led to death. A high proportion of deaths occurs in the fi rst 2 years of life in both diseases-72% for diarrhoea and 81% for pneumonia. The epidemiology of childhood diarrhoea and that of pneumonia overlap, which might be partly because of shared risk factors, such as undernutrition, suboptimum breastfeeding, and zinc defi ciency. Rotavirus is the most common cause of vaccine-preventable severe diarrhoea (associated with 28% of cases), and Streptococcus pneumoniae (18·3%) of vaccine-preventable severe pneumonia. Morbidity and mortality from childhood pneumonia and diarrhoea are falling, but action is needed globally and at country level to accelerate the reduction.
Output: Childhood Pneumonia and Diarrhoea 1 Global burden of childhood pneumonia and diarrhoea
Several serological interrelationships between various members of the coronavirus group have been revealed in neutralization, complement fixation, and geldiffusion tests, using human and hyperimmune animal sera. Several members of this group of human and animal pathogens are shown to cross-react in one or more type of test, but one member, avian infectious bronchitis virus, was shown to be unrelated. Mouse hepatitis virus (MHVs) was found to be antigenieally related to a number of human types of coronavirus. Difficulties were encountered in the investigation of paired human sera in demonstrating the specificity of antibody rises, placing doubt on the values of some serological studies. The significance of these interrelationships is discussed in the light of other investigations. BRADBURNE : Antigenic Relationships amongst Coronaviruses 353 organ cultures of human embryo nasal and tracheal epithelium. These isolates comprise at least three, and probably more, distinct serological types as judged by neutralization tests using convalescent human sera (B~A]) BUR~ and T~R~IiL, 1969; McI~Tos~ et al., 1969). This work describes the detection of several serological relationships between the viruses isolated from man, and those of mouse hepatitis and avian infectious bronchitis. The majority of these results were obtained before similar studies were reported by MCINTos~ et al. (1969); furthermore, different reagents were used and several extra cross-reactions were detected. 2.1. Tissue Cultures These were all propagated in this laboratory. Roller tube neutralization tests were performed in monolayer cultures of human embryo diploid lung cells (HDCS). These were either a strain derived at the Unit, or the WI-38 cell strain. Plaque neutralization tests were made using monolayers of L 132 cells in 50 mm plastic Pctri dishes (Sterilin). The L 132 cell line is a continuous epitheloid cell line which was derived from human embryo lung (DAvis, 1960) and has been shown to be sensitive to several respiratory viruses, including 4 strains of coronaviruses (BRAD-]~Vl~N]~, 1969). All cultures were maintained at 33~ after inoculation.
Output: Antigenic Relationships amongst Coronaviruses
Objectives: To measure the spatial contagion of severe acute respiratory syndrome (SARS) in Beijing and to test the different epidemic factors of the spread of SARS in different periods. Methods: A join-count spatial statistic study was conducted and the given hypothetical processes of the spread of SARS in Beijing were tested using various definitions of 'joins'. Results: The spatial statistics showed that of the six diffusion processes, the highest negative autocorrelation occurred in the doctor-number model (M-5) and the lowest negative autocorrelation was found in the population-amount model (M-3). The results also showed that in the whole 29-day research period, about hour or more days experienced a significant degree of contagion. Conclusions: Spatial analysis is helpful in understanding the spatial diffusion process of an epidemic. The geographical relationships were important during the early phase of the SARS epidemic in Beijing. The statistic based on the number of doctors was significant and more informative than that of the number of hospitals. It reveals that doctors were important in the spread of SARS in Beijing, and hospitals were not as important as doctors in the contagion period. People are the key to the spread of SARS, but the population density was more significant than the population size, although they were both important throughout the whole period.
Output: Understanding the spatial diffusion process of severe acute respiratory syndrome in Beijing
Viruses of the family Filoviridae represent significant health risks as emerging infectious diseases as well as potentially engineered biothreats. While many research efforts have been published offering possibilities toward the mitigation of filoviral infection, there remain no sanctioned therapeutic or vaccine strategies. Current progress in the development of filovirus therapeutics and vaccines is outlined herein with respect to their current level of testing, evaluation, and proximity toward human implementation, specifically with regard to human clinical trials, nonhuman primate studies, small animal studies, and in vitro development. Contemporary methods of supportive care and previous treatment approaches for human patients are also discussed.
Output: Potential Vaccines and Post-Exposure Treatments for Filovirus Infections
Objectives: To synthesize new transitional metal complexes derived from 3-aryl-azo-4-hydroxy coumarin analogues and to evaluate their antimicrobial activities. Methods: The syntheses of complexes of coumarin analogues were accomplished by mixing a hydro-alcoholic solution of 3-aryl-azo-4-hydroxy coumarin analogues with transition metal chlorides. The structural environment of the synthesized molecules was characterized using different instrumental methods. The antimicrobial activity of the compounds was determined by the agar well diffusion method. Results: The cobalt complexes of (E)-3-((4-chlorophenyl) diazenyl)-4-hydroxy-2H-chromen-2-one (HL 1 ): (4a) and (E)-3-((4-methoxyphenyl) diazenyl)-4-hydroxy-2H-chromen-2-one (HL 2 ): (4e) showed excellent antimicrobial activities compared with their ligands. The reports of the antimicrobial investigation showed that the cobalt complexes of 3-aryl-azo-4hydroxy coumarin analogues exhibited potential antimicrobial activity that was stronger than that of their ligands.
Output: Antimicrobial activity of novel synthesized coumarin based transitional metal complexes
Several hitherto unknown (E)-but-2-enyl nucleoside phosphonoamidate analogs (ANPs) were prepared directed with nitrogen reagents by cross-metathesis in water-under ultrasound irradiation. Two diastereoisomers were formally identified by X-ray diffraction. These compounds were evaluated against a large spectrum of DNA and RNA viruses. Among them, the phosphonoamidate thymine analogue 19 emerged as the best prodrug against varicella-zoster virus (VZV) with EC 50 values of 0.33 and 0.39 mM for wild-type and thymidine kinase deficient strains, respectively, and a selectivity index !200 mM. This breakthrough approach paves the way for new purine and pyrimidine (E)-but-2-enyl phosphonoamidate analogs. Abbreviations: VZV, varicella zoster virus; VV, vaccinia virus; HSV, herpes simplex virus; VSV, vesicular stomatitis virus; DNA, deoxyribonucleic acid; RNA, ribonucleic acid; CC50, compound concentration affording 50% inhibition of cell growth; EC50, compound concentration affording 50% inhibition of the viral cytopathicity; MCC, minimum cytotoxic concentration required to afford a microscopically detectable alteration of cell morphology; ACN, acetonitrile; DCM, dichloromethane.
Output: Highly convergent synthesis and antiviral activity of (E)-but-2-enyl nucleoside phosphonoamidates