Spatial modelling of contribution of individual level risk factors for mortality from Middle East respiratory syndrome coronavirus in the Arabian Peninsula.
Middle East respiratory syndrome coronavirus is a contagious respiratory pathogen that is contracted via close contact with an infected subject. Transmission of the pathogen has occurred through animal-to-human contact at first followed by human-to-human contact within families and health care facilities.This study is based on a retrospective analysis of the Middle East respiratory syndrome coronavirus outbreak in the Kingdom of Saudi Arabia between June 2012 and July 2015. A Geoadditive variable model for binary outcomes was applied to account for both individual level risk factors as well spatial variation via a fully Bayesian approach.Out of 959 confirmed cases, 642 (67%) were males and 317 (33%) had died. Three hundred and sixty four (38%) cases occurred in Ar Riyad province, while 325 (34%) cases occurred in Makkah. Individuals with some comorbidity had a significantly higher likelihood of dying from MERS-CoV compared with those who did not suffer comorbidity [Odds ratio (OR) = 2.071; 95% confidence interval (CI): 1.307, 3.263]. Health-care workers were significantly less likely to die from the disease compared with non-health workers [OR = 0.372, 95% CI: 0.151, 0.827]. Patients who had fatal clinical experience and those with clinical and subclinical experiences were equally less likely to die from the disease compared with patients who did not have fatal clinical experience and those without clinical and subclinical experiences respectively. The odds of dying from the disease was found to increase as age increased beyond 25 years and was much higher for individuals with any underlying comorbidities.Interventions to minimize mortality from the Middle East respiratory syndrome coronavirus should particularly focus individuals with comorbidity, non-health-care workers, patients with no clinical fatal experience, and patients without any clinical and subclinical experiences.
Oyelola A. Adegboye, Ezra Gayawan, Fahad Hanna
Modeling the Transmission of Middle East Respirator Syndrome Corona Virus in the Republic of Korea.
The 2015 epidemic of Middle East respiratory syndrome (MERS) in the Republic of Korea has been the largest outbreak outside Middle East. This epidemic had caused 185 laboratory-confirmed cases and 36 deaths in the Republic of Korea until September 2, 2015, which attracted public's attention. Based on the detailed data of patients released by World Health Organization (WHO) and actual propagation of the epidemic, we construct two dynamical models to simulate the propagation processes from May 20 to June 8 and from June 9 to July 10, 2015, respectively and find that the basic reproduction number R0 reaches up to 4.422. The numerical analysis shows that the reasons of the outbreak spread quickly are lack of self-protection sense and targeted control measures. Through partial correction analysis, the parameters β1 and γ have strong correlations with R0, i.e., the infectivity and proportion of the asymptomatic infected cases have much influence on the spread of disease. By sensitivity analysis, strengthening self-protection ability of susceptible and quickly isolating or monitoring close contacts are effective measures to control the disease.
Zhiqiang Xia, Juan Zhang, Yakui Xue, Gui-Quan Sun, Zhen Jin
Size-class effect contributes to tree species assembly through influencing dispersal in tropical forests.
We have investigated the processes of community assembly using size classes of trees. Specifically our work examined (1) whether point process models incorporating an effect of size-class produce more realistic summary outcomes than do models without this effect; (2) which of three selected models incorporating, respectively environmental effects, dispersal and the joint-effect of both of these, is most useful in explaining species-area relationships (SARs) and point dispersion patterns. For this evaluation we used tree species data from the 50-ha forest dynamics plot in Barro Colorado Island, Panama and the comparable 20 ha plot at Bubeng, Southwest China. Our results demonstrated that incorporating an size-class effect dramatically improved the SAR estimation at both the plots when the dispersal only model was used. The joint effect model produced similar improvement but only for the 50-ha plot in Panama. The point patterns results were not improved by incorporation of size-class effects using any of the three models. Our results indicate that dispersal is likely to be a key process determining both SARs and point patterns. The environment-only model and joint-effects model were effective at the species level and the community level, respectively. We conclude that it is critical to use multiple summary characteristics when modelling spatial patterns at the species and community levels if a comprehensive understanding of the ecological processes that shape species' distributions is sought; without this results may have inherent biases. By influencing dispersal, the effect of size-class contributes to species assembly and enhances our understanding of species coexistence.
Yuehua Hu, Roger L. Kitching, Guoyu Lan, Jiao-Lin Zhang, Liqing Sha, Min Cao
Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease.
A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1st October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (Mpro) is expressed; the dimerization of the protein and its relationship to catalysis are investigated.The crystal structure of MERS-CoV Mpro indicates that it shares a similar scaffold to that of other coronaviral Mpro and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV Mpro undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV Mpro is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme.MERS-CoV Mpro shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral Mpro family.
Bo-Lin Ho, Shu-Chun Cheng, Lin SHI, Tingyun Wang, Kuan I Ho, Chi-Yuan Chou
Genomic Analysis and Surveillance of the Coronavirus Dominant in Ducks in China.
The genetic diversity, evolution, distribution, and taxonomy of some coronaviruses dominant in birds other than chickens remain enigmatic. In this study we sequenced the genome of a newly identified coronavirus dominant in ducks (DdCoV), and performed a large-scale surveillance of coronaviruses in chickens and ducks using a conserved RT-PCR assay. The viral genome harbors a tandem repeat which is rare in vertebrate RNA viruses. The repeat is homologous to some proteins of various cellular organisms, but its origin remains unknown. Many substitutions, insertions, deletions, and some frameshifts and recombination events have occurred in the genome of the DdCoV, as compared with the coronavirus dominant in chickens (CdCoV). The distances between DdCoV and CdCoV are large enough to separate them into different species within the genus Gammacoronavirus. Our surveillance demonstrated that DdCoVs and CdCoVs belong to different lineages and occupy different ecological niches, further supporting that they should be classified into different species. Our surveillance also demonstrated that DdCoVs and CdCoVs are prevalent in live poultry markets in some regions of China. In conclusion, this study shed novel insight into the genetic diversity, evolution, distribution, and taxonomy of the coronaviruses circulating in chickens and ducks.
Qingye Zhuang, Kaicheng Wang, Shuo Liu, Guangyu Hou, Wenming JIANG, Suchun Wang, Jinping Li, Jianmin Yu, Jiming Chen
Development and application of an ELISA for the detection of porcine deltacoronavirus IgG antibodies.
Porcine deltacoronavirus (PDCoV), also known as porcine coronavirus HKU15, was first detected in North America in early 2014 and associated with enteric disease in pigs, resulting in an urgent need to further investigate the ecology of this virus. While assays detecting nucleic acids were implemented quickly, assays to detect anti-PDCoV antibodies have not been available. In this study, an indirect anti-PDCoV IgG enzyme-linked immunosorbent assay (ELISA) based on the putative S1 portion of the spike protein was developed and utilized to determine the prevalence of anti-PDCoV IgG in U.S. pigs. The diagnostic sensitivity of the PDCoV ELISA was 91% with a diagnostic specificity of 95%. A total of 968 serum samples were tested including samples with confirmed infection with PDCoV, porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus or porcine respiratory coronavirus. There was no cross-reactivity with any of the other coronaviruses. Among 355 arbitrarily selected serum samples collected in 2014 and originating from 51 farms across 18 U.S. states, anti-PDCoV IgG antibodies were detected in 8.7% of the samples and in 25.5% of the farms whereas anti-PEDV IgG was detected in 22.8% of the samples and in 54.9% of the farms. In addition, anti-PDCoV IgG antibodies were detected in archived samples collected in 2010, perhaps indicating an earlier undetected introduction into the U.S. pig population. Overall, the obtained data suggest that PDCoV seroprevalence in U.S. pigs is lower compared to PEDV and PDCoV may have been introduced to the U.S. prior to PEDV.
Anil Thachil, Priscilla F. Gerber, Chao-Ting Xiao, Yaowei Huang, Tanja Opriessnig
Host tissue and glycan binding specificities of avian viral attachment proteins using novel avian tissue microarrays.
The initial interaction between viral attachment proteins and the host cell is a critical determinant for the susceptibility of a host for a particular virus. To increase our understanding of avian pathogens and the susceptibility of poultry species, we developed novel avian tissue microarrays (TMAs). Tissue binding profiles of avian viral attachment proteins were studied by performing histochemistry on multi-species TMA, comprising of selected tissues from ten avian species, and single-species TMAs, grouping organ systems of each species together. The attachment pattern of the hemagglutinin protein was in line with the reported tropism of influenza virus H5N1, confirming the validity of TMAs in profiling the initial virus-host interaction. The previously believed chicken-specific coronavirus (CoV) M41 spike (S1) protein displayed a broad attachment pattern to respiratory tissues of various avian species, albeit with lower affinity than hemagglutinin, suggesting that other avian species might be susceptible for chicken CoV. When comparing tissue-specific binding patterns of various avian coronaviral S1 proteins on the single-species TMAs, chicken and partridge CoV S1 had predominant affinity for the trachea, while pigeon CoV S1 showed marked preference for lung of their respective hosts. Binding of all coronaviral S1 proteins was dependent on sialic acids; however, while chicken CoV S1 preferred sialic acids type I lactosamine (Gal(1-3)GlcNAc) over type II (Gal(1-4)GlcNAc), the fine glycan specificities of pigeon and partridge CoVs were different, as chicken CoV S1-specific sialylglycopolymers could not block their binding to tissues. Taken together, TMAs provide a novel platform in the field of infectious diseases to allow identification of binding specificities of viral attachment proteins and are helpful to gain insight into the susceptibility of host and organ for avian pathogens.
Iresha N Ambepitiya Wickramasinghe, Robert P. de Vries, Amber M Eggert, Nantaporn Wandee, Cornelis A.M. De Haan, Andrea Gröne, Monique H. Verheije
Building the road to a regional zoonoses strategy: A survey of zoonoses programmes in the Americas.
BACKGROUND:In recent years, global public health security has been threatened by zoonotic disease emergence as exemplified by outbreaks of H5N1 and H1N1 influenza, SARS, and most recently Ebola and Zika. Additionally, endemic zoonoses, such as rabies, burden countries year after year, placing demands on limited finances and personnel. To survey the baseline status of the emerging and endemic zoonoses programmes of the Latin American and the Caribbean (LAC) countries, the Pan American Health Organization (PAHO) conducted a survey of priority emerging and endemic zoonoses, countries´ prioritization criteria and methodologies, and suggestions to strengthen countries capacities and regional approaches to zoonoses control. METHODS:A fillable online questionnaire was sent to the zoonoses programme managers of the Ministries of Health (MOH) and Ministries of Agriculture (MAg) of 33 LAC countries from January to April of 2015. The questionnaire comprised 36 single, multiple choice and open-ended questions to inform the objectives of the survey. A descriptive exploratory analysis was completed. RESULTS:Fifty-four ministries (26 MOH, 25 MAg, and 3 combined responses) in 31 LAC countries responded to the survey. Within the ministries, 22 (85%) MOH, 5 (20%) MAg, and 2 (67%) combined entities indicated they had specialized zoonoses units. For endemic zoonoses, 32 of 54 ministries responded that they conduct formal prioritization exercises, most of them annually (69%). The three priority endemic zoonoses for the MOHs were leptospirosis, rabies, and brucellosis while the three priorities for the MAgs were brucellosis, rabies, and tuberculosis. Diagnosis for rabies and leptospirosis were cited as the capacities most in need of development. The most needed cross-cutting capacity was coordination between stakeholders. For emerging zoonoses, 28 ministries performed formal prioritization exercises. The top prioritization criteria were probability of introduction into the country and impact. The three priority emerging zoonoses for the MOHs were Ebola viral disease, avian influenza, and Chikungunya while for the MAgs were avian influenza, bovine spongiform encephalopathy and West Nile virus disease. Surveillance for avian influenza and Ebola, and diagnosis for BSE were quoted as the capacities most needed. For all zoonoses, the majority of respondents (69%) ranked their relationship with the other Ministry as productive or very productive, and 31% minimally productive. Many countries requested a formal regional network, better regional communication and collaboration, and integrated surveillance. CONCLUSIONS:The survey is the first comprehensive effort to date to inform the status of zoonoses programmes in LAC. The information collected here will be used to develop a regional strategy for zoonoses (both endemic and emerging), increase efforts, advocacy, and promote prompt identification and management of EIDs and improvement of endemic programmes.
Melody J. Maxwell, Mary H Freire de Carvalho, Armando E. Hoet, Marco A.N. Vigilato, Julio C Pompei, Ottorino Cosivi, Víctor J. Del Rio Vilas
High Prevalence and Putative Lineage Maintenance of Avian Coronaviruses in Scandinavian Waterfowl.
Coronaviruses (CoVs) are found in a wide variety of wild and domestic animals, and constitute a risk for zoonotic and emerging infectious disease. In poultry, the genetic diversity, evolution, distribution and taxonomy of some coronaviruses have been well described, but little is known about the features of CoVs in wild birds. In this study we screened 764 samples from 22 avian species of the orders Anseriformes and Charadriiformes in Sweden collected in 2006/2007 for CoV, with an overall CoV prevalence of 18.7%, which is higher than many other wild bird surveys. The highest prevalence was found in the diving ducks--mainly Greater Scaup (Aythya marila; 51.5%)--and the dabbling duck Mallard (Anas platyrhynchos; 19.2%). Sequences from two of the Greater Scaup CoV fell into an infrequently detected lineage, shared only with a Tufted Duck (Aythya fuligula) CoV. Coronavirus sequences from Mallards in this study were highly similar to CoV sequences from the sample species and location in 2011, suggesting long-term maintenance in this population. A single Black-headed Gull represented the only positive sample from the order Charadriiformes. Globally, Anas species represent the largest fraction of avian CoV sequences, and there seems to be no host species, geographical or temporal structure. To better understand the eitiology, epidemiology and ecology of these viruses more systematic surveillance of wild birds and subsequent sequencing of detected CoV is imperative.
Michelle Wille, Shaman Muradrasoli, Anna Nilsson, Josef D. Järhult
SPRi-based strategy to identify specific biomarkers in systemic lupus erythematosus, rheumatoid arthritis and autoimmune hepatitis.
BACKGROUND: Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is a target for antinuclear autoantibodies in systemic Lupus erythematosus (SLE), rheumatoid arthritis (RA), and autoimmune hepatitis (AIH). AIM: To monitor molecular interactions between peptides spanning the entire sequence of hnRNP A2/B1 and sera from patients and healthy controls. METHODS: Sera from 8 patients from each pathology and controls were passed across a surface plasmon resonance Imagery (SPRi) surface containing 39 overlapping peptides of 17 mers covering the human hnRNP B1. Interactions involving the immobilised peptides were followed in real time and dissociation rate constants k(off) for each interaction were calculated. RESULTS: Several significant interactions were observed: i) high stability (lower k(off) values) between P₅₅₋₇₀ and the AIH sera compared to controls (p= 0.003); ii) lower stability (higher k(off) values) between P₁₁₈₋₁₃₃ and P₂₆₂₋₂₇₇ and SLE sera, P₁₄₅₋₁₆₀ and RA sera compared to controls (p=0.006, p=0.002, p=0.007). The binding curves and k(off) values observed after the formation of complexes with anti-IgM and anti-IgG antibodies and after nuclease treatment of the serum indicate that i) IgM isotypes are prevalent and ii) nucleic acids participate in the interaction between anti-hnRNAP B1 and P₅₅₋₇₀ and also between controls and the peptides studied. CONCLUSIONS: These results indicate that P₅₅₋₇₀ of hnRNP B1 is a potential biomarker for AIH in immunological tests and suggest the role of circulating nucleic acids, (eg miRNA), present or absent according to the autoimmune disorders and involved in antigen-antibody stability.
Elvire Beleoken, Hervé Leh, Armelle Arnoux, Béatrice Ducot, Claude Nogues, Eleonora De Martin, Catherine Johanet, Didier Samuel, Mohammad Zahid Mustafa, Jean-Charles Duclos-Vallée, Malcolm Buckle, Eric Ballot