An epidemiological model for SARS-CoV-2

The spread of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is here investigated from an epidemic model considering four pathways of person-to-person transmission. These pathways represent the propagation of this novel coronavirus by asymptomatic and symptomatic infected individuals. In this work, analytical expressions for the disease-free and endemic steady-states are derived. Also, the conditions for eradication of this contagious disease are determined. By taking into account realistic parameter values, the proposed model shows an oscillatory convergence to the endemic steady-state, which means the occurrence of a sequence of peaks in the number of sick individuals as time passes. These results are discussed from a public health standpoint.     

Rabbit haemorrhagic disease: applying Occam's razor to competing hypotheses

Rabbit haemorrhagic disease virus (RHDV) is a highly virulent lagovirus endemic in Europe and Australasian populations of the European rabbit, Oryctolagus cuniculus. It has also caused several unexplained disease outbreaks in domestic European rabbits in North America. Non-pathogenic spread of RHDV leading to persistent infection which later reactivated has recently been proposed as the cause of overt disease and death of a pet rabbit in Canada, the first confirmed case of Rabbit haemorrhagic disease in that country. We suggest that there is little evidence to support non-pathogenic spread of virulent RHDV, some evidence that is contradictory, and evidence to support a simpler alternative hypothesis. RHDV can be spread over long distances between sparse rabbit populations by fomites or flying insects. Although highly pathogenic, RHDV can be limited in its spread within rabbit populations, or its presence masked by closely related but non-pathogenic lagoviruses which can provide protection against acute disease. In the absence of any evidence from clinical studies to support reactivation of persistent RHDV infection, the simpler explanation seems more likely to be correct.     

Eurasian-origin gene segments contribute to the transmissibility, aerosol release, and morphology of the 2009 pandemic H1N1 influenza virus

The epidemiological success of pandemic and epidemic influenza A viruses relies on the ability to transmit efficiently from person-to-person via respiratory droplets. Respiratory droplet (RD) transmission of influenza viruses requires efficient replication and release of infectious influenza particles into the air. The 2009 pandemic H1N1 (pH1N1) virus originated by reassortment of a North American triple reassortant swine (TRS) virus with a Eurasian swine virus that contributed the neuraminidase (NA) and M gene segments. Both the TRS and Eurasian swine viruses caused sporadic infections in humans, but failed to spread from person-to-person, unlike the pH1N1 virus. We evaluated the pH1N1 and its precursor viruses in a ferret model to determine the contribution of different viral gene segments on the release of influenza virus particles into the air and on the transmissibility of the pH1N1 virus. We found that the Eurasian-origin gene segments contributed to efficient RD transmission of the pH1N1 virus likely by modulating the release of influenza viral RNA-containing particles into the air. All viruses replicated well in the upper respiratory tract of infected ferrets, suggesting that factors other than viral replication are important for the release of influenza virus particles and transmission. Our studies demonstrate that the release of influenza viral RNA-containing particles into the air correlates with increased NA activity. Additionally, the pleomorphic phenotype of the pH1N1 virus is dependent upon the Eurasian-origin gene segments, suggesting a link between transmission and virus morphology. We have demonstrated that the viruses are released into exhaled air to varying degrees and a constellation of genes influences the transmissibility of the pH1N1 virus.     

Viral haemorrhagic fevers--evolution of the epidemic potential

In this review modern data on dangerous and particularly dangerous viral haemorrhagic fevers caused by a group of viruses belonging to the families of phylo-, arena-, flavi-, bunya- and togaviruses are presented. Morbidity rates and epidemics caused by Marburg virus, Ebola fever virus, Lassa fever virus, Argentinian and Bolivian haemorrhagic fever viruses, dengue haemorrhagic fever virus, Crimean haemorrhagic fever virus, Hantaviruses are analyzed. Mechanisms of the evolution of the epidemic manifestation of these infections are considered. The importance of the development of tools and methods of diagnosis, rapid prevention and treatment of exotic haemorrhagic fevers is emphasized.     

Individual and Bivalent Vaccines Based on Alphavirus Replicons Protect Guinea Pigs against Infection with Lassa and Ebola Viruses

Lassa and Ebola viruses cause acute, often fatal, hemorrhagic fever diseases, for which no effective vaccines are currently available. Although lethal human disease outbreaks have been confined so far to sub-Saharan Africa, they also pose significant epidemiological concern worldwide as demonstrated by several instances of accidental importation of the viruses into North America and Europe. In the present study, we developed experimental individual vaccines for Lassa virus and bivalent vaccines for Lassa and Ebola viruses that are based on an RNA replicon vector derived from an attenuated strain of Venezuelan equine encephalitis virus. The Lassa and Ebola virus genes were expressed from recombinant replicon RNAs that also encoded the replicase function and were capable of efficient intracellular self-amplification. For vaccinations, the recombinant replicons were incorporated into virus-like replicon particles. Guinea pigs vaccinated with particles expressing Lassa virus nucleoprotein or glycoprotein genes were protected from lethal challenge with Lassa virus. Vaccination with particles expressing Ebola virus glycoprotein gene also protected the animals from lethal challenge with Ebola virus. In order to evaluate a single vaccine protecting against both Lassa and Ebola viruses, we developed dual-expression particles that expressed glycoprotein genes of both Ebola and Lassa viruses. Vaccination of guinea pigs with either dual-expression particles or with a mixture of particles expressing Ebola and Lassa virus glycoprotein genes protected the animals against challenges with Ebola and Lassa viruses. The results showed that immune responses can be induced against multiple vaccine antigens coexpressed from an alphavirus replicon and suggested the possibility of engineering multivalent vaccines based upon alphavirus vectors for arenaviruses, filoviruses, and possibly other emerging pathogens.     

Everyday contact spread of viral hepatitis B

The results obtained in the study of the characteristic features of the spread of viral hepatitis B under the conditions of family foci are presented. Children with viral hepatitis B have been found to infect 4-5 persons per 1,000 contacts, while adults infect not more than 1 person per 1,000 contacts. The results of the study have led to the conclusion that the idea of the potential danger of hepatitis B patients as the source of infection depends on the forms of the infectious process taken into account in evaluating its epidemiological significance. Latent cases of hepatitis B virus infection appear more frequently among the contacts of sick children than among those of sick adults, but the manifest forms of the disease are more frequently caused by infection contacted from sick adults.     

Growth of H5N1 influenza A viruses in the upper respiratory tracts of mice

Highly pathogenic avian H5N1 influenza A viruses have spread throughout Asia, Europe, and Africa, raising serious worldwide concern about their pandemic potential. Although more than 250 people have been infected with these viruses, with a consequent high rate of mortality, the molecular mechanisms responsible for the efficient transmission of H5N1 viruses among humans remain elusive. We used a mouse model to examine the role of the amino acid at position 627 of the PB2 viral protein in efficient replication of H5N1 viruses in the mammalian respiratory tract. Viruses possessing Lys at position 627 of PB2 replicated efficiently in lungs and nasal turbinates, as well as in cells, even at the lower temperature of 33 degrees C. Those viruses possessing Glu at this position replicated less well in nasal turbinates than in lungs, and less well in cells at the lower temperature. These results suggest that Lys at PB2-627 confers to avian H5N1 viruses the advantage of efficient growth in the upper and lower respiratory tracts of mammals. Therefore, efficient viral growth in the upper respiratory tract may provide a platform for the adaptation of avian H5N1 influenza viruses to humans and for efficient person-to-person virus transmission, in the context of changes in other viral properties including specificity for human (sialic acid alpha-2,6-galactose containing) receptors.     

Four Categories of Viral Infection Describe the Health Status of Honey Bee Colonies

Honey bee virus prevalence data are an essential prerequisite for managing epidemic events in a population. A survey study was carried out for seven viruses in colonies representing a healthy Danish honey bee population. In addition, colonies from apiaries with high level Varroa infestation or high level of winter mortality were also surveyed. Results from RT-qPCR showed a considerable difference of virus levels between healthy and sick colonies. In the group of healthy colonies, no virus was detected in 36% of cases, while at least one virus was found in each of the sick colonies. Virus titers varied among the samples, and multiple virus infections were common in both groups with a high prevalence of Sacbrood virus (SBV), Black queen cell virus (BQCV) and Deformed wing virus (DWV). Based on the distribution of virus titers, we established four categories of infection: samples free of virus (C = 0), samples with low virus titer (estimated number of virus copies 0 < C < 10³), samples with medium virus titer (10³ ≤ C < 10⁷) and samples with high virus titer (C ≥ 10⁷). This allowed us to statistically compare virus levels in healthy and sick colonies. Using categories to communicate virus diagnosis results to beekeepers may help them to reach an informed decision on management strategies to prevent further spread of viruses among colonies.     

Complete genomic sequence of a dengue type 2 virus from the French West Indies

Severe forms of dengue fever, dengue haemorrhagic fever, and dengue shock syndrome, were not prominent in the Americas until the epidemic of Cuba in 1981. Since that time, they have spread to other countries in Central and South America, correlating with the spread of dengue type 2 viruses related to Southeast Asian strains. We report here the complete genomic sequence of a dengue type 2 virus isolated during the epidemic in La Martinique in 1998. This constitutes the first complete genetic characterization of a dengue virus strain from French West Indies, and also the first molecular identification in this region of a dengue 2 strain phylogenetically related to the emerging American type 2 dengue viruses.     

Etiological aspects of leukemias in primates including man

Attempts have been made to induce viral leukemia in monkeys (Papio hamadryas and Macaca arctoides) by inoculating them with blood from humans with different types of leukemias. In hamadryas baboons, the disease spread horizontally. By today 218 P. hamadryas and 5 M. arctoides monkeys had died of malignant lymphoma. The following viruses have been isolated from sick monkeys: lymphotropic baboon herpes virus (HVP), endogenous baboon C type viruses--xenotropic (BILN), and ecotropic (EVPG). C type oncovirus called "plasmic", which differs immunologically from the endogenous one, was also detected in the blood of sick animals. Altogether 165 sera from baboons, different species of macacas and chimpanzee were examined by the immunofluorescent technique for antibodies to HTLV virus isolated recently from sick humans with T cell leukemia/lymphoma. Antibodies to HTLV virus were detected only in monkeys (P. hamadryas and M. arctoides) with malignant lymphomas or in those which had been in close contact with them. Possible origin of simian HTLV-like virus is discussed. It originates either from leukemic patients or there is a family of primate HTLV like viruses related to the occurrence of leukemia.     

Immunological precursors of influenza epidemics]

The authors studied the immuno-epidemiological manifestations of ciculation and variability of the influenza virus during the periods preceding the officiallly recorded rise of the incidence of this disease. The following epidemic precursors were revealed: a) an increase of the number of persons who fell sick with subclinical form of the disease, accompanied by a rise in the population of the antibody level to the type of influenza virus whose latest variant later caused an epidemic morbidity elevation; b) a progressive predominance of the causative agent of the developing epidemic in the etiology of influenza; c) a growth of the collective immunity indices from the "minimal" to the "critical" levels; d) an increase of the sero-conversion multiplicity and of the antibody level in those who sustained the disease during the epidemic development. These precursors could be revealed at the period of from 1 1/2 to 6 months before the beginning of the morbidity growth caused by viruses of endogenous or of exogenous origin.     

An emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of Hand Foot and Mouth Disease in Fuyang city of China

Molecular characterization of wild-type measles viruses in China during 1995-2004 demonstrated that genotype H1 was endemic and widely distributed throughout the country. H1-associated cases and outbreaks caused a resurgence of measles beginning in 2005. A total of 210,094 measles cases and 101 deaths were reported by National Notifiable Diseases Reporting System (NNDRS) and Chinese Measles Laboratory Network (LabNet) from 2006 to 2007, and the incidences of measles were 6.8/100,000 population and 7.2/100,000 population in 2006 and 2007, respectively. Five hundred and sixty-five wild-type measles viruses were isolated from 24 of 31 provinces in mainland China during 2006 and 2007, and all of the wild type virus isolates belonged to cluster 1 of genotype H1. These results indicated that H1-cluster 1 viruses were the predominant viruses circulating in China from 2006 to 2007. This study contributes to previous efforts to generate critical baseline data about circulating wild-type measles viruses in China that will allow molecular epidemiologic studies to help measure the progress made toward China's goal of measles elimination by 2012.     

抵御新发、突发病毒性传染病的新思路——天然免疫机制的系统医学研究和针对宿主的广谱抗病毒药物的研发

病毒性传染疾病是人类社会的重大威胁,严重危害人民生命安全和国家、社会安定.随着国内外经济发展,城镇化、都市化、全球化的进程加快,新发和突发病毒性传染病呈现不断增高的趋势,如艾滋病病毒、严重急性呼吸综合征病毒、禽流感病毒、甲流感病毒、埃博拉病毒等近年来一次又一次在世界不同地区频繁发生并蔓延、流行.本次埃博拉病毒在西非的爆发和疫情失控更再次警示我国和国际社会关于发展有效防治新发、突发病毒性传染病措施的重要性和紧迫性.天然免疫与宿主抗病研究领域的突破性进展为解决该世界性难题开辟了新的思路和途径.     

Biological basis of rabies virus neurovirulence in mice: comparative pathogenesis study using the immunoperoxidase technique.

The CVS strain of fixed rabies virus causes acute, fatal encephalomyelitis in young adult ICR mice. Variant RV194-2, which was selected from CVS virus in cell culture with a neutralizing antiglycoprotein monoclonal antibody, has a single amino acid change in the glycoprotein. The infections caused by CVS virus and RV194-2 virus were compared in mice for 14 days postinoculation of 5 x 10(7) PFU into the right masseter muscle. All CVS virus-infected mice died (mean time to death, 7.9 days), compared with a mortality rate of 8.5% for RV194-2 virus-infected mice. RV194-2 virus spread to the ipsilateral trigeminal ganglion during the first 2 days postinoculation, and both viruses spread to the ipsilateral motor nucleus of the trigeminal nerve in the pons. Both viruses spread centrifugally and caused infection of bilateral trigeminal ganglia on day 3. The viruses spread throughout the central nervous system (CNS) at similar rates, but CVS virus infected many more neurons than did RV194-2 virus. Rabies virus antigen was observed in only occasional CNS neurons after day 6 of RV194-2 virus infection. By this time, CVS virus had caused severe widespread infection. In this model, virulence depends on improved efficiency of viral spread between CNS neurons rather than the rate of spread or topographical distribution of the infection.     

Molecular phylogeny of the psittacid herpesviruses causing Pacheco's disease: correlation of genotype with phenotypic expression

Fragments of 419 bp of the UL16 open reading frame from 73 psittacid herpesviruses (PsHVs) from the United States and Europe were sequenced. All viruses caused Pacheco's disease, and serotypes of the European isolates were known. A phylogenetic tree derived from these sequences demonstrated that the PsHVs that cause Pacheco's disease comprised four major genotypes, with each genotype including between two and four variants. With the exception of two viruses, the serotypes of the virus isolates could be predicted by the genotypes. Genotypes 1 and 4 corresponded to serotype 1 isolates, genotype 2 corresponded to serotype 2 isolates, and genotype 3 corresponded to serotype 3 isolates. The single serotype 4 virus mapped to genotype 4. DNA from a virus with a unique serotype could not be amplified with primers that amplified DNA from all other PsHVs, and its classification remains unknown. Viruses representing all four genotypes were found in both the United States and Europe, and it was therefore predicted that serotypes 1, 2, and 3 were present in the United States. Serotype 4 was represented by a single European isolate that could not be genetically distinguished from serotype 1 viruses; therefore, the presence of serotype 4 in the United States could not be predicted. Viruses of genotype 4 were found to be the most commonly associated with Pacheco's disease in macaws and conures and were least likely to be isolated in chicken embryo fibroblasts in the United States. All four genotypes caused deaths in Amazon parrots, but genotype 4 was associated with Pacheco's disease only in Amazons in Europe. Genotypes 2, 3, and 4, but not 1, were found in African grey parrots. Although parrots from the Pacific distribution represent a relatively small percentage of the total number of birds with Pacheco's disease, all four genotypes were found to cause disease in these species.     

A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus

CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus).     

Serosurvey for selected infectious disease agents in free-ranging black and white rhinoceros in Africa

Two hundred and eighty one serum samples collected from free-ranging black (Diceros bicornis) and white (Ceratotherium simum) rhinoceros, in the Republic of South Africa (RSA), Namibia, and Kenya from 1987-97, were examined for antibody to 16 different infectious agents. Positive antibody titers were detected against Akabane (59.8%), bluetongue (55%), African horse sickness (27.9%), epizootic haemorrhagic disease of deer (19.4%), parainfluenza type 3 (25.3%), bovine herpes virus 1 (3.1%), equine herpes virus 1 (8.8%) and bovine viral diarrhea (1.2%) viruses, and four serovars of Leptospira interrogans, (ranging 1.2 to 8.8%). No antibody was detected against Rift Valley fever virus, encephalomyocarditis virus, Brucella abortus, and Trypanosoma equiperdum. Interspecies differences were detected for African horse sickness, epizootic haemorrhagic disease of deer and parainfluenza type 3 viruses. There appeared to be some geographic variation in the prevalence of antibody for African horse sickness, bluetongue, epizootic haemorrhagic disease of deer, parainfluenza type 3, equine herpes virus 1 and Leptospira interrogans serovar bratislava.     

Subtypes of human immunodeficiency virus 1:classification,the origin and circulation in Europe

The modern classification of human immunodeficiency viruses of type 1 (HIV-1) is presented. The hypotheses concerning the origin of this virus are discussed. The data on the spread of the subtypes of HIV-1 in different countries of Western and Eastern Europe and in different risk groups are presented.     

Conservation of T cell epitopes between seasonal influenza viruses and the novel influenza A H7N9 virus

A novel avian influenza A (H7N9) virus recently emerged in the Yangtze River delta and caused diseases, often severe, in over 130 people. This H7N9 virus appeared to infect humans with greater ease than previous avian influenza virus subtypes such as H5N1 and H9N2. While there are other potential explanations for this large number of human infections with an avian influenza virus, we investigated whether a lack of conserved T-cell epitopes between endemic H1N1 and H3N2 influenza viruses and the novel H7N9 virus contributes to this observation. Here we demonstrate that a number of T cell epitopes are conserved between endemic H1N1 and H3N2 viruses and H7N9 virus. Most of these conserved epitopes are from viral internal proteins. The extent of conservation between endemic human seasonal influenza and avian influenza H7N9 was comparable to that with the highly pathogenic avian influenza H5N1. Thus, the ease of inter-species transmission of H7N9 viruses (compared with avian H5N1 viruses) cannot be attributed to the lack of conservation of such T cell epitopes. On the contrary, our findings predict significant T-cell based cross-reactions in the human population to the novel H7N9 virus. Our findings also have implications for H7N9 virus vaccine design.     

Low Virulence and Lack of Airborne Transmission of the Dutch Highly Pathogenic Avian Influenza Virus H5N8 in Ferrets

Highly pathogenic avian influenza (HPAI) H5N8 viruses that emerged in poultry in East Asia spread to Europe and North America by late 2014. Here we show that the European HPAI H5N8 viruses differ from the Korean and Japanese HPAI H5N8 viruses by several amino acids and that a Dutch HPAI H5N8 virus had low virulence and was not transmitted via the airborne route in ferrets. The virus did not cross-react with sera raised against pre-pandemic H5 vaccine strains. This data is useful for public health risk assessments.