New Strain Of Influenza Research Articles

Heterotypic Influenza Infections Mitigate Susceptibility to Secondary Bacterial Infection.

Influenza-associated bacterial superinfections have devastating impacts on the lung and can result in increased risk of mortality. New strains of influenza circulate throughout the population yearly, promoting the establishment of immune memory. Nearly all individuals have some degree of influenza memory before adulthood. Due to this, we sought to understand the role of immune memory during bacterial superinfections. An influenza heterotypic immunity model was established using influenza A/Puerto Rico/8/34 and influenza A/X31. We report in this article that influenza-experienced mice are more resistant to secondary bacterial infection with methicillin-resistant Staphylococcus aureus as determined by wasting, bacterial burden, pulmonary inflammation, and lung leak, despite significant ongoing lung remodeling. Multidimensional flow cytometry and lung transcriptomics revealed significant alterations in the lung environment in influenza-experienced mice compared with naive animals. These include changes in the lung monocyte and T cell compartments, characterized by increased expansion of influenza tetramer-specific CD8+ T cells. The protection that was seen in the memory-experienced mouse model is associated with the reduction in inflammatory mechanisms, making the lung less susceptible to damage and subsequent bacterial colonization. These findings provide insight into how influenza heterotypic immunity reshapes the lung environment and the immune response to a rechallenge event, which is highly relevant to the context of human infection.

Designing a multi-epitope vaccine to provoke the robust immune response against influenza A H7N9

A new strain of Influenza A Virus (IAV), so-called "H7N9 Avian Influenza", is the first strain of this virus in which a human is infected by transmitting the N9 of influenza virus. Although continuous human-to-human transmission has not been reported, the occurrence of various H7N9-associated epidemics and the lack of production of strong antibodies against H7N9 in humans warn of the potential for H7N9 to become a new pandemic. Therefore, the need for effective vaccination against H7N9 as a life-threatening viral pathogen has become a major concern. The current study reports the design of a multi-epitope vaccine against Hemagglutinin (HA) and Neuraminidase (NA) proteins of H7N9 Influenza A virus by prediction of Cytotoxic T lymphocyte (CTL), Helper T lymphocyte (HTL), IFN-γ and B-cell epitopes. Human β-defensin-3 (HβD-3) and pan HLA DR-binding epitope (PADRE) sequence were considered as adjuvant. EAAAK, AAY, GPGPG, HEYGAEALERAG, KK and RVRR linkers were used as a connector for epitopes. The final construct contained 777 amino acids that are expected to be a recombinant protein of about ~ 86.38 kDa with antigenic and non-allergenic properties after expression. Modeled protein analysis based on the tertiary structure validation, docking studies, and molecular dynamics simulations results like Root-mean-square deviation (RMSD), Gyration, Root-mean-square fluctuation (RMSF) and Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) showed that this protein has a stable construct and capable of being in interaction with Toll-like receptor 7 (TLR7), TLR8 and m826 antibody. Analysis of the obtained data the demonstrates that suggested vaccine has the potential to induce the immune response by stimulating T and Bcells, and may be utilizable for prevention purposes against Avian Influenza A (H7N9).

Why Pandemics Matter to the History of U.S. State Development

When a new strain of influenza circled the globe in the fall and winter of 1918, it swept through the United States at terrifying speed, infecting at least 25 million Americans—roughly one-quarter of the population—over the next two years. Based on any metric, the pandemic was the country's largest mass-mortality episode of the twentieth century, killing approximately 675,000 Americans and surpassing the death toll of World War I. Even as the virus struck the United States with unprecedented ferocity, however, the federal government left most public health decisions to the states, producing a disjointed and hyper-localized approach to a crisis that was national and global in scope. In the absence of a strong federal role, state governments carved out their own policy paths, adopting widely divergent strategies to stem the spread of the disease. This preventive playing field was wildly uneven. Some states were well-equipped with robust public health infrastructures; others lacked the tools to manage the disease's rampant spread.

Broad-Spectrum Antiviral Strategies and Nucleoside Analogues.

The emergence or re-emergence of viruses with epidemic and/or pandemic potential, such as Ebola, Zika, Middle East Respiratory Syndrome (MERS-CoV), Severe Acute Respiratory Syndrome Coronavirus 1 and 2 (SARS and SARS-CoV-2) viruses, or new strains of influenza represents significant human health threats due to the absence of available treatments. Vaccines represent a key answer to control these viruses. However, in the case of a public health emergency, vaccine development, safety, and partial efficacy concerns may hinder their prompt deployment. Thus, developing broad-spectrum antiviral molecules for a fast response is essential to face an outbreak crisis as well as for bioweapon countermeasures. So far, broad-spectrum antivirals include two main categories: the family of drugs targeting the host-cell machinery essential for virus infection and replication, and the family of drugs directly targeting viruses. Among the molecules directly targeting viruses, nucleoside analogues form an essential class of broad-spectrum antiviral drugs. In this review, we will discuss the interest for broad-spectrum antiviral strategies and their limitations, with an emphasis on virus-targeted, broad-spectrum, antiviral nucleoside analogues and their mechanisms of action.

Transmission of Acute Respiratory Infections in a City: Agent-Based Approach

An incidence curve of acute respiratory infections in Moscow has three picks between September and April and reaches its maximum in January- February. The emergence of new strains of influenza A could account for only one pick a year. The most cases of common cold are caused by ubiquitous low pathogenic viruses. In order to simulate weekly fluctuation of incidence rate of acute respiratory illnesses we developed an agent-based model. It contains 10 millions agents with such attributes as sex, age, social status, levels of specific immune memory and lists of contacts. Each agent can contact with members of its household, colleagues or classmates. Through such contacts susceptible agent can be infected with one of seven circulating respiratory viruses. Viruses differ in their immunologic properties and assume to present influenza A virus, influenza B virus, parainfluenza, adenovirus, coronavirus, rhinovirus and respiratory syncytial virus. The rate of transmission depends on duration of contact, vulnerability of susceptible agent, infectivity of infected agent and air temperature. Proposed network of social interactions proved to be sufficiently detailed as it provided good fitting for observed incidence rate including periods of school holidays and winter public holidays. Additionally, the estimates of basic reproductive rate for the viruses confirm that all these viruses except new strains of influenza A are relatively harmless and unable to cause significant growth of acute respiratory infections morbidity.

Prevalence and Determinants of Flu Vaccination in a Working Population

Introduction: Influenza viruses are highly contagious. Frequently, new strains of influenza are identified. Influenza vaccination is the most effective way of influenza prevention. Numerous jobs experience a risk of occupational exposure to influenza; this may conduct to the transmission of the infection to other people and coworkers. The aim is to determine influenza vaccination rates and factors, which influence the vaccination decision regarding a working population exposed to variable contamination risks. Methodology: A cross sectional survey was conducted during 2015-2016’s influenza vaccination campaign. The study concerns a representative sample of a population of 50,000 workers belonging to a large distribution of occupational branches. Workers were asked, during their occupational medical examination, to complete a brief questionnaire containing a list of reasons for either being vaccinated or not. The number of contacts with people during work, which is supposedly influencing the flu contamination, was also taken into account. Results: The annual influenza vaccination rate was quite low for all groups of workers. But the intention to receive vaccination was twice higher for the most exposed group, which may be subject to contamination during work. One of their most common reasons for not being vaccinated was to have a good health and not feeling concerned by flu. The main reason given about immunization against the flu was in order to avoid contamination by family or co-workers. Discussion: The low rate of flu vaccination indicated that most of workers were susceptible to infection. International data shows highly variable vaccination rates. The most important tool regarding the decision making of performing influenza vaccination could be related to internal and external communications. The low coverage achieved is an occupational and public health problem. This finding confirms the importance of a comprehensive approach towards the influenza vaccination, ensuring that workers are correctly informed about flu vaccine.

Perceived concern about the new strain of the influenza and obtaining the vaccine in China, Japan and South Korea.

This study compares the factors, which influence individuals from the countries of China, Japan and South Korea to obtain any type of influenza vaccines and their perceived concerns about the new strain of the influenza - pandemic (H1N1) 2009. The data analyzed was from the East Asian Social Survey (EASS), Cross-National Survey Data Sets: Health and Society in East Asia, 2010 (ICPSR 34608) (N=7938). The results of this study suggest that individuals who are concerned about the new strain of influenza are more likely to have obtained influenza vaccine. In these countries, perceived concerns may be directly related to vaccine-related behaviors. The results of this study also indicate that there are variations within each country regarding as to why individuals do or do not obtain the influenza vaccine. Over all, this project provides new insights about the acquisition of the influenza vaccine within China, Japan and South Korea, which will be useful for medical practice within these countries and future research.

Seroprevalence of Pandemic A(H1N1) pmd09 Virus Antibodies in Mexican Health Care Workers Before and After Vaccination

In April 2009, a new strain of influenza A(H1N1) was identified in Mexico and in the U.S. In June 2009, WHO declared this a pandemic. Health care workers constituted a risk group for their close contact with infected individuals. The aim was to estimate seropositivity for A(H1N1)pdm09 in health staff at the Instituto Mexicano del Seguro Social. A two-stage cross-sectional study, before and after vaccination in the same workers, was performed on a random sample of health-care workers. A socio-occupational questionnaire was applied and serum antibodies against influenza A(H1N1)pdm09 were determined through neutralization of retroviral pseudotypes; two logistic regression models for both were constructed. The average (median/mean) age of 1378 participants from 13 work centers was 41.7 years and 68.7% (947) were women. Seroprevalence for the first stage was 26.5% (365) (7.4-43%) vs. 20.8% (11) in a control group from the blood bank; for the second stage, the vaccinated group was 33% (215) (18.2-47%) and 27% (196) (11.6-50%) for the unvaccinated group. In regression models, seropositivity was associated with occupational exposure to suspected influenza infected patients, being physicians, and being vaccinated. Seropositivity against pandemic virus is similar to what was reported, both for vaccinated (2.8-40.9%) and unvaccinated (18.8-64.7%). Low seroprevalence in the vaccinated group indicates that between 67% and 73% were susceptible to infection. Given the relatively low vaccine-induced seropositivity, it is imperative to increase, hygiene and safety for health staff and at-risk populations, and strengthen epidemiological surveillance.

An Empirical Analysis of Extended Meanings of Lexical Items in a H1N1 Corpus

The year 2009 has witnessed a global outbreak of a new strain of influenza A virus subtype H1N1. Despite the high exposure on the mass media, few researches have been conducted on the discourse related to the H1N1 event. This study examined six frequently-occurred lexical items in a pandemic (H1N1) corpus: influenza, pandemic, cases, virus, transmission and death, using Sinclair's (2004) descriptive model of lexical items. WordSmith 5.0 (Scott, 2010) was used to generate a keyword list and concordances. The randomly-selected concordances were then analysed from five perspectives, the core, collocation, colligation, semantic preference and semantic prosody. The findings show that the extended meanings of the lexical items are specific in the context of pandemic H1N1 event and they are interrelated in the context. It is argued that it is the study of lexical items rather than single words that enables language learners to better understand the meanings of words.

Pandemic H1N1 2009 among Pediatric Age Group in Tamilnadu, June 2009 - Aug 2010

Influenza A viruses causes recurrent outbreaks on local or global scale with potentially severe consequences on human health and the global economy. The new strain of Influenza A virus - H1N1 2009 had caused pandemic disease among human, probably owing to little or no preexisting immunity to the new strain. This is a retrospective analysis of the impact of H1N12009 on the pediatric population of Tamil Nadu during the pandemic period of June 2009- August 2010. Throat and nasal swabs were taken from the suspected cases admitted in pediatric wards and intensive care units (ICUs) and were subjected to Real time RT PCR. A total of 6245 suspected pediatric cases were screened, of which 787 (12.60%) were found to be positive for H1N12009. A majority of cases belonged to the 6–12 age group (35.58%). Male children were more affected than female children. Despite a fall in the number of positives in 2010, there is a concern about the probability of a new reasssortment of H1N1 2009 with other viruses of either human or animal hosts during the next season that could result in a potentially pathogenic strain.

An Epidemiological Study on Influenza A(H1N1) in Makkah

The flu pandemic is a global outbreak of a new strain of influenza A virus subtype H1N1, termed Pandemic H1N1/09 virus by the World Health Organization (WHO), which was first identified in April 2009. The disease has also been termed novel Influenza A(H1N1) and 2009 H1N1 flu by the US Centers for Disease Control and Prevention (CDC), and is commonly known as swine flu. The main strain of the virus has been termed A/California/07/2009 (H1N1) by scientists. This study was conducted to describe the epidemiology of influenza A(H1N1) infections in KSA during 2009. A descriptive study was carried out among attendants at hospitals and primary health care centers in Makkah during 2009, irrespective of age and sex. The data were collected by interviewing suspected persons using a pre-designed questionnaire, clinical examination, and specific laboratory investigation. A total of 1138 subjects were included in the study. Among the study population, 25% of the cases between 15 and 24 years old were found positive for influenza A(H1N1) by PCR technique. Although a significant population was affected by influenza A(H1N1) during 2009 in Makkah, the efforts and steps taken by health authorities at all levels―especially those in Directorate of Health Affairs of Makkah—helped to avert the mortality associated with the H1N1 influenza among the residents and those coming for Umrah and Hajj to Makkah by providing and timely diagnosis.

Virological Investigation of Avian Influenza Virus on Postglacial Species of Phasianidae and Tetraonidae in the Italian Alps

Land-based birds, belonging to Galliformes order are considered to be potential intermediaries in the emergence of new strains of influenza A viruses (AIVs), but the viral circulation in these birds remains largely unknown. To gain insights into the circulation of AIV in the wild Galliformes populations in Italian Alps, we conducted a virological survey on rock partridge (Alectoris graeca saxatilis) belonging to Phasianidae family and on tetraonids including rock ptarmigan (Lagopus mutus helveticus) and black grouse (Tetrao tetrix tetrix). In 2003 and 2004, during the hunting seasons, 79 wild Galliformes, categorised into age and sex classes, were hunted in the Sondrio Province (Central Alps). Cloacal swabs were collected from 11 rock partridges and from 68 tetraonids including 23 alpine rock ptarmigans and 45 black grouses. We tested cloacal swabs by a high sensitive reverse transcription- (RT-) PCR detecting the matrix gene of AIV. No AIV was detected in the investigated samples, thus, suggesting the lack of AIV circulation in these relict populations in the study period. In terms of threatened species conservation, during wildlife management activities, it is very important to exclude the introduction of AIV-carrier birds in shared territories, a fact representing a health risk for these populations.

Using public health scenarios to predict the utility of a national syndromic surveillance programme during the 2012 London Olympic and Paralympic Games.

During 2012 real-time syndromic surveillance formed a key part of the daily public health surveillance for the London Olympic and Paralympic Games. It was vital that these systems were evaluated prior to the Games; in particular what types and scales of incidents could and could not be detected. Different public health scenarios were created covering a range of potential incidents that the Health Protection Agency would require syndromic surveillance to rapidly detect and monitor. For the scenarios considered it is now possible to determine what is likely to be detectable and how incidents are likely to present using the different syndromic systems. Small localized incidents involving food poisoning are most likely to be detected the next day via emergency department surveillance, while a new strain of influenza is more likely to be detected via GP or telephone helpline surveillance, several weeks after the first seed case is introduced.

Balancing Societal Needs and Regulatory Certainty: The Case Study of Peramivir in Japan

Regulators must balance societal and medical requirements against the need for certainty about benefit and risk for new medicines. This is described in a case study of the expedited review and approval of peramivir, a novel neuraminidase inhibitor, in Japan in the context of the emergence of new strain of influenza in 2009. The case illustrates the importance of regulatory science and transparency in supporting such decision making.

INFLUENZA A (H1N1) AND THE RESISTANCE TO OSELTAMIVIR

Influenza is an acute infection of the respiratory system usually self-limiting, evolving towards complete cure due to the immunological response of the infected organism, but that can have serious complications, such as pneumonia and death. It is a disease widely distributed around the world, associated with several pandemics for over a century. The most recent pandemic occurred in 2009, when a new strain of influenza A (H1N1) virus caused an outbreak in Veracruz, Mexico, and rapidly spread though all the continents, causing over 12 thousand deaths in less than a year. Considering that this new strain of the virus is only sensitive to neuraminidase inhibitors (oseltamivir and zanamivir) and that the protocol of the World Health Organization recommends the use of oseltamivir as a single drug therapy, this study was performed with the intention of collecting and compiling data about the occurrence of resistance to this medication, in particular due to a H274Y substitution. In addition to mapping the occurrence of resistant virus, data was also collect about the person-to-person transmission of the virus with the mutation H274Y, as well as about the association of the appearance of resistance with the use of the drug. DOI: http://dx.doi.org/10.17525/vrrjournal.v17i1-2.56

Theoretical Studies on the Susceptibility of Oseltamivir against Variants of 2009 A/H1N1 Influenza Neuraminidase

The outbreak and high speed global spread of the new strain of influenza A/H1N1 virus in 2009 posed a serious threat to global health. It is more likely that drug-resistant influenza strains will arise after the extensive use of anti-influenza drugs. Consequently, the identification of the potential resistant sites for drugs in advance and the understanding of the corresponding molecular mechanisms that cause drug resistance are quite important in the design of new drug candidates with better potency to combat drug resistance. Here, we performed molecular simulations to evaluate the potency of oseltamivir to combat drug resistance caused by the mutations in 2009 A/H1N1 neuraminidase (NA). We examined three representative drug-resistant mutations in NA, consisting of H274Y, N294S, and Y252H. First, a theoretical structure of A/H1N1 NA in complex with oseltamivir was constructed using homology modeling. Then, molecular dynamics (MD) simulations, molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) calculations, and MM/GBSA free energy decomposition were used to characterize the binding of oseltamivir with the wild type (WT) and three mutated NAs. Our predictions show that N294S and H274Y, two popular drug-resistant mutations in different variants of NA, still cause significant resistance to oseltamivir. However, the Y252H mutation does not impair the interactions between oseltamivir and A/H1N1 NA. An examination of individual energy components shows that the loss of polar interactions is the key source for the resistance of the studied mutations to oseltamivir. Moreover, free energy decomposition analysis and structural analysis reveal that the N294S or H274Y mutation triggers the large-scale conformational changes of the binding pocket and then impairs the affinity of oseltamivir. We expect that our results will be useful for the rational design of NA inhibitors with high potency against drug-resistant A/H1N1 mutants.

Infectious disease emergence and global change: thinking systemically in a shrinking world.

BackgroundConcern intensifying that emerging infectious diseases and global environmental changes that could generate major future human pandemics.MethodA focused literature review was undertaken, partly informed by a forthcoming report on environment, agriculture and infectious diseases of poverty, facilitated by the Special Programme for Tropical Diseases.ResultsMore than ten categories of infectious disease emergence exist, but none formally analyse past, current or future burden of disease. Other evidence suggests that the dominant public health concern focuses on two informal groupings. Most important is the perceived threat of newly recognised infections, especially viruses that arise or are newly discovered in developing countries that originate in species exotic to developed countries, such as non-human primates, bats and rodents. These pathogens may be transmitted by insects or bats, or via direct human contact with bushmeat. The second group is new strains of influenza arising from intensively farmed chickens or pigs, or emerging from Asian “wet markets” where several bird species have close contact. Both forms appear justified because of two great pandemics: HIV/AIDS (which appears to have originated from bushmeat hunting in Africa before emerging globally) and Spanish influenza, which killed up to 2.5% of the human population around the end of World War I. Insufficiently appreciated is the contribution of the milieu which appeared to facilitate the high disease burden in these pandemics. Additionally, excess anxiety over emerging infectious diseases diverts attention from issues of greater public health importance, especially: (i) existing (including neglected) infectious diseases and (ii) the changing milieu that is eroding the determinants of immunity and public health, caused by adverse global environmental changes, including climate change and other components of stressed life and civilisation-supporting systems.ConclusionsThe focus on novel pathogens and minor forms of anti-microbial resistance in emerging disease literature is unjustified by their burden of disease, actual and potential, and diverts attention from far more important health problems and determinants. There is insufficient understanding of systemic factors that promote pandemics. Adverse global change could generate circumstances conducive to future pandemics with a high burden of disease, arising via anti-microbial and insecticidal resistance, under-nutrition, conflict, and public health breakdown.

Influenza A/H1N1 (2009) Infection as a Cause of Unexpected Out‐of‐Hospital Death in the Young*

: In March 2009, a new strain of influenza A/H1N1 virus was identified in Mexico, responsible for a pandemic. Worldwide, more than 13,500 patients died, most often from acute respiratory distress syndrome. Because sudden death cases were rare, involving mostly young apparently healthy persons, influenza A/H1N1 (2009)‐related deaths may be misdiagnosed, which can raise medico‐legal issues. Case history: we report on an unexpected out‐of‐hospital death involving a young male with no past medical history and no vaccination. Fever was his only symptom. Laboratory tests: histology showed patchy necrotic foci with mononuclear inflammation in the lungs. The heart was histologically normal, but virological analyses using molecular biology on frozen myocardial samples showed high virus load. In conclusion, this case report shows that influenza A/H1N1 (2009) virus can be a cause of sudden cardiac death in the young and demonstrates the importance of quantitative virological analyses for the diagnosis of myocarditis.

Experience with Pandemic 2009 H1N1 Influenza in a Large Pediatric Hospital

In 2009, a new strain of influenza A, H1N1, was detected in two children in the United States. It spread quickly and became pandemic (pH1N1), disproportionately affecting children. The aim of the present study was to describe our experience with pH1N1 in a large pediatric hospital. We reviewed the clinical records of all of the children diagnosed as having influenza A at Children's Hospital, New Orleans, LA, for the period April 2009 to May 2010. Diagnosis was made by rapid influenza test or direct fluorescent antibody. Specimens form hospitalized children were sent to the Louisiana Office of Public Health for confirmation by reverse-transcription-polymerase chain reaction. During the 14-month study period, 10,470 children were tested and 1463 (14%) tested positive for influenza A. Boys were more commonly infected than girls (53% vs 47%, P < .001). Of the cases, 1308 (89%) were ambulatory and 155 (11%) were hospitalized. Hospitalized children were younger, more frequently white, had non-Medicaid insurance, and had comorbidity. Of the 155 admissions, 14 (9%) were admitted to the intensive care unit. Having a comorbidity increased and being black decreased the chances of being admitted to the intensive care unit. Three children died, all with severe neurologic or respiratory predisposing illness. Eight cases of hospital-onset influenza and 6 of repeat infection were detected. pH1N1 burdened pediatric facilities during the 2009-2010 influenza season. Even though most cases were mild and self-limited, some resulted in severe disease and long-term complications.

Sociodemographic factors and clinical conditions associated to hospitalization in influenza A (H1N1) 2009 virus infected patients in Spain, 2009-2010.

The emergence and pandemic spread of a new strain of influenza A (H1N1) virus in 2009 resulted in a serious alarm in clinical and public health services all over the world. One distinguishing feature of this new influenza pandemic was the different profile of hospitalized patients compared to those from traditional seasonal influenza infections. Our goal was to analyze sociodemographic and clinical factors associated to hospitalization following infection by influenza A(H1N1) virus. We report the results of a Spanish nationwide study with laboratory confirmed infection by the new pandemic virus in a case-control design based on hospitalized patients. The main risk factors for hospitalization of influenza A (H1N1) 2009 were determined to be obesity (BMI≥40, with an odds-ratio [OR] 14.27), hematological neoplasia (OR 10.71), chronic heart disease, COPD (OR 5.16) and neurological disease, among the clinical conditions, whereas low education level and some ethnic backgrounds (Gypsies and Amerinds) were the sociodemographic variables found associated to hospitalization. The presence of any clinical condition of moderate risk almost triples the risk of hospitalization (OR 2.88) and high risk conditions raise this value markedly (OR 6.43). The risk of hospitalization increased proportionally when for two (OR 2.08) or for three or more (OR 4.86) risk factors were simultaneously present in the same patient. These findings should be considered when a new influenza virus appears in the human population.