Cause Of Respiratory Disease Research Articles

DETECTION OF MYCOPLASMA AND CHLAMYDIA IN PYTHONS WITH AND WITHOUT SERPENTOVIRUS INFECTION.

Serpentoviruses (order Nidovirales) are an important cause of respiratory disease in snakes. Although transmission studies have shown that serpentoviruses can cause respiratory disease in pythons, the possible role of additional potential pathogens is not yet understood. Very little information is available on the role of mycoplasma and chlamydia infections in disease in pythons. Diagnostic samples from 271 pythons of different genera submitted to a laboratory for detection of serpentoviruses were also screened for mycoplasma and chlamydia infections by PCR. Most of the samples were oral swabs. Almost 30% of the samples were positive for serpentoviruses, and mycoplasmas were detected in more than 60% of the pythons. The occurrence of these two pathogens correlated significantly (P < 0.001). Additionally, about 3% of the snakes tested positive for Chlamydia. This study found a high prevalence of mycoplasmas in the tested pythons and a correlation between infections with these bacteria and serpentoviruses in python samples submitted for diagnostic testing. Because the role mycoplasmas play in respiratory diseases of snakes is still largely unknown, further investigations are necessary to evaluate the role of mixed infections in disease.

Multisector Partnerships and Service Colocation to Increase Adoption of Influenza Vaccines and Address Food Insecurity.

Multisector Partnerships and Service Colocation to Increase Adoption of Influenza Vaccines and Address Food Insecurity.

Upper and lower respiratory tract correlates of protection against respiratory syncytial virus following vaccination of nonhuman primates

Respiratory syncytial virus (RSV) infection is a major cause of respiratory illness in infants and the elderly. Although several vaccines have been developed, none have succeeded in part due to our incomplete understanding of the correlates of immune protection. While both Tcells and antibodies play a role, emerging data suggest that antibody-mediated mechanisms alone may be sufficient to provide protection. Therefore, to map the humoral correlates of immunity against RSV, antibody responses across six different vaccines were profiled in a highly controlled nonhuman primate-challenge model. Viral loads were monitored in both the upper and lower respiratory tracts, and machine learning was used to determine the vaccine platform-agnostic antibody features associated with protection. Upper respiratory control was associated with virus-specific IgA levels, neutralization, and complement activity, whereas lower respiratory control was associated with Fc-mediated effector mechanisms. These findings provide critical compartment-specific insights toward the rational development of future vaccines.

CPD article: Felid lungworms: from complete strangers to major parasites

The parasitic nematodes Aelurostrongylus abstrusus, Troglostrongylus brevior and Capillaria aerophila affect the respiratory system of cats and are a primary cause of respiratory disease in cats in many countries. While they have been underestimated for a long time, in recent years academics and veterinarians have become more aware of their importance, and now felid lungworms are recognised as primary agents of respiratory disease. Therefore, timely diagnosis and treatment, and efficacious prevention methods are a priority in feline clinical practice. Recent data have unveiled many features of diseases caused by these nematodes, and this article reviews and discusses practical and clinical knowledge, as well as recent updates on clinical management of aelurostrongylosis, troglostrongylosis and capillariosis in cats.

Role of metapneumoviral glycoproteins in the evasion of the host cell innate immune response.

Human metapneumovirus (HMPV), an unsegmented negative-strand RNA virus, is the second most detected respiratory pathogen and one of the leading causes of respiratory illness in infants and immunodeficient individuals. HMPV infection of permissive cells in culture triggers a transient IFN response, which is efficiently suppressed later in infection. We report that two structural glycoproteins of the virus - namely G (Glycoprotein) and SH (Small Hydrophobic) - suppress the type I interferon (IFN) response in cell culture. This is manifested by inhibition of diverse steps of IFN induction and response, such as phosphorylation and nuclear translocation of IFN regulatory factor-3 and -7 (IRF3, IRF7), major transcription factors of the IFN gene. Furthermore, HMPV suppresses the cellular response to IFN by inhibiting the phosphorylation of STAT1 (Signal Transducer and Activator of Transcription 1), required for the induction of IFN-stimulated genes that act as antivirals. Site-directed mutagenesis revealed an important role of critical cysteine (Cys) residues in the Cys-rich carboxy terminal region of the SH protein in IFN suppression, whereas for G, the ectodomain plays a role. These results shed light on the mechanism of IFN suppression by HMPV, and may also offer avenues for new antiviral approaches in the future.

Effect of electric potential across electrodes for trapping joss smoke particles in DBD plasma atmospheric pressure

Particulate matters (PM) in air pollution have been known to be the cause of respiratory diseases. Many researchers have investigated methods of trapping the particulate matter. In this work, the trapping of smoke particles generated from a joss stick by using a dielectric barrier discharge (DBD) system operated under the atmospheric pressure condition was investigated. DBD system consists of an inner electrode which is made of aluminum wire filaments that are placed inside the acrylic cylindrical tube, and the outer electrode is made of metallic wrap around the tube. The electrodes were connected to a 50 Hz high voltage AC source which was adjusted to 0 V, 5kV, 7kV, and 10kV. A ventilating fan was used for draining the smoke particle from the joss stick through the inner electrode with an airflow velocity of 2.68 m/s. The effect of electric field and plasma trapping the smoke particles was investigated. Results from the experiment were further compared with a study by simulation. It was found that the smoke particle density measured by applying an electric potential difference of 0 V and 5 kV was similar; both conditions showed the highest smoke density values. On the other hand, when the electric potential difference was adjusted to 7 kV and 10kV, it was found that the smoke particles density decreased by 90%. The experiment also illustrated when the electric potential difference was increased high enough such that plasma was produced at 7 kV and 10 kV, the smoke particle density released from the tube was similar. Nevertheless, when comparing the mass of particles collected from the inner electrode with the plasma condition, it was found that the mass collected increased more than the operating condition with an electric potential difference of 0 kV and 5 kV without plasma.

Contribution of Nanotechnologies to Vaccine Development and Drug Delivery against Respiratory Viruses.

According to the Center for Disease Control and Prevention (CDC), the coronavirus disease 2019, a respiratory viral illness linked to significant morbidity, mortality, production loss, and severe economic depression, was the third-largest cause of death in 2020. Respiratory viruses such as influenza, respiratory syncytial virus, SARS-CoV-2, and adenovirus, are among the most common causes of respiratory illness in humans, spreading as pandemics or epidemics throughout all continents. Nanotechnologies are particles in the nanometer range made from various compositions. They can be lipid-based, polymer-based, protein-based, or inorganic in nature, but they are all bioinspired and virus-like. In this review, we aimed to present a short review of the different nanoparticles currently studied, in particular those which led to publications in the field of respiratory viruses. We evaluated those which could be beneficial for respiratory disease-based viruses; those which already have contributed, such as lipid nanoparticles in the context of COVID-19; and those which will contribute in the future either as vaccines or antiviral drug delivery systems. We present a short assessment based on a critical selection of evidence indicating nanotechnology's promise in the prevention and treatment of respiratory infections.

Coexpression of respiratory syncytial virus (RSV) fusion (F) protein and attachment glycoprotein (G) in a vesicular stomatitis virus (VSV) vector system provides synergistic effects against RSV infection in a cotton rat model

Respiratory syncytial virus (RSV) is one of the most important causes of respiratory disease in infants, immunocompromised individuals, and the elderly. Natural infection does not result in long-term immunity, and there is no licensed vaccine. Vesicular stomatitis virus (VSV) is a commonly used vaccine vector platform against infectious diseases, and has been used as a vector for a licensed Ebola vaccine. In this study, we expressed the RSV fusion (F) protein, the RSV F protein stabilized in either a pre-fusion or a post-fusion configuration, the attachment glycoprotein (G), or the G and F proteins of RSV in combination in a VSV vector. Cotton rats were immunized with these recombinants intranasally or subcutaneously to test immunogenicity. RSV F stabilized in either a pre-fusion or a post-fusion configuration proved to be poorly immunogenic and protective when compared to unmodified F. RSV G provided partial protection and moderate levels of neutralizing antibody production, both of which improved with intranasal administration compared to subcutaneous inoculation. The most successful vaccine vector was VSV expressing both the G and F proteins after intranasal inoculation. Immunization with this recombinant induced neutralizing antibodies and provided protection from RSV challenge in the upper and lower respiratory tract for at least 80 days. Our results demonstrate that co-expression of F and G proteins in a VSV vector provides synergistic effects in inducing RSV-specific neutralizing antibodies and protection against RSV infection.

Human coronavirus OC43 simulating COVID-19 pneumonia

Human coronavirus OC43 is a common cause of respiratory illness, especially in immunocompromised persons, including children and elderly adults. We report a 42-yearold immunocompetent woman with acute hypoxemic respiratory failure and positive results on OC43 coronavirus testing. This case indicates the need to consider other viral pathogens during this COVID-19 pandemic. Keywords: OC43 Coronavirus, COVID-19, pneumonia

Chloroquine and pyrimethamine inhibit the replication of human respiratory syncytial virus A.

Human respiratory syncytial virus (hRSV) is a major cause of respiratory illness in young children and can cause severe infections in the elderly or in immunocompromised adults. To date, there is no vaccine to prevent hRSV infections, and disease management is limited to preventive care by palivizumab in infants and supportive care for adults. Intervention with small-molecule antivirals specific for hRSV represents a good alternative, but no such compounds are currently approved. The investigation of existing drugs for new therapeutic purposes (drug repositioning) can be a faster approach to address this issue. In this study, we show that chloroquine and pyrimethamine inhibit the replication of human respiratory syncytial virus A (long strain) and synergistically increase the anti-replicative effect of ribavirin in cellulo. Moreover, chloroquine, but not pyrimethamine, inhibits hRSV replication in the mouse model. Our results show that chloroquine can potentially be an interesting compound for treatment of hRSV infection in monotherapy or in combination with other antivirals.

Formulasi Nasal Spray Anti-Influenza yang Mengandung Nanopartikel Perak

Influenza A virus is one of the most common causes of respiratory disease in the world. Even though, vaccines and anti-influenza virus are become the first line for therapy, but the mutation ability of influenza virus is able to cause several outbreaks in the world. Silver nanoparticles (AgNP) have been proven to exhibit antiviral activity; however, the use of AgNP in pharmaceutical products is still limited. In this study, we aimed to formulate nasal spray containing AgNP, to evaluate its physicochemical properties, and its antiviral activity toward H5N1 influenza A virus. AgNP were synthesized using chemical reduction method with polyvinyl alcohol as stabilizer, and further prepared into nasal spray product. Physicochemical properties and anti-hemagglutination activity of nasal spray were further evaluated. The nasal spray contained different size of AgNP (less and more than 50 nm) showed physical stability after 28 days storage. However, Anti-influenza evaluation of nasal spray contained AgNP less than 50 nm exhibited better anti-hemagglutination activity against influenza A virus.

The role of melatonin hormone and its receptor (type1A) as anti-cancer against carcinogenic effect of polyaromatic hydrocarbons in Iraqi refinery workers

Air pollution is a global health threat and causes millions of human deaths annually. Outdoor and indoor air pollutants such as polycyclic aromatic hydrocarbons (PAHs) are the most prevalent cause of respiratory disorders, lung disease, pregnancy disorders, endocrine disturbances, diabetes, obesity, cardiovascular disease and cancer because pollutants can alter gene expression via epigenetics like DNA methylation and histone modifications which can initiate tumorigenesis and progressed to cancer. Carcinogenicity of PAHs can be eliminated by endogenous melatonin hormone (MT) via binding to its receptor (MTNR1A) that act as free radicals scavenger therefore it protects the body from developing occupational cancer. Aims of studyTo predict the protective effect of melatonin hormone as anti-cancer through binding to its receptor (MTNR1A) against any type of cancer that can be induced by chronic exposure to air pollutants. Subjects and methodsThis study includes 168 participants, they have been divided into three groups (control, refinery field workers and refinery office workers). PAH was analyzed for each participant by GC/MS whereas melatonin hormone and MTNR1A were measured by ELISA technique. ResultsPAHs were absent in the blood of control, and they were elevated in refinery worker’s specimens. Concentration of MT was higher in field worker than in office and control group as well as MTNR1A, also there is a relation between their levels and duration of exposure. ConclusionExposure to PAHs can lead to oxidative stress that can damage DNA resulting in many types of cancer but this carcinogenic effects of PAHs can be eliminated by natural endogenous biomolecules such as MT and its receptor (MTNR1A) therefore their elevation has a beneficial effect as anti-cancer to reduce the oxidative stress and prevent tumorigenesis.

Virological Surveillance and Molecular Characterization of Human Parainfluenzavirus Infection in Children with Acute Respiratory Illness: Germany, 2015-2019.

Human parainfluenza viruses (HPIVs) are important causes of respiratory illness, especially in young children. However, surveillance for HPIV is rarely performed continuously, and national-level epidemiologic and genetic data are scarce. Within the German sentinel system, to monitor acute respiratory infections (ARI), 4463 respiratory specimens collected from outpatients < 5 years of age between October 2015 and September 2019 were retrospectively screened for HPIV 1–4 using real-time PCR. HPIV was identified in 459 (10%) samples. HPIV-3 was the most common HPIV-type, with 234 detections, followed by HPIV-1 (113), HPIV-4 (61), and HPIV-2 (49). HPIV-3 was more frequently associated with age < 2 years, and HPIV-4 was more frequently associated with pneumonia compared to other HPIV types. HPIV circulation displayed distinct seasonal patterns, which appeared to vary by type. Phylogenetic characterization clustered HPIV-1 in Clades 2 and 3. Reclassification was performed for HPIV-2, provisionally assigning two distinct HPIV-2 groups and six clades, with German HPIV-2s clustering in Clade 2.4. HPIV-3 clustered in C1, C3, C5, and, interestingly, in A. HPIV-4 clustered in Clades 2.1 and 2.2. The results of this study may serve to inform future approaches to diagnose and prevent HPIV infections, which contribute substantially to ARI in young children in Germany.

Numerical assessment of natural respiration and particles deposition in the computed tomography scan airway with a glomus tumour

The human respiratory tract has a complex airflow pattern. If any obstruction is present in the airways, it will change the airflow pattern and deposit particles inside the airways. This is the concern of breath quality (inspired air), and it is decreasing due to the unplanned production of material goods. This is a primary cause of respiratory illness (asthma, cancer, etc.). Therefore, it is important to identify the flow characteristics in the human airways and airways with a glomus tumour with particle deposition. A numerical diagnosis is presented with an asymmetric unsteady-state light breathing condition (10 l/min). An in vitro human respiratory tract model has been reconstructed using computed tomography scan techniques and an artificial glomus tumour developed 2 cm above a carina on the posterior wall of the trachea. The transient flow characteristics are numerically simulated with a realizable (low Reynolds number) k–ɛ turbulence model. The flow disturbance is captured around the tumour, which influenced the upstream and downstream of the flow. The flow velocity pattern, wall shear stress and probable area of inflammation (hotspot) due to suspended particle deposition are determined, which may assist doctors more effectively in aerosol therapy and prosthetics of human airways illness.

Isolation, Antimicrobial Resistance Phenotypes, and Virulence Genes of Bordetella bronchiseptica From Pigs in China, 2018-2020.

Bordetella bronchiseptica is a leading cause of respiratory diseases in pigs. However, epidemiological data of B. bronchiseptica in pigs particularly in China, the largest pig rearing country in the world is still limited. We isolated 181 B. bronchiseptica strains from 4259 lung samples of dead pigs with respiratory diseases in 14 provinces in China from 2018 to 2020. The average isolation rate of this 3-year period was 4.25% (181/4259). Antimicrobial susceptibility testing performed by disc diffusion method revealed that most of the B. bronchiseptica isolates in this study were resistant to ampicillin (83.98%), while a proportion of isolates were resistant to cefotaxime (30.39%%), chloramphenicol (12.71%), gentamicin (11.60%), florfenicol (11.60%), tetracycline (8.84%), amoxicillin (8.29%), tobramycin (6.63%), ceftriaxone (4.97%), and cefepime (0.55%). There were no isolates with resistant phenotypes to imipenem, meropenem, polymyxin B, ciprofloxacin, enrofloxacin, and amikacin. In addition, ~13.18% of the isolates showed phenotypes of multidrug resistance. Detection of antimicrobial resistance genes (ARGs) by PCR showed that 16.57% of the B. bronchiseptica isolates in this study was positive to aac(3)-IV, while 3.87%, 2.21%, 1.10%, 0.55%, 0.55%, and 0.55% of the isolates were positive to aac6'-Ib, rmtA, blaTEM, blaSHV, oqxB, and tetA, respectively. Detection of virulence factors encoding genes (VFGs) by conventional PCR showed that over 90% of the pig B. bronchiseptica isolates in this study were positive to the five VFGs examined (fhaB, 97.24%; prn, 91.16%; cyaA, 98.34%; dnt, 98.34%; betA, 92.82%). These results demonstrate B. bronchiseptica as an important pathogen associated with pig respiratory disorders in China. The present work contributes to the current understanding of the prevalence, antimicrobial resistance and virulence genes of B. bronchiseptica in pigs.

Sendai Virus-Vectored Vaccines That Express Envelope Glycoproteins of Respiratory Viruses.

Human respiratory syncytial virus (HRSV), human metapneumovirus (HMPV), and human parainfluenza viruses (HPIVs) are leading causes of respiratory disease in young children, the elderly, and individuals of all ages with immunosuppression. Vaccination strategies against these pneumoviruses and paramyxoviruses are vast in number, yet no licensed vaccines are available. Here, we review development of Sendai virus (SeV), a versatile pediatric vaccine that can (a) serve as a Jennerian vaccine against HPIV1, (b) serve as a recombinant vaccine against HRSV, HPIV2, HPIV3, and HMPV, (c) accommodate foreign genes for viral glycoproteins in multiple intergenic positions, (d) induce durable, mucosal, B-cell, and T-cell immune responses without enhanced immunopathology, (e) protect cotton rats, African green monkeys, and chimpanzees from infection, and (f) be formulated into a vaccine cocktail. Clinical phase I safety trials of SeV have been completed in adults and 3–6-year-old children. Clinical testing of SeVRSV, an HRSV fusion (F) glycoprotein gene recombinant, has also been completed in adults. Positive results from these studies, and collaborative efforts with the National Institutes of Health and the Serum Institute of India assist advanced development of SeV-based vaccines. Prospects are now good for vaccine successes in infants and consequent protection against serious viral disease.

Respiratory syncytial virus M2-1 protein associates non-specifically with viral messenger RNA and with specific cellular messenger RNA transcripts.

Respiratory syncytial virus (RSV) is a major cause of respiratory disease in infants and the elderly. RSV is a non-segmented negative strand RNA virus. The viral M2-1 protein plays a key role in viral transcription, serving as an elongation factor to enable synthesis of full-length mRNAs. M2-1 contains an unusual CCCH zinc-finger motif that is conserved in the related human metapneumovirus M2-1 protein and filovirus VP30 proteins. Previous biochemical studies have suggested that RSV M2-1 might bind to specific virus RNA sequences, such as the transcription gene end signals or poly A tails, but there was no clear consensus on what RSV sequences it binds. To determine if M2-1 binds to specific RSV RNA sequences during infection, we mapped points of M2-1:RNA interactions in RSV-infected cells at 8 and 18 hours post infection using crosslinking immunoprecipitation with RNA sequencing (CLIP-Seq). This analysis revealed that M2-1 interacts specifically with positive sense RSV RNA, but not negative sense genome RNA. It also showed that M2-1 makes contacts along the length of each viral mRNA, indicating that M2-1 functions as a component of the transcriptase complex, transiently associating with nascent mRNA being extruded from the polymerase. In addition, we found that M2-1 binds specific cellular mRNAs. In contrast to the situation with RSV mRNA, M2-1 binds discrete sites within cellular mRNAs, with a preference for A/U rich sequences. These results suggest that in addition to its previously described role in transcription elongation, M2-1 might have an additional role involving cellular RNA interactions.

Cat Respiratory Nematodes: Current Knowledge, Novel Data and Warranted Studies on Clinical Features, Treatment and Control.

The nematodes Aelurostrongylus abstrusus, Troglostrongylus brevior and Capillaria aerophila are the most important parasites inhabiting the airways of cats. They are receiving growing attention from academia, pharmaceutical companies and veterinarians, and are now considered a primary cause of respiratory diseases in feline clinical practice and parasitology. In the past few years, several studies have been conducted in both natural and experimental settings to increase knowledge, provide new insights and fill gaps on respiratory parasitoses of cats. Awareness and knowledge of clinical scenarios towards appropriate and timely diagnosis and prompt and efficacious treatment options have become a priority to investigate. At the same time, chemopreventative approaches have been evaluated to assess the geographical spreading of these parasites and the rise in the number of clinical cases in cat populations of different countries. Given the intense accumulation of novel data, this review presents and discusses the state of the art and the latest updates on the clinical features, treatment, and control of major respiratory parasitoses of cats. Moreover, food for thought is also provided with the aim of spurring on new studies in the near future.

Fine Particles in Wildfire Smoke and Pediatric Respiratory Health in California.

Exposure to airborne fine particles with diameters ≤2.5 μm (PM2.5) pollution is a well-established cause of respiratory diseases in children; whether wildfire-specific PM2.5 causes more damage, however, remains uncertain. We examine the associations between wildfire-specific PM2.5 and pediatric respiratory health during the period 2011-2017 in San Diego County, California, and compare these results with other sources of PM2.5. Visits to emergency and urgent care facilities of Rady's Children Hospital network in San Diego County, California, by individuals (aged ≤19 years) with ≥1 of the following respiratory conditions: difficulty breathing, respiratory distress, wheezing, asthma, or cough were regressed on daily, community-level exposure to wildfire-specific PM2.5 and PM2.5 from ambient sources (eg, traffic emissions). A 10-unit increase in PM2.5 (from nonsmoke sources) was estimated to increase the number of admissions by 3.7% (95% confidence interval: 1.2% to 6.1%). In contrast, the effect of PM2.5 attributable to wildfire was estimated to be a 30.0% (95% confidence interval: 26.6% to 33.4%) increase in visits. Wildfire-specific PM2.5 was found to be ∼10 times more harmful on children's respiratory health than PM2.5 from other sources, particularly for children aged 0 to 5 years. Even relatively modest wildfires and associated PM2.5 resolved on our record produced major health impacts, particularly for younger children, in comparison with ambient PM2.5.

Effectiveness of the quadrivalent high-dose influenza vaccine for prevention of cardiovascular and respiratory events in people aged 65 years and above: Rationale and design of a real-world pragmatic randomized clinical trial

BackgroundInfluenza has been an acknowledged cause of respiratory disease for decades. However, considerable related, and often unappreciated, disease burden stems from cardiovascular complications, exacerbations of underlying medical conditions and secondary respiratory complications, with the highest burden in the elderly. This novel study combines the gold standard method of a randomized controlled trial with real-world data collection through national registries, to assess the relative effectiveness of high-dose (QIV-HD) vs standard-dose quadrivalent influenza vaccine (QIV-SD) in preventing cardio-respiratory hospitalizations in a large cohort of adults aged ≥65 years. Methods and resultsThis trial (NCT04137887) is a Phase III/IV, modified double-blinded, randomized, registry-based trial, conducted by the Finnish Institute for Health and Welfare (THL). Participants (n>120 000) are being enrolled over multiple influenza seasons and randomized (1:1) to receive QIV-HD or QIV-SD. Participant follow-up is based on data collection up to 11 months post-vaccination using Finnish national health registries. The primary objective is to demonstrate the relative superior effectiveness of QIV-HD over QIV-SD in preventing cardio-respiratory hospitalizations up to 6 months post-vaccination. Safety will be assessed using automated online tools throughout the study, with causality assessed using statistical and probabilistic methods; serious adverse reactions and adverse events of special interest will be investigated individually. ConclusionThis large, real-world, randomized study will provide valuable insight into the contribution of influenza in causing severe cardio-respiratory events, and the role of vaccination with QIV-HD in reducing these outcomes compared to the current standard of care. FundingSanofi Pasteur