Global epidemiology of Equine Influenza viruses; “A possible emerging zoonotic threat in future” an extensive systematic review with evidence

There are different opinions around the World regarding the zoonotic capability of H3N8 equine influenza viruses. In this report, we have tried to summarize the findings of different research and review articles from Chinese, English, and Mongolian Scientific Literature reporting the evidence for equine influenza virus infections in human beings. Different search engines i.e. CNKI, PubMed, ProQuest, Chongqing Database, Mongol Med, and Web of Knowledge yielded 926 articles, of which 32 articles met the inclusion criteria for this review. Analyzing the epidemiological and Phylogenetic data from these articles, we found a considerable experimental and observational evidence of H3N8 equine influenza viruses infecting human being in different parts of the World in the past. Recently published articles from Pakistan and China have highlighted the emerging threat and capability of equine influenza viruses for an epidemic in human beings in future. In this review article we have summarized the salient scientific reports published on the epidemiology of equine influenza viruses and their zoonotic aspect. Additionally, several recent developments in the start of 21st century, including the transmission and establishment of equine influenza viruses in different animal species i.e. camels and dogs, and presumed encephalopathy associated to influenza viruses in horses, have documented the unpredictable nature of equine influenza viruses. In sum up, several reports has highlighted the unpredictable nature of H3N8 EIVs highlighting the need of continuous surveillance for H3N8 in equines and humans in contact with them for novel and threatening mutations.

Derivation and External Validation of a Simple Prediction Rule for the Development of Respiratory Failure in Hospitalized Patients With Influenza

BACKGROUND: Influenza viruses cause seasonal epidemics worldwide with a significant morbimortality burden. Clinical spectrum of Influenza is wide, being respiratory failure (RF) one of its most severe complications. This study aims to elaborate a clinical prediction rule of RF in hospitalized Influenza patients.METHODS: a prospective cohort study was conducted during two consecutive Influenza seasons (December 2016 - March 2017 and December 2017 - April 2018) including hospitalized adults with confirmed A or B Influenza infection. A prediction rule was derived using logistic regression and recursive partitioning, followed by internal cross-validation. External validation was performed on a retrospective cohort in a different hospital between December 2018 - May 2019. RESULTS: Overall, 707 patients were included in the derivation cohort and 285 in the validation cohort. RF rate was 6.8% and 11.6%, respectively. Chronic obstructive pulmonary disease, immunosuppression, radiological abnormalities, respiratory rate, lymphopenia, lactate dehydrogenase and C-reactive protein at admission were associated with RF. A four category-grouped seven point-score was derived including radiological abnormalities, lymphopenia, respiratory rate and lactate dehydrogenase. Final model area under the curve was 0.796 (0.714-0.877) in the derivation cohort and 0.773 (0.687-0.859) in the validation cohort (p<0.001 in both cases). The predicted model showed an adequate fit with the observed results (Fisher’s test p>0.43). CONCLUSION: we present a simple, discriminating, well-calibrated rule for an early prediction of the development of RF in hospitalized Influenza patients, with proper performance in an external validation cohort. This tool can be helpful in patient´s stratification during seasonal Influenza epidemics.

Mapping inhibitory sites on the RNA polymerase of the 1918 pandemic influenza virus using nanobodies

Influenza A viruses cause seasonal epidemics and global pandemics, representing a considerable burden to healthcare systems. Central to the replication cycle of influenza viruses is the viral RNA-dependent RNA polymerase which transcribes and replicates the viral RNA genome. The polymerase undergoes conformational rearrangements and interacts with viral and host proteins to perform these functions. Here we determine the structure of the 1918 influenza virus polymerase in transcriptase and replicase conformations using cryo-electron microscopy (cryo-EM). We then structurally and functionally characterise the binding of single-domain nanobodies to the polymerase of the 1918 pandemic influenza virus. Combining these functional and structural data we identify five sites on the polymerase which are sensitive to inhibition by nanobodies. We propose that the binding of nanobodies at these sites either prevents the polymerase from assuming particular functional conformations or interactions with viral or host factors. The polymerase is highly conserved across the influenza A subtypes, suggesting these sites as effective targets for potential influenza antiviral development.

Association of Common Zoonotic Pathogens With Concentrated Animal Feeding Operations

Animal farming has intensified significantly in recent decades, with the emergence of concentrated animal feeding operations (CAFOs) in industrialized nations. The congregation of susceptible animals in CAFOs can lead to heavy environmental contamination with pathogens, promoting the emergence of hyper-transmissible, and virulent pathogens. As a result, CAFOs have been associated with emergence of highly pathogenic avian influenza viruses, hepatitis E virus, Escherichia coli O157:H7, Streptococcus suis, livestock-associated methicillin-resistant Staphylococcus aureus, and Cryptosporidium parvum in farm animals. This has led to increased transmission of zoonotic pathogens in humans and changes in disease patterns in general communities. They are exemplified by the common occurrence of outbreaks of illnesses through direct and indirect contact with farm animals, and wide occurrence of similar serotypes or subtypes in both humans and farm animals in industrialized nations. Therefore, control measures should be developed to slow down the dispersal of zoonotic pathogens associated with CAFOs and prevent the emergence of new pathogens of epidemic and pandemic potential.