Outbreak Of Acute Respiratory Disease Research Articles

Surviving 2019 novel coronavirus pneumonia: A successful critical case report

Background. An outbreak of acute respiratory illness was proved to be infected by a novel coronavirus, officially named Coronavirus Disease 2019 (COVID-19) from World Health Organization (WHO), was confirmed first in Wuhan, China, and has become endemic worldwide, which was a serious threaten to public health all over the world. Herein, we reported a successful critical case of COVID-19 and shared our experience of treatment, which would do a favor for other COVID-19 patients. Case summary. A 65-year-old man, Wuhan citizen, was infected by COVID-19, and his pulmonary lesions progressed quickly in five days. On admission to Tongji Hospital, Wuhan, China, the immediate arterial blood gas(ABG) analysis showed the PaO2/FiO2(P/F) ratio was 134.4mmHg, moderate acute respiratory distress syndrome(ARDS) was diagnosed. Emergency tracheal intubation was performed, and the initial ventilator mode and parameters were set up based on the lung-protective ventilation strategy, but the P/F ratio could not be improved, and then the prone position ventilation was carried out for four consecutive days, as long as 16 hours every day, the P/F ratio rose to 180mmHg approximately, which still did not reach to the standard of extubation. And then we found that it was complicated with acute cor pulmonale(ACP) by ultrasound examination, dobutamine and diuretic were used for the treatment of ACP caused by ARDS successfully, and the P/F ratio went up to about 250mmHg. Seven days later after admission, the endotracheal intubation was successfully removed, after extubation, High-Flow nasal cannula(HFNC) oxygen therapy was used as a sequential strategy to prevent reintubation. Ultimately, he was discharged on day 34 after admission. Conclusion. Our case presented the treatment process of a critical COVID-19. Effective therapy was crucial to heal COVID-19, and organ function support therapy, especially the cardiorespiratory function support therapy, was the core of treatment.

A descriptive study of acute outbreaks of respiratory disease in Norwegian fattening pig herds

BackgroundRespiratory diseases are major health concerns in the pig production sector worldwide, contributing adversely to morbidity and mortality. Over the past years there was a rise in reported incidents of respiratory disease in pigs in Norway, despite population wide freedom from Aujeszky´s disease, porcine reproductive and respiratory syndrome, porcine respiratory corona virus and enzootic pneumonia. The main objective of this study was to investigate acute outbreaks of respiratory disease in conventional Norwegian fattening pig herds. The study included 14 herds. In seven herds with reported outbreaks of acute respiratory disease, data on clinical signs was recorded and samples for laboratory examination were collected. Diagnostic protocols were compared by parallel analysis of clinically healthy pigs from seven non-outbreak herds.ResultsThe most commonly reported clinical signs were sudden deaths and dyspnea. An average compartment morbidity of 60%, mortality of 4% and case fatality of 9% was recorded in the outbreak herds. Post-mortem examinations revealed acute lesions resembling porcine pleuropneumonia in all 28 pigs investigated from the outbreak herds and in 2 of the 24 (8%) pigs from the non-outbreak herds. Chronic lesions were recorded in another 2 pigs (8%) from the non-outbreak herds. Actinobacillus pleuropneumoniae serovar 8 was isolated from lungs and/or pleura from all tested pigs (n = 28) in the outbreak herds, and from 2 out of 24 pigs (8%) in the non-outbreak herds, one pig with an acute and another pig with a chronic infection. No other significant bacterial findings were made. Seroconversion to A. pleuropneumoniae antibodies was detectable in all outbreak herds analyzed and in six out of seven non-outbreak herds, but the risk ratio for seroconversion of individual pigs was higher (risk ratio 2.3 [1.50- 3.43 95% CI; P < 0.001]) in the outbreak herds. All herds tested positive for porcine circovirus type 2 and negative for influenza A viruses on oral fluid RT-qPCR.ConclusionThe main etiological pathogen found during acute outbreaks of respiratory disease was A. pleuropneumoniae serovar 8. All pigs from outbreak herds had typical lesions of acute porcine pleuropneumonia, and only A. pleuropneumoniae serovar 8 was identified. Co-infections were not found to impact disease development.

Risk estimation of the SARS-CoV-2 acute respiratory disease outbreak outside China

BackgroundOn December 31, 2019, the World Health Organization was alerted to the occurrence of cases of pneumonia in Wuhan, Hubei Province, China, that were caused by an unknown virus, which was later identified as a coronavirus and named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to estimate the reproductive number of SARS-CoV-2 in the Hubei Province and evaluate the risk of an acute respiratory coronavirus disease (COVID-19) outbreak outside China by using a mathematical model and stochastic simulations.ResultsWe constructed a mathematical model of SARS-CoV-2 transmission dynamics, estimated the rate of transmission, and calculated the reproductive number in Hubei Province by using case-report data from January 11 to February 6, 2020. The possible number of secondary cases outside China was estimated by stochastic simulations in various scenarios of reductions in the duration to quarantine and rate of transmission. The rate of transmission was estimated as 0.8238 (95% confidence interval [CI] 0.8095–0.8382), and the basic reproductive number as 4.1192 (95% CI 4.0473–4.1912). Assuming the same rate of transmission as in Hubei Province, the possibility of no local transmission is 54.9% with a 24-h quarantine strategy, and the possibility of more than 20 local transmission cases is 7% outside of China.ConclusionThe reproductive number for SARS-CoV-2 transmission dynamics is significantly higher compared to that of the previous SARS epidemic in China. This implies that human-to-human transmission is a significant factor for contagion in Hubei Province. Results of the stochastic simulation emphasize the role of quarantine implementation, which is critical to prevent and control the SARS-CoV-2 outbreak outside China.

Editorial :The SARS-COV2 (COVID-19) Pandemic: What Clinicians should Knew

Up to 1st of June 2020 COVID 19 pandemic affected more than 6 million people worldwide with more than 350,000 case fatalities , putting healthcare systems under severe strain . At this issue of Afro-Egyptian Journal of Infectious and Endemic Diseases ; a review article titled ”The SARS-COV2 (COVID-19) Pandemic: What clinicians should knew”(page:65-92) discussing virology, pathogenesis, clinical picture, investigations and treatment of covid19 which is a novel coronavirus, now designated SARS-CoV-2, emerged and was identified as the cause of an outbreak of acute respiratory illness in Wuhan, a city in China in late 2019.

The SARS-COV2 (COVID-19) Pandemic: What Clinicians should knew

In late 2019, a novel coronavirus, now designated SARS-CoV-2, emerged and was identified as the cause of an outbreak of acute respiratory illness in Wuhan, a city in China, named as COVID-19. Since then the waves of the virus exponentially hit many countries around the globe with high rates of spread associated with variable degrees of morbidity and mortality. The WHO announced the pandemic state of the infection in March 2020 and by June 1st 2020 more than 6 million individuals and more than 370 thousands case fatalities were documented worldwide. In this article, we discussed many aspects regarding this emerged infection based on the available evidence aiming to help clinician to improve not only their knowledge but also their practices toward this infection.

Characterization of Influenza A and B Viruses Circulating in Southern China During the 2017-2018 Season.

The trivalent seasonal influenza vaccine was the only approved and available vaccine during the 2016–2018 influenza seasons. It did not include the B/Yamagata strain. In this study, we report an acute respiratory disease outbreak associated with influenza B/Yamagata infections in Guangzhou, Southern China (January through March, 2018). Among the 9914 patients, 2241 (22.6%) were positive for the influenza B virus, with only 312 (3.1%) positive for the influenza A virus. The influenza B/Yamagata lineage dominated during this period in Southern China. The highest incidence of influenza A virus infection occurred in the children aged 5–14 years. In contrast, populations across all age groups were susceptible to the influenza B virus. Phylogenetic, mutations, and 3D structure analyses of hemagglutinin (HA) genes were performed to assess the vaccine-virus relatedness. The recommended A/H1N1 vaccine strain (A/Michigan/45/2015) during both 2017–2018 and 2018–2019 was antigen-specific for these circulating isolates (clade 6B.1) in Spring 2018. An outbreak of influenza B/Yamagata (clade 3) infections in 2018 occurred during the absence of the corresponding vaccine during 2016–2018. The recommended influenza B/Yamagata vaccine strain (B/Phuket/3073/2013) for the following season (2018–2019) was antigen-specific. Although there were only a few influenza B/Victoria infections in Spring 2018, five amino acid mutations were identified in the HA antigenic sites of the 19 B/Victoria isolates (clade 1A), when compared with the 2016–2018 B/Victoria vaccine strain. The number was larger than expected and suggested that the influenza B HA gene may be more variable than previously thought. One of the mutations (K180N) was noted to likely alter the epitope and to potentially affect the viral antigenicity. Seven mutations were also identified in the HA antigenic sites of 2018–2020 B/Victoria vaccine strain, of which some or all may reduce immunogenicity and the protective efficacy of the vaccine, perhaps leading to more outbreaks in subsequent seasons. The combined epidemiological, phylogenetic, mutations, and 3D structural analyses of the HA genes of influenza strains reported here contribute to the understanding and evaluation of how HA mutations affect vaccine efficacy, as well as to providing important data for screening and selecting more specific, appropriate, and effective influenza vaccine candidate strains.

Construction and Characterization of a Novel Recombinant Attenuated and Replication-Deficient Candidate Human Adenovirus Type 3 Vaccine: "Adenovirus Vaccine Within an Adenovirus Vector".

Human adenoviruses (HAdVs) are highly contagious and result in large number of acute respiratory disease (ARD) cases with severe morbidity and mortality. Human adenovirus type 3 (HAdV-3) is the most common type that causes ARD outbreaks in Asia, Europe, and the Americas. However, there is currently no vaccine approved for its general use. The hexon protein contains the main neutralizing epitopes, provoking strong and lasting immunogenicity. In this study, a novel recombinant and attenuated adenovirus vaccine candidate against HAdV-3 was constructed based on a commercially-available replication-defective HAdV-5 gene therapy and vaccine vector. The entire HAdV-3 hexon gene was integrated into the E1 region of the vector by homologous recombination using a bacterial system. The resultant recombinants expressing the HAdV-3 hexon protein were rescued in AD293 cells, identified and characterized by RT-PCR, Western blots, indirect immunofluorescence, and electron microscopy. This potential vaccine candidate had a similar replicative efficacy as the wild-type HAdV-3 strain. However, and importantly, the vaccine strain had been rendered replication-defective and was incapable of replication in A549 cells after more than twenty-generation passages in AD293 cells. This represents a significant safety feature. The mice immunized both intranasally and intramuscularly by this vaccine candidate raised significant neutralizing antibodies against HAdV-3. Therefore, this recombinant, attenuated, and safe adenovirus vaccine is a promising HAdV-3 vaccine candidate. The strategy of using a clinically approved and replication-defective HAdV-5 vector provides a novel approach to develop universal adenovirus vaccine candidates against all the other types of adenoviruses causing ARDs and perhaps other adenovirus-associated diseases.

Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China

BackgroundIn late December 2019, an outbreak of acute respiratory illness, coronavirus disease 2019 (COVID-19), emerged in Wuhan, China. We aimed to study the epidemiology, clinical features and short-term outcomes of patients with COVID-19 in Wuhan, China. MethodsWe performed a single center, retrospective case series study in 221 patients with laboratory confirmed SARS-CoV-2 pneumonia at a university hospital, including 55 severe patients and 166 non-severe patients, from January 2, 2020 to February 10, 2020. ResultsOf the 221 patients with COVID-19, the median age was 55.0 years and 48.9% were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe pneumonia patients, the median age of the severe patients was significantly older, and they were more likely to have chronic comorbidities. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 33.0% patients showed leukopenia and 73.8% showed lymphopenia. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications. As of February 15, 2020, 19.0% patients had been discharged and 5.4% patients died. 80% of severe cases received ICU (intensive care unit) care, and 52.3% of them transferred to the general wards due to relieved symptoms, and the mortality rate of severe patients in ICU was 20.5%. ConclusionsPatients with elder age, chronic comorbidities, blood leukocyte/lymphocyte count, procalcitonin level, co-infection and severe complications might increase the risk of poor clinical outcomes.

Clinical Features and Treatment of 221 Patients with COVID-19 in Wuhan, China

Background: In late December 2019, an outbreak of acute respiratory illness, now officially named as COVID-19, or coronavirus disease 2019, emerged in Wuhan, China. We aimed to study the epidemiology and clinical features of patients diagnosed as coronavirus disease 2019 (COVID-19) and their treatment and outcome in Wuhan, China. Methods: We did a single center, retrospective case series study in patients from Zhongnan Hospital of Wuhan University, Wuhan, China. 221 admitted patients with laboratory confirmed SARS-CoV-2 infection, including 55 severe patients and 166 non-severe patients, were recruited from January 2, 2020 to February 10, 2020. Data of epidemiology, clinic, laboratory exams, radiology and treatment were collected from standardized case report forms and compared between the severe and non-severe patients with COVID-19. Specifically, the outcome of corticosteroid therapy was analyzed in the severe patients in intensive care unit (ICU). Findings: Of the 221 patients with COVID-19, 108 (48.9%) of them were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe patients, the median age of the severe patients was significantly older (62.0 vs 51.0 years), and they were more likely to have chronic comorbidities, including hypertension, cardiovascular disease and cerebrovascular disease. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 73 (33.0%) of the 221 patients showed leukopenia and 163 (73.8%) showed lymphopenia. The laboratory results showed more severity of aberrant coagulation pathway, hepatic injury, myocardial injury and kidney injury in the severe patients. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications, including acute respiratory distress syndrome (ARDS), arrhythmia, acute cardiac injury, shock and acute kidney injury. As of Feb 15, 2020, a total of 42 (19.0%) patients had been discharged and 12 (5.4%) patients died. In the 55 severe patients, 44 (80%) of them received ICU care, and 23 of them transferred to the general wards due to relieved symptoms, and the mortality rate was 21.8%. Interpretation: In this single-center case series of 221 hospitalized patients with confirmed COVID-19 in Wuhan, China, 55 severe patients with elder age and chronic comorbidities, developed more than one complication. The mortality rate was significantly higher in the severe patients compared to that in the non-severe patients (21.8% vs 0.0%). Older and male patients with higher APACHE II & SOFA scores, elevated PCT level, excessive fluid volume input, as well as the delayed use of corticosteroid might increase the risk of death in ICU. Funding Statement: This work was supported by the National Natural Science Foundation of China (grant no. 81700493 to Dr. Pan; grant no. 81971816 to Dr. Peng). Declaration of Interests: The authors declared no conflicts. Ethics Approval Statement: This study was approved by the National Health Commission of China and Ethics Commission of Zhongnan Hospital. Written informed consent was waived by the Ethics Commission for emerging infectious disease.

COVID-19 and lessons learned from the pandemic wave of meningococcal meningitis (1985-1990).

A novel coronavirus was first identified in late 2019 to cause an outbreak of acute respiratory illness in Wuhan city in China. The disease was designated COVID-19 (coronavirus disease 2019) by the World Health Organization (WHO) in February 2020. Worldwide, the infection spread affecting more than 3 million confirmed cases, mainly in Europe and USA, and was characterised by the WHO as a pandemic in March 2020. During 1985-1990, a similar pandemic wave of meningococcal (MC) meningitis spread over vast territories in Asia (including Saudi Arabia) and Africa (including Sudan and Ethiopia with more than 70,000 cases). The Sudanese Journal of Paediatrics (SJP) is taking the opportunity to document the history of this pandemic in Sudan, which has been successfully managed within Sudan/Sweden scientific link program involving the University of Khartoum, Sudan and Uppsala University, Sweden. This joint research project evaluated a rapid antigen test for the diagnosis of acute bacterial meningitis which later proved to be adaptable to the field situation during the 1988 MC epidemic. It also constituted one of the pioneering works in molecular epidemiology and proved to be vital in controlling epidemic meningitis worldwide. Based on this and other bacteriologic and epidemiologic data, a new conjugate vaccine was later developed which put an end to Group A meningococcal epidemics. Lessons learnt from this pandemic, which also applied in case of coronavirus disease 2019 (COVID-19), are also highlighted.

Transmission and evolutionary dynamics of human coronavirus OC43 strains in coastal Kenya investigated by partial spike sequence analysis, 2015-16.

Human coronavirus OC43 (HCoV-OC43) is a major contributor to seasonal outbreaks of acute respiratory illness (ARI). The origins of locally circulating HCoV-OC43 strains and characteristics of their genetic diversity are unknown for most settings despite significance to effective HCoV control strategies. Between December 2015 and June 2016, we undertook ARI surveillance in coastal Kenya in nine outpatients and one inpatient health facility (HF). Ninety-two patient samples tested HCoV-OC43 positive and forty (43.5%) were successfully sequenced in spike (S) gene region (2,864 long, ∼70%). Phylogenetic analysis confirmed co-circulation of two distinct HCoV-OC43 clades that closely clustered with genotype G (n = 34, 85%) and genotype H (n = 6, 15%) reference strains. Local viruses within the same clade displayed low genetic diversity yielding identical sequences in multiple HF. Furthermore, the newly sequenced Kenyan viruses showed close phylogenetic relationship to other contemporaneous sampled strains (2015–16) including those originating from distant places (e.g. USA and China). Using a genetic similarity threshold of 99.1 per cent at nucleotide level, the HCoV-OC43 strains sampled globally between 1967 and 2019 fell into nine sequence clusters. Notably, some of these clusters appeared to have become extinct, or occurred only sporadically in a few geographical areas while others persisted globally for multiple years. In conclusion, we found that HCoV-OC43 strains spread rapidly both locally and across the globe with limited genetic evolution in the spike gene. Full-genome sequences that are spatio-temporally representative are required to advance understanding of the transmission pathways of this important human respiratory pathogen.

Molecular insight into the therapeutic promise of xuebijing injection against coronavirus disease 2019

Background: The potential human-to-human transmission of the coronavirus pneumonia (coronavirus disease 2019 [COVID-19]) has caused an outbreak of acute respiratory illness. Xuebijing injection is recommended as first-line treatment for the severe and critical patients with COVID-19. The aim of present study is to interpret the pharmacological mechanisms and molecular connections of Xuebijing injection against COVID-19 by utilizing the approaches of network pharmacology and molecular docking. Materials and Methods: Active ingredients of Xuebijing injection were collected by Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and putative therapeutic targets were screened from TCMSP, SwissTargetPrediction, and STITCH databases. Moreover, the protein–protein interactions, topological analysis, and pathway enrichment were established to distinguish the hub targets and pathways by employing STRING database, Cytoscape software, DAVID database, respectively. In addition, the potential interaction and binding activity of candidate ingredients in Xuebijing injection with core targets were revealed by molecular docking simulation (AutoDock software). Results: A total of 115 bioactive components in Xuebijing injection were collected, and416 targets including AKT1, TP53, VEGFA, ALB, TNF and so on were responsible for treating COVID-19. Bioinformatics analysis revealed that matching core targets were closely associated with the inhibition of cytokine storm for its clinical beneficial effects in severe cases. The results of enrichment analysis indicated that PI3K-Akt signaling pathway, human T-cell leukemia virus type 1 infection, mitogen-activated protein kinase signaling pathway, tuberculosis, focal adhesion, TNF signaling pathway, and small-cell lung cancer were represented pathways of Xuebijing injection against COVID-19 in terms of lung inflammation, virus infection, and lung injury. Meanwhile, the active ingredients of Xuebijing injection exerted superior binding activities with 3CLpro and angiotensin-converting enzyme 2 as observed via molecular docking simulation. Conclusions: Through the comprehensive analysis of network pharmacology, the current research preliminarily elaborated the molecular regulation of therapeutic mechanisms for Xuebijing injection against COVID-19 and binding activity between active components and core targets, which provided scientific evidence to facilitate the development of Xuebijing injection and clinical treatment for COVID-19.

The Use of Large-Particle Aerosol Exposure to Nipah Virus to Mimic Human Neurological Disease Manifestations in the African Green Monkey.

Nipah virus (NiV) is an emerging virus associated with outbreaks of acute respiratory disease and encephalitis. To develop a neurological model for NiV infection, we exposed 6 adult African green monkeys to a large-particle (approximately 12 μm) aerosol containing NiV (Malaysian isolate). Brain magnetic resonance images were obtained at baseline, every 3 days after exposure for 2 weeks, and then weekly until week 8 after exposure. Four of six animals showed abnormalities reminiscent of human disease in brain magnetic resonance images. Abnormalities ranged from cytotoxic edema to vasogenic edema. The majority of lesions were small infarcts, and a few showed inflammatory or encephalitic changes. Resolution or decreased size in some lesions resembled findings reported in patients with NiV infection. Histological lesions in the brain included multifocal areas of encephalomalacia, corresponding to known ischemic foci. In other regions of the brain there was evidence of vasculitis, with perivascular infiltrates of inflammatory cells and rare intravascular fibrin thrombi. This animal model will help us better understand the acute neurological features of NiV infection and develop therapeutic approaches for managing disease caused by NiV infection.

Outbreak of macrolide-resistant mycoplasma pneumoniae in a primary school in Beijing, China in 2018

BackgroundOn 7th June, 2018, a primary school in Beijing, China notified Shunyi CDC of an outbreak of acute respiratory disease characterized by fever and cough among students and resulting in nine hospitalization cases during the preceding 2 weeks. We started an investigation to identify the etiologic agent, find additional cases, develop and implement control measures.MethodsWe defined probable cases as students, teachers and other staffs in the school developed fever (T ≥ 37.5 °C) with cough or sore throat; or a diagnosis of pneumonia during May 1–June 31, 2018. Confirmed cases were probable cases with Mycoplasma pneumoniae detected in oropharyngeal (OP) swabs by quantitative real-time polymerase chain reaction (qPCR). We searched case by reviewing school absenteeism records and interviewing students, teachers and staff in this school. Oropharyngeal swabs were collected from symptomatic students. Two qPCR) assay, a duplex qPCR assay, and sequencing were performed to determine the pathogen, genotype and macrolide resistance at the gene level, respectively.ResultsFrom May 1st to June 31st, 2018, we identified 55 cases (36 probable and 19 confirmed), of whom 25 (45%) were hospitalized for complications. All cases were students, none of the teachers and other staffs in the school were with similar symptoms. The attack rate (AR) was 3.9% (55/1398) for all students. The cases were mainly male (58%), with an age range of 7–8 years (median: 7 years). 72% (18/25) of inpatients had radiograph findings consistent with pneumonia, and some cases were hospitalized for up to 4 weeks. Pathogen detection results indicated that Mycoplasma pneumonia (M. pneumoniae) P1 type 1 was the causative agent in this outbreak, and the strain harbored one point mutation of A to G at position 2063.ConclusionsThe infections by macrolide-resistant M. pneumoniae are not always mild and pneumonia was common and M. pneumoniae could causes serious complications which require long-term hospitalization. In the future infectious disease prevention and control practice, M. pneumoniae should be paid more attention. It is necessary to establish and improve the pathogen and drug resistance surveillance system in order to prevent and control such mutated strains of M. pneumoniae from causing future outbreaks or epidemics in China.

Investigation of an outbreak of acute respiratory disease in an indigenous village in Brazil: Contribution of Influenza A(H1N1)pdm09 and human respiratory syncytial viruses.

Analyses of the 2009 H1N1 influenza pandemic and post-pandemic years showed high attack rates and severity among indigenous populations. This study presents the characteristics of the first documented influenza outbreak in indigenous peoples in Brazil, that occurred from 30th March to 14th April 2016 in a Guarani village in Southeast Region. Acute respiratory infections were prospectively investigated. The majority of the 73 cases were influenza-like illness (ILI) (63.0%) or severe acute respiratory infection (SARI) (20.5%). The ILI+SARI attack rate (35.9%) decreased with increasing age. There was a high influenza vaccination rate (86.3%), but no statistically significant difference in vaccination rates between severe and non-severe cases was seen (p = 0.334). Molecular analyses of 19.2% of the cases showed 100% positivity for influenza A(H1N1)pdm09 and/or hRSV. Influenza A(H1N1)pdm09 was included in the 6B.1 genetic group, a distinct cluster with 13 amino acid substitutions of A/California/07/2009-like. The hRSV were clustered in the BA-like genetic group. The early arrival of the influenza season overlapping usual hRSV season, the circulation of a drifted influenza virus not covered by vaccine and the high prevalence of risk factors for infection and severity in the village jointly can explain the high attack rate of ARI, even with a high rate of influenza vaccination. The results reinforce the importance of surveillance of respiratory viruses, timely vaccination and controlling risk factors for infection and severity of in the indigenous populations in order to preventing disease and related deaths, particularly in children.

Whole Genome Sequencing of the First H3N8 Equine Influenza Virus Identified in Malaysia.

In August 2015, Malaysia experienced an outbreak of acute respiratory disease in racehorses. Clinical signs observed were consistent with equine influenza (EI) infection. The index cases were horses recently imported from New Zealand. Rapid control measures, including temporary cancellation of racing, were implemented to minimize the impact of the outbreak. By November, the disease outbreak was resolved, and movement restrictions were lifted. The aim of this study was to confirm the clinical diagnosis and characterize the causal virus. A pan-reactive influenza type A real-time RT-PCR was used for confirmatory diagnosis. Antigenic characterization by haemagglutinin inhibition using a panel of specific ferret antisera indicated that the causal virus belonged to clade 1 of the H3N8 Florida sub-lineage. The genetic characterization was achieved by the whole genome sequencing of positive nasal swabs from clinically affected animals. Pylogenetic analysis of the haemagglutinin (HA) and neuraminidase (NA) genes demonstrated ≥99% homology with several EI strains that had recently circulated in the USA and Japan. The antigenic and genetic characterization did not indicate that the current World Organisation for Animal Health (OIE) recommendations for EI vaccine composition required modification.

Temporally Related Rise in Enterovirus D68 and Acute Flaccid Myelitis

Starting in the fall of 2014, outbreaks of acute respiratory illness associated with enterovirus D68 (EV-D68) were reported to the CDC. Since that

Effect of oral KETOPROFEN treatment in acute respiratory disease outbreaks in finishing pigs

BackgroundInfection with respiratory pathogens can influence production as well as animal welfare. There is an economical and ethical need to treat pigs that suffer from respiratory diseases. Our aim was the evaluation of the possible effects of oral NSAID medication given in feed in acute outbreaks of respiratory disease in finishing pigs. The short- and long-term impact of NSAID dosing on clinical signs, daily weight gain, blood parameters and behaviour of growing pigs in herds with acute respiratory infections were evaluated. Four finishing pig farms suffering from acute outbreaks of respiratory disease were visited thrice after outbreak onset (DAY 0, DAY 3 and DAY 30). Pigs with the most severe clinical signs (N = 160) were selected as representative pigs for the herd condition. These pigs were blood sampled, weighed, evaluated clinically and their behaviour was observed. After the first visit, half of the pens (five pigs per pen in four pens totalling 20 representative pigs per herd, altogether 80 pigs in four herds) were treated with oral ketoprofen (target dose 3 mg/kg) mixed in feed for three days and the other half (80 pigs) with a placebo. In three of the herds, some pigs were treated also with antimicrobials, and in one herd the only pharmaceutical treatment was ketoprofen or placebo.ResultsCompared to the placebo treatment, dosing of ketoprofen reduced sickness behaviour and lowered the rectal temperature of the pigs. Clinical signs, feed intake or blood parameters were not different between the treatment groups. Ketoprofen treatment was associated with somewhat reduced weight gain over the 30-day follow-up period. Concentration analysis of the S- and R-enantiomers of ketoprofen in serum samples collected on DAY 3 indicated successful oral drug administration.ConclusionsKetoprofen mainly influenced the behaviour of the pigs, while it had no effect on recovery from respiratory clinical signs. However, the medication may have been started after the most severe clinical phase of the respiratory disease was over, and this delay might complicate the evaluation of treatment effects. Possible negative impact of ketoprofen on production parameters requires further evaluation.

Whole-genome sequencing and antigenic analysis of the first equine influenza virus identified in Turkey.

BackgroundIn 2013, there was an outbreak of acute respiratory disease in racehorses in Turkey. The clinical signs were consistent with equine influenza (EI).ObjectiveThe aim was to confirm the cause of the outbreak and characterise the causal virus.MethodsA pan‐reactive influenza type A real‐time RT‐PCR and a rapid antigen detection kit were used for confirmatory diagnosis of equine influenza virus (EIV). Immunological susceptibility to EIV was examined using single radial haemolysis and ELISA. Antigenic characterisation was completed by haemagglutinin inhibition using a panel of specific ferret antisera. Genetic characterisation was achieved by whole‐genome sequencing using segment‐specific primers with M13 tags.ResultsA H3N8 EIV of the Florida clade 2 sublineage (FC2) was confirmed as the causal agent. The index cases were unvaccinated and immunologically susceptible. Phylogenetic analysis of the HA1 and NA genes demonstrated that A/equine/Ankara/1/2013 clustered with the FC2 strains circulating in Europe. Antigenic characterisation confirmed the FC2 classification and demonstrated the absence of significant drift. Whole‐genome sequencing indicated that A/equine/Ankara/1/2013 is most closely related to the viruses described as the 179 group based on the substitution I179V in HA1, for example A/equine/East Renfrewshire/2/2011, A/equine/Cambremer/1/2012 and A/equine/Saone et Loire/1/2015. The greatest diversity was observed in the NS1 segment and the polymerase complex.ConclusionsThe first recorded outbreak of EI in Turkey was caused by an FC2 virus closely related to viruses circulating in Europe. Antigenic and genetic characterisation gave no indication that the current OIE recommendations for EI vaccine composition require modification.

Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model

BackgroundMesenchymal stem (stromal) cells (MSCs) mediate their immunoregulatory and tissue repair functions by secreting paracrine factors, including extracellular vesicles (EVs). In several animal models of human diseases, MSC-EVs mimic the beneficial effects of MSCs. Influenza viruses cause annual outbreaks of acute respiratory illness resulting in significant mortality and morbidity. Influenza viruses constantly evolve, thus generating drug-resistant strains and rendering current vaccines less effective against the newly generated strains. Therefore, new therapies that can control virus replication and the inflammatory response of the host are needed. The objective of this study was to examine if MSC-EV treatment can attenuate influenza virus-induced acute lung injury in a preclinical model.MethodsWe isolated EVs from swine bone marrow-derived MSCs. Morphology of MSC-EVs was determined by electron microscopy and expression of mesenchymal markers was examined by flow cytometry. Next, we examined the anti-influenza activity of MSC-EVs in vitro in lung epithelial cells and anti-viral and immunomodulatory properties in vivo in a pig model of influenza virus.ResultsMSC-EVs were isolated from MSC-conditioned medium by ultracentrifugation. MSC-EVs were round-shaped and, similarly to MSCs, expressed mesenchymal markers and lacked the expression of swine leukocyte antigens I and II. Incubation of PKH-26-labeled EVs with lung epithelial cells revealed that MSC-EVs incorporated into the epithelial cells. Next, we examined the anti-influenza and anti-inflammatory properties of MSC-EVs. MSC-EVs inhibited the hemagglutination activity of avian, swine, and human influenza viruses at concentrations of 1.25–5 μg/ml. MSC-EVs inhibited influenza virus replication and virus-induced apoptosis in lung epithelial cells. The anti-influenza activity of MSC-EVs was due to transfer of RNAs from EVs to epithelial cells since pre-incubation of MSC-EVs with RNase enzyme abrogated the anti-influenza activity of MSC-EVs. In a pig model of influenza virus, intratracheal administration of MSC-EVs 12 h after influenza virus infection significantly reduced virus shedding in the nasal swabs, influenza virus replication in the lungs, and virus-induced production of proinflammatory cytokines in the lungs of influenza-infected pigs. The histopathological findings revealed that MSC-EVs alleviated influenza virus-induced lung lesions in pigs.ConclusionsOur data demonstrated in a relevant preclinical large animal model of influenza virus that MSC-EVs possessed anti-influenza and anti-inflammatory properties and that EVs may be used as cell-free therapy for influenza in humans.