Dembo polymerase chain reaction technique for detection of bovine abortion, diarrhea, and respiratory disease complex infectious agents in potential vectors and reservoirs.

PubMed

Rahpaya, Sayed Samim; Tsuchiaka, Shinobu; Kishimoto, Mai; Oba, Mami; Katayama, Yukie; Nunomura, Yuka; Kokawa, Saki; Kimura, Takashi; Kobayashi, Atsushi; Kirino, Yumi; Okabayashi, Tamaki; Nonaka, Nariaki; Mekata, Hirohisa; Aoki, Hiroshi; Shiokawa, Mai; Umetsu, Moeko; Morita, Tatsushi; Hasebe, Ayako; Otsu, Keiko; Asai, Tetsuo; Yamaguchi, Tomohiro; Makino, Shinji; Murata, Yoshiteru; Abi, Ahmad Jan; Omatsu, Tsutomu; Mizutani, Tetsuya

2018-05-31

Bovine abortion, diarrhea, and respiratory disease complexes, caused by infectious agents, result in high and significant economic losses for the cattle industry. These pathogens are likely transmitted by various vectors and reservoirs including insects, birds, and rodents. However, experimental data supporting this possibility are scarce. We collected 117 samples and screened them for 44 bovine abortive, diarrheal, and respiratory disease complex pathogens by using Dembo polymerase chain reaction (PCR), which is based on TaqMan real-time PCR. Fifty-seven samples were positive for at least one pathogen, including bovine viral diarrhea virus, bovine enterovirus, Salmonella enterica ser. Dublin, Salmonella enterica ser. Typhimurium, and Neospora caninum ; some samples were positive for multiple pathogens. Bovine viral diarrhea virus and bovine enterovirus were the most frequently detected pathogens, especially in flies, suggesting an important role of flies in the transmission of these viruses. Additionally, we detected the N. caninum genome from a cockroach sample for the first time. Our data suggest that insects (particularly flies), birds, and rodents are potential vectors and reservoirs of abortion, diarrhea, and respiratory infectious agents, and that they may transmit more than one pathogen at the same time.

Is There Still Room for Novel Viral Pathogens in Pediatric Respiratory Tract Infections?

PubMed Central

Taboada, Blanca; Espinoza, Marco A.; Isa, Pavel; Aponte, Fernando E.; Arias-Ortiz, María A.; Monge-Martínez, Jesús; Rodríguez-Vázquez, Rubén; Díaz-Hernández, Fidel; Zárate-Vidal, Fernando; Wong-Chew, Rosa María; Firo-Reyes, Verónica; del Río-Almendárez, Carlos N.; Gaitán-Meza, Jesús; Villaseñor-Sierra, Alberto; Martínez-Aguilar, Gerardo; Salas-Mier, Ma. del Carmen; Noyola, Daniel E.; Pérez-Gónzalez, Luis F.; López, Susana; Santos-Preciado, José I.; Arias, Carlos F.

2014-01-01

Viruses are the most frequent cause of respiratory disease in children. However, despite the advanced diagnostic methods currently in use, in 20 to 50% of respiratory samples a specific pathogen cannot be detected. In this work, we used a metagenomic approach and deep sequencing to examine respiratory samples from children with lower and upper respiratory tract infections that had been previously found negative for 6 bacteria and 15 respiratory viruses by PCR. Nasal washings from 25 children (out of 250) hospitalized with a diagnosis of pneumonia and nasopharyngeal swabs from 46 outpatient children (out of 526) were studied. DNA reads for at least one virus commonly associated to respiratory infections was found in 20 of 25 hospitalized patients, while reads for pathogenic respiratory bacteria were detected in the remaining 5 children. For outpatients, all the samples were pooled into 25 DNA libraries for sequencing. In this case, in 22 of the 25 sequenced libraries at least one respiratory virus was identified, while in all other, but one, pathogenic bacteria were detected. In both patient groups reads for respiratory syncytial virus, coronavirus-OC43, and rhinovirus were identified. In addition, viruses less frequently associated to respiratory infections were also found. Saffold virus was detected in outpatient but not in hospitalized children. Anellovirus, rotavirus, and astrovirus, as well as several animal and plant viruses were detected in both groups. No novel viruses were identified. Adding up the deep sequencing results to the PCR data, 79.2% of 250 hospitalized and 76.6% of 526 ambulatory patients were positive for viruses, and all other children, but one, had pathogenic respiratory bacteria identified. These results suggest that at least in the type of populations studied and with the sampling methods used the odds of finding novel, clinically relevant viruses, in pediatric respiratory infections are low. PMID:25412469

Human quarantine: Toward reducing infectious pressure on chimpanzees at the Taï Chimpanzee Project, Côte d'Ivoire.

PubMed

Grützmacher, Kim; Keil, Verena; Leinert, Vera; Leguillon, Floraine; Henlin, Arthur; Couacy-Hymann, Emmanuel; Köndgen, Sophie; Lang, Alexander; Deschner, Tobias; Wittig, Roman M; Leendertz, Fabian H

2018-01-01

Due to their genetic relatedness, great apes are highly susceptible to common human respiratory pathogens. Although most respiratory pathogens, such as human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV), rarely cause severe disease in healthy human adults, they are associated with considerable morbidity and mortality in wild great apes habituated to humans for research or tourism. To prevent pathogen transmission, most great ape projects have established a set of hygiene measures ranging from keeping a specific distance, to the use of surgical masks and establishment of quarantines. This study investigates the incidence of respiratory symptoms and human respiratory viruses in humans at a human-great ape interface, the Taï Chimpanzee Project (TCP) in Côte d'Ivoire, and consequently, the effectiveness of a 5-day quarantine designed to reduce the risk of potential exposure to human respiratory pathogens. To assess the impact of quarantine as a preventative measure, we monitored the quarantine process and tested 262 throat swabs for respiratory viruses, collected during quarantine over a period of 1 year. Although only 1 subject tested positive for a respiratory virus (HRSV), 17 subjects developed symptoms of infection while in quarantine and were subsequently kept from approaching the chimpanzees, preventing potential exposure in 18 cases. Our results suggest that quarantine-in combination with monitoring for symptoms-is effective in reducing the risk of potential pathogen exposure. This research contributes to our understanding of how endangered great apes can be protected from human-borne infectious disease. © 2017 Wiley Periodicals, Inc.

Transcriptome responses to respiratory virus infection of pigs within the tracheobronchial lymphnode following infection with PRRSV, PCV2 or IAV

USDA-ARS?s Scientific Manuscript database

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major respiratory pathogen of swine that has become extremely costly to the swine industry worldwide, often causing losses in production and animal life due to their ease of spread. However, the intracellular changes that occur in pigs...

Comparison of NxTAG Respiratory Pathogen Panel and Anyplex II RV16 Tests for Multiplex Detection of Respiratory Pathogens in Hospitalized Children

PubMed Central

Brotons, Pedro; Henares, Desiree; Latorre, Irene; Cepillo, Antonio; Launes, Cristian

2016-01-01

Multiplex molecular techniques can detect a diversity of respiratory viruses and bacteria that cause childhood acute respiratory infection rapidly and conveniently. However, currently available techniques show high variation in performance. We sought to compare the diagnostic accuracy of the novel multiplex NxTAG respiratory pathogen panel (RPP) RUO test versus a routine multiplex Anyplex II RV16 assay in respiratory specimens collected from children <18 years of age hospitalized with nonspecific symptoms of acute lower respiratory infection. Parallel testing was performed on nasopharyngeal aspirates prospectively collected at referral Children's Hospital Sant Joan de Déu (Barcelona, Spain) between June and November 2015. Agreement values between the two tests and kappa coefficients were assessed. Bidirectional sequencing was performed for the resolution of discordant results. A total of 319 samples were analyzed by both techniques. A total of 268 (84.0%) of them yielded concordant results. Positive percent agreement values ranged from 83.3 to 100%, while the negative percent agreement was more than 99% for all targets except for enterovirus/rhinovirus (EV/RV; 94.4%). Kappa coefficients ranged from 0.83 to 1.00. Discrepancy analysis confirmed 66.0% of NxTAG RPP RUO results. A total of 260 viruses were detected, with EV/RV (n = 105, 40.4%) being the most prevalent target. Viral coinfections were found in 44 (14.2%) samples. In addition, NxTAG RPP RUO detected single bacterial and mixed viral-bacterial infections in seven samples. NxTAG RPP RUO showed high positive and negative agreement with Anyplex II RV16 for main viruses that cause acute respiratory infections in children, coupled with an additional capability to detect some respiratory bacteria. PMID:27629904

Evaluation of the Luminex xTAG Respiratory Viral Panel FAST v2 assay for detection of multiple respiratory viral pathogens in nasal and throat swabs in Vietnam

PubMed Central

Thi Ty Hang, Vu; Thi Han Ny, Nguyen; My Phuc, Tran; Thi Thanh Tam, Pham; Thao Huong, Dang; Dang Trung Nghia, Ho; Tran Anh Vu, Nguyen; Thi Hong Phuong, Pham; Van Xang, Nguyen; Dong, Nguyen; Nhu Hiep, Pham; Van Hung, Nguyen; Tinh Hien, Tran; Rabaa, Maia; Thwaites, Guy E.; Baker, Stephen; Van Tan, Le; van Doorn, H.Rogier

2018-01-01

Background: Acute respiratory infections (ARI) are among the leading causes of hospitalization in children ≤5 years old. Rapid diagnostics of viral pathogens is essential to avoid unnecessary antibiotic treatment, thereby slowing down antibiotic-resistance. We evaluated the diagnostic performance of the Luminex xTAG Respiratory Viral Panel FAST v2 against viral specific PCR as reference assays for ARI in Vietnam. Methods: Four hundred and forty two nose and throat swabs were collected in viral transport medium, and were tested with Luminex xTAG Respiratory Viral Panel FAST v2. Multiplex RT-PCR and single RT-PCR were used as references.    Results: Overall, sensitivity of the Luminex against reference assays was 91.8%, 95% CI 88.1-94.7 (270/294), whilst 112/6336 (1.8%, 95% CI, 1.4-2.1) of pathogens were detected by the Luminex, but not by reference assays. Frequency of pathogens detected by Luminex and reference assays was 379 and 292, respectively. The diagnostic yield was 66.7% (295/442, 95%CI 62.1-71.1%) for the Luminex assay and 54.1% (239/442, 95% CI, 49.3-58.8%) for reference assays. The Luminex kit had higher yields for all viruses except influenza B virus, respiratory syncytial virus, and human bocavirus. High agreements between both methods [mean (range): 0.91 (0.83-1.00)] were found for 10/15 viral agents. Conclusions: The Luminex assay is a high throughput multiplex platform for rapid detection of common viral pathogens causing ARI. Although the current high cost may prevent Luminex assays from being widely used, especially in limited resource settings where ARI are felt most, its introduction in clinical diagnostics may help reduce unnecessary use of antibiotic prescription. PMID:29503874

Early emergence of Yersinia pestis as a severe respiratory pathogen

PubMed Central

Zimbler, Daniel L.; Schroeder, Jay A.; Eddy, Justin L.; Lathem, Wyndham W.

2015-01-01

Yersinia pestis causes the fatal respiratory disease pneumonic plague. Y. pestis recently evolved from the gastrointestinal pathogen Y. pseudotuberculosis; however, it is not known at what point Y. pestis gained the ability to induce a fulminant pneumonia. Here we show that the acquisition of a single gene encoding the protease Pla was sufficient for the most ancestral, deeply rooted strains of Y. pestis to cause pneumonic plague, indicating that Y. pestis was primed to infect the lungs at a very early stage in its evolution. As Y. pestis further evolved, modern strains acquired a single amino-acid modification within Pla that optimizes protease activity. While this modification is unnecessary to cause pneumonic plague, the substitution is instead needed to efficiently induce the invasive infection associated with bubonic plague. These findings indicate that Y. pestis was capable of causing pneumonic plague before it evolved to optimally cause invasive infections in mammals. PMID:26123398

Early emergence of Yersinia pestis as a severe respiratory pathogen.

PubMed

Zimbler, Daniel L; Schroeder, Jay A; Eddy, Justin L; Lathem, Wyndham W

2015-06-30

Yersinia pestis causes the fatal respiratory disease pneumonic plague. Y. pestis recently evolved from the gastrointestinal pathogen Y. pseudotuberculosis; however, it is not known at what point Y. pestis gained the ability to induce a fulminant pneumonia. Here we show that the acquisition of a single gene encoding the protease Pla was sufficient for the most ancestral, deeply rooted strains of Y. pestis to cause pneumonic plague, indicating that Y. pestis was primed to infect the lungs at a very early stage in its evolution. As Y. pestis further evolved, modern strains acquired a single amino-acid modification within Pla that optimizes protease activity. While this modification is unnecessary to cause pneumonic plague, the substitution is instead needed to efficiently induce the invasive infection associated with bubonic plague. These findings indicate that Y. pestis was capable of causing pneumonic plague before it evolved to optimally cause invasive infections in mammals.

Legionella waltersii--a novel cause of pneumonia?

PubMed

König, Corinne; Hebestreit, Helge; Valenza, Guiseppe; Abele-Horn, Marianne; Speer, Christian P

2005-10-01

A 5-y-old girl was admitted to our hospital with fever, cough, respiratory distress and rapidly increasing oxygen requirements. A chest radiograph showed bilateral central infiltrates. PCR was performed with pharyngeal washings and revealed Legionella DNA, while no genetic materials of other pathogens such as respiratory viruses, Mycoplasma and Chlamydia were detected. The clinical condition improved gradually after administration of steroids and therapy with clarithromycin. Further sequencing of Legionella DNA led to the identification of Legionella waltersii. This Legionella species has never been described as a human pathogen before. For the first time, L. waltersii was identified as a cause of severe pneumonia. Since L. waltersii is not detected by routine laboratory tests, it may be speculated that these bacteria, like other Legionella species, are underestimated as a probable cause of community-acquired pneumonia.

A Role for Neutrophils in Viral Respiratory Disease.

PubMed

Camp, Jeremy V; Jonsson, Colleen B

2017-01-01

Neutrophils are immune cells that are well known to be present during many types of lung diseases associated with acute respiratory distress syndrome (ARDS) and may contribute to acute lung injury. Neutrophils are poorly studied with respect to viral infection, and specifically to respiratory viral disease. Influenza A virus (IAV) infection is the cause of a respiratory disease that poses a significant global public health concern. Influenza disease presents as a relatively mild and self-limiting although highly pathogenic forms exist. Neutrophils increase in the respiratory tract during infection with mild seasonal IAV, moderate and severe epidemic IAV infection, and emerging highly pathogenic avian influenza (HPAI). During severe influenza pneumonia and HPAI infection, the number of neutrophils in the lower respiratory tract is correlated with disease severity. Thus, comparative analyses of the relationship between IAV infection and neutrophils provide insights into the relative contribution of host and viral factors that contribute to disease severity. Herein, we review the contribution of neutrophils to IAV disease pathogenesis and to other respiratory virus infections.

The diagnosis and management of respiratory viral infections in cystic fibrosis.

PubMed

Flight, William; Jones, Andrew

2017-03-01

Respiratory viruses, such as those that cause influenza and the common cold, are a regular feature of life for the entire human population. Among people with CF, these viruses are associated with prolonged respiratory illness and show a clear association with pulmonary exacerbations which in turn are associated with lung function decline and risk of death. Human rhinovirus is the most commonly encountered respiratory viral pathogen in CF although adenovirus, bocavirus, coronavirus, influenza, parainfluenza, metapneumovirus and respiratory syncytial virus are all also responsible for infections in this population. Areas covered: This article reviews the epidemiology, clinical impact and therapeutic options for respiratory virus infection in both children and adults with CF. Expert commentary: The management of CF to date has largely focused on airway clearance strategies, nutritional support and aggressive antibacterial therapy. We highlight the significant role that respiratory viruses play in CF lung disease and argue that these pathogens represent an under-exploited target in the battle to control patients' symptoms and disease progression.

Novel, host-restricted genotypes of Bordetella bronchiseptica associated with phocine respiratory tract isolates

USDA-ARS?s Scientific Manuscript database

Bordetella bronchiseptica is a widespread respiratory pathogen in a variety of wild and domesticated animals. During a succession of phocine morbillivirus outbreaks occurring over the past 25 years, it was identified as a frequent secondary invader, often believed to be the cause of death. Prior a...

Pathogenicity and Molecular Characterization of Emerging Porcine Reproductive and Respiratory Syndrome Virus in Vietnam in 2007

USDA-ARS?s Scientific Manuscript database

In 2007, Vietnam experienced swine disease outbreaks causing clinical signs similar to the "porcine high fever disease" that occurred in China during 2006. Analysis of diagnostic samples from the disease outbreaks in Vietnam identified porcine reproductive and respiratory syndrome virus (PRRSV) and ...

The role and regulation of catalase in respiratory tract opportunistic bacterial pathogens.

PubMed

Eason, Mia M; Fan, Xin

2014-09-01

Respiratory tract bacterial pathogens are the etiologic agents of a variety of illnesses. The ability of these bacteria to cause disease is imparted through survival within the host and avoidance of pathogen clearance by the immune system. Respiratory tract pathogens are continually bombarded by reactive oxygen species (ROS), which may be produced by competing bacteria, normal metabolic function, or host immunological responses. In order to survive and proliferate, bacteria have adapted defense mechanisms to circumvent the effects of ROS. Bacteria employ the use of anti-oxidant enzymes, catalases and catalase-peroxidases, to relieve the effects of the oxidative stressors to which they are continually exposed. The decomposition of ROS has been shown to provide favorable conditions in which respiratory tract opportunistic bacterial pathogens such as Haemophilus influenzae, Mycobacterium tuberculosis, Legionella pneumophila, and Neisseria meningitidis are able to withstand exposure to highly reactive molecules and yet survive. Bacteria possessing mutations in the catalase gene have a decreased survival rate, yet may be able to compensate for the lack of catalatic activity if peroxidatic activity is present. An incomplete knowledge of the mechanisms by which catalase and catalase-peroxidases are regulated still persists, however, in some bacterial species, a regulatory factor known as OxyR has been shown to either up-regulate or down-regulate catalase gene expression. Yet, more research is still needed to increase the knowledge base in relation to this enzyme class. As with this review, we focus on major respiratory tract opportunistic bacterial pathogens in order to elucidate the function and regulation of catalases. The importance of the research could lead to the development of novel treatments against respiratory bacterial infections. Copyright © 2014 Elsevier Ltd. All rights reserved.

Streptococcus suis - The "Two Faces" of a Pathobiont in the Porcine Respiratory Tract.

PubMed

Vötsch, Désirée; Willenborg, Maren; Weldearegay, Yenehiwot B; Valentin-Weigand, Peter

2018-01-01

Streptococcus (S.) suis is a frequent early colonizer of the upper respiratory tract of pigs. In fact, it is difficult to find S. suis -free animals under natural conditions, showing the successful adaptation of this pathogen to its porcine reservoir host. On the other hand, S. suis can cause life-threatening diseases and represents the most important bacterial cause of meningitis in pigs worldwide. Notably, S. suis can also cause zoonotic infections, such as meningitis, septicemia, endocarditis, and other diseases in humans. In Asia, it is classified as an emerging zoonotic pathogen and currently considered as one of the most important causes of bacterial meningitis in adults. The "two faces" of S. suis , one of a colonizing microbe and the other of a highly invasive pathogen, have raised many questions concerning the interpretation of diagnostic detection and the definition of virulence. Thus, one major research challenge is the identification of virulence-markers which allow differentiation of commensal and virulent strains. This is complicated by the high phenotypic and genotypic diversity of S. suis , as reflected by the occurrence of (at least) 33 capsular serotypes. In this review, we present current knowledge in the context of S. suis as a highly diverse pathobiont in the porcine respiratory tract that can exploit disrupted host homeostasis to flourish and promote inflammatory processes and invasive diseases in pigs and humans.

Streptococcus suis – The “Two Faces” of a Pathobiont in the Porcine Respiratory Tract

PubMed Central

Vötsch, Désirée; Willenborg, Maren; Weldearegay, Yenehiwot B.; Valentin-Weigand, Peter

2018-01-01

Streptococcus (S.) suis is a frequent early colonizer of the upper respiratory tract of pigs. In fact, it is difficult to find S. suis-free animals under natural conditions, showing the successful adaptation of this pathogen to its porcine reservoir host. On the other hand, S. suis can cause life-threatening diseases and represents the most important bacterial cause of meningitis in pigs worldwide. Notably, S. suis can also cause zoonotic infections, such as meningitis, septicemia, endocarditis, and other diseases in humans. In Asia, it is classified as an emerging zoonotic pathogen and currently considered as one of the most important causes of bacterial meningitis in adults. The “two faces” of S. suis, one of a colonizing microbe and the other of a highly invasive pathogen, have raised many questions concerning the interpretation of diagnostic detection and the definition of virulence. Thus, one major research challenge is the identification of virulence-markers which allow differentiation of commensal and virulent strains. This is complicated by the high phenotypic and genotypic diversity of S. suis, as reflected by the occurrence of (at least) 33 capsular serotypes. In this review, we present current knowledge in the context of S. suis as a highly diverse pathobiont in the porcine respiratory tract that can exploit disrupted host homeostasis to flourish and promote inflammatory processes and invasive diseases in pigs and humans. PMID:29599763

Host response to bovine respiratory pathogens.

PubMed

Czuprynski, Charles J

2009-12-01

Bovine respiratory disease (BRD) involves complex interactions amongst viral and bacterial pathogens that can lead to intense pulmonary inflammation (fibrinous pleuropneumonia). Viral infection greatly increases the susceptibility of cattle to secondary infection of the lung with bacterial pathogens like Mannheimia haemolytica and Histophilus somni. The underlying reason for this viral/bacterial synergism, and the manner in which cattle respond to the virulence strategies of the bacterial pathogens, is incompletely understood. Bovine herpesvirus type 1 (BHV-1) infection of bronchial epithelial cells in vitro enhances the binding of M. haemolytica and triggers release of inflammatory mediators that attract and enhance binding of neutrophils. An exotoxin (leukotoxin) released from M. haemolytica further stimulates release of inflammatory mediators and causes leukocyte death. Cattle infected with H. somni frequently display vasculitis. Exposure of bovine endothelial cells to H. somnii or its lipooligosaccharide (LOS) increases endothelium permeability, and makes the surface of the endothelial cells pro-coagulant. These processes are amplified in the presence of platelets. The above findings demonstrate that bovine respiratory pathogens (BHV-1, M. haemolytica and H. somni) interact with leukocytes and other cells (epithelial and endothelial cells) leading to the inflammation that characterizes BRD.

Bacterial Pathogens Associated with Community-acquired Pneumonia in Children Aged Below Five Years.

PubMed

Das, Anusmita; Patgiri, Saurav J; Saikia, Lahari; Dowerah, Pritikar; Nath, Reema

2016-03-01

To determine the spectrum of bacterial pathogens causing community-acquired pneumonia in children below 5 years of age. Children aged below 5 years satisfying the WHO criteria for pneumonia, severe pneumonia or very severe pneumonia, and with the presence of lung infiltrates on chest X-ray were enrolled. Two respiratory samples, one for culture and the other for PCR analysis, and a blood sample for culture were collected from every child. Of the 180 samples processed, bacterial pathogens were detected in 64.4%. Streptococcus pneumoniae and Hemophilus influenzae were most frequently detected. The performance of PCR analysis and culture were identical for the typical bacterial pathogens; atypical pathogens were detected by PCR analysis only. S. pneumoniae and H. influenza were the most commonly detected organisms from respiratory secretions of children with community acquired pneumonia.

[Human coronavirus infections: importance and diagnosis].

PubMed

Vabret, A; Brouard, J; Petitjean, J; Eugene-Ruellan, G; Freymuth, F

1998-11-14

POORLY-KNOWN VIRUS: Coronaviruses, so named because of their sun-ray-like aspect, were discovered in the sixties. The biology of these RNA viruses is complex and poorly understood. KNOWN PATHOGENS: Coronaviruses are known pathogens in veterinary medicine, causing disease states in several domestic species. In human medicine, they can cause benign respiratory infections, but few laboratories include coronaviruses in their routine diagnostic tests. SUSPECTED PATHOGENS: There is some data in the literature suggesting coronaviruses might be implicated in more severe diseases including multiple sclerosis, necrotizing enterocolitis, and lower respiratory tract infections, particularly in infants. IMPROVING DIAGNOSTIC METHODS: Due to the lack of reliable and sensitive diagnostic techniques, it is impossible to date to correctly assess the medical impact of these ubiquitous and endemic viruses. Molecular biology techniques enabling detection of human coronavirus infections should be applied to verifying the suspected implication of these viruses in diverse disease states.

Respiratory Diseases among U.S. Military Personnel: Countering Emerging Threats

PubMed Central

Callahan, Johnny D.; Hawksworth, Anthony W.; Fisher, Carol A.; Gaydos, Joel C.

1999-01-01

Emerging respiratory disease agents, increased antibiotic resistance, and the loss of effective vaccines threaten to increase the incidence of respiratory disease in military personnel. We examine six respiratory pathogens (adenoviruses, influenza viruses, Streptococcus pneumoniae, Streptococcus pyogenes, Mycoplasma pneumoniae, and Bordetella pertussis) and review the impact of the diseases they cause, past efforts to control these diseases in U.S. military personnel, as well as current treatment and surveillance strategies, limitations in diagnostic testing, and vaccine needs. PMID:10341174

[A case of pulmonary abscess in which Haemophilus parainfluenzae and Streptococcus intermedius were isolated by percutaneous needle aspiration].

PubMed

Miyamoto, Atsushi; Tsuboi, Eiyasu; Takaya, Hisashi; Sugino, Keishi; Sakamoto, Susumu; Kawabata, Masateru; Kishi, Kazuma; Narui, Koji; Homma, Sakae; Nakatani, Tatsuo; Nakata, Koichiro; Yoshimura, Kunihiko

2006-08-01

Some microbes, including the Bacteroides species, Staphylococcus aureus and Streptococcus milleri groups, can cause pulmonary abscess. Haemophilus parainfluenzae is usually categorized as one of the normal flora which colonizes in the ears and the nasopharynx, and it has been long considered that H. parainfluenzae has little pathogenicity in the lower respiratory tract and lung parenchymal. In this report, we present a case of pulmonary abscess caused by both H. parainfluenzae and Streptococcus intermedius. The patient was a 75-year-old man who had had total esophageo-gastrectomy because of esophageal cancer. He presented with purulent sputum, and chest X-ray film showed a dense consolidation in the right upper lung field. CT-guided transcutaneous fine needle aspiration was performed as a diagnostic procedure. Since both H. parainfluenzae and S. intermedius had been isolated from the lesion, pulmonary abscess caused by these two pathogens was diagnosed. The patient was treated with panipenem/betamipron, and his symptoms and pulmonary infiltrates on the chest X-ray film improved thereafter. So far, very few cases have been reported in which H. parainfluenzae caused lower respiratory tract infection. Although S. intermedius is known as one of the pathogens of pulmonary abscess, it is possible that H. parainfluenzae could also be pathogenic in infectious diseases of the lung.

Draft genome sequences for ten isolates of the swine respiratory pathogen Haemophilus Parasuis

USDA-ARS?s Scientific Manuscript database

Haemophilus parasuis is a swine pathogen that causes pneumonia and Glässer’s disease, a systemic syndrome of polyserositis, arthritis, and meningitis. We report here the draft genomes of ten geographically diverse isolates collectively representing the full virulence spectrum of H. parasuis. These...

Calculation of genomic predicted transmitting abilities for bovine respiratory disease complex in Holsteins

USDA-ARS?s Scientific Manuscript database

Bovine Respiratory Disease Complex is a disease that is very costly to the dairy industry. Genomic selection may be an effective tool to improve host resistance to the pathogens that cause this disease. Use of genomic predicted transmitting abilities (GPTA) for selection has had a dramatic effect on...

Role of bibersteinia trehalosi, respiratory syncytial virus, and parainfluenza-3 virus in bighorn sheep pneumonia

USDA-ARS?s Scientific Manuscript database

Pneumonic bighorn sheep (BHS) have been found to be culture- and/or sero-positive for Bibersteinia trehalosi, respiratory syncytial virus (RSV), and parainfluenza-3 virus (PI-3). The objective of this study was to determine whether these pathogens can cause fatal pneumonia in BHS. In the first study...

Pigeon paramyxovirus type 1 from a fatal human case induces pneumonia in experimentally infected cynomolgus macaques (Macaca fascicularis).

PubMed

Kuiken, Thijs; Buijs, Pascal; van Run, Peter; van Amerongen, Geert; Koopmans, Marion; van den Hoogen, Bernadette

2017-11-21

Although avian paramyxovirus type 1 is known to cause mild transient conjunctivitis in human beings, there are two recent reports of fatal respiratory disease in immunocompromised human patients infected with the pigeon lineage of the virus (PPMV-1). In order to evaluate the potential of PPMV-1 to cause respiratory tract disease, we inoculated a PPMV-1 isolate (hPPMV-1/Netherlands/579/2003) from an immunocompromised human patient into three healthy cynomolgus macaques (Macaca fascicularis) and examined them by clinical, virological, and pathological assays. In all three macaques, PPMV-1 replication was restricted to the respiratory tract and caused pulmonary consolidation affecting up to 30% of the lung surface. Both alveolar and bronchiolar epithelial cells expressed viral antigen, which co-localized with areas of diffuse alveolar damage. The results of this study demonstrate that PPMV-1 is a primary respiratory pathogen in cynomolgus macaques, and support the conclusion that PPMV-1 may cause fatal respiratory disease in immunocompromised human patients.

Overactive Epidermal Growth Factor Receptor Signaling Leads to Increased Fibrosis after Severe Acute Respiratory Syndrome Coronavirus Infection

PubMed Central

Venkataraman, Thiagarajan; Coleman, Christopher M.

2017-01-01

ABSTRACT Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic respiratory virus that causes morbidity and mortality in humans. After infection with SARS-CoV, the acute lung injury caused by the virus must be repaired to regain lung function. A dysregulation in this wound healing process leads to fibrosis. Many survivors of SARS-CoV infection develop pulmonary fibrosis (PF), with higher prevalence in older patients. Using mouse models of SARS-CoV pathogenesis, we have identified that the wound repair pathway, controlled by the epidermal growth factor receptor (EGFR), is critical to recovery from SARS-CoV-induced tissue damage. In mice with constitutively active EGFR [EGFR(DSK5) mice], we find that SARS-CoV infection causes enhanced lung disease. Importantly, we show that during infection, the EGFR ligands amphiregulin and heparin-binding EGF-like growth factor (HB-EGF) are upregulated, and exogenous addition of these ligands during infection leads to enhanced lung disease and altered wound healing dynamics. Our data demonstrate a key role of EGFR in the host response to SARS-CoV and how it may be implicated in lung disease induced by other highly pathogenic respiratory viruses. IMPORTANCE PF has many causative triggers, including severe respiratory viruses such as SARS-CoV. Currently there are no treatments to prevent the onset or limit the progression of PF, and the molecular pathways underlying the development of PF are not well understood. In this study, we identified a role for the balanced control of EGFR signaling as a key factor in progression to PF. These data demonstrate that therapeutic treatment modulating EGFR activation could protect against PF development caused by severe respiratory virus infection. PMID:28404843

Overactive Epidermal Growth Factor Receptor Signaling Leads to Increased Fibrosis after Severe Acute Respiratory Syndrome Coronavirus Infection.

PubMed

Venkataraman, Thiagarajan; Coleman, Christopher M; Frieman, Matthew B

2017-06-15

Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic respiratory virus that causes morbidity and mortality in humans. After infection with SARS-CoV, the acute lung injury caused by the virus must be repaired to regain lung function. A dysregulation in this wound healing process leads to fibrosis. Many survivors of SARS-CoV infection develop pulmonary fibrosis (PF), with higher prevalence in older patients. Using mouse models of SARS-CoV pathogenesis, we have identified that the wound repair pathway, controlled by the epidermal growth factor receptor (EGFR), is critical to recovery from SARS-CoV-induced tissue damage. In mice with constitutively active EGFR [EGFR(DSK5) mice], we find that SARS-CoV infection causes enhanced lung disease. Importantly, we show that during infection, the EGFR ligands amphiregulin and heparin-binding EGF-like growth factor (HB-EGF) are upregulated, and exogenous addition of these ligands during infection leads to enhanced lung disease and altered wound healing dynamics. Our data demonstrate a key role of EGFR in the host response to SARS-CoV and how it may be implicated in lung disease induced by other highly pathogenic respiratory viruses. IMPORTANCE PF has many causative triggers, including severe respiratory viruses such as SARS-CoV. Currently there are no treatments to prevent the onset or limit the progression of PF, and the molecular pathways underlying the development of PF are not well understood. In this study, we identified a role for the balanced control of EGFR signaling as a key factor in progression to PF. These data demonstrate that therapeutic treatment modulating EGFR activation could protect against PF development caused by severe respiratory virus infection. Copyright © 2017 American Society for Microbiology.

Divergence in substrate specificity by the vOTU domain of various strains of highly-pathogenic PRRSV and the implications to pathogenicity

USDA-ARS?s Scientific Manuscript database

Porcine reproductive and respiratory syndrome virus (PRRSV) is widespread with a high variation in sequence and virulence among the divergent strains and causes an economically destructive disease. A viral ovarian domain protease (vOTU) has been previously identified within the nonstructural protein...

Infectivity, transmission and pathogenicity of avian influenza viruses for domestic and wild birds

USDA-ARS?s Scientific Manuscript database

Individual avian influenza (AI) virus strains vary in their ability to infect, transmit and cause disease and death in different bird species. Low pathogenicity AI (LPAI) viruses are maintained in wild birds, and must be adapted to pass to domestic poultry, where they replicate in respiratory and in...

Bovine respiratory disease model based on dual infections with infection with bovine viral diarrhea virus and bovine corona virus

USDA-ARS?s Scientific Manuscript database

Bovine respiratory disease complex (BRDC) is the leading cause of economic loss in the U.S. cattle industry. BRDC likely results from simultaneous or sequential infections with multiple pathogens including both viruses and bacteria. Bovine viral diarrhea virus (BVDV) and bovine corona virus (BoCV...

Identification and genome characterization of genotype B and genotype C bovine parainfluenza type 3 viruses isolated in the United States

USDA-ARS?s Scientific Manuscript database

Background: Bovine parainfluenza 3 viruses (BPI3V) are respiratory pathogens of cattle that cause disease singly but are often associated with bovine respiratory disease complex (BRDC) in conjunction with other viral and bacterial agents. Bovine vaccines currently contain BPI3V to provide protection...

Differential expression of miRNA-423-5p in serum from cattle challenged with bovine viral diarrhea virus

USDA-ARS?s Scientific Manuscript database

Bovine viral diarrhea virus (BVDV) is an RNA virus that causes respiratory disease in cattle. MicroRNAs have been proposed as indicators of exposure to respiratory pathogens. However, microRNA profiles in cattle exposed to BVDV are currently nonexistent and few studies have been reported; therefore,...

The Potential of Avian H1N1 Influenza A Viruses to Replicate and Cause Disease in Mammalian Models

PubMed Central

Koçer, Zeynep A.; Krauss, Scott; Stallknecht, David E.; Rehg, Jerold E.; Webster, Robert G.

2012-01-01

H1N1 viruses in which all gene segments are of avian origin are the most frequent cause of influenza pandemics in humans; therefore, we examined the disease-causing potential of 31 avian H1N1 isolates of American lineage in DBA/2J mice. Thirty of 31 isolates were very virulent, causing respiratory tract infection; 22 of 31 resulted in fecal shedding; and 10 of 31 were as pathogenic as the pandemic 2009 H1N1 viruses. Preliminary studies in BALB/cJ mice and ferrets showed that 1 of 4 isolates tested was more pathogenic than the pandemic 2009 H1N1 viruses in BALB/cJ mice, and 1 of 2 strains transmitted both by direct and respiratory-droplet contact in ferrets. Preliminary studies of other avian subtypes (H2, H3, H4, H6, H10, H12) in DBA/2J mice showed lower pathogenicity than the avian H1N1 viruses. These findings suggest that avian H1N1 influenza viruses are unique among influenza A viruses in their potential to infect mammals. PMID:22848544

Structured literature review of responses of cattle to viral and bacterial pathogens causing bovine respiratory disease complex.

PubMed

Grissett, G P; White, B J; Larson, R L

2015-01-01

Bovine respiratory disease (BRD) is an economically important disease of cattle and continues to be an intensely studied topic. However, literature summarizing the time between pathogen exposure and clinical signs, shedding, and seroconversion is minimal. A structured literature review of the published literature was performed to determine cattle responses (time from pathogen exposure to clinical signs, shedding, and seroconversion) in challenge models using common BRD viral and bacterial pathogens. After review a descriptive analysis of published studies using common BRD pathogen challenge studies was performed. Inclusion criteria were single pathogen challenge studies with no treatment or vaccination evaluating outcomes of interest: clinical signs, shedding, and seroconversion. Pathogens of interest included: bovine viral diarrhea virus (BVDV), bovine herpesvirus type 1 (BHV-1), parainfluenza-3 virus, bovine respiratory syncytial virus, Mannheimia haemolytica, Mycoplasma bovis, Pastuerella multocida, and Histophilus somni. Thirty-five studies and 64 trials were included for analysis. The median days to the resolution of clinical signs after BVDV challenge was 15 and shedding was not detected on day 12 postchallenge. Resolution of BHV-1 shedding resolved on day 12 and clinical signs on day 12 postchallenge. Bovine respiratory syncytial virus ceased shedding on day 9 and median time to resolution of clinical signs was on day 12 postchallenge. M. haemolytica resolved clinical signs 8 days postchallenge. This literature review and descriptive analysis can serve as a resource to assist in designing challenge model studies and potentially aid in estimation of duration of clinical disease and shedding after natural pathogen exposure. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Mycoplasma pneumoniae respiratory tract infections among Greek children

PubMed Central

Almasri, M; Diza, E; Papa, A; Eboriadou, M; Souliou, E

2011-01-01

Background: M. pneumoniae is a common cause of respiratory tract infections (RTIs) of variable severity especially in children. New diagnostic techniques offered more reliable information about the epidemiology of infection by this pathogen. Aim: The aim of this study was to investigate the prevalence and epidemiology of acute M. pneumoniae infections among Greek children hospitalized for RTIs using more advanced techniques. Material and Methods: The study included 225 Greek children hospitalized for RTIs during a 15-month period. Throat swab specimens were tested by PCR for the detection of M. pneumoniae, while IgG and IgM antibodies were determined by ELISA and, in certain cases, also by western-blot. In parallel, specimens were tested for the presence of additional respiratory pathogens. Results: M. pneumoniae infection was diagnosed as the only pathogen in 25 (11.1%) cases, being the second (after respiratory syncytial virus- RSV) most often detected pathogen. The proportion of cases with M. pneumoniae infection in age group 8-14 years (23.3%) was significantly higher than that in <3 years age group. Conclusion: During our study period, M. pneumoniae was the second causative agent of RTIs after RSV. The proportion of children with M. pneumoniae RTIs increased with age, while most cases were reported during summer and autumn. PMID:22110297

Prevalence and Seasonal Distribution of Respiratory Viruses During the 2014 - 2015 Season in Istanbul

PubMed Central

Goktas, Safak; Sirin, Mumtaz Cem

2016-01-01

Background Acute respiratory tract infection (ARTI) is one of the most common infections worldwide, causing significant morbidity and mortality. Objectives This study was conducted to determine the prevalence and seasonal distribution of respiratory viruses in our region, in children and adults with a pre-diagnosis of ARTI. Methods A total of 845 nasopharyngeal swab specimens were analyzed with the RespiFinder Smart 22 kit (PathoFinder BV, Netherlands) and the Rotor-Gene 6000 real-time PCR system. Results At least one pathogen was detected in 612 (72.4%) of the specimens. Overall, 902 pathogens were detected; 821 (91%) were viruses and 81 (9%) were bacteria. The most commonly detected pathogens were influenza A virus (IFV-A) (n = 219), influenza B virus (IFV-B) (n=157), rhinovirus/enterovirus (n = 107), human bocavirus (HBoV) (n = 91), respiratory syncytial virus (RSV) A/B (n = 64), adenovirus (n = 56), human coronaviruses (n = 51), Mycoplasma pneumoniae (n = 49), parainfluenza viruses (n = 40), human metapneumovirus (n = 36), Bordetella pertussis (n = 15), Legionella pneumophila (n = 11), and Chlamydophila pneumoniae (n = 6), respectively. Among the 215 (25.4%) co-infected cases, IFV-A/HBoV and IFV-A/IFV-B were the most common co-infections. IFV-A was the most prevalent agent in all age groups except for children under 5 years of age, in whom RSV A/B was the most common pathogen. Approximately two thirds of the respiratory viruses were detected in early spring and winter, with peaks in January, March, and April. Conclusions With regard to the prevalence and seasonal distribution of respiratory viruses, our epidemiological data for the 2014 - 2015 season in Istanbul showed a predominance of IFV-A infections with a peak activity in early spring. Enhanced surveillance and early detection of respiratory viral pathogens can be useful in the diagnosis, treatment, and prevention of ARTIs, and for guiding the development of appropriate public health strategies. PMID:27800148

Severe Pneumonia Caused by Legionella pneumophila: Differential Diagnosis and Therapeutic Considerations.

PubMed

Chahin, Abdullah; Opal, Steven M

2017-03-01

Severe legionella pneumonia poses a diagnostic challenge and requires early intervention. Legionnaire's disease can have several presenting signs, symptoms, and laboratory abnormalities that suggest that Legionella pneumophila is the pathogen, but none of these are sufficient to distinguish L pneumophila pneumonia from other respiratory pathogens. L pneumophila is primarily an intracellular pathogen and needs treatment with antibiotics that efficiently enter the intracellular space. Copyright © 2016 Elsevier Inc. All rights reserved.

Bovine gamma delta T cells contribute to exacerbated IL-17 production in response to co-infection with Bovine RSV and Mannheimia haemolytica

USDA-ARS?s Scientific Manuscript database

Human respiratory syncytial virus (HRSV) is a leading cause of severe lower respiratory tract infection in children under five years of age. IL-17 and Th17 responses are increased in children infected with HRSV and have been implicated in both protective and pathogenic roles during infection. Bovi...

The bovine paranasal sinuses: Bacterial flora, epithelial expression of nitric oxide and potential role in the in-herd persistence of respiratory disease pathogens.

PubMed

Murray, Gerard M; O'Neill, Rónan G; Lee, Alison M; McElroy, Máire C; More, Simon J; Monagle, Aisling; Earley, Bernadette; Cassidy, Joseph P

2017-01-01

The bovine paranasal sinuses are a group of complex cavernous air-filled spaces, lined by respiratory epithelium, the exact function of which is unclear. While lesions affecting these sinuses are occasionally reported in cattle, their microbial flora has not been defined. Furthermore, given that the various bacterial and viral pathogens causing bovine respiratory disease (BRD) persist within herds, we speculated that the paranasal sinuses may serve as a refuge for such infectious agents. The paranasal sinuses of clinically normal cattle (n = 99) and of cattle submitted for post-mortem examination (PME: n = 34) were examined by microbial culture, PCR and serology to include bacterial and viral pathogens typically associated with BRD: Mycoplasma bovis, Histophilus somni, Mannheimia haemolytica and Pasteurella multocida, bovine respiratory syncytial virus (BRSV) and bovine parainfluenza-3 virus (BPIV-3). Overall, the paranasal sinuses were either predominantly sterile or did not contain detectable microbes (83.5%: 94.9% of clinically normal and 50.0% of cattle submitted for PME). Bacteria, including BRD causing pathogens, were identified in relatively small numbers of cattle (<10%). While serology indicated widespread exposure of both clinically normal and cattle submitted for PME to BPIV-3 and BRSV (seroprevalences of 91.6% and 84.7%, respectively), PCR identified BPIV-3 in only one animal. To further explore these findings we investigated the potential role of the antimicrobial molecule nitric oxide (NO) within paranasal sinus epithelium using immunohistochemistry. Expression of the enzyme responsible for NO synthesis, inducible nitric oxide synthase (iNOS), was detected to varying degrees in 76.5% of a sub-sample of animals suggesting production of this compound plays a similar protective role in the bovine sinus as it does in humans.

Universal and reusable virus deactivation system for respiratory protection

NASA Astrophysics Data System (ADS)

Quan, Fu-Shi; Rubino, Ilaria; Lee, Su-Hwa; Koch, Brendan; Choi, Hyo-Jick

2017-01-01

Aerosolized pathogens are a leading cause of respiratory infection and transmission. Currently used protective measures pose potential risk of primary/secondary infection and transmission. Here, we report the development of a universal, reusable virus deactivation system by functionalization of the main fibrous filtration unit of surgical mask with sodium chloride salt. The salt coating on the fiber surface dissolves upon exposure to virus aerosols and recrystallizes during drying, destroying the pathogens. When tested with tightly sealed sides, salt-coated filters showed remarkably higher filtration efficiency than conventional mask filtration layer, and 100% survival rate was observed in mice infected with virus penetrated through salt-coated filters. Viruses captured on salt-coated filters exhibited rapid infectivity loss compared to gradual decrease on bare filters. Salt-coated filters proved highly effective in deactivating influenza viruses regardless of subtypes and following storage in harsh environmental conditions. Our results can be applied in obtaining a broad-spectrum, airborne pathogen prevention device in preparation for epidemic and pandemic of respiratory diseases.

Universal and reusable virus deactivation system for respiratory protection

PubMed Central

Quan, Fu-Shi; Rubino, Ilaria; Lee, Su-Hwa; Koch, Brendan; Choi, Hyo-Jick

2017-01-01

Aerosolized pathogens are a leading cause of respiratory infection and transmission. Currently used protective measures pose potential risk of primary/secondary infection and transmission. Here, we report the development of a universal, reusable virus deactivation system by functionalization of the main fibrous filtration unit of surgical mask with sodium chloride salt. The salt coating on the fiber surface dissolves upon exposure to virus aerosols and recrystallizes during drying, destroying the pathogens. When tested with tightly sealed sides, salt-coated filters showed remarkably higher filtration efficiency than conventional mask filtration layer, and 100% survival rate was observed in mice infected with virus penetrated through salt-coated filters. Viruses captured on salt-coated filters exhibited rapid infectivity loss compared to gradual decrease on bare filters. Salt-coated filters proved highly effective in deactivating influenza viruses regardless of subtypes and following storage in harsh environmental conditions. Our results can be applied in obtaining a broad-spectrum, airborne pathogen prevention device in preparation for epidemic and pandemic of respiratory diseases. PMID:28051158

Avian influenza virus, Streptococcus suis serotype 2, severe acute respiratory syndrome-coronavirus and beyond: molecular epidemiology, ecology and the situation in China.

PubMed

Ma, Ying; Feng, Youjun; Liu, Di; Gao, George F

2009-09-27

The outbreak and spread of severe acute respiratory syndrome-associated coronavirus and the subsequent identification of its animal origin study have heightened the world's awareness of animal-borne or zoonotic pathogens. In addition to SARS, the highly pathogenic avian influenza virus (AIV), H5N1, and the lower pathogenicity H9N2 AIV have expanded their host ranges to infect human beings and other mammalian species as well as birds. Even the 'well-known' reservoir animals for influenza virus, migratory birds, became victims of the highly pathogenic H5N1 virus. Not only the viruses, but bacteria can also expand their host range: a new disease, streptococcal toxic shock syndrome, caused by human Streptococcus suis serotype 2 infection, has been observed in China with 52 human fatalities in two separate outbreaks (1998 and 2005, respectively). Additionally, enterohaemorrhagic Escherichia coli O157:H7 infection has increased worldwide with severe disease. Several outbreaks and sporadic isolations of this pathogen in China have made it an important target for disease control. A new highly pathogenic variant of porcine reproductive and respiratory syndrome virus (PRRSV) has been isolated in both China and Vietnam recently; although PRRSV is not a zoonotic human pathogen, its severe outbreaks have implications for food safety. All of these pathogens occur in Southeast Asia, including China, with severe consequences; therefore, we discuss the issues in this article by addressing the situation of the zoonotic threat in China.

Pathogenic influenza B virus in the ferret model establishes lower respiratory tract infection.

PubMed

Huang, Stephen S H; Banner, David; Paquette, Stephane G; Leon, Alberto J; Kelvin, Alyson A; Kelvin, David J

2014-10-01

Influenza B viruses have become increasingly more prominent during influenza seasons. Influenza B infection is typically considered a mild disease and receives less attention than influenza A, but has been causing 20 to 50 % of the total influenza incidence in several regions around the world. Although there is increasing evidence of mid to lower respiratory tract diseases such as bronchitis and pneumonia in influenza B patients, little is known about the pathogenesis of recent influenza B viruses. Here we investigated the clinical and pathological profiles of infection with strains representing the two current co-circulating B lineages (B/Yamagata and B/Victoria) in the ferret model. Specifically, we studied two B/Victoria (B/Brisbane/60/2008 and B/Bolivia/1526/2010) and two B/Yamagata (B/Florida/04/2006 and B/Wisconsin/01/2010) strain infections in ferrets and observed strain-specific but not lineage-specific pathogenicity. We found B/Brisbane/60/2008 caused the most severe clinical illness and B/Brisbane/60/2008 and the B/Yamagata strains instigated pathology in the middle to lower respiratory tract. Importantly, B/Brisbane/60/2008 established efficient lower respiratory tract infection with high viral burden. Our phylogenetic analyses demonstrate profound reassortment among recent influenza B viruses, which indicates the genetic make-up of B/Brisbane/60/2008 differs from the other strains. This may explain the pathogenicity difference post-infection in ferrets. © 2014 The Authors.

A molecular arms race between host innate antiviral response and emerging human coronaviruses.

PubMed

Wong, Lok-Yin Roy; Lui, Pak-Yin; Jin, Dong-Yan

2016-02-01

Coronaviruses have been closely related with mankind for thousands of years. Community-acquired human coronaviruses have long been recognized to cause common cold. However, zoonotic coronaviruses are now becoming more a global concern with the discovery of highly pathogenic severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses causing severe respiratory diseases. Infections by these emerging human coronaviruses are characterized by less robust interferon production. Treatment of patients with recombinant interferon regimen promises beneficial outcomes, suggesting that compromised interferon expression might contribute at least partially to the severity of disease. The mechanisms by which coronaviruses evade host innate antiviral response are under intense investigations. This review focuses on the fierce arms race between host innate antiviral immunity and emerging human coronaviruses. Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. On the other hand, the counter-measures evolved by SARS and MERS coronaviruses to circumvent host defense are also dissected. With a better understanding of the dynamic interaction between host and coronaviruses, it is hoped that insights on the pathogenesis of newly-identified highly pathogenic human coronaviruses and new strategies in antiviral development can be derived.

Influenza virus isolation.

PubMed

Krauss, Scott; Walker, David; Webster, Robert G

2012-01-01

The isolation of influenza viruses is important for the diagnosis of respiratory diseases in lower animals and humans, for the detection of the infecting agent in surveillance programs, and is an essential element in the development and production of vaccine. Since influenza is caused by a zoonotic virus it is necessary to do surveillance in the reservoir species (aquatic waterfowls), intermediate hosts (quails, pigs), and in affected mammals including humans. Two of the hemagglutinin (HA) subtypes of influenza A viruses (H5 and H7) can evolve into highly pathogenic (HP) strains for gallinaceous poultry; some HP H5 and H7 strains cause lethal infection of humans. In waterfowls, low pathogenic avian influenza (LPAI) isolates are obtained primarily from the cloaca (or feces); in domestic poultry, the virus is more often recovered from the respiratory tract than from cloacal samples; in mammals, the virus is most often isolated from the respiratory tract, and in cases of high pathogenic avian influenza (HPAI) from the blood and internal organs of infected birds. Virus isolation procedures are performed by inoculation of clinical specimens into embryonated eggs (primarily chicken eggs) or onto a variety of primary or continuous tissue culture systems. Successful isolation of influenza virus depends on the quality of the sample and matching the appropriate culture method to the sample type.

Whole Genome Sequence Analysis of Pig Respiratory Bacterial Pathogens with Elevated Minimum Inhibitory Concentrations for Macrolides.

PubMed

Dayao, Denise Ann Estarez; Seddon, Jennifer M; Gibson, Justine S; Blackall, Patrick J; Turni, Conny

2016-10-01

Macrolides are often used to treat and control bacterial pathogens causing respiratory disease in pigs. This study analyzed the whole genome sequences of one clinical isolate of Actinobacillus pleuropneumoniae, Haemophilus parasuis, Pasteurella multocida, and Bordetella bronchiseptica, all isolated from Australian pigs to identify the mechanism underlying the elevated minimum inhibitory concentrations (MICs) for erythromycin, tilmicosin, or tulathromycin. The H. parasuis assembled genome had a nucleotide transition at position 2059 (A to G) in the six copies of the 23S rRNA gene. This mutation has previously been associated with macrolide resistance but this is the first reported mechanism associated with elevated macrolide MICs in H. parasuis. There was no known macrolide resistance mechanism identified in the other three bacterial genomes. However, strA and sul2, aminoglycoside and sulfonamide resistance genes, respectively, were detected in one contiguous sequence (contig 1) of A. pleuropneumoniae assembled genome. This contig was identical to plasmids previously identified in Pasteurellaceae. This study has provided one possible explanation of elevated MICs to macrolides in H. parasuis. Further studies are necessary to clarify the mechanism causing the unexplained macrolide resistance in other Australian pig respiratory pathogens including the role of efflux systems, which were detected in all analyzed genomes.

Clinical and epidemiological profiles including meteorological factors of low respiratory tract infection due to human rhinovirus in hospitalized children.

PubMed

Yan, Yongdong; Huang, Li; Wang, Meijuan; Wang, Yuqing; Ji, Wei; Zhu, Canhong; Chen, Zhengrong

2017-03-07

Lower respiratory tract infection (LRTI) is a major cause of morbidity and mortality in children. Human rhinovirus (HRV) is confirmed to be associated with pediatric lower respiratory tract infection. Seasonal and meteorological factors may play a key role in the epidemiology of HRV. The purposes of this study were to investigate the frequency, seasonal distribution, and clinical characteristics of hospitalized children with LRTI caused by HRVs. In addition, associations between incidence of HRVs and meteorological factors in a subtropical region of China were discussed. Hospitalized children <14 years old admitted to the Respiratory Department of the Children's Hospital, which is affiliated to Soochow University, between January 1, 2013 and December 31, 2015, were enrolled in this study. Multi-pathogens were detected in nasopharyngeal aspirate samples. Meanwhile, meteorological factors were recorded. The average incidence of HRVs infection was 11.4% (707/6194) and 240 cases of which were co-infection cases with other pathogens. Children with co-infection presented more frequent fever and tachypnea compared to children infected with HRVs only (both P < 0.05). Among 707 HRV positive children, the mean age was 23.2 months (range 1 to 140 months). Among all respiratory infections, the highest incidence of HRVs cases occurred in children age 13-36 months old (15.1%, 203/1341). Of all 228 HRV cases in 2014, 85 cases (37.3%) were HRV-C positive. HRVs and HRV-C infection occurred throughout the year during the study period, although a higher incidence was observed in summer and autumn seasons. HRVs or HRV-C incidence in hospitalized children with LRTI was associated with the monthly mean temperature (both P < 0.05). HRV was one of the most common viral pathogen detected in hospitalized children with LRTI at the Children's Hospital of Suzhou, China, and had its own seasonal distribution including HRV-C, which was partly caused by temperature.

Detection of Viral and Bacterial Pathogens in Hospitalized Children With Acute Respiratory Illnesses, Chongqing, 2009–2013

PubMed Central

Wei, Lan; Liu, Wei; Zhang, Xiao-Ai; Liu, En-Mei; Wo, Yin; Cowling, Benjamin J.; Cao, Wu-Chun

2015-01-01

Abstract Acute respiratory infections (ARIs) cause large disease burden each year. The codetection of viral and bacterial pathogens is quite common; however, the significance for clinical severity remains controversial. We aimed to identify viruses and bacteria in hospitalized children with ARI and the impact of mixed detections. Hospitalized children with ARI aged ≤16 were recruited from 2009 to 2013 at the Children's Hospital of Chongqing Medical University, Chongqing, China. Nasopharyngeal aspirates (NPAs) were collected for detection of common respiratory viruses by reverse transcription polymerase chain reaction (RT-PCR) or PCR. Bacteria were isolated from NPAs by routine culture methods. Detection and codetection frequencies and clinical features and severity were compared. Of the 3181 hospitalized children, 2375 (74.7%) were detected with ≥1 virus and 707 (22.2%) with ≥1 bacteria, 901 (28.3%) with ≥2 viruses, 57 (1.8%) with ≥2 bacteria, and 542 (17.0%) with both virus and bacteria. The most frequently detected were Streptococcus pneumoniae, respiratory syncytial virus, parainfluenza virus, and influenza virus. Clinical characteristics were similar among different pathogen infections for older group (≥6 years old), with some significant difference for the younger. Cases with any codetection were more likely to present with fever; those with ≥2 virus detections had higher prevalence of cough; cases with virus and bacteria codetection were more likely to have cough and sputum. No significant difference in the risk of pneumonia, severe pneumonia, and intensive care unit admission were found for any codetection than monodetection. There was a high codetection rate of common respiratory pathogens among hospitalized pediatric ARI cases, with fever as a significant predictor. Cases with codetection showed no significant difference in severity than those with single pathogens. PMID:25906103

Comparison of Asian porcine high fever disease isolates of porcine reproductive and respiratory syndrome virus to United States isolates for their ability to cause disease and secondary bacterial infection in swine

USDA-ARS?s Scientific Manuscript database

Epidemiologic data from Asian outbreaks of highly-pathogenic (HP) porcine reproductive and respiratory syndrome virus (PRRSV) suggest that disease severity was associated with both the virulence of the PRRSV isolates and secondary bacterial infections. Previous reports have indicated that U.S. isola...

Potential for Low-Pathogenic Avian H7 Influenza A Viruses To Replicate and Cause Disease in a Mammalian Model

PubMed Central

Zanin, Mark; Koçer, Zeynep A.; Poulson, Rebecca L.; Gabbard, Jon D.; Howerth, Elizabeth W.; Jones, Cheryl A.; Friedman, Kimberly; Seiler, Jon; Danner, Angela; Kercher, Lisa; McBride, Ryan; Paulson, James C.; Wentworth, David E.; Krauss, Scott; Tompkins, Stephen M.; Stallknecht, David E.

2016-01-01

ABSTRACT H7 subtype influenza A viruses are widely distributed and have been responsible for human infections and numerous outbreaks in poultry with significant impact. Despite this, the disease-causing potential of the precursor low-pathogenic (LP) H7 viruses from the wild bird reservoir has not been investigated. Our objective was to assess the disease-causing potential of 30 LP H7 viruses isolated from wild avian species in the United States and Canada using the DBA/2J mouse model. Without prior mammalian adaptation, the majority of viruses, 27 (90%), caused mortality in mice. Of these, 17 (56.7%) caused 100% mortality and 24 were of pathogenicity similar to that of A/Anhui/1/2013 (H7N9), which is highly pathogenic in mice. Viruses of duck origin were more pathogenic than those of shorebird origin, as 13 of 18 (72.2%) duck origin viruses caused 100% mortality while 4 of 12 (33.3%) shorebird origin viruses caused 100% mortality, despite there being no difference in mean lung viral titers between the groups. Replication beyond the respiratory tract was also evident, particularly in the heart and brain. Of the 16 viruses studied for fecal shedding, 11 were detected in fecal samples. These viruses exhibited a strong preference for avian-type α2,3-linked sialic acids; however, binding to mammalian-type α2,6-linked sialic acids was also detected. These findings indicate that LP avian H7 influenza A viruses are able to infect and cause disease in mammals without prior adaptation and therefore pose a potential public health risk. IMPORTANCE Low-pathogenic (LP) avian H7 influenza A viruses are widely distributed in the avian reservoir and are the precursors of numerous outbreaks of highly pathogenic avian influenza viruses in commercial poultry farms. However, unlike highly pathogenic H7 viruses, the disease-causing potential of LP H7 viruses from the wild bird reservoir has not been investigated. To address this, we studied 30 LP avian H7 viruses isolated from wild avian species in the United States and Canada using the DBA/2J mouse model. Surprisingly, the majority of these viruses, 90%, caused mortality in mice without prior mammalian adaptation, and 56.7% caused 100% mortality. There was also evidence of spread beyond the respiratory tract and fecal shedding. Therefore, the disease-causing potential of LP avian H7 influenza A viruses in mammals may be underestimated, and these viruses therefore pose a potential public health risk. PMID:27852855

Avian influenza viruses in humans.

PubMed

Malik Peiris, J S

2009-04-01

Past pandemics arose from low pathogenic avian influenza (LPAI) viruses. In more recent times, highly pathogenic avian influenza (HPAI) H5N1, LPAI H9N2 and both HPAI and LPAI H7 viruses have repeatedly caused zoonotic disease in humans. Such infections did not lead to sustained human-to-human transmission. Experimental infection of human volunteers and seroepidemiological studies suggest that avian influenza viruses of other subtypes may also infect humans. Viruses of the H7 subtype appear to have a predilection to cause conjunctivitis and influenza-like illness (ILI), although HPAI H7N7 virus has also caused fatal respiratory disease. Low pathogenic H9N2 viruses have caused mild ILI and its occurrence may be under-recognised for this reason. In contrast, contemporary HPAI H5N1 viruses are exceptional in their virulence for humans and differ from human seasonal influenza viruses in their pathogenesis. Patients have a primary viral pneumonia progressing to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome. Over 380 human cases have been confirmed to date, with an overall case fatality of 63%. The zoonotic transmission of avian influenza is a rare occurrence, butthe greater public health concern is the adaptation of such viruses to efficient human transmission, which could lead to a pandemic. A better understanding of the ecology of avian influenza viruses and the biological determinants of transmissibility and pathogenicity in humans is important for pandemic preparedness.

Secondary Bacterial Infections Associated with Influenza Pandemics

PubMed Central

Morris, Denise E.; Cleary, David W.; Clarke, Stuart C.

2017-01-01

Lower and upper respiratory infections are the fourth highest cause of global mortality (Lozano et al., 2012). Epidemic and pandemic outbreaks of respiratory infection are a major medical concern, often causing considerable disease and a high death toll, typically over a relatively short period of time. Influenza is a major cause of epidemic and pandemic infection. Bacterial co/secondary infection further increases morbidity and mortality of influenza infection, with Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus reported as the most common causes. With increased antibiotic resistance and vaccine evasion it is important to monitor the epidemiology of pathogens in circulation to inform clinical treatment and development, particularly in the setting of an influenza epidemic/pandemic. PMID:28690590

Immunopathogenesis of Staphylococcus aureus pulmonary infection

PubMed Central

Parker, Dane; Prince, Alice

2013-01-01

Staphylococcus aureus is a common human pathogen highly evolved as both a component of the commensal flora and as a major cause of invasive infection. Severe respiratory infection due to staphylococci has been increasing due to the prevalence of more virulent USA300 CA-MRSA strains in the general population. The ability of S. aureus to adapt to the milieu of the respiratory tract has facilitated its emergence as a respiratory pathogen. Its metabolic versatility, the ability to scavenge iron, coordinate gene expression, and the horizontal acquisition of useful genetic elements have all contributed to its success as a component of the respiratory flora, in hospitalized patients, as a complication of influenza and in normal hosts. The expression of surface adhesins facilitates its persistence in the airways. In addition, the highly sophisticated interactions of the multiple S. aureus virulence factors, particularly the α-hemolysin and protein A, with diverse immune effectors in the lung such as ADAM10, TNFR1, EGFR, immunoglobulin, and complement all contribute to the pathogenesis of staphylococcal pneumonia. PMID:22037948

The Lung Immune Response to Nontypeable Haemophilus influenzae (Lung Immunity to NTHi)

PubMed Central

King, Paul T.; Sharma, Roleen

2015-01-01

Haemophilus influenzae is divided into typeable or nontypeable strains based on the presence or absence of a polysaccharide capsule. The typeable strains (such as type b) are an important cause of systemic infection, whilst the nontypeable strains (designated as NTHi) are predominantly respiratory mucosal pathogens. NTHi is present as part of the normal microbiome in the nasopharynx, from where it may spread down to the lower respiratory tract. In this context it is no longer a commensal and becomes an important respiratory pathogen associated with a range of common conditions including bronchitis, bronchiectasis, pneumonia, and particularly chronic obstructive pulmonary disease. NTHi induces a strong inflammatory response in the respiratory tract with activation of immune responses, which often fail to clear the bacteria from the lung. This results in recurrent/persistent infection and chronic inflammation with consequent lung pathology. This review will summarise the current literature about the lung immune response to nontypeable Haemophilus influenzae, a topic that has important implications for patient management. PMID:26114124

Respiratory pathogens in Québec dairy calves and their relationship with clinical status, lung consolidation, and average daily gain.

PubMed

Francoz, D; Buczinski, S; Bélanger, A M; Forté, G; Labrecque, O; Tremblay, D; Wellemans, V; Dubuc, J

2015-01-01

Bovine respiratory disease (BRD) is 1 of the 2 most important causes of morbidity and mortality in dairy calves. Surprisingly, field data are scant concerning the prevalence of respiratory pathogens involved in BRD in preweaned dairy calves, especially in small herds. To identify the main respiratory pathogens isolated from calves in Québec dairy herds with a high incidence of BRD, and to determine if there is an association between the presence of these pathogens and clinical signs of pneumonia, lung consolidation, or average daily gain. Cross-sectional study using a convenience sample of 95 preweaned dairy calves from 11 dairy herds. At enrollment, calves were weighed, clinically examined, swabbed (nasal and nasopharyngeal), and lung ultrasonography was performed. One month later, all calves were reweighed. Twenty-two calves had clinical BRD and 49 had ultrasonographic evidence of lung consolidation. Pasteurella multocida, Mannheimia haemolytica, and Histophilus somni were isolated in 54, 17, and 12 calves, respectively. Mycoplasma bovis was identified by PCR testing or culture in 19 calves, and 78 calves were found to be positive for Mycoplasma spp. Bovine coronavirus was detected in 38 calves and bovine respiratory syncytial virus in 1. Only the presence of M. bovis was associated with higher odds of clinical signs, lung consolidation, and lower average daily gain. Results suggested that nasopharyngeal carriage of M. bovis was detrimental to health and growth of dairy calves in small herds with a high incidence of BRD. Copyright © 2015 by the American College of Veterinary Internal Medicine.

Review of Non-Bacterial Infections in Respiratory Medicine: Viral Pneumonia.

PubMed

Galván, José María; Rajas, Olga; Aspa, Javier

2015-11-01

Although bacteria are the main pathogens involved in community-acquired pneumonia, a significant number of community-acquired pneumonia are caused by viruses, either directly or as part of a co-infection. The clinical picture of these different pneumonias can be very similar, but viral infection is more common in the pediatric and geriatric populations, leukocytes are not generally elevated, fever is variable, and upper respiratory tract symptoms often occur; procalcitonin levels are not generally affected. For years, the diagnosis of viral pneumonia was based on cell culture and antigen detection, but since the introduction of polymerase chain reaction techniques in the clinical setting, identification of these pathogens has increased and new microorganisms such as human bocavirus have been discovered. In general, influenza virus type A and syncytial respiratory virus are still the main pathogens involved in this entity. However, in recent years, outbreaks of deadly coronavirus and zoonotic influenza virus have demonstrated the need for constant alert in the face of new emerging pathogens. Neuraminidase inhibitors for viral pneumonia have been shown to reduce transmission in cases of exposure and to improve the clinical progress of patients in intensive care; their use in common infections is not recommended. Ribavirin has been used in children with syncytial respiratory virus, and in immunosuppressed subjects. Apart from these drugs, no antiviral has been shown to be effective. Prevention with anti-influenza virus vaccination and with monoclonal antibodies, in the case of syncytial respiratory virus, may reduce the incidence of pneumonia. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Bovine Gamma Delta T Cells Contribute to Exacerbated IL-17 Production in Response to Co-Infection with Bovine RSV and Mannheimia haemolytica

PubMed Central

McGill, Jodi L.; Rusk, Rachel A.; Guerra-Maupome, Mariana; Briggs, Robert E.; Sacco, Randy E.

2016-01-01

Human respiratory syncytial virus (HRSV) is a leading cause of severe lower respiratory tract infection in children under five years of age. IL-17 and Th17 responses are increased in children infected with HRSV and have been implicated in both protective and pathogenic roles during infection. Bovine RSV (BRSV) is genetically closely related to HRSV and is a leading cause of severe respiratory infections in young cattle. While BRSV infection in the calf parallels many aspects of human infection with HRSV, IL-17 and Th17 responses have not been studied in the bovine. Here we demonstrate that calves infected with BRSV express significant levels of IL-17, IL-21 and IL-22; and both CD4 T cells and γδ T cells contribute to this response. In addition to causing significant morbidity from uncomplicated infections, BRSV infection also contributes to the development of bovine respiratory disease complex (BRDC), a leading cause of morbidity in both beef and dairy cattle. BRDC is caused by a primary viral infection, followed by secondary bacterial pneumonia by pathogens such as Mannheimia haemolytica. Here, we demonstrate that in vivo infection with M. haemolytica results in increased expression of IL-17, IL-21 and IL-22. We have also developed an in vitro model of BRDC and show that co-infection of PBMC with BRSV followed by M. haemolytica leads to significantly exacerbated IL-17 production, which is primarily mediated by IL-17-producing γδ T cells. Together, our results demonstrate that calves, like humans, mount a robust IL-17 response during RSV infection; and suggest a previously unrecognized role for IL-17 and γδ T cells in the pathogenesis of BRDC. PMID:26942409

The etiologic and epidemiologic spectrum of bronchiolitis in pediatric practice.

PubMed

Henderson, F W; Clyde, W A; Collier, A M; Denny, F W; Senior, R J; Sheaffer, C I; Conley, W G; Christian, R M

1979-08-01

To develop a broad understanding of the causes and patterns of occurrence of wheezing associated respiratory infections, we analyzed data from an 11-year study of acute lower respiratory illness in a pediatric practice. Although half of the WARI occurred in children less than 2 years of age, wheezing continued to be observed in 19% of children greater than 9 years of age who had lower respiratory illness. Males experienced LRI 1.25 times more often than did females; the relative risk of males for WARI was 1.35. A nonbacterial pathogen was recovered from 21% of patients with WARI; respiratory syncytial virus, parainfluenza virus types 1 and 3, adenoviruses, and Mycoplasma pneumoniae accounted for 81% of the isolates. Patient age influenced the pattern of recovery of these agents. The most common cause of WARI in children under 5 years of age was RSV whereas Mycoplasma pneumoniae was the most frequent isolate from school age children with wheezing illness. The data expand our understanding of the causes of WARI and are useful to diagnosticians and to researchers interested in the control of lower respiratory disease.

Epidemiologic analysis of respiratory viral infections among Singapore military servicemen in 2016.

PubMed

Lau, Yuk-Fai; Koh, Wee-Hong Victor; Kan, Clement; Dua, Poh-Choo Alethea; Lim, Ai-Sim Elizabeth; Liaw, Chin-Wen Jasper; Gao, Qiu-Han; Chng, Jeremiah; Lee, Vernon J; Tan, Boon-Huan; Loh, Jin-Phang

2018-03-12

Respiratory illnesses have been identified as a significant factor leading to lost training time and morbidity among Singapore military recruits. A surveillance programme has been put in place to determine etiological agents responsible for febrile, as well as afebrile respiratory illnesses in a military camp. The goal of the study is to better understand the epidemiology of these diseases and identify potential countermeasures to protect military recruits against them. From Jan 2016 - Jan 2017, a total of 2647 respiratory cases were enrolled into the surveillance programme. The cases were further stratified into Febrile Respiratory Illness (FRI, with body temperature > 37.5 °C) or Acute Respiratory Illness (ARI, with body temperature < 37.5 °C). Nasal washes were collected and tested by multiplex PCR to detect 26 different pathogens. One thousand ninety five cases (41% of total cases) met the criteria of FRI in which 932 cases (85% of FRI cases) were screened positive for at least one virus. The most common etiological agents for FRI mono-infection cases were Adenovirus E and Rhinovirus. Recruits infected with H3N2 influenza, Influenza B and Adenovirus E viruses were most likely presented as FRI cases. Notably, H3N2 influenza resulted in the greatest rise in body temperature. The remaining 1552 cases (59% of total cases) met the criteria of ARI in which 1198 cases (77% of ARI cases) were screened positive for at least one virus. The most common etiological agent for ARI mono-infection was Rhinovirus. The distribution pattern for dual infections was different for ARI and FRI cases. Maximum number of pathogens detected in a sample was five for both groups. Previous studies on respiratory diseases in military focused largely on FRI cases. With the expanded surveillance to ARI cases, this study allows unbiased evaluation of the impact of respiratory disease pathogens among recruits in a military environment. The results show that several pathogens have a much bigger role in causing respiratory diseases in this cohort.

The detection and differentiation of canine respiratory pathogens using oligonucleotide microarrays.

PubMed

Wang, Lih-Chiann; Kuo, Ya-Ting; Chueh, Ling-Ling; Huang, Dean; Lin, Jiunn-Horng

2017-05-01

Canine respiratory diseases are commonly seen in dogs along with co-infections with multiple respiratory pathogens, including viruses and bacteria. Virus infections in even vaccinated dogs were also reported. The clinical signs caused by different respiratory etiological agents are similar, which makes differential diagnosis imperative. An oligonucleotide microarray system was developed in this study. The wild type and vaccine strains of canine distemper virus (CDV), influenza virus, canine herpesvirus (CHV), Bordetella bronchiseptica and Mycoplasma cynos were detected and differentiated simultaneously on a microarray chip. The detection limit is 10, 10, 100, 50 and 50 copy numbers for CDV, influenza virus, CHV, B. bronchiseptica and M. cynos, respectively. The clinical test results of nasal swab samples showed that the microarray had remarkably better efficacy than the multiplex PCR-agarose gel method. The positive detection rate of microarray and agarose gel was 59.0% (n=33) and 41.1% (n=23) among the 56 samples, respectively. CDV vaccine strain and pathogen co-infections were further demonstrated by the microarray but not by the multiplex PCR-agarose gel. The oligonucleotide microarray provides a highly efficient diagnosis alternative that could be applied to clinical usage, greatly assisting in disease therapy and control. Copyright © 2017 Elsevier B.V. All rights reserved.

[Study on the classification of dominant pathogens related to febrile respiratory syndrome, based on the method of Bayes discriminant analysis].

PubMed

Li, X C; Li, J S; Meng, L; Bai, Y N; Yu, D S; Liu, X N; Liu, X F; Jiang, X J; Ren, X W; Yang, X T; Shen, X P; Zhang, J W

2017-08-10

Objective: To understand the dominant pathogens of febrile respiratory syndrome (FRS) patients in Gansu province and to establish the Bayes discriminant function in order to identify the patients infected with the dominant pathogens. Methods: FRS patients were collected in various sentinel hospitals of Gansu province from 2009 to 2015 and the dominant pathogens were determined by describing the composition of pathogenic profile. Significant clinical variables were selected by stepwise discriminant analysis to establish the Bayes discriminant function. Results: In the detection of pathogens for FRS, both influenza virus and rhinovirus showed higher positive rates than those caused by other viruses (13.79%, 8.63%), that accounting for 54.38%, 13.73% of total viral positive patients. Most frequently detected bacteria would include Streptococcus pneumoniae , and haemophilus influenza (44.41%, 18.07%) that accounting for 66.21% and 24.55% among the bacterial positive patients. The original-validated rate of discriminant function, established by 11 clinical variables, was 73.1%, with the cross-validated rate as 70.6%. Conclusion: Influenza virus, Rhinovirus, Streptococcus pneumoniae and Haemophilus influenzae were the dominant pathogens of FRS in Gansu province. Results from the Bayes discriminant analysis showed both higher accuracy in the classification of dominant pathogens, and applicative value for FRS.

Multiplex detection of respiratory pathogens

DOEpatents

McBride, Mary [Brentwood, CA; Slezak, Thomas [Livermore, CA; Birch, James M [Albany, CA

2012-07-31

Described are kits and methods useful for detection of respiratory pathogens (influenza A (including subtyping capability for H1, H3, H5 and H7 subtypes) influenza B, parainfluenza (type 2), respiratory syncytial virus, and adenovirus) in a sample. Genomic sequence information from the respiratory pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay to successfully identify the presence or absence of pathogens in a sample.

Searching for animal models and potential target species for emerging pathogens: Experience gained from Middle East respiratory syndrome (MERS) coronavirus.

PubMed

Vergara-Alert, Júlia; Vidal, Enric; Bensaid, Albert; Segalés, Joaquim

2017-06-01

Emerging and re-emerging pathogens represent a substantial threat to public health, as demonstrated with numerous outbreaks over the past years, including the 2013-2016 outbreak of Ebola virus in western Africa. Coronaviruses are also a threat for humans, as evidenced in 2002/2003 with infection by the severe acute respiratory syndrome coronavirus (SARS-CoV), which caused more than 8000 human infections with 10% fatality rate in 37 countries. Ten years later, a novel human coronavirus (Middle East respiratory syndrome coronavirus, MERS-CoV), associated with severe pneumonia, arose in the Kingdom of Saudi Arabia. Until December 2016, MERS has accounted for more than 1800 cases and 35% fatality rate. Finding an animal model of disease is key to develop vaccines or antivirals against such emerging pathogens and to understand its pathogenesis. Knowledge of the potential role of domestic livestock and other animal species in the transmission of pathogens is of importance to understand the epidemiology of the disease. Little is known about MERS-CoV animal host range. In this paper, experimental data on potential hosts for MERS-CoV is reviewed. Advantages and limitations of different animal models are evaluated in relation to viral pathogenesis and transmission studies. Finally, the relevance of potential new target species is discussed.

Bacterial lysates improve the protective antibody response against respiratory viruses through Toll-like receptor 4

PubMed Central

Coviello, Silvina; Wimmenauer, Vera; Polack, Fernando P; Irusta, Pablo M

2014-01-01

Respiratory viruses cause significant morbidity and mortality in infants and young children worldwide. Current strategies to modulate the immune system and prevent or treat respiratory viral infections in this age group have shown limited success. Here, we demonstrate that a lysate derived from Gram-positive and Gram-negative organisms positively modulates protective antibody responses against both respiratory syncytial virus (RSV) and influenza virus in murine models of infection. Interestingly, despite the complex mixture of Toll-like receptor (TLR) agonists present in the bacterial lysate, the modulatory effects were mostly dependent on TLR4 signaling. Our results indicate that the use of simple formulations of TLR-agonists can significantly improve the immune response against critical pediatric respiratory pathogens. PMID:25483455

Nosocomial Outbreak of Serious Canine Infectious Tracheobronchitis (Kennel Cough) Caused by Canine Herpesvirus Infection▿

PubMed Central

Kawakami, Kazuo; Ogawa, Hiroyuki; Maeda, Ken; Imai, Ayako; Ohashi, Emi; Matsunaga, Satoru; Tohya, Yukinobu; Ohshima, Takahisa; Mochizuki, Masami

2010-01-01

Canine herpesvirus (CHV; Canid herpesvirus 1) is principally a perinatal pathogen of pregnant bitches and newborn pups and secondarily a respiratory tract pathogen of older pups and dogs. Infectious disease of the canine respiratory tract frequently occurs among dogs in groups, in which it is called “ infectious tracheobronchitis” (ITB). Mortality from ITB is generally negligible, and the clinical importance of CHV as an ITB pathogen is considered to be low. The present report describes a novel ITB outbreak accompanied by death among aged dogs in an animal medical center. Most inpatient dogs had received medications that could induce immunosuppression. CHV was the only pathogen identified, and several CHV isolates were recovered in cell culture. No other viral pathogens or significant bacterial pathogens were found. Molecular and serological analyses revealed that the causative CHV isolates were from a single source but that none was a peculiar strain when the strains were compared with previous CHV strains. The virus had presumably spread among the dogs predisposed to infection in the center. The present results serve as a warning to canine clinics that, under the specific set of circumstances described, such serious CHV outbreaks may be expected wherever canine ITB occurs. PMID:20107103

Human rhinovirus and disease severity in children.

PubMed

Costa, Lourenço Faria; Queiróz, Divina Aparecida Oliveira; Lopes da Silveira, Hélio; Bernardino Neto, Morun; de Paula, Nayhanne Tizzo; Oliveira, Thelma Fátima Mattos Silva; Tolardo, Aline Lavado; Yokosawa, Jonny

2014-02-01

To evaluate retrospectively human rhinovirus (HRV) infections in children up to 5 years old and factors involved in disease severity. Nasopharyngeal aspirates from 434 children presenting a broad range of respiratory infection symptoms and severity degrees were tested for presence of HRV and 8 other respiratory viruses. Presence of host risk factors was also assessed. HRV was detected in 181 (41.7%) samples, in 107 of them as the only agent and in 74 as coinfections, mostly with respiratory syncytial virus (RSV; 43.2%). Moderate to severe symptoms were observed in 28.9% (31/107) single infections and in 51.3% (38/74) coinfections (P = .004). Multivariate analyses showed association of coinfections with lower respiratory tract symptoms and some parameters of disease severity, such as hospitalization. In coinfections, RSV was the most important virus associated with severe disease. Prematurity, cardiomyopathies, and noninfectious respiratory diseases were comorbidities that also were associated with disease severity (P = .007). Our study showed that HRV was a common pathogen of respiratory disease in children and was also involved in severe cases, causing symptoms of the lower respiratory tract. Severe disease in HRV infections were caused mainly by presence of RSV in coinfections, prematurity, congenital heart disease, and noninfectious respiratory disease.

Adenovirus type 4 respiratory infections with a concurrent outbreak of coxsackievirus A21 among United States Army Basic Trainees, a retrospective viral etiology study using next-generation sequencing.

PubMed

Hang, Jun; Vento, Todd J; Norby, Erica A; Jarman, Richard G; Keiser, Paul B; Kuschner, Robert A; Binn, Leonard N

2017-08-01

Human adenoviruses (HAdV), in particular types 4 and 7, frequently cause acute respiratory disease (ARD) during basic military training. HAdV4 and HAdV7 vaccines reduced the ARD risk in U.S. military. It is important to identify other respiratory pathogens and assess their potential impact on military readiness. In 2002, during a period when the HAdV vaccines were not available, throat swabs were taken from trainees (n = 184) with respiratory infections at Fort Jackson, South Carolina. Viral etiology was investigated initially with viral culture and neutralization assay and recently in this study by sequencing the viral isolates. Viral culture and neutralization assays identified 90 HAdV4 isolates and 27 additional cultures that showed viral cytopathic effects (CPE), including some with picornavirus-like CPE. Next-generation sequencing confirmed these results and determined viral genotypes, including 77 HAdV4, 4 HAdV3, 1 HAdV2, 17 coxsackievirus A21 (CAV21), and 1 enterovirus D68. Two samples were positive for both HAdV4 and CAV21. The identified genotypes are phylogenetically close to but distinct from those found during other years or in other military/non-military sites. HAdV4 is the predominant respiratory pathogen in unvaccinated military trainee. HAdV4 has temporal and demographic variability. CAV21 is a significant respiratory pathogen and needs to be evaluated for its current significance in military basic trainees. © 2017 Wiley Periodicals, Inc.

Probiotic bacteria inhibit the bovine respiratory pathogen Mannheimia haemolytica serotype 1 in vitro.

PubMed

Amat, S; Subramanian, S; Timsit, E; Alexander, T W

2017-05-01

This study evaluated the potential of probiotic bacteria to inhibit growth and cell adhesion of the bovine respiratory pathogen Mannheimia haemoltyica serotype 1. The inhibitory effects of nine probiotic strains (Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus helveticus, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactococcus lactis, Streptococcus thermophilus and two Paenibacillus polymyxa strains) against M. haemolytica were evaluated using a spot-on-lawn method. Probiotic strains were then tested for their adherence to bovine bronchial epithelial (BBE) cells and the ability to displace and compete against M. haemolytica on BBE. Except for S. thermophilus, all probiotic strains inhibited the growth of M. haemolytica, with zones of inhibition ranging between 12 and 19 mm. Lactobacillus strains and Lactococcus lactis displayed greater (P < 0·05) BBE adhesion compared with M. heamolytica (8·3%) and other probiotics (<2·2%). Strains of P. polymyxa and L. acidophilus caused the greatest reduction in M. haemolytica adherence, through both displacement and competition, compared with other probiotics. The results of this study suggest that probiotics may have the potential to colonize the bovine respiratory tract, and exert antagonistic effects against M. haemolytica serotype 1. A common method to control bovine respiratory disease (BRD) in feedlots is through mass medication with antibiotics upon cattle entry (i.e. metaphylaxis). Increasingly, antimicrobial resistance in BRD bacterial pathogens has been observed in feedlots, which may have important implications for cattle health. In this study, probiotic strains were shown to adhere to bovine respiratory cells and inhibit the BRD pathogen M. haemolytica serotype 1 through competition and displacement. Probiotics may therefore offer a mitigation strategy to reduce BRD bacterial pathogens, in place of metaphylactic antimicrobials. © 2017 Her Majesty the Queen in Right of Canada Letters in Applied Microbiology © 2017 The Society for Applied Microbiology Reproduced with the permission of the Minister of Agriculture and Agri-Food Canada.

Non-specific Effect of Vaccines: Immediate Protection against Respiratory Syncytial Virus Infection by a Live Attenuated Influenza Vaccine.

PubMed

Lee, Young J; Lee, Jeong Y; Jang, Yo H; Seo, Sang-Uk; Chang, Jun; Seong, Baik L

2018-01-01

The non-specific effects (NSEs) of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV) induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV). The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses. The vaccination induced an immediate release of cytokines and infiltration of leukocytes into the respiratory tract, moderating the immune perturbation caused by RSV infection. The potency of protection against RSV challenge was significantly reduced in TLR3 -/- TLR7 -/- mice, confirming that the TLR3/7 signaling pathways are necessary for the observed immediate and short-term protection. The results suggest that CAIVs provide short-term, non-specific protection against genetically unrelated respiratory pathogens. The additional benefits of CAIVs in mitigating acute respiratory infections for which vaccines are not yet available need to be assessed in future studies.

Morphology of the Oligoryzomys nigripes respiratory system.

PubMed

Mario, Lara Carolina; Borghesi, Jéssica; G Hayashi, Rafael; O Favaron, Phelipe; N Rodrigues, Marcio; C Carvalho, Rafael; Miglino, Maria A

2018-06-04

Rodents are important in the transmission of infectious diseases that affect the respiratory tract, including simple infections and those caused by specific pathogens. These animals are natural reservoirs of zoonoses that cause many public health diseases. Basic knowledge on the morphology of these animals is important as basic research is useful for applied studies, such as the development of clinical, therapeutic, surgical and clinical models. Morphological data of respiratory tract in Oligoryzomys nigripes are absent in the literature. Therefore, the aim of this study was to perform a morphological analysis of the respiratory tract of O. nigripes. Five adult females from the environmental reserve in São Joaquim da Barra, São Paulo were used, donated to the Museum of Veterinary Anatomy (FMVZ/USP). Several morphological features follow the same pattern seen in rodents; however, this species showed some differences such as the presence of three lobar bronchi, nonlobed left lung and the right lung constituted by two lobes. Respiratory epithelium lined the whole respiratory tract and was seen using scanning electron microscopy the oval shape of the parenchyma and alveoli. © 2018 Blackwell Verlag GmbH.

Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses.

PubMed

Su, Shuo; Wong, Gary; Shi, Weifeng; Liu, Jun; Lai, Alexander C K; Zhou, Jiyong; Liu, Wenjun; Bi, Yuhai; Gao, George F

2016-06-01

Human coronaviruses (HCoVs) were first described in the 1960s for patients with the common cold. Since then, more HCoVs have been discovered, including those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), two pathogens that, upon infection, can cause fatal respiratory disease in humans. It was recently discovered that dromedary camels in Saudi Arabia harbor three different HCoV species, including a dominant MERS HCoV lineage that was responsible for the outbreaks in the Middle East and South Korea during 2015. In this review we aim to compare and contrast the different HCoVs with regard to epidemiology and pathogenesis, in addition to the virus evolution and recombination events which have, on occasion, resulted in outbreaks amongst humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

Productive Infection of Human Embryonic Stem Cell-Derived NKX2.1+ Respiratory Progenitors with Human Rhinovirus.

PubMed

Jenny, Robert A; Hirst, Claire; Lim, Sue Mei; Goulburn, Adam L; Micallef, Suzanne J; Labonne, Tanya; Kicic, Anthony; Ling, Kak-Ming; Stick, Stephen M; Ng, Elizabeth S; Trounson, Alan; Giudice, Antonietta; Elefanty, Andrew G; Stanley, Edouard G

2015-06-01

Airway epithelial cells generated from pluripotent stem cells (PSCs) represent a resource for research into a variety of human respiratory conditions, including those resulting from infection with common human pathogens. Using an NKX2.1-GFP reporter human embryonic stem cell line, we developed a serum-free protocol for the generation of NKX2.1(+) endoderm that, when transplanted into immunodeficient mice, matured into respiratory cell types identified by expression of CC10, MUC5AC, and surfactant proteins. Gene profiling experiments indicated that day 10 NKX2.1(+) endoderm expressed markers indicative of early foregut but lacked genes associated with later stages of respiratory epithelial cell differentiation. Nevertheless, NKX2.1(+) endoderm supported the infection and replication of the common respiratory pathogen human rhinovirus HRV1b. Moreover, NKX2.1(+) endoderm upregulated expression of IL-6, IL-8, and IL-1B in response to infection, a characteristic of human airway epithelial cells. Our experiments provide proof of principle for the use of PSC-derived respiratory epithelial cells in the study of cell-virus interactions. This report provides proof-of-principle experiments demonstrating, for the first time, that human respiratory progenitor cells derived from stem cells in the laboratory can be productively infected with human rhinovirus, the predominant cause of the common cold. ©AlphaMed Press.

The Human Polymeric Immunoglobulin Receptor Facilitates Invasion of Epithelial Cells by Streptococcus pneumoniae in a Strain-Specific and Cell Type-Specific Manner

PubMed Central

Brock, Sean C.; McGraw, Patricia A.; Wright, Peter F.; Crowe Jr., James E.

2002-01-01

Streptococcus pneumoniae is a gram-positive bacterial pathogen that causes invasive life-threatening disease worldwide. This organism also commonly colonizes the upper respiratory epithelium in an asymptomatic fashion. To invade, this pathogen must traverse the respiratory epithelial barrier, allowing it to cause disease locally or disseminate hematogenously throughout the body. Previous work has demonstrated that S. pneumoniae choline-binding protein A, a pneumococcal surface protein, interacts specifically with the human polymeric immunoglobulin receptor, which is expressed by cells in the respiratory epithelium. Choline-binding protein A is required for efficient colonization of the nasopharynx in vivo. Additionally, a recent study showed that the R6x laboratory strain of S. pneumoniae invades a human pharyngeal cell line in a human polymeric immunoglobulin receptor-dependent manner. These findings raised the possibility that the interaction between choline-binding protein A and human polymeric immunoglobulin receptor may be a key determinant of S. pneumoniae pathogenesis. However, the strain used in prior invasion studies, R6x, is an unencapsulated, nonpathogenic strain. In the present study we determined the relative ability of strain R6x or pathogenic strains to invade a variety of human polymeric immunoglobulin receptor-expressing epithelial cell lines. The results of this work suggest that human polymeric immunoglobulin receptor-dependent enhanced invasion of epithelial cells by S. pneumoniae is a limited phenomenon that occurs in a strain-specific and cell type-specific manner. PMID:12183558

Clinical and microbiologic characteristics of vulvovaginitis in Korean prepubertal girls, 2009-2014: a single center experience.

PubMed

Kim, Hounyoung; Chai, Sun Myung; Ahn, Eun Hee; Lee, Mee-Hwa

2016-03-01

To update information on the clinical and microbiologic characteristics of pediatric vulvovaginitis in Korean prepubertal girls. A total of 120 girls (aged 0 to 9 years) with culture-confirmed pediatric vulvovaginitis, diagnosed between 2009 and 2014, were enrolled in the study. The epidemiologic and microbiologic characteristics, and clinical outcomes were assessed. Patients with sexual precocity, as well as those who were referred for suspected sexual abuse, were excluded. Girls aged 4 to 6 years were at the highest risk of pediatric vulvovaginitis. Seasonal distribution indicated obvious peaks in summer and winter. Of the 120 subjects, specific pathogens were identified in the genital specimens in only 20 cases (16.7%). Streptococcus pyogenes (n=12, 60%) was the leading cause of specific vulvovaginitis. Haemophilus influenzae was isolated in one patient. No cases presented with enteric pathogens, such as Shigella or Yersinia. A history of recent upper respiratory tract infection, swimming, and bubble bath use was reported in 37.5%, 15.8%, and 10.0% of patients, respectively. Recent upper respiratory tract infection was not significantly correlated with the detection of respiratory pathogens in genital specimens (P>0.05). Of 104 patients who underwent perineal hygienic care, 80 (76.9%) showed improvement of symptoms without antibiotic treatment. Furthermore, the efficacy of hygienic care was not significantly different between patients with or without specific pathogens (P>0.05). Specific pathogens were only found in 16.7% of pediatric vulvovaginitis cases. Our results indicate an excellent outcome with hygienic care, irrespective of the presence of specific pathogens.

Clinical and microbiologic characteristics of vulvovaginitis in Korean prepubertal girls, 2009–2014: a single center experience

PubMed Central

Kim, Hounyoung; Chai, Sun Myung; Ahn, Eun Hee

2016-01-01

Objective To update information on the clinical and microbiologic characteristics of pediatric vulvovaginitis in Korean prepubertal girls. Methods A total of 120 girls (aged 0 to 9 years) with culture-confirmed pediatric vulvovaginitis, diagnosed between 2009 and 2014, were enrolled in the study. The epidemiologic and microbiologic characteristics, and clinical outcomes were assessed. Patients with sexual precocity, as well as those who were referred for suspected sexual abuse, were excluded. Results Girls aged 4 to 6 years were at the highest risk of pediatric vulvovaginitis. Seasonal distribution indicated obvious peaks in summer and winter. Of the 120 subjects, specific pathogens were identified in the genital specimens in only 20 cases (16.7%). Streptococcus pyogenes (n=12, 60%) was the leading cause of specific vulvovaginitis. Haemophilus influenzae was isolated in one patient. No cases presented with enteric pathogens, such as Shigella or Yersinia. A history of recent upper respiratory tract infection, swimming, and bubble bath use was reported in 37.5%, 15.8%, and 10.0% of patients, respectively. Recent upper respiratory tract infection was not significantly correlated with the detection of respiratory pathogens in genital specimens (P>0.05). Of 104 patients who underwent perineal hygienic care, 80 (76.9%) showed improvement of symptoms without antibiotic treatment. Furthermore, the efficacy of hygienic care was not significantly different between patients with or without specific pathogens (P>0.05). Conclusion Specific pathogens were only found in 16.7% of pediatric vulvovaginitis cases. Our results indicate an excellent outcome with hygienic care, irrespective of the presence of specific pathogens. PMID:27004204

Addressing the Analytic Challenges of Cross-Sectional Pediatric Pneumonia Etiology Data.

PubMed

Hammitt, Laura L; Feikin, Daniel R; Scott, J Anthony G; Zeger, Scott L; Murdoch, David R; O'Brien, Katherine L; Deloria Knoll, Maria

2017-06-15

Despite tremendous advances in diagnostic laboratory technology, identifying the pathogen(s) causing pneumonia remains challenging because the infected lung tissue cannot usually be sampled for testing. Consequently, to obtain information about pneumonia etiology, clinicians and researchers test specimens distant to the site of infection. These tests may lack sensitivity (eg, blood culture, which is only positive in a small proportion of children with pneumonia) and/or specificity (eg, detection of pathogens in upper respiratory tract specimens, which may indicate asymptomatic carriage or a less severe syndrome, such as upper respiratory infection). While highly sensitive nucleic acid detection methods and testing of multiple specimens improve sensitivity, multiple pathogens are often detected and this adds complexity to the interpretation as the etiologic significance of results may be unclear (ie, the pneumonia may be caused by none, one, some, or all of the pathogens detected). Some of these challenges can be addressed by adjusting positivity rates to account for poor sensitivity or incorporating test results from controls without pneumonia to account for poor specificity. However, no classical analytic methods can account for measurement error (ie, sensitivity and specificity) for multiple specimen types and integrate the results of measurements for multiple pathogens to produce an accurate understanding of etiology. We describe the major analytic challenges in determining pneumonia etiology and review how the common analytical approaches (eg, descriptive, case-control, attributable fraction, latent class analysis) address some but not all challenges. We demonstrate how these limitations necessitate a new, integrated analytical approach to pneumonia etiology data. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Addressing the Analytic Challenges of Cross-Sectional Pediatric Pneumonia Etiology Data

PubMed Central

Feikin, Daniel R.; Scott, J. Anthony G.; Zeger, Scott L.; Murdoch, David R.; O’Brien, Katherine L.; Deloria Knoll, Maria

2017-01-01

Abstract Despite tremendous advances in diagnostic laboratory technology, identifying the pathogen(s) causing pneumonia remains challenging because the infected lung tissue cannot usually be sampled for testing. Consequently, to obtain information about pneumonia etiology, clinicians and researchers test specimens distant to the site of infection. These tests may lack sensitivity (eg, blood culture, which is only positive in a small proportion of children with pneumonia) and/or specificity (eg, detection of pathogens in upper respiratory tract specimens, which may indicate asymptomatic carriage or a less severe syndrome, such as upper respiratory infection). While highly sensitive nucleic acid detection methods and testing of multiple specimens improve sensitivity, multiple pathogens are often detected and this adds complexity to the interpretation as the etiologic significance of results may be unclear (ie, the pneumonia may be caused by none, one, some, or all of the pathogens detected). Some of these challenges can be addressed by adjusting positivity rates to account for poor sensitivity or incorporating test results from controls without pneumonia to account for poor specificity. However, no classical analytic methods can account for measurement error (ie, sensitivity and specificity) for multiple specimen types and integrate the results of measurements for multiple pathogens to produce an accurate understanding of etiology. We describe the major analytic challenges in determining pneumonia etiology and review how the common analytical approaches (eg, descriptive, case-control, attributable fraction, latent class analysis) address some but not all challenges. We demonstrate how these limitations necessitate a new, integrated analytical approach to pneumonia etiology data. PMID:28575372

Evolution of Bordetellae from Environmental Microbes to Human Respiratory Pathogens: Amoebae as a Missing Link.

PubMed

Taylor-Mulneix, Dawn L; Hamidou Soumana, Illiassou; Linz, Bodo; Harvill, Eric T

2017-01-01

The genus Bordetella comprises several bacterial species that colonize the respiratory tract of mammals. It includes B. pertussis , a human-restricted pathogen that is the causative agent of Whooping Cough. In contrast, the closely related species B. bronchiseptica colonizes a broad range of animals as well as immunocompromised humans. Recent metagenomic studies have identified known and novel bordetellae isolated from different environmental sources, providing a new perspective on their natural history. Using phylogenetic analysis, we have shown that human and animal pathogenic bordetellae have most likely evolved from ancestors that originated from soil and water. Our recent study found that B. bronchiseptica can evade amoebic predation and utilize Dictyostelium discoideum as an expansion and transmission vector, which suggests that the evolutionary pressure to evade the amoebic predator enabled the rise of bordetellae as respiratory pathogens. Interactions with amoeba may represent the starting point for bacterial adaptation to eukaryotic cells. However, as bacteria evolve and adapt to a novel host, they can become specialized and restricted to a specific host. B. pertussis is known to colonize and cause infection only in humans, and this specialization to a closed human-to-human lifecycle has involved genome reduction and the loss of ability to utilize amoeba as an environmental reservoir. The discoveries from studying the interaction of Bordetella species with amoeba will elicit a better understanding of the evolutionary history of these and other important human pathogens.

Secondary infection with Streptococcus suis serotype 7 increases the virulence of highly pathogenic porcine reproductive and respiratory syndrome virus in pigs

PubMed Central

2010-01-01

Background Porcine reproductive and respiratory syndrome virus (PRRSV) and Streptococcus suis are common pathogens in pigs. In samples collected during the porcine high fever syndrome (PHFS) outbreak in many parts of China, PRRSV and S. suis serotype 7 (SS7) have always been isolated together. To determine whether PRRSV-SS7 coinfection was the cause of the PHFS outbreak, we evaluated the pathogenicity of PRRSV and/or SS7 in a pig model of single and mixed infection. Results Respiratory disease, diarrhea, and anorexia were observed in all infected pigs. Signs of central nervous system (CNS) disease were observed in the highly pathogenic PRRSV (HP-PRRSV)-infected pigs (4/12) and the coinfected pigs (8/10); however, the symptoms of the coinfected pigs were clearly more severe than those of the HP-PRRSV-infected pigs. The mortality rate was significantly higher in the coinfected pigs (8/10) than in the HP-PRRSV- (2/12) and SS7-infected pigs (0/10). The deceased pigs of the coinfected group had symptoms typical of PHFS, such as high fever, anorexia, and red coloration of the ears and the body. The isolation rates of HP-PRRSV and SS7 were higher and the lesion severity was greater in the coinfected pigs than in monoinfected pigs. Conclusion HP-PRRSV infection increased susceptibility to SS7 infection, and coinfection of HP-PRRSV with SS7 significantly increased the pathogenicity of SS7 to pigs. PMID:20696031

Secondary infection with Streptococcus suis serotype 7 increases the virulence of highly pathogenic porcine reproductive and respiratory syndrome virus in pigs.

PubMed

Xu, Min; Wang, Shujie; Li, Linxi; Lei, Liancheng; Liu, Yonggang; Shi, Wenda; Wu, Jiabin; Li, Liqin; Rong, Fulong; Xu, Mingming; Sun, Guangli; Xiang, Hua; Cai, Xuehui

2010-08-09

Porcine reproductive and respiratory syndrome virus (PRRSV) and Streptococcus suis are common pathogens in pigs. In samples collected during the porcine high fever syndrome (PHFS) outbreak in many parts of China, PRRSV and S. suis serotype 7 (SS7) have always been isolated together. To determine whether PRRSV-SS7 coinfection was the cause of the PHFS outbreak, we evaluated the pathogenicity of PRRSV and/or SS7 in a pig model of single and mixed infection. Respiratory disease, diarrhea, and anorexia were observed in all infected pigs. Signs of central nervous system (CNS) disease were observed in the highly pathogenic PRRSV (HP-PRRSV)-infected pigs (4/12) and the coinfected pigs (8/10); however, the symptoms of the coinfected pigs were clearly more severe than those of the HP-PRRSV-infected pigs. The mortality rate was significantly higher in the coinfected pigs (8/10) than in the HP-PRRSV- (2/12) and SS7-infected pigs (0/10). The deceased pigs of the coinfected group had symptoms typical of PHFS, such as high fever, anorexia, and red coloration of the ears and the body. The isolation rates of HP-PRRSV and SS7 were higher and the lesion severity was greater in the coinfected pigs than in monoinfected pigs. HP-PRRSV infection increased susceptibility to SS7 infection, and coinfection of HP-PRRSV with SS7 significantly increased the pathogenicity of SS7 to pigs.

Exome-based analysis of cardiac arrhythmia, respiratory control, and epilepsy genes in sudden unexpected death in epilepsy.

PubMed

Bagnall, Richard D; Crompton, Douglas E; Petrovski, Slavé; Lam, Lien; Cutmore, Carina; Garry, Sarah I; Sadleir, Lynette G; Dibbens, Leanne M; Cairns, Anita; Kivity, Sara; Afawi, Zaid; Regan, Brigid M; Duflou, Johan; Berkovic, Samuel F; Scheffer, Ingrid E; Semsarian, Christopher

2016-04-01

The leading cause of epilepsy-related premature mortality is sudden unexpected death in epilepsy (SUDEP). The cause of SUDEP remains unknown. To search for genetic risk factors in SUDEP cases, we performed an exome-based analysis of rare variants. Demographic and clinical information of 61 SUDEP cases were collected. Exome sequencing and rare variant collapsing analysis with 2,936 control exomes were performed to test for genes enriched with damaging variants. Additionally, cardiac arrhythmia, respiratory control, and epilepsy genes were screened for variants with frequency of <0.1% and predicted to be pathogenic with multiple in silico tools. The 61 SUDEP cases were categorized as definite SUDEP (n = 54), probable SUDEP (n = 5), and definite SUDEP plus (n = 2). We identified de novo mutations, previously reported pathogenic mutations, or candidate pathogenic variants in 28 of 61 (46%) cases. Four SUDEP cases (7%) had mutations in common genes responsible for the cardiac arrhythmia disease, long QT syndrome (LQTS). Nine cases (15%) had candidate pathogenic variants in dominant cardiac arrhythmia genes. Fifteen cases (25%) had mutations or candidate pathogenic variants in dominant epilepsy genes. No gene reached genome-wide significance with rare variant collapsing analysis; however, DEPDC5 (p = 0.00015) and KCNH2 (p = 0.0037) were among the top 30 genes, genome-wide. A sizeable proportion of SUDEP cases have clinically relevant mutations in cardiac arrhythmia and epilepsy genes. In cases with an LQTS gene mutation, SUDEP may occur as a result of a predictable and preventable cause. Understanding the genetic basis of SUDEP may inform cascade testing of at-risk family members. © 2016 American Neurological Association.

Legionnaires disease: historical perspective.

PubMed Central

Winn, W C

1988-01-01

In the summer of 1976, a mysterious epidemic of fatal respiratory disease in Philadelphia launched an intensive investigation that resulted in the definition of a new family of pathogenic bacteria, the Legionellaceae. In retrospect, members of the family had been isolated from clinical specimens as early as 1943. Unsolved epidemics of acute respiratory disease dating to the 1950s were subsequently attributed to the newly described pathogens. In the intervening years, the Legionellaceae have been firmly established as important causes of sporadic and epidemic respiratory disease. The sources of the infecting bacteria are environmental, and geographic variation in the frequency of infection has been documented. Airborne dissemination of bacteria from cooling towers and evaporative condensers has been responsible for some epidemics, but potable water systems are perhaps more important sources. The mode of transmission from drinking water is unclear. The Legionellaceae are gram-negative, facultative, intracellular pathogens. The resident alveolar macrophage, usually an effective antibacterial defense, is the primary site of growth. Cell-mediated immunity appears to be the most important immunological defense; the role of humoral immunity is less clear. Erythromycin remains the antibiotic of choice for therapy of infected patients, but identification and eradication of environmental sources are also essential for the control of infection. Images PMID:3060246

Influenza Virus Respiratory Infection and Transmission Following Ocular Inoculation in Ferrets

PubMed Central

Belser, Jessica A.; Gustin, Kortney M.; Maines, Taronna R.; Pantin-Jackwood, Mary J.; Katz, Jacqueline M.; Tumpey, Terrence M.

2012-01-01

While influenza viruses are a common respiratory pathogen, sporadic reports of conjunctivitis following human infection demonstrates the ability of this virus to cause disease outside of the respiratory tract. The ocular surface represents both a potential site of virus replication and a portal of entry for establishment of a respiratory infection. However, the properties which govern ocular tropism of influenza viruses, the mechanisms of virus spread from ocular to respiratory tissue, and the potential differences in respiratory disease initiated from different exposure routes are poorly understood. Here, we established a ferret model of ocular inoculation to explore the development of virus pathogenicity and transmissibility following influenza virus exposure by the ocular route. We found that multiple subtypes of human and avian influenza viruses mounted a productive virus infection in the upper respiratory tract of ferrets following ocular inoculation, and were additionally detected in ocular tissue during the acute phase of infection. H5N1 viruses maintained their ability for systemic spread and lethal infection following inoculation by the ocular route. Replication-independent deposition of virus inoculum from ocular to respiratory tissue was limited to the nares and upper trachea, unlike traditional intranasal inoculation which results in virus deposition in both upper and lower respiratory tract tissues. Despite high titers of replicating transmissible seasonal viruses in the upper respiratory tract of ferrets inoculated by the ocular route, virus transmissibility to naïve contacts by respiratory droplets was reduced following ocular inoculation. These data improve our understanding of the mechanisms of virus spread following ocular exposure and highlight differences in the establishment of respiratory disease and virus transmissibility following use of different inoculation volumes and routes. PMID:22396651

Capsular Polysaccharide Interferes With Biofilm Formation by Pasteurella Multocida Serogroup A

USDA-ARS?s Scientific Manuscript database

Pasteurella multocida is an important multihost animal and zoonotic pathogen that is capable of causing respiratory and multisystemic diseases, bacteremia,and bite wound infections. The glycosaminoglycan capsule of P. multocida is an essential virulence factor that protects the bacterium from host d...

Evidence to Support Tooth Brushing in Critically Ill Patients

PubMed Central

Ames, Nancy J.

2012-01-01

Tooth brushing in critically ill patients has been advocated by many as a standard of care despite the limited evidence to support this practice. Attention has been focused on oral care as the evidence accumulates to support an association between the bacteria in the oral microbiome and those respiratory pathogens that cause pneumonia. It is plausible to assume that respiratory pathogens originating in the oral cavity are aspirated into the lungs, causing infection. A recent study of the effects of a powered toothbrush on the incidence of ventilator-associated pneumonia was stopped early because of a lack of effect in the treatment group. This review summarizes the evidence that supports the effectiveness of tooth brushing in critically ill adults and children receiving mechanical ventilation. Possible reasons for the lack of benefit of tooth brushing demonstrated in clinical trials are discussed. Recommendations for future trials in critically ill patients are suggested. With increased emphasis being placed on oral care, the evidence that supports this intervention must be evaluated carefully. PMID:21532045

Evidence to support tooth brushing in critically ill patients.

PubMed

Ames, Nancy J

2011-05-01

Tooth brushing in critically ill patients has been advocated by many as a standard of care despite the limited evidence to support this practice. Attention has been focused on oral care as the evidence accumulates to support an association between the bacteria in the oral microbiome and those respiratory pathogens that cause pneumonia. It is plausible to assume that respiratory pathogens originating in the oral cavity are aspirated into the lungs, causing infection. A recent study of the effects of a powered toothbrush on the incidence of ventilator-associated pneumonia was stopped early because of a lack of effect in the treatment group. This review summarizes the evidence that supports the effectiveness of tooth brushing in critically ill adults and children receiving mechanical ventilation. Possible reasons for the lack of benefit of tooth brushing demonstrated in clinical trials are discussed. Recommendations for future trials in critically ill patients are suggested. With increased emphasis being placed on oral care, the evidence that supports this intervention must be evaluated carefully.

Pathogenesis, Transmissibility, and Ocular Tropism of a Highly Pathogenic Avian Influenza A (H7N3) Virus Associated with Human Conjunctivitis

PubMed Central

Belser, Jessica A.; Davis, C. Todd; Balish, Amanda; Edwards, Lindsay E.; Zeng, Hui; Maines, Taronna R.; Gustin, Kortney M.; Martínez, Irma López; Fasce, Rodrigo; Cox, Nancy J.; Katz, Jacqueline M.

2013-01-01

H7 subtype influenza A viruses, responsible for numerous outbreaks in land-based poultry in Europe and the Americas, have caused over 100 cases of confirmed or presumed human infection over the last decade. The emergence of a highly pathogenic avian influenza H7N3 virus in poultry throughout the state of Jalisco, Mexico, resulting in two cases of human infection, prompted us to examine the virulence of this virus (A/Mexico/InDRE7218/2012 [MX/7218]) and related avian H7 subtype viruses in mouse and ferret models. Several high- and low-pathogenicity H7N3 and H7N9 viruses replicated efficiently in the respiratory tract of mice without prior adaptation following intranasal inoculation, but only MX/7218 virus caused lethal disease in this species. H7N3 and H7N9 viruses were also detected in the mouse eye following ocular inoculation. Virus from both H7N3 and H7N9 subtypes replicated efficiently in the upper and lower respiratory tracts of ferrets; however, only MX/7218 virus infection caused clinical signs and symptoms and was capable of transmission to naive ferrets in a direct-contact model. Similar to other highly pathogenic H7 viruses, MX/7218 replicated to high titers in human bronchial epithelial cells, yet it downregulated numerous genes related to NF-κB-mediated signaling transduction. These findings indicate that the recently isolated North American lineage H7 subtype virus associated with human conjunctivitis is capable of causing severe disease in mice and spreading to naive-contact ferrets, while concurrently retaining the ability to replicate within ocular tissue and allowing the eye to serve as a portal of entry. PMID:23487452

Lethal Respiratory Disease Associated with Human Rhinovirus C in Wild Chimpanzees, Uganda, 2013.

PubMed

Scully, Erik J; Basnet, Sarmi; Wrangham, Richard W; Muller, Martin N; Otali, Emily; Hyeroba, David; Grindle, Kristine A; Pappas, Tressa E; Thompson, Melissa Emery; Machanda, Zarin; Watters, Kelly E; Palmenberg, Ann C; Gern, James E; Goldberg, Tony L

2018-02-01

We describe a lethal respiratory outbreak among wild chimpanzees in Uganda in 2013 for which molecular and epidemiologic analyses implicate human rhinovirus C as the cause. Postmortem samples from an infant chimpanzee yielded near-complete genome sequences throughout the respiratory tract; other pathogens were absent. Epidemiologic modeling estimated the basic reproductive number (R 0 ) for the epidemic as 1.83, consistent with the common cold in humans. Genotyping of 41 chimpanzees and examination of 24 published chimpanzee genomes from subspecies across Africa showed universal homozygosity for the cadherin-related family member 3 CDHR3-Y 529 allele, which increases risk for rhinovirus C infection and asthma in human children. These results indicate that chimpanzees exhibit a species-wide genetic susceptibility to rhinovirus C and that this virus, heretofore considered a uniquely human pathogen, can cross primate species barriers and threatens wild apes. We advocate engineering interventions and prevention strategies for rhinovirus infections for both humans and wild apes.

Understanding the role of ORF-C gene in the pathogenicity of infectious laryngotracheitis virus

USDA-ARS?s Scientific Manuscript database

Infectious laryngotracheitis (ILT) is a very serious and widespread respiratory disease of chickens caused by infectious laryngotracheitis virus (ILTV). Conventional attenuated ILT vaccines, obtained by continuous passages in chicken embryos and tissue culture, had been the main tools utilized by th...

Human Wound Infection with Mannheimia glucosida following Lamb Bite

PubMed Central

Omaleki, Lida; Turni, Conny; Barber, Stuart Richard; Francis, Michelle J.; Graham, Maryza

2015-01-01

Mannheimia spp. are veterinary pathogens that can cause mastitis and pneumonia in domestic cattle and sheep. While Mannheimia glucosida can be found as normal flora in oral and respiratory mucosa in sheep, there have been no reported cases of human infection with this organism. PMID:26202121

How recent advances in molecular tests could impact the diagnosis of pneumonia.

PubMed

Murdoch, David R

2016-01-01

Molecular diagnostic tests have been the single major development in pneumonia diagnostics over recent years. Nucleic acid detection tests (NATs) have greatly improved the ability to detect respiratory viruses and bacterial pathogens that do not normally colonize the respiratory tract. In contrast, NATs do not yet have an established role for diagnosing pneumonia caused by bacteria that commonly colonize the nasopharynx due to difficulties discriminating between pathogens and coincidental carriage strains. New approaches are needed to distinguish infection from colonization, such as through use of quantitative methods and identification of discriminating cut-off levels. The recent realization that the lung microbiome exists has provided new insights into the pathogenesis of pneumonia involving the interaction between multiple microorganisms. New developments in molecular diagnostics must account for this new paradigm.

Surveillance of Severe Acute Respiratory Infection (SARI) for Hospitalized Patients in Northern Vietnam, 2011-2014.

PubMed

Nguyen, Hang Khanh Le; Nguyen, Son Vu; Nguyen, Anh Phuong; Hoang, Phuong Mai Vu; Le, Thanh Thi; Nguyen, Thach Co; Hoang, Huong Thu; Vuong, Cuong Duc; Tran, Loan Thi Thanh; Le, Mai Quynh

2017-09-25

Severe acute respiratory infections (SARI) are leading causes of hospitalization, morbidity, and mortality in children worldwide. The aim of this study was to identify viral pathogens responsible for SARI in northern Vietnam in the period from 2011 to 2014. Throat swabs and tracheal aspirates were collected from SARI patients according to WHO guidelines. The presence of 13 different viral pathogens (influenza A[H1N1]pdm09; A/H3N2; A/H5; A/H7 and B; para influenza 1,2,3; RSV; HMPV; adeno; severe acute respiratory syndrome-CoV and rhino) was tested by conventional/real-time reverse transcription-polymerase chain reaction. During the study period, 975 samples were collected and tested. More than 30% (32.1%, 313 samples) of the samples showed evidence of infection with influenza viruses, including A/H3N2 (48 samples), A (H1N1) pdm09 (221 samples), influenza B (42 samples), and co-infection of A (H1N1) pdm09 or A/H3N2 and influenza B (2 samples). Other respiratory pathogens were detected in 101 samples, including rhinovirus (73 samples), adenovirus (10 samples), hMPV (9 samples), parainfluenza 3 (5 samples), parainfluenza 2 (3 samples), and RSV (1 sample). Influenza A/H5, A/H7, or SARS-CoV were not detected. Respiratory viral infection, particularly infection of influenza and rhinoviruses, were associated with high rates of SARI hospitalization, and future studies correlating the clinical aspects are needed to design interventions, including targeted vaccination.

Development of a one-run real-time PCR detection system for pathogens associated with bovine respiratory disease complex.

PubMed

Kishimoto, Mai; Tsuchiaka, Shinobu; Rahpaya, Sayed Samim; Hasebe, Ayako; Otsu, Keiko; Sugimura, Satoshi; Kobayashi, Suguru; Komatsu, Natsumi; Nagai, Makoto; Omatsu, Tsutomu; Naoi, Yuki; Sano, Kaori; Okazaki-Terashima, Sachiko; Oba, Mami; Katayama, Yukie; Sato, Reiichiro; Asai, Tetsuo; Mizutani, Tetsuya

2017-03-18

Bovine respiratory disease complex (BRDC) is frequently found in cattle worldwide. The etiology of BRDC is complicated by infections with multiple pathogens, making identification of the causal pathogen difficult. Here, we developed a detection system by applying TaqMan real-time PCR (Dembo respiratory-PCR) to screen a broad range of microbes associated with BRDC in a single run. We selected 16 bovine respiratory pathogens (bovine viral diarrhea virus, bovine coronavirus, bovine parainfluenza virus 3, bovine respiratory syncytial virus, influenza D virus, bovine rhinitis A virus, bovine rhinitis B virus, bovine herpesvirus 1, bovine adenovirus 3, bovine adenovirus 7, Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Trueperella pyogenes, Mycoplasma bovis and Ureaplasma diversum) as detection targets and designed novel specific primer-probe sets for nine of them. The assay performance was assessed using standard curves from synthesized DNA. In addition, the sensitivity of the assay was evaluated by spiking solutions extracted from nasal swabs that were negative by Dembo respiratory-PCR for nucleic acids of pathogens or synthesized DNA. All primer-probe sets showed high sensitivity. In this study, a total of 40 nasal swab samples from cattle on six farms were tested by Dembo respiratory-PCR. Dembo respiratory-PCR can be applied as a screening system with wide detection targets.

Virulence factors and resistance mechanisms of Serratia marcescens. A short review.

PubMed

Rodrigues, Ana P; Holanda, A R M; Lustosa, G P; Nóbrega, S M B; Santana, Willma J; Souza, Luciana B S; Coutinho, H D M

2006-03-01

Serratia marcescens, a Gram-negative bacillus that belongs to the family Enterobacteriaceae, is a human opportunistic pathogen bacterium that causes many diseases, such as urinary tract infections, respiratory tract infections, bacteremia, conjunctivitis, endocarditis, meningitis and wound infections. Many plasmides that confers multi-drug resistance were discovered, such as virulence factors, like cytotoxins that damage epithelial cells. The main topic of this paper presents a review about the molecular traits evolved in the pathogenic processes mediated by Serratia and its mechanism of resistance to drugs.

The genetic diversity of contemporary swine influenza A viruses in the United States

USDA-ARS?s Scientific Manuscript database

Introduction: Influenza A virus (IAV) is one of the most important respiratory pathogens of swine. It impacts mortality and causes significant financial losses through decreased production and the costs associated with vaccination and treatment. Further, due to the susceptibility of swine to transie...

Mannheimia haemolytica A1-induced fibrinosuppurative meningoencephalitis in a naturally-infected Holstein-Friesian calf

USDA-ARS?s Scientific Manuscript database

Mannheimia haemolytica is an opportunistic bacterium that is widely recognized among the bovine respiratory disease complex as the predominant pathogen associated with pleuropneumonia in cattle. Among the characterized M. haemolytica serotypes, A1 is the major cause of severe pulmonary lesions in ca...

Identification of Bordetella bronchseptica in fatal pneumonia of dogs and cats

USDA-ARS?s Scientific Manuscript database

Infection with Bordetella bronchiseptica is a common cause of tracheobronchitis and upper respiratory disease in dogs and cats, but it can also lead to fatal pneumonia. Identification of this pathogen is important due the risk of transmission to other animals, availability of vaccines and potential...

Pathogenesis of Influenza A/H5N1 virus infection in ferrets differs between intranasal and intratracheal routes of inoculation.

PubMed

Bodewes, Rogier; Kreijtz, Joost H C M; van Amerongen, Geert; Fouchier, Ron A M; Osterhaus, Albert D M E; Rimmelzwaan, Guus F; Kuiken, Thijs

2011-07-01

Most patients infected with highly pathogenic avian influenza A/H5N1 virus develop severe pneumonia resulting in acute respiratory distress syndrome, with extrarespiratory disease as an uncommon complication. Intranasal inoculation of ferrets with influenza A/H5N1 virus causes lesions in both the respiratory tract and extrarespiratory organs (primarily brain). However, the route of spread to extrarespiratory organs and the relative contribution of extrarespiratory disease to pathogenicity are largely unknown. In the present study, we characterized lesions in the respiratory tract and central nervous system (CNS) of ferrets (n = 8) inoculated intranasally with influenza virus A/Indonesia/5/2005 (H5N1). By 7 days after inoculation, only 3 of 8 ferrets had a mild or moderate bronchointerstitial pneumonia. In contrast, all 8 ferrets had moderate or severe CNS lesions, characterized by meningoencephalitis, choroiditis, and ependymitis, and centered on tissues adjoining the cerebrospinal fluid. These findings indicate that influenza A/H5N1 virus spread directly from nasal cavity to brain, and that CNS lesions contributed more than pulmonary lesions to the pathogenicity of influenza A/H5N1 virus infection in ferrets. In comparison, intratracheal inoculation of ferrets with the same virus reproducibly caused severe bronchointerstitial pneumonia. The method of virus inoculation requires careful consideration in the design of ferret experiments as a model for influenza A/H5N1 in humans. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Bactericidal activity of tracheal antimicrobial peptide against respiratory pathogens of cattle.

PubMed

Taha-Abdelaziz, Khaled; Perez-Casal, José; Schott, Courtney; Hsiao, Jason; Attah-Poku, Samuel; Slavić, Durđa; Caswell, Jeff L

2013-04-15

Tracheal antimicrobial peptide (TAP) is a β-defensin produced by mucosal epithelial cells of cattle. Although effective against several human pathogens, the activity of this bovine peptide against the bacterial pathogens that cause bovine respiratory disease have not been reported. This study compared the antibacterial effects of synthetic TAP against Mannheimia haemolytica, Histophilus somni, Pasteurella multocida, and Mycoplasma bovis. Bactericidal activity against M. bovis was not detected. In contrast, the Pasteurellaceae bacteria showed similar levels of susceptibility to that of Escherichia coli, with 0.125μg TAP inhibiting growth in a radial diffusion assay and minimum inhibitory concentrations of 1.56-6.25μg/ml in a bactericidal assay. Significant differences among isolates were not observed. Sequencing of exon 2 of the TAP gene from 23 cattle revealed a prevalent non-synonymous single nucleotide polymorphism (SNP) A137G, encoding either serine or asparagine at residue 20 of the mature peptide. The functional effect of this SNP was tested against M. haemolytica using synthetic peptides. The bactericidal effect of the asparagine-containing peptide was consistently higher than the serine-containing peptide. Bactericidal activities were similar for an acapsular mutant of M. haemolytica compared to the wild type. These findings indicate that the Pasteurellaceae bacteria that cause bovine respiratory disease are susceptible to killing by bovine TAP and appear not to have evolved resistance, whereas M. bovis appears to be resistant. A non-synonymous SNP was identified in the coding region of the TAP gene, and the corresponding peptides vary in their bactericidal activity against M. haemolytica. Copyright © 2013 Elsevier B.V. All rights reserved.

Antibiotic therapy of community respiratory tract infections: strategies for optimal outcomes and minimized resistance emergence.

PubMed

Ball, P; Baquero, F; Cars, O; File, T; Garau, J; Klugman, K; Low, D E; Rubinstein, E; Wise, R

2002-01-01

Widespread, increasing antibiotic resistance amongst the major respiratory pathogens has compromised traditional therapy of the major infective respiratory syndromes, including bacterial pneumonia and acute exacerbations of chronic bronchitis. Guidelines for antibiotic prescribing dating from the 1980s to 1990s, which attempted to address such problems, were commonly too prescriptive and difficult to apply, and took little account of end-user practice or locally prevalent resistance levels. Further confusion was caused by conflicting recommendations emanating from differing specialty groups. The evidence that such guidelines benefited either clinical outcomes or treatment costs has been disputed. They have probably had little effect on resistance emergence. We report the recommendations of an independent, multi-national, inter-disciplinary group, which met to identify principles underlying prescribing and guideline formulation in an age of increasing bacterial resistance. Unnecessary prescribing was recognized as the major factor in influencing resistance and costs. Antibiotic therapy must be limited to syndromes in which bacterial infection is the predominant cause and should attempt maximal reduction in bacterial load, with the ultimate aim of bacterial eradication. It should be appropriate in type and context of local resistance prevalence, and optimal in dosage for the pathogen(s) involved. Prescribing should be based on pharmacodynamic principles that predict efficacy, bacterial eradication and prevention of resistance emergence. Pharmacoeconomic analyses confirm that bacteriologically more effective antibiotics can reduce overall management costs, particularly with respect to consequential morbidity and hospital admission. Application of these principles should positively benefit therapeutic outcomes, resistance avoidance and management costs and will more accurately guide antibiotic choices by both individuals and formulary/guideline committees.

Opportunistic respiratory pathogens in the oral cavity of the elderly.

PubMed

Tada, Akio; Hanada, Nobuhiro

2010-10-01

The oral cavity of the hospitalized or bedridden elderly is often a reservoir for opportunistic pathogens associated with respiratory diseases. Commensal flora and the host interact in a balanced fashion and oral infections are considered to appear following an imbalance in the oral resident microbiota, leading to the emergence of potentially pathogenic bacteria. The definition of the process involved in colonization by opportunistic respiratory pathogens needs to elucidate the factors responsible for the transition of the microbiota from commensal to pathogenic flora. The regulatory factors influencing the oral ecosystem can be divided into three major categories: the host defense system, commensal bacteria, and external pathogens. In this article, we review the profile of these categories including the intricate cellular interaction between immune factors and commensal bacteria and the disturbance in homeostasis in the oral cavity of hospitalized or bedridden elderly, which facilitates oral colonization by opportunistic respiratory pathogens. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Chronic Azithromycin Use in Cystic Fibrosis and Risk of Treatment-Emergent Respiratory Pathogens.

PubMed

Cogen, Jonathan D; Onchiri, Frankline; Emerson, Julia; Gibson, Ronald L; Hoffman, Lucas R; Nichols, David P; Rosenfeld, Margaret

2018-02-23

Azithromycin has been shown to improve lung function and reduce the number of pulmonary exacerbations in cystic fibrosis patients. Concerns remain, however, regarding the potential emergence of treatment-related respiratory pathogens. To determine if chronic azithromycin use (defined as thrice weekly administration) is associated with increased rates of detection of eight specific respiratory pathogens. We performed a new-user, propensity-score matched retrospective cohort study utilizing data from the Cystic Fibrosis Foundation Patient Registry. Incident azithromycin users were propensity-score matched 1:1 with contemporaneous non-users. Kaplan-Meier curves and Cox proportional hazards regression were used to evaluate the association between chronic azithromycin use and incident respiratory pathogen detection. Analyses were performed separately for each pathogen, limited to patients among whom that pathogen had not been isolated in the two years prior to cohort entry. After propensity score matching, mean age of the cohorts was ~12 years. Chronic azithromycin users had a significantly lower risk of detection of new methicillin-resistant Staphylococcus aureus, non-tuberculous mycobacteria, and Burkholderia cepacia complex compared to non-users. The risk of acquiring the remaining five pathogens was not significantly different between users and non-users. Using an innovative new-user, propensity-score matched study design to minimize indication and selection biases, we found in a predominantly pediatric cohort that chronic azithromycin users had a lower risk of acquiring several cystic fibrosis-related respiratory pathogens. These results may ease concerns that chronic azithromycin exposure increases the risk of acquiring new respiratory pathogens among pediatric cystic fibrosis patients.

Incidence of nontuberculous mycobacterial disease in New Zealand, 2004.

PubMed

Freeman, Joshua; Morris, Arthur; Blackmore, Timothy; Hammer, David; Munroe, Sean; McKnight, Leo

2007-06-15

To record the incidence and clinical significance of nontuberculous mycobacteria (NTM) infection in New Zealand (NZ) in 2004. In 2004 each of NZ's mycobacterium reference laboratories collected data on NTM isolates. The clinical significance of isolates was decided by contacting the requesting clinician. American Thoracic Society criteria were used to assign clinical significance to respiratory isolates. 368 patients had NTM isolated from various sites. 21% (78/368) were clinically significant [15% (47/316) of respiratory isolates, 100% (17/17) lymph node and 89% (8/9) of soft tissue isolates]. Of the significant isolates, Mycobacterium avium intracellulare complex (MAIC) was the most common, accounting for 83%, 88%, and 44% of respiratory, lymph node, and soft tissue infections respectively. Rapidly growing mycobacteria (RGM) were the second most common cause of significant infection. Of 47 patients with significant respiratory isolates 79% were female and 83% had underlying lung disease. The incidence of disease caused by NTM in NZ in 2004 was 1.92/100,000 population. The specific incidence of pulmonary, lymph node and soft tissue infections was 1.17, 0.39, and 0.24 per 100,000 population respectively. The incidence of NTM respiratory disease in NZ during 2004 is approximately twice that recorded for Australia in 2000 (0.56/100,000). MAIC is the most common pathogen, followed by RGM. Both organisms most commonly cause respiratory infections in elderly female patients with underlying lung disease.

Streptococcus dysgalactiae subsp. dysgalactiae isolated from milk of the bovine udder as emerging pathogens: In vitro and in vivo infection of human cells and zebrafish as biological models.

PubMed

Alves-Barroco, Cinthia; Roma-Rodrigues, Catarina; Raposo, Luís R; Brás, Catarina; Diniz, Mário; Caço, João; Costa, Pedro M; Santos-Sanches, Ilda; Fernandes, Alexandra R

2018-03-25

Streptococcus dysgalactiae subsp. dysgalactiae (SDSD) is a major cause of bovine mastitis and has been regarded as an animal-restricted pathogen, although rare infections have been described in humans. Previous studies revealed the presence of virulence genes encoded by phages of the human pathogen Group A Streptococcus pyogenes (GAS) in SDSD isolated from the milk of bovine udder with mastitis. The isolates SDSD VSD5 and VSD13 could adhere and internalize human primary keratinocyte cells, suggesting a possible human infection potential of bovine isolates. In this work, the in vitro and in vivo potential of SDSD to internalize/adhere human cells of the respiratory track and zebrafish as biological models was evaluated. Our results showed that, in vitro, bovine SDSD strains could interact and internalize human respiratory cell lines and that this internalization was dependent on an active transport mechanism and that, in vivo, SDSD are able to cause invasive infections producing zebrafish morbidity and mortality. The infectious potential of these isolates showed to be isolate-specific and appeared to be independent of the presence or absence of GAS phage-encoded virulence genes. Although the infection ability of the bovine SDSD strains was not as strong as the human pathogenic S. pyogenes in the zebrafish model, results suggested that these SDSD isolates are able to interact with human cells and infect zebrafish, a vertebrate infectious model, emerging as pathogens with zoonotic capability. © 2018 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Detection of Influenza C Viruses Among Outpatients and Patients Hospitalized for Severe Acute Respiratory Infection, Minnesota, 2013-2016.

PubMed

Thielen, Beth K; Friedlander, Hannah; Bistodeau, Sarah; Shu, Bo; Lynch, Brian; Martin, Karen; Bye, Erica; Como-Sabetti, Kathryn; Boxrud, David; Strain, Anna K; Chaves, Sandra S; Steffens, Andrea; Fowlkes, Ashley L; Lindstrom, Stephen; Lynfield, Ruth

2018-03-19

Existing literature suggests that influenza C typically causes mild respiratory tract disease. However, clinical and epidemiological data are limited. Four outpatient clinics and 3 hospitals submitted clinical data and respiratory specimens through a surveillance network for acute respiratory infection (ARI) from May 2013 through December 2016. Specimens were tested using multitarget nucleic acid amplification for 19-22 respiratory pathogens, including influenza C. Influenza C virus was detected among 59 of 10 202 (0.58%) hospitalized severe ARI cases and 11 of 2282 (0.48%) outpatients. Most detections occurred from December to March, 73% during the 2014-2015 season. Influenza C detections occurred among patients of all ages, with rates being similar between inpatients and outpatients. The highest rate of detection occurred among children aged 6-24 months (1.2%). Among hospitalized cases, 7 required intensive care. Medical comorbidities were reported in 58% of hospitalized cases and all who required intensive care. At least 1 other respiratory pathogen was detected in 40 (66%) cases, most commonly rhinovirus/enterovirus (25%) and respiratory syncytial virus (20%). The hemagglutinin-esterase-fusion gene was sequenced in 37 specimens, and both C/Kanagawa and C/Sao Paulo lineages were detected in inpatients and outpatients. We found seasonal circulation of influenza C with year-to-year variability. Detection was most frequent among young children but occurred in all ages. Some cases that were positive for influenza C, particularly those with comorbid conditions, had severe disease, suggesting a need for further study of the role of influenza C virus in the pathogenesis of respiratory disease.

Viral etiology, seasonality and severity of hospitalized patients with severe acute respiratory infections in the Eastern Mediterranean Region, 2007-2014.

PubMed

Horton, Katherine C; Dueger, Erica L; Kandeel, Amr; Abdallat, Mohamed; El-Kholy, Amani; Al-Awaidy, Salah; Kohlani, Abdul Hakim; Amer, Hanaa; El-Khal, Abel Latif; Said, Mayar; House, Brent; Pimentel, Guillermo; Talaat, Maha

2017-01-01

Little is known about the role of viral respiratory pathogens in the etiology, seasonality or severity of severe acute respiratory infections (SARI) in the Eastern Mediterranean Region. Sentinel surveillance for SARI was conducted from December 2007 through February 2014 at 20 hospitals in Egypt, Jordan, Oman, Qatar and Yemen. Nasopharyngeal and oropharyngeal swabs were collected from hospitalized patients meeting SARI case definitions and were analyzed for infection with influenza, respiratory syncytial virus (RSV), adenovirus (AdV), human metapneumovirus (hMPV) and human parainfluenza virus types 1-3 (hPIV1-3). We analyzed surveillance data to calculate positivity rates for viral respiratory pathogens, describe the seasonality of those pathogens and determine which pathogens were responsible for more severe outcomes requiring ventilation and/or intensive care and/or resulting in death. At least one viral respiratory pathogen was detected in 8,753/28,508 (30.7%) samples tested for at least one pathogen and 3,497/9,315 (37.5%) of samples tested for all pathogens-influenza in 3,345/28,438 (11.8%), RSV in 3,942/24,503 (16.1%), AdV in 923/9,402 (9.8%), hMPV in 617/9,384 (6.6%), hPIV1 in 159/9,402 (1.7%), hPIV2 in 85/9,402 (0.9%) and hPIV3 in 365/9,402 (3.9%). Multiple pathogens were identified in 501/9,316 (5.4%) participants tested for all pathogens. Monthly variation, indicating seasonal differences in levels of infection, was observed for all pathogens. Participants with hMPV infections and participants less than five years of age were significantly less likely than participants not infected with hMPV and those older than five years of age, respectively, to experience a severe outcome, while participants with a pre-existing chronic disease were at increased risk of a severe outcome, compared to those with no reported pre-existing chronic disease. Viral respiratory pathogens are common among SARI patients in the Eastern Mediterranean Region. Ongoing surveillance is important to monitor changes in the etiology, seasonality and severity of pathogens of interest.

Differences between Human and Rodent Plasmacytoid Dendritic Cells May Explain the Pathogenic Disparity of Hantavirus Infection

DTIC Science & Technology

2016-06-01

cause two acute febrile diseases in humans: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardio-pulmonary syndrome (HCPS). The purpose...of Biochemistry, School of Medicine, University of Nevada, Reno, NV, USA Hantavirus pulmonary syndrome (HPS) is an acute zoonotic disease transmitted...bling acute respiratory distress syndrome (10). Rapidly progress- ing pulmonary edema, myocardial depression, and hypovolemia are the leading cause of

Clinical requirements in the treatment of today's respiratory tract infections.

PubMed

Höffken, G

1993-01-01

Respiratory tract infections (RTIs) are among the most frequent infections in man and lower tract infections account substantially for the overall mortality in hospitals. Regarding the etiology of pneumonias, one has to consider different pathogenic mechanisms, age of the patients, underlying diseases, concomitant medications, symptomatologies, seasonal influences, and clinical conditions, e.g. intensive care environment and mechanical ventilation. To optimize the rational management of respiratory infections, identification of the etiologic agent would be desirable. The decision of how to treat is often based on epidemiologic, clinical, and radiological assessments. Epidemiologic studies have shown a pronounced difference in the etiologic spectrum between community- and hospital-acquired RTIs. In community-acquired pneumonias, pneumococci, Haemophilus influenzae, Legionella, Mycoplasma and viruses predominate, whereas in nosocomially acquired pneumonias, Enterobacteriaceae, e.g. Klebsiella, Proteus, Enterobacter as well as Pseudomonas and staphylococci comprise the most frequent isolates. Empirical therapy has to cover all possible etiologic pathogens which most likely cause the infection. In addition, an adequate kinetic profile, e.g. once or twice daily dosing, sufficient pulmonary tissue or fluid penetration, and acceptable tolerance and costs are prerequisites for optimal therapy. Drugs of choice for the treatment of community-acquired pneumonia are aminobenzylpenicillins or macrolides. Oral cephalosporins exhibit excellent activity against many bacterial pathogens of typical community-acquired pneumonia, and are active against beta-lactamase-producing H. influenzae.

Experimental Infection of Syrian Hamsters with Aerosolized Nipah virus.

PubMed

Escaffre, Olivier; Hill, Terence; Ikegami, Tetsuro; Juelich, Terry L; Smith, Jennifer K; Zhang, Lihong; Perez, David E; Atkins, Colm; Park, Arnold; Lawrence, William S; Sivasubramani, Satheesh K; Peel, Jennifer E; Peterson, Johnny W; Lee, Benhur; Freiberg, Alexander N

2018-06-15

Nipah virus (NiV) is a paramyxovirus (genus henipavirus) that can cause severe respiratory illness and encephalitis in humans. Transmission occurs through consumption of NiV-contaminated foods, and contact with NiV-infected animals or human body fluids. However, it is unclear whether aerosols derived from aforesaid sources or others also contribute to transmission, and current knowledge on NiV-induced pathogenicity after small particle aerosol exposure is still limited. infectivity, pathogenicity and real-time dissemination of aerosolized NiV in Syrian hamsters was evaluated using NiV-Malaysia (NiV-M) and/or its recombinant expressing firefly luciferase (rNiV-Fluc NP). both viruses had an equivalent pathogenicity in hamsters that developed respiratory and neurological symptoms of disease, similar to using intranasal route, with no direct correlations to the dose. Finally, we show that virus replication was predominantly initiated in the lower respiratory tract, and although delayed, also intensely in the oronasal cavity and possibly the brain, with gradual increase of signal in these regions until at least day 5-6 post-infection. hamsters infected with small-particle aerosolized NiV undergo similar clinical manifestations of the disease as previously described using liquid inoculum, and exhibit histopathological lesions consistent with NiV patient reports. NiV droplets could therefore play a role in transmission by close contact.

Detection of pathogens in Boidae and Pythonidae with and without respiratory disease.

PubMed

Schmidt, V; Marschang, R E; Abbas, M D; Ball, I; Szabo, I; Helmuth, R; Plenz, B; Spergser, J; Pees, M

2013-03-02

Respiratory diseases in boid snakes are common in captivity, but little information is available on their aetiology. This study was carried out to determine the occurrence of lung associated pathogens in boid snakes with and without respiratory signs and/or pneumonia. In total, 80 boid snakes of the families Boidae (n = 30) and Pythonidae (n = 50) from 48 private and zoo collections were included in this survey. Husbandry conditions were evaluated using a detailed questionnaire. All snakes were examined clinically and grouped into snakes with or without respiratory signs. Tracheal wash samples from all snakes were examined bacteriologically as well as virologically. All snakes were euthanased, and a complete pathological examination was performed. Respiratory signs and pneumonia were detected more often in pythons than in boas. An acute catarrhal pneumonia was diagnosed more often in snakes without respiratory signs than in snakes with respiratory signs, which revealed fibrinous and fibrous pneumonia. Poor husbandry conditions are an important trigger for the development of respiratory signs and pneumonia. Different bacterial pathogens were isolated in almost all snakes with pneumonia, with Salmonella species being the most common. Ferlavirus (formerly known as ophidian paramyxovirus)-RNA was detected only in pythons. Inclusion body disease was rarely seen in pythons but often in boas. Adenovirus and Mycoplasma were other pathogens that were diagnosed in single snakes with pneumonia. In living boid snakes with respiratory signs, tracheal wash samples were found to be a useful diagnostic tool for the detection of viral and bacterial pathogens.

A Review of Eight High-Priority, Economically Important Viral Pathogens of Poultry within the Caribbean Region

PubMed Central

Gongora, Victor; Hartley, Dane; Oura, Christopher

2018-01-01

Viral pathogens cause devastating economic losses in poultry industries worldwide. The Caribbean region, which boasts some of the highest rates of poultry consumption in the world, is no exception. This review summarizes evidence for the circulation and spread of eight high-priority, economically important poultry viruses across the Caribbean region. Avian influenza virus (AIV), infectious bronchitis virus (IBV), Newcastle disease virus (NDV), infectious laryngotracheitis virus (ILTV), avian metapneumovirus (aMPV), infectious bursal disease virus (IBDV), fowl adenovirus group 1 (FADV Gp1), and egg drop syndrome virus (EDSV) were selected for review. This review of serological, molecular, and phylogenetic studies across Caribbean countries reveals evidence for sporadic outbreaks of respiratory disease caused by notifiable viral pathogens (AIV, IBV, NDV, and ILTV), as well as outbreaks of diseases caused by immunosuppressive viral pathogens (IBDV and FADV Gp1). This review highlights the need to strengthen current levels of surveillance and reporting for poultry diseases in domestic and wild bird populations across the Caribbean, as well as the need to strengthen the diagnostic capacity and capability of Caribbean national veterinary diagnostic laboratories. PMID:29373488

Evidence-based effectiveness of vaccination against Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni in feedlot cattle for mitigating the incidence and effect of bovine respiratory disease complex.

PubMed

Larson, R L; Step, D L

2012-03-01

Bovine respiratory disease complex is the leading cause of morbidity and mortality in feedlot cattle. A number of vaccines against bacterial respiratory pathogens are commercially available and researchers have studied their impact on morbidity, mortality, and other disease outcome measures in feedlot cattle. A systematic review will provide veterinarians with a rigorous and transparent evaluation of the published literature to estimate the extent of vaccine effect. Unfortunately, the published body of evidence does not provide a consistent estimate of the direction and magnitude of effectiveness in feedlot cattle vaccination against Mannheimia haemolytica, Pasteurella multocida, or Histophilus somni.

Mycoplasma hyorhinis is a potential pathogen of porcine respiratory disease complex that aggravates pneumonia caused by porcine reproductive and respiratory syndrome virus.

PubMed

Lee, Jung-Ah; Oh, Yu-Ri; Hwang, Min-A; Lee, Joong-Bok; Park, Seung-Yong; Song, Chang-Seon; Choi, In-Soo; Lee, Sang-Won

2016-09-01

The porcine respiratory disease complex (PRDC) caused by numerous bacterial and viral agents has a great impact on pig industry worldwide. Although Mycoplasma hyorhinis (Mhr) has been frequently isolated from lung lesions from pigs with PRDC, the pathological importance of Mhr may have been underestimated. In this study, 383 serum samples obtained from seven herds with a history of PRDC were tested for specific antibodies to Mhr, Mycoplasma hyopneumoniae (Mhp), and porcine reproductive and respiratory syndrome virus (PRRSV). Seropositive rates of PRRSV were significantly correlated with those of Mhr (correlation coefficient, 0.862; P-value, 0.013), but not with those of Mhp (correlation coefficient, -0.555; P-value, 0.196). In vivo experiments demonstrated that pigs co-infected with Mhr and PRRSV induced more severe lung lesions than pigs infected with Mhr or PRRSV alone. These findings suggest that Mhr is closely associated with pneumonia caused by PRRSV and provide important information on Mhr pathogenesis within PRDC. Therefore, effective PRDC control strategies should also consider the potential impact of Mhr in the pathogenesis of PRDC. Copyright © 2016 Elsevier B.V. All rights reserved.

Respiratory Viruses and Treatment Failure in Children With Asthma Exacerbation.

PubMed

Merckx, Joanna; Ducharme, Francine M; Martineau, Christine; Zemek, Roger; Gravel, Jocelyn; Chalut, Dominic; Poonai, Naveen; Quach, Caroline

2018-06-04

: media-1vid110.1542/5771275574001PEDS-VA_2017-4105 Video Abstract OBJECTIVES: Respiratory pathogens commonly trigger pediatric asthma exacerbations, but their impact on severity and treatment response remains unclear. We performed a secondary analysis of the Determinants of Oral Corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY) study, a prospective cohort study of children (aged 1-17 years) presenting to the emergency department with moderate or severe exacerbations. Nasopharyngeal specimens were analyzed by RT-PCR for 27 respiratory pathogens. We investigated the association between pathogens and both exacerbation severity (assessed with the Pediatric Respiratory Assessment Measure) and treatment failure (hospital admission, emergency department stay >8 hours, or relapse) of a standardized severity-specific treatment. Logistic multivariate regressions were used to estimate average marginal effects (absolute risks and risk differences [RD]). Of 958 participants, 61.7% were positive for ≥1 pathogen (rhinovirus was the most prevalent [29.4%]) and 16.9% experienced treatment failure. The presence of any pathogen was not associated with higher baseline severity but with a higher risk of treatment failure (20.7% vs 12.5%; RD = 8.2% [95% confidence interval: 3.3% to 13.1%]) compared to the absence of a pathogen. Nonrhinovirus pathogens were associated with an increased absolute risk (RD) of treatment failure by 13.1% (95% confidence interval: 6.4% to 19.8%), specifically, by 8.8% for respiratory syncytial virus, 24.9% for influenza, and 34.1% for parainfluenza. Although respiratory pathogens were not associated with higher severity on presentation, they were associated with increased treatment failure risk, particularly in the presence of respiratory syncytial virus, influenza, and parainfluenza. This supports influenza prevention in asthmatic children, consideration of pathogen identification on presentation, and exploration of treatment intensification for infected patients at higher risk of treatment failure. Copyright © 2018 by the American Academy of Pediatrics.

Diseases and pathogens associated with mortality in Ontario beef feedlots.

PubMed

Gagea, Mihai I; Bateman, Kenneth G; van Dreumel, Tony; McEwen, Beverly J; Carman, Susy; Archambault, Marie; Shanahan, Rachel A; Caswell, Jeff L

2006-01-01

This study determined the prevalence of diseases and pathogens associated with mortality or severe morbidity in 72 Ontario beef feedlots in calves that died or were euthanized within 60 days after arrival. Routine pathologic and microbiologic investigations, as well as immunohistochemical staining for detection of bovine viral diarrhea virus (BVDV) antigen, were performed on 99 calves that died or were euthanized within 60 days after arrival. Major disease conditions identified included fibrinosuppurative bronchopneumonia (49%), caseonecrotic bronchopneumonia or arthritis (or both) caused by Mycoplasma bovis (36%), viral respiratory disease (19%), BVDV-related diseases (21%), Histophilus somni myocarditis (8%), ruminal bloat (2%), and miscellaneous diseases (8%). Viral infections identified were BVDV (35%), bovine respiratory syncytial virus (9%), bovine herpesvirus-1 (6%), parainfluenza-3 virus (3%), and bovine coronavirus (2%). Bacteria isolated from the lungs included M. bovis (82%), Mycoplasma arginini (72%), Ureaplasma diversum (25%), Mannheimia haemolytica (27%), Pasteurella multocida (19%), H. somni (14%), and Arcanobacterium pyogenes (19%). Pneumonia was the most frequent cause of mortality of beef calves during the first 2 months after arrival in feedlots, representing 69% of total deaths. The prevalence of caseonecrotic bronchopneumonia caused by M. bovis was similar to that of fibrinosuppurative bronchopneumonia, and together, these diseases were the most common causes of pneumonia and death. M. bovis pneumonia and polyarthritis has emerged as an important cause of mortality in Ontario beef feedlots.

Influenza A (H10N7) Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets.

PubMed

van den Brand, Judith M A; Wohlsein, Peter; Herfst, Sander; Bodewes, Rogier; Pfankuche, Vanessa M; van de Bildt, Marco W G; Seehusen, Frauke; Puff, Christina; Richard, Mathilde; Siebert, Ursula; Lehnert, Kristina; Bestebroer, Theo; Lexmond, Pascal; Fouchier, Ron A M; Prenger-Berninghoff, Ellen; Herbst, Werner; Koopmans, Marion; Osterhaus, Albert D M E; Kuiken, Thijs; Baumgärtner, Wolfgang

2016-01-01

Avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease. Recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype H10N7 (Seal/H10N7) in harbor seals (Phoca vitulina). This epidemic caused high mortality in seals along the north-west coast of Europe and represented a potential risk for human health. To characterize the spectrum of lesions and to identify the target cells and viral distribution, findings in 16 harbor seals spontaneously infected with Seal/H10N7 are described. The seals had respiratory tract inflammation extending from the nasal cavity to bronchi associated with intralesional virus antigen in respiratory epithelial cells. Virus infection was restricted to the respiratory tract. The fatal outcome of the viral infection in seals was most likely caused by secondary bacterial infections. To investigate the pathogenic potential of H10N7 infection for humans, we inoculated the seal virus intratracheally into six ferrets and performed pathological and virological analyses at 3 and 7 days post inoculation. These experimentally inoculated ferrets displayed mild clinical signs, virus excretion from the pharynx and respiratory tract inflammation extending from bronchi to alveoli that was associated with virus antigen expression exclusively in the respiratory epithelium. Virus was isolated only from the respiratory tract. In conclusion, Seal/H10N7 infection in naturally infected harbor seals and experimentally infected ferrets shows that respiratory epithelial cells are the permissive cells for viral replication. Fatal outcome in seals was caused by secondary bacterial pneumonia similar to that in fatal human cases during influenza pandemics. Productive infection of ferrets indicates that seal/H10N7 may possess a zoonotic potential. This outbreak of LPAI from wild birds to seals demonstrates the risk of such occasions for mammals and thus humans.

Trichosporon mycotoxinivorans, a Novel Respiratory Pathogen in Patients with Cystic Fibrosis▿

PubMed Central

Hickey, Patrick W.; Sutton, Deanna A.; Fothergill, Annette W.; Rinaldi, Michael G.; Wickes, Brian L.; Schmidt, Howard J.; Walsh, Thomas J.

2009-01-01

This report describes the molecular epidemiology, in vitro susceptibility, colonial and microscopic morphologies, and biochemical features of Trichosporon mycotoxinivorans, a newly recognized pathogen that appears to have a propensity for patients with cystic fibrosis. The index patient died with histologically documented Trichosporon pneumonia complicating cystic fibrosis. This is also the first report of disease caused by a Trichosporon species in a nontransplant patient with cystic fibrosis. As T. mycotoxinivorans has not previously been recognized as a respiratory pathogen, the significance of its recovery from sputum samples was not initially appreciated. Genetic analysis of archived clinical samples found three additional cases of T. mycotoxinivorans infection which had previously been identified as other members of the genus. An additional isolate of T. mycotoxinivorans was identified from a clinical sample on initial testing. Three of these four cases were also patients with cystic fibrosis. All isolates had MICs at 48 h of amphotericin B of ≥1 μg/ml and of echinocandins of ≥16 μg/ml, but they displayed various susceptibilities to the triazoles. In summary, Trichosporon mycotoxinivorans is a newly recognized human pathogen that is associated with cystic fibrosis. PMID:19656976

Evolution of amoxicillin/clavulanate in the treatment of adults with acute bacterial rhinosinusitis and community-acquired pneumonia in response to antimicrobial-resistance patterns.

PubMed

File, Thomas M; Benninger, Michael S; Jacobs, Michael R

2004-06-01

Current treatment guidelines for community-acquired respiratory tract infections no longer depend solely on the characteristics of the patient and the clinical syndrome, but on those of the offending pathogen, including presence and level of antimicrobial resistance. The most common respiratory tract pathogens known to cause acute bacterial rhinosinusitis (ABRS) and community-acquired pneumonia (CAP) include Streptococcus pneumoniae and Haemophilus influenzae. The prevalence of antimicrobial resistance, especially b-lactum and macrolide resistance, among S pneumoniae and H influenzae has increased dramatically during the past 2 decades, diminishing the activity of many older antimicrobials against resistant organisms. A pharmacokinetically enhanced formulation of amoxicillin/clavulanate has been developed to fulfill the need for an oral b-lactam antimicrobial that achieves a greater time that the serum drug concentration exceeds the minimum inhibitory concentration (T > MIC) of antimicrobials against pathogens than conventional formulations to improve activity against S pneumoniae with reduced susceptibility to penicillin. The b-lactamase inhibitor clavulanate allows for coverage of b-lactamase-producing pathogens, such as H influenzae and M catarrhalis. This article reviews the rationale for, and evolution of, oral amoxicillin clavulanate for ABRS and CAP

Evasion of Neutrophil Extracellular Traps by Respiratory Pathogens.

PubMed

Storisteanu, Daniel M L; Pocock, Joanna M; Cowburn, Andrew S; Juss, Jatinder K; Nadesalingam, Angalee; Nizet, Victor; Chilvers, Edwin R

2017-04-01

The release of neutrophil extracellular traps (NETs) is a major immune mechanism intended to capture pathogens. These histone- and protease-coated DNA structures are released by neutrophils in response to a variety of stimuli, including respiratory pathogens, and have been identified in the airways of patients with respiratory infection, cystic fibrosis, acute lung injury, primary graft dysfunction, and chronic obstructive pulmonary disease. NET production has been demonstrated in the lungs of mice infected with Staphylococcus aureus, Klebsiella pneumoniae, and Aspergillus fumigatus. Since the discovery of NETs over a decade ago, evidence that "NET evasion" might act as an immune protection strategy among respiratory pathogens, including group A Streptococcus, Bordetella pertussis, and Haemophilus influenzae, has been growing, with the majority of these studies being published in the past 2 years. Evasion strategies fall into three main categories: inhibition of NET release by down-regulating host inflammatory responses; degradation of NETs using pathogen-derived DNases; and resistance to the microbicidal components of NETs, which involves a variety of mechanisms, including encapsulation. Hence, the evasion of NETs appears to be a widespread strategy to allow pathogen proliferation and dissemination, and is currently a topic of intense research interest. This article outlines the evidence supporting the three main strategies of NET evasion-inhibition, degradation, and resistance-with particular reference to common respiratory pathogens.

Evasion of Neutrophil Extracellular Traps by Respiratory Pathogens

PubMed Central

Storisteanu, Daniel M. L.; Pocock, Joanna M.; Cowburn, Andrew S.; Juss, Jatinder K.; Nadesalingam, Angalee; Nizet, Victor

2017-01-01

The release of neutrophil extracellular traps (NETs) is a major immune mechanism intended to capture pathogens. These histone- and protease-coated DNA structures are released by neutrophils in response to a variety of stimuli, including respiratory pathogens, and have been identified in the airways of patients with respiratory infection, cystic fibrosis, acute lung injury, primary graft dysfunction, and chronic obstructive pulmonary disease. NET production has been demonstrated in the lungs of mice infected with Staphylococcus aureus, Klebsiella pneumoniae, and Aspergillus fumigatus. Since the discovery of NETs over a decade ago, evidence that “NET evasion” might act as an immune protection strategy among respiratory pathogens, including group A Streptococcus, Bordetella pertussis, and Haemophilus influenzae, has been growing, with the majority of these studies being published in the past 2 years. Evasion strategies fall into three main categories: inhibition of NET release by down-regulating host inflammatory responses; degradation of NETs using pathogen-derived DNases; and resistance to the microbicidal components of NETs, which involves a variety of mechanisms, including encapsulation. Hence, the evasion of NETs appears to be a widespread strategy to allow pathogen proliferation and dissemination, and is currently a topic of intense research interest. This article outlines the evidence supporting the three main strategies of NET evasion—inhibition, degradation, and resistance—with particular reference to common respiratory pathogens. PMID:27854516

Variation in pestivirus growth in testicle primary cell culture is more dependent on the individual cell donor than cattle breed

USDA-ARS?s Scientific Manuscript database

Bovine respiratory disease complex (BRDC) affects cattle from all breeds living in all regions. However, different breeds of cattle appear to have different susceptibilities to developing BRDC. The causes of BRDC are multifactorial and include infection with both viral and bacterial pathogens. Infec...

Attenuation, transmission, and immunogenicity of an ORF-C gene deleted strain of infectious laryngotracheitis virus (ILTV) in specific pathogen free chickens

USDA-ARS?s Scientific Manuscript database

Infectious laryngotracheitis (ILT) is a very serious and widespread respiratory disease of chickens caused by infectious laryngotracheitis virus (ILTV). Conventional attenuated ILT vaccines, obtained by continuous passages in chicken embryos and tissue culture, had been the main tools utilized by th...

H9N2 avian influenza transmission and antigenicity

USDA-ARS?s Scientific Manuscript database

Low pathogenic H9N2 avian influenza has become endemic in parts of Asia, the Middle East and North Africa causing respiratory disease with occasional mortality. The use of vaccination has become common to try and control the clinical disease, but vaccination has not been shown to be an effective er...

Communicable Diseases Prioritized for Surveillance and Epidemiological Research: Results of a Standardized Prioritization Procedure in Germany, 2011

PubMed Central

Balabanova, Yanina; Gilsdorf, Andreas; Buda, Silke; Burger, Reinhard; Eckmanns, Tim; Gärtner, Barbara; Groß, Uwe; Haas, Walter; Hamouda, Osamah; Hübner, Johannes; Jänisch, Thomas; Kist, Manfred; Kramer, Michael H.; Ledig, Thomas; Mielke, Martin; Pulz, Matthias; Stark, Klaus; Suttorp, Norbert; Ulbrich, Uta; Wichmann, Ole; Krause, Gérard

2011-01-01

Introduction To establish strategic priorities for the German national public health institute (RKI) and guide the institute's mid-term strategic decisions, we prioritized infectious pathogens in accordance with their importance for national surveillance and epidemiological research. Methods We used the Delphi process with internal (RKI) and external experts and a metric-consensus approach to score pathogens according to ten three-tiered criteria. Additional experts were invited to weight each criterion, leading to the calculation of a median weight by which each score was multiplied. We ranked the pathogens according to the total weighted score and divided them into four priority groups. Results 127 pathogens were scored. Eighty-six experts participated in the weighting; “Case fatality rate” was rated as the most important criterion. Twenty-six pathogens were ranked in the highest priority group; among those were pathogens with internationally recognised importance (e.g., Human Immunodeficiency Virus, Mycobacterium tuberculosis, Influenza virus, Hepatitis C virus, Neisseria meningitides), pathogens frequently causing large outbreaks (e.g., Campylobacter spp.), and nosocomial pathogens associated with antimicrobial resistance. Other pathogens in the highest priority group included Helicobacter pylori, Respiratory Syncytial Virus, Varicella zoster virus and Hantavirus. Discussion While several pathogens from the highest priority group already have a high profile in national and international health policy documents, high scores for other pathogens (e.g., Helicobacter pylori, Respiratory syncytial virus or Hantavirus) indicate a possible under-recognised importance within the current German public health framework. A process to strengthen respective surveillance systems and research has been started. The prioritization methodology has worked well; its modular structure makes it potentially useful for other settings. PMID:21991334

New and emerging pathogens in canine infectious respiratory disease.

PubMed

Priestnall, S L; Mitchell, J A; Walker, C A; Erles, K; Brownlie, J

2014-03-01

Canine infectious respiratory disease is a common, worldwide disease syndrome of multifactorial etiology. This review presents a summary of 6 viruses (canine respiratory coronavirus, canine pneumovirus, canine influenza virus, pantropic canine coronavirus, canine bocavirus, and canine hepacivirus) and 2 bacteria (Streptococcus zooepidemicus and Mycoplasma cynos) that have been associated with respiratory disease in dogs. For some pathogens a causal role is clear, whereas for others, ongoing research aims to uncover their pathogenesis and contribution to this complex syndrome. Etiology, clinical disease, pathogenesis, and epidemiology are described for each pathogen, with an emphasis on recent discoveries or novel findings.

New therapeutic options for respiratory tract infections.

PubMed

Bassetti, Matteo; Righi, Elda; Carnelutti, Alessia

2016-04-01

The progressive increase of respiratory tract infections caused by multidrug-resistant organisms (MDROs) has been associated with delays in the prescription of an adequate antibiotic treatment and increased mortality, representing a major concern in both community and hospital settings. When infections because of methicillin-resistant Staphylococcus aureus (MRSA) are suspected, vancomycin still represents the first choice, although its efficacy has been recently questioned in favor of new drugs, reported to provide better clinical outcomes. Moreover, few therapeutic options are currently available for the treatment of severe infections caused by Multidrug-resistant (MDR) Gram-negative pathogens, which are frequently resistant to all the available β-lactams, including carbapenems. We have reviewed the therapeutic options for the treatment of respiratory tract infections that have recently become available with promising implications for clinical practice, including ceftaroline, ceftrobiprole, tedizolid, telavancin, delafloxacin, eravacycline, and new β-lactams/β-lactamase inhibitors. A number of new antimicrobials with activity against MDROs have been recently approved for the treatment of respiratory tract infections, and other agents are under investigation. Recent developments, with a specific focus on the possible advantages of new drugs for the management of respiratory tract infections caused by MDROs in everyday clinical practice are discussed. Newly approved and investigational drugs for the treatment of respiratory tract infections are expected to offer many advantages for the management of patients with suspected or confirmed infections caused by MDROs. Most promising features among new compounds include the broad spectrum of activity against both MRSA and MDR Gram-negative bacteria, a limited risk of antimicrobial resistance, the availability of oral formulations, and a promising safety profile.

MTO1 mutations are associated with hypertrophic cardiomyopathy and lactic acidosis and cause respiratory chain deficiency in humans and yeast.

PubMed

Baruffini, Enrico; Dallabona, Cristina; Invernizzi, Federica; Yarham, John W; Melchionda, Laura; Blakely, Emma L; Lamantea, Eleonora; Donnini, Claudia; Santra, Saikat; Vijayaraghavan, Suresh; Roper, Helen P; Burlina, Alberto; Kopajtich, Robert; Walther, Anett; Strom, Tim M; Haack, Tobias B; Prokisch, Holger; Taylor, Robert W; Ferrero, Ileana; Zeviani, Massimo; Ghezzi, Daniele

2013-11-01

We report three families presenting with hypertrophic cardiomyopathy, lactic acidosis, and multiple defects of mitochondrial respiratory chain (MRC) activities. By direct sequencing of the candidate gene MTO1, encoding the mitochondrial-tRNA modifier 1, or whole exome sequencing analysis, we identified novel missense mutations. All MTO1 mutations were predicted to be deleterious on MTO1 function. Their pathogenic role was experimentally validated in a recombinant yeast model, by assessing oxidative growth, respiratory activity, mitochondrial protein synthesis, and complex IV activity. In one case, we also demonstrated that expression of wt MTO1 could rescue the respiratory defect in mutant fibroblasts. The severity of the yeast respiratory phenotypes partly correlated with the different clinical presentations observed in MTO1 mutant patients, although the clinical outcome was highly variable in patients with the same mutation and seemed also to depend on timely start of pharmacological treatment, centered on the control of lactic acidosis by dichloroacetate. Our results indicate that MTO1 mutations are commonly associated with a presentation of hypertrophic cardiomyopathy, lactic acidosis, and MRC deficiency, and that ad hoc recombinant yeast models represent a useful system to test the pathogenic potential of uncommon variants, and provide insight into their effects on the expression of a biochemical phenotype. © 2013 The Authors. *Human Mutation published by Wiley Periodicals, Inc.

Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Induces Prostaglandin E2 Production through Cyclooxygenase 1, Which Is Dependent on the ERK1/2-p-C/EBP-β Pathway

PubMed Central

Bi, Yanmin; Guo, Xue-kun; Zhao, Haiyan; Gao, Li; Wang, Lianghai; Tang, Jun

2014-01-01

ABSTRACT Atypical porcine reproductive and respiratory syndrome (PRRS) caused by highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) is characterized by high fever and high mortality. However, the mechanism underlying the fever induction is still unknown. Prostaglandin E2 (PGE2), synthesized by cyclooxygenase type 1/2 (COX-1/2) enzymes, is essential for inducing fever. In this study, we found that PGE2, together with COX-1, was significantly elevated by HP-PRRSV. We subsequently demonstrated that extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated ERK (p-ERK) were the key nodes to trigger COX-1 expression after HP-PRRSV infection. Furthermore, we proved the direct binding of p-C/EBP-β to the COX-1 promoter by luciferase reporter and chromatin immunoprecipitation assays. In addition, silencing of C/EBP-β remarkably impaired the enhancement of COX-1 production induced by HP-PRRSV infection. Taken together, our results indicate that HP-PPRSV elicits the expression of COX-1 through the ERK1/2-p-C/EBP-β signaling pathway, resulting in the increase of PGE2, which might be the cause of high fever in infected pigs. Our findings might provide new insights into the molecular mechanisms underlying the pathogenesis of HP-PRRSV infection. IMPORTANCE The atypical PRRS caused by HP-PRRSV was characterized by high fever, high morbidity, and high mortality in pigs of all ages, yet how HP-PRRSV induces high fever in pigs remains unknown. In the present study, we found out that HP-PRRSV infection could increase PGE2 production by upregulation of COX-1, and we subsequently characterized the underlying mechanisms about how HP-PRRSV enhances COX-1 production. PGE2 plays a critical role in inducing high temperature in hosts during pathogen infections. Thus, our findings here could help us have a better understanding of HP-PRRSV pathogenesis. PMID:24352469

Bacterial pathogens of the bovine respiratory disease complex.

PubMed

Griffin, Dee; Chengappa, M M; Kuszak, Jennifer; McVey, D Scott

2010-07-01

Pneumonia caused by the bacterial pathogens discussed in this article is the most significant cause of morbidity and mortality of the BRDC. Most of these infectious bacteria are not capable of inducing significant disease without the presence of other predisposing environmental factors, physiologic stressors, or concurrent infections. Mannheimia haemolytica is the most common and serious of these bacterial agents and is therefore also the most highly characterized. There are other important bacterial pathogens of BRD, such as Pasteurella multocida, Histophulus somni, and Mycoplasma bovis. Mixed infections with these organisms do occur. These pathogens have unique and common virulence factors but the resulting pneumonic lesions may be similar. Although the amount and quality of research associated with BRD has increased, vaccination and therapeutic practices are not fully successful. A greater understanding of the virulence mechanisms of the infecting bacteria and pathogenesis of pneumonia, as well as the characteristics of the organisms that allow tissue persistence, may lead to improved management, therapeutics, and vaccines. Copyright 2010 Elsevier Inc. All rights reserved.

Taking forward a 'One Health' approach for turning the tide against the Middle East respiratory syndrome coronavirus and other zoonotic pathogens with epidemic potential.

PubMed

Zumla, Alimuddin; Dar, Osman; Kock, Richard; Muturi, Matthew; Ntoumi, Francine; Kaleebu, Pontiano; Eusebio, Macete; Mfinanga, Sayoki; Bates, Matthew; Mwaba, Peter; Ansumana, Rashid; Khan, Mishal; Alagaili, Abdulaziz N; Cotten, Matthew; Azhar, Esam I; Maeurer, Markus; Ippolito, Giuseppe; Petersen, Eskild

2016-06-01

The appearance of novel pathogens of humans with epidemic potential and high mortality rates have threatened global health security for centuries. Over the past few decades new zoonotic infectious diseases of humans caused by pathogens arising from animal reservoirs have included West Nile virus, Yellow fever virus, Ebola virus, Nipah virus, Lassa Fever virus, Hanta virus, Dengue fever virus, Rift Valley fever virus, Crimean-Congo haemorrhagic fever virus, severe acute respiratory syndrome coronavirus, highly pathogenic avian influenza viruses, Middle East Respiratory Syndrome Coronavirus, and Zika virus. The recent Ebola Virus Disease epidemic in West Africa and the ongoing Zika Virus outbreak in South America highlight the urgent need for local, regional and international public health systems to be be more coordinated and better prepared. The One Health concept focuses on the relationship and interconnectedness between Humans, Animals and the Environment, and recognizes that the health and wellbeing of humans is intimately connected to the health of animals and their environment (and vice versa). Critical to the establishment of a One Health platform is the creation of a multidisciplinary team with a range of expertise including public health officers, physicians, veterinarians, animal husbandry specialists, agriculturalists, ecologists, vector biologists, viral phylogeneticists, and researchers to co-operate, collaborate to learn more about zoonotic spread between animals, humans and the environment and to monitor, respond to and prevent major outbreaks. We discuss the unique opportunities for Middle Eastern and African stakeholders to take leadership in building equitable and effective partnerships with all stakeholders involved in human and health systems to take forward a 'One Health' approach to control such zoonotic pathogens with epidemic potential. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The Naval Health Research Center Respiratory Disease Laboratory.

PubMed

Ryan, M; Gray, G; Hawksworth, A; Malasig, M; Hudspeth, M; Poddar, S

2000-07-01

Concern about emerging and reemerging respiratory pathogens prompted the development of a respiratory disease reference laboratory at the Naval Health Research Center. Professionals working in this laboratory have instituted population-based surveillance for pathogens that affect military trainees and responded to threats of increased respiratory disease among high-risk military groups. Capabilities of this laboratory that are unique within the Department of Defense include adenovirus testing by viral shell culture and microneutralization serotyping, influenza culture and hemagglutination inhibition serotyping, and other special testing for Streptococcus pneumoniae, Streptococcus pyogenes, Mycoplasma pneumonia, and Chlamydia pneumoniae. Projected capabilities of this laboratory include more advanced testing for these pathogens and testing for other emerging pathogens, including Bordetella pertussis, Legionella pneumoniae, and Haemophilus influenzae type B. Such capabilities make the laboratory a valuable resource for military public health.

Concurrent infection with porcine reproductive and respiratory syndrome virus and Haemophilus parasuis in two types of porcine macrophages: apoptosis, production of ROS and formation of multinucleated giant cells.

PubMed

Kavanová, Lenka; Matiašková, Katarína; Levá, Lenka; Štěpánová, Hana; Nedbalcová, Kateřina; Matiašovic, Ján; Faldyna, Martin; Salát, Jiří

2017-05-04

Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant and economically important infectious diseases affecting swine worldwide and can predispose pigs to secondary bacterial infections caused by, e.g. Haemophilus parasuis. The aim of the presented study was to compare susceptibility of two different types of macrophages which could be in contact with both pathogens during infection with PRRS virus (PRRSV) and in co-infection with H. parasuis. Alveolar macrophages (PAMs) as resident cells provide one of the first lines of defence against microbes invading lung tissue. On the other hand, monocyte derived macrophages (MDMs) represent inflammatory cells accumulating at the site of inflammation. While PAMs were relatively resistant to cytopathogenic effect caused by PRRSV, MDMs were much more sensitive to PRRSV infection. MDMs infected with PRRSV increased expression of pro-apoptotic Bad, Bax and p53 mRNA. Increased mortality of MDMs may be also related to a higher intensity of ROS production after infection with PRRSV. In addition, MDMs (but not PAMs) infected with H. parasuis alone formed multinucleated giant cells (MGC); these cells were not observed in MDMs infected with both pathogens. Higher sensitivity of MDMs to PRRSV infection, which is associated with limited MDMs survival and restriction of MGC formation, could contribute to the development of multifactorial respiratory disease of swine.

Successful topical respiratory tract immunization of primates against Ebola virus.

PubMed

Bukreyev, Alexander; Rollin, Pierre E; Tate, Mallory K; Yang, Lijuan; Zaki, Sherif R; Shieh, Wun-Ju; Murphy, Brian R; Collins, Peter L; Sanchez, Anthony

2007-06-01

Ebola virus causes outbreaks of severe viral hemorrhagic fever with high mortality in humans. The virus is highly contagious and can be transmitted by contact and by the aerosol route. These features make Ebola virus a potential weapon for bioterrorism and biological warfare. Therefore, a vaccine that induces both systemic and local immune responses in the respiratory tract would be highly beneficial. We evaluated a common pediatric respiratory pathogen, human parainfluenza virus type 3 (HPIV3), as a vaccine vector against Ebola virus. HPIV3 recombinants expressing the Ebola virus (Zaire species) surface glycoprotein (GP) alone or in combination with the nucleocapsid protein NP or with the cytokine adjuvant granulocyte-macrophage colony-stimulating factor were administered by the respiratory route to rhesus monkeys--in which HPIV3 infection is mild and asymptomatic--and were evaluated for immunogenicity and protective efficacy against a highly lethal intraperitoneal challenge with Ebola virus. A single immunization with any construct expressing GP was moderately immunogenic against Ebola virus and protected 88% of the animals against severe hemorrhagic fever and death caused by Ebola virus. Two doses were highly immunogenic, and all of the animals survived challenge and were free of signs of disease and of detectable Ebola virus challenge virus. These data illustrate the feasibility of immunization via the respiratory tract against the hemorrhagic fever caused by Ebola virus. To our knowledge, this is the first study in which topical immunization through respiratory tract achieved prevention of a viral hemorrhagic fever infection in a primate model.

Comparison of Luminex NxTAG Respiratory Pathogen Panel and xTAG Respiratory Viral Panel FAST Version 2 for the Detection of Respiratory Viruses

PubMed Central

Lee, Chun Kiat; Lee, Hong Kai; Ng, Christopher Wei Siong; Chiu, Lily; Tang, Julian Wei-Tze; Loh, Tze Ping

2017-01-01

Owing to advancements in molecular diagnostics, recent years have seen an increasing number of laboratories adopting respiratory viral panels to detect respiratory pathogens. In December 2015, the NxTAG respiratory pathogen panel (NxTAG RPP) was approved by the United States Food and Drug Administration. We compared the clinical performance of this new assay with that of the xTAG respiratory viral panel (xTAG RVP) FAST v2 using 142 clinical samples and 12 external quality assessment samples. Discordant results were resolved by using a laboratory-developed respiratory viral panel. The NxTAG RPP achieved 100% concordant negative results and 86.6% concordant positive results. It detected one coronavirus 229E and eight influenza A/H3N2 viruses that were missed by the xTAG RVP FAST v2. On the other hand, the NxTAG RPP missed one enterovirus/rhinovirus and one metapneumovirus that were detected by FAST v2. Both panels correctly identified all the pathogens in the 12 external quality assessment samples. Overall, the NxTAG RPP demonstrated good diagnostic performance. Of note, it was better able to subtype the influenza A/H3N2 viruses compared with the xTAG RVP FAST v2. PMID:28224774

Acute Respiratory Infections in Travelers Returning from MERS-CoV–Affected Areas

PubMed Central

Olsha, Romy; Kristjanson, Erik; Marchand-Austin, Alex; Peci, Adriana; Winter, Anne-Luise; Gubbay, Jonathan B.

2015-01-01

We examined which respiratory pathogens were identified during screening for Middle East respiratory syndrome coronavirus in 177 symptomatic travelers returning to Ontario, Canada, from regions affected by the virus. Influenza A and B viruses (23.1%) and rhinovirus (19.8%) were the most common pathogens identified among these travelers. PMID:26291541

Chlamydia Infection Across Host Species Boundaries Promotes Distinct Sets of Transcribed Anti-Apoptotic Factors

PubMed Central

Messinger, Joshua E.; Nelton, Emmalin; Feeney, Colleen; Gondek, David C.

2015-01-01

Chlamydiae, obligate intracellular bacteria, cause significant human and veterinary associated diseases. Having emerged an estimated 700-million years ago, these bacteria have twice adapted to humans as a host species, causing sexually transmitted infection (C. trachomatis) and respiratory associated disease (C. pneumoniae). The principle mechanism of host cell defense against these intracellular bacteria is the induction of cell death via apoptosis. However, in the “arms race” of co-evolution, Chlamydiae have developed mechanisms to promote cell viability and inhibit cell death. Herein we examine the impact of Chlamydiae infection across multiple host species on transcription of anti-apoptotic genes. We found mostly distinct patterns of gene expression (Mcl1 and cIAPs) elicited by each pathogen-host pair indicating Chlamydiae infection across host species boundaries does not induce a universally shared host response. Understanding species specific host-pathogen interactions is paramount to deciphering how potential pathogens become emerging diseases. PMID:26779446

Causes of Pneumonia Epizootics among Bighorn Sheep, Western United States, 2008–2010

PubMed Central

Highland, Margaret A.; Baker, Katherine; Cassirer, E. Frances; Anderson, Neil J.; Ramsey, Jennifer M.; Mansfield, Kristin; Bruning, Darren L.; Wolff, Peregrine; Smith, Joshua B.; Jenks, Jonathan A.

2012-01-01

Epizootic pneumonia of bighorn sheep is a devastating disease of uncertain etiology. To help clarify the etiology, we used culture and culture-independent methods to compare the prevalence of the bacterial respiratory pathogens Mannheimia haemolytica, Bibersteinia trehalosi, Pasteurella multocida, and Mycoplasma ovipneumoniae in lung tissue from 44 bighorn sheep from herds affected by 8 outbreaks in the western United States. M. ovipneumoniae, the only agent detected at significantly higher prevalence in animals from outbreaks (95%) than in animals from unaffected healthy populations (0%), was the most consistently detected agent and the only agent that exhibited single strain types within each outbreak. The other respiratory pathogens were frequently but inconsistently detected, as were several obligate anaerobic bacterial species, all of which might represent secondary or opportunistic infections that could contribute to disease severity. These data provide evidence that M. ovipneumoniae plays a primary role in the etiology of epizootic pneumonia of bighorn sheep. PMID:22377321

Modulating airway defenses against microbes.

PubMed

Reynolds, Herbert Y

2002-05-01

Prevention and treatment of respiratory infections remain an important health care challenge as the US population ages, contains more susceptible or high-risk people, and encounters new pathogens or antibiotic resistant bacteria. Reasonably protective vaccines against very common microbes are available for childhood and adult immunization, but, generally, these are underutilized. A broader definition of higher risk individuals is evolving, which will include more for immunization. Different approaches to vaccine development through design of new component vaccines are necessary. This review has updated host defense mechanisms at three levels in the human respiratory tract: naso-oropharynx (upper airways), conducting airways, and alveolar space. Examples of representative pathogenic microbes have been inserted at the respective airway segment where they may colonize or create infection (influenza, measles virus, Porphyromonas gingivalis causing periodontitis, Bordetella pertussis, Chlamydia pneumoniae, Streptococcus pneumoniae, and Bacillus anthracis ). Hopefully, microbe-host interactions will suggest new approaches for preventing these kinds of infections.

The impact of commercial rapid respiratory virus diagnostic tests on patient outcomes and health system utilization.

PubMed

Ko, Fiona; Drews, Steven J

2017-10-01

Acute respiratory tract infections due to influenza A/B and respiratory syncytial virus (RSV) are major causes of morbidity and mortality globally. Rapid tests for detection of these pathogens include antigen detection point of care tests (POC) and newer easy to use molecular tests. From experience, these assays improve both laboratory workflow and assay interpretation issues. However, the question of the benefits of using rapid test technology compared to routine laboratory testing for respiratory viral pathogens is still often asked. Areas covered: Specifically, this review aims to; 1) identify clinical/patient indicators that can be measured prior to and following the implementation of rapid diagnostic test for influenza and RSV, 2) provide multiple perspectives on the extent of impact of a rapid diagnostic test, including direct and indirect outcomes, and 3) identify the technological advancements in the development of rapid testing, demonstrating a timeline that transitions from antigen-based assays to molecular assays. Expert commentary: Key benefits to the use of either antigen-based or molecular rapid tests for patient care, patient flow within institutions, as well as laboratory utilization are identified. Due to improved test characteristics, the authors feel that rapid molecular tests have greater benefits than antigen-based detection methods.

Interaction of SARS and MERS Coronaviruses with the Antiviral Interferon Response.

PubMed

Kindler, E; Thiel, V; Weber, F

2016-01-01

Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are the most severe coronavirus (CoV)-associated diseases in humans. The causative agents, SARS-CoV and MERS-CoV, are of zoonotic origin but may be transmitted to humans, causing severe and often fatal respiratory disease in their new host. The two coronaviruses are thought to encode an unusually large number of factors that allow them to thrive and replicate in the presence of efficient host defense mechanisms, especially the antiviral interferon system. Here, we review the recent progress in our understanding of the strategies that highly pathogenic coronaviruses employ to escape, dampen, or block the antiviral interferon response in human cells. © 2016 Elsevier Inc. All rights reserved.

The clinical features of respiratory infections caused by the Streptococcus anginosus group.

PubMed

Noguchi, Shingo; Yatera, Kazuhiro; Kawanami, Toshinori; Yamasaki, Kei; Naito, Keisuke; Akata, Kentaro; Shimabukuro, Ikuko; Ishimoto, Hiroshi; Yoshii, Chiharu; Mukae, Hiroshi

2015-10-26

The Streptococcus anginosus group (SAG) play important roles in respiratory infections. It is ordinarily difficult to distinguish them from contaminations as the causative pathogens of respiratory infections because they are often cultured in respiratory specimens. Therefore, it is important to understand the clinical characteristics and laboratory findings of respiratory infections caused by the SAG members. The aim of this study is to clarify the role of the SAG bacteria in respiratory infections. A total of 30 patients who were diagnosed with respiratory infections which were caused by the SAG bacteria between January 2005 and February 2015 were retrospectively evaluated. Respiratory infections caused by the SAG were mostly seen in male patients with comorbid diseases and were typically complicated with pleural effusion. Pleural effusion was observed in 22 (73.3%) patients. Empyema was observed in half of the 22 patients with pleural effusion. S. intermedius, S. constellatus and S. anginosus were detected in 16 (53.3 %), 11 (36.7 %) and 3 (10.0 %) patients, respectively. Six patients had mixed-infections. The duration from the onset of symptoms to the hospital visit was significantly longer in "lung abscess" patients than in "pneumonia" patients among the 24 patients with single infections, but not among the six patients with mixed-infection. The peripheral white blood cell counts of the "pneumonia" patients were higher than those of the "lung abscess" patients and S. intermedius was identified significantly more frequently in patients with pulmonary and pleural infections (pneumonia and lung abscess) than in patients with bacterial pleurisy only. In addition, the patients in whom S. intermedius was cultured were significantly older than those in whom S. constellatus was cultured. Respiratory infections caused by the SAG bacteria tended to be observed more frequently in male patients with comorbid diseases and to more frequently involve purulent formation. In addition, S. intermedius was mainly identified in elderly patients with having pulmonary infection complicated with pleural effusion, and the aspiration of oral secretions may be a risk factor in the formation of empyema thoracis associated with pneumonia due to S. intermedius.

Enhancement of innate immunity with granulocyte colony-stimulating factor did not mitigate disease in pigs infected with a highly pathogenic Chinese PRRSV strain

USDA-ARS?s Scientific Manuscript database

Porcine reproductive and respiratory syndrome virus (PRRSV) is responsible for one of the most economically important diseases in swine worldwide. It causes reproductive failure in sows and pneumonia in pigs that predisposes them to secondary bacterial infections. Methods to control PRRSV and/or lim...

Viral etiology, seasonality and severity of hospitalized patients with severe acute respiratory infections in the Eastern Mediterranean Region, 2007–2014

PubMed Central

Dueger, Erica L.; Kandeel, Amr; Abdallat, Mohamed; El-Kholy, Amani; Al-Awaidy, Salah; Kohlani, Abdul Hakim; Amer, Hanaa; El-Khal, Abel Latif; Said, Mayar; House, Brent; Pimentel, Guillermo; Talaat, Maha

2017-01-01

Introduction Little is known about the role of viral respiratory pathogens in the etiology, seasonality or severity of severe acute respiratory infections (SARI) in the Eastern Mediterranean Region. Methods Sentinel surveillance for SARI was conducted from December 2007 through February 2014 at 20 hospitals in Egypt, Jordan, Oman, Qatar and Yemen. Nasopharyngeal and oropharyngeal swabs were collected from hospitalized patients meeting SARI case definitions and were analyzed for infection with influenza, respiratory syncytial virus (RSV), adenovirus (AdV), human metapneumovirus (hMPV) and human parainfluenza virus types 1–3 (hPIV1-3). We analyzed surveillance data to calculate positivity rates for viral respiratory pathogens, describe the seasonality of those pathogens and determine which pathogens were responsible for more severe outcomes requiring ventilation and/or intensive care and/or resulting in death. Results At least one viral respiratory pathogen was detected in 8,753/28,508 (30.7%) samples tested for at least one pathogen and 3,497/9,315 (37.5%) of samples tested for all pathogens–influenza in 3,345/28,438 (11.8%), RSV in 3,942/24,503 (16.1%), AdV in 923/9,402 (9.8%), hMPV in 617/9,384 (6.6%), hPIV1 in 159/9,402 (1.7%), hPIV2 in 85/9,402 (0.9%) and hPIV3 in 365/9,402 (3.9%). Multiple pathogens were identified in 501/9,316 (5.4%) participants tested for all pathogens. Monthly variation, indicating seasonal differences in levels of infection, was observed for all pathogens. Participants with hMPV infections and participants less than five years of age were significantly less likely than participants not infected with hMPV and those older than five years of age, respectively, to experience a severe outcome, while participants with a pre-existing chronic disease were at increased risk of a severe outcome, compared to those with no reported pre-existing chronic disease. Conclusions Viral respiratory pathogens are common among SARI patients in the Eastern Mediterranean Region. Ongoing surveillance is important to monitor changes in the etiology, seasonality and severity of pathogens of interest. PMID:28704440

Prevalence and clinical significance of respiratory viruses and bacteria detected in tuberculosis patients compared to household contact controls in Tanzania: a cohort study.

PubMed

Mhimbira, F; Hiza, H; Mbuba, E; Hella, J; Kamwela, L; Sasamalo, M; Ticlla, M; Said, K; Mhalu, G; Chiryamkubi, M; Schindler, C; Reither, K; Gagneux, S; Fenner, L

2018-03-23

To describe the prevalence of respiratory pathogens in tuberculosis (TB) patients and in their household contact controls, and to determine the clinical significance of respiratory pathogens in TB patients. We studied 489 smear-positive adult TB patients and 305 household contact controls without TB with nasopharyngeal swab samples within an ongoing prospective cohort study in Dar es Salaam, Tanzania, between 2013 and 2015. We used multiplex real-time PCR to detect 16 respiratory viruses and seven bacterial pathogens from nasopharyngeal swabs. The median age of the study participants was 33 years; 61% (484/794) were men, and 21% (168/794) were HIV-positive. TB patients had a higher prevalence of HIV (28.6%; 140/489) than controls (9.2%; 28/305). Overall prevalence of respiratory viral pathogens was 20.4% (160/794; 95%CI 17.7-23.3%) and of bacterial pathogens 38.2% (303/794; 95%CI 34.9-41.6%). TB patients and controls did not differ in the prevalence of respiratory viruses (Odds Ratio [OR] 1.00, 95%CI 0.71-1.44), but respiratory bacteria were less frequently detected in TB patients (OR 0.70, 95%CI 0.53-0.94). TB patients with both respiratory viruses and respiratory bacteria were likely to have more severe disease (adjusted OR [aOR] 1.6, 95%CI 1.1-2.4; p 0.011). TB patients with respiratory viruses tended to have more frequent lung cavitations (aOR 1.6, 95%CI 0.93-2.7; p 0.089). Respiratory viruses are common for both TB patients and household controls. TB patients may present with more severe TB disease, particularly when they are co-infected with both bacteria and viruses. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Pathogens, patterns of pneumonia, and epidemiologic risk factors associated with respiratory disease in recently weaned cattle in Ireland.

PubMed

Murray, Gerard M; More, Simon J; Sammin, Dónal; Casey, Mìcheàl J; McElroy, Máire C; O'Neill, Rónan G; Byrne, William J; Earley, Bernadette; Clegg, Tracy A; Ball, Hywel; Bell, Colin J; Cassidy, Joseph P

2017-01-01

We examined the pathogens, morphologic patterns, and risk factors associated with bovine respiratory disease (BRD) in 136 recently weaned cattle ("weanlings"), 6-12 mo of age, that were submitted for postmortem examination to regional veterinary laboratories in Ireland. A standardized sampling protocol included routine microbiologic investigations as well as polymerase chain reaction and immunohistochemistry. Lungs with histologic lesions were categorized into 1 of 5 morphologic patterns of pneumonia. Fibrinosuppurative bronchopneumonia (49%) and interstitial pneumonia (48%) were the morphologic patterns recorded most frequently. The various morphologic patterns of pulmonary lesions suggest the involvement of variable combinations of initiating and compounding infectious agents that hindered any simple classification of the etiopathogenesis of the pneumonias. Dual infections were detected in 58% of lungs, with Mannheimia haemolytica and Histophilus somni most frequently recorded in concert. M. haemolytica (43%) was the most frequently detected respiratory pathogen; H. somni was also shown to be frequently implicated in pneumonia in this age group of cattle. Bovine parainfluenza virus 3 (BPIV-3) and Bovine respiratory syncytial virus (16% each) were the viral agents detected most frequently. Potential respiratory pathogens (particularly Pasteurella multocida, BPIV-3, and H. somni) were frequently detected (64%) in lungs that had neither gross nor histologic pulmonary lesions, raising questions regarding their role in the pathogenesis of BRD. The breadth of respiratory pathogens detected in bovine lungs by various detection methods highlights the diagnostic value of parallel analyses in respiratory disease postmortem investigation.

Etiology, seasonality, and clinical characterization of viral respiratory infections among hospitalized children in Beirut, Lebanon.

PubMed

Finianos, Mayda; Issa, Randi; Curran, Martin D; Afif, Claude; Rajab, Maryam; Irani, Jihad; Hakimeh, Noha; Naous, Amal; Hajj, Marie-Joelle; Hajj, Pierre; El Jisr, Tamima; El Chaar, Mira

2016-11-01

Acute respiratory tract viral infections occur worldwide and are one of the major global burdens of diseases in children. The aim of this study was to determine the viral etiology of respiratory infections in hospitalized children, to understand the viral seasonality in a major Lebanese hospital, and to correlate disease severity and the presence of virus. Over a 1-year period, nasal and throat swabs were collected from 236 pediatric patients, aged 16-year old or less and hospitalized for acute respiratory illness. Samples collected were tested for the presence of 17 respiratory viruses using multiplex real-time RT-PCR. Pathogens were identified in 165 children (70%) and were frequently observed during fall and winter seasons. Co-infection was found in 37% of positive samples. The most frequently detected pathogens were human Rhinovirus (hRV, 23%), Respiratory Syncytial Virus (RSV, 19%), human Bocavirus (hBov, 15%), human Metapneumovirus (hMPV, 10%), and human Adenovirus (hAdV, 10%). A total of 48% of children were diagnosed with bronchiolitis and 25% with pneumonia. While bronchiolitis was often caused by RSV single virus infection and hAdV/hBoV coinfection, pneumonia was significantly associated with hBoV and HP1V1 infections. No significant correlation was observed between a single viral etiology infection and a specific clinical symptom. This study provides relevant facts on the circulatory pattern of respiratory viruses in Lebanon and the importance of using PCR as a useful tool for virus detection. Early diagnosis at the initial time of hospitalization may reduce the spread of the viruses in pediatric units. J. Med. Virol. 88:1874-1881, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Herpes simplex type 1 pneumonitis and acute respiratory distress syndrome in a patient with chronic lymphatic leukemia: a case report.

PubMed

Luginbuehl, Miriam; Imhof, Alexander; Klarer, Alexander

2017-11-23

Pulmonary pathogenicity of herpes simplex virus type 1 in patients in intensive care without classic immunosuppression as well as the necessity of antiviral treatment in the case of herpes simplex virus detection in respiratory specimens in these patients is controversial. We present a case of acute respiratory distress syndrome in a patient with stable chronic lymphatic leukemia not requiring treatment, in whom we diagnosed herpes simplex virus type 1 bronchopneumonitis based on herpes simplex virus type 1 detection in bronchoalveolar lavage fluid and clinical response to antiviral treatment. A 72-year-old white man presented with symptoms of lower respiratory tract infection. His medical history was significant for chronic lymphatic leukemia, which had been stable without treatment, arterial hypertension, multiple squamous cell carcinomas of the scalp, and alcohol overuse. Community-acquired pneumonia was suspected and appropriate broad-spectrum antibacterial treatment was initiated. Within a few hours, rapid respiratory deterioration led to cardiac arrest. He was successfully resuscitated, but developed acute respiratory distress syndrome. Furthermore, he remained febrile and inflammation markers remained elevated despite antibacterial treatment. Polymerase chain reaction from bronchoalveolar lavage fluid and viral culture from tracheobronchial secretions tested positive for herpes simplex virus type 1. We initiated antiviral treatment with acyclovir. Concomitantly we further escalated the antibacterial treatment, although no bacterial pathogen had been isolated at any point. Defervescence occurred rapidly and his C-reactive protein and leukocyte levels decreased. He was successfully weaned from mechanical ventilation, transferred to the ward, and eventually discharged to home. Herpes simplex virus should be considered a cause for lower respiratory tract infection in critically ill patients, especially in the setting of an underlying disease.

Haemophilus influenzae and the lung (Haemophilus and the lung)

PubMed Central

2012-01-01

Haemophilus influenzae is present as a commensal organism in the nasopharynx of most healthy adults from where it can spread to cause both systemic and respiratory tract infection. This bacterium is divided into typeable forms (such as type b) or nontypeable forms based on the presence or absence of a tough polysaccharide capsule. Respiratory disease is predominantly caused by the nontypeable forms (NTHi). Haemophilus influenzae has evolved a number of strategies to evade the host defense including the ability to invade into local tissue. Pathogenic properties of this bacterium as well as defects in host defense may result in the spread of this bacterium from the upper airway to the bronchi of the lung. This can result in airway inflammation and colonization particularly in chronic obstructive pulmonary disease. Treatment of respiratory tract infection with Haemophilus influenzae is often only partially successful with ongoing infection and inflammation. Improvement in patient outcome will be dependent on a better understanding of the pathogenesis and host immune response to this bacterium. PMID:23369277

Respiratory pathogens mediate the association between lung function and temperature in cystic fibrosis.

PubMed

Collaco, Joseph M; Raraigh, Karen S; Appel, Lawrence J; Cutting, Garry R

2016-11-01

Mean annual ambient temperature is a replicated environmental modifier of cystic fibrosis (CF) lung disease with warmer temperatures being associated with lower lung function. The mechanism of this relationship is not completely understood. However, Pseudomonas aeruginosa, a pathogen that infects the lungs of CF individuals and decreases lung function, also has a higher prevalence in individuals living in warmer climates. We therefore investigated the extent to which respiratory pathogens mediated the association between temperature and lung function. Thirteen respiratory pathogens observed on CF respiratory cultures were assessed in multistep fashion using clustered linear and logistic regression to determine if any mediated the association between temperature and lung function. Analysis was performed in the CF Twin-Sibling Study (n=1730; primary population); key findings were then evaluated in the U.S. CF Foundation Data Registry (n=15,174; replication population). In the primary population, three respiratory pathogens (P. aeruginosa, mucoid P. aeruginosa, and methicillin-resistant Staphylococcus aureus) mediated the association between temperature and lung function. P. aeruginosa accounted for 19% of the association (p=0.003), mucoid P. aeruginosa for 31% (p=0.001), and MRSA for 13% (p=0.023). The same three pathogens mediated association in the replication population (7%, p<0.001; 7%, p=0.002; and 4%, (p=0.002), respectively). Three important respiratory pathogens in CF mediate the association between lower lung function and warmer temperatures. These findings have implications for understanding regional variations in clinical outcomes, and interpreting results of epidemiologic studies and clinical trials that encompass regions with different ambient temperatures. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Highly pathogenic avian influenza.

PubMed

Swayne, D E; Suarez, D L

2000-08-01

Highly pathogenic (HP) avian influenza (AI) (HPAI) is an extremely contagious, multi-organ systemic disease of poultry leading to high mortality, and caused by some H5 and H7 subtypes of type A influenza virus, family Orthomyxoviridae. However, most AI virus strains are mildly pathogenic (MP) and produce either subclinical infections or respiratory and/or reproductive diseases in a variety of domestic and wild bird species. Highly pathogenic avian influenza is a List A disease of the Office International des Epizooties, while MPAI is neither a List A nor List B disease. Eighteen outbreaks of HPAI have been documented since the identification of AI virus as the cause of fowl plague in 1955. Mildly pathogenic avian influenza viruses are maintained in wild aquatic bird reservoirs, occasionally crossing over to domestic poultry and causing outbreaks of mild disease. Highly pathogenic avian influenza viruses do not have a recognised wild bird reservoir, but can occasionally be isolated from wild birds during outbreaks in domestic poultry. Highly pathogenic avian influenza viruses have been documented to arise from MPAI viruses through mutations in the haemagglutinin surface protein. Prevention of exposure to the virus and eradication are the accepted methods for dealing with HPAI. Control programmes, which imply allowing a low incidence of infection, are not an acceptable method for managing HPAI, but have been used during some outbreaks of MPAI. The components of a strategy to deal with MPAI or HPAI include surveillance and diagnosis, biosecurity, education, quarantine and depopulation. Vaccination has been used in some control and eradication programmes for AI.

Development and Function of the Mucosal Immune System in the Upper Respiratory Tract of Neonatal Calves.

PubMed

Osman, Rahwa; Malmuthuge, Nilusha; Gonzalez-Cano, Patricia; Griebel, Philip

2018-02-15

Respiratory infections remain the second most common cause of clinical disease and mortality in newborn calves, which has led to increased interest in using vaccines early in life to mitigate this risk. Intranasal vaccination of neonatal calves can be an effective strategy to circumvent vaccine interference by maternal antibody, but this raises questions regarding onset of immune competence in the upper respiratory tract (URT) following birth. Little is known, however, about the development and function of mucosa-associated lymphoid tissue (MALT) in the URT of newborn calves and what factors, including the commensal microbiome, contribute to this early development. We review the structure, development, and function of MALT in the bovine URT during the first six weeks of life and identify knowledge gaps regarding this early developmental time. This information is critical when designing vaccination programs for young calves, especially when targeting respiratory pathogens that may reside within the commensal microbiome.

Respiratory syncytial virus and influenza are the key viral pathogens in children <2 years hospitalized with bronchiolitis and pneumonia in Islamabad Pakistan.

PubMed

Bashir, Uzma; Nisar, Nadia; Arshad, Yasir; Alam, Muhammad Masroor; Ashraf, Asiya; Sadia, Hajra; Kazi, Birjees Mazher; Zaidi, Syed Sohail Zahoor

2017-03-01

Pneumonia remains a leading cause of morbidity and mortality in developing countries. Comprehensive surveillance data are needed to review the prevention and control strategies. We conducted active surveillance of acute lower respiratory infections among children aged <2 years hospitalized at two hospitals of Islamabad, Pakistan. Viral etiology was determined using real-time PCR on respiratory specimens collected during March 2011-April 2012. The overall mean age was 7.83 ± 5.25 months while no statistical difference between age or sex distribution of patients with positive and negative viral etiology (p > 0.05). The average weight of the study group was 6.1 ± 2.25 kg. ≥1 viral pathogens were detected in 75% cases. Major respiratory viruses included RSV-A: 44%, RSV-B: 23%, Influenza-A: 24.5%, Influenza-B: 7%, Adenovirus: 8.4% and HmPV: 5.2%. A single, dual or multiple viral pathogens were detected in 43%, 27% and 5.2% patients respectively. Common symptoms were cough (95%), apnoea (84%), fever (78%), wheeze (64.5%), nasal congestion (55%) and rhinorrhea (48%). Among the RSV positive cases, 2-6 months age group had highest detection rate for RSV-A (30%, n = 21/69) and RSV-B (20%, n = 14/69) while patients infected with Influenza-A were in 2.1-6 months age group (61%, 23/38). Statistically significant difference was observed between RSV-positive and negative cases for nutrition status (p = 0.001), cigarette/wood smoke exposure (p = 0.001) and concomitant clinical findings. Most patients had successful outcome on combination therapy with bronchodilators, inhaled steroids and antibiotics. Our findings underscore high burden of ALRI in Pakistan. Interventions targeting viral pathogens coupled with improved diagnostic approaches are critical for better prevention and control.

Seasonal variations of respiratory viruses detected from children with respiratory tract infections in Riyadh, Saudi Arabia.

PubMed

Albogami, Saad S; Alotaibi, Meshal R; Alsahli, Saud A; Masuadi, Emad; Alshaalan, Mohammad

ARTIs have a huge impact in health systems in which 20-30% of all hospital admissions and 30-60% of practitioner visits are related to respiratory tract infections. The aim of this study is to determine the prevalence, age distribution, and seasonal variation of respiratory viruses. This study was descriptive retrospective study in which all patients 14 years of age and below who presented with signs and symptoms of ARTIs between January 2013 and December 2014 and had respiratory specimen tested by direct immunofluorescence assays for viruses identification were included in the study. During that period, a total of 4611 patients who presented with ARTIs from January 2013 to December 2014 were investigated, viruses were detected in 1115 (24%). RSV was associated with 97.4% of the total viral pathogens. Viruses were detected throughout all the two years with a peak in winter; Dec (n: 265), Jan (n: 418), Feb (n: 218), and Mar (n: 109). Viral pathogens are very important cause of ARTIs in our region. RSV was the most common virus detected with the highest detection rate in children who are two years old and below. A multi-center surveillance with more sensitive detection methods like PCR may help to provide a comprehensive understanding of virus distribution in our area, which may contribute implant an effective prevention approach for each virus. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Respiratory viruses are associated with common respiratory pathogens in cystic fibrosis.

PubMed

Esther, Charles R; Lin, Feng-Chang; Kerr, Alan; Miller, Melissa B; Gilligan, Peter H

2014-09-01

Test the hypothesis that the link between respiratory viruses and pulmonary exacerbation in cystic fibrosis (CF) reflects increased frequency or severity of lower airways infection. Molecular respiratory viral panels (RVPs), cell counts, and quantitative bacterial cultures were assessed in 235 bronchoalveolar lavage fluid (BALF) samples from 138 children with CF. Relationships among the data were analyzed using multivariate methods. RVPs were positive in 67 (28.5%) BALF samples from 52 (37.7%) patients, with rhinovirus/enterovirus most common (82.4% of RVP+). RVP+ patients were younger (5.4 years, IQR 3.0-9.7 vs. 8.0 years, IQR 3.5-12.9; P < 0.01), more likely to have respiratory symptoms (74.6% vs. 55.2%, P < 0.01), and had higher BALF percent neutrophils (70.5%, IQR 46-85% vs. 59.3%, IQR 34-77%; P < 0.05). Percent predicted FEV1 at bronchoscopy was diminished from baseline in both groups, but recovered in the RVP- (90.2 ± 22.2% vs. 89.6 ± 19.7%, P = 0.62) but not the RVP+ subjects (95.7 ± 21.1% vs. 89.1 ± 18.0%, P < 0.05). RVP status did not alter recovery rates of typical CF respiratory pathogens including Staphylococcus aureus (44.8% vs. 42.9%) and Pseudomonas aeruginosa (25.4% vs. 25.6%). However, common respiratory pathogens (Haemophilus species, Moraxella species, and Streptococcus pneumoniae) were recovered more frequently from RVP+ samples independent of age (OR 3.6, 95% CI 1.8-7.5, P < 0.001). Respiratory viruses were frequently detected in BALF from CF patients and associated with markers of disease severity. Respiratory viruses did not impact frequency or severity of infection with typical CF pathogens, but rates of infection with common respiratory pathogens were increased. This finding may have treatment implications. © 2013 Wiley Periodicals, Inc.

Anti-Aspergillus Activities of the Respiratory Epithelium in Health and Disease.

PubMed

Bertuzzi, Margherita; Hayes, Gemma E; Icheoku, Uju J; van Rhijn, Norman; Denning, David W; Osherov, Nir; Bignell, Elaine M

2018-01-08

Respiratory epithelia fulfil multiple roles beyond that of gaseous exchange, also acting as primary custodians of lung sterility and inflammatory homeostasis. Inhaled fungal spores pose a continual antigenic, and potentially pathogenic, challenge to lung integrity against which the human respiratory mucosa has developed various tolerance and defence strategies. However, respiratory disease and immune dysfunction frequently render the human lung susceptible to fungal diseases, the most common of which are the aspergilloses, a group of syndromes caused by inhaled spores of Aspergillus fumigatus . Inhaled Aspergillus spores enter into a multiplicity of interactions with respiratory epithelia, the mechanistic bases of which are only just becoming recognized as important drivers of disease, as well as possible therapeutic targets. In this mini-review we examine current understanding of Aspergillus -epithelial interactions and, based upon the very latest developments in the field, we explore two apparently opposing schools of thought which view epithelial uptake of Aspergillus spores as either a curative or disease-exacerbating event.

Next Generation Respiratory Viral Vaccine System: Advanced and Emerging Bioengineered Human Lung Epithelia Model (HLEM) Organoid Technology

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.; Schneider, Sandra L.; MacIntosh, Victor; Gibbons, Thomas F.

2010-01-01

Acute respiratory infections, including pneumonia and influenza, are the S t" leading cause of United States and worldwide deaths. Newly emerging pathogens signaled the need for an advanced generation of vaccine technology.. Human bronchial-tracheal epithelial tissue was bioengineered to detect, identify, host and study the pathogenesis of acute respiratory viral disease. The 3-dimensional (3D) human lung epithelio-mesechymal tissue-like assemblies (HLEM TLAs) share characteristics with human respiratory epithelium: tight junctions, desmosomes, microvilli, functional markers villin, keratins and production of tissue mucin. Respiratory Syntial Virus (RSV) studies demonstrate viral growth kinetics and membrane bound glycoproteins up to day 20 post infection in the human lung-orgainoid infected cell system. Peak replication of RSV occurred on day 10 at 7 log10 particles forming units per ml/day. HLEM is an advanced virus vaccine model and biosentinel system for emergent viral infectious diseases to support DoD global surveillance and military readiness.

Synonymous deoptimization of the foot-and-mouth disease virus P1 coding region causes attenuation in vivo while inducing a strong neutralizing antibody response

USDA-ARS?s Scientific Manuscript database

Codon bias deoptimization has been previously used to successfully attenuate human pathogens including polio, respiratory syncytial and influenza viruses. We have applied a similar technology to deoptimize the capsid coding region (P1 region) of the cDNA infectious clone of foot-and-mouth disease vi...

Interactions of Cryptococcus with Dendritic Cells

PubMed Central

Wozniak, Karen L.

2018-01-01

The fungal pathogens Cryptococcus neoformans and Cryptococcus gattii can cause life-threatening infections in immune compromised and immune competent hosts. These pathogens enter the host via inhalation, and respiratory tract innate immune cells such as dendritic cells (DCs) are one of the first host cells they encounter. The interactions between Cryptococcus and innate immune cells play a critical role in the progression of disease in the host. This review will focus specifically on the interactions between Cryptococcus and dendritic cells (DCs), including recognition/processing by DCs, effects of immune mediators on DC recruitment and activity, and the potential for DC vaccination against cryptococcosis. PMID:29543719

Interactions of Cryptococcus with Dendritic Cells.

PubMed

Wozniak, Karen L

2018-03-15

The fungal pathogens Cryptococcus neoformans and Cryptococcus gattii can cause life-threatening infections in immune compromised and immune competent hosts. These pathogens enter the host via inhalation, and respiratory tract innate immune cells such as dendritic cells (DCs) are one of the first host cells they encounter. The interactions between Cryptococcus and innate immune cells play a critical role in the progression of disease in the host. This review will focus specifically on the interactions between Cryptococcus and dendritic cells (DCs), including recognition/processing by DCs, effects of immune mediators on DC recruitment and activity, and the potential for DC vaccination against cryptococcosis.

Severe Legionnaire's disease caused by Legionella longbeachae in a long-term renal transplant patient: the importance of safe living strategies after transplantation.

PubMed

Wright, A J; Humar, A; Gourishankar, S; Bernard, K; Kumar, D

2012-08-01

Legionella species are intracellular gram-negative bacilli that require specific culture media for growth. Transplant recipients with impaired cellular immunity are at particular risk for infection with this pathogen. Most human disease is caused by Legionella pneumophila; disease caused by non-L. pneumophila species is reported mainly in immunosuppressed patients with the exception of Legionella longbeachae. L. longbeachae is a common cause of Legionnaires' disease in Australia and New Zealand, and is associated with exposure to potting soil. We report the case of a patient, 26 years post kidney transplant, who presented with severe and rapidly progressive respiratory illness. L. longbeachae serogroup 1 was isolated from respiratory cultures. Further investigation revealed that she had significant soil exposure before the onset of illness. We highlight the importance of following safe living strategies to prevent exposure-related illness even in long-term transplant recipients. © 2012 John Wiley & Sons A/S.

KLF6 and iNOS regulates apoptosis during respiratory syncytial virus infection

PubMed Central

Mgbemena, Victoria; Segovia, Jesus; Chang, Te-Hung; Bose, Santanu

2013-01-01

Human respiratory syncytial virus (RSV) is a highly pathogenic lung-tropic virus that causes severe respiratory diseases. Enzymatic activity of inducible nitric oxide (iNOS) is required for NO generation. Although NO contributes to exaggerated lung disease during RSV infection, the role of NO in apoptosis during infection is not known. In addition, host trans-activator(s) required for iNOS gene expression during RSV infection is unknown. In the current study we have uncovered the mechanism of iNOS gene induction by identifying kruppel-like factor 6 (KLF6) as a critical transcription factor required for iNOS gene expression during RSV infection. Furthermore, we have also uncovered the role of iNOS as a critical host factor regulating apoptosis during RSV infection. PMID:23831683

Aspergillus fumigatus in Poultry

PubMed Central

Arné, Pascal; Thierry, Simon; Wang, Dongying; Deville, Manjula; Le Loc'h, Guillaume; Desoutter, Anaïs; Féménia, Françoise; Nieguitsila, Adélaïde; Huang, Weiyi; Chermette, René; Guillot, Jacques

2011-01-01

Aspergillus fumigatus remains a major respiratory pathogen in birds. In poultry, infection by A. fumigatus may induce significant economic losses particularly in turkey production. A. fumigatus develops and sporulates easily in poor quality bedding or contaminated feedstuffs in indoor farm environments. Inadequate ventilation and dusty conditions increase the risk of bird exposure to aerosolized spores. Acute cases are seen in young animals following inhalation of spores, causing high morbidity and mortality. The chronic form affects older birds and looks more sporadic. The respiratory tract is the primary site of A. fumigatus development leading to severe respiratory distress and associated granulomatous airsacculitis and pneumonia. Treatments for infected poultry are nonexistent; therefore, prevention is the only way to protect poultry. Development of avian models of aspergillosis may improve our understanding of its pathogenesis, which remains poorly understood. PMID:21826144

Effects of Human Metapneumovirus and Respiratory Syncytial Virus Antigen Insertion in Two 3′ Proximal Genome Positions of Bovine/Human Parainfluenza Virus Type 3 on Virus Replication and Immunogenicity

PubMed Central

Tang, Roderick S.; Schickli, Jeanne H.; MacPhail, Mia; Fernandes, Fiona; Bicha, Leenas; Spaete, Joshua; Fouchier, Ron A. M.; Osterhaus, Albert D. M. E.; Spaete, Richard; Haller, Aurelia A.

2003-01-01

A live attenuated bovine parainfluenza virus type 3 (PIV3), harboring the fusion (F) and hemagglutinin-neuraminidase (HN) genes of human PIV3, was used as a virus vector to express surface glycoproteins derived from two human pathogens, human metapneumovirus (hMPV) and respiratory syncytial virus (RSV). RSV and hMPV are both paramyxoviruses that cause respiratory disease in young children, the elderly, and immunocompromised individuals. RSV has been known for decades to cause acute lower respiratory tract infections in young children, which often result in hospitalization, while hMPV has only been recently identified as a novel human respiratory pathogen. In this study, the ability of bovine/human PIV3 to express three different foreign transmembrane surface glycoproteins and to induce a protective immune response was evaluated. The RNA-dependent RNA polymerase of paramyxoviruses binds to a single site at the 3′ end of the viral RNA genome to initiate transcription of viral genes. The genome position of the viral gene determines its level of gene expression. The promoter-proximal gene is transcribed with the highest frequency, and each downstream gene is transcribed less often due to attenuation of transcription at each gene junction. This feature of paramyxoviruses was exploited using the PIV3 vector by inserting the foreign viral genes at the 3′ terminus, at position 1 or 2, of the viral RNA genome. These locations were expected to yield high levels of foreign viral protein expression stimulating a protective immune response. The immunogenicity and protection results obtained with a hamster model showed that bovine/human PIV3 can be employed to generate bivalent PIV3/RSV or PIV3/hMPV vaccine candidates that will be further evaluated for safety and efficacy in primates. PMID:14512532

Insights into host-pathogen interactions from state-of-the-art animal models of respiratory Pseudomonas aeruginosa infections.

PubMed

Lorenz, Anne; Pawar, Vinay; Häussler, Susanne; Weiss, Siegfried

2016-11-01

Pseudomonas aeruginosa is an important opportunistic pathogen that can cause acute respiratory infections in immunocompetent patients or chronic infections in immunocompromised individuals and in patients with cystic fibrosis. When acquiring the chronic infection state, bacteria are encapsulated within biofilm structures enabling them to withstand diverse environmental assaults, including immune reactions and antimicrobial therapy. Understanding the molecular interactions within the bacteria, as well as with the host or other bacteria, is essential for developing innovative treatment strategies. Such knowledge might be accumulated in vitro. However, it is ultimately necessary to confirm these findings in vivo. In the present Review, we describe state-of-the-art in vivo models that allow studying P. aeruginosa infections in molecular detail. The portrayed mammalian models exclusively focus on respiratory infections. The data obtained by alternative animal models which lack lung tissue, often provide molecular insights that are easily transferable to mammals. Importantly, these surrogate in vivo systems reveal complex molecular interactions of P. aeruginosa with the host. Herein, we also provide a critical assessment of the advantages and disadvantages of such models. © 2016 Federation of European Biochemical Societies.

Microbiome in the pathogenesis of cystic fibrosis and lung transplant-related disease.

PubMed

Cribbs, Sushma K; Beck, James M

2017-01-01

Significant advances in culture-independent methods have expanded our knowledge about the diversity of the lung microbial environment. Complex microorganisms and microbial communities can now be identified in the distal airways in a variety of respiratory diseases, including cystic fibrosis (CF) and the posttransplantation lung. Although there are significant methodologic concerns about sampling the lung microbiome, several studies have now shown that the microbiome of the lower respiratory tract is distinct from the upper airway. CF is a disease characterized by chronic airway infections that lead to significant morbidity and mortality. Traditional culture-dependent methods have identified a select group of pathogens that cause exacerbations in CF, but studies using bacterial 16S rRNA gene-based microarrays have shown that the CF microbiome is an intricate and dynamic bacterial ecosystem, which influences both host immune health and disease pathogenesis. These microbial communities can shift with external influences, including antibiotic exposure. In addition, there have been a number of studies suggesting a link between the gut microbiome and respiratory health in CF. Compared with CF, there is significantly less knowledge about the microbiome of the transplanted lung. Risk factors for bronchiolitis obliterans syndrome, one of the leading causes of death, include microbial infections. Lung transplant patients have a unique lung microbiome that is different than the pretransplanted microbiome and changes with time. Understanding the host-pathogen interactions in these diseases may suggest targeted therapies and improve long-term survival in these patients. Published by Elsevier Inc.

Toll-Like Receptor 3 Signaling via TRIF Contributes to a Protective Innate Immune Response to Severe Acute Respiratory Syndrome Coronavirus Infection

PubMed Central

Totura, Allison L.; Whitmore, Alan; Agnihothram, Sudhakar; Schäfer, Alexandra; Katze, Michael G.; Heise, Mark T.

2015-01-01

ABSTRACT Toll-like receptors (TLRs) are sensors that recognize molecular patterns from viruses, bacteria, and fungi to initiate innate immune responses to invading pathogens. The emergence of highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) is a concern for global public health, as there is a lack of efficacious vaccine platforms and antiviral therapeutic strategies. Previously, it was shown that MyD88, an adaptor protein necessary for signaling by multiple TLRs, is a required component of the innate immune response to mouse-adapted SARS-CoV infection in vivo. Here, we demonstrate that TLR3−/−, TLR4−/−, and TRAM−/− mice are more susceptible to SARS-CoV than wild-type mice but experience only transient weight loss with no mortality in response to infection. In contrast, mice deficient in the TLR3/TLR4 adaptor TRIF are highly susceptible to SARS-CoV infection, showing increased weight loss, mortality, reduced lung function, increased lung pathology, and higher viral titers. Distinct alterations in inflammation were present in TRIF−/− mice infected with SARS-CoV, including excess infiltration of neutrophils and inflammatory cell types that correlate with increased pathology of other known causes of acute respiratory distress syndrome (ARDS), including influenza virus infections. Aberrant proinflammatory cytokine, chemokine, and interferon-stimulated gene (ISG) signaling programs were also noted following infection of TRIF−/− mice that were similar to those seen in human patients with poor disease outcome following SARS-CoV or MERS-CoV infection. These findings highlight the importance of TLR adaptor signaling in generating a balanced protective innate immune response to highly pathogenic coronavirus infections. PMID:26015500

Airway inflammation and upper respiratory tract infection in athletes: is there a link?

PubMed

Bermon, Stéphane

2007-01-01

Upper Respiratory Tract Infection (URTI) is regarded as the most common medical condition affecting both highly trained and elite athletes, in particular those participating in endurance events. The causes of these disturbances, also occurring during training, remain unclear. Viruses such as rhinovirus, adenovirus and para-influenza virus are frequently reported as the source of URTI. However, in a few comprehensive laboratory and epidemiological studies which reported at least a 30% incidence of URTI, no identifiable pathogens were either reported or studied. A recent, longitudinal study investigated symptomatology and pathogenic etiology in sedentary controls, recreational and elite athletes. The highest incidence of URTI occurred in elite athletes. However; only 11 out of 37 illness episodes overall had pathogenic origins, and most of the unidentified upper respiratory illnesses were shorter in duration and less severe than infectious ones. This concept of inflammation without infection in athletes is quite new and leads us to consider other explanatory pathophysiological conditions. Increases in airway neutrophils, eosinophils and lymphocytes have been described under resting conditions in endurance sports, swimmers and cross-country skiers. These inflammatory patterns may be due to pollutants or chlorine-related compounds in swimmers. After intense exercise similar airways cellular profiles have been reported, with a high amount of bronchial epithelial cells. This increase in airway inflammatory cells in athletes can result from a hyperventilation-induced increase in airway osmolarity stimulating bronchial epithelial cells to release chemotactic factors. Fortunately, in most cases, these inflammatory cells express rather low level of adhesion molecules, explaining why airway inflammation may appear blunted in athletes despite numerous inflammatory cellular elements. However it can be hypothesized that a transient loss of control of this local inflammation, due to various external physico-chemical strains, might occur. This might account for some of the unidentified upper respiratory illnesses.

Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures.

PubMed

Essaidi-Laziosi, Manel; Brito, Francisco; Benaoudia, Sacha; Royston, Léna; Cagno, Valeria; Fernandes-Rocha, Mélanie; Piuz, Isabelle; Zdobnov, Evgeny; Huang, Song; Constant, Samuel; Boldi, Marc-Olivier; Kaiser, Laurent; Tapparel, Caroline

2018-06-01

The leading cause of acute illnesses, respiratory viruses, typically cause self-limited diseases, although severe complications can occur in fragile patients. Rhinoviruses (RVs), respiratory enteroviruses (EVs), influenza virus, respiratory syncytial viruses (RSVs), and coronaviruses are highly prevalent respiratory pathogens, but because of the lack of reliable animal models, their differential pathogenesis remains poorly characterized. We sought to compare infections by respiratory viruses isolated from clinical specimens using reconstituted human airway epithelia. Tissues were infected with RV-A55, RV-A49, RV-B48, RV-C8, and RV-C15; respiratory EV-D68; influenza virus H3N2; RSV-B; and human coronavirus (HCoV)-OC43. Replication kinetics, cell tropism, effect on tissue integrity, and cytokine secretion were compared. Viral adaptation and tissue response were assessed through RNA sequencing. RVs, RSV-B, and HCoV-OC43 infected ciliated cells and caused no major cell death, whereas H3N2 and EV-D68 induced ciliated cell loss and tissue integrity disruption. H3N2 was also detected in rare goblet and basal cells. All viruses, except RV-B48 and HCoV-OC43, altered cilia beating and mucociliary clearance. H3N2 was the strongest cytokine inducer, and HCoV-OC43 was the weakest. Persistent infection was observed in all cases. RNA sequencing highlighted perturbation of tissue metabolism and induction of a transient but important immune response at 4 days after infection. No majority mutations emerged in the viral population. Our results highlight the differential in vitro pathogenesis of respiratory viruses during the acute infection phase and their ability to persist under immune tolerance. These data help to appreciate the range of disease severity observed in vivo and the occurrence of chronic respiratory tract infections in immunocompromised hosts. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Effects of Mycotoxins on Mucosal Microbial Infection and Related Pathogenesis

PubMed Central

Park, Seong-Hwan; Kim, Dongwook; Kim, Juil; Moon, Yuseok

2015-01-01

Mycotoxins are fungal secondary metabolites detected in many agricultural commodities and water-damaged indoor environments. Susceptibility to mucosal infectious diseases is closely associated with immune dysfunction caused by mycotoxin exposure in humans and other animals. Many mycotoxins suppress immune function by decreasing the proliferation of activated lymphocytes, impairing phagocytic function of macrophages, and suppressing cytokine production, but some induce hypersensitive responses in different dose regimes. The present review describes various mycotoxin responses to infectious pathogens that trigger mucosa-associated diseases in the gastrointestinal and respiratory tracts of humans and other animals. In particular, it focuses on the effects of mycotoxin exposure on invasion, pathogen clearance, the production of cytokines and immunoglobulins, and the prognostic implications of interactions between infectious pathogens and mycotoxin exposure. PMID:26529017

Comparison of the FilmArray Respiratory Panel and Prodesse Real-Time PCR Assays for Detection of Respiratory Pathogens ▿ †

PubMed Central

Loeffelholz, M. J.; Pong, D. L.; Pyles, R. B.; Xiong, Y.; Miller, A. L.; Bufton, K. K.; Chonmaitree, T.

2011-01-01

We compared the diagnostic performance and overall respiratory pathogen detection rate of the premarket version of the FilmArray Respiratory Panel (RP) multiplex PCR assay (Idaho Technology, Inc., Salt Lake City, UT) with those of the Food and Drug Administration (FDA)-cleared Prodesse ProFlu+, ProFAST+, ProParaflu+, Pro hMPV+, and ProAdeno+ real-time PCR assays (Gen-Probe, San Diego, CA). The assays were performed on a panel of 192 nasopharyngeal-secretion specimens collected from 81 children under 1 year of age with upper respiratory tract symptoms. To resolve discordant results and confirm pathogens detected only by the larger FilmArray panel, we performed laboratory-developed real-time PCR assays. Among viruses detectable by both commercial assays (adenovirus, human metapneumovirus, influenza A virus, influenza B virus, parainfluenza viruses 1 to 3, and respiratory syncytial virus), the FilmArray and Prodesse assays showed good overall agreement (181/192 [94.3%]; kappa = 0.87; 95% CI, 0.79 to 0.94). FilmArray RP detected more parainfluenza viruses 1 and 3 than ProParaflu+ (18 versus 13) while ProAdeno+ detected more adenoviruses (11 versus 6), but these differences were not statistically significant. Additionally, FilmArray RP detected 138 pathogens (confirmed as true positives) not included in the Prodesse assays (rhinovirus [RV]/enterovirus [EV], 118; bocavirus, 8; coronavirus, 7; parainfluenza virus 4, 4; Mycoplasma pneumoniae, 1). FilmArray RP was cleared by the FDA following the completion of this study. The FDA-cleared version includes the following targets: adenovirus, coronaviruses HKU1 and NL63, human metapneumovirus (hMPV), influenza A virus (to type level only), influenza A H1 seasonal virus, influenza A H3 seasonal virus, influenza A virus H1-2009, influenza B virus, parainfluenza viruses 1 to 4, respiratory syncytial virus (RSV), and RV/EV (no differentiation). The larger panel in the FilmArray RP assay allowed the detection of additional respiratory pathogens compared to the Prodesse assays. In this population of young children with upper respiratory tract infection, RV/EV accounted for the majority of the additional pathogens detected by FilmArray RP. PMID:21998418

Host specific glycans are correlated with susceptibility to infection by lagoviruses, but not with their virulence.

PubMed

Lopes, Ana M; Breiman, Adrien; Lora, Mónica; Le Moullac-Vaidye, Béatrice; Galanina, Oxana; Nyström, Kristina; Marchandeau, Stephane; Le Gall-Reculé, Ghislaine; Strive, Tanja; Neimanis, Aleksija; Bovin, Nicolai V; Ruvoën-Clouet, Nathalie; Esteves, Pedro J; Abrantes, Joana; Le Pendu, Jacques

2017-11-29

The rabbit hemorrhagic disease virus (RHDV) and the European brown hare syndrome virus (EBHSV) are two lagoviruses from the family Caliciviridae that cause fatal diseases in two leporid genera, Oryctolagus and Lepus , respectively. In the last few years, several examples of host jumps of lagoviruses among leporids were recorded. In addition, a new pathogenic genotype of RHDV emerged and many non-pathogenic strains of lagoviruses have been described. The molecular mechanisms behind host shifts and the emergence of virulence are unknown. Since RHDV uses glycans of the histo-blood group antigen type as attachment factors to initiate infection, we studied if glycan specificities of the new pathogenic RHDV genotype, non-pathogenic lagoviruses and EBHSV potentially play a role in determining host range and virulence of lagoviruses. We observed binding to A, B or H antigens of the histo-blood group family for all strains known to primarily infect European rabbits ( Oryctolagus cuniculus ), that have recently been classified as GI strains. Yet, we could not explain the emergence of virulence since similar glycan specificities were found between several pathogenic and non-pathogenic strains. By contrast, EBHSV, recently classified as GII.1, bound to terminal β-linked N-acetylglucosamine residues of O-glycans. Expression of these attachment factors in the upper respiratory and digestive tracts in three lagomorph species ( Oryctolagus cuniculus, Lepus europaeus and Sylvilagus floridanus ) showed species-specific patterns regarding the susceptibility to infection by these viruses, indicating that species-specific glycan expression is likely a major contributor to lagoviruses host specificity and range. IMPORTANCE Lagoviruses constitute a genus of the Caliciviridae family, comprising highly pathogenic viruses, RHDV and EBHSV, which infect rabbits and hares, respectively. Recently, non-pathogenic strains were discovered and new pathogenic strains have emerged. In addition, host jumps between lagomorphs are observed. The mechanisms responsible for the emergence of pathogenicity and host-species range are unknown. Previous studies showed that RHDV strains attach to glycans expressed in the upper respiratory and digestive tracts of rabbits, the likely doors of virus entry. Here we studied the glycan-binding properties of novel pathogenic and non-pathogenic strains looking for a link between glycan-binding and virulence or between glycan specificity and host range. We found that glycan binding did not correlate with virulence. However, expression of glycan motifs in the upper respiratory and digestive tracts of lagomorphs revealed species-specific patterns associated with the host range of the virus strains, suggesting that glycan diversity contributes to lagoviruses' host range. Copyright © 2017 American Society for Microbiology.

An overview of resistance profiles ESKAPE pathogens from 2010-2015 in a tertiary respiratory center in Romania.

PubMed

Peneş, Nicolae Ovidiu; Muntean, Andrei Alexandru; Moisoiu, Adriana; Muntean, Mădălina Maria; Chirca, Alexandru; Bogdan, Miron Alexandru; Popa, Mircea Ioan

2017-01-01

Lower respiratory tract infections (LRTIs) is an umbrella term that covers a wide spectrum of diseases, comprising mild and severe, acute and chronic conditions. A wide spectrum of pathogens can be implicated, from viruses to pyogenic and atypical bacteria. A special place should be reserved for slow growing bacteria (Mycobacteria spp., Nocardia spp.) and parasites (i.e., hydatic cysts caused by Echinococcus granulosus). The objective of this study is to observe, analyze and establish the drug susceptibility patterns for Enterococcus spp., Staphylococcus aureus, Klebsiella spp., Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. (the ESKAPE pathogens) in the "Marius Nasta" Institute for Pulmonary Medicine (MNIPM), Bucharest, Romania. A retrospective healthcare record based study was undertaken to establish the drug susceptibility patterns. We assessed all antibiograms of the ESKAPE pathogens isolated from respiratory samples from adult inpatients hospitalized between 2010-2015 at the MNIPM. We analyzed 2859 isolates (61% of the 4683 ESKAPE isolates). P. aeruginosa was the most frequent pathogen, while Enterococcus spp. and Enterobacter spp. were practically non-present. The antibiotic profile of P. aeruginosa isolates presented more resistance in the Intensive Care Unit (ICU)÷Surgery wards, probably resulting from antibiotic pressure. The other non-fermenter, A. baumannii, while less frequent (and the only pathogen more frequent in the surgery department) had an even more resistant profile, to almost all antibiotics, with the exception of Colistin. Methicillin-resistant S. aureus (MRSA) accounted for about 60% of all isolates, more in the ICU÷Surgery ward. K. pneumoniae presents a less resistance and shows more stability when analyzing the antibiogram pattern in the Medical wards. For methodological or procedural reasons, Enterococcus spp. and Enterobacter spp. were underrepresented in the study. Interventional programs comprising antibiotic stewardship and active surveillance need to be implemented to alleviate the antibiotic profile. Further research needs to focus on more detailed characterization of the molecular mechanisms leading to the high resistance detailed herein. This study adds to the body of literature reporting the antibiotic resistance landscape in Romania, for these highly resistant pathogens.

Proanthocyanidin-rich extracts from cranberry fruit (Vaccinium macrocarpon Ait.) selectively inhibit the growth of human pathogenic fungi Candida spp. and Cryptococcus neoformans.

PubMed

Patel, Kunal D; Scarano, Frank J; Kondo, Miwako; Hurta, Robert A R; Neto, Catherine C

2011-12-28

Cranberry ( Vaccinium macrocarpon ) has been shown in clinical studies to reduce infections caused by Escherichia coli and other bacteria, and proanthocyanidins are believed to play a role. The ability of cranberry to inhibit the growth of opportunistic human fungal pathogens that cause oral, skin, respiratory, and systemic infections has not been well-studied. Fractions from whole cranberry fruit were screened for inhibition of five Candida species and Cryptococcus neoformans , a causative agent of fungal meningitis. Candida glabrata , Candida lusitaniae , Candida krusei , and Cryptococcus neoformans showed significant susceptibility to treatment with cranberry proanthocyanidin fractions in a broth microdilution assay, with minimum inhibitory concentrations as low as 1 μg/mL. MALDI-TOF MS analysis of subfractions detected epicatechin oligomers of up to 12 degrees of polymerization. Those containing larger oligomers caused the strongest inhibition. This study suggests that cranberry has potential as an antifungal agent.

The role of influenza, RSV and other common respiratory viruses in severe acute respiratory infections and influenza-like illness in a population with a high HIV sero-prevalence, South Africa 2012-2015.

PubMed

Pretorius, Marthi A; Tempia, Stefano; Walaza, Sibongile; Cohen, Adam L; Moyes, Jocelyn; Variava, Ebrahim; Dawood, Halima; Seleka, Mpho; Hellferscee, Orienka; Treurnicht, Florette; Cohen, Cheryl; Venter, Marietjie

2016-02-01

Viruses detected in patients with acute respiratory infections may be the cause of illness or asymptomatic shedding. To estimate the attributable fraction (AF) and the detection rate attributable to illness for each of the different respiratory viruses We compared the prevalence of 10 common respiratory viruses (influenza A and B viruses, parainfluenza virus 1-3; respiratory syncytial virus (RSV); adenovirus, rhinovirus, human metapneumovirus (hMPV) and enterovirus) in both HIV positive and negative patients hospitalized with severe acute respiratory illness (SARI), outpatients with influenza-like illness (ILI), and control subjects who did not report any febrile, respiratory or gastrointestinal illness during 2012-2015 in South Africa. We enrolled 1959 SARI, 3784 ILI and 1793 controls with a HIV sero-prevalence of 26%, 30% and 43%, respectively. Influenza virus (AF: 86.3%; 95%CI: 77.7-91.6%), hMPV (AF: 85.6%; 95%CI: 72.0-92.6%), and RSV (AF: 83.7%; 95%CI: 77.5-88.2%) infections were associated with severe disease., while rhinovirus (AF: 46.9%; 95%CI: 37.6-56.5%) and adenovirus (AF: 36.4%; 95%CI: 20.6-49.0%) were only moderately associated. Influenza, RSV and hMPV can be considered pathogens if detected in ILI and SARI while rhinovirus and adenovirus were commonly identified in controls suggesting that they may cause only a proportion of clinical disease observed in positive patients. Nonetheless, they may be important contributors to disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Respiratory infections during air travel.

PubMed

Leder, K; Newman, D

2005-01-01

An increasing number of individuals undertake air travel annually. Issues regarding cabin air quality and the potential risks of transmission of respiratory infections during flight have been investigated and debated previously, but, with the advent of severe acute respiratory syndrome and influenza outbreaks, these issues have recently taken on heightened importance. Anecdotally, many people complain of respiratory symptoms following air travel. However, studies of ventilation systems and patient outcomes indicate the spread of pathogens during flight occurs rarely. In the present review, aspects of the aircraft cabin environment that affect the likelihood of transmission of respiratory pathogens on airplanes are outlined briefly and evidence for the occurrence of outbreaks of respiratory illness among airline passengers are reviewed.

Leigh syndrome caused by a novel m.4296G>A mutation in mitochondrial tRNA isoleucine.

PubMed

Cox, Rachel; Platt, Julia; Chen, Li Chieh; Tang, Sha; Wong, Lee-Jun; Enns, Gregory M

2012-03-01

Leigh syndrome is a severe neurodegenerative disease with heterogeneous genetic etiology. We report a novel m.4296G>A variant in the mitochondrial tRNA isoleucine gene in a child with Leigh syndrome, mitochondrial proliferation, lactic acidosis, and abnormal respiratory chain enzymology. The variant is present at >75% heteroplasmy in blood and cultured fibroblasts from the proband, <5% in asymptomatic maternal relatives, and is absent in 3000 controls. It is located in the highly conserved anticodon region of tRNA(Ile) where three other pathogenic changes have been described. We conclude that there is strong evidence to classify m.4296G>A as a pathogenic mutation causing Leigh syndrome. Copyright © 2011 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Antimicrobial active herbal compounds against Acinetobacter baumannii and other pathogens.

PubMed

Tiwari, Vishvanath; Roy, Ranita; Tiwari, Monalisa

2015-01-01

Bacterial pathogens cause a number of lethal diseases. Opportunistic bacterial pathogens grouped into ESKAPE pathogens that are linked to the high degree of morbidity, mortality and increased costs as described by Infectious Disease Society of America. Acinetobacter baumannii is one of the ESKAPE pathogens which cause respiratory infection, pneumonia and urinary tract infections. The prevalence of this pathogen increases gradually in the clinical setup where it can grow on artificial surfaces, utilize ethanol as a carbon source and resists desiccation. Carbapenems, a β-lactam, are the most commonly prescribed drugs against A. baumannii. The high level of acquired and intrinsic carbapenem resistance mechanisms acquired by these bacteria makes their eradication difficult. The pharmaceutical industry has no solution to this problem. Hence, it is an urgent requirement to find a suitable alternative to carbapenem, a commonly prescribed drug for Acinetobacter infection. In order to do this, here we have made an effort to review the active compounds of plants that have potent antibacterial activity against many bacteria including carbapenem resistant strain of A. baumannii. We have also briefly highlighted the separation and identification methods used for these active compounds. This review will help researchers involved in the screening of herbal active compounds that might act as a replacement for carbapenem.

ICTV Virus Taxonomy Profile: Picornaviridae.

PubMed

Zell, R; Delwart, E; Gorbalenya, A E; Hovi, T; King, A M Q; Knowles, N J; Lindberg, A M; Pallansch, M A; Palmenberg, A C; Reuter, G; Simmonds, P; Skern, T; Stanway, G; Yamashita, T; Ictv Report Consortium

2017-10-01

The family Picornaviridae comprises small non-enveloped viruses with RNA genomes of 6.7 to 10.1 kb, and contains >30 genera and >75 species. Most of the known picornaviruses infect mammals and birds, but some have also been detected in reptiles, amphibians and fish. Many picornaviruses are important human and veterinary pathogens and may cause diseases of the central nervous system, heart, liver, skin, gastrointestinal tract or upper respiratory tract. Most picornaviruses are transmitted by the faecal-oral or respiratory routes. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Picornaviridae, which is available at www.ictv.global/report/picornaviridae.

Viral Pneumonia in Patients with Hematologic Malignancy or Hematopoietic Stem Cell Transplantation.

PubMed

Vakil, Erik; Evans, Scott E

2017-03-01

Viral pneumonias in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation cause significant morbidity and mortality. Advances in diagnostic techniques have enabled rapid identification of respiratory viral pathogens from upper and lower respiratory tract samples. Lymphopenia, myeloablative and T-cell depleting chemotherapy, graft-versus-host disease, and other factors increase the risk of developing life-threatening viral pneumonia. Chest imaging is often nonspecific but may aid in diagnoses. Bronchoscopy with bronchoalveolar lavage is recommended in those at high risk for viral pneumonia who have new infiltrates on chest imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

Specificity and Effector Functions of Human RSV-Specific IgG from Bovine Milk.

PubMed

den Hartog, Gerco; Jacobino, Shamir; Bont, Louis; Cox, Linda; Ulfman, Laurien H; Leusen, Jeanette H W; van Neerven, R J Joost

2014-01-01

Respiratory syncytial virus (RSV) infection is the second most important cause of death in the first year of life, and early RSV infections are associated with the development of asthma. Breastfeeding and serum IgG have been shown to protect against RSV infection. Yet, many infants depend on bovine milk-based nutrition, which at present lacks intact immunoglobulins. To investigate whether IgG purified from bovine milk (bIgG) can modulate immune responses against human RSV. ELISAs were performed to analyse binding of bIgG to human respiratory pathogens. bIgG or hRSV was coated to plates to assess dose-dependent binding of bIgG to human Fcγ receptors (FcγR) or bIgG-mediated binding of myeloid cells to hRSV respectively. S. Epidermidis and RSV were used to test bIgG-mediated binding and internalisation of pathogens by myeloid cells. Finally, the ability of bIgG to neutralise infection of HEp2 cells by hRSV was evaluated. bIgG recognised human RSV, influenza haemagglutinin and Haemophilus influenza. bIgG bound to FcγRII on neutrophils, monocytes and macrophages, but not to FcγRI and FcγRIII, and could bind simultaneously to hRSV and human FcγRII on neutrophils. In addition, human neutrophils and dendritic cells internalised pathogens that were opsonised with bIgG. Finally, bIgG could prevent infection of HEp2 cells by hRSV. The data presented here show that bIgG binds to hRSV and other human respiratory pathogens and induces effector functions through binding to human FcγRII on phagocytes. Thus bovine IgG may contribute to immune protection against RSV.

Effect of cleaning and disinfection of toys on infectious diseases and micro-organisms in daycare nurseries.

PubMed

Ibfelt, T; Engelund, E H; Schultz, A C; Andersen, L P

2015-02-01

The rising number of children in daycare nurseries increases opportunities for the transmission of infectious diseases. Pathogens may be transmitted directly from child to child via sneezing, coughing and touching, or indirectly via the environment. Toys are among the fomites with the highest pathogen load, but their role in disease transmission is unknown. To determine if washing and disinfection of toys can reduce sickness absence and microbial pathogen load in the nursery environment. Twelve nurseries (caring for 587 children) were randomized to intervention and control groups. The intervention consisted of washing and disinfection of toys and linen every two weeks for three months by a commercial cleaning company. The extent and causes of sickness absence among the children were recorded in both groups before and after introduction of the intervention. Ten sampling points in each nursery were examined for bacteria and respiratory viruses. The presence of respiratory virus DNA/RNA was widespread, but very few pathogenic bacteria were found in the environment. The intervention reduced the presence of adenovirus [odds ratio (OR) 2.4, 95% confidence interval (CI) 1.1-5.0], rhinovirus (OR 5.3, 95% CI 2.3-12.4) and respiratory syncytial virus (OR 4.1, 95% CI 1.5-11.2) compared with the control group, but the intervention had no effect on sickness absence or disease patterns in the nurseries. Although cleaning and disinfection of toys every two weeks can decrease the microbial load in nurseries, it does not appear to reduce sickness absence among nursery children. Copyright © 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Multiple virulence factors regulated by quorum sensing may help in establishment and colonisation of urinary tract by Pseudomonas aeruginosa during experimental urinary tract infection.

PubMed

Gupta, P; Gupta, R K; Harjai, K

2013-01-01

Damage caused by an organism during infection is attributed to production of virulence factors. Different virulence factors produced by the organism contribute to its pathogenicity, individually. During infectious conditions, role of virulence factors produced by the pathogen is different, depending upon the site of involvement. Pseudomonas aeruginosa is an opportunistic nosocomial pathogen known to cause infections of the respiratory tract, burn wound, urinary tract and eye. Importance of virulence factors produced by P. Aeruginosa during infections such as keratitis, burn wound and respiratory tract is known. The present study was designed to understand the importance of different virulence factors of P. aeruginosa in urinary tract infection in vivo. An ascending urinary tract infection model was established in mice using standard parent strain PAO1 and its isogenic mutant, JP2. Mice were sacrificed at different time intervals and renal tissue homogenates were used for estimation of renal bacterial load and virulence factors. Both parent and mutant strains were able to reach the renal tissue. PAO 1 PAO1 was isolated from renal tissue till day 5 post-infection. However, the mutant strain was unable to colonise the renal tissue. Failure of mutant strain to colonise was attributed to its inability to produce protease, elastase and rhamnolipid. This study suggests that protease, elastase and rhamnolipid contribute to pathogenesis and survival of P. aeruginosa during urinary tract infection.

Secretomes of Mycoplasma hyopneumoniae and Mycoplasma flocculare reveal differences associated to pathogenesis.

PubMed

Paes, Jéssica A; Lorenzatto, Karina R; de Moraes, Sofia N; Moura, Hercules; Barr, John R; Ferreira, Henrique B

2017-02-10

Mycoplasma hyopneumoniae and Mycoplasma flocculare cohabit the porcine respiratory tract. However, M. hyopneumoniae causes the porcine enzootic pneumonia, while M. flocculare is a commensal bacterium. Comparative analyses demonstrated high similarity between these species, which includes the sharing of all predicted virulence factors. Nevertheless, studies related to soluble secretomes of mycoplasmas were little known, although they are important for bacterial-host interactions. The aim of this study was to perform a comparative analysis between the soluble secreted proteins repertoires of the pathogenic Mycoplasma hyopneumoniae and its closely related commensal Mycoplasma flocculare. For that, bacteria were cultured in medium with reduced serum concentration and secreted proteins were identified by a LC-MS/MS proteomics approach. Altogether, 62 and 26 proteins were identified as secreted by M. hyopneumoniae and M. flocculare, respectively, being just seven proteins shared between these bacteria. In M. hyopneumoniae secretome, 15 proteins described as virulence factors were found; while four putative virulence factors were identified in M. flocculare secretome. For the first time, clear differences related to virulence were found between these species, helping to elucidate the pathogenic nature of M. hyopneumoniae to swine hosts. For the first time, the secretomes of two porcine respiratory mycoplasmas, namely the pathogenic M. hyopneumoniae and the commensal M. flocculare were compared. The presented results revealed previously unknown differences between these two genetically related species, some of which are associated to the M. hyopneumoniae ability to cause porcine enzootic pneumonia. Copyright © 2016 Elsevier B.V. All rights reserved.

The burden of seasonal respiratory infections on a national telehealth service in England.

PubMed

Morbey, R A; Harcourt, S; Pebody, R; Zambon, M; Hutchison, J; Rutter, J; Thomas, H; Smith, G E; Elliot, A J

2017-07-01

Seasonal respiratory illnesses present a major burden on primary care services. We assessed the burden of respiratory illness on a national telehealth system in England and investigated the potential for providing early warning of respiratory infection. We compared weekly laboratory reports for respiratory pathogens with telehealth calls (NHS 111) between week 40 in 2013 and week 29 in 2015. Multiple linear regression was used to identify which pathogens had a significant association with respiratory calls. Children aged <5 and 5-14 years, and adults over 65 years were modelled separately as were time lags of up to 4 weeks between calls and laboratory specimen dates. Associations with respiratory pathogens explained over 83% of the variation in cold/flu, cough and difficulty breathing calls. Based on the first two seasons available, the greatest burden was associated with respiratory syncytial virus (RSV) and influenza, with associations found in all age bands. The most sensitive signal for influenza was calls for 'cold/flu', whilst for RSV it was calls for cough. The best-fitting models showed calls increasing a week before laboratory specimen dates. Daily surveillance of these calls can provide early warning of seasonal rises in influenza and RSV, contributing to the national respiratory surveillance programme.

Nebulization of Antiinfective Agents in Invasively Mechanically Ventilated Adults: A Systematic Review and Meta-analysis.

PubMed

Solé-Lleonart, Candela; Rouby, Jean-Jacques; Blot, Stijn; Poulakou, Garyfallia; Chastre, Jean; Palmer, Lucy B; Bassetti, Matteo; Luyt, Charles-Edouard; Pereira, Jose M; Riera, Jordi; Felton, Tim; Dhanani, Jayesh; Welte, Tobias; Garcia-Alamino, Jose M; Roberts, Jason A; Rello, Jordi

2017-05-01

Nebulization of antiinfective agents is a common but unstandardized practice in critically ill patients. A systematic review of 1,435 studies was performed in adults receiving invasive mechanical ventilation. Two different administration strategies (adjunctive and substitute) were considered clinically relevant. Inclusion was restricted to studies using jet, ultrasonic, and vibrating-mesh nebulizers. Studies involving children, colonized-but-not-infected adults, and cystic fibrosis patients were excluded. Five of the 11 studies included had a small sample size (fewer than 50 patients), and only 6 were randomized. Diversity of case-mix, dosage, and devices are sources of bias. Only a few patients had severe hypoxemia. Aminoglycosides and colistin were the most common antibiotics, being safe regarding nephrotoxicity and neurotoxicity, but increased respiratory complications in 9% (95% CI, 0.01 to 0.18; I = 52%), particularly when administered to hypoxemic patients. For tracheobronchitis, a significant decrease in emergence of resistance was evidenced (risk ratio, 0.18; 95% CI, 0.05 to 0.64; I = 0%). Similar findings were observed in pneumonia by susceptible pathogens, without improvement in mortality or ventilation duration. In pneumonia caused by resistant pathogens, higher clinical resolution (odds ratio, 1.96; 95% CI, 1.30 to 2.96; I = 0%) was evidenced. These findings were not consistently evidenced in the assessment of efficacy against pneumonia caused by susceptible pathogens. Performance of randomized trials evaluating the impact of nebulized antibiotics with more homogeneous populations, standardized drug delivery, predetermined clinical efficacy, and safety outcomes is urgently required. Infections by resistant pathogens might potentially have higher benefit from nebulized antiinfective agents. Nebulization, without concomitant systemic administration of the drug, may reduce nephrotoxicity but may also be associated with higher risk of respiratory complications.

Clinical and virological factors associated with gastrointestinal symptoms in patients with acute respiratory infection: a two-year prospective study in general practice medicine.

PubMed

Minodier, Laetitia; Masse, Shirley; Capai, Lisandru; Blanchon, Thierry; Ceccaldi, Pierre-Emmanuel; van der Werf, Sylvie; Hanslik, Thomas; Charrel, Remi; Falchi, Alessandra

2017-11-22

Gastrointestinal (GI) symptoms, such as diarrhea, vomiting, abdominal pain and nausea are not an uncommon manifestation of an acute respiratory infection (ARI). We therefore evaluated clinical and microbiological factors associated with the presence of GI symptoms in patients consulting a general practitioner (GP) for ARI. Nasopharyngeal swabs, stool specimens and clinical data from patients presenting to GPs with an ARI were prospectively collected during two winter seasons (2014-2016). Samples were tested by quantitative real-time PCR for 12 respiratory pathogen groups and for 12 enteric pathogens. Two hundred and four of 331 included patients (61.6%) were positive for at least one respiratory pathogen. Sixty-nine stools (20.8%) were positive for at least one pathogen (respiratory and/or enteric). GI symptoms were more likely declared in case of laboratory confirmed-enteric infection (adjusted odds ratio (aOR) = 3.2; 95% confidence interval [CI] [1.2-9.9]; p = 0.02) or human coronavirus (HCoV) infection (aOR = 2.7; [1.2-6.8]; p = 0.02). Consumption of antipyretic medication before the consultation seemed to reduce the risk of developing GI symptoms for patients with laboratory-confirmed influenza (aOR = 0.3; [0.1-0.6]; p = 0.002). The presence of GI symptoms in ARI patients could not be explained by the detection of respiratory pathogens in stools. However, the detection of enteric pathogens in stool samples could explained by the presence of GI symptoms in some of ARI cases. The biological mechanisms explaining the association between the presence of HCoVs in nasopharynx and GI symptoms need to be explored.

Detection of respiratory viruses and bacteria in children using a twenty-two target reverse-transcription real-time PCR (RT-qPCR) panel.

PubMed

Ellis, Chelsey; Misir, Amita; Hui, Charles; Jabbour, Mona; Barrowman, Nicholas; Langill, Jonathan; Bowes, Jennifer; Slinger, Robert

2016-05-01

Rapid detection of the wide range of viruses and bacteria that cause respiratory infection in children is important for patient care and antibiotic stewardship. We therefore designed and evaluated a ready-to-use 22 target respiratory infection reverse-transcription real-time polymerase chain reaction (RT-qPCR) panel to determine if this would improve detection of these agents at our pediatric hospital. RT-qPCR assays for twenty-two target organisms were dried-down in individual wells of 96 well plates and saved at room temperature. Targets included 18 respiratory viruses and 4 bacteria. After automated nucleic acid extraction of nasopharyngeal aspirate (NPA) samples, rapid qPCR was performed. RT-qPCR results were compared with those obtained by the testing methods used at our hospital laboratories. One hundred fifty-nine pediatric NPA samples were tested with the RT-qPCR panel. One or more respiratory pathogens were detected in 132/159 (83%) samples. This was significantly higher than the detection rate of standard methods (94/159, 59%) (P<0.001). This difference was mainly due to improved RT-qPCR detection of rhinoviruses, parainfluenza viruses, bocavirus, and coronaviruses. The panel internal control assay performance remained stable at room temperature storage over a two-month testing period. The RT-qPCR panel was able to identify pathogens in a high proportion of respiratory samples. The panel detected more positive specimens than the methods in use at our hospital. The pre-made panel format was easy to use and rapid, with results available in approximately 90 minutes. We now plan to determine if use of this panel improves patient care and antibiotic stewardship.

Multicenter Clinical Evaluation of the Luminex Aries Flu A/B & RSV Assay for Pediatric and Adult Respiratory Tract Specimens.

PubMed

Juretschko, Stefan; Mahony, James; Buller, Richard S; Manji, Ryhana; Dunbar, Sherry; Walker, Kimberly; Rao, Arundhati

2017-08-01

Influenza A and B viruses and respiratory syncytial virus (RSV) are three common viruses implicated in seasonal respiratory tract infections and are a major cause of morbidity and mortality in adults and children worldwide. In recent years, an increasing number of commercial molecular tests have become available to diagnose respiratory viral infections. The Luminex Aries Flu A/B & RSV assay is a fully automated sample-to-answer molecular diagnostic assay for the detection of influenza A, influenza B, and RSV. The clinical performance of the Aries Flu A/B & RSV assay was prospectively evaluated in comparison to that of the Luminex xTAG respiratory viral panel (RVP) at four North American clinical institutions over a 2-year period. Of the 2,479 eligible nasopharyngeal swab specimens included in the prospective study, 2,371 gave concordant results between the assays. One hundred eight specimens generated results that were discordant with those from the xTAG RVP and were further analyzed by bidirectional sequencing. Final clinical sensitivity values of the Aries Flu A/B & RSV assay were 98.1% for influenza A virus, 98.0% for influenza B virus, and 97.7% for RSV. Final clinical specificities for all three pathogens ranged from 98.6% to 99.8%. Due to the low prevalence of influenza B, an additional 40 banked influenza B-positive specimens were tested at the participating clinical laboratories and were all accurately detected by the Aries Flu A/B & RSV assay. This study demonstrates that the Aries Flu A/B & RSV assay is a suitable method for rapid and accurate identification of these causative pathogens in respiratory infections. Copyright © 2017 Juretschko et al.

From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.

PubMed

Hilgenfeld, Rolf; Peiris, Malik

2013-10-01

This article introduces a series of invited papers in Antiviral Research marking the 10th anniversary of the outbreak of severe acute respiratory syndrome (SARS), caused by a novel coronavirus that emerged in southern China in late 2002. Until that time, coronaviruses had not been recognized as agents causing severe disease in humans, hence, the emergence of the SARS-CoV came as a complete surprise. Research during the past ten years has revealed the existence of a diverse pool of coronaviruses circulating among various bat species and other animals, suggesting that further introductions of highly pathogenic coronaviruses into the human population are not merely probable, but inevitable. The recent emergence of another coronavirus causing severe disease, Middle East respiratory syndrome (MERS), in humans, has made it clear that coronaviruses pose a major threat to human health, and that more research is urgently needed to elucidate their replication mechanisms, identify potential drug targets, and develop effective countermeasures. In this series, experts in many different aspects of coronavirus replication and disease will provide authoritative, up-to-date reviews of the following topics: - clinical management and infection control of SARS; - reservoir hosts of coronaviruses; - receptor recognition and cross-species transmission of SARS-CoV; - SARS-CoV evasion of innate immune responses; - structures and functions of individual coronaviral proteins; - anti-coronavirus drug discovery and development; and - the public health legacy of the SARS outbreak. Each article will be identified in the last line of its abstract as belonging to the series "From SARS to MERS: 10years of research on highly pathogenic human coronaviruses." Copyright © 2013 Elsevier B.V. All rights reserved.

An adenovirus vectored mucosal adjuvant augments protection of mice immunized intranasally with an adenovirus-vectored foot-and-mouth disease virus subunit vaccine

USDA-ARS?s Scientific Manuscript database

Foot-and-mouth disease virus (FMDV) is a highly contagious pathogen that causes severe morbidity and economic losses to the livestock industry in many countries. The oral and respiratory mucosae are the main ports of entry of FMDV, so the stimulation of local immunity in these tissues may help preve...

Complete Genome Sequence of Mycobacterium chimaera SJ42, a Nonoutbreak Strain from an Immunocompromised Patient with Pulmonary Disease.

PubMed

Hasan, Nabeeh A; Warren, René L; Epperson, L Elaine; Malecha, Allyson; Alexander, David C; Turenne, Christine Y; MacMillan, Daniel; Birol, Inanc; Pleasance, Stephen; Coope, Robin; Jones, Steven J M; Romney, Marc G; Ng, Monica; Chan, Tracy; Rodrigues, Mabel; Tang, Patrick; Gardy, Jennifer L; Strong, Michael

2017-09-14

Mycobacterium chimaera , a nontuberculous mycobacterium (NTM) belonging to the Mycobacterium avium complex (MAC), is an opportunistic pathogen that can cause respiratory and disseminated disease. We report the complete genome sequence of a strain, SJ42, isolated from an immunocompromised male presenting with MAC pneumonia, assembled from Illumina and Oxford Nanopore data. Copyright © 2017 Hasan et al.

Mucosal immunoglobulins at respiratory surfaces mark an ancient association that predates the emergence of tetrapods

PubMed Central

Xu, Zhen; Takizawa, Fumio; Parra, David; Gómez, Daniela; von Gersdorff Jørgensen, Louise; LaPatra, Scott E.; Sunyer, J. Oriol

2016-01-01

Gas-exchange structures are critical for acquiring oxygen, but they also represent portals for pathogen entry. Local mucosal immunoglobulin responses against pathogens in specialized respiratory organs have only been described in tetrapods. Since fish gills are considered a mucosal surface, we hypothesized that a dedicated mucosal immunoglobulin response would be generated within its mucosa on microbial exposure. Supporting this hypothesis, here we demonstrate that following pathogen exposure, IgT+ B cells proliferate and generate pathogen-specific IgT within the gills of fish, thus providing the first example of locally induced immunoglobulin in the mucosa of a cold-blooded species. Moreover, we demonstrate that gill microbiota is predominantly coated with IgT, thus providing previously unappreciated evidence that the microbiota present at a respiratory surface of a vertebrate is recognized by a mucosal immunoglobulin. Our findings indicate that respiratory surfaces and mucosal immunoglobulins are part of an ancient association that predates the emergence of tetrapods. PMID:26869478

Clinical outcomes in cystic fibrosis patients with Trichosporon respiratory infection.

PubMed

Esther, Charles R; Plongla, Rongpong; Kerr, Alan; Lin, Feng-Chang; Gilligan, Peter

2016-09-01

Relationships between clinical outcomes and novel respiratory pathogens such as Trichosporon are not well understood. Respiratory cultures from CF patients were screened for novel pathogens Trichosporon and Chryseobacterium as well as other pathogens over 28months. Relationships between microbiologic and clinical data were assessed using univariate and multivariate methods. Of 4934 respiratory cultures from 474 CF patients, 37 cultures from 10 patients were Trichosporon positive. Patients with positive Trichosproron cultures had a greater decline in FEV1 over time (-3.9%/year vs. -1.3%/year, p<0.05), whereas Chryseobacterium did not influence lung function. These findings were confirmed in multivariate analyses that included age, gender, and other common pathogens as confounders. Treatment of Trichosporon infected patients was associated with improved lung function. Trichosporon can be recovered from a small but clinically meaningful fraction of CF patients. The presence of Trichosporon, but not Chryseobacterium, is associated with greater declines in lung function. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Complement-mediated neutrophil activation in sepsis- and trauma-related adult respiratory distress syndrome. Clarification with radioaerosol lung scans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tennenberg, S.D.; Jacobs, M.P.; Solomkin, J.S.

Complement-mediated neutrophil activation (CMNA) has been proposed as an important pathogenic mechanism causing acute microvascular lung injury in the adult respiratory distress syndrome (ARDS). To clarify the relationship between CMNA and evolving lung injury, we studied 26 patients with multiple trauma and sepsis within 24 hours of risk establishment for ARDS. Pulmonary alveolar-capillary permeability (PACP) was quantified as the clearance rate of a particulate radioaerosol. Seventeen patients (65%) had increased PACP (six developed ARDS) while nine (35%) had normal PACP (none developed ARDS; clearance rates of 3.4%/min and 1.5%/min, respectively). These patients, regardless of evidence of early lung injury, hadmore » elevated plasma C3adesArg levels and neutrophil chemotactic desensitization to C5a/C5adesArg. Plasma C3adesArg levels correlated weakly, but significantly, with PACP. Thus, CMNA may be a necessary, but not a sufficient, pathogenic mechanism in the evolution of ARDS.« less

Evolution of Influenza A Virus by Mutation and Re-Assortment

PubMed Central

Shao, Wenhan; Li, Xinxin; Goraya, Mohsan Ullah; Wang, Song; Chen, Ji-Long

2017-01-01

Influenza A virus (IAV), a highly infectious respiratory pathogen, has continued to be a significant threat to global public health. To complete their life cycle, influenza viruses have evolved multiple strategies to interact with a host. A large number of studies have revealed that the evolution of influenza A virus is mainly mediated through the mutation of the virus itself and the re-assortment of viral genomes derived from various strains. The evolution of influenza A virus through these mechanisms causes worldwide annual epidemics and occasional pandemics. Importantly, influenza A virus can evolve from an animal infected pathogen to a human infected pathogen. The highly pathogenic influenza virus has resulted in stupendous economic losses due to its morbidity and mortality both in human and animals. Influenza viruses fall into a category of viruses that can cause zoonotic infection with stable adaptation to human, leading to sustained horizontal transmission. The rapid mutations of influenza A virus result in the loss of vaccine optimal efficacy, and challenge the complete eradication of the virus. In this review, we highlight the current understanding of influenza A virus evolution caused by the mutation and re-assortment of viral genomes. In addition, we discuss the specific mechanisms by which the virus evolves. PMID:28783091

Viruses as Sole Causative Agents of Severe Acute Respiratory Tract Infections in Children.

PubMed

Moesker, Fleur M; van Kampen, Jeroen J A; van Rossum, Annemarie M C; de Hoog, Matthijs; Koopmans, Marion P G; Osterhaus, Albert D M E; Fraaij, Pieter L A

2016-01-01

Respiratory syncytial virus (RSV) and influenza A viruses are known to cause severe acute respiratory tract infections (SARIs) in children. For other viruses like human rhinoviruses (HRVs) this is less well established. Viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections. The study aims at identifying viruses that may cause SARI in children in the absence of viral and bacterial co-infections, at identifying disease characteristics associated with these single virus infections, and at identifying a possible correlation between viral loads and disease severities. Between April 2007 and March 2012, we identified children (<18 year) with or without a medical history, admitted to our paediatric intensive care unit (PICU) with SARI or to the medium care (MC) with an acute respiratory tract infection (ARTI) (controls). Data were extracted from the clinical and laboratory databases of our tertiary care paediatric hospital. Patient specimens were tested for fifteen respiratory viruses with real-time reverse transcriptase PCR assays and we selected patients with a single virus infection only. Typical bacterial co-infections were considered unlikely to have contributed to the PICU or MC admission based on C-reactive protein-levels or bacteriological test results if performed. We identified 44 patients admitted to PICU with SARI and 40 patients admitted to MC with ARTI. Twelve viruses were associated with SARI, ten of which were also associated with ARTI in the absence of typical bacterial and viral co-infections, with RSV and HRV being the most frequent causes. Viral loads were not different between PICU-SARI patients and MC-ARTI patients. Both SARI and ARTI may be caused by single viral pathogens in previously healthy children as well as in children with a medical history. No relationship between viral load and disease severity was identified.

The bioactivity of plant extracts against representative bacterial pathogens of the lower respiratory tract

PubMed Central

Bocanegra-García, Virgilio; del Rayo Camacho-Corona, María; Ramírez-Cabrera, Mónica; Rivera, Gildardo; Garza-González, Elvira

2009-01-01

Background Lower respiratory tract infections are a major cause of illness and death. Such infections are common in intensive care units (ICU) and their lethality persists despite advances in diagnosis, treatment and prevention. In Mexico, some plants are used in traditional medicine to treat respiratory diseases or ailments such as cough, bronchitis, tuberculosis and other infections. Medical knowledge derived from traditional societies has motivated searches for new bioactive molecules derived from plants that show potent activity against bacterial pathogens. Therefore, the aim of this study was to evaluate the effect of hexanic, chloroformic (CLO), methanolic (MET) and aqueous extracts from various plants used in Mexican traditional medicine on various microorganisms associated with respiratory disease. Methods thirty-five extracts prepared from nine plants used in Mexican traditional medicine for the treatment of respiratory infections were evaluated against 15 control bacterial species and clinical isolates. Results Both chloroformic (CLO) and methanolic (MET) extracts of Larrea tridentata were active against Methicillin-resistant S. aureus, B. subtilis and L. monocytogenes. A MET extract of L. tridentata was also active against S. aureus, S. pneumoniae, S. maltophilia, E. faecalis and H. influenzae and the CLO extract was active against A. baumannii. An Aqueous extract of M. acumitata and a MET extract of N. officinale were active against S. pneumoniae. CLO and MET extracts of L. tridentata were active against clinical isolates of S. aureus, S. pneumoniae and E. faecalis. Conclusion Overall, our results support the potential use of L. tridentata as a source of antibacterial compounds. PMID:19486533

Chemicals or mutations that target mitochondrial translation can rescue the respiratory deficiency of yeast bcs1 mutants.

PubMed

Panozzo, C; Laleve, A; Tribouillard-Tanvier, D; Ostojić, J; Sellem, C H; Friocourt, G; Bourand-Plantefol, A; Burg, A; Delahodde, A; Blondel, M; Dujardin, G

2017-12-01

Bcs1p is a chaperone that is required for the incorporation of the Rieske subunit within complex III of the mitochondrial respiratory chain. Mutations in the human gene BCS1L (BCS1-like) are the most frequent nuclear mutations resulting in complex III-related pathologies. In yeast, the mimicking of some pathogenic mutations causes a respiratory deficiency. We have screened chemical libraries and found that two antibiotics, pentamidine and clarithromycin, can compensate two bcs1 point mutations in yeast, one of which is the equivalent of a mutation found in a human patient. As both antibiotics target the large mtrRNA of the mitoribosome, we focused our analysis on mitochondrial translation. We found that the absence of non-essential translation factors Rrf1 or Mif3, which act at the recycling/initiation steps, also compensates for the respiratory deficiency of yeast bcs1 mutations. At compensating concentrations, both antibiotics, as well as the absence of Rrf1, cause an imbalanced synthesis of respiratory subunits which impairs the assembly of the respiratory complexes and especially that of complex IV. Finally, we show that pentamidine also decreases the assembly of complex I in nematode mitochondria. It is well known that complexes III and IV exist within the mitochondrial inner membrane as supramolecular complexes III 2 /IV in yeast or I/III 2 /IV in higher eukaryotes. Therefore, we propose that the changes in mitochondrial translation caused by the drugs or by the absence of translation factors, can compensate for bcs1 mutations by modifying the equilibrium between illegitimate, and thus inactive, and active supercomplexes. Copyright © 2017. Published by Elsevier B.V.

Efficacy/safety of amoxicillin/clavulanate in adults with bacterial rhinosinusitis.

PubMed

Anon, Jack B; Berkowitz, Elchonon; Breton, John; Twynholm, Monique

2006-01-01

Acute bacterial rhinosinusitis (ABRS) is a common and uncomfortable condition, frequently caused by Streptococcus pneumoniae or Haemophilus influenzae. Antibacterial resistance among these and other common respiratory pathogens is now widespread and of concern. Pharmacokinetically enhanced amoxicillin/clavulanate 2000/125 mg was developed to be effective against the common respiratory pathogens, including many resistant strains. This open-label, noncomparative study assessed the bacteriologic and clinical efficacy of amoxicillin/clavulanate 2000/125 mg in adult patients with ABRS. Requirements for study entry included a clinical diagnosis of ABRS supported by radiologic findings. In addition, sinus puncture for bacteriologic assessment was required at study entry. Overall, bacteriologic success (eradication or clinical evidence of eradication) at the follow-up visit (days 17-28) was achieved in 87.8% (722/822) of patients with 1 or more pathogen isolated at screening, in 93.2% (246/264) of patients with S pneumoniae, in 96.7% (29/30) of those with penicillin-resistant S pneumoniae (penicillin minimum inhibitory concentrations >or=2 microg/mL), and in 88.7% (110/124) of patients with beta-lactamase-positive pathogens. Bacteriologic success was achieved against 6 of 7 S pneumoniae isolates with amoxicillin/clavulanic acid minimum inhibitory concentrations of 4/2 microg/mL or higher. Amoxicillin/clavulanate 2000/125 mg was generally well tolerated. This new amoxicillin/clavulanate formulation provides a suitable option for empiric therapy for ABRS in adults.

Etiology of respiratory disease in non-vaccinated, non-medicated calves in rearing herds.

PubMed

Autio, T; Pohjanvirta, T; Holopainen, R; Rikula, U; Pentikäinen, J; Huovilainen, A; Rusanen, H; Soveri, T; Sihvonen, L; Pelkonen, S

2007-01-31

The aim of this study was to examine the occurrence of bacterial, mycoplasmal and viral pathogens in the lower respiratory tract of calves in all-in all-out calf-rearing units. According to clinical status, non-medicated calves with and without respiratory disease signs were selected of the 40 herds investigated to analyse the micro-organisms present in healthy and diseased calves. Tracheobronchial lavage (TBL) and paired serum samples were analysed for bacteria, mycoplasmas, respiratory syncytial virus (RSV), parainfluenza virus 3 (PIV3), bovine corona virus (BCV) and bovine adenovirus (BAV). Pasteurella multocida was the most common bacterial pathogen. It was isolated from 34% of the TBL samples in 28 herds and was associated with clinical respiratory disease (p < 0.05) when other pathogenic bacteria or mycoplasma were present in the sample. Mannheimia spp. and Histophilus somni were rarely found. Mycoplasma bovis was not detected at all. Ureaplasma diversum was associated with clinical respiratory disease (p < 0.05). TBL samples from healthy or suspect calves were more often negative in bacterial culture than samples from diseased calves (p < 0.05). No viral infections were detected in six herds, while 16-21 herds had RSV, BCV, BAV or PIV3. In the herds that had calves seroconverted to BCV, respiratory shedding of BCV was more frequently observed than faecal shedding. This study showed that the microbial combinations behind BRD were diverse between herds. M. bovis, an emerging pathogen in many countries, was not detected.

Bighorn sheep (Ovis canadensis) sinus tumors are associated with coinfections by potentially pathogenic bacteria in the upper respiratory tract.

PubMed

Fox, Karen A; Rouse, Natalie M; Huyvaert, Kathryn P; Griffin, Karen A; Killion, Halcyon J; Jennings-Gaines, Jessica; Edwards, William H; Quackenbush, Sandra L; Miller, Michael W

2015-01-01

Bighorn sheep (Ovis canadensis) sinus tumors are hyperplastic to neoplastic, predominantly stromal masses of the paranasal sinuses that expand the sinus lining and obstruct the sinus cavities. Obstruction of the sinus cavities and disruption of normal sinus lining anatomy may interfere with clearance of bacterial pathogens from the upper respiratory tract. To examine this possibility, we explored whether the presence of sinus tumor features (tumor score) affected the likelihood of detecting potentially pathogenic bacteria from upper respiratory sinus lining tissues in bighorn sheep. We developed or used existing PCR assays for the detection of leukotoxigenic Pasteurellaceae and Mycoplasma ovipneumoniae in sinus lining tissues collected from 97 bighorn sheep in Colorado, US from 2009 to 2012. With the use of logistic regression analyses we found that tumor score was a good predictor of the probability of detecting potentially pathogenic bacteria in sinus lining tissues; we were more likely to detect potentially pathogenic bacteria from samples with high tumor scores. These findings add to our understanding of possible mechanisms for the maintenance and shedding of bacterial agents from the upper respiratory tracts of bighorn sheep.

Glycoprotein G deficient infectious laryngotracheitis virus is a candidate attenuated vaccine.

PubMed

Devlin, Joanne M; Browning, Glenn F; Hartley, Carol A; Gilkerson, James R

2007-05-04

Infectious laryngotracheitis virus (ILTV), an alphaherpesvirus, causes respiratory disease in chickens and is currently controlled by vaccination with conventionally attenuated virus strains. These vaccines have limitations because of residual pathogenicity and reversion to virulence, suggesting that a novel vaccine strain that lacks virulence gene(s) may enhance disease control. Glycoprotein G (gG) has recently been identified as a virulence factor in ILTV. In this study the immunogenicity and relative pathogenicity of gG deficient ILTV was investigated in SPF chickens. Birds vaccinated with gG deficient ILTV were protected against clinical signs of disease following challenge with virulent ILTV and gG deficient ILTV was also shown to be less pathogenic than currently available commercial vaccine strains. Thus gG deficient ILTV appears to have potential as a vaccine candidate.

Pasteurellaceae isolated from bighorn sheep (Ovis canadensis) from Idaho, Oregon, and Wyoming.

PubMed

Miller, David S; Weiser, Glen C; Ward, Alton C S; Drew, Mark L; Chapman, Phillip L

2012-07-01

To elucidate the species and biovariants of Pasteurellaceae isolated from clinically normal bighorn sheep (Ovis canadensis) or bighorn sheep with evidence of respiratory disease. 675 Pasteurellaceae isolates from 290 free-ranging bighorn sheep in Idaho, Oregon and Wyoming. Nasal and oropharyngeal swab specimens were inoculated onto selective and nonselective blood agar media. Representatives of each colony type were classified via a biovariant scheme. The association of respective β-hemolytic isolates with respiratory disease was evaluated via χ(2) analyses. Bacterial isolates belonged to 4 species: Histophilus somni, Mannheimia haemolytica, Pasteurella multocida, and Bibersteinia (Pasteurella) trehalosi. Within the latter 3 species, 112 subspecies, biotypes, and biovariants were identified. Bibersteinia trehalosi 2 and B trehalosi 2B constituted 345 of 675 (51%) isolates. Most (597/618 [97%]) isolates from adult sheep were from clinically normal animals, whereas most (47/57 [82%]) isolates from lambs were from animals with evidence of respiratory disease. Twenty-two Pasteurellaceae biovariants were isolated from sheep with respiratory disease; 17 of these biovariants were also isolated from clinically normal sheep. The ability of isolates to cause β-hemolysis on blood agar was associated with respiratory disease in adult bighorn sheep (OR, 2.59; 95% confidence interval, 1.10 to 6.07). Bighorn lambs appeared more susceptible to respiratory disease caused by Pasteurellaceae than did adult sheep. β-Hemolytic Pasteurellaceae isolates were more likely to be associated with respiratory disease than were non-β-hemolytic isolates in adult sheep. Identification of Pasteurellaceae with the greatest pathogenic potential will require studies to estimate the risk of disease from specific biovariants.

The effect of tar spot pathogen on host plant carbon balance and its possible consequences on a tundra ecosystem.

PubMed

Masumoto, Shota; Uchida, Masaki; Tojo, Motoaki; Herrero, Maria Luz; Mori, Akira S; Imura, Satoshi

2018-03-01

In Arctic tundra, plant pathogens have substantial effects on the growth and survival of hosts, and impacts on the carbon balance at the scale of ecological systems. To understand these effects on carbon dynamics across different scales including plant organ, individual, population and ecosystem, we focused on two primary factors: host productivity reduction and carbon consumption by the pathogen. We measured the effect of the pathogen on photosynthetic and respiratory activity in the host. We also measured respiration and the amount of carbon in the pathogen. We constructed a model based on these two factors, and calculated pathogenic effects on the carbon balance at different organismal and ecological scales. We found that carbon was reduced in infected leaves by 118% compared with healthy leaves; the major factor causing this loss was pathogenic carbon consumption. The carbon balance at the population and ecosystem levels decreased by 35% and 20%, respectively, at an infection rate of 30%. This case study provides the first evidence that a host plant can lose more carbon through pathogenic carbon consumption than through a reduction in productivity. Such a pathogenic effect could greatly change ecosystem carbon cycling without decreasing annual productivity.

Targeting the mitochondrial respiratory chain of Cryptococcus through antifungal chemosensitization: a model for control of non-fermentative pathogens

USDA-ARS?s Scientific Manuscript database

Enhanced control of species of Cryptococcus, non-fermentative yeast pathogens, was achieved by chemosensitization through co-application of certain compounds with a conventional antimicrobial drug. The species of Cryptococcus tested showed higher sensitivity to mitochondrial respiratory chain inhibi...

Limited pathogenicity and transmissibility of Korean highly pathogenic avian influenza H5N6 clade 2.3.4.4 in ferrets.

PubMed

Noh, J-Y; Lee, D-H; Yuk, S-S; Kwon, J-H; Tseren-Ochir, E-O; Hong, W-T; Jeong, J-H; Jeong, S; Song, C-S

2018-04-19

The pathogenicity and transmissibility of a reassortant clade 2.3.4.4 avian influenza A (H5N6) virus were evaluated in ferrets. Virus excretion was detected in the upper respiratory tract, but the ferrets did not show any clinical signs of infection. Transmission did not occur between cohoused or respiratory droplet-contact ferrets. © 2018 Blackwell Verlag GmbH.

Oxidative stress in Nipah virus-infected human small airway epithelial cells.

PubMed

Escaffre, Olivier; Halliday, Hailey; Borisevich, Viktoriya; Casola, Antonella; Rockx, Barry

2015-10-01

Nipah virus (NiV) is a zoonotic emerging pathogen that can cause severe and often fatal respiratory disease in humans. The pathogenesis of NiV infection of the human respiratory tract remains unknown. Reactive oxygen species (ROS) produced by airway epithelial cells in response to viral infections contribute to lung injury by inducing inflammation and oxidative stress; however, the role of ROS in NiV-induced respiratory disease is unknown. To investigate whether NiV induces oxidative stress in human respiratory epithelial cells, we used oxidative stress markers and monitored antioxidant gene expression. We also used ROS scavengers to assess their role in immune response modulation. Oxidative stress was confirmed in infected cells and correlated with the reduction in antioxidant enzyme gene expression. Infected cells treated by ROS scavengers resulted in a significant decrease of the (F2)-8-isoprostane marker, inflammatory responses and virus replication. In conclusion, ROS are induced during NiV infection in human respiratory epithelium and contribute to the inflammatory response. Understanding how oxidative stress contributes to NiV pathogenesis is crucial for therapeutic development.

Mycoplasma pneumoniae Epidemiology in England and Wales: A National Perspective.

PubMed

Brown, Rebecca J; Nguipdop-Djomo, Patrick; Zhao, Hongxin; Stanford, Elaine; Spiller, O Brad; Chalker, Victoria J

2016-01-01

Investigations of patients with suspected Mycoplasma pneumoniae infection have been undertaken in England since the early 1970s. M. pneumoniae is a respiratory pathogen that is a common cause of pneumonia and may cause serious sequelae such as encephalitis and has been documented in children with persistent cough. The pathogen is found in all age groups, with higher prevalence in children aged 5-14 years. In England, recurrent epidemic periods have occurred at ~4-yearly intervals. In addition, low-level sporadic infection occurs with seasonal peaks from December to February. Voluntarily reports from regional laboratories and hospitals in England from 1975 to 2015 were collated by Public Health England for epidemiological analysis. Further data pertaining cases of note and specimens submitted to Public Health England from 2005 to 2015 for confirmation, molecular typing is included.

Differential expression of small non-coding RNAs in serum from cattle challenged with viruses causing bovine respiratory disease

USDA-ARS?s Scientific Manuscript database

MicroRNAs and tRNA-derived RNA fragments (tRFs) are the two most abundant groups of small non-coding RNAs. The potential for microRNAs and tRFs to be used as pathogen exposure indicators is yet to be fully explored. Our objective was to identify microRNAs and tRFs in cattle challenged with a non-cy...

Molecular characterization of influenza B virus outbreak on a cruise ship in Brazil 2012.

PubMed

Borborema, Samanta Etel Treiger; Silva, Daniela Bernardes Borges da; Silva, Kátia Corrêa Oliveira; Pinho, Margarete Aparecida Benega; Curti, Suely Pires; Paiva, Terezinha Maria de; Santos, Cecília Luiza Simões

2014-01-01

In February 2012, an outbreak of respiratory illness occurred on the cruise ship MSC Armonia in Brazil. A 31-year-old female crew member was hospitalized with respiratory failure and subsequently died. To study the etiology of the respiratory illness, tissue taken at necropsy from the deceased woman and respiratory specimens from thirteen passengers and crew members with respiratory symptoms were analyzed. Influenza real-time RT-PCR assays were performed, and the full-length hemagglutinin (HA) gene of influenza-positive samples was sequenced. Influenza B virus was detected in samples from seven of the individuals, suggesting that it was the cause of this respiratory illness outbreak. The sequence analysis of the HA gene indicated that the virus was closely related to the B/Brisbane/60/2008-like virus, Victoria lineage, a virus contained in the 2011-12 influenza vaccine for the Southern Hemisphere. Since the recommended composition of the influenza vaccine for use during the 2013 season changed, an intensive surveillance of viruses circulating worldwide is crucial. Molecular analysis is an important tool to characterize the pathogen responsible for an outbreak such as this. In addition, laboratory disease surveillance contributes to the control measures for vaccine-preventable influenza.

The aetiology of paediatric inflammatory vulvovaginitis.

PubMed

Cuadros, Juan; Mazón, Ana; Martinez, Rocío; González, Pilar; Gil-Setas, Alberto; Flores, Uxua; Orden, Beatriz; Gómez-Herruz, Peña; Millan, Rosario

2004-02-01

Vulvovaginitis is the most common gynaecological problem in prepubertal girls and clear-cut data on the microbial aetiology of moderate to severe infections are lacking. Many microorganisms have been reported in several studies, but frequently the paediatrician does not know the pathogenic significance of an isolate reported in vaginal specimens of girls with vulvovaginitis. A multicentre study was performed, selecting 74 girls aged 2 to 12 years old with a clinical picture of vulvovaginitis and inflammatory cells on Gram stain. All the specimens were cultured following standard microbiological techniques and the paediatricians completed a questionnaire to highlight risk factors after interviewing the parents or tutors. The data were compared with those obtained in a control group of 11 girls without vulvovaginitis attending a clinic. Streptococcus pyogenesand Haemophilus spp.were isolated in 47 and 12 cases, respectively. Upper respiratory infection in the previous month ( P<0.001) and vulvovaginitis in the previous year ( P<0.05) were identified as significant risk factors. Foreign bodies, sexual abuse, poor hygiene and bad socioeconomic situation were not identified as risk factors for the infection. Paediatric inflammatory vulvovaginitis is mainly caused by pathogens of the upper respiratory tract and the most common risk factor for this infection is to have suffered an upper respiratory tract infection in the previous month.

Detection of Shigella sonnei in a respiratory specimen in a patient with subacute atypical pneumonia.

PubMed

Nahid, Hiwa; Staub, Désirée; Hächler, Herbert; Albrich, Werner C

2017-04-01

Pneumonia caused by shigellosis with or without typical dysentery in immunocompetent patients is an uncommon entity. We describe a case of pneumonia in an immunocompetent, previously healthy middle-aged man from Switzerland without relevant travel history which was presumably caused by Shigella sonnei. He was originally admitted for suspected lung cancer. The clinical picture was remarkable as the patient presented with cough and purulent sputum production, but otherwise no classical signs of pneumonia. Furthermore, there was no diarrhoeal episode in the recent history. It is an uncommon presentation of shigellosis in an immunocompetent person without underlying severe predisposing conditions. We report an unusual identification of S. sonnei as the only identified pathogen from respiratory specimens, which we therefore consider the most likely etiology of this subacute atypical pneumonia. This case illustrates the importance of a complete work-up in a patient whose suspected malignancy could not be proven.

Comparison of the pathogenic potential of highly pathogenic avian influenza (HPAI) H5N6, and H5N8 viruses isolated in South Korea during the 2016-2017 winter season.

PubMed

Kwon, Hyeok-Il; Kim, Eun-Ha; Kim, Young-Il; Park, Su-Jin; Si, Young-Jae; Lee, In-Won; Nguyen, Hiep Dinh; Yu, Kwang Min; Yu, Min-Ah; Jung, Ju Hwan; Choi, Won-Suk; Kwon, Jin Jung; Ahn, Su Jeong; Baek, Yun Hee; Van Lai, Dam; Lee, Ok-Jun; Kim, Si-Wook; Song, Min-Suk; Yoon, Sun-Woo; Kim, Chul-Joong; Webby, Richard J; Mo, In-Pil; Choi, Young Ki

2018-03-14

Highly pathogenic avian influenza (HPAI) A(H5N6) and A(H5N8) virus infections resulted in the culling of more than 37 million poultry in the Republic of Korea during the 2016/17 winter season. Here we characterize two representative viruses, A/Environment/Korea/W541/2016 [Em/W541(H5N6)] and A/Common Teal/Korea/W555/2017 [CT/W555(H5N8)], and evaluate their zoonotic potential in various animal models. Both Em/W541(H5N6) and CT /W555(H5N8) are novel reassortants derived from various gene pools of wild bird viruses present in migratory waterfowl arising from eastern China. Despite strong preferential binding to avian virus-type receptors, the viruses were able to grow in human respiratory tract tissues. Em/W541(H5N6) was found to be highly pathogenic in both chickens and ducks, while CT/W555(H5N8) caused lethal infections in chickens but did not induce remarkable clinical illness in ducks. In mice, both viruses appeared to be moderately pathogenic and displayed limited tissue tropism relative to HPAI H5N1 viruses. Em/W541(H5N6) replicated to moderate levels in the upper respiratory tract of ferrets and was detected in the lungs, brain, spleen, liver, and colon. Unexpectedly, two of three ferrets in direct contact with Em/W541(H5N6)-infected animals shed virus and seroconverted at 14 dpi. CT/W555(H5N8) was less pathogenic than the H5N6 virus in ferrets and no transmission was detected. Given the co-circulation of different, phenotypically distinct, subtypes of HPAI H5Nx viruses for the first time in South Korea, detailed virologic investigations are imperative given the capacity of these viruses to evolve and cause human infections.

History of the restoration of adenovirus type 4 and type 7 vaccine, live oral (Adenovirus Vaccine) in the context of the Department of Defense acquisition system.

PubMed

Hoke, Charles H; Snyder, Clifford E

2013-03-15

Respiratory pathogens cause morbidity and mortality in US military basic trainees. Following the influenza pandemic of 1918, and stimulated by WWII, the need to protect military personnel against epidemic respiratory disease was evident. Over several decades, the US military elucidated etiologies of acute respiratory diseases and invented and deployed vaccines to prevent disease caused by influenza, meningococcus, and adenoviruses. In 1994, the Adenovirus Vaccine manufacturer stopped its production. By 1999, supplies were exhausted and adenovirus-associated disease, especially serotype 4-associated febrile respiratory illness, returned to basic training installations. Advisory bodies persuaded Department of Defense leaders to initiate restoration of Adenovirus Vaccine. In 2011, after 10 years of effort by government and contractor personnel and at a cost of about $100 million, the Adenovirus Vaccine was restored to use at all military basic training installations. Disease and adenovirus serotype 4 isolation rates have fallen dramatically since vaccinations resumed in October 2011 and remain very low. Mindful of the adage that "The more successful a vaccine is, the more quickly the need for it will be forgotten.", sustainment of the supply of the Adenovirus Vaccine may be a challenge, and careful management will be required for such sustainment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mobile Microbiome

PubMed Central

Han, Y.W.; Wang, X.

2013-01-01

The link between oral infections and adverse systemic conditions has attracted much attention in the research community. Several mechanisms have been proposed, including spread of the oral infection due to transient bacteremia resulting in bacterial colonization in extra-oral sites, systemic injury by free toxins of oral pathogens, and systemic inflammation caused by soluble antigens of oral pathogens. Mounting evidence supports a major role of the systemic spread of oral commensals and pathogens to distant body sites causing extra-oral infections and inflammation. We review here the most recent findings on systemic infections and inflammation complicated by oral bacteria, including cardiovascular disease, adverse pregnancy outcomes, rheumatoid arthritis, inflammatory bowel disease and colorectal cancer, respiratory tract infections, and organ inflammations and abscesses. The recently identified virulence mechanisms of oral species Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus mutans, and Campylobacter rectus are also reviewed. A pattern emerges indicating that only select subtype(s) of a given species, e.g., F. nucleatum subspecies animalis and polymorphum and S. mutans non-c serotypes, are prone to extra-oral translocation. These findings advocate the importance of identification and quantification of potential pathogens at the subtype levels for accurate prediction of disease potential. PMID:23625375

In-vitro susceptibility of 1982 respiratory tract pathogens and 1921 urinary tract pathogens against 19 antimicrobial agents: a Canadian multicentre study. Canadian Antimicrobial Study Group.

PubMed

Blondeau, J M; Yaschuk, Y; Suter, M; Vaughan, D

1999-03-01

A total of 3903 pathogens from 48 Canadian medical centres were tested against 19 antimicrobial agents. Five agents showed activity against > or = 90% of all 1982 respiratory tract pathogens tested (ciprofloxacin, 90%; cefoperazone, 91%; ticarcillin/clavulanate, 92%; ceftazidime and imipenem, 93% each). Nine agents had > or = 90% activity against Enterobacteriaceae from respiratory tract infection (cefotaxime and ticarcillin/clavulanate, 90% each; aztreonam, ceftizoxime and ceftriaxone, 91% each; ceftazidime, 93%; ciprofloxacin, 97%; imipenem and netilmicin, 98% each). Similarly, five agents had activity against > or = 90% of all 1921 urinary tract pathogens tested (ciprofloxacin and ticarcillin/clavulanate, 90% each; cefoperazone and netilmicin, 91% each; imipenem, 99%). Nine agents had > or = 95% activity against Enterobacteriaceae from urinary tract infection (ciprofloxacin, 95%; cefotetan, 97%; aztreonam, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone and netilmicin, 98% each; imipenem, 99%). Seventeen agents had activity against > or = 95% of Staphylococcus aureus strains. Susceptibility of Pseudomonas aeruginosa isolates ranged from 2% to 91%.

Effects of Air Pollutants on Innate Immunity: The Role of Toll-like receptors and nucleotide-binding oligomerization domain-like receptors

EPA Science Inventory

Interactions between exposure to ambient air pollutants and respiratory pathogens have been shown to modify respiratory immune responses. Emerging data suggest key roles for toll-like receptor (TLR) and NOD-like receptor (NLR) signaling in pathogen-induced immune responses. Simil...

Macrolones Are a Novel Class of Macrolide Antibiotics Active against Key Resistant Respiratory Pathogens In Vitro and In Vivo.

PubMed

Čipčić Paljetak, Hana; Verbanac, Donatella; Padovan, Jasna; Dominis-Kramarić, Miroslava; Kelnerić, Željko; Perić, Mihaela; Banjanac, Mihailo; Ergović, Gabrijela; Simon, Nerrisa; Broskey, John; Holmes, David J; Eraković Haber, Vesna

2016-09-01

As we face an alarming increase in bacterial resistance to current antibacterial chemotherapeutics, expanding the available therapeutic arsenal in the fight against resistant bacterial pathogens causing respiratory tract infections is of high importance. The antibacterial potency of macrolones, a novel class of macrolide antibiotics, against key respiratory pathogens was evaluated in vitro and in vivo MIC values against Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, and Haemophilus influenzae strains sensitive to macrolide antibiotics and with defined macrolide resistance mechanisms were determined. The propensity of macrolones to induce the expression of inducible erm genes was tested by the triple-disk method and incubation in the presence of subinhibitory concentrations of compounds. In vivo efficacy was assessed in a murine model of S. pneumoniae-induced pneumonia, and pharmacokinetic (PK) profiles in mice were determined. The in vitro antibacterial profiles of macrolones were superior to those of marketed macrolide antibiotics, including the ketolide telithromycin, and the compounds did not induce the expression of inducible erm genes. They acted as typical protein synthesis inhibitors in an Escherichia coli transcription/translation assay. Macrolones were characterized by low to moderate systemic clearance, a large volume of distribution, a long half-life, and low oral bioavailability. They were highly efficacious in a murine model of pneumonia after intraperitoneal application even against an S. pneumoniae strain with constitutive resistance to macrolide-lincosamide-streptogramin B antibiotics. Macrolones are the class of macrolide antibiotics with an outstanding antibacterial profile and reasonable PK parameters resulting in good in vivo efficacy. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

European surveillance of emerging pathogens associated with canine infectious respiratory disease.

PubMed

Mitchell, Judy A; Cardwell, Jacqueline M; Leach, Heather; Walker, Caray A; Le Poder, Sophie; Decaro, Nicola; Rusvai, Miklos; Egberink, Herman; Rottier, Peter; Fernandez, Mireia; Fragkiadaki, Eirini; Shields, Shelly; Brownlie, Joe

2017-12-01

Canine infectious respiratory disease (CIRD) is a major cause of morbidity in dogs worldwide, and is associated with a number of new and emerging pathogens. In a large multi-centre European study the prevalences of four key emerging CIRD pathogens; canine respiratory coronavirus (CRCoV), canine pneumovirus (CnPnV), influenza A, and Mycoplasma cynos (M. cynos); were estimated, and risk factors for exposure, infection and clinical disease were investigated. CIRD affected 66% (381/572) of the dogs studied, including both pet and kennelled dogs. Disease occurrence and severity were significantly reduced in dogs vaccinated against classic CIRD agents, canine distemper virus (CDV), canine adenovirus 2 (CAV-2) and canine parainfluenza virus (CPIV), but substantial proportions (65.7%; 201/306) of vaccinated dogs remained affected. CRCoV and CnPnV were highly prevalent across the different dog populations, with overall seropositivity and detection rates of 47% and 7.7% for CRCoV, and 41.7% and 23.4% for CnPnV, respectively, and their presence was associated with increased occurrence and severity of clinical disease. Antibodies to CRCoV had a protective effect against CRCoV infection and more severe clinical signs of CIRD but antibodies to CnPnV did not. Involvement of M. cynos and influenza A in CIRD was less apparent. Despite 45% of dogs being seropositive for M. cynos, only 0.9% were PCR positive for M. cynos. Only 2.7% of dogs were seropositive for Influenza A, and none were positive by PCR. Copyright © 2017 Elsevier B.V. All rights reserved.

Macrolones Are a Novel Class of Macrolide Antibiotics Active against Key Resistant Respiratory Pathogens In Vitro and In Vivo

PubMed Central

Verbanac, Donatella; Padovan, Jasna; Dominis-Kramarić, Miroslava; Kelnerić, Željko; Perić, Mihaela; Banjanac, Mihailo; Ergović, Gabrijela; Simon, Nerrisa; Broskey, John; Holmes, David J.; Eraković Haber, Vesna

2016-01-01

As we face an alarming increase in bacterial resistance to current antibacterial chemotherapeutics, expanding the available therapeutic arsenal in the fight against resistant bacterial pathogens causing respiratory tract infections is of high importance. The antibacterial potency of macrolones, a novel class of macrolide antibiotics, against key respiratory pathogens was evaluated in vitro and in vivo. MIC values against Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, and Haemophilus influenzae strains sensitive to macrolide antibiotics and with defined macrolide resistance mechanisms were determined. The propensity of macrolones to induce the expression of inducible erm genes was tested by the triple-disk method and incubation in the presence of subinhibitory concentrations of compounds. In vivo efficacy was assessed in a murine model of S. pneumoniae-induced pneumonia, and pharmacokinetic (PK) profiles in mice were determined. The in vitro antibacterial profiles of macrolones were superior to those of marketed macrolide antibiotics, including the ketolide telithromycin, and the compounds did not induce the expression of inducible erm genes. They acted as typical protein synthesis inhibitors in an Escherichia coli transcription/translation assay. Macrolones were characterized by low to moderate systemic clearance, a large volume of distribution, a long half-life, and low oral bioavailability. They were highly efficacious in a murine model of pneumonia after intraperitoneal application even against an S. pneumoniae strain with constitutive resistance to macrolide-lincosamide-streptogramin B antibiotics. Macrolones are the class of macrolide antibiotics with an outstanding antibacterial profile and reasonable PK parameters resulting in good in vivo efficacy. PMID:27353268

Meningitis and septicemia caused by nontypeable Haemophilus influenzae in a previously healthy 2-year-old girl.

PubMed

Ito, Takao; Shibata, Hironori; Nakazawa, Mie; Myokai, Michiko; Ikegaya, Kazuko; Tsuchiya, Ken; Kamimaki, Tsutomu

2011-08-01

Nontypeable Haemophilus influenzae (NTHi) commonly colonizes the upper respiratory tract of children and causes otitis media, sinusitis, and bronchitis. Invasive NTHi diseases such as meningitis and septicemia have rarely been reported, especially in children with underlying predisposing conditions such as head trauma and immune compromise. However, we report a previously healthy 2-year-old girl who developed meningitis and septicemia caused by NTHi biotype ΙΙΙ. She was treated with dexamethasone, meropenem, and ceftriaxone, and recovered uneventfully. We wish to emphasize that NTHi should be borne in mind as a potential pathogen that can cause meningitis and septicemia, even in previously healthy children.

Research Gaps in Protecting Healthcare Workers From SARS and Other Respiratory Pathogens: An Interdisciplinary, Multi-Stakeholder, Evidence-Based Approach

PubMed Central

Yassi, Annalee; Moore, David; FitzGerald, J. Mark; Bigelow, Philip; Hon, Chun-Yip; Bryce, Elizabeth

2016-01-01

Objective To identify priorities for further research in protecting healthcare workers (HCWs) from severe acute respiratory syndrome (SARS) and other respiratory pathogens by summarizing the basic science of infectious bioaerosols and the efficacy of facial protective equipment; the organizational, environmental, and individual factors that influence the success of infection control and occupational health programs; and factors identified by HCWs as important. Method An extensive literature review was conducted and 15 focus groups held, mostly with frontline HCWs in Toronto. Critical gaps in knowledge were identified and prioritized. Results Highest priority was given to organizational factors that create a climate of safety. Other priority areas included understanding aerosolization risks and practical measures to control bioaerosols at the source. Conclusions Further research is warranted to improve safety climate in health care and, specifically, to provide greater protection against respiratory pathogens. PMID:15643158

Factors Associated with Lower Respiratory Tract Infections in HIV-Exposed Uninfected Infants.

PubMed

Weinberg, Adriana; Mussi-Pinhata, Marisa M; Yu, Qilu; Cohen, Rachel A; Almeida, Volia C; Amaral, Fabiana R; Freimanis, Laura; Harris, Donald Robert; Smith, Christiana; Siberry, George

2018-06-01

To identify factors that predispose human immunodeficiency virus (HIV)-exposed uninfected infants (HEUs) to higher incidence of severe infections, hospitalization, and death in the first 6-24 months of life compared with HEUs with and without lower respiratory tract infection (LRTI) in the first 6 months of life. Nested case-control study of 107 LRTI+ infants enrolled in the International Site Development Initiative (NISDI) Perinatal and Longitudinal Study in Latin American Countries (LILAC) studies with and 140 LRTI- in the first 6 months, matched by date and place of birth. Infants and mothers had plasma antibodies measured against respiratory syncytial virus (RSV), parainfluenza (PIV) 1, 2, 3, influenza, and pneumococcus 1, 5, 6B, and 14. Compared with LRTI-, mothers of LRTI+ HEUs had lower years of education, lower CD4 + cells, and higher HIV plasma viral load at delivery, but similar use of antiretrovirals and cotrimoxazole and other sociodemographic characteristics. LRTI+ and LRTI- HEUs had similar demographic and hematological characteristics and antibody concentrations against respiratory pathogens at birth. At 6 months, the rates of seroconversions to respiratory pathogens and antibody responses to tetanus vaccine were also similar. However, antibody concentrations to RSV were significantly higher in LRTI+ compared with LRTI- HEUs and marginally higher to PIV1. Maternal factors associated with advanced HIV disease, but unrelated to the use of antiretrovirals, cotrimoxazole, or the level of maternal antibodies against respiratory pathogens, contribute to the increased risk of LRTI in HEUs. In HEUs, antiretroviral and cotrimoxazole use, exposure to respiratory pathogens and humoral immune responses were not associated with the incidence of LRTI.

Simultaneous Detection of 13 Key Bacterial Respiratory Pathogens by Combination of Multiplex PCR and Capillary Electrophoresis.

PubMed

Jiang, Lu Xi; Ren, Hong Yu; Zhou, Hai Jian; Zhao, Si Hong; Hou, Bo Yan; Yan, Jian Ping; Qin, Tian; Chen, Yu

2017-08-01

Lower respiratory tract infections continue to pose a significant threat to human health. It is important to accurately and rapidly detect respiratory bacteria. To compensate for the limits of current respiratory bacteria detection methods, we developed a combination of multiplex polymerase chain reaction (PCR) and capillary electrophoresis (MPCE) assay to detect thirteen bacterial pathogens responsible for lower respiratory tract infections, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Mycoplasma pneumoniae, Legionella spp., Bordetella pertussis, Mycobacterium tuberculosis complex, Corynebacterium diphtheriae, and Streptococcus pyogenes. Three multiplex PCR reactions were built, and the products were analyzed by capillary electrophoresis using the high-throughput DNA analyzer. The specificity of the MPCE assay was examined and the detection limit was evaluated using DNA samples from each bacterial strain and the simulative samples of each strain. This assay was further evaluated using 152 clinical specimens and compared with real-time PCR reactions. For this assay, three nested-multiplex-PCRs were used to detect these clinical specimens. The detection limits of the MPCE assay for the 13 pathogens were very low and ranged from 10-7 to 10-2 ng/μL. Furthermore, analysis of the 152 clinical specimens yielded a specificity ranging from 96.5%-100.0%, and a sensitivity of 100.0% for the 13 pathogens. This study revealed that the MPCE assay is a rapid, reliable, and high-throughput method with high specificity and sensitivity. This assay has great potential in the molecular epidemiological survey of respiratory pathogens. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Extended release amoxicillin/clavulanate: optimizing a product for respiratory infections based on pharmacodynamic principles.

PubMed

Jacobs, Michael R

2005-06-01

Acute bacterial respiratory tract infections cause a great deal of human morbidity and mortality. Treatment guidelines for these infections include macrolides, doxycycline, beta-lactams and beta-lactam/beta-lactamase inhibitor combinations such as amoxicillin/clavulanic acid to provide coverage for the common respiratory pathogens, including penicillin and macrolide nonsusceptible Streptococcus pneumoniae, as well as beta-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis. In response to recent guidelines recommending higher dose amoxicillin to extend coverage to a higher percentage of S. pneumoniae, a new formulation of amoxicillin/clavulanic acid was developed. This formulation includes a higher amoxicillin dose, with part of the amoxicillin dose being in an extended release formulation, without increasing the clavulanate dose, for twice-daily oral treatment of these infections. Clinical studies of community-acquired pneumonia and acute rhinosinusitis have shown that the new formulation is well tolerated and highly efficacious, with clinical outcomes equivalent to comparators.

Identification of novel drug targets in bovine respiratory disease: an essential step in applying biotechnologic techniques to develop more effective therapeutic treatments

PubMed Central

Sakharkar, Meena Kishore; Rajamanickam, Karthic; Chandra, Ramesh; Khan, Haseeb A; Alhomida, Abdullah S; Yang, Jian

2018-01-01

Background Bovine Respiratory Disease (BRD) is a major problem in cattle production which causes substantial economic loss. BRD has multifactorial aetiologies, is multi-microbial, and several of the causative pathogens are unknown. Consequently, primary management practices such as metaphylactic antimicrobial injections for BRD prevention are used to reduce the incidence of BRD in feedlot cattle. However, this poses a serious threat in the form of development of antimicrobial resistance and demands an urgent need to find novel interventions that could reduce the effects of BRD drastically and also delay/prevent bacterial resistance. Materials and methods We have employed a subtractive genomics approach that helps delineate essential, host-specific, and druggable targets in pathogens responsible for BRD. We also proposed antimicrobials from FDA green and orange book that could be repositioned for BRD. Results We have identified 107 putative targets that are essential, selective and druggable. We have also confirmed the susceptibility of two BRD pathogens to one of the proposed antimicrobials – oxytetracycline. Conclusion This approach allows for repositioning drugs known for other infections to BRD, predicting novel druggable targets for BRD infection, and providing a new direction in developing more effective therapeutic treatments for BRD. PMID:29765203

Applying definitions for multidrug resistance, extensive drug resistance and pandrug resistance to clinically significant livestock and companion animal bacterial pathogens.

PubMed

Sweeney, Michael T; Lubbers, Brian V; Schwarz, Stefan; Watts, Jeffrey L

2018-06-01

Standardized definitions for MDR are currently not available in veterinary medicine despite numerous reports indicating that antimicrobial resistance may be increasing among clinically significant bacteria in livestock and companion animals. As such, assessments of MDR presented in veterinary scientific reports are inconsistent. Herein, we apply previously standardized definitions for MDR, XDR and pandrug resistance (PDR) used in human medicine to animal pathogens and veterinary antimicrobial agents in which MDR is defined as an isolate that is not susceptible to at least one agent in at least three antimicrobial classes, XDR is defined as an isolate that is not susceptible to at least one agent in all but one or two available classes and PDR is defined as an isolate that is not susceptible to all agents in all available classes. These definitions may be applied to antimicrobial agents used to treat bovine respiratory disease (BRD) caused by Mannheimia haemolytica, Pasteurella multocida and Histophilus somni and swine respiratory disease (SRD) caused by Actinobacillus pleuropneumoniae, P. multocida and Streptococcus suis, as well as antimicrobial agents used to treat canine skin and soft tissue infections (SSTIs) caused by Staphylococcus and Streptococcus species. Application of these definitions in veterinary medicine should be considered static, whereas the classification of a particular resistance phenotype as MDR, XDR or PDR could change over time as more veterinary-specific clinical breakpoints or antimicrobial classes and/or agents become available in the future.

Incidence and etiology of hospitalized acute respiratory infections in the Egyptian Delta.

PubMed

Rowlinson, Emily; Dueger, Erica; Mansour, Adel; Azzazy, Nahed; Mansour, Hoda; Peters, Lisa; Rosenstock, Summer; Hamid, Sarah; Said, Mayar M; Geneidy, Mohamed; Abd Allah, Monier; Kandeel, Amr

2017-01-01

Acute Respiratory Infections (ARI) are responsible for nearly two million childhood deaths worldwide. A limited number of studies have been published on the epidemiology of viral respiratory pathogens in Egypt. A total of 6113 hospitalized patients >1 month of age with suspected ARI were enrolled between June 23, 2009 and December 31, 2013. Naso- and oropharyngeal specimens were collected and tested for influenza A and B, respiratory syncytial virus, human metapneumovirus, adenovirus, and parainfluenza viruses 1-3. Blood specimens from children 1-11 months were cultured and bacterial growth was identified by polymerase chain reaction. Results from a healthcare utilization survey on the proportion of persons seeking care for ARI was used to calculate adjusted ARI incidence rates in the surveillance population. The proportion of patients with a viral pathogen detected decreased with age from 67% in patients age 1-11 months to 19% in patients ≥65 years of age. Influenza was the dominant viral pathogen detected in patients ≥1 year of age (13.9%). The highest incidence rates for hospitalized ARI were observed in children 1-11 months (1757.9-5537.5/100 000 population) and RSV was the most commonly detected pathogen in this age group. In this study population, influenza is the largest viral contributor to hospitalized ARIs and children 1-11 months of age experience a high rate of ARI hospitalizations. This study highlights a need for surveillance of additional viral pathogens and alternative detection methods for bacterial pathogens, which may reveal a substantial proportion of as yet unidentified etiologies in adults. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion

PubMed Central

Coleman, Christopher M.; Sisk, Jeanne M.; Mingo, Rebecca M.; Nelson, Elizabeth A.; White, Judith M.

2016-01-01

ABSTRACT The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) cause significant morbidity and morality. There is currently no approved therapeutic for highly pathogenic coronaviruses, even as MERS-CoV is spreading throughout the Middle East. We previously screened a library of FDA-approved drugs for inhibitors of coronavirus replication in which we identified Abelson (Abl) kinase inhibitors, including the anticancer drug imatinib, as inhibitors of both SARS-CoV and MERS-CoV in vitro. Here we show that the anti-CoV activity of imatinib occurs at the early stages of infection, after internalization and endosomal trafficking, by inhibiting fusion of the virions at the endosomal membrane. We specifically identified the imatinib target, Abelson tyrosine-protein kinase 2 (Abl2), as required for efficient SARS-CoV and MERS-CoV replication in vitro. These data demonstrate that specific approved drugs can be characterized in vitro for their anticoronavirus activity and used to identify host proteins required for coronavirus replication. This type of study is an important step in the repurposing of approved drugs for treatment of emerging coronaviruses. IMPORTANCE Both SARS-CoV and MERS-CoV are zoonotic infections, with bats as the primary source. The 2003 SARS-CoV outbreak began in Guangdong Province in China and spread to humans via civet cats and raccoon dogs in the wet markets before spreading to 37 countries. The virus caused 8,096 confirmed cases of SARS and 774 deaths (a case fatality rate of ∼10%). The MERS-CoV outbreak began in Saudi Arabia and has spread to 27 countries. MERS-CoV is believed to have emerged from bats and passed into humans via camels. The ongoing outbreak of MERS-CoV has resulted in 1,791 cases of MERS and 640 deaths (a case fatality rate of 36%). The emergence of SARS-CoV and MERS-CoV provides evidence that coronaviruses are currently spreading from zoonotic sources and can be highly pathogenic, causing serious morbidity and mortality in humans. Treatment of SARS-CoV and MERS-CoV infection is limited to providing supportive therapy consistent with any serious lung disease, as no specific drugs have been approved as therapeutics. Highly pathogenic coronaviruses are rare and appear to emerge and disappear within just a few years. Currently, MERS-CoV is still spreading, as new infections continue to be reported. The outbreaks of SARS-CoV and MERS-CoV and the continuing diagnosis of new MERS cases highlight the need for finding therapeutics for these diseases and potential future coronavirus outbreaks. Screening FDA-approved drugs streamlines the pipeline for this process, as these drugs have already been tested for safety in humans. PMID:27466418

The role of influenza in the severity and transmission of respiratory bacterial disease.

PubMed

Mina, Michael J; Klugman, Keith P

2014-09-01

Infections with influenza viruses and respiratory bacteria each contribute substantially to the global burden of morbidity and mortality. Simultaneous or sequential infection with these pathogens manifests in complex and difficult-to-treat disease processes that need extensive antimicrobial therapy and cause substantial excess mortality, particularly during annual influenza seasons and pandemics. At the host level, influenza viruses prime respiratory mucosal surfaces for excess bacterial acquisition and this supports increased carriage density and dissemination to the lower respiratory tract, while greatly constraining innate and adaptive antibacterial defences. Driven by virus-mediated structural modifications, aberrant immunological responses to sequential infection, and excessive immunopathological responses, co-infections are noted by short-term and long-term departures from immune homoeostasis, inhibition of appropriate pathogen recognition, loss of tolerance to tissue damage, and general increases in susceptibility to severe bacterial disease. At the population level, these effects translate into increased horizontal bacterial transmission and excess use of antimicrobial therapies. With increasing concerns about future possible influenza pandemics, the past decade has seen rapid advances in our understanding of these interactions. In this Review, we discuss the epidemiological and clinical importance of influenza and respiratory bacterial co-infections, including the foundational efforts that laid the groundwork for today's investigations, and detail the most important and current advances in our understanding of the structural and immunological mechanisms underlying the pathogenesis of co-infection. We describe and interpret what is known in sequence, from transmission and phenotypic shifts in bacterial dynamics to the immunological, cellular, and molecular modifications that underlie these processes, and propose avenues of further research that might be most valuable for prevention and treatment strategies to best mitigate excess disease during future influenza pandemics. Copyright © 2014 Elsevier Ltd. All rights reserved.

The role of influenza in the severity and transmission of respiratory bacterial disease

PubMed Central

Mina, Michael J; Klugman, Keith P

2016-01-01

Infections with influenza viruses and respiratory bacteria each contribute substantially to the global burden of morbidity and mortality. Simultaneous or sequential infection with these pathogens manifests in complex and difficult-to-treat disease processes that need extensive antimicrobial therapy and cause substantial excess mortality, particularly during annual influenza seasons and pandemics. At the host level, influenza viruses prime respiratory mucosal surfaces for excess bacterial acquisition and this supports increased carriage density and dissemination to the lower respiratory tract, while greatly constraining innate and adaptive antibacterial defences. Driven by virus-mediated structural modifications, aberrant immunological responses to sequential infection, and excessive immunopathological responses, co-infections are noted by short-term and long-term departures from immune homoeostasis, inhibition of appropriate pathogen recognition, loss of tolerance to tissue damage, and general increases in susceptibility to severe bacterial disease. At the population level, these effects translate into increased horizontal bacterial transmission and excess use of antimicrobial therapies. With increasing concerns about future possible influenza pandemics, the past decade has seen rapid advances in our understanding of these interactions. In this Review, we discuss the epidemiological and clinical importance of influenza and respiratory bacterial co-infections, including the foundational efforts that laid the groundwork for today’s investigations, and detail the most important and current advances in our understanding of the structural and immunological mechanisms underlying the pathogenesis of co-infection. We describe and interpret what is known in sequence, from transmission and phenotypic shifts in bacterial dynamics to the immunological, cellular, and molecular modifications that underlie these processes, and propose avenues of further research that might be most valuable for prevention and treatment strategies to best mitigate excess disease during future influenza pandemics. PMID:25131494

Mortality attributable to pandemic influenza A (H1N1) 2009 in San Luis Potosí, Mexico

PubMed Central

Comas‐García, Andreu; García‐Sepúlveda, Christian A.; Méndez‐de Lira, José J.; Aranda‐Romo, Saray; Hernández‐Salinas, Alba E.; Noyola, Daniel E.

2010-01-01

Please cite this paper as: Comas‐García et al. (2011) Mortality attributable to pandemic influenza A (H1N1) 2009 in San Luis Potosí, Mexico. Influenza and Other Respiratory Viruses 5(2), 76–82. Background  Acute respiratory infections are a leading cause of morbidity and mortality worldwide. Starting in 2009, pandemic influenza A(H1N1) 2009 virus has become one of the leading respiratory pathogens worldwide. However, the overall impact of this virus as a cause of mortality has not been clearly defined. Objectives  To determine the impact of pandemic influenza A(H1N1) 2009 on mortality in a Mexican population. Methods  We assessed the impact of pandemic influenza virus on mortality during the first and second outbreaks in San Luis Potosí, Mexico, and compared it to mortality associated with seasonal influenza and respiratory syncytial virus (RSV) during the previous winter seasons. Results  We estimated that, on average, 8·1% of all deaths that occurred during the 2003–2009 seasons were attributable to influenza and RSV. During the first pandemic influenza A(H1N1) 2009 outbreak, there was an increase in mortality in persons 5–59 years of age, but not during the second outbreak (Fall of 2009). Overall, pandemic influenza A (H1N1) 2009 outbreaks had similar effects on mortality to those associated with seasonal influenza virus epidemics. Conclusions  The impact of influenza A(H1N1) 2009 virus on mortality during the first year of the pandemic was similar to that observed for seasonal influenza. The establishment of real‐time surveillance systems capable of integrating virological, morbidity, and mortality data may result in the timely identification of outbreaks so as to allow for the institution of appropriate control measures to reduce the impact of emerging pathogens on the population. PMID:21306570

Molecular surveillance of traditional and emerging pathogens associated with canine infectious respiratory disease.

PubMed

Decaro, Nicola; Mari, Viviana; Larocca, Vittorio; Losurdo, Michele; Lanave, Gianvito; Lucente, Maria Stella; Corrente, Marialaura; Catella, Cristiana; Bo, Stefano; Elia, Gabriella; Torre, Giorgio; Grandolfo, Erika; Martella, Vito; Buonavoglia, Canio

2016-08-30

A molecular survey for traditional and emerging pathogens associated with canine infectious respiratory disease (CIRD) was conducted in Italy between 2011 and 2013 on a total of 138 dogs, including 78 early acute clinically ill CIRD animals, 22 non-clinical but exposed to clinically ill CIRD dogs and 38 CIRD convalescent dogs. The results showed that canine parainfluenza virus (CPIV) was the most commonly detected CIRD pathogen, followed by canine respiratory coronavirus (CRCoV), Bordetella bronchiseptica, Mycoplasma cynos, Mycoplasma canis and canine pneumovirus (CnPnV). Some classical CIRD agents, such as canine adenoviruses, canine distemper virus and canid herpesvirus 1, were not detected at all, as were not other emerging respiratory viruses (canine influenza virus, canine hepacivirus) and bacteria (Streptococcus equi subsp. zooepidemicus). Most severe forms of respiratory disease were observed in the presence of CPIV, CRCoV and M. cynos alone or in combination with other pathogens, whereas single CnPnV or M. canis infections were detected in dogs with no or very mild respiratory signs. Interestingly, only the association of M. cynos (alone or in combination with either CRCoV or M. canis) with severe clinical forms was statistically significant. The study, while confirming CPIV as the main responsible for CIRD occurrence, highlights the increasing role of recently discovered viruses, such as CRCoV and CnPnV, for which effective vaccines are not available in the market. Copyright © 2016 Elsevier B.V. All rights reserved.

Cage size, movement in and out of housing during daily care, and other environmental and population health risk factors for feline upper respiratory disease in nine North American animal shelters.

PubMed

Wagner, Denae C; Kass, Philip H; Hurley, Kate F

2018-01-01

Upper respiratory infection (URI) is not an inevitable consequence of sheltering homeless cats. This study documents variation in risk of URI between nine North American shelters; determines whether this reflects variation in pathogen frequency on intake or differences in transmission and expression of disease; and identifies modifiable environmental and group health factors linked to risk for URI. This study demonstrated that although periodic introduction of pathogens into shelter populations may be inevitable, disease resulting from those pathogens is not. Housing and care of cats, particularly during their first week of stay in an animal shelter environment, significantly affects the rate of upper respiratory infection.

Resequencing microarray probe design for typing genetically diverse viruses: human rhinoviruses and enteroviruses

PubMed Central

Wang, Zheng; Malanoski, Anthony P; Lin, Baochuan; Kidd, Carolyn; Long, Nina C; Blaney, Kate M; Thach, Dzung C; Tibbetts, Clark; Stenger, David A

2008-01-01

Background Febrile respiratory illness (FRI) has a high impact on public health and global economics and poses a difficult challenge for differential diagnosis. A particular issue is the detection of genetically diverse pathogens, i.e. human rhinoviruses (HRV) and enteroviruses (HEV) which are frequent causes of FRI. Resequencing Pathogen Microarray technology has demonstrated potential for differential diagnosis of several respiratory pathogens simultaneously, but a high confidence design method to select probes for genetically diverse viruses is lacking. Results Using HRV and HEV as test cases, we assess a general design strategy for detecting and serotyping genetically diverse viruses. A minimal number of probe sequences (26 for HRV and 13 for HEV), which were potentially capable of detecting all serotypes of HRV and HEV, were determined and implemented on the Resequencing Pathogen Microarray RPM-Flu v.30/31 (Tessarae RPM-Flu). The specificities of designed probes were validated using 34 HRV and 28 HEV strains. All strains were successfully detected and identified at least to species level. 33 HRV strains and 16 HEV strains could be further differentiated to serotype level. Conclusion This study provides a fundamental evaluation of simultaneous detection and differential identification of genetically diverse RNA viruses with a minimal number of prototype sequences. The results demonstrated that the newly designed RPM-Flu v.30/31 can provide comprehensive and specific analysis of HRV and HEV samples which implicates that this design strategy will be applicable for other genetically diverse viruses. PMID:19046445

Two avian H10 influenza A virus strains with different pathogenicity for mink (Mustela vison).

PubMed

Englund, L; Hård af Segerstad, C

1998-01-01

We compared two strains of avian influenza A viruses of subtype H10 by exposing mink to aerosols of A/mink/Sweden/3,900/84 (H10N4) naturally pathogenic for mink, or A/chicken/Germany/N/49, (H10N7). Lesions in the respiratory tract during the first week after infection were studied and described. Both virus strains caused inflammatory reactions in the lungs and antibody production in exposed mink but only mink/84 virus was reisolated. The lesions caused by mink/84 virus were more severe with higher area density of pneumonia, lower daily weight gain, and more virus in the tissues detected by immunohistochemistry. The results indicate that mink/84 (H10N4), but not chicken/49 virus (H10N7), established multiple cycle replication in infected cells in the mink.

Developing collaborative works for faster progress on fungal respiratory infections in cystic fibrosis.

PubMed

Schwarz, Carsten; Vandeputte, Patrick; Rougeron, Amandine; Giraud, Sandrine; Dugé de Bernonville, Thomas; Duvaux, Ludovic; Gastebois, Amandine; Alastruey-Izquierdo, Ana; Martín-Gomez, Maria Teresa; Mazuelos, Estrella Martin; Sole, Amparo; Cano, Josep; Pemán, Javier; Quindos, Guillermo; Botterel, Françoise; Bougnoux, Marie-Elisabeth; Chen, Sharon; Delhaès, Laurence; Favennec, Loïc; Ranque, Stéphane; Sedlacek, Ludwig; Steinmann, Joerg; Vazquez, Jose; Williams, Craig; Meyer, Wieland; Le Gal, Solène; Nevez, Gilles; Fleury, Maxime; Papon, Nicolas; Symoens, Françoise; Bouchara, Jean-Philippe

2018-04-01

Cystic fibrosis (CF) is the major genetic inherited disease in Caucasian populations. The respiratory tract of CF patients displays a sticky viscous mucus, which allows for the entrapment of airborne bacteria and fungal spores and provides a suitable environment for growth of microorganisms, including numerous yeast and filamentous fungal species. As a consequence, respiratory infections are the major cause of morbidity and mortality in this clinical context. Although bacteria remain the most common agents of these infections, fungal respiratory infections have emerged as an important cause of disease. Therefore, the International Society for Human and Animal Mycology (ISHAM) has launched a working group on Fungal respiratory infections in Cystic Fibrosis (Fri-CF) in October 2006, which was subsequently approved by the European Confederation of Medical Mycology (ECMM). Meetings of this working group, comprising both clinicians and mycologists involved in the follow-up of CF patients, as well as basic scientists interested in the fungal species involved, provided the opportunity to initiate collaborative works aimed to improve our knowledge on these infections to assist clinicians in patient management. The current review highlights the outcomes of some of these collaborative works in clinical surveillance, pathogenesis and treatment, giving special emphasis to standardization of culture procedures, improvement of species identification methods including the development of nonculture-based diagnostic methods, microbiome studies and identification of new biological markers, and the description of genotyping studies aiming to differentiate transient carriage and chronic colonization of the airways. The review also reports on the breakthrough in sequencing the genomes of the main Scedosporium species as basis for a better understanding of the pathogenic mechanisms of these fungi, and discusses treatment options of infections caused by multidrug resistant microorganisms, such as Scedosporium and Lomentospora species and members of the Rasamsonia argillacea species complex.

Antiviral activity in vitro of two preparations of the herbal medicinal product Sinupret® against viruses causing respiratory infections.

PubMed

Glatthaar-Saalmüller, B; Rauchhaus, U; Rode, S; Haunschild, J; Saalmüller, A

2011-12-15

Sinupret(®), a herbal medicinal product made from Gentian root, Primula flower, Elder flower, Sorrel herb, and Verbena herb is frequently used in the treatment of acute and chronic rhinosinusitis and respiratory viral infections such as common cold. To date little is known about its potential antiviral activity. Therefore experiments have been performed to measure the antiviral activity of Sinupret(®) oral drops (hereinafter referred to as "oral drops") and Sinupret(®) dry extract (hereinafter referred to as "dry extract"), in vitro against a broad panel of both enveloped and non-enveloped human pathogenic RNA and DNA viruses known to cause infections of the upper respiratory tract: influenza A, Chile 1/83 (H1N1) virus (FluA), Porcine Influenza A/California/07/2009 (H1N1) virus (pFluA), parainfluenza type 3 virus (Para 3), respiratory syncytial virus, strain Long (RSV), human rhinovirus B subtype 14 (HRV 14), coxsackievirus subtype A9 (CA9), and adenovirus C subtype 5 (Adeno 5). Concentration-dependent antiviral activity (EC(50) between 13.8 and 124.8 μg/ml) of Sinupret(®) was observed against RNA as well as DNA viruses independent of a viral envelope. Remarkable antiviral activity was shown against Adeno 5, HRV 14 and RSV in which dry extract was significantly superior to oral drops. This could be ascertained with different assays as plaque-reduction assays in plaque forming units (PFU), the analyses of a cytopathogenic effect (CPE) and with enzyme immunoassays (ELISA) to determine the amount of newly synthesised virus. Our results demonstrate that Sinupret(®) shows a broad spectrum of antiviral activity in vitro against viruses commonly known to cause respiratory infections. Copyright © 2011 Elsevier GmbH. All rights reserved.

One-Step Multiplex RT-qPCR Assay for the Detection of Peste des petits ruminants virus, Capripoxvirus, Pasteurella multocida and Mycoplasma capricolum subspecies (ssp.) capripneumoniae.

PubMed

Settypalli, Tirumala Bharani Kumar; Lamien, Charles Euloge; Spergser, Joachim; Lelenta, Mamadou; Wade, Abel; Gelaye, Esayas; Loitsch, Angelika; Minoungou, Germaine; Thiaucourt, Francois; Diallo, Adama

2016-01-01

Respiratory infections, although showing common clinical symptoms like pneumonia, are caused by bacterial, viral or parasitic agents. These are often reported in sheep and goats populations and cause huge economic losses to the animal owners in developing countries. Detection of these diseases is routinely done using ELISA or microbiological methods which are being reinforced or replaced by molecular based detection methods including multiplex assays, where detection of different pathogens is carried out in a single reaction. In the present study, a one-step multiplex RT-qPCR assay was developed for simultaneous detection of Capripoxvirus (CaPV), Peste de petits ruminants virus (PPRV), Pasteurella multocida (PM) and Mycoplasma capricolum ssp. capripneumonia (Mccp) in pathological samples collected from small ruminants with respiratory disease symptoms. The test performed efficiently without any cross-amplification. The multiplex PCR efficiency was 98.31%, 95.48%, 102.77% and 91.46% whereas the singleplex efficiency was 93.43%, 98.82%, 102.55% and 92.0% for CaPV, PPRV, PM and Mccp, respectively. The correlation coefficient was greater than 0.99 for all the targets in both multiplex and singleplex. Based on cycle threshold values, intra and inter assay variability, ranged between the limits of 2%-4%, except for lower concentrations of Mccp. The detection limits at 95% confidence interval (CI) were 12, 163, 13 and 23 copies/reaction for CaPV, PPRV, PM and Mccp, respectively. The multiplex assay was able to detect CaPVs from all genotypes, PPRV from the four lineages, PM and Mccp without amplifying the other subspecies of mycoplasmas. The discriminating power of the assay was proven by accurate detection of the targeted pathogen (s) by screening 58 viral and bacterial isolates representing all four targeted pathogens. Furthermore, by screening 81 pathological samples collected from small ruminants showing respiratory disease symptoms, CaPV was detected in 17 samples, PPRV in 45, and PM in six samples. In addition, three samples showed a co-infection of PPRV and PM. Overall, the one-step multiplex RT-qPCR assay developed will be a valuable tool for rapid detection of individual and co-infections of the targeted pathogens with high specificity and sensitivity.

Association of serum Clara cell protein CC16 with respiratory infections and immune response to respiratory pathogens in elite athletes.

PubMed

Kurowski, Marcin; Jurczyk, Janusz; Jarzębska, Marzanna; Moskwa, Sylwia; Makowska, Joanna S; Krysztofiak, Hubert; Kowalski, Marek L

2014-04-15

Respiratory epithelium integrity impairment caused by intensive exercise may lead to exercise-induced bronchoconstriction. Clara cell protein (CC16) has anti-inflammatory properties and its serum level reflects changes in epithelium integrity and airway inflammation. This study aimed to investigate serum CC16 in elite athletes and to seek associations of CC16 with asthma or allergy, respiratory tract infections (RTIs) and immune response to respiratory pathogens. The study was performed in 203 Olympic athletes. Control groups comprised 53 healthy subjects and 49 mild allergic asthmatics. Serum levels of CC16 and IgG against respiratory viruses and Mycoplasma pneumoniae were assessed. Allergy questionnaire for athletes was used to determine symptoms and exercise pattern. Current versions of ARIA and GINA guidelines were used when diagnosing allergic rhinitis and asthma, respectively. Asthma was diagnosed in 13.3% athletes, of whom 55.6% had concomitant allergic rhinitis. Allergic rhinitis without asthma was diagnosed in 14.8% of athletes. Mean CC16 concentration was significantly lower in athletes versus healthy controls and mild asthmatics. Athletes reporting frequent RTIs had significantly lower serum CC16 and the risk of frequent RTIs was more than 2-fold higher in athletes with low serum CC16 (defined as equal to or less than 4.99 ng/ml). Athletes had significantly higher anti-adenovirus IgG than healthy controls while only non-atopic athletes had anti-parainfluenza virus IgG significantly lower than controls. In all athletes weak correlation of serum CC16 and anti-parainfluenza virus IgG was present (R = 0.20, p < 0.01). In atopic athletes a weak positive correlations of CC16 with IgG specific for respiratory syncytial virus (R = 0.29, p = 0.009), parainfluenza virus (R = 0.31, p = 0.01) and adenovirus (R = 0.27, p = 0.02) were seen as well. Regular high-load exercise is associated with decrease in serum CC16 levels. Athletes with decreased CC16 are more susceptible to respiratory infections. Atopy may be an additional factor modifying susceptibility to infections in subjects performing regular high-load exercise.

Influenza C in Lancaster, UK, in the winter of 2014–2015

PubMed Central

Atkinson, Kate V.; Bishop, Lisa A.; Rhodes, Glenn; Salez, Nicolas; McEwan, Neil R.; Hegarty, Matthew J.; Robey, Julie; Harding, Nicola; Wetherell, Simon; Lauder, Robert M.; Pickup, Roger W.; Wilkinson, Mark; Gatherer, Derek

2017-01-01

Influenza C is not included in the annual seasonal influenza vaccine, and has historically been regarded as a minor respiratory pathogen. However, recent work has highlighted its potential role as a cause of pneumonia in infants. We performed nasopharyngeal or nasal swabbing and/or serum sampling (n = 148) in Lancaster, UK, over the winter of 2014–2015. Using enzyme-linked immunosorbent assay (ELISA), we obtain seropositivity of 77%. By contrast, only 2 individuals, both asymptomatic adults, were influenza C-positive by polymerase chain reaction (PCR). Deep sequencing of nasopharyngeal samples produced partial sequences for 4 genome segments in one of these patients. Bayesian phylogenetic analysis demonstrated that the influenza C genome from this individual is evolutionarily distant to those sampled in recent years and represents a novel genome constellation, indicating that it may be a product of a decades-old reassortment event. Although we find no evidence that influenza C was a significant respiratory pathogen during the winter of 2014–2015 in Lancaster, we confirm previous observations of seropositivity in the majority of the population. (170 words). PMID:28406194

[Diagnostics and antimicrobial therapy of severe community-acquired pneumonia].

PubMed

Sinopalnikov, A I; Zaitsev, A A

2015-04-01

In the current paper authors presented the latest information concerning etiology of severe community-acquired pneumonia. Most cases are caused by a relatively small number ofpathogenic bacterial and viral natures. The frequency of detection of various pathogens of severe community-acquired pneumonia may vary greatly depending on the region, season and clinical profile of patients, availability of relevant risk factors. Authors presented clinical characteristics of severe community-acquired pneumonia and comparative evaluation of a number of scales to assess the risk of adverse outcome of the disease. Diagnosis of severe community-acquired pneumonia includes the following: collecting of epidemiological history, identification of pneumonia, detection of sepsis and identification of multiple organ dysfunction syndrome, detection of acute respiratory failure, assessment of comorbidity. Authors gave recommendations concerning evaluation of the clinical manifestations of the disease, the use of instrumental and laboratory methods for diagnosis of severe community-acquired pneumonia. To select the mode of antimicrobial therapy is most important local monitoring antimicrobial resistance of pathogens. The main criteria for the effectiveness of treatment are to reduce body temperature, severe intoxication, respiratory and organ failure.

A genomic window into the virulence of Histophilus somni.

PubMed

Sandal, Indra; Inzana, Thomas J

2010-02-01

Histophilus somni is an obligate inhabitant of the respiratory and genital mucosal surfaces of bovines and ovines. An individual strain can be a primary pathogen, an opportunistic pathogen, or a commensal, but can also move between these classifications if introduced into an appropriate site (e.g. the lungs) under conditions that favor bacterial persistence. H. somni is one of the bacterial agents responsible for bovine respiratory disease complex and can also cause a variety of systemic diseases in cattle and sheep. Isolates from disease sites, such as the lungs, heart, and brain, express a wide array of virulence factors (including biofilm formation) designed to evade host defense mechanisms. By contrast, some isolates from the healthy genital tract often lack many of these virulence factors. The genomic sequences of two bovine isolates, one from pneumonic lung and the other from healthy prepuce, have aided in deciphering the differences in phenotype and virulence between the two strains, and reveal their striking genetic similarity to Haemophilus influenzae and other members of the Pasteurellaceae. (c) 2009 Elsevier Ltd. All rights reserved.

Integrated DNA and RNA extraction and purification on an automated microfluidic cassette from bacterial and viral pathogens causing community-acquired lower respiratory tract infections.

PubMed

Van Heirstraeten, Liesbet; Spang, Peter; Schwind, Carmen; Drese, Klaus S; Ritzi-Lehnert, Marion; Nieto, Benjamin; Camps, Marta; Landgraf, Bryan; Guasch, Francesc; Corbera, Antoni Homs; Samitier, Josep; Goossens, Herman; Malhotra-Kumar, Surbhi; Roeser, Tina

2014-05-07

In this paper, we describe the development of an automated sample preparation procedure for etiological agents of community-acquired lower respiratory tract infections (CA-LRTI). The consecutive assay steps, including sample re-suspension, pre-treatment, lysis, nucleic acid purification, and concentration, were integrated into a microfluidic lab-on-a-chip (LOC) cassette that is operated hands-free by a demonstrator setup, providing fluidic and valve actuation. The performance of the assay was evaluated on viral and Gram-positive and Gram-negative bacterial broth cultures previously sampled using a nasopharyngeal swab. Sample preparation on the microfluidic cassette resulted in higher or similar concentrations of pure bacterial DNA or viral RNA compared to manual benchtop experiments. The miniaturization and integration of the complete sample preparation procedure, to extract purified nucleic acids from real samples of CA-LRTI pathogens to, and above, lab quality and efficiency, represent important steps towards its application in a point-of-care test (POCT) for rapid diagnosis of CA-LRTI.

Simultaneous virus identification and characterization of severe unexplained pneumonia cases using a metagenomics sequencing technique.

PubMed

Zou, Xiaohui; Tang, Guangpeng; Zhao, Xiang; Huang, Yan; Chen, Tao; Lei, Mingyu; Chen, Wenbing; Yang, Lei; Zhu, Wenfei; Zhuang, Li; Yang, Jing; Feng, Zhaomin; Wang, Dayan; Wang, Dingming; Shu, Yuelong

2017-03-01

Many viruses can cause respiratory diseases in humans. Although great advances have been achieved in methods of diagnosis, it remains challenging to identify pathogens in unexplained pneumonia (UP) cases. In this study, we applied next-generation sequencing (NGS) technology and a metagenomic approach to detect and characterize respiratory viruses in UP cases from Guizhou Province, China. A total of 33 oropharyngeal swabs were obtained from hospitalized UP patients and subjected to NGS. An unbiased metagenomic analysis pipeline identified 13 virus species in 16 samples. Human rhinovirus C was the virus most frequently detected and was identified in seven samples. Human measles virus, adenovirus B 55 and coxsackievirus A10 were also identified. Metagenomic sequencing also provided virus genomic sequences, which enabled genotype characterization and phylogenetic analysis. For cases of multiple infection, metagenomic sequencing afforded information regarding the quantity of each virus in the sample, which could be used to evaluate each viruses' role in the disease. Our study highlights the potential of metagenomic sequencing for pathogen identification in UP cases.

Plague in China 2014-All sporadic case report of pneumonic plague.

PubMed

Li, Yun-Fang; Li, De-Biao; Shao, Hong-Sheng; Li, Hong-Jun; Han, Yue-Dong

2016-02-19

Yersinia pestis is the pathogen of the plague and caused three pandemics worldwide. Pneumonic plague is rarer than bubonic and septicemic plague. We report detailed clinical and pathogenic data for all the three sporadic cases of pneumonic plagues in China in 2014. All the three patients are herders in Gansu province of China. They were all infected by Yersinia pestis and displayed in the form of pneumonic plague respectively without related. We tested patient specimens from the upper (nasopharyngeal swabs) or the lower (sputum) respiratory tract and whole blood, plasma, and serum specimens for Yersinia pestis. All patients had fever, cough and dyspnea, and for patient 2 and 3, unconscious. Respiratory symptoms were predominant with acute respiratory failure. The chest X-ray showed signs consistent with necrotizing inflammation with multiple lobar involvements. Despite emergency treatment, all patients died of refractory multiple organ failure within 24 h after admission to hospital. All the contacts were quarantined immediately and there were no secondary cases. Nowadays, the plague is epidemic in animals and can infect people who contact with the infected animals which may cause an epidemic in human. We think dogs maybe an intermediate vector for plague and as a source of risk for humans who are exposed to pet animals or who work professionally with canines. If a patient has been exposed to a risk factor and has fever and dyspnea, plague should be considered. People who had contact with a confirmed case should be isolated and investigated for F1 antigen analysis and receive post-exposure preventive treatment. A vaccination strategy might be useful for individuals who are occupationally exposed in areas where endemically infected reservoirs of plague-infected small mammals co-exist.

Sparse evidence of MERS-CoV infection among animal workers living in Southern Saudi Arabia during 2012

PubMed Central

Memish, Ziad A; Alsahly, Ahmad; Masri, Malak al; Heil, Gary L; Anderson, Benjamin D; Peiris, Malik; Khan, Salah Uddin; Gray, Gregory C

2015-01-01

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging viral pathogen that primarily causes respiratory illness. We conducted a seroprevalence study of banked human serum samples collected in 2012 from Southern Saudi Arabia. Sera from 300 animal workers (17% with daily camel exposure) and 50 non-animal-exposed controls were examined for serological evidence of MERS-CoV infection by a pseudoparticle MERS-CoV spike protein neutralization assay. None of the sera reproducibly neutralized the MERS-CoV-pseudotyped lentiviral vector. These data suggest that serological evidence of zoonotic transmission of MERS-CoV was not common among animal workers in Southern Saudi Arabia during July 2012. PMID:25470665

Bayesian evidence and epidemiological implications of environmental contamination from acute respiratory infection in long-term care facilities.

PubMed

Diaz-Decaro, J D; Launer, B; Mckinnell, J A; Singh, R; Dutciuc, T D; Green, N M; Bolaris, M; Huang, S S; Miller, L G

2018-05-01

Skilled nursing home facilities (SNFs) house a vulnerable population frequently exposed to respiratory pathogens. Our study aims to gain a better understanding of the transmission of nursing home-acquired viral respiratory infections in non-epidemic settings. Symptomatic surveillance was performed in three SNFs for residents exhibiting acute respiratory symptoms. Environmental surveillance of five high-touch areas was performed to assess possible transmission. All resident and environmental samples were screened using a commercial multiplex polymerase chain reaction platform. Bayesian methods were used to evaluate environmental contamination. Among nursing home residents with respiratory symptoms, 19% had a detectable viral pathogen (parainfluenza-3, rhinovirus/enterovirus, RSV, or influenza B). Environmental contamination was found in 20% of total room surface swabs of symptomatic residents. Environmental and resident results were all concordant. Target period prevalence among symptomatic residents ranged from 5.5 to 13.3% depending on target. Bayesian analysis quantifies the probability of environmental shedding due to parainfluenza-3 as 92.4% (95% CI: 86.8-95.8%) and due to rhinovirus/enterovirus as 65.6% (95% CI: 57.9-72.5%). Our findings confirm that non-epidemic viral infections are common among SNF residents exhibiting acute respiratory symptoms and that environmental contamination may facilitate further spread with considerable epidemiological implications. Findings further emphasise the importance of environmental infection control for viral respiratory pathogens in long-term care facilities.

Synthetic Nanovaccines Against Respiratory Pathogens (SYNARP)

DTIC Science & Technology

2012-07-01

to other respiratory infections, such as pulmonary F. tularemia , and test the nanovaccines efficacy in animal models (unfunded option). Focusing on...nanovaccine platforms to other respiratory infections, such as pulmonary F. tularemia , and test the nanovaccines efficacy in animal models

76 FR 27327 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

... Hospitalized Persons Study; FOA IP11-011, Spectrum of Respiratory Pathogens in Acute Respiratory Tract... Developing Countries; FOA IP11-013, Influenza and Other Respiratory Diseases in Southern Hemisphere; and FOA...

Microbiological and pathological examination of fatal calf pneumonia cases induced by bacterial and viral respiratory pathogens.

PubMed

Szeredi, Levente; Jánosi, Szilárd; Pálfi, Vilmos

2010-09-01

The infectious origin of fatal cases of calf pneumonia was studied in 48 calves from 27 different herds on postmortem examination. Lung tissue samples were examined by pathological, histological, bacterial culture, virus isolation and immunohistochemical methods for the detection of viral and bacterial infections. Pneumonia was diagnosed in 47/48 cases and infectious agents were found in 40/47 (85%) of those cases. The presence of multiple respiratory pathogens in 23/40 (57.5%) cases indicated the complex origin of fatal calf pneumonia. The most important respiratory pathogens were Mannheimia-Pasteurella in 36/40 (90%) cases, followed by Arcanobacterium pyogenes in 16/40 (40%) cases, Mycoplasma bovis in 12/40 (30%) cases, and bovine respiratory syncytial virus in 4/40 (10%) cases. Histophilus somni was detected in 2/40 (5%) cases, while bovine herpesvirus-1, bovine viral diarrhoea virus and parainfluenza virus-3 were each found in 1/40 (2.5%) case. Mastadenovirus, bovine coronavirus, influenza A virus or Chlamydiaceae were not detected.

Pneumonia research in Papua New Guinea: 1967-1986.

PubMed

Riley, Ian D

2010-01-01

Between 1967 and 1985 research on pneumonia in Papua New Guinea (PNG) was fundamental not only to standard treatments of disease in PNG, but also to the establishment of the World Health Organization's global Program for Control of Acute Respiratory Infections. Pneumonia was the leading cause of death in both population-based and hospital studies. Research that began in 1967 revealed a pattern of disease in adults reminiscent of that seen in industrialized countries in the early 20th century. Streptococcus pneumoniae (pneumococcus) was the predominant causative organism. Pneumococci were commensals of the upper respiratory tract that invaded first the lungs and then the blood stream. Some serotypes were more invasive than others and case fatality increased with deeper levels of invasion. The pandemic of Hong Kong (H3N2) influenza spread to the Southern Highlands in 1969 resulting in 2000 deaths. The conclusion that pneumococcal pneumonia had been the principal cause of death led to the establishment of a pneumonia research unit in Tari. A field trial of pneumococcal polysaccharide vaccine showed the vaccine to be most effective in preventing invasive disease. Vaccination reduced pneumonia mortality by 44% in previously healthy adults. The epidemiological situation was more complex in children than in adults because many different species and serotypes of bacteria could be isolated from lung aspirate. Although many of these organisms would normally have been regarded as non-pathogenic, S. pneumoniae and Haemophilus influenzae, recognized pathogens, were the principal causes of severe morbidity and mortality. The same principles of carriage of and invasion by upper respiratory commensals applied as much to children as they did to adults, and the rank order of invasive serotypes of S. pneumoniae and H. influenzae was the same in different age groups. Slow maturation of a child's immune system meant, however, that children could be susceptible to invasion by particular serotypes. Infants were frequently colonized by pathogenic bacteria within days of birth. Nasal discharge, which was extremely common, was most probably a result of domestic smoke pollution and low standards of hygiene. Aspiration of infected secretions was a likely explanation for the variety of organisms isolated from lung aspirate. A trial of pneumococcal polysaccharide vaccine showed the vaccine to be effective in preventing death from pneumonia in children 6-9 months of age provided pneumonia was not associated with other causes of death; this result was shown to be consistent with the principles of infection and invasion described above. Principles of antibiotic therapy for child pneumonia were also established at this time.

Characterization of Candida species isolated from cases of lower respiratory tract infection.

PubMed

Jha, B J; Dey, S; Tamang, M D; Joshy, M E; Shivananda, P G; Brahmadatan, K N

2006-01-01

(1) To identify and characterize the Candida species isolates from lower respiratory tract infection. (2) to determine the rate of isolation of Candida species from sputum samples. This study was carried out in the Department of Microbiology, Manipal Teaching Hospital, Pokhara, Nepal from June 2002 to January 2003. A total of 462 sputum samples were collected from patients suspected lower respiratory tract infection. The samples were processed as Gram staining to find out the suitability of the specimen, cultured on Sabouraud's Dextrose Agar (SDA) and also on blood agar and chocolate agar to identify the potential lower respiratory tract pathogens. For the identification of Candida, sputum samples were processed for Gram stain, culture, germ tube test, production of chlamydospore, sugar fermentation and assimilation test. For the identification of bacteria, Gram stain, culture, and biochemical tests were performed by standardized procedure. Out of 462 samples, 246 (53.24%) samples grew potential pathogens of lower respiratory tract. Among them Haemophilus influenzae 61(24.79%) and Streptococcus pneumoniae 57 (23.17%) were the predominant bacterial pathogens. Candida species were isolated from 30 samples (12.2%). The majority of Candida species amongst the Candida isolates were Candida albicans 21(70%) followed by Candida tropicalis 4(13.33%). Candida krusei 3(10%), Candida parapsilosis 1(3.33%) and Candida stellatoidea 1(3.33%). The highest rate of isolation of Candida was between the age of 71 and 80. Candida isolation from sputum samples is important as found in the present study in which Candida species were the third most common pathogen isolated from patients with lower respiratory tract infection.

Public preferences for vaccination programmes during pandemics caused by pathogens transmitted through respiratory droplets - a discrete choice experiment in four European countries, 2013.

PubMed

Determann, Domino; Korfage, Ida J; Fagerlin, Angela; Steyerberg, Ewout W; Bliemer, Michiel C; Voeten, Helene A; Richardus, Jan Hendrik; Lambooij, Mattijs S; de Bekker-Grob, Esther W

2016-06-02

This study aims to quantify and compare preferences of citizens from different European countries for vaccination programme characteristics during pandemics, caused by pathogens which are transmitted through respiratory droplets. Internet panel members, nationally representative based on age, sex, educational level and region, of four European Union Member States (Netherlands, Poland, Spain, and Sweden, n = 2,068) completed an online discrete choice experiment. These countries, from different geographical areas of Europe, were chosen because of the availability of high-quality Internet panels and because of the cooperation between members of the project entitled Effective Communication in Outbreak Management: development of an evidence-based tool for Europe (ECOM). Data were analysed using panel latent class regression models. In the case of a severe pandemic scenario, vaccine effectiveness was the most important characteristic determining vaccination preference in all countries, followed by the body that advises on vaccination. In Sweden, the advice of family and/or friends and the advice of physicians strongly affected vaccine preferences, in contrast to Poland and Spain, where the advice of (international) health authorities was more decisive. Irrespective of pandemic scenario or vaccination programme characteristics, the predicted vaccination uptakes were lowest in Sweden, and highest in Poland. To increase vaccination uptake during future pandemics, the responsible authorities should align with other important stakeholders in the country and communicate in a coordinated manner.

Microbiological Features of Upper Respiratory Tract Infections in Bulgarian Children for the Period 1998-2014.

PubMed

Gergova, Raina Tzvetanova; Petrova, Guergana; Gergov, Stefan; Minchev, Petko; Mitov, Ivan; Strateva, Tanya

2016-11-01

Across the globe, upper respiratory tract infections (URTIs) are the most prevalent cause of morbidity in childhood. The aim of our study is to analyze the incidence and etiology of bacterial URTIs in Bulgarian children, as well as the increasing antimicrobial resistance to the most common etiologic agents over a period of 17 years. Retrospective study. The study material comprised the data from 4768 patients (aged 1-16 years) with URTI during the period from 1998-2014. Specific microbiology agent detection was performed by culture examination. Susceptibilities to the investigated pathogens were determined by the disk diffusion method and minimal inhibitory concentration according to the criteria of the Clinical and Laboratory Standards Institute (CLSI). Polymerase chain reaction was used to detect the presence of β-lactam resistance genes. We identified the following as the most common URTI bacterial pathogens: Streptococcus pneumoniae (40.94%), Streptococcus pyogenes (34.16%), Haemophilus influenzae (44.23%), Moraxella catarrhalis (39.19%) and Staphylococcus aureus (23.88%). In more than 70% of cases, a polymicrobial etiology was found. The most commonly affected individuals were pre-school-aged children, which accounted for more than 36% of all patients. During the study period, a dramatic increase in resistance to antibiotic agents was observed. The most frequent types of resistance were the enzymatic inactivation of penicillins and cephalosporins (close to 100% in staphylococci and moraxellae) and inducible macrolide-lincozamide resistance (about 20% of Gram-positive cocci). Due to mandatory immunization against pneumococci and H. influenzae in Bulgaria and the vast expanding resistance to the most popular antimicrobial agents changes in the etiology of URTI have recently been noted. Regular analysis of this etiological dynamic and the antimicrobial resistance of respiratory pathogens is important for choosing the correct therapy and successful treatment.

Host Immune Response to Histophilus somni.

PubMed

Corbeil, Lynette B

2016-01-01

Histophilus somni is known to cause several overlapping syndromes or to be found in genital or upper respiratory carrier states in ruminants. Vaccines have been used for decades, yet efficacy is controversial and mechanisms of protective immunity are not well understood. Since H. somni survives phagocytosis, it has sometimes been considered to be a facultative intercellular parasite, implying that cell-mediated immunity would be critical in protection. However, H. somni not only inhibits phagocyte function, but also is cytotoxic for macrophages. Therefore, it does not live for long periods in healthy phagocytes. Protection of calves against H. somni pneumonia by passive immunization is also evidence that H. somni is more like an extracellular pathogen than an intracellular pathogen. Several studies showed that bovine IgG2 antibodies are more protective than IgG1 antibodies. Even the IgG2 allotypes tend to vary in protection. Of course, antigenic specificity also determines protection. So far, there is most evidence for protection by a 40 K outer membrane protein and by Immunoglobulin binding protein A fibrils. Serology and immunohistochemistry have both been used for immunodiagnosis. Many evasive mechanisms by H. somni have been defined, including decreased phagocyte function, antibodies bound by shed antigens, decreased immune stimulation, and antigenic variation. Interaction of H. somni with other bovine respiratory disease organisms is another layer of pathogenesis. Studies of bovine respiratory syncytial virus (BRSV) and H. somni in calfhood pneumonia revealed an increase in IgE antibodies to H. somni, which were associated with more severe disease of longer duration than with either agent alone. Innate immune mechanisms at the epithelial cell level are also affected by dual infection by BRSV and H. somni as compared to either pathogen alone. Although much more work needs to be done, the complex mechanisms of H. somni immunity are becoming clearer.

Role of viral and bacterial pathogens in causing pneumonia among Western Australian children: a case–control study protocol

PubMed Central

Bhuiyan, Mejbah Uddin; Snelling, Thomas L; West, Rachel; Lang, Jurissa; Rahman, Tasmina; Borland, Meredith L; Thornton, Ruth; Kirkham, Lea-Ann; Sikazwe, Chisha; Martin, Andrew C; Richmond, Peter C; Smith, David W; Jaffe, Adam; Blyth, Christopher C

2018-01-01

Introduction Pneumonia is the leading cause of childhood morbidity and mortality globally. Introduction of the conjugate Haemophilus influenzae B and multivalent pneumococcal vaccines in developed countries including Australia has significantly reduced the overall burden of bacterial pneumonia. With the availability of molecular diagnostics, viruses are frequently detected in children with pneumonia either as primary pathogens or predispose to secondary bacterial infection. Many respiratory pathogens that are known to cause pneumonia are also identified in asymptomatic children, so the true contribution of these pathogens to childhood community-acquired pneumonia (CAP) remains unclear. Since the introduction of pneumococcal vaccines, very few comprehensive studies from developed countries have attempted to determine the bacterial and viral aetiology of pneumonia. We aim to determine the contribution of bacteria and viruses to childhood CAP to inform further development of effective diagnosis, treatment and preventive strategies. Methods and analysis We are conducting a prospective case–control study (PneumoWA) where cases are children with radiologically confirmed pneumonia admitted to Princess Margaret Hospital for Children (PMH) and controls are healthy children identified from PMH outpatient clinics and from local community immunisation clinics. The case–control ratio is 1:1 with 250 children to be recruited in each arm. Nasopharyngeal swabs are collected from both cases and controls to detect the presence of viruses and bacteria by PCR; pathogen load will be assessed by quantitative PCR. The prevalence of pathogens detected in cases and controls will be compared, the OR of detection and population attributable fraction to CAP for each pathogen will be determined; relationships between pathogen load and disease status and severity will be explored. Ethics and dissemination This study has been approved by the human research ethics committees of PMH, Perth, Australia (PMH HREC REF 2014117EP). Findings will be disseminated at research conferences and in peer-reviewed journals. PMID:29549211

Attenuated Phenotype of a Recent House Finch-Associated Mycoplasma gallisepticum Isolate in Domestic Poultry.

PubMed

Pflaum, K; Tulman, E R; Beaudet, J; Liao, X; Dhondt, K V; Dhondt, A A; Hawley, D M; Ley, D H; Kerr, K M; Geary, S J

2017-06-01

Mycoplasma gallisepticum , known primarily as a respiratory pathogen of domestic poultry, has emerged since 1994 as a significant pathogen of the house finch ( Haemorhous mexicanus ) causing severe conjunctivitis and mortality. House finch-associated M. gallisepticum (HFMG) spread rapidly and increased in virulence for the finch host in the eastern United States. In the current study, we assessed virulence in domestic poultry with two temporally distant, and yet geographically consistent, HFMG isolates which differ in virulence for house finches-Virginia 1994 (VA1994), the index isolate of the epidemic, and Virginia 2013 (VA2013), a recent isolate of increased house finch virulence. Here we report a significant difference between VA1994 and VA2013 in their levels of virulence for chickens; notably, this difference correlated inversely to the difference in their levels of virulence for house finches. VA1994, while moderately virulent in house finches, displayed significant virulence in the chicken respiratory tract. VA2013, while highly virulent in the house finch, was significantly attenuated in chickens relative to VA1994, displaying less-severe pathological lesions in, and reduced bacterial recovery from, the respiratory tract. Overall, these data indicate that a recent isolate of HFMG is greatly attenuated in the chicken host relative to the index isolate, notably demonstrating a virulence phenotype in chickens inversely related to that in the finch host. Copyright © 2017 American Society for Microbiology.

Respiratory infection rates differ between geographically distant paediatric cystic fibrosis cohorts

PubMed Central

Hart, Emily; Turkovic, Lidija; Padros-Goossens, Marc; Stick, Stephen M.; Ranganathan, Sarath C.

2016-01-01

Respiratory infections are a major cause of pulmonary decline in children with cystic fibrosis (CF). We compared the prevalence of infection in early life at geographically distant CF treatment centres participating in the same surveillance programme in Australia. Lower airway microbiology, inflammation and structural lung disease at annual review were evaluated for 260 children 0–8 years old with CF at 1032 visits to CF treatment centres in Melbourne or Perth. Melbourne patients were more likely to be culture-positive for common respiratory pathogens at all age groups (odds ratio (OR) 1.85, 95% CI 1.33–2.58). Subjects <2 years old in Melbourne were also more likely to have neutrophil elastase present (OR 3.11, 95% CI 1.62–5.95). Bronchiectasis (OR 2.02, 95% CI 1.21–3.38) and air trapping (OR 2.53, 95% CI 1.42–4.51) in subjects 2–5 years old was more common in Melbourne subjects. The severity of structural lung disease was also worse in Melbourne patients >5 years old. Patients at both centres had a similar rate of hospitalisations and prescribed antibiotics. No procedural differences were identified that could explain the disparity between pathogen prevalence. Geographical differences in early acquisition of infection may contribute to variability in outcomes between CF centres. PMID:27957481

European Respiratory Society guidelines for the management of adult bronchiectasis.

PubMed

Polverino, Eva; Goeminne, Pieter C; McDonnell, Melissa J; Aliberti, Stefano; Marshall, Sara E; Loebinger, Michael R; Murris, Marlene; Cantón, Rafael; Torres, Antoni; Dimakou, Katerina; De Soyza, Anthony; Hill, Adam T; Haworth, Charles S; Vendrell, Montserrat; Ringshausen, Felix C; Subotic, Dragan; Wilson, Robert; Vilaró, Jordi; Stallberg, Bjorn; Welte, Tobias; Rohde, Gernot; Blasi, Francesco; Elborn, Stuart; Almagro, Marta; Timothy, Alan; Ruddy, Thomas; Tonia, Thomy; Rigau, David; Chalmers, James D

2017-09-01

Bronchiectasis in adults is a chronic disorder associated with poor quality of life and frequent exacerbations in many patients. There have been no previous international guidelines.The European Respiratory Society guidelines for the management of adult bronchiectasis describe the appropriate investigation and treatment strategies determined by a systematic review of the literature.A multidisciplinary group representing respiratory medicine, microbiology, physiotherapy, thoracic surgery, primary care, methodology and patients considered the most relevant clinical questions (for both clinicians and patients) related to management of bronchiectasis. Nine key clinical questions were generated and a systematic review was conducted to identify published systematic reviews, randomised clinical trials and observational studies that answered these questions. We used the GRADE approach to define the quality of the evidence and the level of recommendations. The resulting guideline addresses the investigation of underlying causes of bronchiectasis, treatment of exacerbations, pathogen eradication, long term antibiotic treatment, anti-inflammatories, mucoactive drugs, bronchodilators, surgical treatment and respiratory physiotherapy.These recommendations can be used to benchmark quality of care for people with bronchiectasis across Europe and to improve outcomes. Copyright ©ERS 2017.

Human metapneumovirus-associated hospital admissions over five consecutive epidemic seasons: evidence for alternating circulation of different genotypes.

PubMed

Apostoli, Paola; Zicari, Sonia; Lo Presti, Alessandra; Ciccozzi, Massimo; Ciotti, Marco; Caruso, Arnaldo; Fiorentini, Simona

2012-03-01

Human metapneumovirus (hMPV) is a pathogen of the respiratory tract with a worldwide distribution. The purpose of this study was to identify hMPV as the cause of acute respiratory diseases in children admitted at Spedali Civili, a public hospital in Brescia, Italy. Eight hundred forty-six nasopharyngeal aspirate samples negative for the presence of other common respiratory viruses were tested for the presence of hMPV RNA by reverse transcription-polymerase chain reaction. Of the 846 samples, 79 (9.3%) were positive for hMPV. Polymerase chain reaction products, obtained by amplification of the partial nucleotide sequence of gene F, were sequenced and compared with sequences deposited in GenBank. All four hMPV subtypes were identified, including the proposed subtype A2 sublineages "A" and "B". In successive epidemic seasons, large outbreaks of hMPV alternated with small outbreaks in a biannual pattern. This local study provides further evidence that hMPV infection should be considered as a reason for hospital admission for acute respiratory disease in children. Copyright © 2012 Wiley Periodicals, Inc.

Antimicrobial Susceptibility of Bacteria That Cause Bovine Respiratory Disease Complex in Alberta, Canada.

PubMed

Anholt, R Michele; Klima, Cassidy; Allan, Nick; Matheson-Bird, Heather; Schatz, Crystal; Ajitkumar, Praseeda; Otto, Simon Jg; Peters, Delores; Schmid, Karin; Olson, Merle; McAllister, Tim; Ralston, Brenda

2017-01-01

Bovine respiratory disease (BRD) is the most important illness of feedlot cattle. Disease management targets the associated bacterial pathogens, Mannheimia haemolytica, Mycoplasma bovis, Pasteurella multocida, Histophilus somni , and Trueperella pyogenes . We conducted a cross-sectional study to measure the frequencies of antimicrobial-resistant BRD pathogens using a collaborative network of veterinarians, industry, government, and a diagnostic laboratory. Seven private veterinary practices in southern Alberta collected samples from both living and dead BRD-affected animals at commercial feedlots. Susceptibility testing of 745 isolates showed that 100% of the M. haemolytica, M. bovis, P. multocida , and T. pyogenes isolates and 66.7% of the H. somni isolates were resistant to at least one antimicrobial class. Resistance to macrolide antimicrobials (90.2% of all isolates) was notable for their importance to beef production and human medicine. Multidrug resistance (MDR) was high in all target pathogens with 47.2% of the isolates resistant to four or five antimicrobial classes and 24.0% resistance to six to nine classes. We compared the MDR profiles of isolates from two feedlots serviced by different veterinary practices. Differences in the average number of resistant classes were found for M. haemolytica ( p  < 0.001) and P. multocida ( p  = 0.002). Compared to previous studies, this study suggests an increasing trend of resistance in BRD pathogens against the antimicrobials used to manage the disease in Alberta. For the veterinary clinician, the results emphasize the importance of ongoing susceptibility testing of BRD pathogens to inform treatment protocols. Surveillance studies that collect additional epidemiological information and manage sampling bias will be necessary to develop strategies to limit the spread of resistance.

Antimicrobial Susceptibility of Bacteria That Cause Bovine Respiratory Disease Complex in Alberta, Canada

PubMed Central

Anholt, R. Michele; Klima, Cassidy; Allan, Nick; Matheson-Bird, Heather; Schatz, Crystal; Ajitkumar, Praseeda; Otto, Simon JG; Peters, Delores; Schmid, Karin; Olson, Merle; McAllister, Tim; Ralston, Brenda

2017-01-01

Bovine respiratory disease (BRD) is the most important illness of feedlot cattle. Disease management targets the associated bacterial pathogens, Mannheimia haemolytica, Mycoplasma bovis, Pasteurella multocida, Histophilus somni, and Trueperella pyogenes. We conducted a cross-sectional study to measure the frequencies of antimicrobial-resistant BRD pathogens using a collaborative network of veterinarians, industry, government, and a diagnostic laboratory. Seven private veterinary practices in southern Alberta collected samples from both living and dead BRD-affected animals at commercial feedlots. Susceptibility testing of 745 isolates showed that 100% of the M. haemolytica, M. bovis, P. multocida, and T. pyogenes isolates and 66.7% of the H. somni isolates were resistant to at least one antimicrobial class. Resistance to macrolide antimicrobials (90.2% of all isolates) was notable for their importance to beef production and human medicine. Multidrug resistance (MDR) was high in all target pathogens with 47.2% of the isolates resistant to four or five antimicrobial classes and 24.0% resistance to six to nine classes. We compared the MDR profiles of isolates from two feedlots serviced by different veterinary practices. Differences in the average number of resistant classes were found for M. haemolytica (p < 0.001) and P. multocida (p = 0.002). Compared to previous studies, this study suggests an increasing trend of resistance in BRD pathogens against the antimicrobials used to manage the disease in Alberta. For the veterinary clinician, the results emphasize the importance of ongoing susceptibility testing of BRD pathogens to inform treatment protocols. Surveillance studies that collect additional epidemiological information and manage sampling bias will be necessary to develop strategies to limit the spread of resistance. PMID:29255716

Human infection with a novel, highly pathogenic avian influenza A (H5N6) virus: Virological and clinical findings.

PubMed

Pan, Ming; Gao, Rongbao; Lv, Qiang; Huang, Shunhe; Zhou, Zhonghui; Yang, Lei; Li, Xiaodan; Zhao, Xiang; Zou, Xiaohui; Tong, Wenbin; Mao, Suling; Zou, Shumei; Bo, Hong; Zhu, Xiaoping; Liu, Lei; Yuan, Heng; Zhang, Minghong; Wang, Daqing; Li, Zumao; Zhao, Wei; Ma, Maoli; Li, Yaqiang; Li, Tianshu; Yang, Huiping; Xu, Jianan; Zhou, Lijun; Zhou, Xingyu; Tang, Wei; Song, Ying; Chen, Tao; Bai, Tian; Zhou, Jianfang; Wang, Dayan; Wu, Guizhen; Li, Dexin; Feng, Zijian; Gao, George F; Wang, Yu; He, Shusen; Shu, Yuelong

2016-01-01

Severe infection with avian influenza A (H5N6) virus in humans was identified first in 2014 in China. Before that, it was unknown or unclear if the disease or the pathogen affected people. This study illustrates the virological and clinical findings of a fatal H5N6 virus infection in a human patient. We obtained and analyzed the clinical, epidemiological, and virological data from the patient. Reverse transcription polymerase chain reaction (RT-PCR), viral culture, and sequencing were conducted for determination of the causative pathogen. The patient, who presented with fever, severe pneumonia, leucopenia, and lymphopenia, developed septic shock and acute respiratory distress syndrome (ARDS), and died on day 10 after illness onset. A novel reassortant avian-origin influenza A (H5N6) virus was isolated from the throat swab or trachea aspirate of the patient. The virus was reassorted with the HA gene of clade 2.3.4.4 H5, the internal genes of clade 2.3.2.1 H5, and the NA gene of the H6N6 avian virus. The cleavage site of the HA gene contained multiple basic amino acids, indicating that the novel H5N6 virus was highly pathogenic in chicken. A novel, highly pathogenic avian influenza H5N6 virus with a backbone of H5N1 virus acquired from the NA gene from the H6N6 virus has been identified. It caused human infection resulting in severe respiratory disease. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Alveolar Type II Epithelial Cells Contribute to the Anti-Influenza A Virus Response in the Lung by Integrating Pathogen- and Microenvironment-Derived Signals.

PubMed

Stegemann-Koniszewski, S; Jeron, Andreas; Gereke, Marcus; Geffers, Robert; Kröger, Andrea; Gunzer, Matthias; Bruder, Dunja

2016-05-03

Influenza A virus (IAV) periodically causes substantial morbidity and mortality in the human population. In the lower lung, the primary targets for IAV replication are type II alveolar epithelial cells (AECII), which are increasingly recognized for their immunological potential. So far, little is known about their reaction to IAV and their contribution to respiratory antiviral immunity in vivo Therefore, we characterized the AECII response during early IAV infection by analyzing transcriptional regulation in cells sorted from the lungs of infected mice. We detected rapid and extensive regulation of gene expression in AECII following in vivo IAV infection. The comparison to transcriptional regulation in lung tissue revealed a strong contribution of AECII to the respiratory response. IAV infection triggered the expression of a plethora of antiviral factors and immune mediators in AECII with a high prevalence for interferon-stimulated genes. Functional pathway analyses revealed high activity in pathogen recognition, immune cell recruitment, and antigen presentation. Ultimately, our analyses of transcriptional regulation in AECII and lung tissue as well as interferon I/III levels and cell recruitment indicated AECII to integrate signals provided by direct pathogen recognition and surrounding cells. Ex vivo analysis of AECII proved a powerful tool to increase our understanding of their role in respiratory immune responses, and our results clearly show that AECII need to be considered a part of the surveillance and effector system of the lower respiratory tract. In order to confront the health hazard posed by IAV, we need to complete our understanding of its pathogenesis. AECII are primary targets for IAV replication in the lung, and while we are beginning to understand their importance for respiratory immunity, the in vivo AECII response during IAV infection has not been analyzed. In contrast to studies addressing the response of AECII infected with IAV ex vivo, we have performed detailed gene transcriptional profiling of AECII isolated from the lungs of infected mice. Thereby, we have identified an exceptionally rapid and versatile response to IAV infection that is shaped by pathogen-derived as well as microenvironment-derived signals and aims at the induction of antiviral measures and the recruitment and activation of immune cells. In conclusion, our study presents AECII as active players in antiviral defense in vivo that need to be considered part of the sentinel and effector immune system of the lung. Copyright © 2016 Stegemann-Koniszewski et al.

A novel porcine model of ventilator-associated pneumonia caused by oropharyngeal challenge with Pseudomonas aeruginosa.

PubMed

Li Bassi, Gianluigi; Rigol, Montserrat; Marti, Joan-Daniel; Saucedo, Lina; Ranzani, Otavio T; Roca, Ignasi; Cabanas, Maria; Muñoz, Laura; Giunta, Valeria; Luque, Nestor; Rinaudo, Mariano; Esperatti, Mariano; Fernandez-Barat, Laia; Ferrer, Miquel; Vila, Jordi; Ramirez, Jose; Torres, Antoni

2014-05-01

Animal models of ventilator-associated pneumonia (VAP) in primates, sheep, and pigs differ in the underlying pulmonary injury, etiology, bacterial inoculation methods, and time to onset. The most common ovine and porcine models do not reproduce the primary pathogenic mechanism of the disease, through the aspiration of oropharyngeal pathogens, or the most prevalent human etiology. Herein the authors characterize a novel porcine model of VAP due to aspiration of oropharyngeal secretions colonized by Pseudomonas aeruginosa. Ten healthy pigs were intubated, positioned in anti-Trendelenburg, and mechanically ventilated for 72 h. Three animals did not receive bacterial challenge, whereas in seven animals, a P. aeruginosa suspension was instilled into the oropharynx. Tracheal aspirates were cultured and respiratory mechanics were recorded. On autopsy, lobar samples were obtained to corroborate VAP through microbiological and histological studies. In animals not challenged, diverse bacterial colonization of the airways was found and monolobar VAP rarely developed. In animals with P. aeruginosa challenge, colonization of tracheal secretion increased up to 6.39 ± 0.34 log colony-forming unit (cfu)/ml (P < 0.001). VAP was confirmed in six of seven pigs, in 78% of the cases developed in the dependent lung segments (right medium and lower lobes, P = 0.032). The static respiratory system elastance worsened to 41.5 ± 5.8 cm H2O/l (P = 0.001). The authors devised a VAP model caused by aspiration of oropharyngeal P. aeruginosa, a frequent causative pathogen of human VAP. The model also overcomes the practical and legislative limitations associated with the use of primates. The authors' model could be employed to study pathophysiologic mechanisms, as well as novel diagnostic/preventive strategies.

Destruction-free procedure for the isolation of bacteria from sputum samples for Raman spectroscopic analysis.

PubMed

Kloß, Sandra; Lorenz, Björn; Dees, Stefan; Labugger, Ines; Rösch, Petra; Popp, Jürgen

2015-11-01

Lower respiratory tract infections are the fourth leading cause of death worldwide. Here, a timely identification of the causing pathogens is crucial to the success of the treatment. Raman spectroscopy allows for quick identification of bacterial cells without the need for time-consuming cultivation steps, which is the current gold standard to detect pathogens. However, before Raman spectroscopy can be used to identify pathogens, they have to be isolated from the sample matrix, i.e., sputum in case of lower respiratory tract infections. In this study, we report an isolation protocol for single bacterial cells from sputum samples for Raman spectroscopic identification. Prior to the isolation, a liquefaction step using the proteolytic enzyme mixture Pronase E is required in order to deal with the high viscosity of sputum. The extraction of the bacteria was subsequently performed via different filtration and centrifugation steps, whereby isolation ratios between 46 and 57 % were achieved for sputa spiked with 6·10(7) to 6·10(4) CFU/mL of Staphylococcus aureus. The compatibility of such a liquefaction and isolation procedure towards a Raman spectroscopic classification was shown for five different model species, namely S. aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa. A classification of single-cell Raman spectra of these five species with an accuracy of 98.5 % could be achieved on the basis of a principal component analysis (PCA) followed by a linear discriminant analysis (LDA). These classification results could be validated with an independent test dataset, where 97.4 % of all spectra were identified correctly. Graphical Abstract Development of an isolation protocol of bacterial cells out of sputum samples followed by Raman spectroscopic measurement and species identification using chemometrical models.

76 FR 13413 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP); Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-11

... Hospitalized Persons Study, FOA IP11-011; Spectrum of Respiratory Pathogens in Acute Respiratory Tract... Tropical and Developing Countries, FOA IP11-013; and Influenza and Other Respiratory Diseases in Southern...-Associated Community-Acquired Pneumonia in Hospitalized Persons Study, FOA IP11-011; Spectrum of Respiratory...

Mechanisms of Disease: Host-Pathogen Interactions between Burkholderia Species and Lung Epithelial Cells

PubMed Central

David, Jonathan; Bell, Rachel E.; Clark, Graeme C.

2015-01-01

Members of the Burkholderia species can cause a range of severe, often fatal, respiratory diseases. A variety of in vitro models of infection have been developed in an attempt to elucidate the mechanism by which Burkholderia spp. gain entry to and interact with the body. The majority of studies have tended to focus on the interaction of bacteria with phagocytic cells with a paucity of information available with regard to the lung epithelium. However, the lung epithelium is becoming more widely recognized as an important player in innate immunity and the early response to infections. Here we review the complex relationship between Burkholderia species and epithelial cells with an emphasis on the most pathogenic species, Burkholderia pseudomallei and Burkholderia mallei. The current gaps in knowledge in our understanding are highlighted along with the epithelial host-pathogen interactions that offer potential opportunities for therapeutic intervention. PMID:26636042

Cystic fibrosis swine fail to secrete airway surface liquid in response to inhalation of pathogens.

PubMed

Luan, Xiaojie; Belev, George; Tam, Julian S; Jagadeeshan, Santosh; Hassan, Noman; Gioino, Paula; Grishchenko, Nikolay; Huang, Yanyun; Carmalt, James L; Duke, Tanya; Jones, Teela; Monson, Bev; Burmester, Monique; Simovich, Tomer; Yilmaz, Orhan; Campanucci, Veronica A; Machen, Terry E; Chapman, L Dean; Ianowski, Juan P

2017-10-05

Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) channel, which can result in chronic lung disease. The sequence of events leading to lung disease is not fully understood but recent data show that the critical pathogenic event is the loss of the ability to clear bacteria due to abnormal airway surface liquid secretion (ASL). However, whether the inhalation of bacteria triggers ASL secretion and whether this is abnormal in cystic fibrosis has never been tested. Here we show, using a novel synchrotron-based in vivo imaging technique, that wild-type pigs display both a basal and a Toll-like receptor-mediated ASL secretory response to the inhalation of cystic fibrosis relevant bacteria. Both mechanisms fail in CFTR -/- swine, suggesting that cystic fibrosis airways do not respond to inhaled pathogens, thus favoring infection and inflammation that may eventually lead to tissue remodeling and respiratory disease.Cystic fibrosis is caused by mutations in the CFTR chloride channel, leading to reduced airway surface liquid secretion. Here the authors show that exposure to bacteria triggers secretion in wild-type but not in pig models of cystic fibrosis, suggesting an impaired response to pathogens contributes to infection.

An Outbreak of Respiratory Tularemia Caused by Diverse Clones of Francisella tularensis

PubMed Central

Johansson, Anders; Lärkeryd, Adrian; Widerström, Micael; Mörtberg, Sara; Myrtännäs, Kerstin; Öhrman, Caroline; Birdsell, Dawn; Keim, Paul; Wagner, David M.; Forsman, Mats; Larsson, Pär

2014-01-01

Background. The bacterium Francisella tularensis is recognized for its virulence, infectivity, genetic homogeneity, and potential as a bioterrorism agent. Outbreaks of respiratory tularemia, caused by inhalation of this bacterium, are poorly understood. Such outbreaks are exceedingly rare, and F. tularensis is seldom recovered from clinical specimens. Methods. A localized outbreak of tularemia in Sweden was investigated. Sixty-seven humans contracted laboratory-verified respiratory tularemia. F. tularensis subspecies holarctica was isolated from the blood or pleural fluid of 10 individuals from July to September 2010. Using whole-genome sequencing and analysis of single-nucleotide polymorphisms (SNPs), outbreak isolates were compared with 110 archived global isolates. Results. There were 757 SNPs among the genomes of the 10 outbreak isolates and the 25 most closely related archival isolates (all from Sweden/Finland). Whole genomes of outbreak isolates were >99.9% similar at the nucleotide level and clustered into 3 distinct genetic clades. Unexpectedly, high-sequence similarity grouped some outbreak and archival isolates that originated from patients from different geographic regions and up to 10 years apart. Outbreak and archival genomes frequently differed by only 1–3 of 1 585 229 examined nucleotides. Conclusions. The outbreak was caused by diverse clones of F. tularensis that occurred concomitantly, were widespread, and apparently persisted in the environment. Multiple independent acquisitions of F. tularensis from the environment over a short time period suggest that natural outbreaks of respiratory tularemia are triggered by environmental cues. The findings additionally caution against interpreting genome sequence identity for this pathogen as proof of a direct epidemiological link. PMID:25097081

Multicenter Evaluation of the ePlex Respiratory Pathogen Panel for the Detection of Viral and Bacterial Respiratory Tract Pathogens in Nasopharyngeal Swabs

PubMed Central

England, Matthew R.; Jurcic Smith, Kristen L.; He, Taojun; Wijetunge, Dona Saumya; Chamberland, Robin R.; Menegus, Marilyn; Swierkosz, Ella M.; Jerris, Robert C.; Greene, Wallace

2017-01-01

ABSTRACT The performance of the new ePlex Respiratory Pathogen (RP) panel (GenMark Diagnostics) for the simultaneous detection of 19 viruses (influenza A virus; influenza A H1 virus; influenza A 2009 H1 virus; influenza A H3 virus; influenza B virus; adenovirus; coronaviruses [HKU1, OC43, NL63, and 229E]; human rhinovirus/enterovirus; human metapneumovirus; parainfluenza viruses 1, 2, 3, and 4; and respiratory syncytial virus [RSV] [RSV subtype A and RSV subtype B]) and 2 bacteria (Mycoplasma pneumoniae and Chlamydia pneumoniae) was evaluated. Prospectively and retrospectively collected nasopharyngeal swab (NPS) specimens (n = 2,908) were evaluated by using the ePlex RP panel, with the bioMérieux/BioFire FilmArray Respiratory Panel (BioFire RP) as the comparator method. Discordance analysis was performed by using target-specific PCRs and bidirectional sequencing. The reproducibility of the assay was evaluated by using reproducibility panels comprised of 6 pathogens. The overall agreement between the ePlex RP and BioFire RP results was >95% for all targets. Positive percent agreement with the BioFire RP result for viruses ranged from 85.1% (95% confidence interval [CI], 80.2% to 88.9%) to 95.1% (95% CI, 89.0% to 97.9%), while negative percent agreement values ranged from 99.5% (95% CI, 99.1% to 99.7%) to 99.8% (95% CI, 99.5% to 99.9%). Additional testing of discordant targets (12%; 349/2,908) confirmed the results of ePlex RP for 38% (131/349) of samples tested. Reproducibility was 100% for all targets tested, with the exception of adenovirus, for which reproducibilities were 91.6% at low virus concentrations and 100% at moderate virus concentrations. The ePlex RP panel offers a new, rapid, and sensitive “sample-to-answer” multiplex panel for the detection of the most common viral and bacterial respiratory pathogens. PMID:29212701

Epidemiology and clinical profile of pathogens responsible for the hospitalization of children in Sousse area, Tunisia

PubMed Central

Guerrero, Aida; Hannachi, Naila; Bouguila, Jihene; Orth-Höller, Dorothea; Bouhlel, Amira; Boughamoura, Lamia; Hetzer, Benjamin; Borena, Wegene; Schiela, Britta; Von Laer, Dorothee; Boukadida, Jalel; Stoiber, Heribert

2017-01-01

This study aimed to identify a broad spectrum of respiratory pathogens from hospitalized and not-preselected children with acute respiratory tract infections in the Farhat Hached University-hospital of Sousse, Tunisia. Between September 2013 and December 2014, samples from 372 children aged between 1 month and 5 years were collected, and tested using multiplex real-time RT-PCR by a commercial assay for 21 respiratory pathogens. In addition, samples were screened for the presence of Streptococcus pneumoniae 16S rDNA using real-time PCR. The viral distribution and its association with clinical symptoms were statistically analyzed. Viral pathogens were detected in 342 (91.93%) of the samples of which 28.76% were single positive and 63.17% had multiple infections. The most frequent detected viruses were rhinovirus (55.64%), respiratory syncytial virus A/B (33.06%), adenovirus (25.00%), coronavirus NL63, HKU1, OC43, and 229E (21.50%), and metapneumovirus A/B (16.12%). Children in the youngest age group (1–3 months) exhibited the highest frequencies of infection. Related to their frequency of detection, RSV A/B was the most associated pathogen with patient’s demographic situation and clinical manifestations (p<0.05). Parainfluenza virus 1–4 and parechovirus were found to increase the risk of death (p<0.05). Adenovirus was statistically associated to the manifestation of gastroenteritis (p = 0.004). Rhinovirus infection increases the duration of oxygen support (p = 0.042). Coronavirus group was statistically associated with the manifestation of bronchiolitis (p = 0.009) and laryngitis (p = 0.017). Streptococcus pneumoniae DNA was detected in 143 (38.44%) of tested samples. However, only 53 samples had a concentration of C-reactive protein from equal to higher than 20 milligrams per liter, and 6 of them were single positive for Streptocuccus pneumoniae. This study confirms the high incidence of respiratory viruses in children hospitalized for acute respiratory tract infections in the Sousse area, Tunisia. PMID:29149199

Epidemiology and clinical profile of pathogens responsible for the hospitalization of children in Sousse area, Tunisia.

PubMed

Brini, Ines; Guerrero, Aida; Hannachi, Naila; Bouguila, Jihene; Orth-Höller, Dorothea; Bouhlel, Amira; Boughamoura, Lamia; Hetzer, Benjamin; Borena, Wegene; Schiela, Britta; Von Laer, Dorothee; Boukadida, Jalel; Stoiber, Heribert

2017-01-01

This study aimed to identify a broad spectrum of respiratory pathogens from hospitalized and not-preselected children with acute respiratory tract infections in the Farhat Hached University-hospital of Sousse, Tunisia. Between September 2013 and December 2014, samples from 372 children aged between 1 month and 5 years were collected, and tested using multiplex real-time RT-PCR by a commercial assay for 21 respiratory pathogens. In addition, samples were screened for the presence of Streptococcus pneumoniae 16S rDNA using real-time PCR. The viral distribution and its association with clinical symptoms were statistically analyzed. Viral pathogens were detected in 342 (91.93%) of the samples of which 28.76% were single positive and 63.17% had multiple infections. The most frequent detected viruses were rhinovirus (55.64%), respiratory syncytial virus A/B (33.06%), adenovirus (25.00%), coronavirus NL63, HKU1, OC43, and 229E (21.50%), and metapneumovirus A/B (16.12%). Children in the youngest age group (1-3 months) exhibited the highest frequencies of infection. Related to their frequency of detection, RSV A/B was the most associated pathogen with patient's demographic situation and clinical manifestations (p<0.05). Parainfluenza virus 1-4 and parechovirus were found to increase the risk of death (p<0.05). Adenovirus was statistically associated to the manifestation of gastroenteritis (p = 0.004). Rhinovirus infection increases the duration of oxygen support (p = 0.042). Coronavirus group was statistically associated with the manifestation of bronchiolitis (p = 0.009) and laryngitis (p = 0.017). Streptococcus pneumoniae DNA was detected in 143 (38.44%) of tested samples. However, only 53 samples had a concentration of C-reactive protein from equal to higher than 20 milligrams per liter, and 6 of them were single positive for Streptocuccus pneumoniae. This study confirms the high incidence of respiratory viruses in children hospitalized for acute respiratory tract infections in the Sousse area, Tunisia.

Human coronavirus and severe acute respiratory infection in Southern Brazil.

PubMed

Trombetta, Hygor; Faggion, Heloisa Z; Leotte, Jaqueline; Nogueira, Meri B; Vidal, Luine R R; Raboni, Sonia M

2016-05-01

Human coronaviruses (HCoVs) are an important cause of respiratory tract infection and are responsible for causing the common cold in the general population. Thus, adequate surveillance of HCoV is essential. This study aimed to analyze the impact of HCoV infections and their relation to severe acute respiratory infection (SARI) in a hospitalized population in Southern Brazil. A cross-sectional study was conducted at a tertiary care hospital, and assessed inpatients under investigation for SARI by the hospital epidemiology department, and all patients who had nasopharyngeal aspirates collected from January 2012 to December 2013 to detect respiratory viruses (RVs). Viral infection was detected by multiplex reverse transcriptase polymerase chain reaction (RT-PCR), with primers specific to the subtypes HCoV-229E/NL63 and OC43/HKU1. The overall positivity rate was 58.8% (444/755), and HCoVs were detected in 7.6% (n = 34) of positive samples. Children below two years of age were most frequently affected (62%). Comorbidities were more likely to be associated with HCoVs than with other RVs. Immunosuppression was an independent risk factor for HCoV infection (OR = 3.5, 95% CI 1.6-7.6). Dyspnea was less frequently associated with HCoV infection (p < 0.001), and HCoV accounted for 6% of the SARI cases. Three patients infected with HCoV (9%) died from respiratory infection. HCoVs are important respiratory pathogens, especially in hospitalized children under 2 years of age and in immunosuppressed patients. They may account for a small proportion of SARI diagnoses, increased need for mechanical ventilation, intensive care unit admission, and death.

Amoxicillin/clavulanate potassium extended release tablets: a new antimicrobial for the treatment of acute bacterial sinusitis and community-acquired pneumonia.

PubMed

Benninger, Michael S

2003-10-01

Community-acquired bacterial respiratory tract infections are among the most common health disorders requiring medical care and are associated with substantial morbidity, mortality, and direct and indirect costs. Recent increases in the prevalence of antimicrobial resistance have resulted in reduced susceptibility of the most common respiratory tract bacterial pathogens to a number of antimicrobials. Amoxicillin/clavulanate potassium extended release (ER) tablets (Augmentin XR, GlaxoSmithKline) is a new formulation of amoxicillin/clavulanate that retains activity against betalactamase-producing organisms whilst increasing the activity against Streptococcus pneumoniae through elevated and sustained plasma amoxicillin concentrations. The bilayer tablet provides immediate release of clavulanate and both immediate and sustained release of amoxicillin to maintain therapeutic concentrations of amoxicillin over longer periods of the dosing interval. In clinical trials of acute bacterial sinusitis (ABS) and community-acquired pneumonia (CAP), amoxicillin/clavulanate ER was shown to have excellent bacteriological and clinical success rates, even in patients infected with antimicrobial-resistant pathogens, and was found to be generally well tolerated. Amoxicillin/clavulanate ER is approved in the US for the treatment of patients with ABS or CAP caused by beta-lactamase-producing pathogens (ie, Haemophilus influenzae, Moraxella catarrhalis, Haemophilus parainfluenzae, Klebsiella pneumoniae, or methicillin-susceptible Staphylococcus aureus) and S. pneumoniae with reduced susceptibility to penicillin (penicillin minimum inhibitory concentration = 2.0 microg/ml).

Seasonality of acquisition of respiratory bacterial pathogens in young children with cystic fibrosis.

PubMed

Psoter, Kevin J; De Roos, Anneclaire J; Wakefield, Jon; Mayer, Jonathan D; Rosenfeld, Margaret

2017-06-09

Seasonal variations are often observed for respiratory tract infections; however, limited information is available regarding seasonal patterns of acquisition of common cystic fibrosis (CF)-related respiratory pathogens. We previously reported differential seasonal acquisition of Pseudomonas aeruginosa in young children with CF and no such variation for methicillin-susceptible Staphylococcus aureus acquisition. The purpose of this study was to describe and compare the seasonal incidence of acquisition of other respiratory bacterial pathogens in young children with CF. We conducted a retrospective study to describe and compare the seasonal incidence of methicillin-resistant Staphylococcus aureus (MRSA), Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Haemophilus influenzae acquisition in young CF patients residing in the U.S. using the Cystic Fibrosis Foundation National Patient Registry, 2003-2009. Log-linear overdispersed Poisson regression was used to evaluate seasonal acquisition of each of these pathogens. A total of 4552 children met inclusion criteria. During follow-up 910 (20%), 1161 (26%), 228 (5%), and 2148 (47%) children acquired MRSA, S. maltophilia, A. xylosoxidans and H. influenzae, respectively. Compared to winter season, MRSA was less frequently acquired in spring (Incidence Rate Ratio [IRR]: 0.79; 95% Confidence Interval [CI]: 0.65, 0.96) and summer (IRR: 0.69; 95% CI: 0.57, 0.84) seasons. Similarly, a lower rate of A. xylosoxidans acquisition was observed in spring (IRR: 0.59; 95% CI: 0.39, 0.89). For H. influenzae, summer (IRR: 0.88; 95% CI: 0.78, 0.99) and autumn (IRR: 0.78; 95% CI: 0.69, 0.88) seasons were associated with lower acquisition rates compared to winter. No seasonal variation was observed for S. maltophilia acquisition. Acquisition of CF-related respiratory pathogens displays seasonal variation in young children with CF, with the highest rate of acquisition for most pathogens occurring in the winter. Investigation of factors underlying these observed associations may contribute to our understanding of the aetiology of these infections and guide future infection control strategies.

Roadmap to developing a recombinant coronavirus S protein receptor-binding domain vaccine for severe acute respiratory syndrome

PubMed Central

Jiang, Shibo; Bottazzi, Maria Elena; Du, Lanying; Lustigman, Sara; Tseng, Chien-Te Kent; Curti, Elena; Jones, Kathryn; Zhan, Bin; Hotez, Peter J

2013-01-01

A subunit vaccine, RBD-S, is under development to prevent severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV), which is classified by the US NIH as a category C pathogen. This vaccine is comprised of a recombinant receptor-binding domain (RBD) of the SARS-CoV spike (S) protein and formulated on alum, together with a synthetic glucopyranosyl lipid A. The vaccine would induce neutralizing antibodies without causing Th2-type immunopathology. Vaccine development is being led by the nonprofit product development partnership; Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development in collaboration with two academic partners (the New York Blood Center and University of Texas Medical Branch); an industrial partner (Immune Design Corporation); and Walter Reed Army Institute of Research. A roadmap for the product development of the RBD-S SARS vaccine is outlined with a goal to manufacture the vaccine for clinical testing within the next 5 years. PMID:23252385

Respiratory Infections and Antibiotic Usage in Common Variable Immunodeficiency.

PubMed

Sperlich, Johannes M; Grimbacher, Bodo; Workman, Sarita; Haque, Tanzina; Seneviratne, Suranjith L; Burns, Siobhan O; Reiser, Veronika; Vach, Werner; Hurst, John R; Lowe, David M

Patients with common variable immunodeficiency (CVID) suffer frequent respiratory tract infections despite immunoglobulin replacement and are prescribed significant quantities of antibiotics. The clinical and microbiological nature of these exacerbations, the symptomatic triggers to take antibiotics, and the response to treatment have not been previously investigated. To describe the nature, frequency, treatment, and clinical course of respiratory tract exacerbations in patients with CVID and to describe pathogens isolated during respiratory tract exacerbations. We performed a prospective diary card exercise in 69 patients with CVID recruited from a primary immunodeficiency clinic in the United Kingdom, generating 6210 days of symptom data. We collected microbiology (sputum microscopy and culture, atypical bacterial PCR, and mycobacterial culture) and virology (nasopharyngeal swab multiplex PCR) samples from symptomatic patients with CVID. There were 170 symptomatic exacerbations and 76 exacerbations treated by antibiotics. The strongest symptomatic predictors for commencing antibiotics were cough, shortness of breath, and purulent sputum. There was a median delay of 5 days from the onset of symptoms to commencing antibiotics. Episodes characterized by purulent sputum responded more quickly to antibiotics, whereas sore throat and upper respiratory tract symptoms responded less quickly. A pathogenic virus was isolated in 56% of respiratory exacerbations and a potentially pathogenic bacteria in 33%. Patients with CVID delay and avoid treatment of symptomatic respiratory exacerbations, which could result in structural lung damage. However, viruses are commonly represented and illnesses dominated by upper respiratory tract symptoms respond poorly to antibiotics, suggesting that antibiotic usage could be better targeted. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

A novel HRM assay for differentiating classical strains and highly pathogenic strains of type 2 porcine reproductive and respiratory syndrome virus.

PubMed

Sun, Junying; Bingga, Gali; Liu, Zhicheng; Zhang, Chunhong; Shen, Haiyan; Guo, Pengju; Zhang, Jianfeng

2018-06-01

Differentiation of classical strains and highly pathogenic strains of porcine reproductive and respiratory syndrome virus is crucial for effective vaccination programs and epidemiological studies. We used nested PCR and high resolution melting curve analysis with unlabeled probe to distinguish between the classical and the highly pathogenic strains of this virus. Two sets of primers and a 20 bp unlabeled probe were designed from the NSP3 gene. The unlabeled probe included two mutations specific for the classical and highly pathogenic strains of the virus. An additional primer set from the NSP2 gene of the highly pathogenic vaccine strain JXA1-R was used to detect its exclusive single nucleotide polymorphism. We tested 107 clinical samples, 21 clinical samples were positive for PRRSV (consistent with conventional PCR assay), among them four were positive for the classical strain with the remainder 17 for the highly pathogenic strain. Around 10 °C difference between probe melting temperatures showed the high discriminatory power of this method. Among highly pathogenic positive samples, three samples were determined as positive for JXA1-R vaccine-related strain with a 95% genotype confidence percentage. All these genotyping results using the high resolution melting curve assay were confirmed with DNA sequencing. This unlabeled probe method provides an alternative means to differentiate the classical strains from the highly pathogenic porcine reproductive and respiratory syndrome virus strains rapidly and accurately. Copyright © 2018. Published by Elsevier Ltd.

Convergent Evolution of Pathogen Effectors toward Reactive Oxygen Species Signaling Networks in Plants.

PubMed

Jwa, Nam-Soo; Hwang, Byung Kook

2017-01-01

Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS) act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants. The perception of PAMPs by pattern recognition receptors leads to the rapid and strong production of ROS through activation of NADPH oxidase Respiratory Burst Oxidase Homologs (RBOHs) as well as peroxidases. Specific pathogen effectors directly or indirectly interact with plant nucleotide-binding leucine-rich repeat receptors to induce ROS production and the hypersensitive response in plant cells. By contrast, virulent pathogens possess effectors capable of suppressing plant ROS bursts in different ways during infection. PAMP-triggered ROS bursts are suppressed by pathogen effectors that target mitogen-activated protein kinase cascades. Moreover, pathogen effectors target vesicle trafficking or metabolic priming, leading to the suppression of ROS production. Secreted pathogen effectors block the metabolic coenzyme NADP-malic enzyme, inhibiting the transfer of electrons to the NADPH oxidases (RBOHs) responsible for ROS generation. Collectively, pathogen effectors may have evolved to converge on a common host protein network to suppress the common plant immune system, including the ROS burst and cell death response in plants.

Comparative analytical evaluation of the respiratory TaqMan Array Card with real-time PCR and commercial multi-pathogen assays.

PubMed

Harvey, John J; Chester, Stephanie; Burke, Stephen A; Ansbro, Marisela; Aden, Tricia; Gose, Remedios; Sciulli, Rebecca; Bai, Jing; DesJardin, Lucy; Benfer, Jeffrey L; Hall, Joshua; Smole, Sandra; Doan, Kimberly; Popowich, Michael D; St George, Kirsten; Quinlan, Tammy; Halse, Tanya A; Li, Zhen; Pérez-Osorio, Ailyn C; Glover, William A; Russell, Denny; Reisdorf, Erik; Whyte, Thomas; Whitaker, Brett; Hatcher, Cynthia; Srinivasan, Velusamy; Tatti, Kathleen; Tondella, Maria Lucia; Wang, Xin; Winchell, Jonas M; Mayer, Leonard W; Jernigan, Daniel; Mawle, Alison C

2016-02-01

In this study, a multicenter evaluation of the Life Technologies TaqMan(®) Array Card (TAC) with 21 custom viral and bacterial respiratory assays was performed on the Applied Biosystems ViiA™ 7 Real-Time PCR System. The goal of the study was to demonstrate the analytical performance of this platform when compared to identical individual pathogen specific laboratory developed tests (LDTs) designed at the Centers for Disease Control and Prevention (CDC), equivalent LDTs provided by state public health laboratories, or to three different commercial multi-respiratory panels. CDC and Association of Public Health Laboratories (APHL) LDTs had similar analytical sensitivities for viral pathogens, while several of the bacterial pathogen APHL LDTs demonstrated sensitivities one log higher than the corresponding CDC LDT. When compared to CDC LDTs, TAC assays were generally one to two logs less sensitive depending on the site performing the analysis. Finally, TAC assays were generally more sensitive than their counterparts in three different commercial multi-respiratory panels. TAC technology allows users to spot customized assays and design TAC layout, simplify assay setup, conserve specimen, dramatically reduce contamination potential, and as demonstrated in this study, analyze multiple samples in parallel with good reproducibility between instruments and operators. Copyright © 2015 Elsevier B.V. All rights reserved.

A cluster of three cases of botulism due to Clostridium baratii type F, France, August 2015.

PubMed

Tréhard, Hélène; Poujol, Isabelle; Mazuet, Christelle; Blanc, Quentin; Gillet, Yves; Rossignol, Frédérique; Popoff, Michel-Robert; Jourdan Da Silva, Nathalie

2016-01-01

A cluster of three cases of food-borne botulism due to Clostridium baratii type F occurred in France in August 2015. All cases required respiratory assistance. Consumption of a Bolognese sauce at the same restaurant was the likely source of contamination. Clostridium baratii was isolated both from stool specimens from the three patients and ground meat used to prepare the sauce. This is the second episode reported in France caused by this rare pathogen.

Mortality of live export cattle on long-haul voyages: pathologic changes and pathogens.

PubMed

Moore, S Jo; O'Dea, Mark A; Perkins, Nigel; Barnes, Anne; O'Hara, Amanda J

2014-03-01

The cause of death in 215 cattle on 20 long-haul live export voyages from Australia to the Middle East, Russia, and China was investigated between 2010 and 2012 using gross, histologic, and/or molecular pathology techniques. A quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay was used to detect nucleic acids from viruses and bacteria known to be associated with respiratory disease in cattle: Bovine coronavirus (Betacoronavirus 1), Bovine herpesvirus 1, Bovine viral diarrhea virus 1 and 2, Bovine respiratory syncytial virus, Bovine parainfluenza virus 3, Histophilus somni, Mycoplasma bovis, Mannheimia haemolytica, and Pasteurella multocida. The most commonly diagnosed cause of death was respiratory disease (107/180, 59.4%), followed by lameness (n = 22, 12.2%), ketosis (n = 12, 6.7%), septicemia (n = 11, 6.1%), and enteric disease (n = 10, 5.6%). Two thirds (130/195) of animals from which lung samples were collected had histologic changes and/or positive qRT-PCR results indicative of infectious lung disease: 93 out of 130 (72%) had evidence of bacterial infection, 4 (3%) had viral infection, and 29 (22%) had mixed bacterial and viral infections, and for 4 (3%) the causative organism could not be identified. Bovine coronavirus was detected in up to 13% of cattle tested, and this finding is likely to have important implications for the management and treatment of respiratory disease in live export cattle. Results from the current study indicate that although overall mortality during live export voyages is low, further research into risk factors for developing respiratory disease is required.

Mycobacterium chimaera pulmonary infection complicating cystic fibrosis: a case report.

PubMed

Cohen-Bacrie, Stéphan; David, Marion; Stremler, Nathalie; Dubus, Jean-Christophe; Rolain, Jean-Marc; Drancourt, Michel

2011-09-22

Mycobacterium chimaera is a recently described species within the Mycobacterium avium complex. Its pathogenicity in respiratory tract infection remains disputed. It has never been isolated during cystic fibrosis respiratory tract infection. An 11-year-old boy of Asian ethnicity who was born on Réunion Island presented to our hospital with cystic fibrosis after a decline in his respiratory function over the course of seven years. We found that the decline in his respiratory function was correlated with the persistent presence of a Mycobacterium avium complex organism further identified as M. chimaera. Using sequencing-based methods of identification, we observed that M. chimaera organisms contributed equally to respiratory tract infections in patients with cystic fibrosis when compared with M. avium subsp. hominissuis isolates. We believe that M. chimaera should be regarded as an emerging opportunistic respiratory pathogen in patients with cystic fibrosis, including young children, and that its detection warrants long-lasting appropriate anti-mycobacterial treatment to eradicate it.

Detection of Mycoplasma pneumoniae by real-time PCR.

PubMed

Winchell, Jonas M; Mitchell, Stephanie L

2013-01-01

Mycoplasma pneumoniae is a significant cause of respiratory disease, accounting for approximately 20% of cases of community-acquired pneumonia. Although several diagnostic methods exist to detect M. pneumoniae in respiratory specimens, real-time PCR has emerged as a significant improvement for the rapid diagnosis of this pathogen. The method described herein details the procedure for the detection of M. pneumoniae by real-time PCR (qPCR). The qPCR assay described can be performed with three targets specific for M. pneumoniae (Mp181, Mp3, and Mp7) and one marker for the detection of the RNaseP gene found in human nucleic acid as an internal control reaction. Recent studies have demonstrated the ability of this procedure to reliably identify this agent and facilitate the timely recognition of an outbreak.

[Infection due to Rothia mucilaginosa. A respiratory pathogen?].

PubMed

Ramos, José M; Mateo, Ignacio; Vidal, Inmaculada; Rosillo, Eva M; Merino, Esperanza; Portilla, Joaquín

2014-05-01

To describe the spectrum of infections caused by Rothia mucilaginosa. Retrospective study of 20 cases diagnosed with R. mucilaginosa from 2009 to 2012. Pulmonary infection was the most frequent clinical presentation (n=14, 70%): bronchiectasis infected (10), followed by pleural empyema (2), pneumonia (1) and acute bronchitis (1). Two episodes were of gastrointestinal origin: cholangitis secondary to biliary drainage and secondary peritonitis. Two episodes included bacteremia in patients with hematological malignancy. One patient had a surgical wound infection with bacteremia, and another had a bacteremic urinary tract infection in a patient with nephrostomy. R. mucilaginosa may be responsible for infections of the lower respiratory tract in predisposed patients. Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Preparation of armored RNA as a control for multiplex real-time reverse transcription-PCR detection of influenza virus and severe acute respiratory syndrome coronavirus.

PubMed

Yu, Xin-Fen; Pan, Jing-Cao; Ye, Rong; Xiang, Hai-Qing; Kou, Yu; Huang, Zhi-Cheng

2008-03-01

The common respiratory viruses, including influenza A, influenza B, and newly emerging severe acute respiratory syndrome (SARS) viruses, may cause similar clinical symptoms. Therefore, differential diagnosis of these virus pathogens is frequently required for single clinical samples. In addition, there is an urgent need for noninfectious and stable RNA standards and controls for multivirus detection. In this study, reverse transcription-PCR (RT-PCR) targeting of the RNAs of influenza A and influenza B viruses and SARS coronavirus was performed, and the resulting products were spliced into a fragment which was packaged into armored RNA for use as a noninfectious, quantifiable synthetic substitute. Furthermore, in the present study we developed a multiplex real-time RT-PCR assay in which the armored RNA was used as an external positive control and the three RNA viruses could be detected simultaneously in a single reaction mix. The detection limit of the multiplex real-time PCR was 10 copies/microl of armored RNA.

Interaction Between Allergy and Middle Ear Infection.

PubMed

Oh, Jeong-Hoon; Kim, Woo Jin

2016-09-01

Recent studies have attempted to identify interactions among the causes of otitis media with effusion (OME). This review discusses the interaction between allergy and infection with regard to host and environmental factors in terms of the development of OME. Protection of the upper airway against microbial invasion requires active interaction between the defense mechanisms of the respiratory epithelium, including innate and adaptive immunity, and mechanical factors. The impairment of these defenses due to allergy and/or increased bacterial resistance may lead to increased susceptibility to infectious organisms in the respiratory tract and middle ear mucosa. Recent genetic studies have provided valuable information about the association of Toll-like receptor signaling variations with clinical phenotypes and the risk of infection in the middle ear. Among the causal factors of OME, allergy not only induces an inflammatory reaction in the middle ear cavity but also facilitates the invasion of infectious pathogens. There is also evidence that allergy can affect the susceptibility of patients to infection of the upper respiratory tract, including the middle ear cavity.

Aspergillus infections in cystic fibrosis.

PubMed

King, Jill; Brunel, Shan F; Warris, Adilia

2016-07-05

Patients with cystic fibrosis (CF) suffer from chronic lung infection and airway inflammation. Respiratory failure secondary to chronic or recurrent infection remains the commonest cause of death and accounts for over 90% of mortality. Bacteria as Staphylococcus aureus, Pseudomonas aeruginosa and Burkholderia cepacia complex have been regarded the main CF pathogens and their role in progressive lung decline has been studied extensively. Little attention has been paid to the role of Aspergillus spp. and other filamentous fungi in the pathogenesis of non-ABPA (allergic bronchopulmonary aspergillosis) respiratory disease in CF, despite their frequent recovery in respiratory samples. It has become more apparent however, that Aspergillus spp. may play an important role in chronic lung disease in CF. Research delineating the underlying mechanisms of Aspergillus persistence and infection in the CF lung and its link to lung deterioration is lacking. This review summarizes the Aspergillus disease phenotypes observed in CF, discusses the role of CFTR (cystic fibrosis transmembrane conductance regulator)-protein in innate immune responses and new treatment modalities. Copyright © 2016. Published by Elsevier Ltd.

[Immune system and influenza virus].

PubMed

Wierzbicka-Woś, Anna; Tokarz-Deptuła, Beata; Deptuła, Wiesław

2015-02-15

Influenza viruses are a significant cause of respiratory infections, causing 3-5 million clinical infections and 250-500 thousand deaths per year. Infections caused by the influenza virus induce a host immune response at the non-specific and specific level (defined as natural and acquired), which leads to limitation of virus replication. Moreover the elements of immunological memory are induced so that they can protect against subsequent infection by the influenza virus. However, there is still no effective way for the total elimination of this virus, and the only effective method to combat this pathogen appears to be vaccination, which through immune system activation greatly limits its spread. The present paper presents the immune reaction at different levels in response to the influenza virus after entering the body and the mechanisms of the influenza virus for avoiding reactions of the immune system, which correspond to its high variability at the molecular level. Moreover, in this paper we describe various methods of stimulating the organism's immune systems with different generations of vaccines and their effectiveness in the fight against this pathogen.

Prediction of Pan-Specific B-Cell Epitopes From Nucleocapsid Protein of Hantaviruses Causing Hantavirus Cardiopulmonary Syndrome.

PubMed

Kalaiselvan, Sagadevan; Sankar, Sathish; Ramamurthy, Mageshbabu; Ghosh, Asit Ranjan; Nandagopal, Balaji; Sridharan, Gopalan

2017-08-01

Hantaviruses are emerging viral pathogens that causes hantavirus cardiopulmonary syndrome (HCPS) in the Americas, a severe, sometimes fatal, respiratory disease in humans with a case fatality rate of ≥50%. IgM and IgG-based serological detection methods are the most common approaches used for laboratory diagnosis of hantaviruses. Such emerging viral pathogens emphasizes the need for improved rapid diagnostic devices and vaccines incorporating pan-specific epitopes of genotypes. We predicted linear B-cell epitopes for hantaviruses that are specific to genotypes causing HCPS in humans using in silico prediction servers. We modeled the Andes and Sin Nombre hantavirus nucleocapsid protein to locate the identified epitopes. Based on the mean percent prediction probability score, epitope IMASKSVGS/TAEEKLKKKSAF was identified as the best candidate B-cell epitope specific for hantaviruses causing HCPS. Promiscuous epitopes were identified in the C-terminal of the protein. Our study for the first time has reported pan-specific B-cell epitopes for developing immunoassays in the detection of antibodies to hantaviruses causing HCPS. Identification of epitopes with pan-specific recognition of all genotypes causing HCPS could be valuable for the development of immunodiagnositic tools toward pan-detection of hantavirus antibodies in ELISA. J. Cell. Biochem. 118: 2320-2324, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

DIFFERENTIAL GENE EXPRESSION INDUCED BY RESPIRATORY SYNCTIAL VIRUS IN HUMAN BRONCHIAL EPITHELIAL CELLS

EPA Science Inventory

Respiratory syncytial virus (RSV), a negative-stranded RNA virus, is a common viral pathogen for respiratory infection in both children and immunocompromised adults. Early host defense may play a critical role in determining the severity of the infection. To gain further insight ...

Respiratory Microbiome of Endangered Southern Resident Killer Whales and Microbiota of Surrounding Sea Surface Microlayer in the Eastern North Pacific.

PubMed

Raverty, Stephen A; Rhodes, Linda D; Zabek, Erin; Eshghi, Azad; Cameron, Caroline E; Hanson, M Bradley; Schroeder, J Pete

2017-03-24

In the Salish Sea, the endangered Southern Resident Killer Whale (SRKW) is a high trophic indicator of ecosystem health. Three major threats have been identified for this population: reduced prey availability, anthropogenic contaminants, and marine vessel disturbances. These perturbations can culminate in significant morbidity and mortality, usually associated with secondary infections that have a predilection to the respiratory system. To characterize the composition of the respiratory microbiota and identify recognized pathogens of SRKW, exhaled breath samples were collected between 2006-2009 and analyzed for bacteria, fungi and viruses using (1) culture-dependent, targeted PCR-based methodologies and (2) taxonomically broad, non-culture dependent PCR-based methodologies. Results were compared with sea surface microlayer (SML) samples to characterize the respective microbial constituents. An array of bacteria and fungi in breath and SML samples were identified, as well as microorganisms that exhibited resistance to multiple antimicrobial agents. The SML microbes and respiratory microbiota carry a pathogenic risk which we propose as an additional, fourth putative stressor (pathogens), which may adversely impact the endangered SRKW population.

What is the true clinical relevance of Simkania negevensis and other emerging Chlamydiales members?

PubMed

Vouga, M; Kebbi-Beghdadi, C; Liénard, J; Baskin, L; Baud, D; Greub, G

2018-05-01

Waddlia   chondrophila and Simkania negevensis are emerging Chlamydia- related bacteria. Similar to the pathogenic organisms Chlamydia pneumoniae and Chlamydia trachomatis, these emerging bacteria are implicated in human genital infections and respiratory diseases. We used a screening strategy based on a newly developed S. negevensis -specific quantitative real-time PCR (qPCR) and a pan- Chlamydiales qPCR. We could not detect S. negevensis in 458 respiratory, genitourinary, cardiac and hepatic samples tested. One urethral swab was positive for W. chondrophila. We observed a low prevalence of Chlamydiales in respiratory samples (1/200, 0.5%), which suggests that C. pneumoniae is an uncommon respiratory pathogen. Furthermore, we screened 414 human serum samples from Switzerland, England and Israel and observed a low prevalence (<1%) of exposure to S. negevensis. Conversely, humans were commonly exposed to W. chondrophila, with seroprevalences ranging from 8.6% to 32.5%. S. negevensis is not a clinically relevant pathogen, but further research investigating the role of W. chondrophila is needed.

Systematic detection of positive selection in the human-pathogen interactome and lasting effects on infectious disease susceptibility.

PubMed

Corona, Erik; Wang, Liuyang; Ko, Dennis; Patel, Chirag J

2018-01-01

Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS) to detect recent positive selection in genes that interact with proteins from 26 different pathogens. We used the Human Genome Diversity Panel to identify specific populations harboring pathogen-interacting genes that have undergone positive selection. We found that human genes that interact with 9 pathogen species show evidence of recent positive selection. These pathogens are Yersenia pestis, human immunodeficiency virus (HIV) 1, Zaire ebolavirus, Francisella tularensis, dengue virus, human respiratory syncytial virus, measles virus, Rubella virus, and Bacillus anthracis. For HIV-1, GWAS demonstrate that some naturally selected variants in the host-pathogen protein interaction networks continue to have functional consequences for susceptibility to these pathogens. We show that selected human genes were enriched for HIV susceptibility variants (identified through GWAS), providing further support for the hypothesis that ancient humans were exposed to lentivirus pandemics. Human genes in the Italian, Miao, and Biaka Pygmy populations that interact with Y. pestis show significant signs of selection. These results reveal some of the genetic footprints created by pathogens in the human genome that may have left lasting marks on susceptibility to infectious disease.

Prospective evaluation of a high multiplexing real-time polymerase chain reaction array for the rapid identification and characterization of bacteria causative of nosocomial pneumonia from clinical specimens: a proof-of-concept study.

PubMed

Roisin, S; Huang, T-D; de Mendonça, R; Nonhoff, C; Bogaerts, P; Hites, M; Delaere, B; Hamels, S; de Longueville, F; Glupczynski, Y; Denis, O

2018-01-01

The purpose of this study was evaluation of the VAPChip assay based on the "Rapid-Array-PCR-technology" which targets 13 respiratory pathogens and 24 β-lactam resistance genes directly on respiratory clinical specimens. The first step included analysis of 45 respiratory specimens in order to calibrate and determine the threshold for target genes. The second prospective step involved 85 respiratory samples from patients suspected of nosocomial pneumonia collected in two academic hospitals over an 8-month period. Results of the VAPChip assay were compared to routine methods. The first step showed a large proportion of positive signals for H. influenzae and/or S. pneumoniae. For identification, discrepancies were observed in seven samples. Thresholds were adapted and two probes were re-designed to create a new version of the cartridge. In the second phase, sensitivity and specificity of the VAPchip for bacterial identification were 72.9% and 99.1%, respectively. Seventy (82%) pathogens were correctly identified by both methods. Nine pathogens detected by the VAPChip were culture negative and 26 pathogens identified by culture were VAPChip negative. For resistance mechanisms, 11 probes were positive without identification of pathogens with an antimicrobial-susceptibility testing compatible by culture. However, the patient's recent microbiological history was able to explain most of these positive signals. The VAPChip assay simultaneously detects different pathogens and resistance mechanisms directly from clinical samples. This system seems very promising but the extraction process needs to be automated for routine implementation. This kind of rapid point-of-care automated platform permitting a syndromic approach will be the future challenge in the management of infectious diseases.

In vitro activities of nine peptide deformylase inhibitors and five comparator agents against respiratory and skin pathogens.

PubMed

Bowker, K E; Noel, A R; MacGowan, A P

2003-12-01

The activity of nine peptide deformylase (PDF) inhibitors undergoing clinical evaluation were compared with co-amoxiclav, levofloxacin, moxifloxacin, erythromycin and telithromycin against a range of respiratory and skin pathogens (n=166). The PDF inhibitor showed good activity against Streptococcus pneumoniae, Moxarella catarrhalis, Group A streptococci and Staphylococcus aureus irrespective of beta-lactam or fluoroquinolone susceptibility. Against Haemophilus influenzae, MIC(90) values were generally higher. BB-88488 was the most active compound. Overall these data suggest that PDF inhibitors are an interesting new class of antimicrobial worthy of further investigation in the treatment of respiratory tract and skin infections.

Mucosal Vaccination against Tuberculosis Using Inert Bioparticles

PubMed Central

Reljic, Rajko; Sibley, Laura; Huang, Jen-Min; Pepponi, Ilaria; Hoppe, Andreas; Hong, Huynh A.

2013-01-01

Needle-free, mucosal immunization is a highly desirable strategy for vaccination against many pathogens, especially those entering through the respiratory mucosa, such as Mycobacterium tuberculosis. Unfortunately, mucosal vaccination against tuberculosis (TB) is impeded by a lack of suitable adjuvants and/or delivery platforms that could induce a protective immune response in humans. Here, we report on a novel biotechnological approach for mucosal vaccination against TB that overcomes some of the current limitations. This is achieved by coating protective TB antigens onto the surface of inert bacterial spores, which are then delivered to the respiratory tract. Our data showed that mice immunized nasally with coated spores developed humoral and cellular immune responses and multifunctional T cells and, most importantly, presented significantly reduced bacterial loads in their lungs and spleens following pathogenic challenge. We conclude that this new vaccine delivery platform merits further development as a mucosal vaccine for TB and possibly also other respiratory pathogens. PMID:23959722

A brief review of moxifloxacin in the treatment of elderly patients with community-acquired pneumonia (CAP)

PubMed Central

Ferrara, Anna M

2007-01-01

Community-acquired pneumonia (CAP) remains a common cause of morbidity and a potentially life-threatening illness throughout the world mainly in elderly patients. Initial antibacterial treatment, usually empirical, should be as effective as possible in order to assure rapid clinical resolution and reduce high rates of hospitalization and mortality especially affecting aged patients. New fluoroquinolones with potent activity against the most important respiratory pathogens including Streptococcus pneumoniae, a key pathogen mainly in old patients with CAP, have been recently suggested by several international guidelines as monotherapy for the treatment of most CAP patient categories. Among newer derivatives, moxifloxacin, an advanced generation 8-methoxy quinolone, has demonstrated good clinical and bacteriological efficacy in large, well designed clinical trials both in adults and old patients with CAP, achieving also in aged people efficacy comparable with that of standard treatments. Good pharmacokinetic characteristics such as excellent penetration into respiratory tract tissues and fluids, optimal bioavailability, simplicity of once-daily dosing, and good tolerability, represent potential advantages of moxifloxacin over other therapies. In addition, primarily due to a shorter length of hospital stay, moxifloxacin has been shown to save costs compared with standard therapy. PMID:18044134

Varying susceptibility of clinical and environmental Scedosporium isolates to chemical oxidative stress in conidial germination.

PubMed

Staerck, Cindy; Godon, Charlotte; Bouchara, Jean-Philippe; Fleury, Maxime J J

2018-04-01

Scedosporium species are opportunistic pathogens causing a great variety of infections in both immunocompetent and immunocompromised individuals. The Scedosporium genus ranks the second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF), after Aspergillus fumigatus, and most species are capable to chronically colonize the respiratory tract of these patients. Nevertheless, few data are available regarding evasion of the inhaled conidia to the host immune response. Upon microbial infection, macrophages and neutrophils release reactive oxygen species (ROS). To colonize the respiratory tract, the conidia need to germinate despite the oxidative stress generated by phagocytic cells. Germination of spores from different clinical or environmental isolates of the major Scedosporium species was investigated in oxidative stress conditions. All tested species showed susceptibility to oxidative stress. However, when comparing clinical and environmental isolates, differences in germination capabilities under oxidative stress conditions were seen between species as well as within each species. Among environmental isolates, Scedosporium aurantiacum isolates were the most resistant to oxidative stress whereas Scedosporium dehoogii were the most susceptible. Overall, the differences observed between Scedosporium species in the capacity to germinate under oxidative stress conditions could explain their varying prevalence and pathogenicity.

Thermal inactivation of avian influenza and Newcastle disease viruses in chicken meat.

PubMed

Thomas, Colleen; King, Daniel J; Swayne, David E

2008-06-01

Avian influenza viruses (AIV) and Newcastle disease viruses (NDV) of high pathogenicity cause severe systemic disease with high mortality in chickens and can be isolated from the meat of infected chickens. Although AIV and NDV strains of low pathogenicity are typically not present in chicken meat, virus particles in respiratory secretions or feces are possible sources of carcass contamination. Because spread of AIV and NDV is associated with movement of infected birds or their products, the presence of these viruses in chicken meat is cause for concern. This study presents thermal inactivation data for two viruses of high pathogenicity in chickens (AIV strain A/chicken/Pennsylvania/1370/1983 and NDV strain APMV-1/ chicken/California/S0212676/2002) and two viruses of low pathogenicity in chickens (AIV strain A/chicken/Texas/298313/ 2004 and NDV strain APMV-1/chicken/Northern Ireland/Ulster/1967). Under the conditions of the assay, high-pathogenicity AIV was inactivated more slowly in meat from naturally infected chickens than in artificially infected chicken meat with a similar virus titer. In contrast, high-pathogenicity NDV was inactivated similarly in naturally and artificially infected meat. Linear regression models predicted that the current U.S. Department of Agriculture-Food Safety and Inspection Service time-temperature guidelines for cooking chicken meat to achieve a 7-log reduction of Salmonella also would effectively inactivate the AIV and NDV strains tested. Experimentally, the AIV and NDV strains used in this study (and the previously studied H5N1 high-pathogenicity AIV strain A/chicken/Korea/ES/2003) were effectively inactivated in chicken meat held at 70 or 73.9 degrees C for less than 1 s.

Epidemiology of respiratory pathogen carriage in the homeless population within two shelters in Marseille, France, 2015-2017: cross sectional 1-day surveys.

PubMed

Ly, T D A; Edouard, S; Badiaga, S; Tissot-Dupont, H; Hoang, V T; Pommier de Santi, V; Brouqui, P; Raoult, D; Gautret, P

2018-05-17

To assess risk factors for respiratory tract infection symptoms and signs in sheltered homeless people in Marseille during the winter season, including pathogen carriage. Data on 479 male participants within two shelters who completed questionnaires and a total of 950 nasal and pharyngeal samples were collected during the winters of 2015-2017. Respiratory pathogen carriage including seven viruses and four bacteria was assessed by quantitative PCR. The homeless population was characterized by a majority of individuals of North African origin (300/479, 62.6%) with a relatively high prevalence of chronic homelessness (175/465, 37.6%). We found a high prevalence of respiratory symptoms and signs (168/476, 35.3%), a very high prevalence of bacterial carriage (313/477, 65.6%), especially Haemophilus influenzae (280/477, 58.7%), and a lower prevalence of virus carriage (51/473, 10.8%) with human rhinovirus being the most frequent (25/473, 5.3%). Differences were observed between the microbial communities of the nose and throat. Duration of homelessness (odds ratio (OR) 1.77, p 0.017), chronic respiratory diseases (OR 5.27, p <0.0001) and visiting countries of origin for migrants (OR 1.68, p 0.035) were identified as independent risk factors for respiratory symptoms and signs. A strong association between virus (OR 2.40, p 0.012) or Streptococcus pneumoniae (OR 2.32, p 0.014) carriage and respiratory symptoms and signs was also found. These findings allowed identification of the individuals at higher risk for contracting respiratory tract infections to better target preventive measures aimed at limiting the transmission of these diseases in this setting. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Analysis of Canadian and Irish forage, oats and commercially available equine concentrate feed for pathogenic fungi and mycotoxins

PubMed Central

2007-01-01

Respiratory infections, recurrent airway obstruction (RAO) and exercise induced pulmonary haemorrhage (EIPH) are major causes of poor performance in horses. Fungi and mycotoxins are now recognised as a major cause of these conditions. The most notable fungi are Aspergillus and Fusarium. Fungal spores can originate from forage, bedding and feed and, in turn, these fungal spores can produce a series of mycotoxins as secondary metabolites. This study set out to ascertain the degree of fungal and mycotoxin contamination in feed and fodder used in Irish racing yards over a one-year period. Weather conditions in forage producing areas were sampled by Met Eireann and the Canadian Meteorological Service. Fifty per cent of Irish hay, 37% of haylage and 13% of Canadian hay contained pathogenic fungi. Of the mycotoxins, T2 and zearalenone were most prominent. Twenty-one per cent of Irish hay and 16% of pelleted feed contained zearalenone. Forty per cent of oats and 54% of pelleted feed contained T2 toxins. PMID:21851693

Analysis of Canadian and Irish forage, oats and commercially available equine concentrate feed for pathogenic fungi and mycotoxins.

PubMed

Buckley, Thomas; Creighton, Alan; Fogarty, Ursula

2007-04-01

Respiratory infections, recurrent airway obstruction (RAO) and exercise induced pulmonary haemorrhage (EIPH) are major causes of poor performance in horses. Fungi and mycotoxins are now recognised as a major cause of these conditions. The most notable fungi are Aspergillus and Fusarium. Fungal spores can originate from forage, bedding and feed and, in turn, these fungal spores can produce a series of mycotoxins as secondary metabolites.This study set out to ascertain the degree of fungal and mycotoxin contamination in feed and fodder used in Irish racing yards over a one-year period. Weather conditions in forage producing areas were sampled by Met Eireann and the Canadian Meteorological Service.Fifty per cent of Irish hay, 37% of haylage and 13% of Canadian hay contained pathogenic fungi. Of the mycotoxins, T2 and zearalenone were most prominent. Twenty-one per cent of Irish hay and 16% of pelleted feed contained zearalenone. Forty per cent of oats and 54% of pelleted feed contained T2 toxins.

Estimating the burden of respiratory syncytial virus (RSV) on respiratory hospital admissions in children less than five years of age in England, 2007-2012.

PubMed

Reeves, Rachel Melanie; Hardelid, Pia; Gilbert, Ruth; Warburton, Fiona; Ellis, Joanna; Pebody, Richard G

2017-03-01

Respiratory syncytial virus (RSV) is a leading cause of hospital admission in young children. With several RSV vaccines candidates undergoing clinical trials, recent estimates of RSV burden are required to provide a baseline for vaccine impact studies. To estimate the number of RSV-associated hospital admissions in children aged <5 years in England over a 5-year period from 2007 using ecological time series modelling of national hospital administrative data. Multiple linear regression modelling of weekly time series of laboratory surveillance data and Hospital Episode Statistics (HES) data was used to estimate the number of hospital admissions due to major respiratory pathogens including RSV in children <5 years of age in England from mid-2007 to mid-2012, stratified by age group (<6 months, 6-11 months, 1-4 years) and primary diagnosis: bronchiolitis, pneumonia, unspecified lower respiratory tract infection (LRTI), bronchitis and upper respiratory tract infection (URTI). On average, 33 561 (95% confidence interval 30 429-38 489) RSV-associated hospital admissions in children <5 years of age occurred annually from 2007 to 2012. Average annual admission rates were 35.1 (95% CI: 32.9-38.9) per 1000 children aged <1 year and 5.31 (95% CI: 4.5-6.6) per 1000 children aged 1-4 years. About 84% (95% CI: 81-91%) of RSV-associated admissions were for LRTI. The diagnosis-specific burden of RSV-associated admissions differed significantly by age group. RSV remains a significant cause of hospital admissions in young children in England. Individual-level analysis of RSV-associated admissions is required to fully describe the burden by age and risk group and identify optimal prevention strategies. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Epidemiological Features and Antibiotic Resistance Patterns of Haemophilus influenzae Originating from Respiratory Tract and Vaginal Specimens in Pediatric Patients.

PubMed

Li, Jian-Ping; Hua, Chun-Zhen; Sun, Li-Ying; Wang, Hong-Jiao; Chen, Zhi-Min; Shang, Shi-Qiang

2017-12-01

Haemophilus influenzae (H. influenzae) is a common pathogen of respiratory tract infections in children, however, as a possible cause of vulvovaginitis in prepubertal girls, its epidemiological features, antibiotic-resistance patterns, and treatment are seldom noted. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Specimens obtained from patients were inoculated on Haemophilus selective medium; and drug-sensitivities tests were determined using the disk diffusion method. A cefinase disk was used to detect β-lactamase. A total of 610 H. influenzae strains, 81.6% (498/610) from the respiratory tract and 18.0% (110/610) from the vagina, were identified in the Children's Hospital in 2015. The age of the children with respiratory tract strains were significantly younger than those with vaginal strains (P < .001). The H. influenzae isolation rate in May was the highest. The β-lactamase positive rate was 51.5% (314/610), and 52.5% (320/610) were resistant to ampicillin. The susceptibilities rates to cefuroxime, ampicillin/sulbactam, cefotaxime, clarithromycin, and sulfamethoxazole-trimethoprim were 72.1% (440/610), 95.9%, 96.4% (588/610), 81.8% (499/610), and 36.4% (222/610), respectively. Higher resistance to ampicillin, cefuroxime, clarithromycin, and sulfamethoxazole-trimethoprim were found in respiratory tract strains, compared with vaginal strains (P < .05). All of the patients with H. influenzae in the respiratory tract were cured with oral or intravenous β-lactam antibiotics. Of all patients with vaginal strains, 50% (55/110) were cured with topical ofloxacin gel, and 44.5% (49/110) were cured with oral β-lactam antibiotics. The drug-resistance rates of H. influenzae isolated from vagina were lower than those from the respiratory tract. Topical ofloxacin gel or oral β-lactam antibiotics are effective treatments to eliminate the H. influenza causing infection in the vagina. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Characterization of hospital and community-acquired respiratory syncytial virus in children with severe lower respiratory tract infections in Ho Chi Minh City, Vietnam, 2010

PubMed Central

Tuan, Tran Anh; Thanh, Tran Tan; Hai, Nguyen thi Thanh; Tinh, Le Binh Bao; Kim, Le thi Ngoc; Do, Lien Anh Ha; Chinh B'Krong, Nguyen thi Thuy; Tham, Nguyen thi; Hang, Vu thi Ty; Merson, Laura; Farrar, Jeremy; Thuong, Tang Chi; de Jong, Menno D; Schultsz, Constance; van Doorn, H Rogier

2015-01-01

Background Human respiratory syncytial virus (RSV) is an important community and nosocomial pathogen in developed countries but data regarding the importance of RSV in developing countries are relatively scarce. Methods During a 1-year surveillance study in 2010, we took serial samples from children admitted to the Emergency Unit of the Respiratory Ward of Children's Hospital 1 in Ho Chi Minh City, Vietnam. RSV was detected within 72 hours of admission to the ward in 26% (376/1439; RSV A: n = 320; RSV B: n = 54; and RSV A and B: n = 2). Among those negative in the first 72 hours after admission, 6·6% (25/377) acquired nosocomial RSV infection during hospitalization (RSV A: n = 22; and RSV B: n = 3). Results Children with nosocomial RSV infection were younger (P = 0·001) and had a longer duration of hospitalization (P < 0·001). The rate of incomplete recovery among children with nosocomial RSV infection was significantly higher than among those without (P < 0·001). Phylogenetic analysis of partial G gene sequences obtained from 79% (316/401) of positive specimens revealed the co-circulation of multiple genotypes with RSV A NA1 being predominant (A NA1: n = 275; A GA5: n = 5; B BA3: n = 3; B BA9: n = 26; and B BA10: n = 7). The RSV A GA5 and RSV B BA3 genotypes have not been reported from Vietnam, previously. Conclusion Besides emphasizing the importance of RSV as a cause of respiratory infection leading to hospitalization in young children and as a nosocomial pathogen, data from this study extend our knowledge on the genetic diversity of RSV circulating in Vietnam. PMID:25702707

Fatal disseminated Rasamsonia infection in cystic fibrosis post-lung transplantation.

PubMed

Hong, Gina; White, Marissa; Lechtzin, Noah; West, Natalie E; Avery, Robin; Miller, Heather; Lee, Richard; Lovari, Robert J; Massire, Christian; Blyn, Lawrence B; Liang, Xinglun; Sutton, Deanna A; Fu, Jianmin; Wickes, Brian L; Wiederhold, Nathan P; Zhang, Sean X

2017-03-01

Disseminated fungal infections are a known serious complication in individuals with cystic fibrosis (CF) following orthotopic lung transplantation. Aspergillus fumigatus and Scedosporium species are among the more common causes of invasive fungal infection in this population. However, it is also important for clinicians to be aware of other emerging fungal species which may require markedly different antifungal therapies. We describe the first laboratory-documented case of a fatal disseminated fungal infection caused by Rasamsonia aegroticola in a 21-year-old female CF patient status post-bilateral lung transplantation, which was only identified post-mortem. Molecular analysis revealed the presence of the identical Rasamsonia strains in the patient's respiratory cultures preceding transplantation. We propose that the patient's disseminated fungal disease and death occurred as a result of recrudescence of Rasamsonia infection from her native respiratory system in the setting of profound immunosuppression post-operatively. Since Rasamsonia species have been increasingly recovered from the respiratory tract of CF patients, we further review the literature on these fungi and discuss their association with invasive fungal infections in the CF lung transplant host. Our report suggests Rasamsonia species may be important fungal pathogens that may have fatal consequences in immunosuppressed CF patients after solid organ transplantation. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Equine herpesvirus-1 infection disrupts interferon regulatory factor-3 (IRF-3) signaling pathways in equine endothelial cells.

PubMed

Sarkar, Sanjay; Balasuriya, Udeni B R; Horohov, David W; Chambers, Thomas M

2016-05-01

Equine herpesvirus-1 (EHV-1) is a major respiratory viral pathogen of horses, causing upper respiratory tract disease, abortion, neonatal death, and neurological disease that may lead to paralysis and death. EHV-1 replicates initially in the respiratory epithelium and then spreads systemically to endothelial cells lining the small blood vessels in the uterus and spinal cord leading to abortion and EHM in horses. Like other herpesviruses, EHV-1 employs a variety of mechanisms for immune evasion including suppression of type-I interferon (IFN) production in equine endothelial cells (EECs). Previously we have shown that the neuropathogenic T953 strain of EHV-1 inhibits type-I IFN production in EECs and this is mediated by a viral late gene product. But the mechanism of inhibition was not known. Here we show that T953 strain infection of EECs induced degradation of endogenous IRF-3 protein. This in turn interfered with the activation of IRF-3 signaling pathways. EHV-1 infection caused the activation of the NF-κB signaling pathways, suggesting that inhibition of type-I IFN production is probably due to interference in IRF-3 and not NF-κB signal transduction. Copyright © 2016 Elsevier B.V. All rights reserved.

E-mail-based symptomatic surveillance combined with self-collection of nasal swabs: a new tool for acute respiratory infection epidemiology.

PubMed

Akmatov, Manas K; Krebs, Stephan; Preusse, Matthias; Gatzemeier, Anja; Frischmann, Ursula; Schughart, Klaus; Pessler, Frank

2011-11-01

We examined the feasibility of combining communication by e-mail and self-collection of nasal swabs for the prospective detection of acute respiratory infections in a non-medical setting. The study was conducted among a convenience sample of employees (n=53) at a research institution (December 2009-April 2010). Real-time data on the occurrence of acute respiratory symptoms and a nasal self-swab were collected prospectively, with automated weekly e-mails as a reminder mechanism. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect respiratory viral pathogens in the swabs. Fifty-one out of 53 participants completed the study. The study design was well accepted. Thirty (∼57%) participants reported at least one episode of acute respiratory infection and returned the nasal swab during the study period (eight participants reported two episodes). The majority had no difficulties taking the self-swab and preferred this to swabbing by study personnel. Most participants obtained and returned the swabs within the recommended time. Viral respiratory pathogens were detected in 19 of 38 swabs (50%), with coronaviruses 229E/NL63 and OC43 and rhinoviruses A and B constituting 17 positive swabs (89%). Combining e-mail-based symptomatic surveillance with nasal self-swabbing promises to be a powerful tool for the real-time identification of incident cases of acute respiratory infections and the associated pathogens in population-based studies. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Protective efficacy of a virus-vectored multi-component vaccine against porcine reproductive and respiratory syndrome virus, porcine circovirus type 2 and swine influenza virus.

PubMed

Tian, Debin; Sooryanarain, Harini; Matzinger, Shannon R; Gauger, Phil C; Karuppannan, Anbu K; Elankumaran, Subbiah; Opriessnig, Tanja; Meng, Xiang-Jin

2017-12-01

Porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2 (PCV2) and swine influenza virus (SIV) are three of the most economically important swine pathogens, causing immense economic losses to the global swine industry. Monovalent commercial vaccines against each of the three viruses are routinely used in pig farms worldwide. A trivalent vaccine against all three pathogens would greatly simplify the vaccination programme and reduce the financial burden to the swine industry. In this study, by using an attenuated strain of PRRSV (strain DS722) as a live virus vector, we generated a multi-component vaccine virus, DS722-SIV-PCV2, which expresses the protective antigens from SIV and PCV2. The DS722-SIV-PCV2 trivalent vaccine virus replicates well, and expresses PCV2 capsid and SIV HA proteins in vitro. A subsequent vaccination and challenge study in 48 pigs revealed that the DS722-SIV-PCV2-vaccinated pigs had significantly reduced lung lesions and viral RNA loads when challenged with PRRSV. Upon challenge with PCV2, the vaccinated pigs had partially reduced lymphoid lesions and viral DNA loads, and when challenged with SIV the vaccinated pigs had significantly reduced acute respiratory sign scores. The results from this study demonstrate the potential of DS722-SIV-PCV2 as a candidate trivalent vaccine, and also shed light on exploring PRRSV as a potential live virus vaccine vector.

Viral chimeras decrypt the role of enterovirus capsid proteins in viral tropism, acid sensitivity and optimal growth temperature

PubMed Central

Royston, Léna; Essaidi-Laziosi, Manel; Piuz, Isabelle; Geiser, Johan; Huang, Song; Kaiser, Laurent; Garcin, Dominique

2018-01-01

Despite their genetic similarities, enteric and respiratory enteroviruses (EVs) have highly heterogeneous biophysical properties and cause a vast diversity of human pathologies. In vitro differences include acid sensitivity, optimal growth temperature and tissue tropism, which reflect a preferential in vivo replication in the respiratory or gastrointestinal tract and are thus key determinants of EV virulence. To investigate the underlying cause of these differences, we generated chimeras at the capsid-level between EV-D68 (a respiratory EV) and EV-D94 (an enteric EV). Although some chimeras were nonfunctional, EV-D94 with both the capsid and 2A protease or the capsid only of EV-D68 were both viable. Using this latter construct, we performed several functional assays, which indicated that capsid proteins determine acid sensitivity and tropism in cell lines and in respiratory, intestinal and neural tissues. Additionally, capsid genes were shown to also participate in determining the optimal growth temperature, since EV-D94 temperature adaptation relied on single mutations in VP1, while constructs with EV-D68 capsid could not adapt to higher temperatures. Finally, we demonstrate that EV-D68 maintains residual binding-capacity after acid-treatment despite a loss of infectivity. In contrast, non-structural rather than capsid proteins modulate the innate immune response in tissues. These unique biophysical insights expose another layer in the phenotypic diversity of one of world’s most prevalent pathogens and could aid target selection for vaccine or antiviral development. PMID:29630666

Community-acquired pneumonia requiring hospitalization among U.S. children.

PubMed

Jain, Seema; Williams, Derek J; Arnold, Sandra R; Ampofo, Krow; Bramley, Anna M; Reed, Carrie; Stockmann, Chris; Anderson, Evan J; Grijalva, Carlos G; Self, Wesley H; Zhu, Yuwei; Patel, Anami; Hymas, Weston; Chappell, James D; Kaufman, Robert A; Kan, J Herman; Dansie, David; Lenny, Noel; Hillyard, David R; Haynes, Lia M; Levine, Min; Lindstrom, Stephen; Winchell, Jonas M; Katz, Jacqueline M; Erdman, Dean; Schneider, Eileen; Hicks, Lauri A; Wunderink, Richard G; Edwards, Kathryn M; Pavia, Andrew T; McCullers, Jonathan A; Finelli, Lyn

2015-02-26

Incidence estimates of hospitalizations for community-acquired pneumonia among children in the United States that are based on prospective data collection are limited. Updated estimates of pneumonia that has been confirmed radiographically and with the use of current laboratory diagnostic tests are needed. We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among children younger than 18 years of age in three hospitals in Memphis, Nashville, and Salt Lake City. We excluded children with recent hospitalization or severe immunosuppression. Blood and respiratory specimens were systematically collected for pathogen detection with the use of multiple methods. Chest radiographs were reviewed independently by study radiologists. From January 2010 through June 2012, we enrolled 2638 of 3803 eligible children (69%), 2358 of whom (89%) had radiographic evidence of pneumonia. The median age of the children was 2 years (interquartile range, 1 to 6); 497 of 2358 children (21%) required intensive care, and 3 (<1%) died. Among 2222 children with radiographic evidence of pneumonia and with specimens available for bacterial and viral testing, a viral or bacterial pathogen was detected in 1802 (81%), one or more viruses in 1472 (66%), bacteria in 175 (8%), and both bacterial and viral pathogens in 155 (7%). The annual incidence of pneumonia was 15.7 cases per 10,000 children (95% confidence interval [CI], 14.9 to 16.5), with the highest rate among children younger than 2 years of age (62.2 cases per 10,000 children; 95% CI, 57.6 to 67.1). Respiratory syncytial virus was more common among children younger than 5 years of age than among older children (37% vs. 8%), as were adenovirus (15% vs. 3%) and human metapneumovirus (15% vs. 8%). Mycoplasma pneumoniae was more common among children 5 years of age or older than among younger children (19% vs. 3%). The burden of hospitalization for children with community-acquired pneumonia was highest among the very young, with respiratory viruses the most commonly detected causes of pneumonia. (Funded by the Influenza Division of the National Center for Immunization and Respiratory Diseases.).

An outbreak of respiratory tularemia caused by diverse clones of Francisella tularensis.

PubMed

Johansson, Anders; Lärkeryd, Adrian; Widerström, Micael; Mörtberg, Sara; Myrtännäs, Kerstin; Ohrman, Caroline; Birdsell, Dawn; Keim, Paul; Wagner, David M; Forsman, Mats; Larsson, Pär

2014-12-01

The bacterium Francisella tularensis is recognized for its virulence, infectivity, genetic homogeneity, and potential as a bioterrorism agent. Outbreaks of respiratory tularemia, caused by inhalation of this bacterium, are poorly understood. Such outbreaks are exceedingly rare, and F. tularensis is seldom recovered from clinical specimens. A localized outbreak of tularemia in Sweden was investigated. Sixty-seven humans contracted laboratory-verified respiratory tularemia. F. tularensis subspecies holarctica was isolated from the blood or pleural fluid of 10 individuals from July to September 2010. Using whole-genome sequencing and analysis of single-nucleotide polymorphisms (SNPs), outbreak isolates were compared with 110 archived global isolates. There were 757 SNPs among the genomes of the 10 outbreak isolates and the 25 most closely related archival isolates (all from Sweden/Finland). Whole genomes of outbreak isolates were >99.9% similar at the nucleotide level and clustered into 3 distinct genetic clades. Unexpectedly, high-sequence similarity grouped some outbreak and archival isolates that originated from patients from different geographic regions and up to 10 years apart. Outbreak and archival genomes frequently differed by only 1-3 of 1 585 229 examined nucleotides. The outbreak was caused by diverse clones of F. tularensis that occurred concomitantly, were widespread, and apparently persisted in the environment. Multiple independent acquisitions of F. tularensis from the environment over a short time period suggest that natural outbreaks of respiratory tularemia are triggered by environmental cues. The findings additionally caution against interpreting genome sequence identity for this pathogen as proof of a direct epidemiological link. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Pathogenic human viruses in coastal waters

USGS Publications Warehouse

Griffin, Dale W.; Donaldson, Kim A.; Paul, J.H.; Rose, Joan B.

2003-01-01

This review addresses both historical and recent investigations into viral contamination of marine waters. With the relatively recent emergence of molecular biology-based assays, a number of investigations have shown that pathogenic viruses are prevalent in marine waters being impacted by sewage. Research has shown that this group of fecal-oral viral pathogens (enteroviruses, hepatitis A viruses, Norwalk viruses, reoviruses, adenoviruses, rotaviruses, etc.) can cause a broad range of asymptomatic to severe gastrointestinal, respiratory, and eye, nose, ear, and skin infections in people exposed through recreational use of the water. The viruses and the nucleic acid signature survive for an extended period in the marine environment. One of the primary concerns of public health officials is the relationship between the presence of pathogens and the recreational risk to human health in polluted marine environments. While a number of studies have attempted to address this issue, the relationship is still poorly understood. A contributing factor to our lack of progress in the field has been the lack of sensitive methods to detect the broad range of both bacterial and viral pathogens. The application of new and advanced molecular methods will continue to contribute to our current state of knowledge in this emerging and

Coronavirus infection in intensively managed cattle with respiratory disease.

PubMed

Hick, P M; Read, A J; Lugton, I; Busfield, F; Dawood, K E; Gabor, L; Hornitzky, M; Kirkland, P D

2012-10-01

A detailed laboratory investigation identified bovine coronavirus (BCoV) as the aetiological agent in an outbreak of respiratory disease at a semi-intensive beef cattle feedlot in south-east Australia. The outbreak caused 30% morbidity in the resident population and also affected two cohorts of cattle that were newly introduced to the property. At slaughter, pulmonary consolidation and inflammatory lesions in the trachea were identified in 15 of 49 animals. Pasteurella multocida or Histophilus somni was cultured from 3 of 7 animals with lesions. Histopathological examination revealed multifocal non-suppurative bronchointerstitial pneumonia with formation of epithelial syncytial cells, sometimes associated with suppurative bronchopneumonia. BCoV was detected in nasal swabs and pulmonary lesions using real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) assay and virus isolation. There was serological evidence of previous exposure to bovine viral diarrhoea virus, bovine respiratory syncytial virus and bovine parainfluenza virus type 3, but not to bovine herpesvirus type 1. None of these viral pathogens or Mycoplasma bovis was identified by qRT-PCR. This is believed to be the first report of BCoV in association with bovine respiratory disease complex in Australia. © 2012 The Authors. Australian Veterinary Journal © 2012 Australian Veterinary Association.

Real-Time Sequence-Validated Loop-Mediated Isothermal Amplification Assays for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

PubMed Central

Bhadra, Sanchita; Jiang, Yu Sherry; Kumar, Mia R.; Johnson, Reed F.; Hensley, Lisa E.; Ellington, Andrew D.

2015-01-01

The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF)1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD) for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50 PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens. PMID:25856093

Managing Pseudomonas aeruginosa respiratory infections in cystic fibrosis.

PubMed

Langan, Katherine M; Kotsimbos, Tom; Peleg, Anton Y

2015-12-01

The current guidelines and recent clinical research in the management of Pseudomonas aeruginosa respiratory infections in cystic fibrosis (CF) are reviewed. Areas where further research is required will also be highlighted. P. aeruginosa is a key respiratory pathogen in CF. Inhaled tobramycin or colistin is recommended for early eradication to prevent establishment of chronic infection. Other antibiotic options are currently being investigated. The long-term success of eradication strategies is also now being assessed. The use of inhaled antibiotics in the management of chronic P. aeruginosa infection is an area of active investigation. Acute pulmonary exacerbations are still a major cause of morbidity and mortality. Guidelines continue to recommend combination intravenous therapy but further research is required to clarify the advantage of this approach. Multidrug resistance is common and potentially more effective antipseudomonal antibiotics may soon become available. The management of P. aeruginosa respiratory infection in CF remains a challenging area, especially in the setting of multidrug resistance. The role of inhaled antibiotics continues to be expanded. Further research is required in the key areas of eradication and management of chronic infection and acute pulmonary exacerbations to identify those treatments that optimize long-term, clinical benefits.

Wildlife translocation: the conservation implications of pathogen exposure and genetic heterozygosity

PubMed Central

2011-01-01

Background A key challenge for conservation biologists is to determine the most appropriate demographic and genetic management strategies for wildlife populations threatened by disease. We explored this topic by examining whether genetic background and previous pathogen exposure influenced survival of translocated animals when captive-bred and free-ranging bighorn sheep (Ovis canadensis) were used to re-establish a population that had been extirpated in the San Andres Mountains in New Mexico, USA. Results Although the free-ranging source population had significantly higher multi-locus heterozygosity at 30 microsatellite loci than the captive bred animals, neither source population nor genetic background significantly influenced survival or cause of death. The presence of antibodies to a respiratory virus known to cause pneumonia was associated with increased survival, but there was no correlation between genetic heterozygosity and the presence of antibodies to this virus. Conclusions Although genetic theory predicts otherwise, increased heterozygosity was not associated with increased fitness (survival) among translocated animals. While heterosis or genetic rescue effects may occur in F1 and later generations as the two source populations interbreed, we conclude that previous pathogen exposure was a more important marker than genetic heterozygosity for predicting survival of translocated animals. Every wildlife translocation is an experiment, and whenever possible, translocations should be designed and evaluated to test hypotheses that will further improve our understanding of how pathogen exposure and genetic variability influence fitness. PMID:21284886

Wildlife translocation: the conservation implications of pathogen exposure and genetic heterozygosity.

PubMed

Boyce, Walter M; Weisenberger, Mara E; Penedo, M Cecilia T; Johnson, Christine K

2011-02-01

A key challenge for conservation biologists is to determine the most appropriate demographic and genetic management strategies for wildlife populations threatened by disease. We explored this topic by examining whether genetic background and previous pathogen exposure influenced survival of translocated animals when captive-bred and free-ranging bighorn sheep (Ovis canadensis) were used to re-establish a population that had been extirpated in the San Andres Mountains in New Mexico, USA. Although the free-ranging source population had significantly higher multi-locus heterozygosity at 30 microsatellite loci than the captive bred animals, neither source population nor genetic background significantly influenced survival or cause of death. The presence of antibodies to a respiratory virus known to cause pneumonia was associated with increased survival, but there was no correlation between genetic heterozygosity and the presence of antibodies to this virus. Although genetic theory predicts otherwise, increased heterozygosity was not associated with increased fitness (survival) among translocated animals. While heterosis or genetic rescue effects may occur in F1 and later generations as the two source populations interbreed, we conclude that previous pathogen exposure was a more important marker than genetic heterozygosity for predicting survival of translocated animals. Every wildlife translocation is an experiment, and whenever possible, translocations should be designed and evaluated to test hypotheses that will further improve our understanding of how pathogen exposure and genetic variability influence fitness.

The mitochondrial alternative oxidase Aox1 is needed to cope with respiratory stress but dispensable for pathogenic development in Ustilago maydis

PubMed Central

Piñón-Zárate, Gabriela; Matus-Ortega, Genaro; Guerra, Guadalupe; Feldbrügge, Michael; Pardo, Juan Pablo

2017-01-01

The mitochondrial alternative oxidase is an important enzyme that allows respiratory activity and the functioning of the Krebs cycle upon disturbance of the respiration chain. It works as a security valve in transferring excessive electrons to oxygen, thereby preventing potential damage by the generation of harmful radicals. A clear biological function, besides the stress response, has so far convincingly only been shown for plants that use the alternative oxidase to generate heat to distribute volatiles. In fungi it was described that the alternative oxidase is needed for pathogenicity. Here, we investigate expression and function of the alternative oxidase at different stages of the life cycle of the corn pathogen Ustilago maydis (Aox1). Interestingly, expression of Aox1 is specifically induced during the stationary phase suggesting a role at high cell density when nutrients become limiting. Studying deletion strains as well as overexpressing strains revealed that Aox1 is dispensable for normal growth, for cell morphology, for response to temperature stress as well as for filamentous growth and plant pathogenicity. However, during conditions eliciting respiratory stress yeast-like growth as well as hyphal growth is strongly affected. We conclude that Aox1 is dispensable for the normal biology of the fungus but specifically needed to cope with respiratory stress. PMID:28273139

Rapid diagnostic tests apply for pediatric infections at outpatient clinic setting.

PubMed

Ushijima, Hiroshi; Thongprachum, Aksara; Tran, Dinh Nguyen; Fujimoto, Tsuguto; Hanaoka, Nozomu; Okitsu, Shoko; Takanashi, Sayaka; Mizuguchi, Masashi; Hayakawa, Satoshi

2015-01-01

Early identification of the etiology of infection is beneficial. Most infections are treated as outpatients. However, facilities for rapid diagnosis are not available in clinic settings. We applied Immunochromatography (IC) and Loop-mediated Isothermal Amplification (LAMP) methods to rapidly diagnose pathogens among 31 children with respiratory infection and 12 with gastroenteritis at a clinic in Saitama prefecture, Japan. Pathogens were then screened by multiplex conventional and real-time PCRs and bacterial culture. Respiratory pathogens were found in 64.5%. Despite the narrow spectrum, rapid tests identified pathogens in 28.6% of cases with a high agreement rate of 89.3% with PCR. Gastroenteritis pathogens were found in 66.7%. E. coli was positive in 3 cases and all were negative for verotoxin by LAMP. The agreement rate of IC and PCR assay was high, 100%. IC and LAMP are reliable and suitable methods in limited-resource settings for early pathogenic identification, which will help appropriate management, avoid unnecessary intervention, and cost saving.

Role of carriers in the transmission of pneumonia in bighorn sheep (Ovis canadensis)

PubMed Central

Raghavan, Bindu; Erickson, Kayla; Kugadas, Abirami; Batra, Sai A.; Call, Douglas R.; Davis, Margaret A.; Foreyt, William J.

2016-01-01

ABSTRACT In the absence of livestock contact, recurring lamb mortality in bighorn sheep (Ovis canadensis) populations previously exposed to pneumonia indicates the likely presence of carriers of pneumonia-causing pathogens, and possibly inadequate maternally derived immunity. To investigate this problem we commingled naïve, pregnant ewes (n=3) with previously exposed rams (n=2). Post-commingling, all ewes and lambs born to them acquired pneumonia-causing pathogens (leukotoxin-producing Pasteurellaceae and Mycoplasma ovipneumoniae), with subsequent lamb mortality between 4-9 weeks of age. Infected ewes became carriers for two subsequent years and lambs born to them succumbed to pneumonia. In another experiment, we attempted to suppress the carriage of leukotoxin-producing Pasteurellaceae by administering an antibiotic to carrier ewes, and evaluated lamb survival. Lambs born to both treatment and control ewes (n=4 each) acquired pneumonia and died. Antibody titers against leukotoxin-producing Pasteurellaceae in all eight ewes were ‘protective’ (>1:800 and no apparent respiratory disease); however their lambs were either born with comparatively low titers, or with high (but non-protective) titers that declined rapidly within 2-8 weeks of age, rendering them susceptible to fatal disease. Thus, exposure to pneumonia-causing pathogens from carrier ewes, and inadequate titers of maternally derived protective antibodies, are likely to render bighorn lambs susceptible to fatal pneumonia. PMID:27185269

75 FR 54018 - Implantation or Injectable Dosage Form New Animal Drugs; Florfenicol and Flunixin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-03

... respiratory disease (BRD) pathogens for which use of an injectable solution containing florfenicol and.... For treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella...

Paramyxovirus Assembly and Budding: Building Particles that Transmit Infections

PubMed Central

Harrison, Megan S.; Sakaguchi, Takemasa; Schmitt, Anthony P.

2010-01-01

The paramyxoviruses define a diverse group of enveloped RNA viruses that includes a number of important human and animal pathogens. Examples include human respiratory syncytial virus and the human parainfluenza viruses, which cause respiratory illnesses in young children and the elderly; measles and mumps viruses, which have caused recent resurgences of disease in developed countries; the zoonotic Hendra and Nipah viruses, which have caused several outbreaks of fatal disease in Australia and Asia; and Newcastle disease virus, which infects chickens and other avian species. Like other enveloped viruses, paramyxoviruses form particles that assemble and bud from cellular membranes, allowing the transmission of infections to new cells and hosts. Here, we review recent advances that have improved our understanding of events involved in paramyxovirus particle formation. Contributions of viral matrix proteins, glycoproteins, nucleocapsid proteins, and accessory proteins to particle formation are discussed, as well as the importance of host factor recruitment for efficient virus budding. Trafficking of viral structural components within infected cells is described, together with mechanisms that allow for the selection of specific sites on cellular membranes for the coalescence of viral proteins in preparation of bud formation and virion release. PMID:20398786

Convergent Evolution of Pathogen Effectors toward Reactive Oxygen Species Signaling Networks in Plants

PubMed Central

Jwa, Nam-Soo; Hwang, Byung Kook

2017-01-01

Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS) act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants. The perception of PAMPs by pattern recognition receptors leads to the rapid and strong production of ROS through activation of NADPH oxidase Respiratory Burst Oxidase Homologs (RBOHs) as well as peroxidases. Specific pathogen effectors directly or indirectly interact with plant nucleotide-binding leucine-rich repeat receptors to induce ROS production and the hypersensitive response in plant cells. By contrast, virulent pathogens possess effectors capable of suppressing plant ROS bursts in different ways during infection. PAMP-triggered ROS bursts are suppressed by pathogen effectors that target mitogen-activated protein kinase cascades. Moreover, pathogen effectors target vesicle trafficking or metabolic priming, leading to the suppression of ROS production. Secreted pathogen effectors block the metabolic coenzyme NADP-malic enzyme, inhibiting the transfer of electrons to the NADPH oxidases (RBOHs) responsible for ROS generation. Collectively, pathogen effectors may have evolved to converge on a common host protein network to suppress the common plant immune system, including the ROS burst and cell death response in plants. PMID:29033963

Enterovirus D68 Infection in an Adult.

PubMed

Ward, Nicholas S; Hughes, Brenna L; Mermel, Leonard A

2016-03-01

The first confirmed US case of severe respiratory tract infection caused by enterovirus D68 in an adult occurred in a pregnant woman with no history of asthma in August 2014. Before she came to the hospital, she had a productive cough, headache, and increasing dyspnea. At the hospital, she was hypoxic and required admittance to the intensive care unit and management with noninvasive bilevel positive pressure assistance. Analysis of a nasopharyngeal swab sent to the Centers for Disease Control and Prevention for a viral respiratory panel of tests confirmed enterovirus D68 infection. She eventually had an uneventful vaginal delivery, was discharged without oxygen supplementation, and has resumed normal activities. This case suggests that pregnant women may be a sentinel group infected with this pathogen, similar to what has been described for influenza virus infection. ©2016 American Association of Critical-Care Nurses.

COMPARISON OF CURRENT METHODS FOR THE DETECTION OF CHRONIC MYCOPLASMAL URTD IN WILD POPULATIONS OF THE MOJAVE DESERT TORTOISE (GOPHERUS AGASSIZII).

PubMed

Sandmeier, Franziska C; Weitzman, Chava L; Maloney, K Nichole; Tracy, C Richard; Nieto, Nathan; Teglas, Mike B; Hunter, Kenneth W; DuPré, Sally; Gienger, C M; Tuma, Michael W

2017-01-01

Pathogens that cause subclinical diseases or exhibit low infection intensities are difficult to quantify in wild populations. Mojave desert tortoises ( Gopherus agassizii ) have been the focus of much research aimed at measuring the presence of upper respiratory disease (URTD) and URTD-associated pathogens, and techniques used to quantify disease in Gopherus species have also been used for disease surveillance in other species of turtles and tortoises of conservation concern. Published surveys of G. agassizii populations have found a relatively low prevalence of URTD, with most URTD-positive animals exhibiting moderate, intermittent signs of morbidity. Therefore, multiple tests have been developed to quantify URTD including genetic detection of the pathogens Mycoplasma agassizii and Mycoplasma testudineum , detection of M. agassizii -specific antibodies, and standardized quantification of clinical signs of URTD and body condition. These diagnostic tests have only been compared in diseased or moribund, semicaptive animals. We compared diagnostic techniques (TaqMan® and SYBR™ Green qPCR, serology, and visible examination) to detect M. agassizii -associated URTD in 126 wild desert tortoises sampled in Nevada and California, US in 2010. All had healthy body condition indices and none exhibited more than mild-to-moderate visual signs of URTD. Pairwise comparisons of diagnostic techniques indicated poor performance in diagnosing disease in individual animals. We found stronger, but inconsistent, statistical associations among diagnostic techniques at the population level. Our findings have implications for quantifying subclinical respiratory disease in tortoises.

[A retrospective study of one case of human infection by the highly pathogenic avian influenza A (H5N1)].

PubMed

Zhou, Chao; Fang, Ping; Liu, You-ning; Hu, Bin; Ding, Hong-mei; Xu, Xiao-ling; Wu, Hao; Wang, Jin; Lin, Lin; Pan, Hua; Wu, Tong-sheng; Song, You-liang

2006-01-01

To describe the clinical features of the infection caused by the highly pathogenic avian influenza A (H(5)N(1)). A previously healthy 24 year old woman presented to our hospital on November 7, 2005. She was confirmed to be an H(5)N(1) infected case after death. The clinical, radiological and epidemiological data were analyzed. The patient had a history of direct contact with diseased and dead poultry (chicken and duck). The disease course was 10 days from onset of illness to death, and fever preceded dyspnea by 5 days. On admission, the striking characteristics were acute community-acquired pneumonia (CAP) and acute respiratory distress syndrome (ARDS), and the major radiographic abnormalities included extensive infiltration bilaterally, focal consolidation and air bronchograms. The radiographic and clinical deterioration was rapid, and the patient died in less than 3 days after hospitalization. The diagnosis of influenza A (H(5)N(1)) was confirmed by means of reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time PCR on specimens of the lower respiratory tract, performed by Chinese Center for Disease Control. The postmortem examination showed bronchial hyperemia, extensive consolidation, serous cavity effusions, disseminated intravascular coagulation (DIC) and multiple organ failure (MOF). Human infection by the highly pathogenic avian influenza A (H(5)N(1)) is a fatal communicable disease. Information of avian influenza A (H(5)N(1)) virus, more attention to the epidemiologic data, and early intervention are critical in reducing the mortality.

The etiology of community-acquired pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most appropriate therapy.

PubMed

Charles, Patrick G P; Whitby, Michael; Fuller, Andrew J; Stirling, Robert; Wright, Alistair A; Korman, Tony M; Holmes, Peter W; Christiansen, Keryn J; Waterer, Grant W; Pierce, Robert J P; Mayall, Barrie C; Armstrong, John G; Catton, Michael G; Nimmo, Graeme R; Johnson, Barbara; Hooy, Michelle; Grayson, M L

2008-05-15

Available data on the etiology of community-acquired pneumonia (CAP) in Australia are very limited. Local treatment guidelines promote the use of combination therapy with agents such as penicillin or amoxycillin combined with either doxycycline or a macrolide. The Australian CAP Study (ACAPS) was a prospective, multicenter study of 885 episodes of CAP in which all patients underwent detailed assessment for bacterial and viral pathogens (cultures, urinary antigen testing, serological methods, and polymerase chain reaction). Antibiotic agents and relevant clinical outcomes were recorded. The etiology was identified in 404 (45.6%) of 885 episodes, with the most frequent causes being Streptococcus pneumoniae (14%), Mycoplasma pneumoniae (9%), and respiratory viruses (15%; influenza, picornavirus, respiratory syncytial virus, parainfluenza virus, and adenovirus). Antibiotic-resistant pathogens were rare: only 5.4% of patients had an infection for which therapy with penicillin plus doxycycline would potentially fail. Concordance with local antibiotic recommendations was high (82.4%), with the most commonly prescribed regimens being a penicillin plus either doxycycline or a macrolide (55.8%) or ceftriaxone plus either doxycycline or a macrolide (36.8%). The 30-day mortality rate was 5.6% (50 of 885 episodes), and mechanical ventilation or vasopressor support were required in 94 episodes (10.6%). Outcomes were not compromised by receipt of narrower-spectrum beta-lactams, and they did not differ on the basis of whether a pathogen was identified. The vast majority of patients with CAP can be treated successfully with narrow-spectrum beta-lactam treatment, such as penicillin combined with doxycycline or a macrolide. Greater use of such therapy could potentially reduce the emergence of antibiotic resistance among common bacterial pathogens.

Value of lower respiratory tract surveillance cultures to predict bacterial pathogens in ventilator-associated pneumonia: systematic review and diagnostic test accuracy meta-analysis.

PubMed

Brusselaers, Nele; Labeau, Sonia; Vogelaers, Dirk; Blot, Stijn

2013-03-01

In ventilator-associated pneumonia (VAP), early appropriate antimicrobial therapy may be hampered by involvement of multidrug-resistant (MDR) pathogens. A systematic review and diagnostic test accuracy meta-analysis were performed to analyse whether lower respiratory tract surveillance cultures accurately predict the causative pathogens of subsequent VAP in adult patients. Selection and assessment of eligibility were performed by three investigators by mutual consideration. Of the 525 studies retrieved, 14 were eligible for inclusion (all in English; published since 1994), accounting for 791 VAP episodes. The following data were collected: study and population characteristics; in- and exclusion criteria; diagnostic criteria for VAP; microbiological workup of surveillance and diagnostic VAP cultures. Sub-analyses were conducted for VAP caused by Staphylococcus aureus, Pseudomonas spp., and Acinetobacter spp., MDR microorganisms, frequency of sampling, and consideration of all versus the most recent surveillance cultures. The meta-analysis showed a high accuracy of surveillance cultures, with pooled sensitivities up to 0.75 and specificities up to 0.92 in culture-positive VAP. The area under the curve (AUC) of the hierarchical summary receiver-operating characteristic curve demonstrates moderate accuracy (AUC: 0.90) in predicting multidrug resistance. A sampling frequency of >2/week (sensitivity 0.79; specificity 0.96) and consideration of only the most recent surveillance culture (sensitivity 0.78; specificity 0.96) are associated with a higher accuracy of prediction. This study provides evidence for the benefit of surveillance cultures in predicting MDR bacterial pathogens in VAP. However, clinical and statistical heterogeneity, limited samples sizes, and bias remain important limitations of this meta-analysis.

Comparison of direct-plating and broth-enrichment culture methods for detection of potential bacterial pathogens in respiratory secretions.

PubMed

Kaur, Ravinder; Wischmeyer, Jareth; Morris, Matthew; Pichichero, Michael E

2017-11-01

We compared the recovery of potential respiratory bacterial pathogens and normal flora from nasopharyngeal specimens collected from children during health and at the onset of acute otitis media (AOM) by selective direct-plating and overnight broth-enrichment. Overall, 3442 nasal wash (NW) samples collected from young children were analysed from a 10-year prospective study. NWs were cultured by (1) direct-plating to TSAII/5 % sheep blood agar and chocolate agar plates and (2) overnight broth-enrichment in BacT/ALERT SA-broth followed by plating. Standard microbiology techniques were applied to identify three dominant respiratory bacterial pathogens: Streptococcus pneumoniae (Spn), Haemophilus influenzae (Hflu) and Moraxella catarrhalis (Mcat) as well as two common nasal flora, Staphylococcus aureus (SA) and alpha-haemolytic Streptococci (AHS).Results/Key findings. Direct-plating of NW resulted in isolation of Spn from 37.8 %, Hflu from 13.6 % and Mcat from 33.2 % of samples. In comparison, overnight broth-enrichment isolated fewer Spn (30.1 %), Hflu (6.2 %) and Mcat (16.2 %) (P<0.001-0.0001). Broth-enrichment resulted in significant increased isolation of SA (6.0 %) and AHS (30.1 %) (P<0.0001). Competition between bacterial species in broth when both species were detected by direct-plating was assessed, and it was found that SA and AHS out-competed other species during broth-enrichment when samples were collected from healthy children but not during AOM. In middle ear fluids (MEF) at the onset of AOM, broth-enrichment resulted in higher recovery of Spn (+10.4 %, P<0.001), Hflu (+4.4 %, P=0.39) and Mcat (+13.5 %, <0.001). Broth-enrichment significantly reduces the accurate detection of bacterial respiratory pathogens and increases identification of SA and AHS in NW. Broth-enrichment improves detection of bacterial respiratory pathogens in MEF samples.

Detection of respiratory allergies caused by environmental chemical allergen via measures of hyper-activation and degranulation of mast cells in lungs of NC/Nga mice.

PubMed

Nishino, Risako; Fukuyama, Tomoki; Watanabe, Yuko; Kurosawa, Yoshimi; Koasaka, Tadashi; Harada, Takanori

2016-09-01

Respiratory allergy triggered by exposure to environmental chemical allergen is a serious problem in many Asian countries and has the potential to cause severe health problems. Here, we aimed to elucidate the pathogenic mechanisms of this disease and develop an in vivo detection method for respiratory allergy induced by environmental chemical allergen. Both BALB/c and NC/Nga mice were sensitized topically for 3 weeks and were then subjected to inhalation challenge with pulverized trimellitic anhydride into particles measuring 2-μm in diameter. On the day after the final challenge, all mice were sacrificed, and IgE levels, immunocyte counts, and cytokine levels in the serum, hilar lymph nodes, and bronchoalveolar lavage fluid were measured. We also monitored the expression of genes encoding pro-inflammatory cytokines in the lung. We found that all endpoints were significantly increased in mice of both strains subjected to trimellitic anhydride inhalation as compared with the respective control groups. However, worsening of respiratory status was noted only in NC/Nga mice. Interestingly, type 2 helper T-cell reactions were significantly increased in BALB/c mice compared with that in NC/Nga mice. In contrast, the number of mast cells, levels of mast cell-related cytokine/chemokines, and production of histamine in NC/Nga mice were significantly higher than those in BALB/c mice. Thus, environmental chemical allergen induced respiratory allergy in NC/Nga mice in terms of functional and inflammatory symptoms. Furthermore, mast cells may be involved in the aggravation of airway allergic symptoms induced by environmental chemical allergens.

A case of group A streptococcal meningitis in an adult

PubMed Central

Pattullo, Andrew LS; Bow, Eric J

1993-01-01

Group A streptococci are an important cause of soft tissue infections but have rarely been reported as the cause of pyogenic meningitis since the advent of antibiotics. A case of group A streptococcal meningitis in an adult is presented along with a review of similar cases reported in the literature. This case serves to illustrate the virulent nature of this pathogen in infections of the meninges, the potential for associated complications, and the need for rapid diagnosis and appropriate treatment. The source of infection in this and many other cases in the literature is the upper respiratory tract. The case presented responded well to antibiotics but resulted in permanent auditory-vestibular dysfunction. PMID:22346453

A Nonfatal Case of Dobrava Hantavirus Hemorrhagic Fever with Renal Syndrome Combined with Hantavirus Cardiopulmonary Syndrome.

PubMed

Dreshaj, Shemsedin; Ajazaj, Lindita; Hasani, Nderim; Halili, Bahrije; Ponosheci, Albina; Jakupi, Xhevat

2018-01-01

Among hantaviruses (HTNV), 22 are known as pathogenic for humans. HTNV can cause two clinical entities: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome or hantavirus cardiopulmonary syndrome (HCPS). In most countries of Eastern Europe as well as in Kosovo, HTNV infection is presented mainly as HFRS. Here, we report a 20-year-old man with HFRS and HCPS caused by Dobrava hantavirus strain, successfully treated in Intensive Care Unit of Infectious Diseases Clinic, University Clinical Center of Kosovo. In HFRS endemic areas, patients with acute respiratory distress syndrome need to be evaluated for Dobrava hantavirus strain as a possible causative agent.

[Infectious endocarditis due to Gemella morbillorum found by splenic infarction--a case report].

PubMed

Hosaka, Yumiko; Kimura, Takuma; Suzuki, Ryo; Chong, Tonghyo; Shoji, Michi; Aoki, Yasuko

2010-09-01

A 64-year-old man with prostate cancer and bone metastasis admitted for nausea, left abdominal pain showed no abnormal, and fever, abdominal ultrasound or chest X-ray findings. Despite antibiotics, left abdominal pain persisted for several days. Abdominal computed tomography (CT), showed splenic infarction. Transesophageal echocardiography suggested infectious endocarditis (IE) as a possible infarction cause, and roth spots were found on the retina. Gemella morbillorum was detected from blood culture. IE commonly causes Fever of Unknown Origin found by infarction. G. morbillorum, an anaerobic gram-positive, viridans group streptococci, is indigenous to the oropharynx, upper respiratory, urogenital, and gastrointestinal tracts, and is thought to have weak toxicity and pathogenicity in the body.

Respiratory tract immune response to microbial pathogens.

PubMed

Wilkie, B N

1982-11-15

Effective resistance to respiratory tract infection depends principally on specific immunity on mucosal surfaces of the upper or lower respiratory tract. Respiratory tract immune response comprises antibody and cell-mediated systems and may be induced most readily by surface presentation of replicating agents but can result from parenteral or local presentation of highly immunogenic antigens. Upper and lower respiratory tract systems differ in immunologic competence, with the lungs having a greater inventory of protective mechanisms than the trachea or nose. Several effective vaccines have been developed for prevention or modification of respiratory tract diseases.

A Prospective One-Year Microbiologic Survey of Combined Pneumonia and Respiratory Failure.

PubMed

Fisher, Kristen; Trupka, Tracy; Micek, Scott T; Juang, Paul; Kollef, Marin H

2017-10-01

Pneumonia and respiratory failure are common problems in the intensive care unit (ICU) setting, often occurring together. The relative prevalence of pneumonia types (community acquired, hospital acquired, ventilator associated) and causative pathogens is not well described in patients with respiratory failure. This was a prospective observational cohort study conducted in the medical ICU (34 beds) of Barnes-Jewish Hospital, an academic referral center of 1,300 beds from January 2016-December 2016. All patients who were prospectively adjudicated to have respiratory failure and pneumonia (RFP) regardless of pneumonia type were classified into one of four microbiologic categories: pathogen negative, antibiotic-susceptible pathogen (according to ceftriaxone susceptibility), antibiotic-resistant pathogen, and viruses. The primary outcomes assessed were the hospital mortality rate and inappropriate initial antibiotic therapy (IIAT) for non-viral pathogens. Among 364 consecutive patients with RFP, 63 (17.3%) had organisms that were antibiotic susceptible, 104 (28.6%) had antibiotic-resistant organisms, 118 (32.4%) were pathogen negative, and 79 (21.7%) had viral infections. For these categories, IIAT occurred in 3.2%, 21.2%, 0.8%, and 0, respectively (p < 0.001). Vasopressor-requiring shock was present in 61.9%, 72.1%, 68.6%, and 67.1%, respectively (p = 0.585), and the hospital mortality rates were 27.0%, 48.1%, 31.4%, and 36.7%, respectively (p = 0.020). Multivariable logistic regression analysis identified IIAT as an independent predictor of in-hospital death (adjusted odds ratio 5.28; 95% confidence interval 2.72-10.22; p = 0.012). Male gender, increasing Acute Physiology and Chronic Health Evaluation (APACHE) II scores, greater age, and the presence of shock also predicted death. Microbiologic categorization of patients with RFP suggests that antibiotic-resistant pathogens and viruses are associated with the highest mortality rates. Vasopressor-requiring shock was common regardless of the microbiologic categorization of RFP. Future development and use of rapid diagnostics and novel therapeutics targeting specific RFP pathogens may allow more timely administration of appropriate antimicrobial therapy and enhance antibiotic stewardship practices.

Lipids Derived from Virulent Francisella tularensis Broadly Inhibit Pulmonary Inflammation via Toll-Like Receptor 2 and Peroxisome Proliferator-Activated Receptor α

PubMed Central

Crane, Deborah D.; Ireland, Robin; Alinger, Joshua B.; Small, Pamela

2013-01-01

Francisella tularensis is a Gram-negative facultative intracellular pathogen that causes an acute lethal respiratory disease in humans. The heightened virulence of the pathogen is linked to its unique ability to inhibit Toll-like receptor (TLR)-mediated inflammatory responses. The bacterial component and mechanism of this inhibition are unknown. Here we show that lipids isolated from virulent but not attenuated strains of F. tularensis are not detected by host cells, inhibit production of proinflammatory cytokines by primary macrophages in response to known TLR ligands, and suppress neutrophil recruitment in vivo. We further show that lipid-mediated inhibition of inflammation is dependent on TLR2, MyD88, and the nuclear hormone and fatty acid receptor peroxisome proliferator-activated receptor α (PPARα). Pathogen lipid-mediated interference with inflammatory responses through the engagement of TLR2 and PPARα represents a novel manipulation of host signaling pathways consistent with the ability of highly virulent F. tularensis to efficiently evade host immune responses. PMID:23925884

Droplets and modes of respiratory disease transmission

NASA Astrophysics Data System (ADS)

Bourouiba, Lydia

2014-11-01

Direct observation of violent expirations such as sneezes and coughs events reveal that such flows are multiphase turbulent buoyant clouds with suspended droplets of various sizes. The effects of ambient conditions indoors, such as moisture and temperature, coupled with the water content of such clouds are key in shaping the pathogen footprint emitted by potentially sick individuals. Such pathogen footprint can change the patterns of respiratory disease transmission. We discuss how the fluid dynamics of violent expirations can help inform how.

Early progressive encephalopathy in boys and MECP2 mutations.

PubMed

Kankirawatana, P; Leonard, H; Ellaway, C; Scurlock, J; Mansour, A; Makris, C M; Dure, L S; Friez, M; Lane, J; Kiraly-Borri, C; Fabian, V; Davis, M; Jackson, J; Christodoulou, J; Kaufmann, W E; Ravine, D; Percy, A K

2006-07-11

MECP2 mutations mainly occur in females with Rett syndrome. Mutations have been described in 11 boys with progressive encephalopathy: seven of nine with affected sisters and two de novo. The authors report four de novo occurrences: three pathogenic and one potentially pathogenic. Common features include failure to thrive, respiratory insufficiency, microcephaly, and abnormal motor control. MECP2 mutations should be assessed in boys with progressive encephalopathy and one or more of respiratory insufficiency, abnormal movements or tone, and intractable seizures.

Improved patient safety through reduced airway infection rates in a paediatric cystic fibrosis programme after a quality improvement effort to enhance infection prevention and control measures.

PubMed

Savant, Adrienne P; O'Malley, Catherine; Bichl, Stacy; McColley, Susanna A

2014-04-01

To reduce the risk of pathogen transmission between patients with cystic fibrosis (CF) and decrease the rate of acquisition of new CF pathogens in our patients. Using the Model for Improvement, we developed a new process for infection prevention and control in our outpatient CF clinics. Paediatric CF programme at Ann & Robert H. Lurie Children's Hospital of Chicago; approximately 180 paediatric patients aged birth to 21 years. All paediatric patients enrolled in the Cystic Fibrosis Foundation Patient Data Registry at this institution. Implemented contact precautions with all patients, regardless of respiratory tract culture results. Respiratory tract culture rates of specific pathogens by quarter were compared prior to and after implementation. Our percentage of patients with a positive respiratory tract culture for Pseudomonas aeruginosa dropped from 30% to 21% (p<0.0001) and for methicillin-resistant Staphylococcus aureus (MRSA) dropped from 10.8% to 8.7% (p=0.008). Use of contact precautions by all care providers, for all patients, regardless of respiratory tract culture results resulted in decreased P aeruginosa and MRSA infection rates.

Efficacy of Fostera® PRRS modified live virus (MLV) vaccination strategy against a Thai highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) infection.

PubMed

Charoenchanikran, Ponlakrit; Kedkovid, Roongtham; Sirisereewan, Chaitawat; Woonwong, Yonlayong; Arunorat, Jirapat; Sitthichareonchai, Panchan; Sopipan, Natthawan; Jittimanee, Suphattra; Kesdangsakonwut, Sawang; Thanawongnuwech, Roongroje

2016-10-01

Recently, the Chinese highly pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) (HP-PRRSV) belonging to lineage 8 causes severe symptom with high morbidity and high mortality rates to the Asian pig industry. A recent study showed that pigs immunized with Fostera® PRRS modified live virus (MLV) of lineage 8 could provide a degree of protection against a Vietnamese HP-PRRSV infection. It should be noted that PRRSV commonly found after weaning causes porcine respiratory disease complex (PRDC). Vaccination strategy should be evaluated in each farm scenario. Eighty-one PRRSV-free piglets obtained from a PRRS-free herd were divided into two experiments with the major difference of infection timing after vaccination, 42 days in experiment 1 (n = 42) and 28 days in experiment 2 (n = 39). Each experiment had similar protocol containing three groups including a negative control, unvaccinated challenged, and vaccinated challenged groups. Pigs in vaccination groups were immunized with Fostera® PRRS MLV vaccine at 3 weeks of age. Then, unvaccinated challenged and vaccinated challenged groups were intranasally inoculated with a Thai HP-PRRSV (10PL01). Vaccinated challenged pigs showed significantly lower levels of mean rectal temperatures, clinical severity, lung lesion scores, and viral titers in serum and lung tissue compared to the unvaccinated challenged pigs (p < 0.05). Vaccinated challenged pigs had higher survival rate than those of unvaccinated challenged pigs in both experiments. It should be noted that pigs challenged 42 days after vaccination showed a better performance than pigs challenged 28 days after vaccination. In conclusion, Fostera® PRRS MLV vaccine was able to improve the survival rate against the Thai HP-PRRSV infection in both 42- and 28-day vaccination-to-infection protocols.

Inhibition of Protein Synthesis on the Ribosome by Tildipirosin Compared with Other Veterinary Macrolides

PubMed Central

Andersen, Niels Møller; Poehlsgaard, Jacob; Warrass, Ralf

2012-01-01

Tildipirosin is a 16-membered-ring macrolide developed to treat bacterial pathogens, including Mannheimia haemolytica and Pasteurella multocida, that cause respiratory tract infections in cattle and swine. Here we evaluated the efficacy of tildipirosin at inhibiting protein synthesis on the ribosome (50% inhibitory concentration [IC50], 0.23 ± 0.01 μM) and compared it with the established veterinary macrolides tylosin, tilmicosin, and tulathromycin. Mutation and methylation at key rRNA nucleotides revealed differences in the interactions of these macrolides within their common ribosomal binding site. PMID:22926570

Comparison of commercial systems for extraction of nucleic acids from DNA/RNA respiratory pathogens.

PubMed

Yang, Genyan; Erdman, Dean E; Kodani, Maja; Kools, John; Bowen, Michael D; Fields, Barry S

2011-01-01

This study compared six automated nucleic acid extraction systems and one manual kit for their ability to recover nucleic acids from human nasal wash specimens spiked with five respiratory pathogens, representing Gram-positive bacteria (Streptococcus pyogenes), Gram-negative bacteria (Legionella pneumophila), DNA viruses (adenovirus), segmented RNA viruses (human influenza virus A), and non-segmented RNA viruses (respiratory syncytial virus). The robots and kit evaluated represent major commercially available methods that are capable of simultaneous extraction of DNA and RNA from respiratory specimens, and included platforms based on magnetic-bead technology (KingFisher mL, Biorobot EZ1, easyMAG, KingFisher Flex, and MagNA Pure Compact) or glass fiber filter technology (Biorobot MDX and the manual kit Allprep). All methods yielded extracts free of cross-contamination and RT-PCR inhibition. All automated systems recovered L. pneumophila and adenovirus DNA equivalently. However, the MagNA Pure protocol demonstrated more than 4-fold higher DNA recovery from the S. pyogenes than other methods. The KingFisher mL and easyMAG protocols provided 1- to 3-log wider linearity and extracted 3- to 4-fold more RNA from the human influenza virus and respiratory syncytial virus. These findings suggest that systems differed in nucleic acid recovery, reproducibility, and linearity in a pathogen specific manner. Published by Elsevier B.V.

Review and comparison between the Wells-Riley and dose-response approaches to risk assessment of infectious respiratory diseases.

PubMed

Sze To, G N; Chao, C Y H

2010-02-01

Infection risk assessment is very useful in understanding the transmission dynamics of infectious diseases and in predicting the risk of these diseases to the public. Quantitative infection risk assessment can provide quantitative analysis of disease transmission and the effectiveness of infection control measures. The Wells-Riley model has been extensively used for quantitative infection risk assessment of respiratory infectious diseases in indoor premises. Some newer studies have also proposed the use of dose-response models for such purpose. This study reviews and compares these two approaches to infection risk assessment of respiratory infectious diseases. The Wells-Riley model allows quick assessment and does not require interspecies extrapolation of infectivity. Dose-response models can consider other disease transmission routes in addition to airborne route and can calculate the infectious source strength of an outbreak in terms of the quantity of the pathogen rather than a hypothetical unit. Spatial distribution of airborne pathogens is one of the most important factors in infection risk assessment of respiratory disease. Respiratory deposition of aerosol induces heterogeneous infectivity of intake pathogens and randomness on the intake dose, which are not being well accounted for in current risk models. Some suggestions for further development of the risk assessment models are proposed. This review article summarizes the strengths and limitations of the Wells-Riley and the dose-response models for risk assessment of respiratory diseases. Even with many efforts by various investigators to develop and modify the risk assessment models, some limitations still persist. This review serves as a reference for further development of infection risk assessment models of respiratory diseases. The Wells-Riley model and dose-response model offer specific advantages. Risk assessors can select the approach that is suitable to their particular conditions to perform risk assessment.

Epidemiology and clinical characteristics of respiratory syncytial virus infections among children and adults in Mexico.

PubMed

Gamiño-Arroyo, Ana E; Moreno-Espinosa, Sarbelio; Llamosas-Gallardo, Beatriz; Ortiz-Hernández, Ana A; Guerrero, M Lourdes; Galindo-Fraga, Arturo; Galán-Herrera, Juan F; Prado-Galbarro, Francisco J; Beigel, John H; Ruiz-Palacios, Guillermo M; Noyola, Daniel E

2017-01-01

Respiratory syncytial virus (RSV) is a leading etiological agent of acute respiratory tract infections and hospitalizations in children. However, little information is available regarding RSV infections in Latin American countries, particularly among adult patients. To describe the epidemiology of RSV infection and to analyze the factors associated with severe infections in children and adults in Mexico. Patients ≥1 month old, who presented with an influenza-like illness (ILI) to six hospitals in Mexico, were eligible for participation in the study. Multiplex reverse-transcriptase polymerase chain reaction identified viral pathogens in nasal swabs from 5629 episodes of ILI. Patients in whom RSV was detected were included in this report. Respiratory syncytial virus was detected in 399 children and 171 adults. RSV A was detected in 413 cases and RSV B in 163, including six patients who had coinfection with both subtypes; 414 (72.6%) patients required hospital admission, including 96 (16.8%) patients that required admission to the intensive care unit. Coinfection with one or more respiratory pathogens other than RSV was detected in 159 cases. Young age (in children) and older age (in adults) as well as the presence of some underlying conditions were associated with more severe disease. This study confirms that RSV is an important respiratory pathogen in children in Mexico. In addition, a substantial number of cases in adults were also detected highlighting the relevance of this virus in all ages. It is important to identify subjects at high risk of complications who may benefit from current or future preventive interventions. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

[Infections related to recreational waters].

PubMed

Doménech-Sánchez, Antonio; Olea, Francisco; Berrocal, Clara I

2008-11-01

Recreational waters are a source of infection by several microorganisms causing acute gastrointestinal, cutaneous and respiratory illnesses. Cryptosporidium, noroviruses and enteropathogenic Escherichia coli strains are the most important causes of diarrhea, while Pseudomonas and Staphylococcus aureus are the main causes of cutaneous infections, and Legionella is the major cause of acute lower respiratory disease. Approximately 90% of outbreaks occur in treated recreational waters (swimming pools, spas and recreational parks), while the remaining 10% arise from natural waters used for leisure (bathing in rivers, beaches, etc). In spas, most infections are caused by thermophilic bacteria, such as Pseudomonas and Legionella, since overgrowth of these bacteria is facilitated by the direct effect of temperature and, indirectly, by the evaporation of the disinfectant. Outbreaks related to recreational waters usually reflect deficient control of the system: a low level of disinfectant, or the use of an inappropriate disinfectant, insufficient maintenance and cleaning of the installation, higher than recommended usage, and failure of the disinfectant dosage system. The correct design, maintenance and use of these facilities drastically lower the risk of infections from recreational waters. Thus, other key actions to minimize this risk are the existence of, and compliance with, regulatory rules, as well as educational campaigns on good hygiene practices directed at users. Rapid etiologic diagnosis of affected patients, together with an epidemiological survey and detection of the pathogen implicated in water samples are the keys to outbreak control.

Detection of Pneumonia Associated Pathogens Using a Prototype Multiplexed Pneumonia Test in Hospitalized Patients with Severe Pneumonia

PubMed Central

Schulte, Berit; Eickmeyer, Holm; Heininger, Alexandra; Juretzek, Stephanie; Karrasch, Matthias; Denis, Olivier; Roisin, Sandrine; Pletz, Mathias W.; Klein, Matthias; Barth, Sandra; Lüdke, Gerd H.; Thews, Anne; Torres, Antoni; Cillóniz, Catia; Straube, Eberhard; Autenrieth, Ingo B.; Keller, Peter M.

2014-01-01

Severe pneumonia remains an important cause of morbidity and mortality. Polymerase chain reaction (PCR) has been shown to be more sensitive than current standard microbiological methods – particularly in patients with prior antibiotic treatment – and therefore, may improve the accuracy of microbiological diagnosis for hospitalized patients with pneumonia. Conventional detection techniques and multiplex PCR for 14 typical bacterial pneumonia-associated pathogens were performed on respiratory samples collected from adult hospitalized patients enrolled in a prospective multi-center study. Patients were enrolled from March until September 2012. A total of 739 fresh, native samples were eligible for analysis, of which 75 were sputa, 421 aspirates, and 234 bronchial lavages. 276 pathogens were detected by microbiology for which a valid PCR result was generated (positive or negative detection result by Curetis prototype system). Among these, 120 were identified by the prototype assay, 50 pathogens were not detected. Overall performance of the prototype for pathogen identification was 70.6% sensitivity (95% confidence interval (CI) lower bound: 63.3%, upper bound: 76.9%) and 95.2% specificity (95% CI lower bound: 94.6%, upper bound: 95.7%). Based on the study results, device cut-off settings were adjusted for future series production. The overall performance with the settings of the CE series production devices was 78.7% sensitivity (95% CI lower bound: 72.1%) and 96.6% specificity (95% CI lower bound: 96.1%). Time to result was 5.2 hours (median) for the prototype test and 43.5 h for standard-of-care. The Pneumonia Application provides a rapid and moderately sensitive assay for the detection of pneumonia-causing pathogens with minimal hands-on time. Trial Registration Deutsches Register Klinischer Studien (DRKS) DRKS00005684 PMID:25397673

[Molecular characterization of pathogenic bacteria of the respiratory tract in peruvian patients with cystic fibrosis].

PubMed

Aquino, Ruth; Gonzáles, Emely; Samaniego, Sol; Rivera, Juan; Cedeño, Virna; Urbina, Yrene; Diringer, Benoit

2017-01-01

To molecularly characterize the pathogenic bacteria of the respiratory tract isolated from patients with cystic fibrosis (CF) in Peru. Bacterial communities cultured from sputum samples of pediatric and adult patients with CF admitted to the Edgardo Rebagliati Martins National Hospital and the National Institute of Child Health were characterized. Standard microbiological techniques were used for bacterial culture, and gene sequencing of 16S rRNA and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and tandem MALDI-TOF mass spectrometry (MALDI TOF/TOF) were used for molecular characterization. Seventeen bacterial strains were characterized by 16S rRNA sequencing, and the identified pathogenic bacteria were Pseudomonas aeruginosa (31.5%), Staphylococcus aureus (12.6%), Pseudomonas spp. (11.8%), and Klebsiella oxytoca (3.1%). MALDI-TOF analysis generated a series of spectra representative of each isolated bacterial species, whereas MALDI TOF/TOF analysis identified the peptides and proteins of the most common strains and provided data on pathogenicity and sensitivity to antibiotics. The primary pathogenic microorganisms found in the respiratory tract of patients with CF in Peru were the same as those found in other countries. This study is the first to perform 16S rRNA sequencing as well as MALDI-TOF and MALDI-TOF/TOF analysis of the bacterial pathogens circulating in Peru. The inclusion of proteomic analysis further allowed for the identification of native microorganisms involved in CF.

Global research trends of World Health Organization's top eight emerging pathogens.

PubMed

Sweileh, Waleed M

2017-02-08

On December 8 th , 2015, World Health Organization published a priority list of eight pathogens expected to cause severe outbreaks in the near future. To better understand global research trends and characteristics of publications on these emerging pathogens, we carried out this bibliometric study hoping to contribute to global awareness and preparedness toward this topic. Scopus database was searched for the following pathogens/infectious diseases: Ebola, Marburg, Lassa, Rift valley, Crimean-Congo, Nipah, Middle Eastern Respiratory Syndrome (MERS), and Severe Respiratory Acute Syndrome (SARS). Retrieved articles were analyzed to obtain standard bibliometric indicators. A total of 8619 journal articles were retrieved. Authors from 154 different countries contributed to publishing these articles. Two peaks of publications, an early one for SARS and a late one for Ebola, were observed. Retrieved articles received a total of 221,606 citations with a mean ± standard deviation of 25.7 ± 65.4 citations per article and an h-index of 173. International collaboration was as high as 86.9%. The Centers for Disease Control and Prevention had the highest share (344; 5.0%) followed by the University of Hong Kong with 305 (4.5%). The top leading journal was Journal of Virology with 572 (6.6%) articles while Feldmann, Heinz R. was the most productive researcher with 197 (2.3%) articles. China ranked first on SARS, Turkey ranked first on Crimean-Congo fever, while the United States of America ranked first on the remaining six diseases. Of retrieved articles, 472 (5.5%) were on vaccine - related research with Ebola vaccine being most studied. Number of publications on studied pathogens showed sudden dramatic rise in the past two decades representing severe global outbreaks. Contribution of a large number of different countries and the relatively high h-index are indicative of how international collaboration can create common health agenda among distant different countries.

Pathogenic Link Between Postextubation Pneumonia and Ventilator-Associated Pneumonia: An Experimental Study.

PubMed

Rezoagli, Emanuele; Zanella, Alberto; Cressoni, Massimo; De Marchi, Lorenzo; Kolobow, Theodor; Berra, Lorenzo

2017-04-01

The presence of an endotracheal tube is the main cause for developing ventilator-associated pneumonia (VAP), but pneumonia can still develop in hospitalized patients after endotracheal tube removal (postextubation pneumonia [PEP]). We hypothesized that short-term intubation (24 hours) can play a role in the pathogenesis of PEP. To test such hypothesis, we initially evaluated the occurrence of lung colonization and VAP in sheep that were intubated and mechanically ventilated for 24 hours. Subsequently, we assessed the incidence of lung colonization and PEP at 48 hours after extubation in sheep previously ventilated for 24 hours. To simulate intubated intensive care unit patients placed in semirecumbent position, 14 sheep were intubated and mechanically ventilated with the head elevated 30° above horizontal. Seven of them were euthanized after 24 hours (Control Group), whereas the remaining were euthanized after being awaken, extubated, and left spontaneously breathing for 48 hours after extubation (Awake Group). Criteria of clinical diagnosis of pneumonia were tested. Microbiological evaluation was performed on autopsy in all sheep. Only 1 sheep in the Control Group met the criteria of VAP after 24 hours of mechanical ventilation. However, heavy pathogenic bacteria colonization of trachea, bronchi, and lungs (range, 10-10 colony-forming unit [CFU]/g) was reported in 4 of 7 sheep (57%). In the Awake Group, 1 sheep was diagnosed with VAP and 3 developed PEP within 48 hours after extubation (42%), with 1 euthanized at 30 hours because of respiratory failure. On autopsy, 5 sheep (71%) confirmed pathogenic bacterial growth in the lower respiratory tract (range, 10-10 CFU/g). Twenty-four hours of intubation and mechanical ventilation in semirecumbent position leads to significant pathogenic colonization of the lower airways, which can promote the development of PEP. Strategies directed to prevent pathogenic microbiological colonization before and after mechanical ventilation should be considered to avert the onset of PEP.

Microbiological Features of Upper Respiratory Tract Infections in Bulgarian Children for the Period 1998–2014

PubMed Central

Gergova, Raina Tzvetanova; Petrova, Guergana; Gergov, Stefan; Minchev, Petko; Mitov, Ivan; Strateva, Tanya

2016-01-01

Background Across the globe, upper respiratory tract infections (URTIs) are the most prevalent cause of morbidity in childhood. Aims The aim of our study is to analyze the incidence and etiology of bacterial URTIs in Bulgarian children, as well as the increasing antimicrobial resistance to the most common etiologic agents over a period of 17 years. Study Design Retrospective study. Methods The study material comprised the data from 4768 patients (aged 1–16 years) with URTI during the period from 1998–2014. Specific microbiology agent detection was performed by culture examination. Susceptibilities to the investigated pathogens were determined by the disk diffusion method and minimal inhibitory concentration according to the criteria of the Clinical and Laboratory Standards Institute (CLSI). Polymerase chain reaction was used to detect the presence of β-lactam resistance genes. Results We identified the following as the most common URTI bacterial pathogens: Streptococcus pneumoniae (40.94%), Streptococcus pyogenes (34.16%), Haemophilus influenzae (44.23%), Moraxella catarrhalis (39.19%) and Staphylococcus aureus (23.88%). In more than 70% of cases, a polymicrobial etiology was found. The most commonly affected individuals were pre-school-aged children, which accounted for more than 36% of all patients. During the study period, a dramatic increase in resistance to antibiotic agents was observed. The most frequent types of resistance were the enzymatic inactivation of penicillins and cephalosporins (close to 100% in staphylococci and moraxellae) and inducible macrolide-lincozamide resistance (about 20% of Gram-positive cocci). Conclusion Due to mandatory immunization against pneumococci and H. influenzae in Bulgaria and the vast expanding resistance to the most popular antimicrobial agents changes in the etiology of URTI have recently been noted. Regular analysis of this etiological dynamic and the antimicrobial resistance of respiratory pathogens is important for choosing the correct therapy and successful treatment. PMID:27994923

Antimicrobial activity of tigecycline against recent isolates of respiratory pathogens from Asian countries.

PubMed

Ko, Kwan Soo; Song, Jae-Hoon; Lee, Mi Young; Park, Sulhee; Kwon, Ki Tae; Heo, Sang Taek; Ryu, Seong Yeol; Oh, Won Sup; Peck, Kyong Ran; Lee, Nam Yong

2006-08-01

In vitro activities of tigecycline were compared with 15 other comparator agents against recent clinical isolates of respiratory pathogens (623 Streptococcus pneumoniae, 105 Staphylococcus aureus, 92 Klebsiella pneumoniae, and 84 Haemophilus influenzae isolates) collected from 11 Asian countries. All isolates of S. pneumoniae from Asian countries were susceptible to tigecycline regardless of penicillin susceptibility with MIC90 of

Susceptibility to Lower Respiratory Infections in Childhood is Associated with Perturbation of the Cytokine Response to Pathogenic Airway Bacteria.

PubMed

Vissing, Nadja Hawwa; Larsen, Jeppe Madura; Rasmussen, Morten Arendt; Chawes, Bo Lund Krogsgaard; Thysen, Anna Hammerich; Bønnelykke, Klaus; Brix, Susanne; Bisgaard, Hans

2016-05-01

Neonatal colonization of the airways with respiratory pathogens is associated with increased risk of lower respiratory infections (LRI) in early childhood. Therefore, we hypothesized that children developing LRI have an aberrant immune response to pathogenic bacteria in infancy. The objective was to characterize in vitro the early life systemic immune response to pathogenic bacteria and study the possible association with incidence of LRI during the first 3 years of life. The Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) is a clinical birth cohort study of 411 children born of mothers with asthma. LRI incidence was prospectively captured from 6-monthly planned visits and visits at acute respiratory episodes. The in vitro systemic immune response to Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae was characterized by the production of TNF-α, IFN-γ, IL-2, IL-5, IL-10, IL-13 and IL-17 in peripheral blood mononuclear cells isolated at age 6 months from 291 infants. Data were analyzed by Poisson regression against incidence of LRI in infancy. A multivariable model including all cytokine responses from the 3 different bacterial stimulations significantly identified children at risk of LRI (P = 0.006). The immune response pattern associated with LRI was characterized by perturbed production of several cytokines rather than production of one specific cytokine, and was independent of concurrent asthma. TNF-α and IL-5 were key drivers but did not explain the entire variation in LRI susceptibility. Children at risk of future LRI present a perturbed systemic immune response upon exposure to common airway pathogens in early life.

Massively multiplexed microbial identification using resequencing DNA microarrays for outbreak investigation

NASA Astrophysics Data System (ADS)

Leski, T. A.; Ansumana, R.; Jimmy, D. H.; Bangura, U.; Malanoski, A. P.; Lin, B.; Stenger, D. A.

2011-06-01

Multiplexed microbial diagnostic assays are a promising method for detection and identification of pathogens causing syndromes characterized by nonspecific symptoms in which traditional differential diagnosis is difficult. Also such assays can play an important role in outbreak investigations and environmental screening for intentional or accidental release of biothreat agents, which requires simultaneous testing for hundreds of potential pathogens. The resequencing pathogen microarray (RPM) is an emerging technological platform, relying on a combination of massively multiplex PCR and high-density DNA microarrays for rapid detection and high-resolution identification of hundreds of infectious agents simultaneously. The RPM diagnostic system was deployed in Sierra Leone, West Africa in collaboration with Njala University and Mercy Hospital Research Laboratory located in Bo. We used the RPM-Flu microarray designed for broad-range detection of human respiratory pathogens, to investigate a suspected outbreak of avian influenza in a number of poultry farms in which significant mortality of chickens was observed. The microarray results were additionally confirmed by influenza specific real-time PCR. The results of the study excluded the possibility that the outbreak was caused by influenza, but implicated Klebsiella pneumoniae as a possible pathogen. The outcome of this feasibility study confirms that application of broad-spectrum detection platforms for outbreak investigation in low-resource locations is possible and allows for rapid discovery of the responsible agents, even in cases when different agents are suspected. This strategy enables quick and cost effective detection of low probability events such as outbreak of a rare disease or intentional release of a biothreat agent.

Inclusion Body Myositis: A Case Presenting with Respiratory Failure and Autopsy Findings Leading to the Hypothesis of a Paraneoplastic Cause.

PubMed

Dardis, Christopher; Antezana, Ariel; Tanji, Kurenai; Maccabee, Paul J

2017-06-23

BACKGROUND Sporadic inclusion body myositis (IBM) is the most common acquired myopathy seen in adults aged over 50 years, with a prevalence estimated at between 1 and 70 per million. Weakness of the diaphragm with loss of vital capacity is almost universal in IBM. This is almost always asymptomatic. When respiratory complications occur, they are most often due to aspiration. Respiratory failure due to diaphragmatic weakness is exceptionally rare, particularly as the presenting symptom of the disease. It is not currently considered to be a paraneoplastic syndrome. CASE REPORT Our patient presented with hypercarbic respiratory failure. This is the first such reported case without signs of weakness elsewhere of which we are aware. We suspected IBM based on her history of progressive weakness and findings on electromyography. There was a delay of 5 years in obtaining biopsy for confirmation, during which she presented with recurrent episodes of respiratory failure despite using non-invasive ventilation. An autopsy revealed the presence of papillary thyroid carcinoma with spread to local lymph nodes. On the basis that these co-morbidities are unlikely to have occurred by chance (we estimate 1×10-17), we hypothesize that IBM may be a paraneoplastic condition. We acknowledge that proof would require demonstrating a pathogenic antibody. CONCLUSIONS IBM should be considered in older patients (age >45) presenting with otherwise unexplained respiratory failure. A workup for possible malignancy in this setting appears reasonable.

[Etiological analysis and establishment of a discriminant model for lower respiratory tract infections in hospitalized patients].

PubMed

Chen, Y S; Lin, X H; Li, H R; Hua, Z D; Lin, M Q; Huang, W S; Yu, T; Lyu, H Y; Mao, W P; Liang, Y Q; Peng, X R; Chen, S J; Zheng, H; Lian, S Q; Hu, X L; Yao, X Q

2017-12-12

Objective: To analyze the pathogens of lower respiratory tract infection(LRTI) including bacterial, viral and mixed infection, and to establish a discriminant model based on clinical features in order to predict the pathogens. Methods: A total of 243 hospitalized patients with lower respiratory tract infections were enrolled in Fujian Provincial Hospital from April 2012 to September 2015. The clinical data and airway (sputum and/or bronchoalveolar lavage) samples were collected. Microbes were identified by traditional culture (for bacteria), loop-mediated isothermal amplification(LAMP) and gene sequencing (for bacteria and atypical pathogen), or Real-time quantitative polymerase chain reaction (Real-time PCR)for viruses. Finally, a discriminant model was established by using the discriminant analysis methods to help to predict bacterial, viral and mixed infections. Results: Pathogens were detected in 53.9% (131/243) of the 243 cases.Bacteria accounted for 23.5%(57/243, of which 17 cases with the virus, 1 case with Mycoplasma pneumoniae and virus), mainly Pseudomonas Aeruginosa and Klebsiella Pneumonia. Atypical pathogens for 4.9% (12/243, of which 3 cases with the virus, 1 case of bacteria and viruses), all were mycoplasma pneumonia. Viruses for 34.6% (84/243, of which 17 cases of bacteria, 3 cases with Mycoplasma pneumoniae, 1 case with Mycoplasma pneumoniae and bacteria) of the cases, mainly Influenza A virus and Human Cytomegalovirus, and other virus like adenovirus, human parainfluenza virus, respiratory syncytial virus, human metapneumovirus, human boca virus were also detected fewly. Seven parameters including mental status, using antibiotics prior to admission, complications, abnormal breath sounds, neutrophil alkaline phosphatase (NAP) score, pneumonia severity index (PSI) score and CRUB-65 score were enrolled after univariate analysis, and discriminant analysis was used to establish the discriminant model by applying the identified pathogens as the dependent variable. The total positive predictive value was 64.7%(77/119), with 66.7% for bacterial infection, 78.0% for viral infection and 33.3% for the mixed infection. Conclusions: The mostly detected pathogens were Pseudomonas aeruginosa, atypitcal pathogens, Klebsiella pneumoniae, influenza A virus and human cytomegalovirus in hospitalized patients with LRTI in this hospital. The discriminant diagnostic model established by clinical features may contribute to predict the pathogens of LRTI.

Highlights of the 11th International Bordetella Symposium: from Basic Biology to Vaccine Development

PubMed Central

Wirsing von König, Carl Heinz; Lan, Ruiting; Cotter, Peggy A.; Deora, Rajendar; Merkel, Tod J.; van Els, Cécile A.; Locht, Camille; Hozbor, Daniela; Rodriguez, Maria E.

2016-01-01

Pertussis is a severe respiratory disease caused by infection with the bacterial pathogen Bordetella pertussis. The disease affects individuals of all ages but is particularly severe and sometimes fatal in unvaccinated young infants. Other Bordetella species cause diseases in humans, animals, and birds. Scientific, clinical, public health, vaccine company, and regulatory agency experts on these pathogens and diseases gathered in Buenos Aires, Argentina from 5 to 8 April 2016 for the 11th International Bordetella Symposium to discuss recent advances in our understanding of the biology of these organisms, the diseases they cause, and the development of new vaccines and other strategies to prevent these diseases. Highlights of the meeting included pertussis epidemiology in developing nations, genomic analysis of Bordetella biology and evolution, regulation of virulence factor expression, new model systems to study Bordetella biology and disease, effects of different vaccines on immune responses, maternal immunization as a strategy to prevent newborn disease, and novel vaccine development for pertussis. In addition, the group approved the formation of an International Bordetella Society to promote research and information exchange on bordetellae and to organize future meetings. A new Bordetella.org website will also be developed to facilitate these goals. PMID:27655886

Human Metapneumovirus Infection is Associated with Severe Respiratory Disease in Preschool Children with History of Prematurity

PubMed Central

Pancham, Krishna; Sami, Iman; Perez, Geovanny F.; Huseni, Shehlanoor; Kurdi, Bassem; Rose, Mary C.; Rodriguez-Martinez, Carlos E.; Nino, Gustavo

2017-01-01

Rationale Human metapneumovirus (HMPV) is a recently discovered respiratory pathogen of the family Paramyxoviridae, the same of Respiratory Syncytial Virus (RSV). Premature children are at high risk of severe RSV infections, but it is unclear whether HMPV infection is more severe in hospitalized children with history of severe prematurity. Methods We conducted a retrospective analysis of the clinical respiratory presentation of all PCR-confirmed HMPV infections in preschool age children (≤5 yrs.) with and without history of severe prematurity (<32 weeks gestation). Respiratory distress scores were developed to examine the clinical severity of HMPV infections. Demographic and clinical variables were obtained from reviewing electronic medical records (EMR). Results A total of 571 pre-school children were identified by PCR-confirmed viral respiratory tract infection during the study period. HMPV was identified as a causative organism in 63 cases (11%). Fifty–eight (n=58) preschool age children with HMPV infection were included in this study after excluding those with significant co-morbidities. Our data demonstrated that 32.7% of children admitted with HMPV had history of severe prematurity. Preschool children with history of prematurity had more severe HMPV disease as illustrated by longer hospitalizations, new or increased need for supplemental O2, and higher severity scores independently of age, ethnicity and history of asthma. Conclusion Our study suggests that HMPV infection causes significant disease burden among preschool children with history of prematurity leading to severe respiratory infections and increasing health care resource utilization due to prolonged hospitalizations. PMID:26117550

Human Metapneumovirus Infection is Associated with Severe Respiratory Disease in Preschool Children with History of Prematurity.

PubMed

Pancham, Krishna; Sami, Iman; Perez, Geovanny F; Huseni, Shehlanoor; Kurdi, Bassem; Rose, Mary C; Rodriguez-Martinez, Carlos E; Nino, Gustavo

2016-02-01

Human metapneumovirus (HMPV) is a recently discovered respiratory pathogen of the family Paramyxoviridae, the same family as that of respiratory syncytial virus (RSV). Premature children are at high risk of severe RSV infections, however, it is unclear whether HMPV infection is more severe in hospitalized children with a history of severe prematurity. We conducted a retrospective analysis of the clinical respiratory presentation of all polymerase chain reaction-confirmed HMPV infections in preschool-age children (≤5 years) with and without history of severe prematurity (<32 weeks gestation). Respiratory distress scores were developed to examine the clinical severity of HMPV infections. Demographic and clinical variables were obtained from reviewing electronic medical records. A total of 571 preschool children were identified using polymerase chain reaction-confirmed viral respiratory tract infection during the study period. HMPV was identified as a causative organism in 63 cases (11%). Fifty-eight (n = 58) preschool-age children with HMPV infection were included in this study after excluding those with significant comorbidities. Our data demonstrated that 32.7% of children admitted with HMPV had a history of severe prematurity. Preschool children with a history of prematurity had more severe HMPV disease as illustrated by longer hospitalizations, new or increased need for supplemental O2, and higher severity scores independently of age, ethnicity, and history of asthma. Our study suggests that HMPV infection causes significant disease burden among preschool children with a history of prematurity leading to severe respiratory infections and increasing health care resource utilization due to prolonged hospitalizations. Copyright © 2016. Published by Elsevier B.V.

Recombinant Influenza Virus Carrying the Conserved Domain of Respiratory Syncytial Virus (RSV) G Protein Confers Protection against RSV without inflammatory disease

PubMed Central

Lee, Yu-Na; Hwang, Hye Suk; Kim, Min-Chul; Lee, Young-Tae; Cho, Min-Kyoung; Kwon, Young-Man; Lee, Jong Seok; Plemper, Richard K.; Kang, Sang-Moo

2014-01-01

Respiratory syncytial virus (RSV) is one of the most important causes for viral lower respiratory tract disease in humans. There is no licensed RSV vaccine. Here, we generated recombinant influenza viruses (PR8/RSV.HA-G) carrying the chimeric constructs of hemagglutinin (HA) and central conserved-domains of the RSV G protein. PR8/RSV.HA-G virus showed lower pathogenicity without compromising immunogenicity in mice. Single intranasal inoculation of mice with PR8/RSV.HA-G induced IgG2a isotype dominant antibodies and RSV neutralizing activity. Mice with single intranasal inoculation of PR8/RSV.HA-G were protected against RSV infection as evidenced by significant reduction of lung viral loads to a detection limit upon RSV challenge. PR8/RSV.HA-G inoculation of mice did not induce pulmonary eosinophilia and inflammation upon RSV infection. These findings support a concept that recombinant influenza viruses carrying the RSV G conserved-domain can be developed as a promising RSV vaccine candidate without pulmonary disease. PMID:25553517

Zoonotic Infection with Pigeon Paramyxovirus Type 1 linked to Fatal Pneumonia.

PubMed

Kuiken, Thijs; Breitbart, Mya; Beer, Martin; Grund, Christian; Höper, Dirk; van den Hoogen, Bernadette; Kerkhoffs, Jean-Louis H; Kroes, Aloys C M; Rosario, Karyna; van Run, Peter; Schwarz, Matthias; Svraka, Sanela; Teifke, Jens; Koopmans, Marion

2018-01-24

The characteristics and risk factors of pigeon paramyxovirus type 1 (PPMV-1) infection in humans are poorly known. We performed virological, pathological and epidemiological analyses of a Dutch case, and compared the results with those of a US case. Both infections occurred in transplant patients under immunosuppressive therapy and caused fatal respiratory failure. Both virus isolates clustered with avian paramyxovirus type 1 (APMV-1) genotype VIb/1, which has pigeons and doves as reservoir. Experimentally inoculated pigeons became infected and transmitted the virus to naïve pigeons. Likely route of transmission to both patients was direct or indirect contact with infected pigeons or doves. Given the large populations of feral pigeons with endemic PPMV-1 infection in cities, increasing urbanisation and a higher proportion of immunocompromised individuals, the risk of severe human PPMV-1 infections may increase. We recommend to test for APMV-1, including PPMV-1, in respiratory disease cases where common respiratory pathogens cannot be identified. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Molecular Identification and Epidemiological Features of Human Adenoviruses Associated with Acute Respiratory Infections in Hospitalized Children in Southern China, 2012-2013.

PubMed

Chen, Yi; Liu, Fanghua; Wang, Changbing; Zhao, Mingqi; Deng, Li; Zhong, Jiayu; Zhang, Yingying; Ye, Jun; Jing, Shuping; Cheng, Zetao; Guan, Yongxin; Ma, Yi; Sun, Yuanyuan; Zhu, Bing; Zhang, Qiwei

2016-01-01

Acute respiratory infections (ARI) are the major worldwide health problem associated with high morbidity and mortality rates. Human adenovirus (HAdV) is one of the most common pathogens associated with viral ARI, and thus calls for specific diagnosis and better understanding of the epidemiology and clinical characteristics. Total 4,130 children with ARI requiring hospitalization from 2012 to 2013 were retrospectively studied. Throat swab specimens were collected from each patient. Fluorescence Quantitative PCR was performed to detect adenovirus as well as other common ARI-related pathogens. The seven HAdV hypervariable regions (HVRs) of the hexon gene from fifty-seven HAdVs-positive samples collected in the seasonal peaks were sequenced. Phylogenetic analysis of HVRs was also conducted to confirm the molecular types and genetic variation. In addition, epidemiological features and co-infection with other human respiratory pathogens were investigated and analyzed. Of 4,130 hospitalized pediatric patients tested, the positive rates of respiratory syncytial virus (RSV), Mycoplasma pneumoniae (MP), and HAdV were 13.7%, 13.2%, and 12.0%, respectively. The HAdV positive patients accounted for 7.9%, 17.2%, 17.5% and 10.7% in age groups <1, 1-3, 3-6 and 6-14 years, respectively. Eighty-four HAdV positive children were co-infected with other respiratory pathogens (84/495, 17.0%). The most common co-infection pathogens with HAdV were MP (57.1%) and Human Bocavirus (HBoV) (16.7%). The majority of HAdV infected patients were totally recovered (96.9%, 480/495); However, four (0.8%) patients, who were previously healthy and at the age of 2 years or younger died of pneumonia. Seasonal peaks of HAdV infection occurred in the summer season of 2012 and 2013; the predominant HAdV type was HAdV-3 (70%), followed by HAdV-7 (28%). These epidemiological features were different from those in Northern China. The HAdV-55 was identified and reported for the first time in Guangzhou metropolitan area. Phylogenetic analysis indicated that all the HVR sequences of the hexon gene of HAdV-3 and -7 strains have high similarity within their individual types, and these strains were also similar to those circulating in China currently, indicating the conservation of hexon genes of both HAdV-3 and HAdV-7. Knowledge of the epidemiological features and molecular types of HAdV, a major pathogen of pediatric ARI, as well as other co-infected respiratory pathogens circulating in Guangzhou, southern China, is vital to predict and prevent future disease outbreaks in children. This study will certainly facilitate HAdV vaccine development and treatment of HAdV infections in children.

A recombinant subunit vaccine for bovine RSV and Histophilus somni protects calves against dual pathogen challenge.

PubMed

Gershwin, Laurel J; Behrens, Nicole E; McEligot, Heather A; Carvallo-Chaigneau, Francisco R; Crum, Lauren T; Gunnarson, Brianna M; Corbeil, Lynette B

2017-04-04

Bovine respiratory syncytial virus (BRSV) and Histophilus somni synergize to cause respiratory disease in cattle. These pathogens cause enhanced disease during dual-infection and an IgE response to antigens of H. somni in dual-infected but not singly infected calves. Vaccines containing whole inactivated BRSV or H. somni have been associated with IgE responses A vaccine strategy that avoids stimulation of IgE antibodies would provide superior protection from dual infection. We hypothesized that a subunit vaccine consisting of the nucleoprotein (NP) from BRSV and the recombinant antigen IbpA DR2 (a surface antigen of H. somni with two toxic fic motifs) in Quil A adjuvant would elicit protection without disease enhancement. Three groups of calves were vaccinated twice with either: Formalin inactivated BRSV (FI) plus Somnivac®, NP & IbpA DR2 plus Quil A or Quil A alone, followed by BRSV and H. somni challenge. Clinical scores and antibody levels (to whole pathogens and to the subunits) were evaluated. Lungs were examined at necropsy on day 23 after infection. Clinical scores were significantly greatest for the FI & Somnivac® group and both clinical scores and lung pathology were lowest for the subunit group. All calves shed BRSV in nasal secretions. FI & Somnivac® induced IgE antibodies to H. somni and BRSV, but not to NP or DR2. The subunit vaccine did not induce an IgE antibody response to IbpA DR2 antigen and induced little IgE to H. somni. It did not induce an IgG antibody response to BRSV and H. somni, but stimulated production of IgG antibodies against the subunits. In summary, the subunit vaccine, consisting of the BRSV NP and H. somni IbpA DR2 in Quil A, protected against severe clinical signs and decreased lung pathology but did not prevent viral shedding. Importantly it prevented synergistic disease expression in response to dual infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Classification, Identification, and Clinical Significance of Haemophilus and Aggregatibacter Species with Host Specificity for Humans

PubMed Central

2014-01-01

SUMMARY The aim of this review is to provide a comprehensive update on the current classification and identification of Haemophilus and Aggregatibacter species with exclusive or predominant host specificity for humans. Haemophilus influenzae and some of the other Haemophilus species are commonly encountered in the clinical microbiology laboratory and demonstrate a wide range of pathogenicity, from life-threatening invasive disease to respiratory infections to a nonpathogenic, commensal lifestyle. New species of Haemophilus have been described (Haemophilus pittmaniae and Haemophilus sputorum), and the new genus Aggregatibacter was created to accommodate some former Haemophilus and Actinobacillus species (Aggregatibacter aphrophilus, Aggregatibacter segnis, and Aggregatibacter actinomycetemcomitans). Aggregatibacter species are now a dominant etiology of infective endocarditis caused by fastidious organisms (HACEK endocarditis), and A. aphrophilus has emerged as an important cause of brain abscesses. Correct identification of Haemophilus and Aggregatibacter species based on phenotypic characterization can be challenging. It has become clear that 15 to 20% of presumptive H. influenzae isolates from the respiratory tracts of healthy individuals do not belong to this species but represent nonhemolytic variants of Haemophilus haemolyticus. Due to the limited pathogenicity of H. haemolyticus, the proportion of misidentified strains may be lower in clinical samples, but even among invasive strains, a misidentification rate of 0.5 to 2% can be found. Several methods have been investigated for differentiation of H. influenzae from its less pathogenic relatives, but a simple method for reliable discrimination is not available. With the implementation of identification by matrix-assisted laser desorption ionization–time of flight mass spectrometry, the more rarely encountered species of Haemophilus and Aggregatibacter will increasingly be identified in clinical microbiology practice. However, identification of some strains will still be problematic, necessitating DNA sequencing of multiple housekeeping gene fragments or full-length 16S rRNA genes. PMID:24696434

Role of the Dermonecrotic Toxin of Bordetella bronchiseptica in the Pathogenesis of Respiratory Disease in Swine

PubMed Central

Brockmeier, Susan L.; Register, Karen B.; Magyar, Tibor; Lax, Alistair J.; Pullinger, Gillian D.; Kunkle, Robert A.

2002-01-01

Bordetella bronchiseptica is one of the etiologic agents causing atrophic rhinitis and pneumonia in swine. It produces several purported virulence factors, including the dermonecrotic toxin (DNT), which has been implicated in the turbinate atrophy seen in cases of atrophic rhinitis. The purpose of these experiments was to clarify the role of this toxin in respiratory disease by comparing the pathogenicity in swine of two isogenic dnt mutants to their virulent DNT+ parent strains. Two separate experiments were performed, one with each of the mutant-parent pairs. One-week-old cesarean-derived, colostrum-deprived pigs were inoculated intranasally with the parent strain, the dnt mutant strain, or phosphate-buffered saline. Weekly nasal washes were performed to monitor colonization of the nasal cavity, and the pigs were euthanized 4 weeks after inoculation to determine colonization of tissues and to examine the respiratory tract for pathology. There was evidence that colonization of the upper respiratory tract, but not the lower respiratory tract, was slightly greater for the parent strains than for the dnt mutants. Moderate turbinate atrophy and bronchopneumonia were found in most pigs given the parent strains, while there was no turbinate atrophy or pneumonia in pigs challenged with the dnt mutant strains. Therefore, production of DNT by B. bronchiseptica is necessary to produce the lesions of turbinate atrophy and bronchopneumonia in pigs infected with this organism. PMID:11796573

Evaluation of a PCR/ESI-MS platform to identify respiratory viruses from nasopharyngeal aspirates.

PubMed

Lin, Yong; Fu, Yongfeng; Xu, Menghua; Su, Liyun; Cao, Lingfeng; Xu, Jin; Cheng, Xunjia

2015-11-01

Acute respiratory tract infection is a major cause of morbidity and mortality worldwide, particularly in infants and young children. High-throughput, accurate, broad-range tools for etiologic diagnosis are critical for effective epidemic control. In this study, the diagnostic capacities of an Ibis platform based on the PCR/ESI-MS assay were evaluated using clinical samples. Nasopharyngeal aspirates (NPAs) were collected from 120 children (<5 years old) who were hospitalized with lower respiratory tract infections between November 2010 and October 2011. The respiratory virus detection assay was performed using the PCR/ESI-MS assay and the DFA. The discordant PCR/ESI-MS and DFA results were resolved with RT-PCR plus sequencing. The overall agreement for PCR/ESI-MS and DFA was 98.3% (118/120). Compared with the results from DFA, the sensitivity and specificity of the PCR/ESI-MS assay were 100% and 97.5%, respectively. The PCR/ESI-MS assay also detected more multiple virus infections and revealed more detailed subtype information than DFA. Among the 12 original specimens with discordant results between PCR/ESI-MS and DFA, 11 had confirmed PCR/ESI-MS results. Thus, the PCR/ESI-MS assay is a high-throughput, sensitive, specific and promising method to detect and subtype conventional viruses in respiratory tract infections and allows rapid identification of mixed pathogens. © 2015 Wiley Periodicals, Inc.

Respiratory Tract Infections and the Role of Biologically Active Polysaccharides in Their Management and Prevention.

PubMed

Jesenak, Milos; Urbancikova, Ingrid; Banovcin, Peter

2017-07-20

Respiratory tract infections (RTIs) are the most common form of infections in every age category. Recurrent respiratory tract infections (RRTIs), a specific form of RTIs, represent a typical and common problem associated with early childhood, causing high indirect and direct costs on the healthcare system. They are usually the consequence of immature immunity in children and high exposure to various respiratory pathogens. Their rational management should aim at excluding other severe chronic diseases associated with increased morbidity (e.g., primary immunodeficiency syndromes, cystic fibrosis, and ciliary dyskinesia) and at supporting maturity of the mucosal immune system. However, RRTIs can also be observed in adults (e.g., during exhausting and stressful periods, chronic inflammatory diseases, secondary immunodeficiencies, or in elite athletes) and require greater attention. Biologically active polysaccharides (e.g., β-glucans) are one of the most studied natural immunomodulators with a pluripotent mode of action and biological activity. According to many studies, they possess immunomodulatory, anti-inflammatory, and anti-infectious activities and therefore could be suggested as an effective part of treating and preventing RTIs. Based on published studies, the application of β-glucans was proven as a possible therapeutic and preventive approach in managing and preventing recurrent respiratory tract infections in children (especially β-glucans from Pleurotus ostreatus ), adults (mostly the studies with yeast-derived β-glucans), and in elite athletes (studies with β-glucans from Pleurotus ostreatus or yeast).

The full genome sequences of 8 equine herpesvirus type 4 isolates from horses in Japan.

PubMed

Izume, Satoko; Kirisawa, Rikio; Ohya, Kenji; Ohnuma, Aiko; Kimura, Takashi; Omatsu, Tsutomu; Katayama, Yukie; Mizutani, Tetsuya; Fukushi, Hideto

2017-01-24

Equine herpesvirus type 4 (EHV-4) is one of the most important pathogens in horses. To clarify the key genes of the EHV-4 genome that cause abortion in female horses, we determined the whole genome sequences of a laboratory strain and 7 Japanese EHV-4 isolates that were isolated from 2 aborted fetuses and nasal swabs of 5 horses with respiratory disease. The full genome sequences and predicted amino acid sequences of each gene of these isolates were compared with of the reference EHV-4 strain NS80567 and Australian isolates that were reported in 2015. The EHV-4 isolates clustered in 2 groups which did not reflect their pathogenicity. A comparison of the predicted amino acid sequences of the genes did not reveal any genes that were associated with EHV-4-induced abortion.

Synthetic Nanovaccines Against Respiratory Pathogens (SYNARP)

DTIC Science & Technology

2011-07-01

platforms to other respiratory infections, such as pulmonary F. tularemia , and test the nanovaccines efficacy in animal models (unfunded option...such as pulmonary F. tularemia , and test the nanovaccines efficacy in animal models (unfunded option). BODY OF REPORT Platform A

Virucidal activities of medium- and long-chain fatty alcohols and lipids against respiratory syncytial virus and parainfluenza virus type 2: comparison at different pH levels.

PubMed

Hilmarsson, H; Traustason, B S; Kristmundsdóttir, T; Thormar, H

2007-01-01

Recent studies have shown that some lipids and fatty alcohols have microbicidal activities against a broad variety of pathogens. In this study, virucidal activities of fatty acids, monoglycerides and fatty alcohols were tested against respiratory syncytial virus (RSV) and human parainfluenza virus type 2 (HPIV2) at different concentrations, times and pH levels. The most active compounds were mixed with milk products and fruit juices and the mixtures tested for virucidal effects. The aim was to determine which compounds are the most active against these respiratory viruses and could possibly be used in pharmaceutical formulations or as additives to milk products or juice. Several compounds caused a significant inactivation of virus, and there was generally a good agreement between the activities against RSV and parainfluenza virus. By changing the pH from 7 to 4.2, the virucidal activities of some of the compounds were greatly increased, i.e., they inactivated virus in a shorter time and at lower concentrations. The most active compound tested was 1-monoglyceride of capric acid, monocaprin, which also showed activity against influenza A virus and significant virucidal activities after addition to milk products and fruit juices, even at a concentration as low as 0.06-0.12%. The significant virucidal activities of fatty alcohols and lipids on RSV and parainfluenza virus demonstrated in this in vitro study raise the question of the feasibility of using such compounds as ingredients in pharmaceutical dosage forms against respiratory infections caused by these viruses, and possibly other paramyxo- and myxoviruses.

Transcriptomic analysis reveals the potential of highly pathogenic PRRS virus to modulate immune system activation related to host-pathogen and damage associated signaling in infected porcine monocytes

USDA-ARS?s Scientific Manuscript database

One of the largest risks to the continued stability of the swine industry is by pathogens like porcine reproductive and respiratory syndrome virus (PRRSV) that can decimate production as it spreads among individuals. These infections can be low or highly pathogenic, and because it infects monocytic ...

Bacterial and viral pathogen spectra of acute respiratory infections in under-5 children in hospital settings in Dhaka city

PubMed Central

Bhuyan, Golam Sarower; Hossain, Mohammad Amir; Sarker, Suprovath Kumar; Rahat, Asifuzzaman; Islam, Md Tarikul; Haque, Tanjina Noor; Begum, Noorjahan; Qadri, Syeda Kashfi; Muraduzzaman, A. K. M.; Islam, Nafisa Nawal; Islam, Mohammad Sazzadul; Sultana, Nusrat; Jony, Manjur Hossain Khan; Khanam, Farhana; Mowla, Golam; Matin, Abdul; Begum, Firoza; Shirin, Tahmina; Ahmed, Dilruba; Saha, Narayan; Qadri, Firdausi

2017-01-01

The study aimed to examine for the first time the spectra of viral and bacterial pathogens along with the antibiotic susceptibility of the isolated bacteria in under-5 children with acute respiratory infections (ARIs) in hospital settings of Dhaka, Bangladesh. Nasal swabs were collected from 200 under-five children hospitalized with clinical signs of ARIs. Nasal swabs from 30 asymptomatic children were also collected. Screening of viral pathogens targeted ten respiratory viruses using RT-qPCR. Bacterial pathogens were identified by bacteriological culture methods and antimicrobial susceptibility of the isolates was determined following CLSI guidelines. About 82.5% (n = 165) of specimens were positive for pathogens. Of 165 infected cases, 3% (n = 6) had only single bacterial pathogens, whereas 43.5% (n = 87) cases had only single viral pathogens. The remaining 36% (n = 72) cases had coinfections. In symptomatic cases, human rhinovirus was detected as the predominant virus (31.5%), followed by RSV (31%), HMPV (13%), HBoV (11%), HPIV-3 (10.5%), and adenovirus (7%). Streptococcus pneumoniae was the most frequently isolated bacterial pathogen (9%), whereas Klebsiella pneumaniae, Streptococcus spp., Enterobacter agglomerans, and Haemophilus influenzae were 5.5%, 5%, 2%, and 1.5%, respectively. Of 15 multidrug-resistant bacteria, a Klebsiella pneumoniae isolate and an Enterobacter agglomerans isolate exhibited resistance against more than 10 different antibiotics. Both ARI incidence and predominant pathogen detection rates were higher during post-monsoon and winter, peaking in September. Pathogen detection rates and coinfection incidence in less than 1-year group were significantly higher (P = 0.0034 and 0.049, respectively) than in 1–5 years age group. Pathogen detection rate (43%) in asymptomatic cases was significantly lower compared to symptomatic group (P<0.0001). Human rhinovirus, HPIV-3, adenovirus, Streptococcus pneumonia, and Klebsiella pneumaniae had significant involvement in coinfections with P values of 0.0001, 0.009 and 0.0001, 0.0001 and 0.001 respectively. Further investigations are required to better understand the clinical roles of the isolated pathogens and their seasonality. PMID:28346512

Generalized herd effects and vaccine evaluation: impact of live influenza vaccine on off-target bacterial colonisation.

PubMed

Mina, Michael J

2017-06-01

Interactions between pathogens and commensal microbes are major contributors to health and disease. Infectious diseases however are most often considered independent, viewed within a one-host one-pathogen paradigm and, by extension, the interventions used to treat and prevent them are measured and evaluated within this same paradigm. Vaccines, especially live vaccines, by stimulating immune responses or directly interacting with other microbes can alter the environment in which they act, with effects that span across pathogen species. Live attenuated infl uenza vaccines for example, while safe, increase upper respiratory tract bacterial carriage density of important human commensal pathogens like Streptococcus pneumoniae and Staphylococcus aureus. Further, by altering the ecological niche and dynamics of phylogenetically distinct microbes within the host, vaccines may unintentionally affect transmission of non-vaccine targeted pathogens. Thus, vaccine effects may span across species and across scales, from the individual to the population level. In keeping with traditional vaccine herd-effects that indirectly protect even unvaccinated individuals by reducing population prevalence of vaccine-targeted pathogens, we call these cross-species cross-scale effects "generalized herd-effects". As opposed to traditional herd-effects, "generalized" relaxes the assumption that the effect occurs at the level of the vaccine-target pathogen and "herd effect" implies, as usual, that the effects indirectly impact the population at large, including unvaccinated bystanders. Unlike traditional herd-effects that decrease population prevalence of the vaccine-target, generalized herd-effects may decrease or increase prevalence and disease by the off-target pathogen. LAIV, for example, by increasing pneumococcal density in the upper respiratory tract of vaccine recipients, especially children, may increase pneumococcal transmission and prevalence, leading to excess pneumococcal invasive disease in the population, especially among the elderly and others most susceptible to pneumococcal disease. However, these effects may also be beneficial, for example the large reductions in all-cause mortality noted following measles vaccines. Here we discuss evidence for these novel vaccine effects and suggest that vaccine monitoring and evaluation programs should consider generalized herd effects to appreciate the full impacts of vaccines, beneficial or detrimental, across species and scales that are inevitably hiding in plain sight, affecting human health and disease. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Spastic Paraplegia Type 7 Is Associated with Multiple Mitochondrial DNA Deletions

PubMed Central

Wedding, Iselin Marie; Koht, Jeanette; Tran, Gia Tuong; Misceo, Doriana; Selmer, Kaja Kristine; Holmgren, Asbjørn; Frengen, Eirik; Bindoff, Laurence; Tallaksen, Chantal M. E.; Tzoulis, Charalampos

2014-01-01

Spastic paraplegia 7 is an autosomal recessive disorder caused by mutations in the gene encoding paraplegin, a protein located at the inner mitochondrial membrane and involved in the processing of other mitochondrial proteins. The mechanism whereby paraplegin mutations cause disease is unknown. We studied two female and two male adult patients from two Norwegian families with a combination of progressive external ophthalmoplegia and spastic paraplegia. Sequencing of SPG7 revealed a novel missense mutation, c.2102A>C, p.H 701P, which was homozygous in one family and compound heterozygous in trans with a known pathogenic mutation c.1454_1462del in the other. Muscle was examined from an additional, unrelated adult female patient with a similar phenotype caused by a homozygous c.1047insC mutation in SPG7. Immunohistochemical studies in skeletal muscle showed mosaic deficiency predominantly affecting respiratory complex I, but also complexes III and IV. Molecular studies in single, microdissected fibres showed multiple mitochondrial DNA deletions segregating at high levels (38–97%) in respiratory deficient fibres. Our findings demonstrate for the first time that paraplegin mutations cause accumulation of mitochondrial DNA damage and multiple respiratory chain deficiencies. While paraplegin is not known to be directly associated with the mitochondrial nucleoid, it is known to process other mitochondrial proteins and it is possible therefore that paraplegin mutations lead to mitochondrial DNA deletions by impairing proteins involved in the homeostasis of the mitochondrial genome. These studies increase our understanding of the molecular pathogenesis of SPG7 mutations and suggest that SPG7 testing should be included in the diagnostic workup of autosomal recessive, progressive external ophthalmoplegia, especially if spasticity is present. PMID:24466038

Ongoing developments in RSV prophylaxis: a clinician's analysis.

PubMed

Rezaee, Fariba; Linfield, Debra T; Harford, Terri J; Piedimonte, Giovanni

2017-06-01

Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children worldwide. Lower respiratory tract infection due to RSV is one of the most common causes of hospitalization for infants, especially those born premature or with chronic lung or heart disease. Furthermore, RSV infection is an important cause of morbidity in adults, particularly in the elderly and immunocompromised individuals. The acute phase of this infection is often followed by episodes of wheezing that recur for months or years and usually lead to a physician diagnosis of asthma. RSV was discovered more than 50 years ago, and despite extensive research to identify pharmacological therapies, the most effective management of this infection remains supportive care. The trial of a formalin-inactivated RSV vaccine in the 1960s resulted in priming the severe illness upon natural infection. Currently, Palivizumab is the only available option for RSV prophylaxis, and because of restricted clinical benefits and high costs, it has been limited to a group of high-risk infants. There are several ongoing trials in preclinical, Phase-I, Phase-II, or Phase-III clinical stages for RSV vaccine development based on various strategies. Here we review the existing available prophylactic options, the current stages of RSV vaccine clinical trials, different strategies, and major hurdles in the development of an effective RSV vaccine. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Impact of micro-environmental changes on respiratory tract infections with intracellular bacteria.

PubMed

Shima, Kensuke; Coopmeiners, Jonas; Graspeuntner, Simon; Dalhoff, Klaus; Rupp, Jan

2016-11-01

Community-acquired pneumonia is caused by intra- and extracellular bacteria, with some of these bacteria also being linked to the pathogenesis of chronic lung diseases, including asthma and chronic obstructive pulmonary disease. Chlamydia pneumoniae is an obligate intracellular pathogen that is highly sensitive to micro-environmental conditions controlling both pathogen growth and host immune responses. The availability of nutrients, as well as changes in oxygen, pH and interferon-γ levels, have been shown to directly influence the chlamydial life cycle and clearance. Although the lung has been traditionally regarded as a sterile environment, sequencing approaches have enabled the identification of a large number of bacteria in healthy and diseased lungs. The influence of the lung microbiota on respiratory infections has not been extensively studied so far and data on chlamydial infections are currently unavailable. In the present study, we speculate on how lung microbiota might interfere with acute and chronic infections by focusing exemplarily on the obligate intracellular C. pneumoniae. Furthermore, we consider changes in the gut microbiota as an additional player in the control of lung infections, especially in view the increasing evidence suggesting the involvement of the gut microbiota in various immunological processes throughout the human body. © 2016 Federation of European Biochemical Societies.

Multifaceted Role of Pneumolysin in the Pathogenesis of Myocardial Injury in Community-Acquired Pneumonia.

PubMed

Anderson, Ronald; Nel, Jan G; Feldman, Charles

2018-04-11

Pneumolysin (PLY), a member of the family of Gram-positive bacterial, cholesterol-dependent, β-barrel pore-forming cytolysins, is the major protein virulence factor of the dangerous respiratory pathogen, Streptococcus pneumoniae (pneumococcus). PLY plays a major role in the pathogenesis of community-acquired pneumonia (CAP), promoting colonization and invasion of the upper and lower respiratory tracts respectively, as well as extra-pulmonary dissemination of the pneumococcus. Notwithstanding its role in causing acute lung injury in severe CAP, PLY has also been implicated in the development of potentially fatal acute and delayed-onset cardiovascular events, which are now recognized as being fairly common complications of this condition. This review is focused firstly on updating mechanisms involved in the immunopathogenesis of PLY-mediated myocardial damage, specifically the direct cardiotoxic and immunosuppressive activities, as well as the indirect pro-inflammatory/pro-thrombotic activities of the toxin. Secondly, on PLY-targeted therapeutic strategies including, among others, macrolide antibiotics, natural product antagonists, cholesterol-containing liposomes, and fully humanized monoclonal antibodies, as well as on vaccine-based preventive strategies. These sections are preceded by overviews of CAP in general, the role of the pneumococcus as the causative pathogen, the occurrence and types of CAP-associated cardiac complication, and the structure and biological activities of PLY.

Differentiation of Acute Q Fever from Other Infections in Patients Presenting to Hospitals, the Netherlands1

PubMed Central

Krijger, Elmer; Delsing, Corine E.; Sprong, Tom; Nabuurs-Franssen, Marrigje H.; Bleeker-Rovers, Chantal P.

2015-01-01

Differentiating acute Q fever from infections caused by other pathogens is essential. We conducted a retrospective case–control study to evaluate differences in clinical signs, symptoms, and outcomes for 82 patients with acute Q fever and 52 control patients who had pneumonia, fever and lower respiratory tract symptoms, or fever and hepatitis, but had negative serologic results for Q fever. Patients with acute Q fever were younger and had higher C-reactive protein levels but lower leukocyte counts. However, a large overlap was found. In patients with an indication for prophylaxis, chronic Q fever did not develop after patients received prophylaxis but did develop in 50% of patients who did not receive prophylaxis. Differentiating acute Q fever from other respiratory infections, fever, or hepatitis is not possible without serologic testing or PCR. If risk factors for chronic Q fever are present, prophylactic treatment is advised. PMID:26196955

Gene expression profile of the plant pathogen Fusarium graminearum under the antagonistic effect of Pantoea agglomerans.

PubMed

Pandolfi, V; Jorge, E C; Melo, C M R; Albuquerque, A C S; Carrer, H

2010-07-06

The pathogenic fungus Fusarium graminearum is an ongoing threat to agriculture, causing losses in grain yield and quality in diverse crops. Substantial progress has been made in the identification of genes involved in the suppression of phytopathogens by antagonistic microorganisms; however, limited information regarding responses of plant pathogens to these biocontrol agents is available. Gene expression analysis was used to identify differentially expressed transcripts of the fungal plant pathogen F. graminearum under antagonistic effect of the bacterium Pantoea agglomerans. A macroarray was constructed, using 1014 transcripts from an F. graminearum cDNA library. Probes consisted of the cDNA of F. graminearum grown in the presence and in the absence of P. agglomerans. Twenty-nine genes were either up (19) or down (10) regulated during interaction with the antagonist bacterium. Genes encoding proteins associated with fungal defense and/or virulence or with nutritional and oxidative stress responses were induced. The repressed genes coded for a zinc finger protein associated with cell division, proteins containing cellular signaling domains, respiratory chain proteins, and chaperone-type proteins. These data give molecular and biochemical evidence of response of F. graminearum to an antagonist and could help develop effective biocontrol procedures for pathogenic plant fungi.

Unraveling the Molecular Mechanisms Underlying the Nasopharyngeal Bacterial Community Structure.

PubMed

de Steenhuijsen Piters, Wouter A A; Bogaert, Debby

2016-02-02

The upper respiratory tract is colonized by a diverse array of commensal bacteria that harbor potential pathogens, such as Streptococcus pneumoniae. As long as the local microbial ecosystem-also called "microbiome"-is in balance, these potentially pathogenic bacterial residents cause no harm to the host. However, similar to macrobiological ecosystems, when the bacterial community structure gets perturbed, potential pathogens can overtake the niche and cause mild to severe infections. Recent studies using next-generation sequencing show that S. pneumoniae, as well as other potential pathogens, might be kept at bay by certain commensal bacteria, including Corynebacterium and Dolosigranulum spp. Bomar and colleagues are the first to explore a specific biological mechanism contributing to the antagonistic interaction between Corynebacterium accolens and S. pneumoniae in vitro [L. Bomar, S. D. Brugger, B. H. Yost, S. S. Davies, K. P. Lemon, mBio 7(1):e01725-15, 2016, doi:10.1128/mBio.01725-15]. The authors comprehensively show that C. accolens is capable of hydrolyzing host triacylglycerols into free fatty acids, which display antipneumococcal properties, suggesting that these bacteria might contribute to the containment of pneumococcus. This work exemplifies how molecular epidemiological findings can lay the foundation for mechanistic studies to elucidate the host-microbe and microbial interspecies interactions underlying the bacterial community structure. Next, translation of these results to an in vivo setting seems necessary to unveil the magnitude and importance of the observed effect in its natural, polymicrobial setting. Copyright © 2016 de Steenhuijsen Piters and Bogaert.

Unraveling the Molecular Mechanisms Underlying the Nasopharyngeal Bacterial Community Structure

PubMed Central

de Steenhuijsen Piters, Wouter A. A.

2016-01-01

ABSTRACT The upper respiratory tract is colonized by a diverse array of commensal bacteria that harbor potential pathogens, such as Streptococcus pneumoniae. As long as the local microbial ecosystem—also called “microbiome”—is in balance, these potentially pathogenic bacterial residents cause no harm to the host. However, similar to macrobiological ecosystems, when the bacterial community structure gets perturbed, potential pathogens can overtake the niche and cause mild to severe infections. Recent studies using next-generation sequencing show that S. pneumoniae, as well as other potential pathogens, might be kept at bay by certain commensal bacteria, including Corynebacterium and Dolosigranulum spp. Bomar and colleagues are the first to explore a specific biological mechanism contributing to the antagonistic interaction between Corynebacterium accolens and S. pneumoniae in vitro [L. Bomar, S. D. Brugger, B. H. Yost, S. S. Davies, K. P. Lemon, mBio 7(1):e01725-15, 2016, doi:10.1128/mBio.01725-15]. The authors comprehensively show that C. accolens is capable of hydrolyzing host triacylglycerols into free fatty acids, which display antipneumococcal properties, suggesting that these bacteria might contribute to the containment of pneumococcus. This work exemplifies how molecular epidemiological findings can lay the foundation for mechanistic studies to elucidate the host-microbe and microbial interspecies interactions underlying the bacterial community structure. Next, translation of these results to an in vivo setting seems necessary to unveil the magnitude and importance of the observed effect in its natural, polymicrobial setting. PMID:26838716

High frequency of pathogenic Aspergillus species among nonsporulating moulds from respiratory tract samples.

PubMed

Dufresne, Philippe J; Moonjely, Soumya S; Ozaki, Koyomi; Tremblay, Cécile; Laverdière, Michel; Dufresne, Simon F

2017-02-01

Nonsporulating moulds (NSM) represent an identification challenge for clinical laboratories. Data on the prevalence of pathogenic species among NSM are lacking. We prospectively investigated consecutive thermotolerant (36°C) clinical NSM isolates from respiratory tract samples. A total of 123 isolates were identified by DNA sequencing and phenotypically characterized. Of those, 13 (11%) were pathogenic species (Aspergillus fumigatus, n = 10; A. flavus, n = 1; A. hiratsukae, n = 1; Schizophyllum commune, n = 1). Presumptive identification of Aspergillus species among NSM can be achieved by simple phenotypic testing. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Fluorocycline TP-271 Is Potent against Complicated Community-Acquired Bacterial Pneumonia Pathogens

PubMed Central

Fyfe, Corey; O’Brien, William; Hackel, Meredith; Minyard, Mary Beth; Waites, Ken B.; Dubois, Jacques; Murphy, Timothy M.; Slee, Andrew M.; Weiss, William J.; Sutcliffe, Joyce A.

2017-01-01

ABSTRACT TP-271 is a novel, fully synthetic fluorocycline antibiotic in clinical development for the treatment of respiratory infections caused by susceptible and multidrug-resistant pathogens. TP-271 was active in MIC assays against key community respiratory Gram-positive and Gram-negative pathogens, including Streptococcus pneumoniae (MIC90 = 0.03 µg/ml), methicillin-sensitive Staphylococcus aureus (MSSA; MIC90 = 0.25 µg/ml), methicillin-resistant S. aureus (MRSA; MIC90 = 0.12 µg/ml), Streptococcus pyogenes (MIC90 = 0.03 µg/ml), Haemophilus influenzae (MIC90 = 0.12 µg/ml), and Moraxella catarrhalis (MIC90 ≤0.016 µg/ml). TP-271 showed activity (MIC90 = 0.12 µg/ml) against community-acquired MRSA expressing Panton-Valentine leukocidin (PVL). MIC90 values against Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae were 0.004, 1, and 4 µg/ml, respectively. TP-271 was efficacious in neutropenic and immunocompetent animal pneumonia models, generally showing, compared to the burden at the start of dosing, ~2 to 5 log10 CFU reductions against MRSA, S. pneumoniae, and H. influenzae infections when given intravenously (i.v.) and ~1 to 4 log10 CFU reductions when given orally (p.o.). TP-271 was potent against key community-acquired bacterial pneumonia (CABP) pathogens and was minimally affected, or unaffected, by tetracycline-specific resistance mechanisms and fluoroquinolone or macrolide drug resistance phenotypes. IMPORTANCE Rising resistance rates for macrolides, fluoroquinolones, and β-lactams in the most common pathogens associated with community-acquired bacterial pneumonia (CABP) are of concern, especially for cases of moderate to severe infections in vulnerable populations such as the very young and the elderly. New antibiotics that are active against multidrug-resistant Streptococcus pneumoniae and Staphylococcus aureus are needed for use in the empirical treatment of the most severe forms of this disease. TP-271 is a promising new fluorocycline antibiotic demonstrating in vitro potency and nonclinical efficacy by intravenous and oral administration against the major pathogens associated with moderate to severe CABP. PMID:28251179

Immunological Response to Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex: An RNA-Sequence Analysis of the Bronchial Lymph Node Transcriptome.

PubMed

Tizioto, Polyana C; Kim, JaeWoo; Seabury, Christopher M; Schnabel, Robert D; Gershwin, Laurel J; Van Eenennaam, Alison L; Toaff-Rosenstein, Rachel; Neibergs, Holly L; Taylor, Jeremy F

2015-01-01

Susceptibility to bovine respiratory disease (BRD) is multi-factorial and is influenced by stress in conjunction with infection by both bacterial and viral pathogens. While vaccination is broadly used in an effort to prevent BRD, it is far from being fully protective and cases diagnosed from a combination of observed clinical signs without any attempt at identifying the causal pathogens are usually treated with antibiotics. Dairy and beef cattle losses from BRD are profound worldwide and genetic studies have now been initiated to elucidate host loci which underlie susceptibility with the objective of enabling molecular breeding to reduce disease prevalence. In this study, we employed RNA sequencing to examine the bronchial lymph node transcriptomes of controls and beef cattle which had individually been experimentally challenged with bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Pasteurella multocida, Mannheimia haemolytica or Mycoplasma bovis to identify the genes that are involved in the bovine immune response to infection. We found that 142 differentially expressed genes were located in previously described quantitative trait locus regions associated with risk of BRD. Mutations affecting the expression or amino acid composition of these genes may affect disease susceptibility and could be incorporated into molecular breeding programs. Genes involved in innate immunity were generally found to be differentially expressed between the control and pathogen-challenged animals suggesting that variation in these genes may lead to a heritability of susceptibility that is pathogen independent. However, we also found pathogen-specific expression profiles which suggest that host genetic variation for BRD susceptibility is pathogen dependent.

Etiologic Diagnosis of Lower Respiratory Tract Bacterial Infections Using Sputum Samples and Quantitative Loop-Mediated Isothermal Amplification

PubMed Central

Peng, Peichao; Cheng, Xiaoxing; Wang, Guoqing; Qian, Minping; Gao, Huafang; Han, Bei; Chen, Yusheng; Hu, Yinghui; Geng, Rong; Hu, Chengping; Zhang, Wei; Yang, Jingping; Wan, Huanying; Yu, Qin; Wei, Liping; Li, Jiashu; Tian, Guizhen; Wang, Qiuyue; Hu, Ke; Wang, Siqin; Wang, Ruiqin; Du, Juan; He, Bei; Ma, Jianjun; Zhong, Xiaoning; Mu, Lan; Cai, Shaoxi; Zhu, Xiangdong; Xing, Wanli; Yu, Jun; Deng, Minghua; Gao, Zhancheng

2012-01-01

Etiologic diagnoses of lower respiratory tract infections (LRTI) have been relying primarily on bacterial cultures that often fail to return useful results in time. Although DNA-based assays are more sensitive than bacterial cultures in detecting pathogens, the molecular results are often inconsistent and challenged by doubts on false positives, such as those due to system- and environment-derived contaminations. Here we report a nationwide cohort study on 2986 suspected LRTI patients across P. R. China. We compared the performance of a DNA-based assay qLAMP (quantitative Loop-mediated isothermal AMPlification) with that of standard bacterial cultures in detecting a panel of eight common respiratory bacterial pathogens from sputum samples. Our qLAMP assay detects the panel of pathogens in 1047(69.28%) patients from 1533 qualified patients at the end. We found that the bacterial titer quantified based on qLAMP is a predictor of probability that the bacterium in the sample can be detected in culture assay. The relatedness of the two assays fits a logistic regression curve. We used a piecewise linear function to define breakpoints where latent pathogen abruptly change its competitive relationship with others in the panel. These breakpoints, where pathogens start to propagate abnormally, are used as cutoffs to eliminate the influence of contaminations from normal flora. With help of the cutoffs derived from statistical analysis, we are able to identify causative pathogens in 750 (48.92%) patients from qualified patients. In conclusion, qLAMP is a reliable method in quantifying bacterial titer. Despite the fact that there are always latent bacteria contaminated in sputum samples, we can identify causative pathogens based on cutoffs derived from statistical analysis of competitive relationship. Trial Registration ClinicalTrials.gov NCT00567827 PMID:22719933

Endogenous Molecules Induced by a Pathogen-Associated Molecular Pattern (PAMP) Elicit Innate Immunity in Shrimp

PubMed Central

Chen, Yu-Yuan; Chen, Jiann-Chu; Lin, Yong-Chin; Kitikiew, Suwaree; Li, Hui-Fang; Bai, Jia-Chin; Tseng, Kuei-Chi; Lin, Bo-Wei; Liu, Po-Chun; Shi, Yin-Ze; Kuo, Yi-Hsuan; Chang, Yu-Hsuan

2014-01-01

Invertebrates rely on an innate immune system to combat invading pathogens. The system is initiated in the presence of cell wall components from microbes like lipopolysaccharide (LPS), β-1,3-glucan (βG) and peptidoglycan (PG), altogether known as pathogen-associated molecular patterns (PAMPs), via a recognition of pattern recognition protein (PRP) or receptor (PRR) through complicated reactions. We show herein that shrimp hemocytes incubated with LPS, βG, and PG caused necrosis and released endogenous molecules (EMs), namely EM-L, EM-β, and EM-P, and found that shrimp hemocytes incubated with EM-L, EM-β, and EM-P caused changes in cell viability, degranulation and necrosis of hemocytes, and increased phenoloxidase (PO) activity and respiratory burst (RB) indicating activation of immunity in vitro. We found that shrimp receiving EM-L, EM-β, and EM-P had increases in hemocyte count and other immune parameters as well as higher phagocytic activity toward a Vibrio pathogen, and found that shrimp receiving EM-L had increases in proliferation cell ratio and mitotic index of hematopoietic tissues (HPTs). We identified proteins of EMs deduced from SDS-PAGE and LC-ESI-MS/MS analyses. EM-L and EM-P contained damage-associated molecular patterns (DAMPs) including HMGBa, HMGBb, histone 2A (H2A), H2B, and H4, and other proteins including proPO, Rab 7 GPTase, and Rab 11 GPTase, which were not observed in controls (EM-C, hemocytes incubated in shrimp salt solution). We concluded that EMs induced by PAMPs contain DAMPs and other immune molecules, and they could elicit innate immunity in shrimp. Further research is needed to identify which individual molecule or combined molecules of EMs cause the results, and determine the mechanism of action in innate immunity. PMID:25517999

Riboflavin transporter deficiency mimicking mitochondrial myopathy caused by complex II deficiency.

PubMed

Nimmo, Graeme A M; Ejaz, Resham; Cordeiro, Dawn; Kannu, Peter; Mercimek-Andrews, Saadet

2018-02-01

Biallelic likely pathogenic variants in SLC52A2 and SLC52A3 cause riboflavin transporter deficiency. It is characterized by muscle weakness, ataxia, progressive ponto-bulbar palsy, amyotrophy, and sensorineural hearing loss. Oral riboflavin halts disease progression and may reverse symptoms. We report two new patients whose clinical and biochemical features were mimicking mitochondrial myopathy. Patient 1 is an 8-year-old male with global developmental delay, axial and appendicular hypotonia, ataxia, and sensorineural hearing loss. His muscle biopsy showed complex II deficiency and ragged red fibers consistent with mitochondrial myopathy. Whole exome sequencing revealed a homozygous likely pathogenic variant in SLC52A2 (c.917G>A; p.Gly306Glu). Patient 2 is a 14-month-old boy with global developmental delay, respiratory insufficiency requiring ventilator support within the first year of life. His muscle biopsy revealed combined complex II + III deficiency and ragged red fibers consistent with mitochondrial myopathy. Whole exome sequencing identified a homozygous likely pathogenic variant in SCL52A3 (c.1223G>A; p.Gly408Asp). We report two new patients with riboflavin transporter deficiency, caused by mutations in two different riboflavin transporter genes. Both patients presented with complex II deficiency. This treatable neurometabolic disorder can mimic mitochondrial myopathy. In patients with complex II deficiency, riboflavin transporter deficiency should be included in the differential diagnosis to allow early treatment and improve neurodevelopmental outcome. © 2017 Wiley Periodicals, Inc.

Human airway epithelial cell cultures for modeling respiratory syncytial virus infection.

PubMed

Pickles, Raymond J

2013-01-01

Respiratory syncytial virus (RSV) is an important human respiratory pathogen with narrow species tropism. Limited availability of human pathologic specimens during early RSV-induced lung disease and ethical restrictions for RSV challenge studies in the lower airways of human volunteers has slowed our understanding of how RSV causes airway disease and greatly limited the development of therapeutic strategies for reducing RSV disease burden. Our current knowledge of RSV infection and pathology is largely based on in vitro studies using nonpolarized epithelial cell-lines grown on plastic or in vivo studies using animal models semipermissive for RSV infection. Although these models have revealed important aspects of RSV infection, replication, and associated inflammatory responses, these models do not broadly recapitulate the early interactions and potential consequences of RSV infection of the human columnar airway epithelium in vivo. In this chapter, the pro et contra of in vitro models of human columnar airway epithelium and their usefulness in respiratory virus pathogenesis and vaccine development studies will be discussed. The use of such culture models to predict characteristics of RSV infection and the correlation of these findings to the human in vivo situation will likely accelerate our understanding of RSV pathogenesis potentially identifying novel strategies for limiting the severity of RSV-associated airway disease.

ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh syndrome.

PubMed

Sakai, Chika; Yamaguchi, Seiji; Sasaki, Masayuki; Miyamoto, Yusaku; Matsushima, Yuichi; Goto, Yu-ichi

2015-02-01

The human ECHS1 gene encodes the short-chain enoyl coenzyme A hydratase, the enzyme that catalyzes the second step of β-oxidation of fatty acids in the mitochondrial matrix. We report on a boy with ECHS1 deficiency who was diagnosed with Leigh syndrome at 21 months of age. The patient presented with hypotonia, metabolic acidosis, and developmental delay. A combined respiratory chain deficiency was also observed. Targeted exome sequencing of 776 mitochondria-associated genes encoded by nuclear DNA identified compound heterozygous mutations in ECHS1. ECHS1 protein expression was severely depleted in the patient's skeletal muscle and patient-derived myoblasts; a marked decrease in enzyme activity was also evident in patient-derived myoblasts. Immortalized patient-derived myoblasts that expressed exogenous wild-type ECHS1 exhibited the recovery of the ECHS1 activity, indicating that the gene defect was pathogenic. Mitochondrial respiratory complex activity was also mostly restored in these cells, suggesting that there was an unidentified link between deficiency of ECHS1 and respiratory chain. Here, we describe the patient with ECHS1 deficiency; these findings will advance our understanding not only the pathology of mitochondrial fatty acid β-oxidation disorders, but also the regulation of mitochondrial metabolism. © 2014 WILEY PERIODICALS, INC.

Nasopharyngeal carriage of respiratory pathogens in Warao Amerindians: significant relationship with stunting.

PubMed

Verhagen, Lilly M; Hermsen, Meyke; Rivera-Olivero, Ismar A; Sisco, María Carolina; de Jonge, Marien I; Hermans, Peter W M; de Waard, Jacobus H

2017-04-01

To assess risk factors for nasopharyngeal carriage of potential pathogens in geographically isolated Warao Amerindians in Venezuela. In this point prevalence survey, nasopharyngeal swabs were obtained from 1064 Warao Amerindians: 504 children aged 0-4 years, 227 children aged 5-10 years and 333 caregivers. Written questionnaires were completed to obtain information on demographics and environmental risk factors. Anthropometric measurements were performed in children aged 0-4 years. Carriage rates of Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis were 51%, 7%, 1% and 13%, respectively. Crowding index, method of cooking and tobacco exposure were not associated with increased carriage. In multivariable analysis, an increase in height-for-age Z score (i.e. improved chronic nutritional status) was associated with decreased odds of S. pneumoniae colonisation (OR 0.76, 95% CI 0.70-0.83) in children aged 0-4 years. Better knowledge of demographic and environmental risk factors facilitates better understanding of the dynamics of colonisation with respiratory bacteria in an Amerindian population. Poor chronic nutritional status was associated with increased pathogen carriage in children <5 years of age. The high rates of stunting generally observed in indigenous children may fuel the acquisition of respiratory bacteria that can lead to respiratory and invasive disease. © 2017 John Wiley & Sons Ltd.

Airway-Resident Memory CD8 T Cells Provide Antigen-Specific Protection against Respiratory Virus Challenge through Rapid IFN-γ Production.

PubMed

McMaster, Sean R; Wilson, Jarad J; Wang, Hong; Kohlmeier, Jacob E

2015-07-01

CD8 airway resident memory T (TRM) cells are a distinctive TRM population with a high turnover rate and a unique phenotype influenced by their localization within the airways. Their role in mediating protective immunity to respiratory pathogens, although suggested by many studies, has not been directly proven. This study provides definitive evidence that airway CD8 TRM cells are sufficient to mediate protection against respiratory virus challenge. Despite being poorly cytolytic in vivo and failing to expand after encountering Ag, airway CD8 TRM cells rapidly express effector cytokines, with IFN-γ being produced most robustly. Notably, established airway CD8 TRM cells possess the ability to produce IFN-γ faster than systemic effector memory CD8 T cells. Furthermore, naive mice receiving intratracheal transfer of airway CD8 TRM cells lacking the ability to produce IFN-γ were less effective at controlling pathogen load upon heterologous challenge. This direct evidence of airway CD8 TRM cell-mediated protection demonstrates the importance of these cells as a first line of defense for optimal immunity against respiratory pathogens and suggests they should be considered in the development of future cell-mediated vaccines. Copyright © 2015 by The American Association of Immunologists, Inc.

"To rid oneself of the uninvited guest": Robert Koch, Sergei Winogradsky and competing styles of practice in medical microbiology.

PubMed

Attenborough, Frederick Thomas

2012-01-01

Does an infectious disease have one, singular pathogenic cause, or many interacting causes? In the discipline of medical microbiology, there is no definitive theoretical answer to this question: there, the conditions of aetiological possibility exist in a curious tension. Ever since the late 19th century, the “germ theory of disease”–“one disease, one cause”– has co-existed with a much less well known theory of “multifactorality”–“one disease, many interacting causes”. And yet, in practice, it is always a singular and never a multifactorial aetiology that emerges once the pathogenic world is brought into the field of medical perception. This paper seeks to understand why. Performing a detailed, genealogical reading of the 2003 severe acute respiratory syndrome (SARS) outbreak, it foregrounds a set of links that connect the practical diagnostic tools at work within contemporary, 21st century laboratories to the philosophical assumptions at work within late-19th century understandings of the “germ theory of disease”.

Rapid changes in the serum total protein and globulin levels in complications caused by facultatively pathogenic Gram-negative bacteria.

PubMed

Petrás, G; Kiss, S; Juraszek, J; Merétey, K

1978-01-01

The changes in the levels of total protein and four globulin fractions were followed up throughout the entire course of complications caused by Gram-negative facultative pathogens in 37 acute cases of respiratory insufficiency accompanying different underlying illnesses and in 9 chronic, bedridden patients given artificial ventilation. At the onset of the infectious complications, in the first place in septic shock, the levels of various globulin fractions showed a decrease corresponding to a half-life of 2 to 4 days. Neither the increased catabolism, nor the protein losses by the urine and tracheal secretions offer a sufficient explanation for the escape of globulins of this extent from the plasma. It seems that this is a consequence of the increase in capillary permeability due to the effect of antigen-antibody reactions and that of endotoxin. As a result, in the critical phase of the infectious complications, at the point of culmination, e.g. in septic shock, diminished amount of different globulins is transported to the site of utilization, that is, to the inflammatory area.

Characteristics of human infection with avian influenza viruses and development of new antiviral agents

PubMed Central

Liu, Qiang; Liu, Dong-ying; Yang, Zhan-qiu

2013-01-01

Since 1997, several epizootic avian influenza viruses (AIVs) have been transmitted to humans, causing diseases and even deaths. The recent emergence of severe human infections with AIV (H7N9) in China has raised concerns about efficient interpersonal viral transmission, polygenic traits in viral pathogenicity and the management of newly emerging strains. The symptoms associated with viral infection are different in various AI strains: H5N1 and newly emerged H7N9 induce severe pneumonia and related complications in patients, while some H7 and H9 subtypes cause only conjunctivitis or mild respiratory symptoms. The virulence and tissue tropism of viruses as well as the host responses contribute to the pathogenesis of human AIV infection. Several preventive and therapeutic approaches have been proposed to combat AIV infection, including antiviral drugs such as M2 inhibitors, neuraminidase inhibitors, RNA polymerase inhibitors, attachment inhibitors and signal-transduction inhibitors etc. In this article, we summarize the recent progress in researches on the epidemiology, clinical features, pathogenicity determinants, and available or potential antivirals of AIV. PMID:24096642

Infection Risk for Persons Exposed to Highly Pathogenic Avian Influenza A H5 Virus-Infected Birds, United States, December 2014-March 2015.

PubMed

Arriola, Carmen S; Nelson, Deborah I; Deliberto, Thomas J; Blanton, Lenee; Kniss, Krista; Levine, Min Z; Trock, Susan C; Finelli, Lyn; Jhung, Michael A

2015-12-01

Newly emerged highly pathogenic avian influenza (HPAI) A H5 viruses have caused outbreaks among birds in the United States. These viruses differ genetically from HPAI H5 viruses that previously caused human illness, most notably in Asia and Africa. To assess the risk for animal-to-human HPAI H5 virus transmission in the United States, we determined the number of persons with self-reported exposure to infected birds, the number with an acute respiratory infection (ARI) during a 10-day postexposure period, and the number with ARI who tested positive for influenza by real-time reverse transcription PCR or serologic testing for each outbreak during December 15, 2014-March 31, 2015. During 60 outbreaks in 13 states, a total of 164 persons were exposed to infected birds. ARI developed in 5 of these persons within 10 days of exposure. H5 influenza virus infection was not identified in any persons with ARI, suggesting a low risk for animal-to-human HPAI H5 virus transmission.

Multi-spectral fluorescent reporter influenza viruses (Color-flu) as powerful tools for in vivo studies

PubMed Central

Fukuyama, Satoshi; Katsura, Hiroaki; Zhao, Dongming; Ozawa, Makoto; Ando, Tomomi; Shoemaker, Jason E.; Ishikawa, Izumi; Yamada, Shinya; Neumann, Gabriele; Watanabe, Shinji; Kitano, Hiroaki; Kawaoka, Yoshihiro

2015-01-01

Seasonal influenza A viruses cause annual epidemics of respiratory disease; highly pathogenic avian H5N1 and the recently emerged H7N9 viruses cause severe infections in humans, often with fatal outcomes. Although numerous studies have addressed the pathogenicity of influenza viruses, influenza pathogenesis remains incompletely understood. Here we generate influenza viruses expressing fluorescent proteins of different colours (‘Color-flu’ viruses) to facilitate the study of viral infection in in vivo models. On adaptation to mice, stable expression of the fluorescent proteins in infected animals allows their detection by different types of microscopy and by flow cytometry. We use this system to analyse the progression of viral spread in mouse lungs, for live imaging of virus-infected cells, and for differential gene expression studies in virus antigen-positive and virus antigen-negative live cells in the lungs of Color-flu-infected mice. Collectively, Color-flu viruses are powerful tools to analyse virus infections at the cellular level in vivo to better understand influenza pathogenesis. PMID:25807527

Mutations in mitochondrial complex I assembly factor NDUFAF3 cause Leigh syndrome.

PubMed

Baertling, Fabian; Sánchez-Caballero, Laura; Timal, Sharita; van den Brand, Mariël Am; Ngu, Lock Hock; Distelmaier, Felix; Rodenburg, Richard Jt; Nijtmans, Leo Gj

2017-03-01

NDUFAF3 is an assembly factor of mitochondrial respiratory chain complex I. Variants in NDUFAF3 have been identified as a cause of severe multisystem mitochondrial disease. In a patient presenting with Leigh syndrome, which has hitherto not been described as a clinical feature of NDUFAF3 deficiency, we identified a novel homozygous variant and confirmed its pathogenicity in patient fibroblasts studies. Furthermore, we present an analysis of complex I assembly routes representative of each functional module and, thereby, link NDUFAF3 to a specific step in complex I assembly. Therefore, our report expands the phenotype of NDUFAF3 deficiency and further characterizes the role of NDUFAF3 in complex I biogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Mild Respiratory Illness Among Young Children Caused by Highly Pathogenic Avian Influenza A (H5N1) Virus Infection in Dhaka, Bangladesh, 2011.

PubMed

Chakraborty, Apurba; Rahman, Mahmudur; Hossain, M Jahangir; Khan, Salah Uddin; Haider, M Sabbir; Sultana, Rebeca; Ali Rimi, Nadia; Islam, M Saiful; Haider, Najmul; Islam, Ausraful; Sultana Shanta, Ireen; Sultana, Tahmina; Al Mamun, Abdullah; Homaira, Nusrat; Goswami, Doli; Nahar, Kamrun; Alamgir, A S M; Rahman, Mustafizur; Mahbuba Jamil, Khondokar; Azziz-Baumgartner, Eduardo; Simpson, Natosha; Shu, Bo; Lindstrom, Stephen; Gerloff, Nancy; Davis, C Todd; Katz, Jaqueline M; Mikolon, Andrea; Uyeki, Timothy M; Luby, Stephen P; Sturm-Ramirez, Katharine

2017-09-15

In March 2011, a multidisciplinary team investigated 2 human cases of highly pathogenic avian influenza A(H5N1) virus infection, detected through population-based active surveillance for influenza in Bangladesh, to assess transmission and contain further spread. We collected clinical and exposure history of the case patients and monitored persons coming within 1 m of a case patient during their infectious period. Nasopharyngeal wash specimens from case patients and contacts were tested with real-time reverse-transcription polymerase chain reaction, and virus culture and isolates were characterized. Serum samples were tested with microneutralization and hemagglutination inhibition assays. We tested poultry, wild bird, and environmental samples from case patient households and surrounding areas for influenza viruses. Two previously healthy case patients, aged 13 and 31 months, had influenzalike illness and fully recovered. They had contact with poultry 7 and 10 days before illness onset, respectively. None of their 57 contacts were subsequently ill. Clade 2.2.2.1 highly pathogenic avian influenza H5N1 viruses were isolated from the case patients and from chicken fecal samples collected at the live bird markets near the patients' dwellings. Identification of H5N1 cases through population-based surveillance suggests possible additional undetected cases throughout Bangladesh and highlights the importance of surveillance for mild respiratory illness among populations frequently exposed to infected poultry. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Septic Pulmonary Embolism Requiring Critical Care: Clinicoradiological Spectrum, Causative Pathogens and Outcomes

PubMed Central

Chou, Deng-Wei; Wu, Shu-Ling; Chung, Kuo-Mou; Han, Shu-Chen; Cheung, Bruno Man-Hon

2016-01-01

OBJECTIVES: Septic pulmonary embolism is an uncommon but life-threatening disorder. However, data on patients with septic pulmonary embolism who require critical care have not been well reported. This study elucidated the clinicoradiological spectrum, causative pathogens and outcomes of septic pulmonary embolism in patients requiring critical care. METHODS: The electronic medical records of 20 patients with septic pulmonary embolism who required intensive care unit admission between January 2005 and December 2013 were reviewed. RESULTS: Multiple organ dysfunction syndrome developed in 85% of the patients, and acute respiratory failure was the most common organ failure (75%). The most common computed tomographic findings included a feeding vessel sign (90%), peripheral nodules without cavities (80%) or with cavities (65%), and peripheral wedge-shaped opacities (75%). The most common primary source of infection was liver abscess (40%), followed by pneumonia (25%). The two most frequent causative pathogens were Klebsiella pneumoniae (50%) and Staphylococcus aureus (35%). Compared with survivors, nonsurvivors had significantly higher serum creatinine, arterial partial pressure of carbon dioxide, and Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores, and they were significantly more likely to have acute kidney injury, disseminated intravascular coagulation and lung abscesses. The in-hospital mortality rate was 30%. Pneumonia was the most common cause of death, followed by liver abscess. CONCLUSIONS: Patients with septic pulmonary embolism who require critical care, especially those with pneumonia and liver abscess, are associated with high mortality. Early diagnosis, appropriate antibiotic therapy, surgical intervention and respiratory support are essential. PMID:27759843

In vitro activity of Ceftaroline against bacterial pathogens isolated from patients with skin and soft tissue and respiratory tract infections in African and Middle Eastern countries: AWARE global surveillance program 2012-2014.

PubMed

Karlowsky, James A; Biedenbach, Douglas J; Bouchillon, Samuel K; Hackel, Meredith; Iaconis, Joseph P; Sahm, Daniel F

2016-10-01

The objective of this report was to document antimicrobial susceptibility testing surveillance data for ceftaroline and comparative agents from the AWARE (Assessing Worldwide Antimicrobial Resistance Evaluation) global surveillance program for bacterial pathogens causing skin and soft tissue and respiratory tract infections in African and Middle Eastern countries from 2012 through 2014. Pathogen identities were confirmed by MALDI-TOF and antimicrobial susceptibility testing performed by CLSI broth microdilution methodology in a central laboratory. All methicillin-susceptible Staphylococcus aureus (MSSA) (n= 923; MIC90, 0.25 μg/mL) and 91.8% of methicillin-resistant S. aureus (MRSA) (n= 1161; MIC90, 1 μg/mL) tested were susceptible to ceftaroline. The maximum ceftaroline MIC observed for isolates of MRSA was 2 μg/mL. All Streptococcus pyogenes (n= 174; MIC90, 0.008 μg/mL), Streptococcus agalactiae (n= 44; MIC90, 0.015 μg/mL), Streptococcus pneumoniae (n= 351; MIC90, 0.25 μg/mL), and Haemophilus influenzae (n= 84; MIC90, ≤0.015 μg/mL) were susceptible to ceftaroline. Rates of susceptibility to ceftaroline among ESBL-negative Escherichia coli (n= 338), Klebsiella pneumoniae (n= 241), and Klebsiella oxytoca (n= 97) were 89.1% (MIC90, 1 μg/mL), 94.2% (MIC90, 0.5 μg/mL), and 99.0% (MIC90, 0.5 μg/mL), respectively. Copyright © 2016. Published by Elsevier Inc.

Smog exposure and host resistance to respiratory pathogens

EPA Science Inventory

The US EPA is evaluating the health effects of photochemical smog on respiratory, cardiovascular and metabolic health (https://www.epa.gov/air-research/secondary-organic-aerosol-soas-research). Smog exposure has been associated with an increased risk of allergy and decreased res...

Genome Sequence of Canine Polyomavirus in Respiratory Secretions of Dogs with Pneumonia of Unknown Etiology

PubMed Central

Kapusinszky, Beatrix; Pesavento, Patricia A.; Estrada, Marko; Seguin, M. Alexis

2017-01-01

ABSTRACT We report here the first canine polyomavirus genome, identified by metagenomics in respiratory secretions of two dogs with severe pneumonia, which tested negative for all canine respiratory pathogens except Mycoplasma cynos. The isolate, Canis familiaris polyomavirus 1 (DogPyV-1), is a beta polyomavirus whose closest known LT antigen relatives are primate polyomaviruses. PMID:28729262

Genome Sequence of Canine Polyomavirus in Respiratory Secretions of Dogs with Pneumonia of Unknown Etiology.

PubMed

Delwart, Eric; Kapusinszky, Beatrix; Pesavento, Patricia A; Estrada, Marko; Seguin, M Alexis; Leutenegger, Christian M

2017-07-20

We report here the first canine polyomavirus genome, identified by metagenomics in respiratory secretions of two dogs with severe pneumonia, which tested negative for all canine respiratory pathogens except Mycoplasma cynos The isolate, Canis familiaris polyomavirus 1 (DogPyV-1), is a beta polyomavirus whose closest known LT antigen relatives are primate polyomaviruses. Copyright © 2017 Delwart et al.

A multiplexed reverse transcriptase PCR assay for identification of viral respiratory pathogens at point-of-care

DOE Office of Scientific and Technical Information (OSTI.GOV)

Letant, S E; .Ortiz, J I; Tammero, L

2007-04-11

We have developed a nucleic acid-based assay that is rapid, sensitive, specific, and can be used for the simultaneous detection of 5 common human respiratory pathogens including influenza A, influenza B, parainfluenza type 1 and 3, respiratory syncytial virus, and adenovirus group B, C, and E. Typically, diagnosis on an un-extracted clinical sample can be provided in less than 3 hours, including sample collection, preparation, and processing, as well as data analysis. Such a multiplexed panel would enable rapid broad-spectrum pathogen testing on nasal swabs, and therefore allow implementation of infection control measures, and timely administration of antiviral therapies. Thismore » article presents a summary of the assay performance in terms of sensitivity and specificity. Limits of detection are provided for each targeted respiratory pathogen, and result comparisons are performed on clinical samples, our goal being to compare the sensitivity and specificity of the multiplexed assay to the combination of immunofluorescence and shell vial culture currently implemented at the UCDMC hospital. Overall, the use of the multiplexed RT-PCR assay reduced the rate of false negatives by 4% and reduced the rate of false positives by up to 10%. The assay correctly identified 99.3% of the clinical negatives, 97% of adenovirus, 95% of RSV, 92% of influenza B, and 77% of influenza A without any extraction performed on the clinical samples. The data also showed that extraction will be needed for parainfluenza virus, which was only identified correctly 24% of the time on un-extracted samples.« less

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2012: General view of the pathogens' antibacterial susceptibility.

PubMed

Yanagihara, Katsunori; Watanabe, Akira; Aoki, Nobuki; Matsumoto, Tetsuya; Yoshida, Masaki; Sato, Junko; Wakamura, Tomotaro; Sunakawa, Keisuke; Kadota, Junichi; Kiyota, Hiroshi; Iwata, Satoshi; Kaku, Mitsuo; Hanaki, Hideaki; Ohsaki, Yoshinobu; Fujiuchi, Satoru; Takahashi, Manabu; Takeuchi, Kenichi; Takeda, Hiroaki; Ikeda, Hideki; Miki, Makoto; Nakanowatari, Susumu; Takahashi, Hiroshi; Utagawa, Mutsuko; Nishiya, Hajime; Kawakami, Sayoko; Morino, Eriko; Takasaki, Jin; Mezaki, Kazuhisa; Chonabayashi, Naohiko; Tanaka, Chie; Sugiura, Hideko; Goto, Hajime; Saraya, Takeshi; Kurai, Daisuke; Katono, Yasuhiro; Inose, Rika; Niki, Yoshihito; Takuma, Takahiro; Kudo, Makoto; Ehara, Shigeru; Sato, Yoshimi; Tsukada, Hiroki; Watabe, Nobuei; Honma, Yasuo; Mikamo, Hiroshige; Yamagishi, Yuka; Nakamura, Atsushi; Ohashi, Minoru; Seki, Masafumi; Hamaguchi, Shigeto; Toyokawa, Masahiro; Fujikawa, Yasunori; Mitsuno, Noriko; Ukimura, Akira; Miyara, Takayuki; Nakamura, Takahito; Mikasa, Keiichi; Kasahara, Kei; Ui, Koji; Fukuda, Saori; Nakamura, Akihiro; Morimura, Mika; Yamashita, Mikio; Takesue, Yoshio; Wada, Yasunao; Sugimoto, Keisuke; Kusano, Nobuchika; Nose, Motoko; Mihara, Eiichirou; Kuwabara, Masao; Doi, Masao; Watanabe, Yaeko; Tokuyasu, Hirokazu; Hino, Satoshi; Negayama, Kiyoshi; Mukae, Hiroshi; Kawanami, Toshinori; Ota, Toshiyuki; Fujita, Masaki; Honda, Junichi; Hiramatsu, Kazufumi; Aoki, Yosuke; Fukuoka, Mami; Magarifuchi, Hiroki; Nagasawa, Zenzo; Kaku, Norihito; Fujita, Jiro; Higa, Futoshi; Tateyama, Masao

2017-09-01

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by Japanese Society of Chemotherapy, Japanese association for infectious diseases and Japanese society for Clinical Microbiology in 2012. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between January and December in 2012 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standard Institutes. Susceptibility testing was evaluated in 1236 strains (232 Staphylococcus aureus, 225 Streptococcus pneumoniae, 16 Streptococcus pyogenes, 231 Haemophilus influenzae, 147 Moraxella catarrhalis, 167 Klebsiella pneumoniae and 218 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 51.3%, and those of penicillin-intermediate S. pneumoniae was 0.4%. Among H. influenzae, 5.6% of them were found to be β-lactamase-producing ampicillin-resistant strains, and 37.2% to be β-lactamase-non-producing ampicillin-resistant strains. Extended spectrum β-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo β-lactamase were 4.2% and 3.2%, respectively. Continuous national surveillance is important to determine the actual situation of the resistance shown by bacterial respiratory pathogens to antimicrobial agents. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Glycan shield and fusion activation of a deltacoronavirus spike glycoprotein fine-tuned for enteric infections.

PubMed

Xiong, Xiaoli; Tortorici, M Alejandra; Snijder, Joost; Yoshioka, Craig; Walls, Alexandra C; Li, Wentao; McGuire, Andrew T; Rey, Félix A; Bosch, Berend-Jan; Veesler, David

2017-11-01

Coronaviruses recently emerged as major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle-East respiratory syndrome. They utilize the spike (S) glycoprotein anchored in the viral envelope to mediate host attachment and fusion of the viral and cellular membranes to initiate infection. The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response. We report here the 3.5 Å resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified delta genus. Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved when compared with the human respiratory coronavirus HCoV-NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts. The structure further reveals a shortened S 2 ' activation loop, containing a reduced number of basic amino acids, which participates to rendering the spike largely protease-resistant. This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity. IMPORTANCE Coronaviruses use transmembrane spike (S) glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes. We determined a near-atomic resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic porcine deltacoronavirus (PDCoV), which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide. Structural and glycoproteomics data reveal that PDCoV S is decorated with 78 N-linked glycans obstructing the protein surface to limit accessibility to neutralizing antibodies in a way reminiscent of what has recently been described for a human respiratory coronavirus. PDCoV S is largely protease-resistant which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts. Copyright © 2017 American Society for Microbiology.

[Principles of management in biological infections].

PubMed

Płusa, Tadeusz

2012-11-01

The effectiveness of the management in respiratory infection is depending on the nature of the biological pathogen and the immune status of the patient. For this reason, providing assistance to victims the organ function support, similarly as defining the pathogen and targeted antibiotic therapy should be applied. Available diagnostic tests provide rapid ability to identify the pathogen and antibiotics are able to control infection. Lack of efficacy of treatment may indicate the diversity of the pathogen than previously known and raises suspicion of biological warfare pathogen.

A Three-way Comparative Genomic Analysis of Mannheimia haemolytica Isolates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lawrence, Paulraj; Kittichotirat, Weerayuth; McDermott, Jason E.

2010-10-04

Mannhemia haemolytica is a Gram- negative bacterium and the principal etiological agent associated with bovine respiratory disease complex. They transform from a benign commensal to a deadly pathogen during stress such as viral infection and transportation to feedlots, and cause acute pleuropneumonia commonly known as shipping fever. The U.S beef industry alone loses more than one billion dollars annually to shipping fever and despite its enormous economic importance there are no specific and accurate genetic markers, which would aid in understanding M. haemolytica pathogenesis and epidemiology at molecular level and assist in devising an effective control strategy.

Fatal Purpureocillium lilacinum pneumonia in a green tree python.

PubMed

Meyer, Jean; Loncaric, Igor; Richter, Barbara; Spergser, Joachim

2018-03-01

A 10-y-old female green tree python ( Morelia viridis) died of fungal pneumonia caused by Purpureocillium lilacinum, which was confirmed histologically and by PCR and subsequent DNA sequencing. The same fungal species was cultivated from a swab taken from the terrarium in which the snake was housed. Clinical and environmental P. lilacinum isolates were indistinguishable by the typing method applied, strongly suggesting clonal relatedness of both isolates. Because no other underlying predisposing respiratory infection could be detected by virus-specific PCR or histopathology, P. lilacinum was considered a primary pulmonary pathogen in this tree python.

Porcine reproductive and respiratory syndrome virus (PRRSV): pathogenesis and interaction with the immune System

USDA-ARS?s Scientific Manuscript database

This review addresses important issues of porcine reproductive and respiratory syndrome virus (PRRSV) infection, immunity, pathogenesis and control. Worldwide PRRS is the most economically important infectious disease of pigs. We highlight the latest information on viral genome structure, pathogenic...

Interplay of PA-X and NS1 Proteins in Replication and Pathogenesis of a Temperature-Sensitive 2009 Pandemic H1N1 Influenza A Virus.

PubMed

Nogales, Aitor; Rodriguez, Laura; DeDiego, Marta L; Topham, David J; Martínez-Sobrido, Luis

2017-09-01

Influenza A viruses (IAVs) cause seasonal epidemics and occasional pandemics, representing a serious public health concern. It has been described that one mechanism used by some IAV strains to escape the host innate immune responses and modulate virus pathogenicity involves the ability of the PA-X and NS1 proteins to inhibit the host protein synthesis in infected cells. It was reported that for the 2009 pandemic H1N1 IAV (pH1N1) only the PA-X protein had this inhibiting capability, while the NS1 protein did not. In this work, we have evaluated, for the first time, the combined effect of PA-X- and NS1-mediated inhibition of general gene expression on virus pathogenesis, using a temperature-sensitive, live-attenuated 2009 pandemic H1N1 IAV (pH1N1 LAIV). We found that viruses containing PA-X and NS1 proteins that simultaneously have (PA WT + /NS1 MUT + ) or do not have (PA MUT - /NS1 WT - ) the ability to block host gene expression showed reduced pathogenicity in vivo However, a virus where the ability to inhibit host protein expression was switched between PA-X and NS1 (PA MUT - /NS1 MUT + ) presented pathogenicity similar to that of a virus containing both wild-type proteins (PA WT + /NS1 WT - ). Our findings suggest that inhibition of host protein expression is subject to a strict balance, which can determine the successful progression of IAV infection. Importantly, knowledge obtained from our studies could be used for the development of new and more effective vaccine approaches against IAV. IMPORTANCE Influenza A viruses (IAVs) are one of the most common causes of respiratory infections in humans, resulting in thousands of deaths annually. Furthermore, IAVs can cause unpredictable pandemics of great consequence when viruses not previously circulating in humans are introduced into humans. The defense machinery provided by the host innate immune system limits IAV replication; however, to counteract host antiviral activities, IAVs have developed different inhibition mechanisms, including prevention of host gene expression mediated by the viral PA-X and NS1 proteins. Here, we provide evidence demonstrating that optimal control of host protein synthesis by IAV PA-X and/or NS1 proteins is required for efficient IAV replication in the host. Moreover, we demonstrate the feasibility of genetically controlling the ability of IAV PA-X and NS1 proteins to inhibit host immune responses, providing an approach to develop more effective vaccines to combat disease caused by this important respiratory pathogen. Copyright © 2017 American Society for Microbiology.

Guiding Principles for the use of Fluroquinolones in Out-patient Community Settings of India: Panel Consensus.

PubMed

Vora, Agam; Krishnaprasad, K

2017-08-01

Respiratory tract infections have been an important cause of morbidity and mortality worldwide that is looming large especially in context of antibiotic resistance that is confronted both by a pulmonologist as well as a general practitioner. A reflection to this trend has been the rising phenomenon of MICs as shown the respiratory pathogens towards conventional antibiotics including macrolides or β lactam/β lactamase inhibitor combinations. Respiratory fluoroquinolones offer broad yet potent cover of respiratory pathogens leading to their obvious choice for empirical therapy for clinical persisters or high risk cases with prior history of antibiotics not-withstanding the clinical concerns in tropical countries. To further assess the clinical role of respiratory quinolones in outpatient settings of India especially in line with the known endemicity of chronic infections or tuberculosis. Cross-sectional, national survey questionnaire survey to explore the clinical perceptions, attitude and insights on the clinical use of respiratory fluoroquinolones was rolled out amongst pulmonologists and consultant physicians practicing respiratory medicine in India. Descriptive statistics was utilized to describe the numerical and categorical data. Nationwide representative sample of fourteen pulmonologists provided response and clinical insight on the current management strategies for community acquired pneumonia (CAP) with 'respiratory' fluoroquinolones. Each of the doctor in the panel agreed that the ideal antibiotic for the treatment in CAP or lower respiratory tract infection (LRTI) should be highly effective with lesser side effects and broader spectrum covering atypical bacteria. Doctors agreed that most the fixed dose combination (FDC) has gone into disrepute probably because of pharmacokinetic incompatibility that could have further fuelled the epidemic of antibiotic resistance. 9 (64%) doctors suggested that there is omnipresence if not overwhelming presence of patient poor response to beta-lactam or fluoroquinolones in clinical practice. It was agreed that fluoroquinolones would be the rightful choice for patients with prior history of antibiotic use with or without comorbidities. Amongst the newer fluoroquinolones available, Garenoxacin offers broad and potent action against resistant strains for CAP. Despite the overwhelming concern of tropical infection in Indian context, Garenoxacin could be considered for mono- or add-on therapy in moderate to severe yet stable cases of CAP. Short course therapy of 5 to 10 days should offer no complimentary masking of anti-mycobacterial activity since the relevant minimum inhibitory concentration (MIC90) are high that are beyond the comprehension of suggested therapeutic dose of 400 mg tablets. The growing incidence of Macrolide resistance suggests the clinical role of new generation fluoroquinolones including Garenoxacin as a clinically useful therapeutic strategy for moderate to severe CAP as monotherapy or in combination.

Serum inflammatory biomarkers and clinical outcomes of COPD exacerbation caused by different pathogens.

PubMed

Kawamatawong, Theerasuk; Apiwattanaporn, Apitch; Siricharoonwong, Warisara

2017-01-01

COPD exacerbation is characterized by worsening of symptoms, warranting change in treatment. Systemic and airway inflammation play roles in the pathogenesis of COPD exacerbation. We hypothesized whether increased serum inflammatory biomarkers are associated with the clinical outcomes of COPD exacerbation caused by different infectious pathogens. COPD patients with exacerbation were recruited from a hospital emergency department during 2014-2015. Serum procalcitonin (PCT) and C-reactive protein (CRP) were measured. Dyspnea, eosinopenia, consolidation, acidemia, and atrial fibrillation (DECAF) score was calculated for predicting mortality. Multiplex polymerase chain reaction was carried out for respiratory viral assay from nasopharyngeal swabs, and sputum bacterial culture was also performed. Hospital mortality, invasive mechanical ventilation requirement, and length of hospital stay (LOS) were evaluated, and their associations with clinical characteristics, DECAF score, and serum biomarkers were examined. A total of 62 COPD patients were enrolled. These patients were classified as Global Initiative for Obstructive Lung Disease (GOLD) stage 2, 3, and 4 in 12.9%, 6.4%, and 80.7% of cases, respectively. Isolated bacterial exacerbation was recovered in 30.6% of exacerbation episodes: Klebsiella pneumoniae was the most commonly identified bacteria. Viral pathogens and coinfections were noted in 9.6% and 16.1% of exacerbated patients, respectively. Influenza was the most commonly detected viral pathogen. Serum biomarkers and DECAF score for viruses, bacteria, coinfection, and noninfectious causes of exacerbations were similar. Neither DECAF score nor serum biomarkers were able to differentiate patients with and without mortality or requiring mechanical ventilation. Increased serum PCT was noted in patients with LOS ≥7 days when compared with those with LOS <7 days (0.38 ng/mL vs 0.1 ng/mL; P =0.035). Increased serum PCT is associated with longer LOS in COPD exacerbation. However, CRP and DECAF score play limited roles in predicting clinical outcome and lack an association with causes of exacerbation.

Chest Wall Diseases: Respiratory Pathophysiology.

PubMed

Tzelepis, George E

2018-06-01

The chest wall consists of various structures that function in an integrated fashion to ventilate the lungs. Disorders affecting the bony structures or soft tissues of the chest wall may impose elastic loads by stiffening the chest wall and decreasing respiratory system compliance. These alterations increase the work of breathing and lead to hypoventilation and hypercapnia. Respiratory failure may occur acutely or after a variable period of time. This review focuses on the pathophysiology of respiratory function in specific diseases and disorders of the chest wall, and highlights pathogenic mechanisms of respiratory failure. Copyright © 2018 Elsevier Inc. All rights reserved.

Bronchiectasis: Current Concepts in Pathogenesis, Immunology, and Microbiology.

PubMed

Boyton, Rosemary J; Altmann, Daniel M

2016-05-23

Bronchiectasis is a disorder of persistent lung inflammation and recurrent infection, defined by a common pathological end point: irreversible bronchial dilatation arrived at through diverse etiologies. This suggests an interplay between immunogenetic susceptibility, immune dysregulation, bacterial infection, and lung damage. The damaged epithelium impairs mucus removal and facilitates bacterial infection with increased cough, sputum production, and airflow obstruction. Lung infection is caused by respiratory bacterial and fungal pathogens, including Pseudomonas aeruginosa, Haemophilus, Aspergillus fumigatus, and nontuberculous mycobacteria. Recent studies have highlighted the relationship between the lung microbiota and microbial-pathogen niches. Disease may result from environments favoring interleukin-17-driven neutrophilia. Bronchiectasis may present in autoimmune disease, as well as conditions of immune dysregulation, such as combined variable immune deficiency, transporter associated with antigen processing-deficiency syndrome, and hyperimmunoglobulin E syndrome. Differences in prevalence across geography and ethnicity implicate an etiological mix of genetics and environment underpinning susceptibility.

The Biology of Neisseria Adhesins

PubMed Central

Hung, Miao-Chiu; Christodoulides, Myron

2013-01-01

Members of the genus Neisseria include pathogens causing important human diseases such as meningitis, septicaemia, gonorrhoea and pelvic inflammatory disease syndrome. Neisseriae are found on the exposed epithelia of the upper respiratory tract and the urogenital tract. Colonisation of these exposed epithelia is dependent on a repertoire of diverse bacterial molecules, extending not only from the surface of the bacteria but also found within the outer membrane. During invasive disease, pathogenic Neisseriae also interact with immune effector cells, vascular endothelia and the meninges. Neisseria adhesion involves the interplay of these multiple surface factors and in this review we discuss the structure and function of these important molecules and the nature of the host cell receptors and mechanisms involved in their recognition. We also describe the current status for recently identified Neisseria adhesins. Understanding the biology of Neisseria adhesins has an impact not only on the development of new vaccines but also in revealing fundamental knowledge about human biology. PMID:24833056

Quantitative proteomics to study carbapenem resistance in Acinetobacter baumannii

PubMed Central

Tiwari, Vishvanath; Tiwari, Monalisa

2014-01-01

Acinetobacter baumannii is an opportunistic pathogen causing pneumonia, respiratory infections and urinary tract infections. The prevalence of this lethal pathogen increases gradually in the clinical setup where it can grow on artificial surfaces, utilize ethanol as a carbon source. Moreover it resists desiccation. Carbapenems, a β-lactam, are the most commonly prescribed drugs against A. baumannii. Resistance against carbapenem has emerged in Acinetobacter baumannii which can create significant health problems and is responsible for high morbidity and mortality. With the development of quantitative proteomics, a considerable progress has been made in the study of carbapenem resistance of Acinetobacter baumannii. Recent updates showed that quantitative proteomics has now emerged as an important tool to understand the carbapenem resistance mechanism in Acinetobacter baumannii. Present review also highlights the complementary nature of different quantitative proteomic methods used to study carbapenem resistance and suggests to combine multiple proteomic methods for understanding the response to antibiotics by Acinetobacter baumannii. PMID:25309531

Internet-based biosurveillance methods for vector-borne diseases: Are they novel public health tools or just novelties?

PubMed

Pollett, Simon; Althouse, Benjamin M; Forshey, Brett; Rutherford, George W; Jarman, Richard G

2017-11-01

Internet-based surveillance methods for vector-borne diseases (VBDs) using "big data" sources such as Google, Twitter, and internet newswire scraping have recently been developed, yet reviews on such "digital disease detection" methods have focused on respiratory pathogens, particularly in high-income regions. Here, we present a narrative review of the literature that has examined the performance of internet-based biosurveillance for diseases caused by vector-borne viruses, parasites, and other pathogens, including Zika, dengue, other arthropod-borne viruses, malaria, leishmaniasis, and Lyme disease across a range of settings, including low- and middle-income countries. The fundamental features, advantages, and drawbacks of each internet big data source are presented for those with varying familiarity of "digital epidemiology." We conclude with some of the challenges and future directions in using internet-based biosurveillance for the surveillance and control of VBD.

Melioidosis and glanders modulation of the innate immune system: barriers to current and future vaccine approaches.

PubMed

Aschenbroich, Sophie A; Lafontaine, Eric R; Hogan, Robert J

2016-09-01

Burkholderia pseudomallei and Burkholderia mallei are pathogenic bacteria causing fatal infections in animals and humans. Both organisms are classified as Tier 1 Select Agents owing to their highly fatal nature, potential/prior use as bioweapons, severity of disease via respiratory exposure, intrinsic resistance to antibiotics, and lack of a current vaccine. Disease manifestations range from acute septicemia to chronic infection, wherein the facultative intracellular lifestyle of these organisms promotes persistence within a broad range of hosts. This ability to thrive intracellularly is thought to be related to exploitation of host immune response signaling pathways. There are currently considerable gaps in our understanding of the molecular strategies employed by these pathogens to modulate these pathways and evade intracellular killing. A better understanding of the specific molecular basis for dysregulation of host immune responses by these organisms will provide a stronger platform to identify novel vaccine targets and develop effective countermeasures.

Internet-based biosurveillance methods for vector-borne diseases: Are they novel public health tools or just novelties?

PubMed Central

Pollett, Simon; Althouse, Benjamin M.; Forshey, Brett; Rutherford, George W.; Jarman, Richard G.

2017-01-01

Internet-based surveillance methods for vector-borne diseases (VBDs) using “big data” sources such as Google, Twitter, and internet newswire scraping have recently been developed, yet reviews on such “digital disease detection” methods have focused on respiratory pathogens, particularly in high-income regions. Here, we present a narrative review of the literature that has examined the performance of internet-based biosurveillance for diseases caused by vector-borne viruses, parasites, and other pathogens, including Zika, dengue, other arthropod-borne viruses, malaria, leishmaniasis, and Lyme disease across a range of settings, including low- and middle-income countries. The fundamental features, advantages, and drawbacks of each internet big data source are presented for those with varying familiarity of “digital epidemiology.” We conclude with some of the challenges and future directions in using internet-based biosurveillance for the surveillance and control of VBD. PMID:29190281

Climate Change and Respiratory Infections.

PubMed

Mirsaeidi, Mehdi; Motahari, Hooman; Taghizadeh Khamesi, Mojdeh; Sharifi, Arash; Campos, Michael; Schraufnagel, Dean E

2016-08-01

The rate of global warming has accelerated over the past 50 years. Increasing surface temperature is melting glaciers and raising the sea level. More flooding, droughts, hurricanes, and heat waves are being reported. Accelerated changes in climate are already affecting human health, in part by altering the epidemiology of climate-sensitive pathogens. In particular, climate change may alter the incidence and severity of respiratory infections by affecting vectors and host immune responses. Certain respiratory infections, such as avian influenza and coccidioidomycosis, are occurring in locations previously unaffected, apparently because of global warming. Young children and older adults appear to be particularly vulnerable to rapid fluctuations in ambient temperature. For example, an increase in the incidence in childhood pneumonia in Australia has been associated with sharp temperature drops from one day to the next. Extreme weather events, such as heat waves, floods, major storms, drought, and wildfires, are also believed to change the incidence of respiratory infections. An outbreak of aspergillosis among Japanese survivors of the 2011 tsunami is one such well-documented example. Changes in temperature, precipitation, relative humidity, and air pollution influence viral activity and transmission. For example, in early 2000, an outbreak of Hantavirus respiratory disease was linked to a local increase in the rodent population, which in turn was attributed to a two- to threefold increase in rainfall before the outbreak. Climate-sensitive respiratory pathogens present challenges to respiratory health that may be far greater in the foreseeable future.

Expanding severe acute respiratory infection (SARI) surveillance beyond influenza: The process and data from 1 year of implementation in Vietnam.

PubMed

Alroy, Karen A; Do, Trang Thuy; Tran, Phu Dac; Dang, Tan Quang; Vu, Long Ngoc; Le, Nga Thi Hang; Dang, Anh Duc; Ngu, Nghia Duy; Ngo, Tu Huy; Hoang, Phuong Vu Mai; Phan, Lan Trong; Nguyen, Thuong Vu; Nguyen, Long Thanh; Nguyen, Thinh Viet; Vien, Mai Quang; Le, Huy Xuan; Dao, Anh The; Nguyen, Trieu Bao; Pham, Duoc Tho; Nguyen, Van Thi Tuyet; Pham, Thanh Ngoc; Phan, Binh Hai; Whitaker, Brett; Do, Thuy Thi Thu; Dao, Phuong Anh; Balajee, S Arunmozhi; Mounts, Anthony W

2018-05-13

In 2016, as a component of the Global Health Security Agenda, the Vietnam Ministry of Health expanded its existing influenza sentinel surveillance for severe acute respiratory infections (SARI) to include testing for 7 additional viral respiratory pathogens. This article describes the steps taken to implement expanded SARI surveillance in Vietnam and reports data from 1 year of expanded surveillance. The process of expanding the suite of pathogens for routine testing by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) included laboratory trainings, procurement/distribution of reagents, and strengthening and aligning SARI surveillance epidemiology practices at sentinel sites and regional institutes (RI). Surveillance data showed that of 4003 specimens tested by the RI laboratories, 20.2% (n = 810) were positive for influenza virus. Of the 3193 influenza-negative specimens, 41.8% (n = 1337) were positive for at least 1 non-influenza respiratory virus, of which 16.2% (n = 518), 13.4% (n = 428), and 9.6% (n = 308) tested positive for respiratory syncytial virus, rhinovirus, and adenovirus, respectively. The Government of Vietnam has demonstrated that expanding respiratory viral surveillance by strengthening and building upon an influenza platform is feasible, efficient, and practical. © 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Induction of influenza-specific local CD8 T-cells in the respiratory tract after aerosol delivery of vaccine antigen or virus in the Babraham inbred pig.

PubMed

Tungatt, Katie; Dolton, Garry; Morgan, Sophie B; Attaf, Meriem; Fuller, Anna; Whalley, Thomas; Hemmink, Johanneke D; Porter, Emily; Szomolay, Barbara; Montoya, Maria; Hammond, John A; Miles, John J; Cole, David K; Townsend, Alain; Bailey, Mick; Rizkallah, Pierre J; Charleston, Bryan; Tchilian, Elma; Sewell, Andrew K

2018-05-01

There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume. It may also be an important vector in the birds to human infection cycle. A major drawback of the current pig model is the inability to analyze antigen-specific CD8+ T-cell responses, which are critical to respiratory immunity. Here we address this knowledge gap using an established in-bred pig model with a high degree of genetic identity between individuals, including the MHC (Swine Leukocyte Antigen (SLA)) locus. We developed a toolset that included long-term in vitro pig T-cell culture and cloning and identification of novel immunodominant influenza-derived T-cell epitopes. We also generated structures of the two SLA class I molecules found in these animals presenting the immunodominant epitopes. These structures allowed definition of the primary anchor points for epitopes in the SLA binding groove and established SLA binding motifs that were used to successfully predict other influenza-derived peptide sequences capable of stimulating T-cells. Peptide-SLA tetramers were constructed and used to track influenza-specific T-cells ex vivo in blood, the lungs and draining lymph nodes. Aerosol immunization with attenuated single cycle influenza viruses (S-FLU) induced large numbers of CD8+ T-cells specific for conserved NP peptides in the respiratory tract. Collectively, these data substantially increase the utility of pigs as an effective model for studying protective local cellular immunity against respiratory pathogens.

Induction of influenza-specific local CD8 T-cells in the respiratory tract after aerosol delivery of vaccine antigen or virus in the Babraham inbred pig

PubMed Central

Morgan, Sophie B.; Attaf, Meriem; Szomolay, Barbara; Miles, John J.; Townsend, Alain; Bailey, Mick; Charleston, Bryan; Tchilian, Elma

2018-01-01

There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume. It may also be an important vector in the birds to human infection cycle. A major drawback of the current pig model is the inability to analyze antigen-specific CD8+ T-cell responses, which are critical to respiratory immunity. Here we address this knowledge gap using an established in-bred pig model with a high degree of genetic identity between individuals, including the MHC (Swine Leukocyte Antigen (SLA)) locus. We developed a toolset that included long-term in vitro pig T-cell culture and cloning and identification of novel immunodominant influenza-derived T-cell epitopes. We also generated structures of the two SLA class I molecules found in these animals presenting the immunodominant epitopes. These structures allowed definition of the primary anchor points for epitopes in the SLA binding groove and established SLA binding motifs that were used to successfully predict other influenza-derived peptide sequences capable of stimulating T-cells. Peptide-SLA tetramers were constructed and used to track influenza-specific T-cells ex vivo in blood, the lungs and draining lymph nodes. Aerosol immunization with attenuated single cycle influenza viruses (S-FLU) induced large numbers of CD8+ T-cells specific for conserved NP peptides in the respiratory tract. Collectively, these data substantially increase the utility of pigs as an effective model for studying protective local cellular immunity against respiratory pathogens. PMID:29772011

Emerging treatment options for acute bacterial skin and skin structure infections: focus on intravenous delafloxacin

PubMed Central

Righi, Elda; Carnelutti, Alessia; Vena, Antonio; Bassetti, Matteo

2018-01-01

The increase in hospitalization due to acute bacterial skin and skin structure infections (ABSSSI) caused by resistant pathogens supports the need for new treatment options. Antimicrobial options for ABSSSI that provide broad-spectrum coverage, including gram-negative pathogens and multidrug-resistant gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are limited. Delafloxacin is a novel fluoroquinolone available as intravenous and oral formulations and is characterized by an increased efficacy in acidic environments and activity on bacterial biofilm. Delafloxacin displays enhanced in vitro activity against MRSA, and enterococci, while maintaining efficacy against gram-negative pathogens and anaerobes. Delafloxacin has been studied for the treatment of ABSSSI and respiratory infections. Phase III studies have demonstrated noninferiority of delafloxacin compared to vancomycin, linezolid, tigecycline, and the combination of vancomycin plus aztreonam in the treatment of ABSSSI. Due to its favorable pharmacokinetic characteristics, the wide spectrum of action, and the potential for sequential therapy, delafloxacin represents a promising option in the empirical and targeted treatment of ABSSSI, both in hospital- and in community-based care. PMID:29670380

Emerging treatment options for acute bacterial skin and skin structure infections: focus on intravenous delafloxacin.

PubMed

Righi, Elda; Carnelutti, Alessia; Vena, Antonio; Bassetti, Matteo

2018-01-01

The increase in hospitalization due to acute bacterial skin and skin structure infections (ABSSSI) caused by resistant pathogens supports the need for new treatment options. Antimicrobial options for ABSSSI that provide broad-spectrum coverage, including gram-negative pathogens and multidrug-resistant gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are limited. Delafloxacin is a novel fluoroquinolone available as intravenous and oral formulations and is characterized by an increased efficacy in acidic environments and activity on bacterial biofilm. Delafloxacin displays enhanced in vitro activity against MRSA, and enterococci, while maintaining efficacy against gram-negative pathogens and anaerobes. Delafloxacin has been studied for the treatment of ABSSSI and respiratory infections. Phase III studies have demonstrated noninferiority of delafloxacin compared to vancomycin, linezolid, tigecycline, and the combination of vancomycin plus aztreonam in the treatment of ABSSSI. Due to its favorable pharmacokinetic characteristics, the wide spectrum of action, and the potential for sequential therapy, delafloxacin represents a promising option in the empirical and targeted treatment of ABSSSI, both in hospital- and in community-based care.

A BSL-4 high-throughput screen identifies sulfonamide inhibitors of Nipah virus.

PubMed

Tigabu, Bersabeh; Rasmussen, Lynn; White, E Lucile; Tower, Nichole; Saeed, Mohammad; Bukreyev, Alexander; Rockx, Barry; LeDuc, James W; Noah, James W

2014-04-01

Nipah virus is a biosafety level 4 (BSL-4) pathogen that causes severe respiratory illness and encephalitis in humans. To identify novel small molecules that target Nipah virus replication as potential therapeutics, Southern Research Institute and Galveston National Laboratory jointly developed an automated high-throughput screening platform that is capable of testing 10,000 compounds per day within BSL-4 biocontainment. Using this platform, we screened a 10,080-compound library using a cell-based, high-throughput screen for compounds that inhibited the virus-induced cytopathic effect. From this pilot effort, 23 compounds were identified with EC50 values ranging from 3.9 to 20.0 μM and selectivities >10. Three sulfonamide compounds with EC50 values <12 μM were further characterized for their point of intervention in the viral replication cycle and for broad antiviral efficacy. Development of HTS capability under BSL-4 containment changes the paradigm for drug discovery for highly pathogenic agents because this platform can be readily modified to identify prophylactic and postexposure therapeutic candidates against other BSL-4 pathogens, particularly Ebola, Marburg, and Lassa viruses.

A BSL-4 High-Throughput Screen Identifies Sulfonamide Inhibitors of Nipah Virus

PubMed Central

Tigabu, Bersabeh; Rasmussen, Lynn; White, E. Lucile; Tower, Nichole; Saeed, Mohammad; Bukreyev, Alexander; Rockx, Barry; LeDuc, James W.

2014-01-01

Abstract Nipah virus is a biosafety level 4 (BSL-4) pathogen that causes severe respiratory illness and encephalitis in humans. To identify novel small molecules that target Nipah virus replication as potential therapeutics, Southern Research Institute and Galveston National Laboratory jointly developed an automated high-throughput screening platform that is capable of testing 10,000 compounds per day within BSL-4 biocontainment. Using this platform, we screened a 10,080-compound library using a cell-based, high-throughput screen for compounds that inhibited the virus-induced cytopathic effect. From this pilot effort, 23 compounds were identified with EC50 values ranging from 3.9 to 20.0 μM and selectivities >10. Three sulfonamide compounds with EC50 values <12 μM were further characterized for their point of intervention in the viral replication cycle and for broad antiviral efficacy. Development of HTS capability under BSL-4 containment changes the paradigm for drug discovery for highly pathogenic agents because this platform can be readily modified to identify prophylactic and postexposure therapeutic candidates against other BSL-4 pathogens, particularly Ebola, Marburg, and Lassa viruses. PMID:24735442

Protective immunity against H7N3 highly pathogenic avian influenza induced following inoculation of chickens with H7 low pathogenic avian influenza virus

USDA-ARS?s Scientific Manuscript database

In the poultry industry, live virus vaccines are used to induce immunity against numerous respiratory pathogens. These are typically lower virulent forms of virus which are limited in replication and pathology, but induce mucosal, humoral, and cellular immunity. Because of the potential for revers...

[Immunomodulators in Therapy of Respiratory Infections].

PubMed

Isakov, V A; Isakov, D V

2014-01-01

Viral infections provoke dysbalance in the interferon system and inhibition of the cellular and phagocytic responses of the host. Long-term persistence of pathogenic viruses and bacteria induce atopy and could aggravate chronic respiratory diseases. The up-to-date classification of immunomodulators is described. High efficacy of interferon inductors, such as cycloferon and some others as auxiliary means in therapy or prophylaxis (immunorehabilitation) of viral respiratory infections in adults and children was shown.

Is there a genetic solution to bovine respiratory disease complex?

USDA-ARS?s Scientific Manuscript database

Bovine respiratory disease complex (BRDC) is a complex multi-factor disease, which increases costs and reduces revenue from feedlot cattle. Multiple stressors and pathogens (viral and bacterial) have been implicated in the etiology of BRDC, therefore multiple approaches will be needed to evaluate a...

Influenza A virus pathogenesis and vaccination in swine

USDA-ARS?s Scientific Manuscript database

Swine influenza is an acute respiratory disease of pigs that is characterized by fever followed by lethargy, anorexia, and serous nasal discharge. The disease progresses rapidly and may be complicated when associated with other respiratory pathogens. Influenza A virus (IAV) is one of the most preval...

Stenotrophomonas maltophilia: an Emerging Global Opportunistic Pathogen

PubMed Central

2012-01-01

Summary: Stenotrophomonas maltophilia is an emerging multidrug-resistant global opportunistic pathogen. The increasing incidence of nosocomial and community-acquired S. maltophilia infections is of particular concern for immunocompromised individuals, as this bacterial pathogen is associated with a significant fatality/case ratio. S. maltophilia is an environmental bacterium found in aqueous habitats, including plant rhizospheres, animals, foods, and water sources. Infections of S. maltophilia can occur in a range of organs and tissues; the organism is commonly found in respiratory tract infections. This review summarizes the current literature and presents S. maltophilia as an organism with various molecular mechanisms used for colonization and infection. S. maltophilia can be recovered from polymicrobial infections, most notably from the respiratory tract of cystic fibrosis patients, as a cocolonizer with Pseudomonas aeruginosa. Recent evidence of cell-cell communication between these pathogens has implications for the development of novel pharmacological therapies. Animal models of S. maltophilia infection have provided useful information about the type of host immune response induced by this opportunistic pathogen. Current and emerging treatments for patients infected with S. maltophilia are discussed. PMID:22232370

Respiratory Tract Infections and the Role of Biologically Active Polysaccharides in Their Management and Prevention

PubMed Central

Jesenak, Milos; Urbancikova, Ingrid; Banovcin, Peter

2017-01-01

Respiratory tract infections (RTIs) are the most common form of infections in every age category. Recurrent respiratory tract infections (RRTIs), a specific form of RTIs, represent a typical and common problem associated with early childhood, causing high indirect and direct costs on the healthcare system. They are usually the consequence of immature immunity in children and high exposure to various respiratory pathogens. Their rational management should aim at excluding other severe chronic diseases associated with increased morbidity (e.g., primary immunodeficiency syndromes, cystic fibrosis, and ciliary dyskinesia) and at supporting maturity of the mucosal immune system. However, RRTIs can also be observed in adults (e.g., during exhausting and stressful periods, chronic inflammatory diseases, secondary immunodeficiencies, or in elite athletes) and require greater attention. Biologically active polysaccharides (e.g., β-glucans) are one of the most studied natural immunomodulators with a pluripotent mode of action and biological activity. According to many studies, they possess immunomodulatory, anti-inflammatory, and anti-infectious activities and therefore could be suggested as an effective part of treating and preventing RTIs. Based on published studies, the application of β-glucans was proven as a possible therapeutic and preventive approach in managing and preventing recurrent respiratory tract infections in children (especially β-glucans from Pleurotus ostreatus), adults (mostly the studies with yeast-derived β-glucans), and in elite athletes (studies with β-glucans from Pleurotus ostreatus or yeast). PMID:28726737

The Use of Kosher Phenotyping for Mapping QTL Affecting Susceptibility to Bovine Respiratory Disease

PubMed Central

Eitam, Harel; Yishay, Moran; Schiavini, Fausta; Soller, Morris; Bagnato, Alessandro; Shabtay, Ariel

2016-01-01

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in feedlot cattle, caused by multiple pathogens that become more virulent in response to stress. As clinical signs often go undetected and various preventive strategies failed, identification of genes affecting BRD is essential for selection for resistance. Selective DNA pooling (SDP) was applied in a genome wide association study (GWAS) to map BRD QTLs in Israeli Holstein male calves. Kosher scoring of lung adhesions was used to allocate 122 and 62 animals to High (Glatt Kosher) and Low (Non-Kosher) resistant groups, respectively. Genotyping was performed using the Illumina BovineHD BeadChip according to the Infinium protocol. Moving average of -logP was used to map QTLs and Log drop was used to define their boundaries (QTLRs). The combined procedure was efficient for high resolution mapping. Nineteen QTLRs distributed over 13 autosomes were found, some overlapping previous studies. The QTLRs contain polymorphic functional and expression candidate genes to affect kosher status, with putative immunological and wound healing activities. Kosher phenotyping was shown to be a reliable means to map QTLs affecting BRD morbidity. PMID:27077383

Bovine herpes virus-1 (BoHV-1) in cattle–a review with emphasis on reproductive impacts and the emergence of infection in Ireland and the United Kingdom

PubMed Central

2013-01-01

Bovine reproductive disease attributable to bovine herpes virus-1 (BoHV-1) was first described in Germany in the 19th century, being recognised primarily as the cause of infectious vulvovaginitis and balanoposthitis until the mid-1950s when a more virulent strain of the virus (BoHV-1.1) associated with respiratory disease (infectious bovine rhinotracheitis; IBR) emerged in the western United States. Subsequently, IBR emerged as a clinical condition in Europe, from the 1970s onward. While the ability of BoHV-1 to produce respiratory disease is now well recognised, the potential negative outcomes of infection on fertility and reproduction are less frequently considered. This review was conducted against the background of the prioritization of disease caused by BoHV-1 as one of several diseases to be addressed by Animal Health Ireland, with the twin goals of summarizing the published literature on the potential outcomes of infection at different stages of breeding and pregnancy, and of describing the emergence of BoHV-1 as a significant pathogen in Ireland and the UK. PMID:23916092

Aloe vera enhances the innate immune response of pacu (Piaractus mesopotamicus) after transport stress and combined heat killed Aeromonas hydrophila infection.

PubMed

Zanuzzo, Fábio S; Sabioni, Rafael E; Montoya, Luz Natalia F; Favero, Gisele; Urbinati, Elisabeth C

2017-06-01

In this study, pacu (Piaractus mesopotamicus) were fed with diets containing Aloe vera for 10 days prior to transport stress and infection with heat killed Aeromonas hydrophila. A. vera is popular around the world due to its medicinal properties, including immunostimulatory effects which was observed in this study. The results show that transport causes immunosuppression, an effect that was prevented by A. vera. Specifically, A. vera prevented reductions of both leukocyte respiratory burst and hemolytic activity of complement system caused by transport. Further, fish fed with A. vera also showed significantly higher leukocyte respiratory burst, serum lysozyme concentrations and activity of complement system 24 h after bacterial infection. Additionally, we observed that A. vera may modulate the innate response through activation of complement system during bacterial immune stimulation. In summary, A. vera extract enhanced innate immune parameters and consequently the ability of fish to cope with pathogens following transport stress. These findings show that A. vera has promise for use in aquaculture and add further evidence that medicinal herbs added to fish feed assist to prevent disease outbreaks. Copyright © 2017 Elsevier Ltd. All rights reserved.

c-di-GMP enhances protective innate immunity in a murine model of pertussis.

PubMed

Elahi, Shokrollah; Van Kessel, Jill; Kiros, Tedele G; Strom, Stacy; Hayakawa, Yoshihiro; Hyodo, Mamoru; Babiuk, Lorne A; Gerdts, Volker

2014-01-01

Innate immunity represents the first line of defense against invading pathogens in the respiratory tract. Innate immune cells such as monocytes, macrophages, dendritic cells, NK cells, and granulocytes contain specific pathogen-recognition molecules which induce the production of cytokines and subsequently activate the adaptive immune response. c-di-GMP is a ubiquitous second messenger that stimulates innate immunity and regulates biofilm formation, motility and virulence in a diverse range of bacterial species with potent immunomodulatory properties. In the present study, c-di-GMP was used to enhance the innate immune response against pertussis, a respiratory infection mainly caused by Bordetella pertussis. Intranasal treatment with c-di-GMP resulted in the induction of robust innate immune responses to infection with B. pertussis characterized by enhanced recruitment of neutrophils, macrophages, natural killer cells and dendritic cells. The immune responses were associated with an earlier and more vigorous expression of Th1-type cytokines, as well as an increase in the induction of nitric oxide in the lungs of treated animals, resulting in significant reduction of bacterial numbers in the lungs of infected mice. These results demonstrate that c-di-GMP is a potent innate immune stimulatory molecule that can be used to enhance protection against bacterial respiratory infections. In addition, our data suggest that priming of the innate immune system by c-di-GMP could further skew the immune response towards a Th1 type phenotype during subsequent infection. Thus, our data suggest that c-di-GMP might be useful as an adjuvant for the next generation of acellular pertussis vaccine to mount a more protective Th1 phenotype immune response, and also in other systems where a Th1 type immune response is required.

c-di-GMP Enhances Protective Innate Immunity in a Murine Model of Pertussis

PubMed Central

Elahi, Shokrollah; Van Kessel, Jill; Kiros, Tedele G.; Strom, Stacy; Hayakawa, Yoshihiro; Hyodo, Mamoru; Babiuk, Lorne A.; Gerdts, Volker

2014-01-01

Innate immunity represents the first line of defense against invading pathogens in the respiratory tract. Innate immune cells such as monocytes, macrophages, dendritic cells, NK cells, and granulocytes contain specific pathogen-recognition molecules which induce the production of cytokines and subsequently activate the adaptive immune response. c-di-GMP is a ubiquitous second messenger that stimulates innate immunity and regulates biofilm formation, motility and virulence in a diverse range of bacterial species with potent immunomodulatory properties. In the present study, c-di-GMP was used to enhance the innate immune response against pertussis, a respiratory infection mainly caused by Bordetella pertussis. Intranasal treatment with c-di-GMP resulted in the induction of robust innate immune responses to infection with B. pertussis characterized by enhanced recruitment of neutrophils, macrophages, natural killer cells and dendritic cells. The immune responses were associated with an earlier and more vigorous expression of Th1-type cytokines, as well as an increase in the induction of nitric oxide in the lungs of treated animals, resulting in significant reduction of bacterial numbers in the lungs of infected mice. These results demonstrate that c-di-GMP is a potent innate immune stimulatory molecule that can be used to enhance protection against bacterial respiratory infections. In addition, our data suggest that priming of the innate immune system by c-di-GMP could further skew the immune response towards a Th1 type phenotype during subsequent infection. Thus, our data suggest that c-di-GMP might be useful as an adjuvant for the next generation of acellular pertussis vaccine to mount a more protective Th1 phenotype immune response, and also in other systems where a Th1 type immune response is required. PMID:25333720

Investigation of antibacterial activities of Albizia gummifera and Ferula communis on Streptococcus pneumoniae and Streptoccus pyogenes.

PubMed

Unasho, Abayneh; Geyid, Aberra; Melaku, Abebe; Debela, Asfaw; Mekasha, Amha; Girma, Samson; Kebede, Tesfaye; Fantaw, Surafael; Asaminew, Nega; Mamo, Kidanemariam

2009-01-01

Respiratory Tract infections continue to be a major cause of morbidity and mortality world wide. There is a failure to treat respiratory infections due to the emergence of antibiotic resistant strains among the most common respiratory pathogens. To evaluate the in vitro antibacterial activities of two traditionally used plants: Albizia gummifera (Ambabesa-Muka, Oromifa, Sessa-Amharic.) and Ferula communis (Doge-Oromifa, Dog-Amharic) against clinical isolates of S. pyogenes and S. pneumoniae. The study involving the antibacterial susceptibility test of traditionally used plant species against Gram-positive bacterial pathogens was conducted over a period of 5 months (January - August, 2004) at the Ethiopian Health, and Nutrition Research Institute. The in vitro antibacterial activities of 80% methanol crude extracts prepared from the seeds of Ablizia gummifera and, roots of Ferula communis as well as their respective hydro alcoholic solvent fractionates of both plant species were tested for inhibitory activity against the clinical isolates of six S. pneumonae and twenty two S. pyogenes using agar dilution method. Eighty percent ethanol solubilized fractions of both plants were found to have antibacterial effects to all assayed bacteria while aqueous solubilized fractions did not exhibit any effect. Minimum inhibitory concentration (MIC) of the 80% ethanol solubilized fractions was determined and the MIC of the fractions ranged from 500 mg/ ml to 1000 mg/ml for both plants showing the extracts may contain bioactive compounds of therapeutic interest. All extracts showed antibacterial activities against clinical isolates of S. pyogenes and S. pneumoniae. The extracts may contain compounds with potential therapeutic activity. Further purification and identification are needed to be tested using animal models.

GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization.

PubMed

Halstead, E Scott; Umstead, Todd M; Davies, Michael L; Kawasawa, Yuka Imamura; Silveyra, Patricia; Howyrlak, Judie; Yang, Linlin; Guo, Weichao; Hu, Sanmei; Hewage, Eranda Kurundu; Chroneos, Zissis C

2018-01-05

Influenza A viruses cause life-threatening pneumonia and lung injury in the lower respiratory tract. Application of high GM-CSF levels prior to infection has been shown to reduce morbidity and mortality from pathogenic influenza infection in mice, but the mechanisms of protection and treatment efficacy have not been established. Mice were infected intranasally with influenza A virus (PR8 strain). Supra-physiologic levels of GM-CSF were induced in the airways using the double transgenic GM-CSF (DTGM) or littermate control mice starting on 3 days post-infection (dpi). Assessment of respiratory mechanical parameters was performed using the flexiVent rodent ventilator. RNA sequence analysis was performed on FACS-sorted airway macrophage subsets at 8 dpi. Supra-physiologic levels of GM-CSF conferred a survival benefit, arrested the deterioration of lung mechanics, and reduced the abundance of protein exudates in bronchoalveolar (BAL) fluid to near baseline levels. Transcriptome analysis, and subsequent validation ELISA assays, revealed that excess GM-CSF re-directs macrophages from an "M1-like" to a more "M2-like" activation state as revealed by alterations in the ratios of CXCL9 and CCL17 in BAL fluid, respectively. Ingenuity pathway analysis predicted that GM-CSF surplus during IAV infection elicits expression of anti-inflammatory mediators and moderates M1 macrophage pro-inflammatory signaling by Type II interferon (IFN-γ). Our data indicate that application of high levels of GM-CSF in the lung after influenza A virus infection alters pathogenic "M1-like" macrophage inflammation. These results indicate a possible therapeutic strategy for respiratory virus-associated pneumonia and acute lung injury.

Genome Expression Profiling-Based Identification and Administration Efficacy of Host-Directed Antimicrobial Drugs against Respiratory Infection by Nontypeable Haemophilus influenzae

PubMed Central

Euba, Begoña; Moleres, Javier; Segura, Víctor; Viadas, Cristina; Morey, Pau; Moranta, David; Leiva, José; de-Torres, Juan Pablo; Bengoechea, José Antonio

2015-01-01

Therapies that are safe, effective, and not vulnerable to developing resistance are highly desirable to counteract bacterial infections. Host-directed therapeutics is an antimicrobial approach alternative to conventional antibiotics based on perturbing host pathways subverted by pathogens during their life cycle by using host-directed drugs. In this study, we identified and evaluated the efficacy of a panel of host-directed drugs against respiratory infection by nontypeable Haemophilus influenzae (NTHi). NTHi is an opportunistic pathogen that is an important cause of exacerbation of chronic obstructive pulmonary disease (COPD). We screened for host genes differentially expressed upon infection by the clinical isolate NTHi375 by analyzing cell whole-genome expression profiling and identified a repertoire of host target candidates that were pharmacologically modulated. Based on the proposed relationship between NTHi intracellular location and persistence, we hypothesized that drugs perturbing host pathways used by NTHi to enter epithelial cells could have antimicrobial potential against NTHi infection. Interfering drugs were tested for their effects on bacterial and cellular viability, on NTHi-epithelial cell interplay, and on mouse pulmonary infection. Glucocorticoids and statins lacked in vitro and/or in vivo efficacy. Conversely, the sirtuin-1 activator resveratrol showed a bactericidal effect against NTHi, and the PDE4 inhibitor rolipram showed therapeutic efficacy by lowering NTHi375 counts intracellularly and in the lungs of infected mice. PDE4 inhibition is currently prescribed in COPD, and resveratrol is an attractive geroprotector for COPD treatment. Together, these results expand our knowledge of NTHi-triggered host subversion and frame the antimicrobial potential of rolipram and resveratrol against NTHi respiratory infection. PMID:26416856

Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection

PubMed Central

Euba, Begoña; Moleres, Javier; Viadas, Cristina; Barberán, Montserrat; Caballero, Lucía; Grilló, María-Jesús; Bengoechea, José Antonio; de-Torres, Juan Pablo; Liñares, Josefina; Leiva, José

2015-01-01

Nontypeable Haemophilus influenzae (NTHI) is an opportunistic pathogen that is an important cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). COPD is an inflammatory disease of the airways, and exacerbations are acute inflammatory events superimposed on this background of chronic inflammation. Azithromycin (AZM) is a macrolide antibiotic with antibacterial and anti-inflammatory properties and a clinically proven potential for AECOPD prevention and management. Relationships between AZM efficacy and resistance by NTHI and between bactericidal and immunomodulatory effects on NTHI respiratory infection have not been addressed. In this study, we employed two pathogenic NTHI strains with different AZM susceptibilities (NTHI 375 [AZM susceptible] and NTHI 353 [AZM resistant]) to evaluate the prophylactic and therapeutic effects of AZM on the NTHI-host interplay. At the cellular level, AZM was bactericidal toward intracellular NTHI inside alveolar and bronchial epithelia and alveolar macrophages, and it enhanced NTHI phagocytosis by the latter cell type. These effects correlated with the strain MIC of AZM and the antibiotic dose. Additionally, the effect of AZM on NTHI infection was assessed in a mouse model of pulmonary infection. AZM showed both preventive and therapeutic efficacies by lowering NTHI 375 bacterial counts in lungs and bronchoalveolar lavage fluid (BALF) and by reducing histopathological inflammatory lesions in the upper and lower airways of mice. Conversely, AZM did not reduce bacterial loads in animals infected with NTHI 353, in which case a milder anti-inflammatory effect was also observed. Together, the results of this work link the bactericidal and anti-inflammatory effects of AZM and frame the efficacy of this antibiotic against NTHI respiratory infection. PMID:25712355

Enrofloxacin and Macrolides Alone or in Combination with Rifampicin as Antimicrobial Treatment in a Bovine Model of Acute Chlamydia psittaci Infection

PubMed Central

Prohl, Annette; Lohr, Markus; Ostermann, Carola; Liebler-Tenorio, Elisabeth; Berndt, Angela; Schroedl, Wieland; Rothe, Michael; Schubert, Evelyn; Sachse, Konrad; Reinhold, Petra

2015-01-01

Chlamydia psittaci is a zoonotic bacterium with a wide host range that can cause respiratory disease in humans and cattle. In the present study, effects of treatment with macrolides and quinolones applied alone or in combination with rifampicin were tested in a previously established bovine model of respiratory C. psittaci infection. Fifty animals were inoculated intrabronchially at the age of 6–8 weeks. Seven served as untreated controls, the others were assigned to seven treatment groups: (i) rifampicin, (ii) enrofloxacin, (iii) enrofloxacin + rifampicin, (iv) azithromycin, (v) azithromycin + rifampicin, (vi) erythromycin, and (vii) erythromycin + rifampicin. Treatment started 30 hours after inoculation and continued until 14 days after inoculation (dpi), when all animals were necropsied. The infection was successful in all animals and sufficient antibiotic levels were detected in blood plasma and tissue of the treated animals. Reisolation of the pathogen was achieved more often from untreated animals than from other groups. Nevertheless, pathogen detection by PCR was possible to the same extent in all animals and there were no significant differences between treated and untreated animals in terms of local (i.e. cell count and differentiation of BALF-cells) and systemic inflammation (i.e. white blood cells and concentration of acute phase protein LBP), clinical signs, and pathological findings at necropsy. Regardless of the reduced reisolation rate in treated animals, the treatment of experimentally induced respiratory C. psittaci infection with enrofloxacin, azithromycin or erythromycin alone or in combination with rifampicin was without obvious benefit for the host, since no significant differences in clinical and pathological findings or inflammatory parameters were detected and all animals recovered clinically within two weeks. PMID:25768665

Inactivation dynamics of 222 nm krypton-chlorine excilamp irradiation on Gram-positive and Gram-negative foodborne pathogenic bacteria.

PubMed

Kang, Jun-Won; Kim, Sang-Soon; Kang, Dong-Hyun

2018-07-01

The object of this study was to elucidate the bactericidal mechanism of a 222 nm Krypton Chlorine (KrCl) excilamp compared with that of a 254 nm Low Pressure mercury (LP Hg) lamp. The KrCl excilamp had higher bactericidal capacity against Gram-positive pathogenic bacteria (Staphylococcus aureus and L. monocytogenes) and Gram-negative pathogenic bacteria (S. Typhimurium and E. coli O157:H7) than did the LP Hg lamp when cell suspensions in PBS were irradiated with each type of UV lamp. It was found out that the KrCl excilamp induced cell membrane damage as a form of depolarization. From the study of respiratory chain dehydrogenase activity and the lipid peroxidation assay, it was revealed that cell membrane damage was attributed to inactivation of enzymes related to generation of membrane potential and occurrence of lipid peroxidation. Direct absorption of UV radiation which led to photoreaction through formation of an excited state was one of the causes inducing cell damage. Additionally, generation of ROS and thus occurrence of secondary damage can be another cause. The LP Hg lamp only induced damage to DNA but not to other components such as lipids or proteins. This difference was derived from differences of UV radiation absorption by cellular materials. Copyright © 2018 Elsevier Ltd. All rights reserved.

Delafloxacin for the treatment of respiratory and skin infections.

PubMed

Bassetti, Matteo; Della Siega, Paola; Pecori, Davide; Scarparo, Claudio; Righi, Elda

2015-03-01

There has been a striking increase in the emergence of multidrug-resistant pathogens in recent times. Delafloxacin is a novel, broad-spectrum fluoroquinolone with antimicrobial activity against resistant Gram-positive, Gram-negative and anaerobic organisms. It has the potential to treat a variety of infections including complicated skin and skin structure infections and respiratory tract infections. In this review, the authors report the microbiological spectrum of activity of delafloxacin as well as its pharmacokinetic characteristics. They also report the results of recent studies investigating its safety and efficacy. The profile of delafloxacin offers several advantages. Delafloxacin presents a broad spectrum of activity against pathogens involved in respiratory infections and complicated skin and skin structure infections (SSSIs), including methicillin-resistant Staphylococcus aureus. It has also shown activity against Gram-negative pathogens, such as quinolone-susceptible and -resistant strains of Escherichia coli and Klebsiella pneumoniae and quinolone-susceptible Pseudomonas aeruginosa. The availability of an oral formulation supports its use in sequential therapy. The efficacy and tolerability of delafloxacin have been demonstrated in Phase II clinical trials in comparison with moxifloxacin for respiratory infections and linezolid and vancomycin in SSSIs. Compared with other quinolones such as moxifloxacin, delafloxacin showed comparable efficacy and a lower rate of adverse effects. The results of new Phase III studies are awaited to confirm delafloxacin's future applications in the treatment of SSSIs.

Nuclear factors involved in mitochondrial translation cause a subgroup of combined respiratory chain deficiency.

PubMed

Kemp, John P; Smith, Paul M; Pyle, Angela; Neeve, Vivienne C M; Tuppen, Helen A L; Schara, Ulrike; Talim, Beril; Topaloglu, Haluk; Holinski-Feder, Elke; Abicht, Angela; Czermin, Birgit; Lochmüller, Hanns; McFarland, Robert; Chinnery, Patrick F; Chrzanowska-Lightowlers, Zofia M A; Lightowlers, Robert N; Taylor, Robert W; Horvath, Rita

2011-01-01

Mutations in several mitochondrial DNA and nuclear genes involved in mitochondrial protein synthesis have recently been reported in combined respiratory chain deficiency, indicating a generalized defect in mitochondrial translation. However, the number of patients with pathogenic mutations is small, implying that nuclear defects of mitochondrial translation are either underdiagnosed or intrauterine lethal. No comprehensive studies have been reported on large cohorts of patients with combined respiratory chain deficiency addressing the role of nuclear genes affecting mitochondrial protein synthesis to date. We investigated a cohort of 52 patients with combined respiratory chain deficiency without causative mitochondrial DNA mutations, rearrangements or depletion, to determine whether a defect in mitochondrial translation defines the pathomechanism of their clinical disease. We followed a combined approach of sequencing known nuclear genes involved in mitochondrial protein synthesis (EFG1, EFTu, EFTs, MRPS16, TRMU), as well as performing in vitro functional studies in 22 patient cell lines. The majority of our patients were children (<15 years), with an early onset of symptoms <1 year of age (65%). The most frequent clinical presentation was mitochondrial encephalomyopathy (63%); however, a number of patients showed cardiomyopathy (33%), isolated myopathy (15%) or hepatopathy (13%). Genomic sequencing revealed compound heterozygous mutations in the mitochondrial transfer ribonucleic acid modifying factor (TRMU) in a single patient only, presenting with early onset, reversible liver disease. No pathogenic mutation was detected in any of the remaining 51 patients in the other genes analysed. In vivo labelling of mitochondrial polypeptides in 22 patient cell lines showed overall (three patients) or selective (four patients) defects of mitochondrial translation. Immunoblotting for mitochondrial proteins revealed decreased steady state levels of proteins in some patients, but normal or increased levels in others, indicating a possible compensatory mechanism. In summary, candidate gene sequencing in this group of patients has a very low detection rate (1/52), although in vivo labelling of mitochondrial translation in 22 patient cell lines indicate that a nuclear defect affecting mitochondrial protein synthesis is responsible for about one-third of combined respiratory chain deficiencies (7/22). In the remaining patients, the impaired respiratory chain activity is most likely the consequence of several different events downstream of mitochondrial translation. Clinical classification of patients with biochemical analysis, genetic testing and, more importantly, in vivo labelling and immunoblotting of mitochondrial proteins show incoherent results, but a systematic review of these data in more patients may reveal underlying mechanisms, and facilitate the identification of novel factors involved in combined respiratory chain deficiency.

Avian Influenza Viruses, Inflammation, and CD8+ T Cell Immunity

PubMed Central

Wang, Zhongfang; Loh, Liyen; Kedzierski, Lukasz; Kedzierska, Katherine

2016-01-01

Avian influenza viruses (AIVs) circulate naturally in wild aquatic birds, infect domestic poultry, and are capable of causing sporadic bird-to-human transmissions. AIVs capable of infecting humans include a highly pathogenic AIV H5N1, first detected in humans in 1997, and a low pathogenic AIV H7N9, reported in humans in 2013. Both H5N1 and H7N9 cause severe influenza disease in humans, manifested by acute respiratory distress syndrome, multi-organ failure, and high mortality rates of 60% and 35%, respectively. Ongoing circulation of H5N1 and H7N9 viruses in wild birds and poultry, and their ability to infect humans emphasizes their epidemic and pandemic potential and poses a public health threat. It is, thus, imperative to understand the host immune responses to the AIVs so we can control severe influenza disease caused by H5N1 or H7N9 and rationally design new immunotherapies and vaccines. This review summarizes our current knowledge on AIV epidemiology, disease symptoms, inflammatory processes underlying the AIV infection in humans, and recent studies on universal pre-existing CD8+ T cell immunity to AIVs. Immune responses driving the host recovery from AIV infection in patients hospitalized with severe influenza disease are also discussed. PMID:26973644

Efficacy of a new pharmacokinetically enhanced formulation of amoxicillin/clavulanate (2000/125 mg) in adults with community-acquired pneumonia caused by Streptococcus pneumoniae, including penicillin-resistant strains.

PubMed

File, Thomas M; Garau, Javier; Jacobs, Michael R; Wynne, Brian; Twynholm, Monique; Berkowitz, Elchonon

2005-02-01

Community-acquired pneumonia (CAP) is a common respiratory illness, frequently caused by Streptococcus pneumoniae. The prevalence of S. pneumoniae resistance to common antimicrobials has increased over recent years. A new pharmacokinetically enhanced formulation of amoxicillin/clavulanate (2000/125 mg) has been developed, designed to combat infections caused by S. pneumoniae, including penicillin-resistant (PRSP, penicillin minimum inhibitory concentrations (MICs) >or=2mg/l) isolates, and those with elevated amoxicillin/clavulanic acid MICs, while maintaining coverage of beta-lactamase-producing pathogens. A pooled efficacy analysis of four randomized (1:1) and one non-comparative clinical trials of amoxicillin/clavulanate, 2000/125 mg, given twice daily, was conducted in adult patients with CAP. Comparator agents were conventional amoxicillin/clavulanate formulations. At follow-up (days 16-39), efficacy (eradication of the initial pathogen or clinical cure in patients for whom no repeat culture was performed) in patients with S. pneumoniae infection was 92.3% (274/297) for amoxicillin/clavulanate, 2000/125 mg and 85.2% (46/54) for comparators (P=0.11). Twenty-four of 25 PRSP-infected patients receiving amoxicillin/clavulanate, 2000/125 mg were treated successfully. Both amoxicillin/clavulanate, 2000/125 mg and comparators were well tolerated, with few patients withdrawing from the studies.

Viral infection of the lungs through the eye.

PubMed

Bitko, Vira; Musiyenko, Alla; Barik, Sailen

2007-01-01

Respiratory syncytial virus (RSV) is the foremost respiratory pathogen in newborns and claims millions of lives annually. However, there has been no methodical study of the pathway(s) of entry of RSV or its interaction with nonrespiratory tissues. We and others have recently established a significant association between allergic conjunctivitis and the presence of RSV in the eye. Here we adopt a BALB/c mouse model and demonstrate that when instilled in the live murine eye, RSV not only replicated robustly in the eye but also migrated to the lung and produced a respiratory disease that is indistinguishable from the standard, nasally acquired RSV disease. Ocularly applied synthetic anti-RSV small interfering RNA prevented infection of the eye as well as the lung. RSV infection of the eye activated a plethora of ocular cytokines and chemokines with profound relevance to inflammation of the eye. Anticytokine treatments in the eye reduced ocular inflammation but had no effect on viral growth in both eye and lung, demonstrating a role of the cytokine response in ocular pathology. These results establish the eye as a major gateway of respiratory infection and a respiratory virus as a bona fide eye pathogen, thus offering novel intervention and treatment options.

Pneumonia Virus of Mice Severe Respiratory Virus Infection in a Natural Host

PubMed Central

Rosenberg, Helene F.; Domachowske, Joseph B.

2008-01-01

Pneumonia virus of mice (PVM; family Paramyxoviridae, genus Pneumovirus) is a natural mouse pathogen that is closely related to the human and bovine respiratory syncytial viruses. Among the prominent features of this infection, robust replication of PVM takes place in bronchial epithelial cells in response to a minimal virus inoculum. Virus replication in situ results in local production of proinflammatory cytokines (MIP-1α, MIP-2, MCP-1 and IFNγ) and granulocyte recruitment to the lung. If left unchecked, PVM infection and the ensuing inflammatory response ultimately lead to pulmonary edema, respiratory compromise and death. In this review, we consider the recent studies using the PVM model that have provided important insights into the role of the inflammatory response in the pathogenesis of severe respiratory virus infection. We also highlight several works that have elucidated acquired immune responses to this pathogen, including T cell responses and the development of humoral immunity. Finally, we consider several immunomodulatory strategies that have been used successfully to reduce morbidity and mortality when administered to PVM infected, symptomatic mice, and thus hold promise as realistic therapeutic strategies for severe respiratory virus infections in human subjects. PMID:18471897

The pathogenesis of ventilator-associated pneumonia: its relevance to developing effective strategies for prevention.

PubMed

Safdar, Nasia; Crnich, Christopher J; Maki, Dennis G

2005-06-01

Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in the intensive care unit and is associated with major morbidity and attributable mortality. Strategies to prevent VAP are likely to be successful only if based upon a sound understanding of pathogenesis and epidemiology. The major route for acquiring endemic VAP is oropharyngeal colonization by the endogenous flora or by pathogens acquired exogenously from the intensive care unit environment, especially the hands or apparel of health-care workers, contaminated respiratory equipment, hospital water, or air. The stomach represents a potential site of secondary colonization and reservoir of nosocomial Gram-negative bacilli. Endotracheal-tube biofilm formation may play a contributory role in sustaining tracheal colonization and also have an important role in late-onset VAP caused by resistant organisms. Aspiration of microbe-laden oropharyngeal, gastric, or tracheal secretions around the cuffed endotracheal tube into the normally sterile lower respiratory tract results in most cases of endemic VAP. In contrast, epidemic VAP is most often caused by contamination of respiratory therapy equipment, bronchoscopes, medical aerosols, water (eg, Legionella) or air (eg, Aspergillus or the severe acute respiratory syndrome virus). Strategies to eradicate oropharyngeal and/or intestinal microbial colonization, such as with chlorhexidine oral care, prophylactic aerosolization of antimicrobials, selective aerodigestive mucosal antimicrobial decontamination, or the use of sucralfate rather than H(2) antagonists for stress ulcer prophylaxis, and measures to prevent aspiration, such as semirecumbent positioning or continuous subglottic suctioning, have all been shown to reduce the risk of VAP. Measures to prevent epidemic VAP include rigorous disinfection of respiratory equipment and bronchoscopes, and infection-control measures to prevent contamination of medical aerosols. Hospital water should be Legionella-free, and high-risk patients, especially those with prolonged granulocytopenia or organ transplants, should be cared for in hospital units with high-efficiency-particulate-arrestor (HEPA) filtered air. Routine surveillance of VAP, to track endemic VAPs and facilitate early detection of outbreaks, is mandatory.

EFFICACY AND SAFETY OF BAN HUANG ORAL LIQUID FOR TREATING BOVINE RESPIRATORY DISEASES

PubMed Central

Li, Bing; Zhou, Xu-Zheng; Niu, Jian-Rong; Wei, Xiao-Juan; Li, Jian-Yong; Yang, Ya-Jun; Liu, Xi-Wang; Cheng, Fu-Sheng; Zhang, Ji-Yu

2017-01-01

Background: Ban Huang oral liquid was developed as a veterinary compound preparation by the Lanzhou Institute of Husbandry and Pharmaceutical Sciences of the Chinese Academy of Agricultural Sciences (CAAS). The purpose of this study was to determine whether the oral liquid preparation of traditional Chinese medicine, Ban Huang, is safe and effective for treating respiratory diseases in cattle. Materials and Methods: Acute oral toxicity experiments were conducted in Wistar rats and Kunming mice via oral administration. The minimum inhibitory concentration of the drug against Mycoplasma bovis in vitro with the double dilution method was 500 mg/mL, indicating good sensitivity. The results of laboratory pathogen testing, analysis of clinical symptoms, and analysis of pathological anatomy were combined to diagnose bovine respiratory diseases in 147 Simmental cattle caused by mixed infections of M. bovis, bovine respiratory syncytial virus, bovine parainfluenza virus type 3, and Mannheimia haemolytica. These cattle were randomly divided into three groups: drug treatment group 1 (treated via Tilmicosin injection), drug treatment group 2 (treated with Shuang Huang Lian oral liquid combined with Tilmicosin injection), and drug treatment group 3 (treated with Ban Huang oral liquid combined with Tilmicosin injection). Treatment effects were observed within 7 days. Results: The results showed no toxicity and a maximum tolerated dose greater than 20 g/kg BW. For the 87 cattle in drug-treatment group, the cure rate was 90.80%, whereas the response rate was 94.25%. The cure rate of drug treatment group was increased by 14.13% in comparison with that of drug control group 1 and by 7.47% in comparison with that of drug control group 2 (both P < 0.05). Conclusion: This study demonstrates that Ban Huang oral liquid is a safe and effective treatment for bovine respiratory diseases, especially for mixed infection caused by M. bovis, bacteria, and viruses. PMID:28573221

Closed genomes of seven histophilus somni isolates from beef calves with bovine respiratory disease complex

USDA-ARS?s Scientific Manuscript database

Histophilus somni is a fastidious gram-negative opportunistic pathogenic Pasteurellacea that affects multiple organ systems and is one of the principle bacterial species contributing to bovine respiratory disease complex (BRDC) in feed yard cattle. Here we present seven closed genomes isolated from...

Closed genomes and phenotypes of seven Histophilus somni isolates from beef calves with bovine respiratory disease complex

USDA-ARS?s Scientific Manuscript database

Background: Histophilus somni is a fastidious gram-negative opportunistic pathogenic Pasteurellacea that affects multiple organ systems and is one of three principle bacterial species contributing to bovine respiratory disease complex (BRDC) in North American feed yard cattle. BRDC outbreaks accoun...

Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients.

PubMed

de Steenhuijsen Piters, Wouter A A; Huijskens, Elisabeth G W; Wyllie, Anne L; Biesbroek, Giske; van den Bergh, Menno R; Veenhoven, Reinier H; Wang, Xinhui; Trzciński, Krzysztof; Bonten, Marc J; Rossen, John W A; Sanders, Elisabeth A M; Bogaert, Debby

2016-01-01

Bacterial pneumonia is a major cause of morbidity and mortality in elderly. We hypothesize that dysbiosis between regular residents of the upper respiratory tract (URT) microbiome, that is balance between commensals and potential pathogens, is involved in pathogen overgrowth and consequently disease. We compared oropharyngeal microbiota of elderly pneumonia patients (n=100) with healthy elderly (n=91) by 16S-rRNA-based sequencing and verified our findings in young adult pneumonia patients (n=27) and young healthy adults (n=187). Microbiota profiles differed significantly between elderly pneumonia patients and healthy elderly (PERMANOVA, P<0.0005). Highly similar differences were observed between microbiota profiles of young adult pneumonia patients and their healthy controls. Clustering resulted in 11 (sub)clusters including 95% (386/405) of samples. We observed three microbiota profiles strongly associated with pneumonia (P<0.05) and either dominated by lactobacilli (n=11), Rothia (n=51) or Streptococcus (pseudo)pneumoniae (n=42). In contrast, three other microbiota clusters (in total n=183) were correlated with health (P<0.05) and were all characterized by more diverse profiles containing higher abundances of especially Prevotella melaninogenica, Veillonella and Leptotrichia. For the remaining clusters (n=99), the association with health or disease was less clear. A decision tree model based on the relative abundance of five bacterial community members in URT microbiota showed high specificity of 95% and sensitivity of 84% (89% and 73%, respectively, after cross-validation) for differentiating pneumonia patients from healthy individuals. These results suggest that pneumonia in elderly and young adults is associated with dysbiosis of the URT microbiome with bacterial overgrowth of single species and absence of distinct anaerobic bacteria. Whether the observed microbiome changes are a cause or a consequence of the development of pneumonia or merely coincide with disease status remains a question for future research.

Antibacterial activity and mechanism of action of Monarda punctata essential oil and its main components against common bacterial pathogens in respiratory tract.

PubMed

Li, Hong; Yang, Tian; Li, Fei-Yan; Yao, Yan; Sun, Zhong-Min

2014-01-01

The aim of the current research work was to study the chemical composition of the essential oil of Monarda punctata along with evaluating the essential oil and its major components for their antibacterial effects against some frequently encountered respiratory infection causing pathogens. Gas chromatographic mass spectrometric analysis revealed the presence of 13 chemical constituents with thymol (75.2%), p-cymene (6.7%), limonene (5.4), and carvacrol (3.5%) as the major constituents. The oil composition was dominated by the oxygenated monoterpenes. Antibacterial activity of the essential oil and its major constituents (thymol, p-cymene, limonene) was evaluated against Streptococcus pyogenes, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, Haemophilus influenzae and Escherichia coli. The study revealed that the essential oil and its constituents exhibited a broad spectrum and variable degree of antibacterial activity against different strains. Among the tested strains, Streptococcus pyogenes, Escherichia coli and Streptococcus pneumoniae were the most susceptible bacterial strain showing lowest MIC and MBC values. Methicillin-resistant Staphylococcus aureus was the most resistant bacterial strain to the essential oil treatment showing relatively higher MIC and MBC values. Scanning electron microscopy revealed that the essential oil induced potent and dose-dependent membrane damage in S. pyogenes and MRSA bacterial strains. The reactive oxygen species generated by the Monarda punctata essential oil were identified using 2', 7'-dichlorofluorescein diacetate (DCFDA).This study indicated that the Monarda punctata essential oil to a great extent and thymol to a lower extent triggered a substantial increase in the ROS levels in S. pyogenes bacterial cultures which ultimately cause membrane damage as revealed by SEM results.

Antibacterial activity and mechanism of action of Monarda punctata essential oil and its main components against common bacterial pathogens in respiratory tract

PubMed Central

Li, Hong; Yang, Tian; Li, Fei-Yan; Yao, Yan; Sun, Zhong-Min

2014-01-01

The aim of the current research work was to study the chemical composition of the essential oil of Monarda punctata along with evaluating the essential oil and its major components for their antibacterial effects against some frequently encountered respiratory infection causing pathogens. Gas chromatographic mass spectrometric analysis revealed the presence of 13 chemical constituents with thymol (75.2%), p-cymene (6.7%), limonene (5.4), and carvacrol (3.5%) as the major constituents. The oil composition was dominated by the oxygenated monoterpenes. Antibacterial activity of the essential oil and its major constituents (thymol, p-cymene, limonene) was evaluated against Streptococcus pyogenes, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, Haemophilus influenzae and Escherichia coli. The study revealed that the essential oil and its constituents exhibited a broad spectrum and variable degree of antibacterial activity against different strains. Among the tested strains, Streptococcus pyogenes, Escherichia coli and Streptococcus pneumoniae were the most susceptible bacterial strain showing lowest MIC and MBC values. Methicillin-resistant Staphylococcus aureus was the most resistant bacterial strain to the essential oil treatment showing relatively higher MIC and MBC values. Scanning electron microscopy revealed that the essential oil induced potent and dose-dependent membrane damage in S. pyogenes and MRSA bacterial strains. The reactive oxygen species generated by the Monarda punctata essential oil were identified using 2’, 7’-dichlorofluorescein diacetate (DCFDA).This study indicated that the Monarda punctata essential oil to a great extent and thymol to a lower extent triggered a substantial increase in the ROS levels in S. pyogenes bacterial cultures which ultimately cause membrane damage as revealed by SEM results. PMID:25550774

A Preliminary Study of Pneumonia Etiology Among Hospitalized Children in Kenya

PubMed Central

Kazungu, Sidi; Morpeth, Susan C.; Gibson, Dustin G.; Mvera, Benedict; Brent, Andrew J.; Mwarumba, Salim; Onyango, Clayton O.; Bett, Anne; Akech, Donald O.; Murdoch, David R.; Nokes, D. James; Scott, J. Anthony G.

2012-01-01

Background. Pneumonia is the leading cause of childhood death in the developing world. Higher-quality etiological data are required to reduce this mortality burden. Methods. We conducted a case-control study of pneumonia etiology among children aged 1–59 months in rural Kenya. Case patients were hospitalized with World Health Organization–defined severe pneumonia (SP) or very severe pneumonia (VSP); controls were outpatient children without pneumonia. We collected blood for culture, induced sputum for culture and multiplex polymerase chain reaction (PCR), and obtained oropharyngeal swab specimens for multiplex PCR from case patients, and serum for serology and nasopharyngeal swab specimens for multiplex PCR from case patients and controls. Results. Of 984 eligible case patients, 810 (84%) were enrolled in the study; 232 (29%) had VSP. Blood cultures were positive in 52 of 749 case patients (7%). A predominant potential pathogen was identified in sputum culture in 70 of 417 case patients (17%). A respiratory virus was detected by PCR from nasopharyngeal swab specimens in 486 of 805 case patients (60%) and 172 of 369 controls (47%). Only respiratory syncytial virus (RSV) showed a statistically significant association between virus detection in the nasopharynx and pneumonia hospitalization (odds ratio, 12.5; 95% confidence interval, 3.1–51.5). Among 257 case patients in whom all specimens (excluding serum specimens) were collected, bacteria were identified in 24 (9%), viruses in 137 (53%), mixed viral and bacterial infection in 39 (15%), and no pathogen in 57 (22%); bacterial causes outnumbered viral causes when the results of the case-control analysis were considered. Conclusions. A potential etiology was detected in >75% of children admitted with SP or VSP. Except for RSV, the case-control analysis did not detect an association between viral detection in the nasopharynx and hospitalization for pneumonia. PMID:22403235

Factors Affecting the Immunity to Respiratory Syncytial Virus: From Epigenetics to Microbiome

PubMed Central

Fonseca, Wendy; Lukacs, Nicholas W.; Ptaschinski, Catherine

2018-01-01

Respiratory syncytial virus (RSV) is a common pathogen that infects virtually all children by 2 years of age and is the leading cause of hospitalization of infants worldwide. While most children experience mild symptoms, some children progress to severe lower respiratory tract infection. Those children with severe disease have a much higher risk of developing childhood wheezing later in life. Many risk factors are known to result in exacerbated disease, including premature birth and early age of RSV infection, when the immune system is relatively immature. The development of the immune system before and after birth may be altered by several extrinsic and intrinsic factors that could lead to severe disease predisposition in children who do not exhibit any currently known risk factors. Recently, the role of the microbiome and the resulting metabolite profile has been an area of intense study in the development of lung disease, including viral infection and asthma. This review explores both known risk factors that can lead to severe RSV-induced disease as well as emerging topics in the development of immunity to RSV and the long-term consequences of severe infection. PMID:29515570

Buying time-the immune system determinants of the incubation period to respiratory viruses.

PubMed

Hermesh, Tamar; Moltedo, Bruno; López, Carolina B; Moran, Thomas M

2010-11-01

Respiratory viruses cause disease in humans characterized by an abrupt onset of symptoms. Studies in humans and animal models have shown that symptoms are not immediate and appear days or even weeks after infection. Since the initial symptoms are a manifestation of virus recognition by elements of the innate immune response, early virus replication must go largely undetected. The interval between infection and the emergence of symptoms is called the incubation period and is widely used as a clinical score. While incubation periods have been described for many virus infections the underlying mechanism for this asymptomatic phase has not been comprehensively documented. Here we review studies of the interaction between human pathogenic respiratory RNA viruses and the host with a particular emphasis on the mechanisms used by viruses to inhibit immunity. We discuss the concept of the "stealth phase", defined as the time between infection and the earliest detectable inflammatory response. We propose that the "stealth phase" phenomenon is primarily responsible for the suppression of symptoms during the incubation period and results from viral antagonism that inhibits major pathways of the innate immune system allowing an extended time of unhindered virus replication.

Host-pathogen interplay at primary infection sites in pigs challenged with Actinobacillus pleuropneumoniae.

PubMed

Sassu, Elena L; Frömbling, Janna; Duvigneau, J Catharina; Miller, Ingrid; Müllebner, Andrea; Gutiérrez, Ana M; Grunert, Tom; Patzl, Martina; Saalmüller, Armin; von Altrock, Alexandra; Menzel, Anne; Ganter, Martin; Spergser, Joachim; Hewicker-Trautwein, Marion; Verspohl, Jutta; Ehling-Schulz, Monika; Hennig-Pauka, Isabel

2017-02-28

Actinobacillus (A.) pleuropneumoniae is the causative agent of porcine pleuropneumonia and causes significant losses in the pig industry worldwide. Early host immune response is crucial for further progression of the disease. A. pleuropneumoniae is either rapidly eliminated by the immune system or switches to a long-term persistent form. To gain insight into the host-pathogen interaction during the early stages of infection, pigs were inoculated intratracheally with A. pleuropneumoniae serotype 2 and humanely euthanized eight hours after infection. Gene expression studies of inflammatory cytokines and the acute phase proteins haptoglobin, serum amyloid A and C-reactive protein were carried out by RT-qPCR from the lung, liver, tonsils and salivary gland. In addition, the concentration of cytokines and acute phase proteins were measured by quantitative immunoassays in bronchoalveolar lavage fluid, serum and saliva. In parallel to the analyses of host response, the impact of the host on the bacterial pathogen was assessed on a metabolic level. For the latter, Fourier-Transform Infrared (FTIR-) spectroscopy was employed. Significant cytokine and acute phase protein gene expression was detected in the lung and the salivary gland however this was not observed in the tonsils. In parallel to the analyses of host response, the impact of the host on the bacterial pathogen was assessed on a metabolic level. For the latter investigations, Fourier-Transform Infrared (FTIR-) spectroscopy was employed. The bacteria isolated from the upper and lower respiratory tract showed distinct IR spectral patterns reflecting the organ-specific acute phase response of the host. In summary, this study implies a metabolic adaptation of A. pleuropneumoniae to the porcine upper respiratory tract already during early infection, which might indicate a first step towards the persistence of A. pleuropneumoniae. Not only in lung, but also in the salivary gland an increased inflammatory gene expression was detectable during the acute stage of infection.

Evaluation of Mycoplasma gallisepticum (MG) ts-304 vaccine as a live attenuated vaccine in turkeys.

PubMed

Kanci, Anna; Wijesurendra, Dinidu S; Wawegama, Nadeeka K; Underwood, Gregory J; Noormohammadi, Amir H; Markham, Philip F; Browning, Glenn F

2018-04-25

Mycoplasma gallisepticum (MG) is an important pathogen of poultry worldwide that causes chronic respiratory disease (CRD) in chickens and infectious sinusitis in turkeys. Vaxsafe MG (strain ts-11) is a live attenuated temperature sensitive vaccine that has been proven to be effective in controlling CRD in chickens, but it is not efficacious in turkeys. The gapA gene, which encodes a mature cytadhesin protein with a molecular weight of approximately 105 kDa, is not expressed in strain ts-11 because a 20 base pair reiterated sequence introduces a frame shift and causes premature truncation of the translated peptide. A GapA positive clone, MG ts-304, isolated from strain ts-11 has been shown to have enhanced efficacy in chickens. Here we describe studies we conducted to assess the safety and efficacy of the MG ts-304 vaccine candidate in turkeys. We found that MG ts-304 was able to colonise the trachea of 3-week-old turkeys and was safe, even at a tenfold overdose, inducing no adverse clinical signs of respiratory disease or significant gross lesions in the respiratory tract (air sacs or trachea), and was poorly transmissible to in-contact birds. We also showed that it was efficacious when administered to 3-week-old turkeys, inducing protective immunity against challenge with the M.gallisepticum wild-type strain Ap3AS. MG ts-304 is therefore a promising live attenuated vaccine candidate for use in turkeys. Copyright © 2018. Published by Elsevier Ltd.

A novel high-throughput assay to quantify the vaccine-induced inhibition of Bordetella pertussis adhesion to airway epithelia.

PubMed

Zanaboni, Elisa; Arato, Vanessa; Pizza, Mariagrazia; Seubert, Anja; Leuzzi, Rosanna

2016-09-15

Pertussis or whooping cough is an acute respiratory illness caused by the Gram-negative pathogen Bordetella pertussis. Despite high vaccination coverage whooping cough is currently re-emerging in many developed countries. Although the causes of pertussis resurgence are matter of debate, emerging evidences suggest that acellular vaccines efficiently protect against the hallmark symptoms of pertussis disease but fail to prevent colonization. This presumably impacts on increased risk of bacterial transmission and consequent spread throughout the population. These evidences suggest that improved vaccines may be required for efficient bacterial clearance in the upper respiratory tract. Consequently, there is a need for novel bioassays to evaluate at pre-clinical or clinical level the impact of different vaccines on B. pertussis colonization. We developed a high-throughput bacterial adhesion inhibition (BAI) assay based on human respiratory cell lines and on live bacteria chemically conjugated to a fluorescent dye. Employing A549 cells as model, we evaluated the impact of antibodies elicited by acellular (aP) and whole cell (wP) vaccines on B. pertussis adhesion in vitro. Moreover, we settled the method also on polarized Calu-3 cells grown at air-liquid interface (ALI), showing that this assay can be extended to more complex cell models mimicking the airway epithelium. We proved that this method is a sensitive, rapid and reproducible system to evaluate the anti-adhesive properties of vaccine-induced antibodies and can be employed to assess improved pertussis vaccines.

Hantavirus pulmonary syndrome.

PubMed

Macneil, Adam; Nichol, Stuart T; Spiropoulou, Christina F

2011-12-01

Hantavirus pulmonary syndrome (HPS) is a severe disease characterized by a rapid onset of pulmonary edema followed by respiratory failure and cardiogenic shock. The HPS associated viruses are members of the genus Hantavirus, family Bunyaviridae. Hantaviruses have a worldwide distribution and are broadly split into the New World hantaviruses, which includes those causing HPS, and the Old World hantaviruses [including the prototype Hantaan virus (HTNV)], which are associated with a different disease, hemorrhagic fever with renal syndrome (HFRS). Sin Nombre virus (SNV) and Andes virus (ANDV) are the most common causes of HPS in North and South America, respectively. Case fatality of HPS is approximately 40%. Pathogenic New World hantaviruses infect the lung microvascular endothelium without causing any virus induced cytopathic effect. However, virus infection results in microvascular leakage, which is the hallmark of HPS. This article briefly reviews the knowledge on HPS-associated hantaviruses accumulated since their discovery, less than 20 years ago. Published by Elsevier B.V.

[Analysis of characteristics of bacteria in respiratory tract infection in 2013-2016 in Heibei 3A hospital: a single-center report of 7 497 patients].

PubMed

Hou, Lili; Liu, Lili; Dang, Ping; Kang, Guannan; Zhang, Qinfeng; Li, Dongling

2017-09-01

To analyze the changes and characteristics of respiratory tract bacteria in Hebei 3A Hospital, and to provide new rationale for clinical diagnosis and treatment. A single-center retrospective analysis was conducted. 7 497 patients with respiratory tract infection admitted to Hebei Chest Hospital from January 2013 to December 2016 were enrolled. Deep sputum was collected, and the bacterial cultures and susceptibility analysis was conducted in sputum and upper respiratory secretions were collected by fiberoptic bronchoscopy. A total of 7 497 patients with respiratory tract infection were enrolled in the study, and 11 909 strains of 13 kinds of dominant pathogens were isolated. The dominant pathogens for respiratory tract infection were Monilia albican (23.7%), Klebsiella pneumoniae (12.9%), Pseudomonas aeruginosa (11.6%), Escherichia coli (9.5%), Candida glabrata (9.1%), Acinetobacter baumanii (7.9%), Aspergillus (6.7%), Stenotrophomonas maltophilia (4.5%), coagulase negative Staphylococcus (3.7%) and some species of Pseudomonas (3.7%), Staphylococcus aureus (3.0%), Aerobacter cloacae (1.9%), and Candida tropicalis (1.8%). A total of 6 198 strains of 7 kinds of Gram negative (G - ) bacilli infection dominant pathogens accounts for 52.0% of all infections, Klebsiella pneumonia (24.8%), Pseudomonas aeruginosa (22.3%), Escherichia coli (18.2%) and Acinetobacter baumanii (15.3%) were the main pathogens, and increased year by year. Susceptibility analysis showed that the preferred antibiotics for G - bacteria were carbapenems, followed by risperidone, sulbactam, cefepime, amikacin, and the third generation of cephalosporins. A total of 798 strains of 2 kinds of Gram positive (G + ) bacilli infection dominant pathogens accounted for 6.7% of all infections, were coagulase negative Staphylococcus (54.8%) and Staphylococcus aureus (45.2%), each had changed little by year. Susceptibility analysis showed that G + bacteria were sensitive to glycopeptides, followed by cefoxitin, cotrimoxazole, the tetracyclines, quinolones, azithromycin, erythromycin and so on. The advantages of 4 species of fungi were 4 913 strains, accounted for all of the 41.3% strains, with 57.5% of Candida albicans, and the trend was increasing year by year. Susceptibility analysis results showed that the antifungal susceptibility of dominant fungi were higher. G - bacilli is still the main source of infection, and showed an upward trend year by year. Fungal infection rate cannot be ignored, and we must pay attention to fungal infection incentives. We should strengthen the rational use of antibiotics.

Unintentional human exposure to tilmicosin (Micotil 300).

PubMed

Von Essen, Susanna; Spencer, Jonathan; Hass, Brian; List, Pam; Seifert, Steven A

2003-01-01

Tilmicosin phosphate is a macrolide antibiotic that is used to treat cattle for pathogens that cause Bovine Respiratory Disease. A 28-year-old man with no prior history of heart disease developed severe chest pain, inverted T waves, and intraventricular conduction delay on EKG and mild elevation of cardiac enzymes 5 hours after unintentional injection of less than half of a 12cc syringe filled with Micotil 300 (tilmicosin phosphate 300 mg/mL, propylene glycol 25%, phosphoric acid, water for injection). The patient made an uneventful recovery after hospitalization. This case provides evidence that unintentional injection of tilmicosin can cause cardiac symptoms and laboratory evidence of myocardial injury. Tilmicosin should always be administered by properly trained personnel who are using techniques designed to reduce the risk of accidental self-injection.

Animal models of disease shed light on Nipah virus pathogenesis and transmission

PubMed Central

de Wit, Emmie; Munster, Vincent J.

2014-01-01

Nipah virus is an emerging virus infection that causes yearly disease outbreaks with high case fatality rates in Bangladesh. Nipah virus causes encephalitis and systemic vasculitis, sometimes in combination with respiratory disease. Pteropus species fruit bats are the natural reservoir of Nipah virus and zoonotic transmission can occur directly or via an intermediate host; human-to-human transmission occurs regularly. In this review we discuss the current state of knowledge on the pathogenesis and transmission of Nipah virus, focusing on dissemination of the virus through its host, known determinants of pathogenicity and routes of zoonotic and human-to-human transmission. Since data from human cases are sparse, this knowledge is largely based on the results of studies performed in animal models that recapitulate Nipah virus disease in humans. PMID:25229234

[An overview on swine influenza viruses].

PubMed

Yang, Shuai; Zhu, Wen-Fei; Shu, Yue-Long

2013-05-01

Swine influenza viruses (SIVs) are respiratory pathogens of pigs. They cause both economic bur den in livestock-dependent industries and serious global public health concerns in humans. Because of their dual susceptibility to human and avian influenza viruses, pigs are recognized as intermediate hosts for genetic reassortment and interspecies transmission. Subtypes H1N1, H1N2, and H3N2 circulate in swine populations around the world, with varied origin and genetic characteristics among different continents and regions. In this review, the role of pigs in evolution of influenza A viruses, the genetic evolution of SIVs and interspecies transmission of SIVs are described. Considering the possibility that pigs might produce novel influenza viruses causing more outbreaks and pandemics, routine epidemiological surveillance of influenza viruses in pig populations is highly recommended.

A case-control study of acute respiratory tract infection in general practice patients in The Netherlands.

PubMed

van Gageldonk-Lafeber, Arianne B; Heijnen, Marie-Louise A; Bartelds, Aad I M; Peters, Marcel F; van der Plas, Simone M; Wilbrink, Berry

2005-08-15

Acute respiratory tract infections (ARTIs) are responsible for considerable morbidity in the community, but little is known about the presence of respiratory pathogens in asymptomatic individuals. We hypothesized that asymptomatic persons could have a subclinical infection and thus act as a source of transmission. During the period of 2000-2003, all patients with ARTI who visited their sentinel general practitioner had their data reported to estimate the incidence of ARTI in Dutch general practices. A random selection of these patients (case patients) and an equal number of asymptomatic persons visiting for other complaints (control subjects) were included in a case-control study. Nose and throat swabs of participants were tested for a broad range of pathogens. The overall incidence of ARTI was 545 cases per 10,000 person-years, suggesting that, in the Dutch population, an estimated 900,000 persons annually consult their general practitioner for respiratory complaints. Rhinovirus was most common in case patients (24%), followed by influenza virus type A (11%) and coronavirus (7%). Viruses were detected in 58% of the case patients, beta -hemolytic streptococci group A were detected in 11%, and mixed infections were detected in 3%. Pathogens were detected in approximately 30% of control subjects, particularly in the youngest age groups. This study confirms that most ARTIs are viral and supports the reserved policy of prescribing antibiotics. In both case and control subjects, rhinovirus was the most common pathogen. Of bacterial infections, only group A beta-hemolytic streptococci were more common in case patients than in control subjects. Furthermore, we demonstrated that asymptomatic persons might be a neglected source of transmission.

Initial presentations and final outcomes of primary pyogenic liver abscess: a cross-sectional study

PubMed Central

2014-01-01

Background Although pyogenic liver abscess (PPLA) fatalities are decreasing owing to early diagnosis and effective treatments, PPLA-associated complications still exist. The purpose of this study was to analyze the characteristic features of initial presentations and final outcomes of PPLA caused by different pathogens. Methods This retrospective study collected and analyzed information regarding initial presentations and final outcomes in patients diagnosed with PPLA at admitted at Changhua Christian Hospital from January 1 to December 31, 2010. Results During the study period, we analyzed the records of a total of 134 patients with documented PPLA. There were no significant causative pathogen-related differences in symptoms at initial presentation. Compared with the survivor group, patients in the mortality group were characterized by male gender (p < 0.001), malignancy (p < 0.001), respiratory distress (p =0.007), low blood pressure (p = 0.024), jaundice (p = < 0.001), rupture of liver abscess (p < 0.001), endophthalmitis (p = 0.003), and multiple organ failure (p < 0.001). No patients received liver transplantation or were diagnosed with HIV during the study period. According to univariate logistic regression analysis, gender (OR = 1.185, 95% CI: 0.284–11.130, p = 0.006), malignancy (OR = 2.067, 95% CI: 1.174–13.130, p = 0.004), respiratory distress (OR = 1.667, 95% CI: 1.164–14.210, p = 0.006), low blood pressure (OR = 2.167, 95% CI: 2.104–13.150, p = 0.003), jaundice (OR = 1.9, 95% CI: 1.246–3.297, p = 0.008), rupture of liver abscess (OR = 5.167, 95% CI: 2.194–23.150, p = 0.003), endophthalmitis (OR = 2.167, 95% CI: 1.234–13.140, p = 0.005), and multiple organ failure (OR = 3.067, 95% CI: 1.184–15.150, p = 0.001) differed significantly between the mortality and survivor groups. Conclusion Although the initial presentations of PPLA caused by different pathogens were similar, there were significant differences in mortality in cases involving: (1) male patients, (2) malignancy, (3) initial respiratory distress, (4) initial low blood pressure, (5) jaundice, (6) rupture of liver abscess, (7) endophthalmitis, , and (8) multiple organ failure. We strongly recommend using a severity score of the disease to determine the risk of mortality for each patient with PPLA. In order to prevent complications and reduce mortality, more attention must be paid to high-risk PPLA patients. PMID:25066384

Association of oral flora with orbital complications of acute sinusitis.

PubMed

Flam, Juliette O; Platt, Michael P; Sobel, Rachel; Devaiah, Anand K; Brook, Christopher D

2016-07-01

Acute and chronic sinusitis in children and adults can spread to the orbit. Oral flora has been seen in orbital infections, but the extent of synergy between pathogens in such infections remains unknown. A retrospective case series of patients with complicated sinusitis that involved the orbit from acute sinusitis who were admitted to a tertiary care hospital from January 2000 to December 2014 and who had surgical cultures obtained. Patients were identified by the International Classification of Diseases, Ninth Revision code for periorbital cellulitis, subperiosteal abscess, or orbital abscess. Sixteen patients underwent surgical drainage via external drainage or endoscopic sinus surgery of an orbital infection associated with sinusitis and had cultures obtained. Nine patients (56%) grew organisms that exist in oral flora, whereas seven patients (44%) grew common respiratory pathogens. The most common organisms recovered were viridans group streptococcus (VGS) (50%), Staphylococcus aureus (31%), Eikenella corrodens (25%), and Prevotella species (19%). Oral flora anaerobes were cultured alongside a VGS species in seven of eight patients (88%) as opposed to the respiratory pathogens, which were less frequently associated with concomitant VGS infection (29%) (p = 0.04). There are two main sources for infectious orbital complications from acute sinusitis: respiratory pathogens and oral flora. The high prevalence of concurrent anaerobic oral flora and VGS infection supports a suspected synergy between VGS and other oral organisms.

Survey of marbofloxacin susceptibility of bacteria isolated from cattle with respiratory disease and mastitis in Europe.

PubMed

Kroemer, S; Galland, D; Guérin-Faublée, V; Giboin, H; Woehrlé-Fontaine, F

2012-01-01

A monitoring programme conducted in Europe since 1994 to survey the marbofloxacin susceptibility of bacterial pathogens isolated from cattle has established the susceptibility of bacterial strains isolated before any antibiotic treatment from bovine mastitis and bovine respiratory disease (BRD) cases between 2002 and 2008. Minimum inhibitory concentration (MIC) was determined by a standardised microdilution technique. For respiratory pathogens, Pasteurella multocida and Mannheimia haemolytica isolates (751 and 514 strains, respectively) were highly susceptible to marbofloxacin (MIC≤0.03 µg/ml for 77.39 per cent of the strains) and only 1.75 per cent of M haemolytica strains were resistant (MIC≥4 µg/ml). Histophilus somni isolates (73 strains) were highly susceptible to marbofloxacin (0.008 to 0.06 µg/ml). Mycoplasma bovis MIC (171 strains) ranged from 0.5 to 4 µg/ml. For mastitis pathogens, the majority of Escherichia coli isolates were highly susceptible to marbofloxacin (95.8 per cent of 617 strains). Staphylococcus aureus and coagulase-negative staphylococci (568 and 280 strains) had a homogenous population with MIC centred on 0.25 µg/ml. Streptococcus uberis and Streptococcus dysgalactiae (660 and 217 strains) were moderately susceptible with MIC centred on 1 µg/ml. Marbofloxacin MIC for these various pathogens appeared stable over the seven years of the monitoring programme and was similar to previously published MIC results.

Sudden infant death syndrome: no significant expression of heat-shock proteins (HSP27, HSP70).

PubMed

Doberentz, Elke; Führing, Sarah; Madea, Burkhard

2016-03-01

In industrialized countries, sudden infant death is the most common cause of death in young children. Although prone sleeping position is a well-known risk factor, hyperthermia might also be important. Pathognomonic findings of premortem hyperthermia do not exist. During stress, including thermal effects, heat-shock protein (HSP) expression increases. This study investigated hyperthermia as a contributing or pathogenic factor for sudden infant death syndrome (SIDS). Immunohistochemical staining for HSP27 and HSP70 in the kidney, heart, and lung from 120 SIDS cases was examined. HSP70 immunostaining was negative in kidney, heart, and lung tissues in all cases and in tissues from the control group. HSP27 staining was positive in the kidney from one case, and was positive in the lungs (respiratory epithelia in 27% of cases; vascular endothelia in 19% of cases) and was negative in the heart. In the control group HSP27 was positive in 8% of renal tubular tissues and in 29% of renal vascular endothelia. Staining for HSP27 in lung tissues was positive in respiratory epithelia in 8% of cases and for vascular endothelia in 29%, whereas tissues from the heart were positive in only 4%. The hypothesis of hyperthermia being a pathogenic factor for SIDS was not supported by immunohistochemical visualization of HSP70 or HSP27.

Genomic Dissection of an Icelandic Epidemic of Respiratory Disease in Horses and Associated Zoonotic Cases

PubMed Central

Björnsdóttir, Sigríður; Harris, Simon R.; Svansson, Vilhjálmur; Gunnarsson, Eggert; Sigurðardóttir, Ólöf G.; Gammeljord, Kristina; Steward, Karen F.; Newton, J. Richard; Robinson, Carl; Charbonneau, Amelia R. L.

2017-01-01

ABSTRACT Iceland is free of the major infectious diseases of horses. However, in 2010 an epidemic of respiratory disease of unknown cause spread through the country’s native horse population of 77,000. Microbiological investigations ruled out known viral agents but identified the opportunistic pathogen Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) in diseased animals. We sequenced the genomes of 257 isolates of S. zooepidemicus to differentiate epidemic from endemic strains. We found that although multiple endemic clones of S. zooepidemicus were present, one particular clone, sequence type 209 (ST209), was likely to have been responsible for the epidemic. Concurrent with the epidemic, ST209 was also recovered from a human case of septicemia, highlighting the pathogenic potential of this strain. Epidemiological investigation revealed that the incursion of this strain into one training yard during February 2010 provided a nidus for the infection of multiple horses that then transmitted the strain to farms throughout Iceland. This study represents the first time that whole-genome sequencing has been used to investigate an epidemic on a national scale to identify the likely causative agent and the link to an associated zoonotic infection. Our data highlight the importance of national biosecurity to protect vulnerable populations of animals and also demonstrate the potential impact of S. zooepidemicus transmission to other animals, including humans. PMID:28765219

The Impact of Fusarium Mycotoxins on Human and Animal Host Susceptibility to Infectious Diseases

PubMed Central

Antonissen, Gunther; Martel, An; Pasmans, Frank; Ducatelle, Richard; Verbrugghe, Elin; Vandenbroucke, Virginie; Li, Shaoji; Haesebrouck, Freddy; Van Immerseel, Filip; Croubels, Siska

2014-01-01

Contamination of food and feed with mycotoxins is a worldwide problem. At present, acute mycotoxicosis caused by high doses is rare in humans and animals. Ingestion of low to moderate amounts of Fusarium mycotoxins is common and generally does not result in obvious intoxication. However, these low amounts may impair intestinal health, immune function and/or pathogen fitness, resulting in altered host pathogen interactions and thus a different outcome of infection. This review summarizes the current state of knowledge about the impact of Fusarium mycotoxin exposure on human and animal host susceptibility to infectious diseases. On the one hand, exposure to deoxynivalenol and other Fusarium mycotoxins generally exacerbates infections with parasites, bacteria and viruses across a wide range of animal host species. Well-known examples include coccidiosis in poultry, salmonellosis in pigs and mice, colibacillosis in pigs, necrotic enteritis in poultry, enteric septicemia of catfish, swine respiratory disease, aspergillosis in poultry and rabbits, reovirus infection in mice and Porcine Reproductive and Respiratory Syndrome Virus infection in pigs. However, on the other hand, T-2 toxin has been shown to markedly decrease the colonization capacity of Salmonella in the pig intestine. Although the impact of the exposure of humans to Fusarium toxins on infectious diseases is less well known, extrapolation from animal models suggests possible exacerbation of, for instance, colibacillosis and salmonellosis in humans, as well. PMID:24476707

Leptospira interrogans causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells

PubMed Central

Sato, Hiromi

2017-01-01

Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1) extracellular matrix, 2) intercellular adhesion molecules and cell surface receptors, 3) intracellular proteins, 4) cell-cell junction proteins, and 5) a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins) and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or pathways including endothelial barrier damage and inflammation, potentially leading to vascular hyperpermeability and severe illness in vivo. This work provides new insights into the pathophysiological mechanisms of Leptospira infection. PMID:28750011