Paracytosis of Haemophilus influenzae through cell layers of NCI-H292 lung epithelial cells

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van Schilfgaarde, M.; van Alphen, L.; Eijk, P.; Everts, V.; Dankert, J.

1995-01-01

Haemophilus influenzae penetrates the respiratory epithelium during carriage and invasive disease, including respiratory tract infections. We developed an in vitro model system consisting of lung epithelial NCI-H292 cells on permeable supports to study the passage of H. influenzae through lung

A review of the role of Haemophilus influenzae in community-acquired pneumonia

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Mary PE Slack

2015-06-01

Full Text Available In an era when Haemophilus influenzae type b (Hib conjugate vaccine is widely used, the incidence of Hib as a cause of community-acquired pneumonia (CAP has dramatically declined. Non-typeable H. influenzae (NTHi strains and, occasionally, other encapsulated serotypes of H. influenzae are now the cause of the majority of invasive H. influenzae infections, including bacteraemic CAP. NTHi have long been recognised as an important cause of lower respiratory tract infection, including pneumonia, in adults, especially those with underlying diseases. The role of NTHi as a cause of non-bacteraemic CAP in children is less clear. In this review the evidence for the role of NTHi and capsulated strains of H. influenzae will be examined.

Haemophilus haemolyticus: A Human Respiratory Tract Commensal to Be Distinguished from Haemophilus influenzae

DEFF Research Database (Denmark)

Murphy, T.F.; Brauer, A.L.; Sethi, S.

2007-01-01

Background. Haemophilus influenzae is a common pathogen in adults with chronic obstructive pulmonary disease (COPD). In a prospective study, selected isolates of apparent H. influenzae had an altered phenotype. We tested the hypothesis that these variant strains were genetically different from...... typical H. influenzae.Methods. A prospective study of adults with COPD was conducted. Strains of apparent H. influenzae obtained from a range of clinical sources were evaluated by ribosomal DNA sequence analysis, multilocus sequence analysis, DNA-DNA hybridization, and sequencing of the conserved P6 gene.......Results. Variant strains were determined to be Haemophilus haemolyticus by means of 4 independent methods. Analysis of 490 apparent H. influenzae strains, identified by standard methods, revealed that 39.5% of sputum isolates and 27.3% of nasopharyngeal isolates were H. haemolyticus. Isolates obtained from...

Nonencapsulated Streptococcus pneumoniae causes otitis media during single-species infection and during polymicrobial infection with nontypeable Haemophilus influenzae.

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Murrah, Kyle A; Pang, Bing; Richardson, Stephen; Perez, Antonia; Reimche, Jennifer; King, Lauren; Wren, John; Swords, W Edward

2015-07-01

Streptococcus pneumoniae strains lacking capsular polysaccharide have been increasingly reported in carriage and disease contexts. Since most cases of otitis media involve more than one bacterial species, we aimed to determine the capacity of a nonencapsulated S. pneumoniae clinical isolate to induce disease in the context of a single-species infection and as a polymicrobial infection with nontypeable Haemophilus influenzae. Using the chinchilla model of otitis media, we found that nonencapsulated S. pneumoniae colonizes the nasopharynx following intranasal inoculation, but does not readily ascend into the middle ear. However, when we inoculated nonencapsulated S. pneumoniae directly into the middle ear, the bacteria persisted for two weeks post-inoculation and induced symptoms consistent with chronic otitis media. During coinfection with nontypeable H. influenzae, both species persisted for one week and induced polymicrobial otitis media. We also observed that nontypeable H. influenzae conferred passive protection from killing by amoxicillin upon S. pneumoniae from within polymicrobial biofilms in vitro. Therefore, based on these results, we conclude that nonencapsulated pneumococci are a potential causative agent of chronic/recurrent otitis media, and can also cause mutualistic infection with other opportunists, which could complicate treatment outcomes. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Aspectos epidemiológicos da infecção por Haemophilus influenzae tipo b Epidemiologic aspects of Haemophilus influenzae type b infection

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Maria Angela Loguercio Bouskela

2000-05-01

Full Text Available O objetivo do presente trabalho foi revisar o papel do Haemophilus influenzae tipo b (Hib como um dos patógenos mais importantes implicados em doenças infecciosas invasivas, especialmente nos 2 primeiros anos de vida. Nos países em desenvolvimento, o H. Influenzae chega a causar 30% dos casos de pneumonia com cultura positiva e de 20 a 60% dos casos de meningite bacteriana. No presente estudo, dados epidemiológicos do Brasil foram comparados com dados internacionais obtidos em bancos de dados (Medline, 1966 a 1995; LILACS, 1982 a 1995; Thesis databank, 1980 a 1995; e Dissertation abstracts, 1988 a 1994. Analisámos o coeficiente de incidência do Hib no Brasil por estado e por faixa etária, com estratificação inclusive para o 1° ano de vida. A meningite foi utilizada como marcador do coeficiente de incidência devido às dificuldades para obter material adequado para a identificação do microrganismo nos outros quadros, como pneumonia, osteomielite, epiglotite ou endocardite. Nossa análise revelou que os dados nacionais mascaram a incidência e a letalidade regionais do H. influenzae: por exemplo, em 1991, a incidência no Brasil foi de 18,4 em 100 000 crianças menores de 1 ano; no mesmo período, a incidência no Distrito Federal foi de 175 em 100 000 crianças entre 4 e 6 meses. Além disso, a letalidade na região Norte foi de 35% em 1987, contra 22% para o Brasil como um todo. Nosso estudo abre a discussão sobre aspectos epidemiológicos relevantes das infecções por Hib e sobre o custo-benefício da profilaxia e vacinação nas faixas etárias de maior risco.This paper reviews the role of Haemophilus influenzae type b (Hib as one of the most important pathogens causing invasive infectious diseases, especially in the first 2 years of life. In developing countries H. influenzae is responsible for 30% of all pneumonia cases with positive cultures and for 20% to 60% of all bacterial meningitis cases. In this study we compared

Immunological characterization of conjugated Haemophilus influenzae type b vaccine failure in infants

NARCIS (Netherlands)

Breukels, M. A.; Spanjaard, L.; Sanders, L. A.; Rijkers, G. T.

2001-01-01

Infant vaccination with conjugated Haemophilus influenzae type b (Hib) vaccine is highly effective in protecting against invasive Hib infections, but vaccine failures do occur. Twenty-one vaccine failures are reported since the introduction of the Hib conjugate vaccine in The Netherlands. Of the 14

Evaluation of new biomarker genes for differentiating Haemophilus influenzae from Haemophilus haemolyticus.

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Theodore, M Jordan; Anderson, Raydel D; Wang, Xin; Katz, Lee S; Vuong, Jeni T; Bell, Melissa E; Juni, Billie A; Lowther, Sara A; Lynfield, Ruth; MacNeil, Jessica R; Mayer, Leonard W

2012-04-01

PCR detecting the protein D (hpd) and fuculose kinase (fucK) genes showed high sensitivity and specificity for identifying Haemophilus influenzae and differentiating it from H. haemolyticus. Phylogenetic analysis using the 16S rRNA gene demonstrated two distinct groups for H. influenzae and H. haemolyticus.

An isolate of Haemophilus haemolyticus produces a bacteriocin-like substance that inhibits the growth of nontypeable Haemophilus influenzae.

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Latham, Roger D; Gell, David A; Fairbairn, Rory L; Lyons, A Bruce; Shukla, Shakti D; Cho, Kum Yin; Jones, David A; Harkness, Nick M; Tristram, Stephen G

2017-04-01

Nontypeable Haemophilus influenzae (NTHi) frequently colonises the upper respiratory tract and is an important cause of respiratory infections. Resistance to antibiotics is an emerging trend in NTHi and alternative prevention or treatment strategies are required. Haemophilus haemolyticus is a common commensal occupying the same niche as NTHi and, if able to produce substances that inhibit NTHi growth, may have a role as a probiotic. In this study, ammonium sulphate extracts from broth culture of 100 H. haemolyticus isolates were tested for the presence of substances inhibitory to NTHi using a well diffusion assay. One isolate produced a substance that consistently inhibited the growth of NTHi. The substance was inactivated by protease enzymes and had a molecular size of ca. 30 kDa as determined by size exclusion chromatography. When the substance was tested against bacteria from eight Gram-negative and three Gram-positive genera, only Haemophilus spp. were inhibited. Quantitative PCR testing showed the substance to be different to 'haemocin', the previously described bacteriocin of H. influenzae type b. These molecular characteristics, together with narrow-spectrum activity, suggest the substance may be a novel bacteriocin, and there is potential for this H. haemolyticus isolate to function as a probiotic for reduction of colonisation and subsequent infection with NTHi. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

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

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Paul T. King

2015-01-01

Full Text Available 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.

Secondary Bacterial Infections Associated with Influenza Pandemics

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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

Secondary Bacterial Infections Associated with Influenza Pandemics

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Denise E. Morris

2017-06-01

Full Text Available 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.

Expression of urease by Haemophilus influenzae during human respiratory tract infection and role in survival in an acid environment

Science.gov (United States)

2011-01-01

Background Nontypeable Haemophilus influenzae is a common cause of otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). Prior studies have shown that H. influenzae expresses abundant urease during growth in the middle ear of the chinchilla and in pooled human sputum, suggesting that expression of urease is important for colonization and infection in the hostile environments of the middle ear and in the airways in adults. Virtually nothing else is known about the urease of H. influenzae, which was characterized in the present study. Results Analysis by reverse transcriptase PCR revealed that the ure gene cluster is expressed as a single transcript. Knockout mutants of a urease structural gene (ureC) and of the entire ure operon demonstrated no detectable urease activity indicating that this operon is the only one encoding an active urease. The ure operon is present in all strains tested, including clinical isolates from otitis media and COPD. Urease activity decreased as nitrogen availability increased. To test the hypothesis that urease is expressed during human infection, purified recombinant urease C was used in ELISA with pre acquisition and post infection serum from adults with COPD who experienced infections caused by H. influenzae. A total of 28% of patients developed new antibodies following infection indicating that H. influenzae expresses urease during airway infection. Bacterial viability assays performed at varying pH indicate that urease mediates survival of H. influenzae in an acid environment. Conclusions The H. influenzae genome contains a single urease operon that mediates urease expression and that is present in all clinical isolates tested. Nitrogen availability is a determinant of urease expression. H. influenzae expresses urease during human respiratory tract infection and urease is a target of the human antibody response. Expression of urease enhances viability in an acid

Low occurrence of 'non-haemolytic Haemophilus haemolyticus' misidentified as Haemophilus influenzae in cystic fibrosis respiratory specimens, and frequent recurrence of persistent H. influenzae clones despite antimicrobial treatment.

Science.gov (United States)

Fenger, Mette G; Ridderberg, Winnie; Olesen, Hanne V; Nørskov-Lauritsen, Niels

2012-12-01

Non-influenzae commensal Haemophilus species of low pathogenicity may be difficult to discriminate from Haemophilus influenzae. We investigated the level of misidentifications in respiratory specimens from cystic fibrosis patients and evaluated the colonisation dynamics of genuine H. influenzae isolates. One hundred and ninety-two presumptive H. influenzae isolates were re-examined by assessment of marker genes sodC and fucK, and isolates with aberrant genotypes were subjected to multilocus sequence typing. Misidentifications (3%) were mainly caused by failure to identify porphyrin-synthesising strains, and only a single strain (0.5%) could be classified as 'non-haemolytic Haemophilus haemolyticus'. Sequential isolates of confirmed H. influenzae isolates from individual patients were typed by pulsed-field gel electrophoresis. Despite the routine prescription of antimicrobial therapy, the majority of H. influenzae isolates were identical with at least one of the strains cultured from the two preceding positive samples from the same patient. Copyright © 2012 Elsevier GmbH. All rights reserved.

Clinical characteristics of Haemophilus influenzae meningitis in Denmark in the post-vaccination era

DEFF Research Database (Denmark)

Pedersen, T.I.; Howitz, M.; Andersen, Christian Østergaard

2010-01-01

P>The introduction of Haemophilus influenzae type b (Hib) vaccine into the Danish childhood vaccination programme in 1993 may have influenced the epidemiology of H. influenzae meningitis (i.e. increasing frequency of other non-vaccine types; presentation in other age groups). Based on nationwide...... registration, clinical information and laboratory findings were collected from all 65 confirmed cases of H. influenzae meningitis during the period 1994-2005. Twenty-nine patients (45%) were 24 years old [median 62 years (range 25...... infected with Hib, two cases (13%) were identified as true vaccine failures. Six patients (9%) died; one premature infant infected with serotype f and five adults (age 83-96 years) with non-typeable H. influenzae. Hearing loss was reported in 16% of the surviving children and in 10% of the surviving adults...

Delineation of the species Haemophilus influenzae by phenotype, multilocus sequence phylogeny, and detection of marker genes

DEFF Research Database (Denmark)

Nørskov-Lauritsen, Niels; Overballe, MD; Kilian, Mogens

2009-01-01

To obtain more information on the much-debated definition of prokaryotic species, we investigated the borders of Haemophilus influenzae by comparative analysis of H. influenzae reference strains with closely related bacteria including strains assigned to Haemophilus haemolyticus, cryptic genospec......To obtain more information on the much-debated definition of prokaryotic species, we investigated the borders of Haemophilus influenzae by comparative analysis of H. influenzae reference strains with closely related bacteria including strains assigned to Haemophilus haemolyticus, cryptic...... genospecies biotype IV, and the never formally validated species "Haemophilus intermedius". Multilocus sequence phylogeny based on six housekeeping genes separated a cluster encompassing the type and the reference strains of H. influenzae from 31 more distantly related strains. Comparison of 16S rRNA gene...

First Necrotizing Fasciitis Caused by Haemophilus influenza Serotype a

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Quach, Giang T.; Frisby, Jared; Kralovich, Kurt; Bohra, Mustafa

2017-01-01

Necrotizing fasciitis (NF) is an infrequently encountered skin infection that has high morbidity and mortality, even with prompt medical and surgical intervention. We describe the case of a 67-year-old male presenting with significant NF in his left lower extremity, despite aggressive surgical intervention, and included multiple surgical debridements, ACell Matrix, split-thickness, and negative wound VAC therapy. Ultimately, this patient required a below the knee amputation. This is the first documented case of Haemophilus influenza type a causing NF. PMID:29124073

Identifying Haemophilus haemolyticus and Haemophilus influenzae by SYBR Green real-time PCR.

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Latham, Roger; Zhang, Bowen; Tristram, Stephen

2015-05-01

SYBR Green real time PCR assays for protein D (hpd), fuculose kinase (fucK) and [Cu, Zn]-superoxide dismutase (sodC) were designed for use in an algorithm for the identification of Haemophilus influenzae and H. haemolyticus. When tested on 127 H. influenzae and 60 H. haemolyticus all isolates were identified correctly. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

NNDSS - Table II. Giardiasis to Haemophilus influenza

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U.S. Department of Health & Human Services — NNDSS - Table II. Giardiasis to Haemophilus influenza - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

NNDSS - Table II. Giardiasis to Haemophilus influenza

Data.gov (United States)

U.S. Department of Health & Human Services — NNDSS - Table II. Giardiasis to Haemophilus influenza - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

NNDSS - Table II. Giardiasis to Haemophilus influenza

Data.gov (United States)

U.S. Department of Health & Human Services — NNDSS - Table II. Giardiasis to Haemophilus influenza - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

NNDSS - Table II. Giardiasis to Haemophilus influenza

Data.gov (United States)

U.S. Department of Health & Human Services — NNDSS - Table II. Giardiasis to Haemophilus influenza - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the...

NNDSS - Table II. Giardiasis to Haemophilus influenza

Data.gov (United States)

U.S. Department of Health & Human Services — NNDSS - Table II. Giardiasis to Haemophilus influenza - 2014. In this Table, all conditions with a 5-year average annual national total of more than or equals 1,000...

Comparison of Established Diagnostic Methodologies and a Novel Bacterial smpB Real-Time PCR Assay for Specific Detection of Haemophilus influenzae Isolates Associated with Respiratory Tract Infections.

Science.gov (United States)

Reddington, Kate; Schwenk, Stefan; Tuite, Nina; Platt, Gareth; Davar, Danesh; Coughlan, Helena; Personne, Yoann; Gant, Vanya; Enne, Virve I; Zumla, Alimuddin; Barry, Thomas

2015-09-01

Haemophilus influenzae is a significant causative agent of respiratory tract infections (RTI) worldwide. The development of a rapid H. influenzae diagnostic assay that would allow for the implementation of infection control measures and also improve antimicrobial stewardship for patients is required. A number of nucleic acid diagnostics approaches that detect H. influenzae in RTIs have been described in the literature; however, there are reported specificity and sensitivity limitations for these assays. In this study, a novel real-time PCR diagnostic assay targeting the smpB gene was designed to detect all serogroups of H. influenzae. The assay was validated using a panel of well-characterized Haemophilus spp. Subsequently, 44 Haemophilus clinical isolates were collected, and 36 isolates were identified as H. influenzae using a gold standard methodology that combined the results of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and a fucK diagnostic assay. Using the novel smpB diagnostic assay, 100% concordance was observed with the gold standard, demonstrating a sensitivity of 100% (95% confidence interval [CI], 90.26% to 100.00%) and a specificity of 100% (95% CI, 63.06% to 100.00%) when used on clinical isolates. To demonstrate the clinical utility of the diagnostic assay presented, a panel of lower RTI samples (n = 98) were blindly tested with the gold standard and smpB diagnostic assays. The results generated were concordant for 94/98 samples tested, demonstrating a sensitivity of 90.91% (95% CI, 78.33% to 97.47%) and a specificity of 100% (95% CI, 93.40% to 100.00%) for the novel smpB assay when used directly on respiratory specimens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Clonal relationship of recent invasive Haemophilus influenzae serotype f isolates from Denmark and the United States

DEFF Research Database (Denmark)

Bruun, B; Gahrn-Hansen, B; Westh, H

2004-01-01

Surveillance performed after the introduction of general Haemophilus influenzae serotype b (Hib) vaccination in Denmark identified 13 cases of invasive bacteraemic H. influenzae serotype f (Hif) disease in adults over a period of 7 years. Bacteraemic respiratory tract infections accounted for 61...... sequences. Multilocus enzyme electrophoresis typing revealed that recent Danish and American isolates belonged to a single Hif clone, which may be undergoing expansion. The need for accurate serotyping of H. influenzae to enable reliable monitoring for Hib replacement by other capsular types is emphasized....

The Comparison of Haemophilus Influenza in the Throat of Healthy Infants with Different Feeding Methods

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A Kazemi

2004-06-01

Full Text Available Background: Haemophilus influenza (HI is the most commonly found pathogenic bacteria in pediatric otitis media and lower respiratory tract infections. Bacterial attachment to pharyngeal cells and proliferation may be necessary for infection. In the presence of human milk, attachment of HI to pharyngeal cells and colonization may be inhibited. To evaluate the protecting role of breast milk, we investigated the incidence of HI isolated from the throat of healthy infants with different feeding methods. Methods: Between August 2002 and March 2003, 210 healthy infants (70 purely breast-fed, 70 purely formula-fed, 70 mixed-fed, aged 1-6 months were enrolled into the study and a throat culture was taken in all of them. The incidence of HI was evaluated using Haemophilus Test Agar Bose (HTAB plates. Results: The incidence of HI in purely breast-fed, mixed-fed and purely formula-fed infants was 2.9%, 42.9% and 75.7% respectively (P = 0.000. The mean age and weight of cases in the three groups were not statistically different. Conclusion: These data suggest that human milk protects the throat of healthy infants from HI colonization especially in purely breast-fed cases. Keywords: Breast milk, Haemophilus influenza, Throat culture

Tipificación capsular mediante PCR de aislamientos de Haemophilus influenzae no tipificables por aglutinación PCR-based capsular typing of Haemophilus influenzae isolates non-typeable by agglutination

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G. Weltman

2005-12-01

Full Text Available Haemophilus influenzae es reconocido como un agente patógeno responsable de infecciones localizadas y sistémicas. Se han descrito 6 tipos de polisacáridos capsulares antigénicamente distintos (a, b, c, d, e, y f que se pueden identificar por aglutinación en lámina con antisueros específicos. También existen cepas no capsuladas (NC fenotípicamente no tipificables (NT. La introducción de la vacuna conjugada produjo una marcada disminución de las enfermedades invasivas causadas por H. influenzae tipo b. En este contexto, la tipificación capsular mediante PCR es el método más apropiado para distinguir las cepas no capsuladas de las mutantes b deficientes en cápsula (b- y detectar la presencia de cepas pertenecientes a otros serotipos que no puedan ser tipificables por aglutinación. Se determinó el genotipo capsular a 38 aislamientos de Haemophilus influenzae no tipificables por aglutinación, derivados al servicio de Bacteriología Clínica del INEI-ANLIS "Dr. Carlos G. Malbrán" en el período 2002-2004. El 78,9% de los aislamientos provenían de hemocultivos y la mayor parte de ellos estaban asociados a foco respiratorio. El 100% de los aislamientos fueron identificados como H. influenzae no capsulados mediante la técnica de PCR.Haemophilus influenzae is recognized as a pathogenic agent responsible of localized and systemic infections. Six antigenically different capsular polysaccharide types have been described (a, b, c, d, e, and f which can be identified by slide agglutination with specific antisera. Besides there are non capsulated strains that cannot be typed by slide agglutination. The introduction of the conjugated vaccine produced an important reduction of invasive diseases caused by H. influenzae type b. Capsular typing by PCR is the most appropriated method for distinguishing non capsulated strains from capsule deficient type b mutants (b- and for detecting strains of other serotypes that cannot be detected by slide

Haemophilus influenzae Type a Meningitis in Immunocompetent Child, Oman, 2015.

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Sawardekar, Kiran P

2017-07-01

Meningitis caused by Haemophilus influenzae type b (Hib) was eliminated in Oman after the introduction of Hib vaccine in 2001. However, a case of H. influenzae type a meningitis was diagnosed in a child from Oman in 2015, which highlights the need to monitor the incidence of invasive non-Hib H. influenzae disease.

Clinical and microbiological features of Haemophilus influenzae vulvovaginitis in young girls

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Cox, R A; Slack, M P E

2002-01-01

Aims: To define the clinical and microbiological features of vulvovaginitis in prepubertal girls whose genital swabs yielded Haemophilus influenzae. Methods: Laboratory based study and retrospective collection of clinical data from the requesting doctors. Results: Thirty eight isolates of non-capsulate Haemophilus influenzae and one of H parainfluenzae were isolated from 32 girls aged 18 months to 11 years. No other pathogens, such as β haemolytic streptococci or yeasts, were present with H influenzae. The most common biotype was biotype II, comprising 57% of the 26 isolates biotyped. Six children had more than one episode of vulvovaginitis caused by H influenzae and a total of 14 children had recurrent vaginal symptoms. Conclusion: Children who have H influenzae vulvovaginitis are at risk of recurrent symptoms. Biotype II is the one most commonly associated with this condition. PMID:12461068

Vaccine-Induced Waning of Haemophilus influenzae Empyema and Meningitis, Angola

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Peltola, Heikki; Bernardino, Luis; Monteiro, Lurdes; Silvestre, Silvia da Conceição; Anjos, Elizabete; Cruzeiro, Manuel Leite; Pitkäranta, Anne; Roine, Irmeli

2014-01-01

In Angola during 2003–2012, we detected Haemophilus influenzae in 18% of 2,634 and 26% of 2,996 bacteriologically positive pleural or cerebrospinal fluid samples, respectively, from children. After vaccination launch in 2006, H. influenzae empyema declined by 83% and meningitis by 86%. Severe H. influenzae pneumonia and meningitis are preventable by vaccination. PMID:25340259

Haemophilus influenzae type b pneumonia in Egyptian children ...

African Journals Online (AJOL)

Haemophilus influenzae (Hi) causes more than 3 million cases of serious disease, mainly meningitis and ... One hundred patients with community-acquired pneumonia were investigated for Hib by both real-time PCR and bacterial culture.

Quorum signaling and sensing by nontypeable Haemophilus influenzae

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W Edward Swords

2012-07-01

Full Text Available Quorum signals are diffusible factors produced by bacteria that coordinate communal responses. For Haemophilus influenzae, a series of recent papers indicate that production and sensing of quorum signals are determinants of biofilm formation/maturation and persistence in vivo. In this mini-review I will summarize the current knowledge about quorum signaling/sensing by H. influenzae, and identify specific topics for additional study.

Inflammatory response of Haemophilus influenzae biotype aegyptius causing Brazilian Purpuric Fever

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Gisele Cristiane Gentile Cury

2014-12-01

Full Text Available The Brazilian Purpuric Fever (BPF is a systemic disease with many clinical features of meningococcal sepsis and is usually preceded by purulent conjunctivitis. The illness is caused by Haemophilus influenza biogroup aegyptius, which was associated exclusively with conjunctivitis. In this work construction of the las gene, hypothetically responsible for this virulence, were fusioned with ermAM cassette in Neisseria meningitidis virulent strains and had its DNA transfer to non BPF H. influenzae strains. The effect of the las transfer was capable to increase the cytokines TNFα and IL10 expression in Hec-1B cells line infected with these transformed mutants (in eight log scale of folding change RNA expression. This is the first molecular study involving the las transfer to search an elucidation of the pathogenic factors by horizontal intergeneric transfer from meningococci to H. influenzae.

Clinical characteristics of Haemophilus influenzae meningitis in Denmark in the post-vaccination era

DEFF Research Database (Denmark)

Pedersen, T.I.; Howitz, Michael Frantz; Andersen, Christian Østergaard

2010-01-01

P>The introduction of Haemophilus influenzae type b (Hib) vaccine into the Danish childhood vaccination programme in 1993 may have influenced the epidemiology of H. influenzae meningitis (i.e. increasing frequency of other non-vaccine types; presentation in other age groups). Based on nationwide...... infected with Hib, two cases (13%) were identified as true vaccine failures. Six patients (9%) died; one premature infant infected with serotype f and five adults (age 83-96 years) with non-typeable H. influenzae. Hearing loss was reported in 16% of the surviving children and in 10% of the surviving adults....... The presence of a lung focus was an independent prognostic factor for an unfavourable outcome (p 0.03). In conclusion, meningitis caused by Hib has been infrequent in Denmark after introduction of the Hib vaccine in the childhood vaccination programme, and no increase in meningitis cases due to non-b type H...

Recurrent Posttraumatic Meningitis due to Nontypable Haemophilus influenzae: Case Report and Review of the Literature

DEFF Research Database (Denmark)

Kunze, W; Müller, L; Kilian, Mogens

2007-01-01

We report a case of relapsing Haemophilus influenzae meningitis in a boy at the age of nearly 3 years and 4.2 years who had been successfully vaccinated against H. influenzae serotype b (Hib). The pathogen was a nonencapsulated (nontypable) H. influenzae strain of biotypes III and VI, respectively....... A rhinobasal impalement injury with development of a posttraumatic encephalocele is considered to be the predisposing condition. Review of the literature reveals that in patients systemically infected by nonencapsulated H. influenzae strains predisposing factors such as cerebrospinal fluid-shunts, implants...... and traumas are often found. To obtain further information on potential new disease patterns H. influenzae isolates from cerebrospinal fluid should be examined for capsule production and, if relevant, further characterized by capsular typing....

Plasmid containing a DNA ligase gene from Haemophilus influenzae

International Nuclear Information System (INIS)

McCarthy, D.; Griffin, K.; Setlow, J.K.

1984-01-01

A ligase gene from Haemophilus influenzae was cloned into the shuttle vector pDM2. Although the plasmid did not affect X-ray sensitivity, it caused an increase in UV sensitivity of the wild-type but not excision-defective H. influenzae and a decrease in UV sensitivity of the rec-1 mutant. 14 references, 2 figures

Haemophilus influenzae type f meningitis in a previously healthy boy

DEFF Research Database (Denmark)

Ronit, Andreas; Berg, Ronan M G; Bruunsgaard, Helle

2013-01-01

Non-serotype b strains of Haemophilus influenzae are extremely rare causes of acute bacterial meningitis in immunocompetent individuals. We report a case of acute bacterial meningitis in a 14-year-old boy, who was previously healthy and had been immunised against H influenzae serotype b (Hib...

Oropharyngeal colonization by Haemophilus influenzae in healthy children from Taubaté (São Paulo, prior to the Haemophilus influenzae type b vaccination program in Brazil Colonização da orofaringe de crianças saudáveis de Taubaté (São Paulo por Haemophilus influenzae, antes da introdução da vacina contra Haemophilus influenzae do tipo b no Brasil

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Lucia Ferro Bricks

2004-01-01

Full Text Available Haemophilus influenzae is one of the most important bacterial agents of otitis and sinusitis. H. influenzae type b (Hib is one of the main causes of meningitis, pneumonia, and septicemia in nonvaccinated children under 6 years of age. The aims of this study were to determine the prevalence of H. influenzae and Hib oropharyngeal colonization prior to the onset of the Hib vaccination program in Brazil in previously healthy children and to assess the susceptibility profile of this microorganism to a selected group of antimicrobials that are used to treat acute respiratory infections. METHOD: Cultures of Haemophilus influenzae were made from oropharynx swabs from 987 children under 6 years of age who were enrolled in 29 day-care centers in Taubaté (a city of São Paulo state, Brazil between July and December 1998. RESULTS: The prevalence of H. influenzae carriers was 17.4%, and only 5.5% of the strains were beta-lactamase producers. The prevalence of Hib carriers was high, 7.3% on average (range, 0.0 - 33.3%. CONCLUSIONS: The low prevalence of colonization by penicillin-resistant strains indicates that it is not necessary to substitute ampicilin or amoxicilin to effectively treat otitis and sinusitis caused by H. influenzae in Taubaté.Haemophilus influenzae é um dos mais importantes agentes bacterianos de otites e sinusites. Em crianças menores de seis anos de idade não vacinadas contra o H. influenzae do tipo b (Hib, essa bactéria é uma das principais causadoras de meningite, pneumonia e sepse. O objetivo deste estudo foi determinar a prevalência da colonização da orofaringe de crianças previamente saudáveis por H. influenzae e Hib e avaliar o perfil de suscetibilidade desses microorganismos a um grupo seleto de antimicrobianos, que habitualmente são utilizados para tratar as infecções respiratórias agudas. MÉTODO: Foram colhidos swabs da orofaringe de 987 crianças menores de seis anos de idade que freqüentavam 29 creches da

Frequent carriage of resistance mechanisms to beta-lactams and biofilm formation in Haemophilus influenzae causing treatment failure and recurrent otitis media in young children

NARCIS (Netherlands)

Garcia-Cobos, Silvia; Moscoso, Miriam; Pumarola, Felix; Arroyo, Margarita; Lara, Noelia; Perez-Vazquez, Maria; Aracil, Belen; Oteo, Jesus; Garcia, Ernesto; Campos, Jose

Objectives: Non-typeable Haemophilus influenzae are a major cause of acute otitis media (AOM), including chronic and recurrent otitis in young children. The objective of this study was to determine whether non-typeable H. influenzae isolates causing these infections produce biofilms and carry

Polyarticular Septic Arthritis Caused by Haemophilus influenzae Serotype f in an 8-Month-Old Immunocompetent Infant: A Case Report and Review of the Literature

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Raheel Ahmed Ali

2015-01-01

Full Text Available Background. The standard use of vaccinations against pathogens has resulted in a decreased incidence of musculoskeletal infections caused by these previously common bacterial pathogens. Consequently, the incidence of infections caused by atypical bacteria is rising. This report presents a case of septic arthritis caused by non-type b H. influenzae in a pediatric patient. Methods. We report a case of an infant with polyarticular septic arthritis caused by H. influenzae serotype f. A literature review was conducted with the inclusion criteria of case reports and studies published between 2004 and 2013 addressing musculoskeletal H. influenzae infections. Results. An 8-month-old female presented with pain and swelling in her right ankle and left elbow. The patient was diagnosed with septic arthritis and underwent incision and drainage. Wound and blood cultures were positive for Haemophilus influenzae serotype f. In addition to treatment with IV antibiotics, the patient underwent immunocompetency studies, which were normal. Subsequent follow-up revealed eradication of the infection. Conclusions. Haemophilus influenzae non-type b may cause serious invasive infections such as sepsis or septic arthritis in children with or without predisposing factors such as immunodeficiency or asplenia. Optimal treatment includes surgical management, culture driven IV antibiotics, and an immunologic workup.

Haemophilus influenzae: an underrated cause of vulvovaginitis in young girls.

Science.gov (United States)

Cox, R A

1997-01-01

AIMS: To establish the common pathogens associated with infective vulvovaginitis in young girls in the local population and to determine current management of this condition. METHODS: A prospective laboratory based survey was carried out over 19 months. A questionnaire was then sent to local general practitioners and hospital doctors. RESULTS: One hundred and six swabs were received during the study period of which 43 (40.5%) yielded organisms recognised as causes of vulvovaginitis. The most common pathogen was group A beta haemolytic streptococcus (19), with Haemophilus influenzae the second most common (11). Candida was isolated on nine occasions. The users' questionnaire had an overall response rate of 52%. Forty one per cent of respondents nominated candida as the most common cause of this condition. Forty six per cent were aware that beta haemolytic streptococci caused juvenile vulvovaginitis, but only four (3.6%) knew that H influenzae was a possible pathogen. The most popular agent for empirical treatment of vulvovaginitis was topical clotrimazole cream, although 24 respondents (22%) prescribed antibiotics that are active against both group A beta haemolytic streptococci and H influenzae. CONCLUSIONS: Although H influenzae is the second most common infective cause of juvenile vulvovaginitis in the local population, most doctors managing these patients were unaware of its importance and may not be prescribing appropriate empirical treatment. Images PMID:9389978

Immunogenicity and effectiveness of Haemophilus influenzae type b conjugate vaccine in HIV infected and uninfected African children.

Science.gov (United States)

Madhi, Shabir A; Kuwanda, Locadiah; Saarinen, Leena; Cutland, Clare; Mothupi, Rosalia; Käyhty, Helena; Klugman, Keith P

2005-12-01

The quantitative (anti-Hib capsular polysaccharide antibody concentrations; anti-HibPS) and qualitative (bactericidal activity and avidity) aspects in immune responses to Haemophilus influenzae type b polyribosyl ribitol phospshate-CRM(197) conjugate vaccine (HibCV; HibTiter) were evaluated in 66 HIV infected children not receiving anti-retroviral therapy and 127 HIV uninfected children. Surveillance was conducted for invasive Hib disease in a cohort of 39,865 (approximately 6.4% of whom were HIV infected) children from March 1998 to June 2004. HIV infected children had lower anti-HibPS geometric mean antibody concentrations 1 month post-immunisation than HIV uninfected children (Por=1.0 microg/ml (RR 0.54; 95% CI 0.43-0.69). A lower proportion of HIV infected children than HIV uninfected children (RR 0.78; 95% CI 0.66-0.93) had measurable anti-Hib serum bactericidal activity (SBA) and the HibPS antibody concentration required for 50% killing of Hib bacteria was greater among HIV infected than HIV uninfected children (P=0.001). The estimated risk of HibCV failure was 35.1-fold greater (95% CI 14.6-84.6) amongst HIV infected than HIV uninfected children.

Invasive Haemophilus Influenzae Disease, Europe, 1996–2006

Centers for Disease Control (CDC) Podcasts

This podcast describes monitoring of Haemophilus influenzae disease in Europe from 1996 through 2006. CDC epidemiologist Stacey Martin discusses what researchers learned about the effect of vaccination on disease prevalence.

Isolation of Haemophilus influenzae and Haemophilus parainfluenzae in urethral exudates from men with acute urethritis: a descriptive study of 52 cases.

Science.gov (United States)

Deza, Gustavo; Martin-Ezquerra, Gemma; Gómez, Julià; Villar-García, Judit; Supervia, August; Pujol, Ramon M

2016-02-01

To describe the clinical characteristics and therapeutic outcomes from male patients diagnosed of Haemophilus spp urethritis. A chart review of patients who presented to our hospital from January 2013 to December 2014 with symptoms of acute urethritis in which Haemophilus spp was isolated in their urethral samples was performed. Haemophilus spp was isolated in 52 out of 413 urethral samples (12.6%) received in our laboratory from patients with symptoms of acute urethritis during the study period. Seven cases corresponded to Haemophilus influenzae and 45 cases to Haemophilus parainfluenzae. The most common clinical presentation was mucopurulent urethral discharge (71%). Eight per cent were HIV-infected patients, and 60% were men who have sex with men. Haemophilus spp was isolated as a single pathogen in 6.8% (28 of 413) of cases. Seventeen per cent of Haemophilus spp were β-lactamase producers. All patients reported having practiced unprotected insertive oral sex the month before consultation, and five of them denied having had another sexual contact apart from this exposure. In all cases in which follow-up was available, empirical treatment achieved a complete clinical resolution. Haemophilus spp was considered a pathogen in at least 6.8% of the patients from the evaluated area. It affected men regardless their sexual orientation or HIV status. Unprotected oral sex could play a role in its transmission. The limitations of the study (small sample size and lack of a representative control group) do not allow to prove the true pathogenic role of Haemophilus spp in acute urethritis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Haemophilus parainfluenzae Strain ATCC 33392 Forms Biofilms In Vitro and during Experimental Otitis Media Infections.

Science.gov (United States)

Pang, Bing; Swords, W Edward

2017-09-01

Haemophilus parainfluenzae is a nutritionally fastidious, Gram-negative bacterium with an oropharyngeal/nasopharyngeal carriage niche that is associated with a range of opportunistic infections, including infectious endocarditis and otitis media (OM). These infections are often chronic/recurrent in nature and typically involve bacterial persistence within biofilm communities that are highly resistant to host clearance. This study addresses the primary hypothesis that H. parainfluenzae forms biofilm communities that are important determinants of persistence in vivo The results from in vitro biofilm studies confirmed that H. parainfluenzae formed biofilm communities within which the polymeric matrix was mainly composed of extracellular DNA and proteins. Using a chinchilla OM infection model, we demonstrated that H. parainfluenzae formed surface-associated biofilm communities containing bacterial and host components that included neutrophil extracellular trap (NET) structures and that the bacteria mainly persisted in these biofilm communities. We also used this model to examine the possible interaction between H. parainfluenzae and its close relative Haemophilus influenzae , which is also commonly carried within the same host environments and can cause OM. The results showed that coinfection with H. influenzae promoted clearance of H. parainfluenzae from biofilm communities during OM infection. The underlying mechanisms for bacterial persistence and biofilm formation by H. parainfluenzae and knowledge about the survival defects of H. parainfluenzae during coinfection with H. influenzae are topics for future work. Copyright © 2017 American Society for Microbiology.

Relationship between secretion of the Anton blood group antigen in saliva and adherence of Haemophilus influenzae to oropharynx epithelial cells

NARCIS (Netherlands)

van Alphen, L.; van Ham, M.; Geelen-van den Broek, L.; Pieters, T.

1989-01-01

Inhibition of adherence of bacteria to epithelial cells contributes to a reduction of infections by these bacteria. We have shown that the Anton blood group antigen, the erythrocyte receptor for Haemophilus influenzae (van Alphen et al. 1986, FEMS Microbiol. Lett. 37, 69-71), occurs in saliva, that

Indirect pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in polymicrobial otitis media occurs via interspecies quorum signaling.

Science.gov (United States)

Armbruster, Chelsie E; Hong, Wenzhou; Pang, Bing; Weimer, Kristin E D; Juneau, Richard A; Turner, James; Swords, W Edward

2010-07-06

Otitis media (OM) is among the leading diseases of childhood and is caused by opportunists that reside within the nasopharynx, such as Haemophilus influenzae and Moraxella catarrhalis. As with most airway infections, it is now clear that OM infections involve multiple organisms. This study addresses the hypothesis that polymicrobial infection alters the course, severity, and/or treatability of OM disease. The results clearly show that coinfection with H. influenzae and M. catarrhalis promotes the increased resistance of biofilms to antibiotics and host clearance. Using H. influenzae mutants with known biofilm defects, these phenotypes were shown to relate to biofilm maturation and autoinducer-2 (AI-2) quorum signaling. In support of the latter mechanism, chemically synthesized AI-2 (dihydroxypentanedione [DPD]) promoted increased M. catarrhalis biofilm formation and resistance to antibiotics. In the chinchilla infection model of OM, polymicrobial infection promoted M. catarrhalis persistence beyond the levels seen in animals infected with M. catarrhalis alone. Notably, no such enhancement of M. catarrhalis persistence was observed in animals infected with M. catarrhalis and a quorum signaling-deficient H. influenzae luxS mutant strain. We thus conclude that H. influenzae promotes M. catarrhalis persistence within polymicrobial biofilms via interspecies quorum signaling. AI-2 may therefore represent an ideal target for disruption of chronic polymicrobial infections. Moreover, these results strongly imply that successful vaccination against the unencapsulated H. influenzae strains that cause airway infections may also significantly impact chronic M. catarrhalis disease by removing a reservoir of the AI-2 signal that promotes M. catarrhalis persistence within biofilm.

Fallos vacunales a vacunas conjugadas de Streptococcus pneumoniae y Haemophilus influenzae tipo b

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Gonzalo Angulo

2016-11-01

Full Text Available Haemophilus influenzae type b and Streptococcus pneumoniae are the main cause agents of otitis, pneumonia, sepsis and meningitis, affecting mainly children under 5 years. Conjugate vaccines for encapsulated germs have dramatically decreased, the various diseases caused by these germs. Despite the decrease in morbidity and mortality, vaccine failures were observed. Children who experienced vaccine failures to Haemophilus influenzae type b had associated comorbidities more frequently than the general population (prematurity, HIV, Down syndrome, tumors, etc.. Nevertheless, most of these children have no medical history or immunological disorders. There is no consensus on whether all patients with vaccine failures should be assessed immunologically and how. There are recommendations to indicate a booster dose to patients with certain comorbidities and patients experiencing vaccine failure even in the absence of theses. Of the vaccine preparations available for Haemophilus influenzae type b association with acellular Bordetella pertussis proved to be less immunogenic and is currently being discouraged. Streptococcus pneumoniae serotypes 6B and 19F are less immunogenics and explain most of the vaccine failures in some series.

Structure of the N-terminal region of Haemophilus Influenzae HI0017: Implications for function

International Nuclear Information System (INIS)

Yu Liping; Mack, Jamey; Hajduk, Phil; Fesik, Stephen W.

2001-01-01

Haemophilus influenzae is a gram-negative pathogen that causes infections ranging from asymptomatic colonization of the human upper respiratory tract to serious invasive diseases such as meningitis. Although the genome of Haemophilus influenzae has been completely sequenced, the structure and function of many of these proteins are unknown. HI0017 is one of these uncharacterized proteins. Here we describe the three-dimensional solution structure of the N-terminal portion of HI0017 as determined by NMR spectroscopy. The structure consists of a five-stranded antiparallel β-sheet and two short α-helices. It is similar to the C-terminal domain of Diphtheria toxin repressor (DtxR). The C-terminal portion of HI0017 has an amino acid sequence that closely resembles pyruvate formate-lyase - an enzyme that converts pyruvate and CoA into acetyl-CoA and formate by a radical mechanism. Based on structural and sequence comparisons, we propose that the C-terminus of HI0017 functions as an enzyme with a glycyl radical mechanism, while the N-terminus participates in protein/protein interactions involving an activase (iron-sulfur protein) and/or the substrate

Structure of the N-terminal region of Haemophilus Influenzae HI0017: Implications for function

Energy Technology Data Exchange (ETDEWEB)

Yu Liping; Mack, Jamey; Hajduk, Phil; Fesik, Stephen W. [Abbott Laboratories, Pharmaceutical Discovery Division, D46Y, AP10/LL (United States)

2001-06-15

Haemophilus influenzae is a gram-negative pathogen that causes infections ranging from asymptomatic colonization of the human upper respiratory tract to serious invasive diseases such as meningitis. Although the genome of Haemophilus influenzae has been completely sequenced, the structure and function of many of these proteins are unknown. HI0017 is one of these uncharacterized proteins. Here we describe the three-dimensional solution structure of the N-terminal portion of HI0017 as determined by NMR spectroscopy. The structure consists of a five-stranded antiparallel {beta}-sheet and two short {alpha}-helices. It is similar to the C-terminal domain of Diphtheria toxin repressor (DtxR). The C-terminal portion of HI0017 has an amino acid sequence that closely resembles pyruvate formate-lyase - an enzyme that converts pyruvate and CoA into acetyl-CoA and formate by a radical mechanism. Based on structural and sequence comparisons, we propose that the C-terminus of HI0017 functions as an enzyme with a glycyl radical mechanism, while the N-terminus participates in protein/protein interactions involving an activase (iron-sulfur protein) and/or the substrate.

Quorum signaling and sensing by nontypeable Haemophilus influenzae.

Science.gov (United States)

Swords, W Edward

2012-01-01

Quorum signals are diffusible factors produced by bacteria that coordinate communal responses. For nontypeable Haemophilus influenzae (NTHi), a series of recent papers indicate that production and sensing of quorum signals are determinants of biofilm formation/maturation and persistence in vivo. In this mini-review I will summarize the current knowledge about quorum signaling/sensing by this organism, and identify specific topics for additional study.

Haemophilus influenzae from Patients with Chronic Obstructive Pulmonary Disease Exacerbation Induce More Inflammation than Colonizers

Science.gov (United States)

Chin, Cecilia L.; Manzel, Lori J.; Lehman, Erin E.; Humlicek, Alicia L.; Shi, Lei; Starner, Timothy D.; Denning, Gerene M.; Murphy, Timothy F.; Sethi, Sanjay; Look, Dwight C.

2005-01-01

Rationale: Airway infection with Haemophilus influenzae causes airway inflammation, and isolation of new strains of this bacteria is associated with increased risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Objective: To determine whether strains of H. influenzae associated with exacerbations cause more inflammation than strains that colonize the airways of patients with COPD. Methods: Exacerbation strains of H. influenzae were isolated from patients during exacerbation of clinical symptoms with subsequent development of a homologous serum antibody response and were compared with colonization strains that were not associated with symptom worsening or an antibody response. Bacterial strains were compared using an in vivo mouse model of airway infection and in vitro cell culture model of bacterial adherence and defense gene and signaling pathway activation in primary human airway epithelial cells. Results: H. influenzae associated with exacerbations caused more airway neutrophil recruitment compared with colonization strains in the mouse model of airway bacterial infection. Furthermore, exacerbation strains adhered to epithelial cells in significantly higher numbers and induced more interleukin-8 release after interaction with airway epithelial cells. This effect was likely mediated by increased activation of the nuclear factor-κB and p38 mitogen-activated protein kinase signaling pathways. Conclusions: The results indicate that H. influenzae strains isolated from patients during COPD exacerbations often induce more airway inflammation and likely have differences in virulence compared with colonizing strains. These findings support the concept that bacteria infecting the airway during COPD exacerbations mediate increased airway inflammation and contribute to decreased airway function. PMID:15805181

Structural Determinants of Autoproteolysis of the Haemophilus influenzae Hap Autotransporter▿

Science.gov (United States)

Kenjale, Roma; Meng, Guoyu; Fink, Doran L.; Juehne, Twyla; Ohashi, Tomoo; Erickson, Harold P.; Waksman, Gabriel; St. Geme, Joseph W.

2009-01-01

Haemophilus influenzae is a gram-negative bacterium that initiates infection by colonizing the upper respiratory tract. The H. influenzae Hap autotransporter protein mediates adherence, invasion, and microcolony formation in assays with respiratory epithelial cells and presumably facilitates colonization. The serine protease activity of Hap is associated with autoproteolytic cleavage and extracellular release of the HapS passenger domain, leaving the Hapβ C-terminal domain embedded in the outer membrane. Cleavage occurs most efficiently at the LN1036-37 peptide bond and to a lesser extent at three other sites. In this study, we utilized site-directed mutagenesis, homology modeling, and assays with a peptide library to characterize the structural determinants of Hap proteolytic activity and cleavage specificity. In addition, we used homology modeling to predict the S1, S2, and S4 subsite residues of the Hap substrate groove. Our results indicate that the P1 and P2 positions at the Hap cleavage sites are critical for cleavage, with leucine preferred over larger hydrophobic residues or other amino acids in these positions. The substrate groove is formed by L263 and N274 at the S1 subsite, R264 at the S2 subsite, and E265 at the S4 subsite. This information may facilitate design of approaches to block Hap activity and interfere with H. influenzae colonization. PMID:19687208

Metabolic versatility in Haemophilus influenzae: a metabolomic and genomic analysis

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Dk Seti Maimonah Pg eOthman

2014-03-01

Full Text Available Haemophilus influenzae is a host adapted human pathogen known to contribute to a variety of acute and chronic diseases of the upper and lower respiratory tract as well as the middle ear. At the sites of infection as well as during growth as a commensal the environmental conditions encountered by H. influenzae will vary significantly, especially in terms of oxygen availability, however, the mechanisms by which the bacteria can adapt their metabolism to cope with such changes have not been studied in detail. Using targeted metabolomics the spectrum of metabolites produced during growth of H. influenzae on glucose in RPMI-based medium was found to change from acetate as the main product during aerobic growth to formate as the major product during anaerobic growth. This is likely caused by a switch in the major pyruvate degrading route. Neither lactate nor succinate or fumarate were major products of H. influenzae growth under any condition studied Gene expression studies and enzyme activity data revealed that despite an identical genetic makeup and very similar metabolite production profiles, H. influenzae strain Rd appeared to favour glucose degradation via the PPP, while strain 2019, a clinical isolate, showed higher expression of enzymes involved in glycolysis. Components of the respiratory chain were most highly expressed during microaerophilic and anaerobic growth in both strains, but again clear differences existed in the expression of genes associated e.g. with NADH oxidation, nitrate and nitrite reduction in the two strains studied.Together our results indicate that H. influenzae uses a specialized type of metabolism that could be termed ‘respiration assisted fermentation’ where the respiratory chain likely serves to alleviate redox imbalances caused by incomplete glucose oxidation, and at the same time provides a means of converting a variety of compounds including nitrite and nitrate that arise as part of the host defence mechanisms.

Antimicrobial susceptibility of Haemophilus influenzae strains isolated from the urethra of men with acute urethritis and/or epididymitis.

Science.gov (United States)

Deguchi, Takashi; Ito, Shin; Hatazaki, Kyoko; Horie, Kengo; Yasuda, Mitsuru; Nakane, Keita; Mizutani, Kosuke; Tsuchiya, Tomohiro; Yokoi, Shigeaki; Hanaoka, Nozomu; Shimuta, Ken; Ohnishi, Makoto; Muratani, Tetsuro; Nakano, Masahiro

2017-11-01

We determined minimum inhibitory concentrations (MICs) of 41 antimicrobial agents for 73 clinical strains of Haemophilus influenzae isolated from the urethra of men with acute urethritis and/or epididymitis and examined the strains for the production of β-lactamase. We also compared their antimicrobial susceptibilities with those of H. influenzae strains from respiratory tract or otorhinolaryngological infections that were reported in Japan. The proportion of β-lactamase-nonproducing ampicillin-resistant strains from acute urethritis and/or epididymitis appeared to be lower, but that of β-lactamase-producing ampicillin-resistant strains appeared to be higher, compared with those from respiratory tract or otorhinolaryngological infections. However, their antimicrobial susceptibilities to a variety of other antimicrobial agents would be similar to those from respiratory tract or otorhinolaryngological infections. Almost all of the strains of H. influenzae from acute urethritis and/or epididymitis were susceptible to the agents, including ceftriaxone, quinolones, macrolides, and tetracyclines, commonly prescribed for treatment of acute urethritis based on the MIC breakpoints recommended by the Clinical and Laboratory Standards Institute. Ceftriaxone and quinolones could be effective on H. influenzae-induced urethritis. However, azithromycin treatment failures were reported in acute urethritis caused by H. influenzae strains considered susceptible to azithromycin. Further studies will be needed to determine MIC breakpoints of antimicrobial agents, which are recommended for treatment of urogenital infections, for H. influenzae strains causing these infections. Nevertheless, this study provides useful data regarding antimicrobial susceptibilities of H. influenzae strains isolated from the urogenital tract, which have rarely been studied. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier

Impacto da vacinação contra o Haemophilus influenzae b na redução de meningites, Goiás

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Simões Luciana Leite Pineli

2004-01-01

Full Text Available OBJETIVO: Avaliar o impacto da vacinação contra o Haemophilus influenzae b na incidência de meningites em crianças menores de cinco anos de idade. MÉTODOS: Utilizou-se o delineamento tipo "antes-depois" para comparar as taxas de incidência de meningites por Haemophilus influenzae b nos períodos pré-vacinação (julho/95-junho/99 e pós-vacinação (julho/99-junho/2001 no Estado de Goiás. A definição de caso de meningite bacteriana seguiu os critérios da Organização Mundial de Saúde. As taxas de meningite por Streptococcus pneumoniae e Neisseria. meningitidis foram utilizadas para efeito de comparação. Para análise estatística foram utilizados o teste de chi2 e o t de Student. Valores de p<0,05 foram considerados estatisticamente significantes. RESULTADOS: Foi detectada meningite bacteriana aguda em 979 crianças no período de estudo. A incidência de meningite por Haemophilus influenzae b diminuiu de 10,8x10(5 no período pré-vacinal para 2,3x10(5 no segundo ano pós-vacina, significando 78% de redução no risco, principalmente na faixa etária de 7-23 meses (p<0,05. Foram prevenidos 65 casos de meningite por Haemophilus influenzae b. Observou-se aumento na incidência de meningite por S. pneumoniae. Foi observada falha vacinal em um caso. CONCLUSÕES: Expressivo declínio da incidência de meningite por Haemophilus influenzae b foi detectado, precocemente, logo após o primeiro ano de introdução da vacina contra o Haemophilus influenzae b. Assim, se faz necessária a vigilância contínua com instrumental de alta acurácia para: (i detectar re-emergência do Haemophilus influenzae b; (ii avaliar possibilidade de falha vacinal; (iii identificar mudanças no padrão dos sorotipos do H. influenzae.

Coinfection with Haemophilus influenzae promotes pneumococcal biofilm formation during experimental otitis media and impedes the progression of pneumococcal disease.

Science.gov (United States)

Weimer, Kristin E D; Armbruster, Chelsie E; Juneau, Richard A; Hong, Wenzhou; Pang, Bing; Swords, W Edward

2010-10-01

Otitis media is an extremely common pediatric infection and is mostly caused by bacteria that are carried within the nasopharyngeal microbiota. It is clear that most otitis media cases involve simultaneous infection with multiple agents. Chinchillas were infected with nontypeable Haemophilus influenzae, Streptococcus pneumoniae, or a combination of both organisms, and the course of disease was compared. In vitro experiments were also performed to address how coinfection impacts biofilm formation. The incidence of systemic disease was reduced in coinfected animals, compared with those infected with pneumococcus alone. Pneumococci were present within surface-attached biofilms in coinfected animals, and a greater proportion of translucent colony type was observed in the coinfected animals. Because this colony type has been associated with pneumococcal biofilms, the impact of coinfection on pneumococcal biofilm formation was investigated. The results clearly show enhanced biofilm formation in vitro by pneumococci in the presence of H. influenzae. Based on these data, we conclude that coinfection with H. influenzae facilitates pneumococcal biofilm formation and persistence on the middle ear mucosal surface. This enhanced biofilm persistence correlates with delayed emergence of opaque colony variants within the bacterial population and a resulting decrease in systemic infection.

Quantitation of antibody-secreting cells in the blood after vaccination with Haemophilus influenzae type b conjugate vaccine

DEFF Research Database (Denmark)

Barington, T; Heilmann, C; Andersen, V

1990-01-01

The human B-lymphocyte response to protein-conjugated polysaccharide antigens has not previously been studied at the cellular level. In order to do so, we developed and evaluated haemolytic plaque-forming cell assays detecting Haemophilus influenzae type b (Hib) capsular polysaccharide-specific a......The human B-lymphocyte response to protein-conjugated polysaccharide antigens has not previously been studied at the cellular level. In order to do so, we developed and evaluated haemolytic plaque-forming cell assays detecting Haemophilus influenzae type b (Hib) capsular polysaccharide...

Invasive Haemophilus Influenzae Disease, Europe, 1996–2006

Centers for Disease Control (CDC) Podcasts

2010-03-15

This podcast describes monitoring of Haemophilus influenzae disease in Europe from 1996 through 2006. CDC epidemiologist Stacey Martin discusses what researchers learned about the effect of vaccination on disease prevalence.  Created: 3/15/2010 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID); National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 4/5/2010.

Economic Evaluation and Budget Impact Analysis of Vaccination against Haemophilus influenzae Type b Infection in Thailand

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Surachai Kotirum

2017-11-01

Full Text Available Current study aimed to estimate clinical and economic outcomes of providing the Haemophilus influenzae type b (Hib vaccination as a national vaccine immunization program in Thailand. A decision tree combined with Markov model was developed to simulate relevant costs and health outcomes covering lifetime horizon in societal and health care payer perspectives. This analysis considered children aged under 5 years old whom preventive vaccine of Hib infection are indicated. Two combined Hib vaccination schedules were considered: three-dose series (3 + 0 and three-dose series plus a booster does (3 + 1 compared with no vaccination. Budget impact analysis was also performed under Thai government perspective. The outcomes were reported as Hib-infected cases averted and incremental cost-effectiveness ratios (ICERs in 2014 Thai baht (THB ($ per quality-adjusted life year (QALY gained. In base-case scenario, the model estimates that 3,960 infected cases, 59 disability cases, and 97 deaths can be prevented by national Hib vaccination program. The ICER for 3 + 0 schedule was THB 1,099 ($34 per QALY gained under societal perspective. The model was sensitive to pneumonia incidence among aged under 5 years old and direct non-medical care cost per episode of Hib pneumonia. Hib vaccination is very cost-effective in the Thai context. The budget impact analysis showed that Thai government needed to invest an additional budget of 110 ($3.4 million to implement Hib vaccination program. Policy makers should consider our findings for adopting this vaccine into national immunization program.

A comparative study of preservation and storage of Haemophilus influenzae

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Olga C Aulet de Saab

2001-05-01

Full Text Available The aim of this study was to compare the efficacy of conservation by freezing the strains of Haemophilus influenzae at -20ºC and -70ºC. Skim milk supplemented with glucose, yeast extract and glycerol allowed highest viability of H. influenzae both at -20ºC and -70ºC from the media analyzed. Trypticase soy broth and brain heart infusion broth supplemented with glycerol, allowed excellent recovery. Use of cotton swaps as supporting material, with or without addition of cryoprotective agents, did not modify H. influenzae viability after six months of storage. Concentration of the initial inoculum positively affected viability when stored at -20ºC. Initial concentration did not influence survival after storage at -70ºC. Thawing at room temperature should not exceed 3 h as to get highest survival percentage.

Multiplex quantitative PCR for detection of lower respiratory tract infection and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.

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Abdeldaim, Guma M K; Strålin, Kristoffer; Korsgaard, Jens; Blomberg, Jonas; Welinder-Olsson, Christina; Herrmann, Björn

2010-12-03

Streptococcus pneumoniae and Haemophilus influenzae cause pneumonia and as Neisseria meningitidis they are important agents of meningitis. Although several PCR methods have been described for these bacteria the specificity is an underestimated problem. Here we present a quantitative multiplex real-time PCR (qmPCR) for detection of S. pneumoniae (9802 gene fragment), H. influenzae (omp P6 gene) and N. meningitidis (ctrA gene). The method was evaluated on bronchoalveolar lavage (BAL) samples from 156 adults with lower respiratory tract infection (LRTI) and 31 controls, and on 87 cerebrospinal fluid (CSF) samples from meningitis patients. The analytical sensitivity was not affected by using a combined mixture of reagents and a combined DNA standard (S. pneumoniae/H. influenzae/N. meningitidis) in single tubes. By blood- and BAL-culture and S. pneumoniae urinary antigen test, S. pneumoniae and H. influenzae were aetiological agents in 21 and 31 of the LTRI patients, respectively. These pathogens were identified by qmPCR in 52 and 72 of the cases, respectively, yielding sensitivities and specificities of 95% and 75% for S. pneumoniae, and 90% and 65% for H. influenzae, respectively. When using a cut-off of 10⁵ genome copies/mL for clinical positivity the sensitivities and specificities were 90% and 80% for S. pneumoniae, and 81% and 85% for H. influenzae, respectively. Of 44 culture negative but qmPCR positive for H. influenzae, 41 were confirmed by fucK PCR as H. influenzae. Of the 103 patients who had taken antibiotics prior to sampling, S. pneumoniae and H. influenzae were identified by culture in 6% and 20% of the cases, respectively, and by the qmPCR in 36% and 53% of the cases, respectively.In 87 CSF samples S. pneumoniae and N. meningitidis were identified by culture and/or 16 S rRNA in 14 and 10 samples and by qmPCR in 14 and 10 samples, respectively, giving a sensitivity of 100% and a specificity of 100% for both bacteria. The PCR provides increased

Multiplex quantitative PCR for detection of lower respiratory tract infection and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis

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Welinder-Olsson Christina

2010-12-01

Full Text Available Abstract Background Streptococcus pneumoniae and Haemophilus influenzae cause pneumonia and as Neisseria meningitidis they are important agents of meningitis. Although several PCR methods have been described for these bacteria the specificity is an underestimated problem. Here we present a quantitative multiplex real-time PCR (qmPCR for detection of S. pneumoniae (9802 gene fragment, H. influenzae (omp P6 gene and N. meningitidis (ctrA gene. The method was evaluated on bronchoalveolar lavage (BAL samples from 156 adults with lower respiratory tract infection (LRTI and 31 controls, and on 87 cerebrospinal fluid (CSF samples from meningitis patients. Results The analytical sensitivity was not affected by using a combined mixture of reagents and a combined DNA standard (S. pneumoniae/H. influenzae/N. meningitidis in single tubes. By blood- and BAL-culture and S. pneumoniae urinary antigen test, S. pneumoniae and H. influenzae were aetiological agents in 21 and 31 of the LTRI patients, respectively. These pathogens were identified by qmPCR in 52 and 72 of the cases, respectively, yielding sensitivities and specificities of 95% and 75% for S. pneumoniae, and 90% and 65% for H. influenzae, respectively. When using a cut-off of 105 genome copies/mL for clinical positivity the sensitivities and specificities were 90% and 80% for S. pneumoniae, and 81% and 85% for H. influenzae, respectively. Of 44 culture negative but qmPCR positive for H. influenzae, 41 were confirmed by fucK PCR as H. influenzae. Of the 103 patients who had taken antibiotics prior to sampling, S. pneumoniae and H. influenzae were identified by culture in 6% and 20% of the cases, respectively, and by the qmPCR in 36% and 53% of the cases, respectively. In 87 CSF samples S. pneumoniae and N. meningitidis were identified by culture and/or 16 S rRNA in 14 and 10 samples and by qmPCR in 14 and 10 samples, respectively, giving a sensitivity of 100% and a specificity of 100% for both

Detection of cryptic genospecies misidentified as Haemophilus influenzae in routine clinical samples by assessment of marker genes fucK, hap, and sodC.

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Nørskov-Lauritsen, Niels

2009-08-01

Clinical isolates of Haemophilus influenzae were assessed for the presence of fucK, hap, and sodC by hybridization with gene-specific probes, and isolates diverging from the expected H. influenzae genotype were characterized by phenotype and 16S rRNA gene sequencing. Two of 480 isolates were finally classified as variant strains ("nonhemolytic Haemophilus haemolyticus").

Detection of Cryptic Genospecies Misidentified as Haemophilus influenzae in Routine Clinical Samples by Assessment of Marker Genes fucK, hap, and sodC▿

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Nørskov-Lauritsen, Niels

2009-01-01

Clinical isolates of Haemophilus influenzae were assessed for the presence of fucK, hap, and sodC by hybridization with gene-specific probes, and isolates diverging from the expected H. influenzae genotype were characterized by phenotype and 16S rRNA gene sequencing. Two of 480 isolates were finally classified as variant strains (“nonhemolytic Haemophilus haemolyticus”). PMID:19535530

Vacinação contra Haemophilus influenzae tipo b: proteção a longo prazo Haemophilus influenzae type b vaccination: long term protection

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Cristiana M. Nascimento-Carvalho

2006-07-01

Full Text Available OBJETIVO: Identificar as evidências sobre o impacto da vacina conjugada para Haemophilus influenzae tipo b (Hib na epidemiologia da doença invasiva por Hib. FONTE DOS DADOS: Pesquisa nas bases de dados do MEDLINE, LILACS, publicações técnicas de organizações internacionais, diretrizes nacionais e internacionais, nos últimos 15 anos (1991-2005, utilizando os seguintes unitermos: Haemophilus influenzae type b, immunization, impact, effectiveness. Foram incluídas as publicações que apresentaram informação para atender o objetivo deste artigo. Artigos publicados em período anterior ao da pesquisa e citados em referências dos artigos incluídos foram analisados quanto à apresentação de informação de interesse. SÍNTESE DOS DADOS: A introdução da vacina conjugada para Hib produziu grande declínio na incidência de casos de doença invasiva por Hib nos diversos países em que seu uso foi incorporado à rotina de vacinação das crianças. No entanto, o ressurgimento de casos com doença invasiva por Hib tem mobilizado vários investigadores na busca das possíveis explicações para esses eventos, bem como a identificação das medidas a serem implementadas para evitar o reaparecimento da doença. CONCLUSÕES: O uso da vacina conjugada para Hib em escala populacional tem sido extremamente efetivo. No entanto, mudanças no esquema vacinal poderão ser necessárias para a manutenção do controle da doença invasiva por Hib, frente ao atual cenário epidemiológico das infecções pelo Hib.OBJECTIVE: To identify evidence of the impact of Haemophilus influenzae type b (Hib conjugate vaccine on the epidemiology of invasive Hib disease. SOURCES OF DATA: This review was based on a search of MEDLINE, LILACS, technical reports, national and international guidelines (publications from 1991 to 2005. The keywords Haemophilus influenzae type b, immunization, impact and effectiveness, alone or in combination, were used to retrieve the

Structural determinants of the interaction between the Haemophilus influenzae Hap autotransporter and fibronectin.

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Spahich, Nicole A; Kenjale, Roma; McCann, Jessica; Meng, Guoyu; Ohashi, Tomoo; Erickson, Harold P; St Geme, Joseph W

2014-06-01

Haemophilus influenzae is a Gram-negative cocco-bacillus that initiates infection by colonizing the upper respiratory tract. Hap is an H. influenzae serine protease autotransporter protein that mediates adherence, invasion and microcolony formation in assays with human epithelial cells and is presumed to facilitate the process of colonization. Additionally, Hap mediates adherence to fibronectin, laminin and collagen IV, extracellular matrix (ECM) proteins that are present in the respiratory tract and are probably important targets for H. influenzae colonization. The region of Hap responsible for adherence to ECM proteins has been localized to the C-terminal 511 aa of the Hap passenger domain (HapS). In this study, we characterized the structural determinants of the interaction between HapS and fibronectin. Using defined fibronectin fragments, we established that Hap interacts with the fibronectin repeat fragment called FNIII(1-2). Using site-directed mutagenesis, we found a series of motifs in the C-terminal region of HapS that contribute to the interaction with fibronectin. Most of these motifs are located on the F1 and F3 faces of the HapS structure, suggesting that the F1 and F3 faces may be responsible for the HapS-fibronectin interaction. © 2014 The Authors.

Meningitis - H. influenzae

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H. influenzae meningitis; H. flu meningitis; Haemophilus influenzae type b meningitis ... H. influenzae meningitis is caused by Haemophilus influenzae type b bacteria. This illness is not the same ...

Structure-based functional annotation of putative conserved proteins having lyase activity from Haemophilus influenzae.

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Shahbaaz, Mohd; Ahmad, Faizan; Imtaiyaz Hassan, Md

2015-06-01

Haemophilus influenzae is a small pleomorphic Gram-negative bacteria which causes several chronic diseases, including bacteremia, meningitis, cellulitis, epiglottitis, septic arthritis, pneumonia, and empyema. Here we extensively analyzed the sequenced genome of H. influenzae strain Rd KW20 using protein family databases, protein structure prediction, pathways and genome context methods to assign a precise function to proteins whose functions are unknown. These proteins are termed as hypothetical proteins (HPs), for which no experimental information is available. Function prediction of these proteins would surely be supportive to precisely understand the biochemical pathways and mechanism of pathogenesis of Haemophilus influenzae. During the extensive analysis of H. influenzae genome, we found the presence of eight HPs showing lyase activity. Subsequently, we modeled and analyzed three-dimensional structure of all these HPs to determine their functions more precisely. We found these HPs possess cystathionine-β-synthase, cyclase, carboxymuconolactone decarboxylase, pseudouridine synthase A and C, D-tagatose-1,6-bisphosphate aldolase and aminodeoxychorismate lyase-like features, indicating their corresponding functions in the H. influenzae. Lyases are actively involved in the regulation of biosynthesis of various hormones, metabolic pathways, signal transduction, and DNA repair. Lyases are also considered as a key player for various biological processes. These enzymes are critically essential for the survival and pathogenesis of H. influenzae and, therefore, these enzymes may be considered as a potential target for structure-based rational drug design. Our structure-function relationship analysis will be useful to search and design potential lead molecules based on the structure of these lyases, for drug design and discovery.

Detection of Haemophilus influenzae in respiratory secretions from pneumonia patients by quantitative real-time polymerase chain reaction.

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Abdeldaim, Guma M K; Strålin, Kristoffer; Kirsebom, Leif A; Olcén, Per; Blomberg, Jonas; Herrmann, Björn

2009-08-01

A quantitative real-time polymerase chain reaction (PCR) based on the omp P6 gene was developed to detect Haemophilus influenzae. Its specificity was determined by analysis of 29 strains of 11 different Haemophilus spp. and was compared with PCR assays having other target genes: rnpB, 16S rRNA, and bexA. The method was evaluated on nasopharyngeal aspirates from 166 adult patients with community-acquired pneumonia. When 10(4) DNA copies/mL was used as cutoff limit for the method, P6 PCR had a sensitivity of 97.5% and a specificity of 96.0% compared with the culture. Of 20 culture-negative but P6 PCR-positive cases, 18 were confirmed by fucK PCR as H. influenzae. Five (5.9%) of 84 nasopharyngeal aspirates from adult controls tested PCR positive. We conclude that the P6 real-time PCR is both sensitive and specific for identification of H. influenzae in respiratory secretions. Quantification facilitates discrimination between disease-causing H. influenzae strains and commensal colonization.

The capsule biosynthesis locus of Haemophilus influenzae show conspicuous similarity to the corresponding locus in Haemophilus sputorum and may have been recruited from this species by horizontal gene transfer

DEFF Research Database (Denmark)

Nielsen, Signe Maria; de Gier, Camilla; Dimopoulou, Chrysoula

2015-01-01

in export and processing of the capsular material, show high similarity to the corresponding genes in capsulate lineages of the pathogenic species Haemophilus influenzae; indeed, standard bexA and bexB PCRs for detection of capsulated strains of H. influenzae give positive results with strains of H....... sputorum was only distantly related to H. influenzae. In contrast to H. influenzae, the capsule locus in H. sputorum is not associated with transposases or other transposable elements. Our data suggest that the capsule locus of capsulate lineages of H. influenzae may relatively recently have been recruited...

Incidence of invasive Haemophilus influenzae type b disease in Italian children

International Nuclear Information System (INIS)

Tozzi, Alberto E.; Salmaso, Stefania; Atti, Marta L. Ciofi degli; Panei, Pietro; Anemona, Alessandra; Scuderi, Gabriella; Wassilak, Steven G.F.

1997-01-01

To estimate the incidence of Haemophilus influenzae type b (Hib) invasive disease in Italian infants we performed a prospective study in a cohort of newborns enrolled for a randomized trial on safety and efficacy of three pertussis vaccines and followed for onset of serious disease or pertussis. The overall cumulative incidence observed in 15,601 children was 51.3/100,000 for all invasive Hib infections and 38.4/100,000 for Hib meningitis, over 27 months of observation. The incidence density of all invasive Hib diseases was 28.7/100,000 person-years, while meningitis occurred with an incidence of 21.5/100,000 person-years. Among the eight cases detected, six were meningitis, one sepsis, and one cellulitis. The child with sepsis died. The incidence and epidemiology of invasive Hib disease in Italy are comparable to those reported from other European countries. Cost-benefit analyses are needed for planning Italian vaccination policy

Antibacterial activity of Artemisia asiatica essential oil against some common respiratory infection causing bacterial strains and its mechanism of action in Haemophilus influenzae.

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Huang, Jiehui; Qian, Chao; Xu, Hongjie; Huang, Yanjie

2018-01-01

The main objective of the current study was to investigate the chemical composition of the essential oil of Artemisia asiatica together with investigating the antibacterial effects it exerts on several common respiratory infection causing bacteria including Haemophilus influenzae. Its mechanism of action was studied using various state-of-the-art assays like scanning electron microscopy, DNA, RNA and protein leakage assays, growth curve assays etc. The essential oil was extracted from the leaves of A. asiatica by supercritical CO 2 fluid extraction technology. Chemical composition of essential oils was analyzed by gas chromatography-mass-spectrometry (GC-MS). The antibacterial activity was evaluated against 6 bacteria by the paper disc diffusion method. The minimum inhibitory concentration (MIC) and minimum bactericide concentration (MBC) values of the essential oil were estimated by agar dilution method. The antibacterial mechanism was evaluated by growth curve, the integrity of cell membrane and scanning electronmicroscope (SEM). Gas chromatographic analysis of the A. asiatica essential oil led to the identification of 16 chemical constituents accounting for 97.2% of the total oil composition. The major components were found to be Piperitone, (z)-davanone, p-cymene and 1, 8-cineole. The essential oil showed maximum growth inhibition against Haemophilus influenzae with a zone of inhibition of 24.5 mm and MIC/MBC values of 1.9/4.5 mg/mL respectively. Bacteria treated with the essential oil led to a rapid decrease in the number of viable cells. On adding the essential oil of A. asiatica to the bacterial culture, the constituents of the bacterial cell got released into the medium and this cell constituent release increased with increasing doses of the essential oil. SEM showed that the bacterial cells treated with the essential oil showed damaged cell wall, deformed cell morphology and shrunken cells. Copyright © 2017. Published by Elsevier Ltd.

Ampicillin resistance in Haemophilus influenzae from COPD patients in the UK

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Maddi S

2017-05-01

Full Text Available Satyanarayana Maddi,1 Umme Kolsum,1 Sarah Jackson,1 Richard Barraclough,2 Barbara Maschera,3 Karen D Simpson,3 Thierry G Pascal,4 Serge Durviaux,4 Edith M Hessel,3 Dave Singh1 1Division of Infection, Immunity and Respiratory Medicine, Medicines Evaluation Unit, University Hospital of South Manchester Foundation Trust, University of Manchester, 2Department of Respiratory Medicine, University Hospital of South Manchester Foundation Trust, Manchester, 3Refractory Respiratory Inflammation DPU, GlaxoSmithKline Medicines Research Centre, Stevenage, Hertfordshire, UK; 4Clinical Laboratory Sciences, GlaxoSmithKline Vaccines, Wavre, Belgium Background: Haemophilus influenzae is commonly isolated from the airways of COPD patients. Antibiotic treatment may cause the emergence of resistant H. influenzae strains, particularly ampicillin-resistant strains, including β-lactamase-negative ampicillin resistance (BLNAR strains. Genetic identification using ftsI sequencing is the optimum method for identifying mutations within BLNAR strains. The prevalence of BLNAR in COPD patients during the stable state has not been reported. We investigated the antibiotic resistance patterns of H. influenzae present in the sputum of stable COPD patients, focusing on ampicillin resistance; the prevalence of enzyme and non-enzyme-mediated ampicillin resistance was determined. A subset of patients was followed up longitudinally to study H. influenzae strain switching and antibiotic sensitivity changes.Patients and methods: Sputum sampling was performed in 61 COPD patients, with 42 samples obtained at baseline; H. influenzae was detected by polymerase chain reaction in 28 samples. In all, 45 patients completed the follow-up for 2 years; 24 H. influenzae isolates were obtained.Results: Disk diffusion showed the highest antibiotic resistance in the penicillin antibiotic group (eg, 67% for ampicillin and macrolides (eg, 46% for erythromycin, whereas all isolates were susceptible to

Methodology optimization and diversification for the investigation of virulence potential in Haemophilus influenzae clinical strains.

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Giucă, Mihaela Cristina; Străuţ, Monica; Surdeanu, Maria; Nica, Maria; Ungureanu, Vasilica; Mihăescu, Grigore

2011-01-01

Ten Haemophilus influenzae strains were isolated from patients aged between 1.6 - 24 years, with various diagnoses (acute meningitis, acute upper respiratory infection, otitis media and acute sinusitis). Identification was based on phenotypic and molecular characteristics; antibiotic susceptibility testing was performed by diffusion method according to CLSI standards 2011 for seven antibiotics. The results of molecular testing showed that all the studied strains produced an amplicon of 1000 bp with ompP2 primers indicating that all strains were H. influenzae. For six strains, the PCR amplicon obtained with bexA specific primers, proving that the strains were capsulated. The results of phenotypic testing showed that four strains were ampicillin nonsusceptible and (beta-lactamase-positive. The virulence potential of H. influenzae clinical strains was investigated by phenotypic methods, including the assessment of the soluble virulence factors on specific media containing the biochemical substratum for the investigated enzymatic factor, as well as the adherence and invasion capacity to HeLa cells monolayer using Cravioto modified method. The studied strains exhibited mainly a diffuse adherence pattern and different adherence indexes. Interestingly, two strains isolated from the same pacient (blood and CSF) showed a different degree of invasiveness, the strain isolated from blood being 20 times more invasive than the one isolated from CSF.

Endogenous and exogenous reinfections by Haemophilus influenzae in patients with chronic obstructive pulmonary disease: the effect of antibiotic treatment on persistence

NARCIS (Netherlands)

Groeneveld, K.; van Alphen, L.; Eijk, P. P.; Visschers, G.; Jansen, H. M.; Zanen, H. C.

1990-01-01

To analyze whether exacerbations in chronic obstructive pulmonary disease (COPD) coincide with reinfection by Haemophilus influenzae, 16 COPD patients were studied longitudinally for 3 years. Exacerbations coincided with reinfection by H. influenzae, either endogenous, by a strain with a DNA

Contribution of the major and minor subunits to fimbria-mediated adherence of Haemophilus influenzae to human epithelial cells and erythrocytes

NARCIS (Netherlands)

van Ham, S. M.; van Alphen, L.; Mooi, F. R.; van Putten, J. P.

1995-01-01

Fimbriae are colonization factors of the human pathogen Haemophilus influenzae in that they mediate bacterial adherence to human eukaryotic cells. The contribution of the major (HifA) and putative minor (HifD and HifE) subunits of H. influenzae fimbriae to fimbria-specific adherence was studied by

Complete Deletion of the Fucose Operon in Haemophilus influenzae Is Associated with a Cluster in Multilocus Sequence Analysis-Based Phylogenetic Group II Related to Haemophilus haemolyticus: Implications for Identification and Typing.

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de Gier, Camilla; Kirkham, Lea-Ann S; Nørskov-Lauritsen, Niels

2015-12-01

Nonhemolytic variants of Haemophilus haemolyticus are difficult to differentiate from Haemophilus influenzae despite a wide difference in pathogenic potential. A previous investigation characterized a challenging set of 60 clinical strains using multiple PCRs for marker genes and described strains that could not be unequivocally identified as either species. We have analyzed the same set of strains by multilocus sequence analysis (MLSA) and near-full-length 16S rRNA gene sequencing. MLSA unambiguously allocated all study strains to either of the two species, while identification by 16S rRNA sequence was inconclusive for three strains. Notably, the two methods yielded conflicting identifications for two strains. Most of the "fuzzy species" strains were identified as H. influenzae that had undergone complete deletion of the fucose operon. Such strains, which are untypeable by the H. influenzae multilocus sequence type (MLST) scheme, have sporadically been reported and predominantly belong to a single branch of H. influenzae MLSA phylogenetic group II. We also found evidence of interspecies recombination between H. influenzae and H. haemolyticus within the 16S rRNA genes. Establishing an accurate method for rapid and inexpensive identification of H. influenzae is important for disease surveillance and treatment. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Changes in outer membrane proteins of nontypable Haemophilus influenzae in patients with chronic obstructive pulmonary disease

NARCIS (Netherlands)

Groeneveld, K.; van Alphen, L.; Eijk, P. P.; Jansen, H. M.; Zanen, H. C.

1988-01-01

Five individual colonies of Haemophilus influenzae were isolated from each of one to three cultures of sputum collected from 18 patients with chronic obstructive pulmonary disease (COPD). The isolates were studied to investigate whether the major outer membrane proteins (MOMPs) changed during

Nontypeable Haemophilus influenzae initiates formation of neutrophil extracellular traps.

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Juneau, Richard A; Pang, Bing; Weimer, Kristin E D; Armbruster, Chelsie E; Swords, W Edward

2011-01-01

Nontypeable Haemophilus influenzae (NTHI) is a leading cause of otitis media infections, which are often chronic and/or recurrent in nature. NTHI and other bacterial species persist in vivo within biofilms during otitis media and other persistent infections. These biofilms have a significant host component that includes neutrophil extracellular traps (NETs). These NETs do not mediate clearance of NTHI, which survives within NET structures by means of specific subpopulations of lipooligosaccharides on the bacterial surface that are determinants of biofilm formation in vitro. In this study, the ability of NTHI and NTHI components to initiate NET formation was examined using an in vitro model system. Both viable and nonviable NTHI strains were shown to promote NET formation, as did preparations of bacterial DNA, outer membrane proteins, and lipooligosaccharide (endotoxin). However, only endotoxin from a parental strain of NTHI exhibited equivalent potency in NET formation to that of NTHI. Additional studies showed that NTHI entrapped within NET structures is resistant to both extracellular killing within NETs and phagocytic killing by incoming neutrophils, due to oligosaccharide moieties within the lipooligosaccharides. Thus, we concluded that NTHI elicits NET formation by means of multiple pathogen-associated molecular patterns (most notably endotoxin) and is highly resistant to killing within NET structures. These data support the conclusion that, for NTHI, formation of NET structures may be a persistence determinant by providing a niche within the middle-ear chamber.

Aislamiento de distintos serotipos de Haemophilus influenzae en muestras profundas de pacientes pediátricos Isolation of Haemophilus influenzae serotypes from sterile sites in sick children

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B.M. Gatti

2004-03-01

Full Text Available Haemophilus influenzae (Hi es responsable de diversas enfermedades humanas como sepsis, meningitis, celulitis y osteoartritis. En este trabajo se investigó la recuperación de distintos serotipos de Hi en muestras profundas de pacientes pediátricos. Se estudiaron 179 aislamientos de 146 niños durante el periodo 1996-2002 en el Laboratorio de Microbiología del Hospital de Niños Superiora Sor María Ludovica, Argentina. La distribución de los serotipos fue la siguiente: 1 a, 112 b, 1 c,1 d, 4 e, 3 f y 24 no tipificables. A partir del establecimiento de la estrategia de vacunación universal anti Hi b en 1998 se observa una disminución notable del serotipo b y un aumento relativo de otros y no tipificables.Haemophilus influenzae (Hi is the causative agent of several human diseases such as sepsis, meningitis, celulitis, and osteoarthritis. We investigated the isolation of Hi serotypes from sterile sites in sick children. One hundred and seventy nine strains from 146 patients were studied, period 1996-2002, at the Microbiology Laboratory, Hospital de Niños Superiora Sor María Ludovica, Argentina. The serotype distribution was:1 a, 112 b,1 c,1 d, 4 e, 3 f y 24 no typable. Since the beginning of universal Hi b vaccination in 1998, we have observed the fast decrease of serotype b and a relative increase of other serotypes.

Molecular surveillance of true nontypeable Haemophilus influenzae: an evaluation of PCR screening assays.

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Binks, Michael J; Temple, Beth; Kirkham, Lea-Ann; Wiertsema, Selma P; Dunne, Eileen M; Richmond, Peter C; Marsh, Robyn L; Leach, Amanda J; Smith-Vaughan, Heidi C

2012-01-01

Unambiguous identification of nontypeable Haemophilus influenzae (NTHi) is not possible by conventional microbiology. Molecular characterisation of phenotypically defined NTHi isolates suggests that up to 40% are Haemophilus haemolyticus (Hh); however, the genetic similarity of NTHi and Hh limits the power of simple molecular techniques such as PCR for species discrimination. Here we assess the ability of previously published and novel PCR-based assays to identify true NTHi. Sixty phenotypic NTHi isolates, classified by a dual 16S rRNA gene PCR algorithm as NTHi (n = 22), Hh (n = 27) or equivocal (n = 11), were further characterised by sequencing of the 16S rRNA and recA genes then interrogated by PCR-based assays targeting the omp P2, omp P6, lgtC, hpd, 16S rRNA, fucK and iga genes. The sequencing data and PCR results were used to define NTHi for this study. Two hpd real time PCR assays (hpd#1 and hpd#3) and the conventional iga PCR assay were equally efficient at differentiating study-defined NTHi from Hh, each with a receiver operator characteristic curve area of 0.90 [0.83; 0.98]. The hpd#1 and hpd#3 assays were completely specific against a panel of common respiratory bacteria, unlike the iga PCR, and the hpd#3 assay was able to detect below 10 copies per reaction. Our data suggest an evolutionary continuum between NTHi and Hh and therefore no single gene target could completely differentiate NTHi from Hh. The hpd#3 real time PCR assay proved to be the superior method for discrimination of NTHi from closely related Haemophilus species with the added potential for quantification of H. influenzae directly from specimens. We suggest the hpd#3 assay would be suitable for routine NTHi surveillance and to assess the impact of antibiotics and vaccines, on H. influenzae carriage rates, carriage density, and disease.

Molecular surveillance of true nontypeable Haemophilus influenzae: an evaluation of PCR screening assays.

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Michael J Binks

Full Text Available BACKGROUND: Unambiguous identification of nontypeable Haemophilus influenzae (NTHi is not possible by conventional microbiology. Molecular characterisation of phenotypically defined NTHi isolates suggests that up to 40% are Haemophilus haemolyticus (Hh; however, the genetic similarity of NTHi and Hh limits the power of simple molecular techniques such as PCR for species discrimination. METHODOLOGY/PRINCIPAL FINDINGS: Here we assess the ability of previously published and novel PCR-based assays to identify true NTHi. Sixty phenotypic NTHi isolates, classified by a dual 16S rRNA gene PCR algorithm as NTHi (n = 22, Hh (n = 27 or equivocal (n = 11, were further characterised by sequencing of the 16S rRNA and recA genes then interrogated by PCR-based assays targeting the omp P2, omp P6, lgtC, hpd, 16S rRNA, fucK and iga genes. The sequencing data and PCR results were used to define NTHi for this study. Two hpd real time PCR assays (hpd#1 and hpd#3 and the conventional iga PCR assay were equally efficient at differentiating study-defined NTHi from Hh, each with a receiver operator characteristic curve area of 0.90 [0.83; 0.98]. The hpd#1 and hpd#3 assays were completely specific against a panel of common respiratory bacteria, unlike the iga PCR, and the hpd#3 assay was able to detect below 10 copies per reaction. CONCLUSIONS/SIGNIFICANCE: Our data suggest an evolutionary continuum between NTHi and Hh and therefore no single gene target could completely differentiate NTHi from Hh. The hpd#3 real time PCR assay proved to be the superior method for discrimination of NTHi from closely related Haemophilus species with the added potential for quantification of H. influenzae directly from specimens. We suggest the hpd#3 assay would be suitable for routine NTHi surveillance and to assess the impact of antibiotics and vaccines, on H. influenzae carriage rates, carriage density, and disease.

Antibody response to Haemophilus influenzae type b capsular polysaccharide conjugated to tetanus toxoid in preterm infants

DEFF Research Database (Denmark)

Kristensen, Kim; Gyhrs, A; Lausen, B

1996-01-01

OBJECTIVE: To evaluate the antibody response to a Haemophilus influenzae type b capsular polysaccharide (HibCP) tetanus toxoid (TT) conjugate vaccine (HibCP-TT) in preterm infants. SUBJECTS: Thirty-five healthy preterm infants with gestational ages (GA) from 27 to 36 weeks and birth weights from...

Radioimmunoassay of capsular polysaccaride antigens of groups A and C meningococci and Haemophilus influenza type b in cerebrospinal fluid

International Nuclear Information System (INIS)

Kaeyhty, H.; Maekelae, P.H.; Ruoslahti, E.

1977-01-01

Sensitive radioimmunoassays capable of measuring 0.5 ng/ml of the Haemophilus influenza type b polysaccharide and 2 ng/ml of the groups A and C meningococcal polysaccharides were developed and used to detect these substances in cerebrospinal fluid (CSF). Polysaccharide of the causative agent was detected in the CSF of 14 out of 15 patients with Haemophilus influenza type b meningitis, in 18 out of 23 patients with group A, and in two out of four patients with group C meningococcal meningitis. In some cases the antigen could be detected even after three days of antibacterial treatment. No false positive reactions were seen. The assay procedure could be shortened to approximately three hours. These assays could be useful in routine diagnostic work and epidemiological investigations. (author)

Meningite por Haemophilus influenzae tipo b em cidades do estado do Paraná, Brasil Haemophilus influenzae type b meningitis in the state of Paraná, Brazil

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Nádia S. Takemura

2001-10-01

Full Text Available OBJETIVO: no segundo semestre de 1996, os municípios de Londrina e Curitiba (Paraná iniciaram a vacinação contra Haemophilus influenzae b (Hib, aproximadamente trinta meses antes de sua introdução no Programa Nacional de Imunização. O presente trabalho objetivou avaliar a incidência da meningite por Hib, entre crianças, em Londrina, Curitiba e nos demais municípios do estado do Paraná, antes e após a introdução da vacina nessas duas cidades. MÉTODOS: foi realizado um estudo observacional retrospectivo de todos os casos de meningite por Hib, entre menores de 5 anos, diagnosticados pelo sistema de vigilância epidemiológica de Londrina e pela Secretaria de Estado da Saúde do Paraná, de 1992 a 1999. Taxas de incidência da meningite por Hib foram calculadas por 100.000 menores de cinco anos. RESULTADOS: comparando com o período anterior à vacinação, houve redução importante do coeficiente de incidência da meningite por Hib em Londrina, passando de 23,91, em 1996, para 2,79 por 100.000 menores de cinco anos, em 1999. Redução semelhante foi observada em Curitiba, enquanto nos demais municípios do Paraná, que não dispunham da vacina até meados de 1999, o coeficiente se manteve praticamente inalterado. CONCLUSÃO: a vacinação contra Hib foi efetiva na redução da incidência da meningite entre menores de cinco anos em Londrina e Curitiba. Para a manutenção dessa baixa incidência devem ser garantidas adequada cobertura vacinal e boa qualidade do serviço de vigilância epidemiológica.OBJECTIVE: during the second half of 1996, the municipalities of Londrina and Curitiba (State of Paraná, Brazil included Haemophilus influenzae type b (Hib vaccine into their routine vaccination regimen, approximately 30 months before its introduction into the National Immunization Program. The present study aimed at verifying the incidence of meningitis caused by Hib among children in Londrina, Curitiba, and in the remaining

Recombinant C-terminal 311 amino acids of HapS adhesin as a vaccine candidate for nontypeable Haemophilus influenzae: A study on immunoreactivity in Balb/C mouse.

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Tabatabaee Bafroee, Akram Sadat; Siadat, Seyed Davar; Mousavi, Seyed Fazlollah; Aghasadeghi, Mohammad Reza; Khorsand, Hashem; Nejati, Mehdi; Sadat, Seyed Mehdi; Mahdavi, Mehdi

2016-09-01

Hap, an auto-transporter protein, is an antigenically conserved adhesion protein which is present on both typeable and nontypeable Haemophilus influenzae. This protein has central role in bacterial attachment to respiratory tract epithelial cells. A 1000bp C-terminal fragment of Hap passenger domain (HapS) from nontypeable Haemophilus influenzae was cloned into a prokaryotic expression vector, pET-24a. BALB/c mice were immunized subcutaneously with purified rC-HapS. Serum IgG responses to purified rC-HapS, serum IgG subclasses were determined by ELISA and functional activity of antibodies was examined by Serum Bactericidal Assay. The output of rC-HapS was approximately 62% of the total bacterial proteins. Serum IgG responses were significantly increased in immunized group with rC-HapS mixed with Freund's adjuvant in comparison with control groups. Analysis of the serum IgG subclasses showed that the IgG1 subclass was predominant after subcutaneous immunization in BALB/c mice (IgG2a/IgG1 HapS immunized animals were strongly bactericidal against nontypeable Haemophilus influenzae. These results suggest that rC-HapS may be a potential vaccine candidate for nontypeable Haemophilus influenzae. Copyright © 2016 Elsevier Ltd. All rights reserved.

Live Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis activate the inflammatory response trhough Toll-like receptors 2, 4, and 9 in species-specific patterns

DEFF Research Database (Denmark)

Mogensen, T.H.; Paludan, Søren Riis; Kilian, Mogens

2006-01-01

activation by live bacteria. Here, we demonstrate that live Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis, the three principal causes of bacterial meningitis, use distinct sets of TLRs to trigger the inflammatory response. Using human embryonic kidney 293 cell lines......, each overexpressing one type of TLR, we found that S. pneumoniae triggered activation of the transcription factor nuclear factor-kappaB and expression of interleukin-8, only in cells expressing TLR2 or -9. The same response was evoked by H. influenzae in cells expressing TLR2 or -4 and by N...... and confirmed the essential role of these TLRs and also identified differential functions of TLRs in activation of the inflammatory response. Collectively, we here demonstrate that S. pneumoniae, H. influenzae, and N. meningitidis each activate several TLRs in species-specific patterns and show that infection...

Systematic Search for Primary Immunodeficiency in Adults With Infections

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2017-12-21

Complement Deficiency; Antibody Deficiency; Chronic Sinus Infection; Meningitis, Bacterial; Pneumonia, Bacterial; Otitis Media; Streptococcal Infection; Neisseria Infections; Haemophilus Influenza; Pneumococcal Infections

Rapid Differentiation of Haemophilus influenzae and Haemophilus haemolyticus by Use of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry with ClinProTools Mass Spectrum Analysis.

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Chen, Jonathan H K; Cheng, Vincent C C; Wong, Chun-Pong; Wong, Sally C Y; Yam, Wing-Cheong; Yuen, Kwok-Yung

2017-09-01

Haemophilus influenzae is associated with severe invasive disease, while Haemophilus haemolyticus is considered part of the commensal flora in the human respiratory tract. Although the addition of a custom mass spectrum library into the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system could improve identification of these two species, the establishment of such a custom database is technically complicated and requires a large amount of resources, which most clinical laboratories cannot afford. In this study, we developed a mass spectrum analysis model with 7 mass peak biomarkers for the identification of H. influenzae and H. haemolyticus using the ClinProTools software. We evaluated the diagnostic performance of this model using 408 H. influenzae and H. haemolyticus isolates from clinical respiratory specimens from 363 hospitalized patients and compared the identification results with those obtained with the Bruker IVD MALDI Biotyper. The IVD MALDI Biotyper identified only 86.9% of H. influenzae (311/358) and 98.0% of H. haemolyticus (49/50) clinical isolates to the species level. In comparison, the ClinProTools mass spectrum model could identify 100% of H. influenzae (358/358) and H. haemolyticus (50/50) clinical strains to the species level and significantly improved the species identification rate (McNemar's test, P mass spectrometry to handle closely related bacterial species when the proprietary spectrum library failed. This approach should be useful for the differentiation of other closely related bacterial species. Copyright © 2017 American Society for Microbiology.

Frequency of Haemophilus spp. in urinary and and genital tract samples

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Tatjana Marijan,

2010-02-01

Full Text Available Aim To determine the prevalence and antibiotic susceptibility of Haemophilus influenzae and H. parainfluenzae isolated from the urinary and genital tracts. Methods Identification of strains bacteria Haemophilus spp. was carried out by using API NH identifi-cation system, and antibiotic susceptibility was performed by Kirby-Bauer disk diffusion method. Results A total number of 50 (0,03% H. influenzae and 14 (0,01% H. parainfluenzae (out of 180, 415 samples were isolated from genitourinary tract. From urine samples of the girls under 15 years of age these bacteria were isolated in 13 (0,88% and two (0,13% cases, respectively, and only in one case(0,11% of the UTI in boys (H. influenzae. In persons of fertile age, it was only H. influenzae bacteria that was found in urine samples of the five women (0,04% and in three men (0,22%. As a cause of vulvovaginitis, H. influenzae was isolated in four (5,63%, and H. parainfluenzae in two (2,82% girls. In persons of fertile age, H. influenzae was isolated from 10 (0,49% smears of the cervix, and in nine (1,74% male samples. H. parainfluenzae was isolated from seven (1,36% male samples. (p<0.01. Susceptibility testing of H. influenzae and H. parainfluenzae revealed that both pathogens were signifi- cantly resistant to cotrimoxasol only (26.0% and 42.9%, respectively. Conclusion In the etiology of genitourinary infections of girls during childhood, genital infections of women in fertile age (especially in pregnant women, and men with cases of epididimytis and/or orchitis,it is important to think about this rare and demanding bacteria in terms of cultivation.

Relative Contribution of P5 and Hap Surface Proteins to Nontypable Haemophilus influenzae Interplay with the Host Upper and Lower Airways

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Viadas, Cristina; Ruiz de los Mozos, Igor; Valle, Jaione; Bengoechea, José Antonio; Garmendia, Junkal

2015-01-01

Nontypable Haemophilus influenzae (NTHi) is a major cause of opportunistic respiratory tract disease, and initiates infection by colonizing the nasopharynx. Bacterial surface proteins play determining roles in the NTHi-airways interplay, but their specific and relative contribution to colonization and infection of the respiratory tract has not been addressed comprehensively. In this study, we focused on the ompP5 and hap genes, present in all H. influenzae genome sequenced isolates, and encoding the P5 and Hap surface proteins, respectively. We employed isogenic single and double mutants of the ompP5 and hap genes generated in the pathogenic strain NTHi375 to evaluate P5 and Hap contribution to biofilm growth under continuous flow, to NTHi adhesion, and invasion/phagocytosis on nasal, pharyngeal, bronchial, alveolar cultured epithelial cells and alveolar macrophages, and to NTHi murine pulmonary infection. We show that P5 is not required for bacterial biofilm growth, but it is involved in NTHi interplay with respiratory cells and in mouse lung infection. Mechanistically, P5NTHi375 is not a ligand for CEACAM1 or α5 integrin receptors. Hap involvement in NTHi375-host interaction was shown to be limited, despite promoting bacterial cell adhesion when expressed in H. influenzae RdKW20. We also show that Hap does not contribute to bacterial biofilm growth, and that its absence partially restores the deficiency in lung infection observed for the ΔompP5 mutant. Altogether, this work frames the relative importance of the P5 and Hap surface proteins in NTHi virulence. PMID:25894755

Towards a sustainable, quality and affordable Haemophilus influenzae type b vaccine for every child in the world

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Hamidi, A.

2016-01-01

Haemophilus influenzae type b (Hib) conjugate vaccine is a safe and effective vaccine that can prevent meningitis and pneumonia caused by Hib disease. Hib vaccine is recommended for all children under 5 years. Despite the availability of safe and effective Hib vaccines since early 1987, Gambia was

No evidence of increasing Haemophilus influenzae non-b infection in Australian Aboriginal children

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Robert I. Menzies

2013-08-01

Full Text Available Background. High, or increasing, rates of invasive Haemophilus influenzae (Hi type a disease have been reported from North American native children from circumpolar regions, raising the question of serotype replacement being driven by vaccination against Hi type b (Hib. Indigenous Australians from remote areas had high rates of invasive Hib disease in the past, comparable to those in North American Indigenous populations. Objective. Evaluate incidence rates of invasive Hi (overall and by serotype in Indigenous Australian children over time. Design. Descriptive study of Hi incidence rates by serotype, in the Northern Territory (NT and South Australia (SA from 2001 to 2011. Comparison of NT data with a study that was conducted in the NT in 1985–1988, before Hib vaccine was introduced. Results. The average annual rate of invasive Hi type a (Hia disease in Indigenous children aged <5 years was 11/100,000 population. Although the incidence of Hi infection in Indigenous children in 2001–2003 was lower than during 2004–2011, this may be due to changes in surveillance. No other trend over time in individual serotypes or total invasive Hi disease, in Indigenous or non-Indigenous people, was identified. Compared to 1985–1988, rates in 2001–2011 were lower in all serotype groupings, by 98% for Hib, 75% for Hia, 79% for other serotypes and 67% for non-typeable Hi. Conclusions. There is no evidence of increases in invasive disease due to Hia, other specific non-b types, or non-typeable Hi in Australian Indigenous children. These data suggest that the increase in Hia some time after the introduction of Hib vaccine, as seen in the North American Arctic Region, is not common to all populations with high pre-vaccine rates of invasive Hib disease. However, small case numbers and the lack of molecular subtyping and PCR confirmation of pre-vaccine results complicate comparisons with North American epidemiology.

Haemophilus influenzae vulvovaginitis associated with rhinitis caused by the same clone in a prepubertal girl.

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Chen, Xiao; Chen, Lifeng; Zeng, Wenjie; Zhao, Xiaofeng

2017-06-01

Vulvovaginitis caused by upper respiratory flora is generally considered to be the most common gynecological problem in prepubertal girls. To date, however, no direct evidence has been obtained for the underlying mechanism of transmission. This report describes a case of non-capsulate Haemophilus influenzae vulvovaginitis in a 6-year-old girl with a history of foreign bodies (cotton wool) in her vagina. Moreover, this girl had recurrent rhinitis for approximately 3 years. On Pulsed Field Gel Electrophoresis (PFGE) analysis the H. influenzae strain isolated from vaginal secretions and the H. influenzae strain isolated from nasal secretions were derived from the same clone. The patient was successfully treated with appropriate antibiotics. The present case might provide the first direct evidence of the nose-hand-vagina method of transmission. © 2017 Japan Society of Obstetrics and Gynecology.

In vitro capability of faropenem to select for resistant mutants of Streptococcus pneumoniae and Haemophilus influenzae.

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Kosowska-Shick, Klaudia; Clark, Catherine; Credito, Kim; Dewasse, Bonifacio; Beachel, Linda; Ednie, Lois; Appelbaum, Peter C

2008-02-01

When tested against nine strains of pneumococci and six of Haemophilus influenzae of various resistotypes, faropenem failed to select for resistant mutants after 50 days of consecutive subculture in subinhibitory concentrations. Faropenem also yielded low rates of spontaneous mutations against all organisms of both species. By comparison, resistant clones were obtained with macrolides, ketolides, and quinolones.

Identification of a group of Haemophilus influenzae penicillin-binding proteins that may have complementary physiological roles

International Nuclear Information System (INIS)

Malouin, F.; Parr, T.R. Jr.; Bryan, L.E.

1990-01-01

[35S]penicillin bound to different Haemophilus influenzae proteins in assays performed at 20, 37, or 42 degrees C. Penicillin-binding proteins 3a, 3b, 4, and 4' formed a group characterized by their affinity for moxalactam, cefotaxime, and piperacillin. Penicillin-binding protein 4' showed specific properties that may reflect its complementary role in septation

[Invasive infections caused by Haemophilus influenzae type b after the institution of the conjugated vaccine on the expanded programm on immunization in Chile].

Science.gov (United States)

Cruces R, Pablo; Donoso F, Alejandro; Camacho A, Jorge; Llorente H, Marcela

2006-03-01

After almost a decade since the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines in Chile (in a 2-4-6 month schedule), Hib invasive infections have dramatically decreased, albeit they remain to occasionally produce disease in pediatric patients. We report our experience with children whom developed Hib invasive disease in children since 2000 to 2004. Medical records of children with Hib were reviewed in order to describe the epidemiology, main clinical and laboratory findings, management and complications. Twenty three patients (17 male), between 1 and 71 months (median 30 months) were identified: pneumonia (7), meningitis (4), pleuropneumonia (2), empyema (2), sepsis (2), cellulitis (2), meningitis and pleuropneumonia (1), purpura fulminans (1), miositis (1) and epiglottitis (1). No deaths were observed and four patients presented severe sequelae at hospital discharge. Twenty patients were considered vaccine failures. Hib remains as a sporadic cause of severe disease in Chile and thus for physicians should still keep it in mind. Case analysis and active surveillance are necessary to monitor the current immunization regimen.

Characterization of the rec-1 gene of Haemophilus influenzae and behavior of the gene in Escherichia coli

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Setlow, J.K.; Spikes, D.; Griffin, K.

1988-09-01

The rec-1 gene of Haemophilus influenzae was cloned into a shuttle vector that replicates in Escherichia coli as well as in H. influenzae. The plasmid, called pRec1, complemented the defects of a rec-1 mutant in repair of UV damage, transformation, and ability of prophage to be induced by UV radiation. Although UV resistance and recombination were caused by pRec1 in E. coli recA mutants, UV induction of lambda and UV mutagenesis were not. We suggest that the ability of the H. influenzae Rec-1 protein to cause cleavage of repressors but not the recombinase function differs from that of the E. coli RecA protein.

Characterization of the rec-1 gene of Haemophilus influenzae and behavior of the gene in Escherichia coli

International Nuclear Information System (INIS)

Setlow, J.K.; Spikes, D.; Griffin, K.

1988-01-01

The rec-1 gene of Haemophilus influenzae was cloned into a shuttle vector that replicates in Escherichia coli as well as in H. influenzae. The plasmid, called pRec1, complemented the defects of a rec-1 mutant in repair of UV damage, transformation, and ability of prophage to be induced by UV radiation. Although UV resistance and recombination were caused by pRec1 in E. coli recA mutants, UV induction of lambda and UV mutagenesis were not. We suggest that the ability of the H. influenzae Rec-1 protein to cause cleavage of repressors but not the recombinase function differs from that of the E. coli RecA protein

Inhibitory effect of 1,2,4-triazole-ciprofloxacin hybrids on Haemophilus parainfluenzae and Haemophilus influenzae biofilm formation in vitro under stationary conditions.

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Kosikowska, Urszula; Andrzejczuk, Sylwia; Plech, Tomasz; Malm, Anna

2016-10-01

Haemophilus parainfluenzae and Haemophilus influenzae, upper respiratory tract microbiota representatives, are able to colonize natural and artificial surfaces as biofilm. The aim of the present study was to assay the effect of ten 1,2,4-triazole-ciprofloxacin hybrids on planktonic or biofilm-forming haemophili cells in vitro under stationary conditions on the basis of MICs (minimal inhibitory concentrations) and MBICs (minimal biofilm inhibitory concentrations). In addition, anti-adhesive properties of these compounds were examined. The reference strains of H. parainfluenzae and H. influenzae were included. The broth microdilution microtiter plate (MTP) method with twofold dilution of the compounds, or ciprofloxacin (reference agent) in 96-well polystyrene microplates, was used. The optical density (OD) reading was made spectrophotometrically at a wavelength of 570 nm (OD570) both to measure bacterial growth and to detect biofilm-forming cells under the same conditions with 0.1% crystal violet. The following values of parameters were estimated for 1,2,4-triazole-ciprofloxacin hybrids - MIC = 0.03-15.63 mg/L, MBIC = 0.03-15.63 mg/L, MBIC/MIC = 0.125-8, depending on the compound, and for ciprofloxacin - MIC = 0.03-0.06 mg/L, MBIC = 0.03-0.12 mg/L, MBIC/MIC = 1-2. The observed strong anti-adhesive properties (95-100% inhibition) of the tested compounds were reversible during long-term incubation at subinhibitory concentrations. Thus, 1,2,4-triazole-ciprofloxacin hybrids may be considered as starting compounds for designing improved agents not only against planktonic but also against biofilm-forming Haemophilus spp. cells. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Influence of prevaccination immunity on the human B-lymphocyte response to a Haemophilus influenzae type b conjugate vaccine

DEFF Research Database (Denmark)

Barington, T; Kristensen, K; Henrichsen, J

1991-01-01

of Haemophilus influenzae type b capsular polysaccharide (PRP) and diphtheria toxoid (DT), and the response was related to the prevaccination levels of PRP and DT antibodies. Positive correlations were found between increases in plasma PRP (median, 32.0 micrograms/ml) and DT (1.14 IU/ml) antibodies and numbers...

[Isolation of Haemophilus influenzae serotypes from deep sites in sick children].

Science.gov (United States)

Gatti, B M; Ramirez Gronda, G A; Etchevarría, M; Vescina, C M; Varea, A M; González Ayala, S E

2004-01-01

Haemophilus influenzae (Hi) is the causative agent of several human diseases such as sepsis, meningitis, celulitis, and osteoarthritis. We investigated the isolation of Hi serotypes from sterile sites in sick children. One hundred and seventy nine strains from 146 patients were studied, period 1996-2002, at the Microbiology Laboratory, Hospital de Niños Superiora Sor María Ludovica, Argentina. The serotype distribution was:1 a, 112 b,1 c,1 d, 4 e, 3 f y 24 no typable. Since the beginning of universal Hi b vaccination in 1998, we have observed the fast decrease of serotype b and a relative increase of other serotypes.

Haemophilus influenzae Sepsis and Placental Abruption in an Unvaccinated Immigrant

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Paul A. Calner

2012-04-01

Full Text Available Background: Haemophilus influenzae infections have declined dramatically in the United States sinceimplementation of the conjugate vaccine. However, in countries where widespread immunization is notroutine, H influenzae remains a significant cause of morbidity and mortality. We report a case of apreviously unvaccinated immigrant with confirmed H influenzae sepsis and placental abruption leadingto spontaneous abortion.Objectives: To alert emergency medicine practitioners that H influenzae should be recognized as amaternal, fetal, and neonatal pathogen. Clinicians should consider this diagnosis in immigrants presentingwith uncertain vaccination history, as H influenzae can cause significant morbidity and mortality.Case Presentation: A 36-year-old female was referred to our emergency department (ED with lowerabdominal pain with some vaginal spotting. The patient had an initial visit with normal laboratoryinvestigations and normal imaging results, with complete resolution of symptoms. The patient returned tothe ED with sudden onset of vaginal bleeding and abdominal pain. She presented at this time with sepsis,which progressed to septic shock, causing placental abruption and ultimately, spontaneous abortion. Thepatient was treated with pressors and antibiotics and was admitted to the medical intensive care unitwhere she received ampicillin, gentamycin, and clindamycin for suspected chorioamnionitis. The patient’sblood cultures came back positive after 1 day for H influenzae. The patient did well and was dischargedfrom the hospital 4 days later.Conclusion: Haemophilus influenzae should be recognized as a neonatal and maternal pathogen.Clinicians should consider this diagnosis in immigrants presenting with uncertain vaccination history,especially in pregnant females, as H influenzae can cause significant morbidity and mortality. [West JEmerg Med. 2012;13(1:133–135.

Mutation induction in Haemophilus influenzae by ICR-191. Pt. 1

International Nuclear Information System (INIS)

Perdue, S.W.; Kimball, R.F.; McGray, P.C.; Tennessee Univ., Oak Ridge

1981-01-01

The investigation of mutagenic mechanisms in Haemophilus influenzae has been confined until now to mutagens that normally produce mainly base pair substitutions. This paper describes the development of a system suitable for detecting frameshift mutations induced by ICR-191. The system involves reversions from thymidine dependence to thymidine independence. Evidence is presented from a comparison of the responses to ICR-191 and to N-methyl-N'-nitro-N-nitrosoguanidine that the system is specific for frameshift mutations. The genetic recombination involved in transformation leads to a marked increase in spontaneous reversion of the frameshift mutations but not of the base substitution mutations. Presumably, this is a consequence of mispairing, with consequent change in the number of bases, during the recombination. (orig.)

'Haemophilus quentini' in the urethra of men complaining of urethritis symptoms.

Science.gov (United States)

Horie, Kengo; Ito, Shin; Hatazaki, Kyoko; Yasuda, Mitsuru; Nakano, Masahiro; Kawakami, Kyojiro; Fujita, Yasunori; Ito, Masafumi; Ezaki, Takayuki; Deguchi, Takashi

2018-01-01

We isolated a cryptic genospecies of Haemophilus influenzae referred to as 'Haemophilus quentini' in the urethra of 3 men complaining of urethritis symptoms. H. influenzae strains, which had been isolated from the urethra in 77 of 1518 men complaining of urethritis symptoms, identified by the conventional test, and stored, were re-cultured for this study. Sixty-seven strains surviving storage were screened by a PCR-based assay specific for the cryptic genital Haemophilus genospecies. Three strains (HI09003, HI11006, and HI14016) were screened by PCR and identified as 'H. quentini' by 16S rRNA sequencing. The men positive for HI09003 and HI11006 were diagnosed as having non-chlamydial non-gonococcal urethritis (NGU), and their demographic and clinical features were similar to those of NGU caused by other pathogens. The man positive for HI14016 was ultimately diagnosed as having condyloma acuminatum on the glans. The 3 strains of 'H. quentini' produced no β-lactamase and were susceptible to ampicillin and other antimicrobial agents, including cephalosporins, fluoroquinolones, tetracyclines, and macrolides, recommended for treatment for urethritis. 'H. quentini' would be an uncommon pathogen in men with urogenital infections. Based on the clinical features of the two patients with 'H. quentini'-positive NGU, it would be difficult to predict the presence of 'H. quentini' in the urethra. The 3 strains of 'H. quentini' were susceptible to a variety of antimicrobial agents. Further accumulation of data regarding 'H. quentini' infections is needed to characterize the pathogenic roles of this genospecies in urogenital infections and to establish appropriate management of 'H. quentini' infections. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Human milk lactoferrin inactivates two putative colonization factors expressed by Haemophilus influenzae.

Science.gov (United States)

Qiu, J; Hendrixson, D R; Baker, E N; Murphy, T F; St Geme, J W; Plaut, A G

1998-10-13

Haemophilus influenzae is a major cause of otitis media and other respiratory tract disease in children. The pathogenesis of disease begins with colonization of the upper respiratory mucosa, a process that involves evasion of local immune mechanisms and adherence to epithelial cells. Several studies have demonstrated that human milk is protective against H. influenzae colonization and disease. In the present study, we examined the effect of human milk on the H. influenzae IgA1 protease and Hap adhesin, two autotransported proteins that are presumed to facilitate colonization. Our results demonstrated that human milk lactoferrin efficiently extracted the IgA1 protease preprotein from the bacterial outer membrane. In addition, lactoferrin specifically degraded the Hap adhesin and abolished Hap-mediated adherence. Extraction of IgA1 protease and degradation of Hap were localized to the N-lobe of the bilobed lactoferrin molecule and were inhibited by serine protease inhibitors, suggesting that the lactoferrin N-lobe may contain serine protease activity. Additional experiments revealed no effect of lactoferrin on the H. influenzae P2, P5, and P6 outer-membrane proteins, which are distinguished from IgA1 protease and Hap by the lack of an N-terminal passenger domain or an extracellular linker region. These results suggest that human milk lactoferrin may attenuate the pathogenic potential of H. influenzae by selectively inactivating IgA1 protease and Hap, thereby interfering with colonization. Future studies should examine the therapeutic potential of lactoferrin, perhaps as a supplement in infant formulas.

Multicentre in-vitro evaluation of the susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis to ciprofloxacin, clarithromycin, co-amoxiclav and sparfloxacin

NARCIS (Netherlands)

HoogkampKorstanje, JAA; DirksGo, SIS; Kabel, P; Manson, WL; Stobberingh, EE; Vreede, RW; Davies, BI

Seven laboratories, including a reference laboratory, tested the susceptibility of Moraxella catarrhalis, Streptococcus pneumoniae and Haemophilus influenzae strains to ciprofloxacin, clarithromycin, co-amoxiclav and sparfloxacin with the Etest. A total of 976 strains were collected. The results

Identification of immunogenic outer membrane proteins of Haemophilus influenzae type b in the infant rat model system

International Nuclear Information System (INIS)

Hansen, E.J.; Frisch, C.F.; McDade, R.L. Jr.; Johnston, K.H.

1981-01-01

Outer membrane proteins of Haemophilus influenzae type b which are immunogenic in infant rats were identified by a radioimmunoprecipitation method. Intact cells of H. influenzae type b were radioiodinated by a lactoperoxidase-catalyzed procedure, and an outer membrane-containing fraction was prepared from these cells. These radioiodinated outer membranes were mixed with sera obtained from rats convalescing from systemic H. influenzae type b disease induced at 6 days of age, and the resultant (antibody-outer membrane protein antigen) complexes were extracted from these membranes by treatment with nonionic detergent and ethylenediaminetetraacetic acid. These soluble antibody-antigen complexes were isolated by means of adsorption to protein A-bearing staphylococci, and the radioiodinated protein antigens were identified by gel electrophoresis followed by autoradiography. Infant rats were shown to mount a readily detectable antibody response to several different proteins present in the outer membrane of H. influenzae type b. Individual infant rats were found to vary both qualitatively and quantitatively in their immune response to these immunogenic outer membrane proteins

DNA repair in Haemophilus influenzae: isolation and characterization of an ultraviolet sensitive mutator mutant

International Nuclear Information System (INIS)

Walter, R.B.

1985-01-01

DNA repair in Haemophilus influenzae appears to be quite different from that seen in Escherichia coli in that H. influenzae shows neither SOS nor adaptation phenomena. Repair of DNA lesions in H. influenzae has been seen to occur via recombinational, excision, and mismatch repair pathways acting independently of one another. The author has isolated an ultraviolet (UV)-sensitive mutator mutant (mutB1) of H. influenzae Rd which shows deficiencies in both recombinational and mismatch repair pathways. This mutant is sensitive to a variety of DNA damaging agents as well as being hypermutable by alkylating agents and base analogues. MutB1 cells do not show post-UV DNA breakdown but do begin excision after UV irradiation. Genetic transformation with UV-irradiated DNA on mut B1 recipients shows that high (HE) and low (LE) efficiency markers are transformed at a ratio of 1.0 as in the mismatch repair deficient hex 1 mutant; however, kinetics of UV-inactivation experiments indicate that HE markers are sensitized and act as LE markers do on wild type recipients. Thus, the mutB gene product appears to play a role in both DNA repair and genetic transformation. A model is outlined which presents a role for a DNA helicase in both DNA repair and genetic transformation of H. influenzae

Nontypeable Haemophilus influenzae in chronic obstructive pulmonary disease and lung cancer

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Seyed Javad Moghaddam

2011-01-01

Full Text Available Seyed Javad Moghaddam1, Cesar E Ochoa1,2, Sanjay Sethi3, Burton F Dickey1,41Department of Pulmonary Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Tecnológico de Monterrey School of Medicine, Monterrey, Nuevo León, Mexico; 3Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY, USA; 4Center for Inflammation and Infection, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, USAAbstract: Chronic obstructive pulmonary disease (COPD is predicted to become the third leading cause of death in the world by 2020. It is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles and gases, most commonly cigarette smoke. Among smokers with COPD, even following withdrawal of cigarette smoke, inflammation persists and lung function continues to deteriorate. One possible explanation is that bacterial colonization of smoke-damaged airways, most commonly with nontypeable Haemophilus influenzae (NTHi, perpetuates airway injury and inflammation. Furthermore, COPD has also been identified as an independent risk factor for lung cancer irrespective of concomitant cigarette smoke exposure. In this article, we review the role of NTHi in airway inflammation that may lead to COPD progression and lung cancer promotion.Keywords: COPD, NTHi, inflammation

Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b

DEFF Research Database (Denmark)

Sun, Yuelian; Christensen, Jakob Christensen; Hviid, Anders

2012-01-01

-acellular pertussis–inactivated poliovirus– Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September 2002. Objective To estimate the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination given at 3, 5, and 12 months. Design, Setting, and Participants A population-based cohort study of 378...

Impact of the Haemophilus influenzae type b vaccination program on HIB meningitis in Brazil Impacto do programa de vacinação contra meningites causadas por Haemophilus influenzae tipo b no Brasil

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Sybelle de Souza Castro Miranzi

2007-07-01

Full Text Available This study aimed to evaluate the impact of vaccination against Haemophilus influenzae type b (HIB in Brazil on the morbidity, mortality, and case fatality of HIB meningitis, using the Ministry of Health database and population data from the Brazilian Institute of Geography and Statistics (Instituto Brasileiro de Geografia e Estatística - IBGE. Impact was evaluated through a time series analysis (1983-2002, using regression forecasting (RF by dividing the time series into two periods: (a historical (1983-1998 and (b validation (1999-2002. Impact of the vaccination was positive, although more significant for incidence and mortality than for case fatality rates.A proposta deste trabalho foi avaliar o impacto da vacinação contra Haemophilus influenzae tipo b (HIB no Brasil sobre a morbi-mortalidade e a letalidade das meningites por HIB, a partir de base de dados fornecida pelo Ministério da Saúde e as estimativas populacionais provenientes do Instituto Brasileiro de Geografia e Estatística (IBGE. Para a avaliação do impacto utilizou-se análise de tendência temporal (1983-2002, aplicando-se a técnica RF (regression forecasting, dividindo-se a série em dois períodos: (a período histórico (1983-1998 e (b período de estimação (1999-2002. O impacto da vacinação foi positivo, embora tenha se revelado mais expressivo sobre a morbi-mortalidade que sobre a letalidade.

Changes in IgA protease expression are conferred by changes in genomes during persistent infection by nontypeable Haemophilus influenzae in chronic obstructive pulmonary disease.

Science.gov (United States)

Gallo, Mary C; Kirkham, Charmaine; Eng, Samantha; Bebawee, Remon S; Kong, Yong; Pettigrew, Melinda M; Tettelin, Hervé; Murphy, Timothy F

2018-05-14

Nontypeable Haemophilus influenzae (NTHi) is an exclusively human pathobiont that plays a critical role in the course and pathogenesis of chronic obstructive pulmonary disease (COPD). NTHi causes acute exacerbations of COPD and also causes persistent infection of the lower airways. NTHi expresses four IgA protease variants (A1, A2, B1, and B2) that play different roles in virulence. Expression of IgA proteases varies among NTHi strains, but little is known about the frequency and mechanisms by which NTHi modulates IgA protease expression during infection in COPD. To assess expression of IgA protease during natural infection in COPD, we studied IgA protease expression of 101 persistent strains (median duration of persistence 161 days, range 2 to 1422) collected longitudinally from patients enrolled in a 20-year study of COPD upon initial acquisition and immediately before clearance from the host. Upon acquisition, 89 (88%) expressed IgA protease. A total of 16 of 101 (16%) strains of NTHi altered expression of IgA protease during persistence. Indels and slipped-strand mispairing of mononucleotide repeats conferred changes in expression of igaA1, igaA2, and igaB1 Strains with igaB2 underwent frequent changes in expression of IgA protease B2 during persistence, mediated by slipped-strand mispairing of a 7-nucleotide repeat, TCAAAAT, within the open reading frame of igaB2 We conclude that changes in iga gene sequences result in changes in expression of IgA proteases by NTHi during persistent infection in the respiratory tract of patients with COPD. Copyright © 2018 American Society for Microbiology.

Development of a diagnostic real-time polymerase chain reaction assay for the detection of invasive Haemophilus influenzae in clinical samples.

LENUS (Irish Health Repository)

Meyler, Kenneth L

2012-12-01

Since the introduction of the Haemophilus influenzae serotype b vaccine, invasive H. influenzae disease has become dominated by nontypeable (NT) strains. Several widely used molecular diagnostic methods have been shown to lack sensitivity or specificity in the detection of some of these strains. Novel real-time assays targeting the fucK, licA, and ompP2 genes were developed and evaluated. The fucK assay detected all strains of H. influenzae tested (n = 116) and had an analytical sensitivity of 10 genome copies\\/polymerase chain reaction (PCR). This assay detected both serotype b and NT H. influenzae in 12 previously positive specimens (culture and\\/or bexA PCR) and also detected H. influenzae in a further 5 of 883 culture-negative blood and cerebrospinal fluid (CSF) samples. The fucK assay has excellent potential as a diagnostic test for detection of typeable and nontypeable strains of invasive H. influenzae in clinical samples of blood and CSF.

Development of a diagnostic real-time polymerase chain reaction assay for the detection of invasive Haemophilus influenzae in clinical samples.

Science.gov (United States)

Meyler, Kenneth L; Meehan, Mary; Bennett, Desiree; Cunney, Robert; Cafferkey, Mary

2012-12-01

Since the introduction of the Haemophilus influenzae serotype b vaccine, invasive H. influenzae disease has become dominated by nontypeable (NT) strains. Several widely used molecular diagnostic methods have been shown to lack sensitivity or specificity in the detection of some of these strains. Novel real-time assays targeting the fucK, licA, and ompP2 genes were developed and evaluated. The fucK assay detected all strains of H. influenzae tested (n = 116) and had an analytical sensitivity of 10 genome copies/polymerase chain reaction (PCR). This assay detected both serotype b and NT H. influenzae in 12 previously positive specimens (culture and/or bexA PCR) and also detected H. influenzae in a further 5 of 883 culture-negative blood and cerebrospinal fluid (CSF) samples. The fucK assay has excellent potential as a diagnostic test for detection of typeable and nontypeable strains of invasive H. influenzae in clinical samples of blood and CSF. Copyright © 2012 Elsevier Inc. All rights reserved.

Chronic cutaneous ulcers secondary to Haemophilus ducreyi infection.

Science.gov (United States)

Peel, Trisha N; Bhatti, Deepak; De Boer, Jim C; Stratov, Ivan; Spelman, Denis W

2010-03-15

Haemophilus ducreyi is a well recognised causative agent of genital ulcers and chancroid. We report two unusual cases of non-sexually transmitted H. ducreyi infection leading to chronic lower limb ulcers. Both patients were Australian expatriates visiting Australia from the Pacific Islands--one from Papua New Guinea and the other from Vanuatu.

A plasmid carrying mucA and mucB genes from pKM101 in Haemophilus influenzae and Escherichia coli

International Nuclear Information System (INIS)

Spikes, D.; Setlow, J.K.

1989-01-01

The plasmid pMucAMucB, constructed from the Haemophilus influenzae vector pDM2, and a similar plasmid, constructed from pBR322, increased the survival after UV irradiation of Escherichia coli AB1157 with the umu-36 mutation and also caused UV-induced mutation in the E. coli strain. In H. influenzae, pMucAMucB caused a small but reproducible increase in survival after UV irradiation in wild-type cells and in a rec-1 mutant, but there was no increase in spontaneous mutation in the wild type or in the rec-1 mutant and no UV-induced mutation

Costo-efectividad de la vacunación contra Haemophilus influenzae tipo b : un análisis de decisión para Cuba

NARCIS (Netherlands)

Carcía, A; Postma, Maarten; Gálvez, AM; Sierra, G

2002-01-01

The objective of the present study was to estimate the cost-effectiveness ratio of the therapeutic and prophylactic alternatives for treatment of meningitis caused by Haemophilus influenzae type b in less than one year old infants applying a mathematical model. A hypothetical setting with two

Quantitative fucK gene polymerase chain reaction on sputum and nasopharyngeal secretions to detect Haemophilus influenzae pneumonia.

Science.gov (United States)

Abdeldaim, Guma M K; Strålin, Kristoffer; Olcén, Per; Blomberg, Jonas; Mölling, Paula; Herrmann, Björn

2013-06-01

A quantitative polymerase chain reaction (PCR) for the fucK gene was developed for specific detection of Haemophilus influenzae. The method was tested on sputum and nasopharyngeal aspirate (NPA) from 78 patients with community-acquired pneumonia (CAP). With a reference standard of sputum culture and/or serology against the patient's own nasopharyngeal isolate, H. influenzae etiology was detected in 20 patients. Compared with the reference standard, fucK PCR (using the detection limit 10(5) DNA copies/mL) on sputum and NPA showed a sensitivity of 95.0% (19/20) in both cases, and specificities of 87.9% (51/58) and 89.5% (52/58), respectively. In a receiver operating characteristic curve analysis, sputum fucK PCR was found to be significantly superior to sputum P6 PCR for detection of H. influenzae CAP. NPA fucK PCR was positive in 3 of 54 adult controls without respiratory symptoms. In conclusion, quantitative fucK real-time PCR provides a sensitive and specific identification of H. influenzae in respiratory secretions. Copyright © 2013 Elsevier Inc. All rights reserved.

ENFERMEDAD INVASORA POR HAEMOPHILUS INFLUENZAE ANTES Y DESPUÉS DE LA CAMPAÑA DE VACUNACIÓN EN LA POBLACIÓN INFANTIL DE LA COMUNIDAD VALENCIANA (1996-2000

Directory of Open Access Journals (Sweden)

Mercedes Goicoechea Sáez

2002-01-01

Full Text Available Fundamento: La introducción de la vacuna conjugada anti Haemophilus influenzae tipo b (Hib en niños ha provocado un llamativo descenso de la incidencia de la enfermedad por H. influenzae. El objetivo de este estudio es analizar las características más relevantes de la enfermedad invasora por H. influenzae en cuanto a la epidemiología, clínica, evolución y estado de vacunación de la población infantil de la Comunidad Valenciana en el periodo 1996-2000. Método: Los datos se recogen de las historias clínicas de los niños menores de 15 años que hayan presentado síntomas y signos clínicos sugestivos de enfermedad invasora con aislamiento de Haemophilus influenzae y/o que cumple con los criterios de definición de caso establecidos, atendidos en todos los hospitales públicos de la Comunidad Valenciana entre 1996 y 2000. La evolución de la incidencia se valoró mediante tasas de incidencia. La clínica y su evolución (secuelas y letalidad mediante la frecuencia y distribución por edad. Resultados: Se registraron un total de 36 casos de enfermedad invasora por Haemophilus influenzae. La tasa de incidencia en niños menores de 15 años pasó de 3,56/105 en 1996 a 1,07/105 en 1997 (coincidiendo con la campaña de vacunación y la posterior inclusión de la vacuna conjugada anti Hib en el Calendario de Vacunaciones Sistemáticas de la Comunidad Valenciana y 0,30/105 en 1998, situación que se sigue manteniendo en los años posteriores. El 53% de los casos se dan en menores de 18 meses. Tanto las secuelas como los fallecimientos se producen en la época anterior a la aplicación rutinaria de la vacuna conjugada. Ningún niño vacunado correctamente falleció. Se registraron 2 casos de H. influenzae tipo no b en niños vacunados. Conclusiones: La incidencia de la infección por Haemophilus influenzae tipo b disminuyó drásticamente desde el inicio de la vacunación sistemática de la población infantil.

Carrier state of Haemophilus influenzae type b (Hib, Streptococcus pneumoniae, Streptococcus pyogenes, Neisseria meningitidis and Corynebacterium diphtheriae among school children in Pokhara, Nepal

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Dharm Raj Bhatta

2014-02-01

Full Text Available Objective: To determine the incidence of carrier state of Haemophilus influenzae type b, Streptococcus pneumoniae (S. pneumoniae, Streptococcus pyogenes, Neisseria meningitidis and Corynebacterium diphtheriae among school children. Methods: Specimen from posterior pharyngeal wall and tonsils were collected on calcium alginate coated swabs from 1 02 participants. Processing of specimen and antimicrobial susceptibility testing was done by standard procedures. Results: Potential pathogens isolated in our study were S. pneumoniae (14.7%, Staphylococcus aureus (12.7%, Corynebacterium diphtheriae (3.9%, Streptococcus pyogenes (3.9% and Haemophilus influenzae (1.9%. Important findings in antibiogram include high resistance of S. pneumoniae to penicillin (73% and resistance of Staphylococcus aureus to oxacillin (23%. Conclusions: Pharyngeal colonization by S. pneumoniae among school children was found high and there is need of introduction of pneumococcal vaccines among children. Despite expected universal vaccination, pharyngeal colonization by Corynebacterium diphtheriae is possible and there is possibility of transmission.

Anti-influenza Hyperimmune Immunoglobulin Enhances Fc-functional Antibody Immunity during Human Influenza Infection.

Science.gov (United States)

Vanderven, Hillary A; Wragg, Kathleen; Ana-Sosa-Batiz, Fernanda; Kristensen, Anne B; Jegaskanda, Sinthujan; Wheatley, Adam K; Wentworth, Deborah; Wines, Bruce D; Hogarth, P Mark; Rockman, Steve; Kent, Stephen J

2018-05-31

New treatments for severe influenza are needed. Passive transfer of influenza-specific hyperimmune pooled immunoglobulin (Flu-IVIG) boosts neutralising antibody responses to past strains in influenza-infected subjects. The effect of Flu-IVIG on antibodies with Fc-mediated functions, which may target diverse influenza strains, is unclear. We studied the capacity of Flu-IVIG, relative to standard IVIG, to bind to Fc receptors and mediate antibody-dependent cellular cytotoxicity in vitro. The effect of Flu-IVIG infusion, compared to placebo infusion, was examined in serial plasma samples from 24 subjects with confirmed influenza infection in the INSIGHT FLU005 pilot study. Flu-IVIG contains higher concentrations of Fc-functional antibodies than IVIG against a diverse range of influenza hemagglutinins. Following infusion of Flu-IVIG into influenza-infected subjects, a transient increase in Fc-functional antibodies was present for 1-3 days against infecting and non-infecting strains of influenza. Flu-IVIG contains antibodies with Fc-mediated functions against influenza virus and passive transfer of Flu-IVIG increases anti-influenza Fc-functional antibodies in the plasma of influenza-infected subjects. Enhancement of Fc-functional antibodies to a diverse range of influenza strains suggests that Flu-IVIG infusion could prove useful in the context of novel influenza virus infections, when there may be minimal or no neutralising antibodies in the Flu-IVIG preparation.

Unexpected effects of absorbed normal rabbit serum and bovine serum albumin on survival of Haemophilus influenzae type b in the infant rat.

Science.gov (United States)

Loeb, M R

1988-01-01

In the course of using the infant rat model to determine the ability of various rabbit antisera to protect against challenge by Haemophilus influenzae type b we made two unexpected observations. In these experiments 4-day-old rats were inoculated s.c. on the dorsum with either rabbit serum or physiological buffers (sham serum) and then were challenged the next day with H. influenzae type b injected i.p. Bacteremia, as a marker for disease, was measured 24 h later on day 6. We observed the following. (i) Pre-immune, i.e., normal rabbit serum, containing minimal levels of antibodies to outer membrane proteins and depleted of antibodies to capsule and lipopolysaccharide, nevertheless significantly (P less than 0.01) protected the rats from challenge with H. influenzae type b when compared to a sham inoculation of buffer; (ii) In the absence of a serum inoculation on day 4 (a buffer was used as a sham serum inoculation), the levels of bacteremia obtained after inoculation with bacteria on day 5 depended upon the composition of the buffer in which the H. influenzae inoculum was suspended. Use of phosphate buffered saline (PBS) resulted in higher levels of bacteremia than PBS containing 0.5% bovine serum albumin (PBS-BSA) (P less than 0.001), i.e. the BSA apparently acted to protect the rats from H. influenzae infection. In fact the use of PBS-BSA as an inoculum buffer masked the protective effect noted above of the absorbed normal rabbit serum.

Nontypeable Haemophilus influenzae induces sustained lung oxidative stress and protease expression.

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Paul T King

Full Text Available Nontypeable Haemophilus influenzae (NTHi is a prevalent bacterium found in a variety of chronic respiratory diseases. The role of this bacterium in the pathogenesis of lung inflammation is not well defined. In this study we examined the effect of NTHi on two important lung inflammatory processes 1, oxidative stress and 2, protease expression. Bronchoalveolar macrophages were obtained from 121 human subjects, blood neutrophils from 15 subjects, and human-lung fibroblast and epithelial cell lines from 16 subjects. Cells were stimulated with NTHi to measure the effect on reactive oxygen species (ROS production and extracellular trap formation. We also measured the production of the oxidant, 3-nitrotyrosine (3-NT in the lungs of mice infected with this bacterium. NTHi induced widespread production of 3-NT in mouse lungs. This bacterium induced significantly increased ROS production in human fibroblasts, epithelial cells, macrophages and neutrophils; with the highest levels in the phagocytic cells. In human macrophages NTHi caused a sustained, extracellular production of ROS that increased over time. The production of ROS was associated with the formation of macrophage extracellular trap-like structures which co-expressed the protease metalloproteinase-12. The formation of the macrophage extracellular trap-like structures was markedly inhibited by the addition of DNase. In this study we have demonstrated that NTHi induces lung oxidative stress with macrophage extracellular trap formation and associated protease expression. DNase inhibited the formation of extracellular traps.

Budesonide Inhibits Intracellular Infection with Non-Typeable Haemophilus influenzae Despite Its Anti-Inflammatory Effects in Respiratory Cells and Human Lung Tissue: A Role for p38 MAP Kinase.

Science.gov (United States)

Wagner, Christopher; Goldmann, Torsten; Rohmann, Kristina; Rupp, Jan; Marwitz, Sebastian; Rotta Detto Loria, Johannes; Limmer, Stefan; Zabel, Peter; Dalhoff, Klaus; Drömann, Daniel

2015-01-01

Inhaled corticosteroids (ICS) are widely used in the treatment of obstructive lung diseases. Recent data suggest a higher pneumonia risk in chronic obstructive pulmonary disease (COPD) patients treated with ICS. Since non-typeable Haemophilus influenzae (NTHi) is the most common pathogen associated with acute exacerbations of COPD, we investigated the effects of budesonide (BUD) on NTHi-induced inflammation and invasive infection. The alveolar epithelial cell line A549 and specimens of human lung tissue (HLT) were used in our experiments. Intracellular infection was determined by a lysis/culture assay of infected cells. Activated p38 mitogen-associated protein kinase (MAPK) was assessed using Western blotting and immunohistochemistry, expression of toll-like receptor 2 (TLR2) was determined by PCR, and CXCL-8 levels were measured using ELISA. Immunohistochemistry was used for detection of CXCL-8, platelet-activating factor receptor (PAF-R) and NTHi. BUD significantly reduced CXCL-8 secretion in A549 cells and lung tissue infected with NTHi. Furthermore, BUD decreased the expression of PAF-R in HLT and A549 cells. In A549 cells and HLT, BUD inhibited intracellular infection and - synergistically with NTHi - increased the expression of TLR2 (in A549 cells). TLR2 stimulation did not influence the intracellular infection of A549 cells, but p38 MAPK inhibition resulted in a significant reduction of infection. The present study adds new insights into the effects of glucocorticoids on pulmonary host defence after NTHi infection. Although the inflammatory response to infection is suppressed by BUD, interestingly, the intracellular infection is also inhibited. This effect seems to depend on the inhibition of p38 MAPK - a key enzyme in many pro-inflammatory pathways - as well as of PAF-R expression. © 2015 S. Karger AG, Basel.

Incidência de meningite por Haemophilus influenzae no RS 1999-2010: impacto da cobertura vacinal Incidence of meningitis caused by Haemophilus influenzae in the state of Rio Grande do Sul 1999-2010: impact of vaccination campaign

Directory of Open Access Journals (Sweden)

Marli Matiko Anraku de Campos

2013-05-01

Full Text Available O objetivo deste artigo é analisar e verificar a situação epidemiológica das meningites causadas pelo agente Haemophilus influenzae tipo b nos últimos 10 anos no Rio Grande do Sul. Estudo retrospectivo, descritivo, utilizando o sistema de dados de notificação de meningites, e cobertura vacinal, armazenados em base on line Tabnet - Tabulação de dados Epidemiológicos - CEVS/SES/RS, abrangendo o período de 1999 a 2010. Foram utilizados casos notificados e confirmados, tendo como critério de seleção o ano de inicio dos sintomas, idade, diagnostico e evolução. Foi analisado o Estado do Rio Grande do Sul, representado por 19 coordenadorias de saúde. Comparações entre proporções foram avaliadas pelo teste de z. No RS foram notificados 3043 casos confirmados de meningite bacteriana, sendo 6,77% dos casos causados por H. influenzae. O coeficiente de incidência da meningite por H. influenzae, sem considerar faixa etária, caiu significativamente (95,6% após 1999, assim como a mortalidade. Crianças menores de um ano continuam sendo as mais acometidas (52%, não havendo alteração na letalidade. Os resultados apresentados revelaram um impacto positivo das estratégias de vacinação contra Hib no Estado do Rio Grande do Sul nos últimos dez anos.This article seeks to analyze and update the epidemiological situation of meningitis caused by Haemophilus influenzae type b in the past 10 years in the state of Rio Grande do Sul (RS. It is a retrospective, descriptive study, which used the data notification system of meningitis and vaccination campaign coverage, stored in the Epidemiological TABNET online database, for the period from 1999 to 2010. Cases notified and confirmed were used and the selection criteria were the year when the symptoms were detected, age, diagnosis, and evolution. Nineteen health centers in the state of Rio Grande do Sul were analyzed. The z-test was used to evaluate comparisons between the proportions. In the

Effect of Multiple Mutations in the Hemoglobin- and Hemoglobin-Haptoglobin-Binding Proteins, HgpA, HgpB, and HgpC, of Haemophilus influenzae Type b

OpenAIRE

Morton, Daniel J.; Whitby, Paul W.; Jin, Hongfan; Ren, Zhen; Stull, Terrence L.

1999-01-01

Haemophilus influenzae requires heme for growth and can utilize hemoglobin and hemoglobin-haptoglobin as heme sources. We previously identified two hemoglobin- and hemoglobin-haptoglobin-binding proteins, HgpA and HgpB, in H. influenzae HI689. Insertional mutation of hgpA and hgpB, either singly or together, did not abrogate the ability to utilize or bind either hemoglobin or the hemoglobin-haptoglobin complex. A hemoglobin affinity purification method was used to isolate a protein of approxi...

Development and validation of an Haemophilus influenzae supragenome hybridization (SGH array for transcriptomic analyses.

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Benjamin A Janto

Full Text Available We previously carried out the design and testing of a custom-built Haemophilus influenzae supragenome hybridization (SGH array that contains probe sequences to 2,890 gene clusters identified by whole genome sequencing of 24 strains of H. influenzae. The array was originally designed as a tool to interrogate the gene content of large numbers of clinical isolates without the need for sequencing, however, the data obtained is quantitative and is thus suitable for transcriptomic analyses. In the current study RNA was extracted from H. influenzae strain CZ4126/02 (which was not included in the design of the array converted to cDNA, and labelled and hybridized to the SGH arrays to assess the quality and reproducibility of data obtained from these custom-designed chips to serve as a tool for transcriptomics. Three types of experimental replicates were analyzed with all showing very high degrees of correlation, thus validating both the array and the methods used for RNA profiling. A custom filtering pipeline for two-condition unpaired data using five metrics was developed to minimize variability within replicates and to maximize the identification of the most significant true transcriptional differences between two samples. These methods can be extended to transcriptional analysis of other bacterial species utilizing supragenome-based arrays.

Genomic Variability of Haemophilus influenzae Isolated from Mexican Children Determined by Using Enterobacterial Repetitive Intergenic Consensus Sequences and PCR

OpenAIRE

Gomez-De-Leon, Patricia; Santos, Jose I.; Caballero, Javier; Gomez, Demostenes; Espinosa, Luz E.; Moreno, Isabel; Piñero, Daniel; Cravioto, Alejandro

2000-01-01

Genomic fingerprints from 92 capsulated and noncapsulated strains of Haemophilus influenzae from Mexican children with different diseases and healthy carriers were generated by PCR using the enterobacterial repetitive intergenic consensus (ERIC) sequences. A cluster analysis by the unweighted pair-group method with arithmetic averages based on the overall similarity as estimated from the characteristics of the genomic fingerprints, was conducted to group the strains. A total of 69 fingerprint...

Influenza virus infection among pediatric patients reporting diarrhea and influenza-like illness

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Uyeki Timothy M

2010-01-01

Full Text Available Abstract Background Influenza is a major cause of morbidity and hospitalization among children. While less often reported in adults, gastrointestinal symptoms have been associated with influenza in children, including abdominal pain, nausea, vomiting, and diarrhea. Methods From September 2005 and April 2008, pediatric patients in Indonesia presenting with concurrent diarrhea and influenza-like illness were enrolled in a study to determine the frequency of influenza virus infection in young patients presenting with symptoms less commonly associated with an upper respiratory tract infection (URTI. Stool specimens and upper respiratory swabs were assayed for the presence of influenza virus. Results Seasonal influenza A or influenza B viral RNA was detected in 85 (11.6% upper respiratory specimens and 21 (2.9% of stool specimens. Viable influenza B virus was isolated from the stool specimen of one case. During the time of this study, human infections with highly pathogenic avian influenza A (H5N1 virus were common in the survey area. However, among 733 enrolled subjects, none had evidence of H5N1 virus infection. Conclusions The detection of influenza viral RNA and viable influenza virus from stool suggests that influenza virus may be localized in the gastrointestinal tract of children, may be associated with pediatric diarrhea and may serve as a potential mode of transmission during seasonal and epidemic influenza outbreaks.

Genomic DNA fingerprinting of clinical Haemophilus influenzae isolates by polymerase chain reaction amplification: comparison with major outer-membrane protein and restriction fragment length polymorphism analysis

NARCIS (Netherlands)

van Belkum, A.; Duim, B.; Regelink, A.; Möller, L.; Quint, W.; van Alphen, L.

1994-01-01

Non-capsulate strains of Haemophilus influenzae were genotyped by analysis of variable DNA segments obtained by amplification of genomic DNA with the polymerase chain reaction (PCR fingerprinting). Discrete fragments of 100-2000 bp were obtained. The reproducibility of the procedure was assessed by

GENOMIC DNA-FINGERPRINTING OF CLINICAL HAEMOPHILUS-INFLUENZAE ISOLATES BY POLYMERASE CHAIN-REACTION AMPLIFICATION - COMPARISON WITH MAJOR OUTER-MEMBRANE PROTEIN AND RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISM ANALYSIS

NARCIS (Netherlands)

VANBELKUM, A; DUIM, B; REGELINK, A; MOLLER, L; QUINT, W; VANALPHEN, L

Non-capsulate strains of Haemophilus influenzae were genotyped by analysis of variable DNA segments obtained by amplification of genomic DNA with the polymerase chain reaction (PCR fingerprinting). Discrete fragments of 100-2000 bp were obtained. The reproducibility of the procedure was assessed by

The C-Terminal Fragment of the Internal 110-Kilodalton Passenger Domain of the Hap Protein of Nontypeable Haemophilus influenzae Is a Potential Vaccine Candidate

OpenAIRE

Liu, Dai-Fang; Mason, Kathryn W.; Mastri, Maria; Pazirandeh, Mehran; Cutter, David; Fink, Doran L.; St. Geme, Joseph W.; Zhu, Duzhang; Green, Bruce A.

2004-01-01

Nontypeable Haemophilus influenzae is a major causative agent of bacterial otitis media in children. H. influenzae Hap autotransporter protein is an adhesin composed of an outer membrane Hapβ region and a moiety of an extracellular internal 110-kDa passenger domain called HapS. The HapS moiety promotes adherence to human epithelial cells and extracellular matrix proteins, and it also mediates bacterial aggregation and microcolony formation. A recent work (D. L. Fink, A. Z. Buscher, B. A. Gree...

The Seroepidemiology of Haemophilus Influenzae Type b in Children Under 6 Years Old in Khorramabad, Iran

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N. Ansari

2015-05-01

Full Text Available Background and Objective: Haemophilus influenzae type b (Hib is now recognized as an agent of bacterial meningitis in Asia. Polyribosil Ribitol Phosphate (PRP capsule are in all of the strains and IgG antibodies can be target. Due to limited studies on H. influenzae type b in the country and the lack of sufficient information on the status of carriers, achieve a comprehensive model of the spread of the bacteria in the carrier's most vulnerable children is the aim of this study. Material and Methods: In this study, 194 (49% female and 51% male serum samples were collected from children under 6 years old referred to medical centers in Korram Abad. The serological study of H. influenzae type b was carried using anti-H. influenzae PRP IgG antibodies kit by indirect enzyme linked immunosorbent assay (ELISA. Results: Of 194 children under 6 years-old screened for H. influenzae-specific IgG antibodies with ELISA, 6 (3 percent were IgG seropositive. Prevalence of bacteria in children under 2 years was 67% that demonstrated no significant association between seropositivity in subjects and place of residence of children with the prevalence of bacteria. Conclusion: The prevalence of H. influenzae type b seropositivity in our study was 3% of the total sample. In current study, a higher percentage of males than females were seropositive and frequency of predominant bacteria in patients younger than 2 years. The age factor is a variable that positively affects serum. Regarding to non-Hib vaccination in children, the presence of the bacteria in children can be important.

Cost-benefit analysis of a Haemophilus influenzae type b meningitis prevention programme in The Philippines.

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Limcangco, M R; Armour, C L; Salole, E G; Taylor, S J

2001-01-01

Haemophilus influenzae type b (Hib) meningitis is associated with high mortality and serious sequelae in children under 5 years of age. Vaccines which can prevent this infection are available. To evaluate the costs and benefits of a 3-dose immunisation schedule in Manila, Philippines. Government and societal perspectives. A cost-benefit analysis based on a birth cohort of 100,000 children. The state of health of the cohort with and without a Hib immunisation programme was modelled over a 5-year period. A survey of medical records of patients with Hib in Manila provided data on the extent and cost of sequelae following infection. A 3-dose Hib vaccination programme given at ages 2, 3 and 4 months. The model predicted that vaccinating children against Hib meningitis would prevent 553 cases per year in a birth cohort of 100,000, at a cost of 56,200 Philippine pesos (PHP) [$US1,605; 1998 exchange rate] per case (base case assumptions of 90% vaccine efficacy rate, 95 per 100,000 Hib incidence rate, 85% vaccination coverage). Results from the cost-benefit analyses indicated that the saving to the government would be around PHP39 million ($US1.11 million), and the saving to society would be PHP255 million ($US7.28 million). There would be a positive economic benefit for the Philippine government and for the Filipino society if a Hib vaccination programme was introduced in Manila.

Haemophilus influenzae tipo b: situação epidemiológica no Estado de Minas Gerais, Brasil, 1993 a 1997 Haemophilus influenzae type b: epidemiological situation in the State of Minas Gerais, Brazil, 1993-1997

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Sybelle de Souza Castro Miranzi

2003-10-01

Full Text Available Entre as doenças invasivas causadas pelo Haemophilus influenzae tipo b (Hib, destacam-se, pela freqüência e gravidade, as pneumonias e as meningites. No período de 1993 a 1997, foram notificados, em Minas Gerais, 720 casos de meningites por Hib, sendo a causa mais freqüente de meningite bacteriana em menores de um ano e a segunda causa no total de meningites. Entretanto, estimou-se uma ocorrência total de 1.160 casos considerando as meningites bacterianas não especificadas. O total de casos estimados de doença invasiva por Hib parece justificar a recente inclusão da vacina no esquema básico de imunizações. O alto custo da vacina reforça a necessidade de melhorar a vigilância epidemiológica da meningite, que constitui uma das fragilidades das ações de controle desta doença.Among Haemophilus influenzae type b (Hib invasive diseases, pneumonia and meningitis are the most relevant in public health due to their frequency and severity. From 1993 to 1997, there were 720 cases of Hib meningitis in Minas Gerais State, Brazil, representing the most frequent cause of bacterial meningitis in infants (< 1 year and the second most frequent among all causes of meningitis. The total estimated cases of invasive Hib diseases thus appear to justify the recent inclusion of the vaccine in the basic immunization protocol. The vaccine's high cost reinforces the need for more precise monitoring of the etiological diagnosis of meningitis cases, representing one of the weaknesses in the prevailing epidemiological surveillance system.

Trends in the epidemiology of invasive Haemophilus influenzae disease in Queensland, Australia from 2000 to 2013: what is the impact of an increase in invasive non-typable H. influenzae (NTHi)?

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Wan Sai Cheong, J; Smith, H; Heney, C; Robson, J; Schlebusch, S; Fu, J; Nourse, C

2015-10-01

Following the introduction of vaccination against Haemophilus influenzae type b (Hib), cases of invasive encapsulated Hib disease have decreased markedly. This study aimed to examine subsequent epidemiological trends in invasive H. influenzae disease in Queensland, Australia and in particular, assess the clinical impact and public health implications of invasive non-typable H. influenzae (NTHi) strains. A multicentre retrospective study was conducted from July 2000 to June 2013. Databases of major laboratories in Queensland including Queensland Forensic and Scientific Services (jurisdictional referral laboratory for isolate typing) were examined to identify cases. Demographic, infection site, Indigenous status, serotype, and mortality data were collected. In total, 737 invasive isolates were identified, of which 586 (79·5%) were serotyped. Hib, NTHi and encapsulated non-b strains, respectively, constituted 12·1%, 69·1% and 18·8% of isolates. The predominant encapsulated non-b strains were f (45·5%) and a (27·3%) serotypes. Of isolates causing meningitis, 48·9% were NTHi, 14·9% Hib, 14·9% Hie, 10·6% Hif, 6·4% Hia and 4·3% were untyped. During the study period, there was an increase in the incidence of invasive NTHi disease (P = 0·007) with seasonal peaks in winter and spring (P 0·001) and Hib (P = 0·039) than non-Indigenous patients. In Queensland, invasive H. influenzae disease is now predominantly encountered in adults and most commonly caused by NTHi strains with demonstrated pathogenicity extending to otherwise young or immunocompetent individuals. Routine public health notification of these strains is recommended and recent available immunization options should be considered.

Identification and Characterization of msf, a Novel Virulence Factor in Haemophilus influenzae.

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Jennifer M Kress-Bennett

Full Text Available Haemophilus influenzae is an opportunistic pathogen. The emergence of virulent, non-typeable strains (NTHi emphasizes the importance of developing new interventional targets. We screened the NTHi supragenome for genes encoding surface-exposed proteins suggestive of immune evasion, identifying a large family containing Sel1-like repeats (SLRs. Clustering identified ten SLR-containing gene subfamilies, each with various numbers of SLRs per gene. Individual strains also had varying numbers of SLR-containing genes from one or more of the subfamilies. Statistical genetic analyses of gene possession among 210 NTHi strains typed as either disease or carriage found a significant association between possession of the SlrVA subfamily (which we have termed, macrophage survival factor, msf and the disease isolates. The PittII strain contains four chromosomally contiguous msf genes. Deleting all four of these genes (msfA1-4 (KO resulted in a highly significant decrease in phagocytosis and survival in macrophages; which was fully complemented by a single copy of the msfA1 gene. Using the chinchilla model of otitis media and invasive disease, the KO strain displayed a significant decrease in fitness compared to the WT in co-infections; and in single infections, the KO lost its ability to invade the brain. The singly complemented strain showed only a partial ability to compete with the WT suggesting gene dosage is important in vivo. The transcriptional profiles of the KO and WT in planktonic growth were compared using the NTHi supragenome array, which revealed highly significant changes in the expression of operons involved in virulence and anaerobiosis. These findings demonstrate that the msfA1-4 genes are virulence factors for phagocytosis, persistence, and trafficking to non-mucosal sites.

Differential interactions of virulent and non-virulent H. parasuis strains with naïve or swine influenza virus pre-infected dendritic cells.

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Mussá, Tufária; Rodríguez-Cariño, Carolina; Sánchez-Chardi, Alejandro; Baratelli, Massimiliano; Costa-Hurtado, Mar; Fraile, Lorenzo; Domínguez, Javier; Aragon, Virginia; Montoya, María

2012-11-16

Pigs possess a microbiota in the upper respiratory tract that includes Haemophilus parasuis. Pigs are also considered the reservoir of influenza viruses and infection with this virus commonly results in increased impact of bacterial infections, including those by H. parasuis. However, the mechanisms involved in host innate responses towards H. parasuis and their implications in a co-infection with influenza virus are unknown. Therefore, the ability of a non-virulent H. parasuis serovar 3 (SW114) and a virulent serovar 5 (Nagasaki) strains to interact with porcine bone marrow dendritic cells (poBMDC) and their modulation in a co-infection with swine influenza virus (SwIV) H3N2 was examined. At 1 hour post infection (hpi), SW114 interaction with poBMDC was higher than that of Nagasaki, while at 8 hpi both strains showed similar levels of interaction. The co-infection with H3N2 SwIV and either SW114 or Nagasaki induced higher levels of IL-1β, TNF-α, IL-6, IL-12 and IL-10 compared to mock or H3N2 SwIV infection alone. Moreover, IL-12 and IFN-α secretion differentially increased in cells co-infected with H3N2 SwIV and Nagasaki. These results pave the way for understanding the differences in the interaction of non-virulent and virulent strains of H. parasuis with the swine immune system and their modulation in a viral co-infection.

CXCR1/2 Antagonism Is Protective during Influenza and Post-Influenza Pneumococcal Infection

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Luciana P. Tavares

2017-12-01

Full Text Available RationaleInfluenza A infections are a leading cause of morbidity and mortality worldwide especially when associated with secondary pneumococcal infections. Inflammation is important to control pathogen proliferation but may also cause tissue injury and death. CXCR1/2 are chemokine receptors relevant for the recruitment of neutrophils. We investigated the role of CXCR1/2 during influenza, pneumococcal, and post-influenza pneumococcal infections.MethodsMice were infected with influenza A virus (IAV or Streptococcus pneumoniae and then treated daily with the CXCR1/2 antagonist DF2162. To study secondary pneumococcal infection, mice were infected with a sublethal inoculum of IAV then infected with S. pneumoniae 14 days later. DF2162 was given in a therapeutic schedule from days 3 to 6 after influenza infection. Lethality, weight loss, inflammation, virus/bacteria counts, and lung injury were assessed.ResultsCXCL1 and CXCL2 were produced at high levels during IAV infection. DF2162 treatment decreased morbidity and this was associated with decreased infiltration of neutrophils in the lungs and reduced pulmonary damage and viral titers. During S. pneumoniae infection, DF2162 treatment decreased neutrophil recruitment, pulmonary damage, and lethality rates, without affecting bacteria burden. Therapeutic treatment with DF2162 during sublethal IAV infection reduced the morbidity associated with virus infection and also decreased the magnitude of inflammation, lung damage, and number of bacteria in the blood of mice subsequently infected with S. pneumoniae.ConclusionModulation of the inflammatory response by blocking CXCR1/2 improves disease outcome during respiratory influenza and pneumococcal infections, without compromising the ability of the murine host to deal with infection. Altogether, inhibition of CXCR1/2 may be a valid therapeutic strategy for treating lung infections caused by these pathogens, especially controlling secondary bacterial

Enfermedad invasora por Haemophilus Influenzae antes y después de la campaña de vacunación en la población infantil de la Comunidad Valenciana (1996-2000

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Goicoechea Sáez Mercedes

2002-01-01

Full Text Available Fundamento: La introducción de la vacuna conjugada anti Haemophilus influenzae tipo b (Hib en niños ha provocado un llamativo descenso de la incidencia de la enfermedad por H. influenzae. El objetivo de este estudio es analizar las características más relevantes de la enfermedad invasora por H. influenzae en cuanto a la epidemiología, clínica, evolución y estado de vacunación de la población infantil de la Comunidad Valenciana en el periodo 1996-2000. Método: Los datos se recogen de las historias clínicas de los niños menores de 15 años que hayan presentado síntomas y signos clínicos sugestivos de enfermedad invasora con aislamiento de Haemophilus influenzae y/o que cumple con los criterios de definición de caso establecidos, atendidos en todos los hospitales públicos de la Comunidad Valenciana entre 1996 y 2000. La evolución de la incidencia se valoró mediante tasas de incidencia. La clínica y su evolución (secuelas y letalidad mediante la frecuencia y distribución por edad. Resultados: Se registraron un total de 36 casos de enfermedad invasora por Haemophilus influenzae. La tasa de incidencia en niños menores de 15 años pasó de 3,56/10(5 en 1996 a 1,07/10(5 en 1997 (coincidiendo con la campaña de vacunación y la posterior inclusión de la vacuna conjugada anti Hib en el Calendario de Vacunaciones Sistemáticas de la Comunidad Valenciana y 0,30/10(5 en 1998, situación que se sigue manteniendo en los años posteriores. El 53% de los casos se dan en menores de 18 meses. Tanto las secuelas como los fallecimientos se producen en la época anterior a la aplicación rutinaria de la vacuna conjugada. Ningún niño vacunado correctamente falleció. Se registraron 2 casos de H. influenzae tipo no b en niños vacunados. Conclusiones: La incidencia de la infección por Haemophilus influenzae tipo b disminuyó drásticamente desde el inicio de la vacunación sistemática de la población infantil.

Capsule Typing of Haemophilus influenzae by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry.

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Månsson, Viktor; Gilsdorf, Janet R; Kahlmeter, Gunnar; Kilian, Mogens; Kroll, J Simon; Riesbeck, Kristian; Resman, Fredrik

2018-03-01

Encapsulated Haemophilus influenzae strains belong to type-specific genetic lineages. Reliable capsule typing requires PCR, but a more efficient method would be useful. We evaluated capsule typing by using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Isolates of all capsule types (a-f and nontypeable; n = 258) and isogenic capsule transformants (types a-d) were investigated. Principal component and biomarker analyses of mass spectra showed clustering, and mass peaks correlated with capsule type-specific genetic lineages. We used 31 selected isolates to construct a capsule typing database. Validation with the remaining isolates (n = 227) showed 100% sensitivity and 92.2% specificity for encapsulated strains (a-f; n = 61). Blinded validation of a supplemented database (n = 50) using clinical isolates (n = 126) showed 100% sensitivity and 100% specificity for encapsulated strains (b, e, and f; n = 28). MALDI-TOF mass spectrometry is an accurate method for capsule typing of H. influenzae.

Haemophilus influenzae Isolated From Men With Acute Urethritis: Its Pathogenic Roles, Responses to Antimicrobial Chemotherapies, and Antimicrobial Susceptibilities.

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Ito, Shin; Hatazaki, Kyoko; Shimuta, Ken; Kondo, Hiromi; Mizutani, Kosuke; Yasuda, Mitsuru; Nakane, Keita; Tsuchiya, Tomohiro; Yokoi, Shigeaki; Nakano, Masahiro; Ohinishi, Makoto; Deguchi, Takashi

2017-04-01

There have been few comprehensive studies on Haemophilus influenza-positive urethritis. In this retrospective study, we enrolled 68 men with H. influenzae-positive urethritis, including coinfections with Neisseria gonorrhoeae, Chlamydia trachomatis, and/or genital mycoplasmas: 2, 3, 20, and 43 treated with ceftriaxone, levofloxacin, sitafloxacin, and extended-release azithromycin (azithromycin-SR), respectively. We assessed microbiological outcomes in 54 men and clinical outcomes in 46 with H. influenzae-positive monomicrobial nongonococcal urethritis. We determined minimum inhibitory concentrations (MICs) of 6 antimicrobial agents for 59 pretreatment isolates. H. influenzae was eradicated from the men treated with ceftriaxone, levofloxacin, or sitafloxacin. The eradication rate with azithromycin-SR was 85.3%. The disappearance or alleviation of urethritis symptoms and the decreases in leukocyte counts in first-voided urine were significantly associated with the eradication of H. influenzae after treatment. For the isolates, ceftriaxone, levofloxacin, sitafloxacin, azithromycin, tetracycline, and doxycycline MICs were ≤0.008-0.25, 0.008-0.5, 0.001-0.008, 0.12-1, 0.25-16, and 0.25-2 μg/mL, respectively. The azithromycin MICs for 3 of 4 strains persisting after azithromycin-SR administration were 1 μg/mL. H. influenzae with an azithromycin MIC of 1 μg/mL increased chronologically. H. influenzae showed good responses to the chemotherapies for urethritis. The significant associations of the clinical outcomes of the chemotherapies with their microbiological outcomes suggested that H. influenzae could play pathogenic roles in urethritis. All isolates, except for one with decreased susceptibility to tetracyclines, were susceptible to the examined agents. However, the increase in H. influenzae with an azithromycin MIC of 1 μg/mL might threaten efficacies of azithromycin regimens on H. influenzae-positive urethritis.

Tendência das meningites por Haemophilus influenzae tipo b no Brasil, em menores de 5 anos, no período de 1983 a 2002 Trends in Haemophilus influenzae type b meningitis in Brazil in children under five years of age from 1983 through 2002

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Sybelle de Souza Castro Miranzi

2006-10-01

Full Text Available Trata-se de um estudo ecológico, tipo série histórica (1983-2002, onde foram calculados os coeficientes de incidência, mortalidade e letalidade de meningites por Haemophilus influenzae , tipo b, no Brasil, e avaliou-se a tendência da morbi-mortalidade em menores de 5 anos. Para a análise de tendência dos coeficientes construíram-se modelos de regressão polinomial para as faixas etárias de The study was based on an ecological design using a historical time series (1983-2002, related to Haemophilus influenzae type b meningitis in Brazil. Incidence, mortality and case-fatality rates, as well as trends in incidence and morbidity-mortality were estimated in children less than 5 years of age. Polynomial regression analysis was used to analyze trends, adopting a significance level of 0.05. 43.9% of confirmed cases occurred in infants less than 1 year old and 38.7% in children 1-4 years old. The observed rates were also highest in these two age strata. The incidence and mortality rates showed an increasing trend, until approximately 1999, when a quick decline was observed. The study results reinforce the effectiveness of the Vaccination Program against HIB in Brazil, which benefited age ranges that did not receive the vaccine (Herd Immunity.

Peroxiredoxin-glutaredoxin and catalase promote resistance of nontypeable Haemophilus influenzae 86-028NP to oxidants and survival within neutrophil extracellular traps.

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Juneau, Richard A; Pang, Bing; Armbruster, Chelsie E; Murrah, Kyle A; Perez, Antonia C; Swords, W Edward

2015-01-01

Nontypeable Haemophilus influenzae (NTHI) is a common commensal and opportunistic pathogen of the human airways. For example, NTHI is a leading cause of otitis media and is the most common cause of airway infections associated with chronic obstructive pulmonary disease (COPD). These infections are often chronic/recurrent in nature and involve bacterial persistence within biofilm communities that are highly resistant to host clearance. Our previous work has shown that NTHI within biofilms has increased expression of factors associated with oxidative stress responses. The goal of this study was to define the roles of catalase (encoded by hktE) and a bifunctional peroxiredoxin-glutaredoxin (encoded by pdgX) in resistance of NTHI to oxidants and persistence in vivo. Isogenic NTHI strain 86-028NP mutants lacking hktE and pdgX had increased susceptibility to peroxide. Moreover, these strains had persistence defects in the chinchilla infection model for otitis media, as well as in a murine model for COPD. Additional work showed that pdgX and hktE were important determinants of NTHI survival within neutrophil extracellular traps (NETs), which we have shown to be an integral part of NTHI biofilms in vivo. Based on these data, we conclude that catalase and peroxiredoxin-glutaredoxin are determinants of bacterial persistence during chronic/recurrent NTHI infections that promote bacterial survival within NETs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Influenza Virus Infection in Nonhuman Primates

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Karlsson, Erik A.; Engel, Gregory A.; Feeroz, M.M.; San, Sorn; Rompis, Aida; Lee, Benjamin P. Y.-H.; Shaw, Eric; Oh, Gunwha; Schillaci, Michael A.; Grant, Richard; Heidrich, John; Schultz-Cherry, Stacey

2012-01-01

To determine whether nonhuman primates are infected with influenza viruses in nature, we conducted serologic and swab studies among macaques from several parts of the world. Our detection of influenza virus and antibodies to influenza virus raises questions about the role of nonhuman primates in the ecology of influenza. PMID:23017256

Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease.

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Pettigrew, Melinda M; Ahearn, Christian P; Gent, Janneane F; Kong, Yong; Gallo, Mary C; Munro, James B; D'Mello, Adonis; Sethi, Sanjay; Tettelin, Hervé; Murphy, Timothy F

2018-04-03

Nontypeable Haemophilus influenzae (NTHi) exclusively colonize and infect humans and are critical to the pathogenesis of chronic obstructive pulmonary disease (COPD). In vitro and animal models do not accurately capture the complex environments encountered by NTHi during human infection. We conducted whole-genome sequencing of 269 longitudinally collected cleared and persistent NTHi from a 15-y prospective study of adults with COPD. Genome sequences were used to elucidate the phylogeny of NTHi isolates, identify genomic changes that occur with persistence in the human airways, and evaluate the effect of selective pressure on 12 candidate vaccine antigens. Strains persisted in individuals with COPD for as long as 1,422 d. Slipped-strand mispairing, mediated by changes in simple sequence repeats in multiple genes during persistence, regulates expression of critical virulence functions, including adherence, nutrient uptake, and modification of surface molecules, and is a major mechanism for survival in the hostile environment of the human airways. A subset of strains underwent a large 400-kb inversion during persistence. NTHi does not undergo significant gene gain or loss during persistence, in contrast to other persistent respiratory tract pathogens. Amino acid sequence changes occurred in 8 of 12 candidate vaccine antigens during persistence, an observation with important implications for vaccine development. These results indicate that NTHi alters its genome during persistence by regulation of critical virulence functions primarily by slipped-strand mispairing, advancing our understanding of how a bacterial pathogen that plays a critical role in COPD adapts to survival in the human respiratory tract.

Transformation of natural genetic variation into Haemophilus influenzae genomes.

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Joshua Chang Mell

2011-07-01

Full Text Available Many bacteria are able to efficiently bind and take up double-stranded DNA fragments, and the resulting natural transformation shapes bacterial genomes, transmits antibiotic resistance, and allows escape from immune surveillance. The genomes of many competent pathogens show evidence of extensive historical recombination between lineages, but the actual recombination events have not been well characterized. We used DNA from a clinical isolate of Haemophilus influenzae to transform competent cells of a laboratory strain. To identify which of the ~40,000 polymorphic differences had recombined into the genomes of four transformed clones, their genomes and their donor and recipient parents were deep sequenced to high coverage. Each clone was found to contain ~1000 donor polymorphisms in 3-6 contiguous runs (8.1±4.5 kb in length that collectively comprised ~1-3% of each transformed chromosome. Seven donor-specific insertions and deletions were also acquired as parts of larger donor segments, but the presence of other structural variation flanking 12 of 32 recombination breakpoints suggested that these often disrupt the progress of recombination events. This is the first genome-wide analysis of chromosomes directly transformed with DNA from a divergent genotype, connecting experimental studies of transformation with the high levels of natural genetic variation found in isolates of the same species.

Identification, distribution, and expression of novel genes in 10 clinical isolates of nontypeable Haemophilus influenzae.

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Shen, Kai; Antalis, Patricia; Gladitz, John; Sayeed, Sameera; Ahmed, Azad; Yu, Shujun; Hayes, Jay; Johnson, Sandra; Dice, Bethany; Dopico, Richard; Keefe, Randy; Janto, Benjamin; Chong, William; Goodwin, Joseph; Wadowsky, Robert M; Erdos, Geza; Post, J Christopher; Ehrlich, Garth D; Hu, Fen Z

2005-06-01

We hypothesize that Haemophilus influenzae, as a species, possesses a much greater number of genes than that found in any single H. influenzae genome. This supragenome is distributed throughout naturally occurring infectious populations, and new strains arise through autocompetence and autotransformation systems. The effect is that H. influenzae populations can readily adapt to environmental stressors. The supragenome hypothesis predicts that significant differences exist between and among the genomes of individual infectious strains of nontypeable H. influenzae (NTHi). To test this prediction, we obtained 10 low-passage NTHi clinical isolates from the middle ear effusions of patients with chronic otitis media. DNA sequencing was performed with 771 clones chosen at random from a pooled genomic library. Homology searching demonstrated that approximately 10% of these clones were novel compared to the H. influenzae Rd KW20 genome, and most of them did not match any DNA sequence in GenBank. Amino acid homology searches using hypothetical translations of the open reading frames revealed homologies to a variety of proteins, including bacterial virulence factors not previously identified in the NTHi isolates. The distribution and expression of 53 of these genes among the 10 strains were determined by PCR- and reverse transcription PCR-based analyses. These unique genes were nonuniformly distributed among the 10 isolates, and transcription of these genes in planktonic cultures was detected in 50% (177 of 352) of the occurrences. All of the novel sequences were transcribed in one or more of the NTHi isolates. Seventeen percent (9 of 53) of the novel genes were identified in all 10 NTHi strains, with each of the remaining 44 being present in only a subset of the strains. These genic distribution analyses were more effective as a strain discrimination tool than either multilocus sequence typing or 23S ribosomal gene typing methods.

Antigen-specific H1N1 influenza antibody responses in acute respiratory tract infections and their relation to influenza infection and disease course.

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Haran, John Patrick; Hoaglin, David C; Chen, Huaiqing; Boyer, Edward W; Lu, Shan

2014-08-01

Early antibody responses to influenza infection are important in both clearance of virus and fighting the disease. Acute influenza antibody titers directed toward H1-antigens and their relation to infection type and patient outcomes have not been well investigated. Using hemagglutination inhibition (HI) assays, we aimed to characterize the H1-specific antibody titers in patients with influenza infection or another respiratory infection before and after the H1N1-pandemic influenza outbreak. Among patients with acute influenza infection we related duration of illness, severity of symptoms, and need for hospitalization to antibody titers. There were 134 adult patients (average age 34.7) who presented to an urban academic emergency department (ED) from October through March during the 2008-2011 influenza seasons with symptoms of fever and a cough. Nasal aspirates were tested by viral culture, and peripheral blood serum was run in seven H1-subtype HI assays. Acutely infected influenza patients had markedly lower antibody titers for six of the seven pseudotype viruses. For the average over the seven titers (log units, base 2) their mean was 7.24 (95% CI 6.88, 7.61) compared with 8.60 (95% CI 8.27, 8.92) among patients who had a non-influenza respiratory illness, pinfection, titers of some antibodies correlated with severity of symptoms and with total duration of illness (pacute respiratory infections, lower concentrations of H1-influenza-specific antibodies were associated with influenza infection. Among influenza-infected patients, higher antibody titers were present in patients with a longer duration of illness and with higher severity-of-symptom scores. Copyright © 2014 Elsevier B.V. All rights reserved.

Phylogeny of the genus Haemophilus as determined by comparison of partial infB sequences

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Hedegaard, J; Okkels, H; Bruun, B

2001-01-01

A 453 bp fragment of infB, the gene encoding translation initiation factor 2, was sequenced and compared from 66 clinical isolates and type strains of Haemophilus species and related bacteria. Analysis of the partial infB sequences obtained suggested that the human isolates dependent on X and V...... factor, H. influenzae, H. haemolyticus, H. aegyptius and some cryptic genospecies of H. influenzae, were closely related to each other. H. parainfluenzae constituted a heterogeneous group within the boundaries of the genus, whereas H. aphrophilus/paraphrophilus and Actinobacillus actinomycetemcomitans...... were only remotely related to the type species of the genus Haemophilus H. parahaemolyticus and H. paraphrohaemolyticus took up an intermediary position and may not belong in the genus Haemophilus sensu stricto. Ambiguous results were obtained with seven isolates tentatively identified as H. segnis...

Applying Central Composite Design and Response Surface Methodology to Optimize Growth and Biomass Production of Haemophilus influenzae Type b.

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Momen, Seyed Bahman; Siadat, Seyed Davar; Akbari, Neda; Ranjbar, Bijan; Khajeh, Khosro

2016-06-01

Haemophilus influenzae type b (Hib) is the leading cause of bacterial meningitis, otitis media, pneumonia, cellulitis, bacteremia, and septic arthritis in infants and young children. The Hib capsule contains the major virulence factor, and is composed of polyribosyl ribitol phosphate (PRP) that can induce immune system response. Vaccines consisting of Hib capsular polysaccharide (PRP) conjugated to a carrier protein are effective in the prevention of the infections. However, due to costly processes in PRP production, these vaccines are too expensive. To enhance biomass, in this research we focused on optimizing Hib growth with respect to physical factors such as pH, temperature, and agitation by using a response surface methodology (RSM). We employed a central composite design (CCD) and a response surface methodology to determine the optimum cultivation conditions for growth and biomass production of H. influenzae type b. The treatment factors investigated were initial pH, agitation, and temperature, using shaking flasks. After Hib cultivation and determination of dry biomass, analysis of experimental data was performed by the RSM-CCD. The model showed that temperature and pH had an interactive effect on Hib biomass production. The dry biomass produced in shaking flasks was about 5470 mg/L, which was under an initial pH of 8.5, at 250 rpm and 35° C. We found CCD and RSM very effective in optimizing Hib culture conditions, and Hib biomass production was greatly influenced by pH and incubation temperature. Therefore, optimization of the growth factors to maximize Hib production can lead to 1) an increase in bacterial biomass and PRP productions, 2) lower vaccine prices, 3) vaccination of more susceptible populations, and 4) lower risk of Hib infections.

Epidemiology of Haemophilus ducreyi Infections.

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González-Beiras, Camila; Marks, Michael; Chen, Cheng Y; Roberts, Sally; Mitjà, Oriol

2016-01-01

The global epidemiology of Haemophilus ducreyi infections is poorly documented because of difficulties in confirming microbiological diagnoses. We evaluated published data on the proportion of genital and nongenital skin ulcers caused by H. ducreyi before and after introduction of syndromic management for genital ulcer disease (GUD). Before 2000, the proportion of GUD caused by H. ducreyi ranged from 0.0% to 69.0% (35 studies in 25 countries). After 2000, the proportion ranged from 0.0% to 15.0% (14 studies in 13 countries). In contrast, H. ducreyi has been recently identified as a causative agent of skin ulcers in children in the tropical regions; proportions ranged from 9.0% to 60.0% (6 studies in 4 countries). We conclude that, although there has been a sustained reduction in the proportion of GUD caused by H. ducreyi, this bacterium is increasingly recognized as a major cause of nongenital cutaneous ulcers.

Evidence for covalent attachment of phospholipid to the capsular polysaccharide of Haemophilus influenzae type b

International Nuclear Information System (INIS)

Kuo, J.S.; Doelling, V.W.; Graveline, J.F.; McCoy, D.W.

1985-01-01

Cells of Haemophilus influenzae type b were grown in a liquid medium containing [ 3 H]palmitate or [ 14 C]ribose or both for two generations of exponential growth. Radiolabeled type-specific capsular polysaccharide, polyribosyl ribitol phosphate (PRP), was purified from the culture supernatant by Cetavlon precipitation, ethanol fractionation, and hydroxylapatite and Sepharose 4B chromatography. The doubly labeled ( [ 3 H]palmitate and [ 14 C]ribose) PRP preparation was found to coelute in a single peak from a Sepharose 4B column, suggesting that both precursors were incorporated into the purified PRP. A singly labeled ( [ 3 H]palmitate) purified PRP preparation was found to be quantitatively immune precipitated by human serum containing antibody against PRP. Only after acid, alkaline, or phospholipase A2 treatment of PRP labeled with [ 3 H]palmitate or [ 3 H]palmitate and [ 14 C]ribose followed by chloroform-methanol extraction could most of the 3 H-radioactivity be recovered in the organic phase. The chloroform-soluble acid-hydrolyzed or phospholipase A2-treated product was identified as palmitic acid after thin-layer chromatography. These results strongly suggest that a phospholipid moiety is covalently associated with the H. influenzae type b polysaccharide PRP

Polymicrobial infective endocarditis caused by Neisseria sicca and Haemophilus parainfluenzae

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Nikoloz Koshkelashvili

2016-01-01

Full Text Available Infective endocarditis is a common clinical problem in industrialized countries. Risk factors include abnormal cardiac valves, a history of endocarditis, intracardiac devices, prosthetic valves and intravenous drug use. We report a case of polymicrobial infective endocarditis in a 33 year-old female with a history chronic heroin use caused by Neisseria sicca and Haemophilus parainfluenzae. We believe the patient was exposed to these microbes by cleansing her skin with saliva prior to injection. Pairing a detailed history with the consideration of atypical agents is crucial in the proper diagnosis and management of endocarditis in patients with high-risk injection behaviors.

Avian Influenza A Virus Infections in Humans

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... people has ranged from mild to severe. Avian Influenza Transmission Avian Influenza Transmission Infographic [555 KB, 2 pages] Spanish [ ... important for public health. Signs and Symptoms of Avian Influenza A Virus Infections in Humans The reported signs ...

Biofilm-specific extracellular matrix proteins of non-typeable Haemophilus influenzae

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Wu, Siva; Baum, Marc M.; Kerwin, James; Guerrero-Given, Debbie; Webster, Simon; Schaudinn, Christoph; VanderVelde, David; Webster, Paul

2014-01-01

Non-typeable Haemophilus influenzae (NTHi), a human respiratory tract pathogen can form colony biofilms in vitro. Bacterial cells and the amorphous extracellular matrix (ECM) constituting the biofilm can be separated using sonication. The ECM from 24 hr and 96 hr NTHi biofilms contained polysaccharides and proteinaceous components as detected by NMR and FTIR spectroscopy. More conventional chemical assays on the biofilm ECM confirmed the presence of these components and also DNA. Proteomics revealed eighteen proteins present in biofilm ECM that were not detected in planktonic bacteria. One ECM protein was unique to 24 hr biofilms, two were found only in 96 hr biofilms, and fifteen were present in the ECM of both 24 hr and 96 hr NTHi biofilms. All proteins identified were either associated with bacterial membranes or were cytoplasmic proteins. Immunocytochemistry showed two of the identified proteins, a DNA-directed RNA polymerase and the outer membrane protein OMP P2, associated with bacteria and biofilm ECM. Identification of biofilm-specific proteins present in immature biofilms is an important step in understanding the in vitro process of NTHi biofilm formation. The presence of a cytoplasmic protein and a membrane protein in the biofilm ECM of immature NTHi biofilms suggests that bacterial cell lysis may be a feature of early biofilm formation. PMID:24942343

Influenza vaccine-mediated protection in older adults: Impact of influenza infection, cytomegalovirus serostatus and vaccine dosage.

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Merani, Shahzma; Kuchel, George A; Kleppinger, Alison; McElhaney, Janet E

2018-07-01

Age-related changes in T-cell function are associated with a loss of influenza vaccine efficacy in older adults. Both antibody and cell-mediated immunity plays a prominent role in protecting older adults, particularly against the serious complications of influenza. High dose (HD) influenza vaccines induce higher antibody titers in older adults compared to standard dose (SD) vaccines, yet its impact on T-cell memory is not clear. The aim of this study was to compare the antibody and T-cell responses in older adults randomized to receive HD or SD influenza vaccine as well as determine whether cytomegalovirus (CMV) serostatus affects the response to vaccination, and identify differences in the response to vaccination in those older adults who subsequently have an influenza infection. Older adults (≥65years) were enrolled (n=106) and randomized to receive SD or HD influenza vaccine. Blood was collected pre-vaccination, followed by 4, 10 and 20weeks post-vaccination. Serum antibody titers, as well as levels of inducible granzyme B (iGrB) and cytokines were measured in PBMCs challenged ex vivo with live influenza virus. Surveillance conducted during the influenza season identified those with laboratory confirmed influenza illness or infection. HD influenza vaccination induced a high antibody titer and IL-10 response, and a short-lived increase in Th1 responses (IFN-γ and iGrB) compared to SD vaccination in PBMCs challenged ex vivo with live influenza virus. Of the older adults who became infected with influenza, a high IL-10 and iGrB response in virus-challenged cells was observed post-infection (week 10 to 20), as well as IFN-γ and TNF-α at week 20. Additionally, CMV seropositive older adults had an impaired iGrB response to influenza virus-challenge, regardless of vaccine dose. This study illustrates that HD influenza vaccines have little impact on the development of functional T-cell memory in older adults. Furthermore, poor outcomes of influenza infection in

MICROBIOLOGICAL CHARACTERISATION OF Haemophilus influenzae STRAINS ISOLATED FROM PATIENTS WITH INVASIVE AND RESPIRATORY DISEASES

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Tomislav Kostyanev

2010-01-01

Full Text Available A total of 175 H. influenzae strains were collected between 1994 and 2009 from all aged patient groups. The strains were isolated from patients with invasive and community-acquired respiratory tract infections. All strains were identified according to standard microbiological methods. Serotyping was done by a coagglutination test and by molecular PCR capsular genotyping. Beta-lactamase production was determined by the chromogenic cephalosporin test with nitrocephin as substrate. Most of the isolated H. influenzae strains were from children under 5 years of age (57.7%. Overall, 61 strains belonged to serotype b (34.9% by the means of PCR capsular typing, 1 strain was type f, and 113 isolates (64.6% were non-typeable (non-encapsulated H. influenzae. Among the infants and children with meningitis or other invasive infections, aged 2 month to 5 years, all strains, except one, were serotype b. In respiratory tract infections (pneumonia, otitis media, sinusitis and people with chronic pulmonary diseases - exacerbations of COPD, bronchiectasis, cystic fibrosis the most common - 96.5% were non-typeable strains in both groups children and adults. Overall, the prevalence of beta-lactamase production was 19.4%. But, it was much higher for invasive strains from CSF isolates - 37.7%, 25% in blood samples, and 37.5% in otitis media causative strains. Beta-lactamase production was less frequent in respiratory tract isolates - in sputum 13.3% and in URT samples - 2.3%. The rate of beta-lactamase production in CSF isolates has not changed for the last 10 years.PCR capsular genotyping method has to be performed for all non-b-type strains. The implementation of Hib vaccine in our country will be accompanied by a reduction in invasive diseases caused by H. influenzae type b in children, but it is not useful in preventing infections caused by non-typeable H. influenzae strains.

Crystal structure of the Haemophilus influenzae Hap adhesin reveals an intercellular oligomerization mechanism for bacterial aggregation

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Meng, Guoyu; Spahich, Nicole; Kenjale, Roma; Waksman, Gabriel; St Geme, Joseph W

2011-01-01

Bacterial biofilms are complex microbial communities that are common in nature and are being recognized increasingly as an important determinant of bacterial virulence. However, the structural determinants of bacterial aggregation and eventual biofilm formation have been poorly defined. In Gram-negative bacteria, a major subgroup of extracellular proteins called self-associating autotransporters (SAATs) can mediate cell–cell adhesion and facilitate biofilm formation. In this study, we used the Haemophilus influenzae Hap autotransporter as a prototype SAAT to understand how bacteria associate with each other. The crystal structure of the H. influenzae HapS passenger domain (harbouring the SAAT domain) was determined to 2.2 Å by X-ray crystallography, revealing an unprecedented intercellular oligomerization mechanism for cell–cell interaction. The C-terminal SAAT domain folds into a triangular-prism-like structure that can mediate Hap–Hap dimerization and higher degrees of multimerization through its F1–F2 edge and F2 face. The intercellular multimerization can give rise to massive buried surfaces that are required for overcoming the repulsive force between cells, leading to bacterial cell–cell interaction and formation of complex microcolonies. PMID:21841773

Individual risk factors associated with nasopharyngeal colonization with Streptococcus pneumoniae and Haemophilus influenzae: a Japanese birth cohort study.

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Otsuka, Taketo; Chang, Bin; Shirai, Takatoshi; Iwaya, Atsushi; Wada, Akihito; Yamanaka, Noboru; Okazaki, Minoru

2013-07-01

The first step in a bacterial disease is the establishment of nasopharyngeal carriage. We conducted a birth cohort study to identify factors associated with colonization in healthy children and evaluate the serotype distributions and resistances of Streptococcus pneumoniae/Haemophilus influenzae. Nasopharyngeal cultures were obtained from 349 subjects at 5 time points coinciding with health checkups (4, 7, 10, 18 and 36 months). A total of 551 S. pneumoniae (penicillin resistance rate: 46.3%) and 301 H. influenzae (ampicillin resistance rate: 44.5%) isolates were obtained from 1654 samples. In this study, 47.5% and 60.9% of S. pneumoniae isolates were included in the serotypes of 7- and 13-valent pneumococcal conjugate vaccines, respectively. Analyzing by Cox proportional hazards models, cohabiting older sibling(s) attending day-care (hazard ratios: 2.064-3.518, P rates. This data indicated that introduction of appropriate antimicrobial usage in areas of overuse of antimicrobials could contribute to lower colonization of S. pneumoniae/H. influenzae, resulting in a decrease in the absolute number of resistant isolates. Strategies to control transmission at day-care centers or from older sibling(s) as well as appropriate use of antimicrobials are essential for reducing colonization and the absolute number of resistant isolates.

The cytolethal distending toxin of Haemophilus ducreyi aggravates dermal lesions in a rabbit model of chancroid.

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Wising, Catharina; Mölne, Lena; Jonsson, Ing-Marie; Ahlman, Karin; Lagergård, Teresa

2005-05-01

Haemophilus ducreyi, the etiologic agent of the sexually transmitted disease chancroid, produces a cytolethal distending toxin (HdCDT) that inhibits cultured cell proliferation, leading to cell death. A rabbit model of dermal infection was used to investigate the roles of H. ducreyi bacteria and HdCDT in the development, clinical appearance, and persistence of infection. A non-toxin producing H. ducreyi strain, and for comparison purposes a non-capsulated Haemophilus influenzae strain, were inoculated intradermally, with and without co-administration of purified HdCDT. Co-administration of HdCDT resulted in significant aggravation of H. ducreyi-induced inflammatory lesions, and development of ulcers in rabbit skin. Less pronounced inflammatory lesions and lack of epithelial eruption were observed after inoculation with H. influenzae. Histopathological sections of the H. ducreyi-induced lesions, in both the presence and absence of HdCDT, showed dense infiltrates of the same type inflammatory cells, with the exception of a prominent endothelial cell proliferation noted in sections from lesions caused by H. ducreyi and toxin. Signs of chronic inflammation with involvement of T cells, macrophages, eosinophils, and granuloma formation were observed after H. ducreyi inoculation both with and without toxin. In conclusion, H. ducreyi causes a pronounced, chronic inflammation with involvement of T cells and macrophages, and in combination with HdCDT production of ulcers in the rabbit model. These pathogenic mechanisms may promote the development and persistence of chancroid ulcers.

Nonencapsulated or nontypeable Haemophilus influenzae are more likely than their encapsulated or serotypeable counterparts to have mutations in their fucose operon.

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Shuel, Michelle L; Karlowsky, Kathleen E; Law, Dennis K S; Tsang, Raymond S W

2011-12-01

Population biology of Haemophilus influenzae can be studied by multilocus sequence typing (MLST), and isolates are assigned sequence types (STs) based on nucleotide sequence variations in seven housekeeping genes, including fucK. However, the ST cannot be assigned if one of the housekeeping genes is absent or cannot be detected by the current protocol. Occasionally, strains of H. influenzae have been reported to lack the fucK gene. In this study, we examined the prevalence of this mutation among our collection of H. influenzae isolates. Of the 704 isolates studied, including 282 encapsulated and 422 nonencapsulated isolates, nine were not typeable by MLST owing to failure to detect the fucK gene. All nine fucK-negative isolates were nonencapsulated and belonged to various biotypes. DNA sequencing of the fucose operon region confirmed complete deletion of genes in the operon in seven of the nine isolates, while in the remaining two isolates, some of the genes were found intact or in parts. The significance of these findings is discussed.

Overexpression and Purification of C-terminal Fragment of the Passenger Domain of Hap Protein from Nontypeable Haemophilus influenzae in a Highly Optimized Escherichia coli Expression System

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Tabatabaee, Akram; Siadat, Seyed Davar; Moosavi, Seyed Fazllolah; Aghasadeghi, Mohammad Reza; Memarnejadian, Arash; Pouriayevali, Mohammad Hassan; Yavari, Neda

2013-01-01

Background Nontypeable Haemophilus influenzae (NTHi) is a common cause of respiratory tract disease and initiates infection by colonization in nasopharynx. The Haemophilus influenzae (H. influenzae) Hap adhesin is an auto transporter protein that promotes initial interaction with human epithelial cells. Hap protein contains a 110 kDa internal passenger domain called “HapS” and a 45 kDa C-terminal translocator domain called “Hapβ”. Hap adhesive activity has been recently reported to be connected to its Cell Binding Domain (CBD) which resides within the 311 C-terminal residues of the internal passenger domain of the protein. Furthermore, immunization with this CBD protein has been shown to prevent bacterial nasopharynx colonization in animal models. Methods To provide enough amounts of pure HapS protein for vaccine studies, we sought to develop a highly optimized system to overexpress and purify the protein in large quantities. To this end, pET24a-cbd plasmid harboring cbd sequence from NTHi ATCC49766 was constructed and its expression was optimized by testing various expression parameters such as growth media, induction temperature, IPTG inducer concentration, induction stage and duration. SDS-PAGE and Western-blotting were used for protein analysis and confirmation and eventually the expressed protein was easily purified via immobilized metal affinity chromatography (IMAC) using Ni-NTA columns. Results The highest expression level of target protein was achieved when CBD expressing E. coli BL21 (DE3) cells were grown at 37°C in 2xTY medium with 1.0 mM IPTG at mid-log phase (OD600 nm equal to 0.6) for 5 hrs. Amino acid sequence alignment of expressed CBD protein with 3 previously published CBD amino acid sequences were more than %97 identical and antigenicity plot analysis further revealed 9 antigenic domains which appeared to be well conserved among different analyzed CBD sequences. Conclusion Due to the presence of high similarity among CBD from NTHi ATCC

Immunoglobulin G avidities in infants in Mexico after primary immunization with three doses of polyribosylribitol phosphate-tetanus toxoid Haemophilus influenzae type b vaccine.

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Gómez-de-León, Patricia; Díaz-García, F Javier; Villaseñor-Sierra, Alberto; Segura, Jorge; Carranza, Martha I; Arredondo-Garcia, José Luis; Santos, José Ignacio

2008-06-01

Serum immunoglobulin G concentrations and avidities specific to Haemophilus influenzae type b (Hib) were measured in 208 children living in Guadalajara and Mexico City. Protective concentrations were found in 98.9% and 100.0% of participants, respectively. Geometric mean concentrations differed between both populations and/or among age groups. Mean avidities differed only among the 7- to 12-month-old children. Diphtheria-tetanus-whole-cell pertussis-hepatitis B-Hib primary vaccination seems to induce protection in Mexican children.

Dps promotes survival of nontypeable Haemophilus influenzae in biofilm communities in vitro and resistance to clearance in vivo.

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Pang, Bing; Hong, Wenzhou; Kock, Nancy D; Swords, W Edward

2012-01-01

Nontypeable Haemophilus influenzae (NTHi) is a common airway commensal and opportunistic pathogen that persists within surface-attached biofilm communities. In this study, we tested the hypothesis that bacterial stress-responses are activated within biofilms. Transcripts for several factors associated with bacterial resistance to environmental stress were increased in biofilm cultures as compared to planktonic cultures. Among these, a homolog of the DNA-binding protein from starved cells (dps) was chosen for further study. An isogenic NTHi 86-028NP dps mutant was generated and tested for resistance to environmental stress, revealing a significant survival defects in high-iron conditions, which was mediated by oxidative stress and was restored by genetic complementation. As expected, NTHi 86-028NP dps had a general stress-response defect, exhibiting decreased resistance to many types of environmental stress. While no differences were observed in density and structure of NTHi 86-028NP and NTHi 86-028NP dps biofilms, bacterial survival was decreased in NTHi 86-028NP dps biofilms as compared to the parental strain. The role of dps persistence in vivo was tested in animal infection studies. NTHi 86-028NP dps had decreased resistance to clearance after pulmonary infection of elastase-treated mice as compared to NTHi 86-028NP, whereas minimal differences were observed in clearance from mock-treated mice. Similarly, lower numbers of NTHi 86-028NP dps were recovered from middle-ear effusions and bullar homogenates in the chinchilla model for otitis media (OM). Therefore, we conclude that Dps promotes bacterial survival within NTHi biofilm communities both in vitro and in chronic infections in vivo.

Dps promotes survival of nontypeable Haemophilus influenzae in biofilm communities in vitro and resistance to clearance in vivo

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Bing ePang

2012-05-01

Full Text Available Nontypeable Haemophilus influenzae (NTHi is a common airway commensal and opportunistic pathogen that persists within surface-attached biofilm communities. In this study, we tested the hypothesis that bacterial stress-responses are activated within biofilms. Transcripts for several factors associated with bacterial resistance to environmental stress were increased in biofilm cultures as compared to planktonic cultures. Among these, a homolog of the DNA-binding protein from starved cells (dps was chosen for further study. An isogenic NTHi 86-028NP dps mutant was generated and tested for resistance to environmental stress, revealing a significant survival defects in high-iron conditions, which was mediated by oxidative stress and was restored by genetic complementation. As expected, NTHi 86-028NP dps had a general stress-response defect, exhibiting decreased resistance to many types of environmental stress. While no differences were observed in density and structure of NTHi 86-028NP and NTHi 86-028NP dps biofilms, bacterial survival was decreased in NTHi 86-028NP dps biofilms as compared to the parental strain. The role of dps persistence in vivo was tested in animal infection studies. NTHi 86-028NP dps had decreased resistance to clearance after pulmonary infection of elastase-treated mice as compared to NTHi 86-028NP, whereas minimal differences were observed in clearance from mock-treated mice. Similarly, lower numbers of NTHi 86-028NP dps were recovered from middle-ear effusions and bullar homogenates in the chinchilla model for otitis media. Therefore, we conclude that Dps promotes bacterial survival within NTHi biofilm communities both in vitro and in chronic infections in vivo.

Oxygen-independent inactivation of Haemophilus influenzae transforming DNA by monochromatic radiation: action spectrum, effect of histidine and repair

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Cabrera-Juarez, E; Setlow, J K; Swenson, P A; Peak, M J

1976-01-01

The action spectrum for the oxygen-independent inactivation of native transforming DNA from Haemophilus influenzae with near-uv radiation revealed a shoulder beginning at 334 and extending to 460 nm. The presence of 0.2 M histidine during irradiation produced a small increase in inactivation at 254, 290 and 313 nm, a large increase at 334 nm and a decrease in inactivation at 365, 405, and 460 nm. Photoreactivation did not reverse the DNA damage produced at pH 7.0 at 334, 365, 405 and 460 nm, but did reactivate the DNA after irradiation at 254, 290 and 313 nm. The inactivation of DNA irradiated at 254, 290 and 313 nm was considerably greater when the transforming ability was assayed in an excision-defective mutant compared with the wild type, although DNA irradiated at 334, 365, 405 and 460 nm showed smaller differences. These results suggest that the oxygen-independent inactivation of H. influenzae DNA at pH 7 by irradiation at 334, 365, 405 and 460 nm is caused by lesions other than pyrimidine dimers.

Susceptibilities of Haemophilus influenzae and Moraxella catarrhalis to ABT-773 compared to their susceptibilities to 11 other agents.

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Credito, K L; Lin, G; Pankuch, G A; Bajaksouzian, S; Jacobs, M R; Appelbaum, P C

2001-01-01

The activity of the ketolide ABT-773 against Haemophilus and Moraxella was compared to those of 11 other agents. Against 210 Haemophilus influenzae strains (39.0% beta-lactamase positive), microbroth dilution tests showed that azithromycin and ABT-773 had the lowest MICs (0.5 to 4.0 and 1.0 to 8.0 microg/ml, respectively), followed by clarithromycin and roxithromycin (4.0 to >32.0 microg/ml). Of the beta-lactams, ceftriaxone had the lowest MICs (32.0 microg/ml). Against 50 Moraxella catarrhalis strains, all of the compounds except amoxicillin and cefprozil were active. Time-kill studies against 10 H. influenzae strains showed that ABT-773, at two times the MIC, was bactericidal against 9 of 10 strains, with 99% killing of all strains at the MIC after 24 h; at 12 h, ABT-773 gave 90% killing of all strains at two times the MIC. At 3 and 6 h, killing by ABT-773 was slower, with 99.9% killing of four strains at two times the MIC after 6 h. Similar results were found for azithromycin, with slightly slower killing by erythromycin, clarithromycin, and roxithromycin, especially at earlier times. beta-Lactams were bactericidal against 8 to 10 strains at two times the MIC after 24 h, with slower killing at earlier time periods. Most compounds gave good killing of five M. catarrhalis strains, with beta-lactams killing more rapidly than other drugs. ABT-773 and azithromycin gave the longest postantibiotic effects (PAEs) of the ketolide-macrolide-azalide group tested (4.4 to >8.0 h), followed by clarithromycin, erythromycin, and roxithromycin. beta-Lactam PAEs were similar and shorter than those of the ketolide-macrolide-azalide group for all strains tested.

Crystal Structure of Homoserine Transacetylase from Haemophilus Influenzae Reveals a New Family of alpha/beta-Hydrolases

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Mirza,I.; Nazi, I.; Korczynska, M.; Wright, G.; Berghuis, A.

2005-01-01

Homoserine transacetylase catalyzes one of the required steps in the biosynthesis of methionine in fungi and several bacteria. We have determined the crystal structure of homoserine transacetylase from Haemophilus influenzae to a resolution of 1.65 A. The structure identifies this enzyme to be a member of the alpha/beta-hydrolase structural superfamily. The active site of the enzyme is located near the end of a deep tunnel formed by the juxtaposition of two domains and incorporates a catalytic triad involving Ser143, His337, and Asp304. A structural basis is given for the observed double displacement kinetic mechanism of homoserine transacetylase. Furthermore, the properties of the tunnel provide a rationale for how homoserine transacetylase catalyzes a transferase reaction vs. hydrolysis, despite extensive similarity in active site architecture to hydrolytic enzymes.

CD4+ T-cell Responses Among Adults and Young Children In Response to Streptococcus pneumoniae and Haemophilus influenzae Vaccine Candidate Protein Antigens

OpenAIRE

Sharma, Sharad K.; Roumanes, David; Almudevar, Anthony; Mosmann, Tim R.; Pichichero, Michael E.

2013-01-01

We characterized cytokine profiles of CD4+ T-helper (h) cells in adults and young children to ascertain if responses occur to next-generation candidate vaccine antigens PspA, PcpA, PhtD, PhtE, Ply, LytB of Streptococcus pneumonia (Spn) and Protein D and OMP26 of non-typeable Haemophilus influenzae (NTHi). Adults had vaccine antigen-specific Th1 - and Th2 cells responsive to all antigens evaluated whereas young children had significant numbers of vaccine antigen-specific CD4+ T cells producing...

Immunomodulatory Activity of Red Ginseng against Influenza A Virus Infection

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Jong Seok Lee

2014-01-01

Full Text Available Ginseng herbal medicine has been known to have beneficial effects on improving human health. We investigated whether red ginseng extract (RGE has preventive effects on influenza A virus infection in vivo and in vitro. RGE was found to improve survival of human lung epithelial cells upon influenza virus infection. Also, RGE treatment reduced the expression of pro-inflammatory genes (IL-6, IL-8 probably in part through interference with the formation of reactive oxygen species by influenza A virus infection. Long-term oral administration of mice with RGE showed multiple immunomodulatory effects such as stimulating antiviral cytokine IFN-γ production after influenza A virus infection. In addition, RGE administration in mice inhibited the infiltration of inflammatory cells into the bronchial lumens. Therefore, RGE might have the potential beneficial effects on preventing influenza A virus infections via its multiple immunomodulatory functions.

Frequency of Streptococcus pneumonia and Haemophilus influenza in acute exacerbation of chronic obstructive airway disease and their sensitivity to levofloxacin

International Nuclear Information System (INIS)

Furqan, S.; Paracha, S.A.U.

2014-01-01

Objective: To determine the frequency of Streptococcus pneumoniae and Haemophilus influenzae in acute exacerbation of chronic obstructive pulmonary disease and their sensitivity to levofloxacin. Methods: The cross-sectional study was conducted at the Department of Medicine, AbbasiShaheed Hospital, Karachi, between July 2009 and January 2010. Patients already diagnosed with chronic obstructive pulmonary disease and admitted with symptoms of acute exacerbation were included in the study and their sputum samples were sent for microbiological evaluation. SPSS 16 was used for statistical analysis. Results: Of the total 105 patients in the study, 90 (85.17%) were males. Overall mean age at presentation was 62+-10.2 years. S. pneumoniae was isolated from sputum culture of 33 (31.4%) patients, while 13 (12.4%) patients showed growth of H. influenzae. Out of the 33 sputum specimens of S. pneumoniae, 32 (97.0%) were sensitive to levofloxacin, while 1 (3.0%) was resistant. All the 13 isolates of H. influenzae were sensitive to levofloxacin. Conclusion: S. pneumoniae and H. influenzae are still the most prevalent organisms isolated in acute exacerbation of chronic obstructive pulmonary disease in our population. Levofloxacin is still considered a highly sensitive antibiotic against these common micro-organisms in our population, but S. pneumoniae has started developing resistance against levofloxacin. Therefore, intermittent surveillance regarding development of resistance pattern of common micro-organisms against commonly prescribed antibiotics is required. (author)

Vigilancia de serotipos en infecciones invasivas por Haemophilus influenzae en la Argentina en la era de la vacuna conjugada contra el serotipo b durante el período 2005-2010

OpenAIRE

Efron, Adriana M.; Moscoloni, María A.; Reijtman, Vanesa R.; Regueira, Mabel

2013-01-01

La introducción de la vacuna contra Haemophilus influenzae tipo b en los programas de inmunización de muchos países produjo una reducción marcada en la incidencia de enfermedad invasiva causada por este serotipo y en su portación y un incremento de otros tipos capsulares y de aislamientos no capsulados. Se estudiaron 313 aislamientos de H. influenzae recuperados de sitio estéril, provenientes de pacientes pediátricos y adultos con enfermedad invasiva atendidos en 90 hospitales de la Red Nacio...

Avian Influenza A Viruses: Evolution and Zoonotic Infection.

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Kim, Se Mi; Kim, Young-Il; Pascua, Philippe Noriel Q; Choi, Young Ki

2016-08-01

Although efficient human-to-human transmission of avian influenza virus has yet to be seen, in the past two decades avian-to-human transmission of influenza A viruses has been reported. Influenza A/H5N1, in particular, has repeatedly caused human infections associated with high mortality, and since 1998 the virus has evolved into many clades of variants with significant antigenic diversity. In 2013, three (A/H7N9, A/H6N1, and A/H10N8) novel avian influenza viruses (AIVs) breached the animal-human host species barrier in Asia. In humans, roughly 35% of A/H7N9-infected patients succumbed to the zoonotic infection, and two of three A/H10N8 human infections were also lethal; however, neither of these viruses cause influenza-like symptoms in poultry. While most of these cases were associated with direct contact with infected poultry, some involved sustained human-to-human transmission. Thus, these events elicited concern regarding potential AIV pandemics. This article reviews the human incursions associated with AIV variants and the potential role of pigs as an intermediate host that may hasten AIV evolution. In addition, we discuss the known influenza A virus virulence and transmission factors and their evaluation in animal models. With the growing number of human AIV infections, constant vigilance for the emergence of novel viruses is of utmost importance. In addition, careful characterization and pathobiological assessment of these novel variants will help to identify strains of particular concern for future pandemics. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Intravenous Immunoglobulin Protects Against Severe Pandemic Influenza Infection

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Steven Rockman

2017-05-01

Full Text Available Influenza is a highly contagious, acute, febrile respiratory infection that can have fatal consequences particularly in individuals with chronic illnesses. Sporadic reports suggest that intravenous immunoglobulin (IVIg may be efficacious in the influenza setting. We investigated the potential of human IVIg to ameliorate influenza infection in ferrets exposed to either the pandemic H1N1/09 virus (pH1N1 or highly pathogenic avian influenza (H5N1. IVIg administered at the time of influenza virus exposure led to a significant reduction in lung viral load following pH1N1 challenge. In the lethal H5N1 model, the majority of animals given IVIg survived challenge in a dose dependent manner. Protection was also afforded by purified F(ab′2 but not Fc fragments derived from IVIg, supporting a specific antibody-mediated mechanism of protection. We conclude that pre-pandemic IVIg can modulate serious influenza infection-associated mortality and morbidity. IVIg could be useful prophylactically in the event of a pandemic to protect vulnerable population groups and in the critical care setting as a first stage intervention.

Influenza and Respiratory Syncytial viral infections in Malaysia: Demographic and Clinical perspective.

Science.gov (United States)

Rahman, M M; Wong, K K; Hanafiah, A; Isahak, I

2014-01-01

Respiratory infections represent a major public health problem worldwide. The study aimed to determine the prevalence of respiratory syncytial and influenza virus infections and analyzed in respect to demography and clinical perspective. Methods : The specimens were processed by cell culture and immunofluorescent assay (IFA) and real-time reverse transcriptase-PCR (rRT-PCR) for detection of respiratory viruses. Results : Out of 505 specimens 189 (37.8%) were positive, in which RSV was positive in 124(24.8%) cases and influenza A was positive in 65(13%) cases. Positive cases for influenza virus A and RSV were analyzed based on demography: age, gender, ethnicity and clinical symptoms. There were no significant differences among gender, ethnicity and clinical symptoms in both RSV and influenza A virus infections. It was observed that children below 3 years of ages were more prone to RSV infections. On the contrary, influenza virus A infected all age groups of humans. RSV infects mostly child below 3 years of age and influenza virus infects all age group. No specificity of RSV and influenza infection in relation to demography.

Influenza infection and heart failure-vaccination may change heart failure prognosis?

Science.gov (United States)

Kadoglou, Nikolaos P E; Bracke, Frank; Simmers, Tim; Tsiodras, Sotirios; Parissis, John

2017-05-01

The interaction of influenza infection with the pathogenesis of acute heart failure (AHF) and the worsening of chronic heart failure (CHF) is rather complex. The deleterious effects of influenza infection on AHF/CHF can be attenuated by specific immunization. Our review aimed to summarize the efficacy, effectiveness, safety, and dosage of anti-influenza vaccination in HF. In this literature review, we searched MEDLINE and EMBASE from January 1st 1966 to December 31st, 2016, for studies examining the association between AHF/CHF, influenza infections, and anti-influenza immunizations. We used broad criteria to increase the sensitivity of the search. HF was a prerequisite for our search. The search fields used included "heart failure," "vaccination," "influenza," "immunization" along with variants of these terms. No restrictions on the type of study design were applied. The most common clinical scenario is exacerbation of pre-existing CHF by influenza infection. Scarce evidence supports a potential positive association of influenza infection with AHF. Vaccinated patients with pre-existing CHF have reduced all-cause morbidity and mortality, but effects are not consistently documented. Immunization with higher antigen quantity may confer additional protection, but such aggressive approach has not been generally advocated. Further studies are needed to delineate the role of influenza infection on AHF/CHF pathogenesis and maintenance. Annual anti-influenza vaccination appears to be an effective measure for secondary prevention in HF. Better immunization strategies and more efficacious vaccines are urgently necessary.

Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate influenza viral infection

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Kohio, Hinissan P.; Adamson, Amy L., E-mail: aladamso@uncg.edu

2013-09-15

As new influenza virus strains emerge, finding new mechanisms to control infection is imperative. In this study, we found that we could control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induced a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis, we found that viral replication was significantly reduced after cells were treated with glycolytic inhibitors. Addition of extracellular ATP after glycolytic inhibition restored influenza infection. We also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase within cells, and increased vacuolar-type ATPase proton-transport activity. The increase of viral infection via high glucose levels could be reversed by inhibition of the proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection. - Highlights: • Increased glucose levels increase Influenza A viral infection of MDCK cells. • Inhibition of the glycolytic enzyme hexokinase inhibited Influenza A viral infection. • Inhibition of hexokinase induced disassembly the V-ATPase. • Disassembly of the V-ATPase and Influenza A infection was bypassed with ATP. • The state of V-ATPase assembly correlated with Influenza A infection of cells.

Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate influenza viral infection

International Nuclear Information System (INIS)

Kohio, Hinissan P.; Adamson, Amy L.

2013-01-01

As new influenza virus strains emerge, finding new mechanisms to control infection is imperative. In this study, we found that we could control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induced a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis, we found that viral replication was significantly reduced after cells were treated with glycolytic inhibitors. Addition of extracellular ATP after glycolytic inhibition restored influenza infection. We also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase within cells, and increased vacuolar-type ATPase proton-transport activity. The increase of viral infection via high glucose levels could be reversed by inhibition of the proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection. - Highlights: • Increased glucose levels increase Influenza A viral infection of MDCK cells. • Inhibition of the glycolytic enzyme hexokinase inhibited Influenza A viral infection. • Inhibition of hexokinase induced disassembly the V-ATPase. • Disassembly of the V-ATPase and Influenza A infection was bypassed with ATP. • The state of V-ATPase assembly correlated with Influenza A infection of cells

Streptococcus pneumoniae and Haemophilus influenzae as etiological agents of conjunctivitis outbreaks in the region of Ribeirão Preto, SP, Brazil

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Marta I. C. MEDEIROS

1998-01-01

Full Text Available In the study of conjunctivitis outbreaks occurring from September 1994 to September 1996 in the region of Ribeirão Preto, conjunctival exudates of 92 patients were cultivated in Instituto Adolfo Lutz Laboratory I, Ribeirão Preto. Most cases occurred in the age range 2-7 years. The etiological agents which were most frequently isolated from the analyzed cases were: Streptococcus pneumoniae and Haemophilus influenzae, in 40.22% and 21.74%, respectively. 51.35% of the S. pneumoniae isolated strains were not typable. The oxacillin-resistant S. pneumoniae strains were submitted to the minimum inhibitory concentration test (MIC and three of them presented intermediate resistance, whereas only one was highly resistant to penicillin.No estudo de surtos de conjuntivite ocorridos no período de setembro de 1994 a setembro de 1996, na região de Ribeirão Preto, foram semeadas no Instituto Adolfo Lutz Laboratório I, Ribeirão Preto, exsudatos conjuntivais de 92 pacientes, sendo que a maioria dos casos estava na faixa etária de 2-7 anos. Os agentes etiológicos mais freqüentemente isolados dos casos analisados foram: Streptococcus pneumoniae e Haemophilus influenzae em 40,22% e 21,74% respectivamente. 51,35% das cepas de S. pneumoniae isoladas foram não tipáveis. As cepas de S. pneumoniae oxacilina resistente foram submetidas ao teste de concentração inibitória mínima (CIM, sendo que três apresentaram resistência intermediária e apenas uma foi altamente resistente à penicilina.

RbsB (NTHI_0632) mediates quorum signal uptake in nontypeable Haemophilus influenzae strain 86-028NP.

Science.gov (United States)

Armbruster, Chelsie E; Pang, Bing; Murrah, Kyle; Juneau, Richard A; Perez, Antonia C; Weimer, Kristin E D; Swords, W Edward

2011-11-01

Nontypeable Haemophilus influenzae (NTHI) is a respiratory commensal and opportunistic pathogen, which persists within biofilms on airway mucosal surfaces. For many species, biofilm formation is impacted by quorum signalling. Our prior work shows that production of autoinducer-2 (AI-2) promotes biofilm development and persistence for NTHI 86-028NP. NTHI 86-028NP encodes an ABC transporter annotated as a ribose transport system that includes a protein (RbsB) with similarity to the Escherichia coli LsrB and Aggregatibacter actinomycetemcomitans RbsB proteins that bind AI-2. In this study, inactivation of rbsB significantly reduced uptake of AI-2 and the AI-2 precursor dihydroxypentanedione (DPD) by NTHI 86-028NP. Moreover, DPD uptake was not competitively inhibited by ribose or other pentose sugars. Transcript levels of rbsB increased in response to DPD and as bacteria approached stationary-phase growth. The NTHI 86-028NP rbsB mutant also formed biofilms with significantly reduced thickness and total biomass and reduced surface phosphorylcholine, similar to a luxS mutant. Infection studies revealed that loss of rbsB impaired bacterial persistence in the chinchilla middle ear, similar to our previous results with luxS mutants. Based on these data, we conclude that in NTHI 86-028NP, RbsB is a LuxS/AI-2 regulated protein that is required for uptake of and response to AI-2. © 2011 Blackwell Publishing Ltd.

Influenza and other respiratory virus infections in outpatients with medically attended acute respiratory infection during the 2011-12 influenza season.

Science.gov (United States)

Zimmerman, Richard K; Rinaldo, Charles R; Nowalk, Mary Patricia; Gk, Balasubramani; Thompson, Mark G; Moehling, Krissy K; Bullotta, Arlene; Wisniewski, Stephen

2014-07-01

Respiratory tract infections are a major cause of outpatient visits, yet only a portion is tested to determine the etiologic organism. Multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) assays for detection of multiple viruses are being used increasingly in clinical settings. During January-April 2012, outpatients with acute respiratory illness (≤ 7 days) were tested for influenza using singleplex RT-PCR (SRT-PCR). A subset was assayed for 18 viruses using MRT-PCR to compare detection of influenza and examine the distribution of viruses and characteristics of patients using multinomial logistic regression. Among 662 participants (6 months-82 years), detection of influenza was similar between the MRT-PCR and SRT-PCR (κ = 0.83). No virus was identified in 267 (40.3%) samples. Commonly detected viruses were human rhinovirus (HRV, 15.4%), coronavirus (CoV, 10.4%), respiratory syncytial virus (RSV, 8.4%), human metapneumovirus (hMPV, 8.3%), and influenza (6%). Co-detections were infrequent (6.9%) and most commonly occurred among those infections (P = 0.008), nasal congestion was more frequent in CoV, HRV, hMPV, influenza and RSV infections (P = 0.001), and body mass index was higher among those with influenza (P = 0.036). Using MRT-PCR, a viral etiology was found in three-fifths of patients with medically attended outpatient visits for acute respiratory illness during the influenza season; co-detected viruses were infrequent. Symptoms varied by viral etiology. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus.

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Kreijtz, J H C M; Bodewes, R; van den Brand, J M A; de Mutsert, G; Baas, C; van Amerongen, G; Fouchier, R A M; Osterhaus, A D M E; Rimmelzwaan, G F

2009-08-06

The transmission of highly pathogenic avian influenza (HPAI) A viruses of the H5N1 subtype from poultry to man and the high case fatality rate fuels the fear for a pandemic outbreak caused by these viruses. However, prior infections with seasonal influenza A/H1N1 and A/H3N2 viruses induce heterosubtypic immunity that could afford a certain degree of protection against infection with the HPAI A/H5N1 viruses, which are distantly related to the human influenza A viruses. To assess the protective efficacy of such heterosubtypic immunity mice were infected with human influenza virus A/Hong Kong/2/68 (H3N2) 4 weeks prior to a lethal infection with HPAI virus A/Indonesia/5/05 (H5N1). Prior infection with influenza virus A/Hong Kong/2/68 reduced clinical signs, body weight loss, mortality and virus replication in the lungs as compared to naive mice infected with HPAI virus A/Indonesia/5/05. Priming by infection with respiratory syncytial virus, a non-related virus did not have a beneficial effect on the outcome of A/H5N1 infections, indicating that adaptive immune responses were responsible for the protective effect. In mice primed by infection with influenza A/H3N2 virus cytotoxic T lymphocytes (CTL) specific for NP(366-374) epitope ASNENMDAM and PA(224-232) SCLENFRAYV were observed. A small proportion of these CTL was cross-reactive with the peptide variant derived from the influenza A/H5N1 virus (ASNENMEVM and SSLENFRAYV respectively) and upon challenge infection with the influenza A/H5N1 virus cross-reactive CTL were selectively expanded. These CTL, in addition to those directed to conserved epitopes, shared by the influenza A/H3N2 and A/H5N1 viruses, most likely contributed to accelerated clearance of the influenza A/H5N1 virus infection. Although also other arms of the adaptive immune response may contribute to heterosubtypic immunity, the induction of virus-specific CTL may be an attractive target for development of broad protective vaccines. Furthermore the

Heavy-chain isotype patterns of human antibody-secreting cells induced by Haemophilus influenzae type b conjugate vaccines in relation to age and preimmunity

DEFF Research Database (Denmark)

Barington, T; Juul, Lars; Gyhrs, A

1994-01-01

The influence of preexisting immunity on the heavy-chain isotypes of circulating antibody-secreting cells (AbSC) induced by vaccination with Haemophilus influenzae type b (Hib) capsular polysaccharide (HibCP) coupled to tetanus toxoid (TT) or diphtheria toxoid (DT) and by vaccination with TT or D...... of natural HibCP antibodies (r = 0.59; P = 0.00002). A possible role of natural exposure for Hib or cross-reactive bacteria on the mucosal surfaces in the shaping of the isotype response to HibCP conjugate vaccines is discussed....

Intranasal vaccination promotes detrimental Th17-mediated immunity against influenza infection.

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Asher Maroof

2014-01-01

Full Text Available Influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. Currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccination against influenza virus in humans. We evaluated the efficacy of a synthetic toll-like receptor 4 agonist CRX-601 as an adjuvant for enhancing vaccine-induced protection against influenza infection. Intranasal administration of CRX-601 adjuvant combined with detergent split-influenza antigen (A/Uruguay/716/2007 (H3N2 generated strong local and systemic immunity against co-administered influenza antigens while exhibiting high efficacy against two heterotypic influenza challenges. Intranasal vaccination with CRX-601 adjuvanted vaccines promoted antigen-specific IgG and IgA antibody responses and the generation of polyfunctional antigen-specific Th17 cells (CD4(+IL-17A(+TNFα(+. Following challenge with influenza virus, vaccinated mice transiently exhibited increased weight loss and morbidity during early stages of disease but eventually controlled infection. This disease exacerbation following influenza infection in vaccinated mice was dependent on both the route of vaccination and the addition of the adjuvant. Neutralization of IL-17A confirmed a detrimental role for this cytokine during influenza infection. The expansion of vaccine-primed Th17 cells during influenza infection was also accompanied by an augmented lung neutrophilic response, which was partially responsible for mediating the increased morbidity. This discovery is of significance in the field of vaccinology, as it highlights the importance of both route of vaccination and adjuvant selection in vaccine development.

Immunoglobulin G Avidities in Infants in Mexico after Primary Immunization with Three Doses of Polyribosylribitol Phosphate-Tetanus Toxoid Haemophilus influenzae Type b Vaccine▿ †

Science.gov (United States)

Gómez-de-León, Patricia; Díaz-García, F. Javier; Villaseñor-Sierra, Alberto; Segura, Jorge; Carranza, Martha I.; Arredondo-Garcia, José Luis; Santos, José Ignacio

2008-01-01

Serum immunoglobulin G concentrations and avidities specific to Haemophilus influenzae type b (Hib) were measured in 208 children living in Guadalajara and Mexico City. Protective concentrations were found in 98.9% and 100.0% of participants, respectively. Geometric mean concentrations differed between both populations and/or among age groups. Mean avidities differed only among the 7- to 12-month-old children. Diphtheria-tetanus-whole-cell pertussis-hepatitis B-Hib primary vaccination seems to induce protection in Mexican children. PMID:18417667

Case Report: Severe Imported Influenza Infections Developed during Travel in Reunion Island.

Science.gov (United States)

Allyn, Jérôme; Brottet, Elise; Antok, Emmanuel; Dangers, Laurence; Persichini, Romain; Coolen-Allou, Nathalie; Roquebert, Bénédicte; Allou, Nicolas; Vandroux, David

2017-12-01

We report two cases of severe influenza infection imported by tourist patients from their country of origin and developed during travel. While studies have reported cases of influenza infections acquired during travel, here we examine two cases of severe influenza infection contracted in the country of origin that led to diagnosis and therapeutic problems in the destination country. No international recommendation exists concerning influenza vaccination before travel, and few countries recommend it for all travelers. Our study suggests that travel should be canceled when infectious signs are observed before departure. Influenza is a very common infection that is often benign, but sometimes very severe. The most severe cases include shock, acute respiratory distress syndrome (ARDS), myocarditis, rhabdomyolysis, and multiple organ failure. Management can require exceptional therapies, such as extracorporeal membrane oxygenation. A number of studies have focused on influenza infection in travelers. Cases of influenza acquired during travel have been reported in this literature, but no study has examined cases of influenza imported from the country of origin and developed while abroad. The latter situation may lead to 1) diagnostic problems during the nonepidemic season or in places where diagnostic techniques are lacking and 2) therapeutic difficulties resulting from the unavailability of techniques for the management of severe influenza infection in tourist areas. Here, we report two cases of extremely severe influenza infection imported by tourists from their country of origin and developed during travel.

Origin of the diversity in DNA recognition domains in phasevarion associated modA genes of pathogenic Neisseria and Haemophilus influenzae.

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Gawthorne, Jayde A; Beatson, Scott A; Srikhanta, Yogitha N; Fox, Kate L; Jennings, Michael P

2012-01-01

Phase variable restriction-modification (R-M) systems have been identified in a range of pathogenic bacteria. In some it has been demonstrated that the random switching of the mod (DNA methyltransferase) gene mediates the coordinated expression of multiple genes and constitutes a phasevarion (phase variable regulon). ModA of Neisseria and Haemophilus influenzae contain a highly variable, DNA recognition domain (DRD) that defines the target sequence that is modified by methylation and is used to define modA alleles. 18 distinct modA alleles have been identified in H. influenzae and the pathogenic Neisseria. To determine the origin of DRD variability, the 18 modA DRDs were used to search the available databases for similar sequences. Significant matches were identified between several modA alleles and mod gene from distinct bacterial species, indicating one source of the DRD variability was via horizontal gene transfer. Comparison of DRD sequences revealed significant mosaicism, indicating exchange between the Neisseria and H. influenzae modA alleles. Regions of high inter- and intra-allele similarity indicate that some modA alleles had undergone recombination more frequently than others, generating further diversity. Furthermore, the DRD from some modA alleles, such as modA12, have been transferred en bloc to replace the DRD from different modA alleles.

A biphasic epigenetic switch controls immunoevasion, virulence and niche adaptation in non-typeable Haemophilus influenzae.

Science.gov (United States)

Atack, John M; Srikhanta, Yogitha N; Fox, Kate L; Jurcisek, Joseph A; Brockman, Kenneth L; Clark, Tyson A; Boitano, Matthew; Power, Peter M; Jen, Freda E-C; McEwan, Alastair G; Grimmond, Sean M; Smith, Arnold L; Barenkamp, Stephen J; Korlach, Jonas; Bakaletz, Lauren O; Jennings, Michael P

2015-07-28

Non-typeable Haemophilus influenzae contains an N(6)-adenine DNA-methyltransferase (ModA) that is subject to phase-variable expression (random ON/OFF switching). Five modA alleles, modA2, modA4, modA5, modA9 and modA10, account for over two-thirds of clinical otitis media isolates surveyed. Here, we use single molecule, real-time (SMRT) methylome analysis to identify the DNA-recognition motifs for all five of these modA alleles. Phase variation of these alleles regulates multiple proteins including vaccine candidates, and key virulence phenotypes such as antibiotic resistance (modA2, modA5, modA10), biofilm formation (modA2) and immunoevasion (modA4). Analyses of a modA2 strain in the chinchilla model of otitis media show a clear selection for ON switching of modA2 in the middle ear. Our results indicate that a biphasic epigenetic switch can control bacterial virulence, immunoevasion and niche adaptation in an animal model system.

Vaccination for the control of childhood bacterial pneumonia - Haemophilus influenzae type b and pneumococcal vaccines

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Diana C Otczyk

2013-01-01

Full Text Available Pneumonia in childhood is endemic in large parts of the world and in particular, in developing countries, as well as in many indigenous communities within developed nations. Haemophilus influenzae type b and Streptococcus pneumoniae conjugate vaccines are currently available against the leading bacterial causes of pneumonia.  The use of the vaccines in both industrialised and developing countries have shown a dramatic reduction in the burden of pneumonia and invasive disease in children.  However, the greatest threat facing pneumococcal conjugate vaccine effectiveness is serotype replacement.  The current vaccines provide serotype-specific, antibody–mediated protection against only a few of the 90+ capsule serotypes.  Therefore, there has been a focus in recent years to rapidly advance technologies that will result in broader disease coverage and more affordable vaccines that can be used in developing countries.  The next generation of pneumococcal vaccines have advanced to clinical trials.

Spontaneous Subconjunctival Abscess Because of Haemophilus influenzae

Science.gov (United States)

2010-07-01

any recent sexually transmitted diseases, vaginal discharge, or sores. Her past medical history included mild seasonal allergies and no history of...culture confirmed a nontypeable strain of H. influenzae. DISCUSSION H. influenzae is a small aerobic Gram-negative cocco- bacillus found mainly in the

Past Life and Future Effects—How Heterologous Infections Alter Immunity to Influenza Viruses

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Aisha Souquette

2018-05-01

Full Text Available Influenza virus frequently mutates due to its error-prone polymerase. This feature contributes to influenza virus’s ability to evade pre-existing immunity, leading to annual epidemics and periodic pandemics. T cell memory plays a key protective role in the face of an antigenically distinct influenza virus strain because T cell targets are often derived from conserved internal proteins, whereas humoral immunity targets are often sites of increased mutation rates that are tolerated by the virus. Most studies of influenza T cell memory are conducted in naive, specific pathogen free mice and do not account for repetitive influenza infection throughout a lifetime, sequential acute heterologous infections between influenza infections, or heterologous chronic co-infections. By contrast to these mouse models, humans often experience numerous influenza infections, encounter heterologous acute infections between influenza infections, and are infected with at least one chronic virus. In this review, we discuss recent advances in understanding the effects of heterologous infections on the establishment and maintenance of CD8+ T cell immunological memory. Understanding the various factors that affect immune memory can provide insights into the development of more effective vaccines and increase reproducibility of translational studies between animal models and clinical results.

Crystal Structures of Active Fully Assembled Substrate- and Product-Bound Complexes of UDP-N-Acetylmuramic Acid:l-Alanine Ligase (MurC) from Haemophilus influenzae

OpenAIRE

Mol, Clifford D.; Brooun, Alexei; Dougan, Douglas R.; Hilgers, Mark T.; Tari, Leslie W.; Wijnands, Robert A.; Knuth, Mark W.; McRee, Duncan E.; Swanson, Ronald V.

2003-01-01

UDP-N-acetylmuramic acid:l-alanine ligase (MurC) catalyzes the addition of the first amino acid to the cytoplasmic precursor of the bacterial cell wall peptidoglycan. The crystal structures of Haemophilus influenzae MurC in complex with its substrate UDP-N-acetylmuramic acid (UNAM) and Mg2+ and of a fully assembled MurC complex with its product UDP-N-acetylmuramoyl-l-alanine (UMA), the nonhydrolyzable ATP analogue AMPPNP, and Mn2+ have been determined to 1.85- and 1.7-Å resolution, respective...

Iota-carrageenan is a potent inhibitor of influenza A virus infection.

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Andreas Leibbrandt

Full Text Available The 2009 flu pandemic and the appearance of oseltamivir-resistant H1N1 influenza strains highlight the need for treatment alternatives. One such option is the creation of a protective physical barrier in the nasal cavity. In vitro tests demonstrated that iota-carrageenan is a potent inhibitor of influenza A virus infection, most importantly also of pandemic H1N1/2009 in vitro. Consequently, we tested a commercially available nasal spray containing iota-carrageenan in an influenza A mouse infection model. Treatment of mice infected with a lethal dose of influenza A PR8/34 H1N1 virus with iota-carrageenan starting up to 48 hours post infection resulted in a strong protection of mice similar to mice treated with oseltamivir. Since alternative treatment options for influenza are rare, we conclude that the nasal spray containing iota-carrageenan is an alternative to neuraminidase inhibitors and should be tested for prevention and treatment of influenza A in clinical trials in humans.

Outer membrane protein P4 is not required for virulence in the human challenge model of Haemophilus ducreyi infection.

Science.gov (United States)

Janowicz, Diane M; Zwickl, Beth W; Fortney, Kate R; Katz, Barry P; Bauer, Margaret E

2014-06-24

Bacterial lipoproteins often play important roles in pathogenesis and can stimulate protective immune responses. Such lipoproteins are viable vaccine candidates. Haemophilus ducreyi, which causes the sexually transmitted disease chancroid, expresses a number of lipoproteins during human infection. One such lipoprotein, OmpP4, is homologous to the outer membrane lipoprotein e (P4) of H. influenzae. In H. influenzae, e (P4) stimulates production of bactericidal and protective antibodies and contributes to pathogenesis by facilitating acquisition of the essential nutrients heme and nicotinamide adenine dinucleotide (NAD). Here, we tested the hypothesis that, like its homolog, H. ducreyi OmpP4 contributes to virulence and stimulates production of bactericidal antibodies. We determined that OmpP4 is broadly conserved among clinical isolates of H. ducreyi. We next constructed and characterized an isogenic ompP4 mutant, designated 35000HPompP4, in H. ducreyi strain 35000HP. To test whether OmpP4 was necessary for virulence in humans, eight healthy adults were experimentally infected. Each subject was inoculated with a fixed dose of 35000HP on one arm and three doses of 35000HPompP4 on the other arm. The overall parent and mutant pustule formation rates were 52.4% and 47.6%, respectively (P = 0.74). These results indicate that expression of OmpP4 in not necessary for H. ducreyi to initiate disease or progress to pustule formation in humans. Hyperimmune mouse serum raised against purified, recombinant OmpP4 did not promote bactericidal killing of 35000HP or phagocytosis by J774A.1 mouse macrophages in serum bactericidal and phagocytosis assays, respectively. Our data suggest that, unlike e (P4), H. ducreyi OmpP4 is not a suitable vaccine candidate. OmpP4 may be dispensable for virulence because of redundant mechanisms in H. ducreyi for heme acquisition and NAD utilization.

[Optimized isolation and purification of non-typeable Haemophilus influenzae Haps protein].

Science.gov (United States)

Li, Wan-yi; Kuang, Yu; Li, Ming-yuan; Yang, Yuan; Jiang, Zhong-hua; Yao, Feng; Chen, Chang-chun

2007-12-01

To optimize the isolation and purification conditions for Hap(s) protein of non-typeable Haemophilus influenzae. Hap(s) protein was purified by ammonium sulfate precipitation, dialysis desalting and Hitrap weak cation exchange columns of CM Sepharose Fast Flow. The condition of the elution was optimized for pH and ionic strength, the absorbance at 280 nm of the elution samples were detected, and the targeted protein band in the collected samples was observed by SDS-PAGE electrophoresis. The Hitrap ion exchange column was eluted with buffer 1, which resulted in a baseline distribution of absorbance at 280 nm. Buffer 2 elution of the column resulted in the presence of peak absorbance with trails, which was identified to be constituted by some low molecular weight bands by subsequent SDS-PAGE. In serial column elution with buffer 3 with different ionic strength, a peak absorbance was observed with the ionic strength of 100 mmol/L NaCl, and SDS-PAGE confirmed that the peak was generated by the target protein. No obvious peaks or bands in SDS-PAGE occurred with the other ionic strengths. The pH of the buffer only affect the elution of the irrelevant proteins rather than the Hap(s) protein, and elution with the buffer containing 100 mmol/L NaCl can be optimal for eluting the Hap(s) protein.

Mutation of Haemophilus influenzae transforming DNA in vitro with near-ultraviolet radiation: action spectrum

Energy Technology Data Exchange (ETDEWEB)

Cabrera-Juarez, E; Setlow, J K [Escuela Nacional de Ciencias Biologicas, Mexico City. Dept. de Bioquimica; Oak Ridge National Lab., Tenn. (USA). Biology Div.)

1976-05-01

Mutations were produced in purified transforming DNA from Haemophilus influenzae by near UV radiation and were assayed as mutants among cells transformed with irradiated DNA. The maximum efficiency of mutation induction was at around 334 nm, and the efficiency dropped off steeply at lower and higher wavelengths. The difference between the action spectrum for mutation and that for the oxygen-independent inactivation of transforming DNA, which had a shoulder at 365 nm, indicates that there are different lesions involved in the inactivating and mutagenic effects of near-UV. The presence of histidine during irradiation enhanced the mutagenic effect at 334 and 365 nm, although it protected against inactivation at 365 nm. The effective near-UV wavelengths for in vitro mutation are to some extent the same as the effective wavelengths for mutation in vivo reported previously. These findings indicate that mutations are produced in vivo by near-UV with DNA as the primary target molecule rather than by a secondary non-photochemical reaction between DNA and some other cell component.

Influenza infection in the intensive care unit: Four years after the 2009 pandemic.

Science.gov (United States)

Pérez-Carrasco, Marcos; Lagunes, Leonel; Antón, Andrés; Gattarello, Simone; Laborda, César; Pumarola, Tomás; Rello, Jordi

2016-03-01

The role of influenza viruses in severe acute respiratory infection (SARI) in Intensive Care Units (ICU) remains unknown. The post-pandemic influenza A(H1N1)pdm09 period, in particular, has been poorly studied. To identify influenza SARI patients in ICU, to assess the usefulness of the symptoms of influenza-like illness (ILI), and to compare the features of pandemic vs. post-pandemic influenza A(H1N1) pdm09 infection. A prospective observational study with SARI patients admitted to ICU during the first three post-pandemic seasons. Patient demographics, characteristics and outcomes were recorded. An influenza epidemic period (IEP) was defined as >100 cases/100,000 inhabitants per week. One hundred sixty-three patients were diagnosed with SARI. ILI was present in 65 (39.9%) patients. Influenza infection was documented in 41 patients, 27 (41.5%) ILI patients, and 14 (14.3%) non-ILI patients, 27 of them during an IEP. Influenza A viruses were mainly responsible. Only five patients had influenza B virus infection, which were non-ILI during an IEP. SARI overall mortality was 22.1%, and 15% in influenza infection patients. Pandemic and post-pandemic influenza infection patients shared similar clinical features. During influenza epidemic periods, influenza infection screening should be considered in all SARI patients. Influenza SARI was mainly caused by subtype A(H1N1)pdm09 and A(H3N2) in post-pandemic seasons, and no differences were observed in ILI and mortality rate compared with a pandemic season. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Immunogenicity of a 2-dose priming and booster vaccination with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine

DEFF Research Database (Denmark)

Silfverdal, Sven Arne; Høgh, Birthe; Bergsaker, Marianne Riise

2009-01-01

BACKGROUND: The immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was determined following a simplified 2-dose priming and the more commonly employed 3-dose priming both followed by a booster dose. METHODS: A total of 351 healthy....... RESULTS: Depending on the serotype, the percentages of subjects reaching the ELISA antibody threshold of 0.2 microg/mL were 92.8% to 98.0% following 2 primary doses and 96.1% to 100% following 3 primary doses except for serotype 6B (55.7% and 63.1%, respectively) and serotype 23F (69.3% and 77...

Vigilancia de los serotipos y susceptibilidad antimicrobiana de Haemophilus influenzae en Colombia, 1994-2002.

Directory of Open Access Journals (Sweden)

María Victoria Ovalle

2003-06-01

Full Text Available La enfermedad invasora causada por Haemophilus influenzae, serotipo b, ha sido una de las mayores causas de morbilidad y mortalidad en la población infantil; afortunadamente, en algunos países con amplia cobertura de la vacuna conjugada esta situación ha cambiado. En 1994 se inició en el Grupo de Microbiología un programa de vigilancia de la susceptibilidad antimicrobiana y de los serotipos de aislamientos invasores de H. influenzae, remitidos por los hospitales y Laboratorios de Salud Pública del país como componente de los programas de vigilancia en red de infección respiratoria aguda y meningitis bacteriana aguda. El objetivo de este trabajo fue determinar la evolución de los serotipos y los patrones de susceptibilidad antimicrobiana de los aislamientos invasores de H. influenzae obtenidos de 1994 al 2002 y realizar un nuevo análisis sobre el impacto de la vacuna conjugada de H. influenzae, serotipo b, en Colombia. De 1994 a 2002 se han estudiado 683 aislamientos; 379 (55,5% de pacientes del género masculino; 370 (54,2% de menores de 1 año; 227 (33,2% de 1 a 5 años; 19 (2,8% de 6 a 14 años; 38 (5,6% de mayores de 14 años, y de 29 (4,2% no se tenía el dato de la edad; 493 (72,2% fueron recuperados de pacientes con meningitis, 181 (26,5% de neumonía y 9 (0,9% de otras enfermedades. El 85,1% de los aislamientos fueron H. influenzae, serotipo b, 12,9% no capsulares y 2,0% de otros serotipos (10 a, 1 d, 1 e y 2 f. Del total de aislamientos, 12% fueron productores de beta-lactamasa; 13,9%, resistentes a ampicilina; 12,7%, a trimetoprim sulfametoxazol (SXT; 5,4%, a cloranfenicol, y 1% a cefuroxima; todos fueron sensibles a ceftriaxona. Durante este período se observó un incremento en la resistencia de los aislamientos a SXT (5% al 13%, pero la diferencia no fue estadísticamente significativa (p=0,1. Con la vigilancia se pudo determinar una disminución significativa de los casos de meningitis en los menores de 1 año y en el

GyrA and/or ParC alterations of Haemophilus influenzae strains isolated from the urethra of men with acute urethritis.

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Kondo, Hiromi; Ito, Shin; Hatazaki, Kyoko; Horie, Kengo; Nakane, Keita; Mizutani, Kosuke; Tsuchiya, Tomohiro; Yasuda, Mitsuru; Yokoi, Shigeaki; Nakano, Masahiro; Deguchi, Takashi

2018-03-01

Of 73 clinical strains of Haemophilus influenzae isolated from the urethra of men with urogenital infections, we enrolled 6 strains (8.2%) with levofloxacin (LVFX) minimum inhibitory concentrations (MICs) of ≥0.03 μg/ml in this study. All the strains were isolated from non-gonococcal urethritis (NGU). We amplified the quinolone resistance-determining region of the gyrA gene and the analogous region of the parC gene from bacterial DNAs by PCR and sequenced the PCR products. Two strains with a LVFX MIC of 0.03 μg/ml had an amino acid change of Asp88 to Gly in GyrA. One with a LVFX MIC of 0.06 μg/ml had a change of Asp88 to Tyr in GyrA. Two with respective LVFX MICs of 0.12 and 0.25 μg/ml had a change of Ser84 to Leu in GyrA. One with a LVFX MIC of 1 μg/ml had changes of Ser84 to Leu in GyrA and of Ser84 to Ile in ParC. Multilocus sequence typing showed two strains with a change of Asp88 to Gly in GyrA had the same sequence type, but the others had sequence types different from each other. Single amino acid changes in GyrA alone or single changes in both GyrA and ParC could contribute to decreased susceptibility to fluoroquinolones in H. influenzae isolates from NGU. Most of the isolates with GyrA and/or ParC alterations would be multiclonal. The prevalence of such isolates would be relatively low, and they would still be susceptible to fluoroquinolones commonly prescribed for treatment of NGU. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DAMPs and influenza virus infection in ageing.

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Samy, Ramar Perumal; Lim, Lina H K

2015-11-01

Influenza A virus (IAV) is a serious global health problem worldwide due to frequent and severe outbreaks. IAV causes significant morbidity and mortality in the elderly population, due to the ineffectiveness of the vaccine and the alteration of T cell immunity with ageing. The cellular and molecular link between ageing and virus infection is unclear and it is possible that damage associated molecular patterns (DAMPs) may play a role in the raised severity and susceptibility of virus infections in the elderly. DAMPs which are released from damaged cells following activation, injury or cell death can activate the immune response through the stimulation of the inflammasome through several types of receptors found on the plasma membrane, inside endosomes after endocytosis as well as in the cytosol. In this review, the detriment in the immune system during ageing and the links between influenza virus infection and ageing will be discussed. In addition, the role of DAMPs such as HMGB1 and S100/Annexin in ageing, and the enhanced morbidity and mortality to severe influenza infection in ageing will be highlighted. Copyright © 2015 Elsevier B.V. All rights reserved.

Social participation and risk of influenza infection in older adults: a cross-sectional study.

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Shobugawa, Yugo; Fujiwara, Takeo; Tashiro, Atsushi; Saito, Reiko; Kondo, Katsunori

2018-01-24

Influenza infection can cause severe pneumonia, which is sometimes fatal, particularly in older adults. Influenza results in 3-5 million cases of severe illness and about 250 000 to 500 000 deaths annually worldwide. Social participation in the context of influenza infection is controversial because, although social participation is beneficial in maintaining physical function and mental health, it also increases the risk of contact with infected people. This study examined the association between social participation and influenza infection in Japanese adults aged 65 years or older. Cross-sectional study. Japanese functionally independent adults aged 65 years or older. Among the respondents to the Japan Gerontological Evaluation Study (JAGES) 2013 survey, which took place during the period from October to December 2013, 12 231 men and 14 091 women responded to questions on influenza vaccination and influenza infection. Using JAGES data for 12 231 men and 14 091 women aged ≥65 years, we examined the association between social participation and influenza infection. The association between influenza infection and number of groups in which respondents participated was investigated among adults aged≥65 years, stratified by vaccination status and sex. Unvaccinated women who participated in two or more social activities were 2.20 times (95% CI 1.47 to 3.29) as likely to report an influenza infection as those who reported no social participation. In contrast, vaccinated women who participated in two or more social groups had no additional risk of influenza infection as compared with female elders with no social participation. Among men, participation in social activities was not significantly associated with influenza infection, regardless of vaccination status. Social participation was associated with a higher risk of influenza infection among unvaccinated older women, which suggests a need for further efforts to promote influenza vaccination

Immunogenicity and safety of two doses of catch-up immunization with Haemophilus influenzae type b conjugate vaccine in Indian children living with HIV.

Science.gov (United States)

Arya, Bikas K; Bhattacharya, Sangeeta Das; Sutcliffe, Catherine G; Saha, Malay K; Bhattacharyya, Subhasish; Niyogi, Swapan Kumar; Moss, William J; Panda, Samiran; Das, Ranjan Saurav; Mallick, Mausom; Mandal, Sutapa

2016-04-27

Children living with HIV are at increased risk of disease from Haemophilus influenzae type b (Hib). Data are limited on the immunogenicity of a two-dose, catch-up schedule for Hib conjugate vaccine (HibCV) among HIV-infected children accessing antiretroviral therapy (ART) late. The objectives of the study were to: (1) evaluate baseline immunity to Hib and the immunogenicity and safety of two doses of HibCV among HIV-infected Indian children; and (2) document the threshold antibody level required to prevent Hib colonization among HIV-infected children following immunization. We conducted a prospective cohort study among HIV-infected children 2-15 years of age and HIV-uninfected children 2-5 years of age. HIV-infected children received two doses of HibCV and uninfected children received one. Serum anti-Hib PRP IgG antibodies were measured at baseline and two months after immunization in the HIV-infected children. Nasopharyngeal (NP) swabs were collected at baseline and follow-up. 125 HIV-infected and 44 uninfected children participated. 40% of HIV-infected children were receiving ART and 26% had a viral load >100,000 copies/mL. The geometric mean concentration of serum anti-Hib PRP antibody increased from 0.25 μg/mL at baseline to 2.65 μg/mL after two doses of HibCV, representing a 10.6-fold increase (pchildren mounted an immune response. Moderate or severe immune suppression, trimethoprim/sulfamethoxazole prophylaxis, and lower baseline antibody levels were associated with lower post-vaccine serum anti-Hib PRP IgG antibodies. A serum anti-Hib PRP IgG antibody level ≥ 3.3 μg/mL was protective against Hib NP colonization. There were no differences in adverse events between HIV-infected and uninfected children. Including a catch-up immunization schedule for older HIV infected children in countries introducing Hib vaccines is important. Older HIV-infected children with delayed access to ART and without suppressed viral loads mounted an adequate immune response

Avian influenza in shorebirds: experimental infection of ruddy turnstones (Arenaria interpres) with avian influenza virus

OpenAIRE

Hall, Jeffrey S.; Krauss, Scott; Franson, J. Christian; TeSlaa, Joshua L.; Nashold, Sean W.; Stallknecht, David E.; Webby, Richard J.; Webster, Robert G.

2012-01-01

Please cite this paper as: Hall et al. (2012) Avian influenza in shorebirds: experimental infection of ruddy turnstones (Arenaria interpres) with avian influenza virus. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2012.00358.x. Background  Low pathogenic avian influenza viruses (LPAIV) have been reported in shorebirds, especially at Delaware Bay, USA, during spring migration. However, data on patterns of virus excretion, minimal infectious doses, and clinical outcome are l...

Prospective study of avian influenza virus infections among rural Thai villagers.

Directory of Open Access Journals (Sweden)

Whitney S Krueger

Full Text Available In 2008, 800 rural Thai adults living within Kamphaeng Phet Province were enrolled in a prospective cohort study of zoonotic influenza transmission. Serological analyses of enrollment sera suggested this cohort had experienced subclinical avian influenza virus (AIV infections with H9N2 and H5N1 viruses.After enrollment, participants were contacted weekly for 24 mos for acute influenza-like illnesses (ILI. Cohort members confirmed to have influenza A infections were enrolled with their household contacts in a family transmission study involving paired sera and respiratory swab collections. Cohort members also provided sera at 12 and 24 months after enrollment. Serologic and real-time RT-PCR assays were performed against avian, swine, and human influenza viruses.Over the 2 yrs of follow-up, 81 ILI investigations in the cohort were conducted; 31 (38% were identified as influenza A infections by qRT-PCR. Eighty-three household contacts were enrolled; 12 (14% reported ILIs, and 11 (92% of those were identified as influenza infections. A number of subjects were found to have slightly elevated antibodies against avian-like A/Hong Kong/1073/1999(H9N2 virus: 21 subjects (2.7% at 12-months and 40 subjects (5.1% at 24-months. Among these, two largely asymptomatic acute infections with H9N2 virus were detected by >4-fold increases in annual serologic titers (final titers 1:80. While controlling for age and influenza vaccine receipt, moderate poultry exposure was significantly associated with elevated H9N2 titers (adjusted OR = 2.3; 95% CI, 1.04-5.2 at the 24-month encounter. One subject had an elevated titer (1:20 against H5N1 during follow-up.From 2008-10, evidence for AIV infections was sparse among this rural population. Subclinical H9N2 AIV infections likely occurred, but serological results were confounded by antibody cross-reactions. There is a critical need for improved serological diagnostics to more accurately detect subclinical AIV infections in

Prospective study of avian influenza virus infections among rural Thai villagers.

Science.gov (United States)

Krueger, Whitney S; Khuntirat, Benjawan; Yoon, In-Kyu; Blair, Patrick J; Chittagarnpitch, Malinee; Putnam, Shannon D; Supawat, Krongkaew; Gibbons, Robert V; Bhuddari, Darunee; Pattamadilok, Sirima; Sawanpanyalert, Pathom; Heil, Gary L; Gray, Gregory C

2013-01-01

In 2008, 800 rural Thai adults living within Kamphaeng Phet Province were enrolled in a prospective cohort study of zoonotic influenza transmission. Serological analyses of enrollment sera suggested this cohort had experienced subclinical avian influenza virus (AIV) infections with H9N2 and H5N1 viruses. After enrollment, participants were contacted weekly for 24 mos for acute influenza-like illnesses (ILI). Cohort members confirmed to have influenza A infections were enrolled with their household contacts in a family transmission study involving paired sera and respiratory swab collections. Cohort members also provided sera at 12 and 24 months after enrollment. Serologic and real-time RT-PCR assays were performed against avian, swine, and human influenza viruses. Over the 2 yrs of follow-up, 81 ILI investigations in the cohort were conducted; 31 (38%) were identified as influenza A infections by qRT-PCR. Eighty-three household contacts were enrolled; 12 (14%) reported ILIs, and 11 (92%) of those were identified as influenza infections. A number of subjects were found to have slightly elevated antibodies against avian-like A/Hong Kong/1073/1999(H9N2) virus: 21 subjects (2.7%) at 12-months and 40 subjects (5.1%) at 24-months. Among these, two largely asymptomatic acute infections with H9N2 virus were detected by >4-fold increases in annual serologic titers (final titers 1:80). While controlling for age and influenza vaccine receipt, moderate poultry exposure was significantly associated with elevated H9N2 titers (adjusted OR = 2.3; 95% CI, 1.04-5.2) at the 24-month encounter. One subject had an elevated titer (1:20) against H5N1 during follow-up. From 2008-10, evidence for AIV infections was sparse among this rural population. Subclinical H9N2 AIV infections likely occurred, but serological results were confounded by antibody cross-reactions. There is a critical need for improved serological diagnostics to more accurately detect subclinical AIV infections in humans.

Localization of influenza virus proteins to nuclear dot 10 structures in influenza virus-infected cells

International Nuclear Information System (INIS)

Sato, Yoshiko; Yoshioka, Kenichi; Suzuki, Chie; Awashima, Satoshi; Hosaka, Yasuhiro; Yewdell, Jonathan; Kuroda, Kazumichi

2003-01-01

We studied influenza virus M1 protein by generating HeLa and MDCK cell lines that express M1 genetically fused to green fluorescent protein (GFP). GFP-M1 was incorporated into virions produced by influenza virus infected MDCK cells expressing the fusion protein indicating that the fusion protein is at least partially functional. Following infection of either HeLa or MDCK cells with influenza A virus (but not influenza B virus), GFP-M1 redistributes from its cytosolic/nuclear location and accumulates in nuclear dots. Immunofluorescence revealed that the nuclear dots represent nuclear dot 10 (ND10) structures. The colocalization of authentic M1, as well as NS1 and NS2 protein, with ND10 was confirmed by immunofluorescence following in situ isolation of ND10. These findings demonstrate a previously unappreciated involvement of influenza virus with ND10, a structure involved in cellular responses to immune cytokines as well as the replication of a rapidly increasing list of viruses

Antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and group A beta-haemolytic streptococci in 2002-2003. Results of the multinational GRASP Surveillance Program

DEFF Research Database (Denmark)

Beekmann, Susan E; Heilmann, Kris P; Richter, Sandra S

2005-01-01

A multinational surveillance study, GRASP, was conducted between November 2002 and April 2003 with the aim of assessing rates of antimicrobial resistance among 2656 isolates of Streptococcus pneumoniae, 2486 isolates of group A beta-haemolytic streptococci, 1358 isolates of Haemophilus influenzae...... and 1047 of Moraxella catarrhalis from 20 countries in Europe, eastern Asia and southern Africa. Conspicuous differences between various countries were noted in the S. pneumoniae resistance rates observed for penicillin (0-79.2%) and erythromycin (4-66%), along with other antimicrobials. The percentage...... of MDR strains was above 25% in 8 of the 20 countries studied. Group A streptococcal macrolide resistance rates ranged from 0% to 35% by country, while rates of beta-lactamase production ranged from 0% to 39% for H. influenzae and 80-100% for M. catarrhalis. Antibiotic resistance in S. pneumoniae remains...

Recurrent meningitis due to pneumococci and non-typable Haemophilus influenzae in a child with a Mondini malformation.

Science.gov (United States)

Valmari, P; Palva, A

1986-01-01

An eight-year-old boy with a congenital inner ear malformation and recurrent otitis media had three episodes of bacteriologically confirmed meningitis within seven months. The first episode was caused by pneumococci, the other two by non-typable Haemophilus influenzae. All episodes were characterized by an abrupt onset. The CSF cultures were positive within 0.5 to 12 hours after the onset of symptoms. Despite misleading laboratory studies, surgical exploration revealed a CSF fistula associated to the inner ear anomaly. No further episodes occurred after the fistula was closed. Careful roentgenographic evaluation, including recently introduced special computed tomography (CT) methods, is indicated in recurrent meningitis. In addition, such evaluations should be considered even after the first episode, when special clinical features suggest a CSF fistula. Such features include an extremely rapid onset and detection of common non-invasive bacteria as causative agents, as illustrated by the present case.

Development and Validation of a Multiplex PCR-Based Assay for the Upper Respiratory Tract Bacterial Pathogens Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis.

Science.gov (United States)

Post; White; Aul; Zavoral; Wadowsky; Zhang; Preston; Ehrlich

1996-06-01

Background: Conventional simplex polymerase chain reaction (PCR)-based assays are limited in that they only provide for the detection of a single infectious agent. Many clinical diseases, however, present in a nonspecific, or syndromic, fashion, thereby necessitating the simultaneous assessment of multiple pathogens. Panel-based molecular diagnostic testing can be accomplished by the development of multiplex PCR-based assays, which can detect, individually or severally, different pathogens that are associated with syndromic illness. As part of a larger program of panel development, an assay that can simultaneously detect Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis was developed. These organisms were chosen as they are the most common bacterial pathogens associated with both the acute and chronic forms of otitis media; they are also responsible for a high percentage of sinus infections in both children and adults. In addition, H. influenzae and S. pneumoniae are commonly associated with septic meningitits. Methods and Results: Multiple individual PCR-based assays were developed for each of the three target organisms which were then evaluated for sensitivity and specificity. Utilizing the simplex assays that met our designated performance criteria, a matrix style approach was used to develop a duplex H. influenzae-S. pneumoniae assay. The duplex assay was then used as a single component in the development of a triplex assay, wherein the various M. catarrhalis primer-probe sets were tested for compatibility with the existing assay. A single-step PCR protocol, with species-specific primers for each of the three target organisms and a liquid hybridization-gel retardation amplimer detection system, was developed, which amplifies and then discriminates among each of the amplification products according to size. This assay is able to detect all three organisms in a specific manner, either individually or severally. Dilutional experiments

Non-epitope-specific suppression of the antibody response to Haemophilus influenzae type b conjugate vaccines by preimmunization with vaccine components

DEFF Research Database (Denmark)

Barington, T; Skettrup, M; Juul, L

1993-01-01

children and adults. Despite its potential importance, the possible influence of preexisting immunity to the components of such conjugates on the vaccination response in humans has been addressed by few studies. To study this issue, we randomized 82 healthy adult volunteers into six groups and vaccinated......Recently, conjugate vaccines containing Haemophilus influenzae type b capsular polysaccharide (HibCP) coupled to protein carriers were introduced for use in infants and certain adult risk groups. Similar conjugate vaccines against other capsulated bacteria are currently under development for both......CP-TT, P = 0.00002; HibCP-TT and then HibCP-DT, P = 0.06) as well as to HibCP itself. Possible mechanisms behind this non-epitope-specific suppression and its relevance for vaccine development are discussed....

[Contemporary threat of influenza virus infection].

Science.gov (United States)

Płusa, Tadeusz

2010-01-01

Swine-origine H1N1 influenza virus (S-OIV) caused a great mobilization of health medical service over the world. Now it is well known that a vaccine against novel virus is expected as a key point in that battle. In the situation when recommended treatment with neuraminidase inhibitors is not sufficient to control influenza A/H1N1 viral infection the quick and precisely diagnostic procedures should be applied to save and protect our patients.

Beta- Lactam Antibiotics Stimulate Biofilm Formation in Non-Typeable Haemophilus influenzae by Up-Regulating Carbohydrate Metabolism

Science.gov (United States)

Wu, Siva; Li, Xiaojin; Gunawardana, Manjula; Maguire, Kathleen; Guerrero-Given, Debbie; Schaudinn, Christoph; Wang, Charles; Baum, Marc M.; Webster, Paul

2014-01-01

Non-typeable Haemophilus influenzae (NTHi) is a common acute otitis media pathogen, with an incidence that is increased by previous antibiotic treatment. NTHi is also an emerging causative agent of other chronic infections in humans, some linked to morbidity, and all of which impose substantial treatment costs. In this study we explore the possibility that antibiotic exposure may stimulate biofilm formation by NTHi bacteria. We discovered that sub-inhibitory concentrations of beta-lactam antibiotic (i.e., amounts that partially inhibit bacterial growth) stimulated the biofilm-forming ability of NTHi strains, an effect that was strain and antibiotic dependent. When exposed to sub-inhibitory concentrations of beta-lactam antibiotics NTHi strains produced tightly packed biofilms with decreased numbers of culturable bacteria but increased biomass. The ratio of protein per unit weight of biofilm decreased as a result of antibiotic exposure. Antibiotic-stimulated biofilms had altered ultrastructure, and genes involved in glycogen production and transporter function were up regulated in response to antibiotic exposure. Down-regulated genes were linked to multiple metabolic processes but not those involved in stress response. Antibiotic-stimulated biofilm bacteria were more resistant to a lethal dose (10 µg/mL) of cefuroxime. Our results suggest that beta-lactam antibiotic exposure may act as a signaling molecule that promotes transformation into the biofilm phenotype. Loss of viable bacteria, increase in biofilm biomass and decreased protein production coupled with a concomitant up-regulation of genes involved with glycogen production might result in a biofilm of sessile, metabolically inactive bacteria sustained by stored glycogen. These biofilms may protect surviving bacteria from subsequent antibiotic challenges, and act as a reservoir of viable bacteria once antibiotic exposure has ended. PMID:25007395

[Clinical evaluations of flomoxef in respiratory tract infections].

Science.gov (United States)

Mikasa, K; Sawaki, M; Ako, H; Narita, N

1987-10-01

Flomoxef (FMOX, 6315-S), a new antibacterial drug, was administered to 9 cases with respiratory tract infections for a duration of 8 approximately 16 days at a daily dose of 2 g. Diagnosis of these patients were bronchopneumonia 5 cases, chronic bronchitis 3 cases and acute bronchitis 1 case. From transtracheal aspiration several organisms were isolated; Haemophilus influenzae was isolated in 3 cases, Streptococcus pneumoniae in 3 cases, H. influenzae plus Branhamella catarrhalis in 1 case, Streptococcus dysgalactiae plus Neisseria meningitidis in 1 case and Corynebacterium pseudodiphtheriticum in 1 case. The clinical efficacy was good in all 9 cases, the efficacy rate was 100%. All the bacteria were eliminated. Side effects were not observed. From these results, it appears that FMOX is a valuable drug in the treatment of respiratory tract infections.

Genetic Reassortment Among the Influenza Viruses (Avian Influenza, Human Influenza and Swine Influenza in Pigs

Directory of Open Access Journals (Sweden)

Dyah Ayu Hewajuli

2012-12-01

Full Text Available Influenza A virus is a hazardous virus and harm to respiratory tract. The virus infect birds, pigs, horses, dogs, mammals and humans. Pigs are important hosts in ecology of the influenza virus because they have two receptors, namely NeuAc 2,3Gal and NeuAc 2,6Gal which make the pigs are sensitive to infection of influenza virus from birds and humans and genetic reassortment can be occurred. Classical swine influenza H1N1 viruses had been circulated in pigs in North America and other countries for 80 years. In 1998, triple reassortant H3N2 swine influenza viruses that contains genes of human influenza A virus (H3N2, swine influenza virus (H1N1 and avian influenza are reported as cause an outbreaks in pigs in North America. Furthermore, the circulation of triple reassortant H3N2 swine influenza virus resulting reassortant H1N1 swine influenza and reassortant H1N2 swine influenza viruses cause infection in humans. Humans who were infected by triple reassortant swine influenza A virus (H1N1 usually made direct contact with pigs. Although without any clinical symptoms, pigs that are infected by triple reassortant swine influenza A (H1N1 can transmit infection to the humans around them. In June 2009, WHO declared that pandemic influenza of reassortant H1N1 influenza A virus (novel H1N1 has reached phase 6. In Indonesia until 2009, there were 1005 people were infected by H1N1 influenza A and 5 of them died. Novel H1N1 and H5N1 viruses have been circulated in humans and pigs in Indonesia. H5N1 reassortant and H1N1 viruses or the seasonal flu may could arise because of genetic reassortment between avian influenza and humans influenza viruses that infect pigs together.

Avian influenza in shorebirds: experimental infection of ruddy turnstones (Arenaria interpres) with avian influenza virus

Science.gov (United States)

Hall, Jeffrey S.; Krauss, Scott; Franson, J. Christian; TeSlaa, Joshua L.; Nashold, Sean W.; Stallknecht, David E.; Webby, Richard J.; Webster, Robert G.

2013-01-01

Background: Low pathogenic avian influenza viruses (LPAIV) have been reported in shorebirds, especially at Delaware Bay, USA, during spring migration. However, data on patterns of virus excretion, minimal infectious doses, and clinical outcome are lacking. The ruddy turnstone (Arenaria interpres) is the shorebird species with the highest prevalence of influenza virus at Delaware Bay. Objectives: The primary objective of this study was to experimentally assess the patterns of influenza virus excretion, minimal infectious doses, and clinical outcome in ruddy turnstones. Methods: We experimentally challenged ruddy turnstones using a common LPAIV shorebird isolate, an LPAIV waterfowl isolate, or a highly pathogenic H5N1 avian influenza virus. Cloacal and oral swabs and sera were analyzed from each bird. Results: Most ruddy turnstones had pre-existing antibodies to avian influenza virus, and many were infected at the time of capture. The infectious doses for each challenge virus were similar (103·6–104·16 EID50), regardless of exposure history. All infected birds excreted similar amounts of virus and showed no clinical signs of disease or mortality. Influenza A-specific antibodies remained detectable for at least 2 months after inoculation. Conclusions: These results provide a reference for interpretation of surveillance data, modeling, and predicting the risks of avian influenza transmission and movement in these important hosts.

Epidemiology of paediatric meningitis in central Côte d'Ivoire after the implementation of Haemophilus influenzae type b vaccination.

Science.gov (United States)

Touré, Fidèle S; Kouame, Samson; Tia, Honoré; Monemo, Pacôme; Cissé, Amadou; Diané, Bamourou; Becker, Sören L; Akoua-Koffi, Chantal

2017-07-01

Infectious meningitis accounts for enormous morbidity worldwide, but there is a paucity of data on its regional epidemiology in resource-constrained settings of sub-Saharan Africa. Here, we present a study on the aetiology of paediatric meningitis in central Côte d'Ivoire. Between June 2012 and December 2013, all cerebrospinal fluid (CSF) samples drawn at the University Teaching Hospital Bouaké were examined for the presence of bacterial and fungal pathogens. A causative agent was detected in 31 out of 833 CSF specimens (3.7%), with the most prevalent pathogens being Streptococcus pneumoniae (n=15) and Neisseria meningitidis (n=5). With the exception of neonates, these two bacteria were the most common agents in all age groups. Of note, only a single case of Haemophilus influenzae meningitis was detected. Hence, this study reports a considerable shift in the epidemiology of paediatric meningitis in central Côte d'Ivoire. Following the implementation of a nation-wide childhood vaccination programme against H. influenzae type b, this pathogen was much less frequently reported than in previous studies. The integration of specific vaccines against S. pneumoniae and N. meningitidis into the childhood vaccination programme in Côted'Ivoire holds promise to further reduce the burden due to infectious meningitis.

Safety and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTPa-IPV/Hib) vaccine in healthy Vietnamese toddlers: An open-label, phase III study.

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Anh, Dang Duc; Van Der Meeren, Olivier; Karkada, Naveen; Assudani, Deepak; Yu, Ta-Wen; Han, Htay Htay

2016-03-03

The introduction of combination vaccines plays a significant role in increasing vaccine acceptance and widening vaccine coverage. Primary vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenza type b (Hib) diseases has been implemented in Vietnam. In this study we evaluated the safety and reactogenicity of combined diphtheria-tetanus-pertussis-inactivated polio (DTPa-IPV)/Hib vaccine when administered as a booster dose in 300 healthy Vietnamese children Vietnamese children aged <2 years.

Characterization of the N-Acetyl-5-neuraminic Acid-binding Site of the Extracytoplasmic Solute Receptor (SiaP) of Nontypeable Haemophilus influenzae Strain 2019

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Johnston, Jason W.; Coussens, Nathan P.; Allen, Simon; Houtman, Jon C.D.; Turner, Keith H.; Zaleski, Anthony; Ramaswamy, S.; Gibson, Bradford W.; Apicella, Michael A. (Iowa); (Buck Inst.)

2012-11-14

Nontypeable Haemophilus influenzae is an opportunistic human pathogen causing otitis media in children and chronic bronchitis and pneumonia in patients with chronic obstructive pulmonary disease. The outer membrane of nontypeable H. influenzae is dominated by lipooligosaccharides (LOS), many of which incorporate sialic acid as a terminal nonreducing sugar. Sialic acid has been demonstrated to be an important factor in the survival of the bacteria within the host environment. H. influenzae is incapable of synthesizing sialic acid and is dependent on scavenging free sialic acid from the host environment. To achieve this, H. influenzae utilizes a tripartite ATP-independent periplasmic transporter. In this study, we characterize the binding site of the extracytoplasmic solute receptor (SiaP) from nontypeable H. influenzae strain 2019. A crystal structure of N-acetyl-5-neuraminic acid (Neu5Ac)-bound SiaP was determined to 1.4 {angstrom} resolution. Thermodynamic characterization of Neu5Ac binding shows this interaction is enthalpically driven with a substantial unfavorable contribution from entropy. This is expected because the binding of SiaP to Neu5Ac is mediated by numerous hydrogen bonds and has several buried water molecules. Point mutations targeting specific amino acids were introduced in the putative binding site. Complementation with the mutated siaP constructs resulted either in full, partial, or no complementation, depending on the role of specific residues. Mass spectrometry analysis of the O-deacylated LOS of the R127K point mutation confirmed the observation of reduced incorporation of Neu5Ac into the LOS. The decreased ability of H. influenzae to import sialic acid had negative effects on resistance to complement-mediated killing and viability of biofilms in vitro, confirming the importance of sialic acid transport to the bacterium.

The Role of α-Defensins 1–3 in Antimicrobial Protection Forming in Children with Recurrent Bronchitis Caused by Bacteria of the Genus Haemophilus

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G.O. Lezhenko

2013-03-01

Full Text Available The level of α-defensins 1–3 (HNP 1–3 has been analyzed in the blood plasma of children with recurrent bronchitis caused by bacteria of the genus Haemophilus. It is shown that the level of HNP 1–3 in the blood plasma depends on the form of Haemophilus. Trigger of HNP 1–3 outflow for neutrophils was the presence of bacterial capsule while presence of L-forms of Haemophilus influenzae wasn’t associated with increase in synthesis of antimicrobial peptides that could be one of the factors of forming of Haemophilus antibiotic resistance.

Erythromycin and azithromycin transport into Haemophilus influenzae ATCC 19418 under conditions of depressed proton motive force (delta mu H)

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Capobianco, J.O.; Goldman, R.C. (Abbott Laboratories, IL (USA))

1990-09-01

The effect of collapsing the electrochemical proton gradient (delta mu H) on ({sup 3}H)erythromycin and ({sup 14}C)azithromycin transport in Haemophilus influenzae ATCC 19418 was studied. The proton gradient and membrane potential were determined from the distribution of (2-{sup 14}C)dimethadione and rubidium-86, respectively. delta mu H was reduced from 124 to 3 mV in EDTA-valinomycin-treated cells at 22{degrees}C with 150 mM KCl and 0.1 mM carbonyl cyanide m-chlorophenylhydrazone. During the collapse of delta mu H, macrolide uptake increased. Erythromycin efflux studies strongly suggested that this increase was not due to an energy-dependent efflux pump but was likely due to increased outer membrane permeability. These data indicated that macrolide entry was not a delta mu H-driven active transport process but rather a passive diffusion process.

Control of mucosal virus infection by influenza nucleoprotein-specific CD8+ cytotoxic T lymphocytes

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Couch Robert B

2007-06-01

Full Text Available Abstract Background MHC class I-restricted CD8+ cytotoxic T lymphocytes (CTL are thought to play a major role in clearing virus and promoting recovery from influenza infection and disease. This has been demonstrated for clearance of influenza virus from the lungs of infected mice. However, human influenza infection is primarily a respiratory mucosal infection involving the nasopharynx and tracheobronchial tree. The role of CD8+ CTL directed toward the influenza nucleoprotein (NP in defense against influenza virus infection at the respiratory mucosa was evaluated in two separate adoptive transfer experiments. Methods Influenza nucleoprotein (NP-specific CD8+ CTL were generated from splenocytes obtained from Balb/c mice previously primed with influenza A/Taiwan/1/86 (H1N1 infection or with influenza A/PR/8/34 (H1N1-derived NP plasmid DNA vaccine followed by infection with A/Hong Kong/68 (H3N2 virus. After in vitro expansion by exposure to an influenza NP-vaccinia recombinant, highly purified CD8+ T cells exhibited significant lysis in vitro of P815 target cells infected with A/Hong Kong/68 (H3N2 virus while the CD8- fraction (CD4+ T cells, B cells and macrophages had no CTL activity. Purified CD8+ and CD8- T cells (1 × 107 were injected intravenously or interperitoneally into naive mice four hours prior to intranasal challenge with A/HK/68 (H3N2 virus. Results The adoptively transferred NP-vaccinia-induced CD8+ T cells caused significant reduction of virus titers in both the lungs and nasal passages when compared to CD8- cells. Neither CD8+ nor CD8- T cells from cultures stimulated with HIV gp120-vaccinia recombinant reduced virus titers. Conclusion The present data demonstrate that influenza NP-specific CD8+ CTL can play a direct role in clearance of influenza virus from the upper respiratory mucosal surfaces.

Comparison of radiometric and conventional culture systems in detecting Haemophilus influenzae type b bacteremia in rats

International Nuclear Information System (INIS)

Mitchell, M.J.; Zwahlen, A.; Elliott, H.L.; Ford, N.K.; Charache, F.P.; Moxon, E.R.

1985-01-01

To compare the efficiency of detecting Haemophilus influenzae type b bacteremia by the BACTEC radiometric system and a conventional Trypticase soy broth blood culture system, the authors developed an in vivo model of bacteremia in rats. After intravenous injection of 50 to 200 CFU into adult rats, there was a linear logarithmic increase in CFU per milliliter of rat blood during the first 10 h (r = 0.98), allowing accurate prediction of the level of bacteremia with time. Culture bottles were inoculated with 0.5 ml of blood obtained by cardiac puncture and processed as clinical samples in the microbiology laboratory with RS and conventional protocols. They found the following. (i) The first detection of bacteremia by RS was similar to that by TSB if a Gram stain of the TSB was done on day 1 and was superior if that smear was omitted (P less than 0.01). (ii) The detection times in both systems were comparable at different magnitudes of bacteremia (10(1) to 10(4) CFU/ml). (iii) Supplementation of inoculated bottles with 2 ml of sterile rat blood interfered with Gram stain detection in TSB but resulted in increased 14 CO 2 production in RS. (iv) No difference in detection time was found between RS and TSB for four different clinical isolates. These studies show that, in a biologically relevant model, the detection of positive blood cultures for H. influenzae type b by RS was comparable to or better than detection by TSB when blood was processed analogously to clinical specimens

Reliability of Haemophilus influenzae biofilm measurement via static method, and determinants of in vitro biofilm production.

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Obaid, Najla A; Tristram, Stephen; Narkowicz, Christian K; Jacobson, Glenn A

2016-12-01

Information is lacking regarding the precision of microtitre plate (MTP) assays used to measure biofilm. This study investigated the precision of an MTP assay to measure biofilm production by nontypeable Haemophilus influenzae (NTHi) and the effects of frozen storage and inoculation technique on biofilm production. The density of bacterial final growth was determined by absorbance after 18-20 h incubation, and biofilm production was then measured by absorbance after crystal violet staining. Biofilm formation was categorised as high and low for each strain. For the high biofilm producing strains of NTHi, interday reproducibility of NTHi biofilm formation measured using the MTP assay was excellent and met the acceptance criteria, but higher variability was observed in low biofilm producers. Method of inoculum preparation was a determinant of biofilm formation with inoculum prepared directly from solid media showing increased biofilm production for at least one of the high producing strains. In general, storage of NTHi cultures at -80 °C for up to 48 weeks did not have any major effect on their ability to produce biofilm.

Targeting Metabolic Reprogramming by Influenza Infection for Therapeutic Intervention

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Heather S. Smallwood

2017-05-01

Full Text Available Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production. BEZ235 treatment ablated the transient induction of c-Myc, restored PI3K/mTOR pathway homeostasis measured by 4E-BP1 and p85 phosphorylation, and reversed infection-induced changes in metabolism. Importantly, BEZ235 reduced infectious progeny but had no effect on the early stages of viral replication. BEZ235 significantly increased survival in mice, while reducing viral titer. We show metabolic reprogramming of host cells by influenza virus exposes targets for therapeutic intervention.

Targeting Metabolic Reprogramming by Influenza Infection for Therapeutic Intervention

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Smallwood, Heather S.; Duan, Susu; Morfouace, Marie; Rezinciuc, Svetlana; Shulkin, Barry L.; Shelat, Anang; Zink, Erika E.; Milasta, Sandra; Bajracharya, Resha; Oluwaseum, Ajayi J.; Roussel, Martine F.; Green, Douglas R.; Pasa-Tolic, Ljiljana; Thomas, Paul G.

2017-05-01

Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production. BEZ235 treatment ablated the transient induction of c-Myc, restored PI3K/mTOR pathway homeostasis measured by 4E-BP1 and p85 phosphorylation, and reversed infection-induced changes in metabolism. Importantly, BEZ235 reduced infectious progeny but had no effect on the early stages of viral replication. BEZ235 significantly increased survival in mice, while reducing viral titer. We show metabolic reprogramming of host cells by influenza virus exposes targets for therapeutic intervention.

Burden of pediatric influenza A virus infection post swine-flu H1N1 pandemic in Egypt.

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Khattab, Adel; Shaheen, Malak; Kamel, Terez; El Faramay, Amel; El Rahman, Safaa Abd; Nabil, Dalia; Gouda, Mohamed

2013-09-01

To screen children with influenza like illness or with symptoms of acute respiratory tract infections for influenza A virus infection - post swine flu pandemic era - using rapid influenza diagnostic tests. During two years (2010 & 2011), 1 200 children with influenza like illness or acute respiratory tract infections (according to World Health Organization criteria) were recruited. Their ages ranged from 2-60 months. Nasopharyngeal aspirates specimens were collected from all children for rapid influenza A diagnostic test. Influenza A virus rapid test was positive in 47.5% of the children; the majority (89.6%) were presented with lower respiratory tract infections. Respiratory rate and temperature were significantly higher among positive rapid influenza test patients. Influenza A virus infection is still a major cause of respiratory tract infections in Egyptian children. It should be considered in all cases with cough and febrile episodes and influenza like symptoms even post swine flu pandemic. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Eosinophils Promote Antiviral Immunity in Mice Infected with Influenza A Virus.

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Samarasinghe, Amali E; Melo, Rossana C N; Duan, Susu; LeMessurier, Kim S; Liedmann, Swantje; Surman, Sherri L; Lee, James J; Hurwitz, Julia L; Thomas, Paul G; McCullers, Jonathan A

2017-04-15

Eosinophils are multifunctional cells of the innate immune system linked to allergic inflammation. Asthmatics were more likely to be hospitalized but less likely to suffer severe morbidity and mortality during the 2009 influenza pandemic. These epidemiologic findings were recapitulated in a mouse model of fungal asthma wherein infection during heightened allergic inflammation was protective against influenza A virus (IAV) infection and disease. Our goal was to delineate a mechanism(s) by which allergic asthma may alleviate influenza disease outcome, focused on the hypothesis that pulmonary eosinophilia linked with allergic respiratory disease is able to promote antiviral host defenses against the influenza virus. The transfer of eosinophils from the lungs of allergen-sensitized and challenged mice into influenza virus-infected mice resulted in reduced morbidity and viral burden, improved lung compliance, and increased CD8 + T cell numbers in the airways. In vitro assays with primary or bone marrow-derived eosinophils were used to determine eosinophil responses to the virus using the laboratory strain (A/PR/08/1934) or the pandemic strain (A/CA/04/2009) of IAV. Eosinophils were susceptible to IAV infection and responded by activation, piecemeal degranulation, and upregulation of Ag presentation markers. Virus- or viral peptide-exposed eosinophils induced CD8 + T cell proliferation, activation, and effector functions. Our data suggest that eosinophils promote host cellular immunity to reduce influenza virus replication in lungs, thereby providing a novel mechanism by which hosts with allergic asthma may be protected from influenza morbidity. Copyright © 2017 by The American Association of Immunologists, Inc.

Human Infection with Avian Influenza A(H7N9) Virus - China

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... response operations Diseases Biorisk reduction Disease outbreak news Human infection with avian influenza A(H7N9) virus – China ... Region (SAR) notified WHO of a laboratory-confirmed human infection with avian influenza A(H7N9) virus and ...

In vitro selection of resistance in haemophilus influenzae by 4 quinolones and 5 beta-lactams.

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Clark, Catherine; Kosowska, Klaudia; Bozdogan, Bülent; Credito, Kim; Dewasse, Bonifacio; McGhee, Pamela; Jacobs, Michael R; Appelbaum, Peter C

2004-05-01

We tested abilities of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, amoxicillin, amoxicillin/clavulanate, cefixime, cefpodoxime, and cefdinir to select resistant mutants in 5 beta-lactamase positive and 5 beta-lactamase negative Haemophilus influenzae strains by single and multistep methodology. In multistep tests, amoxicillin, amoxicillin/clavulanate and cefpodoxime exposure did not cause >4-fold minimum inhibitory concentration (MIC) increase after 50 days. One mutant selected by cefdinir had one amino acid substitution (Gly490Glu) in PBP3 and became resistant to cefdinir. Cefixime exposure caused 8-fold MIC-increase in 1 strain with TEM but the mutant remained cefixime susceptible and had no alteration in PBP3 or TEM. Among 10 strains tested, ciprofloxacin, moxifloxacin, gatifloxacin, levofloxacin caused >4-fold MIC increase in 6, 6, 5, and 2 strain, respectively. Despite the increases in quinolone MICs, none of the mutants became resistant to quinolones by established criteria. Quinolone selected mutants had quindone resistance-determining region (QRDR) alterations in GyrA, GyrB, ParC, ParE. Four quinolone mutants had no QRDR alterations. Among beta-lactams cefdinir and cefixime selected one mutant each with higher MICs however amoxicillin, amoxicillin/clavulanate, and cefpodoxime exposure did not select resistant mutants.

Reduction of Influenza Virus Titer and Protection against Influenza Virus Infection in Infant Mice Fed Lactobacillus casei Shirota

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Yasui, Hisako; Kiyoshima, Junko; Hori, Tetsuji

2004-01-01

We investigated whether oral administration of Lactobacillus casei strain Shirota to neonatal and infant mice ameliorates influenza virus (IFV) infection in the upper respiratory tract and protects against influenza infection. In a model of upper respiratory IFV infection, the titer of virus in the nasal washings of infant mice administered L. casei Shirota (L. casei Shirota group) was significantly (P < 0.05) lower than that in infant mice administered saline (control group) (102.48 ± 100.31...

H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination.

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M Anthony Moody

Full Text Available BACKGROUND: During the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history of recent seasonal trivalent vaccine in younger adults was not associated with protection. METHODS AND FINDINGS: To study hemagglutinin (HA antibody responses in influenza immunization and infection, we have studied the day 7 plasma cell repertoires of subjects immunized with seasonal trivalent inactivated influenza vaccine (TIV and compared them to the plasma cell repertoires of subjects experimentally infected (EI with influenza H3N2 A/Wisconsin/67/2005. The majority of circulating plasma cells after TIV produced influenza-specific antibodies, while most plasma cells after EI produced antibodies that did not react with influenza HA. While anti-HA antibodies from TIV subjects were primarily reactive with single or few HA strains, anti-HA antibodies from EI subjects were isolated that reacted with multiple HA strains. Plasma cell-derived anti-HA antibodies from TIV subjects showed more evidence of clonal expansion compared with antibodies from EI subjects. From an H3N2-infected subject, we isolated a 4-member clonal lineage of broadly cross-reactive antibodies that bound to multiple HA subtypes and neutralized both H1N1 and H3N2 viruses. This broad reactivity was not detected in post-infection plasma suggesting this broadly reactive clonal lineage was not immunodominant in this subject. CONCLUSION: The presence of broadly reactive subdominant antibody responses in some EI subjects suggests that improved vaccine designs that make broadly reactive antibody responses immunodominant could protect against novel influenza strains.

Radiologic findings of childhood lower respiratory tract infection by influenza virus

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Song, Ho Taek; Park, Choong Ki; Shin, Hee Jung; Choi, Yo Won; Jeon, Seok Chol; Hahm, Chang Kok; Hern, Ahn You [Hanyang University College of Medicine, Seoul (Korea, Republic of)

2002-08-01

After the RS (respiratory syncytial) virus, the influenza virus is the most common cause of childhood lower respiratory tract infection. We assessed the radiologic findings of childhood lower respiratory tract infection by the influenza virus. A total of 105 pediatric patients (76 males and 29 females; mean age, 2.4 years) with symptoms of respiratory tract infection were examined between March 1997 and April 2000. Nasopharyngeal aspirates were obtained and influenza virus infection was confirmed by direct or indirect immunofluorescent assays. Peribronchial infiltration, hyperinflation, atelectasis, pulmonary consolidation, and hilar lymphadenopathy were evaluated retrospectively at simple chest radiography. Bilateral perihiler peribronchial infiltration was noted in 78.1% of patients (n=82), hyperinflation in 63.8% (n=67), atelectasis in 3.8% (n=4, segmental 50%, lobar 50%), and pulmonary consolidation in 16.2% [n=17; segmental 70.6% (n=12), lobar 29.4% (n=5)]. Hilar lymphadenopathy was noted in one patient in whom there was no pleural effusion, and subglottic airway narrowing in 12 of 14 in whom the croup symptom complex was present. The major radiologic findings of influenza virus infection were bilateral perihilar peribronchial infiltration and hyperinflation. In some patients, upper respiratory tract infection was combined with subgolttic airway narrowing. Atelectasis or pleural effusion was rare.

Beta- lactam antibiotics stimulate biofilm formation in non-typeable haemophilus influenzae by up-regulating carbohydrate metabolism.

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Siva Wu

Full Text Available Non-typeable Haemophilus influenzae (NTHi is a common acute otitis media pathogen, with an incidence that is increased by previous antibiotic treatment. NTHi is also an emerging causative agent of other chronic infections in humans, some linked to morbidity, and all of which impose substantial treatment costs. In this study we explore the possibility that antibiotic exposure may stimulate biofilm formation by NTHi bacteria. We discovered that sub-inhibitory concentrations of beta-lactam antibiotic (i.e., amounts that partially inhibit bacterial growth stimulated the biofilm-forming ability of NTHi strains, an effect that was strain and antibiotic dependent. When exposed to sub-inhibitory concentrations of beta-lactam antibiotics NTHi strains produced tightly packed biofilms with decreased numbers of culturable bacteria but increased biomass. The ratio of protein per unit weight of biofilm decreased as a result of antibiotic exposure. Antibiotic-stimulated biofilms had altered ultrastructure, and genes involved in glycogen production and transporter function were up regulated in response to antibiotic exposure. Down-regulated genes were linked to multiple metabolic processes but not those involved in stress response. Antibiotic-stimulated biofilm bacteria were more resistant to a lethal dose (10 µg/mL of cefuroxime. Our results suggest that beta-lactam antibiotic exposure may act as a signaling molecule that promotes transformation into the biofilm phenotype. Loss of viable bacteria, increase in biofilm biomass and decreased protein production coupled with a concomitant up-regulation of genes involved with glycogen production might result in a biofilm of sessile, metabolically inactive bacteria sustained by stored glycogen. These biofilms may protect surviving bacteria from subsequent antibiotic challenges, and act as a reservoir of viable bacteria once antibiotic exposure has ended.

Experimental infection with H1N1 European swine influenza virus protects pigs from an infection with the 2009 pandemic H1N1 human influenza virus.

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Busquets, Núria; Segalés, Joaquim; Córdoba, Lorena; Mussá, Tufaria; Crisci, Elisa; Martín-Valls, Gerard E; Simon-Grifé, Meritxell; Pérez-Simó, Marta; Pérez-Maíllo, Monica; Núñez, Jose I; Abad, Francesc X; Fraile, Lorenzo; Pina, Sonia; Majó, Natalia; Bensaid, Albert; Domingo, Mariano; Montoya, María

2010-01-01

The recent pandemic caused by human influenza virus A(H1N1) 2009 contains ancestral gene segments from North American and Eurasian swine lineages as well as from avian and human influenza lineages. The emergence of this A(H1N1) 2009 poses a potential global threat for human health and the fact that it can infect other species, like pigs, favours a possible encounter with other influenza viruses circulating in swine herds. In Europe, H1N1, H1N2 and H3N2 subtypes of swine influenza virus currently have a high prevalence in commercial farms. To better assess the risk posed by the A(H1N1) 2009 in the actual situation of swine farms, we sought to analyze whether a previous infection with a circulating European avian-like swine A/Swine/Spain/53207/2004 (H1N1) influenza virus (hereafter referred to as SwH1N1) generated or not cross-protective immunity against a subsequent infection with the new human pandemic A/Catalonia/63/2009 (H1N1) influenza virus (hereafter referred to as pH1N1) 21 days apart. Pigs infected only with pH1N1 had mild to moderate pathological findings, consisting on broncho-interstitial pneumonia. However, pigs inoculated with SwH1N1 virus and subsequently infected with pH1N1 had very mild lung lesions, apparently attributed to the remaining lesions caused by SwH1N1 infection. These later pigs also exhibited boosted levels of specific antibodies. Finally, animals firstly infected with SwH1N1 virus and latter infected with pH1N1 exhibited undetectable viral RNA load in nasal swabs and lungs after challenge with pH1N1, indicating a cross-protective effect between both strains. © INRA, EDP Sciences, 2010.

Infection and Replication of Influenza Virus at the Ocular Surface.

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Creager, Hannah M; Kumar, Amrita; Zeng, Hui; Maines, Taronna R; Tumpey, Terrence M; Belser, Jessica A

2018-04-01

Although influenza viruses typically cause respiratory tract disease, some viruses, particularly those with an H7 hemagglutinin, have been isolated from the eyes of conjunctivitis cases. Previous work has shown that isolates of multiple subtypes from both ocular and respiratory infections are capable of replication in human ex vivo ocular tissues and corneal or conjunctival cell monolayers, leaving the determinants of ocular tropism unclear. Here, we evaluated the effect of several variables on tropism for ocular cells cultured in vitro and examined the potential effect of the tear film on viral infectivity. All viruses tested were able to replicate in primary human corneal epithelial cell monolayers subjected to aerosol inoculation. The temperature at which cells were cultured postinoculation minimally affected infectivity. Replication efficiency, in contrast, was reduced at 33°C relative to that at 37°C, and this effect was slightly greater for the conjunctivitis isolates than for the respiratory ones. With the exception of a seasonal H3N2 virus, the subset of viruses studied in multilayer corneal tissue constructs also replicated productively after either aerosol or liquid inoculation. Human tears significantly inhibited the hemagglutination of both ocular and nonocular isolates, but the effect on viral infectivity was more variable, with tears reducing the infectivity of nonocular isolates more than ocular isolates. These data suggest that most influenza viruses may be capable of establishing infection if they reach the surface of ocular cells but that this is more likely for ocular-tropic viruses, as they are better able to maintain their infectivity during passage through the tear film. IMPORTANCE The potential spread of zoonotic influenza viruses to humans represents an important threat to public health. Unfortunately, despite the importance of cellular and tissue tropism to pathogenesis, determinants of influenza virus tropism have yet to be fully

Genes from plasmid pKM101 in Haemophilus influenzae: separation of functions of mucA and mucB

International Nuclear Information System (INIS)

Balganesh, M.; Setlow, J.K.

1985-01-01

Haemophilus influenzae, normally not mutable by UV, became UV mutable with a recombinant plasmid insertion. A 7.8-kilobase-pair (kbp) fragment of the plasmid pKM101 containing the mucA and mucB genes was ligated to the shuttle vector pDM2, and a Rec- strain of H. influenzae was transformed with the ligated mixture. All of the transformants, unlike the parent Rec- strain, were resistant to UV, could carry out postreplication repair and Weigle reactivation, showed greatly increased spontaneous mutation, and contained a plasmid carrying an insert of only 1.2 rather than 7.8 kbp. This plasmid in a umuC mutant strain of Escherichia coli complemented a pKM101 derivative lacking mucA function but with an intact mucB gene, although there was no complementation with a mucA+ mucB- plasmid, suggesting that the newly constructed plasmid coded for the mucA protein; this is in accord with the restriction analysis and hybridization between the plasmid and a probe containing all of the mucA gene but only a small fraction of mucB. When one of the H. influenzae Rec- transformants lost the plasmid, the resistance to UV was retained but the high spontaneous mutation and UV mutability were not. The fact that there was hybridization between the chromosome of the cured strain and a probe containing both muc genes but none when almost no mucB was present suggested that at least part of the mucB gene had been integrated into the Rec- chromosome. Five different postreplication repair-proficient strains became UV mutable and had high spontaneous mutation rates caused by the putative mucA plasmid, indicating that these strains already possessed a chromosomal equivalent of the mucB gene

Protein energy malnutrition decreases immunity and increases susceptibility to influenza infection in mice.

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Taylor, Andrew K; Cao, Weiping; Vora, Keyur P; De La Cruz, Juan; Shieh, Wun-Ju; Zaki, Sherif R; Katz, Jacqueline M; Sambhara, Suryaprakash; Gangappa, Shivaprakash

2013-02-01

Protein energy malnutrition (PEM), a common cause of secondary immune deficiency in children, is associated with an increased risk of infections. Very few studies have addressed the relevance of PEM as a risk factor for influenza. We investigated the influence of PEM on susceptibility to, and immune responses following, influenza virus infection using isocaloric diets providing either adequate protein (AP; 18%) or very low protein (VLP; 2%) in a mouse model. We found that mice maintained on the VLP diet, when compared to mice fed with the AP diet, exhibited more severe disease following influenza infection based on virus persistence, trafficking of inflammatory cell types to the lung tissue, and virus-induced mortality. Furthermore, groups of mice maintained on the VLP diet showed significantly lower virus-specific antibody response and a reduction in influenza nuclear protein-specific CD8(+) T cells compared with mice fed on the AP diet. Importantly, switching diets for the group maintained on the VLP diet to the AP diet improved virus clearance, as well as protective immunity to viral challenge. Our results highlight the impact of protein energy on immunity to influenza infection and suggest that balanced protein energy replenishment may be one strategy to boost immunity against influenza viral infections.

Protective Effect of Dietary Xylitol on Influenza A Virus Infection

Science.gov (United States)

Yin, Sun Young; Kim, Hyoung Jin; Kim, Hong-Jin

2014-01-01

Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG) are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1). We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide) and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases. PMID:24392148

Protective effect of dietary xylitol on influenza A virus infection.

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Sun Young Yin

Full Text Available Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1. We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases.

The structure of Haemophilus influenzae prephenate dehydrogenase suggests unique features of bifunctional TyrA enzymes

International Nuclear Information System (INIS)

Chiu, Hsiu-Ju; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Carlton, Dennis; Clayton, Thomas; Das, Debanu; Deller, Marc C.; Duan, Lian; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Anna; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Krishna, S. Sri; Kumar, Abhinav; Marciano, David; McMullan, Daniel; Miller, Mitchell D.; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Reyes, Ron; Tien, Henry J.; Trame, Christine B.; Bedem, Henry van den; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

2010-01-01

The crystal structure of the prephenate dehydrogenase component of the bifunctional H. influenzae TyrA reveals unique structural differences between bifunctional and monofunctional TyrA enzymes. Chorismate mutase/prephenate dehydrogenase from Haemophilus influenzae Rd KW20 is a bifunctional enzyme that catalyzes the rearrangement of chorismate to prephenate and the NAD(P) + -dependent oxidative decarboxylation of prephenate to 4-hydroxyphenylpyruvate in tyrosine biosynthesis. The crystal structure of the prephenate dehydrogenase component (HinfPDH) of the TyrA protein from H. influenzae Rd KW20 in complex with the inhibitor tyrosine and cofactor NAD + has been determined to 2.0 Å resolution. HinfPDH is a dimeric enzyme, with each monomer consisting of an N-terminal α/β dinucleotide-binding domain and a C-terminal α-helical dimerization domain. The structure reveals key active-site residues at the domain interface, including His200, Arg297 and Ser179 that are involved in catalysis and/or ligand binding and are highly conserved in TyrA proteins from all three kingdoms of life. Tyrosine is bound directly at the catalytic site, suggesting that it is a competitive inhibitor of HinfPDH. Comparisons with its structural homologues reveal important differences around the active site, including the absence of an α–β motif in HinfPDH that is present in other TyrA proteins, such as Synechocystis sp. arogenate dehydrogenase. Residues from this motif are involved in discrimination between NADP + and NAD + . The loop between β5 and β6 in the N-terminal domain is much shorter in HinfPDH and an extra helix is present at the C-terminus. Furthermore, HinfPDH adopts a more closed conformation compared with TyrA proteins that do not have tyrosine bound. This conformational change brings the substrate, cofactor and active-site residues into close proximity for catalysis. An ionic network consisting of Arg297 (a key residue for tyrosine binding), a water molecule, Asp206 (from

[Status of acute upper respiratory infection, influenza-like illness, and influenza vaccination coverage among community residents in Jinan].

Science.gov (United States)

Liu, Ying; Song, Shaoxia; Wang, Wei; Geng, Xingyi; Liu, Wen; Han, Debiao; Liu, Ti; Wu, Julong; Li, Zhong; Wang, Xianjun; Bi, Zhenqiang

2015-12-01

To analyze the status of acute upper respiratory infection and influenza-like illness (ILI) among community residents in Jinan in 2015, and to make a understand of the patient's medical treatment behavior and influenza vaccination coverage status in 2014. Balloting method and convenient sampling method were used to launch a household survey. The residents who had been in Jinan for more than 3 months were selected, to investigate the residents' attack ratio of acute upper respiratory and influenza-like from Jan. 8 to Feb. 7, 2015. Totally, 1 300 persons from 410 families were involved in this survey which recovered 1 241 valid questionnaires with the efficiency of 95.5%. Based on the national age-urban demographic statistics in 2010, the attack rates of acute respiratory infections, influenza-like illness were estimated by the direct standardization method, and the influenza vaccination rates were also calculated in this study. χ(2)-test method was used to compare the different status of incidence and vaccination among residents with different features. The attack rate of acute upper respiratory infection and influenza-like illness in Jinan from January 8, 2015 to February 7, 2015 were 30.2% (375 cases), and 6.1% (76 cases), respectively, with a standardized rate of 29.1% and 5.4%. 5.3% (66 cases) of the residents have vaccinated with the influenza vaccine inoculation, with an adjusted rate of 3.8%. The attack rate difference of acute upper respiratory tract infections was statistically significant between each age group (χ(2)=17.121, P= 0.002). The 0-4 age group had a highest attack rate (45.4%) of acute respiratory infection, while the 15-24 age group got the lowest (26.5%). 38.9% (146 cases) of patients went for a treatment in hospital. Among them, 37.7% (55 cases) of them selected the county level hospitals for treatment, 37.7% (55 cases) selected the community level hospitals, and 24.6% (36 cases) selected the individual clinic. Significant differences of

Sparse evidence for equine or avian influenza virus infections among Mongolian adults with animal exposures.

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Khurelbaatar, Nyamdavaa; Krueger, Whitney S; Heil, Gary L; Darmaa, Badarchiin; Ulziimaa, Daramragchaa; Tserennorov, Damdindorj; Baterdene, Ariungerel; Anderson, Benjamin D; Gray, Gregory C

2013-11-01

In recent years, Mongolia has experienced recurrent epizootics of equine influenza virus (EIV) among its 2·1 million horses and multiple incursions of highly pathogenic avian influenza (HPAI) virus via migrating birds. No human EIV or HPAI infections have been reported. In 2009, 439 adults in Mongolia were enrolled in a population-based study of zoonotic influenza transmission. Enrollment sera were examined for serological evidence of infection with nine avian, three human, and one equine influenza virus strains. Seroreactivity was sparse among participants suggesting little human risk of zoonotic influenza infection. © 2013 John Wiley & Sons Ltd.

Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection

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Shahzma Merani

2017-07-01

Full Text Available The number of people over the age of 60 is expected to double by 2050 according to the WHO. This emphasizes the need to ensure optimized resilience to health stressors in late life. In older adults, influenza is one of the leading causes of catastrophic disability (defined as the loss of independence in daily living and self-care activities. Influenza vaccination is generally perceived to be less protective in older adults, with some studies suggesting that the humoral immune response to the vaccine is further impaired in cytomegalovirus (CMV-seropositive older people. CMV is a β-herpes virus infection that is generally asymptomatic in healthy individuals. The majority of older adults possess serum antibodies against the virus indicating latent infection. Age-related changes in T-cell-mediated immunity are augmented by CMV infection and may be associated with more serious complications of influenza infection. This review focuses on the impact of aging and CMV on immune cell function, the response to influenza infection and vaccination, and how the current understanding of aging and CMV can be used to design a more effective influenza vaccine for older adults. It is anticipated that efforts in this field will address the public health need for improved protection against influenza in older adults, particularly with regard to the serious complications leading to loss of independence.

Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection.

Science.gov (United States)

Merani, Shahzma; Pawelec, Graham; Kuchel, George A; McElhaney, Janet E

2017-01-01

The number of people over the age of 60 is expected to double by 2050 according to the WHO. This emphasizes the need to ensure optimized resilience to health stressors in late life. In older adults, influenza is one of the leading causes of catastrophic disability (defined as the loss of independence in daily living and self-care activities). Influenza vaccination is generally perceived to be less protective in older adults, with some studies suggesting that the humoral immune response to the vaccine is further impaired in cytomegalovirus (CMV)-seropositive older people. CMV is a β-herpes virus infection that is generally asymptomatic in healthy individuals. The majority of older adults possess serum antibodies against the virus indicating latent infection. Age-related changes in T-cell-mediated immunity are augmented by CMV infection and may be associated with more serious complications of influenza infection. This review focuses on the impact of aging and CMV on immune cell function, the response to influenza infection and vaccination, and how the current understanding of aging and CMV can be used to design a more effective influenza vaccine for older adults. It is anticipated that efforts in this field will address the public health need for improved protection against influenza in older adults, particularly with regard to the serious complications leading to loss of independence.

Characteristics of atopic children with pandemic H1N1 influenza viral infection: pandemic H1N1 influenza reveals 'occult' asthma of childhood.

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Hasegawa, Shunji; Hirano, Reiji; Hashimoto, Kunio; Haneda, Yasuhiro; Shirabe, Komei; Ichiyama, Takashi

2011-02-01

The number of human cases of pandemic H1N1 influenza viral infection has increased in Japan since April 2009, as it has worldwide. This virus is widespread in the Yamaguchi prefecture in western Japan, where most infected children exhibited respiratory symptoms. Bronchial asthma is thought to be one of the risk factors that exacerbate respiratory symptoms of pandemic H1N1-infected patients, but the pathogenesis remains unclear. We retrospectively investigated the records of 33 children with pandemic H1N1 influenza viral infection who were admitted to our hospital between October and December 2009 and analyzed their clinical features. The percentage of children with asthma attack, with or without abnormal findings on chest radiographs (pneumonia, atelectasis, etc.), caused by pandemic H1N1 influenza infection was significantly higher than that of children with asthma attack and 2008-2009 seasonal influenza infection. Of the 33 children in our study, 22 (66.7%) experienced an asthma attack. Among these children, 20 (90.9%) did not receive long-term management for bronchial asthma, whereas 7 (31.8%) were not diagnosed with bronchial asthma and had experienced their first asthma attack. However, the severity of the attack did not correlate with the severity of the pulmonary complications of pandemic H1N1 influenza viral infection. The pandemic H1N1 influenza virus greatly increases the risk of lower respiratory tract complications such as asthma attack, pneumonia, and atelectasis, when compared to the seasonal influenza virus. Furthermore, our results suggest that pandemic H1N1 influenza viral infection can easily induce a severe asthma attack, pneumonia, and atelectasis in atopic children without any history of either an asthma attack or asthma treatment. © 2011 John Wiley & Sons A/S.

Avian influenza infection alters fecal odor in mallards.

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Bruce A Kimball

Full Text Available Changes in body odor are known to be a consequence of many diseases. Much of the published work on disease-related and body odor changes has involved parasites and certain cancers. Much less studied have been viral diseases, possibly due to an absence of good animal model systems. Here we studied possible alteration of fecal odors in animals infected with avian influenza viruses (AIV. In a behavioral study, inbred C57BL/6 mice were trained in a standard Y-maze to discriminate odors emanating from feces collected from mallard ducks (Anas platyrhynchos infected with low-pathogenic avian influenza virus compared to fecal odors from non-infected controls. Mice could discriminate odors from non-infected compared to infected individual ducks on the basis of fecal odors when feces from post-infection periods were paired with feces from pre-infection periods. Prompted by this indication of odor change, fecal samples were subjected to dynamic headspace and solvent extraction analyses employing gas chromatography/mass spectrometry to identify chemical markers indicative of AIV infection. Chemical analyses indicated that AIV infection was associated with a marked increase of acetoin (3-hydroxy-2-butanone in feces. These experiments demonstrate that information regarding viral infection exists via volatile metabolites present in feces. Further, they suggest that odor changes following virus infection could play a role in regulating behavior of conspecifics exposed to infected individuals.

A novel single virus infection system reveals that influenza virus preferentially infects cells in g1 phase.

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Ryuta Ueda

Full Text Available BACKGROUND: Influenza virus attaches to sialic acid residues on the surface of host cells via the hemagglutinin (HA, a glycoprotein expressed on the viral envelope, and enters into the cytoplasm by receptor-mediated endocytosis. The viral genome is released and transported in to the nucleus, where transcription and replication take place. However, cellular factors affecting the influenza virus infection such as the cell cycle remain uncharacterized. METHODS/RESULTS: To resolve the influence of cell cycle on influenza virus infection, we performed a single-virus infection analysis using optical tweezers. Using this newly developed single-virus infection system, the fluorescence-labeled influenza virus was trapped on a microchip using a laser (1064 nm at 0.6 W, transported, and released onto individual H292 human lung epithelial cells. Interestingly, the influenza virus attached selectively to cells in the G1-phase. To clarify the molecular differences between cells in G1- and S/G2/M-phase, we performed several physical and chemical assays. Results indicated that: 1 the membranes of cells in G1-phase contained greater amounts of sialic acids (glycoproteins than the membranes of cells in S/G2/M-phase; 2 the membrane stiffness of cells in S/G2/M-phase is more rigid than those in G1-phase by measurement using optical tweezers; and 3 S/G2/M-phase cells contained higher content of Gb3, Gb4 and GlcCer than G1-phase cells by an assay for lipid composition. CONCLUSIONS: A novel single-virus infection system was developed to characterize the difference in influenza virus susceptibility between G1- and S/G2/M-phase cells. Differences in virus binding specificity were associated with alterations in the lipid composition, sialic acid content, and membrane stiffness. This single-virus infection system will be useful for studying the infection mechanisms of other viruses.

Evaluation of IFITM3 rs12252 Association With Severe Pediatric Influenza Infection.

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Randolph, Adrienne G; Yip, Wai-Ki; Allen, Emma Kaitlynn; Rosenberger, Carrie M; Agan, Anna A; Ash, Stephanie A; Zhang, Yu; Bhangale, Tushar R; Finkelstein, David; Cvijanovich, Natalie Z; Mourani, Peter M; Hall, Mark W; Su, Helen C; Thomas, Paul G

2017-07-01

Interferon-induced transmembrane protein 3 (IFITM3) restricts endocytic fusion of influenza virus. IFITM3 rs12252_C, a putative alternate splice site, has been associated with influenza severity in adults. IFITM3 has not been evaluated in pediatric influenza. The Pediatric Influenza (PICFLU) study enrolled children with suspected influenza infection across 38 pediatric intensive care units during November 2008 to April 2016. IFITM3 was sequenced in patients and parents were genotyped for specific variants for family-based association testing. rs12252 was genotyped in 54 African-American pediatric outpatients with influenza (FLU09), included in the population-based comparisons with 1000 genomes. Splice site analysis of rs12252_C was performed using PICFLU and FLU09 patient RNA. In PICFLU, 358 children had influenza infection. We identified 22 rs12252_C homozygotes in 185 white non-Hispanic children. rs12252_C was not associated with influenza infection in population or family-based analyses. We did not identify the Δ21 IFITM3 isoform in RNAseq data. The rs12252 genotype was not associated with IFITM3 expression levels, nor with critical illness severity. No novel rare IFITM3 functional variants were identified. rs12252 was not associated with susceptibility to influenza-related critical illness in children or with critical illness severity. Our data also do not support it being a splice site. © 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.

Differential lung NK cell responses in avian influenza virus infected chickens correlate with pathogenicity

OpenAIRE

Jansen, C.A.; de Geus, E.D.; van Haarlem, D.A.; van de Haar, P.M.; Löndt, B.Z; Graham, S.P.; Göbel, T.W.; van Eden, W.; Brookes, S.M.; Vervelde, L.

2013-01-01

Infection of chickens with low pathogenicity avian influenza (LPAI) virus results in mild clinical signs while infection with highly pathogenic avian influenza (HPAI) viruses causes death of the birds within 36–48 hours. Since natural killer (NK) cells have been shown to play an important role in influenza-specific immunity, we hypothesise that NK cells are involved in this difference in pathogenicity. To investigate this, the role of chicken NK-cells in LPAI virus infection was studied. Next...

Little evidence of subclinical avian influenza virus infections among rural villagers in Cambodia.

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Gregory C Gray

Full Text Available In 2008, 800 adults living within rural Kampong Cham Province, Cambodia were enrolled in a prospective cohort study of zoonotic influenza transmission. After enrollment, participants were contacted weekly for 24 months to identify acute influenza-like illnesses (ILI. Follow-up sera were collected at 12 and 24 months. A transmission substudy was also conducted among the family contacts of cohort members reporting ILI who were influenza A positive. Samples were assessed using serological or molecular techniques looking for evidence of infection with human and avian influenza viruses. Over 24 months, 438 ILI investigations among 284 cohort members were conducted. One cohort member was hospitalized with a H5N1 highly pathogenic avian influenza (HPAI virus infection and withdrew from the study. Ninety-seven ILI cases (22.1% were identified as influenza A virus infections by real-time RT-PCR; none yielded evidence for AIV. During the 2 years of follow-up, 21 participants (3.0% had detectable antibody titers (≥ 1:10 against the studied AIVs: 1 against an avian-like A/Migratory duck/Hong Kong/MPS180/2003(H4N6, 3 against an avian-like A/Teal/Hong Kong/w312/97(H6N1, 9 (3 of which had detectible antibody titers at both 12- and 24-month follow-up against an avian-like A/Hong Kong/1073/1999(H9N2, 6 (1 detected at both 12- and 24-month follow-up against an avian-like A/Duck/Memphis/546/74(H11N9, and 2 against an avian-like A/Duck/Alberta/60/76(H12N5. With the exception of the one hospitalized cohort member with H5N1 infection, no other symptomatic avian influenza infections were detected among the cohort. Serological evidence for subclinical infections was sparse with only one subject showing a 4-fold rise in microneutralization titer over time against AvH12N5. In summary, despite conducting this closely monitored cohort study in a region enzootic for H5N1 HPAI, we were unable to detect subclinical avian influenza infections, suggesting either that these

INFLUENZA IMMUNISATION IN HIV-INFECTED PERSONS

African Journals Online (AJOL)

in 1997' (surpassing the 6O'lb vaccine coverage goal for the country's Healthy People 2000 Project). ... (i) are HIV-infected persons at special risk for influenza complications and is annual immunisation .... virus type' 1 rep :cation can be increased in peripheral 0100d of sero- positive patiems aher influenrc. vacdnation.

Structural Analysis of Substrate, Reaction Intermediate, and Product Binding in Haemophilus influenzae Biotin Carboxylase

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Broussard, Tyler C.; Pakhomova, Svetlana; Neau, David B.; Bonnot, Ross; Waldrop, Grover L.

2015-01-01

Acetyl-CoA carboxylase catalyzes the first and regulated step in fatty acid synthesis. In most Gram-negative and Gram-positive bacteria, the enzyme is composed of three proteins: biotin carboxylase, a biotin carboxyl carrier protein (BCCP), and carboxyltransferase. The reaction mechanism involves two half-reactions with biotin carboxylase catalyzing the ATP-dependent carboxylation of biotin-BCCP in the first reaction. In the second reaction, carboxyltransferase catalyzes the transfer of the carboxyl group from biotin-BCCP to acetyl-CoA to form malonyl-CoA. In this report, high-resolution crystal structures of biotin carboxylase from Haemophilus influenzae were determined with bicarbonate, the ATP analogue AMPPCP; the carboxyphosphate intermediate analogues, phosphonoacetamide and phosphonoformate; the products ADP and phosphate; and the carboxybiotin analogue N1′-methoxycarbonyl biotin methyl ester. The structures have a common theme in that bicarbonate, phosphate, and the methyl ester of the carboxyl group of N1′-methoxycarbonyl biotin methyl ester all bound in the same pocket in the active site of biotin carboxylase and as such utilize the same set of amino acids for binding. This finding suggests a catalytic mechanism for biotin carboxylase in which the binding pocket that binds tetrahedral phosphate also accommodates and stabilizes a tetrahedral dianionic transition state resulting from direct transfer of CO2 from the carboxyphosphate intermediate to biotin. PMID:26020841

A Perfect Storm: Increased Colonization and Failure of Vaccination Leads to Severe Secondary Bacterial Infection in Influenza Virus-Infected Obese Mice

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Erik A. Karlsson

2017-09-01

Full Text Available Obesity is a risk factor for developing severe disease following influenza virus infection; however, the comorbidity of obesity and secondary bacterial infection, a serious complication of influenza virus infections, is unknown. To fill this gap in knowledge, lean and obese C57BL/6 mice were infected with a nonlethal dose of influenza virus followed by a nonlethal dose of Streptococcus pneumoniae. Strikingly, not only did significantly enhanced death occur in obese coinfected mice compared to lean controls, but also high mortality was seen irrespective of influenza virus strain, bacterial strain, or timing of coinfection. This result was unexpected, given that most influenza virus strains, especially seasonal human A and B viruses, are nonlethal in this model. Both viral and bacterial titers were increased in the upper respiratory tract and lungs of obese animals as early as days 1 and 2 post-bacterial infection, leading to a significant decrease in lung function. This increased bacterial load correlated with extensive cellular damage and upregulation of platelet-activating factor receptor, a host receptor central to pneumococcal invasion. Importantly, while vaccination of obese mice against either influenza virus or pneumococcus failed to confer protection, antibiotic treatment was able to resolve secondary bacterial infection-associated mortality. Overall, secondary bacterial pneumonia could be a widespread, unaddressed public health problem in an increasingly obese population.

Impact of Haemophilus influenzae type b conjugate vaccine on bacterial meningitis in the Dominican Republic Impacto de la vacuna conjugada contra Haemophilus influenzae tipo b sobre la meningitis bacteriana en la República Dominicana

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Ellen H. Lee

2008-09-01

Full Text Available OBJECTIVES: Widespread use of Haemophilus influenzae type b (Hib vaccines has dramatically reduced the burden of Hib disease throughout the Americas. Few studies have evaluated the impact of Hib vaccination on non-culture-confirmed disease. This study analyzed trends in probable bacterial meningitis before and after the introduction of Hib vaccine in the Dominican Republic and estimated vaccine effectiveness against Hib meningitis. METHODS: Meningitis cases among children OBJETIVOS: El uso generalizado de la vacuna contra Haemophilus influenzae tipo b (Hib ha permitido reducir radicalmente la carga de enfermedad por Hib en las Américas. Pocos estudios han evaluado el impacto de la vacunación contra Hib sobre los casos no confirmados mediante cultivo. En este estudio se analizaron las tendencias en el número de casos probables de meningitis bacteriana antes y después de la introducción de la vacuna contra Hib en la República Dominicana y se estimó la eficacia de la vacuna contra la meningitis. MÉTODOS: Se identificaron los casos de meningitis en niños menores de 5 años a partir de los registros de ingreso del principal hospital pediátrico de Santo Domingo entre 1998 y 2004. Los casos de meningitis con probable etiología bacteriana se clasificaron según criterios de laboratorio; los casos confirmados contaban con cultivo bacteriano positivo o detección de antígenos específicos en el líquido cefalorraquídeo. Se calcularon las tasas de incidencia acumulada de casos confirmados y probables de meningitis en los niños que vivían en el Distrito Nacional. Los casos confirmados de meningitis por Hib se incorporaron a un estudio de casos y controles -pareados según la edad y el barrio de residencia- para calcular la eficacia de la vacuna. RESULTADOS: Antes de la introducción de la vacuna, la tasa anual de meningitis de posible etiología bacteriana era de 49 casos por 100 000 niños menores de 5 años; de los casos confirmados de

The environmental deposition of influenza virus from patients infected with influenza A(H1N1)pdm09: Implications for infection prevention and control.

Science.gov (United States)

Killingley, Benjamin; Greatorex, Jane; Digard, Paul; Wise, Helen; Garcia, Fayna; Varsani, Harsha; Cauchemez, Simon; Enstone, Joanne E; Hayward, Andrew; Curran, Martin D; Read, Robert C; Lim, Wei S; Nicholson, Karl G; Nguyen-Van-Tam, Jonathan S

2016-01-01

In a multi-center, prospective, observational study over two influenza seasons, we sought to quantify and correlate the amount of virus recovered from the nares of infected subjects with that recovered from their immediate environment in community and hospital settings. We recorded the symptoms of adults and children with A(H1N1)pdm09 infection, took nasal swabs, and sampled touched surfaces and room air. Forty-two infected subjects were followed up. The mean duration of virus shedding was 6.2 days by PCR (Polymerase Chain Reaction) and 4.2 days by culture. Surface swabs were collected from 39 settings; 16 (41%) subject locations were contaminated with virus. Overall, 33 of the 671 (4.9%) surface swabs were PCR positive for influenza, of which two (0.3%) yielded viable virus. On illness Day 3, subjects yielding positive surface samples had significantly higher nasal viral loads (geometric mean ratio 25.7; 95% CI 1.75, 376.0, p=0.021) and a positive correlation (r=0.47, p=0.006) was observed between subject nasal viral loads and viral loads recovered from the surfaces around them. Room air was sampled in the vicinity of 12 subjects, and PCR positive samples were obtained for five (42%) samples. Influenza virus shed by infected subjects did not detectably contaminate the vast majority of surfaces sampled. We question the relative importance of the indirect contact transmission of influenza via surfaces, though our data support the existence of super-spreaders via this route. The air sampling results add to the accumulating evidence that supports the potential for droplet nuclei (aerosol) transmission of influenza. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Effect of influenza infection on the phagocytic and bactericidal activities of pulmonary macrophages

International Nuclear Information System (INIS)

Nugent, K.M.; Pesanti, E.L.

1979-01-01

The effect of mouse-adapted influenza A/PR/8/34 virus on pulmonary macrophage function was evaluated by using an in vitro system which allowed direct virus interaction with macrophages and then separate analysis of the steps required for bacterial clearance by macrophages. Infection of macrophages with this virus resulted in the appearance of a hemagglutinating activity on the macrophage surface; expression of this activity was inhibited by amantadine, 2-deoxyglucose, and cycloheximide and by pretreatment of the virus inoculum with with ultraviolet light and specific antiserum. After influenza infection, net ingestion of viable Staphylococcus aureus by macrophage monolayers was unaltered and there was no change in the fraction of the monolayer which ingested cocci over a wide range of bacterial inputs. Influenza-infected microphages also inactivated intracellular S. aureus at a rate indistinguishable from controls. Therefore, these in vitro studies do not support the hypothesis that the defect in pulmonary antibacterial mechanisms associated with influenza infections results from a direct effect of virus infection on either the phagocytic or bactericidal activity of resistant pulmonary macarophages

Influenza C infections in Western Australia and Victoria from 2008 to 2014.

Science.gov (United States)

Jelley, Lauren; Levy, Avram; Deng, Yi-Mo; Spirason, Natalie; Lang, Jurissa; Buettner, Iwona; Druce, Julian; Blyth, Chris; Effler, Paul; Smith, David; Barr, Ian G

2016-11-01

Influenza C is usually considered a minor cause of respiratory illness in humans with many infections being asymptomatic or clinically mild. Large outbreaks can occur periodically resulting in significant morbidity. This study aimed at analyzing the available influenza C clinical samples from two widely separated states of Australia, collected over a 7-year period and to compare them with influenza C viruses detected in other parts of the world in recent years. Between 2008 and 2014, 86 respiratory samples that were influenza C positive were collected from subjects with influenza-like illness living in the states of Victoria and Western Australia. A battery of other respiratory viruses were also tested for in these influenza C-positive samples. Virus isolation was attempted on all of these clinical samples, and gene sequencing was performed on all influenza C-positive cultures. Detections of influenza C in respiratory samples were sporadic in most years studied, but higher rates of infection occurred in 2012 and 2014. Many of the patients with influenza C had coinfections with other respiratory pathogens. Phylogenetic analysis of the full-length hemagglutinin-esterase-fusion (HE) gene found that most of the viruses grouped in the C/Sao Paulo/378/82 clade with the remainder grouping in the C/Kanagawa/1/76 clade. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Influenza interaction with cocirculating pathogens and its impact on surveillance, pathogenesis, and epidemic profile: A key role for mathematical modelling.

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Lulla Opatowski

2018-02-01

Full Text Available Evidence is mounting that influenza virus interacts with other pathogens colonising or infecting the human respiratory tract. Taking into account interactions with other pathogens may be critical to determining the real influenza burden and the full impact of public health policies targeting influenza. This is particularly true for mathematical modelling studies, which have become critical in public health decision-making. Yet models usually focus on influenza virus acquisition and infection alone, thereby making broad oversimplifications of pathogen ecology. Herein, we report evidence of influenza virus interactions with bacteria and viruses and systematically review the modelling studies that have incorporated interactions. Despite the many studies examining possible associations between influenza and Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Neisseria meningitidis, respiratory syncytial virus (RSV, human rhinoviruses, human parainfluenza viruses, etc., very few mathematical models have integrated other pathogens alongside influenza. The notable exception is the pneumococcus-influenza interaction, for which several recent modelling studies demonstrate the power of dynamic modelling as an approach to test biological hypotheses on interaction mechanisms and estimate the strength of those interactions. We explore how different interference mechanisms may lead to unexpected incidence trends and possible misinterpretation, and we illustrate the impact of interactions on public health surveillance using simple transmission models. We demonstrate that the development of multipathogen models is essential to assessing the true public health burden of influenza and that it is needed to help improve planning and evaluation of control measures. Finally, we identify the public health, surveillance, modelling, and biological challenges and propose avenues of research for the coming years.

Viruses associated with acute respiratory infections and influenza-like illness among outpatients from the Influenza Incidence Surveillance Project, 2010-2011.

Science.gov (United States)

Fowlkes, Ashley; Giorgi, Andrea; Erdman, Dean; Temte, Jon; Goodin, Kate; Di Lonardo, Steve; Sun, Yumei; Martin, Karen; Feist, Michelle; Linz, Rachel; Boulton, Rachelle; Bancroft, Elizabeth; McHugh, Lisa; Lojo, Jose; Filbert, Kimberly; Finelli, Lyn

2014-06-01

The Influenza Incidence Surveillance Project (IISP) monitored outpatient acute respiratory infection (ARI; defined as the presence of ≥ 2 respiratory symptoms not meeting ILI criteria) and influenza-like illness (ILI) to determine the incidence and contribution of associated viral etiologies. From August 2010 through July 2011, 57 outpatient healthcare providers in 12 US sites reported weekly the number of visits for ILI and ARI and collected respiratory specimens on a subset for viral testing. The incidence was estimated using the number of patients in the practice as the denominator, and the virus-specific incidence of clinic visits was extrapolated from the proportion of patients testing positive. The age-adjusted cumulative incidence of outpatient visits for ARI and ILI combined was 95/1000 persons, with a viral etiology identified in 58% of specimens. Most frequently detected were rhinoviruses/enteroviruses (RV/EV) (21%) and influenza viruses (21%); the resulting extrapolated incidence of outpatient visits was 20 and 19/1000 persons respectively. The incidence of influenza virus-associated clinic visits was highest among patients aged 2-17 years, whereas other viruses had varied patterns among age groups. The IISP provides a unique opportunity to estimate the outpatient respiratory illness burden by etiology. Influenza virus infection and RV/EV infection(s) represent a substantial burden of respiratory disease in the US outpatient setting, particularly among children.

Host Cell Restriction Factors that Limit Influenza A Infection

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Fernando Villalón-Letelier

2017-12-01

Full Text Available Viral infection of different cell types induces a unique spectrum of host defence genes, including interferon-stimulated genes (ISGs and genes encoding other proteins with antiviral potential. Although hundreds of ISGs have been described, the vast majority have not been functionally characterised. Cellular proteins with putative antiviral activity (hereafter referred to as “restriction factors” can target various steps in the virus life-cycle. In the context of influenza virus infection, restriction factors have been described that target virus entry, genomic replication, translation and virus release. Genome wide analyses, in combination with ectopic overexpression and/or gene silencing studies, have accelerated the identification of restriction factors that are active against influenza and other viruses, as well as providing important insights regarding mechanisms of antiviral activity. Herein, we review current knowledge regarding restriction factors that mediate anti-influenza virus activity and consider the viral countermeasures that are known to limit their impact. Moreover, we consider the strengths and limitations of experimental approaches to study restriction factors, discrepancies between in vitro and in vivo studies, and the potential to exploit restriction factors to limit disease caused by influenza and other respiratory viruses.

Haemophilus ducreyi: from sexually transmitted infection to skin ulcer pathogen.

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Lewis, David A; Mitjà, Oriol

2016-02-01

This article provides an overview of the biology, epidemiology, clinical features, diagnostic tests, and treatment of Haemophilus ducreyi infection, with special reference to the decline of chancroid and the recent emergence of H. ducreyi as a pathogen responsible for chronic limb ulceration clinically similar to yaws. Chancroid has declined in importance as a sexually transmitted infection in most countries where it was previously endemic. Chancroid may be caused by either class I or class II H. ducreyi isolates; these two classes diverged from each other approximately 1.95 million years ago. H. ducreyi has recently emerged as a cause of chronic skin ulceration in the Pacific region and Africa. Based on sequencing of whole genomes and defined genetic loci, it appears that the cutaneous H. ducreyi strains diverged from the class I genital strains relatively recently. H. ducreyi should be considered as a major cause of chronic limb ulceration in both adults and children and appropriate molecular diagnostic assays are required to determine ulcer aetiology. The high prevalence of H. ducreyi-related cutaneous ulceration in yaws-endemic countries has challenged the validity of observational surveys to monitor the effectiveness of the WHO's yaws eradication campaign.

Meningitis and pneumonia in Guatemalan children: the importance of Haemophilus influenzae type b and Streptococcus pneumoniae Meningitis y neumonía en niños guatemaltecos: importancia de Haemophilus influenzae tipo b y de Streptococcus pneumoniae

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Edwin J. Asturias

2003-12-01

Full Text Available OBJECTIVE: To determine the epidemiology of Haemophilus influenzae type b (Hib and Streptococcus pneumoniae invasive infections in hospitalized Guatemalan children. This is an important issue since Hib vaccine has not been incorporated into the routine immunization program in Guatemala and information from hospital records in 1995 indicated a low incidence of Hib and S. pneumoniae as causes of meningitis and invasive infections. METHODS: Children who were hospitalized in Guatemala City with clinical signs compatible with bacterial infections were evaluated for evidence of Hib or S. pneumoniae infection. Normally sterile body fluids were cultured, and antigen detection was performed on cerebrospinal fluid (CSF and pleural fluid. RESULTS: Of 1 203 children 1-59 months of age hospitalized over a 28-month period, 725 of them (60.3% had a primary diagnosis of pneumonia, 357 (29.7% of meningitis, 60 (5.0% of cellulitis, and 61 (5.1% of sepsis and other conditions. Hib was identified in 20.0% of children with meningitis and S. pneumoniae in 12.9%. The average annual incidence of Hib meningitis was 13.8 cases per 100 000 children under 5 years of age, and 32.4% of meningitides caused by Hib and 58.7% of S. pneumoniae meningitides occurred prior to 6 months of age. Case fatality rates were 14.1%, 37.0%, and 18.0%, respectively, for children with Hib, S. pneumoniae, and culture-negative and antigen-negative meningitis. Prior antibiotic therapy was common and was associated with significant reductions in CSF-culture-positive results for children with other evidence of Hib or S. pneumoniae meningitis. CONCLUSIONS: Improvements in case detection, culture methods, and latex agglutination for antigen detection in CSF resulted in identification of Hib and S. pneumoniae as important causes of severe disease in Guatemalan children. Using a cutoff of > 10 white blood cells per cubic millimeter in CSF would improve the sensitivity for detection of bacterial

Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein.

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Cheah, Esther Y; Mann, Tracy S; Burcham, Philip C; Henry, Peter J

2015-02-15

The airway epithelium is an important source of relaxant mediators, and damage to the epithelium caused by respiratory tract viruses may contribute to airway hyperreactivity. The aim of this study was to determine whether influenza A-induced epithelial damage would modulate relaxation responses evoked by acrolein, a toxic and prevalent component of smoke. Male BALB/c mice were inoculated intranasally with influenza A/PR-8/34 (VIRUS-infected) or allantoic fluid (SHAM-infected). On day 4 post-inoculation, isometric tension recording studies were conducted on carbachol pre-contracted tracheal segments isolated from VIRUS and SHAM mice. Relaxant responses to acrolein (30 μM) were markedly smaller in VIRUS segments compared to SHAM segments (2 ± 1% relaxation vs. 28 ± 5%, n=14, pacrolein and SP were reduced in VIRUS segments (>35% reduction, n=6, pacrolein were profoundly diminished in tracheal segments isolated from influenza A-infected mice. The mechanism through which influenza A infection attenuates this response appears to involve reduced production of PGE2 in response to SP due to epithelial cell loss, and may provide insight into the airway hyperreactivity observed with influenza A infection. Copyright © 2014 Elsevier Inc. All rights reserved.

Shifting of Immune Responsiveness to House Dust Mite by Influenza A Infection: Genomic Insights

KAUST Repository

Al-Garawi, A.

2011-12-14

Respiratory viral infections have been associated with an increased incidence of allergic asthma. However, the mechanisms by which respiratory infections facilitate allergic airway disease are incompletely understood.We previously showed that exposure to a low dose of house dust mite (HDM) resulted in enhanced HDM-mediated allergic airway inflammation, and, importantly, marked airway hyperreactivity only when allergen exposure occurred during an acute influenza A infection. In this study, we evaluated the impact of concurrent influenza infection and allergen exposure at the genomic level, using whole-genome micro-array. Our data showed that, in contrast to exposure to a low dose of HDM, influenza A infection led to a dramatic increase in gene expression, particularly of TLRs, C-type lectin receptors, several complement components, as well as FcεR1. Additionally, we observed increased expression of a number of genes encoding chemokines and cytokines associated with the recruitment of proinflammatory cells. Moreover, HDM exposure in the context of an influenza A infection resulted in the induction of unique genes, including calgranulin A (S100a8), an endogenous damage-associated molecular pattern and TLR4 agonist. In addition, we observed significantly increased expression of serum amyloid A (Saa3) and serine protease inhibitor 3n (Serpina3n). This study showed that influenza infection markedly increased the expression of multiple gene classes capable of sensing allergens and amplifying the ensuing immune-inflammatory response. We propose that influenza A infection primes the lung environment in such a way as to lower the threshold of allergen responsiveness, thus facilitating the emergence of a clinically significant allergic phenotype. Copyright © 2012 by The American Association of Immunologists, Inc.

Physician's knowledge, attitudes, and practices regarding seasonal influenza, pandemic influenza, and highly pathogenic avian influenza A (H5N1) virus infections of humans in Indonesia

OpenAIRE

Mangiri, Amalya; Iuliano, A. Danielle; Wahyuningrum, Yunita; Praptiningsih, Catharina Y.; Lafond, Kathryn E.; Storms, Aaron D.; Samaan, Gina; Ariawan, Iwan; Soeharno, Nugroho; Kreslake, Jennifer M.; Storey, J. Douglas; Uyeki, Timothy M.

2016-01-01

Indonesia has reported highest number of fatal human cases of highly pathogenic avian influenza (HPAI) A (H5N1) virus infection worldwide since 2005. There are limited data available on seasonal and pandemic influenza in Indonesia. During 2012, we conducted a survey of clinicians in two districts in western Java, Indonesia, to assess knowledge, attitudes, and practices (KAP) of clinical diagnosis, testing, and treatment of patients with seasonal influenza, pandemic influenza, or HPAI H5N1 vir...

Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine

DEFF Research Database (Denmark)

Kristensen, Anne B; Lay, William N; Ana-Sosa-Batiz, Fernanda

2016-01-01

to immunize this at-risk group. IMPORTANCE: Infection with HIV is associated with increasing disease severity following influenza infections, and annual influenza vaccinations are recommended for this target group. However, HIV-infected individuals respond relatively poorly to vaccination compared to healthy......This study seeks to assess the ability of seasonal trivalent inactivated influenza vaccine (TIV) to induce nonneutralizing antibodies (Abs) with Fc-mediated functions in HIV-uninfected and HIV-infected subjects. Functional influenza-specific Ab responses were studied in 30 HIV-negative and 27 HIV......-positive subjects immunized against seasonal influenza. All 57 subjects received the 2015 TIV. Fc-mediated antihemagglutinin (anti-HA) Ab activity was measured in plasma before and 4 weeks after vaccination using Fc-receptor-binding assays, NK cell activation assays, and phagocytosis assays. At baseline, the HIV...

Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection

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Qasmieh, Saba; Mounts, Anthony Wayne; Alexander, Burmaa; Besselaar, Terry; Briand, Sylvie; Brown, Caroline; Clark, Seth; Dueger, Erica; Gross, Diane; Hauge, Siri; Hirve, Siddhivinayak; Jorgensen, Pernille; Katz, Mark A; Mafi, Ali; Malik, Mamunur; McCarron, Margaret; Meerhoff, Tamara; Mori, Yuichiro; Mott, Joshua; Olivera, Maria Teresa da Costa; Ortiz, Justin R; Palekar, Rakhee; Rebelo-de-Andrade, Helena; Soetens, Loes; Yahaya, Ali Ahmed; Zhang, Wenqing; Vandemaele, Katelijn

2018-01-01

Abstract The formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance. Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing. Optimal case definitions also need to have a balance of sensitivity and specificity that reflects their intended use. After the 2009–2010 H1N1 influenza pandemic, the World Health Organization (WHO) initiated a technical consultation on global influenza surveillance. This prompted improvements in the sensitivity and specificity of the case definition for influenza – i.e. a respiratory disease that lacks uniquely defining symptomology. The revision process not only modified the definition of influenza-like illness, to include a simplified list of the criteria shown to be most predictive of influenza infection, but also clarified the language used for the definition, to enhance interpretability. To capture severe cases of influenza that required hospitalization, a new case definition was also developed for severe acute respiratory infection in all age groups. The new definitions have been found to capture more cases without compromising specificity. Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden. PMID:29403115

Economic evaluations of Haemophilus influenzae type b (Hib) vaccine: a systematic review.

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Chongmelaxme, Bunchai; Hammanee, Maythika; Phooaphirak, Wariya; Kotirum, Surachai; Hutubessy, Raymond; Chaiyakunapruk, Nathorn

2017-10-01

The World Health Organization (WHO) recommends the use of Haemophilus influenzae type b (Hib) conjugate vaccines, but China and Thailand have not used Hib vaccination in their national immunization programs. This systematic review aimed to update published economic evaluations of Hib vaccinations and to determine factors that potentially affected their cost-effectiveness. Searches were performed from the inception until December 2015 using 13 databases: CAB direct; CEA registry; EconLit; EMBASE; E-library; NHSEED; PAHO; POPLINE; PubMed; Redalyc project; RePEc; SciELO; and WHOLIS. Reference lists of relevant studies and grey literature were also searched. Full economic evaluations of Hib vaccination with results of costs and outcomes were included. The WHO checklist was used to evaluate the quality of the included studies. Data from eligible studies were extracted using a standardized data collection form. Out of 830 articles, 27 were included. Almost half of the studies (12/27) were conducted in high-income countries. Twelve studies (12/27) investigated the Hib vaccine as an addition to the existing vaccination program. Most studies (17/27) examined a 3-dose schedule of Hib vaccine. Nineteen studies (19/27) reported the model used, where all were decision tree models. Most of the studies (23/27) demonstrated an economic value of Hib vaccination programs, key influential parameters being incidence rates of Hib disease and vaccine price. Hib vaccination programs are mostly found to be cost-effective across geographic regions and country income levels, and Hib vaccination is recommended for inclusion into all national immunization programs. The findings are expected to support policy-makers for making decisions on allocating limited resources of the Hib vaccination program effectively.

Health-seeking behavior and transmission dynamics in the control of influenza infection among different age groups.

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You, Shu-Han; Chen, Szu-Chieh; Liao, Chung-Min

2018-01-01

It has been found that health-seeking behavior has a certain impact on influenza infection. However, behaviors with/without risk perception on the control of influenza transmission among age groups have not been well quantified. The purpose of this study was to assess to what extent, under scenarios of with/without control and preventive/protective behaviors, the age-specific network-driven risk perception influences influenza infection. A behavior-influenza model was used to estimate the spread rate of age-specific risk perception in response to an influenza outbreak. A network-based information model was used to assess the effect of network-driven risk perception information transmission on influenza infection. A probabilistic risk model was used to assess the infection risk effect of risk perception with a health behavior change. The age-specific overlapping percentage was estimated to be 40%-43%, 55%-60%, and 19%-35% for child, teenage and adult, and elderly age groups, respectively. Individuals perceive the preventive behavior to improve risk perception information transmission among teenage and adult and elderly age groups, but not in the child age group. The population with perceived health behaviors could not effectively decrease the percentage of infection risk in the child age group, whereas for the elderly age group, the percentage of decrease in infection risk was more significant, with a 97.5th percentile estimate of 97%. The present integrated behavior-infection model can help health authorities in communicating health messages for an intertwined belief network in which health-seeking behavior plays a key role in controlling influenza infection.

Susceptibility of bone marrow-derived macrophages to influenza virus infection is dependent on macrophage phenotype.

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Campbell, Gillian M; Nicol, Marlynne Q; Dransfield, Ian; Shaw, Darren J; Nash, Anthony A; Dutia, Bernadette M

2015-10-01

The role of the macrophage in influenza virus infection is complex. Macrophages are critical for resolution of influenza virus infections but implicated in morbidity and mortality in severe infections. They can be infected with influenza virus and consequently macrophage infection is likely to have an impact on the host immune response. Macrophages display a range of functional phenotypes, from the prototypical pro-inflammatory classically activated cell to alternatively activated anti-inflammatory macrophages involved in immune regulation and wound healing. We were interested in how macrophages of different phenotype respond to influenza virus infection and therefore studied the infection of bone marrow-derived macrophages (BMDMs) of classical and alternative phenotype in vitro. Our results show that alternatively activated macrophages are more readily infected and killed by the virus than classically activated. Classically activated BMDMs express the pro-inflammatory markers inducible nitric oxide synthase (iNOS) and TNF-α, and TNF-α expression was further upregulated following infection. Alternatively activated macrophages express Arginase-1 and CD206; however, following infection, expression of these markers was downregulated whilst expression of iNOS and TNF-α was upregulated. Thus, infection can override the anti-inflammatory state of alternatively activated macrophages. Importantly, however, this results in lower levels of pro-inflammatory markers than those produced by classically activated cells. Our results showed that macrophage phenotype affects the inflammatory macrophage response following infection, and indicated that modulating the macrophage phenotype may provide a route to develop novel strategies to prevent and treat influenza virus infection.

A prospective study of Romanian agriculture workers for zoonotic influenza infections.

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Alexandru Coman

Full Text Available In this prospective study we sought to examine seroepidemiological evidence for acute zoonotic influenza virus infection among Romanian agricultural workers.Sera were drawn upon enrollment (2009 and again at 12 and 24 months from 312 adult agriculture workers and 51 age-group matched controls. Participants were contacted monthly for 24 months and queried regarding episodes of acute influenza-like illnesses (ILI. Cohort members meeting ILI criteria permitted respiratory swab collections as well as acute and convalescent serum collection. Serologic assays were performed against 9 avian, 3 swine, and 3 human influenza viruses.During the two-year follow-up, a total of 23 ILI events were reported. Two subjects' specimens were identified as influenza A by rRT-PCR. During the follow-up period, three individuals experienced elevated microneutralization antibody titers ≥1∶80 against three (one each avian influenza viruses: A/Teal/Hong Kong/w312/97(H6N1, A/Hong Kong/1073/1999(H9N2, or A/Duck/Alberta/60/1976(H12N5. However, none of these participants met the criteria for poultry exposure. A number of subjects demonstrated four-fold increases over time in hemagglutination inhibition (HI assay titers for at least one of the three swine influenza viruses (SIVs; however, it seems likely that two of these three responses were due to cross-reacting antibody against human influenza. Only elevated antibody titers against A/Swine/Flanders/1/1998(H3N2 lacked evidence for such confounding. In examining risk factors for elevated antibody against this SIV with multiple logistic regression, swine exposure (adjusted OR = 1.8, 95% CI 1.1-2.8 and tobacco use (adjusted OR = 1.8; 95% CI 1.1-2.9 were important predictors.While Romania has recently experienced multiple incursions of highly pathogenic avian influenza among domestic poultry, this cohort of Romanian agriculture workers had sparse evidence of avian influenza virus infections. In contrast, there was

Haemophilus influenzae : Caracterización de aislamientos recuperados de enfermedades invasivas en Cuba durante el período 2008-2011

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Gilda Toraño

2012-12-01

Full Text Available Con el objetivo de caracterizar los aislamientos de Haemophilus influenzae, responsables de enfermedades invasivas en Cuba, en la etapa posterior a la vacunación se estudió el total de los recuperados durante el período 2008-2011, remitidos al Instituto "Pedro Kourí" desde diferentes provincias del país. La confirmación de especie y determinación de serotipos se realizó atendiendo al requerimiento de los factores V y X y empleando el método de aglutinación en lámina, respectivamente. Se definieron los biotipos a través de las pruebas de indol, urea y ornitina; se determinó la concentración mínima inhibitoria (CMI mediante la prueba del elipsómetro para la ampicilina, la ceftriaxona, el cloranfenicol y la rifampicina. Para 23 aislamientos se corroboró la identificación como H. influenzae : 21 fueron serotipables y 2 no tipables (HNT. El 90,4% de los serotipables fueron serotipo b y se detectaron dos serotipos a. Nueve aislamientos de H. influenzae b pertenecieron al biotipo I y los aislamientos, serotipo a y HNT, al biotipo II. En una cepa se demostró producción de la enzima ß-lactamasa y resistencia para la ampicilina y el cloranfenicol, con valores de CMI= 8 y 12 µg/mL, respectivamente. Se puso en evidencia que a pesar de la disminución de la incidencia de la enfermedad invasiva por Hib, este serotipo aún constituye el más frecuente y se alerta sobre la necesidad de una vigilancia sostenida que permita detectar fallos vacunales. La susceptibilidad antimicrobiana demostrada para este período pudiera considerarse como un beneficio adicional de la introducción de la vacunación en Cuba.

Suppressor of cytokine signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling.

Science.gov (United States)

Kedzierski, Lukasz; Tate, Michelle D; Hsu, Alan C; Kolesnik, Tatiana B; Linossi, Edmond M; Dagley, Laura; Dong, Zhaoguang; Freeman, Sarah; Infusini, Giuseppe; Starkey, Malcolm R; Bird, Nicola L; Chatfield, Simon M; Babon, Jeffrey J; Huntington, Nicholas; Belz, Gabrielle; Webb, Andrew; Wark, Peter Ab; Nicola, Nicos A; Xu, Jianqing; Kedzierska, Katherine; Hansbro, Philip M; Nicholson, Sandra E

2017-02-14

Influenza virus infections have a significant impact on global human health. Individuals with suppressed immunity, or suffering from chronic inflammatory conditions such as COPD, are particularly susceptible to influenza. Here we show that suppressor of cytokine signaling (SOCS) five has a pivotal role in restricting influenza A virus in the airway epithelium, through the regulation of epidermal growth factor receptor (EGFR). Socs5 -deficient mice exhibit heightened disease severity, with increased viral titres and weight loss. Socs5 levels were differentially regulated in response to distinct influenza viruses (H1N1, H3N2, H5N1 and H11N9) and were reduced in primary epithelial cells from COPD patients, again correlating with increased susceptibility to influenza. Importantly, restoration of SOCS5 levels restricted influenza virus infection, suggesting that manipulating SOCS5 expression and/or SOCS5 targets might be a novel therapeutic approach to influenza.

Evidence that UV-inducible error-prone repair is absent in Haemophilus influenzae Rd, with a discussion of the relation to error-prone repair of alkylating-agent damage

International Nuclear Information System (INIS)

Kimball, R.F.; Boling, M.E.; Perdue, S.W.

1977-01-01

Haemophilus influenzae Rd and its derivatives are mutated either not at all or to only a very small extent by ultraviolet radiation, X-rays, methyl methanesulfonate, and nitrogen mustard, though they are readily mutated by such agents as N-methyl-N'-nitro-N-nitrosoguanidine, ethyl methanesulfonate, and nitrosocarbaryl (NC). In these respects H. influenzae Rd resembles the lexA mutants of Escherichia coli that lack the SOS or reclex UV-inducible error-prone repair system. This similarity is further brought out by the observation that chloramphenicol has little or no effect on post-replication repair after UV irradiation. In E. coli, chloramphenicol has been reported to considerably inhibit post-replication repair in the wild type but not in the lexA mutant. Earlier work has suggested that most or all the mutations induced in H. influenzae by NC result from error-prone repair. Combined treatment with NC and either X-rays or UV shows that the NC error-prone repair system does not produce mutations from the lesions induced by these radiations even while it is producing them from its own lesions. It is concluded that the NC error-prone repair system or systems and the reclex error-prone system are different

Hand hygiene to reduce community transmission of influenza and acute respiratory tract infection: a systematic review

Science.gov (United States)

Warren‐Gash, Charlotte; Fragaszy, Ellen; Hayward, Andrew C.

2012-01-01

Please cite this paper as: Warren‐Gash et al. (2012) Hand hygiene to reduce community transmission of influenza and acute respiratory tract infection: a systematic review. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12015. Hand hygiene may be associated with modest protection against some acute respiratory tract infections, but its specific role in influenza transmission in different settings is unclear. We aimed to review evidence that improving hand hygiene reduces primary and secondary transmission of (i) influenza and (ii) acute respiratory tract infections in community settings. We searched Medline, Embase, Global Health and Cochrane databases up to 13 February 2012 for reports in any language of original research investigating the effect of hand hygiene on influenza or acute respiratory tract infection where aetiology was unspecified in community settings including institutions such as schools, and domestic residences. Data were presented and quality rated across outcomes according to the Grading of Recommendations Assessment, Development and Evaluation system. Sixteen articles met inclusion criteria. There was moderate to low‐quality evidence of a reduction in both influenza and respiratory tract infection with hand hygiene interventions in schools, greatest in a lower–middle‐income setting. There was high‐quality evidence of a small reduction in respiratory infection in childcare settings. There was high‐quality evidence for a large reduction in respiratory infection with a hand hygiene intervention in squatter settlements in a low‐income setting. There was moderate‐ to high‐quality evidence of no effect on secondary transmission of influenza in households that had already experienced an index case. While hand hygiene interventions have potential to reduce transmission of influenza and acute respiratory tract infections, their effectiveness varies depending on setting, context and compliance. PMID:23043518

Diagnosing avian influenza infection in vaccinated populations by systems for differentiating infected from vaccinated animals (DIVA).

Science.gov (United States)

Capua, I; Cattoli, G

2007-01-01

Vaccination against avian influenza is recommended as a tool to support control measures in countries affected by avian influenza. Vaccination is known to increase the resistance of susceptible birds to infection and also to reduce shedding; however, it does not always prevent infection. Vaccinated infected flocks can therefore be a source of infection and thus be responsible for the perpetuation of infection. To avoid the spread of infection in a vaccinated population, immunization strategies must allow differentiation of infected from vaccinated animals (DIVA), combined with an appropriate monitoring system. Vaccinated exposed flocks must be identified and managed by restriction policies that include controlled marketing and stamping-out. Several vaccines and diagnostic tests to detect infection in vaccinated populations are available, the tests having various properties and characteristics. In order to achieve eradication, the most appropriate DIVA vaccination strategy must be identified and an appropriate monitoring programme be designed, taking into account risk factors, the epidemiological situation and the socioeconomic implications of the policy.

Immunogenicity of Nontypeable Haemophilus influenzae Outer Membrane Vesicles and Protective Ability in the Chinchilla Model of Otitis Media.

Science.gov (United States)

Winter, Linda E; Barenkamp, Stephen J

2017-10-01

Outer membrane vesicles (OMVs) produced by Gram-negative bacteria are enriched in several outer membrane components, including major and minor outer membrane proteins and lipooligosaccharide. We assessed the functional activity of nontypeable Haemophilus influenzae (NTHi) OMV-specific antisera and the protective ability of NTHi OMVs as vaccine antigens in the chinchilla otitis media model. OMVs were purified from three HMW1/HMW2-expressing NTHi strains, two of which were also engineered to overexpress Hia proteins. OMV-specific antisera raised in guinea pigs were assessed for their ability to mediate killing of representative NTHi in an opsonophagocytic assay. The three OMV-specific antisera mediated killing of 18 of 65, 24 of 65, and 30 of 65 unrelated HMW1/HMW2-expressing NTHi strains. Overall, they mediated killing of 39 of 65 HMW1/HMW2-expressing strains. The two Hia-expressing OMV-specific antisera mediated killing of 17 of 25 and 14 of 25 unrelated Hia-expressing NTHi strains. Overall, they mediated killing of 20 of 25 Hia-expressing strains. OMVs from prototype NTHi strain 12 were used to immunize chinchillas and the course of middle ear infection was monitored following intrabullar challenge with the homologous strain. All control animals developed culture-positive otitis media, as did two of three HMW1/HMW2-immunized animals. All OMV-immunized animals, with or without supplemental HMW1/HMW2 immunization, were completely protected against otitis media. NTHi OMVs are the first immunogens examined in this model that provided complete protection with sterile immunity after NTHi strain 12 challenge. These data suggest that NTHi OMVs hold significant potential as components of protective NTHi vaccines, possibly in combination with HMW1/HMW2 proteins. Copyright © 2017 American Society for Microbiology.

Aging augments the impact of influenza respiratory tract infection on mobility impairments, muscle-localized inflammation, and muscle atrophy.

Science.gov (United States)

Bartley, Jenna M; Pan, Sarah J; Keilich, Spencer R; Hopkins, Jacob W; Al-Naggar, Iman M; Kuchel, George A; Haynes, Laura

2016-04-01

Although the influenza virus only infects the respiratory system, myalgias are commonly experienced during infection. In addition to a greater risk of hospitalization and death, older adults are more likely to develop disability following influenza infection; however, this relationship is understudied. We hypothesized that upon challenge with influenza, aging would be associated with functional impairments, as well as upregulation of skeletal muscle inflammatory and atrophy genes. Infected young and aged mice demonstrated decreased mobility and altered gait kinetics. These declines were more prominent in hind limbs and in aged mice. Skeletal muscle expression of genes involved in inflammation, as well as muscle atrophy and proteolysis, increased during influenza infection with an elevated and prolonged peak in aged mice. Infection also decreased expression of positive regulators of muscle mass and myogenesis components to a greater degree in aged mice. Gene expression correlated to influenza-induced body mass loss, although evidence did not support direct muscle infection. Overall, influenza leads to mobility impairments with induction of inflammatory and muscle degradation genes and downregulation of positive regulators of muscle. These effects are augmented and prolonged with aging, providing a molecular link between influenza infection, decreased resilience and increased risk of disability in the elderly.

Viruses Associated With Acute Respiratory Infections and Influenza-like Illness Among Outpatients From the Influenza Incidence Surveillance Project, 2010–2011

Science.gov (United States)

Fowlkes, Ashley; Giorgi, Andrea; Erdman, Dean; Temte, Jon; Goodin, Kate; Di Lonardo, Steve; Sun, Yumei; Martin, Karen; Feist, Michelle; Linz, Rachel; Boulton, Rachelle; Bancroft, Elizabeth; McHugh, Lisa; Lojo, Jose; Filbert, Kimberly; Finelli, Lyn

2017-01-01

Background The Influenza Incidence Surveillance Project (IISP) monitored outpatient acute respiratory infection (ARI; defined as the presence of ≥2 respiratory symptoms not meeting ILI criteria) and influenza-like illness (ILI) to determine the incidence and contribution of associated viral etiologies. Methods From August 2010 through July 2011, 57 outpatient healthcare providers in 12 US sites reported weekly the number of visits for ILI and ARI and collected respiratory specimens on a subset for viral testing. The incidence was estimated using the number of patients in the practice as the denominator, and the virus-specific incidence of clinic visits was extrapolated from the proportion of patients testing positive. Results The age-adjusted cumulative incidence of outpatient visits for ARI and ILI combined was 95/1000 persons, with a viral etiology identified in 58% of specimens. Most frequently detected were rhinoviruses/enteroviruses (RV/EV) (21%) and influenza viruses (21%); the resulting extrapolated incidence of outpatient visits was 20 and 19/1000 persons respectively. The incidence of influenza virus-associated clinic visits was highest among patients aged 2–17 years, whereas other viruses had varied patterns among age groups. Conclusions The IISP provides a unique opportunity to estimate the outpatient respiratory illness burden by etiology. Influenza virus infection and RV/EV infection(s) represent a substantial burden of respiratory disease in the US outpatient setting, particularly among children. PMID:24338352

Pretreatment of Mice with Oligonucleotide prop5 Protects Them from Influenza Virus Infections

Directory of Open Access Journals (Sweden)

Kang Li

2014-02-01

Full Text Available Influenza A virus is a successful parasite and requires host factors to complete its life cycle. Prop5 is an antisense oligonucleotide, targeting programmed cell death protein 5 (PDCD5. In this study, we tested the antiviral activity of prop5 against mouse-adapted A/FM/1/47 strain of influenza A virus in a mouse model. Prop5 intranasally administered the mice at dosages of 10 and 20 mg/kg/d at 24 h and 30 min before infection, provided 80% and 100% survival rates and prolonged mean survival days in comparison with influenza virus-infected mice (both p < 0.01. Moreover, viral titres in mice pretreated with prop5, at dose of 10 and 20 mg/kg/d, had declined significantly on day two, four, and six post-infection compared with the yields in infected mice (p < 0.05 or p < 0.01; lung index in mice pretreated with prop5 (20 mg/kg/d had been inhibited on day six post-infection (p < 0.05. Western blotting and immunohistochemistry showed that prop5 could down-regulate the PDCD5 protein expression levels in lung tissues of infected mice. These data indicate that antisense oligonucleotide prop5 is a promising drug for prophylaxis and control influenza virus infections and provides an insight into the host-pathogen interaction.

Reduction of influenza virus titer and protection against influenza virus infection in infant mice fed Lactobacillus casei Shirota.

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Yasui, Hisako; Kiyoshima, Junko; Hori, Tetsuji

2004-07-01

We investigated whether oral administration of Lactobacillus casei strain Shirota to neonatal and infant mice ameliorates influenza virus (IFV) infection in the upper respiratory tract and protects against influenza infection. In a model of upper respiratory IFV infection, the titer of virus in the nasal washings of infant mice administered L. casei Shirota (L. casei Shirota group) was significantly (P survival rate of the L. casei Shirota group was significantly (P L. casei Shirota group were significantly greater than those of mice in the control group. These findings suggest that oral administration of L. casei Shirota activates the immature immune system of neonatal and infant mice and protects against IFV infection. Therefore, oral administration of L. casei Shirota may accelerate the innate immune response of the respiratory tract and protect against various respiratory infections in neonates, infants, and children, a high risk group for viral and bacterial infections.

Comparative epidemiology of influenza A and B viral infection in a subtropical region: a 7-year surveillance in Okinawa, Japan

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Yoshikazu Iha

2016-11-01

Full Text Available Abstract Background The epidemic patterns of influenza B infection and their association with climate conditions are not well understood. Influenza surveillance in Okinawa is important for clarifying transmission patterns in both temperate and tropical regions. Using surveillance data, collected over 7 years in the subtropical region of Japan, this study aims to characterize the epidemic patterns of influenza B infection and its association with ambient temperature and relative humidity, in a parallel comparison with influenza A. Methods From January 2007 until March 2014, two individual influenza surveillance datasets were collected from external sources. The first dataset, included weekly rapid antigen test (RAT results from four representative general hospitals, located in the capital city of Okinawa. A nation-wide surveillance of influenza, diagnosed by RAT results and/or influenza-like illness symptoms, included the age distribution of affected patients and was used as the second dataset. To analyze the association between infection and local climate conditions, ambient temperature and relative humidity during the study period were retrieved from the Japanese Meteorological Agency website. Results Although influenza A maintained high number of infections from December through March, epidemics of influenza B infection were observed annually from March through July. The only observed exception was 2010, when the pandemic strain of 2009 dominated. During influenza B outbreaks, influenza patients aged 5 to 9 years old and 10 to 14 years old more frequently visited sentinel sites. Although both ambient temperature and relative humidity are inversely associated with influenza A infection, influenza B infection was found to be directly associated with high relative humidity. Conclusion Further studies are needed to elucidate the complex epidemiology of influenza B and its relationship with influenza A. In the subtropical setting of Okinawa

Influenza A Virus Infection in Pigs Attracts Multifunctional and Cross-Reactive T Cells to the Lung.

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Talker, Stephanie C; Stadler, Maria; Koinig, Hanna C; Mair, Kerstin H; Rodríguez-Gómez, Irene M; Graage, Robert; Zell, Roland; Dürrwald, Ralf; Starick, Elke; Harder, Timm; Weissenböck, Herbert; Lamp, Benjamin; Hammer, Sabine E; Ladinig, Andrea; Saalmüller, Armin; Gerner, Wilhelm

2016-10-15

Pigs are natural hosts for influenza A viruses and play a critical role in influenza epidemiology. However, little is known about their influenza-evoked T-cell response. We performed a thorough analysis of both the local and systemic T-cell response in influenza virus-infected pigs, addressing kinetics and phenotype as well as multifunctionality (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]) and cross-reactivity. A total of 31 pigs were intratracheally infected with an H1N2 swine influenza A virus (FLUAVsw) and consecutively euthanized. Lungs, tracheobronchial lymph nodes, and blood were sampled during the first 15 days postinfection (p.i.) and at 6 weeks p.i. Ex vivo flow cytometry of lung lymphocytes revealed an increase in proliferating (Ki-67(+)) CD8(+) T cells with an early effector phenotype (perforin(+) CD27(+)) at day 6 p.i. Low frequencies of influenza virus-specific IFN-γ-producing CD4(+) and CD8(+) T cells could be detected in the lung as early as 4 days p.i. On consecutive days, influenza virus-specific CD4(+) and CD8(+) T cells produced mainly IFN-γ and/or TNF-α, reaching peak frequencies around day 9 p.i., which were up to 30-fold higher in the lung than in tracheobronchial lymph nodes or blood. At 6 weeks p.i., CD4(+) and CD8(+) memory T cells had accumulated in lung tissue. These cells showed diverse cytokine profiles and in vitro reactivity against heterologous influenza virus strains, all of which supports their potential to combat heterologous influenza virus infections in pigs. Pigs not only are a suitable large-animal model for human influenza virus infection and vaccine development but also play a central role in the emergence of new pandemic strains. Although promising candidate universal vaccines are tested in pigs and local T cells are the major correlate of heterologous control, detailed and targeted analyses of T-cell responses at the site of infection are scarce. With the present study, we

Pandemic (H1N1 2009 Influenza Virus Infection in A Survivor who has recovered from severe H7N9 Virus Infection, China

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Shan-Hui Chen

2016-10-01

Full Text Available We firstly report a patient who presented with severe complications after infection with influenza A(H1N1 pdm2009, more than one year after recovery from severe H7N9 virus infections. The population of patients who recovered from severe H7N9 infections might be at a higher risk to suffer severe complications after seasonal influenza infections, and they should be included in the high-risk populations recommended to receive seasonal influenza vaccination.

Divergent mechanisms for passive pneumococcal resistance to β-lactam antibiotics in the presence of Haemophilus influenzae.

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Weimer, Kristin E D; Juneau, Richard A; Murrah, Kyle A; Pang, Bing; Armbruster, Chelsie E; Richardson, Stephen H; Swords, W Edward

2011-02-15

Otitis media, for which antibiotic treatment failure is increasingly common, is a leading pediatric public health problem. In vitro and in vivo studies using the chinchilla model of otitis media were performed using a β-lactamase-producing strain of nontypeable Haemophilus influenzae (NTHi 86-028NP) and an isogenic mutant deficient in β-lactamase production (NTHi 86-028NP bla) to define the roles of biofilm formation and β-lactamase production in antibiotic resistance. Coinfection studies were done with Streptococcus pneumoniae to determine if NTHi provides passive protection by means of β-lactamase production, biofilm formation, or both. NTHi 86-028NP bla was resistant to amoxicillin killing in biofilm studies in vitro; however, it was cleared by amoxicillin treatment in vivo, whereas NTHi 86-028NP was unaffected in either system. NTHi 86-028NP protected pneumococcus in vivo in both the effusion fluid and bullar homogenate. NTHi 86-028NP bla and pneumococcus were both recovered from the surface-associated bacteria of amoxicillin-treated animals; only NTHi 86-028NP bla was recovered from effusion. Based on these studies, we conclude that NTHi provides passive protection for S. pneumoniae in vivo through 2 distinct mechanisms: production of β-lactamase and formation of biofilm communities.

Comparative supragenomic analyses among the pathogens Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae Using a modification of the finite supragenome model

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Yu Susan

2011-04-01

Full Text Available Abstract Background Staphylococcus aureus is associated with a spectrum of symbiotic relationships with its human host from carriage to sepsis and is frequently associated with nosocomial and community-acquired infections, thus the differential gene content among strains is of interest. Results We sequenced three clinical strains and combined these data with 13 publically available human isolates and one bovine strain for comparative genomic analyses. All genomes were annotated using RAST, and then their gene similarities and differences were delineated. Gene clustering yielded 3,155 orthologous gene clusters, of which 2,266 were core, 755 were distributed, and 134 were unique. Individual genomes contained between 2,524 and 2,648 genes. Gene-content comparisons among all possible S. aureus strain pairs (n = 136 revealed a mean difference of 296 genes and a maximum difference of 476 genes. We developed a revised version of our finite supragenome model to estimate the size of the S. aureus supragenome (3,221 genes, with 2,245 core genes, and compared it with those of Haemophilus influenzae and Streptococcus pneumoniae. There was excellent agreement between RAST's annotations and our CDS clustering procedure providing for high fidelity metabolomic subsystem analyses to extend our comparative genomic characterization of these strains. Conclusions Using a multi-species comparative supragenomic analysis enabled by an improved version of our finite supragenome model we provide data and an interpretation explaining the relatively larger core genome of S. aureus compared to other opportunistic nasopharyngeal pathogens. In addition, we provide independent validation for the efficiency and effectiveness of our orthologous gene clustering algorithm.

Safety and Immunogenicity of Coadministering a Combined Meningococcal Serogroup C and Haemophilus influenzae Type b Conjugate Vaccine with 7-Valent Pneumococcal Conjugate Vaccine and Measles, Mumps, and Rubella Vaccine at 12 Months of Age ▿

OpenAIRE

Miller, Elizabeth; Andrews, Nick; Waight, Pauline; Findlow, Helen; Ashton, Lindsey; England, Anna; Stanford, Elaine; Matheson, Mary; Southern, Joanna; Sheasby, Elizabeth; Goldblatt, David; Borrow, Ray

2010-01-01

The coadministration of the combined meningococcal serogroup C conjugate (MCC)/Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age was investigated to assess the safety and immunogenicity of this regimen compared with separate administration of the conjugate vaccines. Children were randomized to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine or to receive all thr...

Evidence of functional cell-mediated immune responses to nontypeable Haemophilus influenzae in otitis-prone children

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Seppanen, Elke; Tan, Dino; Corscadden, Karli J.; Currie, Andrew J.; Richmond, Peter C.; Thornton, Ruth B.

2018-01-01

Otitis media (OM) remains a common paediatric disease, despite advances in vaccinology. Susceptibility to recurrent acute OM (rAOM) has been postulated to involve defective cell-mediated immune responses to common otopathogenic bacteria. We compared the composition of peripheral blood mononuclear cells (PBMC) from 20 children with a history of rAOM (otitis-prone) and 20 healthy non-otitis-prone controls, and assessed innate and cell-mediated immune responses to the major otopathogen nontypeable Haemophilus influenzae (NTHi). NTHi was a potent stimulator of inflammatory cytokine secretion from PBMC within 4 hours, with no difference in cytokine levels produced between PBMC from cases or controls. In the absence of antigen stimulation, otitis-prone children had more circulating Natural Killer (NK) cells (potitis-prone and non-otitis-prone children (potitis-prone children are functional and respond to NTHi. CD8+ T cells and NK cells from both cases and controls produced IFNγ in response to polyclonal stimulus (Staphylococcal enterotoxin B; SEB), with more IFNγ+ CD8+ T cells present in cases than controls (pOtitis-prone children had more circulating IFNγ-producing NK cells (potitis-prone children mounted innate and T cell-mediated responses to NTHi challenge that were comparable to healthy children. These data provide evidence that otitis-prone children do not have impaired functional cell mediated immunity. PMID:29621281

Demographic and ecological risk factors for human influenza A virus infections in rural Indonesia.

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Root, Elisabeth Dowling; Agustian, Dwi; Kartasasmita, Cissy; Uyeki, Timothy M; Simões, Eric A F

2017-09-01

Indonesia has the world's highest reported mortality for human infections with highly pathogenic avian influenza (HPAI) A(H5N1) virus. Indonesia is an agriculturally driven country where human-animal mixing is common and provides a unique environment for zoonotic influenza A virus transmission. To identify potential demographic and ecological risk factors for human infection with seasonal influenza A viruses in rural Indonesia, a population-based study was conducted in Cileunyi and Soreang subdistricts near Bandung in western Java from 2008 to 2011. Passive influenza surveillance with RT-PCR confirmation of influenza A viral RNA in respiratory specimens was utilized for case ascertainment. A population census and mapping were utilized for population data collection. The presence of influenza A(H3N2) and A(H1N1)pdm09 virus infections in a household was modeled using Generalized Estimating Equations. Each additional child aged <5 years in a household increased the odds of H3N2 approximately 5 times (OR=4.59, 95%CI: 3.30-6.24) and H1N1pdm09 by 3.5 times (OR=3.53, 95%CI: 2.51-4.96). In addition, the presence of 16-30 birds in the house was associated with an increased odds of H3N2 (OR=5.08, 95%CI: 2.00-12.92) and H1N1pdm09 (OR=12.51 95%CI: 6.23-25.13). Our findings suggest an increase in influenza A virus infections in rural Indonesian households with young children and poultry. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Clinical characteristics and factors associated with severe acute respiratory infection and influenza among children in Jingzhou, China.

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Huai, Yang; Guan, Xuhua; Liu, Shali; Uyeki, Timothy M; Jiang, Hui; Klena, John; Huang, Jigui; Chen, Maoyi; Peng, Youxing; Yang, Hui; Luo, Jun; Zheng, Jiandong; Peng, Zhibin; Huo, Xixiang; Xiao, Lin; Chen, Hui; Zhang, Yuzhi; Xing, Xuesen; Feng, Luzhao; Hu, Dale J; Yu, Hongjie; Zhan, Faxian; Varma, Jay K

2017-03-01

Influenza is an important cause of respiratory illness in children, but data are limited on hospitalized children with laboratory-confirmed influenza in China. We conducted active surveillance for severe acute respiratory infection (SARI; fever and at least one sign or symptom of acute respiratory illness) among hospitalized pediatric patients in Jingzhou, Hubei Province, from April 2010 to April 2012. Data were collected from enrolled SARI patients on demographics, underlying health conditions, clinical course of illness, and outcomes. Nasal swabs were collected and tested for influenza viruses by reverse transcription polymerase chain reaction. We described the clinical and epidemiological characteristics of children with influenza and analyzed the association between potential risk factors and SARI patients with influenza. During the study period, 15 354 children aged acute respiratory infection patients aged 5-15 years with confirmed influenza (H3N2) infection were more likely than children without influenza to have radiographic diagnosis of pneumonia (11/31, 36% vs 15/105, 14%. Pacute respiratory infection cases aged 5-15 years diagnosed with influenza were also more likely to have a household member who smoked cigarettes compared with SARI cases without a smoking household member (54/208, 26% vs 158/960, 16%, Pinfection was an important contributor to pneumonia requiring hospitalization. Our results highlight the importance of surveillance in identifying factors for influenza hospitalization, monitoring adherence to influenza prevention and treatment strategies, and evaluating the disease burden among hospitalized pediatric SARI patients. Influenza vaccination promotion should target children. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Airborne Transmission of Highly Pathogenic Influenza Virus during Processing of Infected Poultry.

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Bertran, Kateri; Balzli, Charles; Kwon, Yong-Kuk; Tumpey, Terrence M; Clark, Andrew; Swayne, David E

2017-11-01

Exposure to infected poultry is a suspected cause of avian influenza (H5N1) virus infections in humans. We detected infectious droplets and aerosols during laboratory-simulated processing of asymptomatic chickens infected with human- (clades 1 and 2.2.1) and avian- (clades 1.1, 2.2, and 2.1) origin H5N1 viruses. We detected fewer airborne infectious particles in simulated processing of infected ducks. Influenza virus-naive chickens and ferrets exposed to the air space in which virus-infected chickens were processed became infected and died, suggesting that the slaughter of infected chickens is an efficient source of airborne virus that can infect birds and mammals. We did not detect consistent infections in ducks and ferrets exposed to the air space in which virus-infected ducks were processed. Our results support the hypothesis that airborne transmission of HPAI viruses can occur among poultry and from poultry to humans during home or live-poultry market slaughter of infected poultry.

Epidemiological and molecular surveillance of influenza and respiratory syncytial viruses in children with acute respiratory infections (2004/2005 season

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Alessandra Zappa

2008-03-01

Full Text Available Objective. During the 2004/2005 influenza season an active virological surveillance of influenza viruses and respiratory syncytial virus (RSV was carried out to monitor the epidemiologic trend of acute respiratory infections (ARI in the paediatric community. Materials and methods. 100 patients (51 males, 49 females; mean age: 19 months, either treated at the Emergency Unit or hospitalized in the Pediatric Unit of “San Carlo Borromeo Hospital” (Milan, reporting symptoms related to ARI were enrolled. Pharyngeal swabs were collected for virological investigation by: 1 multiplexnested- PCR for the simultaneous identification of both influenza A and B viruses and RSV; 2 multiplex-nested- PCR for the subtyping of influenza A viruses (H1 and H3. Results. 12% (12/100 subjects were infected with influenza A virus, 4% (4/100 with influenza B virus and 14 (14% with RSV. Of all the 12 influenza A positive samples 4 (33.3% belonged to subtype H1 and 8 (66.7% to subtype H3. Bronchiolitis and bronchitis episodes were significantly higher among RSV-infected subjects than among influenza- infected subjects (42.8% vs 6.2%; p<0.05 and 35.7% vs 6.2%; p<0.05, respectively. Pneumonia episodes occurred similarly both in influenza-infected children and in RSV-infected ones. Conclusions. During the 2004/2005 influenza season, influenza viruses and RSV were liable for high morbidity among paediatric subjects.The present study underlies the importance of planning an active surveillance of respiratory viral infections among paediatric cases requiring hospitalization due to ARI.A thorough analysis of target population features, of viruses antigenic properties and seasonality will be decisive in the evaluation of each clinical event.

Aerosol challenge of calves with Haemophilus somnus and Mycoplasma dispar

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Tegtmeier, C.; Angen, Øystein; Grell, S.N.

2000-01-01

The aim of the study was to examine the ability of Haemophilus somnus and Mycoplasma dispar to induce pneumonia in healthy calves under conditions closely resembling the supposed natural way of infection, viz, by inhalation of aerosol droplets containing the microorganisms. The infections were...

Relation between enzyme-linked immunosorbent assay and radioimmunoassay for detection of antibodies to the capsular polysaccharide of Haemophilus influenzae type b

International Nuclear Information System (INIS)

Kristensen, K.; Weis Bentzon, M.

1992-01-01

The measurement of antibodies to the capsular polysaccharide (PRP) of Haemophilus influenzae type b (Hib) is important because vaccines inducing such antibodies are now available. We developed and evaluated an enzyme-linked immunosorbent assay (ELISA) for detection of these antibodies based on direct coating of the plates with tyraminated PRP. The assay fulfilled the requirements for parallel line assays; it was sensitive, specific, and reproducible with a coefficient of variation between days of 19%. Results from the ELISA were compared with results from radioimmunoassay and a correlation coefficient of 0.93 was found. Results obtained by the two methods were proportional and the relation was indepenedent of the antibody level. The relation between them was also unaffected by the contribution of different antibody isotypes, indicating that these were measured to the same extent by both methods. ELISA employing direct coating of the plates with tyraminated PRP represents a useful alternative for detection of antibodies when studying immunogenicity of Hib vaccines. (au)

A clinical trial examining the effect of increased total CRM(197) carrier protein dose on the antibody response to Haemophilus influenzae type b CRM(197) conjugate vaccine.

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Usonis, Vytautas; Bakasenas, Vytautas; Lockhart, Stephen; Baker, Sherryl; Gruber, William; Laudat, France

2008-08-18

CRM(197) is a carrier protein in certain conjugate vaccines. When multiple conjugate vaccines with the same carrier protein are administered simultaneously, reduced response to vaccines and/or antigens related to the carrier protein may occur. This study examined responses of infants who, in addition to diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine (DTaP) received either diphtheria CRM(197)-based Haemophilus influenzae type b conjugate vaccine (HbOC) or HbOC and a diphtheria CRM(197)-based combination 9-valent pneumococcal conjugate vaccine/meningococcal group C conjugate vaccine. Administration of conjugate vaccines with CRM(197) carrier protein load >50 microg did not reduce response to CRM(197) conjugate vaccines or immunogenicity to immunologically cross-reactive diphtheria toxoid.

The role of neutrophils in the upper and lower respiratory tract during influenza virus infection of mice

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Reading Patrick C

2008-08-01

Full Text Available Abstract Background Neutrophils have been shown to play a role in host defence against highly virulent and mouse-adapted strains of influenza virus, however it is not clear if an effective neutrophil response is an important factor moderating disease severity during infection with other virus strains. In this study, we have examined the role of neutrophils during infection of mice with influenza virus strain HKx31, a virus strain of the H3N2 subtype and of moderate virulence for mice, to determine the role of neutrophils in the early phase of infection and in clearance of influenza virus from the respiratory tract during the later phase of infection. Methods The anti-Gr-1 monoclonal antibody (mAb RB6-8C5 was used to (i identify neutrophils in the upper (nasal tissues and lower (lung respiratory tract of uninfected and influenza virus-infected mice, and (ii deplete neutrophils prior to and during influenza virus infection of mice. Results Neutrophils were rapidly recruited to the upper and lower airways following influenza virus infection. We demonstrated that use of mAb RB6-8C5 to deplete C57BL/6 (B6 mice of neutrophils is complicated by the ability of this mAb to bind directly to virus-specific CD8+ T cells. Thus, we investigated the role of neutrophils in both the early and later phases of infection using CD8+ T cell-deficient B6.TAP-/- mice. Infection of B6.TAP-/- mice with a low dose of influenza virus did not induce clinical disease in control animals, however RB6-8C5 treatment led to profound weight loss, severe clinical disease and enhanced virus replication throughout the respiratory tract. Conclusion Neutrophils play a critical role in limiting influenza virus replication during the early and later phases of infection. Furthermore, a virus strain of moderate virulence can induce severe clinical disease in the absence of an effective neutrophil response.

Optic neuritis and acute anterior uveitis associated with influenza A infection: a case report

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Nakagawa H

2017-01-01

Full Text Available Hayate Nakagawa, Hidetaka Noma, Osamu Kotake, Ryosuke Motohashi, Kanako Yasuda, Masahiko Shimura Department of Ophthalmology, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan Background: A few reports have described ocular complications of influenza A infection, such as impaired ocular movement, parasympathetic ocular nerve, keratitis, macular lesion, and frosted branch angiitis. We encountered a rare case of acute anterior uveitis and optic neuritis associated with influenza A infection. Case presentation: A 70-year-old man presented with symptoms of upper respiratory tract infection. A rapid diagnostic test showed a positive result for influenza A. At the same time, he developed ocular symptoms including blurred vision with optic disk edema and hemorrhage in the left eye, and bilateral red eyes. Multiplex polymerase chain reaction performed on aqueous humor sample detected no viral infection. Visual field testing with a Goldmann perimeter showed central and paracentral scotomas in the left eye. In addition to antiviral agent (oseltamivir phosphate 75 mg, the patient was prescribed topical prednisolone acetate ophthalmic suspension eye drops every 5 hours and high-dose intravenous methylprednisolone 1,000 mg daily for 3 days. Two months later, his best-corrected visual acuity improved to 20/50 with regression of visual field defects in his left eye. Conclusion: We report a case of bilateral acute anterior uveitis and unilateral optic neuritis concomitant with influenza A infection. Topical and systemic corticosteroids were effective to resolve acute anterior uveitis and neuritis. Analysis of aqueous humor sample suggested that acute anterior uveitis and optic neuritis in this case were not caused by influenza A virus infection per se but by autoimmune mechanism. Keywords: optic neuritis, anterior uveitis, influenza virus, multiplex polymerase chain reaction

Viral etiologies of influenza-like illness and severe acute respiratory infections in Thailand.

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Chittaganpitch, Malinee; Waicharoen, Sunthareeya; Yingyong, Thitipong; Praphasiri, Prabda; Sangkitporn, Somchai; Olsen, Sonja J; Lindblade, Kim A

2018-07-01

Information on the burden, characteristics and seasonality of non-influenza respiratory viruses is limited in tropical countries. Describe the epidemiology of selected non-influenza respiratory viruses in Thailand between June 2010 and May 2014 using a sentinel surveillance platform established for influenza. Patients with influenza-like illness (ILI; history of fever or documented temperature ≥38°C, cough, not requiring hospitalization) or severe acute respiratory infection (SARI; history of fever or documented temperature ≥38°C, cough, onset respiratory syncytial virus (RSV), metapneumovirus (MPV), parainfluenza viruses (PIV) 1-3, and adenoviruses by polymerase chain reaction (PCR) or real-time reverse transcriptase-PCR. We screened 15 369 persons with acute respiratory infections and enrolled 8106 cases of ILI (5069 cases respiratory viruses tested, while for SARI cases respiratory viruses, particularly seasonality, although adjustments to case definitions may be required. © 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

In Vitro Capability of Faropenem To Select for Resistant Mutants of Streptococcus pneumoniae and Haemophilus influenzae▿ †

Science.gov (United States)

Kosowska-Shick, Klaudia; Clark, Catherine; Credito, Kim; Dewasse, Bonifacio; Beachel, Linda; Ednie, Lois; Appelbaum, Peter C.

2008-01-01

When tested against nine strains of pneumococci and six of Haemophilus influenzae of various resistotypes, faropenem failed to select for resistant mutants after 50 days of consecutive subculture in subinhibitory concentrations. Faropenem also yielded low rates of spontaneous mutations against all organisms of both species. By comparison, resistant clones were obtained with macrolides, ketolides, and quinolones. PMID:18086853

Cross-Species Infectivity of H3N8 Influenza Virus in an Experimental Infection in Swine.

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Solórzano, Alicia; Foni, Emanuela; Córdoba, Lorena; Baratelli, Massimiliano; Razzuoli, Elisabetta; Bilato, Dania; Martín del Burgo, María Ángeles; Perlin, David S; Martínez, Jorge; Martínez-Orellana, Pamela; Fraile, Lorenzo; Chiapponi, Chiara; Amadori, Massimo; del Real, Gustavo; Montoya, María

2015-11-01

Avian influenza A viruses have gained increasing attention due to their ability to cross the species barrier and cause severe disease in humans and other mammal species as pigs. H3 and particularly H3N8 viruses, are highly adaptive since they are found in multiple avian and mammal hosts. H3N8 viruses have not been isolated yet from humans; however, a recent report showed that equine influenza A viruses (IAVs) can be isolated from pigs, although an established infection has not been observed thus far in this host. To gain insight into the possibility of H3N8 avian IAVs to cross the species barrier into pigs, in vitro experiments and an experimental infection in pigs with four H3N8 viruses from different origins (equine, canine, avian, and seal) were performed. As a positive control, an H3N2 swine influenza virus A was used. Although equine and canine viruses hardly replicated in the respiratory systems of pigs, avian and seal viruses replicated substantially and caused detectable lesions in inoculated pigs without previous adaptation. Interestingly, antibodies against hemagglutinin could not be detected after infection by hemagglutination inhibition (HAI) test with avian and seal viruses. This phenomenon was observed not only in pigs but also in mice immunized with the same virus strains. Our data indicated that H3N8 IAVs from wild aquatic birds have the potential to cross the species barrier and establish successful infections in pigs that might spread unnoticed using the HAI test as diagnostic tool. Although natural infection of humans with an avian H3N8 influenza A virus has not yet been reported, this influenza A virus subtype has already crossed the species barrier. Therefore, we have examined the potential of H3N8 from canine, equine, avian, and seal origin to productively infect pigs. Our results demonstrated that avian and seal viruses replicated substantially and caused detectable lesions in inoculated pigs without previous adaptation. Surprisingly, we

Reemergence of the Natural History of Otolaryngologic Infections: Lessons Learned from 2 American Presidents.

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Naples, James; Schwartz, Marissa; Eisen, Marc

2017-09-01

Presidents George Washington and Theodore Roosevelt suffered complications of epiglottitis and otomastoiditis, respectively. The introduction of antibiotics and vaccinations against Haemophilus influenzae and Streptococcus pneumoniae has significantly reduced the incidence of these otolaryngologic infections, such that the natural history of the disease is rarely encountered. However, antibiotic resistance and pathogenic evolution has raised concern about increased virulence of these common organisms. A retrospective evaluation of the complications suffered by Washington and Roosevelt provides valuable insight to the natural history of common otolaryngologic infections that may reemerge as a result of organism evolution in response to antibiotics and vaccines.

Acute Respiratory Distress Syndrome Caused by Influenza B Virus Infection in a Patient with Diffuse Large B-Cell Lymphoma

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Silvio A. Ñamendys-Silva

2011-01-01

Full Text Available Influenza B virus infections are less common than infections caused by influenza A virus in critically ill patients, but similar mortality rates have been observed for both influenza types. Pneumonia caused by influenza B virus is uncommon and has been reported in pediatric patients and previously healthy adults. Critically ill patients with pneumonia caused by influenza virus may develop acute respiratory distress syndrome. We describe the clinical course of a critically ill patient with diffuse large B-cell lymphoma nongerminal center B-cell phenotype who developed acute respiratory distress syndrome caused by influenza B virus infection. This paper emphasizes the need to suspect influenza B virus infection in critically ill immunocompromised patients with progressive deterioration of cardiopulmonary function despite treatment with antibiotics. Early initiation of neuraminidase inhibitor and the implementation of guidelines for management of severe sepsis and septic shock should be considered.

The dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase from Haemophilus influenzae is a dinuclear metallohydrolase.

Science.gov (United States)

Cosper, Nathaniel J; Bienvenue, David L; Shokes, Jacob E; Gilner, Danuta M; Tsukamoto, Takashi; Scott, Robert A; Holz, Richard C

2003-12-03

The Zn K-edge extended X-ray absorption fine structure (EXAFS) spectra, of the dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) from Haemophilus influenzae have been recorded in the presence of one or two equivalents of Zn(II) (i.e. [Zn_(DapE)] and [ZnZn(DapE)]). The Fourier transforms of the Zn EXAFS are dominated by a peak at ca. 2.0 A, which can be fit for both [Zn_(DapE)] and [ZnZn(DapE)], assuming ca. 5 (N,O) scatterers at 1.96 and 1.98 A, respectively. A second-shell feature at ca. 3.34 A appears in the [ZnZn(DapE)] EXAFS spectrum but is significantly diminished in [Zn_(DapE)]. These data show that DapE contains a dinuclear Zn(II) active site. Since no X-ray crystallographic data are available for any DapE enzyme, these data provide the first glimpse at the active site of DapE enzymes. In addition, the EXAFS data for DapE incubated with two competitive inhibitors, 2-carboxyethylphosphonic acid and 5-mercaptopentanoic acid, are also presented.

Antigen-specific and non-specific CD4+ T cell recruitment and proliferation during influenza infection

International Nuclear Information System (INIS)

Chapman, Timothy J.; Castrucci, Maria R.; Padrick, Ryan C.; Bradley, Linda M.; Topham, David J.

2005-01-01

To track epitope-specific CD4 + T cells at a single-cell level during influenza infection, the MHC class II-restricted OVA 323-339 epitope was engineered into the neuraminidase stalk of influenza/A/WSN, creating a surrogate viral antigen. The recombinant virus, influenza A/WSN/OVA II , replicated well, was cleared normally, and stimulated both wild-type and DO11.10 or OT-II TCR transgenic OVA-specific CD4 + T cells. OVA-specific CD4 T cells proliferated during infection only when the OVA epitope was present. However, previously primed (but not naive) transgenic CD4 + T cells were recruited to the infected lung both in the presence and absence of the OVA 323-339 epitope. These data show that, when primed, CD4 + T cells may traffic to the lung in the absence of antigen, but do not proliferate. These results also document a useful tool for the study of CD4 T cells in influenza infection

Sparse evidence for equine or avian influenza virus infections among Mongolian adults with animal exposures

OpenAIRE

Khurelbaatar, Nyamdavaa; Krueger, Whitney S.; Heil, Gary L.; Darmaa, Badarchiin; Ulziimaa, Daramragchaa; Tserennorov, Damdindorj; Baterdene, Ariungerel; Anderson, Benjamin D.; Gray, Gregory C.

2013-01-01

In recent years, Mongolia has experienced recurrent epizootics of equine influenza virus (EIV) among its 2?1 million horses and multiple incursions of highly pathogenic avian influenza (HPAI) virus via migrating birds. No human EIV or HPAI infections have been reported. In 2009, 439 adults in Mongolia were enrolled in a population?based study of zoonotic influenza transmission. Enrollment sera were examined for serological evidence of infection with nine avian, three human, and one equine inf...

Hand hygiene to reduce community transmission of influenza and acute respiratory tract infection: a systematic review.

Science.gov (United States)

Warren-Gash, Charlotte; Fragaszy, Ellen; Hayward, Andrew C

2013-09-01

Hand hygiene may be associated with modest protection against some acute respiratory tract infections, but its specific role in influenza transmission in different settings is unclear. We aimed to review evidence that improving hand hygiene reduces primary and secondary transmission of (i) influenza and (ii) acute respiratory tract infections in community settings. We searched Medline, Embase, Global Health and Cochrane databases up to 13 February 2012 for reports in any language of original research investigating the effect of hand hygiene on influenza or acute respiratory tract infection where aetiology was unspecified in community settings including institutions such as schools, and domestic residences. Data were presented and quality rated across outcomes according to the Grading of Recommendations Assessment, Development and Evaluation system. Sixteen articles met inclusion criteria. There was moderate to low-quality evidence of a reduction in both influenza and respiratory tract infection with hand hygiene interventions in schools, greatest in a lower-middle-income setting. There was high-quality evidence of a small reduction in respiratory infection in childcare settings. There was high-quality evidence for a large reduction in respiratory infection with a hand hygiene intervention in squatter settlements in a low-income setting. There was moderate- to high-quality evidence of no effect on secondary transmission of influenza in households that had already experienced an index case. While hand hygiene interventions have potential to reduce transmission of influenza and acute respiratory tract infections, their effectiveness varies depending on setting, context and compliance. © 2012 John Wiley & Sons Ltd.

Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2

Energy Technology Data Exchange (ETDEWEB)

Hamilton, Brian S.; Chung, Changik; Cyphers, Soreen Y.; Rinaldi, Vera D.; Marcano, Valerie C.; Whittaker, Gary R., E-mail: grw7@cornell.edu

2014-07-25

Highlights: • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza HA cleavage activation. • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza virus infection. • Comparative analysis of HAI-2 for vesicular stomatitis virus and human parainfluenza virus type-1. • Analysis of the activity of HAI-2 in a mouse model of influenza. - Abstract: Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant to the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza.

Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2

International Nuclear Information System (INIS)

Hamilton, Brian S.; Chung, Changik; Cyphers, Soreen Y.; Rinaldi, Vera D.; Marcano, Valerie C.; Whittaker, Gary R.

2014-01-01

Highlights: • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza HA cleavage activation. • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza virus infection. • Comparative analysis of HAI-2 for vesicular stomatitis virus and human parainfluenza virus type-1. • Analysis of the activity of HAI-2 in a mouse model of influenza. - Abstract: Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant to the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza

Impacto de la vacunación contra Haemophilus influenzae tipo b en Cuba

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Dickinson Félix O.

2001-01-01

Full Text Available Objetivo. Determinar el impacto de la vacunación de menores de 2 años en Cuba contra Haemophilus influenzae tipo b (Hib, principal agente causal de la meningitis bacteriana en ese país. Métodos. La disponibilidad de vacunas conjugadas eficaces contra Hib motivó la vacunación nacional en 1999 de niños menores de 2 años, que alcanzó una cobertura de 97%. El impacto se evaluó mediante el Sistema Nacional de Vigilancia de Meningoencefalitis Bacterianas (SNVMEB. Resultados. La eficacia global de la vacunación se estimó en 99% y la incidencia general de la meningoencefalitis por Hib disminuyó de 1,3 a 0,6 por 100 000 habitantes (46,1%, observándose la mayor reducción en niños menores de 5 años (56,1%. En los menores de 1 año se redujo 70,5% y en el resto de los grupos de menores de 5 años disminuyó entre 25,9 y 49,6%. En el grupo diana para la vacunación, la incidencia se redujo 61,1%; entre los niños de este grupo que contrajeron la meningoencefalitis por Hib, solamente 8 (24,2% estaban vacunados, 7 de ellos con una sola dosis, aplicada 1 mes antes de enfermar. Conclusiones. Se ha demostrado que la vacunación a gran escala de los niños menores de 2 años contra Hib en Cuba a través del SNVMEB ha logrado disminuir notablemente la incidencia de meningoencefalitis por Hib.

ATP catabolism by tissue nonspecific alkaline phosphatase contributes to development of ARDS in influenza-infected mice.

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Woods, Parker S; Doolittle, Lauren M; Hickman-Davis, Judy M; Davis, Ian C

2018-01-01

Influenza A viruses are highly contagious respiratory pathogens that are responsible for significant morbidity and mortality worldwide on an annual basis. We have shown previously that influenza infection of mice leads to increased ATP and adenosine accumulation in the airway lumen. Moreover, we demonstrated that A 1 -adenosine receptor activation contributes significantly to influenza-induced acute respiratory distress syndrome (ARDS). However, we found that development of ARDS in influenza-infected mice does not require catabolism of ATP to adenosine by ecto-5'-nucleotidase (CD73). Hence, we hypothesized that increased adenosine generation in response to infection is mediated by tissue nonspecific alkaline phosphatase (TNAP), which is a low-affinity, high-capacity enzyme that catabolizes nucleotides in a nonspecific manner. In the current study, we found that whole lung and BALF TNAP expression and alkaline phosphatase enzymatic activity increased as early as 2 days postinfection (dpi) of C57BL/6 mice with 10,000 pfu/mouse of influenza A/WSN/33 (H1N1). Treatment at 2 and 4 dpi with a highly specific quinolinyl-benzenesulfonamide TNAP inhibitor (TNAPi) significantly reduced whole lung alkaline phosphatase activity at 6 dpi but did not alter TNAP gene or protein expression. TNAPi treatment attenuated hypoxemia, lung dysfunction, histopathology, and pulmonary edema at 6 dpi without impacting viral replication or BALF adenosine. Treatment also improved epithelial barrier function and attenuated cellular and humoral immune responses to influenza infection. These data indicate that TNAP inhibition can attenuate influenza-induced ARDS by reducing inflammation and fluid accumulation within the lung. They also further emphasize the importance of adenosine generation for development of ARDS in influenza-infected mice.

Overview of the Spleen

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... Neisseria meningitidis , and Haemophilus influenzae . Because of this risk, people receive vaccinations to help protect them from infection with these organisms. People should also be sure they receive the influenza vaccine every year, as is now ... the Spleen ...

[Intestinal disorder of anaerobic bacteria aggravates pulmonary immune pathological injury of mice infected with influenza virus].

Science.gov (United States)

Wu, Sha; Yan, Yuqi; Zhang, Mengyuan; Shi, Shanshan; Jiang, Zhenyou

2016-04-01

To investigate the relationship between the intestinal disorder of anaerobic bacteria and influenza virus infection, and the effect on pulmonary inflammatory cytokines in mice. Totally 36 mice were randomly divided into normal control group, virus-infected group and metronidazole treatment group (12 mice in each group). Mice in the metronidazole group were administrated orally with metronidazole sulfate for 8 days causing anaerobic bacteria flora imbalance; then all groups except the normal control group were treated transnasally with influenza virus (50 μL/d FM1) for 4 days to establish the influenza virus-infected models. Their mental state and lung index were observed, and the pathological morphological changes of lung tissues, caecum and intestinal mucosa were examined by HE staining. The levels of interleukin 4 (IL-4), interferon γ (IFN-γ), IL-10 and IL-17 in the lung homogenates were determined by ELISA. Compared with the virus control group, the metronidazole group showed obviously increased lung index and more serious pathological changes of the lung tissue and appendix inflammation performance. After infected by the FM1 influenza virus, IFN-γ and IL-17 of the metronidazole group decreased significantly and IL-4 and IL-10 levels were raised, but there was no statistically difference between the metronidazole and virus control groups. Intestinal anaerobic bacteria may inhibit the adaptive immune response in the lungs of mice infected with FM1 influenza virus through adjusting the lung inflammatory factors, affect the replication and clean-up time of the FM1 influenza virus, thus further aggravating pulmonary immune pathological injury caused by the influenza virus infection.

Experimental infection of human volunteers with Haemophilus ducreyi: fifteen years of clinical data and experience.

Science.gov (United States)

Janowicz, Diane M; Ofner, Susan; Katz, Barry P; Spinola, Stanley M

2009-06-01

Haemophilus ducreyi causes chancroid, which facilitates transmission of human immunodeficiency virus type 1. To better understand the biology of H. ducreyi, we developed a human inoculation model. In the present article, we describe clinical outcomes for 267 volunteers who were infected with H. ducreyi. There was a relationship between papule formation and estimated delivered dose. The outcome (either pustule formation or resolution) of infected sites for a given subject was not independent; the most important determinants of pustule formation were sex and host effects. When 41 subjects were infected a second time, their outcomes segregated toward their initial outcome, confirming the host effect. Subjects with pustules developed local symptoms that required withdrawal from the study after a mean of 8.6 days. There were 191 volunteers who had tissue biopsy performed, 173 of whom were available for follow-up analysis; 28 (16.2%) of these developed hypertrophic scars, but the model was otherwise safe. Mutant-parent trials confirmed key features in H. ducreyi pathogenesis, and the model has provided an opportunity to study differential human susceptibility to a bacterial infection.

Lethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes.

Directory of Open Access Journals (Sweden)

Cristian Cillóniz

2009-10-01

Full Text Available The enormous toll on human life during the 1918-1919 Spanish influenza pandemic is a constant reminder of the potential lethality of influenza viruses. With the declaration by the World Health Organization of a new H1N1 influenza virus pandemic, and with continued human cases of highly pathogenic H5N1 avian influenza virus infection, a better understanding of the host response to highly pathogenic influenza viruses is essential. To this end, we compared pathology and global gene expression profiles in bronchial tissue from macaques infected with either the reconstructed 1918 pandemic virus or the highly pathogenic avian H5N1 virus A/Vietnam/1203/04. Severe pathology was observed in respiratory tissues from 1918 virus-infected animals as early as 12 hours after infection, and pathology steadily increased at later time points. Although tissues from animals infected with A/Vietnam/1203/04 also showed clear signs of pathology early on, less pathology was observed at later time points, and there was evidence of tissue repair. Global transcriptional profiles revealed that specific groups of genes associated with inflammation and cell death were up-regulated in bronchial tissues from animals infected with the 1918 virus but down-regulated in animals infected with A/Vietnam/1203/04. Importantly, the 1918 virus up-regulated key components of the inflammasome, NLRP3 and IL-1beta, whereas these genes were down-regulated by A/Vietnam/1203/04 early after infection. TUNEL assays revealed that both viruses elicited an apoptotic response in lungs and bronchi, although the response occurred earlier during 1918 virus infection. Our findings suggest that the severity of disease in 1918 virus-infected macaques is a consequence of the early up-regulation of cell death and inflammatory related genes, in which additive or synergistic effects likely dictate the severity of tissue damage.

Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection.

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Yongsheng Huang

2011-08-01

Full Text Available Exposure to influenza viruses is necessary, but not sufficient, for healthy human hosts to develop symptomatic illness. The host response is an important determinant of disease progression. In order to delineate host molecular responses that differentiate symptomatic and asymptomatic Influenza A infection, we inoculated 17 healthy adults with live influenza (H3N2/Wisconsin and examined changes in host peripheral blood gene expression at 16 timepoints over 132 hours. Here we present distinct transcriptional dynamics of host responses unique to asymptomatic and symptomatic infections. We show that symptomatic hosts invoke, simultaneously, multiple pattern recognition receptors-mediated antiviral and inflammatory responses that may relate to virus-induced oxidative stress. In contrast, asymptomatic subjects tightly regulate these responses and exhibit elevated expression of genes that function in antioxidant responses and cell-mediated responses. We reveal an ab initio molecular signature that strongly correlates to symptomatic clinical disease and biomarkers whose expression patterns best discriminate early from late phases of infection. Our results establish a temporal pattern of host molecular responses that differentiates symptomatic from asymptomatic infections and reveals an asymptomatic host-unique non-passive response signature, suggesting novel putative molecular targets for both prognostic assessment and ameliorative therapeutic intervention in seasonal and pandemic influenza.

Pharmacologic inhibition of COX-1 and COX-2 in influenza A viral infection in mice.

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Michelle A Carey

Full Text Available BACKGROUND: We previously demonstrated that cyclooxygenase (COX-1 deficiency results in greater morbidity and inflammation, whereas COX-2 deficiency leads to reduced morbidity, inflammation and mortality in influenza infected mice. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effects of COX-1 and COX-2 inhibitors in influenza A viral infection. Mice were given a COX-1 inhibitor (SC-560, a COX-2 inhibitor (celecoxib or no inhibitor beginning 2 weeks prior to influenza A viral infection (200 PFU and throughout the course of the experiment. Body weight and temperature were measured daily as indicators of morbidity. Animals were sacrificed on days 1 and 4 post-infection and bronchoalveolar lavage (BAL fluid was collected or daily mortality was recorded up to 2 weeks post-infection. Treatment with SC-560 significantly increased mortality and was associated with profound hypothermia and greater weight loss compared to celecoxib or control groups. On day 4 of infection, BAL fluid cells were modestly elevated in celecoxib treated mice compared to SC-560 or control groups. Viral titres were similar between treatment groups. Levels of TNF-alpha and G-CSF were significantly attenuated in the SC-560 and celecoxib groups versus control and IL-6 levels were significantly lower in BAL fluid of celecoxib treated mice versus control and versus the SC-560 group. The chemokine KC was significantly lower in SC-560 group versus control. CONCLUSIONS/SIGNIFICANCE: Treatment with a COX-1 inhibitor during influenza A viral infection is detrimental to the host whereas inhibition of COX-2 does not significantly modulate disease severity. COX-1 plays a critical role in controlling the thermoregulatory response to influenza A viral infection in mice.

Economic evaluation of delivering Haemophilus influenzae type b vaccine in routine immunization services in Kenya.

Science.gov (United States)

Akumu, Angela Oloo; English, Mike; Scott, J Anthony G; Griffiths, Ulla K

2007-07-01

Haemophilus influenzae type b (Hib) vaccine was introduced into routine immunization services in Kenya in 2001. We aimed to estimate the cost-effectiveness of Hib vaccine delivery. A model was developed to follow the Kenyan 2004 birth cohort until death, with and without Hib vaccine. Incidence of invasive Hib disease was estimated at Kilifi District Hospital and in the surrounding demographic surveillance system in coastal Kenya. National Hib disease incidence was estimated by adjusting incidence observed by passive hospital surveillance using assumptions about access to care. Case fatality rates were also assumed dependent on access to care. A price of US$ 3.65 per dose of pentavalent diphtheria-tetanus-pertussis-hep B-Hib vaccine was used. Multivariate Monte Carlo simulations were performed in order to assess the impact on the cost-effectiveness ratios of uncertainty in parameter values. The introduction of Hib vaccine reduced the estimated incidence of Hib meningitis per 100,000 children aged disability adjusted life year (DALY) and per discounted death averted were US$ 38 (95% confidence interval, CI: 26-63) and US$ 1197 (95% CI: 814-2021) respectively. Most of the uncertainty in the results was due to uncertain access to care parameters. The break-even pentavalent vaccine price--where incremental Hib vaccination costs equal treatment costs averted from Hib disease--was US$ 1.82 per dose. Hib vaccine is a highly cost-effective intervention in Kenya. It would be cost-saving if the vaccine price was below half of its present level.

Haemophilus influenzae type b disease in Auckland children during the Hib vaccination era: 1995-2009.

Science.gov (United States)

Leung, Bonnie; Taylor, Susan; Drinkovic, Dragana; Roberts, Sally; Carter, Phil; Best, Emma

2012-11-09

To characterise Haemophilus influenzae type b (Hib) invasive disease in the era of Hib vaccination, in children of the greater Auckland region of New Zealand. Identification of sterile site culture positive Hib via the Auckland hospital laboratories databases and national laboratory surveillance database in the time period; 1995 to 2009. There were a total of 26 cases in the Auckland Region. Over the 15-year period, the annual incidence of invasive Hib disease was 0.61 per 100,000 (95% CI: 0.4-0.9) for children aged under 15 years and 1.65 per 100,000 (95% CI: 1.1-2.5) for children aged under 5 years. Ninety-two percent were under 5 years and 54% were under 1 year. Sixty percent of the children were of Maori and Pacific ethnicity. The predominant diagnosis was meningitis, accounting for 15 cases (60%). There were no fatalities. Forty-eight percent of affected children were completely unimmunised with the Hib vaccine which has been fully funded on the National Immunisation Schedule since 1994. Since the introduction of the Hib vaccine, the disease rates have greatly reduced in the Auckland region. Although ethnic disparities have improved amongst the cases that occur, immunisation rates in cases are low and infants remain most at risk. Current emphasis on intensifying immunisation programmes to achieve higher vaccination rates and timeliness of delivery will help in efforts to achieve elimination of the disease in New Zealand.

Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses

International Nuclear Information System (INIS)

Pan, Yang; Sasaki, Tadahiro; Kubota-Koketsu, Ritsuko; Inoue, Yuji; Yasugi, Mayo; Yamashita, Akifumi; Ramadhany, Ririn; Arai, Yasuha; Du, Anariwa; Boonsathorn, Naphatsawan; Ibrahim, Madiha S.

2014-01-01

Highlights: • Influenza infection can elicit heterosubtypic antibodies to group 1 influenza virus. • Three human monoclonal antibodies were generated from an H1N1-infected patient. • The antibodies predominantly recognized α-helical stem of viral hemagglutinin (HA). • The antibodies inhibited HA structural activation during the fusion process. • The antibodies are potential candidates for future antibody therapy to influenza. - Abstract: Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short α-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the α-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses

Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses

Energy Technology Data Exchange (ETDEWEB)

Pan, Yang [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Sasaki, Tadahiro [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Kubota-Koketsu, Ritsuko [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Inoue, Yuji [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Yasugi, Mayo [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Yamashita, Akifumi; Ramadhany, Ririn; Arai, Yasuha [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Du, Anariwa [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Boonsathorn, Naphatsawan [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Ibrahim, Madiha S. [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Damanhour University, Damanhour (Egypt); and others

2014-07-18

Highlights: • Influenza infection can elicit heterosubtypic antibodies to group 1 influenza virus. • Three human monoclonal antibodies were generated from an H1N1-infected patient. • The antibodies predominantly recognized α-helical stem of viral hemagglutinin (HA). • The antibodies inhibited HA structural activation during the fusion process. • The antibodies are potential candidates for future antibody therapy to influenza. - Abstract: Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short α-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the α-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses.

VACCINE IMMUNIZATION FOR PREVENTION OF PNEUMOCOCCAL, HAEMOPHILUS INFLUENZAE AND FLU AMONG SICKLY CHILDREN, WHO OFTEN SUFFER FROM PERSISTENT HETEROSPECIFIC INFECTIOUS PATHOLOGY OF THE BRONCHOPULMONARY SYSTEM

Directory of Open Access Journals (Sweden)

L.I. Ilienko

2006-01-01

Full Text Available Among serious diseases of the lower respiratory tract a special place is taken by pneumonias and chronic infectious respiratory diseases caused by pneumococcus and Haemophilus influenzae type b (HIB. The research purpose is to determine the effectiveness of vaccine combined application to treat sickly children, who often suffer from persistent infectious pathology of the respiratory tract, for flu, pneumococcal and HIB disease. 110 children aged between 3 and 12 have been vaccinated. The first part of research implied children vaccination by means of Actahib and Pneumo 23 vaccines (Sanofi Pasteur, France, the second one consisted in immunization of children with the same pathology by means of Pneumo 23, Actahib and Vaxigrip vaccines (Sanofi Pasteur, France. The researches established that within a year after HIB and Pneumo 23 vaccination the frequency of upper and lower respiratory tract acerbations reduced by 2,3 times on average; likewise, the number of system antimicrobial dosage reduced by 7,4 times along with the total duration of dosage; the carrier state of S. pneumoniae reduced by 3,7 times, H. influenzae — by 3,9 times. In the course of application of three vaccines, the frequency of persistent heat erospecific infectious bronchopulmonary pathology acerbations reduced by 3,3 times. The carrier state of S. pneumoniae reduced by 2,5 times, H. influenzae — by 4,1 times. Thus, vaccine immunization to treat for flu, pneumococcal and HIB disease in various combinations may be recoma mended for wider application to reduce the frequency and severity of heat erospecific infectious respiratory diseases among sickly children, who often suffer from various illnesses.Key words: children with recurrent diseases, vaccination, prevention, flu, H. Influenzae, S. pneumoniae.

A simplification of the enzyme-linked immunospot technique. Increased sensitivity for cells secreting IgG antibodies to Haemophilus influenzae type b capsular polysaccharide

DEFF Research Database (Denmark)

Barington, T; Sparholt, S; Juul, L

1992-01-01

A simplified enzyme-linked immunospot (ELISPOT) technique is described for the detection of cells secreting antibodies to tetanus toxoid (TT), diphtheria toxoid (DT) or Haemophilus influenzae type b capsular polysaccharide (PRP). By combining the cell suspension with the enzyme-linked secondary...... antibodies in one incubation, the second incubation and washing procedure could be omitted from the original technique. The simplified assay had the same sensitivity for anti-TT and anti-DT spot-forming cells as the ordinary ELISPOT assay. The IgG anti-PRP spots were, however, improved both in quality...... and in quantity (median: 40% more spots), while the detection of IgM and IgA anti-PRP spot-forming cells was the same in the two techniques. This simplified technique can probably also be used to save time in other antigen systems and should be considered when designing ELISPOT assays for the detection...

Hand hygiene to reduce community transmission of influenza and acute respiratory tract infection: a systematic review.

OpenAIRE

Warren-Gash, C; Fragaszy, E; Hayward, AC

2012-01-01

: Please cite this paper as: Warren-Gash et al. (2012) Hand hygiene to reduce community transmission of influenza and acute respiratory tract infection: a systematic review. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12015. Hand hygiene may be associated with modest protection against some acute respiratory tract infections, but its specific role in influenza transmission in different settings is unclear. We aimed to review evidence that improving hand hygiene reduces primary an...

The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase from Haemophilus influenzae contains two active-site histidine residues.

Science.gov (United States)

Gillner, Danuta M; Bienvenue, David L; Nocek, Boguslaw P; Joachimiak, Andrzej; Zachary, Vincentos; Bennett, Brian; Holz, Richard C

2009-01-01

The catalytic and structural properties of the H67A and H349A dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) from Haemophilus influenzae were investigated. On the basis of sequence alignment with the carboxypeptidase from Pseudomonas sp. strain RS-16, both H67 and H349 were predicted to be Zn(II) ligands. The H67A DapE enzyme exhibited a decreased catalytic efficiency (180-fold) compared with wild-type (WT) DapE towards N-succinyldiaminopimelic acid. No catalytic activity was observed for H349A under the experimental conditions used. The electronic paramagnetic resonance (EPR) and electronic absorption data indicate that the Co(II) ion bound to H349A-DapE is analogous to that of WT DapE after the addition of a single Co(II) ion. The addition of 1 equiv of Co(II) to H67A DapE provides spectra that are very different from those of the first Co(II) binding site of the WT enzyme, but that are similar to those of the second binding site. The EPR and electronic absorption data, in conjunction with the kinetic data, are consistent with the assignment of H67 and H349 as active-site metal ligands for the DapE from H. influenzae. Furthermore, the data suggest that H67 is a ligand in the first metal binding site, while H349 resides in the second metal binding site. A three-dimensional homology structure of the DapE from H. influenzae was generated using the X-ray crystal structure of the DapE from Neisseria meningitidis as a template and superimposed on the structure of the aminopeptidase from Aeromonas proteolytica (AAP). This homology structure confirms the assignment of H67 and H349 as active-site ligands. The superimposition of the homology model of DapE with the dizinc(II) structure of AAP indicates that within 4.0 A of the Zn(II) binding sites of AAP all of the amino acid residues of DapE are nearly identical.

Serological characterization of guinea pigs infected with H3N2 human influenza or immunized with hemagglutinin protein

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Bushnell Ruth V

2010-08-01

Full Text Available Abstract Background Recent and previous studies have shown that guinea pigs can be infected with, and transmit, human influenza viruses. Therefore guinea pig may be a useful animal model for better understanding influenza infection and assessing vaccine strategies. To more fully characterize the model, antibody responses following either infection/re-infection with human influenza A/Wyoming/03/2003 H3N2 or immunization with its homologous recombinant hemagglutinin (HA protein were studied. Results Serological samples were collected and tested for anti-HA immunoglobulin by ELISA, antiviral antibodies by hemagglutination inhibition (HI, and recognition of linear epitopes by peptide scanning (PepScan. Animals inoculated with infectious virus demonstrated pronounced viral replication and subsequent serological conversion. Animals either immunized with the homologous HA antigen or infected, showed a relatively rapid rise in antibody titers to the HA glycoprotein in ELISA assays. Antiviral antibodies, measured by HI assay, were detectable after the second inoculation. PepScan data identified both previously recognized and newly defined linear epitopes. Conclusions Infection and/or recombinant HA immunization of guinea pigs with H3N2 Wyoming influenza virus resulted in a relatively rapid production of viral-specific antibody thus demonstrating the strong immunogenicity of the major viral structural proteins in this animal model for influenza infection. The sensitivity of the immune response supports the utility of the guinea pig as a useful animal model of influenza infection and immunization.

Acute immune thrombocytopenic purpura in an adolescent with 2009 novel H1N1 influenza A virus infection

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Chun-Yi Lee

2011-09-01

Full Text Available Although both leukopenia and thrombocytopenia are not uncommon hematological findings among patients with novel 2009 H1N1 influenza virus infection, immune thrombocytopenic purpura has rarely been shown to be associated with this novel influenza A infection. Here, we describe a previously healthy adolescent who presented with fever, influenza-like symptoms and acute onset of generalized petechiae and active oral mucosa bleeding on the third day of his illness. Severe leukopenia and thrombocytopenia were found. There was neither malignancy nor blast cells found by bone marrow aspiration. Real-time reverse transcriptase polymerase chain reaction was positive for novel 2009 H1N1 influenza infection. Novel influenza-associated atypical immune thrombocytopenic purpura was diagnosed. The patient recovered uneventfully after oseltamivir and methylprednisolone therapy.

The innate immunity of guinea pigs against highly pathogenic avian influenza virus infection.

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Zhang, Kun; Xu, Wei Wei; Zhang, Zhaowei; Liu, Jing; Li, Jing; Sun, Lijuan; Sun, Weiyang; Jiao, Peirong; Sang, Xiaoyu; Ren, Zhiguang; Yu, Zhijun; Li, Yuanguo; Feng, Na; Wang, Tiecheng; Wang, Hualei; Yang, Songtao; Zhao, Yongkun; Zhang, Xuemei; Wilker, Peter R; Liu, WenJun; Liao, Ming; Chen, Hualan; Gao, Yuwei; Xia, Xianzhu

2017-05-02

H5N1 avian influenza viruses are a major pandemic concern. In contrast to the highly virulent phenotype of H5N1 in humans and many animal models, guinea pigs do not typically display signs of severe disease in response to H5N1 virus infection. Here, proteomic and transcriptional profiling were applied to identify host factors that account for the observed attenuation of A/Tiger/Harbin/01/2002 (H5N1) virulence in guinea pigs. RIG-I and numerous interferon stimulated genes were among host proteins with altered expression in guinea pig lungs during H5N1 infection. Overexpression of RIG-I or the RIG-I adaptor protein MAVS in guinea pig cell lines inhibited H5N1 replication. Endogenous GBP-1 expression was required for RIG-I mediated inhibition of viral replication upstream of the activity of MAVS. Furthermore, we show that guinea pig complement is involved in viral clearance, the regulation of inflammation, and cellular apoptosis during influenza virus infection of guinea pigs. This work uncovers features of the guinea pig innate immune response to influenza that may render guinea pigs resistant to highly pathogenic influenza viruses.

INFLUENZA AND ACUTE VIRAL RESPIRATORY INFECTIONS IN THE PRACTICE OF THE EMERGENCY CREWS OF MOSCOW

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N. F. Plavunov

2016-01-01

Full Text Available Influenza and acute viral respiratory infections have a great social significance during epidemic rise of morbidity and demand differential diagnosis of pneumonia with bacterial etiology and consultation with an infectious disease doctor in case of seeing patients in non-core hospitals. This article highlights the problem of influenza and acute respiratory viral infections’ early diagnosis. Clinical manifestations of influenza and other respiratory extremely similar. The differential diagnosis must take into account the presence of mixed infection in the same patient. According to the results of consultative infectious ambulance teams in 2014-2016, quality of diagnostics of this infectious pathology was examined. Observed deaths in persons later seeking medical treatment, not receiving timely antiviral therapy and related to high-risk groups: patients with obesity, chronic alcohol intoxication, diabetes, pregnant women. Influenza and acute viral respiratory infections, more complicated by pneumonia, people in the older age group, indicating the need for timely medical evacuation of patients older than 60 years. In some cases, in the diagnosis of influenza was helped by the results of laboratory studies (especially the trend to leukopenia and a positive rapid test. It should be noted that a negative rapid test for influenza was not a reason for exclusion of the diagnosis “influenza”.

Physical size of the donor locus and transmission of Haemophilus influenzae ampicillin resistance genes by deoxyribonucleic acid-mediated transformation

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Bendler, J.W. III

1976-01-01

The properties of donor deoxyribonucleic acid (DNA) from three clinical isolates and its ability to mediate the transformation of competent Rd strains to ampicillin resistance were examined. A quantitative technique for determining the resistance of individual Haemophilus influenzae cells to ampicillin was developed. When this technique was used, sensitive cells failed to tolerate levels of ampicillin greater than 0.1 to 0.2 μg/ml, whereas three resistant type b β-lactamase-producing strains could form colonies 1- to 3-μg/ml levels of the antibiotic. DNA extracted from the resistant strains elicited transformation of the auxotrophic genes in a multiply auxotrophic Rd strain. For two of the donors, transformation to ampicillin resistance occurred after the uptake of a single DNA molecule approximately 10 4 -fold less frequently than transformation of auxotrophic loci and was not observed to occur at all with the third. The frequency of transformation to ampicillin resistance was two- to fivefold higher in strain BC200 (Okinaka and Barnhart, 1974), which was cured of a defective prophage. All three clinical ampicillin-resistant strains were poor recipients, but the presence of the ampicillin resistant genes in strain BC200 did not reduce its competence

Flow cytometric monitoring of influenza A virus infection in MDCK cells during vaccine production

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Reichl Udo

2008-04-01

Full Text Available Abstract Background In cell culture-based influenza vaccine production the monitoring of virus titres and cell physiology during infection is of great importance for process characterisation and optimisation. While conventional virus quantification methods give only virus titres in the culture broth, data obtained by fluorescence labelling of intracellular virus proteins provide additional information on infection dynamics. Flow cytometry represents a valuable tool to investigate the influences of cultivation conditions and process variations on virus replication and virus yields. Results In this study, fluorescein-labelled monoclonal antibodies against influenza A virus matrix protein 1 and nucleoprotein were used for monitoring the infection status of adherent Madin-Darby canine kidney cells from bioreactor samples. Monoclonal antibody binding was shown for influenza A virus strains of different subtypes (H1N1, H1N2, H3N8 and host specificity (human, equine, swine. At high multiplicity of infection in a bioreactor, the onset of viral protein accumulation in adherent cells on microcarriers was detected at about 2 to 4 h post infection by flow cytometry. In contrast, a significant increase in titre by hemagglutination assay was detected at the earliest 4 to 6 h post infection. Conclusion It is shown that flow cytometry is a sensitive and robust method for the monitoring of viral infection in fixed cells from bioreactor samples. Therefore, it is a valuable addition to other detection methods of influenza virus infection such as immunotitration and RNA hybridisation. Thousands of individual cells are measured per sample. Thus, the presented method is believed to be quite independent of the concentration of infected cells (multiplicity of infection and total cell concentration in bioreactors. This allows to perform detailed studies on factors relevant for optimization of virus yields in cell cultures. The method could also be used for process

Influenza A virus infection of healthy piglets in an abattoir in Brazil: animal-human interface and risk for interspecies transmission

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Ariane Ribeiro Amorim

2013-08-01

Full Text Available Asymptomatic influenza virus infections in pigs are frequent and the lack of measures for controlling viral spread facilitates the circulation of different virus strains between pigs. The goal of this study was to demonstrate the circulation of influenza A virus strains among asymptomatic piglets in an abattoir in Brazil and discuss the potential public health impacts. Tracheal samples (n = 330 were collected from asymptomatic animals by a veterinarian that also performed visual lung tissue examinations. No slaughtered animals presented with any noticeable macroscopic signs of influenza infection following examination of lung tissues. Samples were then analysed by reverse transcription-polymerase chain reaction that resulted in the identification of 30 (9% influenza A positive samples. The presence of asymptomatic pig infections suggested that these animals could facilitate virus dissemination and act as a source of infection for the herd, thereby enabling the emergence of influenza outbreaks associated with significant economic losses. Furthermore, the continuous exposure of the farm and abattoir workers to the virus increases the risk for interspecies transmission. Monitoring measures of swine influenza virus infections and vaccination and monitoring of employees for influenza infection should also be considered. In addition regulatory agencies should consider the public health ramifications regarding the potential zoonotic viral transmission between humans and pigs.

Epithelial cells from smokers modify dendritic cell responses in the context of influenza infection

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Epidemiologic evidence suggests that cigarette smoking is a risk factor for infection with influenza, but the mechanisms underlying this susceptibility remain unknown. To ascertain if airway epithelial cells from smokers demonstrate a decreased ability to orchestrate an influenza...

Highly pathogenic avian influenza virus (H5N1) in experimentally infected adult mute swans.

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Kalthoff, Donata; Breithaupt, Angele; Teifke, Jens P; Globig, Anja; Harder, Timm; Mettenleiter, Thomas C; Beer, Martin

2008-08-01

Adult, healthy mute swans were experimentally infected with highly pathogenic avian influenza virus A/Cygnus cygnus/Germany/R65/2006 subtype H5N1. Immunologically naive birds died, whereas animals with preexisting, naturally acquired avian influenza virus-specific antibodies became infected asymptomatically and shed virus. Adult mute swans are highly susceptible, excrete virus, and can be clinically protected by preexposure immunity.

Critical role of constitutive type I interferon response in bronchial epithelial cell to influenza infection.

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Alan C-Y Hsu

Full Text Available Innate antiviral responses in bronchial epithelial cells (BECs provide the first line of defense against respiratory viral infection and the effectiveness of this response is critically dependent on the type I interferons (IFNs. However the importance of the antiviral responses in BECs during influenza infection is not well understood. We profiled the innate immune response to infection with H3N2 and H5N1 virus using Calu-3 cells and primary BECs to model proximal airway cells. The susceptibility of BECs to influenza infection was not solely dependent on the sialic acid-bearing glycoprotein, and antiviral responses that occurred after viral endocytosis was more important in limiting viral replication. The early antiviral response and apoptosis correlated with the ability to limit viral replication. Both viruses reduced RIG-I associated antiviral responses and subsequent induction of IFN-β. However it was found that there was constitutive release of IFN-β by BECs and this was critical in inducing late antiviral signaling via type I IFN receptors, and was crucial in limiting viral infection. This study characterizes anti-influenza virus responses in airway epithelial cells and shows that constitutive IFN-β release plays a more important role in initiating protective late IFN-stimulated responses during human influenza infection in bronchial epithelial cells.

Impact of protein D-containing pneumococcal conjugate vaccines on non-typeable Haemophilus influenzae acute otitis media and carriage.

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Clarke, Christopher; Bakaletz, Lauren O; Ruiz-Guiñazú, Javier; Borys, Dorota; Mrkvan, Tomas

2017-07-01

Protein D-containing vaccines may decrease acute otitis media (AOM) burden and nasopharyngeal carriage of non-typeable Haemophilus influenzae (NTHi). Protein D-containing pneumococcal conjugate vaccine PHiD-CV (Synflorix, GSK Vaccines) elicits robust immune responses against protein D. However, the phase III Clinical Otitis Media and PneumoniA Study (COMPAS), assessing PHiD-CV efficacy against various pneumococcal diseases, was not powered to demonstrate efficacy against NTHi; only trends of protective efficacy against NTHi AOM in children were shown. Areas covered: This review aims to consider all evidence available to date from pre-clinical and clinical phase III studies together with further evidence emerging from post-marketing studies since PHiD-CV has been introduced into routine clinical practice worldwide, to better describe the clinical utility of protein D in preventing AOM due to NTHi and its impact on NTHi nasopharyngeal carriage. Expert commentary: Protein D is an effective carrier protein in conjugate vaccines and evidence gathered from pre-clinical, clinical and observational studies suggest that it also elicits immune response that can help to reduce the burden of AOM due to NTHi. There remains a need to develop improved vaccines for prevention of NTHi disease, which could be achieved by combining protein D with other antigens.

Evidence for avian H9N2 influenza virus infections among rural villagers in Cambodia

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Patrick J. Blair

2013-04-01

Full Text Available Summary: Background: Southeast Asia remains a critical region for the emergence of novel and/or zoonotic influenza, underscoring the importance of extensive sampling in rural areas where early transmission is most likely to occur. Methods: In 2008, 800 adult participants from eight sites were enrolled in a prospective population-based study of avian influenza (AI virus transmission where highly pathogenic avian influenza (HPAI H5N1 virus had been reported in humans and poultry from 2006 to 2008. From their enrollment sera and questionnaires, we report risk factor findings for serologic evidence of previous infection with 18 AI virus strains. Results: Serologic assays revealed no evidence of previous infection with 13 different low-pathogenic AI viruses or with HPAI avian-like A/Cambodia/R0404050/2007(H5N1. However, 21 participants had elevated antibodies against avian-like A/Hong Kong/1073/1999(H9N2, validated with a monoclonal antibody blocking ELISA assay specific for avian H9. Conclusions: Although cross-reaction from antibodies against human influenza viruses cannot be completely excluded, the study data suggest that a number of participants were previously infected with the avian-like A/Hong Kong/1073/1999(H9N2 virus, likely due to as yet unidentified environmental exposures. Prospective data from this cohort will help us better understand the serology of zoonotic influenza infection in a rural cohort in SE Asia. Keywords: Influenza A virus, Avian, Zoonoses, Occupational exposure, Communicable diseases, Emerging, Cohort studies

Association of history of allergies and influenza-like infections with laryngeal cancer in a case-control study.

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Filippidis, Filippos T; Schwartz, Stephen M; Becker, Nikolaus; Dyckhoff, Gerhard; Kirschfink, Michael; Dietz, Andreas; Becher, Heiko; Ramroth, Heribert

2015-08-01

Prior studies suggest that history of allergy and infections early in life might be inversely associated with cancer. We explored the association between allergies, recent influenza infections and laryngeal cancer risk. We used data from a case-control study which included 229 cases of laryngeal cancer and 769 population controls matched for age and sex. History of a physician-diagnosed allergy, influenza-like infections in the past 5 years, smoking, alcohol consumption and occupational exposure to carcinogens were self-reported. Allergies were classified into two groups (Type I and Type IV), according to the underlying immunologic mechanism. Conditional logistic regression models were fitted using laryngeal cancer as the outcome, adjusting for smoking, alcohol consumption and occupational exposure and stratified for age and sex. Having any allergy was not associated significantly with laryngeal cancer. Although Type I and Type IV allergies were non-significantly associated with laryngeal cancer, Type IV allergies showed a strong inverse association after adjusting for smoking and alcohol (OR 0.50, 95 % CI 0.22-1.2). Participants who reported at least one influenza-like infection during the past 5 years were significantly less likely to have laryngeal cancer (OR 0.57, 95 % CI 0.39-0.81). After considering fever (≥38.5 °C) as a criterion for influenza infection, the association between influenza infection and laryngeal cancer was even stronger (OR 0.29, 95 % CI 0.13-0.63). We found no significant association between any allergy and laryngeal cancer, some indication of an inverse association between Type IV allergy and laryngeal cancer, whereas recent influenza infections were inversely associated with laryngeal cancer risk.

Prevalence and risk factors for H1N1 and H3N2 influenza A virus infections in Minnesota turkey premises.

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Corzo, Cesar A; Gramer, Marie; Lauer, Dale; Davies, Peter R

2012-09-01

Influenza virus infections can cause respiratory and systemic disease of variable severity and also result in economic losses for the turkey industry. Several subtypes of influenza can infect turkeys, causing diverse clinical signs. Influenza subtypes of swine origin have been diagnosed in turkey premises; however, it is not known how common these infections are nor the likely routes of transmission. We conducted a cross-sectional study to estimate the prevalence of influenza viruses and examine factors associated with infection on Minnesota turkey premises. Results from influenza diagnostic tests and turkey and pig premise location data were obtained from the Minnesota Poultry Testing Laboratory and the Minnesota Board of Animal Health, respectively, from January 2007 to September 2008. Diagnostic data from 356 premises were obtained, of which 17 premises tested positive for antibodies to influenza A virus by agar gel immunodiffusion assay and were confirmed as either H1N1 or H3N2 influenza viruses by hemagglutination and neuraminidase inhibition assays. Influenza infection status was associated with proximity to pig premises and flock size. The latter had a sparing effect on influenza status. This study suggests that H1N1 and H3N2 influenza virus infections of turkey premises in Minnesota are an uncommon event. The route of influenza virus transmission could not be determined; however, the findings suggest that airborne transmission should be considered in future studies.

Syrian Hamster as an Animal Model for the Study of Human Influenza Virus Infection.

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Iwatsuki-Horimoto, Kiyoko; Nakajima, Noriko; Ichiko, Yurie; Sakai-Tagawa, Yuko; Noda, Takeshi; Hasegawa, Hideki; Kawaoka, Yoshihiro

2018-02-15

Ferrets and mice are frequently used as animal models for influenza research. However, ferrets are demanding in terms of housing space and handling, whereas mice are not naturally susceptible to infection with human influenza A or B viruses. Therefore, prior adaptation of human viruses is required for their use in mice. In addition, there are no mouse-adapted variants of the recent H3N2 viruses, because these viruses do not replicate well in mice. In this study, we investigated the susceptibility of Syrian hamsters to influenza viruses with a view to using the hamster model as an alternative to the mouse model. We found that hamsters are sensitive to influenza viruses, including the recent H3N2 viruses, without adaptation. Although the hamsters did not show weight loss or clinical signs of H3N2 virus infection, we observed pathogenic effects in the respiratory tracts of the infected animals. All of the H3N2 viruses tested replicated in the respiratory organs of the hamsters, and some of them were detected in the nasal washes of infected animals. Moreover, a 2009 pandemic (pdm09) virus and a seasonal H1N1 virus, as well as one of the two H3N2 viruses, but not a type B virus, were transmissible by the airborne route in these hamsters. Hamsters thus have the potential to be a small-animal model for the study of influenza virus infection, including studies of the pathogenicity of H3N2 viruses and other strains, as well as for use in H1N1 virus transmission studies. IMPORTANCE We found that Syrian hamsters are susceptible to human influenza viruses, including the recent H3N2 viruses, without adaptation. We also found that a pdm09 virus and a seasonal H1N1 virus, as well as one of the H3N2 viruses, but not a type B virus tested, are transmitted by the airborne route in these hamsters. Syrian hamsters thus have the potential to be used as a small-animal model for the study of human influenza viruses. Copyright © 2018 American Society for Microbiology.

Accelerating policy decisions to adopt haemophilus influenzae type B vaccine: a global, multivariable analysis.

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Shearer, Jessica C; Stack, Meghan L; Richmond, Marcie R; Bear, Allyson P; Hajjeh, Rana A; Bishai, David M

2010-03-16

Adoption of new and underutilized vaccines by national immunization programs is an essential step towards reducing child mortality. Policy decisions to adopt new vaccines in high mortality countries often lag behind decisions in high-income countries. Using the case of Haemophilus influenzae type b (Hib) vaccine, this paper endeavors to explain these delays through the analysis of country-level economic, epidemiological, programmatic and policy-related factors, as well as the role of the Global Alliance for Vaccines and Immunisation (GAVI Alliance). Data for 147 countries from 1990 to 2007 were analyzed in accelerated failure time models to identify factors that are associated with the time to decision to adopt Hib vaccine. In multivariable models that control for Gross National Income, region, and burden of Hib disease, the receipt of GAVI support speeded the time to decision by a factor of 0.37 (95% CI 0.18-0.76), or 63%. The presence of two or more neighboring country adopters accelerated decisions to adopt by a factor of 0.50 (95% CI 0.33-0.75). For each 1% increase in vaccine price, decisions to adopt are delayed by a factor of 1.02 (95% CI 1.00-1.04). Global recommendations and local studies were not associated with time to decision. This study substantiates previous findings related to vaccine price and presents new evidence to suggest that GAVI eligibility is associated with accelerated decisions to adopt Hib vaccine. The influence of neighboring country decisions was also highly significant, suggesting that approaches to support the adoption of new vaccines should consider supply- and demand-side factors.

Clinical characteristics and outcomes among pediatric patients hospitalized with pandemic influenza A/H1N1 2009 infection

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Eun Lee

2011-08-01

Full Text Available Purpose : The purpose of this article is to describe the clinical and epidemiologic features and outcomes among children hospitalized with pandemic influenza A/H1N1 2009 infection. Methods : We retrospectively reviewed the charts of hospitalized pediatric patients (&lt;18 years diagnosed with pandemic influenza A/H1N1 2009 infection by reverse-transcriptase polymerase chain reaction at a tertiary hospital in Seoul, Korea, between September 2009 and February 2010. Results : A total of 72 children were hospitalized with pandemic influenza A/H1N1 2009 infection (median age, 6.0 years; range, 2 months to 18 years. A total of 40% had at least 1 underlying medical condition, including asthma (17%, malignancies (19%, and heart diseases (17%. Of the 72 patients, 54 (76% children admitted with H1N1 infection showed radiographic alterations compatible with pneumonia. There was no significant difference in pre-existing conditions between pandemic influenza A/H1N1 infected patients with or without pneumonia. Children with pandemic influenza A/ H1N1 pneumonia were more likely to have a lower lymphocyte ratio (P=0.02, higher platelet count (P=0.02, and higher level of serum glucose (P=0.003, and more commonly presented with dyspnea than did those without pneumonia (P=0.04. Conclusion : No significant differences in age, sex, or presence of preexisting conditions were found between children hospitalized with pandemic influenza A/H1N1 H1N1 influenza infection with pneumonia and those without pneumonia. Higher leukocyte count, higher glucose level, and a lower lymphocyte ratio were associated with the development of pandemic A/H1N1 2009 influenza pneumonia.

Reduced incorporation of the influenza B virus BM2 protein in virus particles decreases infectivity

International Nuclear Information System (INIS)

Jackson, David; Zuercher, Thomas; Barclay, Wendy

2004-01-01

BM2 is the fourth integral membrane protein encoded by the influenza B virus genome. It is synthesized late in infection and transported to the plasma membrane from where it is subsequently incorporated into progeny virus particles. It has recently been reported that BM2 has ion channel activity and may be the functional homologue of the influenza A virus M2 protein acting as an ion channel involved in viral entry. Using a reverse genetic approach it was not possible to recover virus which lacked BM2. A recombinant influenza B virus was generated in which the BM2 AUG initiation codon was mutated to GUG. This decreased the efficiency of translation of BM2 protein such that progeny virions contained only 1/8 the amount of BM2 seen in wild-type virus. The reduction in BM2 incorporation resulted in a reduction in infectivity although there was no concomitant decrease in the numbers of virions released from the infected cells. These data imply that the incorporation of sufficient BM2 protein into influenza B virions is required for infectivity of the virus particles

Evidence for subclinical avian influenza virus infections among rural Thai villagers.

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Khuntirat, Benjawan P; Yoon, In-Kyu; Blair, Patrick J; Krueger, Whitney S; Chittaganpitch, Malinee; Putnam, Shannon D; Supawat, Krongkaew; Gibbons, Robert V; Pattamadilok, Sirima; Sawanpanyalert, Pathom; Heil, Gary L; Friary, John A; Capuano, Ana W; Gray, Gregory C

2011-10-01

Regions of Thailand reported sporadic outbreaks of A/H5N1 highly pathogenic avian influenza (HPAI) among poultry between 2004 and 2008. Kamphaeng Phet Province, in north-central Thailand had over 50 HPAI poultry outbreaks in 2004 alone, and 1 confirmed and 2 likely other human HPAI infections between 2004 and 2006. In 2008, we enrolled a cohort of 800 rural Thai adults living in 8 sites within Kamphaeng Phet Province in a prospective study of zoonotic influenza transmission. We studied participants' sera with serologic assays against 16 avian, 2 swine, and 8 human influenza viruses. Among participants (mean age 49.6 years and 58% female) 65% reported lifetime poultry exposure of at least 30 consecutive minutes. Enrollees had elevated antibodies by microneutralization assay against 3 avian viruses: A/Hong Kong/1073/1999(H9N2), A/Thailand/676/2005(H5N1), and A/Thailand/384/2006(H5N1). Bivariate risk factor modeling demonstrated that male gender, lack of an indoor water source, and tobacco use were associated with elevated titers against avian H9N2 virus. Multivariate modeling suggested that increasing age, lack of an indoor water source, and chronic breathing problems were associated with infection with 1 or both HPAI H5N1 strains. Poultry exposure was not associated with positive serologic findings. These data suggest that people in rural central Thailand may have experienced subclinical avian influenza infections as a result of yet unidentified environmental exposures. Lack of an indoor water source may play a role in transmission.

Influenza hospitalization epidemiology from a severe acute respiratory infection surveillance system in Jordan, January 2008-February 2014.

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Al-Abdallat, Mohammad; Dawson, Patrick; Haddadin, Aktham Jeries; El-Shoubary, Waleed; Dueger, Erica; Al-Sanouri, Tarek; Said, Mayar M; Talaat, Maha

2016-03-01

Acute respiratory infections (ARIs) are a major cause of morbidity and mortality worldwide. Influenza typically contributes substantially to the burden of ARI, but only limited data are available on influenza activity and seasonality in Jordan. Syndromic case definitions were used to identify individuals with severe acute respiratory infections (SARI) admitted to four sentinel hospitals in Jordan. Demographic and clinical data were collected. Nasopharyngeal and oropharyngeal swabs were tested for influenza using real-time reverse transcription polymerase chain reaction and typed as influenza A or B, with influenza A further subtyped. From January 2008-February 2014, 2891 SARI cases were tested for influenza, and 257 (9%) were positive. While 73% of all SARI cases were under 5 years of age, only 57% of influenza-positive cases were under 5 years of age. Eight (3%) influenza-positive cases died. An annual seasonal pattern of influenza activity was observed. The proportion of influenza-positive cases peaked during November-January (14-42%) in the non-pandemic years. Influenza is associated with substantial morbidity and mortality in Jordan. The seasonal pattern of influenza aligns with known Northern Hemisphere seasonality. Further characterization of the clinical and financial burden of influenza in Jordan will be critical in supporting decisions regarding disease control activities. © 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Outcome of meningitis caused by Streptococcus pneumoniae and Haemophilus influenzae type b in children in The Gambia.

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Goetghebuer, T; West, T E; Wermenbol, V; Cadbury, A L; Milligan, P; Lloyd-Evans, N; Adegbola, R A; Mulholland, E K; Greenwood, B M; Weber, M W

2000-03-01

In developing countries, endemic childhood meningitis is a severe disease caused most commonly by Streptococcus pneumoniae or Haemophilus influenzae type b (Hib). Although many studies have shown that fatality rates associated with meningitis caused by these organisms are high in developing countries, little is known about the long-term outcome of survivors. The purpose of this study was to assess the importance of disabilities following pneumococcal and Hib meningitis in The Gambia. 257 children aged 0-12 years hospitalized between 1990 and 1995 with culture-proven S. pneumoniae (n = 134) or Hib (n = 123) meningitis were included retrospectively in the study. 48% of children with pneumococcal meningitis and 27% of children with Hib meningitis died whilst in hospital. Of the 160 survivors, 89 (55%) were followed up between September 1996 and October 1997. Of the children with pneumococcal meningitis that were traced, 58% had clinical sequelae; half of them had major disabilities preventing normal adaptation to social life. 38% of survivors of Hib meningitis had clinical sequelae, a quarter of whom had major disabilities. Major handicaps found were hearing loss, mental retardation, motor abnormalities and seizures. These data show that despite treatment with effective antibiotics, pneumococcal and Hib meningitis kill many Gambian children and leave many survivors with severe sequelae. Hib vaccination is now given routinely in The Gambia; an effective pneumococcal vaccine is needed.

Serological Evidence of Human Infection with Avian Influenza A H7virus in Egyptian Poultry Growers.

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Gomaa, Mokhtar R; Kandeil, Ahmed; Kayed, Ahmed S; Elabd, Mona A; Zaki, Shaimaa A; Abu Zeid, Dina; El Rifay, Amira S; Mousa, Adel A; Farag, Mohamed M; McKenzie, Pamela P; Webby, Richard J; Ali, Mohamed A; Kayali, Ghazi

2016-01-01

Avian influenza viruses circulate widely in birds, with occasional human infections. Poultry-exposed individuals are considered to be at high risk of infection with avian influenza viruses due to frequent exposure to poultry. Some avian H7 viruses have occasionally been found to infect humans. Seroprevalence of neutralizing antibodies against influenza A/H7N7 virus among poultry-exposed and unexposed individuals in Egypt were assessed during a three-years prospective cohort study. The seroprevalence of antibodies (titer, ≥80) among exposed individuals was 0%, 1.9%, and 2.1% annually while the seroprevalence among the control group remained 0% as measured by virus microneutralization assay. We then confirmed our results using western blot and immunofluorescence assays. Although human infection with H7 in Egypt has not been reported yet, our results suggested that Egyptian poultry growers are exposed to avian H7 viruses. These findings highlight the need for surveillance in the people exposed to poultry to monitor the risk of zoonotic transmission of avian influenza viruses.

Serological Evidence of Human Infection with Avian Influenza A H7virus in Egyptian Poultry Growers.

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Mokhtar R Gomaa

Full Text Available Avian influenza viruses circulate widely in birds, with occasional human infections. Poultry-exposed individuals are considered to be at high risk of infection with avian influenza viruses due to frequent exposure to poultry. Some avian H7 viruses have occasionally been found to infect humans. Seroprevalence of neutralizing antibodies against influenza A/H7N7 virus among poultry-exposed and unexposed individuals in Egypt were assessed during a three-years prospective cohort study. The seroprevalence of antibodies (titer, ≥80 among exposed individuals was 0%, 1.9%, and 2.1% annually while the seroprevalence among the control group remained 0% as measured by virus microneutralization assay. We then confirmed our results using western blot and immunofluorescence assays. Although human infection with H7 in Egypt has not been reported yet, our results suggested that Egyptian poultry growers are exposed to avian H7 viruses. These findings highlight the need for surveillance in the people exposed to poultry to monitor the risk of zoonotic transmission of avian influenza viruses.

Linezolid Decreases Susceptibility to Secondary Bacterial Pneumonia Post-Influenza Infection in Mice Through its Effects on Interferon-γ

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Breslow-Deckman, Jessica M.; Mattingly, Cynthia M.; Birket, Susan E.; Hoskins, Samantha N.; Ho, Tam N.; Garvy, Beth A.; Feola, David J.

2013-01-01

Influenza infection predisposes patients to secondary bacterial pneumonia that contributes significantly to morbidity and mortality. While this association is well documented, the mechanisms that govern this synergism are poorly understood. A window of hyporesponsiveness following influenza infection has been associated with a substantial increase in local and systemic IFNγ concentrations. Recent data suggests that the oxazolidinone antibiotic linezolid decreases IFNγ and TNFα production in vitro from stimulated peripheral blood mononuclear cells. We therefore sought to determine whether linezolid would reverse immune hyporesponsiveness after influenza infection in mice through its effects on IFNγ. In vivo dose response studies demonstrated that oral linezolid administration sufficiently decreased bronchoalveolar lavage fluid levels of IFNγ at day 7 post-influenza infection in a dose-dependent manner. The drug also decreased morbidity as measured by weight loss compared to vehicle-treated controls. When mice were challenged intranasally with S. pneumoniae 7 days after infection with influenza, linezolid pre-treatment led to decreased IFNγ and TNFα production, decreased weight loss, and lower bacterial burdens at 24 hours post bacterial infection in comparison to vehicle-treated controls. To determine whether these effects were due to suppression of IFNγ, linezolid-treated animals were given intranasal instillations of recombinant IFNγ before challenge with S. pneumoniae. This partially reversed the protective effects observed in the linezolid-treated mice, suggesting that the modulatory effects of linezolid are mediated partially by its ability to blunt IFNγ production. These results suggest that IFNγ, and potentially TNFα, may be useful drug targets for prophylaxis against secondary bacterial pneumonia following influenza infection. PMID:23833238

Modeling genome-wide dynamic regulatory network in mouse lungs with influenza infection using high-dimensional ordinary differential equations.

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Wu, Shuang; Liu, Zhi-Ping; Qiu, Xing; Wu, Hulin

2014-01-01

The immune response to viral infection is regulated by an intricate network of many genes and their products. The reverse engineering of gene regulatory networks (GRNs) using mathematical models from time course gene expression data collected after influenza infection is key to our understanding of the mechanisms involved in controlling influenza infection within a host. A five-step pipeline: detection of temporally differentially expressed genes, clustering genes into co-expressed modules, identification of network structure, parameter estimate refinement, and functional enrichment analysis, is developed for reconstructing high-dimensional dynamic GRNs from genome-wide time course gene expression data. Applying the pipeline to the time course gene expression data from influenza-infected mouse lungs, we have identified 20 distinct temporal expression patterns in the differentially expressed genes and constructed a module-based dynamic network using a linear ODE model. Both intra-module and inter-module annotations and regulatory relationships of our inferred network show some interesting findings and are highly consistent with existing knowledge about the immune response in mice after influenza infection. The proposed method is a computationally efficient, data-driven pipeline bridging experimental data, mathematical modeling, and statistical analysis. The application to the influenza infection data elucidates the potentials of our pipeline in providing valuable insights into systematic modeling of complicated biological processes.

New methods and reagents to improve the ferret model for human influenza infections

DEFF Research Database (Denmark)

Martel, Cyril Jean-Marie; Kirkeby, Svend; Aasted, Bent

The ferret has been extensively used to study human influenza infections. However, its value as a model has suffered from the limited set of reagents and methods available for this animal. We have recently tested a large number of monoclonal antibodies cross-reacting with ferret CD markers (CD8, ...... improvements of the model will aim at establishing a reliable RT-PCR for ferret cytokines, as well as investigating the location of influenza receptors and viral particles in the upper and lower respiratory tract via immunohistochemistry......The ferret has been extensively used to study human influenza infections. However, its value as a model has suffered from the limited set of reagents and methods available for this animal. We have recently tested a large number of monoclonal antibodies cross-reacting with ferret CD markers (CD8, CD...

Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals

NARCIS (Netherlands)

Lee, Laurel Yong-Hwa; Anh, Ha Do Lien; Simmons, Cameron; de Jong, Menno D.; Chau, Nguyen Van Vinh; Schumacher, Reto; Peng, Yan Chun; McMichael, Andrew J.; Farrar, Jeremy J.; Smith, Geoffrey L.; Townsend, Alain R. M.; Askonas, Brigitte A.; Rowland-Jones, Sarah; Dong, Tao

2008-01-01

The threat of avian influenza A (H5N1) infection in humans remains a global health concern. Current influenza vaccines stimulate antibody responses against the surface glycoproteins but are ineffective against strains that have undergone significant antigenic variation. An alternative approach is to

The onset of virus shedding and clinical signs in chickens infected with high-pathogenicity and low-pathogenicity avian influenza viruses.

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Spickler, Anna R; Trampel, Darrell W; Roth, James A

2008-12-01

Some avian influenza viruses may be transmissible to mammals by ingestion. Cats and dogs have been infected by H5N1 avian influenza viruses when they ate raw poultry, and two human H5N1 infections were linked to the ingestion of uncooked duck blood. The possibility of zoonotic influenza from exposure to raw poultry products raises concerns about flocks with unrecognized infections. The present review examines the onset of virus shedding and the development of clinical signs for a variety of avian influenza viruses in chickens. In experimentally infected birds, some high-pathogenicity avian influenza (HPAI) and low-pathogenicity avian influenza (LPAI) viruses can occur in faeces and respiratory secretions as early as 1 to 2 days after inoculation. Some HPAI viruses have also been found in meat 1 day after inoculation and in eggs after 3 days. There is no evidence that LPAI viruses can be found in meat, and the risk of their occurrence in eggs is poorly understood. Studies in experimentally infected birds suggest that clinical signs usually develop within a few days of virus shedding; however, some models and outbreak descriptions suggest that clinical signs may not become evident for a week or more in some H5 or H7 HPAI-infected flocks. During this time, avian influenza viruses might be found in poultry products. LPAI viruses can be shed in asymptomatically infected or minimally affected flocks, but these viruses are unlikely to cause significant human disease.

Productive infection of human skeletal muscle cells by pandemic and seasonal influenza A(H1N1 viruses.

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Marion Desdouits

Full Text Available Besides the classical respiratory and systemic symptoms, unusual complications of influenza A infection in humans involve the skeletal muscles. Numerous cases of acute myopathy and/or rhabdomyolysis have been reported, particularly following the outbreak of pandemic influenza A(H1N1 in 2009. The pathogenesis of these influenza-associated myopathies (IAM remains unkown, although the direct infection of muscle cells is suspected. Here, we studied the susceptibility of cultured human primary muscle cells to a 2009 pandemic and a 2008 seasonal influenza A(H1N1 isolate. Using cells from different donors, we found that differentiated muscle cells (i. e. myotubes were highly susceptible to infection by both influenza A(H1N1 isolates, whereas undifferentiated cells (i. e. myoblasts were partially resistant. The receptors for influenza viruses, α2-6 and α2-3 linked sialic acids, were detected on the surface of myotubes and myoblasts. Time line of viral nucleoprotein (NP expression and nuclear export showed that the first steps of the viral replication cycle could take place in muscle cells. Infected myotubes and myoblasts exhibited budding virions and nuclear inclusions as observed by transmission electron microscopy and correlative light and electron microscopy. Myotubes, but not myoblasts, yielded infectious virus progeny that could further infect naive muscle cells after proteolytic treatment. Infection led to a cytopathic effect with the lysis of muscle cells, as characterized by the release of lactate dehydrogenase. The secretion of proinflammatory cytokines by muscle cells was not affected following infection. Our results are compatible with the hypothesis of a direct muscle infection causing rhabdomyolysis in IAM patients.

Subclinical avian influenza A(H5N1) virus infection in human, Vietnam

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Le, Mai Quynh; Horby, Peter; Fox, Annette; Nguyen, Hien Tran; Le Nguyen, Hang Khanh; Hoang, Phuong Mai Vu; Nguyen, Khanh Cong; de Jong, Menno D.; Jeeninga, Rienk E.; Rogier van Doorn, H.; Farrar, Jeremy; Wertheim, Heiman F. L.

2013-01-01

Laboratory-confirmed cases of subclinical infection with avian influenza A(H5N1) virus in humans are rare, and the true number of these cases is unknown. We describe the identification of a laboratory-confirmed subclinical case in a woman during an influenza A(H5N1) contact investigation in northern

Features of pathology in mice experimentally infected with highly pathogenic H5N1 influenza virus

International Nuclear Information System (INIS)

Ryabchikova, E. I.; Taranov, O. S.; Malkova, E. M.; Gritsyk, O. B.; Demina, O. K.

2009-01-01

Avian influenza became a new threat and has set people thinking about possibility of new influenza pandemic which may be caused by highly pathogenic H5N1 influenza virus. The virus could acquire ability of fast spreading between the humans and new pandemics could kill millions. Influenza virus H5N1 exhibited its deadly essence by taking out many millions of birds in nature and aviculture; other millions of chicks and ducks were killed to prevent spread of the epizootic. The strains isolated in Russia belong to Qinghai group of H5N1 influenza virus, and were imported to Russia by migratory birds. We examined time-course changes in mice blood and lungs after intranasal infection with strains A /Chicken/ Kurgan/ 05/2005, A/ Duck/ Kurgan/08/ 2005 and A/ Chicken/ Suzdalka/ Nov-11/2005 differing in virulence for this animal species. Development of leucopenia and severe damage of hemopoiesis were found in mice infected with all H5N1 influenza virus strains. Pathological changes in mice lungs during the infection with above mentioned strains, and strain-specific features have been examined. Main characteristics of lung pathology in all mice were focal nature of the alterations, severe damage of bronchial epithelium and pronounced alteration of lung vasculature. Strain A/Chicken/Suzdalka/Nov-11/2005 induced massive apoptosis of infected bronchial cells which may be a part of mechanism responsible for avirulent properties of this strain. The most interesting finding was absence of serious direct virus damage of the lung evidencing for principal role of the host humoral mechanisms in pathogenesis of H5N1 influenza in mice.(author)

Swine-origin influenza A (H3N2) virus infection in two children--Indiana and Pennsylvania, July-August 2011.

Science.gov (United States)

2011-09-09

Influenza A viruses are endemic in many animal species, including humans, swine, and wild birds, and sporadic cases of transmission of influenza A viruses between humans and animals do occur, including human infections with avian-origin influenza A viruses (i.e., H5N1 and H7N7) and swine-origin influenza A viruses (i.e., H1N1, H1N2, and H3N2). Genetic analysis can distinguish animal origin influenza viruses from the seasonal human influenza viruses that circulate widely and cause annual epidemics. This report describes two cases of febrile respiratory illness caused by swine-origin influenza A (H3N2) viruses identified on August 19 and August 26, 2011, and the current investigations. No epidemiologic link between the two cases has been identified, and although investigations are ongoing, no additional confirmed human infections with this virus have been detected. These viruses are similar to eight other swine-origin influenza A (H3N2) viruses identified from previous human infections over the past 2 years, but are unique in that one of the eight gene segments (matrix [M] gene) is from the 2009 influenza A (H1N1) virus. The acquisition of the M gene in these two swine-origin influenza A (H3N2) viruses indicates that they are "reassortants" because they contain genes of the swine-origin influenza A (H3N2) virus circulating in North American pigs since 1998 and the 2009 influenza A (H1N1) virus that might have been transmitted to pigs from humans during the 2009 H1N1 pandemic. However, reassortments of the 2009 influenza A (H1N1) virus with other swine influenza A viruses have been reported previously in swine. Clinicians who suspect influenza virus infection in humans with recent exposure to swine should obtain a nasopharyngeal swab from the patient for timely diagnosis at a state public health laboratory and consider empiric neuraminidase inhibitor antiviral treatment to quickly limit potential human transmission.

Maintenance of influenza virus infectivity on the surfaces of personal protective equipment and clothing used in healthcare settings.

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Sakaguchi, Hiroko; Wada, Koji; Kajioka, Jitsuo; Watanabe, Mayumi; Nakano, Ryuichi; Hirose, Tatsuko; Ohta, Hiroshi; Aizawa, Yoshiharu

2010-11-01

The maintenance of infectivity of influenza viruses on the surfaces of personal protective equipment and clothing is an important factor in terms of controlling viral cross-infection in the environment and preventing contact infection. The aim of this study was to determine if laboratory-grown influenza A (H1N1) virus maintained infectivity on the surfaces of personal protective equipment and clothing used in healthcare settings. Influenza A virus (0.5 mL) was deposited on the surface of a rubber glove, an N95 particulate respirator, a surgical mask made of non-woven fabric, a gown made of Dupont Tyvek, a coated wooden desk, and stainless steel. Each sample was left for 1, 8, and 24 h, and hemagglutination (HA) and 50% tissue culture infective dose (TCID(50))/mL were measured. The HA titer of this influenza A virus did not decrease in any of the materials tested even after 24 h. The infectivity of influenza A virus measured by TCID(50) was maintained for 8 h on the surface of all materials, with the exception of the rubber glove for which virus infectivity was maintained for 24 h. Our results indicate that the replacement/renewal of personal protective equipment and clothing by healthcare professionals in cases of exposure to secretions and droplets containing viruses spread by patients is an appropriate procedure to prevent cross-infection.

Evidence for avian H9N2 influenza virus infections among rural villagers in Cambodia.

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Blair, Patrick J; Putnam, Shannon D; Krueger, Whitney S; Chum, Channimol; Wierzba, Thomas F; Heil, Gary L; Yasuda, Chadwick Y; Williams, Maya; Kasper, Matthew R; Friary, John A; Capuano, Ana W; Saphonn, Vonthanak; Peiris, Malik; Shao, Hongxia; Perez, Daniel R; Gray, Gregory C

2013-04-01

Southeast Asia remains a critical region for the emergence of novel and/or zoonotic influenza, underscoring the importance of extensive sampling in rural areas where early transmission is most likely to occur. In 2008, 800 adult participants from eight sites were enrolled in a prospective population-based study of avian influenza (AI) virus transmission where highly pathogenic avian influenza (HPAI) H5N1 virus had been reported in humans and poultry from 2006 to 2008. From their enrollment sera and questionnaires, we report risk factor findings for serologic evidence of previous infection with 18 AI virus strains. Serologic assays revealed no evidence of previous infection with 13 different low-pathogenic AI viruses or with HPAI avian-like A/Cambodia/R0404050/2007(H5N1). However, 21 participants had elevated antibodies against avian-like A/Hong Kong/1073/1999(H9N2), validated with a monoclonal antibody blocking ELISA assay specific for avian H9. Although cross-reaction from antibodies against human influenza viruses cannot be completely excluded, the study data suggest that a number of participants were previously infected with the avian-like A/Hong Kong/1073/1999(H9N2) virus, likely due to as yet unidentified environmental exposures. Prospective data from this cohort will help us better understand the serology of zoonotic influenza infection in a rural cohort in SE Asia. Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. All rights reserved.

Hampered foraging and migratory performance in swans infected with low-pathogenic avian influenza A virus.

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Jan A van Gils

Full Text Available It is increasingly acknowledged that migratory birds, notably waterfowl, play a critical role in the maintenance and spread of influenza A viruses. In order to elucidate the epidemiology of influenza A viruses in their natural hosts, a better understanding of the pathological effects in these hosts is required. Here we report on the feeding and migratory performance of wild migratory Bewick's swans (Cygnus columbianus bewickii Yarrell naturally infected with low-pathogenic avian influenza (LPAI A viruses of subtypes H6N2 and H6N8. Using information on geolocation data collected from Global Positioning Systems fitted to neck-collars, we show that infected swans experienced delayed migration, leaving their wintering site more than a month after uninfected animals. This was correlated with infected birds travelling shorter distances and fuelling and feeding at reduced rates. The data suggest that LPAI virus infections in wild migratory birds may have higher clinical and ecological impacts than previously recognised.

The influenza fingerprints: NS1 and M1 proteins contribute to specific host cell ultrastructure signatures upon infection by different influenza A viruses

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Terrier, Olivier; Moules, Vincent; Carron, Coralie; Cartet, Gaeelle [Equipe VirCell, Laboratoire de Virologie et Pathologie Humaine, VirPath EMR 4610, Universite de Lyon, Universite Claude Bernard Lyon 1, Hospices Civils de Lyon, Faculte de medecine RTH Laennec, rue Guillaume Paradin, F-69008 Lyon (France); Frobert, Emilie [Laboratoire de Virologie, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, 59 boulevard Pinel, F-69677 Bron Cedex, Lyon (France); Yver, Matthieu; Traversier, Aurelien [Equipe VirCell, Laboratoire de Virologie et Pathologie Humaine, VirPath EMR 4610, Universite de Lyon, Universite Claude Bernard Lyon 1, Hospices Civils de Lyon, Faculte de medecine RTH Laennec, rue Guillaume Paradin, F-69008 Lyon (France); Wolff, Thorsten [Division of Influenza/Respiratory Viruses, Robert Koch Institute, Nordufer 20, D-13353 Berlin (Germany); Riteau, Beatrice [Laboratoire de Virologie et Pathologie Humaine, VirPath EMR 4610, Universite de Lyon, Universite Claude Bernard Lyon 1, Hospices Civils de Lyon, Faculte de medecine RTH Laennec, rue Guillaume Paradin, F-69008 Lyon (France); Naffakh, Nadia [Institut Pasteur, Unite de Genetique Moleculaire des Virus Respiratoires, URA CNRS 3015, EA302 Universite Paris Diderot, Paris (France); and others

2012-10-10

Influenza A are nuclear replicating viruses which hijack host machineries in order to achieve optimal infection. Numerous functional virus-host interactions have now been characterized, but little information has been gathered concerning their link to the virally induced remodeling of the host cellular architecture. In this study, we infected cells with several human and avian influenza viruses and we have analyzed their ultrastructural modifications by using electron and confocal microscopy. We discovered that infections lead to a major and systematic disruption of nucleoli and the formation of a large number of diverse viral structures showing specificity that depended on the subtype origin and genomic composition of viruses. We identified NS1 and M1 proteins as the main actors in the remodeling of the host ultra-structure and our results suggest that each influenza A virus strain could be associated with a specific cellular fingerprint, possibly correlated to the functional properties of their viral components.

The influenza fingerprints: NS1 and M1 proteins contribute to specific host cell ultrastructure signatures upon infection by different influenza A viruses

International Nuclear Information System (INIS)

Terrier, Olivier; Moules, Vincent; Carron, Coralie; Cartet, Gaëlle; Frobert, Emilie; Yver, Matthieu; Traversier, Aurelien; Wolff, Thorsten; Riteau, Beatrice; Naffakh, Nadia

2012-01-01

Influenza A are nuclear replicating viruses which hijack host machineries in order to achieve optimal infection. Numerous functional virus–host interactions have now been characterized, but little information has been gathered concerning their link to the virally induced remodeling of the host cellular architecture. In this study, we infected cells with several human and avian influenza viruses and we have analyzed their ultrastructural modifications by using electron and confocal microscopy. We discovered that infections lead to a major and systematic disruption of nucleoli and the formation of a large number of diverse viral structures showing specificity that depended on the subtype origin and genomic composition of viruses. We identified NS1 and M1 proteins as the main actors in the remodeling of the host ultra-structure and our results suggest that each influenza A virus strain could be associated with a specific cellular fingerprint, possibly correlated to the functional properties of their viral components.

Mortality Attributable to Seasonal Influenza A and B Infections in Thailand, 2005–2009: A Longitudinal Study

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Cooper, Ben S.; Kotirum, Surachai; Kulpeng, Wantanee; Praditsitthikorn, Naiyana; Chittaganpitch, Malinee; Limmathurotsakul, Direk; Day, Nicholas P. J.; Coker, Richard; Teerawattananon, Yot; Meeyai, Aronrag

2015-01-01

Influenza epidemiology differs substantially in tropical and temperate zones, but estimates of seasonal influenza mortality in developing countries in the tropics are lacking. We aimed to quantify mortality due to seasonal influenza in Thailand, a tropical middle-income country. Time series of polymerase chain reaction–confirmed influenza infections between 2005 and 2009 were constructed from a sentinel surveillance network. These were combined with influenza-like illness data to derive measures of influenza activity and relationships to mortality by using a Bayesian regression framework. We estimated 6.1 (95% credible interval: 0.5, 12.4) annual deaths per 100,000 population attributable to influenza A and B, predominantly in those aged ≥60 years, with the largest contribution from influenza A(H1N1) in 3 out of 4 years. For A(H3N2), the relationship between influenza activity and mortality varied over time. Influenza was associated with increases in deaths classified as resulting from respiratory disease (posterior probability of positive association, 99.8%), cancer (98.6%), renal disease (98.0%), and liver disease (99.2%). No association with circulatory disease mortality was found. Seasonal influenza infections are associated with substantial mortality in Thailand, but evidence for the strong relationship between influenza activity and circulatory disease mortality reported in temperate countries is lacking. PMID:25899091

Long term immune responses to pandemic influenza A/H1N1 infection in solid organ transplant recipients.

Directory of Open Access Journals (Sweden)

Aliyah Baluch

Full Text Available In solid organ transplant (SOT recipients it is unknown if natural infection with influenza confers protection from re-infection with the same strain during the next influenza season. The purpose of this study was to determine if infection with pandemic influenza A/H1N1 (pH1N1 resulted in a long-term immunologic response. Transplant recipients with microbiologically proven pH1N1 infection in 2009/2010 underwent humoral and cell-mediated immunity (CMI testing for pH1N1 just prior to the next influenza season. Concurrent testing for A/Brisbane/59/2007 was done to rule-out cross-reacting antibody. We enrolled 22 adult transplant patients after pH1N1 infection. Follow up testing was done at a median of 7.4 months (range 5.8-15.4 after infection. After excluding those with cross-reactive antibody, 7/19 (36.8% patients were seroprotected. Detectable pH1N1-specific CD4+ and CD8+ interferon-γ producing T-cells were found in 11/22 (50% and 8/22 (36.4% patients respectively. Humoral immunity had a significant correlation with a CD4 response. This is the first study in transplant patients to evaluate long-term humoral and cellular response after natural influenza infection. We show that a substantial proportion of SOT recipients with previous pH1N1 infection lack long-term humoral and cellular immune responses to pH1N1. These patients most likely are at risk for re-infection.

Bacterial meningitis in children

International Nuclear Information System (INIS)

Marji, S.

2007-01-01

To demonstrate the epidemiology, clinical manifestations and bacteriological profile of bacterial meningitis in children beyond the neonatal period in our hospital. This was a retrospective descriptive study conducted at Prince Rashid Hospital in Irbid, Jordan. The medical records of 50 children with the diagnosis of bacterial meningitis during 4 years period, were reviewed. The main cause of infection was streptococcus pneumoniae, followed by Haemophilus influenza and Niesseria meningitides. Mortality was higher in infants and meningococcal infection, while complications were more encountered in cases of streptococcus pneumoniae. Cerebrospinal fluid culture was positive in 11 cases and Latex agglutination test in 39. There is a significant reduction of the numbers of bacterial meningitis caused by Haemophilus influenza type B species. (author)

Estimating burden of influenza-associated influenza-like illness and severe acute respiratory infection at public healthcare facilities in Romania during the 2011/12-2015/16 influenza seasons.

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Gefenaite, Giedre; Pistol, Adriana; Popescu, Rodica; Popovici, Odette; Ciurea, Daniel; Dolk, Christiaan; Jit, Mark; Gross, Diane

2018-01-01

Influenza is responsible for substantial morbidity and mortality, but there is limited information on reliable disease burden estimates, especially from middle-income countries in the WHO European Region. To estimate the incidence of medically attended influenza-associated influenza-like illness (ILI) and hospitalizations due to severe acute respiratory infection (SARI) presenting to public healthcare facilities in Romania. Sentinel influenza surveillance data for ILI and SARI from 2011/12-2015/16, including virological data, were used to estimate influenza-associated ILI and SARI incidence/100 000 and their 95% confidence intervals (95% CI). The overall annual incidence of ILI and influenza-associated ILI per 100 000 persons in Romania varied between 68 (95% CI: 61-76) and 318 (95% CI: 298-338) and between 23 (95% CI: 19-29) and 189 (95% CI: 149-240), respectively. The highest ILI and influenza incidence was among children aged 0-4 years. We estimated that SARI incidence per 100 000 persons was 6 (95% CI: 5-7) to 9 (95% CI: 8-10), of which 2 (95% CI: 1-2) to 3 (95% CI: 2-4) were due to influenza. Up to 0.3% of the Romanian population were annually reported with ILI, and 0.01% was hospitalized with SARI, of which as much as one-third could be explained by influenza. This evaluation was the first study estimating influenza burden in Romania. We found that during each influenza season, a substantial number of persons in Romania suffer from influenza-related ILI or are hospitalized due to influenza-associated SARI. © 2017 The World Health Organization. Influenza and Other Respiratory Viruses. Published by John Wiley & Sons Ltd.

Does virus-bacteria coinfection increase the clinical severity of acute respiratory infection?

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Damasio, Guilherme A C; Pereira, Luciane A; Moreira, Suzana D R; Duarte dos Santos, Claudia N; Dalla-Costa, Libera M; Raboni, Sonia M

2015-09-01

This retrospective cohort study investigated the presence of bacteria in respiratory secretions of patients hospitalized with acute respiratory infections and analyzed the impact of viral and bacterial coinfection on severity and the mortality rate. A total of 169 patients with acute respiratory infections were included, viruses and bacteria in respiratory samples were detected using molecular methods. Among all samples, 73.3% and 59.7% were positive for viruses and bacteria, respectively; 45% contained both virus and bacteria. Bacterial coinfection was more frequent in patients infected by community respiratory viruses than influenza A H1N1pdm (83.3% vs. 40.6%). The most frequently bacteria detected were Streptococcus pneumoniae and Haemophilus influenzae. Both species were co-detected in 54 patients and identified alone in 22 and 21 patients, respectively. Overall, there were no significant differences in the period of hospitalization, severity, or mortality rate between patients infected with respiratory viruses alone and those coinfected by viruses and bacteria. The detection of mixed respiratory pathogens is frequent in hospitalized patients with acute respiratory infections, but its impact on the clinical outcome does not appear substantial. However, it should be noted that most of the patients received broad-spectrum antibiotic therapy, which may have contributed to this favorable outcome. © 2015 Wiley Periodicals, Inc.

Infection by rhinovirus: similarity of clinical signs included in the case definition of influenza IAn/H1N1.

Science.gov (United States)

de Oña Navarro, Maria; Melón García, Santiago; Alvarez-Argüelles, Marta; Fernández-Verdugo, Ana; Boga Riveiro, Jose Antonio

2012-08-01

Although new influenza virus (IAn/H1N1) infections are mild and indistinguishable from any other seasonal influenza virus infections, there are few data on comparisons of the clinical features of infection with (IAn/H1N1) and with other respiratory viruses. The incidence, clinical aspects and temporal distribution of those respiratory viruses circulating during flu pandemic period were studied. Respiratory samples from patients with acute influenza-like symptoms were collected from May 2009 to December 2009. Respiratory viruses were detected by conventional culture methods and genome amplification techniques. Although IAn/H1N1 was the virus most frequently detected, several other respiratory viruses co-circulated with IAn/H1N1 during the pandemic period, especially rhinovirus. The similarity between clinical signs included in the clinical case definition for influenza and those caused by other respiratory viruses, particularly rhinovirus, suggest that a high percentage of viral infections were clinically diagnosed as case of influenza. Our study offers useful information to face future pandemics caused by influenza virus, indicating that differential diagnoses are required in order to not overestimate the importance of the pandemic. Copyright © 2011 Elsevier España, S.L. All rights reserved.