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E Sarmiento, P Diez, M Arraya, M Jaramillo, L Calahorra, J Fernandez-Yañez, J Palomo, I Sousa, J Hortal, J Barrios, R Alonso, P Muñoz, J Navarro, J Vicario, E Fernandez-Cruz, J Carbone
BACKGROUND: Immunoglobulin G (IgG) hypogammaglobulinemia (HGG) is a risk factor for development of severe infections after heart transplantation. We performed a clinical trial to preliminarily evaluate the efficacy and safety of early administration of intravenous immunoglobulin (IVIG) for prevention of severe infection in heart recipients with post-transplant IgG HGG. METHODS: Twelve heart recipients with IgG HGG detected in a screening phase of the clinical trial (IgG<500 mg/dL) were recruited...
September 17, 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Tamar A Smith-Norowitz, Tehila A Saadia, Natalie Banniettis, Yitzchok M Norowitz, Rauno Joks, Margaret R Hammerschlag, Helen G Durkin, Stephan Kohlhoff
BACKGROUND: Haemophilus influenzae type b (Hib) bacterium causes severe illness in infants and children, but has largely been eliminated by introducing a universal Hib conjugate vaccine. While effects of certain vaccinations on atopic disease have been studied, little is known about the relationship between Hib vaccination and diseases of altered IgE regulation (asthma or atopy). As such, it is necessary to provide more evidence concerning Hib vaccination as a possible risk factor for atopic disease...
May 17, 2016: Minerva Pediatrica
Maria Rosario Z Capeding, Edison Alberto, Amanda Versteilen, Martina Rauscher, Partha Bagchi, Patricia Ibarra de Palacios
OBJECTIVE: To evaluate non-inferiority of three doses of Quinvaxem in a compact prefilled auto-disabled (cPAD) injection system versus Quinvaxem in a single-dose vial administered with conventional syringe in terms of seroconversion/seroprotection rates for all antibodies (anti-hepatitis B (HB), anti-Haemophilus influenzae type b polyribosylribitol phosphate (Hib PRP), anti-diphtheria, anti-tetanus, anti-Bordetella pertussis) at 1 month after primary vaccination. METHODS: Four hundred healthy infants aged 42-65 days were randomized (1:1) to receive Quinvaxem in cPAD or single-dose vial at 6, 10, and 12 weeks of age...
May 2016: International Journal of Infectious Diseases: IJID
Anna Golebiewska, Alicja Kuch, Agnieszka Gawrońska, Piotr Albrecht, Anna Skoczyńska, Andrzej Radzikowski, Ewa Kutylowska, Wojciech Feleszko
After successful introduction of anti-Haemophilus influenzae (Hi) serotype b vaccination program in Poland, invasive non-b or nontypeable H. influenzae infections have been reported more frequently alike in other countries all over the world. In this paper, we report 2 cases of H. influenzae serotype f (Hif) meningitis with severe clinical presentations which are rarely seen in previously healthy children.The first case is a 6-year-old girl who was admitted to pediatric ward with signs of meningitis. Laboratory tests confirmed bacteremic meningitis caused by Hif...
February 2016: Medicine (Baltimore)
Robert Booy, Terry Nolan, Graham Reynolds, Peter Richmond, Michael Nissen, Helen Marshall, Tanya Stoney, Marie Van Der Wielen, Devayani Kolhe, Jacqueline M Miller
BACKGROUND: Antibody persistence is evaluated in healthy Australian children 4 and 5 years postvaccination with a single dose of combined Haemophilus influenzae type b-Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) compared with separately administered Hib-TT and MenC-CRM197 vaccines (Hib + MCC). METHODS: This is another follow-up of a phase III, open, randomized, controlled study (NCT00326118), in which 433 Hib-primed but MenC naïve toddlers aged 12-18 months were randomized 3:1 to receive Hib-MenC-TT or Hib + MCC vaccines...
December 2015: Pediatric Infectious Disease Journal
Jennifer L J Heaney, Anna C Phillips, Douglas Carroll, Mark T Drayson
BACKGROUND: Bacterial infections in the elderly are common and associated with high morbidity and mortality, with pneumonia the second commonest cause of death. Reductions in antibodies against specific bacterial antigens in saliva and serum could contribute to infection risk in older adults, although they have yet to be examined in relation to age. METHOD: IgG, IgA and IgM antibody levels in paired saliva and serum samples were measured against 12 pneumococcal, 4 meningococcal and haemophilus polysaccharide antigens and diphtheria and tetanus toxoids in healthy younger (n = 28, 21-34 years) and older (n = 44, 60-80 years) adults...
December 2015: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Maria Petrecz, Keith P Ramsey, Jon E Stek, Jason C Martin, Stephanie O Klopfer, Barbara Kuter, Florian P Schödel, Andrew W Lee
Open-label, multicenter, randomized study (NCT00289913) evaluated immunogenicity, safety, and tolerability of Vaqta (hepatitis A vaccine) administered with PedvaxHIB (Haemophilus b conjugate vaccine [Meningococcal protein conjugate]) & Infanrix (diphtheria/tetanus/acellular pertussis vaccine) in healthy, 15-month-old children. Five groups were evaluated: Group 1 received Vaqta/Infanrix PedvaxHIB on Day-1 and Vaqta at Week-24; Group 2 received Infanrix PedvaxHIB on Day-1, Vaqta at Week-4, and Vaqta at Week-28; Group 3 received Vaqta/PedvaxHIB on Day-1 and Vaqta Week-24; Group 4 received PedvaxHIB on Day-1, Vaqta at Week-4, and Vaqta at Week-28; and Group 5 (safety only) received Vaqta on Day-1 and Vaqta at Week-24...
2016: Human Vaccines & Immunotherapeutics
Matthew K Siggins, Simren K Gill, Paul R Langford, Yanwen Li, Shamez N Ladhani, John S Tregoning
BACKGROUND: A recently-licensed 10-valent pneumococcal conjugate vaccine (PHiD-CV; Synflorix, GSK) uses Protein D from Haemophilus influenzae as a carrier protein. PHiD-CV therefore has the potential to provide additional protection against nontypeable H. influenzae (NTHi). NTHi frequently causes respiratory tract infections and is associated with significant morbidity and mortality worldwide and there is currently no vaccine. METHODS: We developed mouse models of NTHi infection and influenza/NTHi superinfection...
September 11, 2015: Vaccine
Shakti Dhar Shukla, Sukhwinder Singh Sohal, Ronan F O'Toole, Mathew Suji Eapen, Eugene Haydn Walters
The authors established that cigarette smoke increases airway epithelial platelet activating factor receptor (PAFr) expression and that PAFr is markedly up-regulated in the lungs of chronic obstructive pulmonary disease (COPD) patients. Crucially, PAFr is used by the two key bacterial species involved in chronic infection and acute exacerbations in COPD, that is, Streptococcus pneumoniae and Haemophilus influenzae, as a receptor for lung epithelial colonization. The cognate adhesin of PAFr, phosphorylcholine (ChoP), in the cell wall of these bacterial species may be a key effector that underpins host colonization...
August 2015: Expert Review of Respiratory Medicine
Andreas Hecker, Mira Küllmar, Sigrid Wilker, Katrin Richter, Anna Zakrzewicz, Srebrena Atanasova, Verena Mathes, Thomas Timm, Sabrina Lerner, Jochen Klein, Andreas Kaufmann, Stefan Bauer, Winfried Padberg, Wolfgang Kummer, Sabina Janciauskiene, Martin Fronius, Elke K H Schweda, Günter Lochnit, Veronika Grau
IL-1β is a potent proinflammatory cytokine of the innate immune system that is involved in host defense against infection. However, increased production of IL-1β plays a pathogenic role in various inflammatory diseases, such as rheumatoid arthritis, gout, sepsis, stroke, and transplant rejection. To prevent detrimental collateral damage, IL-1β release is tightly controlled and typically requires two consecutive danger signals. LPS from Gram-negative bacteria is a prototypical first signal inducing pro-IL-1β synthesis, whereas extracellular ATP is a typical second signal sensed by the ATP receptor P2X7 that triggers activation of the NLRP3-containing inflammasome, proteolytic cleavage of pro-IL-1β by caspase-1, and release of mature IL-1β...
September 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Stephanie Zimmermann, Bernd Lepenies
Carbohydrates can be found on the cell surface of nearly every cell ranging from bacteria to fungi right up to mammalian cells. Carbohydrates and their interactions with carbohydrate-binding proteins play crucial roles in multiple biological processes including immunity, homeostasis, cellular communication, cell migration, and the regulation of serum glycoprotein levels. In the last decades, the interest in exploiting the biological activity of glycans as vaccine components has considerably increased. On the one hand, carbohydrates display epitopes to generate protective antibodies against pathogen-derived cell wall structures and on the other hand, glycans have the potential to stimulate the immune system; thus they can act as potent vaccine adjuvants...
2015: Methods in Molecular Biology
Abraham B Roos, Sanjay Sethi, Jake Nikota, Catherine T Wrona, Michael G Dorrington, Caroline Sandén, Carla M T Bauer, Pamela Shen, Dawn Bowdish, Christopher S Stevenson, Jonas S Erjefält, Martin R Stampfli
RATIONALE: Nontypeable Haemophilus influenzae (NTHi) causes acute exacerbation of chronic obstructive pulmonary disease (AECOPD). IL-17A is central for neutrophilic inflammation and has been linked to COPD pathogenesis. OBJECTIVES: We investigated whether IL-17A is elevated in NTHi-associated AECOPD and required for NTHi-exacerbated pulmonary neutrophilia induced by cigarette smoke. METHODS: Experimental studies with cigarette smoke and NTHi infection were pursued in gene-targeted mice and using antibody intervention...
August 15, 2015: American Journal of Respiratory and Critical Care Medicine
Hock L Tay, Gerard E Kaiko, Maximilian Plank, JingJing Li, Steven Maltby, Ama-Tawiah Essilfie, Andrew Jarnicki, Ming Yang, Joerg Mattes, Philip M Hansbro, Paul S Foster
Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to increasing antibiotic resistance and impairment of innate immunity by disease processes and steroid therapy. Manipulation miRNA directly regulating anti-microbial machinery of the innate immune system may boost host defence responses. Here we demonstrate that miR-328 is a key element of the host response to pulmonary infection with non-typeable haemophilus influenzae and pharmacological inhibition in mouse and human macrophages augments phagocytosis, the production of reactive oxygen species, and microbicidal activity...
April 2015: PLoS Pathogens
Michelle Hernandez, Anke Leichtle, Kwang Pak, Nicholas J Webster, Stephen I Wasserman, Allen F Ryan
BACKGROUND: Otitis media is the most common disease of childhood, and represents an important health challenge to the 10-15% of children who experience chronic/recurrent middle ear infections. The middle ear undergoes extensive modifications during otitis media, potentially involving changes in the expression of many genes. Expression profiling offers an opportunity to discover novel genes and pathways involved in this common childhood disease. The middle ears of 320 WBxB6 F1 hybrid mice were inoculated with non-typeable Haemophilus influenzae (NTHi) or PBS (sham control)...
2015: BMC Genomics
Grant A Mackenzie, Usman N A Ikumapayi, Susana Scott, Olubukola Idoko, Aderonke Odutola, Malick Ndiaye, Shah M Sahito, Chidiebereh D Osuorah, Ahmed Manjang, Sheikh Jarju, Abdoulie Bojang, Anna Roca, Ousman Secka, Akram Zaman, Lamin Ceesay, Yamundow Lowe-Jallow, Sana Sambou, Momodou Jasseh, Martin Antonio, Brian Greenwood, Beate Kampmann, Kim Mulholland, Tumani Corrah, Stephen R C Howie
BACKGROUND: In 1997, The Gambia became the first African country to introduce conjugate Haemophilus influenzae type b (Hib) vaccine with good disease control through to 2010. METHODS: Culture-based surveillance for invasive bacterial disease in eastern Gambia, specifically the Basse Health and Demographic Surveillance System (BHDSS) area, was conducted from 12 May 2008 and in Fuladu West district from 12 September 2011 until 31 December 2013. In 2011, Hib serology was measured in 5-34-year-olds...
May 2015: Pediatric Infectious Disease Journal
Shu Mei Teo, Danny Mok, Kym Pham, Merci Kusel, Michael Serralha, Niamh Troy, Barbara J Holt, Belinda J Hales, Michael L Walker, Elysia Hollams, Yury A Bochkov, Kristine Grindle, Sebastian L Johnston, James E Gern, Peter D Sly, Patrick G Holt, Kathryn E Holt, Michael Inouye
The nasopharynx (NP) is a reservoir for microbes associated with acute respiratory infections (ARIs). Lung inflammation resulting from ARIs during infancy is linked to asthma development. We examined the NP microbiome during the critical first year of life in a prospective cohort of 234 children, capturing both the viral and bacterial communities and documenting all incidents of ARIs. Most infants were initially colonized with Staphylococcus or Corynebacterium before stable colonization with Alloiococcus or Moraxella...
May 13, 2015: Cell Host & Microbe
D M Muema, E W Nduati, M Uyoga, M Bashraheil, J A G Scott, L L Hammitt, B C Urban
Memory B cells are long-lived and could contribute to persistence of humoral immunity by maintaining the plasma-cell pool or making recall responses upon re-exposure to an antigen. We determined the ability of a pneumococcal conjugate vaccine to induce anti-pneumococcal memory B cells. Frequencies of memory B cells against pneumococcal capsular polysaccharides from serotypes 1, 6B, 14, 19F and 23F were determined by cultured B cell enzyme-linked immunospot (ELISPOT) in 35 children aged 12-23 months who received pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV)...
August 2015: Clinical and Experimental Immunology
Satoshi Iwata, Naohisa Kawamura, Haruo Kuroki, Yasunobu Tokoeda, Mitsunobu Miyazu, Asayuki Iwai, Tomohiro Oishi, Tomohide Sato, Akari Suyama, Nancy François, Fakrudeen Shafi, Javier Ruiz-Guiñazú, Dorota Borys
This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3-4-5 months of age) and booster vaccination (17-19 months of age)...
2015: Human Vaccines & Immunotherapeutics
Jeong-Im Woo, Sung-Hee Kil, Sejo Oh, Yoo-Jin Lee, Raekil Park, David J Lim, Sung K Moon
Cochlear inflammatory diseases, such as tympanogenic labyrinthitis, are associated with acquired sensorineural hearing loss. Although otitis media is extremely frequent in children, tympanogenic labyrinthitis is not commonly observed, which suggests the existence of a potent anti-inflammatory mechanism modulating cochlear inflammation. In this study, we aimed to determine the molecular mechanism involved in cochlear protection from inflammation-mediated tissue damage, focusing on IL-10 and hemoxygenase-1 (HMOX1) signaling...
April 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Ama-Tawiah Essilfie, Jay C Horvat, Richard Y Kim, Jemma R Mayall, James W Pinkerton, Emma L Beckett, Malcolm R Starkey, Jodie L Simpson, Paul S Foster, Peter G Gibson, Philip M Hansbro
BACKGROUND: Steroid-insensitive endotypes of asthma are an important clinical problem and effective therapies are required. They are associated with bacterial infection and non-eosinophilic inflammatory responses in the asthmatic lung. Macrolide therapy is effective in steroid-insensitive endotypes, such as non-eosinophilic asthma. However, whether the effects of macrolides are due to antimicrobial or anti-inflammatory mechanisms is not known. OBJECTIVE: To determine and assess the efficacy of macrolide (ie, clarithromycin) and non-macrolide (ie, amoxicillin) antibiotic treatments in experimental models of infection-induced, severe, steroid-insensitive neutrophilic allergic airways disease (SSIAAD), compared with steroid-sensitive AAD and to delineate the antimicrobial and anti-inflammatory effects of macrolide therapy...
May 2015: Thorax
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