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1.
Pediatr Infect Dis J ; 39(4): 294-297, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32032175

RESUMEN

BACKGROUND: The epidemiologic characteristics of invasive Haemophilus influenzae type b disease (HIBD) have markedly changed since the introduction of the Haemophilus influenzae type b (Hib) conjugate vaccine worldwide. The immunization schedule against Haemophilus influenzae type b differs in Europe. METHODS: This is a retrospective observational study which evaluates all the data included in the molecular surveillance register for invasive infectious diseases at the Laboratory of Molecular Diagnosis at Meyer Children's University Hospital from December 2008 to December 2018 with a diagnosis of invasive HIBD in children <5 years of age. RESULTS: We identified 4 cases of HIBD: all the cases presented signs or symptoms of invasive infection and the H. influenzae type b was identified in cerebrospinal fluid, or blood or bronchoalveolar lavage by molecular test. The crude incidence for Hib invasive disease in Tuscany is 0.26/100,000 p-y in children younger than 5 years, significantly different from the incidence rate before the introduction of the Hib vaccination. Vaccination effectiveness can be estimated at 97.9% and the impact of hexavalent (2p+1) vaccine at 99.6%. CONCLUSIONS: This work confirms the high impact of the hexavalent vaccine 2p+1 schedule for HIBD in children <5 years, emphasizing the role of molecular test for HIBD diagnosis and surveillance.


Asunto(s)
Monitoreo Epidemiológico , Infecciones por Haemophilus/epidemiología , Vacunas contra Haemophilus/inmunología , Haemophilus influenzae tipo b/genética , Líquido del Lavado Bronquioalveolar/microbiología , Preescolar , Infecciones por Haemophilus/sangre , Infecciones por Haemophilus/líquido cefalorraquídeo , Haemophilus influenzae tipo b/aislamiento & purificación , Haemophilus influenzae tipo b/patogenicidad , Humanos , Esquemas de Inmunización , Incidencia , Lactante , Recién Nacido , Italia/epidemiología , Estudios Retrospectivos , Vacunas Combinadas/inmunología
2.
Vaccine ; 37(36): 5452-5459, 2019 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-31331773

RESUMEN

BACKGROUND: A liquid Pentavalent (DTwP-Hb-Hib) combination vaccine, developed by Human Biologicals Institute, underwent a Phase III clinical study in India. In this randomized, single blind, non-inferiority study, the immunogenicity and safety of this Investigational vaccine was compared with Pentavac SD® vaccine in 6-8 weeks old healthy infants. METHODS: A total of 405 healthy infants aged 6-8 weeks old were randomized in 2:1 ratio to receive three doses of either the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine or Pentavac SD® vaccine at four to six weeks interval. Immunogenicity was compared by estimation of antibody titers before the first dose and 4-6 weeks after the third dose of vaccination. Safety of each vaccine was assessed and compared by collection of data on solicited and unsolicited adverse events throughout the study period. RESULTS: Out of a total of 405 enrolled subjects, 387 subjects completed the study. The seroconversion rates, seroprotection rates and geometric mean titres of the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine group were found to be comparable and non-inferior to the Pentavac SD® vaccine group at 4-6 weeks after the third dose of vaccination. Pain, erythema and swelling at the site of injection were found to be the most common local adverse events whereas fever, irritability and unusual crying were found to be the most common systemic adverse events in both the vaccine groups. No vaccine related serious adverse event was reported. In this study, both the Investigational vaccine as well as the Comparator vaccine were found to be immunogenic and well tolerated. CONCLUSION: After assessment of the results of the study it was concluded that the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine developed by Human Biologicals Institute was immunogenic and safe when administered to infants aged 6-8 weeks and was non-inferior in immunogenicity and safety to Pentavac SD® vaccine. Clinical Trial Registry of India Identifier: CTRI/2016/01/006541.


Asunto(s)
Vacuna contra Difteria, Tétanos y Tos Ferina/uso terapéutico , Vacunas contra Haemophilus/uso terapéutico , Vacuna Antipolio de Virus Inactivados/uso terapéutico , Vacunación/métodos , Vacunas Combinadas/uso terapéutico , Formación de Anticuerpos/inmunología , Formación de Anticuerpos/fisiología , Femenino , Haemophilus influenzae tipo b/inmunología , Haemophilus influenzae tipo b/patogenicidad , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/patogenicidad , Humanos , India , Lactante , Masculino , Método Simple Ciego
3.
Saudi Med J ; 40(4): 405-408, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30957137

RESUMEN

OBJECTIVES: To re-draw attention to the unnecessary prescribing of antibiotics. METHODS: We monitored nasopharyngeal colonization by 3 potentially pathogenic bacteria, Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae type b in 81 children between the ages of 6 and 7 years who attended the same primary school. The children's health status was also monitored, without using antimicrobial treatment for healthy/asymptomatic carriers. Nasopharyngeal swabs were collected on 6 occasions during autumn months, from mid-September to mid-December 2016. The children who fell ill during the study were treated at the Ear, Nose and Throat Clinic, Sisters of Mercy University Hospital Center, Zagreb, Croatia. RESULTS: Four hundred and sixty-three  nasopharyngeal swabs were collected. Each child had at least one positive swab result. Bacterial colonization with Streptococcus pyogenes had the highest colonization rate. During the study, 83% of the children were healthy/asymptomatic carriers with no clinical signs of disease,  while 17% became ill. The statistical results showed that the increase in all examined bacteria was statistically significant. CONCLUSIONS:   Our  study results showed that positive bacterial findings in nasopharyngeal swabs from clinically healthy carriers were not an indication for antibiotic therapy.


Asunto(s)
Antibacterianos , Portador Sano/microbiología , Haemophilus influenzae tipo b/aislamiento & purificación , Prescripción Inadecuada/prevención & control , Nasofaringe/microbiología , Streptococcus pneumoniae/aislamiento & purificación , Streptococcus pyogenes/aislamiento & purificación , Antibacterianos/efectos adversos , Niño , Femenino , Haemophilus influenzae tipo b/patogenicidad , Humanos , Masculino , Instituciones Académicas , Estaciones del Año , Streptococcus pneumoniae/patogenicidad , Streptococcus pyogenes/patogenicidad , Factores de Tiempo
5.
Hum Vaccin Immunother ; 14(1): 36-44, 2018 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-29049002

RESUMEN

OBJECTIVE: The aims of this study were to estimate the cost-effectiveness of the Haemophilus influenzae type b (Hib) vaccine for the prevention of childhood pneumonia, meningitis and other vaccine-preventable diseases in mainland China from a societal perspective and to provide information about the addition of the Hib vaccine to Chinese immunization programs. METHODS: A decision tree and the Markov model were used to estimate the costs and effectiveness of the Hib vaccine versus no Hib vaccine for a birth cohort of 100,000 children in 2016. The disease burden was estimated from the literature, statistical yearbooks and field surveys. Vaccine costs were calculated from government reports and the United Nations International Children's Emergency Fund (UNICEF) website. The WHO cost-effectiveness thresholds were used to evaluate the Hib vaccine intervention. A one-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the parameter uncertainties. RESULTS: Within the hypothetical cohort, under a vaccination coverage of 90%, the Hib vaccine could reduce 91.4% of Hib pneumonia and 88.3% of Hib meningitis; the Hib vaccine could also prevent 25 deaths, 24 meningitis sequelae cases and 9 hearing loss cases caused by Hib infection. From a societal perspective, the incremental cost-effectiveness ratio (ICER) of the Hib vaccine compared with no vaccination was US$ 13,640.1 at the market price, which was less than 3 times the GDP per capita of China in 2016. The ICER of the Hib vaccine was US$ -59,122.9 at the UNICEF price, indicating a cost savings. The largest portion of the uncertainty in the result was caused by the annual incidence of all-cause pneumonia, proportion of pneumonia caused by Hi, vaccine costs per dose, annual incidence of Hib meningitis and costs per episode of meningitis. The models were robust considering parameter uncertainties. CONCLUSION: The Hib vaccine is a cost-effective intervention among children in mainland China. The cost of Hib vaccine should be reduced, and it should be introduced into Chinese immunization programs.


Asunto(s)
Costo de Enfermedad , Análisis Costo-Beneficio , Vacunas contra Haemophilus/economía , Meningitis por Haemophilus/epidemiología , Neumonía/epidemiología , Cápsulas Bacterianas , China/epidemiología , Estudios de Cohortes , Ahorro de Costo , Vacunas contra Haemophilus/uso terapéutico , Haemophilus influenzae tipo b/inmunología , Haemophilus influenzae tipo b/patogenicidad , Costos de la Atención en Salud , Humanos , Incidencia , Lactante , Recién Nacido , Cadenas de Markov , Vacunación Masiva/economía , Meningitis por Haemophilus/economía , Meningitis por Haemophilus/microbiología , Meningitis por Haemophilus/prevención & control , Modelos Estadísticos , Neumonía/economía , Neumonía/microbiología , Neumonía/prevención & control
6.
Med. infant ; 24(4): 320-324, dic. 2017. tab, ilus
Artículo en Español | LILACS | ID: biblio-878278

RESUMEN

Introducción: Las meningitis bacterianas en niños son causa de importante morbimortalidad. Los principales agentes etiológicos son Neisseria meningitidis, Streptococcus pneumoniae y Haemophilus influenzae. En los últimos años, luego de la introducción sucesiva de vacunas conjugadas al calendario nacional de inmunizaciones, se ha visto un cambio en la epidemiología de estas infecciones. Objetivo: Describir las características clínicas, epidemiológicas y evolutivas de los niños hospitalizados con meningitis bacteriana confirmada microbiológicamente entre 2011 y 2016 en un hospital de tercer nivel de complejidad. Materiales y métodos: Cohorte retrospectiva. Se incluyeron niños entre 1 mes de vida y 17 años con cuadro clínico compatible con meningitis bacteriana y cultivo positivo y/o PCR en líquido cefalorraquídeo y/o hemocultivos positivos para Neisseria meningitidis, Streptococcus pneumoniae y Haemophilus influenzae b. Se registraron las características demográficas, clínicas y evolutivas hasta los 30 días del egreso. Se utilizó mediana y rango intercuartilo (RIC) para variables continuas y porcentaje para variables categóricas. Se utilizó Stata 10. Resultados: n=65. Edad: mediana de 9 meses (RIC 4-35). Varones: 58% (n=38). Se identificó Neisseria meningitidis en un 48% (n=31), Haemophilus influenzae b en un 26% (n=17) y Streptococcus pneumoniae en un 26% (n=17). El 26% (n=17) de los pacientes presentaba alguna comorbilidad. Tuvieron hemocultivos positivos el 62% (n = 40) de los pacientes y 86% (n=55) de los líquidos cefalorraquídeos. Todos los pacientes recibieron tratamiento antimicrobiano con ceftriaxona tanto como tratamiento empírico como definitivo y 92% (n=60) recibieron corticoides empíricos. La mediana de días de internación fue de 11 (RIC 8-17). El 28% (n=18) requirió cuidados intensivos, y el 8% (n=5) falleció. Durante el período de estudio se observó que la frecuencia de meningitis por Streptococcus pneumoniae disminuyó en el final del estudio (9% en 2016 vs 60% en 2011), mientras que la frecuencia de meningitis por Neisseria meningitidis en 2016 fue mayor que al inicio del período (64% en 2016 vs. 40% en 2011). La frecuencia de identificación de Haemophilus influenzae b se mantuvo estable. Conclusiones: Las meningitis bacterianas confirmadas por Neisseria meningitidis, Streptococcus pneumoniae y Haemophilus influenzae b prevalecieron en niños menores de 12 meses. En esta cohorte se observó un predominio de las infecciones por Neisseria meningitidis en los últimos años, y una disminución en la frecuencia de meningitis por Streptococcus pneumoniae en el período post introducción de la vacuna conjugada 13 valente al calendario nacional de inmunizaciones. (AU)


Introduction: In children, bacterial meningitis is an important cause of morbidity and mortality. The main etiological agents are Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. Over the last years, the successive introduction of conjugated vaccines in the national immunization calendar has led to a change in the epidemiology of these infections. Objective: To describe the clinical and epidemiological features and outcome of children admitted because of microbiologically confirmed meningitis seen between 2011 and 2016 at a tertiary care hospital. Material and methods: A retrospective cohort study was conducted. Children between 1 month of life and 17 years of age with clinical features compatible with bacterial meningitis and positive cultures and/or PCR in cerebrospinal fluid (CSF) and/or positive blood cultures for Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae b were included. Demographic, clinical, and outcome features were recorded until 30 days after discharge. Median and interquartile range (IQR) were calculated for continuous variables and percentages for categorical variables. The Stata 10 program was used. Results: n=65. Age: median was 9 months (IQR 4-35). Boys: 58% (n=38). Neisseria meningitidis was identified in 48% (n=31), Haemophilus influenzae b in 26% (n=17), and Streptococcus pneumoniae in 26% (n=17). Overall, 26% (n=17) of the patients presented with comorbidities. Positive blood cultures were found in 62% (n = 40) and positive CSF cultures in 86% (n=55) of the patients. All patients received antimicrobial treatment with ceftriaxone both empirically and as final treatment and corticosteroids were empirically started in 92% (n=60). Median hospital stay was 11 days (IQR 8-17). Overall, 28% (n=18) required intensive care and 8% (n=5) of the patients died. The incidence of meningitis due to Streptococcus pneumoniae was observed to diminish at the end of the study period (9% in 2016 vs 60% in 2011), while the incidence of meningitis due to Neisseria meningitidis in 2016 was higher than at the end of the study period (64% in 2016 vs. 40% in 2011). The frequency of identification of Haemophilus influenzae b remained stable. Conclusions: Confirmed bacterial infections due to Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae b were prevalent in infants younger than 12 months of age in this cohort of patients. Infections due to Neisseria meningitidis predominated over the last years and the incidence of meningitis due to Streptococcus pneumoniae diminished after the introduction of the 13 valent conjugated vaccine was introduced in the national immunization calendar.(AU)


Asunto(s)
Humanos , Lactante , Preescolar , Niño , Adolescente , Streptococcus pneumoniae/patogenicidad , Meningitis Bacterianas/diagnóstico , Meningitis Bacterianas/líquido cefalorraquídeo , Meningitis Bacterianas/prevención & control , Meningitis Bacterianas/epidemiología , Haemophilus influenzae tipo b/patogenicidad , Neisseria meningitidis/patogenicidad
7.
Biotechnol Prog ; 33(6): 1508-1519, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28840658

RESUMEN

Haemophilus influenzae type b (Hib), a Gram-negative capsulated bacterium, is a causative agent of meningitis worldwide. The capsular polysaccharide, a high molecular mass polymer consisting of the repeated units of the polyribosyl-ribitol-phosphate, is considered the main virulence factor and it is used as an antigen to vaccines, conjugated to a carrier protein. The industrial production of the polysaccharide requires the cultivation of Hib in rich medium, which impacts process costs and product recovery. In this study, a central composite rotational experimental design strategy was used to access the influence of key components of culture medium (soy peptone, yeast extract and glucose) on biomass formation and polysaccharide production in shake-flasks. The optimized medium formulation, containing half of the usual yeast extract and soytone concentrations, was further validated in batch bioreactor cultivations. High polysaccharide production (∼500 mg/L) was obtained in a cheaper and more competitive production process for use in Hib vaccine production. In addition, simulations of a metabolic model describing Hib central metabolism were used to assess the role of key amino acids on growth. A chemically defined medium supplemented only with amino acids from α-ketoglutarate and oxaloacetate families as well as phenylalanine was suggested as a promising alternative for reduced acetate accumulation and enhanced polysaccharide production in Hib cultures. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1508-1519, 2017.


Asunto(s)
Técnicas de Cultivo de Célula/métodos , Vacunas contra Haemophilus/biosíntesis , Haemophilus influenzae tipo b/crecimiento & desarrollo , Polisacáridos/metabolismo , Cápsulas Bacterianas/genética , Cápsulas Bacterianas/metabolismo , Reactores Biológicos , Medios de Cultivo , Vacunas contra Haemophilus/genética , Vacunas contra Haemophilus/metabolismo , Vacunas contra Haemophilus/uso terapéutico , Haemophilus influenzae tipo b/patogenicidad , Humanos , Meningitis/microbiología , Meningitis/prevención & control , Análisis de Flujos Metabólicos , Polisacáridos/genética , Polisacáridos/inmunología
9.
Emerg Infect Dis ; 23(1): 112-114, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27983486

RESUMEN

During 5 months in 2014, three Amish children in Missouri, USA, were diagnosed with invasive Haemophilus influenzae type b infection. Two were rural neighbors infected with a genetically similar rare strain, sequence type 45. One child had recently traveled, raising the possibility of maintenance of this strain among unvaccinated carriers in Amish communities.


Asunto(s)
Amish/psicología , Infecciones por Haemophilus/etnología , Infecciones por Haemophilus/epidemiología , Haemophilus influenzae tipo b/patogenicidad , Preescolar , Femenino , Infecciones por Haemophilus/prevención & control , Infecciones por Haemophilus/transmisión , Vacunas contra Haemophilus/administración & dosificación , Haemophilus influenzae tipo b/clasificación , Haemophilus influenzae tipo b/genética , Haemophilus influenzae tipo b/aislamiento & purificación , Humanos , Lactante , Masculino , Missouri/epidemiología , Tipificación de Secuencias Multilocus , Vacunación/psicología
10.
Annu Rev Biochem ; 85: 599-630, 2016 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-27145845

RESUMEN

Glycoscience research has been significantly impeded by the complex compositions of the glycans present in biological molecules and the lack of convenient tools suitable for studying the glycosylation process and its function. Polysaccharides and glycoconjugates are not encoded directly by genes; instead, their biosynthesis relies on the differential expression of carbohydrate enzymes, resulting in heterogeneous mixtures of glycoforms, each with a distinct physiological activity. Access to well-defined structures is required for functional study, and this has been provided by chemical and enzymatic synthesis and by the engineering of glycosylation pathways. This review covers general methods for preparing glycans commonly found in mammalian systems and applying them to the synthesis of therapeutically significant glycoconjugates (glycosaminoglycans, glycoproteins, glycolipids, glycosylphosphatidylinositol-anchored proteins) and the development of carbohydrate-based vaccines.


Asunto(s)
Glicoconjugados/síntesis química , Glicoproteínas/síntesis química , Glicosaminoglicanos/síntesis química , Infecciones por Haemophilus/prevención & control , Vacunas contra Haemophilus/administración & dosificación , Polisacáridos/síntesis química , Secuencia de Aminoácidos , Conformación de Carbohidratos , Secuencia de Carbohidratos , Glicoconjugados/inmunología , Glucolípidos/síntesis química , Glucolípidos/inmunología , Glicoproteínas/inmunología , Glicosaminoglicanos/inmunología , Glicosilación , Glicosilfosfatidilinositoles/síntesis química , Glicosilfosfatidilinositoles/inmunología , Infecciones por Haemophilus/inmunología , Infecciones por Haemophilus/microbiología , Vacunas contra Haemophilus/síntesis química , Haemophilus influenzae tipo b/efectos de los fármacos , Haemophilus influenzae tipo b/crecimiento & desarrollo , Haemophilus influenzae tipo b/patogenicidad , Humanos , Polisacáridos/inmunología
11.
Sci Rep ; 6: 22208, 2016 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-26915577

RESUMEN

Three important physical properties which may affect the performance of glycoconjugate vaccines against serious disease are molar mass (molecular weight), heterogeneity (polydispersity), and conformational flexibility in solution. The dilute solution behaviour of native and activated capsular polyribosylribitol (PRP) polysaccharides extracted from Haemophilus influenzae type b (Hib), and the corresponding glycoconjugate made by conjugating this with the tetanus toxoid (TT) protein have been characterized and compared using a combination of sedimentation equilibrium and sedimentation velocity in the analytical ultracentrifuge with viscometry. The weight average molar mass of the activated material was considerably reduced (Mw ~ 0.24 × 10(6) g.mol(-1)) compared to the native (Mw ~ 1.2 × 10(6) g.mol(-1)). Conjugation with the TT protein yielded large polydisperse structures (of Mw ~ 7.4 × 10(6) g.mol(-1)), but which retained the high degree of flexibility of the native and activated polysaccharide, with frictional ratio, intrinsic viscosity, sedimentation conformation zoning behaviour and persistence length all commensurate with highly flexible coil behaviour and unlike the previously characterised tetanus toxoid protein (slightly extended and hydrodynamically compact structure with an aspect ratio of ~3). This non-protein like behaviour clearly indicates that it is the carbohydrate component which mainly influences the physical behaviour of the glycoconjugate in solution.


Asunto(s)
Antígenos Bacterianos/fisiología , Glicoconjugados/fisiología , Haemophilus influenzae tipo b/patogenicidad , Hidrodinámica , Polisacáridos Bacterianos/fisiología , Antígenos Bacterianos/inmunología , Centrifugación por Gradiente de Densidad , Glicoconjugados/inmunología , Vacunas contra Haemophilus/inmunología , Haemophilus influenzae tipo b/inmunología , Humanos , Polisacáridos Bacterianos/inmunología , Toxoide Tetánico/inmunología , Toxoide Tetánico/metabolismo , Vacunas Conjugadas/inmunología
12.
An. pediatr. (2003. Ed. impr.) ; 83(6): 439.e1-439.e7, dic. 2015. tab
Artículo en Español | IBECS | ID: ibc-146527

RESUMEN

La neumonía adquirida en la comunidad (NAC) en la edad pediátrica ha sufrido, en la última década, una serie de cambios epidemiológicos, clínicos, etiológicos y de resistencias a antibióticos, que obligan a replantear su abordaje terapéutico. En este documento, dos de las principales sociedades de especialidades pediátricas involucradas en el diagnóstico y tratamiento de esta entidad, como son la Sociedad Española de Infectología Pediátrica y la Sociedad Española de Neumología Pediátrica, así como el Comité Asesor de Vacunas de la AEP, proponen unas pautas consensuadas de tratamiento y prevención, con el fin de proporcionar a todos los pediatras una guía actualizada. En esta primera parte del consenso, se aborda el tratamiento de los pacientes sin enfermedades de base relevantes con NAC que no precisan ingreso hospitalario, así como la prevención global de esta patología con vacunas. En un siguiente documento se expondrá el abordaje terapéutico tanto de aquellos pacientes en situaciones especiales como de las formas complicadas de la enfermedad


There have been significant changes in community acquired pneumonia (CAP) in children in the last decade. These changes relate to epidemiology and clinical presentation. Resistance to antibiotics is also a changing issue. These all have to be considered when treating CAP. In this document, two of the main Spanish pediatric societies involved in the treatment of CAP in children, propose a consensus concerning therapeutic approach. These societies are the Spanish Society of Paediatric Infectious Diseases and the Spanish Society of Paediatric Chest Diseases. The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP) has also been involved in the prevention of CAP. An attempt is made to provide up-to-date guidelines to all paediatricians. The first part of the statement presents the approach to ambulatory, previously healthy children. We also review the prevention with currently available vaccines. In a next second part, special situations and complicated forms will be addressed


Asunto(s)
Niño , Femenino , Humanos , Masculino , Neumonía/mortalidad , Neumonía/etiología , Neumonía/tratamiento farmacológico , Neumonía/prevención & control , Infecciones Comunitarias Adquiridas/epidemiología , Amoxicilina/administración & dosificación , Amoxicilina/uso terapéutico , Farmacorresistencia Microbiana , Monitoreo Epidemiológico/tendencias , Haemophilus influenzae tipo b/patogenicidad , Streptococcus pneumoniae/patogenicidad , Staphylococcus aureus/patogenicidad , Streptococcus pyogenes/patogenicidad , Vacunas Neumococicas , Vacunas Conjugadas , Vacunas contra Haemophilus , Vacunas contra la Influenza , España/epidemiología
13.
BMC Infect Dis ; 15: 485, 2015 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-26521138

RESUMEN

BACKGROUND: Bacterial meningitis remains an important infection globally, with the greatest burden in children in low-income settings, including Papua New Guinea (PNG). We present serotype, antimicrobial susceptibility and outcome data from paediatric meningitis patients prior to introduction of Haemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines (PCVs) in PNG, providing a baseline for evaluation of immunisation programs. METHODS: Cerebrospinal fluid (CSF) was collected from children admitted to Goroka General Hospital with suspected meningitis between 1996 and 2005. Culture and sensitivity was conducted, and pneumococci and H. influenzae were serotyped. Laboratory findings were linked to clinical outcomes. RESULTS: We enrolled 1884 children. A recognised pathogen was identified in 375 children (19.9%). Streptococcus pneumoniae (n = 180) and Hib (n = 153) accounted for 88.8% of pathogens isolated. 24 different pneumococcal serogroups were identified; non-PCV types 2, 24 and 46 accounted for 31.6% of pneumococcal meningitis. 10- and 13-valent PCVs would cover 44.1% and 45.4% of pneumococcal meningitis respectively. Pneumococcal isolates were commonly resistant to penicillin (21.5%) and 23% of Hib isolates were simultaneously resistant to ampicillin, co-trimoxazole and chloramphenicol. The case fatality rate in patients with a recognised bacterial pathogen was 13.4% compared to 8.5% in culture-negative patients. CONCLUSIONS: If implemented in routine expanded programme of immunisation (EPI) with high coverage, current PCVs could prevent almost half of pneumococcal meningitis cases. Given the diversity of circulating serotypes in PNG serotype replacement is of concern. Ongoing surveillance is imperative to monitor the impact of vaccines. In the longer term vaccines providing broader protection against pneumococcal meningitis will be needed.


Asunto(s)
Antiinfecciosos/farmacología , Haemophilus influenzae tipo b/aislamiento & purificación , Meningitis Bacterianas/microbiología , Meningitis Neumocócica/microbiología , Streptococcus pneumoniae/aislamiento & purificación , Femenino , Haemophilus influenzae tipo b/efectos de los fármacos , Haemophilus influenzae tipo b/patogenicidad , Hospitales Generales , Humanos , Programas de Inmunización , Lactante , Masculino , Meningitis Bacterianas/inmunología , Meningitis Bacterianas/prevención & control , Meningitis Neumocócica/inmunología , Meningitis Neumocócica/prevención & control , Pruebas de Sensibilidad Microbiana , Papúa Nueva Guinea , Vacunas Neumococicas/farmacología , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/patogenicidad , Combinación Trimetoprim y Sulfametoxazol/farmacología , Vacunas Conjugadas/farmacología
14.
J Am Assoc Nurse Pract ; 27(2): 114-9, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24958314

RESUMEN

PURPOSE: Haemophilus influenzae type b bacteria has been responsible for recent increase in invasive disease in the adult population of the United States. This increase in H. influenzae infections is greatest in individuals above 65 years of age. A plausible explanation for this increase may be the changes observed in the epidemiology of invasive H. influenzae type b (Hib) disease and the susceptibility of aggregate hosts. DATA SOURCES: A comprehensive literature review was conducted from multiple data sources, such as PubMed, MEDLINE, CDC, journal articles, reference texts, and Internet websites. CONCLUSIONS: The increase in infectious disease caused by H. influenzae type b bacteria is affecting individuals 65 years and older and is preventable. However, Hib vaccines are currently approved for the pediatric population and susceptible adults with certain immune deficiencies. New trends in this invasive disease require reevaluation of current guidelines to include individuals 65 years and older as target population for the polysaccharide Hib vaccine. IMPLICATIONS FOR PRACTICE: The changing epidemiology of H. influenzae type b bacteria requires reevaluation of current immunization guidelines regarding Hib vaccination so that it is included in the immunization schedule for adults aged 65 and above.


Asunto(s)
Susceptibilidad a Enfermedades/epidemiología , Infecciones por Haemophilus/epidemiología , Vacunas contra Haemophilus/uso terapéutico , Haemophilus influenzae tipo b/patogenicidad , Factores de Edad , Cápsulas Bacterianas , Femenino , Infecciones por Haemophilus/mortalidad , Haemophilus influenzae tipo b/efectos de los fármacos , Humanos , Estados Unidos/epidemiología
15.
Infect Immun ; 82(6): 2378-89, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24664511

RESUMEN

Haemophilus influenzae type b (Hib) escapes the host immune system by recruitment of the complement regulator vitronectin, which inhibits the formation of the membrane attack complex (MAC) by inhibiting C5b-C7 complex formation and C9 polymerization. We reported previously that Hib acquires vitronectin at the surface by using Haemophilus surface fibrils (Hsf). Here we studied in detail the interaction between Hsf and vitronectin and its role in the inhibition of MAC formation and the invasion of lung epithelial cells. The vitronectin-binding region of Hsf was defined at the N-terminal region comprising Hsf amino acids 429 to 652. Moreover, the Hsf recognition site on vitronectin consisted of the C-terminal amino acids 352 to 374. H. influenzae was killed more rapidly in vitronectin-depleted serum than in normal human serum (NHS), and increased MAC deposition was observed at the surface of an Hsf-deficient H. influenzae mutant. In parallel, Hsf-expressing Escherichia coli selectively acquired vitronectin from serum, resulting in significant inhibition of the MAC. Moreover, when vitronectin was bound to Hsf, increased bacterial adherence and internalization into epithelial cells were observed. Taking our findings together, we have defined a fine-tuned protein-protein interaction between Hsf and vitronectin that may contribute to increased Hib virulence.


Asunto(s)
Adhesinas Bacterianas/fisiología , Actividad Bactericida de la Sangre/inmunología , Adhesión Celular/fisiología , Haemophilus influenzae tipo b/inmunología , Vitronectina/metabolismo , Análisis de Varianza , Unión Competitiva , Complejo de Ataque a Membrana del Sistema Complemento/fisiología , Relación Dosis-Respuesta Inmunológica , Haemophilus influenzae tipo b/patogenicidad , Heparina/fisiología , Humanos , Suero/inmunología , Suero/microbiología
17.
Indian J Med Res ; 137(4): 712-20, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23703338

RESUMEN

BACKGROUND & OBJECTIVES: Haemophilus influenzae type b (Hib) is one of the leading bacterial causes of invasive disease in populations without access to Hib conjugate vaccines (Hib-CV). India has recently decided to introduce Hib-CV into the routine immunization programme in selected States. Longitudinal data quantifying the burden of bacterial meningitis and the proportion of disease caused by various bacteria are needed to track the impact of Hib-CV once introduced. A hospital-based sentinel surveillance network was established at four places in the country and this study reports the results of this ongoing surveillance. METHODS: Children aged 1 to 23 months with suspected bacterial meningitis were enrolled in Chennai, Lucknow, New Delhi, and Vellore between July 2008 and June 2010. All cerebrospinal fluid (CSF) samples were tested using cytological, biochemical, and culture methods. Samples with abnormal CSF (≥10 WBC per µl) were tested by latex agglutination test for common paediatric bacterial meningitis pathogens. RESULTS: A total of 708 patients with abnormal CSF were identified, 89 of whom had a bacterial pathogen confirmed. Hib accounted for the majority of bacteriologically confirmed cases, 62 (70%), while Streptococcus pneumoniae and group B Streptococcus were identified in 12 (13%) and seven (8%) cases, respectively. The other eight cases were a mix of other bacteria. The proportion of abnormal CSF and probable bacterial meningitis that was caused by Hib was 74 and 58 per cent lower at Christian Medical College (CMC), Vellore, which had a 41 per cent coverage of Hib-CV among all suspected meningitis cases, compared to the combined average proportion at the other three centres where a coverage between 1 and 8 per cent was seen (P<0.001 and P= 0.05, respectively). INTERPRETATION & CONCLUSIONS: Hib was found to be the predominant cause of bacterial meningitis in young children in diverse geographic locations in India. Possible indications of herd immunity was seen at CMC compared to sites with low immunization coverage with Hib-CV. As Hib is the most common pathogen in bacterial meningitis, Hib-CV would have a large impact on bacterial meningitis in Indian children.


Asunto(s)
Cápsulas Bacterianas , Vacunas contra Haemophilus , Haemophilus influenzae tipo b/patogenicidad , Meningitis por Haemophilus/líquido cefalorraquídeo , Meningitis por Haemophilus/epidemiología , Femenino , Haemophilus influenzae tipo b/aislamiento & purificación , Humanos , Programas de Inmunización , India , Lactante , Masculino , Meningitis por Haemophilus/microbiología , Estudios Prospectivos , Vigilancia de Guardia , Infecciones Estreptocócicas/líquido cefalorraquídeo , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/aislamiento & purificación , Streptococcus agalactiae/patogenicidad , Streptococcus pneumoniae/aislamiento & purificación , Streptococcus pneumoniae/patogenicidad
18.
Vaccine ; 30(33): 4897-906, 2012 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-22683521

RESUMEN

This paper describes the development of a Haemophilus influenzae type b (Hib) conjugate vaccine at the National Institute for Public Health and the Environment/Netherlands Vaccine Institute (RIVM/NVI, Bilthoven, The Netherlands), and the subsequent transfer of its production process to manufacturers in developing countries. In 1998, at the outset of the project, the majority of the world's children were not immunized against Hib because of the high price and limited supply of the conjugate vaccines, due partly to the fact that local manufacturers in developing countries did not master the Hib conjugate production technology. To address this problem, the RIVM/NVI has developed a robust Hib conjugate vaccine production process based on a proven model, and transferred this technology to several partners in India, Indonesia, Korea and China. As a result, emerging manufacturers in developing countries acquired modern technologies previously unavailable to them. This has in turn facilitated their approach to producing other conjugate vaccines. As an additional spin-off from the project, a World Health Organization (WHO) Hib quality control (QC) course was designed and conducted at the RIVM/NVI, resulting in an increased regulatory capacity for conjugate vaccines in developing countries at the National Regulatory Authority (NRA) level. For the local populations, this has translated into an increased and sustainable supply of affordable Hib conjugate-containing combination vaccines. During the course of this project, developing countries have demonstrated their ability to produce large quantities of high-quality modern vaccines after a successful transfer of the technology.


Asunto(s)
Cápsulas Bacterianas/inmunología , Vacunas contra Haemophilus/inmunología , Haemophilus influenzae tipo b/inmunología , Meningitis por Haemophilus/prevención & control , Transferencia de Tecnología , Tecnología Farmacéutica/métodos , Creación de Capacidad , Países en Desarrollo , Haemophilus influenzae tipo b/patogenicidad , Humanos , Vacunas Conjugadas/inmunología
19.
Curr Opin Infect Dis ; 25(3): 266-72, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22561999

RESUMEN

PURPOSE OF REVIEW: In countries with established Haemophilus influenzae serotype b (Hib) immunization programmes, nonencapsulated H. influenzae (ncHi) is responsible for most invasive H. influenzae infections across all age groups and is associated with higher case fatality. A pneumococcal conjugate vaccine has recently been licensed, which may potentially also protect against invasive H. influenzae infections. RECENT FINDINGS: Invasive ncHi disease is uncommon in childhood but has a much higher incidence in the first month of life. Most neonates with invasive ncHi infections are born prematurely and develop septicaemia in the first 48 h of life which can be fatal. After this period, invasive ncHi incidence falls rapidly and remains low throughout childhood. Most infants and children who develop invasive ncHi disease have significant underlying comorbidities, particularly neurological disease, malignancy and other conditions requiring immunosuppressive therapy. Although characteristically associated with respiratory tract infections, at least a quarter of invasive ncHi infections present with meningitis. SUMMARY: A vaccine against ncHi could have an important preventive role in children with comorbidities. Future studies should focus on assessing specific risk factors for neonatal and childhood ncHi disease and long-term outcomes of children with invasive ncHi meningitis.


Asunto(s)
Infecciones por Haemophilus/microbiología , Infecciones por Haemophilus/prevención & control , Vacunas contra Haemophilus/administración & dosificación , Haemophilus influenzae , Gripe Humana/microbiología , Gripe Humana/prevención & control , Adolescente , Niño , Preescolar , Infecciones por Haemophilus/epidemiología , Haemophilus influenzae/inmunología , Haemophilus influenzae/patogenicidad , Haemophilus influenzae tipo b/inmunología , Haemophilus influenzae tipo b/patogenicidad , Humanos , Lactante , Recién Nacido , Factores de Riesgo
20.
Clin Infect Dis ; 54 Suppl 2: S93-101, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22403238

RESUMEN

The Pneumonia Etiology Research for Child Health (PERCH) project is a 7-country, standardized, comprehensive evaluation of the etiologic agents causing severe pneumonia in children from developing countries. During previous etiology studies, between one-quarter and one-third of patients failed to yield an obvious etiology; PERCH will employ and evaluate previously unavailable innovative, more sensitive diagnostic techniques. Innovative and rigorous epidemiologic and analytic methods will be used to establish the causal association between presence of potential pathogens and pneumonia. By strategic selection of study sites that are broadly representative of regions with the greatest burden of childhood pneumonia, PERCH aims to provide data that reflect the epidemiologic situation in developing countries in 2015, using pneumococcal and Haemophilus influenzae type b vaccines. PERCH will also address differences in host, environmental, and/or geographic factors that might determine pneumonia etiology and, by preserving specimens, will generate a resource for future research and pathogen discovery.


Asunto(s)
Protección a la Infancia , Diseño de Investigaciones Epidemiológicas , Neumonía/etiología , Streptococcus pneumoniae/patogenicidad , Niño Hospitalizado , Preescolar , Recolección de Datos/métodos , Recolección de Datos/normas , Países en Desarrollo , Geografía , Infecciones por Haemophilus/epidemiología , Infecciones por Haemophilus/inmunología , Infecciones por Haemophilus/microbiología , Infecciones por Haemophilus/prevención & control , Haemophilus influenzae tipo b/inmunología , Haemophilus influenzae tipo b/patogenicidad , Humanos , Lactante , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/microbiología , Infecciones Neumocócicas/prevención & control , Neumonía/diagnóstico , Neumonía/epidemiología , Neumonía/prevención & control , Factores de Riesgo , Streptococcus pneumoniae/inmunología
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