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1.
Medicine (Baltimore) ; 98(50): e18380, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31852152

RESUMEN

The commonly used vaccine for adults with a high risk of pneumonia is 23-valent pneumococcal polysaccharide vaccine (PPSV23). However, its effectiveness in patients with colorectal cancer has not been investigated. This study aimed to investigate the effectiveness of PPSV23 in reducing the risk of pneumonia among elderly patients with colorectal cancer.A total of 120,605 newly diagnosed patients with colorectal cancer were identified from the Taiwan National Health Insurance Research Database between 1996 and 2010. Of these patients, 18,468 were 75 years or older in 2007 to 2010, and 3515 received PPSV23. People aged 75 years or older have been considered eligible for receiving PPSV23 vaccination in Taiwan since 2007. The specific "vaccination period" of October 2008 to December 2008 was used to minimize the potential immortal time bias. Therefore, 893 patients who received PPSV23 outside this vaccination period or died before 2009 and 2960 unvaccinated patients who died before 2009 were excluded. After the propensity score was matched with a 1:3 ratio, 2622 vaccinated patients and 7866 unvaccinated patients were recruited. A multivariate log-linear Poisson regression model was performed and adjusted for potential confounders, including influenza vaccination, vaccination period, cancer treatment modalities, comorbidities, and sociodemographic variables.After 2 years of follow-up, the incidence rate of the pneumonia hospitalization of the vaccinated patients was significantly lower than that of the unvaccinated patients at 85.53 per 1000 person-years (PYs) of the former and 92.38 per 1000 PYs of the latter. The proportions of patients who had 2, 3, and >3 pneumonia hospitalizations per year were consistently lower in the vaccinated group than in the unvaccinated group (1.9% vs 2.0%, 0.5% vs 0.9%, and 0.7% vs 1.1%, respectively). After adjustment for covariates was made, PPSV23 vaccine was significantly associated with a reduced risk of pneumonia hospitalization, with an adjusted incidence rate ratio of 0.88 (P = .040). The overall pneumonia-free survival rate was also significantly higher in the vaccinated patients than in the unvaccinated patients (P = .001).PPSV23 vaccination was associated with a significantly reduced rate of pneumonia hospitalization in elderly patients with colorectal cancer.


Asunto(s)
Neoplasias Colorrectales/epidemiología , Vacunas Neumococicas/administración & dosificación , Neumonía/epidemiología , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Vacunas Neumococicas/inmunología , Neumonía/complicaciones , Neumonía/prevención & control , Puntaje de Propensión , Estudios Retrospectivos
2.
Yonsei Med J ; 60(11): 1103-1107, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31637893

RESUMEN

The incidence of vaccine-type Streptococcus pneumoniae carriage and disease have declined in vaccinated children as well as in unvaccinated children and adults. However, diseases caused by non-vaccine type (NVT) S. pneumoniae are increasing. In this study, we report an invasive pneumococcal disease (IPD) caused by NVT multidrug-resistant (MDR) S. pneumoniae transmitted from a vaccinated infant to an unvaccinated healthy woman, and the clinical characteristics of this serotype. A 29-year-old previously healthy woman visited our hospital with fever and headache. She had been breastfeeding her baby for 8 months. She was diagnosed with brain abscess and sinusitis caused by S. pneumoniae. Although the patient had no previous exposure to antibiotics, antibiotic susceptibility test identified the pathogen as MDR. The patient's family members were examined using nasopharyngeal swabs for bacterial culture. The serotype of S. pneumoniae identified from the blood, abscess, and sputum of the patient was 15B/C. After investing the patient's family members, we found that the serotype from nasopharyngeal specimen of her baby was the same. We described an invasive MDR pneumococcal disease in an immunocompetent young adult in the community. IPD likely spread to the patient by close contact with her baby, who harbored S. pneumoniae of NVT. The spread of NVT S. pneumoniae in the post-vaccine era has increased in the community, and resistance pattern for S. pneumoniae of 15B/C changed compared to the pre-pneumococcal conjugate vaccine era. The spread of MDR pathogens causing IPD among family members should be monitored.


Asunto(s)
Farmacorresistencia Bacteriana , Infecciones Neumocócicas/microbiología , Infecciones Neumocócicas/transmisión , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/fisiología , Adulto , Niño , Preescolar , Femenino , Hospitales , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Pruebas de Sensibilidad Microbiana , Filogenia , Infecciones Neumocócicas/diagnóstico por imagen , Infecciones Neumocócicas/inmunología , Serogrupo , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/inmunología
5.
In Vivo ; 33(5): 1425-1430, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31471388

RESUMEN

BACKGROUND/AIM: Streptococcus pneumoniae is the leading cause of bacterial pneumonia and an important cause of invasive disease. Despite the antiretroviral therapies, adults infected with human immunodeficiency virus (HIV) are at particular risk for invasive pneumococcal disease (IPD). The purpose of this study was to report the efficacy of the strategies currently being used in pneumococcal vaccination for HIV-infected adults. MATERIALS AND METHODS: A literature search was performed through electronic databases, for original articles in English, from years 2000 to 2019. Clinical trials controlled or randomized, and cohort studies were included. RESULTS: While 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for immunocompromised patients, it has been reported that it is less suitable for HIV-infected patients. Recent guidelines have added pneumococcal conjugate vaccine (PCV) to the list of recommended vaccines. CONCLUSION: Further studies are needed to determine the optimal vaccines and intervals for subsequent revaccinations during the lifetime.


Asunto(s)
Infecciones por VIH/complicaciones , Infecciones Neumocócicas/etiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Vacunación , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Vacuna Neumocócica Conjugada Heptavalente/administración & dosificación , Vacuna Neumocócica Conjugada Heptavalente/inmunología , Humanos , Huésped Inmunocomprometido , Vacunas Neumococicas/administración & dosificación , Vacunación/métodos
6.
J Manag Care Spec Pharm ; 25(9): 989-994, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31456496

RESUMEN

BACKGROUND: Pharmacies have a unique opportunity to address suboptimal adult vaccination rates, but few solutions have proven effective. Such strategies are challenged by the lack of access that many pharmacies have to a patient's complete immunization history; consequently, they are unable to identify which of their patients actually require vaccination. A pharmacy-based strategy that leverages such information could enhance efforts to increase rates of guideline-based vaccination. OBJECTIVE: To determine the effect on vaccination rates of an automated telephonic intervention for adults in need of either pneumococcal vaccination or herpes zoster vaccination, or both. METHODS: Over a 1-year period, patients with identified vaccine gaps at 246 pharmacies of 3 pharmacy chains were randomly assigned to receive either usual care or an automated telephonic prompt for pneumococcal and/or herpes zoster vaccines based on patient records contained in state immunization registries and pharmacy data. The primary outcome was the proportion with administration of at least one of the vaccines offered between March 2016 and January 2017 based on intention-to-treat principles. Subgroup analyses included vaccination rates by age and sex. An as-treated analysis was also performed. RESULTS: 21,971 patients were included in the study, 57% of whom were female, with a mean age of 63 years. Vaccine administration proportions were 0.0214 (236/11,009) in the intervention group, and 0.0205 (225/10,962) in the control group (OR = 1.05, 95% CI = 0.87-1.26). Results did not differ in subgroup analyses based on patient age, sex, or individual pharmacy chain. Among intervention patients, 3,666 (0.333) completed the call by listening to the entire prompt. In an as-treated analysis comparing individuals who completed calls versus control, the intervention increased the odds of vaccination by 26% (OR = 1.26, 95% CI = 1.00-1.61). CONCLUSIONS: The automated prompt did not significantly increase vaccination rates. Potential barriers included intervention technical flaws, low rates of connecting with patients, insufficient follow-up by the pharmacy, and patients placing a relatively low priority on being vaccinated. DISCLOSURES: This project was funded by Pfizer and Merck through a grant from the Pharmacy Quality Alliance. Stolpe was an employee of the Pharmacy Quality Alliance at the onset of this project and an employee of Scientific Technologies Corporation during the data collection phase of the project. Stolpe has also served on the advisory board for Merck. Choudhry has no conflicts of interest to declare.


Asunto(s)
Servicios Comunitarios de Farmacia/estadística & datos numéricos , Inmunización/estadística & datos numéricos , Teléfono/estadística & datos numéricos , Vacunación/estadística & datos numéricos , Femenino , Vacuna contra el Herpes Zóster/inmunología , Humanos , Vacunas contra la Influenza/inmunología , Masculino , Persona de Mediana Edad , Farmacéuticos/estadística & datos numéricos , Vacunas Neumococicas/inmunología , Sistema de Registros , Encuestas y Cuestionarios
7.
Arch Immunol Ther Exp (Warsz) ; 67(5): 325-334, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31363786

RESUMEN

The purpose of this study is to describe both clinical and immunological features in large cohort of adult patients with IgG subclass deficiency, and response to immunoglobulin therapy. This is a retrospective study of data obtained from electronic medical records and paper charts of 78 patients with IgG subclass deficiency seen and followed at our immunology clinics from 2010 to 2016. Both isolated selective IgG subclass deficiency as well as combined (two) subclass deficiencies were observed. IgG3 subclass deficiency, isolated and in combination with other IgG subclass deficiency, is the most frequent of IgG subclass deficiency. A majority of patients presented with upper and lower respiratory tract infections, especially chronic sinusitis. Both allergic and autoimmune manifestations are common; however, there is no subclass preference. The proportions and absolute numbers of CD3+ T cells, CD4+ T and CD8+ T cells, CD19+ B cells, and CD3-CD16+CD56+ NK cells were normal in the majority of patients in all IgG subclass deficiencies. Total serum IgG levels did not correlate with IgG subclass levels across all IgG subclass deficiencies. Anti-pneumococcal polysaccharide antibody responses were impaired in 56% of patients. IgG3 subclass deficiency is the most common IgG subclass deficiency, and anti-polysaccharide antibody responses are distributed among IgG subclasses with modest preference in IgG2 subclass. The majority of patients treated with immunoglobulin responded by reduction in frequency of infections and requirement of antibiotics.


Asunto(s)
Deficiencia de IgG/inmunología , Deficiencia de IgG/patología , Adulto , Anciano , Femenino , Humanos , Deficiencia de IgG/sangre , Deficiencia de IgG/tratamiento farmacológico , Inmunoglobulina G/administración & dosificación , Inmunoglobulina G/sangre , Subgrupos Linfocitarios/inmunología , Subgrupos Linfocitarios/patología , Masculino , Persona de Mediana Edad , Vacunas Neumococicas/inmunología , Infecciones del Sistema Respiratorio/sangre , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/patología , Estudios Retrospectivos , Sinusitis/sangre , Sinusitis/tratamiento farmacológico , Sinusitis/inmunología , Sinusitis/patología , Resultado del Tratamiento , Adulto Joven
8.
Pan Afr Med J ; 32: 203, 2019.
Artículo en Francés | MEDLINE | ID: mdl-31312315

RESUMEN

Pneumococcal meningitis is a global scourge. It is a major cause of morbidity and mortality. In Morocco, 13-valent pneumococcal conjugate vaccine (PCV13) was introduced into the National Immunization Program in October 2010 according to the immunization schedule 2 + 1 and replaced by PCV10 in July 2012, according to the same schedule. Despite the use of the PCV13, which is essential in the fight against pneumococcal disease, the emergence of new non-vaccine serotypes always results in meningitis in children, causing serious sequelae. We report the case of an infant vaccinated with two doses of PCV13 with meningitis caused by Streptococcus pneumoniae serotype 7a. The peculiarity of this case study lies in pneumococcal meningitis due to Streptococcus pneumoniae serotype 7a not included in the PCV13 in an infant immunized by 2 doses of PCV13. We here insist on the need and the importance of an observatory for pneumococcal meningitis and of a wide epidemiological study in order to determine the serotypes in Morocco after the introduction of PCV13 and then of PCV10.


Asunto(s)
Meningitis Neumocócica/diagnóstico , Vacunas Neumococicas/administración & dosificación , Streptococcus pneumoniae/aislamiento & purificación , Humanos , Lactante , Masculino , Meningitis Neumocócica/microbiología , Meningitis Neumocócica/prevención & control , Marruecos , Vacunas Neumococicas/inmunología , Serotipificación , Streptococcus pneumoniae/inmunología , Vacunación
9.
PLoS Med ; 16(7): e1002845, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31269018

RESUMEN

BACKGROUND: In October 2017, the United Kingdom Joint Committee on Vaccination and Immunisation (JCVI) recommended removal of one primary dose of the 13-valent pneumococcal conjugate vaccine (PCV13) from the existing 2+1 schedule (2, 4, 12 months). We conducted a mathematical modelling study to investigate the potential impact of a 1+1 (3, 12 month) schedule on invasive pneumococcal disease (IPD) and pneumococcal community-acquired pneumonia (CAP). Our results and those from a 1+1 immunogenicity study formed the key evidence reviewed by JCVI. METHODS AND FINDINGS: We developed age-structured, dynamic, deterministic models of pneumococcal transmission in England and Wales to describe the impact on IPD of 7-valent PCV (PCV7; introduced in 2006) and PCV13 (introduced in 2010). Key transmission and vaccine parameters were estimated by fitting to carriage data from 2001/2002 and post-PCV IPD data to 2015, using vaccine coverage, mixing patterns between ages, and population data. We considered various models to investigate potential reasons for the rapid increase in non-PCV13 (non-vaccine serotype [NVT]) IPD cases since 2014. After searching a large parameter space, 500 parameter sets were identified with a likelihood statistically close to the maximum and these used to predict future cases (median, prediction range from 500 parameter sets). Our findings indicated that the emergence of individual NVTs with higher virulence resulting from ongoing replacement was likely responsible; the NVT increase was predicted to plateau from 2020. Long-term simulation results suggest that changing to a 1+1 schedule would have little overall impact, as the small increase in vaccine-type IPD would be offset by a reduction in NVT IPD. Our results were robust to changes in vaccine assumptions in a sensitivity analysis. Under the base case scenario, a change to a 1+1 schedule in 2018 was predicted to produce 31 (6, 76) additional IPD cases over five years and 83 (-10, 242) additional pneumococcal-CAP cases, with together 8 (-2, 24) additional deaths, none in children under 15 years. Long-term continuation with the 2+1 schedule, or changing to a 1+1, was predicted to sustain current reductions in IPD cases in under-64-year-olds, but cases in 65+-year-olds would continue to increase because of the effects of an aging population. Limitations of our model include difficulty in fitting to past trends in NVT IPD in some age groups and inherent uncertainty about future NVT behaviour, sparse data for defining the mixing matrix in 65+-year-olds, and the methodological challenge of defining uncertainty on predictions. CONCLUSIONS: Our findings suggest that, with the current mature status of the PCV programme in England and Wales, removing one primary dose in the first year of life would have little impact on IPD or pneumococcal CAP cases or associated deaths at any age. A reduction in the number of priming doses would improve programmatic efficiency and facilitate the introduction of new vaccines by reducing the number of coadministered vaccines given at 2 and 4 months of age in the current UK schedule. Our findings should not be applied to other settings with different pneumococcal epidemiology or with immature programmes and poor herd immunity.


Asunto(s)
Infecciones Comunitarias Adquiridas/prevención & control , Vacuna Neumocócica Conjugada Heptavalente/administración & dosificación , Programas de Inmunización , Esquemas de Inmunización , Inmunogenicidad Vacunal , Modelos Teóricos , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Vacunación , Adolescente , Adulto , Anciano , Niño , Preescolar , Infecciones Comunitarias Adquiridas/inmunología , Infecciones Comunitarias Adquiridas/mortalidad , Infecciones Comunitarias Adquiridas/transmisión , Inglaterra/epidemiología , Vacuna Neumocócica Conjugada Heptavalente/inmunología , Humanos , Inmunidad Colectiva , Incidencia , Lactante , Recién Nacido , Persona de Mediana Edad , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/mortalidad , Infecciones Neumocócicas/transmisión , Vacunas Neumococicas/inmunología , Prevalencia , Evaluación de Programas y Proyectos de Salud , Factores de Tiempo , Gales/epidemiología , Adulto Joven
10.
BMC Infect Dis ; 19(1): 605, 2019 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-31291902

RESUMEN

BACKGROUND: Streptococcus pneumoniae is a major cause of pneumonia, meningitis, and other serious infections among children in India. India introduced the 13-valent pneumococcal conjugate vaccine (PCV) in several states in 2017, and is expected to expand to nationwide coverage in the near future. To establish a baseline for measuring the impact of PCV in India, we assessed overall and serotype-specific nasopharyngeal carriage in two pediatric populations. METHODS: A cross-sectional study was conducted in Palwal District, Haryana, from December 2016 to July 2017, prior to vaccine introduction. Children 2-59 months of age with clinical pneumonia seeking healthcare and those in the community with no clear illness were targeted for enrollment. A nasopharyngeal swab was collected and tested for pneumococcus using conventional culture and sequential multiplex PCR. Isolates were tested for antimicrobial resistance using an E test. Children were considered colonized if pneumococcus was isolated by culture or PCR. The prevalence of pneumococcal and serotype-specific colonization was compared between groups of children using log-binomial regression. RESULTS: Among 601 children enrolled, 91 had clinical pneumonia and 510 were community children. The proportion colonized with S. pneumoniae was 74.7 and 54.5% among children with clinical pneumonia and community children, respectively (adjusted prevalence ratio: 1.38; 95% confidence interval: 1.19, 1.60). The prevalence of PCV13 vaccine-type colonization was similar between children with clinical pneumonia (31.9%) and community children (28.0%; p = 0.46). The most common colonizing serotypes were 6A, 6B, 14, 19A, 19F, and 23F, all of which are included in the PCV13 vaccine product. Antimicrobial resistance to at least one drug was similar between isolates from children with clinical pneumonia (66.1%) and community children (61.5%; p = 0.49); while resistance to at least two drugs was more common among isolates from children with clinical pneumonia (25.8% vs. 16.4%; p = 0.08). Resistance for all drugs was consistently higher for PCV13 vaccine-type serotypes compared to non-vaccine serotypes in both groups. CONCLUSION: This study provides baseline information on the prevalence of serotype-specific pneumococcal colonization among children prior to the introduction of PCV in India. Our results suggest a role for pneumococcal vaccines in reducing pneumococcal colonization and antimicrobial resistant isolates circulating in India.


Asunto(s)
Portador Sano/microbiología , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/inmunología , Antibacterianos/farmacología , Portador Sano/epidemiología , Preescolar , Estudios Transversales , Farmacorresistencia Bacteriana , Femenino , Humanos , India/epidemiología , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Nasofaringe/microbiología , Infecciones Neumocócicas/epidemiología , Prevalencia , Serogrupo , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/genética , Vacunas Conjugadas
11.
BMC Infect Dis ; 19(1): 510, 2019 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-31182036

RESUMEN

BACKGROUND: Pneumococcal infections are major causes of morbidity and mortality worldwide. We use routine hospital admissions data and time-series modelling analysis to estimate the impact of the seven and thirteen valent pneumococcal conjugate vaccines (PCV7 and PCV13) on hospital admissions due to pneumococcal disease in England. METHODS: Hospital admissions for pneumococcal meningitis, bacteraemia and pneumonia between January 1, 2003 and December 31, 2015 were identified from the national Hospital Episode Statistics database for all age groups in England. We model the impact of pneumococcal vaccination using interrupted time series analysis. Hospital admissions prior to vaccine introduction were extrapolated to predict the expected number of admissions in the absence of pneumococcal vaccines. Admissions avoided over time were estimated by comparing the fitted interrupted time series and the expected model for no vaccination in a Bayesian framework. RESULTS: Overall, there were 43,531 (95% credible interval (CrI): 36486-51,346) fewer hospital admissions due to bacteraemia, meningitis and pneumonia in England during the period from 2006 to 2015 than would have been expected if pneumococcal vaccines had not been implemented, with the majority of hospital admissions avoided due to pneumonia. Among young children reductions in meningitis were more common, while among adults reductions in pneumonia admissions were relatively more important, with no evidence for reduced bacteraemia and meningitis among older adults. We estimated that 981 (95% CrI: 391-2018), 749 (95% CrI: 295-1442) and 1464 (95% CrI: 793-2522) bacteraemia, meningitis and pneumonia related hospital admissions, respectively, were averted in children < 2 years of age. CONCLUSIONS: Substantial reductions in hospital admissions for bacteraemia, meningitis and pneumonia in England were estimated after the introduction of childhood vaccination, with indirect effects being responsible for most of the hospital admissions avoided.


Asunto(s)
Hospitalización/estadística & datos numéricos , Infecciones Neumocócicas/diagnóstico , Vacunas Neumococicas/inmunología , Adolescente , Adulto , Anciano , Niño , Preescolar , Inglaterra/epidemiología , Femenino , Humanos , Lactante , Análisis de Series de Tiempo Interrumpido , Masculino , Meningitis Neumocócica/diagnóstico , Meningitis Neumocócica/epidemiología , Persona de Mediana Edad , Infecciones Neumocócicas/epidemiología , Neumonía/diagnóstico , Neumonía/epidemiología , Vacunación , Vacunas Conjugadas/inmunología , Adulto Joven
12.
Nat Microbiol ; 4(8): 1316-1327, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31110357

RESUMEN

The upper respiratory tract is continuously exposed to a vast array of potentially pathogenic viruses and bacteria. Influenza A virus (IAV) has particular synergism with the commensal bacterium Streptococcus pneumoniae in this niche, and co-infection exacerbates pathogenicity and causes significant mortality. However, it is not known whether this synergism is associated with a direct interaction between the two pathogens. We have previously reported that co-administration of a whole-inactivated IAV vaccine (γ-Flu) with a whole-inactivated pneumococcal vaccine (γ-PN) enhances pneumococcal-specific responses. In this study, we show that mucosal co-administration of γ-Flu and γ-PN similarly augments IAV-specific immunity, particularly tissue-resident memory cell responses in the lung. In addition, our in vitro analysis revealed that S. pneumoniae directly interacts with both γ-Flu and with live IAV, facilitating increased uptake by macrophages as well as increased infection of epithelial cells by IAV. These observations provide an additional explanation for the synergistic pathogenicity of IAV and S. pneumoniae, as well as heralding the prospect of exploiting the phenomenon to develop better vaccine strategies for both pathogens.


Asunto(s)
Inmunidad , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Vacunas Neumococicas/inmunología , Animales , Coinfección/inmunología , Coinfección/prevención & control , Citocinas/metabolismo , Modelos Animales de Enfermedad , Perros , Células Epiteliales , Femenino , Humanos , Virus de la Influenza A/patogenicidad , Vacunas contra la Influenza/administración & dosificación , Pulmón/inmunología , Macrófagos , Células de Riñón Canino Madin Darby , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Streptococcus pneumoniae/patogenicidad , Linfocitos T/inmunología
13.
Int J Infect Dis ; 85: 1-6, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31096052

RESUMEN

OBJECTIVES: The aim of this study was to estimate the impact of antimicrobial resistance (AMR) in secondary pneumococcal pneumonia infections on global mortality during the 2009 influenza pandemic, to estimate future pandemic mortality risk and to inform pandemic preparedness. METHODS: Risk analysis modelling was conducted using a multivariate risk formula. Literature reviews were conducted to generate global central estimates for each of the parameters of the risk formula in relation to the 2009 influenza pandemic, secondary pneumococcal pneumonia, rates of AMR, and pneumococcal vaccine efficacy as a component of pandemic preparedness. RESULTS: Global Streptococcus pneumoniae AMR was estimated at 21.8% to 27.6%, and contributed to 1.8% to 2.3% of deaths during the 2009 influenza pandemic. When directly applied to mortality due to multidrug resistance, pneumococcal vaccination could potentially prevent 1277 to 3754 deaths and could have reduced mortality from multidrug-resistant S. pneumoniae to 1% to 1.2%. CONCLUSIONS: AMR in secondary pneumococcal infections contributed towards a small percentage of the global mortality during the 2009 influenza pandemic. Increased S. pneumoniae AMR could result in a three- to four-fold rise in mortality due to secondary pneumococcal infections in future influenza pandemics. Pneumococcal vaccination has an important role in preventing pneumococcal co-infections and combating AMR in all populations, and should be considered a key component of influenza pandemic preparedness or early action plans.


Asunto(s)
Antibacterianos/farmacología , Coinfección/mortalidad , Farmacorresistencia Bacteriana , Gripe Humana/complicaciones , Neumonía Neumocócica/mortalidad , Streptococcus pneumoniae/efectos de los fármacos , Adolescente , Adulto , Coinfección/tratamiento farmacológico , Coinfección/epidemiología , Coinfección/microbiología , Femenino , Humanos , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/efectos adversos , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/genética , Vacunas Neumococicas/inmunología , Neumonía Neumocócica/epidemiología , Neumonía Neumocócica/etiología , Neumonía Neumocócica/microbiología , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/fisiología , Vacunación , Adulto Joven
14.
Cell Host Microbe ; 25(6): 884-891.e6, 2019 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-31126758

RESUMEN

The capacity of Streptococcus pneumoniae to successfully transmit and colonize new human hosts is a critical aspect of pneumococcal population biology and a prerequisite for invasive disease. However, the bacterial mechanisms underlying this process remain largely unknown. To identify bacterial factors required for transmission, we conducted a high-throughput genetic screen with a transposon sequencing (Tn-seq) library of a pneumococcal strain in a ferret transmission model. Key players in both metabolism and transcriptional regulation were identified as required for efficient bacterial transmission. Targeted deletion of the putative C3-degrading protease CppA, iron transporter PiaA, or competence regulatory histidine kinase ComD significantly decreased transmissibility in a mouse model, further validating the screen. Maternal vaccination with recombinant surface-exposed PiaA and CppA alone or in combination blocked transmission in offspring and were more effective than capsule-based vaccines. These data underscore the possibility of targeting pneumococcal transmission as a means of eliminating invasive disease in the population.


Asunto(s)
Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Infecciones Neumocócicas/prevención & control , Infecciones Neumocócicas/transmisión , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/aislamiento & purificación , Factores de Virulencia/genética , Animales , Modelos Animales de Enfermedad , Hurones , Pruebas Genéticas , Ensayos Analíticos de Alto Rendimiento , Ratones , Mutagénesis Insercional , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/aislamiento & purificación , Análisis de Secuencia de ADN , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/aislamiento & purificación , Factores de Virulencia/inmunología
15.
J Med Microbiol ; 68(6): 903-909, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31090535

RESUMEN

PURPOSE: To prevent severe invasive pneumococcal infection, pneumococcal conjugate vaccines (PCVs) were introduced in Japan in 2010, and in 2013 a pneumococcal 13-valent conjugate vaccine (PCV13) was included in the routine vaccination schedule for infants. In this study, we analysed the antimicrobial susceptibilities and capsular types of pneumococci isolated from non-invasive patient sites from 2007 to 2016 to assess the impact of the introduction of PCV13. METHODOLOGY: A total of 618 pneumococcal isolates collected at a teaching hospital from 2007 to 2016 were used. These isolates were characterized by capsular typing, multilocus sequence typing and antimicrobial susceptibility testing. RESULTS: Capsular typing indicated that, after the introduction of the PCV, the proportion of PCV13 serotypes decreased (P<0.01), while non-PCV13 serotypes became diverse. In particular, increases in 22 F, 15A and 23A were noted among non-PCV13 serotypes. Regarding antimicrobial susceptibility, the non-susceptibility rate to penicillin of pneumococci that showed higher minimum inhibitory concentrations (MICs) than the susceptibility breakpoint decreased, and pneumococci tended to become susceptible. However, all type 23A pneumococci and 77.8  % of type 15A pneumococci showed the reverse trend, with low susceptibility to penicillin. Furthermore, all 15A and 23A isolates had macrolide resistance genes. CONCLUSION: These data suggest that PCVs can prevent infections caused by PCV serotypes. However, since non-PCV13-type pneumococci, in particular 15A and 23A, which have acquired multidrug resistance, have already emerged over time, the development of a novel vaccine targeting a broader spectrum of pneumococci is warranted.


Asunto(s)
Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/inmunología , Antibacterianos/farmacología , Cápsulas Bacterianas/inmunología , Técnicas de Tipificación Bacteriana , Portador Sano , Girasa de ADN/genética , Topoisomerasa de ADN IV/genética , Hospitales de Enseñanza , Humanos , Japón/epidemiología , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Penicilinas/farmacología , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/microbiología , Serogrupo , Serotipificación , Streptococcus pneumoniae/genética , Vacunas Conjugadas/inmunología
16.
Int J STD AIDS ; 30(5): 472-478, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30999829

RESUMEN

Invasive pneumococcal diseases (IPDs) remain a significant cause of morbidity and mortality in human immunodeficiency virus (HIV)-positive individuals despite the widespread use of highly active antiretroviral therapy (HAART) and availability of pneumococcal vaccines. The aim of this study was to measure temporal trends in incidence and risk factors for IPD (defined as culture of Streptococcus pneumoniae from blood, cerebrospinal fluid or both) in a cohort of HIV-positive patients attending an ambulatory HIV care centre in Dublin, Ireland over a 10-year period 2006-2015. Incidence of IPD was determined as events per 100,000 person-years' follow-up. Poisson regression was used to assess linear trend in incidence over time. A nested case-control study (four controls per case) was undertaken to assess risk factors for IPD. Forty-seven episodes of IPD were identified in 42 HIV-positive individuals (median [IQR] age 38 years [33-43], 69% male, 86% injecting drug users (IDUs), median CD4 T-cell count 213 cells/mm3) over 16,008 person-years' follow-up (overall incidence rate 293/100,000 person-years). Three patients had two episodes and one patient had three episodes of IPD during the study period. The overall case fatality rate was 15% (95% confidence interval [CI] 4-24%). The incidence of IPD per 100,000 person-years decreased from 728 (95% CI, 455-1002), to 242 (95% CI, 120-365) to 82 (95% CI, 40-154) in calendar periods 2006-2008, 2009-2012 and 2013-2015, respectively (p < 0.01 for linear trend). Older age (p = 0.02), male gender (p = 0.05), detectable HIV viral load (p < 0.01) and non-receipt of pneumococcal vaccine (p = 0.03) were associated with IPD while IDU as risk of acquisition of HIV was of borderline significance (p = 0.06). HIV-positive individuals remain at greater risk of IPD compared to the general population. Pneumococcal vaccine should be seen as a priority to ensure optimal protection for HIV-positive patients.


Asunto(s)
Terapia Antirretroviral Altamente Activa , Infecciones por VIH/tratamiento farmacológico , Seropositividad para VIH/complicaciones , Infecciones Neumocócicas/epidemiología , Streptococcus pneumoniae/aislamiento & purificación , Abuso de Sustancias por Vía Intravenosa/complicaciones , Adulto , Terapia Antirretroviral Altamente Activa/métodos , Estudios de Casos y Controles , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Humanos , Incidencia , Irlanda/epidemiología , Masculino , Infecciones Neumocócicas/complicaciones , Infecciones Neumocócicas/diagnóstico , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/inmunología , Factores de Riesgo , Abuso de Sustancias por Vía Intravenosa/epidemiología
18.
Microbiol Spectr ; 7(2)2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30977464

RESUMEN

The polysaccharide capsule of Streptococcus pneumoniae is the dominant surface structure of the organism and plays a critical role in virulence, principally by interfering with host opsonophagocytic clearance mechanisms. The capsule is the target of current pneumococcal vaccines, but there are 98 currently recognised polysaccharide serotypes and protection is strictly serotype-specific. Widespread use of these vaccines is driving changes in serotype prevalence in both carriage and disease. This chapter summarises current knowledge on the role of the capsule and its regulation in pathogenesis, the mechanisms of capsule synthesis, the genetic basis for serotype differences, and provides insights into how so many structurally distinct capsular serotypes have evolved. Such knowledge will inform ongoing refinement of pneumococcal vaccination strategies.


Asunto(s)
Cápsulas Bacterianas/fisiología , Polisacáridos Bacterianos/fisiología , Streptococcus pneumoniae/fisiología , Animales , Cápsulas Bacterianas/genética , Cápsulas Bacterianas/inmunología , Cápsulas Bacterianas/metabolismo , Humanos , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/inmunología , Polisacáridos Bacterianos/biosíntesis , Polisacáridos Bacterianos/genética , Polisacáridos Bacterianos/inmunología , Streptococcus pneumoniae/inmunología , Streptococcus pneumoniae/metabolismo , Streptococcus pneumoniae/patogenicidad
19.
Expert Opin Drug Saf ; 18(4): 253-259, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30907170

RESUMEN

INTRODUCTION: The introduction of pneumococcal conjugate vaccines (PCVs) in the routine immunization program has resulted in a significant decline in invasive pneumococcal diseases (IPD) around the world. Preterm infants are a special group at a high risk of invasive infection by encapsulated bacteria. However, their slow growth accrual and prolonged hospital stay frequently lead to delays in immunization, which contributes to their risk for severe infections. Areas covered: Authors reviewed the published immunogenicity and safety of the use of PCVs in preterm infants. Expert opinion: PCVs are safe and effective for use in low birth weight and in-hospital preterm infants. Local and systemic reactions are similar for both term and preterm populations. Reports were inconsistent on the risk of apnea, therefore hospitalized extremely premature infants should be kept under observation for at least 48 h after immunization.


Asunto(s)
Recien Nacido Prematuro , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Humanos , Inmunización/métodos , Programas de Inmunización , Inmunogenicidad Vacunal , Recién Nacido , Vacunas Neumococicas/efectos adversos , Vacunas Neumococicas/inmunología , Vacunas Conjugadas/administración & dosificación
20.
Biomed Res Int ; 2019: 3427174, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30895191

RESUMEN

Carriage of pneumococcus is considered as the precursor for development of pneumococcal disease. In sub-Saharan Africa, very little research has been done on the pneumococcus in relation to people with HIV infection in the era of pneumococcal conjugate vaccines. This study investigated pneumococcal carriage among HIV/AIDS patients in southern Ghana to determine the prevalence, risk factors, serotypes and antibiotic resistance of the organism. This was a cross sectional study involving 245 HIV/AIDS patients recruited from Korle Bu Teaching Hospital and Princess Marie Louis Hospital in Accra from November 2016 to March 2017. Epidemiological data on demographic, household and clinical features of the study participants were collected. Nasopharyngeal (NP) swabs were also collected from the study participants and cultured for Streptococcus pneumoniae; the isolates were serotyped by latex agglutination and Quellung reaction. Antimicrobial disc susceptibility was performed on the isolates, and antibiotics tested included tetracycline, erythromycin, cotrimoxazole, levofloxacin, oxacillin and ceftriaxone. Prevalence of pneumococcal carriage among the study participants was 11% (95% CI: 7.4 to 15.6); carriage among children and adults was 25% (95% CI: 14% to 38.9%) and 7.3% (95% CI: 4% to 11.9%) respectively. School attendance (p=0.001) and history of pneumococcal disease in the past year (p=0.001) were significantly associated with pneumococcal carriage. The most prevalent pneumococcal serotypes carried by the study participants were 19A (15.4%) and 23F (15.4%). Serotype coverage of the various pneumococcal vaccines were PCV10 (23.1%), PCV13 (42.3%) and PPV23 (50%). The prevalence of pneumococcal multidrug resistance was 18.5%. In conclusion, pneumococcal carriage among HIV-infected children was three-fold higher compared to carriage among HIV-infected adults. Pneumococcal carriage among both HIV-infected children and adults in the study area tends to be characterized by a predominance of non-vaccine serotypes and a considerable level of multidrug resistance.


Asunto(s)
Portador Sano/epidemiología , Portador Sano/inmunología , Infecciones por VIH/inmunología , Infecciones por VIH/microbiología , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/fisiología , Vacunas Conjugadas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Farmacorresistencia Microbiana , Composición Familiar , Femenino , Ghana/epidemiología , Infecciones por VIH/epidemiología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Factores de Riesgo , Serogrupo , Streptococcus pneumoniae/aislamiento & purificación , Adulto Joven
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