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1.
BMC Infect Dis ; 20(1): 940, 2020 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-33297987

RESUMEN

BACKGROUND: Pneumococcal nasopharyngeal colonization (PNC) generally precedes pneumococcal disease. The purpose of this study was to determine the prevalence of PNC and to identify the pneumococcal serotypes circulating among Bhutanese children under five years of age admitted with clinical pneumonia, before the introduction of pneumococcal conjugate vaccine (PCV13) in the country. We also aimed to contribute to the understanding of the interplay between PNC and viral co-infection among this population. METHODS: This was a prospective study conducted at the Jigme Dorji Wangchuck National Referral Hospital in Bhutan over 12 consecutive months. Children aged 2 to 59 months admitted with WHO-defined clinical pneumonia were eligible for recruitment. We collected blood for bacterial culture and molecular identification of S. pneumoniae, and nasopharyngeal washing for screening of respiratory viruses, and for the detection and capsular typing of S. pneumoniae by real-time polymerase chain reaction (RT-PCR). RESULTS: Overall, 189 children were recruited, and PNC was tested in 121 of them (64.0%). PNC was found in 76/121 children (62.8%) and S. pneumoniae was identified in blood (both by culture and RT-PCR) in a single child. Respiratory viruses were detected in a similar proportion among children with (62/70; 88.6%) and without PNC (36/40; 90.0%; p = 1.000), but rhinovirus detection was less common among children with PNC (20/70; 28.6% versus 19/40; 47.5%; p = 0.046). Capsular typing identified 30 different serotypes. Thirty-nine children (51.3%) were colonised with two to five different serotypes. A third of the children presented with serotypes considered highly invasive. Over half of the children (44/76; 57.9%) were carrying at least one serotype included in PCV13. CONCLUSIONS: This study provides baseline information on the status of PNC among Bhutanese children admitted with clinical pneumonia prior to the introduction of PCV13, which is valuable to monitor its potential impact. PCV13 could theoretically have averted up to 58% of the pneumococcal infections among the children in this study, suggesting a future role for the vaccine to significantly reduce the burden associated with S. pneumoniae in Bhutan.


Asunto(s)
Coinfección/epidemiología , Hospitalización , Nasofaringe/microbiología , Infecciones Neumocócicas/epidemiología , Neumonía/epidemiología , Serogrupo , Streptococcus pneumoniae/genética , Virosis/epidemiología , Bután/epidemiología , Preescolar , Coinfección/virología , Estudios Transversales , Femenino , Humanos , Lactante , Masculino , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/inmunología , Neumonía/microbiología , Prevalencia , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa , Streptococcus pneumoniae/inmunología , Vacunas Conjugadas/inmunología , Virosis/virología
2.
BMC Infect Dis ; 20(1): 878, 2020 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-33228556

RESUMEN

BACKGROUND: Germinal center derived memory B cells and plasma cells constitute, in health and during EBV reactivation, the largest functional EBV reservoir. Hence, by reducing germinal center derived formation of memory B cells and plasma cells, EBV loads may be reduced. Animal and in-vitro models have shown that IL-21 can support memory B and plasma cell formation and thereby potentially contribute to EBV persistence. However, IL-21 also displays anti-viral effects, as mice models have shown that CD4+ T cell produced IL-21 is critical for the differentiation, function and survival of anti-viral CD8+ T cells able to contain chronic virus infections. CASE PRESENTATION: We present immunological work-up (flow-cytometry, ELISA and genetics) related to a patient suffering from a condition resembling B cell chronic active EBV infection, albeit with moderately elevated EBV copy numbers. No mutations in genes associated with EBV disease, common variable immunodeficiency or pertaining to the IL-21 signaling pathway (including hypermorphic IL-21 mutations) were found. Increased (> 5-fold increase 7 days post-vaccination) CD4+ T cell produced (p < 0.01) and extracellular IL-21 levels characterized our patient and coexisted with: CD8+ lymphopenia, B lymphopenia, hypogammaglobulinemia, compromised memory B cell differentiation, absent induction of B-cell lymphoma 6 protein (Bcl-6) dependent peripheral follicular helper T cells (pTFH, p = 0.01), reduced frequencies of peripheral CD4+ Bcl-6+ T cells (p = 0.05), compromised plasmablast differentiation (reduced protein vaccine responses (p < 0.001) as well as reduced Treg frequencies. Supporting IL-21 mediated suppression of pTFH formation, pTFH and CD4+ IL-21+ frequencies were strongly inversely correlated, prior to and after vaccination, in the patient and in controls, Spearman's rho: - 0.86, p < 0.001. CONCLUSIONS: To the best of our knowledge, this is the first report of elevated CD4+ IL-21+ T cell frequencies in human EBV disease. IL-21 overproduction may, apart from driving T cell mediated anti-EBV responses, disrupt germinal center derived memory B cell and plasma cell formation, and thereby contribute to EBV disease control.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4/inmunología , Interleucinas/metabolismo , Anciano , Linfocitos B/inmunología , Linfocitos T CD8-positivos/inmunología , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/virología , Espacio Extracelular/metabolismo , Femenino , Herpesvirus Humano 4/genética , Humanos , Interleucinas/genética , Activación de Linfocitos/inmunología , Mutación , Vacunas Neumococicas/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Vacunación , Vacunas Conjugadas/inmunología
3.
PLoS Med ; 17(10): e1003326, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33095759

RESUMEN

BACKGROUND: Vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPV23) is available in the United Kingdom to adults aged 65 years or older and those in defined clinical risk groups. We evaluated the vaccine effectiveness (VE) of PPV23 against vaccine-type pneumococcal pneumonia in a cohort of adults hospitalised with community-acquired pneumonia (CAP). METHODS AND FINDINGS: Using a case-control test-negative design, a secondary analysis of data was conducted from a prospective cohort study of adults (aged ≥16 years) with CAP hospitalised at 2 university teaching hospitals in Nottingham, England, from September 2013 to August 2018. The exposure of interest was PPV23 vaccination at any time point prior to the index admission. A case was defined as PPV23 serotype-specific pneumococcal pneumonia and a control as non-PPV23 serotype pneumococcal pneumonia or nonpneumococcal pneumonia. Pneumococcal serotypes were identified from urine samples using a multiplex immunoassay or from positive blood cultures. Multivariable logistic regression was used to derive adjusted odds of case status between vaccinated and unvaccinated individuals; VE estimates were calculated as (1 - odds ratio) × 100%. Of 2,357 patients, there were 717 PPV23 cases (48% vaccinated) and 1,640 controls (54.5% vaccinated). The adjusted VE (aVE) estimate against PPV23 serotype disease was 24% (95% CI 5%-40%, p = 0.02). Estimates were similar in analyses restricted to vaccine-eligible patients (n = 1,768, aVE 23%, 95% CI 1%-40%) and patients aged ≥65 years (n = 1,407, aVE 20%, 95% CI -5% to 40%), but not in patients aged ≥75 years (n = 905, aVE 5%, 95% CI -37% to 35%). The aVE estimate in relation to PPV23/non-13-valent pneumococcal conjugate vaccine (PCV13) serotype pneumonia (n = 417 cases, 43.7% vaccinated) was 29% (95% CI 6%-46%). Key limitations of this study are that, due to high vaccination rates, there was a lack of power to reject the null hypothesis of no vaccine effect, and that the study was not large enough to allow robust subgroup analysis in the older age groups. CONCLUSIONS: In the setting of an established national childhood PCV13 vaccination programme, PPV23 vaccination of clinical at-risk patient groups and adults aged ≥65 years provided moderate long-term protection against hospitalisation with PPV23 serotype pneumonia. These findings suggest that PPV23 vaccination may continue to have an important role in adult pneumococcal vaccine policy, including the possibility of revaccination of older adults.


Asunto(s)
Vacunas Neumococicas/farmacología , Neumonía Neumocócica/inmunología , Neumonía Neumocócica/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Infecciones Comunitarias Adquiridas/prevención & control , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Estudios Prospectivos , Serogrupo , Streptococcus pneumoniae/inmunología , Reino Unido , Vacunación/métodos , Vacunas Conjugadas/inmunología
4.
PLoS Biol ; 18(10): e3000878, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33091022

RESUMEN

Predicting how pathogen populations will change over time is challenging. Such has been the case with Streptococcus pneumoniae, an important human pathogen, and the pneumococcal conjugate vaccines (PCVs), which target only a fraction of the strains in the population. Here, we use the frequencies of accessory genes to predict changes in the pneumococcal population after vaccination, hypothesizing that these frequencies reflect negative frequency-dependent selection (NFDS) on the gene products. We find that the standardized predicted fitness of a strain, estimated by an NFDS-based model at the time the vaccine is introduced, enables us to predict whether the strain increases or decreases in prevalence following vaccination. Further, we are able to forecast the equilibrium post-vaccine population composition and assess the invasion capacity of emerging lineages. Overall, we provide a method for predicting the impact of an intervention on pneumococcal populations with potential application to other bacterial pathogens in which NFDS is a driving force.


Asunto(s)
Evolución Molecular Dirigida , Streptococcus pneumoniae/fisiología , Simulación por Computador , Modelos Biológicos , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/inmunología
5.
JAMA ; 324(11): 1068-1077, 2020 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-32930758

RESUMEN

Importance: The standard schedule of national immunization programs for infants may not be sufficient to protect extremely and very preterm infants. Objective: To evaluate the immunogenicity of routine vaccinations administered to preterm infants. Design, Setting, and Participants: A multicenter, prospective, observational cohort study of preterm infants stratified according to gestational age recruited from 8 hospitals across the Netherlands between October 2015 and October 2017, with follow-up until 12 months of age (October 2018). In total, 296 premature infants were enrolled and compared with a control group of 66 healthy term infants from a 2011 study, immunized according to the same schedule with the same vaccines. Exposures: Three primary doses of the diphtheria-tetanus toxoids-acellular pertussis-inactivated poliomyelitis-Haemophilus influenza type b-hepatitis B combination vaccine were given at 2, 3, and 4 months after birth followed by a booster at 11 months and a 10-valent pneumococcal conjugate vaccine at 2, 4, and 11 months after birth. Main Outcomes and Measures: Primary end points were (1) proportion of preterm infants who achieved IgG antibody against vaccine antigens at concentrations above the internationally defined threshold for protection after the primary series and booster dose and (2) serum IgG geometric mean concentrations after the primary series and booster vaccination. Proportions and geometric mean concentrations were compared in preterm infants and the control group of term infants. Results: Of 296 preterm infants (56.1% male; mean gestational age, 30 weeks), complete samples before vaccination, 1 month after the primary series, and 1 month after the booster were obtained from 220 preterm infants (74.3%). After the primary series, the proportion of preterm infants across all gestational age groups who achieved protective IgG antibody levels against pertussis toxin, diphtheria, tetanus and 6 of 10 pneumococcal serotypes varied between 83.0% and 100%, Haemophilus influenzae type b between 34.7% and 46.2% (40.6% among all preterm infants overall), and pneumococcal serotypes 4, 6B, 18C, and 23F between 45.8% and 75.1%. After the booster dose, protective antibody levels were achieved in more than 95% of all preterm groups, except for Haemophilus influenzae type b (88.1%). In general, geometric mean concentrations of all vaccine-induced antibodies were significantly lower in all preterm infants vs term infants, except for pertussis toxin and pneumococcal serotypes 4 and 19F after the primary series and booster vaccination. Conclusions and Relevance: Among preterm infants, administration of routine vaccinations during the first year of life was associated with protective antibody levels against most antigens in the majority of infants after the primary series and booster, except for Haemophilus influenzae type b. However, antibody concentrations were generally lower among preterm infants compared with historical controls.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Anticuerpos Antivirales/sangre , Inmunoglobulina G/sangre , Recien Nacido Prematuro/inmunología , Vacunas/inmunología , Estudios de Cohortes , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Femenino , Vacunas contra Haemophilus/inmunología , Estudio Históricamente Controlado , Humanos , Inmunización Secundaria , Lactante , Masculino , Vacunas Neumococicas/inmunología , Vacuna Antipolio de Virus Inactivados/inmunología , Vacunas Conjugadas/inmunología
6.
PLoS One ; 15(9): e0239848, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32997698

RESUMEN

BACKGROUND: A significant reduction in invasive pneumococcal disease (IPD) has been reported, across all ages, following the implementation of 7-valent conjugate pneumococcal vaccine (PCV7) globally, as part of infant immunization programs. We explored the additional impact of PCV13 on IPD over a 14-year period. METHODS: Using provincial laboratory surveillance and hospitalization data (N = 5791), we calculated the annual incidence of IPD following the implementation of PCV13 vaccine. Poisson regression was used to evaluate changes in the overall incidence of IPD, and serotype-specific IPD between PCV7 (2004-10) and PCV13 (2011-2015) eras. RESULTS: Overall, IPD rates have seen a modest decline in the PCV13 compared to the PCV7 era (IRR 0.84; 95% CI: 0.79-0.89); this was seen in children ≤2 years of age, and the majority of the adult cohort. Rates of vaccine-type IPD (PCV7 and PCV13) also decreased in the PCV13 era. In contrast, IPD incidence related to non-PCV13 (IRR: 1.56; 95%CI:1.43-1.72) and non-vaccine serotypes (IRR: 2.12; 95%CI:1.84-2.45) increased in the PCV13 era compared to the PCV7 era. CONCLUSIONS: A modest reduction in IPD from the PCV13 vaccine was observed, with gains limited to the immunized cohort and adults. However, a significant increase in non-vaccine serotypes emphasizes the need for continued surveillance.


Asunto(s)
Infecciones Neumocócicas/epidemiología , Vacunas Neumococicas/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Colombia Británica/epidemiología , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Infecciones Neumocócicas/mortalidad , Infecciones Neumocócicas/prevención & control , Estudios Retrospectivos , Serogrupo , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/inmunología , Streptococcus pneumoniae/aislamiento & purificación , Tasa de Supervivencia , Adulto Joven
7.
Lancet Infect Dis ; 20(12): 1426-1436, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32857992

RESUMEN

BACKGROUND: Routine childhood immunisation with pneumococcal conjugate vaccine (PCV) has changed the epidemiology of pneumococcal disease across age groups, providing an opportunity to reconsider PCV dosing schedules. We aimed to evaluate the post-booster dose immunogenicity of ten-valent (PCV10) and 13-valent (PCV13) PCVs between infants randomly assigned to receive a single-dose compared with a two-dose primary series. METHODS: We did an open-label, non-inferiority, randomised study in HIV-unexposed infants at a single centre in Soweto, South Africa. Infants were randomly assigned to receive one priming dose of PCV10 or PCV13 at ages 6 weeks (6w + 1 PCV10 and 6w + 1 PCV13 groups) or 14 weeks (14w + 1 PCV10 and 14w + 1 PCV13 groups) or two priming doses of PCV10 or PCV13, one each at ages 6 weeks and 14 weeks (2 + 1 PCV10 and 2 + 1 PCV13 groups); all participants then received a booster dose of PCV10 or PCV13 at 40 weeks of age. The primary endpoint was geometric mean concentrations (GMCs) of serotype-specific IgG 1 month after the booster dose, which was assessed in all participants who received PCV10 or PCV13 as per the assigned randomisation group and for whom laboratory results were available at that timepoint. The 1 + 1 vaccine schedule was considered non-inferior to the 2 + 1 vaccine schedule if the lower bound of the 96% CI for the GMC ratio was greater than 0·5 for at least ten PCV13 serotypes and eight PCV10 serotypes. Safety was a secondary endpoint. This trial is registered with ClinicalTrials.gov (NCT02943902) and is ongoing. FINDINGS: Of 1695 children assessed, 600 were enrolled and randomly assigned to one of the six groups between Jan 9 and Sept 20, 2017; 542 were included in the final analysis of the primary endpoint (86-93 per group). For both PCV13 and PCV10, a 1+1 dosing schedule (either beginning at 6 or 14 weeks) was non-inferior to a 2 + 1 schedule. For PCV13, the lower limit of the 96% CI for the ratio of GMCs between the 1 + 1 and 2 + 1 groups was higher than 0·5 for ten serotypes in the 6w+1 group (excluding 6B, 14, and 23F) and 11 serotypes in the 14w + 1 group (excluding 6B and 23F). For PCV10, the lower limit of the 96% CI for the ratio of GMCs was higher than 0·5 for all ten serotypes in the 6w+1 and 14w + 1 groups. 84 serious adverse events were reported in 72 (12%) of 600 participants. 15 occurred within 28 days of vaccination, but none were considered to be related to PCV injection. There were no cases of culture-confirmed invasive pneumococcal disease. INTERPRETATION: The non-inferiority in post-booster immune responses following a single-dose compared with a two-dose primary series of PCV13 or PCV10 indicates the potential for reducing PCV dosing schedules from a 2 + 1 to 1 + 1 series in low-income and middle-income settings with well established PCV immunisation programmes. FUNDING: The Bill & Melinda Gates Foundation (OPP1 + 152352).


Asunto(s)
Esquemas de Inmunización , Inmunogenicidad Vacunal , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Anticuerpos Antibacterianos/sangre , Femenino , Humanos , Inmunoglobulina G/sangre , Lactante , Masculino , Infecciones Neumocócicas/epidemiología , Vacunas Neumococicas/administración & dosificación , Sudáfrica/epidemiología
8.
Allergol Immunopathol (Madr) ; 48(5): 500-506, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32771236

RESUMEN

The reasons for the relative resistance of children to certain infections such as that caused by coronavirus SARS-CoV2 are not yet fully clear. Deciphering these differences can provide important information about the pathogenesis of the disease. Regarding the SARS-CoV2 virus, children are at the same risk of infection as the general population of all ages, with the most serious cases being found in infants. However, it has been reported that the disease is much less frequent than in adults and that most cases are benign or moderate (even with high viral loads), provided there are no other risk factors or underlying diseases. It is not clear why they have lower morbidity and virtually no mortality. A series of findings, relationships and behavioral patterns between the infectious agent and the child host may account for the lower incidence and a greatly attenuated clinical presentation of the disease in children.


Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/patología , Neumonía Viral/epidemiología , Neumonía Viral/patología , Adulto , Factores de Edad , Portador Sano/transmisión , Portador Sano/virología , Niño , Coinfección/epidemiología , Coinfección/inmunología , Coinfección/patología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/transmisión , Humanos , Sistema Inmunológico , Estilo de Vida , Melatonina/inmunología , Melatonina/metabolismo , Pandemias , Peptidil-Dipeptidasa A/inmunología , Peptidil-Dipeptidasa A/metabolismo , Vacunas Neumococicas/inmunología , Neumonía Viral/inmunología , Neumonía Viral/transmisión , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/patología
9.
Int J Infect Dis ; 99: 204-213, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32735953

RESUMEN

BACKGROUND: Epidemiological studies suggest that there is a link between pneumococcal infection and adverse cardiovascular outcomes such as myocardial infarction. Multiple studies have evaluated the protective effect of the 23-valent polysaccharide pneumococcal vaccination (PPV23), but results have varied. Therefore, a meta-analysis was conducted to summarize available evidence on the impact of PPV23 on cardiovascular disease. METHODS: A literature search from January 1946 to September 2019 was conducted across Embase, Medline and Cochrane. All studies were included that evaluated PPV23 compared with a control (placebo, no vaccine or another vaccine) for any cardiovascular events, including: myocardial infarction (MI), heart failure and cerebrovascular events. Risk ratios (RRs) were pooled using random effects models. RESULTS: Eighteen studies were included, with a total of 716,108 participants. Vaccination with PPV23 was associated with decreased risk of any cardiovascular event (RR: 0.91; 95% CI: 0.84-0.99), and MI (RR: 0.88; 95% CI: 0.79-0.98) in all age groups, with a significant effect in those aged ≥65 years, but not in the younger age group. Similarly, PPV23 vaccine was associated with significant risk reduction in all-cause mortality in all ages (RR: 0.78; 95% CI: 0.68-0.88), specifically in those aged ≥65 years (RR: 0.71; 95% CI: 0.60-0.84). A significant risk reduction in cerebrovascular disease was not observed following pneumococcal vaccination. CONCLUSIONS: Polysaccharide pneumococcal vaccination decreased the risk for some adverse cardiovascular events, specifically acute MI in the vaccinated population, particularly for those individuals aged ≥65 years. It would be highly beneficial to vaccinate the population who is at greater risk of cardiovascular diseases.


Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Vacunas Neumococicas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Infarto del Miocardio/prevención & control , Oportunidad Relativa , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología
10.
Neurology ; 95(14): e1999-e2008, 2020 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-32727835

RESUMEN

OBJECTIVE: The phase IIIb A Study to Evaluate the Effects of Ocrelizumab on Immune Responses in Participants With Relapsing Forms of Multiple Sclerosis (VELOCE) study (NCT02545868) assessed responses to selected vaccines in ocrelizumab (OCR)-treated patients with relapsing multiple sclerosis. METHODS: Patients were randomized 2:1 into the OCR group (n = 68; OCR 600 mg) or control group (n = 34; interferon beta or no disease-modifying therapy). All received tetanus toxoid (TT)-containing vaccine, Pneumovax (23-valent pneumococcal polysaccharide vaccine [23-PPV]), and keyhole limpet hemocyanin (KLH). The OCR group was subdivided into OCR1 (n = 33) and OCR2 (n = 35) at randomization. The OCR1 group received Prevnar (13-valent conjugate pneumococcal vaccine) 4 weeks after 23-PPV; the OCR2 and control groups received influenza vaccine. Vaccinations started 12 weeks after OCR initiation (OCR group) or on day 1 (control group). RESULTS: Positive response rate to TT vaccine at 8 weeks was 23.9% in the OCR vs 54.5% in the control group. Positive response rate to ≥5 serotypes in 23-PPV at 4 weeks was 71.6% in the OCR and 100% in the control group. Prevnar did not enhance response to pneumococcal serotypes in common with Pneumovax. Humoral response to KLH was decreased in the OCR vs control group. Seroprotection rates at 4 weeks against 5 influenza strains ranged from 55.6% to 80.0% in the OCR2 group and 75.0% to 97.0% in the control group. CONCLUSION: Peripherally B-cell-depleted OCR recipients mounted attenuated humoral responses to clinically relevant vaccines and the neoantigen KLH, suggesting that use of standard nonlive vaccines while on OCR treatment remains a consideration. For seasonal influenza vaccines, it is recommended to vaccinate patients on OCR because a potentially protective humoral response, even if attenuated, can be expected. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence confirming that the humoral response to nonlive vaccines in patients with relapsing multiple sclerosis after OCR treatment is attenuated compared with untreated or interferon beta-treated patients, but they can still be expected to be protective. CLINICALTRIALSGOV IDENTIFIER: NCT02545868.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Inmunogenicidad Vacunal/efectos de los fármacos , Factores Inmunológicos/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/inmunología , Adulto , Femenino , Hemocianinas/inmunología , Humanos , Masculino , Vacunas Neumococicas/inmunología , Toxoide Tetánico/inmunología
11.
Int J Infect Dis ; 97: 182-189, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32474199

RESUMEN

OBJECTIVES: To evaluate the cost-effectiveness of introducing a domestic pneumococcal conjugate vaccine (PCV7-TT) into the Cuban National Immunization Program (NIP). METHODS: We compared PCV7-TT given at two, four and six months of age to a scenario without PCV7-TT, over a ten-year period (2020-2029). We calculated the cost (Cuban pesos - CUP) per Disability Adjusted Life Year (DALY) averted from a Government perspective. We compared results from a static cohort model and a parsimonious prediction model informed by the serotype distribution among pneumococcal carriers and cases. We ran probabilistic and deterministic uncertainty analyses. RESULTS: PCV7-TT could prevent 6897 (95% uncertainty interval, 4344-8750) hospitalizations and 189 (115-253) deaths in children <5 years of age, over the period 2020-2029. This could cost around 25 million (20-31) discounted CUP but would be offset by treatment cost savings of around 23 million (14-31). A parsimonious model predicted less favourable impact and cost-effectiveness but the cost per DALY averted was still less than 0.4 times the current GDP per capita. CONCLUSIONS: PCV7-TT is likely to be cost-effective in Cuba. The impact of the vaccine would need to be carefully monitored following its introduction into the NIP.


Asunto(s)
Programas de Inmunización/economía , Infecciones Neumocócicas/economía , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/economía , Algoritmos , Preescolar , Estudios de Cohortes , Análisis Costo-Beneficio , Cuba , Femenino , Costos de la Atención en Salud , Hospitalización/economía , Humanos , Lactante , Masculino , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/inmunología , Años de Vida Ajustados por Calidad de Vida , Streptococcus pneumoniae/inmunología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/economía , Vacunas Conjugadas/inmunología
12.
BMC Infect Dis ; 20(1): 423, 2020 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-32552726

RESUMEN

BACKGROUND: Streptococcus pneumoniae infections can lead to severe morbidity and mortality, especially in patients with invasive pneumococcal disease (IPD). This study evaluated factors associated with pneumococcal disease, pneumococcal vaccine effectiveness, and risk factors for all-cause mortality in hospitalised adults with pneumococcal disease in Singapore. METHODS: Retrospective case-control study of patients tested for pneumococcal disease with streptococcal urinary antigen testing and at least one sterile site culture, during their admission to a tertiary hospital in Singapore from 2015 to 2017. Patients were defined as cases of IPD or non-IPD, or as controls, based on laboratory results and clinical diagnoses. Multivariable models were constructed to determine factors associated with IPD/non-IPD, and risk factors for mortality from pneumococcal disease. Vaccine effectiveness against IPD/non-IPD was estimated using a variation of the test-negative design. RESULTS: We identified 496 pneumococcal disease cases, of whom 92 (18.5%) had IPD. The mean age of cases was 69.1 ± 15.4 years, and 65.5% were male. Compared with controls (N = 9181), IPD patients were younger (mean age 61.5 ± 16.3 years, vs 72.2 ± 16.1 years in controls; p < 0.001) and with less co-morbidities [median Charlson's score 1 (IQR 0-4), vs 3 (1-5) in controls; p < 0.001]. IPD patients also had the highest proportions with intensive care unit (ICU) admission (20.7%), inpatient mortality (26.1%) and longest median length of stay [9 (IQR 8-17) days]. On multivariable analysis, IPD was negatively associated with prior pneumococcal vaccination (adjusted relative risk ratio = 0.20, 95%CI 0.06-0.69; p = 0.011). Risk factors for mortality among pneumococcal disease patients were ICU admission, diagnosis of IPD, age ≥ 85 years and Charlson's score > 3. CONCLUSION: Patients with pneumococcal disease (especially IPD) were younger and had less co-morbidities than controls, but had higher risk of severe clinical outcomes and mortality. Pneumococcal vaccination effectiveness against IPD was estimated to be about 80%, and should be encouraged among high-risk patients.


Asunto(s)
Hospitalización , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/inmunología , Vacunación , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Morbilidad , Infecciones Neumocócicas/mortalidad , Infecciones Neumocócicas/orina , Estudios Retrospectivos , Factores de Riesgo , Singapur/epidemiología , Centros de Atención Terciaria , Resultado del Tratamiento
13.
Int J Infect Dis ; 98: 194-199, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32553718

RESUMEN

INTRODUCTION: Community-Acquired Pneumonia (CAP) is one of the most frequent causes of hospital admission in children. Our objective is to measure the impact of the introduction of pneumococcal conjugate vaccines on the hospitalization of previously healthy children due to CAP. METHOD: From 2011 to 2016, a partially retrospective, prospective, and descriptive study was carried out on healthy pediatric patients (3 months-14 years old) with CAP, who required hospital admission. Clinical, epidemiological, and demographic characteristics were collected, and vaccination status was obtained from medical records. RESULTS: A total of 292 cases were included, with a mean age of 33.4 months, 54% males. There was a progressive and significant 42% decrease in the number of admissions each year, without significant changes in the annual percentage of parapneumonic pleural effusion (PPE). Fifty-six percent of patients were immunized with a pneumococcal conjugate vaccine (PCV). The percentage of children who were not vaccinated decreased by 14%, and the coverage with PCV-13 increased by 46%. This revealed a significant increase of PPE in vaccinated patients with PCV-7 (63%) compared with unvaccinated (45%) and with PCV-13 (57%), without association with the presence of severe PPE. Moreover, no significant differences in severity or hospital stay were observed in unvaccinated patients, compared to those who were vaccinated. In >2-year-olds, we observed a significant increase in PPE (59%) compared to 45% in younger children. CONCLUSIONS: The increase in vaccination coverage with PCV-13 resulted in a decrease in hospitalizations due to CAP and PPE. Vaccination with PCV-7 is associated in our sample with an increase in PPE but not with severe PPE nor an increase in the hospital stay. There was an epidemiological shift of severe forms of pneumonia and empyema at later ages (>2 years).


Asunto(s)
Infecciones Comunitarias Adquiridas/terapia , Vacunas Neumococicas/administración & dosificación , Neumonía/terapia , Vacunas Conjugadas/administración & dosificación , Adolescente , Niño , Preescolar , Infecciones Comunitarias Adquiridas/prevención & control , Femenino , Hospitalización , Humanos , Inmunización , Lactante , Tiempo de Internación , Masculino , Derrame Pleural/microbiología , Vacunas Neumococicas/inmunología , Neumonía/prevención & control , Estudios Prospectivos , Estudios Retrospectivos , Vacunación , Vacunas Conjugadas/inmunología
14.
Int J Infect Dis ; 98: 113-120, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32562849

RESUMEN

BACKGROUND: Streptococcus pneumoniae remains a major contributor to childhood infections and deaths globally. In Cameroon, the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in July 2011, using a 3-dose Expanded programme on immunization (EPI) schedule administered to infants at 6, 10 and 14 weeks of age. To evaluate PCV13 effects, we assessed pneumococcal nasopharyngeal colonization and serotype distribution among Cameroonian children after PCV13 introduction. METHODS: Nasopharyngeal (NP) swabs were collected from eligible children aged 24-36 months in two cross-sectional surveys conducted from March to July: in 2013 (PCV13-unvaccinated), and in 2015 (PCV13-vaccinated). Using a systematic World Health Organization (WHO) cluster coverage sampling technique in 40 communities, NP swabs collected were processed following WHO recommendations. Standard bacterial culture techniques were used for the isolation of S. pneumoniae from gentamicin-blood agar plates and identification using optochin susceptibility testing. Serotyping was performed using sequential multiplex polymerase chain reaction, supplemented with Quellung test. RESULTS: Among the PCV13-vaccinated children, overall pneumococcal carriage prevalence was 61.8% (426/689) and PCV13 vaccine-type carriage prevalence was 18.0% (123/689). Eleven out of the 13 vaccine serotypes were detected in the vaccinated children. The most common serotypes were 19F (4.5%, 31/689) and 15B/C (7.3%, 50/689). CONCLUSION: In Cameroon, four years after infant vaccination nearly all of the PCV13-serotypes continued to circulate in the population. This suggests that the direct and indirect effects of the vaccination programme have not resulted in expected low levels of vaccine-type transmission. Continuous monitoring is needed to assess the long term effects of the PCV13 on nasopharyngeal carriage and disease.


Asunto(s)
Nasofaringe/microbiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Streptococcus pneumoniae/inmunología , Camerún/epidemiología , Portador Sano/epidemiología , Portador Sano/inmunología , Portador Sano/microbiología , Preescolar , Estudios Transversales , Femenino , Humanos , Programas de Inmunización , Esquemas de Inmunización , Masculino , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/inmunología , Prevalencia , Serogrupo , Serotipificación , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/crecimiento & desarrollo , Streptococcus pneumoniae/aislamiento & purificación , Vacunación
15.
Artículo en Inglés | MEDLINE | ID: mdl-32418510

RESUMEN

The number of notified cases of invasive pneumococcal disease (IPD) in the second quarter of 2019 was higher than the previous quarter as well as the second quarter of 2018. Following the July 2011 replacement of the 7-valent pneumococcal conjugate vaccine (7vPCV) in the childhood immunisation program with the 13-valent pneumococcal conjugate vaccine (13vPCV), there was an initial relatively rapid decline in disease due to the additional six serotypes covered by the 13vPCV across all age groups, however more recently this decline is no longer evident. Over this period the number of cases due to the eleven serotypes additionally covered by the 23-valent pneumococcal polysaccharide vaccine (23vPPV), and also those serotypes not covered by any available vaccine, has been increasing steadily across all age groups.


Asunto(s)
Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Vigilancia de la Población , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Australia , Niño , Preescolar , Notificación de Enfermedades , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Vacunas Neumococicas/administración & dosificación , Streptococcus pneumoniae/inmunología , Factores de Tiempo , Adulto Joven
16.
Artículo en Inglés | MEDLINE | ID: mdl-32418512

RESUMEN

The number of notified cases of invasive pneumococcal disease (IPD) in the third quarter of 2019 was higher than in the previous quarter, but lower than in the third quarter of 2018. Following the July 2011 replacement of the 7-valent pneumococcal conjugate vaccine (7vPCV) in the childhood immunisation program with the 13-valent pneumococcal conjugate vaccine (13vPCV), there was an initial relatively rapid decline in disease due to the additional six serotypes covered by the 13vPCV across all age groups, however more recently this decline is no longer evident. Over this period the number of cases due to the eleven serotypes additionally covered by the 23-valent pneumococcal polysaccharide vaccine (23vPPV), and also those serotypes not covered by any available vaccine, has been increasing steadily across all age groups.


Asunto(s)
Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Vigilancia de la Población , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Australia , Niño , Preescolar , Notificación de Enfermedades , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Vacunas Neumococicas/administración & dosificación , Serogrupo , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/inmunología , Factores de Tiempo , Adulto Joven
17.
Epidemiol Infect ; 148: e187, 2020 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-32418558

RESUMEN

Surveillance of new cases of invasive pneumococcal disease (IPD) in Italy was started in 2007 by the Ministry of Health (MoH). In 2012, pneumococcal childhood vaccination was introduced at the national level and, in 2017, for citizens aged 65 years and over. We describe here IPD epidemiology in Italy over the past 10 years investigating the impact of the vaccine programme on disease burden. Reports of IPD cases, data on serotype and vaccination coverage (VC) data were obtained from MoH annual reports, for the period 2007-2017. IPD notification rate and proportion by year, region, age and serotype were calculated. In 2007, 525 cases were reported (rate 0.88/100 000), rising to 1703 cases (rate 2.82/100 000) in 2017. The distribution of IPD cases by age group over time registered the largest share among individuals aged 65 years and over. A decreasing trend in notification rate was observed among those aged 0-4 years. During the same period, the 24-month VC increased, ranging from 80.9% to 96.7% in 2017. Molecular data indicated re-emergence of PPSV23-specific serotypes and non-vaccine serotypes. We observed an increase in IPD notifications during 2007-2017, likely due to an improved surveillance system, at least in some regions, with the relative quota of IPD notifications decreasing among vaccinated children cohorts. Further strengthening of IPD surveillance system, including molecular and vaccine coverage data, would be needed to assess and inform pneumococcal vaccination strategies in Italy.


Asunto(s)
Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Vacunación/estadística & datos numéricos , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Italia/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
18.
Nature ; 581(7806): 94-99, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32376956

RESUMEN

Vaccines may reduce the burden of antimicrobial resistance, in part by preventing infections for which treatment often includes the use of antibiotics1-4. However, the effects of vaccination on antibiotic consumption remain poorly understood-especially in low- and middle-income countries (LMICs), where the burden of antimicrobial resistance is greatest5. Here we show that vaccines that have recently been implemented in the World Health Organization's Expanded Programme on Immunization reduce antibiotic consumption substantially among children under five years of age in LMICs. By analysing data from large-scale studies of households, we estimate that pneumococcal conjugate vaccines and live attenuated rotavirus vaccines confer 19.7% (95% confidence interval, 3.4-43.4%) and 11.4% (4.0-18.6%) protection against antibiotic-treated episodes of acute respiratory infection and diarrhoea, respectively, in age groups that experience the greatest disease burden attributable to the vaccine-targeted pathogens6,7. Under current coverage levels, pneumococcal and rotavirus vaccines prevent 23.8 million and 13.6 million episodes of antibiotic-treated illness, respectively, among children under five years of age in LMICs each year. Direct protection resulting from the achievement of universal coverage targets for these vaccines could prevent an additional 40.0 million episodes of antibiotic-treated illness. This evidence supports the prioritization of vaccines within the global strategy to combat antimicrobial resistance8.


Asunto(s)
Antibacterianos , Países en Desarrollo/economía , Utilización de Medicamentos/estadística & datos numéricos , Vacunas , Antibacterianos/administración & dosificación , Antibacterianos/economía , Preescolar , Diarrea/tratamiento farmacológico , Diarrea/prevención & control , Diarrea/virología , Farmacorresistencia Microbiana , Utilización de Medicamentos/economía , Humanos , Incidencia , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/inmunología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/prevención & control , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/inmunología , Vacunas/administración & dosificación , Vacunas/economía , Vacunas/inmunología , Organización Mundial de la Salud/organización & administración
19.
BMC Infect Dis ; 20(1): 279, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-32293324

RESUMEN

BACKGROUND: The 13-valent Pneumococcal Conjugate Vaccine (PCV-13) was introduced in the National Immunization Programme (NIP) schedule in Russia in March 2014. Previously, the 7-valent Pneumococcal Conjugate Vaccine (PCV-7) was marketed in Russia in 2009 but has never been offered for mass vaccination. A carriage study was performed among children in Arkhangelsk in 2006. The objective was to determine the prevalence of carriage, serotype distribution, antimicrobial susceptibility and the molecular structure of Streptococcus pneumoniae strains before marketing and introduction of PCV-13. METHODS: A cross-sectional study was conducted on a cluster-randomized sample of children and a self-administrated questionnaire for parents/guardians.  Nasopharyngeal samples were collected from 438 children younger than 7 years attending nurseries and kindergartens in the Arkhangelsk region, Russia. Detailed demographic data, as well as information about the child's health, traveling, exposure to antimicrobials within the last 3 months and anthropometric measurements were collected for all study subjects. Variables extracted from the questionnaire were analysed using statistic regression models to estimate the risk of carriage. All pneumococcal  isolates were examined with susceptibility testing, serotyping and multilocus sequence typing. RESULTS: The overall prevalence of asymptomatic carriage was high and peaking at 36 months with a rate of 57%. PCV-13 covered 67.3% of the detected strains. High rates of non-susceptibility to penicillin, macrolides and multidrug resistance were associated with specific vaccine serotypes, pandemic clones, and local sequence types. Nine percent of isolates represented three globally disseminated disease-associated pandemic clones; penicillin- and macrolide-resistant clones NorwayNT-42 and Poland6B-20, as well as penicillin- and macrolide-susceptible clone Netherlands3-31. A high level of antimicrobial consumption was noted by the study. According to the parent's reports, 89.5% of the children used at least one antimicrobial regime since birth. None of the hypothesised predictors of S. pneumoniae carriage were statistically significant in univariable and multivariable logistic models. CONCLUSIONS: The study identified a high coverage of the PCV-13-vaccine, but serotype replacement and expansion of globally disseminated disease-associated clones with non-vaccine serotypes may be expected. Further surveillance of antimicrobial resistance and serotype distribution is therefore required.


Asunto(s)
Portador Sano/epidemiología , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/inmunología , Vacunas Conjugadas/inmunología , Antibacterianos/uso terapéutico , Portador Sano/microbiología , Niño , Preescolar , Estudios Transversales , Farmacorresistencia Bacteriana Múltiple , Femenino , Humanos , Lactante , Macrólidos/uso terapéutico , Masculino , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Nasofaringe/microbiología , Penicilinas/uso terapéutico , Infecciones Neumocócicas/tratamiento farmacológico , Prevalencia , Federación de Rusia/epidemiología , Serogrupo , Serotipificación , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/aislamiento & purificación
20.
Epidemiol Infect ; 148: e91, 2020 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-32299523

RESUMEN

Studies on community-acquired pneumonia (CAP) and pneumococcal pneumonia (PP) related to the 13-valent pneumococcal conjugate vaccine (PCV13) introduction in Asia are scarce. This study aimed to investigate the epidemiological and microbiological determinants of hospitalised CAP and PP after PCV13 was introduced in Japan. This observational hospital-based surveillance study included children aged ⩽15 years, admitted to hospitals in and around Chiba City, Japan. Participants had bacterial pneumonia based on a positive blood or sputum culture for bacterial pathogens. Serotype and antibiotic-susceptibility testing of Streptococcus pneumoniae and Haemophilus influenzae isolates from patients with bacterial pneumonia were assessed. The CAP hospitalisation rate per 1000 child-years was 17.7, 14.3 and 9.7 in children aged <5 years and 1.18, 2.64 and 0.69 in children aged 5-15 years in 2008, 2012 and 2018, respectively. There was a 45% and 41% reduction in CAP hospitalisation rates, between the pre-PCV7 and PCV13 periods, respectively. Significant reductions occurred in the proportion of CAP due to PP and PCV13 serotypes. Conversely, no change occurred in the proportion of CAP caused by H. influenzae. The incidence of hospitalised CAP in children aged ⩽15 years was significantly reduced after the introduction of PCV13 in Japan. Continuous surveillance is necessary to detect emerging PP serotypes.


Asunto(s)
Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/microbiología , Programas de Inmunización , Vacunas Neumococicas/inmunología , Neumonía Neumocócica/epidemiología , Neumonía Neumocócica/prevención & control , Adolescente , Antibacterianos/farmacología , Niño , Preescolar , Farmacorresistencia Bacteriana , Femenino , Hospitales , Humanos , Lactante , Japón/epidemiología , Masculino , Serogrupo , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/genética , Vacunas Conjugadas
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