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1.
Transpl Infect Dis ; 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32473046

RESUMO

BACKGROUND: The risk of invasive pneumococcal disease is significant among solid organ transplant (SOT) recipients. The optimal pneumococcal vaccination strategy for SOT patients is not known. METHODS: The potential kidney transplant recipients in dialysis were randomised into two arms: to receive a 23-valent pneumococcal polysaccharide vaccine (PPV23) before transplantation or to receive a 13-valent pneumococcal conjugate vaccine (PCV13) before transplantation and a second dose of PCV13 six months after the transplantation. Serotype-specific antibody concentrations and opsonophagocytic activity (OPA) were measured before and after the first vaccination (visits V1,V2) and six and seven months after the transplantation, e.g. before and after the second PCV13 (visits V3,V4). RESULTS: Out of 133 participants, 48 (PCV13 arm) and 46 (PPV23 arm) received a kidney transplant, and 37 + 37 in both arms completed the study. After the first vaccination , the geometric mean concentrations (GMCs) in the PCV13 arm were significantly higher for 9/13 serotypes and the OPA geometric mean titres (GMTs) were significantly higher for 4/13 serotypes. At V3, the antibody levels had declined but OPA remained significantly higher for 7/13 (PCV13) vs 4/13 (PPV23) serotypes. At V4, the GMCs for 9/13 serotypes and the GMTs for 12/13 serotypes were significantly higher in the PCV13 arm. The GMCs but not GMTs were lower than at V2. There was no difference in adverse effects. No vaccine-related allograft rejection was detected. CONCLUSIONS: The immunogenicity of PCV13 was better in dialysis patients, and revaccination with PCV13 was immunogenic and safe .

2.
Hum Vaccin Immunother ; 15(12): 2910-2913, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31216225

RESUMO

The 23-valent pneumococcal polysaccharide vaccine (PPV23) given alone is ineffective in patients with chronic lymphocytic leukemia (CLL) and better antibody response is achieved with pneumococcal conjugate vaccines (PCVs). In this study, we determine whether CLL patients would achieve a significant antibody response and broaden their serotype coverage against invasive pneumococcal disease (IPD) with PPV23 given five years after the 7-valent conjugate vaccine (PCV7). A total of 24 patients with CLL and eight controls were vaccinated with PPV23 five years after PCV7. Blood samples for evaluation of antibody response to PCV7 serotypes and PPV23 serotypes 5 and 7 were taken before vaccination and one month after it. Post-vaccination samples were available from 20 patients. IgG antibodies were measured with ELISA. Antibody concentrations after PPV23 were significantly lower in CLL patients for six of the PCV7 serotypes and for both PPV23 serotypes. Only 10% to 15% of CLL patients achieved an antibody response suggested to be protective against IPD. Hence, PCV7 given five years before PPV23 did not improve antibody response in patients with CLL. Based on our results, PPV23 given after a PCV primer is not useful against IPD in CLL patients.

3.
J Immunol Methods ; 460: 72-78, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29935210

RESUMO

The aim of this study was to compare the results of serological assays using pneumococcal proteins or polysaccharides for the detection of pneumococcal infection in childhood pneumonia. Serological assays measured IgG against eight pneumococcal proteins (Ply,CbpA,PspA1,PspA2,PcpA,PhtD,StkP-C,PcsB-N), C-polysaccharide [in the whole study population, n = 183], or 19 pneumococcal capsular polysaccharides (1,2,4,5,6B,7F,8,9 V,10A,11A,12F,14,15B,17F,18C,19F,20,23F,33F) [only in a subgroup of patients, n = 53] in paired serum samples of children aged <5 years-old hospitalized with clinical and radiological diagnosis of community-acquired pneumonia. We also performed an inhibition of binding test with the anti-capsular polysaccharide assay in order to confirm the specificity of the antibody responses detected. Invasive pneumococcal pneumonia was investigated by blood culture and PCR (ply-primer). Among 183 children, the anti-protein assay detected antibody response in 77/183(42.1%) patients and the anti-C-polysaccharide assay in 28/183(15.3%) patients. In a subgroup of 53 children, the anti-protein assay detected response in 32/53(60.4%) patients, the anti-C-polysaccharide assay in 11/53(20.8%) patients, and the anti-capsular polysaccharide in 25/53(47.2%) patients. Simultaneous antibody responses against ≥2 different capsular polysaccharides were detected in 11/53(20.8%) patients and this finding could not be explained by cross-reactivity between different serotypes. Among 13 patients with invasive pneumococcal pneumonia, the sensitivity of the anti-protein assay was 92.3%(12/13), of the anti-C-polysaccharide assay 30.8%(4/13), and of the anti-capsular polysaccharide assay 46.2%(6/13). The serological assay using pneumococcal proteins is more sensitive for the detection of pneumococcal infection in children with pneumonia than the assay using pneumococcal polysaccharides. Future studies on childhood pneumonia aetiology should consider applying serological assays using pneumococcal proteins.


Assuntos
Anticorpos Antibacterianos , Proteínas de Bactérias/química , Infecções Comunitárias Adquiridas , Pneumonia Pneumocócica , Polissacarídeos Bacterianos/química , Streptococcus pneumoniae , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Lactente , Masculino , Pneumonia Pneumocócica/sangue , Pneumonia Pneumocócica/diagnóstico , Pneumonia Pneumocócica/imunologia , Estudos Prospectivos , Sensibilidade e Especificidade , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/metabolismo
4.
Infect Dis (Lond) ; 50(9): 705-713, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29688138

RESUMO

BACKGROUND: We studied Immunoglobulin G (IgG) antibody responses against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in young children with acute viral type respiratory infection and analyzed the findings in a multivariate model including age, nasopharyngeal carriage of the tested bacteria and pneumococcal vaccination. METHODS: We included 227 children aged 6-23 months with acute respiratory infection. Nasopharyngeal aspirates were tested for bacterial carriage through detection of messenger RNA (mRNA) transcript with nCounter analysis. Acute and convalescent serum samples were tested for IgG antibody response against eight pneumococcal proteins, three proteins from H. influenzae and five proteins from M. catarrhalis in a fluorescent multiplex immunoassay. RESULTS: A two-fold or greater increase in antibodies to S. pneumoniae, H. influenzae and M. catarrhalis was detected in 27.8, 9.7 and 14.1%, respectively. Nasopharyngeal carriage of each of the studied bacteria was not associated with antibody response detection against each respective bacterium. Furthermore, neither age nor pneumococcal vaccination were independently associated to detection of antibody response against the studied bacteria. Children who carried H. influenzae had higher frequency of colonization by M. catarrhalis (175 [80.3%] vs. 2 [22.2%]; p < .001) than those without H. influenzae. Also, children with acute otitis media tended to have higher frequency of antibody response to S. pneumoniae. CONCLUSION: Nasopharyngeal colonization by S. pneumoniae, H. influenzae and M. catarrhalis did not induce significant increases in antibody levels to these bacteria. Carriage of pathogenic bacteria in the nasopharynx is not able to elicit antibody responses to protein antigens similar to those caused by symptomatic infections.


Assuntos
Portador Sadio/microbiologia , Haemophilus influenzae/imunologia , Nasofaringe/microbiologia , Infecções Respiratórias/imunologia , Streptococcus pneumoniae/imunologia , Doença Aguda , Anticorpos Antibacterianos/sangue , Feminino , Haemophilus influenzae/genética , Haemophilus influenzae/isolamento & purificação , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Lactente , Masculino , /isolamento & purificação , Análise Multivariada , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/imunologia , Infecções Respiratórias/microbiologia , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação
5.
Vaccine ; 36(20): 2774-2782, 2018 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-29655626

RESUMO

BACKGROUND: We compared PCV7 serological response and protection against carriage in infants receiving 3 doses (2, 4, 6 months; 3+0 schedule) to those receiving a booster (12 months; 3+1). METHODS: A prospective, randomized controlled study, conducted between 2005 and 2008, before PCVs were implemented in Israel. Healthy infants were randomized 1:1:1 to receive 3+1, 3+0 and 0+2 (control group; 12, 18 months doses). Nasopharyngeal/oropharyngeal swabs were obtained at all visits. Serum serotype-specific IgG concentrations and opsonic activities (OPA) were measured at 2, 7, 13 and 19 months. This study was registered with Current Controlled Trials, Ltd. ISRCTN28445844. RESULTS: Overall, 544 infants were enrolled: 3+1 (n = 178), 3+0 (n = 178) and 0+2 (n = 188). Post-priming (7 months), antibody concentrations were similar in both groups, except for serotype 18C (higher in 3+0). Post-booster (13, 19 months), ELISA and OPA levels were significantly higher in 3+1 than in 3+0 group. Nasopharyngeal/oropharyngeal cultures were positive for Streptococcus pneumoniae in 2673 (54.3%) visits. Acquisition rates (vaccine and non-vaccine serotypes) were similar for 3+1 and 3+0 groups at 7-30 months and for 0+2 group at 19-30 months. CONCLUSIONS: PCV7 booster after 3 priming doses increased substantially IgG concentrations but did not further reduced vaccine-serotype nasopharyngeal acquisition, suggesting that protection from pneumococcal carriage does not depend primarily on serum IgG.


Assuntos
Portador Sadio/microbiologia , Vacina Pneumocócica Conjugada Heptavalente/imunologia , Imunização Secundária , Imunoglobulina G/sangue , Infecções Pneumocócicas/prevenção & controle , Streptococcus pneumoniae/imunologia , Anticorpos Antibacterianos/sangue , Feminino , Vacina Pneumocócica Conjugada Heptavalente/administração & dosagem , Humanos , Lactente , Israel , Masculino , Nasofaringe/microbiologia , Orofaringe/microbiologia , Estudos Prospectivos , Sorogrupo , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologia
6.
Hum Vaccin Immunother ; 14(6): 1471-1474, 2018 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-29420116

RESUMO

Patients with chronic lymphocytic leukemia (CLL) are at a high risk for infections caused by Streptococcus pneumoniae. A pneumococcal conjugate vaccine (PCV) can induce a significant antibody response for some CLL patients. In this study we investigated antibody persistence after PCV7 in patients with CLL. The study material comprised 24 patients with CLL and 8 immunocompetent controls. The median antibody concentrations five years after PCV7 were lower for six pneumococcal serotypes in patients with CLL compared to controls, but the difference was not statistically significant. Depending on the serotype, the percentage of the CLL patients with antibody levels suggested to provide protection against invasive pneumococcal disease (IPD) varied from 29 to 71% five years after vaccination. This data suggests that PCV could result in antibody persistence at least five years in CLL patients.


Assuntos
Anticorpos Antibacterianos/sangue , Vacina Pneumocócica Conjugada Heptavalente/imunologia , Leucemia Linfocítica Crônica de Células B/complicações , Infecções Pneumocócicas/prevenção & controle , Streptococcus pneumoniae/imunologia , Assistência ao Convalescente , Idoso , Idoso de 80 Anos ou mais , Feminino , Vacina Pneumocócica Conjugada Heptavalente/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
7.
J. pediatr. (Rio J.) ; 94(1): 23-30, Jan.-Feb. 2018. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-894095

RESUMO

Abstract Objective: Community-acquired pneumonia is an important cause of morbidity in childhood, but the detection of its causative agent remains a diagnostic challenge. The authors aimed to evaluate the role of the chest radiograph to identify cases of community-aquired pneumonia caused by typical bacteria. Methods: The frequency of infection by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis was compared in non-hospitalized children with clinical diagnosis of community acquired pneumonia aged 2-59 months with or without radiological confirmation (n = 249 and 366, respectively). Infection by S. pneumoniae was diagnosed by the detection of a serological response against at least one of eight pneumococcal proteins (defined as an increase ≥2-fold in the IgG levels against Ply, CbpA, PspA1 and PspA2, PhtD, StkP-C, and PcsB-N, or an increase ≥1.5-fold against PcpA). Infection by H. influenzae and M. catarrhalis was defined as an increase ≥2-fold on the levels of microbe-specific IgG. Results: Children with radiologically confirmed pneumonia had higher rates of infection by S. pneumoniae. The presence of pneumococcal infection increased the odds of having radiologically confirmed pneumonia by 2.8 times (95% CI: 1.8-4.3). The negative predictive value of the normal chest radiograph for infection by S. pneumoniae was 86.3% (95% CI: 82.4-89.7%). There was no difference on the rates of infection by H. influenzae and M. catarrhalis between children with community-acquired pneumonia with and without radiological confirmation. Conclusions: Among children with clinical diagnosis of community-acquired pneumonia submitted to chest radiograph, those with radiologically confirmed pneumonia present a higher rate of infection by S. pneumoniae when compared with those with a normal chest radiograph.


Resumo Objetivo: Avaliar o papel do raios X de tórax na identificação de casos de pneumonia adquirida na comunidade (PAC) causada por agentes bacterianos. Métodos: A frequência de infecção por Streptococcus pneumoniae, Haemophilus influenzae e Moraxella catarrhalis em crianças com PAC não hospitalizadas foi comparada com a presença de confirmação radiológica da pneumonia (n = 249 crianças com pneumonia radiologicamente confirmada e 366 crianças com raios X de tórax normal). Infecção por S. pneumoniae foi diagnosticada com base na resposta sorológica a pelo menos uma dentre oito proteínas pneumocócicas investigadas (aumento ≥ 2 vezes nos níveis de IgG em relação a Ply, CbpA, PspA1 e 2, PhtD, StkP-C e PcsB-N ou aumento≥ 1,5 vez em relação aPcpA). Infecção por H. influenzae e M. catarrhalis foi definida por aumento ≥ 2 vezes nos níveis de IgG específica a antígenos de cada agente. Resultados: Crianças com pneumonia radiologicamente confirmada apresentaram maior taxa de infecção pelo pneumococo. Além disso, a presença de infecção pneumocócica foi um fator preditor de pneumonia radiologicamente confirmada, o que aumenta sua chance de detecção em 2,8 vezes (IC 95%: 1,8-4,3). O valor preditivo negativo do raios X normal para a infecção por S. pneumoniae foi 86,3% (IC95%: 82,4%-89,7%). Não houve diferença nas frequências de infecção por H. influenzae e M. catarrhalis entre crianças com PAC com ou sem confirmação radiológica. Conclusão: Crianças com diagnóstico clínico de PAC submetidas a um raios X de tórax que apresentam confirmação radiológica têm maior taxa de infecção por S. pneumoniae comparadas com as crianças com raios X normal.

8.
J Pediatr (Rio J) ; 94(1): 23-30, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28668258

RESUMO

OBJECTIVE: Community-acquired pneumonia is an important cause of morbidity in childhood, but the detection of its causative agent remains a diagnostic challenge. The authors aimed to evaluate the role of the chest radiograph to identify cases of community-aquired pneumonia caused by typical bacteria. METHODS: The frequency of infection by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis was compared in non-hospitalized children with clinical diagnosis of community acquired pneumonia aged 2-59 months with or without radiological confirmation (n=249 and 366, respectively). Infection by S. pneumoniae was diagnosed by the detection of a serological response against at least one of eight pneumococcal proteins (defined as an increase ≥2-fold in the IgG levels against Ply, CbpA, PspA1 and PspA2, PhtD, StkP-C, and PcsB-N, or an increase ≥1.5-fold against PcpA). Infection by H. influenzae and M. catarrhalis was defined as an increase ≥2-fold on the levels of microbe-specific IgG. RESULTS: Children with radiologically confirmed pneumonia had higher rates of infection by S. pneumoniae. The presence of pneumococcal infection increased the odds of having radiologically confirmed pneumonia by 2.8 times (95% CI: 1.8-4.3). The negative predictive value of the normal chest radiograph for infection by S. pneumoniae was 86.3% (95% CI: 82.4-89.7%). There was no difference on the rates of infection by H. influenzae and M. catarrhalis between children with community-acquired pneumonia with and without radiological confirmation. CONCLUSIONS: Among children with clinical diagnosis of community-acquired pneumonia submitted to chest radiograph, those with radiologically confirmed pneumonia present a higher rate of infection by S. pneumoniae when compared with those with a normal chest radiograph.


Assuntos
Infecções por Haemophilus/diagnóstico por imagem , Infecções por Moraxellaceae/diagnóstico por imagem , Pneumonia Bacteriana/diagnóstico por imagem , Pneumonia Bacteriana/microbiologia , Radiografia Torácica , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/sangue , Pré-Escolar , Infecções Comunitárias Adquiridas/diagnóstico por imagem , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Haemophilus influenzae/imunologia , Haemophilus influenzae/isolamento & purificação , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Lactente , Masculino , /isolamento & purificação , Pneumonia Pneumocócica/diagnóstico por imagem , Estudos Prospectivos , Sensibilidade e Especificidade , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/isolamento & purificação
9.
Vaccine ; 35(6): 909-915, 2017 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-28069358

RESUMO

OBJECTIVES: Pneumococcal vaccination is recommended to lower the risk of posttraumatic meningitis, and early vaccination may be of importance. After both trauma and central nervous system injury, immune-suppression may occur, which could affect T-cell function and the response to T-cell dependent vaccines. We therefore aimed to investigate the response to early vaccination with a T-cell independent pneumococcal polysaccharide vaccine (PPSV). METHODS: Thirty-three patients with basilar skull fracture and 23 patients undergoing transsphenoidal pituitary gland surgery were vaccinated with PPSV within 10days after neurotrauma or neurosurgery. Twenty-nine neurosurgical patients vaccinated ⩾3weeks after neurotrauma or neurosurgery served as controls. Serotype-specific anti-polysaccharide binding IgG antibody levels to serotypes 4, 6B, 9V, 14, 18C, 19F and 23F were determined by enzyme immunoassay. RESULTS: The vaccination was safe and a highly significant antibody response was found against all serotypes in all groups (p<0.001 for each of the serotypes). There were no differences between groups or in the group by time interaction in any of the serotypes. After early and late vaccination, protective levels were found in >80% for serotypes 9V, 14, 18C, 19F and 23F and in 70% and 50% for serotypes 6B and 4, respectively. CONCLUSION: Patients vaccinated with PPSV within 10days after neurotrauma or neurosurgery respond similarly to those vaccinated after ⩾3weeks, indicating that PPSV can be administered early after neurotrauma or neurosurgery. CLINICAL TRIALS REGISTRATION: NCT02806284.


Assuntos
Anticorpos Antibacterianos/biossíntese , Hipófise/imunologia , Vacinas Pneumocócicas/administração & dosagem , Pneumonia Pneumocócica/prevenção & controle , Fratura da Base do Crânio/imunologia , Vacinação , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Esquemas de Imunização , Imunoglobulina G/biossíntese , Masculino , Pessoa de Meia-Idade , Hipófise/patologia , Hipófise/cirurgia , Pneumonia Pneumocócica/imunologia , Pneumonia Pneumocócica/microbiologia , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/imunologia , Sorogrupo , Fratura da Base do Crânio/patologia , Fratura da Base do Crânio/cirurgia , Osso Esfenoide/imunologia , Osso Esfenoide/cirurgia , Streptococcus pneumoniae/imunologia , Fatores de Tempo
11.
Clin Vaccine Immunol ; 23(11): 878-883, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27581439

RESUMO

Conserved protein antigens have been investigated as vaccine candidates against respiratory pathogens. We evaluated the natural development of antibodies against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis proteins during childhood. Serum samples were collected from 50 healthy children from their first months to age 13 years (median sampling interval, 6 months). We also analyzed serum samples from 24 adults. Serum IgG antibodies against eight pneumococcal proteins (Ply, CbpA, PspA 1 and 2, PcpA, PhtD, StkP-C, and PcsB-N), three H. influenzae proteins, and five M. catarrhalis proteins were measured using a multiplexed bead-based immunoassay. Antibody levels were analyzed using multilevel mixed-effects regression and Spearman's correlation. Antibody levels against pneumococcal proteins peaked at 3 to 5 years of age and then reached a plateau. Antibody levels against H. influenzae proteins peaked during the second year and then stabilized. Antibody levels against M. catarrhalis proteins peaked during the first year and then slowly decreased. Peak antibody levels during childhood were higher than those of adults. Correlations among pneumococcal antibody levels were highest among anti-CbpA, anti-PcpA, and anti-PhtD antibodies (r = 0.71 to 0.75; P < 0.001). The children presented 854 symptomatic respiratory infections on 586 occasions. Symptomatic respiratory infections did not improve prediction of antibody levels in the regression model. The maturation of immune responses against the investigated pneumococcal proteins shares similarities, especially among CbpA, PcpA, and PhtD. Antibody production against H. influenzae and M. catarrhalis proteins starts early in life and reaches peak levels earlier than antibody production against the pneumococcal proteins. Basal antibody levels are not related to the occurrence of symptomatic respiratory infections.


Assuntos
Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Haemophilus influenzae/imunologia , Streptococcus pneumoniae/imunologia , Adolescente , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/química , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino
12.
J Immunol Methods ; 433: 31-7, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26928648

RESUMO

The etiological diagnosis of infection by Streptococcus pneumoniae in children is difficult, and the use of indirect techniques is frequently warranted. We aimed to study the use of pneumococcal proteins for the serological diagnosis of pneumococcal infection in children with pneumonia. We analyzed paired serum samples from 13 Brazilian children with invasive pneumococcal pneumonia (positive control group) and 23 Finnish children with viral pharyngitis (negative control group), all aged <5years-old. Children with pharyngitis were evaluated for oropharyngeal colonization, and none of them carried S. pneumoniae. We used a multiplex bead-based assay with eight proteins: Ply, CbpA, PspA1 and 2, PcpA, PhtD, StkP and PcsB. The optimal cut-off for increase in antibody level for the diagnosis of pneumococcal infection was determined for each antigen by ROC curve analysis. The positive control group had a significantly higher rate of ≥2-fold rise in antibody levels against all pneumococcal proteins, except Ply, compared to the negative controls. The cut-off of ≥2-fold increase in antibody levels was accurate for pneumococcal infection diagnosis for all investigated antigens. However, there was a substantial increase in the accuracy of the test with a cut-off of ≥1.52-fold rise in antibody levels for PcpA. When using the investigated protein antigens for the diagnosis of pneumococcal infection, the detection of response against at least one antigen was highly sensitive (92.31%) and specific (91.30%). The use of serology with pneumococcal proteins is a promising method for the diagnosis of pneumococcal infection in children with pneumonia. The use of a ≥2-fold increase cut-off is adequate for most pneumococcal proteins.


Assuntos
Anticorpos Antibacterianos/sangue , Imunoensaio/métodos , Pneumonia Pneumocócica/diagnóstico , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Brasil , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Microesferas , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Testes Sorológicos , Streptococcus pneumoniae/isolamento & purificação
13.
Pediatr Infect Dis J ; 35(6): 683-9, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26954601

RESUMO

BACKGROUND: Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are common causative agents of respiratory infections. Pneumococcal conjugate vaccines have been introduced recently, but their effect on the natural immunity against protein antigens from these pathogens has not been elucidated. METHODS: This was an age-matched observational controlled study that evaluated the influence of 10-valent pneumococcal conjugate vaccines on the levels of antibodies and frequencies of antibody responses against proteins from S. pneumoniae, H. influenzae and M. catarrhalis in serum samples of children with community-acquired pneumonia. Eight pneumococcal proteins (pneumolysin, choline-binding protein A, pneumococcal surface protein A families 1 and 2, pneumococcal choline-binding protein A, pneumococcal histidine triad protein D, serine/threonine protein kinase, protein required for cell wall separation of group B streptococcus), 3 proteins from H. influenzae (including protein D) and 5 M. catarrhalis proteins were investigated. RESULTS: The study group comprised 38 vaccinated children and 114 age-matched controls (median age: 14.5 vs. 14.6 months, respectively; P = 0.997), all with community-acquired pneumonia. There was no difference on clinical baseline characteristics between vaccinated and unvaccinated children. Vaccinated children had significantly lower levels of antibodies against 4 of the studied pneumococcal antigens (P = 0.048 for Ply, P = 0.018 for pneumococcal surface protein A, P = 0.001 for StkP and P = 0.028 for PcsB) and higher levels of antibodies against M. catarrhalis (P = 0.015). Nevertheless, the vaccination status did not significantly affect the rates of antibody responses against S. pneumoniae, H. influenzae and M. catarrhalis. CONCLUSIONS: In spite of the differences that have been found on the level of natural antibodies, no effect from pneumococcal vaccination was observed on the rate of immune responses associated with community-acquired pneumonia against protein antigens from S. pneumoniae, H. influenzae and M. catarrhalis.


Assuntos
Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Haemophilus influenzae/imunologia , Vacinas Pneumocócicas/imunologia , Pneumonia Bacteriana/microbiologia , Streptococcus pneumoniae/imunologia , Formação de Anticorpos , Proteínas de Bactérias/imunologia , Pré-Escolar , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Haemophilus influenzae/isolamento & purificação , Humanos , Lactente , Masculino , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/isolamento & purificação
14.
Lancet Infect Dis ; 15(4): 365-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25701562

Assuntos
Feminino , Humanos , Masculino
15.
J Infect ; 70(6): 577-84, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25562448

RESUMO

BACKGROUND: Recent international guidelines recommend vaccination with a 13-valent pneumococcal conjugate vaccine to reduce the risk of meningitis after neurotrauma with cerebrospinal fluid leak. The antibody response and optimal time point for vaccination have not been established and because the risk of meningitis is at the highest shortly after trauma, early vaccination is preferable. This study aimed to investigate the antibody response and to ensure that central nervous system injury-induced immunodepression did not affect the response to a T-cell-dependent conjugate vaccine when administered shortly after the injury. METHODS: So as not to interfere with routine pneumococcal vaccination, a conjugate vaccine against Haemophilus influenza type b (Hib) was chosen for the study. Thirty-three patients with basilar skull fracture and 23 patients undergoing transsphenoidal pituitary gland surgery were vaccinated within 10 days after trauma/surgery and 29 control patients at least three weeks after trauma/surgery. Sera were collected pre- and post-vaccination for analysis of anti-Hib concentration. RESULTS: Four patients with post-vaccination target antibody concentration before vaccination were excluded from analysis. In the neurotrauma and neurosurgery groups 10/32 (31%) and 5/20 (25%) patients, respectively, were non-responders compared with 3/29 (10%) in the control group. Log10 anti-Hib concentrations in the neurotrauma, neurosurgery and control groups were 1.52 ± 0.15, 1.38 ± 0.15 and 1.81 ± 0.12 µg/ml, respectively. CONCLUSIONS: The majority of the patients responded to vaccination. However, the number of responders was significantly decreased and antibody concentration significantly lower in patients vaccinated early after the trauma/surgery. Investigation of the pneumococcal conjugate vaccine response in neurotrauma patients is therefore urgent.


Assuntos
Anticorpos Antibacterianos/sangue , Vacinas Anti-Haemophilus/administração & dosagem , Haemophilus influenzae tipo b/imunologia , Vacinas Pneumocócicas/administração & dosagem , Vacinação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/imunologia , Feminino , Vacinas Anti-Haemophilus/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Neurocirurgia , Linfócitos T/imunologia , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologia , Adulto Jovem
16.
J Immunol Methods ; 405: 130-43, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24530690

RESUMO

Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are pathogens commonly associated with infectious diseases in childhood. This study aimed to develop a fluorescent multiplexed bead-based immunoassay (FMIA) using recombinant proteins for the quantitation of serum IgG antibodies against these bacteria. Eight pneumococcal proteins (Ply, CbpA, PspA1, PspA2, PcpA, PhtD, SP1732-3 and SP2216-1), 3 proteins of H. influenzae (NTHi Protein D, NTHi0371-1, NTHi0830), and 5 proteins of M. catarrhalis (MC Omp CD, MC_RH4_2506, MC_RH4_1701, MC_RH4_3729-1, MC_RH4_4730) were used to develop the FMIA. Optimal coupling concentrations for each protein, comparison of singleplex and multiplex assays, specificity, reproducibility, and correlation to ELISA for six pneumococcal antigens were determined for validation. FMIA was then used to analyze acute and convalescent paired serum samples of 50 children with non-severe pneumonia. The coupling concentrations varied for different antigens, ranging from 1.6 to 32µg of protein/million beads. Correlation between singleplexed and multiplexed assays was excellent, with R≥0.987. The FMIA was specific, reaching >92% homologous inhibition for all specificities; heterologous inhibition ≥20% was found only in six cases. The assay was repeatable, with averages of intra-assay variation ≤10.5%, day-to-day variation ≤9.7% and variation between technicians ≤9.1%. Comparison with ELISA for pneumococcal antigens demonstrated good correlation with R ranging from 0.854 (PspA2) to 0.976 (PcpA). The samples from children showed a wide range of antibody concentrations and increases in convalescent samples. In conclusion, the FMIA was sensitive, specific, and repeatable, using small amounts of recombinant proteins and sera to detect antibodies against S. pneumoniae, H. influenzae and M. catarrhalis. The methodology would be suitable for studies investigating etiological diagnosis and in experimental vaccine studies.


Assuntos
Proteínas de Bactérias/imunologia , Haemophilus influenzae/imunologia , Imunoensaio/métodos , Imunoglobulina G/imunologia , Streptococcus pneumoniae/imunologia , Doença Aguda , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/imunologia , Fluorescência , Humanos , Imunoglobulina G/sangue , Lactente , Microesferas , Otite Média/sangue , Otite Média/diagnóstico , Otite Média/microbiologia , Pneumonia/sangue , Pneumonia/diagnóstico , Pneumonia/imunologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
Vaccine ; 32(1): 153-8, 2013 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-24016803

RESUMO

Evaluating vaccine efficacy for protection against colonisation (VEcol) with bacterial pathogens is an area of growing interest. In this article, we consider estimation of VEcol for colonisation with Streptococcus pneumoniae (the pneumococcus). Colonisation is a common, recurrent and multi-type endpoint that requires both careful definition of the vaccine efficacy parameter and the corresponding method of estimation. We review recent developments in the area and provide practical guidelines for choosing the estimand and the estimation method in trials with a colonisation endpoint. We concentrate on methods that are based on a cross-sectional study design, in which only one nasopharyngeal sample is obtained per study subject.


Assuntos
Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Portador Sadio/microbiologia , Estudos Transversais , Humanos , Nasofaringe/imunologia , Nasofaringe/microbiologia , Infecções Pneumocócicas/epidemiologia , Prevalência
18.
Vaccine ; 32(1): 159-64, 2013 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-23871614

RESUMO

Evaluation of vaccine efficacy for protection against colonisation (VEcol) with Streptococcus pneumoniae and other bacterial pathogens is often based on a cross-sectional study design, in which only one nasopharyngeal sample is obtained per study subject. Here we investigate the feasibility of this study design by investigating a number of practical design problems. Specific questions are related to the timing of colonisation measurement with respect to the time of vaccination, the adjustment for the within-host replacement of vaccine-type colonisation by the non-vaccine type pneumococci, and the impact of multiple serotype colonisation on VEcol estimation. We also discuss the issue of choosing the control vaccine, including comparison of two active pneumococcal vaccines, as well as the sample size and the statistical power of colonisation endpoint trials. In addition, the statistical design with the specific aim to include information about VEcol in the licensure process of new pneumococcal vaccine products is discussed.


Assuntos
Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Ensaios Clínicos como Assunto , Estudos Transversais , Humanos , Nasofaringe/imunologia , Nasofaringe/microbiologia , Streptococcus pneumoniae/isolamento & purificação , Fatores de Tempo , Vacinação
19.
Clin Vaccine Immunol ; 20(7): 1034-40, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23658394

RESUMO

To provide more extensive evidence of long-term effects of vaccination on immunity against Streptococcus pneumoniae, a follow-up study of the Finnish Otitis Media (FinOM) Vaccine Trial was conducted. One of the objectives was to assess the persistence and avidity of pneumococcal antibodies 4 years after pneumococcal vaccination given in infancy. Children with complete follow-up in the FinOM trial up to 24 months of age were invited to a single visit in their fifth year of life. A blood sample was taken from all children for determination of anticapsular antibody concentrations to vaccine serotypes and avidity of antibodies to three serotypes. Children had been vaccinated at 2, 4, 6, and 12 months of age with 7-valent pneumococcal capsular polysaccharide, CRM197 conjugate vaccine (PCV7), or a control vaccine. Serum IgG antibody concentrations to vaccine serotypes remained significantly higher in children who had received PCV7 than in control children for 4 years after the fourth PCV7 dose. Concentrations of antibodies to frequently carried serotypes (6B and 19F) declined less than those of antibodies to a rarely carried serotype (4), suggesting that natural boosting contributed to antibody persistence. Furthermore, antibody avidity was significantly higher in PCV7 than control vaccine recipients. Four doses of PCV7 given in infancy elicit long-lasting antibody responses with high avidity. (This study has been registered at ClinicalTrials.gov under registration no. NCT00378417.).


Assuntos
Anticorpos Antibacterianos/sangue , Afinidade de Anticorpos , Imunização/métodos , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Pré-Escolar , Feminino , Finlândia , Seguimentos , Vacina Pneumocócica Conjugada Heptavalente , Humanos , Imunoglobulina G/sangue , Lactente , Masculino , Vacinas Pneumocócicas/administração & dosagem , Fatores de Tempo
20.
Clin Vaccine Immunol ; 19(10): 1618-23, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22875604

RESUMO

In immunogenicity trials of pneumococcal conjugate vaccines (PCVs), only IgG antibody concentrations to pneumococcal capsular polysaccharides (PPSs) are usually determined, along with the opsonophagocytic activity (OPA) of antipneumococcal antibodies. We aimed to determine the role of both IgG and IgM in OPA in toddlers receiving one dose of 9-valent PCV (PCV9). The IgG and IgM antibody concentrations to PPSs of serotypes 6A, 9V, 14, 19F, and 23F were measured by enzyme immunoassay in sera from toddlers (ages 18 to 35 months) 1 month after a single PCV9 dose. The OPA for the same serotypes was measured by multiplexed opsonophagocytosis assay (MOPA). Further, IgG and IgM concentrations and MOPA were measured to PPS of serotypes 6A, 14, and 19F in sera collected 12 months after vaccination. The detected MOPA titers were high in comparison to the IgG concentrations 1 month after immunization. The IgM concentrations were higher than IgG concentrations for serotypes 6A and 14 (P < 0.001) and as high as IgG for serotypes 9V, 19F, and 23F. Correlation of the IgM antibody concentrations with MOPA (r = 0.35 to 0.65) was stronger compared to that of the IgG antibodies (r = 0.07 to 0.41). The depletion of IgG antibodies in three sets of pooled sera only slightly decreased the OPA activity against serotype 14. At 12 months after immunization, 50 to 100% of serum samples still showed detectable MOPA activity against serotypes 6A, 14, and 19F. Our results suggest that IgM contributes to OPA 1 month after a single PCV9 vaccination in toddlers and that functionally active IgM and IgG antibodies persist for at least a year.


Assuntos
Anticorpos Antibacterianos/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Fagocitose , Vacinas Pneumocócicas/imunologia , Vacinas Conjugadas/imunologia , Anticorpos Antibacterianos/imunologia , Pré-Escolar , Humanos , Imunização , Lactente , Proteínas Opsonizantes/imunologia , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Polissacarídeos Bacterianos/imunologia , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/imunologia , Vacinas Conjugadas/administração & dosagem
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