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1.
J Infect Dis ; 229(1): 95-107, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-37477875

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. METHODS: Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. RESULTS: Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2. CONCLUSIONS: ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration. NCT03636906.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Humanos , Lactente , Anticorpos Neutralizantes , Anticorpos Antivirais , Vetores Genéticos , Imunogenicidade da Vacina , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sincicial Respiratório Humano/genética
2.
N Engl J Med ; 385(16): 1485-1495, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34644472

RESUMO

BACKGROUND: Cell-culture-derived influenza vaccines may enable a closer antigenic match to circulating strains of influenza virus by avoiding egg-adapted mutations. METHODS: We evaluated the efficacy of a cell-culture-derived quadrivalent inactivated influenza vaccine (IIV4c) using a Madin-Darby canine kidney cell line in children and adolescents 2 to less than 18 years of age. During three influenza seasons, participants from eight countries were enrolled in an observer-blinded, randomized clinical trial comparing IIV4c with a noninfluenza vaccine (meningococcal ACWY). All the participants received a dose of a trial vaccine. Children 2 to less than 9 years of age without previous influenza vaccination who were assigned to the IIV4c group received a second dose on day 29; their counterparts who were assigned to the comparator group received placebo. Participants were followed for at least 180 days for efficacy and safety. The presence of influenza virus in nasopharyngeal swabs from participants with influenza-like illness was confirmed by reverse-transcriptase-polymerase-chain-reaction assay and viral culture. A Cox proportional-hazards model was used to evaluate the efficacy of IIV4c as measured by the first occurrence of laboratory-confirmed type A or B influenza (primary end point). RESULTS: Between 2017 and 2019, a total of 4514 participants were randomly assigned to receive IIV4c or the meningococcal ACWY vaccine. Laboratory-confirmed influenza occurred in 175 of 2257 participants (7.8%) in the IIV4c group and in 364 of 2252 participants (16.2%) in the comparator group, and the efficacy of IIV4c was 54.6% (95% confidence interval [CI], 45.7 to 62.1). Efficacy was 80.7% (95% CI, 69.2 to 87.9) against influenza A/H1N1, 42.1% (95% CI, 20.3 to 57.9) against influenza A/H3N2, and 47.6% (95% CI, 31.4 to 60.0) against influenza B. IIV4c showed consistent vaccine efficacy in subgroups according to age, sex, race, and previous influenza vaccination. The incidences of adverse events were similar in the IIV4c group and the comparator group. CONCLUSIONS: IIV4c provided protection against influenza in healthy children and adolescents across seasons, regardless of previous influenza vaccination. (Funded by Seqirus; EudraCT number, 2016-002883-15; ClinicalTrials.gov number, NCT03165617.).


Assuntos
Imunogenicidade da Vacina , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Adolescente , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Feminino , Humanos , Vacinas contra Influenza/efeitos adversos , Masculino , Vacinas Meningocócicas/imunologia , Orthomyxoviridae/isolamento & purificação , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Método Simples-Cego , Vacinas de Produtos Inativados/imunologia
3.
BMC Infect Dis ; 18(1): 186, 2018 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-29669531

RESUMO

BACKGROUND: GSK has modified the licensed monovalent bulk manufacturing process for its split-virion inactivated quadrivalent influenza vaccine (IIV4) to harmonize the process among different strains, resulting in an increased number of finished vaccine doses, while compensating for the change from inactivated trivalent influenza vaccine (IIV3) to IIV4. To confirm the manufacturing changes do not alter the profile of the vaccine, a clinical trial was conducted to compare IIV4 made by the currently licensed process with a vaccine made by the new (investigational) process (IIV4-I). The main objectives were to compare the reactogenicity and safety of IIV4-I versus IIV4 in all age groups, and to demonstrate the non-inferiority of the hemagglutination-inhibition (HI) antibody responses based on the geometric mean titer ratio of IIV4-I versus IIV4 in children. METHODS: The Phase III, randomized, double-blind, multinational study included three cohorts: adults (18-49 years; N = 120), children (3-17 years; N = 821), and infants (6-35 months; N = 940). Eligible subjects in each cohort were randomized 1:1 to receive IIV4-I or IIV4. Both vaccines contained 15 µg of hemagglutinin antigen for each of the four seasonal virus strains. Adults and vaccine-primed children received one dose of vaccine, and vaccine-unprimed children received two doses of vaccine 28 days apart. All children aged ≥9 years were considered to be vaccine-primed and received one dose of vaccine. RESULTS: The primary immunogenicity objective of the study was met in demonstrating immunogenic non-inferiority of IIV4-I versus IIV4 in children. The IIV4-I was immunogenic against all four vaccine strains in each age cohort. The reactogenicity and safety profile of IIV4-I was similar to IIV4 in each age cohort, and there was no increase in the relative risk of fever (≥38 °C) with IIV4-I versus IIV4 within the 7-day post-vaccination period in infants (1.06; 95% Confidence Interval: 0.75, 1.50; p = 0.786). CONCLUSIONS: The study demonstrated that in adults, children, and infants, the IIV4-I made using an investigational manufacturing process was immunogenic with a reactogenicity and safety profile that was similar to licensed IIV4. These results support that the investigational process used to manufacture IIV4-I is suitable to replace the current licensed process. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02207413 ; trial registration date: August 4, 2014.


Assuntos
Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Método Duplo-Cego , Feminino , Febre/etiologia , Testes de Inibição da Hemaglutinação , Humanos , Lactente , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Vacinas de Produtos Inativados/uso terapêutico
4.
Pediatr Res ; 81(5): 752-758, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28060791

RESUMO

BACKGROUND: Growth is an essential outcome measure for evaluating the safety of infant formulas (IF). We investigated the effects of consumption of IF supplemented with prebiotics (fructooligosaccharides, FOS, and galactooligosaccharides, GOS) compared with synbiotics (FOS/GOS and Lactobacillus paracasei ssp. paracasei strain F19) on the growth of healthy infants. METHODS: 182 full-term infants who were weaned completely from breast milk to IF at 28 d of age were randomly assigned to receive prebiotic- or synbiotic-supplemented, otherwise identical, IF until 6 mo of age (intervention period). RESULTS: A total of 146 (80%) infants were included in the intention-to-treat analysis at 6 mo. Anthropometric parameters were similar in the two groups during the intervention and follow-up period until 12 mo of age. Compared with the prebiotic group, a significant reduction in the cumulative incidence of lower respiratory tract infections was found in the synbiotic group; however, the confidence interval of the estimate was wide, resulting in uncertainty. CONCLUSION: The lack of a significant difference between the formula-fed groups in growth, or the occurrence of serious adverse events, supports the safety of using IF supplemented with synbiotics. Further studies are needed to evaluate the effects of such formula on lower-respiratory tract infections.


Assuntos
Alimentação com Mamadeira/métodos , Desenvolvimento Infantil , Fórmulas Infantis , Lacticaseibacillus paracasei/crescimento & desenvolvimento , Oligossacarídeos/administração & dosagem , Prebióticos/administração & dosagem , Simbióticos/administração & dosagem , Fatores Etários , Alimentação com Mamadeira/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Lactente , Recém-Nascido , Análise de Intenção de Tratamento , Masculino , Oligossacarídeos/efeitos adversos , Polônia , Prebióticos/efeitos adversos , Simbióticos/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
5.
BMJ Open ; 13(11): e080182, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-38011984

RESUMO

INTRODUCTION: Bronchiolitis is an acute viral infection of the lower respiratory tract. It is most commonly caused by respiratory syncytial virus. Being a common reason for hospitalisation, it affects 13-17% of all hospitalised children younger than 2 years. Only supportive therapy, including suctioning nasal secretions, water-electrolyte balance maintenance and oxygen supplementation when needed, is recommended. However, non-evidence-based diagnostic and therapeutic approaches, including the use of inhaled bronchodilators, nebulised epinephrine, and nebulised and systemic steroids, are common. The inhalation of 3% hypertonic saline is not recommended in bronchiolitis management. However, a recently published meta-analysis revealed that the inhalation of hypertonic saline can reduce the risk of hospitalisation for outpatients with bronchiolitis, while resulting in a shorter length of hospital stay and reduced severity of respiratory distress for inpatients, although the evidence is of low certainty. We aim to assess the efficacy of nebulised hypertonic saline for the treatment of children hospitalised with bronchiolitis. METHODS AND ANALYSIS: This will be a randomised, double-blinded, parallel-group, controlled trial. Children younger than 2 years who are hospitalised due to bronchiolitis will be recruited from at least three paediatric departments in Poland. Bronchiolitis is defined as an apparent viral respiratory tract infection associated with airway obstruction that is manifested by at least one of following symptoms: tachypnoea, increased respiratory effort, crackles and/or wheezing. A total of 140 children will be randomised (1:1) to receive either hypertonic saline nebulisation (5 mL, three times a day) or normal saline at the same dose. The primary outcome measure will be the duration of hospitalisation. ETHICS AND DISSEMINATION: The Bioethics Committee of the Lower Silesia Medical Chamber in Wroclaw approved the study protocol (4/PNDR/2023). Caregivers will receive oral and written information about the study and written informed consent will be obtained by the study physicians. The findings of the study will be submitted to a peer-reviewed journal, and abstracts will be submitted to relevant national and international conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT06069336).


Assuntos
Bronquiolite , Solução Salina , Criança , Humanos , Lactente , Solução Salina/uso terapêutico , Nebulizadores e Vaporizadores , Bronquiolite/tratamento farmacológico , Solução Salina Hipertônica/uso terapêutico , Administração por Inalação , Método Duplo-Cego , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
6.
Acta Paediatr ; 101(10): e458-64, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22860693

RESUMO

AIM: To assess the efficacy and safety of a new oral rehydration solution (ORS) with improved flavour in the management of children with acute gastroenteritis (AGE). METHODS: Children 4 to 48 months of age with AGE (≥3 loose or watery stools per day for >1 but <5 days) with mild-to-moderate dehydration (3% to 9% loss of body weight) according to the World Health Organization criteria randomly received regular hypotonic ORS (Na 60 mmol/L, glucose 78 mmol/L) or the same hypotonic ORS with an apple taste. RESULTS: Of the 147 children randomized, 130 (88.4%) were available for intention-to-treat analysis. The proportion of children with the resolution of signs of dehydration in the experimental group compared with the control group was similar at 24 h (49/63 vs. 57/67, respectively, p = 0.28). There were also no significant differences in adequate weight gain (p = 0.48) and urine production at 24 h (p = 0.95) between groups. There were no differences between groups in any of the secondary outcome measures, including ORS intake. No adverse events were observed in the study groups. CONCLUSIONS: In an outpatient setting, there was no difference in efficacy between the study products. Both ORSs were equally effective and may be used interchangeably.


Assuntos
Desidratação/terapia , Diarreia/terapia , Aromatizantes/normas , Gastroenterite/terapia , Soluções para Reidratação/normas , Doença Aguda , Administração Oral , Pré-Escolar , Desidratação/etiologia , Desidratação/prevenção & controle , Diarreia/complicações , Feminino , Gastroenterite/complicações , Humanos , Lactente , Masculino , Adesão à Medicação , Polônia , Soluções para Reidratação/administração & dosagem , Paladar
7.
Vaccines (Basel) ; 11(1)2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36679920

RESUMO

Tuberculosis (TB) was the predominant cause of death from a single infectious agent worldwide before the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. Although TB vaccines have been successfully used for about 100 years, their full effect is still unknown. In previous studies, a reduced incidence and mortality from a coronavirus disease in TB-vaccinated populations were reported. In this article, we present the secondary analysis of a randomised controlled trial, reporting the results of a serological assessment evaluating the effect of the Bacillus Calmette-Guérin (BCG) vaccine on SARS-CoV-2. Participants-healthcare workers-were assessed 1-2 and 8 months after the second dose of the coronavirus disease 2019 (COVID-19) vaccine. We found no associations between antibody concentration, BCG revaccination, and additional characteristics, such as age, gender, or Body Mass Index. The effect of BCG vaccination on the immunological response against SARS-CoV-2 requires further research.

8.
Vaccines (Basel) ; 10(2)2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35214772

RESUMO

Tuberculosis vaccines (Bacillus Calmette-Guérin, BCG) were introduced 100 years ago and are still recommended by the World Health Organization to prevent the disease. Studies have shown that BCG vaccination can stimulate non-specific immune responses and reduce the incidence of certain diseases. At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, it was hypothesised that the incidence of COVID-19 was lower in countries with BCG prevention. In an attempt to verify this thesis, we conducted a multicenter, randomised, double-blind, placebo-controlled study on a group of 695 health care workers aged 25 years and over in Poland. All participants in the study had a tuberculin test, after which those who were negative were randomised (1:1) and received either the BCG- or placebo vaccine. From then on, these people were subjected to three months of observation for the occurrence of COVID-19 symptoms. The statistical analysis did not reveal any significant correlation between the frequency of incidents suspected of COVID-19 and BCG-10 vaccination, the result of the tuberculin test and the number of scars. The only statistically significant feature was the type of medical profession-nurses became infected more often than doctors or other medical workers (p = 0.02). The results differ from similar trials in other countries. Perhaps this is due to the lack of an unvaccinated control group. The impact of BCG vaccination on the course of COVID-19 requires further research.

9.
Hum Vaccin Immunother ; 17(12): 5475-5486, 2021 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-34714720

RESUMO

A quadrivalent high-dose inactivated influenza vaccine (IIV4-HD) is licensed for adults ≥65 y of age based on immunogenicity and efficacy studies. However, IIV4-HD has not been evaluated in adults aged 60-64 y. This study compared immunogenicity and safety of IIV4-HD with a standard-dose quadrivalent influenza vaccine (IIV4-SD) in adults aged ≥60 y. This Phase III, randomized, modified double-blind, active-controlled study enrolled 1,528 participants aged ≥60 y, randomized 1:1 to a single injection of IIV4-HD or IIV4-SD. Hemagglutination inhibition (HAI) geometric mean titers (GMTs) were measured at baseline and D 28 and seroconversion assessed. Safety was described for 180 d after vaccination. The primary immunogenicity objective was superiority of IIV4-HD versus IIV4-SD, for all four influenza strains 28 d post vaccination in participants aged 60-64 and ≥65 y. IIV4-HD induced a superior immune response versus IIV4-SD in terms of GMTs in participants aged 60-64 y and those aged ≥65 y for all four influenza strains. IIV4-HD induced higher GMTs in those aged 60-64 y than those aged ≥65 y. Seroconversion rates were higher for IIV4-HD versus IIV4-SD in each age-group for all influenza strains. Both vaccines were well tolerated in participants ≥60 y of age, with no safety concerns identified. More solicited reactions were reported with IIV4-HD than with IIV4-SD. IIV4-HD provided superior immunogenicity versus IIV4-SD and was well tolerated in adults aged ≥60 y. IIV4-HD is assumed to offer improved protection against influenza compared with IIV4-SD in adults aged ≥60 y, as was previously assessed for adults aged ≥65 y.


Assuntos
Vacinas contra Influenza , Influenza Humana , Adulto , Anticorpos Antivirais , Método Duplo-Cego , Testes de Inibição da Hemaglutinação , Humanos , Imunogenicidade da Vacina , Influenza Humana/prevenção & controle , Vacinas Combinadas , Vacinas de Produtos Inativados
10.
Lancet Respir Med ; 9(1): 21-32, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002427

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of severe lower respiratory tract infection, with a high global health burden. There are no effective treatments available. ALX-0171 is a novel trivalent Nanobody with antiviral properties against RSV. We aimed to assess the safety and antiviral activity of nebulised ALX-0171 in children admitted to hospital with RSV lower respiratory tract infection. METHODS: This double-blind, randomised, placebo-controlled, phase 2b trial was done in 50 hospital paediatric departments across 16 countries. Previously healthy children aged between 28 days to younger than 24 months who were admitted to hospital with RSV acute severe lower respiratory tract infection were randomly assigned in three sequential safety cohorts (3:1) to receive nebulised ALX-0171 (cohort 1 received 3 mg/kg, cohort 2 received 6 mg/kg, and cohort 3 received 9 mg/kg) or placebo once daily for 3 days using web-based randomisation in the sequential safety part (first block size 12, subsequently four). In a parallel part of the study, participants (cohort 4) were randomly assigned (parallel 1:1:1:1) to receive nebulised ALX-0171 3 mg/kg, 6 mg/kg, 9 mg/kg, or placebo (blocks of eight by restricted randomisation). Study drug masking was by two consecutive nebulisations (each either ALX-0171 or placebo) depending on assigned treatment group. The primary outcome was to evaluate time for the RSV viral load to drop to below quantifiable limit, measured by plaque assay on mid-turbinate nasal swabs. Safety, clinical efficacy, pharmacokinetics, viral load by RT-qPCR, and immunogenicity were secondary outcomes. Analysis, including of the primary outcome, was by modified intention to treat (participants receiving at least one dose of study drug as assigned), and safety was assessed in all children who received at least one administration of study drug, as treated. This trial is registered with EudraCT, 2016-001651-49. FINDINGS: Between Jan 10, 2017, and April 26, 2018, 175 children (median age 4·8 months [IQR 2·0-10·8]), received at least one dose of study drug (45 received 3 mg/kg of ALX-0171, 43 received 6 mg/kg of ALX-0171, 45 received 9 mg/kg of ALX-0171, and 42 received placebo; the modified intention-to-treat population) commencing at a mean 3·3 days (SD 1·1) from symptom onset. Median time for the viral load to drop to below quantifiable limit on plaque assay was significantly faster for the 3 mg/kg group (median 14·2 h [IQR 5·0-28·0]), 6 mg/kg group (5·1 h [4·7-28·5]), and 9 mg/kg group (5·1 h [4·6-5·9]) than the placebo group (46·1 h [25·2-116·7]; hazard ratio [HR] all ALX-0171 groups vs placebo 2·6 [1·7-3·9]; p<0·0001). Median time for the viral load to drop below quantification limit with RT-qPCR was 95·9 h (IQR 26·7 to not estimable) for the placebo group (n=35) versus 49·4 h (25·1 to 351·4) for all ALX-0171 groups (n=118). Clinical outcomes were not improved by ALX-0171 compared with placebo, with no difference in time to clinical response (oxygen saturation >92% for 4 h in room air and adequate oral feeding) in ALX-0171 groups and the placebo group (median 43·8 h [IQR 21·7-68·5] vs 47·9 h [22·5-76·4]; HR 1·1 [95% CI 0·8-1·6]) or change in the global severity score from baseline to 5 h post-dose on day 2 (-4 [IQR -6 to -2] vs -4 [-6 to -1]; difference in least-squares mean -0·45 [95% CI -1·39 to 0·49]). Serum concentrations of ALX-0171 on day 2 exceeded the concentration estimated to give full RSV neutralisation in the lung at 6 mg/kg and 9 mg/kg doses. Treatment-emergent antidrug antibodies were detected at day 14 in 46 (34%) of 135 patients who received ALX-0171 and ten (26%) of 39 patients who received placebo. Serious adverse events were reported in five (13%) of 40 children in the placebo group and ten (7%) of 135 children in all ALX-0171 groups, leading to study drug discontinuation in three children (two in the 3 mg/kg group and one in the 6 mg/kg group). 13 of 15 serious adverse events (three of four in the 3 mg/kg group, two of three in the 6 mg/kg group, three of three in the 9 mg/kg group, and five of five in the placebo group) were related to worsening respiratory status, and none were considered to be related to the study drug. INTERPRETATION: Antivirals against RSV might be unable to improve clinical course once RSV lower respiratory tract infection is established. Future studies of RSV antivirals should focus on earlier intervention and more precise measurement of objective outcomes before the onset of significant lower respiratory tract inflammation. FUNDING: Ablynx, a Sanofi Company.


Assuntos
Antivirais/uso terapêutico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Vírus Sinciciais Respiratórios , Infecções Respiratórias/tratamento farmacológico , Anticorpos de Domínio Único/uso terapêutico , Administração por Inalação , Antivirais/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Nebulizadores e Vaporizadores , Infecções Respiratórias/virologia , Anticorpos de Domínio Único/administração & dosagem , Carga Viral/efeitos dos fármacos
11.
J Pediatr ; 157(6): 984-988.e1, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20619853

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of zinc in the treatment of acute gastroenteritis (AGE) in children in Poland. STUDY DESIGN: Children aged 3 to 48 months with AGE were enrolled in a randomized, double-blind, placebo-controlled trial in which they received zinc sulfate (10 or 20 mg/day depending on age) or placebo for 10 days. A total of 141 of 160 children recruited were available for intention-to-treat analysis. The primary outcome was the duration of diarrhea. RESULTS: In the experimental group (n = 69) compared with the control group (n = 72), there was no significant difference in the duration of diarrhea (P > .05). Similarly, there was no significant difference in the groups in secondary outcome measures such as stool frequency on days 1, 2, and 3, vomiting frequency, intravenous fluid intake, and the number of children with diarrhea lasting >7 days. CONCLUSION: Children living in a country where zinc deficiency is rare do not appear to benefit from the use of zinc in the treatment of AGE.


Assuntos
Gastroenterite/tratamento farmacológico , Sulfato de Zinco/administração & dosagem , Doença Aguda , Administração Oral , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Lactente , Masculino , Polônia
12.
Acta Biochim Pol ; 67(3): 393-399, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32945647

RESUMO

We compared fecal samples from responders and non-responders to administration of Lactobacillus reuteri DSM 17938. Data for this post hoc analysis were collected from an RCT assessing the efficacy of L. reuteri for the management of acute gastroenteritis. Responders were defined as subjects with diarrhea lasting no longer than 48 h. 44 children (17 responders and 27 non-responders) were analyzed. There were no differences in clinical characteristics and gut colonization between both groups. In the responder group, there were significantly lower levels of five metabolites before beginning of the intervention: lactate, choline, ethanol, creatine, and formate. The fecal calprotectin level did not differ between groups prior to the intervention, but its level was significantly lower after intervention in the responder group. Possibly, the responder group with a "metabolic niche", including lower level of metabolites, especially lactate, that are potential products of Lactobacillus genus, would determine the response to probiotic treatment. These findings need to be confirmed, but identification of some differences in the fecal metabolomics and the calprotectin level suggests that further studies are warranted.


Assuntos
Diarreia/dietoterapia , Suplementos Nutricionais/microbiologia , Fezes/química , Fezes/microbiologia , Gastroenterite/dietoterapia , Limosilactobacillus reuteri/metabolismo , Probióticos/uso terapêutico , Doença Aguda , Pré-Escolar , Diarreia/metabolismo , Método Duplo-Cego , Feminino , Gastroenterite/metabolismo , Humanos , Lactente , Complexo Antígeno L1 Leucocitário/análise , Complexo Antígeno L1 Leucocitário/metabolismo , Masculino , Metaboloma , Resultado do Tratamento
13.
Pediatr Infect Dis J ; 39(1): e1-e10, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31725115

RESUMO

BACKGROUND: We evaluated an inactivated quadrivalent influenza vaccine (IIV4) in children 6-35 months of age in a phase III, observer-blind trial. METHODS: The aim of this analysis was to estimate vaccine efficacy (VE) in preventing laboratory-confirmed influenza in each of 5 independent seasonal cohorts (2011-2014), as well as vaccine impact on healthcare utilization in 3 study regions (Europe/Mediterranean, Asia-Pacific and Central America). Healthy children were randomized 1:1 to IIV4 or control vaccines. VE was estimated against influenza confirmed by reverse transcription polymerase chain reaction on nasal swabs. Cultured isolates were characterized as antigenically matched/mismatched to vaccine strains. RESULTS: The total vaccinated cohort included 12,018 children (N = 1777, 2526, 1564, 1501 and 4650 in cohorts 1-5, respectively). For reverse transcription polymerase chain reaction confirmed influenza of any severity (all strains combined), VE in cohorts 1-5 was 57.8%, 52.9%, 73.4%, 30.3% and 41.4%, respectively, with the lower limit of the 95% confidence interval >0 for all estimates. The proportion of vaccine match for all strains combined in each cohort was 0.9%, 79.3%, 72.5%, 24.1% and 28.6%, respectively. Antibiotic use associated with influenza illness was reduced with IIV4 by 71% in Europe, 36% in Asia Pacific and 59% in Central America. CONCLUSIONS: IIV4 prevented influenza in children 6-35 months of age in each of 5 separate influenza seasons in diverse geographical regions. A possible interaction between VE, degree of vaccine match and socioeconomic status was observed. The IIV4 attenuated the severity of breakthrough influenza illness and reduced healthcare utilization, particularly antibiotic use.


Assuntos
Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Aceitação pelo Paciente de Cuidados de Saúde , Vacinas de Produtos Inativados/imunologia , Feminino , Geografia Médica , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/imunologia , Vírus da Influenza B/genética , Vírus da Influenza B/imunologia , Vacinas contra Influenza/administração & dosagem , Masculino , Avaliação de Resultados em Cuidados de Saúde , Vigilância em Saúde Pública , Estações do Ano , Vacinas de Produtos Inativados/administração & dosagem
14.
Pediatr Infect Dis J ; 38(10): e237-e242, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31033909

RESUMO

OBJECTIVE: To assess the efficacy of Lactobacillus reuteri DSM 17938 (L. reuteri) for the treatment of acute gastroenteritis in children. STUDY DESIGN: Children younger than 5 years with acute diarrhea, defined as a change in stool consistency to a loose or liquid form and/or an increase in the frequency of evacuations (≥3 in 24 hours), lasting for no longer than 5 days, were eligible for inclusion. Participants (n = 100) were recruited from the pediatrics department of a Polish hospital and randomly assigned to receive L. reuteri in a dose 2 × 10 colony-forming units or placebo, for 5 days, in addition to standard rehydration therapy. The primary outcome measure was duration of diarrhea. RESULTS: Ninety-one of the 100 children randomized were included in the intention-to-treat analysis (L. reuteri n = 44; placebo n = 47). The duration of diarrhea after randomization in both groups was similar (P = 0.6). The groups were also similar with respect to all secondary outcome measures, with one exception. Compared with the placebo group, patients in the L. reuteri group had a shorter duration of hospitalization (P = 0.048). Adverse events were similar in both groups. CONCLUSIONS: Among children with acute gastroenteritis who were younger than 5 years of age, L. reuteri compared with placebo, as an adjunct to rehydration therapy, did not reduce the duration of diarrhea; however, it reduced the duration of hospitalization.


Assuntos
Gastroenterite/terapia , Limosilactobacillus reuteri/crescimento & desenvolvimento , Probióticos/administração & dosagem , Fenômenos Químicos , Pré-Escolar , Terapia Combinada/métodos , Diarreia/terapia , Método Duplo-Cego , Fezes/química , Feminino , Hidratação/métodos , Hospitais , Humanos , Lactente , Masculino , Placebos/administração & dosagem , Polônia , Resultado do Tratamento
15.
Pediatr Infect Dis J ; 38(8): 866-872, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31306399

RESUMO

BACKGROUND: In an exploratory analysis of an inactivated quadrivalent influenza vaccine (IIV4) trial in children 6-35 months without risk factors for influenza, we evaluated clinical presentation of influenza illness and vaccine impact on health outcomes. METHODS: This phase III trial was conducted in 13 geographically diverse countries across 5 influenza seasons (2011-2014). Children were randomized 1:1 to IIV4 or control. Active surveillance was performed for influenza-like episodes (ILE); influenza was confirmed by reverse transcription polymerase chain reaction (RT-PCR). The total vaccinated cohort was evaluated (N = 12,018). RESULTS: 5702 children experienced ≥1 ILE; 356 (IIV4 group) and 693 (control group) children had RT-PCR-confirmed influenza. Prevalence of ILE was similar in RT-PCR-positive and RT-PCR-negative cases regardless of vaccination. Breakthrough influenza illness was attenuated in children vaccinated with IIV4; moderate-to-severe illness was 41% less likely to be reported in the IIV4 group than the control group [crude odds ratio: 0.59 (95% confidence intervals: 0.44-0.77)]. Furthermore, fever >39°C was 46% less frequent following vaccination with IIV4 than with control [crude odds ratio: 0.54 (95% confidence intervals: 0.39-0.75)] in children with breakthrough illness. Health outcome analysis showed that, each year, IIV4 would prevent 54 influenza cases per 1000 children and 19 children would need to be vaccinated to prevent 1 new influenza case. CONCLUSIONS: In addition to preventing influenza in 50% of participants, IIV4 attenuated illness severity and disease burden in children who had a breakthrough influenza episode despite vaccination.


Assuntos
Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Pré-Escolar , Feminino , Hospitalização , Humanos , Lactente , Vacinas contra Influenza/administração & dosagem , Influenza Humana/diagnóstico , Masculino , Razão de Chances , Prevalência , Modelos de Riscos Proporcionais , Vigilância em Saúde Pública , Índice de Gravidade de Doença , Avaliação de Sintomas , Vacinação , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia
16.
Digestion ; 78(1): 13-7, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18701826

RESUMO

AIM: To determine the efficacy of a combination of Bifidobacterium longum PL03, Lactobacillus rhamnosus KL53A and Lactobacillus plantarum PL02 for the prevention of antibiotic-associated diarrhea in children. METHODS: Seventy-eight children (age: 5 months to 16 years) with otitis media, and/or respiratory tract infections, and/or urinary tract infections were enrolled in a double-blind randomized control trial in which they received standard antibiotic treatment plus a food supplement containing 10(8) colony-forming units of B. longum, L. rhamnosus and L. plantarum (n = 40) or a placebo (n = 38) orally twice daily for the duration of antibiotic treatment. RESULTS: Patients receiving probiotics had a similar rate of diarrhea (> or =3 loose or watery stools/day for > or =48 h occurring during or up to 2 weeks after the antibiotic therapy) as those receiving placebo (relative risk 0.5, 95% CI 0.06-3.5). The mean number of stools per day was significantly lower in the experimental group (mean difference -0.3 stool/day, 95% CI -0.5 to -0.07). No adverse events were reported. CONCLUSION: The administration of the 3 probiotics did not significantly alter the rate of diarrhea, although it reduced the frequency of stools per day. As the overall frequency of diarrhea was surprisingly low, these results should be interpreted with caution.


Assuntos
Antibacterianos/efeitos adversos , Bifidobacterium , Diarreia/prevenção & controle , Lacticaseibacillus rhamnosus , Lactobacillus plantarum , Probióticos/uso terapêutico , Adolescente , Criança , Pré-Escolar , Diarreia/induzido quimicamente , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Lactente , Masculino , Otite Média/tratamento farmacológico , Projetos Piloto , Infecções Respiratórias/tratamento farmacológico , Resultado do Tratamento , Infecções Urinárias/tratamento farmacológico
17.
Hum Vaccin Immunother ; 14(3): 596-608, 2018 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-28968138

RESUMO

Here, we report a randomized multicenter phase III trial assessing the lot-to-lot consistency of the 2014-2015 Northern Hemisphere quadrivalent split-virion inactivated influenza vaccine (IIV4; Sanofi Pasteur) and comparing its immunogenicity and safety with that of trivalent inactivated influenza vaccine (IIV3) in younger and older adults (EudraCT no. 2014-000785-21). Younger (18-60 y, n = 1114) and older (>60 y, n = 1111) adults were randomized 2:2:2:1:1 to receive a single dose of one of three lots of IIV4, the licensed IIV3 containing the B Yamagata lineage strain, or an investigational IIV3 containing the B Victoria lineage strain. Post-vaccination (day 21) hemagglutination inhibition antibody titers were equivalent for the three IIV4 lots. For the pooled IIV4s vs. IIV3, hemagglutination inhibition antibody titers were also non-inferior for the A strains, non-inferior for the B strain when present in the comparator IIV3, and superior for the B strain lineage when absent from the comparator IIV3. For all vaccine strains, seroprotection rates were ≥98% in younger adults and ≥90% in older adults. IIV4 also increased seroneutralizing antibody titers against all three vaccine strains of influenza. All vaccines were well tolerated, with no safety concerns identified. Solicited injection-site reactions were similar for IIV4 and IIV3 and mostly grade 1 and transient. This study showed that in younger and older adults, IIV4 had a similar safety profile as the licensed IIV3 and that including a second B strain lineage in IIV4 provided superior immunogenicity for the added B strain without affecting the immunogenicity of the three IIV3 strains.


Assuntos
Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Adolescente , Adulto , Anticorpos Antivirais/imunologia , Método Duplo-Cego , Feminino , Testes de Inibição da Hemaglutinação/métodos , Humanos , Vírus da Influenza B/imunologia , Masculino , Pessoa de Meia-Idade , Vacinação/métodos , Vírion/imunologia , Adulto Jovem
18.
Lancet Child Adolesc Health ; 2(5): 338-349, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-30169267

RESUMO

BACKGROUND: Despite the importance of vaccinating children younger than 5 years, few studies evaluating vaccine prevention of influenza have been reported in this age group. We evaluated efficacy of an inactivated quadrivalent influenza vaccine (IIV4) in children aged 6-35 months. METHODS: In this phase 3, observer-blinded, multinational trial, healthy children from 13 countries in Europe, Central America, and Asia were recruited in five independent cohorts, each in a different influenza season. Participants were randomly assigned (1:1) to either IIV4 (15 µg haemagglutinin antigen per strain per 0·5 mL dose; a single dose on day 0 for vaccine-primed children, and two doses, on days 0 and 28, for vaccine-unprimed children) or to one or two doses of a non-influenza control vaccine. Primary endpoints were moderate-to-severe influenza or all influenza (irrespective of disease severity) confirmed by RT-PCR on nasal swabs. Cultured isolates were further characterised as antigenically matched or mismatched to vaccine strains. Efficacy was assessed in the per-protocol cohort and total vaccinated cohort (time-to-event analysis), and safety was assessed in the total vaccinated cohort. FINDINGS: Between Oct 1, 2011, and Dec 31, 2014, 12 018 children were recruited into the total vaccinated cohort (6006 children in the IIV4 group and 6012 children in the control group). 356 (6%) children in the IIV4 group and 693 (12%) children in the control group had at least one case of RT-PCR-confirmed influenza. Of these 1049 influenza strains, 138 (13%) were A/H1N1, 529 (50%) were A/H3N2, 69 (7%) were B/Victoria, and 316 (30%) were B/Yamagata. Overall, 539 (64%) of 848 antigenically characterised isolates were vaccine-mismatched (16 [15%] of 105 for A/H1N1; 368 [97%] of 378 for A/H3N2; 54 [86%] of 63 for B/Victoria; 101 [33%] of 302 for B/Yamagata). Vaccine efficacy was 63% (97·5% CI 52-72) against moderate-to-severe influenza and 50% (42-57) against all influenza in the per-protocol cohort, and 64% (53-73) against moderate-to-severe influenza and 50% (42-57) against all influenza in the total vaccinated cohort. There were no clinically meaningful safety differences between IIV4 and control. INTERPRETATION: IIV4 prevented influenza A and B in children aged 6-35 months despite high levels of vaccine mismatch. Vaccine efficacy was highest against moderate-to-severe disease, which is the most clinically important endpoint associated with greatest burden. FUNDING: GlaxoSmithKline Biologicals SA.


Assuntos
Vacinas contra Influenza , Influenza Humana/prevenção & controle , Pré-Escolar , Feminino , Humanos , Lactente , Influenza Humana/epidemiologia , Internacionalidade , Masculino , Estações do Ano , Método Simples-Cego
19.
JMIR Res Protoc ; 6(8): e164, 2017 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-28835355

RESUMO

BACKGROUND: Acute gastroenteritis (AGE) is one of the most common diseases among children. Oral rehydration therapy is the key treatment. However, despite proven efficacy, it remains underused. This is because oral rehydration solution neither reduces the frequency of bowel movements and fluid loss nor shortens the duration of illness. Hence, there is interest in adjunctive treatments. According to the 2014 guidelines developed by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition, the use of the following probiotics may be considered in the management of children with AGE in addition to rehydration therapy: Lactobacillus rhamnosus GG (low quality of evidence; strong recommendation) and Saccharomyces boulardii (low quality of evidence; strong recommendation). Less compelling evidence is available for Lactobacillus reuteri DSM 17938 (very low quality of evidence; weak recommendation). OBJECTIVE: Considering that evidence on L reuteri remains limited, the goal of the study is to assess the effectiveness of L reuteri DSM 17938 in the treatment of AGE in children. Children vaccinated and not vaccinated against rotavirus will be evaluated separately. METHODS: This will be a double-blind, placebo-controlled, randomized trial. Children between 1 and 60 months of age with AGE, defined as a change in stool consistency to loose or liquid form (according to the Bristol Stool Form scale or Amsterdam Stool Form scale) and/or an increase in the frequency of evacuations (typically ≥3 in 24 h) lasting for no longer than 5 days, will be recruited. A total of 72 children will receive either L reuteri DSM 17938 at a dose of 2×108colony-forming units twice daily or matching placebo for 5 consecutive days. A similar sample size for rotavirus vaccinated and nonvaccinated children is planned. The primary outcome measure is the duration of diarrhea. Two separate studies and reports for rotavirus vaccinated and nonvaccinated children are planned. RESULTS: The recruitment started in January 2017 and is planned to be finalized in June 2018 for rotavirus nonvaccinated children. The recruitment of rotavirus-vaccinated children may be slower due to a relatively low coverage rate in Poland. Data analysis and submission to a peer-reviewed journal is expected within 3 months after completion of the study. CONCLUSION: This study will add to current knowledge on the efficacy of L reuteri DSM 17938 for the management of AGE. TRIAL REGISTRATION: ClinicalTrials.gov NCT02989350; https://clinicaltrials.gov/ct2/show/NCT02989350 (Archived by WebCite at http://www.webcitation.org/6slOFkyTH).

20.
Vaccine ; 35(15): 1926-1935, 2017 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-28262330

RESUMO

OBJECTIVE: Prophylactic antipyretic use during pediatric vaccination is common. This study assessed whether paracetamol or ibuprofen prophylaxis interfere with immune responses to the 13-valent pneumococcal conjugate vaccine (PCV13) given concomitantly with the combined DTaP/HBV/IPV/Hib vaccine. METHODS: Subjects received prophylactic paracetamol or ibuprofen at 0, 6-8, and 12-16 h after vaccination, or 6-8 and 12-16 h after vaccination at 2, 3, 4, and 12months of age. At 5 and 13months, immune responses were evaluated versus responses in controls who received no prophylaxis. RESULTS: After the infant series, paracetamol recipients had lower levels of circulating serotype-specific pneumococcal anticapsular immunoglobulin G than controls, reaching significance (P<0.0125) for 5 serotypes (serotypes 3, 4, 5, 6B, and 23F) when paracetamol was started at vaccination. Opsonophagocytic activity assay (OPA) results were similar between groups. Ibuprofen did not affect pneumococcal responses, but significantly (P<0.0125) reduced antibody responses to pertussis filamentous hemagglutinin and tetanus antigens after the infant series when started at vaccination. No differences were observed for any group after the toddler dose. CONCLUSIONS: Prophylactic antipyretics affect immune responses to vaccines; these effects vary depending on the vaccine, antipyretic agent, and time of administration. In infants, paracetamol may interfere with immune responses to pneumococcal antigens, and ibuprofen may reduce responses to pertussis and tetanus antigens. The use of antipyretics for fever prophylaxis during infant vaccination merits careful consideration. ClinicalTrials.gov identifier: NCT01392378https://clinicaltrials.gov/ct2/show/NCT01392378?term=NCT01392378&rank=1.


Assuntos
Acetaminofen/administração & dosagem , Antipiréticos/administração & dosagem , Quimioprevenção/métodos , Febre/prevenção & controle , Ibuprofeno/administração & dosagem , Vacinas Pneumocócicas/efeitos adversos , Vacinas Pneumocócicas/imunologia , Anticorpos Antibacterianos/sangue , Vacina contra Difteria, Tétano e Coqueluche/efeitos adversos , Interações Medicamentosas , Feminino , Vacinas Anti-Haemophilus/efeitos adversos , Vacinas contra Hepatite B/efeitos adversos , Humanos , Lactente , Masculino , Proteínas Opsonizantes/sangue , Fagocitose , Vacinas Pneumocócicas/administração & dosagem , Vacina Antipólio de Vírus Inativado/efeitos adversos , Vacinas Combinadas/efeitos adversos
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