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1.
Acta Paediatr ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31365152

RESUMO

AIM: We explored the impact of vaccination on bacterial meningitis in a well-defined population of children on the island of Crete, Greece, over a 27-y period. METHODS: This was a retrospective observational study of all mandatory notifications of bacterial meningitis in patients aged 1 mo-14 y from 1991 to 2017. RESULTS: There were 245 patients with proven (n = 227) or suspected (n = 18) bacterial meningitis, and eight deaths were recorded, giving a case fatality rate of 3.3%. The mean annual incidence rate (IR) per 100 000 children was 4.9 for Neisseria meningitidis, 2.2 for Streptococcus pneumoniae and 0.4 for Haemophilus influenzae type b (Hib). Cases of meningitis C dropped significantly after the conjugate meningitis C vaccine was licensed for routine vaccination in Greece in 2000 (IR of 1.5 vs 0.3, P < 0.028) while the Streptococcus pneumoniae cases showed a threefold decrease after the PCV13 vaccine was licensed in Greece in 2009 (IR 2.7 vs 1.0, P < 0.03). Vaccination had already eliminated Hib in Greece in the 1990s. CONCLUSION: Bacterial meningitis cases decreased in children following the introduction of the meningitis C and PCV13 vaccines in Greece. Hib had already disappeared and significant reductions in meningitis C and Streptococcus pneumoniae were observed.

2.
Int Rev Immunol ; 38(2): 70-78, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30939053

RESUMO

Asthma is a heterogeneous chronic respiratory disease characterized by an increased burden of infections. Respiratory tract infections associated with an increased risk for asthma especially when occurring in the first months of life, also represent the most common cause of asthma exacerbations. The association between asthma and the increased frequency of infections and microbiota dysbiosis might be explained by a common mechanism, such as an underlying immune system defect. Apart from the well-established association between primary immunodeficiencies and asthma, several alterations in the immune response following infection have also been observed in asthmatic patients. An impairment in lung epithelial barrier integrity exists and is associated with both an increased susceptibility to infections and the development of asthma. Asthmatic patients are also found to have a deficient interferon (IFN) response upon infection. Additionally, defects in Toll-like receptor (TLR) signaling are observed in asthma and are correlated with both recurrent infections and asthma development. In this review, we summarize the common pathophysiological background of asthma and infections, highlighting the importance of an underlying immune system defect that predispose individuals to recurrent infections and asthma.

3.
Blood ; 133(24): 2586-2596, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31015189

RESUMO

DiGeorge syndrome (DGS) is a primary immunodeficiency characterized by various degrees of T-cell deficiency. In partial DGS (pDGS), other risk factors could predispose to recurrent infections, autoimmunity, and allergy. The aim of this study was to assess the effect of different factors in the development of infections, autoimmunity, and/or allergy in patients with pDGS. We studied 467 pDGS patients in follow-up at Great Ormond Street Hospital. Using a multivariate approach, we observed that palatal anomalies represent a risk factor for the development of recurrent otitis media with effusion. Gastroesophageal reflux/dysphagia and asthma/rhinitis represent a risk factor for the development of recurrent upper respiratory tract infections. Allergy and autoimmunity were associated with persistently low immunoglobulin M levels and lymphopenia, respectively. Patients with autoimmunity showed lower levels of CD3+, CD3+CD4+, and naïve CD4+CD45RA+CD27+ T lymphocytes compared with pDGS patients without autoimmunity. We also observed that the physiological age-related decline of the T-cell number was slower in pDGS patients compared with age-matched controls. The age-related recovery of the T-cell number depended on a homeostatic peripheral proliferation of T cells, as suggested by an accelerated decline of the naïve T lymphocytes in pDGS as well as a more skewed T-cell repertoire in older pDGS patients. These evidences suggest that premature CD4+ T-cell aging and lymphopenia induced spontaneous peripheral T-cell proliferation might contribute to the pathogenesis of autoimmunity in patients with pDGS. Infections in these patients represent, in most of the cases, a complication of anatomical or gastroenterological anomalies rather than a feature of the underlying immunodeficiency.

4.
Pediatr Int ; 61(1): 16-22, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30248214

RESUMO

The immune system poses one of the greatest challenges for the scientific community. The general pediatrician should be able to screen and identify an immunodeficient patient based on certain clinical indications. Further investigation is crucial for the distinction between primary or secondary immunodeficiency as well as for between cellular and humoral immunity defects. Full blood count is the best initial laboratory test when suspecting a primary immunodeficiency, focusing on the absolute lymphocyte count, while lymphocyte subset count offers the advantage of detecting the cell type that causes the immune defect. The aim of the present review was to guide the general pediatrician in the investigation and diagnosis of an immunodeficient patient. Even though an immunodeficiency may seem a very difficult disease to diagnose, a balanced and rational way of thinking, along with the help of modern technological advances, can easily guide us in the right direction.


Assuntos
Síndromes de Imunodeficiência/diagnóstico , Contagem de Linfócitos/métodos , Subpopulações de Linfócitos/imunologia , Humanos , Pediatras
5.
Pediatr Int ; 61(3): 246-251, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30593708

RESUMO

BACKGROUND: Urinary tract infection (UTI) is the most common serious bacterial infection in childhood. The aim of the present study was therefore to identify the organisms responsible for community-acquired febrile UTI in children, to investigate their susceptibility to commonly used antibiotics, and to identify possible risk factors for antibiotic resistance. METHODS: A total of 284 children (male, 38%; female, 62%), who were hospitalized due to a community-acquired UTI over a 5 year period in a general district hospital of southern Greece, were enrolled in the study. RESULTS: Escherichia coli was the leading uropathogen followed by Klebsiella spp. (9.15%) and Proteus spp. (5.28%). E. coli isolates were most commonly resistant to ampicillin (41.8%), followed by piperacillin (40.3%), amoxicillin-clavulanic acid (28.6%) and trimethoprim-sulfamethoxazole (17.8%), while 27 strains (12.6%) were multi-drug resistant (MDR). Of the E. coli strains, 4.21% were producing extended-spectrum beta-lactamases. Parenteral second- and third-generation cephalosporins, the most commonly used antibiotic agents (81.3%) in the present cohort, remained highly active against E. coli and other urinary isolates, given that >95% of E. coli strains were susceptible to cefuroxime and cefotaxime. Vesicoureteral reflux was a significant risk factor for MDR (P = 0.04). CONCLUSION: Contrary to current local practice, amoxicillin/clavulanic acid may not be the best option for the empirical treatment of community-acquired UTI in southern Greece.


Assuntos
Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Infecções Urinárias/microbiologia , Adolescente , Criança , Criança Hospitalizada/estatística & dados numéricos , Pré-Escolar , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Grécia , Humanos , Lactente , Masculino , Estudos Retrospectivos , Fatores de Risco , Infecções Urinárias/tratamento farmacológico
6.
Blood Adv ; 2(7): 777-786, 2018 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-29618462

RESUMO

Patients with juvenile idiopathic arthritis (JIA) can experience a severe disease course, with progressive destructive polyarthritis refractory to conventional therapy with disease-modifying antirheumatic drugs including biologics, as well as life-threatening complications including macrophage activation syndrome (MAS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative immunomodulatory strategy for patients with such refractory disease. We treated 16 patients in 5 transplant centers between 2007 and 2016: 11 children with systemic JIA and 5 with rheumatoid factor-negative polyarticular JIA; all were either refractory to standard therapy, had developed secondary hemophagocytic lymphohistiocytosis/MAS poorly responsive to treatment, or had failed autologous HSCT. All children received reduced toxicity fludarabine-based conditioning regimens and serotherapy with alemtuzumab. Fourteen of 16 patients are alive with a median follow-up of 29 months (range, 2.8-96 months). All patients had hematological recovery. Three patients had grade II-IV acute graft-versus-host disease. The incidence of viral infections after HSCT was high, likely due to the use of alemtuzumab in already heavily immunosuppressed patients. All patients had significant improvement of arthritis, resolution of MAS, and improved quality of life early following allo-HSCT; most importantly, 11 children achieved complete drug-free remission at the last follow-up. Allo-HSCT using alemtuzumab and reduced toxicity conditioning is a promising therapeutic option for patients with JIA refractory to conventional therapy and/or complicated by MAS. Long-term follow-up is required to ascertain whether disease control following HSCT continues indefinitely.


Assuntos
Artrite Juvenil/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Terapia de Salvação/métodos , Adolescente , Alemtuzumab/uso terapêutico , Artrite Juvenil/complicações , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunossupressão/métodos , Lactente , Linfo-Histiocitose Hemofagocítica/etiologia , Masculino , Transplante Homólogo , Resultado do Tratamento
7.
Int Rev Immunol ; 37(2): 111-118, 2018 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-28876962

RESUMO

Primary immune deficiencies (PID) in children are a rare but serious group of genetic disorders of the immune system which apart from the host's defenses, can also affect every system of the human body, including the gastrointestinal tract. In their severe form they can lead to increased susceptibility to serious infections during infancy and even death. In the less severe form, they can present later in childhood or adolescence with subtle signs and symptoms. As PID can often mimic gastrointestinal diseases, children presenting with atypical gastrointestinal disease and/or failure to respond to conventional therapy should be evaluated for an underlying primary immune disorder and initiated appropriate treatment. The current review of the literature will summarize the gastrointestinal manifestations of primary immune deficiencies in children.


Assuntos
Gastroenteropatias/imunologia , Trato Gastrointestinal/imunologia , Síndromes de Imunodeficiência/imunologia , /imunologia , Adolescente , Animais , Criança , Diagnóstico Diferencial , Gastroenteropatias/diagnóstico , Humanos , Síndromes de Imunodeficiência/diagnóstico , Lactente , Risco
8.
Int Rev Immunol ; 36(6): 352-359, 2017 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-28800262

RESUMO

Rituximab (RTX) is a monoclonal antibody against CD20, commonly used in the treatment of hematological malignancies and autoimmune diseases. The use of RTX is related to the development of hypogammaglobulinemia and infections. Aim of this review is to summarize the evidence supporting the association of specific risk factors with the development of hypogammaglobulinemia and infections post-RTX. Immunological complications are more common in patients with malignant diseases as compared to non-malignant diseases. Moreover, the use of more than one dose of RTX, maintenance regimens, low pre-treatment basal immunoglobulin levels and the association with Mycophenolate and purine analogues represent risk factors for the development of hypogammaglobulinemia. The number of RTX courses, the evidence of low IgG levels for more than 6 months, the use of G-CSF, the occurrence of chronic lung disease, cardiac insufficiency, extra-articular involvement in patients with rheumatoid arthritis, low levels of IgG and older age have been correlated with a higher risk of infections. Even though the heterogeneity of the studies in terms of study population age and underlying disease, RTX schedules as well as differences in pre-treatment or concomitant therapy doesn't allow drawing definitive conclusions, the study of the literature highlight the association of specific risk factors with the occurrence of hypogammaglobulinemia and/or infections. A long term randomized controlled clinical trial could be useful to define a personalized evidence-based risk management plan for patients treated with RTX.


Assuntos
Agamaglobulinemia/epidemiologia , Fatores Etários , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Pneumopatias/epidemiologia , Rituximab/efeitos adversos , Agamaglobulinemia/etiologia , Animais , Antígenos CD20/imunologia , Humanos , Fatores de Risco , Rituximab/uso terapêutico
9.
Arch Dis Child Educ Pract Ed ; 101(3): 129-35, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26987724

RESUMO

Children are often referred to immunologists for the evaluation of reduced serum immunoglobulins. Knowledge of the immunoglobulin levels in healthy children of different ages is necessary when estimating immunological deficiency states of various kinds. After the measurement of the serum levels of the three major isotypes, examination of the capacity of the child to form antibodies to several antigens is a reasonable next step in the evaluation. We can rely on vaccine responses to make the distinction between significant primary immunodeficiency diseases and transiently low immunoglobulin levels. On the other hand, normal values of IgM, IgG and IgA are not always enough to exclude a more serious condition. Regardless of immunoglobulin concentrations, if a child's history indicates that further evaluation is warranted, a complete humoral immunity study should be carried out, including IgG subclasses, specific antibody responses and identification of B lymphocyte populations.


Assuntos
Biomarcadores/sangue , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/imunologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Síndromes de Imunodeficiência/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Síndromes de Imunodeficiência/diagnóstico , Lactente , Masculino
10.
Acta Paediatr ; 104(7): e324-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25736706

RESUMO

AIM: Information on the epidemiology of childhood urinary tract infections (UTIs) is scarce and mostly based on retrospective data. This study investigated incidence rates, morbidity and risk factors for UTIs in a prospective cohort of children. METHODS: We explored UTIs in a representative cohort of 1049 neonates from birth to 6 years of age, using maternal interviews that were verified by hospital records. The majority (88.2%) completed the first-year, and more than half (56.2%) completed the 6-year follow-up. RESULTS: By 6 years of age, more than 10% of our sample had been affected by UTIs. The cumulative incidence for the first year of life was 3.77%, without significant differences between genders, and for one to 6 years, it was 6.81% and 5.7 times higher in girls than boys. Clinical information was available for 63 children: 25 were hospitalised, 16 suffered recurrences, 10 received prophylaxis, eight had urinary tract malformations, three required surgery, and two had impaired renal function. CONCLUSION: UTIs affected approximately 4% and 10% of children by the ages of one and 6 years, respectively, and their incidence was related to gender and age. Morbidity was considerable, recurrences were common, and despite advances in management, long-term consequences may still be encountered.


Assuntos
Infecções Urinárias/complicações , Infecções Urinárias/epidemiologia , Fatores Etários , Criança , Pré-Escolar , Feminino , Grécia , Hospitalização , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Infecções Urinárias/terapia
11.
Arch Dis Child ; 95(12): 1004-8, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20876557

RESUMO

OBJECTIVE: To prospectively investigate the effects of breastfeeding on the frequency and severity of infections in a well-defined infant population with adequate vaccination coverage and healthcare standards. STUDY DESIGN: In a representative sample of 926 infants, successfully followed up for 12 months, feeding mode and all infectious episodes, including acute otitis media (AOM), acute respiratory infection (ARI), gastroenteritis, urinary tract infection, conjunctivitis and thrush, were recorded at 1, 3, 6, 9 and 12 months of life. RESULTS: Infants exclusively breastfed for 6 months, as per WHO recommendations, presented with fewer infectious episodes than their partially breastfed or non-breastfed peers and this protective effect persisted after adjustment for potential confounders for ARI (OR 0.58, 95% CI 0.36 to 0.92), AOM (OR 0.37, 95% CI 0.13 to 1.05) and thrush (OR 0.14, 95% CI 0.02 to 1.02). Prolonged exclusive breastfeeding was associated with fewer infectious episodes (r(s)=-0.07, p=0.019) and fewer admissions to hospital for infection (r(s)=-0.06, p=0.037) in the first year of life. Partial breastfeeding was not related to protective effect. Several confounding factors, including parental age and education, ethnicity, presence of other siblings, environmental tobacco smoke exposure and season of birth were demonstrated to have an effect on frequency of infections during infancy. CONCLUSIONS: Findings from this large-scale prospective study in a well-defined infant population with adequate healthcare standards suggest that exclusive breastfeeding contributes to protection against common infections during infancy regarding and lessens the frequency and severity of infectious episodes. Partial breastfeeding did not seem to provide this protective effect.


Assuntos
Aleitamento Materno/estatística & dados numéricos , Controle de Infecções/métodos , Candidíase Bucal/epidemiologia , Candidíase Bucal/prevenção & controle , Conjuntivite/epidemiologia , Conjuntivite/prevenção & controle , Feminino , Seguimentos , Gastroenterite/epidemiologia , Gastroenterite/prevenção & controle , Grécia/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Masculino , Otite Média/epidemiologia , Otite Média/prevenção & controle , Estudos Prospectivos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/prevenção & controle , Infecções Urinárias/epidemiologia , Infecções Urinárias/prevenção & controle
12.
J Infect ; 61(1): 49-53, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20394772

RESUMO

SUMMARY BACKGROUND: Factors predisposing to acute otitis media (AOM) are not thoroughly understood. OBJECTIVES: In this study we prospectively investigated incidence rates and risk factors of AOM in a systematic sample of infants in a well-defined population. DESIGN AND SUBJECTS: Following interview soon after delivery in a representative sample of 1049 mother-infant pairs, information was collected 1, 3, 6, 9 and 12 months after birth. Episodes of AOM were recorded as by parental reports of diagnosis made by a physician. AOM frequency was further analyzed against 21 social, maternal, paternal, prenatal, perinatal and infantile factors. RESULTS: Successful 12-month follow-up was achieved for 926/1049 infants (88.3%), of whom 265 (28.6%) were reported with episodes of AOM; 153 with a single, 55 with two, and 57 with three to six episodes (16.5%, 5.94%, and 6.16% respectively). Factors founded by multivariate analysis to predispose to AOM included presence of siblings (P<0.001), out-of-home daycare (P<0.001), ill health in pregnancy (P<0.01), and suboptimal breastfeeding (P<0.01). Multiple (3 or more) episodes were related to presence of siblings (P<0.0001), out-of-home daycare (P<0.001), ill health in pregnancy (P<0.001), and low parental education (P<0.001). 28 infants were hospitalized (10.6% of infants with AOM, 3.02% of the total cohort). Hospitalization was related to young maternal age (P<0.05). CONCLUSIONS: Our findings confirm the high morbidity of AOM during infancy and point to several infant- and family-related predisposing factors, some of which are liable to intervention.


Assuntos
Otite Média/epidemiologia , Adulto , Causalidade , Saúde da Família , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Estudos Prospectivos
13.
Acta Paediatr ; 96(10): 1441-4, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17850395

RESUMO

AIM: To identify maternal and infantile factors affecting intention to breastfeed, early weaning and duration of breastfeeding. DESIGN/SUBJECTS: In a prospective cohort study, 1049 mothers were interviewed after delivery and at 1, 3, 6, 9 and 12 months post-partum. RESULTS: Of 1049 mothers, 942 (89.7%) intended to breastfeed. Negative attitude was associated with lack of breastfeeding previous offspring, multiparity, admission to neonatal ward, tobacco use, prematurity and male gender (OR: 10.1, 2.67, 3.02, 2.63, 2.40 and 1.54, respectively). Six hundred and twenty-three mothers (60.7%) were breastfeeding at month 1. Early weaning was associated with lack of breastfeeding previous offspring, tobacco use, prematurity, admission to neonatal ward, caesarean section (OR: 12.3, 3.39, 2.33, 2.22, 1.34), low education (p < 0.0001) and young age (p = 0.034). Factors negatively affecting total duration of breastfeeding included lack of breastfeeding previous offspring (3.91 vs. 16.2 weeks, p < 0.001), tobacco use (6.78 vs. 15.9 weeks, p < 0.001), low education (p < 0.001), early re-employment (12.5 vs. 15.1 weeks, p < 0.01) and prematurity (p < 0.005). CONCLUSION: Maternal negative attitude, tobacco use and early re-employment are factors negatively affecting breastfeeding that can be liable to intervention. All health professionals involved in perinatal medicine share a part of responsibility in sustaining breastfeeding, particularly in high-risk groups of mothers.


Assuntos
Atitude Frente a Saúde , Aleitamento Materno/psicologia , Relações Mãe-Filho , Mães/psicologia , Desmame , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Recém-Nascido , Entrevistas como Assunto , Masculino , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo
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