RESUMO
SETTING: As conclusive data on the performance of interferon-gamma release assays (IGRAs) in paediatric TB are lacking, many guidelines do not recommend their use for TB diagnosis in this population in Brazil. OBJECTIVE: To evaluate the performance of an IGRA by investigating its concordance with the tuberculin skin test (TST) and the role of IGRAs in clinical management and treatment outcomes in children with TB. DESIGN: A historic cohort study was used to evaluate the performance of T-SPOT®.TB (ELISpot) and other tests, such as the TST, in paediatric patients with or without immunodeficiency who were under investigation for latent tuberculous infection (LTBI) or active tuberculosis (TB). RESULTS: Of 86 paediatric patients evaluated, 41 (48%) were immunocompetent and 45 (52%) immunocompromised. All patients underwent T-SPOT.TB, while 63 underwent both ELISpot and TST; test results were concordant in 50 patients (79.4%): 22/31 (71%) in immunocompetent (κ = 0.418, P = 0.02) and 28/32 (87.5%) in immunocompromised patients (κ = 0.526, P = 0.003). TB was diagnosed on the basis of the ELISpot result in 21% (18/86) cases; the contribution of the ELISpot assay was greater in immunocompetent patients than in those who were immunocompromised (13/41, 31.7% vs. 5/45, 11.1%, χ2 P = 0.038). CONCLUSION: ELISpot and TST results were moderately concordant in both groups of patients. ELISpot contribution was higher among immunocompetent patients than among immunocompromised patients.
Assuntos
ELISPOT/estatística & dados numéricos , Testes de Liberação de Interferon-gama/estatística & dados numéricos , Teste Tuberculínico/estatística & dados numéricos , Tuberculose/diagnóstico , Adolescente , Brasil , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Hospedeiro Imunocomprometido , Lactente , Masculino , Adulto JovemRESUMO
BACKGROUND: This is a prospective study that assessed pneumococcal antibody levels in PID patients under intravenous immunoglobulin (IVIG) treatment using different brands. METHODS: Twenty-one patients receiving regular IVIG every 28 days were invited to participate: 12 with common variable immunodeficiency, six with X-linked agammaglobulinaemia and three with hyper-IgM syndrome. One blood sample was collected from each patient just prior to IVIG administration at a three-month time interval during one year. A questionnaire was filled in with patient's demographic data and history of infections during the study period. Streptococcus pneumoniae antibodies against six serotypes (1, 5, 6B, 9V, 14 and 19F) were assessed by ELISA both in patients' serum (trough levels) and in IVIG samples. RESULTS: Median total IgG trough serum levels were 7.91g/L (range, 4.59-12.20). All patients had antibody levels above 0.35µg/mL to the six serotypes on all four measurements. However, only 28.6% of patients had pneumococcal antibodies for the six analysed serotypes above 1.3µg/mL on all four evaluations during the one-year period. No correlation was found between IgG trough levels and pneumococcal specific antibodies. Eighteen of the 21 patients (85.7%) had infections at some point during the 12-month follow-up, 62/64 (96.9%) clinically classified in respiratory tract infections, four of which were pneumonia. CONCLUSIONS: Pneumococcal antibodies are present in a high range of concentrations in sera from PID patients and also in IVIG preparations. Even maintaining a recommended IgG trough level, these patients can be susceptible to these bacteria and that may contribute to recurrent respiratory infections.
Assuntos
Anticorpos Antibacterianos/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/imunologia , Pneumonia Pneumocócica/imunologia , Streptococcus pneumoniae/imunologia , Adolescente , Adulto , Brasil , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Imunoglobulina G/sangue , Síndromes de Imunodeficiência/terapia , Masculino , Pneumonia Pneumocócica/terapia , Estudos Prospectivos , Adulto JovemRESUMO
Tuberculosis (TB) infection was evaluated in Brazilian immunocompetent children and adolescents exposed and unexposed (control group) to adults with active pulmonary TB. Both groups were analysed by clinical and radiological assessment, TST, QFT-IT and T-SPOT.TB. The three tests were repeated after 8 weeks in the TB-exposed group if results were initially negative. Individuals with latent tuberculosis infection (LTBI) were treated and tests were repeated after treatment. Fifty-nine TB-exposed and 42 controls were evaluated. Rate of infection was 69·5% and 9·5% for the exposed and control groups, respectively. The exposed group infection rate was 61% assessed by TST, 57·6% by T-SPOT.TB, and 59·3%, by QFT-IT. No active TB was diagnosed. Agreement between the three tests was 83·1% and 92·8% in the exposed and control groups, respectively. In the exposed group, T-SPOT.TB added four TB diagnoses [16%, 95% confidence interval (CI) 1·6-30·4] and QFT-IT added three TB diagnoses (12%, 95% CI 0-24·7) in 25 individuals with negative tuberculin skin test (TST). Risk factors associated to TB infection were contact with an adult with active TB [0-60 days: odds ratio (OR) 6·9; >60 days: OR 27·0] and sleeping in the same room as an adult with active TB (OR 5·2). In Brazilian immunocompetent children and adolescents, TST had a similar performance to interferon-gamma release assays and detected a high rate of LTBI.
Assuntos
Testes de Liberação de Interferon-gama/métodos , Mycobacterium tuberculosis/isolamento & purificação , Teste Tuberculínico/métodos , Tuberculose/epidemiologia , Adolescente , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Prevalência , Fatores de Risco , Tuberculose/microbiologiaRESUMO
Children born to female kidney recipients are exposed to immunosuppressive drugs during gestation. Little is known about their immune system at birth or in the long term. Twenty-eight children born to female kidney recipients and 40 full-term children born to healthy mothers were evaluated. T, B, NK, NKT, γδT cells were assessed by flow cytometry and functional evaluation of T and dendritic cells after in vitro activation was performed at birth and at 8 months of age. At birth, infants born to female kidney recipients showed lower numbers of CD4+ T, NKT and intense reduction of B cells (median cells/mm(3) , transplant: 153.7 X control: 512.4; p < 0.001). There was also a reduced percentage of activated CD8+ T and of CD4+ regulatory T cells. Activated memory and exhausted memory B cells showed higher percentages among children exposed to immunosuppressors when compared to control group. At 8 months, most immune alterations were no longer observed, but four children still had low numbers of some lymphocyte subsets at this age. Children born to female kidney recipients had 4.351 (95% CI: 1.026-15.225; p = 0.046) higher risk of hospital admission in the first months of life-some, with severe clinical manifestations-than those born to healthy women.
Assuntos
Hospitalização/estatística & dados numéricos , Imunofenotipagem , Infecções/epidemiologia , Transplante de Rim , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Transplantados , Imunidade Adaptativa/efeitos dos fármacos , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Idade Gestacional , Rejeição de Enxerto/prevenção & controle , Humanos , Imunidade Inata/efeitos dos fármacos , Imunossupressores/efeitos adversos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Lactente , Recém-Nascido , Gravidez , Fatores de Risco , Linfócitos T Reguladores/patologia , Adulto JovemRESUMO
An increased incidence of pertussis has been observed recently in adults, and healthcare workers (HCWs) are considered a risk group for transmission to infants. Prevalence of recent pertussis infection was assessed in HCWs from a paediatric department of a tertiary care hospital in Brazil. Serum pertussis toxin IgG antibodies were measured by enzyme-linked immunosorbent assay. Of 388 HCWs included in the analysis, 6.4% had serology suggestive of recent infection. Medical residents [odds ratio (OR): 4.15; 95% confidence interval (CI): 1.42-12.14; P = 0.009] and those working >40 h a week (OR: 3.29; 95% CI: 1.17-9.26; P = 0.024) had increased risk of pertussis infection.
Assuntos
Infecção Hospitalar/epidemiologia , Transmissão de Doença Infecciosa/prevenção & controle , Transmissão de Doença Infecciosa/estatística & dados numéricos , Pessoal de Saúde/estatística & dados numéricos , Hospitais Pediátricos/estatística & dados numéricos , Centros de Atenção Terciária/estatística & dados numéricos , Coqueluche/epidemiologia , Adulto , Idoso , Bordetella pertussis , Brasil/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto JovemRESUMO
BACKGROUND: PIDs are a heterogeneous group of genetic illnesses, and delay in their diagnosis is thought to be caused by a lack of awareness among physicians concerning PIDs. The latter is what we aimed to evaluate in Brazil. METHODS: Physicians working at general hospitals all over the country were asked to complete a 14-item questionnaire. One of the questions described 25 clinical situations that could be associated with PIDs and a score was created based on percentages of appropriate answers. RESULTS: A total of 4026 physicians participated in the study: 1628 paediatricians (40.4%), 1436 clinicians (35.7%), and 962 surgeons (23.9%). About 67% of the physicians had learned about PIDs in medical school or residency training, 84.6% evaluated patients who frequently took antibiotics, but only 40.3% of them participated in the immunological evaluation of these patients. Seventy-seven percent of the participating physicians were not familiar with the warning signs for PIDs. The mean score of correct answers for the 25 clinical situations was 48.08% (±16.06). Only 18.3% of the paediatricians, 7.4% of the clinicians, and 5.8% of the surgeons answered at least 2/3 of these situations appropriately. CONCLUSIONS: There is a lack of medical awareness concerning PIDs, even among paediatricians, who have been targeted with PID educational programmes in recent years in Brazil. An increase in awareness with regard to these disorders within the medical community is an important step towards improving recognition and treatment of PIDs.
Assuntos
Competência Clínica/estatística & dados numéricos , Síndromes de Imunodeficiência/epidemiologia , Médicos/estatística & dados numéricos , Brasil , Estudos Transversais , Cirurgia Geral , Hospitais Gerais , Humanos , Síndromes de Imunodeficiência/diagnóstico , Medicina Interna , Pediatria , Papel do Médico , Prática Profissional , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Severe combined immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency. The objectives of this study were to analyze the diagnosis, treatment, and prognosis of SCID in Brazil and to document the impact of BCG vaccine. METHODS: We actively searched for cases by contacting all Brazilian referral centers. RESULTS: We contacted 23 centers and 70 patients from 65 families. Patients were born between 1996 and 2011, and 49 (70%) were male. More than half (39) of the diagnoses were made after 2006. Mean age at diagnosis declined from 9.7 to 6.1 months (P = .058) before and after 2000, respectively, and mean delay in diagnosis decreased from 7.9 to 4.2 months (P = .009). Most patients (60/70) were vaccinated with BCG before the diagnosis, 39 of 60 (65%) had complications related to BCG vaccine, and the complication was disseminated in 29 of 39 (74.3%). Less than half of the patients (30, 42.9%) underwent hematopoietic stem cell transplantation (HSCT). Half of the patients died (35, 50%), and 23 of these patients had not undergone HSCT. Disseminated BCG was the cause of death, either alone or in association with other causes, in 9 of 31 cases (29%, no data for 4 cases). CONCLUSIONS: In Brazil, diagnosis of SCID has improved over the last decade, both in terms of the number of cases and age at diagnosis, although a much higher number of cases had been expected. Mortality is higher than in developed countries. Complications of BCG vaccine are an important warning sign for the presence of SCID and account for significant morbidity during disease progression.
Assuntos
Vacina BCG/efeitos adversos , Imunodeficiência Combinada Severa/terapia , Adolescente , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/epidemiologiaRESUMO
BACKGROUND: Patients with common variable immunodeficiency (CVID) present with low antibody levels, impaired lymphocyte function, and chronic inflammation. Vitamin A and zinc are essential components of the immune system and can be redistributed in the body as a result of inflammation. OBJECTIVE: To compare levels of retinol, beta-carotene, and zinc in patients with CVID and healthy controls after evaluating a series of parameters for each participant. PATIENTS AND METHODS: We performed a cross-sectional study of CVID patients and healthy controls matched for age and gender. All participants underwent a nutritional and laboratory evaluation comprising a complete blood count and determination of levels of C-reactive protein (CRP), lipopolysaccharide (LPS), soluble CD14 (sCD14), retinol, beta-carotene, and serum and erythrocyte zinc. RESULTS: We included 17 patients (mean age, 28.54 years) and 17 controls. Mean (SD) retinol levels were lower in patients: 1.99 (0.67) micromol/L vs 2.72 (0.96) micromol/L. Median beta-carotene levels were similar in both groups (0.30 micromol/L). Median serum zinc levels were 50.0 microg/dL (50-100 microg/dL) in the patients and 100.0 microg/dL (50-150 microg/dL) in the controls. Mean levels of erythrocyte zinc were lower among patients: 37.32 (10.51) microgZn/gHb vs 44.91 (7.67) microgZn/gHb in the controls. Median CRP levels were significantly higher among patients: 4.99 (0.15-34.51) mg/L vs 0.55 (0.17-6.06) mg/L. No differences in translocation marker levels were observed between the groups. CONCLUSIONS: CVID patients had lower levels of retinol and zinc than controls. Since micronutrient deficiency could aggravate their disease and contribute to chronic inflammation, micronutrient status should always be assessed in patients with primary immunodeficiency.
Assuntos
Imunodeficiência de Variável Comum/diagnóstico , Estado Nutricional/imunologia , Vitamina A/sangue , Zinco/metabolismo , Adolescente , Adulto , Proteína C-Reativa/metabolismo , Imunodeficiência de Variável Comum/metabolismo , Eritrócitos/metabolismo , Feminino , Humanos , Receptores de Lipopolissacarídeos/sangue , Masculino , Adulto Jovem , beta Caroteno/sangueRESUMO
A flow cytometry-adapted fluorescent antibody to membrane antigen (FAMA) assay to detect IgG antibodies against varicella-zoster virus (VZV) was developed and tested in 62 serum samples, showing 90.32% accuracy obtained from a receiver operating characteristic (ROC) curve with a 0.9125 (95% confidence interval [CI], 0.829 to 1.00) area below the curve compared to the result with standard FAMA.
Assuntos
Anticorpos Antivirais/sangue , Citometria de Fluxo , Imunofluorescência , Herpesvirus Humano 3/imunologia , Imunidade , Antígenos de Superfície , Humanos , Imunoglobulina G/sangue , Curva ROC , Sensibilidade e EspecificidadeRESUMO
The immune consequences of in utero HIV exposure to uninfected children whose mothers were submitted to highly active antiretroviral therapy (HAART) during gestation are not well defined. We evaluated 45 HIV-exposed uninfected (ENI) neonates and 45 healthy unexposed control (CT) neonates. All HIV-infected mothers received HAART during pregnancy, and the viral load at delivery was <50 copies/mL for 56.8%. Twenty-three ENI neonates were further evaluated after 12 months and compared to 23 unexposed healthy age-matched infants. Immunophenotyping was performed by flow cytometry in cord and peripheral blood. Cord blood lymphocyte numbers did not differ between groups. However, ENI neonates had a lower percentage of naive T cells than CT neonates (CD4+, 76.6 vs 83.1%, P < 0.001; CD8+, 70.9 vs 79.6%, P = 0.003) and higher percentages of central memory T cells than CT neonates (CD4+, 13.9 vs 8.7%, P < 0.001; CD8+, 8.6 vs 4.8%, P = 0.001). CD38 mean fluorescence intensity of T cells was higher in ENI neonates (CD4+, 62.2 vs 52.1, P = 0.007; CD8+, 47.7 vs 35.3, P < 0.001). At 12 months, ENI infants still had higher mean fluorescence intensity of CD38 on T cells (CD4+, 34.2 vs 23.3, P < 0.001; CD8+, 26.8 vs 19.4, P = 0.035). Despite effective maternal virologic control at delivery, HIV-exposed uninfected children were born with lower levels of naive T cells. Immune activation was present at birth and remained until at least 12 months of age, suggesting that in utero exposure to HIV causes subtle immune abnormalities.