Marcos Tadeu Nolasco da Silva

Impaired Humoral Response to Vaccines among HIV-Exposed Uninfected Infants

ABSTRACT Little is known about the vaccine protective response for infants born from HIV-infected mothers. We evaluated the antibody response to hepatitis B, tetanus, and diphtheria vaccine in vertically HIV-exposed uninfected infants and compared them to those of control infants not exposed to the virus. The quantitative determination of specific neutralizing antibodies against hepatitis B, diphtheria, and tetanus were performed blindly on serum samples. The results showed that 6.7% of the HIV-exposed uninfected individuals were nonresponders to hepatitis B vaccine (anti-HBs titer, <10 mIU/ml), and 64.4% were very good responders (anti-HBs titer, ≥1,000 mIU/ml), whereas only 3.6% of the nonexposed infants were nonresponders (χ2=10.93; 1 df). The HIV-exposed uninfected infants showed protective titers for diphtheria and tetanus but lower geometric mean anti-tetanus titers compared to those of the HIV-unexposed infants. Our data point to the necessity of evaluating vaccine immune responses in these children and reinforced that alterations in lymphocyte numbers and functions reported for newborns from HIV-infected mothers interfere with the vaccine response.

Impaired Bacillus Calmette-Guérin cellular immune response in HIV-exposed, uninfected infants.

Objective:To evaluate cell-mediated immune response to Bacillus Calmette–Guérin (BCG) vaccination in uninfected, HIV-1-exposed infants, comparing it with unexposed children. Design:It is designed as a cross-sectional study. Methods:BCG-specific lymphoproliferation and T-cell subsets (CD4+, CD8+ and TCR &ggr;&dgr;+) by flow cytometry and interleukin-10, interferon-&ggr; (IFN-&ggr;) and tumor necrosis factor-&agr; (TNF-&agr;) concentration by ELISA were analyzed in HIV-exposed and unexposed infants. Whole blood lymphocyte immunophenotyping and blood counts were performed in exposed children. Nonparametric tests were used (P < 0.05). Results:Given the ontogeny of the immune system, exposed infants were separated into three groups according to age: exposed 1 (E1, aged 6.1–8.8 months), E2 (aged 9.1–17.1 months) and E3 (aged 18.1–26.3 months). Unexposed infants (UE group) and E1 were matched for age. Cell proliferation was not different among the three exposed groups, neither for BCG nor for phytohemagglutinin (PHA)-stimulated cultures. Furthermore, BCG-stimulated lymphoproliferation was reduced in the E1 group in comparison with the UE group. T-lymphocyte subpopulations also showed differences, with the youngest HIV-exposed groups (E1 and E2) showing a predominant proliferation of CD4+ T cells in cultures with BCG, whereas E3 and UE groups had a robust &ggr;&dgr;+ T-cell expansion. There was lower IFN-&ggr; concentration in the samples from E1 group in comparison with all of the other groups. The unexposed infants showed higher TNF-&agr; concentration in cultures with BCG and PHA in comparison with E1 group. Conclusion:BCG-specific T-cell proliferation was reduced in HIV-exposed uninfected infants and IFN-&ggr; concentration was lower in younger exposed infants, showing a delay in immune system maturation of HIV-exposed infants.

Respiratory syncytial virus (RSV) in infants hospitalized for acute lower respiratory tract disease: incidence and associated risks

Respiratory syncytial virus (RSV) is one of the main causes of acute lower respiratory tract infections worldwide. We examined the incidence and associated risks for RSV infection in infants hospitalized in two university hospitals in the state of São Paulo. We made a prospective cohort study involving 152 infants hospitalized for acute lower respiratory tract infections (ALRTI) in two university hospitals in Campinas, São Paulo, Brazil, between April and September 2004. Clinical and epidemiological data were obtained at admission. RSV was detected by direct immunofluorescence of nasopharyngeal secretions. Factors associated with RSV infection were assessed by calculating the relative risk (RR). The incidence of RSV infection was 17.5%. Risk factors associated with infection were: gestational age less than 35 weeks (RR: 4.17; 95% confidence interval (CI) 2.21-7.87); birth weight less than or equal to 2,500 grams (RR: 2.69; 95% CI 1.34-5.37); mothers educational level less than five years of schooling (RR: 2.28; 95% CI 1.13-4.59) and pulse oximetry at admission to hospital lower than 90% (RR: 2.19; 95% CI 1.10-4.37). Low birth weight and prematurity are factors associated with respiratory disease due to RSV in infants. Low educational level of the mother and poor socioeconomic conditions also constitute risk factors. Hypoxemia in RSV infections at admission indicates potential severity and a need for early oxygen therapy.

Immunogenicity of a Whole-Cell Pertussis Vaccine with Low Lipopolysaccharide Content in Infants

ABSTRACT The lack of a clear correlation between the levels of antibody to pertussis antigens and protection against disease lends credence to the possibility that cell-mediated immunity provides primary protection against disease. This phase I comparative trial had the aim of comparing the in vitro cellular immune response and anti-pertussis toxin (anti-PT) immunoglobulin G (IgG) titers induced by a cellular pertussis vaccine with low lipopolysaccharide (LPS) content (wPlow vaccine) with those induced by the conventional whole-cell pertussis (wP) vaccine. A total of 234 infants were vaccinated at 2, 4, and 6 months with the conventional wP vaccine or the wPlow vaccine. Proliferation of CD3+ T cells was evaluated by flow cytometry after 6 days of peripheral blood mononuclear cell culture with stimulation with heat-killed Bordetella pertussis or phytohemagglutinin (PHA). CD3+, CD4+, CD8+, and T-cell receptor γδ-positive (γδ+) cells were identified in the gate of blast lymphocytes. Gamma interferon, tumor necrosis factor alpha, interleukin-4 (IL-4), and IL-10 levels in supernatants and serum anti-PT IgG levels were determined using enzyme-linked immunosorbent assay (ELISA). The net percentage of CD3+ blasts in cultures with B. pertussis in the group vaccinated with wP was higher than that in the group vaccinated with the wPlow vaccine (medians of 6.2% for the wP vaccine and 3.9% for the wPlow vaccine; P = 0.029). The frequencies of proliferating CD4+, CD8+, and γδ+ cells, cytokine concentrations in supernatants, and the geometric mean titers of anti-PT IgG were similar for the two vaccination groups. There was a significant difference between the T-cell subpopulations for B. pertussis and PHA cultures, with a higher percentage of γδ+ cells in the B. pertussis cultures (P < 0.001). The overall data did suggest that wP vaccination resulted in modestly better specific CD3+ cell proliferation, and γδ+ cell expansions were similar with the two vaccines.

Usefulness of pharmacy dispensing records in the evaluation of adherence to antiretroviral therapy in Brazilian children and adolescents.

INTRODUCTION Adherence, which is crucial to the success of antiretroviral therapy (HAART), is currently a major challenge in the care of children and adolescents living with HIV/AIDS. OBJECTIVE To evaluate the prevalence of nonadherence to HAART using complementary instruments in a cohort of children and adolescents with HIV/AIDS followed in a reference service in Campinas, Brazil. METHODS The level of adherence of 108 patients and caregivers was evaluated by an adapted standardized questionnaire and pharmacy dispensing records (PDR). Non-adherence was defined as a drug intake lower than 95% (on 24-hour or seven-day questionnaires), or as an interval of 38 days or more for pharmacy refills. The association between adherence and clinical, immunological, virological, and psychosocial characteristics was assessed by multivariate analysis. RESULTS Non-adherence prevalence varied from 11.1% (non-adherent in three instruments), 15.8% (24-hour self-report), 27.8% (seven-day self-report), 45.4% (PDR), and 56.3% (at least one of the outcomes). 24-hour and seven-day self-reports, when compared to PDR, showed low sensitivity (29% and 43%, respectively) but high specificity (95% and 85%, respectively). In multivariate analysis, medication intolerance, difficulty of administration by caregiver, HAART intake by the patient, lower socioeconomical class, lack of virological control, missed appointments in the past six months, and lack of religious practice by caregiver were significantly associated with non-adherence. CONCLUSION A high prevalence of HAART non-adherence was observed in the study population, and PDR was the most sensitive of the tested instruments. The instruments employed were complementary in the identification of non-adherence.

Associação entre índice de ventilação e tempo de ventilação mecânica em lactentes com bronquiolite viral aguda

OBJETIVO: Avaliar a associacao entre tempo de ventilacao mecânica e variaveis antropometricas, clinicas e de funcao pulmonar, precocemente, em lactentes com insuficiencia respiratoria por bronquiolite viral aguda em ventilacao mecânica invasiva, e a evolucao temporal das variaveis significativamente correlacionadas. METODOS: Foram estudados 29 lactentes admitidos na unidade de terapia intensiva pediatrica do Hospital de Clinicas da UNICAMP, com diagnostico de bronquiolite viral aguda, definido por criterios clinicos e radiologicos. Lactentes com doencas cronicas ou instabilidade hemodinâmica foram excluidos. Todas as medidas foram feitas entre 24 e 72 horas em ventilacao mecânica, usando capnografia volumetrica e analise dos gases sanguineos. O tempo de ventilacao mecânica foi dividido em: menor ou igual que 7 dias e maior que 7 dias. A associacao entre o tempo de ventilacao e as variaveis analisadas foi determinada pelo coeficiente de correlacao de Spearman (rs) RESULTADOS: O tempo de ventilacao mecânica apresentou correlacao positiva significativa com a PaCO2 (rs = 0,45, p = 0,01) e com o indice de ventilacao (rs = 0,51, p = 0,005), e negativa com o pH (rs = -0,40, p = 0,03). Indice de ventilacao com valor de 37, avaliado do primeiro ao quinto dia, foi associado a risco progressivamente aumentado de tempo de ventilacao mecânica maior que 7 dias (OR = 4,2 no primeiro dia a 15,71 no quarto dia) CONCLUSOES: Indice ventilatorio, PaCO2 e pH, precocemente medidos, foram associados com tempo prolongado em ventilacao mecânica, refletindo a gravidade do disturbio ventilatorio e necessidade de suporte.

Evolution of nutritional status of infants infected with the human immunodeficiency virus

CONTEXT There are today only a limited number of studies defining growth parameters and nutritional status for HIV children. OBJECTIVE To study the nutritional status of infants infected with the human immunodeficiency virus. TYPE OF STUDY Longitudinal study. SETTING Department of Pediatrics, Faculty of Medical Sciences, UNICAMP, Campinas, Brazil. PARTICIPANTS One hundred and twenty-four children born to HIV infected mothers were evaluated from birth until the age of two years. They were subdivided into two groups: 71 infected children and 53 non-infected children. MAIN MEASUREMENTS Growth was evaluated in both groups by comparing Z-scores for weight/age (w/a), length/age (H/a) and weight/length (w/H) (using the NCHS curves as reference). RESULTS The Z-score analyses showed that there was a significant difference between the two groups for all the variables studied, except for the H/a value at 3 months of age and the W/H value at 21 months of age, which showed P > 0.05. CONCLUSIONS The growth of infected infants was observed to be severely affected in comparison with that of seroreversed infants in the same age groups. Although clinical manifestations may take time to appear, the onset of growth changes begin soon after birth.

Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy.

CONTEXT AND OBJECTIVE Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART). We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS Medical records of 152 children and adolescents (54.6% male; median age 7.48 years) were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6), A (29), B (78) and C (39). Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN), grade 2 (5.0-9.9 times ULN), grade 3 (10.0-15.0 times ULN) and grade 4 (> 15.0 times ULN). To assess hepatotoxicity risk factors, odds ratios (OR) and adjusted odds ratios (aOR) for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS We observed grade 1 hepatotoxicity in 19.7 % (30/152) patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95% confidence interval (CI), 1.50-8.70; aOR, 3.58; 95% CI, 1.44-8.85) and antituberculous agents (OR, 9.23; 95% CI, 1.60-53.08; aOR, 9.05; 95% CI, 1.48-55.25). No toxicity was associated with ART. CONCLUSIONS One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.

Lack of association between nutritional status and change in clinical category among HIV-infected children in Brazil

CONTEXT AND OBJECTIVE Malnutrition is common among HIV-infected children. Our objective was to study the occurrence of malnutrition and its relationship with changes in clinical category among HIV-infected children. DESIGN AND SETTING Longitudinal study, at the Pediatrics Department and Pediatrics Investigation Center (CIPED), Faculdade de Ciências Médicas da Universidade Estadual de Campinas (Unicamp). METHODS We reviewed the hospital records of 127 vertically HIV-infected children. Anthropometric measurements were obtained at the beginning of follow-up, at clinical category change and five months later. These were converted to z-scores of weight/age, height/age and weight/height. Data were presented as means, standard deviations, frequency counts and percentages. The Wilcoxon and Kruskal-Wallis tests and odds ratios were used in the analysis. RESULTS We found that 51 (40.2%) were undernourished and 40 (31.5%) were stunted, with higher risk of being included in clinical category C. There was an association between nutritional condition and the clinical categories of the Centers for Disease Control classification (1994), and with age at symptom onset (except for height z-score). During follow-up, 36 patients (28.4%) changed their clinical category, which occurred early among the undernourished patients. The group that changed its clinical category maintained the same z-score distribution for weight, height and weight/height throughout follow-up. CONCLUSION Aids manifestation severity was associated with nutritional status and with age at symptom onset, but change in clinical category was not followed by worsening of nutritional status.

O papel do hormônio de crescimento no tratamento dos distúrbios endócrino-metabólicos do paciente com a síndrome da imunodeficiência adquirida (Aids): [revisão]

Acquired Immunodeficiency Syndrome (Aids) was initially related to HIV-associated wasting syndrome, and its metabolic disturbances to altered body composition. After Highly Active Antiretroviral Therapy (HAART) was started, malnutrition has declined and HIV-associated lipodystrophy syndrome has emerged as an important metabolic disorder. Aids is also characterized by hormonal disturbances, principally in growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis. The use of recombinant human GH (hrGH) was formerly indicated to treat wasting syndrome, in order to increase lean body mass. Even though the use of hrGH in lipodystrophy syndrome has been considered, the decrease in insulin sensitivity is a limitation for its use, which has not been officially approved yet. Diversity in therapeutic regimen is another limitation to its use in Aids patients. The present study has reviewed the main HIV-related endocrine-metabolic disorders as well as the use of hrGH in such conditions.