Contribution of the interferon-gamma release assay to tuberculosis diagnosis in children and adolescents.

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.

Expression of human endogenous retrovirus K and W in babies.

Here we determined the relative expression of HERV-K and W proviruses in HIV infected and non-infected mothers as well as their respective babies up to 1 year-old. HIV-infected mothers, their babies and uninfected control groups presented expression of both HERV-K and HERV-W with relatively high frequency. While the level of HERV-K expression was similar among groups, the level of HERV-W expression in HIV-infected mothers was four-fold higher than the uninfected mothers from the control group (p < 0.01). HERV-W was down regulated in HIV-exposed babies in comparison to non-exposed babies. To our knowledge, this is the first report of HERV transcriptional activity in babies from 0-1 year-old.

Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART.

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.

Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART

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 percent. 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 percent, P < 0.001; CD8+, 70.9 vs 79.6 percent, P = 0.003) and higher percentages of central memory T cells than CT neonates (CD4+, 13.9 vs 8.7 percent, P < 0.001; CD8+, 8.6 vs 4.8 percent, 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.

Manifestaçoes neurológicas em crianças e adolecentes infectados e expostos ao HIV-1 / Neurological findings in a group of children and adolescents exposed and infected by HIV-1

The CNS infection by HIV-1 in infancy could be present immediately after infection or became manifest later. Microcephalia, mental retardation, pyramidal signs, humor and behavioral disorders and antiretroviral therapy complications are common. This is an observational, sectional and descriptive study about findings on neurological examination of 173 patients in a group of children and adolescents infected and exposed to HIV-1 in perinatal period. Most of them had more than one neurological finding or different diagnosis. The more common findings were: encephalopathy, mental retardation, language delay, pyramidal signs, hyporeflexia. The neurological examination was abnormal in 67% of all patients even in seroreverters. We suggest that this group has a high risk to neurological disease and the development of co-morbidity is directly correlated to clinical deterioration by HIV-1 infection.

O envolvimento do sistema nervoso central SNC na infecção pelo HIV-1 em crianças pode estar evidente desde o início ou demorar muitos anos para se manifestar. Microcefalia, rebaixamento cognitivo, sinais piramidais, distúrbios do humor e do comportamento e complicações pelo uso da terapia antiretroviral são comuns. Este é um trabalho observacional, descritivo e seccional cuja finalidade é descrever as alterações do exame neurológico em um grupo de crianças e adolescentes expostos pelo HIV-1 durante o período perinatal. Foram avaliados 173 pacientes. Muitos pacientes tinham superposição de alterações de exame neurológico e/ou mais de um diagnóstico. As alterações mais comuns foram: retardo do desenvolvimento neuropsicomotor, atraso de linguagem, deficiência mental, síndrome piramidal, hiporreflexia. O exame neurológico foi alterado em 67% dos casos, mesmo naqueles pacientes soro-revertidos. Sugerimos que existe alto risco para doença neurológica nesse grupo de pacientes e que a progressão da infecção pelo HIV-1 acentua o aparecimento de co-morbidades e comprometimento de seu prognóstico.

Immunogenicity and tolerability of hepatitis A vaccine in HIV-infected children.

The immunogenicity and tolerability of hepatitis A virus vaccine was evaluated in a group of 32 children with human immunodeficiency virus (HIV) infection and 27 children with seroreversion. After 2 doses of vaccine, 100% of children experienced seroconversion with good toleration of the vaccine. There were no differences in variation of virus load between immunized HIV-positive children and a group of 31 nonimmunized HIV-positive children with similar characteristics.

Seroprevalence of human herpesvirus 8 infection in children born to HIV-1-infected women in São Paulo, Brazil.

Human herpesvirus-8 (HHV-8) appears to be transmitted mainly by sexual contact. However, several studies suggest that in developing countries the infection may be acquired early in life by routes other than sexual transmission. The present study estimated the seroprevalence of HHV-8 in Brazilian children born to HIV-1-infected mothers. The serum samples were collected in a cross-sectional cohort study from 99 children born to HIV-infected mothers (median age 3.27 years; range 1.5-13.8 years) attending the outpatient clinic of the Federal University of Sao Paulo. IgG antibodies to HHV-8 latency-associated nuclear antigen and lytic phase antigens were detected by immunofluorescence assays. The samples tested were collected from children aged 12 months or older to exclude the possibility of cross-placental antibody transport. The total prevalence of anti-lytic antibodies in this population (5/99; 5%) reveals that HHV-8 infection can occur during childhood. Children aged 1.5 to 2 years had a seroprevalence of 2% (1/50) and children aged 3.25 to 13.8 years had a seroprevalence of 8% (4/49). This difference was not statistically significant, probably because of the small size of the sample, but it suggests that HHV-8 infection occurs more commonly late in infancy. Further prospective studies are necessary to evaluate the timing and risk factors for primary HHV-8 infection in the pediatric population.

Seroprevalence of human herpesvirus 8 infection in children born to HIV-1- infected women in São Paulo, Brazil

Human herpesvirus-8 (HHV-8) appears to be transmitted mainly by sexual contact. However, several studies suggest that in developing countries the infection may be acquired early in life by routes other than sexual transmission. The present study estimated the seroprevalence of HHV-8 in Brazilian children born to HIV-1-infected mothers. The serum samples were collected in a cross-sectional cohort study from 99 children born to HIV-infected mothers (median age 3.27 years; range 1.5-13.8 years) attending the outpatient clinic of the Federal University of São Paulo. IgG antibodies to HHV-8 latency-associated nuclear antigen and lytic phase antigens were detected by immunofluorescence assays. The samples tested were collected from children aged 12 months or older to exclude the possibility of cross-placental antibody transport. The total prevalence of anti-lytic antibodies in this population (5/99; 5 percent) reveals that HHV-8 infection can occur during childhood. Children aged 1.5 to 2 years had a seroprevalence of 2 percent (1/50) and children aged 3.25 to 13.8 years had a seroprevalence of 8 percent (4/49). This difference was not statistically significant, probably because of the small size of the sample, but it suggests that HHV-8 infection occurs more commonly late in infancy. Further prospective studies are necessary to evaluate the timing and risk factors for primary HHV-8 infection in the pediatric population.

Crianças com SIDA: efeitos da Terapia antiretroviral no desenvolvimento cognitivo

O objetivo do presente estudo foi verificar os efeitos da terapia antiretroviral no desenvolvimento cognitivo de crianças com SIDA. A amostra constituiu-se de 44 crianças entre 2 e 10 anos de idade, de ambos os sexos. 29 (65,9

) crianças faziam uso da terapia antiretroviral e 15 (34,1

) crianças não recebiam tratamento médico. Após um tempo mínimo de nove meses de uso da terapia antiretroviral. 29 destas crianças foram retestadas. Verificamos que não houve modificação no desempenho da habilidade cognitiva geral com o uso da medicação. Observamos melhora significativa nas habilidades de Linguagem nos dois grupos, no segundo momento de avaliação. Apontamos para a necessidade de atendimento multiprofissional às crianças infectadas pelo HIV devido aos fatores psicossociais associados à SIDA influenciarem o desenvolvimento global das crianças(AU)

[Vitamin A serum level in children with visceral leishmaniasis]. / Nível sérico da vitamina A em crianças portadoras de leishmaniose visceral.

Vitamin A is considered an anti-infectious disease vitamin, and its deficiency is associated with severe infections such as in measles. In developing countries the low concentrations of vitamin A are a public health problem. The aim of this study is to describe serum vitamin A concentrations among children with visceral leishmaniasis (VL). Blood sample was collected from 22 children with VL, and stored in a freezer, 9 siblings, with no clinical signs of the VL patients had their blood collected for a control group. Samples were assayed by high performance liquid chromatography. The median vitamin A concentration in the LV group was 21.38 microg/100ml and in the control group it was 31.39 microg/100. The mean in the LV was statistically lower than in the control group, using Student's t test, p<0.01.

Nível sérico da vitamina A em crianças portadoras de leishmaniose visceral / Vitamin A serum level in children with visceral leishmaniasis

A vitamina A tem sido considerada uma vitamina anti-infecciosa e sua deficiência está associada a um maior risco de infecções graves, como ocorre por exemplo no sarampo. Nos países em desenvolvimento a hipovitaminose A é um grave problema de saúde pública. O objetivo deste estudo é quantificar o nível sérico da vitamina A em pacientes pediátricos portadores da leismaniose visceral (LV). Amostras de sangue foram coletadas de 22 crianças portadoras de LV, estocadas em freezer e posteriormente, quantificado o nível de vitamina A usando-se a cromatrografia líquída de alta eficiência, nove irmãos assintomáticos dos pacientes foram usados como controles. A média do nível sérico da vitamina A nos portadores de LV foi de 21,38µg/100ml e no grupo controle foi de 31,39µg/100ml. Entre os pacientes estudados com LV a média do nível sérico de vitamina A encontrado foi significativamente menor, utilizando-se o teste t de Student para um p<0,01 que dos controles.

Vitamin A is considered an anti-infectious disease vitamin, and its deficiency is associated with severe infections such as in measles. In developing countries the low concentrations of vitamin A are a public health problem. The aim of this study is to describe serum vitamin A concentrations among children with visceral leishmaniasis (VL). Blood sample was collected from 22 children with VL, and stored in a freezer, 9 siblings, with no clinical signs of the VL patients had their blood collected for a control group. Samples were assayed by high performance liquid chromatography. The median vitamin A concentration in the LV group was 21.38 microg/100ml and in the control group it was 31.39 microg/100. The mean in the LV was statistically lower than in the control group, using Student's t test, p<0.01.

[Acquired immunodeficiency syndrome in children: pathogenesis, prognostic markers, and treatment] / Síndrome da imunodeficiência adquirida na criança. Aspectos da patogênese, marcadores prognósticos e tratamento.

OBJECTIVE: To review recent knowledge about Acquired Immunodeficiency Syndrome in children to help pediatricians provide care for these patients.METHOD: We reviewed the most recent papers about pathogenesis, prognostic markers and treatment of the HIV- infected child.RESULTS: We present the main HIV features that may interfere in the pathogenesis of this syndrome and that should be taken into consideration when the antiretroviral therapy starts.CONCLUSIONS: Viral replication in children is very intense, and the persistence of high levels of viral load may be a sign of immunological immaturity. Viral load measurement and CD4+ lymphocytes count are important markers of the disease progression. At least two drugs should be administered as antiretroviral therapy, which should aim at reducing the viral load to undetectable levels. This will slow down the progression of the disease and the emergence of resistant viral strains.

[Diagnostic of congenital syphilis: a comparison between serological tests in mothers and their newborns]. / Diagnóstico de sífilis congênita: comparação entre testes sorológicos na mãe e no recém-nascido.

For the purpose of establishing the incidence of maternal and congenital syphilis among pregnant women at delivery and their respective newborns, a study was carried out to determine treponemic and non-treponemic serology in one thousand (1,000) parturient women and their children at Santa Marcelina Hospital - São Paulo, between June 95 and July 96. All blood samples (maternal venous, umbilical cord and newborn venous) were VDRL-tested, treponemic tests (TPHA, ELISA IgG, ELISA IgM) being applied whenever one of the samples from mother or newborn proved positive. Further, an anti-HIV search was run through ELISA among VDRL-positive mothers. Among the 1,000 parturients, 24 (2.4%) were found to be VDRL-reactive; 18 (1.8%) newborn children of these 24 mothers presented positive serology in their umbilical cord blood and 19 (1.9%) in venous blood. No positive newborns were found for negative mothers. From the high occurrence of maternal and congenital syphilis in this group of patients, we propose a VDRL maternal test as a way of selecting gestational and congenital syphilis cases, since this test appeared to be sufficiently capable of such diagnoses. Of the treponemic tests, the ELISA test did not enhance diagnostic sensitivity.

[Hepatitis C virus (HCV) in children and adolescent hemophiliacs] / Hepatite pelo vírus C (HCV) em crianças e adolescentes hemofílicos.

OBJECTIVE: To evaluate the prevalence of infection by HCV among hemophiliacs in the State of Pará (Brazil), and its possible relation to hepatic enzymes serum level, type of hemophilia involved, age, level of severity, kinds and combinations of treatment, as well as date in which treatment with hemoderivates was started.METHODS: Cross-sectional epidemiological investigation, analyzing 62 hemophilic patients of the Centro de Hemoterapia do Pará (HEMOPA), all born after 01/01/80, by means of the review of the medical records, physical examination and laboratory tests: Anti-HCV (ELISA 3.0), polymerase chain reaction - PCR - (HCV-RNA), and dosage of transaminases serum levels. Statistical analysis was carried out using Chi-square and Fisher's Exact Test, the results being considered significant if p

Ceftriaxona em meningites na infância: possibilidade de tratamento ambulatorial / Ceftriaxone in miningitis childhood

Devido ao amplo espectro antimicrobiano e seu esquema de dose única diária, a ceftriaxona tem sido largamente usada para o tratamento de infecçöes graves, incluindo meningite bacteriana. Entre os importantes problemas enfrentados por médicos e pacientes em países desenvolvidos, estäo a falta de leitos hospitalares e a alta incidência de hospitalares. Por estas razöes e baseados em nossa experiência prévia com o uso de ceftriaxona, decidimos estudar a possibilidade de um regime terapêutico que permitisse tratamento ambulatorial de pacientes com meningite bacteriana. Vinte crianças com idades variando entre 3 e 75 meses e com diagnóstico de meningite bacteriana causada por N. meningitidis, S. pneumoniae ou H. influenzae, foram tratadas com dose única...

Comprometimento cardiacao no sarampo. / Cardiac involvement in measles

A revisao da literatura mostra poucas citacoes de alteracoes cardiacas complicando o sarampo. Como na pratica o achado destas alteracoes cardiacas nos pareciam bastante frequentes, realizamos um estudo em 93 criancas de tres meses a oito anos de idade que foram internadas em nosso servico com diagnostico de sarampo. Em todas elas foram realizados estudos eletrocardiograficos na internacao e feito o seguinte pertinente. Em 86 criancas apareceram alteracoes do tracado, o que da um indice de 92,4%. Taquicardia sinusal e alteracoes de repolarizacao ventricular foram os achados mais frequentes. A porcentagem de alteracoes nos casos com ou sem complicacoes nao difere significativamente