Serological biomarkers for monitoring response to treatment of pulmonary and extrapulmonary tuberculosis in children and adolescents.

Key measures to halt the spread of tuberculosis (TB) include early diagnosis, effective treatment, and monitoring disease management. We sought to evaluate the use of serum immunoglobulin levels against antigens present in cell envelope of Mycobacterium tuberculosis to monitor TB treatment response in children and adolescents with pulmonary (PTB) or extrapulmonary TB (EPTB). Blood samples were collected prior to and one, two, and six months following treatment initiation. Serum immunoglobulin levels against cardiolipin, sulfatide, mycolic acid and Mce1A protein were measured by ELISA. Serum from 53 TB patients and 12 healthy participants were analyzed. After six months of successful treatment, there was a significant decrease (p < 0.0001) in IgM levels against cardiolipin, sulfatide, mycolic acid and Mce1A protein and IgG levels against Mce1A protein when compared to baseline immunoglobulin levels. There was no significant variation in antibody levels during follow-up between participants with PTB and EPTB, confirmed and unconfirmed TB diagnosis, and HIV infection status. Antibody levels in control participants without TB did not decrease during follow-up. These results suggest that immunoglobulin responses to mycobacterial cell wall products may be a useful tool to monitor treatment response in children and adolescents with PTB or EPTB.

Direct effect of the 13-valent pneumococcal conjugate vaccine use on pneumococcal colonization among children in Brazil.

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) has been commercially available in Brazil since 2010. We investigated the carriage prevalence, capsular types, and antimicrobial resistance among pneumococci isolated from children immunized with PCV13 in Brazil. METHODS: We analyzed 500 children < 6 years old attending public (n = 270) and private (n = 230) clinics in Niterói/RJ, Brazil, in 2014. We determined the antimicrobial susceptibility and capsular types for all isolates. RESULTS: Thirty-eight (7.6%) of 500 children had received at least one PCV13 dose. Since only two (0.7%) of 270 children at the public clinic were vaccinated with PCV13, major analyses focused on 36 (15.7%) of 230 children attending private clinics. Nine (25%) of 36 children were pneumococcal carriers. Characteristics associated with carriage were age ≥ 2 years, cough/expectoration, and childcare center attendance (p ≤ 0.01). The capsular types found were 15B/C (n = 2), 6C, 11A/D, 16F, 23A, and 23F. Two isolates were non-typeable (NT). Three (33.3%) isolates were multidrug resistant. We found four (44.4%) penicillin non-susceptible pneumococci, with penicillin and ceftriaxone MICs ranging from 0.12 to 4.0 µg/ml and 0.023-0.5 µg/ml, respectively. We also detected two (22.2%) erythromycin-resistant isolates (MICs of 3.0 and 256 µg/ml). CONCLUSIONS: Colonization with PCV13 serotype was rare among the vaccinated children. Increasing PCV13 coverage might help reduce the frequency of major serotypes currently associated with invasive pneumococcal diseases in Brazil, such as 3 and 19A. The isolation of multidrug-resistant serotype 6C and NT isolates in carriage, however, requires close monitoring.

Pneumococcal carriage among children after four years of routine 10-valent pneumococcal conjugate vaccine use in Brazil: The emergence of multidrug resistant serotype 6C.

BACKGROUND: In 2010, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced free of charge in Brazil as part of the public immunization program. Here we investigated the carriage prevalence, colonization risk factors, capsular types, and antimicrobial resistance among pneumococcal isolates obtained from children in Brazil four years after routine PCV10 use. METHODS: Between September and December 2014, we conducted a cross-sectional study among children<6years old who attended one public and two private clinics in Niterói, RJ, Brazil to evaluate pneumococcal nasopharyngeal carriage. Antimicrobial susceptibility and capsular types were determined for all isolates. RESULTS: Of 522 children, 118 (22.6%) were pneumococcal carriers. Being≥2years old, attending childcare center, presenting with any symptoms, having acute or chronic respiratory disease, and residing in a slum were associated with pneumococcal carriage. The most prevalent capsular types were 6C (14.5%), 15B/C (11.5%), 11A/D (9.2%), and 6A (7.6%). PCV10 serotypes represented 2.5%. All isolates were susceptible to levofloxacin, rifampicin, and vancomycin. Penicillin non-susceptible pneumococci (PNSP) comprised 39%, with penicillin and ceftriaxone MICs ranging from 0.12-8.0µg/ml and 0.012-1.0µg/ml, respectively. The 33 (28%) erythromycin-resistant isolates (MICs of 1.5 to >256µg/ml) displayed the cMLSB (72.7%) or M (27.3%) phenotypes, harboring the erm(B) and/or mef(A/E) genes. High non-susceptibility rates (>20%) to clindamycin, erythromycin, penicillin, and tetracycline were largely explained by the prevalence of multidrug resistant (MDR) serotype 6C isolates. CONCLUSIONS: Effects of universal childhood PCV10 use on carriage were evident, with the near elimination of PCV10 serotypes. The emergence of MDR serotype 6C isolates, however, is a concern. Ongoing surveillance to monitor serotype 6C increase in invasive diseases is warranted.

Children and Adolescents with Perinatal HIV-1 Infection: Factors Associated with Adherence to Treatment in the Brazilian Context.

Challenges to the adherence to combination antiretroviral therapy among the pediatric population should be understood in the context of the trajectories of families, their interaction with healthcare services, and their access to material and symbolic goods. The present study analyzed individual, institutional and social factors that might be associated with the caregivers' role in the treatment adherence of children and adolescents living with HIV (CALHIV). Based on semi-structured interviews and questionnaires applied to 69 caregivers seen at pediatric AIDS services of five Brazilian macro-regions, we observed that adherent caregivers had better acceptance of diagnosis and treatment, were less likely to face discrimination and social isolation secondary to AIDS-related stigma and tended to believe in the efficacy of treatment, and to be more optimistic about life perspectives of CALHIV. Interventions aiming to improve adherence and to promote the health of CALHIV should take in consideration the interplay of such different factors.

Perinatally infected adolescents living with human immunodeficiency virus (perinatally human immunodeficiency virus).

The availability of highly potent antiretroviral treatment during the last decades has transformed human immunodeficiency virus (HIV) infection into a chronic disease. Children that were diagnosed during the first months or years of life and received treatment, are living longer and better and are presently reaching adolescence and adulthood. Perinatally HIV-infected adolescents (PHIV) and young adults may present specific clinical, behavior and social characteristics and demands. We have performed a literature review about different aspects that have to be considered in the care and follow-up of PHIV. The search included papers in the MEDLINE database via PubMed, located using the keywords "perinatally HIV-infected" AND "adolescents". Only articles published in English or Portuguese from 2003 to 2014 were selected. The types of articles included original research, systematic reviews, and quantitative or qualitative studies; case reports and case series were excluded. Results are presented in the following topics: "Puberal development and sexual maturation", "Growth in weight and height", "Bone metabolism during adolescence", "Metabolic complications", "Brain development, cognition and mental health", "Reproductive health", "Viral drug resistance" and "Transition to adult outpatient care". We hope that this review will support the work of pediatricians, clinicians and infectious diseases specialists that are receiving these subjects to continue treatment.

Draft Genome Sequence of a Community-Associated Methicillin-Resistant Panton-Valentine Leukocidin-Positive Staphylococcus aureus Sequence Type 30 Isolate from a Pediatric Patient with a Lung Infection in Brazil.

The sequence of methicillin-resistant Staphylococcus aureus strain B6 (sequence type 30 [ST30], spa type t433, staphylococcal chromosomal cassette mec element [SCCmec] type IVc, Panton-Valentine leukocidin [PVL] positive), isolated from a pediatric patient with a lung infection in Niterói, Rio de Janeiro, Brazil, is described here. The draft genome sequence includes a 2.8-Mb chromosome, accompanied by a 20-kb plasmid containing blaZ and two small cryptic plasmids.

Viral suppression and adherence among HIV-infected children and adolescents on antiretroviral therapy: results of a multicenter study / Supressão viral e adesão entre crianças e adolescentes vivendo com HIV na terapia antirretroviral: resultados de um estudo multicêntrico

OBJECTIVE: To evaluate treatment adherence among perinatally-infected pediatric human immunodeficiency virus (HIV) patients followed in pediatric centers in Brazil. METHODS: This was a cross-sectional multicenter study. Medical records were reviewed and adherence scale, assessment of caregivers' quality of life (WHOQOL-BREF), anxiety, depression, and alcohol/substances use/abuse were assessed. Outcomes included self-reported 100% adherence in the last three days and HIV viral load (VL) < 50 copies/mL. Statistical analyses included contingency tables and respective statistics, and multivariable logistic regression. RESULTS: 260 subjects were enrolled: 78% children and 22% adolescents; 93% of caregivers for the children and 77% of adolescents reported 100% adherence; 57% of children and 49% of adolescents had VL < 50 copies/mL. In the univariate analyses, HIV diagnosis for screening due to maternal infection, lower caregiver scores for anxiety, and higher scores in physical and psychological domains of WHOQOL-BREF were associated with 100% adherence. Shorter intervals between pharmacy visits were associated with VL < 50 copies/mL (p ≤ 0.01). Multivariable regression demonstrated that caregivers who did not abuse alcohol/other drugs (OR = 0.49; 95% CI: 0.27-0.89) and median interval between pharmacy visits < 33 days (OR = 0.97; 95% CI: 0.95-0.98) were independently associated with VL < 50 copies/mL; whereas lower caregiver scores for anxiety (OR = 2.57; 95% CI: 1.27-5.19) and children's HIV diagnosis for screening due to maternal infection (OR = 2.25; 95% CI: 1.12-4.50) were found to be independently associated with 100% adherence. CONCLUSIONS: Pediatric HIV programs should perform routine assessment of caregivers' quality of life, and anxiety and depression symptoms. In this setting, pharmacy records are essential to help identify less-than-optimal adherence. .

OBJETIVO: Avaliar a adesão ao tratamento antirretroviral entre portadores de HIV acompanhados em centros pediátricos. MÉTODOS: Trata-se de estudo transversal multicêntrico. Os prontuários ambulatoriais foram revistos e aplicadas escala de adesão, avaliação de qualidade de vida (WHOQOL-BREF), ansiedade, depressão e uso indevido de álcool/substâncias entre cuidadores. Os desfechos incluíram autorrelato 100% de adesão nos últimos três dias e carga viral do HIV (CV) < 50 cópias/mL. RESULTADOS: 260 indivíduos foram incluídos, 79% crianças e 21% adolescentes; 93% das crianças e 77% dos adolescentes relataram 100% de adesão; 57% das crianças e 49% dos adolescentes tinham CV < 50 cópias /mL. Na análise univariada, diagnóstico do HIV por triagem devido à infecção materna, cuidador com pontuação menor para ansiedade e maior nos domínios físico e psicológico do WHOQOL-BREF se mostraram independentemente associados a 100% de adesão. Intervalos mais curtos entre visitas de farmácia foram associados com CV < 50 cópias /mL (p ≤ 0,01). Regressão multivariada mostrou que os cuidadores sem abuso de álcool/outras drogas (OR = 0,49; IC95% 0,27-0,89) e o intervalo médio entre visitas de farmácia < 33 dias (OR = 0,97; IC95% 0,95-0,98) foram associados com CV < 50 cópias/mL; cuidador com menores escores para ansiedade (OR = 2,57; IC95% 1,27-5,19) e diagnóstico de crianças por triagem devido à infecção materna (OR = 2,25; IC95% 1,12-4,50) foram associados com 100% de adesão. CONCLUSÕES: Programas de HIV pediátrico devem avaliar qualidade de vida e sintomas de ansiedade e depressão dos cuidadores. Registros de farmácia são essenciais na identificação de adesão ...

Viral suppression and adherence among HIV-infected children and adolescents on antiretroviral therapy: results of a multicenter study.

OBJECTIVE: To evaluate treatment adherence among perinatally-infected pediatric human immunodeficiency virus (HIV) patients followed in pediatric centers in Brazil. METHODS: This was a cross-sectional multicenter study. Medical records were reviewed and adherence scale, assessment of caregivers' quality of life (WHOQOL-BREF), anxiety, depression, and alcohol/substances use/abuse were assessed. Outcomes included self-reported 100% adherence in the last three days and HIV viral load (VL)<50 copies/mL. Statistical analyses included contingency tables and respective statistics, and multivariable logistic regression. RESULTS: 260 subjects were enrolled: 78% children and 22% adolescents; 93% of caregivers for the children and 77% of adolescents reported 100% adherence; 57% of children and 49% of adolescents had VL<50 copies/mL. In the univariate analyses, HIV diagnosis for screening due to maternal infection, lower caregiver scores for anxiety, and higher scores in physical and psychological domains of WHOQOL-BREF were associated with 100% adherence. Shorter intervals between pharmacy visits were associated with VL<50 copies/mL (p ≤ 0.01). Multivariable regression demonstrated that caregivers who did not abuse alcohol/other drugs (OR=0.49; 95% CI: 0.27-0.89) and median interval between pharmacy visits<33 days (OR=0.97; 95% CI: 0.95-0.98) were independently associated with VL<50 copies/mL; whereas lower caregiver scores for anxiety (OR=2.57; 95% CI: 1.27-5.19) and children's HIV diagnosis for screening due to maternal infection (OR=2.25; 95% CI: 1.12-4.50) were found to be independently associated with 100% adherence. CONCLUSIONS: Pediatric HIV programs should perform routine assessment of caregivers' quality of life, and anxiety and depression symptoms. In this setting, pharmacy records are essential to help identify less-than-optimal adherence.

Assessment of the prognostic value of the World Health Organization clinical staging system for HIV/AIDS in HIV-infected children and adolescents in a cohort in Belo Horizonte, Brazil.

This study aimed to evaluate the prognostic value of WHO clinical staging system in HIV-infected children and adolescents in Belo Horizonte, Brazil. WHO clinical stages were evaluated for risk of disease progression in 335 patients admitted from 1989 to 2003. In Kaplan-Meier analysis, age, clinical stage, CD4% <15% and viral load >5 log(10) were statistically significant. In Cox proportional hazards model, the relative risk of disease progression for Stage 4 at admission and in the worst moment were 3.47 [confidence interval (CI) 95% CI = 1.92-6.26] and 2.89 (95% CI = 1.44-5.79). Stages 2 and 3 were neutral as predictors of risk either of disease progression. CD4% <15% and viral load > 5 log(10) remained statistically significant in multivariate analysis. WHO clinical Stage 4 was a good predictor of risk of progression in this cohort. The findings support WHO proposition to start antiretroviral treatment for patients at a more advanced clinical stage.

Pregnancy in HIV vertically infected adolescents and young women: a new generation of HIV-exposed infants.

BACKGROUND: Vertically infected individuals are reaching childbearing age and the new generation of HIV-exposed infants is coming to pediatric care. METHODS: Chart review of pregnancies among HIV vertically infected adolescents and young women. RESULTS: Fifteen pregnancies were reviewed. Girls had HIV diagnosis at median age 10.1 years (range 1.3-20). They started sexual life at median age 15 years (range 13-19); median age at pregnancy was 16.9 years (range 14-21.5); 36.4% had presented an AIDS-defining clinical event; have been followed for median 8.5 years (range 2.9-15.8) and had used median two antiretroviral regimens (range 0-7). Fourteen (93.3%) received antiretroviral drugs during pregnancy; median CD4 cell count during pregnancy was 394 (range 117-651) cells/µl and median viral load was 4800 copies/ml (range 50-100 000); 54% had undetectable viral load near delivery. All patients delivered by elective c-section. Median birth weight was 2650 g (range 2085-3595), median length was 47.3 cm (range 42-51) and median gestational age 38 weeks (range 37-39). All newborn received zidovudine for 6 weeks of life and none was breastfed. Fourteen (93%) infants were considered HIV-uninfected; one was lost to follow-up. CONCLUSIONS: This group of adolescents seems to have sexual behavior similar to that of HIV-uninfected. Since this is an experimented antiretroviral population, new drugs may be necessary for adequate viral suppression to avoid HIV mother-to-child transmission. Follow-up of this third generation of HIV-exposed infants needs to be addressed within HIV adolescent care.

Evaluation of hematological, virologic and anthropometric parameters as progression markers in HIV-1 infected children / Avaliação dos parâmetros hematológicos, virológicos e antropométricos como marcadores de progressão em crianças infectadas pelo HIV-1

OBJETIVO: Analisar a utilidade da contagem total de linfócitos, contagem global de leucócitos, hemoglobina, estado nutricional, contagem de linfócitos T CD4+ e carga viral como marcadores de progressão da doença e/ou óbito em crianças infectadas pelo HIV. MÉTODOS: Estudo de coorte retrospectiva em população de crianças infectadas pelo HIV, assintomáticas ou com sintomas leves e/ou moderados e virgens de tratamento antirretroviral. Os eventos de interesse foram: progressão para categoria clínica C (de acordo com a classificação dos Centers for Disease Control and Prevention - CDC, de 1994) ou óbito. Valores da contagem global de leucócitos, contagem total de linfócitos, hemoglobina, escore z peso/idade, contagem de linfócitos T CD4+ e carga viral plasmática obtidos à admissão foram considerados na análise do risco de ocorrência dos eventos de interesse. A população foi estratificada em faixas etárias: <12, > 12 e < 36, > 36 e < 60 meses. RESULTADOS: Cento e vinte pacientes, admitidos entre 1997 e 2003, preencheram os critérios para inclusão deste estudo. A mediana global do tempo de acompanhamento foi de 7,4 meses (intervalo interquartil 25-75% = 3,8-21,1). Em análise multivariada, apenas a contagem de linfócitos T CD4+, segundo as categorias da Organização Mundial da Saúde, e o escore z peso/idade ≤ -2 foram preditores do risco de progressão da doença em crianças maiores de 12 meses de idade. Em menores de 12 meses, nenhuma das variáveis analisadas esteve associada ao risco de progressão. CONCLUSÃO: Evidencia-se a importância do estado nutricional na avaliação do risco de progressão da doença em crianças maiores de 12 meses de idade infectadas pelo HIV.

OBJECTIVE: To analyze total lymphocyte count, total leukocyte count, hemoglobin levels, nutritional status, CD4+ T-lymphocyte count and viral load as markers of disease progression and/or death in HIV-infected children. METHODS: This retrospective cohort study assessed antiretroviral naïve HIV-infected children who were asymptomatic or had mild and/or moderate symptoms. The events of interest were: progression to clinical category C (according to the classification of the Centers for Disease Control and Prevention - CDC, 1994) or death. Values of total leukocyte count, total lymphocyte count, hemoglobin, weight-for-age z score, CD4+ T-lymphocyte count and plasma viral load obtained at admission were considered in the risk analysis of events of interest. The population was stratified into age groups: < 12, > 12 to < 36, > 36 to < 60 months. RESULTS: One hundred and twenty patients, admitted between 1997 and 2003, met the inclusion criteria for the present study. The total median of follow-up duration was 7.4 months (25-75% interquartile range = 3.8-21.1). In the multivariate analysis, only CD4+ T-lymphocytes count, according to the categories of the World Health Organization, and weight-for-age z score ≤ -2 were predictors of risk for disease progression in children older than 12 months. In children younger than 12 months, none of the variables was associated with risk of progression. CONCLUSION: Nutritional status is an important aspect in the assessment of risk of disease progression in HIV-infected children older than 12 months.

Evaluation of hematological, virologic and anthropometric parameters as progression markers in HIV-1 infected children.

OBJECTIVE: To analyze total lymphocyte count, total leukocyte count, hemoglobin levels, nutritional status, CD4+ T-lymphocyte count and viral load as markers of disease progression and/or death in HIV-infected children. METHODS: This retrospective cohort study assessed antiretroviral naïve HIV-infected children who were asymptomatic or had mild and/or moderate symptoms. The events of interest were: progression to clinical category C (according to the classification of the Centers for Disease Control and Prevention - CDC, 1994) or death. Values of total leukocyte count, total lymphocyte count, hemoglobin, weight-for-age z score, CD4+ T-lymphocyte count and plasma viral load obtained at admission were considered in the risk analysis of events of interest. The population was stratified into age groups: < 12, >or= 12 to < 36, >or= 36 to < 60 months. RESULTS: One hundred and twenty patients, admitted between 1997 and 2003, met the inclusion criteria for the present study. The total median of follow-up duration was 7.4 months (25-75% interquartile range = 3.8-21.1). In the multivariate analysis, only CD4+ T-lymphocytes count, according to the categories of the World Health Organization, and weight-for-age z score

Impact of highly active antiretroviral therapy (HAART) on the incidence of opportunistic infections, hospitalizations and mortality among children and adolescents living with HIV/AIDS in Belo Horizonte, Minas Gerais State, Brazil.

The impact of highly active antiretroviral therapy (HAART) can be evaluated using indicators, such as rates of opportunistic infections, hospitalizations by cause of infection, and associated death. This study aimed to estimate the impact of HAART on the incidence of these indicators, in children and adolescents with HIV/AIDS. It was a hybrid cohort study; 371 patients were followed from 1989 to 2003. In December 2003, 76% of the patients were still being followed, while 12.1% had died, 9.5% had dropped out, and 2.4% had been transferred. The overall rate of opportunistic infections was 18.32 infections/100 persons-year and 2.63 in the pre- and post-HAART periods, respectively. In the multivariate analysis, the risk of developing an opportunistic infection was 5.4 times greater and 3.3 times greater for hospitalization risk before HAART. Respiratory causes represented 65% of the hospitalizations and they were reduced by 44.6% with therapeutic intervention. The average hospital stay of 15 days was reduced to 9. There was a post-HAART decline in deaths of 38%. This study demonstrates the effectiveness of HAART in significantly reducing opportunistic infections, hospitalizations, and deaths in this Brazilian cohort.

Impact of highly active antiretroviral therapy (HAART) on the incidence of opportunistic infections, hospitalizations and mortality among children and adolescents living with HIV/AIDS in Belo Horizonte, Minas Gerais State, Brazil

The impact of highly active antiretroviral therapy (HAART) can be evaluated using indicators, such as rates of opportunistic infections, hospitalizations by cause of infection, and associated death. This study aimed to estimate the impact of HAART on the incidence of these indicators, in children and adolescents with HIV/AIDS. It was a hybrid cohort study; 371 patients were followed from 1989 to 2003. In December 2003, 76 percent of the patients were still being followed, while 12.1 percent had died, 9.5 percent had dropped out, and 2.4 percent had been transferred. The overall rate of opportunistic infections was 18.32 infections/100 persons-year and 2.63 in the pre- and post-HAART periods, respectively. In the multivariate analysis, the risk of developing an opportunistic infection was 5.4 times greater and 3.3 times greater for hospitalization risk before HAART. Respiratory causes represented 65 percent of the hospitalizations and they were reduced by 44.6 percent with therapeutic intervention. The average hospital stay of 15 days was reduced to 9.There was a post-HAART decline in deaths of 38 percent. This study demonstrates the effectiveness of HAART in significantly reducing opportunistic infections, hospitalizations, and deaths in this Brazilian cohort.

O impacto da terapia anti-retroviral de alta potência ativa (HAART) pode ser avaliado utilizando-se indicadores, como taxas de incidências de infecções oportunistas, hospitalizações por causas infecciosas e mortalidade associada. O objetivo deste trabalho foi estimar o impacto da HAART na incidência desses indicadores em crianças e adolescentes com HIV/AIDS. Trata-se de uma coorte híbrida, na qual foram acompanhados 371 pacientes no período de 1989-2003. Em dezembro de 2003, 76 por cento dos pacientes permaneciam em acompanhamento, 12,1 por cento faleceram, 9,5 por cento foram perda de seguimento e 2,4 por cento transferidos. A taxa de incidência global de infecções oportunistas foi de 18,32 infecções/100 pessoas-ano e 2,63 nos períodos pré e pós-HAART, respectivamente. Na análise multivariada, risco relativo de desenvolvimento de infecção oportunista foi 5,4 vezes maior e 3,3 vezes maior para hospitalizações, antes da HAART. Causas respiratórias representaram 65 por cento das hospitalizações, sendo reduzidas em 44,6 por cento com a intervenção terapêutica. A mediana de duração das hospitalizações apresentou queda: 15 para 9 dias. Houve 38 por cento de declínio nos óbitos pós-HAART. Este estudo demonstrou a efetividade da HAART, associando-a com significativa redução na incidência das infecções oportunistas, hospitalizações e mortalidade nesta coorte brasileira.