Zika virus outbreak in Brazil-Lessons learned and perspectives for a safe and effective vaccine.

Zika virus (ZIKV) is an emerging pathogen of public health concern, associated with a dramatic burden in places where the virus caused outbreaks between 2015 and 2017. In the Americas, the ZIKV was first reported in Brazil and rapidly spread through the Americas. Since its first report, a number of studies have been published as we continue to learn, not only about modes of transmission, but also clinical manifestations, risk of congenital anomalies, including microcephaly and neurological malformations in fetuses born from mothers infected during pregnancy. Interventions to reduce the burden of ZIKV infection are restricted to mosquito control, and for Aedes spp mosquitoes the strategies implemented to that end proved to be unsuccessful so far. Hence the lessons we can learn following the ZIKV epidemics become of paramount importance in the development of drug treatments and in search for a vaccine.

Infections in children with diabetes / Infecções na criança com diabetes

Abstract Objective The association between diabetes mellitus and infections is very common. These infections, even when mild, interfere with blood glucose control. The aim of this review is to describe infections that occur in children and adolescents with DM, as well as to provide recommendations on glycemia management during these episodes. Source of data A non-systematic review was carried out in the PubMed database, using the terms "diabetes mellitus," "infection," "children," and "adolescents." The most relevant publications were selected. Synthesis of data In addition to the usual community diseases, some infections may occur predominantly in diabetic patients, especially when there is inadequate glycemic control, and common infections can be more severe in these patients. Alterations caused by the disease itself and the immune response are responsible for the risk of higher frequency and severity of infections. During infections, an increase in blood glucose occurs and usually an increase in insulin dose is required. Conclusions Pediatric patients with diabetes have some immune system disorders that, when associated with high glycemia, increase the risk of infections and their severity, and should be promptly identified and treated. The presence of an infectious condition, in turn, raises blood glucose and increases the risk of decompensation, and pediatricians should be cautioned to intensify monitoring and insulin therapy, and to avoid the risk of DKA. It should also be noted that many infections are preventable and can be avoided with adequate vaccine coverage.

Resumo Objetivo A associação entre diabetes mellitus e infecções é muito frequente. Essas infecções, mesmo quando leves, interferem no controle da glicemia. O objetivo desta revisão é descrever as infecções que ocorrem em crianças e adolescentes com DM, bem como orientar o manejo glicêmico nestes episódios. Fonte dos dados Foi feita uma revisão não sistemática na base de dados PubMed, com os termos "diabetes mellitus", "infecção", "crianças" e "adolescentes". Foram selecionadas as publicações mais relevantes. Síntese dos dados Além de infecções comunitárias habituais, algumas infecções ocorrem predominantemente no paciente com diabetes, principalmente quando não há um controle glicêmico adequado, e infecções comuns podem ser mais graves nesse paciente. Alterações da própria doença e da resposta imune, em conjunto com alterações do microbioma, são responsáveis pela maior frequência e gravidade das infecções. Durante as infecções, ocorre um aumento da glicemia e habitualmente é necessário o aumento da dose de insulina. Conclusões O paciente pediátrico com diabetes apresenta algumas desordens imunes que, quando associadas a elevaçao da glicemia, aumentam o risco de infecção e sua gravidade. A presença da infecção, por sua vez, eleva a glicemia e aumenta o risco de descompensação. Desta forma, a monitorização da glicemia, bem como o aumento da dose de insulina, são fundamentais para evitar o risco de cetoacidose diabética. Destaca-se ainda que muitas infecções são imunopreveníveis e podem ser evitadas com uma cobertura vacinal adequada.

Infections in children with diabetes.

OBJECTIVE: The association between diabetes mellitus and infections is very common. These infections, even when mild, interfere with blood glucose control. The aim of this review is to describe infections that occur in children and adolescents with DM, as well as to provide recommendations on glycemia management during these episodes. SOURCE OF DATA: A non-systematic review was carried out in the PubMed database, using the terms "diabetes mellitus," "infection," "children," and "adolescents." The most relevant publications were selected. SYNTHESIS OF DATA: In addition to the usual community diseases, some infections may occur predominantly in diabetic patients, especially when there is inadequate glycemic control, and common infections can be more severe in these patients. Alterations caused by the disease itself and the immune response are responsible for the risk of higher frequency and severity of infections. During infections, an increase in blood glucose occurs and usually an increase in insulin dose is required. CONCLUSIONS: Pediatric patients with diabetes have some immune system disorders that, when associated with high glycemia, increase the risk of infections and their severity, and should be promptly identified and treated. The presence of an infectious condition, in turn, raises blood glucose and increases the risk of decompensation, and pediatricians should be cautioned to intensify monitoring and insulin therapy, and to avoid the risk of DKA. It should also be noted that many infections are preventable and can be avoided with adequate vaccine coverage.

Sources of pertussis infection in young babies from São Paulo State, Brazil.

Household contacts are important sources of Bordetella pertussis in infants. A total of 353 household contacts of 97 index cases were evaluated for pertussis by culture and polymerase chain reaction. Twenty eight contacts were positive (8.0%). The presence of symptoms did not influence the rate of diagnosed bacteriologic pertussis in communicants. We conclude that contacts with an index case can be positive for B. pertussis independently of the presence of symptoms.

Diversidade e prevalência das mutações de resistência genotípica aos antirretrovirais entre crianças infectadas pelo HIV-1 / Diversity and prevalence of antiretroviral genotypic resistance mutations among HIV-1-infected children

Objective: To evaluate genotyping and subtyping in antiretroviral (ARV) naïve and experienced children, as well as drug resistance profiles through genotyping in these children. Methods: This retrospective study assessed ARV-naïve HIV children and HIV children failing highly active antiretroviral treatment (HAART) followed up at Santa Casa de São Paulo. Genotypingwas performed using purified polymerase chain reaction (PCR) products from retrotranscribed RNA using Kit Viroseq HIV-1 Genotyping System 2.0 or nested PCR in-house. Sequencing was performed using automatic equipment (ABI 3100). ARV resistance mutations were analyzed in the Stanford HIV Drug Resistance Database and subtypingwas performed at the National Center for Biotechnology Information (NCBI), using SimPlot analysis, together with phylogenetic analysis. Results: No primary ARV resistance mutation was detected in the 24 ARV-naïve children, although there were mutations that may contribute to resistance to nucleoside analogue reverse transcriptase inhibitors (NRTI) (12.5%) and to protease inhibitors (PI) (95.8%). For the 23 children failing HAART, we found ARV resistance mutations to NRTI in 95.6% and to non-nucleoside analogue reverse transcriptase inhibitors (NNRTI) in 60.8%. For PI, we found ARV resistance mutations in 95.7%, 47.8% of which had only polymorfisms. In the subtyping analyses, 78.3% of the sequences clustered in HIV-1 subtype B, 4.3% in C, 13% in F and 4.4% in recombinant forms. Conclusion: Our results show low rates of primary resistance in ARV-naïve children and high rates of resistance in children failing ARV treatment, which is compatible with ARV use in these patients.

Objetivo: Avaliar a genotipagem e subtipagem em crianças experimentadas e virgens de tratamento, assimcomoperfis de resistência a medicamentos através da genotipagem nessas crianças. Métodos: Estudo retrospectivo de crianças HIV positivas virgens de tratamento e HIV positivas que não responderam ao tratamento pela terapia antirretroviral altamente ativa (HAART), acompanhadas na Santa Casa de São Paulo (SP). A genotipagem foi realizada com produtos purificados de reação em cadeia da polimerase (PCR) de RNA retrotranscrito, utilizando-se o kit comercial Viroseq HIV-1 Genotyping System 2.0 ou a técnica de nested PCR in-house. O sequenciamento foi realizado com equipamento automático (ABI 3100). As mutações de resistência antirretroviral (ARV) foram analisadas no Stanford HIV Drug Resistance Database e a subtipagem realizada no U.S. National Center for Biotechnology Information (NCBI), utilizando-se o programa de análises SimPlot, juntamente com a análise filogenética. Resultados: Não foi detectada nenhuma mutação de resistência primária ARV nas 24 crianças virgens de tratamento, embora tenham ocorrido mutações que podem contribuir para a resistência aos inibidores da transcriptase reversa análogos de nucleosídeos (ITRN) (12,5%) e aos inibidores da protease (IP) (95,8%). Para as 23 crianças que não responderam à HAART, foram encontradas mutações de resistência ARV aos ITR Nem 95,6% e aos inibidores da transcriptase reversa não-análogos de nucleosídeos (ITRNN) em 60,8%. Para os IP, foram observadas mutações de resistência ARV em 95,7%, 47,8% das quais apresentavam apenas polimorfismos. Nas análises de subtipagem,78,3%das sequências agruparam-se no subtipo B do HIV-1, 4,3% no C, 13% no F e 4,4% em formas recombinantes. Conclusões: Nossos resultados mostrambaixas taxas de resistência primária em crianças virgens de tratamento e altas taxas de resistência emcrianças que não responderamao tratamento ARV, o que é compatível com o uso ARV nesses pacientes.

Brazilian adolescents infected by HIV: epidemiologic characteristics and adherence to treatment.

Over the last 3 decades since the first AIDS cases appeared, we have witnessed great progress in therapeutic methodologies that have transformed the evolution of the disease from debilitating and fatal, into chronic and controllable. HIV-infected children are arriving at adolescence and bringing specific challenges, not only to themselves, but also to their families and caregivers. This retrospective study sets forth epidemiological and treatment characteristics of 46 HIV-infected adolescents followed in a specialized university service relating said characteristics to therapy adherence assessed through a combination of three indirect methods. Therapy adherence did not reveal any association with either epidemiologic characteristics regarding age, sex, school level, household composition, age at diagnosis, mode of infection, knowledge of diagnosis, treatment time, or initial antiretroviral scheme. Patients with good therapy adherence presented lower viral load and used a smaller number of antiretroviral schemes.

Diversity and prevalence of antiretroviral genotypic resistance mutations among HIV-1-infected children / Diversidade e prevalência das mutações de resistência genotípica aos antirretrovirais entre crianças infectadas pelo HIV-1

OBJETIVO: Avaliar a genotipagem e subtipagem em crianças experimentadas e virgens de tratamento, assim como perfis de resistência a medicamentos através da genotipagem nessas crianças. MÉTODOS: Estudo retrospectivo de crianças HIV positivas virgens de tratamento e HIV positivas que não responderam ao tratamento pela terapia antirretroviral altamente ativa (HAART), acompanhadas na Santa Casa de São Paulo (SP). A genotipagem foi realizada com produtos purificados de reação em cadeia da polimerase (PCR) de RNA retrotranscrito, utilizando-se o kit comercial Viroseq HIV-1 Genotyping System 2.0 ou a técnica de nested PCR in-house. O sequenciamento foi realizado com equipamento automático (ABI 3100). As mutações de resistência antirretroviral (ARV) foram analisadas no Stanford HIV Drug Resistance Database e a subtipagem realizada no U.S. National Center for Biotechnology Information (NCBI), utilizando-se o programa de análises SimPlot, juntamente com a análise filogenética. RESULTADOS: Não foi detectada nenhuma mutação de resistência primária ARV nas 24 crianças virgens de tratamento, embora tenham ocorrido mutações que podem contribuir para a resistência aos inibidores da transcriptase reversa análogos de nucleosídeos (ITRN) (12,5%) e aos inibidores da protease (IP) (95,8%). Para as 23 crianças que não responderam à HAART, foram encontradas mutações de resistência ARV aos ITRN em 95,6% e aos inibidores da transcriptase reversa não-análogos de nucleosídeos (ITRNN) em 60,8%. Para os IP, foram observadas mutações de resistência ARV em 95,7%, 47,8% das quais apresentavam apenas polimorfismos. Nas análises de subtipagem, 78,3% das sequências agruparam-se no subtipo B do HIV-1, 4,3% no C, 13% no F e 4,4% em formas recombinantes. CONCLUSÕES: Nossos resultados mostram baixas taxas de resistência primária em crianças virgens de tratamento e altas taxas de resistência...

OBJECTIVE: To evaluate genotyping and subtyping in antiretroviral (ARV) naïve and experienced children, as well as drug resistance profiles through genotyping in these children. METHODS: This retrospective study assessed ARV-naïve HIV children and HIV children failing highly active antiretroviral treatment (HAART) followed up at Santa Casa de São Paulo. Genotyping was performed using purified polymerase chain reaction (PCR) products from retrotranscribed RNA using Kit Viroseq HIV-1 Genotyping System 2.0 or nested PCR in-house. Sequencing was performed using automatic equipment (ABI 3100). ARV resistance mutations were analyzed in the Stanford HIV Drug Resistance Database and subtyping was performed at the National Center for Biotechnology Information (NCBI), using SimPlot analysis, together with phylogenetic analysis. RESULTS: No primary ARV resistance mutation was detected in the 24 ARV-naïve children, although there were mutations that may contribute to resistance to nucleoside analogue reverse transcriptase inhibitors (NRTI) (12.5%) and to protease inhibitors (PI) (95.8%). For the 23 children failing HAART, we found ARV resistance mutations to NRTI in 95.6% and to non-nucleoside analogue reverse transcriptase inhibitors (NNRTI) in 60.8%. For PI, we found ARV resistance mutations in 95.7%, 47.8% of which had only polymorfisms. In the subtyping analyses, 78.3 percent of the sequences clustered in HIV-1 subtype B, 4.3% in C, 13% in F and 4.4% in recombinant forms. CONCLUSION: Our results show low rates of primary resistance in ARV-naïve children and high rates of resistance in children failing ARV treatment, which is compatible with ARV use in these patients.

Diversity and prevalence of antiretroviral genotypic resistance mutations among HIV-1-infected children.

OBJECTIVE: To evaluate genotyping and subtyping in antiretroviral (ARV) naïve and experienced children, as well as drug resistance profiles through genotyping in these children. METHODS: This retrospective study assessed ARV-naïve HIV children and HIV children failing highly active antiretroviral treatment (HAART) followed up at Santa Casa de São Paulo. Genotyping was performed using purified polymerase chain reaction (PCR) products from retrotranscribed RNA using Kit Viroseq HIV-1 Genotyping System 2.0 or nested PCR in-house. Sequencing was performed using automatic equipment (ABI 3100). ARV resistance mutations were analyzed in the Stanford HIV Drug Resistance Database and subtyping was performed at the National Center for Biotechnology Information (NCBI), using SimPlot analysis, together with phylogenetic analysis. RESULTS: No primary ARV resistance mutation was detected in the 24 ARV-naïve children, although there were mutations that may contribute to resistance to nucleoside analogue reverse transcriptase inhibitors (NRTI) (12.5%) and to protease inhibitors (PI) (95.8%). For the 23 children failing HAART, we found ARV resistance mutations to NRTI in 95.6% and to non-nucleoside analogue reverse transcriptase inhibitors (NNRTI) in 60.8%. For PI, we found ARV resistance mutations in 95.7%, 47.8% of which had only polymorfisms. In the subtyping analyses, 78.3% of the sequences clustered in HIV-1 subtype B, 4.3% in C, 13% in F and 4.4% in recombinant forms. CONCLUSION: Our results show low rates of primary resistance in ARV-naïve children and high rates of resistance in children failing ARV treatment, which is compatible with ARV use in these patients.

Streptococcus pyogenes meningitis in children: report of two cases and literature review.

Streptococcus pyogenes meningitis (SPM) occurs sporadically, even with the increase of invasive streptococcal disease observed in the past years. We reported two cases of SPM in infants to alert pediatricians for the possibility of this agent as a cause of meningitis in previously healthy children.

Streptococcus pyogenes meningitis in children: report of two cases and literature review

Streptococcus pyogenes meningitis (SPM) occurs sporadically, even with the increase of invasive streptococcal disease observed in the past years. We reported two cases of SPM in infants to alert pediatricians for the possibility of this agent as a cause of meningitis in previously healthy children.