CCR5 genotypes and progression to HIV disease in perinatally infected children

The CCR5 molecule, a chemokine receptor, is the most important co-receptor for macrophage-tropic HIV-1. A 32-bp deletion in the gene encoding CCR5 (CCR5-del32) confers nearly complete resistance to HIV-1 infection in homozygotes, and slows the rate of progression to AIDS in heterozygous adults. The aim of this study was to describe the CCR5 genotypes and the characteristics of HIV disease progression in perinatally infected children. From a total of 51 children analyzed for the CCR5-del32 mutation, 18 (35%) were considered to be rapid progressors, 28 (55%) were moderate progressors and 5 (10%) were slow progressors. A portion of the CCR5 gene was amplified by PCR from genomic DNA followed by agarose gel electrophoresis. Forty-nine children (96%) carried the homozygous wild type genotype for CCR5 while 2 (4%) carried the heterozygous wt/del32 genotype. In the population studied, the CCR5 genotype was unable to account for the differences in pattern of the disease progression among the three groups (rapid, moderate and slow progressors), and the allele frequency of CCR5-del32 was too low to allow statistical comparisons with adequate resolving power. Studies on larger populations may help to further elucidate the role of this allele and other host factors in the regulation of HIV-1 pathogenesis in children.USP HCFM Institute of Tropical Medicine of São PauloUNIFESP Federal University of São PauloUNIFESP, UNIFESPSciEL

Characterization of Torquetenovirus in amniotic fluid at the time of in utero fetal surgery: correlation with early premature delivery and respiratory distress

Torquetenovirus (TTV) is a commensal virus present in many healthy individuals. Although considered to be non-pathogenic, its presence and titer have been shown to be indicative of altered immune status in individuals with chronic infections or following allogeneic transplantations. We evaluated if TTV was present in amniotic fluid (AF) at the time of in utero surgery to correct a fetal neurological defect, and whether its detection was predictive of adverse post-surgical parameters. AF was collected from 27 women by needle aspiration prior to a uterine incision. TTV titer in the AF was measured by isolation of viral DNA followed by gene amplification and analysis. The TTV genomes were further characterized and sequenced by metagenomics. Pregnancy outcome parameters were subsequently obtained by chart review. Three of the AFs (11.1%) were positive for TTV at 3.36, 4.16, and 4.19 log10 copies/mL. Analysis of their genomes revealed DNA sequences similar to previously identified TTV isolates. Mean gestational age at delivery was >2  weeks earlier (32.5 vs. 34.6  weeks) and the prevalence of respiratory distress was greater (100% vs. 20.8%) in the TTV-positive pregnancies. TTV detection in AF prior to intrauterine surgery may indicate elevated post-surgical risk for earlier delivery and newborn respiratory distress

Contracepção hormonal e lesões cervicais pelo Papilomavírus Humano: uma revisão de literatura / Hormonal contraception and cervical injuries by Human Papillomavirus: a literature review

Introdução: A infecção pelo papilomavírus humano (HPV) é a doença sexualmente transmissível (DST) mais comum, afetando 50% da população mundial. Estima-se que entre 75 e 80% da de indivíduos sexualmente ativos adquirirão algum subtipo de HPV ao longo da vida. No Brasil, a taxa de prevalência de HPV varia de 13,7 a 54,3%, de acordo com a população e as regiões estudadas. Assim, este artigo tem como objetivo analisar a associação entre os hormônios contracepção e o aparecimento de lesões induzidas por HPV em o colo uterino. Metodologia: O presente estudo foi elaborado por meio de uma pesquisa bibliográfica, realizada eletronicamente, procurando registros sobre o desenvolvimento de lesões induzidas por HPV em colo uterino e hormônios de contracepção. Objetivando com isso identificar através da literatura a associação entre os hormônios de contracepção e o aparecimento de lesões induzidas por HPV em colo uterino. Para a realização do mesmo foram analisados artigos publicados em revistas científicas, utilizando as bases de dados da BVS (Biblioteca Virtual da Saúde), como: Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) e Scielo (Scientific Electronic Library Online). Resultados: Após a seleção, restaram nove artigos para a discussão. Podemos observar os artigos escolhidos no quadro, composto pelos autores, título, metodologia, resultados e conclusão que cada um encontrou. Em seguida foi realizada uma discussão acerca destes artigos. Conclusão: Muitos estudos relataram que os mecanismos envolvidos na persistência e incidência de lesões de HPV estão longe de ser esclarecidas, e que novas estudos são necessários para elucidar melhores abordagens em relação ao tipo de contracepção, via de administração e doses hormonal que não estão associadas a lesões induzidas por HPV

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Influenza A and B in a cohort of outpatient children and adolescent with influenza like-illness during two consecutive influenza seasons

INTRODUCTION: Influenza is an important cause of morbimortality worldwide. Although people at the extremes of age have a greater risk of complications, influenza has been more frequently investigated in the elderly than in children, and inpatients than outpatients. Yearly vaccination with trivalent or quadrivalent vaccines is the main strategy to control influenza. OBJECTIVES: Determine the clinical and molecular characteristics of influenza A and B infections in children and adolescents with influenza-like illness (ILI). METHODS: A cohort of outpatient children and adolescents with ILI was followed for 20 months. Influenza was diagnosed with commercial multiplex PCR platforms. RESULTS: 179 patients had 277 episodes of ILI, being 79 episodes of influenza A and 20 episodes of influenza B. Influenza A and B cases were mild and had similar presentation. Phylogenetic tree of influenza B viruses showed that 91.6% belonged to the B/Yamagata lineage, which is not included in trivalent vaccines. CONCLUSIONS: Influenza A and B are often detected in children and adolescents with ILI episodes, with similar and mild presentation in outpatients. The mismatch between the circulating influenza viruses and the trivalent vaccine offered in Brazil may have contributed to the high frequency of influenza A and B in this population

Analysis of HIV- type 1 protease and reverse transcriptase in Brazilian children failing highly active antiretroviral therapy (HAART) Análise da protease e transcriptase reversa do HIV-1 em crianças com falha terapêutica em uso de terapia anti-retroviral altamente eficaz (HAART)

The aim of this study was to evaluate the genotypic resistance profiles of HIV-1 in children failing highly active antiretroviral therapy (HAART). Forty-one children (median age = 67 months) receiving HAART were submitted to genotypic testing when virological failure was detected. cDNA was extracted from PBMCs and amplified by nested PCR for the reverse transcriptase and protease regions of the pol gene. Drug resistance genotypes were determined from DNA sequencing. According to the genotypic analysis, 12/36 (33.3%) and 6/36 (16.6%) children showed resistance and possible resistance, respectively, to ZDV; 5/36 (14%) and 4/36 (11.1%), respectively, showed resistance and possible resistance to ddI; 4/36 (11.1%) showed resistance to 3TC and D4T; and 3/36 (8.3%) showed resistance to Abacavir. A high percentage (54%) of children exhibited mutations conferring resistance to NNRTI class drugs. Respective rates of resistance and possible resistance to PIs were: RTV (12.2%, 7.3%); APV (2.4%, 12.1%); SQV(0%, 12.1%); IDV (14.6%, 4.9%), NFV (22%, 4.9%), LPV/RTV (2.4%, 12.1%). Overall, 37/41 (90%) children exhibited virus with mutations related to drug resistance, while 9% exhibited resistance to all three antiretroviral drug classes.<br>O objetivo deste estudo foi avaliar o perfil de resistência genotípica do HIV-1 em crianças com falha terapêutica ao tratamento anti-retroviral (HAART). Quarenta e uma crianças (idade mediana = 67 meses) em uso de HAART foram submetidas ao teste de genotipagem no momento da detecção de falha ao tratamento. Foi realizada extração de cDNA de células periféricas mononucleares e amplificação do mesmo (regiões da transcriptase reversa e protease do gene pol) através de PCR-nested. O perfil genotípico foi determinado através do seqüenciamnto de nucleotídeos. De acordo com a análise genotípica, 12/36 (33,3%) e 6/36 (16,6%) crianças apresentaram, respectivamente, resistência e possível resistência ao AZT; 5/36 (14%) e 4/36 (11,1%), respectivamente, eram resistentes e possivelmente resistentes ao ddI; 4/36 %11,1%) apresentaram resistência ao 3TC e D4T, e 3/36 (8,3%) eram resistentes ao ABC. Uma alta porcentagem de crianças (54%) apresentou mutações relacionadas à resistência aos inibidores da trancriptase reversa não-análogos de nucleosídeos. As taxas de resistência e possível resistência aos inibidores da protease foram, respectivamente: RTV (12,2%; 7,3%); APV (2,4%; 12,1%); SQV (0%; 12,1%); IDV (14,6%; 4,9%); NFV (22%; 4,9%); LPV/RTV (2,4%; 12,1%). No total, 37/41 (90%) crianças apresentaram vírus com mutações relacionadas à resistência a alguma droga, sendo que 9% delas tinham vírus resistentes às três classes de drogas anti-retrovirais disponíveis

SARS-CoV-2 Detection and Culture in Different Biological Specimens from Immunocompetent and Immunosuppressed COVID-19 Patients Infected with Two Different Viral Strains

Introduction—The dynamics of SARS-CoV-2 shedding and replication in humans remain incompletely understood. Methods—We analyzed SARS-CoV-2 shedding from multiple sites in individuals with an acute COVID-19 infection by weekly sampling for five weeks in 98 immunocompetent and 25 immunosuppressed individuals. Samples and culture supernatants were tested via RT-PCR for SARS-CoV-2 to determine viral clearance rates and in vitro replication. Results—A total of 2447 clinical specimens were evaluated, including 557 nasopharyngeal swabs, 527 saliva samples, 464 urine specimens, 437 anal swabs and 462 blood samples. The SARS-CoV-2 genome sequences at each site were classified as belonging to the B.1.128 (ancestral strain) or Gamma lineage. SARS-CoV-2 detection was highest in nasopharyngeal swabs regardless of the virus strain involved or the immune status of infected individuals. The duration of viral shedding varied between clinical specimens and individual patients. Prolonged shedding of potentially infectious virus varied from 10 days up to 191 days, and primarily occurred in immunosuppressed individuals. Virus was isolated in culture from 18 nasal swab or saliva samples collected 10 or more days after onset of disease. Conclusions—Our findings indicate that persistent SARS-CoV-2 shedding may occur in both competent or immunosuppressed individuals, at multiple clinical sites and in a minority of subjects is capable of in vitro replication