RESUMO
BACKGROUND: Brazil´s case fatality rate (CFR) of pediatric multisystem inflammatory syndrome in children and adolescents (MIS-C) is among the highest worldwide. Despite these concerns, limited hospital-based and comprehensive pediatric data have been published on MIS-C in Brazilian children. METHODS: We performed a descriptive analysis of the MIS-C scores in 16 public and private hospitals providing secondary and tertiary care in the metropolitan area of São Paulo, Brazil. Clinical and demographic information were systematically extracted from the electronic medical records of each patient. Logistic regression analysis was performed to identify the combined effects of MIS-C phenotype, disease severity and comorbidity as dependent variables. RESULTS: A total of 101 patients met the MIS-C criteria and were evaluated. The median age was 67 months, 60% were male, 28.7% were black or afrodescendant and 62.3% were admitted to public hospitals. Underlying medical conditions were observed in 16.8% of patients and were associated with a longer duration of hospitalization. A Kawasaki disease-like phenotype was observed in 43.5% of patients, and they demonstrated a trend of lower median age. Children with severe MIS-C were older (median age 91 months vs. 36 months) and had a nonspecific phenotype, more cardiovascular and respiratory involvement and kidney injury; 73.3% required intensive care, 20.8% required mechanical ventilation and 35.6% required inotropic support. Four deaths occurred (CFR = 3.9%), three of which were in healthy participants. CONCLUSION: We identified a lower median age, particularly among children with Kawasaki disease-like phenotypes, those with a significant need for intensive care, and a high CFR in MIS-C. Our findings confirmed the increased severity of the disease in the selected Brazilian population.
RESUMO
Importance: Multiple SARS-CoV-2 variants have emerged over the COVID-19 pandemic. The implications for COVID-19 severity in children worldwide are unclear. Objective: To determine whether the dominant circulating SARS-CoV-2 variants of concern (VOCs) were associated with differences in COVID-19 severity among hospitalized children. Design, Setting, and Participants: Clinical data from hospitalized children and adolescents (younger than 18 years) who were SARS-CoV-2 positive were obtained from 9 countries (Australia, Brazil, Italy, Portugal, South Africa, Switzerland, Thailand, UK, and the US) during 3 different time frames. Time frames 1 (T1), 2 (T2), and 3 (T3) were defined to represent periods of dominance by the ancestral virus, pre-Omicron VOCs, and Omicron, respectively. Age groups for analysis were younger than 6 months, 6 months to younger than 5 years, and 5 to younger than 18 years. Children with an incidental positive test result for SARS-CoV-2 were excluded. Exposures: SARS-CoV-2 hospitalization during the stipulated time frame. Main Outcomes and Measures: The severity of disease was assessed by admission to intensive care unit (ICU), the need for ventilatory support, or oxygen therapy. Results: Among 31â¯785 hospitalized children and adolescents, the median age was 4 (IQR 1-12) years and 16â¯639 were male (52.3%). In children younger than 5 years, across successive SARS-CoV-2 waves, there was a reduction in ICU admission (T3 vs T1: risk ratio [RR], 0.56; 95% CI, 0.42-0.75 [younger than 6 months]; RR, 0.61, 95% CI; 0.47-0.79 [6 months to younger than 5 years]), but not ventilatory support or oxygen therapy. In contrast, ICU admission (T3 vs T1: RR, 0.39, 95% CI, 0.32-0.48), ventilatory support (T3 vs T1: RR, 0.37; 95% CI, 0.27-0.51), and oxygen therapy (T3 vs T1: RR, 0.47; 95% CI, 0.32-0.70) decreased across SARS-CoV-2 waves in children 5 years to younger than 18 years old. The results were consistent when data were restricted to unvaccinated children. Conclusions and Relevance: This study provides valuable insights into the impact of SARS-CoV-2 VOCs on the severity of COVID-19 in hospitalized children across different age groups and countries, suggesting that while ICU admissions decreased across the pandemic in all age groups, ventilatory and oxygen support generally did not decrease over time in children aged younger than 5 years. These findings highlight the importance of considering different pediatric age groups when assessing disease severity in COVID-19.
Assuntos
COVID-19 , Adolescente , Humanos , Criança , Masculino , Lactente , Pré-Escolar , Feminino , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias , OxigênioRESUMO
Background: In 2020, Brazil became the epicentre of the coronavirus disease (COVID-19) pandemic in Latin America, resulting in an unparalleled health catastrophe. Nevertheless, comprehensive clinical reports in Brazilian children are not available. Methods: This retrospective, hospital-based, active surveillance study was performed to identify paediatric patients with COVID-19 who presented at a private academic medical centre in a large urban area between March 2020 and March 2021. Clinical and demographic information was analysed for those requiring hospitalization, those with severe illness and those with clinical syndromes. Results: In total, 964 symptomatic cases were evaluated; of these, 17.7% required hospitalization, and 27.5% of hospitalized cases were classified as severe/critical. Acute bronchiolitis and pneumonia were the most common causes of hospitalization among the severe cases. Twenty-seven hospitalized children fulfilled the diagnostic criteria for multi-system inflammatory syndrome (median age 29 months; 85.2% cases were non-severe). A significant co-existing condition was present in 29% of hospitalized children. The risk of hospitalization was higher in children with at least one comorbidity, children aged <2 years and obese children. Increased risk of severe disease was described among those with leukopenia, leukocytosis or any significant comorbidity. No deaths occurred among the study population. Conclusion: Although most children with COVID-19 experienced mild disease, and no deaths occurred among the study population, a significant proportion of cases required hospitalization and developed severe illness. Obesity, young age, underlying comorbidity, leukopenia and leukocytosis were risk factors for hospitalization or severe disease.
RESUMO
BACKGROUND: Brazil has one of the highest numbers of births with sickle-cell disease (SCD) in the Americas. Despite the risk of severe illnesses and death due to both vaccine-preventable infections, vaccination uptake in pediatric patients with SCD is unknown. MATERIAL AND METHODS: Children under 18 years with SCD presenting to routine medical consultations had their vaccination status evaluated according to the national recommendations. Data obtained were classified as 'Adequate', 'Delayed' or 'Missing' vaccination and compared among age groups. RESULTS: From 117 children screened, 100 had their vaccination card available. Vaccination coverage of routine vaccines was above 95% for all primary series and both age groups, with varied rates of delays and low missing doses. Among SCD extended vaccination, the most frequently delayed and missed vaccines were those specifically recommended to individuals with SCD as per national guidelines-and particularly those against encapsulated bacteria. Significant and varied rates of missing doses occurred in primary series and booster doses for PPSV23, Hib, menC, hepatitis A and varicella. The average influenza vaccination rate was 69.5%, with higher rates among younger children. CONCLUSIONS: Children with SCD have alarming under-vaccination rates. Basic prevention strategies in Brazil should be reassessed in this specific population.
Assuntos
Anemia Falciforme , Doenças Transmissíveis , Adolescente , Anemia Falciforme/complicações , Brasil/epidemiologia , Criança , Humanos , Lactente , Vacinação , Cobertura VacinalRESUMO
BACKGROUND: Brazil became the epicenter of the COVID-19 pandemic in Latin America since May 2020, reporting the highest number of cases and deaths in the region. Healthcare workers (HCWs) are at increased risk of SARS-CoV-2 infection, experiencing a significant burden from COVID-19. Identifying and understanding the clinical characteristics and risk factors associated with infection are of paramount importance to inform screening strategies and infection control practices in this scenario. The aims of this study were to investigate the prevalence and clinical characteristics of HCWs with COVID-19 symptoms. METHODS: Between March 21st and May 22nd, 2020 a cross-sectional study was performed in a tertiary university hospital in São Paulo. Prevalence of SARS-CoV-2 infection among HCWs with COVID-19 symptoms was determined by RT-PCR testing on nasopharyngeal and oropharyngeal samples. Participants were asked to complete an electronic structured questionnaire including clinical and demographic data. RESULTS: Overall, 125 (42.37%) of 295 symptomatic HCWs tested positive for SARS-CoV-2. Over the 10-week study period, positivity rates varied from 22.2% (95% CI 15.9-60.3%) in the second week to 55.9% (95% CI 43.2-68.6%) in the sixth week, reaching a plateau (38-46%) thereafter. Median (SD) age was 34.2 (9.9) years and 205 (69.5%) were female. We did not find significant differences in the prevalence of the most commonly reported underlying medical condition among healthcare workers that tested positive or negative for SARS-CoV-2 infection. After multivariable analysis, using logistic regression, anosmia (adjusted OR 4.4 95% CI 2.21-8.74) and ocular pain (adjusted OR 1.95 95% CI 1.14-3.33) were the only symptoms independently associated with positivity for SARS-CoV-2 infection. Follow-up information on clinical outcomes showed that 9 (7.2%) HCWs were hospitalized (seven were male) and 2 (1.6%) died. CONCLUSIONS: The findings of this study confirmed the high burden of SARS-CoV-2 infection among healthcare workers in the hardest hit city by the pandemic in Latin America. Anosmia and ocular pain were symptoms independently associated with COVID-19 diagnosis. In low and middle-income countries, where limited availability of tests is frequent, these findings may contribute to optimize a targeted symptom-oriented screening strategy.
Assuntos
COVID-19/epidemiologia , Pessoal de Saúde , Hospitais Universitários , Pandemias , SARS-CoV-2/genética , Centros de Atenção Terciária , Adulto , Brasil/epidemiologia , COVID-19/virologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Controle de Infecções , Masculino , Prevalência , Fatores de Risco , Adulto JovemRESUMO
Abstract Objective: Respiratory syncytial virus is a pathogen frequently involved in nosocomial outbreaks. Although several studies have reported nosocomial outbreaks in neonatal intensive care units, molecular epidemiology data are scarce. Here, the authors describe two consecutive respiratory syncytial virus outbreaks caused by genotypes ON-1 and NA-2 in a neonatal intensive care unit in São Paulo, Brazil. Methods: A prospective search for respiratory syncytial virus was performed after diagnosing the index case and four other symptomatic newborns in the neonatal intensive care unit. Nasopharyngeal aspirate samples of all patients in the neonatal intensive care unit were tested for 17 respiratory viruses using real-time reverse transcriptase polymerase chain reaction. Genotyping was performed using nucleotide sequencing. Results: From May to August 2013, two different outbreaks were detected in the neonatal intensive care unit. A total of 20 infants were infected with respiratory syncytial virus-A (ten and 14 with ON-1 and NA-2 genotypes, respectively). The mean age of the infants was 10 days, mean birth weight was 1,961 g, and the mean gestational age was 33 weeks. Risk factors (heart disease, lung disease, and prematurity) were present in 80% and 85.7% of infants in the ON-1 and NA-2 groups, respectively. In total, 45.8% of infants were asymptomatic and 20.8% required mechanical ventilation. Coinfections were not detected during the outbreaks. Conclusions: Infants in a neonatal intensive care unit who develop abrupt respiratory symptoms should be tested for respiratory viruses, especially respiratory syncytial virus. Even in the absence of severe symptoms, respiratory syncytial virus detection can prevent nosocomial transmission through infection control measures. A better understanding of respiratory syncytial virus molecular epidemiology is essential for developing new vaccines and antiviral drugs against respiratory syncytial virus.
Resumo Objetivo O vírus sincicial respiratório é um patógeno frequentemente envolvido em surtos nosocomiais. Embora vários estudos tenham relatado tais surtos em unidades de terapia intensiva neonatal, os dados epidemiológicos moleculares são escassos. Neste artigo, descrevemos dois surtos consecutivos de vírus sincicial respiratório causados pelos genótipos ON-1 e NA-2 em uma unidade de terapia intensiva neonatal em São Paulo, Brasil. Métodos Uma busca prospectiva por vírus sincicial respiratório foi realizada após o diagnóstico do caso índice e outros quatro recém-nascidos sintomáticos na unidade de terapia intensiva neonatal. Amostras de aspirado nasofaríngeo de todos os pacientes da unidade de terapia intensiva neonatal foram testadas para 17 vírus respiratórios com reação em cadeia da polimerase via transcriptase reversa em tempo real. A genotipagem realizada utilizando sequenciamento de nucleotídeos. Resultados De maio a agosto de 2013, foram detectados dois surtos diferentes na unidade de terapia intensiva neonatal. Vinte e quatro crianças foram infectadas com vírus sincicial respiratório-A (10 e 14 com os genótipos ON-1 e NA-2, respectivamente). A média da idade dos lactentes era de 10 dias, o peso médio ao nascer foi de 1961 g e a idade gestacional média de 33 semanas. Fatores de risco (doença cardíaca, doença pulmonar e prematuridade) estavam presentes em 80% e 85,7% dos bebês nos grupos ON-1 e NA-2, respectivamente. No total, 45,8% dos lactentes eram assintomáticos e 20,8% necessitaram de ventilação mecânica. Não foram detectadas coinfecções durante os surtos. Conclusões Bebês em unidade de terapia intensiva neonatal que desenvolvem sintomas respiratórios abruptos devem ser testados para vírus respiratórios, especialmente o vírus sincicial respiratório. Mesmo na ausência de sintomas graves, a detecção de vírus sincicial respiratório pode prevenir a transmissão nosocomial através de medidas de controle de infecção. Um melhor entendimento da epidemiologia molecular do vírus sincicial respiratório é essencial para o desenvolvimento de novas vacinas e drogas antivirais contra o vírus sincicial respiratório.
Assuntos
Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Infecção Hospitalar , Brasil , Surtos de Doenças , Estudos Prospectivos , Infecções por Vírus Respiratório Sincicial , GenótipoRESUMO
Hepatopulmonary hydatidosis in young children is a rare and atypical presentation of Echinococcus granulosus infection. We report the first case of cystic echinococcosis caused by a microvariant of E. granulosus sensu stricto. Chemotherapy and systemic corticoids were administered before curative surgery was performed. Recurrence was not observed for more than 24 months of follow-up.
Assuntos
Albendazol/administração & dosagem , Equinococose Hepática/diagnóstico por imagem , Equinococose Pulmonar/diagnóstico por imagem , Echinococcus granulosus/isolamento & purificação , Animais , Pré-Escolar , Equinococose Hepática/terapia , Equinococose Pulmonar/terapia , Feminino , Seguimentos , Humanos , Toracoscopia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
OBJECTIVE: Respiratory syncytial virus is a pathogen frequently involved in nosocomial outbreaks. Although several studies have reported nosocomial outbreaks in neonatal intensive care units, molecular epidemiology data are scarce. Here, the authors describe two consecutive respiratory syncytial virus outbreaks caused by genotypes ON-1 and NA-2 in a neonatal intensive care unit in São Paulo, Brazil. METHODS: A prospective search for respiratory syncytial virus was performed after diagnosing the index case and four other symptomatic newborns in the neonatal intensive care unit. Nasopharyngeal aspirate samples of all patients in the neonatal intensive care unit were tested for 17 respiratory viruses using real-time reverse transcriptase polymerase chain reaction. Genotyping was performed using nucleotide sequencing. RESULTS: From May to August 2013, two different outbreaks were detected in the neonatal intensive care unit. A total of 20 infants were infected with respiratory syncytial virus-A (ten and 14 with ON-1 and NA-2 genotypes, respectively). The mean age of the infants was 10 days, mean birth weight was 1,961g, and the mean gestational age was 33 weeks. Risk factors (heart disease, lung disease, and prematurity) were present in 80% and 85.7% of infants in the ON-1 and NA-2 groups, respectively. In total, 45.8% of infants were asymptomatic and 20.8% required mechanical ventilation. Coinfections were not detected during the outbreaks. CONCLUSIONS: Infants in a neonatal intensive care unit who develop abrupt respiratory symptoms should be tested for respiratory viruses, especially respiratory syncytial virus. Even in the absence of severe symptoms, respiratory syncytial virus detection can prevent nosocomial transmission through infection control measures. A better understanding of respiratory syncytial virus molecular epidemiology is essential for developing new vaccines and antiviral drugs against respiratory syncytial virus.
Assuntos
Infecção Hospitalar , Unidades de Terapia Intensiva Neonatal , Brasil , Surtos de Doenças , Genótipo , Humanos , Recém-Nascido , Estudos Prospectivos , Infecções por Vírus Respiratório SincicialRESUMO
Abstract Hepatopulmonary hydatidosis in young children is a rare and atypical presentation of Echinococcus granulosus infection. We report the first case of cystic echinococcosis caused by a microvariant of E. granulosus sensu stricto. Chemotherapy and systemic corticoids were administered before curative surgery was performed. Recurrence was not observed for more than 24 months of follow-up.
Assuntos
Humanos , Animais , Feminino , Albendazol/administração & dosagem , Echinococcus granulosus/isolamento & purificação , Equinococose Hepática/tratamento farmacológico , Equinococose Pulmonar/diagnóstico por imagem , Toracoscopia , Tomografia Computadorizada por Raios X , Seguimentos , Resultado do Tratamento , Equinococose Hepática/terapia , Equinococose Pulmonar/terapiaRESUMO
Spontaneous bacterial peritonitis is an uncommon manifestation of invasive pneumococcal disease and frequently occurs when an underlying hepatic disease is present. Bacterial identification through culture can be particularly challenging in patients with prior or concurrent antimicrobial use. DNA amplification detects very few copies of target DNA under ideal conditions in CSF or pleural effusion and, therefore, can be useful in selected infections. A culture-negative spontaneous pneumococcal peritonitis without preexisting peritoneal disease diagnosed by qPCR is herein described.
RESUMO
OBJECTIVE: Weight and height growth impairment is one of the most frequent manifestations in HIV-infected children and may be the first sign of disease, being considered a marker of disease progression and an independent risk factor for death. The aim of this review is to evaluate the influence of antiretroviral therapy on the growth pattern of children and adolescents living with HIV/AIDS. SOURCE OF DATA: A non-systematic review was carried out in the PubMed database, with the terms "HIV", "Weight and height growth", "ART" and "children". The most relevant publications were selected. DATA SYNTHESIS: Antiretroviral therapy has significantly reduced morbidity and mortality in HIV-infected children and is clearly associated with recovery of weight and height-for-age Z-scores, especially when started early, in the asymptomatic child still without weight-height impairment. Therapeutic strategies involving the GH/IGF-1 axis, especially for children with growth impairment, are still being studied. CONCLUSIONS: HIV-infected children show early weight-height impairment; antiretroviral therapy improves the anthropometric profile of these children.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Estatura/efeitos dos fármacos , Desenvolvimento Infantil/fisiologia , Transtornos do Crescimento/fisiopatologia , Crescimento e Desenvolvimento/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Adolescente , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Pré-Escolar , Progressão da Doença , Feminino , Transtornos do Crescimento/induzido quimicamente , Crescimento e Desenvolvimento/fisiologia , Infecções por HIV/fisiopatologia , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
Abstract Objective: Weight and height growth impairment is one of the most frequent manifestations in HIV-infected children and may be the first sign of disease, being considered a marker of disease progression and an independent risk factor for death. The aim of this review is to evaluate the influence of antiretroviral therapy on the growth pattern of children and adolescents living with HIV/AIDS. Source of data: A non-systematic review was carried out in the PubMed database, with the terms "HIV", "Weight and height growth", "ART" and "children". The most relevant publications were selected. Data Synthesis: Antiretroviral therapy has significantly reduced morbidity and mortality in HIV-infected children and is clearly associated with recovery of weight and height-for-age Z-scores, especially when started early, in the asymptomatic child still without weight-height impairment. Therapeutic strategies involving the GH/IGF-1 axis, especially for children with growth impairment, are still being studied. Conclusions: HIV-infected children show early weight-height impairment; antiretroviral therapy improves the anthropometric profile of these children.
Resumo Objetivo: O acometimento do desenvolvimento pondero-estatural é uma das manifestações mais frequentes nas crianças infectadas pelo HIV e pode ser o primeiro sinal de doença, é considerado um marcador de progressão para doença e um fator de risco independente para morte. O objetivo desta revisão é avaliar a influência da terapia antirretroviral no padrão de crescimento em crianças e adolescentes vivendo com HIV/Aids. Fonte dos dados: Foi feita uma revisão não sistemática na base de dados PubMed, com os termos "HIV", "desenvolvimento pondero estatural", "TARV" e "crianças". Foram selecionadas as publicações mais relevantes. Síntese dos dados: A terapia antirretroviral reduziu substancialmente a morbimortalidade em crianças infectadas pelo HIV e está claramente associada à recuperação do escore-z de peso e de estatura para idade, principalmente quando iniciada precocemente, na criança assintomática e ainda sem comprometimento pondero-estatural. Estratégias terapêuticas que envolvem o eixo GH/IGF-1, principalmente para crianças com comprometimento do crescimento, ainda estão em estudo. Conclusões: As crianças infectadas pelo HIV apresentam comprometimento pondero-estatural precoce e a terapia antirretroviral melhora o perfil antropométrico dessas crianças.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Estatura/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Desenvolvimento Infantil/fisiologia , Fármacos Anti-HIV/uso terapêutico , Crescimento e Desenvolvimento/efeitos dos fármacos , Transtornos do Crescimento/fisiopatologia , Infecções por HIV/fisiopatologia , Desenvolvimento Infantil/efeitos dos fármacos , Progressão da Doença , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Crescimento e Desenvolvimento/fisiologia , Transtornos do Crescimento/induzido quimicamenteRESUMO
Sepsis caused by Streptococcus pneumoniae is rare in neonates although associated with high morbidity and mortality. We report a fatal case of invasive pneumococcal disease in a term neonate whose mother was healthy and did not receive any pneumococcal vaccine. Investigation of the infection source yielded negative results. Acquisition of infection through the birth canal was considered unlikely.
Assuntos
Sepse Neonatal/diagnóstico , Sepse Neonatal/patologia , Infecções Pneumocócicas/diagnóstico , Infecções Pneumocócicas/patologia , Streptococcus pneumoniae/isolamento & purificação , Adolescente , Evolução Fatal , Feminino , Humanos , Recém-NascidoRESUMO
Transmitted drug resistance mutations (TDRM) have been a constant threat to treatment efficacy. We evaluated TDRM in plasma RNA of 217 antiretroviral therapy-naive patients from sites in the São Paulo metropolitan area, collected from 2012 to 2014. The partial HIV-1 polymerase region was sequenced using Big Dye terminators at an ABI 3130 Genetic Analyzer. TDRM was defined according to the Stanford database calibrated population resistance (CPR v.6.0), but other drug resistance mutations (DRM) considered at the IAS list (IAS, 2014) and at the Stanford HIV Database Genotyping Resistance Interpretation (GRI-HIVdb) were also described. Out of 78% (170/217) of patients with information on the time of diagnosis, most (83%, 141/170) had been recently diagnosed, with the first positive HIV serology at a median of 58 days (IQR 18-184). Subtype B predominated (70%), followed by subtype F (10%), BF (7.5%), C (7.5%), and BC (5%). TDRMs were observed in 9.2% (20/217, CI 95% 5.9% to 13.6%), mostly (5.2%) to nonnucleoside reverse transcriptase inhibitor (NNRTI) antiretroviral class. Among children and adolescents, only a single patient showed TDRMs. Additional non-CPR mutations were observed: 11.5% (25/217) according to IAS or 4.6% (10/217) according to GRI-HIVdb. Overall, 23.5% (51/217) of the cases had one or more DRM identified. TDRM prevalence differed significantly among some sites. These trends deserve continuous and systematic surveillance, especially with the new policies of treatment as prevention being implemented in the country.
Assuntos
Transmissão de Doença Infecciosa , Farmacorresistência Viral , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Criança , Pré-Escolar , Feminino , Genótipo , HIV-1/enzimologia , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA , Adulto Jovem , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genéticaRESUMO
Management of children with HIV/AIDS is specially challenging. Age-related issues do not allow for direct transposition of adult observations to this population. CXCR4 tropism has been associated with disease progression in adults. The geno2pheno web-base is a friendly tool to predict viral tropism on envelope V3 sequences, generating a false positive rate for a CXCR4 prediction. We evaluated the association of HIV-1 tropism prediction with clinical and laboratory outcome of 73 children with HIV/AIDS in São Paulo, Brazil. The CXCR4 tropism was strongly associated with a lower (nadir) CD4 documented during follow-up (p < 0.0001) and with disease severity (clinical event and/or CD4 below 200 cells/mm3) at the last observation, using commonly applied clinical cutoffs, such as10%FPRclonal (p = 0.001). When variables obtained during follow-up are included, both treatment adherence and viral tropism show a significant association with disease severity. As for viremia suppression, 30% (22/73) were undetectable at the last observation, with only adherence strongly associated with suppression after adjustment. The study brings further support to the notion that antiretroviral treatment adherence is pivotal to management of HIV disease, but suggests that tropism prediction may provide an additional prognostic marker to monitor HIV disease in children.
Assuntos
Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , HIV-1 , Progressão da Doença , Infecções por HIV/virologia , /fisiologia , Tropismo Viral/fisiologia , Antirretrovirais/uso terapêutico , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/fisiopatologia , RNA Viral/sangue , Carga ViralRESUMO
Management of children with HIV/AIDS is specially challenging. Age-related issues do not allow for direct transposition of adult observations to this population. CXCR4 tropism has been associated with disease progression in adults. The geno2pheno web-base is a friendly tool to predict viral tropism on envelope V3 sequences, generating a false positive rate for a CXCR4 prediction. We evaluated the association of HIV-1 tropism prediction with clinical and laboratory outcome of 73 children with HIV/AIDS in São Paulo, Brazil. The CXCR4 tropism was strongly associated with a lower (nadir) CD4 documented during follow-up (p<0.0001) and with disease severity (clinical event and/or CD4 below 200cells/mm(3)) at the last observation, using commonly applied clinical cutoffs, such as (10%)FPRclonal (p=0.001). When variables obtained during follow-up are included, both treatment adherence and viral tropism show a significant association with disease severity. As for viremia suppression, 30% (22/73) were undetectable at the last observation, with only adherence strongly associated with suppression after adjustment. The study brings further support to the notion that antiretroviral treatment adherence is pivotal to management of HIV disease, but suggests that tropism prediction may provide an additional prognostic marker to monitor HIV disease in children.
Assuntos
Progressão da Doença , Infecções por HIV/virologia , HIV-1/fisiologia , Receptores CXCR4/fisiologia , Tropismo Viral/fisiologia , Adolescente , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Feminino , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/fisiopatologia , Humanos , Lactente , Masculino , RNA Viral/sangue , Carga ViralRESUMO
HIV drug resistance genotype testing, performed on 39 HIV-infected treatment-naive children from 2000 to 2011, identified 5 children (12.8%) with drug resistance mutations: 5.3% to nucleoside reverse transcriptase inhibitors, 5.3% to nonnucleoside reverse transcriptase inhibitors and 7.7% to protease inhibitors. There was a trend for increasing prevalence of drug resistance mutations during the 11-year study period.
Assuntos
Farmacorresistência Viral , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Mutação de Sentido Incorreto , Adolescente , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Genótipo , Infecções por HIV/epidemiologia , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Masculino , PrevalênciaRESUMO
HIV-1 genetic diversity information from a pediatric population is scarce. This study enrolled 128 children living with HIV/AIDS, 103 antiretroviral-treated and 25 naive, from the Sao Paulo metropolitan area. Gag, pol and env regions were amplified, and drug resistance mutations, V3 loop, tropism and viral clades were evaluated. Drug resistance mutations among naïve children infected by vertical transmission were uncommon (4.2%), whereas most ARV-experienced children showed extensive mutation patterns. Clade B predominated at the pol region, but the analysis of the three regions concatenated showed 28% with BF mosaic structures. The most common V3 motif was GPGR, followed by GWGR in clade B samples and GPGQ in clade F samples. A predicted X4 phenotype was observed in 27%, without correlation to HIV clade. These findings expand the limited information on molecular characteristics of HIV-1 among children living with HIV/AIDS in the area and may provide information useful for monitoring the epidemic.