ABSTRACT
Chagas disease remains a major social and public health problem in Latin America. Benznidazole (BZN) is the main drug with activity against Trypanosoma cruzi. Due to the high number of adverse drug reactions (ADRs), BZN is underprescribed. The goal of this study was to evaluate the genetic and transcriptional basis of BZN adverse reactions. METHODS: A prospective cohort with 102 Chagas disease patients who underwent BZN treatment was established to identify ADRs and understand their genetic basis. The patients were classified into two groups: those with at least one ADR (n = 73), and those without ADRs (n = 29). Genomic analyses were performed comparing single nucleotide polymorphisms between groups. Transcriptome data were obtained comparing groups before and after treatment, and signaling pathways related to the main ADRs were evaluated. RESULTS: A total of 73 subjects (71.5%) experienced ADRs. Dermatological symptoms were most frequent (45.1%). One region of chromosome 16, at the gene LOC102724084 (rs1518601, rs11861761, and rs34091595), was associated with ADRs (p = 5.652 × 10-8). Transcriptomic data revealed three significantly enriched signaling pathways related to BZN ADRs. CONCLUSIONS: These data suggest that part of adverse BZN reactions might be genetically determined and may facilitate patient risk stratification prior to starting BZN treatment.
Subject(s)
Chagas Disease/drug therapy , Chagas Disease/genetics , Nitroimidazoles/adverse effects , Polymorphism, Single Nucleotide , Transcriptome , Trypanocidal Agents/adverse effects , Trypanosoma cruzi/drug effects , Brazil/epidemiology , Chagas Disease/epidemiology , Chagas Disease/parasitology , Female , Gene Regulatory Networks , Genome-Wide Association Study , Genotype , Humans , Male , Middle Aged , Prospective Studies , Risk , Signal Transduction/geneticsABSTRACT
BACKGROUND: A linked donor-recipient study was conducted during epidemics in 2 cities in Brazil to investigate transfusion-transmitted (TT) dengue virus (DENV) by DENV RNA-positive donations. METHODS: During February-June 2012, samples were collected from donors and recipients and retrospectively tested for DENV RNA by transcription-mediated amplification. Recipient chart review, using a case (DENV positive)-control (DENV negative and not known to be exposed) design, was conducted to assess symptoms. RESULTS: Of 39 134 recruited blood donors, DENV-4 viremia was confirmed in 0.51% of donations from subjects in Rio de Janeiro and 0.80% of subjects in Recife. Overall, 42 DENV RNA-positive units were transfused into 35 recipients. Of these, 16 RNA-positive units transfused into 16 susceptible recipients were identified as informative: 5 cases were considered probable TT cases, 1 possible TT case, and 10 nontransmissions. The TT rate was 37.5% (95% confidence interval [CI], 15.2%-64.6%), significantly higher than the viremia rate of 0.93% (95% CI, .11%-3.34%) in nonexposed recipients (P < .0001). Chart review did not find significant differences between cases and controls in symptoms or mortality. CONCLUSIONS: During a large epidemic of DENV-4 infection in Brazil, >0.5% of donations were RNA positive, and approximately one third of components resulted in TT. However, no significant clinical differences were evident between RNA-positive and RNA-negative recipients.
Subject(s)
Dengue Virus/isolation & purification , Dengue/epidemiology , Dengue/transmission , Epidemics , Transfusion Reaction , Blood Donors , Brazil/epidemiology , Humans , RNA, Viral/blood , RNA, Viral/isolation & purificationABSTRACT
A vacina contra hepatite B é recomendada em pacientes com insuficiência renal crônica (IRC). Controvérsias existem acerca da melhor vacina, do melhor esquema vacinal e do período da vacinaçao, principalmente em crianças. Empregamos uma vacina recombinante contra hepatite B (Engerix Bâ, Smith Kline Biologicals), via intramuscular, no esquema #0, #1 e #6 meses, doses simples em 25 crianças (Grupo I) e doses duplas em 22 (Grupo II), todas em fase de tratamento conservador. Avaliamos a resposta pelos níveis de anticorpos anti-HBs após 1 mês da terceira dose (títulos protetores acima de 100 mUI/ml). Os pacientes do Grupo I respondenram com eficácia em 64 por cento dos casos e os do Grupo II em 86 por cento. Reforço vacinal com dose dupla foi administrado quando os títulos foram negativos ou nao protetores. O reforço produziu títulos protetores de anti-HBs em 57 por cento dos casos no Grupo I e em 100 por cento dos casos no Grupo II. O seguimento longitudinal, ainda que restrito, mostrou que os títulos de Ac anti-HBs permanecem protetores por mais tempo nas crianças do Grupo II do que nas do Grupo I. Nossos dados sugerem que crianças com IRC sob tratamento conservador devam receber a vacina recombinante (Engerix Bâ) contra hepatite B, em doses duplas no esquema habitual. A avaliaçao da resposta vacinal deve ser realizada 1 mês após a terceira dose da vacina. A manutençao de títulos protetores de anti-HBs deve ser verificada semenstralmente.
