Gerusa Gibson

Single nucleotide polymorphisms in candidate genes and dengue severity in children: A case–control, functional and meta-analysis study

Dengue is an arthropod-borne emerging viral disease with high morbidity and mortality risk in tropical countries like Brazil. Clinical manifestations are vast, ranging from asymptomatic to most severe forms of dengue such as shock. Previous data have shown that host genetics play a role in disease susceptibility and severity. Herein, we have tested the association of single nucleotide polymorphisms (SNPs) at TNF, IL10, MIF, DCSIGN, CLEC5A, NOD2, CCR5 and MRC1 as candidate genes using a matched case-control study design including 88 severe children cases of dengue patients and 335 healthy unrelated subjects that was also separated in IgG(+) and IgG(-) controls. We demonstrated that the TT genotype of CLEC5A SNP (rs1285933 C>T) is associated with dengue severity (OR=2.25; p=0.03) and that GG genotype of -336G>A DCSIGN (CD209) SNP is associated with protection to severe dengue (OR=0.12; p=0.04). Both comparisons were borderline significant when cases were compared with IgG(+) controls subgroup. Nevertheless, genotype-phenotype correlation was also assessed using serum levels of TNF from infected patients at the onset of dengue fever, and CT/TT carriers in CLEC5A secreted higher levels of TNF than CC individuals in 5-7 days of infection. No significant difference was observed in TNF levels between genotypes GG versus AG/AA at DCSIGN promoter. Next, we performed a meta-analysis retrieving results from the literature for -336G>A DCSIGN and -308G>A TNF SNPs demonstrating that the consensus estimates of these SNPs indicated no association with dengue severity (when compared to Dengue fever) in the overall analysis. But, a subgroup analysis in the -336G>A DCSIGN, the G allele was associated with severe dengue susceptibility in Asians (ORallele=2.77; p=0.0001; ORcarriers=2.99; p=0.0001) and protection in Brazilians (ORallele=0.66; p=0.013). In summary, our results suggest that genetic variations at CLEC5A increase the risk and regulate TNF secretion in dengue severity among Brazilians. Also, combined data of the literature suggest population-specific effect of the -336 DCSIGN SNP more prominent in Asians and in a different direction than Brazilians.

Consumo de agrotóxicos e distribuição temporal da proporção de nascimentos masculinos no Estado do Paraná, Brasil

OBJETIVO: Investigar a tendencia temporal da proporcao de nascimentos masculinos para o Estado do Parana no periodo entre 1994 e 2004 e a correlacao dessa tendencia com o volume de vendas de agrotoxicos no Estado em 1985. METODO: No presente estudo ecologico, foram empregados como fontes de dados o Instituto Brasileiro de Geografia e Estatistica (volume de vendas de agrotoxicos) e o banco DATASUS (nascidos vivos segundo o sexo). Foram analisados 308 municipios, divididos em quartis conforme o consumo de agrotoxicos, resultando em quatro estratos contendo 77 municipios cada um, sendo o quarto quartil o de maior consumo. A proporcao de nascimentos masculinos foi obtida ano a ano para cada municipio e, ao final do periodo (1994 a 2004), um valor mediano foi calculado para cada uma das localidades. Foi realizada uma analise bivariada e calculados os coeficientes de Pearson para cada quartil de municipios. Uma analise exploratoria e comparativa dos quartis foi realizada, na qual se calculou o consumo medio per capita para os mesmos. Posteriormente, foram selecionados e analisados individualmente 10 municipios com intensa atividade agropecuaria quanto ao perfil agricola e a tendencia da proporcao de nascimentos masculinos ao longo do periodo de estudo. RESULTADOS: Foi observada uma discreta tendencia de declinio na proporcao de nascidos vivos do sexo masculino para o Estado como um todo. A magnitude desse declinio foi visivelmente maior quando se analisou individualmente o grupo de 10 municipios, cujos valores observados ao final da serie mostraram-se muito abaixo daqueles normalmente descritos na literatura (proporcao de nascimentos masculinos < 50%). Em relacao aos quartis, todos apresentaram correlacao negativa, ainda que sem significância estatistica. CONCLUSOES: A tendencia de declinio estatisticamente significativa na proporcao de nascimentos masculinos em alguns municipios paranaenses sugere que o fenomeno possa ser decorrente da alta exposicao ambiental aos agrotoxicos nessas localidades. Sendo assim, recomendam-se estudos futuros que visem a esclarecer e a dimensionar a forca do impacto da contaminacao ambiental por agrotoxicos na saude reprodutiva, representada aqui pela razao de sexos ao nascimento.

From primary care to hospitalization: clinical warning signs of severe dengue fever in children and adolescents during an outbreak in Rio de Janeiro, Brazil

The purpose of the study was to assess the influence of socioeconomic risk factors, food security, health, and key anthropometric measures on body mass index (BMI) in a group of teenagers from Medellin, Colombia, in the third trimester of pregnancy. A cross-sectional study was carried out with 294 pregnant teenagers. Data were analyzed using bivariate and multivariate logistic regression analysis. Pregnant teenagers whose families earned less than one minimum wage were more likely to have low weight (OR = 5.8; 95%CI: 1.97-16.8). Age under 15 years was associated with a fourfold increase in low gestational weight. Arm and calf circumference greater than 24cm and 32cm, respectively, were associated with a 94% reduction in low gestational weight (arm circumference: OR = 0.1; 95%CI: 0.0-0.2) (calf circumference: OR = 0.1; 95%CI: 0.0-0.2). In conclusion, low income and young age were associated with low gestational weight. Arm and calf circumference correlated with maternal weight.

Time Trend of the Male Proportion at Birth in Brazil, 1979–2004

Several studies suggest that exposure to environmental endocrine disrupters can reduce the number of male births, and therefore, the male proportion at birth (also denominated birth ratio or sex ratio at birth) can be used as a sentinel health indicator. This work aimed to analyze the trend of male births in Brazil, according to their distribution by states and capitals. An ecological descriptive time series was carried out using polynomial regression, showing a declining trend for male proportion at birth in Brazil (1979–1994), followed by an upward trend until 2004. A decline on the proportion of male births was observed in Brazil between 1979 and 1993, followed by a subsequent rise of this ratio between 1995 and 2004, wherein the mean proportion of male births in Brazil rose from 51.05 to 51.18, representing a relative increase of 0.25%. The states of São Paulo (Southwest region) and Acre (Western Amazon), as well as some capitals–Cuiabá (Western Region), Palmas (Amazon) and Rio Branco (Amazon)–showed increasing trends, which suggests the influence of socio-demographic changes. In contrast, a declining trend in the State of Ceará State (Northeast region), with a 0.35% yearly decrease was observed. As a whole, these results suggest the influence of different environmental factors (demographic changes, public health services distribution, and population exposure to endocrine disruptor substances) influencing the time trend of birth ratio in the Brazilian population during the last decades.

Conditions of the household and peridomicile and severe dengue: a case-control study in Brazil

Introduction The potential influence of high-vector-density environments where people are supposedly more exposed to mosquito bites may have a relation to the clinical severity of dengue fever, an association that has been poorly discussed in the literature. Objective This study aimed at analyzing the association between anthropic environmental factors, particularly those related to the conditions of domicile and peridomicile, and the occurrence of severe dengue cases during the 2008 epidemic in the state of Rio de Janeiro. Methods We conducted a retrospective case–control study with a sample of 88 severe patients aged 2–18. They were selected through chart review in four childrens tertiary care centers. The 367 controls were neighbors of the cases, paired by age. Data were collected through interviews and systematic assessment of house conditions as well as peridomicile area conditions, and they were later analyzed by conditional logistic regression. Results The presence of three or more high-volume capacity containers, which were without a lid or were inadequately sealed (water tanks, wells, cisterns, cement tanks, and pools), was significantly more frequent in households with severe cases when compared with households of controls (OR=1.6; CI 95%=1.36–20.01; p=0.015). Discussion The presence of such larger reservoirs that could potentially produce more adult forms of the vector is consistent with a situation where people are more exposed to mosquito bites, and consequently are more prone to have multiple infections over a short period of time. Conclusion The emergence of severe dengue cases in a high-transmission context underpins the importance of constant vigilance and interventions in those types of reservoirs, which result from precarious household structures and irregular water supply services.

Da atenção primária à hospitalização: sinais clínicos de alarme para dengue grave em crianças e adolescentes durante uma epidemia no Rio de Janeiro, Brasil

Foram avaliados fatores associados a ocorrencia de casos graves de dengue em criancas/adolescentes hospitalizados durante a epidemia de 2007/2008 no Rio de Janeiro, Brasil. Trata-se de estudo caso-controle retrospectivo com 88 casos graves de dengue, admitidos em quatro hospitais de atencao terciaria infantil. Os controles foram 22 criancas com dengue nao grave residentes na vizinhanca dos casos. Foram observadas diferencas na prevalencia de sinais clinicos - dor abdominal, dificuldade respiratoria, sonolencia/irritabilidade - a partir do terceiro dia do inicio dos sintomas, ainda na presenca da febre. Casos e controles receberam o primeiro atendimento medico no mesmo estagio clinico da doenca. Contudo, as hospitalizacoes dos casos graves ocorreram mais tardiamente, em media entre o terceiro e quarto dia da doenca. A liberacao precoce de pacientes com quadro febril e potencialmente graves pode ter sido consequencia do atendimento medico prestado nas unidades de atencao primaria, sugerindo deficiencias na aplicacao do protocolo de classificacao de risco de dengue e triagem de pacientes.We analyzed factors associated with severe cases of dengue in children and adolescents hospitalized during the 2007/2008 epidemic in Rio de Janeiro, Brazil. This is a retrospective case-control study that covers 88 cases of severe dengue in patients admitted to four tertiary care childrens hospitals. Controls consisted of 22 children with non-severe dengue living in the same neighborhood as the patients with severe dengue. Differences in prevalence of the clinical signs - abdominal pain, breathing difficulty, drowsiness or irritability - emerged on the third day after the onset of symptoms, in the febrile stage. Cases and controls received first medical care at the same clinical stage of disease. However, hospital admission of severe cases occurred later, on average between the third and fourth day after the onset of the disease. Early discharge of patients with fever whose condition could have progressed to severe dengue may have been a consequence of the type of medical assistance provided by primary care units, suggesting deficiencies both in the use of the risk classification protocol and patient triage.

Occurrence of severe dengue in Rio de Janeiro: an ecological study

INTRODUCTION This study aimed to analyze the relationship between the incidence of severe dengue during the 2008 epidemic in Rio de Janeiro, Brazil, and socioeconomic indicators, as well as indicators of health service availability and previous circulation of the dengue virus serotype-3 (DENV-3). METHODS In this ecological study, the units of analysis were the districts of Rio de Janeiro. The data were incorporated into generalized linear models, and the incidence of severe dengue in each district was the outcome variable. RESULTS The districts with more cases of dengue fever in the 2001 epidemic and a higher percentage of residents who declared their skin color or race as black had higher incidence rates of severe dengue in the 2008 epidemic [incidence rate ratio (IRR)= 1.21; 95% confidence interval (95%CI)= 1.05-1.40 and IRR= 1.34; 95%CI= 1.16-1.54, respectively]. In contrast, the districts with Family Health Strategy (FHS) clinics were more likely to have lower incidence rates of severe dengue in the 2008 epidemic (IRR= 0.81; 95%CI= 0.70-0.93). CONCLUSIONS At the ecological level, our findings suggest the persistence of health inequalities in this region of Brazil that are possibly due to greater social vulnerability among the self-declared black population. Additionally, the protective effect of FHS clinics may be due to the ease of access to other levels of care in the health system or to a reduced vulnerability to dengue transmission that is afforded by local practices to promote health.