EVALUATION OF INVASIVE METHODS TO DIAGNOSIS Helicobacter pylori INFECTION IN CHILDREN AND ADOLESCENTS WITH DYSPEPSIA INVASIVE METHODS TO DIAGNOSE Hp INFECTION

Apesar do uso rotineiro de biópsias endoscópicas para o diagnóstico da infecção por Helicobacter pylori em nosso meio, há poucos estudos pediátricos, avaliando a acurácia dos métodos invasivos. Métodos: Foram avaliados prospectivamente 120 pacientes submetidos à endoscopia para investigação de sintomas dispépticos. Foram obtidos seis biópsias de região antral para detecção do Helicobacter pylori através do teste rápido da urease, histologia e cultura. Os pacientes foram considerados infectados, se a cultura ou a histologia e o teste rápido da urease resultaram positivos. Resultados: A idade variou de 3m a 17anos (média: 10a1m); 54% do sexo feminino e 46% masculino; 44% (53/120) estavam infectados. O exame endoscópico foi normal em 54% (65/120) e anormal em 46% (55/120). O diagnóstico foi gastrite - 69% (38/55), esofagite - 13% (13/55), úlcera duodenal - 13% (7/55) e duodenite - 5% (3/55). Os 3 métodos concordaram em 72,5% (87/120), foram todos negativos em 48% (58/120) e todos positivos em 24,5% (29/120). A melhor concordância ocorreu entre a histologia e o teste rápido da urease (91,7%), seguido pela cultura e histologia (78,3%) e, finalmente, a cultura e o teste rápido da urease (75%). A sensibilidade do teste rápido da urease foi 100%,  seguido pela histologia (98,1%) e pela cultura (56,6%). A especificidade da histologia foi de 97%, seguida pelo teste rápido da urease (89,5%). Conclusão: A associação histologia e o teste rápido da urease mostraram maior acurácia na detecção da infecção por Helicobacter pylori devido a sua alta sensibilidade (teste rápido da urease) e alta especificidade (histologia), além do baixo custo e praticidade. A cultura isolada não deve ser utilizada como padrão-ouro devido à baixa sensibilidade.  In our country there are few studies evaluating the accuracy of invasive methods in children, although the usual practice of endoscopic gastric biopsies to diagnose Helicobacter pylori infection. Methods: We evaluated prospectively 120 patients submitted to endoscopy for investigation of dyspeptic symptoms. Six antral biopsies were taken to detect Helicobacter pylori by rapid urease test, histology and culture. Patients were considerate infected if culture was positive or if histology and rapid urease test were positive. Results: The age ranges from 3mo to 17y (Median: 10y1mo); 54% were female and 46% were male; 44% (53/120) were infected. The endoscopic examination was normal in 54% (65/120) and abnormal in 46% (55/120). The diagnosis was gastritis - 69% (38/55), esophagitis - 13% (13/55), duodenal ulcer - 13% (7/55) and duodenitis - 5% (3/55). The 3 methods agreed in 72.5% (87/120), and were all negative in 48% (58/120) and all positive in 24.5% (29/120). The best agreement occurred between histology and rapid urease test (91.7%), followed by culture and histology (78.3%) and finally culture and rapid urease test (75%). The sensitivity of the rapid urease test was 100%, followed by histology (98.1%) and culture (56.6%). The specificity of histology was 97%, followed by rapid urease test (89.5%). Conclusions: The histology and rapid urease test combination was the most accurate to identify Helicobacter pylori infection in account of high sensitivity of rapid urease test and high specificity of histology, besides they were low cost and practicable. The culture alone must not be considered gold standard due to its low sensitivity 

Soroprevalência da infecção por Helicobacter pylori em crianças de baixo nível sócio-econômico em São Paulo

CONTEXT AND OBJECTIVE: Helicobacter pylori infection is mainly acquired during childhood, and is associated with significant morbidity in adults. The aim here was to evaluate the seroprevalence and risk factors of H. pylori infection among children of low socioeconomic level attended at a public hospital in São Paulo, Brazil. DESIGN AND SETTING: Cross-sectional study, among patients attended at an outpatient clinic. METHODS: 326 children were evaluated (150 boys and 176 girls; mean age 6.82 ± 4.07 years) in a cross-sectional study. Patients with chronic diseases or previous H. pylori treatment, and those whose participation was not permitted by the adult responsible for the child, were excluded. The adults answered a demographic questionnaire and blood samples were collected. The serological test used was Cobas Core II, a second-generation test. Titers > 5 U/ml were considered positive. RESULTS: H. pylori infection was diagnosed in 116 children (35.6%). Infected children were older than uninfected children (7.77 ± 4.08 years versus 5.59 ± 3.86 years; p 5 U/ml. RESULTADOS: Infecção por H. pylori foi diagnosticada em 116 (35,6%). A idade dos pacientes infectados foi maior que a dos demais (7,77 ± 4,08 anos versus 5,59 ± 3,86 anos; p < 0,0001). A prevalência aumenta de 20,8% entre dois e quatro anos de idade para 58,3% entre maiores de 12 anos. Não houve relação significativa entre soropositividade e sexo, raça, aleitamento materno, número de pessoas ou de cômodos na casa, compartilhamento de camas, domicílio em favela, escolaridade materna, renda familiar ou estado nutricional. Na análise multivariada, a única variável significativamente associada a soropositividade foi idade. CONCLUSÃO: A infecção possui prevalência intermediária na população estudada, e a idade foi associada a maior prevalência.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Division of Pediatric GastroenterologyUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Department of PediatricsUNIFESP, EPM, Division of Pediatric GastroenterologyUNIFESP, EPM, Department of PediatricsSciEL

Prevalence of intestinal parasitoses in children at the Xingu Indian Reservation

OBJECTIVE: To evaluate the prevalence of intestinal parasitoses in Native Brazilian children from 2 to 9 years old. METHODS: A search for ova and parasites was conducted in the stools of children between 2 to 9 years old living in six indigenous villages located in the Middle and Lower Xingu River, to wit: Pavuru, Moygu, Tuiararé, Diauarum, Capivara, and Ngojwere. The study utilized the Paratest kit® (Diagnostek, Brazil) to preserve collected stools. Fecal samples were shipped to the Laboratory of the Pediatric Gastroenterology Division of the UNIFESP/EPM, in São Paulo, for analysis. The search for ova and parasites was performed utilizing the Hoffman method, and later through optical microscopic evaluation. Fecal samples were collected one year apart from each other. RESULTS: There were no significant statistical differences between the mean ages of the children from the six indigenous villages studied. The search for ova and parasites found positive results for the stools of 97.5% (198/202) and 96.1% (98/102) of children in the first and second collections, respectively. There was no statistical association with the children's age. The search performed one year later found no differences in the proportion of parasites identified in the first collection for protozoa (93.3% in 2007 versus 93.3% in 2008, McNemar = 0.01, p = 0.1) or for helminths (37.1% in 2007 versus 38.2% in 2008, McNemar = 0.03, p = 0.85). There were significant differences in prevalence of Entamoeba coli between 2007 (43.8%) and 2008 (61.8%) (McNemar Chi 6.1; p = 0.0135). There were no significant differences for other parasites when comparing the results of the two studies. CONCLUSION: The high prevalence of intestinal parasitosis matched the elevated rates of environmental contamination in this indigenous community.OBJETIVO: Avaliar a prevalência da parasitose intestinal em crianças indígenas de 2 a 9 anos. MÉTODOS: Para a realização do exame protoparasitológico, foram convidadas todas as crianças de 2 a 9 anos, de seis aldeias localizadas no Médio e Baixo Xingu: Pavuru, Moygu, Tuiararé, Diauarum, Capivara e Ngojwere. Para a conservação das amostras de fezes, foi utilizado o kit coletor Paratest® (Diagnostek, Brasil). As amostras foram transportadas para São Paulo. A pesquisa de helmintos e protozoários foi feita através do método de Hoffman, com posterior pesquisa de ovos e cistos por microscopia óptica. Foram feitas duas coletas com intervalo de 1 ano. RESULTADOS: Não houve diferença significativa entre as idades médias das crianças provenientes das seis aldeias. Resultaram positivas para a presença de parasitas, 97,5% (198/202) e 96,1% (98/102) na primeira e segunda coletas, respectivamente, sem associação estatística entre a idade. Realizaram o exame parasitológico de fezes nos 2 anos, 89/102 (87,3%). Após 1 ano, não houve diferença na proporção de pacientes infestados por protozoários (93,3% em 2007 contra 93,3% em 2008, McNemar = 0,01, p = 0, 1) ou por helmintos (37,1% em 2007 contra 38,2% em 2008, McNemar = 0,03, p = 0,85). Houve diferença significativa quanto à prevalência de Entamoeba coli em 2007 (43,8%) e 2008 (61,8%) (McNemar's Chi 6,1; p = 0,0135). Não houve diferenças significativas quanto aos outros parasitas após comparação dos dois resultados. CONCLUSÃO: A alta prevalência de parasitose intestinal foi compatível com o alto índice de contaminação ambiental dessa comunidade.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PediatriaUNIFESP-EPM Projeto XinguUNIFESPUNIFESP, EPM, Depto. de PediatriaUNIFESP, EPM Projeto XinguUNIFESPSciEL

Evaluation of invasive and non-invasive methods for the diagnosis of Helicobacter pylori infection in symptomatic children and adolescents

CONTEXT: Multiple diagnostic methods are available for the detection of Helicobacter pylori infection, but at present no single one can be used as the gold standard. OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy of 3 invasive and 2 non-invasive methods for detection of Helicobacter pylori infection in symptomatic children and adolescents. DESIGN: Prospective cohort study SETTING: Peptic Disease outpatients service, Discipline of Pediatric Gastroenterology, Universidade Federal de São Paulo (UNIFESP) / Escola Paulista de Medicina. PATIENTS: Forty-seven patients who underwent endoscopy because of dyspeptic symptoms. DIAGNOSTIC METHODS: Endoscopy with gastric biopsies for 3 invasive (rapid urease test, histology and culture) and 2 non-invasive methods (a commercial ELISA serology and 13carbon urea breath test - isotope ratio mass spectrometry) for detection of Helicobacter pylori infection. MAIN MEASUREMENTS: Sensitivity, specificity, positive and negative predictive values of each method and agreement and disagreement rates between the methods. RESULTS: Forty-seven patients [mean age, 11y9mo (SD 2y10mo), 27 female and 20 male]; 62% of them were Helicobacter pylori-positive. All methods agreed in 61%, and were negative in 21% and positive in 40%. The greatest concordance between 2 methods occurred between the invasive methods: histology and rapid urease test (89.6%) and histology and culture (87.5%). The greatest sensitivity, considering Helicobacter pylori-positive cases, for any combination of 3 or more tests, was achieved by the rapid urease test (S=100%), followed by histology, serology and 13carbon-urea breath test (S=93.1%) and lastly by culture (S=79.3%). The highest specificity was obtained by histology (100%) and culture (100%), followed by the rapid urease test (84.2%), serology (78.9%) and 13carbon-urea breath test (78.9%). CONCLUSIONS: Our results suggest that among invasive methods, an association between the rapid urease test and histology constituted the best choice for the detection of Helicobacter pylori infection. If results of histology and the rapid urease test are different, serology may be recommended.CONTEXTO: Vários métodos diagnósticos estão disponíveis para a detecção da infecção por Helicobacter pylori (Hp), porém, até o presente momento, não há um teste que possa ser utilizado isoladamente como padrão-ouro. OBJETIVO: Avaliar a acurácia de três métodos invasivos e dois não-invasivos na detecção da infecção por Hp em crianças e adolescentes sintomáticos. TIPO DE ESTUDO: Estudo coorte prospectivo. LOCAL: Ambulatório de Doença Péptica, Disciplina de Gastroenterologia Pediátrica, Universidade Federal de São Paulo (UNIFESP) / Escola Paulista de Medicina. PACIENTES: 47 pacientes sintomáticos que realizaram exame endoscópico devido a sintomas dispépticos. MÉTODOS DIAGNÓSTICOS: Exame endoscópico com biopsias gástricas para três métodos invasivos (teste rápido da urease, histologia e cultura) e dois métodos não-invasivos (teste sorológico ELISA industrializado e teste respiratório com uréia marcada com Carbono13). VARIÁVEIS ESTUDADAS: Sensibilidade, especificidade, valor preditivo positivo e negativo de cada método e taxas de concordância e discordância entre os métodos. RESULTADOS: 47 pacientes [idade média de 11a9m (DP 2a10m), 27 do sexo feminino e 20 do masculino], 62% deles com infecção por Hp. Todos os 5 métodos concordaram em 61%, sendo negativo em 21% e positivo em 40%. As maiores concordâncias entre dois métodos ocorreram entre os métodos invasivos: histologia e teste rápido da urease (89,6%) e entre a histologia e cultura (87,5%). A maior sensibilidade, considerando como Hp positivo, qualquer combinação de 3 ou mais testes, foi encontrada no teste rápido da urease (S=100%), seguido pela histologia, sorologia e o teste respiratório com uréia marcada com Carbono13 (S=93,1%) e por fim a cultura (S=79,3%). A maior especificidade foi obtida pela histologia e cultura (100%), seguidos pelo teste rápido da urease (84,2%), sorologia (78,9%) e teste respiratório com uréia marcada com Carbono13 (78,9%). CONCLUSÕES: Nossos resultados sugerem que, entre os métodos invasivos, a associação do teste rápido da urease e histologia constituem a melhor escolha para a detecção da infecção por Hp. Se os resultados da histologia e do teste rápido da urease forem discordantes é recomendada a sorologia.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Pediatric DepartmentUNIFESP, EPM, Pediatric DepartmentSciEL

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. FUNDING: Bill & Melinda Gates Foundation

Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older. Methods Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health. Findings Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week. Interpretation Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.Peer reviewe

Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016

The UN’s Sustainable Development Goals (SDGs) are grounded in the global ambition of “leaving no one behind”. Understanding today’s gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990–2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030