A multivariate analysis of socio-demographic factors, water contact patterns and Schistosoma mansoni infection in an endemic area in Brazil

Associations between socio-demographic factors, water contact patterns and Schistosoma mansoni infection were investigated in 506 individuals (87% of inhabitants over 1 year of age) in an endemic area in Brazil (Divino), aiming at determining priorities for public health measures to prevent the infection. Those who eliminated S. mansoni eggs (n = 198) were compared to those without eggs in the stools (n = 308). The following explanatory variables were considered: age, sex, color, previous treatment with schistosomicide, place of birth, quality of the houses, water supply for the household, distance from houses to stream, and frequency and reasons for water contact. Factors found to be independently associated with the infection were age (10-19 and > 20 yrs old), and water contact for agricultural activities, fishing, and swimming or bathing (Adjusted relative odds = 5.0, 2.4, 3.2, 2.1 and 2.0, respectively). This suggests the need for public health measures to prevent the infection, emphasizing water contact for leisure and agricultural activities in this endemic area.

Possible risk factors for vertical transmission of Chagas' disease

The author emphasizes the importance of the congenital transmission of Chagas' disease and discusses the possible risk factors for transmission such as age, origin, obstetrical history and maternal form of disease. Exacerbation of infection during pregnancy is also considered as a possible risk factor for transmission. Besides, a relationship between the frequency of transmission and gestational age is presented. Concerning breast-feeding, the risk of transmission is directly related to the acute phase of maternal disease and bleeding nipples. The deleterious effects of chagasic infection on the fetus and newborn are also considered.

Immunohistochemical molecular phenotypes of gastric cancer based on SOX2 and CDX2 predict patient outcome

Background Gastric cancer remains a serious health concern worldwide. Patients would greatly benefit from the discovery of new biomarkers that predict outcome more accurately and allow better treatment and follow-up decisions. Here, we used a retrospective, observational study to assess the expression and prognostic value of the transcription factors SOX2 and CDX2 in gastric cancer. Methods SOX2, CDX2, MUC5AC and MUC2 expression were assessed in 201 gastric tumors by immunohistochemistry. SOX2 and CDX2 expression were crossed with clinicopathological and follow-up data to determine their impact on tumor behavior and outcome. Moreover, SOX2 locus copy number status was assessed by FISH (N = 21) and Copy Number Variation Assay (N = 62). Results SOX2 was expressed in 52% of the gastric tumors and was significantly associated with male gender, T stage and N stage. Moreover, SOX2 expression predicted poorer patient survival, and the combination with CDX2 defined two molecular phenotypes, SOX2+CDX2- versus SOX2-CDX2+, that predict the worst and the best long-term patients’ outcome. These profiles combined with clinicopathological parameters stratify the prognosis of patients with intestinal and expanding tumors and in those without signs of venous invasion. Finally, SOX2 locus copy number gains were found in 93% of the samples reaching the amplification threshold in 14% and significantly associating with protein expression. Conclusions We showed, for the first time, that SOX2 combined with CDX2 expression profile in gastric cancer segregate patients into different prognostic groups, complementing the clinicopathological information. We further demonstrate a molecular mechanism for SOX2 expression in a subset of gastric cancer cases.

Schistosomiasis mansoni in an area of low transmission: II. Risk factors for infection

Risk factors for Schistosoma mansoni infection were identified using a 1:1 matched case-control design. The work was conducted in the municipality of Pedro de Toledo, São Paulo State, Brazil, an area where the snail host is Biomphalaria tenagophila. Information on water contact patterns, knowledge, attitudes and pratices (kap), socioeconomic and sanitary conditions were obtained by mean of questionnaires. The crude odds ratio estimates and the adjusted odds ratio estimates using the logistic regression model are presented. Most of the examined individuals admitted recent water contacts (90.6% of the cases). The most frequent reason for contact was swimming, playing and fishing and the preferential site of contact was the river. According to the logistic regression technique, the main risk factors for infection were: a) water contact through swimming, playing and fishing; b) fording; c) bad hygiene. We concluded that recreational activities are the main reasons for schistosomiasis transmission in Pedro de Toledo and leisure alternatives should be offered to the local population.

Estrogen receptor dependent genetic and epigenetic factors of tamoxifen resistance

Resumo: A decisão da terapêutica hormonal no tratamento do cancro da mama baseiase na determinação do receptor de estrogénio alfa por imunohistoquímica (IHC). Contudo, a presença deste receptor não prediz a resposta em todas as situações, em parte devido a limitações do método IHC. Investigámos se a expressão dos genes ESR1 e ESR2, bem como a metilação dos respectivos promotores, pode estar relacionada com a evolução desfavorável de uma proporção de doentes tratados com tamoxifeno assim como com a perda dos receptores de estrogénio alfa (ERα) e beta (ERß). Amostras de 211 doentes com cancro da mama diagnosticado entre 1988 e 2004, fixadas em formalina e preservadas em parafina, foram utilizadas para a determinação por IHC da presença dos receptores ERα e ERß. O mRNA total do gene ESR1 e os níveis específicos do transcrito derivado do promotor C (ESR1_C), bem como dos transcritos ESR2_ß1, ESR2_ß2/cx, and ESR2_ß5 foram avaliados por Real-time PCR. Os promotores A e C do gene ESR1 e os promotores 0K e 0N do gene ESR2 foram investigados por análise de metilação dos dinucleotidos CpG usando bisulfite-PCR para análise com enzimas de restrição, ou para methylation specific PCR. Atendendo aos resultados promissores relacionados com a metilação do promotor do gene ESR1, complementamos o estudo com um método quantitativo por matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) suportado pelo software Epityper para a medição da metilação nos promotores A e C. Fez-se a avaliação da estabilidade do mRNA nas linhas celulares de cancro da mama MCF-7 e MDA-MB-231 tratadas com actinomicina D. Baixos níveis do transcrito ESR1_C associaram-se a uma melhor sobrevivência global (p = 0.017). Níveis elevados do transcrito ESR1_C associaram-se a uma resposta inferior ao tamoxifeno (HR = 2.48; CI 95% 1.24-4.99), um efeito mais pronunciado em doentes com tumores de fenótipo ERα/PgR duplamente positivo (HR = 3.41; CI 95% 1.45-8.04). A isoforma ESR1_C mostrou ter uma semi-vida prolongada, bem como uma estrutura secundária da região 5’UTR muito mais relaxada em comparação com a isoforma ESR1_A. A análise por Western-blot mostrou que ao nível da 21 proteína, a selectividade de promotores é indistinguivel. Não se detectou qualquer correlação entre os níveis das isoformas do gene ESR2 ou entre a metilação dos promotores do gene ESR2, e a detecção da proteína ERß. A metilação do promotor C do gene ESR1, e não do promotor A, foi responsável pela perda do receptor ERα. Estes resultados sugerem que os níveis do transcrito ESR1_C sejam usados como um novo potencial marcador para o prognóstico e predição de resposta ao tratamento com tamoxifeno em doentes com cancro da mama. Abstract: The decision of endocrine breast cancer treatment relies on ERα IHC-based assessment. However, ER positivity does not predict response in all cases in part due to IHC methodological limitations. We investigated whether ESR1 and ESR2 gene expression and respective promoter methylation may be related to non-favorable outcome of a proportion of tamoxifen treated patients as well as to ERα and ERß loss. Formalin-fixed paraffin-embedded breast cancer samples from 211 patients diagnosed between 1988 and 2004 were submitted to IHC-based ERα and ERß protein determination. ESR1 whole mRNA and promoter C specific transcript levels, as well as ESR2_ß1, ESR2_ß2/cx, and ESR2_ß5 transcripts were assessed by real-time PCR. ESR1 promoters A and C, and ESR2 promoters 0N and 0K were investigated by CpG methylation analysis using bisulfite-PCR for restriction analysis, or methylation specific PCR. Due to the promising results related to ESR1 promoter methylation, we have used a quantification method by matrixassisted laser desorption/ionization time-of-flight mass spectrometry (MALDITOF MS) together with Epityper software to measure methylation at promoters A and C. mRNA stability was assessed in actinomycin D treated MCF-7 and MDA-MB-231 cells. ERα protein was quantified using transiently transfected breast cancer cells. Low ESR1_C transcript levels were associated with better overall survival (p = 0.017). High levels of ESR1_C transcript were associated with non-favorable response in tamoxifen treated patients (HR = 2.48; CI 95% 1.24-4.99), an effect that was more pronounced in patients with ERα/PgR double-positive tumors (HR = 3.41; CI 95% 1.45-8.04). The ESR1_C isoform had a prolonged mRNA half-life and a more relaxed 5’UTR structure compared to ESR1_A isoform. Western-blot analysis showed that at protein level, the promoter selectivity is undistinguishable. There was no correlation between levels of ESR2 isoforms or ESR2 promoter methylation and ERß protein staining. ESR1 promoter C CpG methylation and not promoter A was responsible for ERα loss. We propose ESR1_C levels as a putative novel marker for breast cancer prognosis and prediction of tamoxifen response.

Risk factors associated with the professional performance of civil servants with impairment

Apresentação realizada na "8th Conference of European Academy of Occupational Health Psychology", que decorreu em Valência, Espanha, de 12 a 14 novembro de 2008

Prognostic modelling of breast cancer patients: a benchmark of predictive models with external validation

Dissertação apresentada para obtenção do Grau de Doutor em Engenharia Electrotécnica e de Computadores – Sistemas Digitais e Percepcionais pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Identification of factors and groups at risk of infection with Schistosoma mansoni: a strategy for the implementation of control measures?

A fourteen year schistosomiasis control program in Peri-Peri (Capim Branco, MG) reduced prevalence from 43.5 to 4.4%; incidence from 19.0 to 2.9%, the geometric mean of the number of eggs from 281 to 87 and the level of the hepatoesplenic form cases from 5.9 to 0.0%. In 1991, three years after the interruption of the program, the prevalence had risen to 19.6%. The district consists of Barbosa (a rural area) and Peri-Peri itself (an urban area). In 1991, the prevalence in the two areas was 28.4% and 16.0% respectively. A multivariate analysis of risk factors for schistosomiasis indicated the domestic agricultural activity with population attributive risk (PAR) of 29.82%, the distance (< 10 m) from home to water source (PAR = 25.93%) and weekly fishing (PAR = 17.21%) as being responsible for infections in the rural area. The recommended control measures for this area are non-manual irrigation and removal of homes to more than ten meters from irrigation ditches. In the urban area, it was observed that swimming at weekly intervals (PAR = 20.71%), daily domestic agricultural activity (PAR = 4.07%) and the absence of drinking water in the home (PAR=4.29%) were responsible for infections. Thus, in the urban area the recommended control measures are the substitution of manual irrigation with an irrigation method that avoids contact with water, the creation of leisure options of the population and the provision of a domestic water supply. The authors call attention to the need for the efficacy of multivariate analysis of risk factors to be evaluated for schistosomiasis prior to its large scale use as a indicator of the control measures to be implemented.

Anti-HCV related to HCV PCR and risk factors analysis in a blood donor population of Central Brazil

Data concerning HCV infection in Central Brazil are rare. Upon testing 2,350 voluntary blood donors from this region, we found anti-HCV prevalence rates of 2.2% by a second generation ELISA and 1.4% after confirmation by a line immunoassay. Antibodies against core, NS4, and NS5 antigens of HCV were detected in 81.8%, 72.7%, and 57.5%, respectively, of the positive samples in the line immunoassay. HCV viremia was present in 76.6% of the anti-HCV-positive blood donors. A relation was observed between PCR positivity and serum reactivity in recognizing different HCV antigens in the line immunoassay. The majority of the positive donors had history of previous parenteral exposure. While the combination of ALT>50 IU/l and anti-HBc positivity do not appear to be good surrogate markers for HCV infection, the use of both ALT anti-HCV tests is indicated in the screening of Brazilian blood donors.

Bancroftian filariasis in two urban areas of Recife, Brasil: the role of individual risk factors

Bancroftian filariasis is spreading in towns of endemic areas as in Recife, northeastern Brazil, where it is a major public health problem. This paper deals with the prevalence of microfilaraemia and filarial disease in two urban areas of Recife, studying their association with individual characteristics and variables related to the exposure to the vectors. The parasitologic survey was performed through a "door-to-door" census and microfilaraemia was examined by the thick-drop technique using 45µl of peripheral blood collected between 20:00 and 24:00 o' clock. 2,863 individuals aged between 5 and 65 years were interviewed and submitted to clinical examination. Males aged between 15 and 44 years old presented the greatest risk of being microfilaraemic. Microfilaraemia was also significantly associated with no use of bednet to sleep. The risk of being microfilaraemic was greater among those who had lived in the studied areas for more than 5 years. The overall disease prevalence was 6.3%. Males presented the greatest risk of developing acute disease. The risk of developing chronic manifestations was also greater among males and increased with age. We found no association between time of residence, bednet use, microfilaraemia and acute and chronic disease. We may conclude that in endemic areas there are subgroups of individuals who has a higher risk of being microfilariae carriers due to different behaviours in relation to vector contact.

Risk factors and prevalence of antibodies against hepatitis A virus (HAV) in children from day-care centers, in Goiania, Brazil

A seroepidemiologic survey about hepatitis A virus (HAV) infection was carried out in a group comprising 310 children, ranging in age from 3 months to 9 years, from day-care centers, in Goiania, a middle sized city in the central region of Brazil. The biomarkers employed in the investigation of previous infection include total IgG and IgM anti-HAV antibodies, and for the detection of more recent infection, IgM anti-HAV antibodies were analyzed. The study was performed in 1991 and 1992. According to the results, 69.7% of the children presented total IgG/IgM anti-HAV antibodies, with 60% of the group in the age range of 1 to 3 years. Among 10 day-care centers analyzed, the prevalence of the biomarker IgM anti-HAV was 3.2%, with an uniform distribution of the cases in the group of children ranging in age from 1 to 4 years. Multi-variate analysis was performed to investigate the sociodemographic factors that could influence the results. It was verified that the risk for the infection increased with the length of the attendance in the day-care centers, i.e., the risk for children with attendance of one year or more was 4.7 times higher, when compared with children with one month attendance (CI 95% 2.3-9.9). According to the results, hepatitis A is an endemic infection in day-care centers in the study area. The length of attendance in the day-care settings was demonstrated to be a risk factor for the HAV infection. Such findings suggest that if hepatits A vaccination becomes available as a routine policy in our region, the target group should be children under one year. Moreover, those children should receive the vaccine before they start to attend the day-care centers.

Anemia de células falciformes na idade pediátrica : contribuição para o estudo das suas principais complicações e indicadores de prognóstico

RESMO: Introdução: A anemia de células falciformes doença hereditária, com repercussão multi-orgânica, tem grande variabilidade na sua expressão clínica. Daí o interesse do estudo de indicadores de prognóstico. A investigação realizada foi precedida de um resumo histórico incidindo sobre a compreensão de aspectos fundamentais da doença ao longo dos tempos. Na primeira parte do estudo e após revisão bibliográfica, foram referidos dados da fisiopatologia como base para os estudos que integram a presente dissertação. Abordou-se o estado da arte relativamente às complicações, aos indicadores de prognóstico e à terapêutica utilizada. Objectivos: Constituíram objectivos deste estudo realizado numa amostra populacional representativa: identificar as lesões a nível dos sistemas cardio-respiratório e nervoso central, avaliando-se as respectivas repercussões; avaliar a presença de indicadores de prognóstico entre as variáveis seleccionadas; estudar a eficácia e toxicidade da HU nos doentes com as formas graves da ACF. Para a prossecução destes objectivos foram delineados para além do estudo global três estudos específicos: Estudo 1- repercussão no sistema cardio-respiratório; Estudo 2- repercussão no sistema nervoso central; Estudo 3- terapêutica com hidroxiureia. Doentes e métodos: Procedeu-se a um estudo prospectivo e multi-institucional durante um período de três anos tendo-se seleccionado para a amostra, e de acordo com critérios pré-definidos, 30 doentes com ACF na fase estável da doença, com idades compreendidas entre os sete e os 18 anos, todos de origem africana à excepção de um caucasiano. O diagnóstico baseou-se em técnicas de electroforese e estudo molecular que definiu o genotipo da doença e a presença da delecção da -talassémia assim como os haplotipos da amostra populacional. Foram utilizadas diferentes metodologias para avaliar a existência de lesão pulmonar e cerebral. Através do estudo estatístico foram seleccionadas diversas variáveis como hipotéticos indicadores de prognóstico. Estudo 1. Para determinar a existência de lesão a nível pulmonar usaram-se duas metodologias diferentes, a avaliação da função pulmonar com estudo da saturação da Hb em O2 no sangue arterial e a tomografia computadorizada de alta resolução. Estudou-se também a possível disfunção cardíaca como repercussão da lesão pulmonar, através do ecocardiograma, e os indicadores de prognóstico com significado estatístico para a lesão encontrada. Estudo 2. O desenho deste estudo foi sobreponível ao anterior, mas com metodologia adequada para o SNC. Procedeu-se ao estudo das lesões cerebrais por meio de exames imagiológicos, (RMN-CE e DTC) e de testes psicológicos. Correlacionaram-se as três metodologias utilizadas e a importância de cada uma para a decisão de atitudes terapêuticas preventivas. Estudo 3. Consistiu num estudo aberto prospectivo não controlado com nove crianças e adolescentes com formas graves de ACF, com o objectivo de avaliar a eficácia da terapêutica com hidroxiureia, durante um período de 24 meses. Todos os doentes completaram no mínimo 15 meses de terapêutica, com uma dose final média de 194 mg/K/dia. Resultados globais: Durante o período anterior à investigação caracterizou-se a amostra populacional estudada quanto ao fenotipo genético, clínico e hematológico de acordo com os critérios utilizados por outros investigadores. Verificou-se: predomínio do haplotipo Bantu na forma homozigótica em 53% dos doentes; número total de EVO ≥3/ano em 87,5% dos doentes; crises de sequestração em 18,75%; dactilites no primeiro ano de vida em 31,2%; quadro de sépsis grave apenas num doente; crises de hiper-hemólise em 50%; e STA em 59,38% dos doentes. Quanto ao fenotipo hematológico evidenciaram-se como factores de risco reticulocitose (13,1x103/l) e hiperbilirrubinémia (2,5 mg/dl) e como factores de bom prognóstico a presença de delecção de um gene da -talassémia em 46,9% dos doentes e valor médio de Hb 8,1 g/dl. Resultados dos estudos parcelares: Estudo 1. Deste estudo infere-se que a DPR ligeira foi diagnosticada em 70% dos doentes, uma vez que as alterações da difusão não foram estatisticamente significativas, o estudo dos gases no sangue não evidenciaram resultados anormais e a TCAR evidenciou alterações em 43,3% dos doentes. Apenas num doente se verificou doença pulmonar obstrutiva relacionada com maior número da STA.O estudo da disfunção cardíaca encontrada em 86,7% dos doentes não reflecte a repercussão da DPR a nível cardíaco, podendo estar associada às alterações fisiopatológicas da própria anemia crónica. Encontraram-se indicadores de prognóstico hematológicos e clínicos. Entre os primeiros, valores de Hb ≥8,5 g/dl e de HbF ≥13% foram considerados indicadores de bom prognóstico para a lesão pulmonar. Em relação aos parâmetros clínicos, as STA não foram consideradas indicadoras de prognóstico para a DPR ao contrário do que se verificou com o número de EVO. Pela análise dos parâmetros genéticos e socio-económicos provou-se a ausência de relação estatisticamente significativa com lesão pulmonar. Estudo 2. Pela RMN-CE foram diagnosticados ES em 33,3% com uma localização preferencial na substância branca profunda em 26,6% dos doentes. Relativamente aos parâmetros hematológicos seleccionados, o valor médio da HbF 8,6% constituíu um indicador de bom prognóstico para o aparecimento de ES, enquanto o valor médio de leucócitos 12.39x103/μl foi considerado um indicador de mau prognóstico. No estudo do DTC apenas um doente apresentou aumento da velocidade do fluxo cerebral na ACM igual a 196 cm/segundos, associado a vasculopatia grave. Os testes psicológicos alterados em 80% dos doentes mostraram ser o método mais sensível para detectar alterações do neurodesenvolvimento, mas sem correlação com os ES em 10% dos doentes. Realça-se a baixa percentagem de DTC patológicos encontrados neste estudo em relação ao número elevado de ES e de testes psicológicos alterados, não se verificando concordância entre os três exames. Dos indicadores de prognóstico estudados a -talassémia foi considerada um factor de protecção para o coeficiente de inteligência da escala de Wechsler. Em relação a parâmetros clínicos estudados os doentes com maior número de EVO, tem em média valores inferiores nos testes psicológicos. Estudo 3. Neste estudo verificou-se que o valor médio da HbF aumentou significativamente de 7,0±4% para 13,7±5,3% (p=0,028) ao fim de 15 meses de terapêutica com hidroxiureia. Clinicamente todos os doentes responderam significativamente com uma redução de 80% no número de EVO, 69% no número de internamentos, 76% no número de dias de hospitalização e 67% no número de transfusões. Deste modo comprovou-se não só a eficácia desta terapêutica neste grupo pediátrico como também a falta de efeitos secundários significativos. Considera-se a necessidade de estudos mais prolongados e em grande séries, para com segurança se usar a HU antes que a lesão orgânica se estabeleça, portanto logo nos primeiros anos de vida. Conclusão: Na amostra populacional estudada foram evidenciadas lesões pulmonares e cerebrais na grande maioria dos doentes que condicionaram a sua qualidade de vida. Foram identificados indicadores de prognóstico que poderão eventualmente ditar medidas terapêuticas precoces com o objectivo de diminuir a morbilidade e a mortalidade neste grupo etário. Demonstrou-se que a terapêutica com a HU foi eficaz e bem tolerada----------ABSTRACT: Background: Sickle cell anemia (SCA), a hereditary disease characterized by pain and lifetime multi-organic lesion, is a challenge for all that work with carriers of this disease. The clinical expression variability of SCA is a constant reality and a problem to be solved in the current world of investigation, for which the knowledge of prognostic indicators responsible for the different aspects of clinical evolution diversity wiil be an added value. The study is preceded by a historical summary of the most important factors in the evolution of SCA, which are in themselves, an incentive for future research. In the first part of the study, after an extensive bibliographical revision, physiopathology data is referred to in general and specifically regarding the target organs, that constituted the base for the studies presented in the dissertation. The state of the art for the complications to be studied, the choice of prognostic indicators and the therapeutics application, were approached for the renewed interest in the theme. Aims: In regard to the investigation, the objective was to study the lesions in the most affected organs of a chosen pediatric group, to investigate prognostic indicators for lung and cerebral lesions and to evaluate the protective effect of hydroxyurea in children with severe outcomes. Patients and methods: A prospective and multi-institutional study was carried out during a three-year period, February 1998 to March 2001, with children and adolescents followed up at a Immunohematology Outpatient Clinic of Dona Estefânia's Hospital, Lisbon. Based in predefined criteria, 30 children with SCA were selected in a stable phase of the disease, aged from seven to 18 years old, all of whom were of African origin with exception of one who was Caucasian. The diagnosis was based on electrophoresis techniques and molecular study that allowed to define the genotype, the presence of deletional alpha-thalassemia as well as haplotypes in the population. Different methodologies were used to evaluate the existence of lung and cerebral lesion. Statistical study of the different variables selected the prognostic indicators. In Study 1, to determine the existence of lung lesion two different methodologies were used: pulmonar function study with arterial blood gases determination; and high resolution computerized tomography. Heart dysfunction as a repercussion of lung lesion was also studied through echocardiography, and prognostic indicators were statistically significant for lesions found. The design of Study 2 was similar to Study 1, but with the appropriate methodology for CNS. After neurological examination, which was normal in all patients (control group), cerebral lesions were studied with imagiologic exams (MRN-CE and TCD) and psychological tests. These three methodologies were correlated and the importance of each one in the decision of the therapeutic profilactic attitudes. Study 3 consisted of a controlled prospective open study in children with severe forms of SCA, with the aim of the evaluating therapeutic effectiveness of hydroxyurea, during a period of 24 months. Results: In the global overall study preceding the Studies 1,2 and 3, there were a prevalence of haplotype Bantu (53%) and other risk factors, namely the number of VOC (87,5%), sequestration crisis (18,75%), dactilytis in first year of life(31,2%), hyperhemolysis crisis (50%) and ATC in more than half of the patients (59,38%). This group of bad prognostic indicators, associated with the population of the lower class according to the Graffar scale, demonstrates the importance of primary health care services, information provided to the children and their relatives, as well as the interest in prophylactic therapeutics, specific screening and prenatal diagnosis. Study 1. It was evident from this study that slight RPD was diagnosed in 70% of the patients, because alterations of the diffusion had no statistical significance and arterial blood gases determinations were normal. Only one patient had restrictive lung disease related with numerous ACS. However ACS was not considered a prognostic indicator for RPD, contrary to the number of EVO. HRTC revealed discreet fibrotic lines that could be related with slight RPD, but the lack of correlation of these two exams (33%) supports the value of lung function tests for precocious diagnosis of RPD. Heart dysfunction was found in 86,7% of patients, does not reflect the repercussion of RPD, but with the physiopathology of chronic anemia. Hematologic and clinical prognostic indicators were found. Good prognostic indicators for the non-evolution of RPD with average Hb values of ≥ 8,5 g/dl and average HbF values of ≥13%, respectively. The genetic and social-economic factors had no statistical significance; nevertheless, they were more prevalent among Bantu haplotype (53,3%) in patients with RPD. Study 2. RMN-CE detected SI in 33,3% of the patients, with preferential location in deep white substance in 26,6% and in front lobe in 20%. This distribution can be related to structural aspects of the brain and with the high sensibility of this organ to hypoxia. From the hematological parameters selected, average HbF value 8,6% and average leucocyte count 12.39x103/μl were prognostic indicators with different meaning to SI. The increase in the total bilirubin related to hyperhemolysis clinically explains the genesis of SI In the TCD study, only one patient had increased cerebral flow speed >196 cm/sec in CMA, which corresponded to serious vasculopathy in AngioMR. This patient never present previously neurological symptoms and had several hyperhemolysis crisis and VOC as risk factors. Low percentage of pathological TCD in this study, in relation to the high number of SI and altered tests, although without correlation among the three exams, is probably attributed to factors related to the methodology, aspects of cerebral physiopathology or perhaps a sign of good prognostic if the duration of study had not been so short. TCD should be used as a screening method in the age groups with higher risk of AVC and should never be considered separately in prophylactic therapeutics indication. Psychological tests were the most sensitive method to detect neurodevelopment impairment; in 80% of patients the neuropsychologics tests were altered, but without correlation with SI (10%). Since SI can become evident during the first two years of life and develop with time, the first psychological tests should be carried out between 3 and 5 years of age to timely be referred to special education and stimulation programs. Prognostic indicators to psychological tests were also found: alpha-thalassemia was found to be a protection factor of the IQ, just as other hematologic factors (hematocrit, MGCV and erythrocytes count). In relation to clinical parameters, although without statistical significance, patients with larger number of VOC had average lower scores versus the average in tests, except in TP. Results from different studies were conclusive as to the type of lesion found and the importance of prognostic indicators. Study 3. All the patients completed a minimum of 15 months therapeutic treatment with the final average daily dose of 19±4 mg/kg/day. The average value of the fetal hemoglobin increased significantly from 7,0±3,9% to 13,7±5,3% (p=0.028). The HbF average values increased from 6% to 15% after 15 months of therapeutic treatment. Clinically there was a reduction of 80% in the number of VOE , 69% in the number of hospitalization, 76% in the number of days of hospitalization and 67% in the number of transfusions. Once again the effectiveness of this treatment in this pediatric group, as well as the lack of any significant secondary effects, was evident. The study confirms the need for further detailed research in order to safely effect the appropriate treatment prior to the development of organic lesions, which ideally should be in the first year of life. Conclusions: These results allow us to clarify the importance of either pulmonary lesions or either nervous central system impairment among patients, children and adolescents, with sickle cell anemia. These lesions were demonstrated in most of the patients studied compromising their quality of life and the mortality. The treatment with HU is proved to be effective and having low toxicity.

Water-contact patterns and risk factors for Schistosoma mansoni infection in a rural village of Northeast Brazil

Schistosomiasis mansoni in the Serrano village, municipality of Cururupu, state of Maranhão, Brazil, is a widely spread disease. The PECE (Program for the Control of Schistosomiasis), undertaken since 1979 has reduced the prevalence of S. mansoni infection and the hepatosplenic form of the disease. Nevertheless piped water is available in 84% of the households, prevalence remains above 20%. In order to identify other risk factors responsible for the persistence of high prevalence levels, a cross-sectional survey was carried out in a systematic sample of 294 people of varying ages. Socioeconomic, environmental and demographic variables, and water contact patterns were investigated. Fecal samples were collected and analyzed by the Kato-Katz technique. Prevalence of S. mansoni infection was 24.1%, higher among males (35.5%) and between 10-19 years of age (36.6%). The risk factors identified in the univariable analysis were water contacts for vegetable extraction (Risk Ratio - RR = 2.92), crossing streams (RR = 2.55), bathing (RR = 2.35), fishing (RR = 2.19), hunting (RR = 2.17), cattle breeding (RR = 2.04), manioc culture (RR = 1.90) and leisure (RR = 1.56). After controlling for confounding variables by proportional hazards model the risks remained higher for males, vegetable extraction, bathing in rivers and water contact in rivers or in periodically inundated parts of riverine woodland (swamplands)