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Showing papers by "Oswaldo Cruz Foundation published in 2005"


Journal ArticleDOI
Najib M. El-Sayed1, Peter J. Myler2, Peter J. Myler3, Daniella Castanheira Bartholomeu4, Daniel Nilsson5, Gautam Aggarwal3, Anh-Nhi Tran5, Elodie Ghedin1, Elizabeth A. Worthey3, Arthur L. Delcher, Gaëlle Blandin4, Scott J. Westenberger6, Elisabet Caler4, Gustavo C. Cerqueira7, Carole Branche5, Brian J. Haas4, Atashi Anupama3, Erik Arner5, Lena Åslund8, Philip Attipoe3, Esteban J. Bontempi5, Frédéric Bringaud9, Peter Burton10, Eithon Cadag3, David A. Campbell6, Mark Carrington11, Jonathan Crabtree4, Hamid Darban5, José Franco da Silveira12, Pieter J. de Jong13, Kimberly Edwards5, Paul T. Englund14, Gholam Fazelina3, Tamara Feldblyum4, Marcela Ferella5, Alberto C.C. Frasch15, Keith Gull16, David Horn17, Lihua Hou4, Yiting Huang3, Ellen Kindlund5, Michele M. Klingbeil18, Sindy Kluge5, Hean Koo4, Daniela R. Lacerda19, Mariano J. Levin20, Hernan Lorenzi20, Tin Louie3, Carlos Renato Machado7, Richard McCulloch10, Alan McKenna5, Yumi Mizuno5, Jeremy C. Mottram10, Siri Nelson3, Stephen Ochaya5, Kazutoyo Osoegawa13, Grace Pai4, Marilyn Parsons2, Marilyn Parsons3, Martin Pentony3, Ulf Pettersson8, Mihai Pop4, José Luis Ramírez21, Joel Rinta3, Laura Robertson3, Steven L. Salzberg, Daniel O. Sánchez15, Amber Seyler3, Reuben Sunil Kumar Sharma11, Jyoti Shetty4, Anjana J. Simpson4, Ellen Sisk3, Martti T. Tammi22, Martti T. Tammi5, Rick L. Tarleton23, Santuza M. R. Teixeira7, Susan Van Aken4, Christy Vogt3, Pauline N. Ward10, Bill Wickstead16, Jennifer R. Wortman4, Owen White4, Claire M. Fraser4, Kenneth Stuart2, Kenneth Stuart3, Björn Andersson5 
15 Jul 2005-Science
TL;DR: Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.
Abstract: Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.

1,349 citations


Journal ArticleDOI
TL;DR: It is concluded that sexual difficulties are relatively common among mature adults throughout the world, and tend to be more associated with physical health and aging among men than women.
Abstract: The Global Study of Sexual Attitudes and Behaviors (GSSAB) is an international survey of various aspects of sex and relationships among adults aged 40–80 y. An analysis of GSSAB data was performed to estimate the prevalence and correlates of sexual problems in 13 882 women and 13 618 men from 29 countries. The overall response rate was modest; however, the estimates of prevalence of sexual problems are comparable with published values. Several factors consistently elevated the likelihood of sexual problems. Age was an important correlate of lubrication difficulties among women and of several sexual problems, including a lack of interest in sex, the inability to reach orgasm, and erectile difficulties among men. We conclude that sexual difficulties are relatively common among mature adults throughout the world. Sexual problems tend to be more associated with physical health and aging among men than women.

1,230 citations


Journal ArticleDOI
TL;DR: These findings suggest that larger, more mature infants are developing severe ROP in countries with low/moderate levels of development compared with highly developed countries.
Abstract: OBJECTIVE: Retinopathy of prematurity (ROP) is a potentially avoidable cause of blindness in children. The proportion of blindness as a result of ROP varies greatly among countries depending on their level of development, being influenced by the availability of neonatal care, neonatal outcomes, and whether effective screening and treatment programs are in place. The objective of this study was to compare characteristics of premature infants who developed severe ROP between 1996 and 2002 in highly developed countries with less developed countries. METHODS: This was an observational study. A questionnaire was completed by ophthalmologists in countries with low, moderate, and high development rankings (3 highly developed countries and from 10 less well-developed countries) who screen for ROP in which they supplied birth weights and gestational ages (GAs) of infants who were treated for threshold ROP or identified with more advanced stages of the disease. Birth weights and GAs of infants with severe ROP were measured. RESULTS: The mean birth weights of infants from highly developed countries ranged from 737 to 763 g compared with values ranging from 903 to 1527 g in less developed countries. Mean GAs of infants from highly developed countries ranged from 25.3 to 25.6 weeks compared with 26.3 to 33.5 weeks in less developed countries. A total of 13.0% of 1091 infants from poorly developed countries exceeded United Kingdom screening criteria; 3.6% exceeded a criteria of <34 weeks' GA and/or <1750 g birth weight. CONCLUSIONS: These findings suggest that larger, more mature infants are developing severe ROP in countries with low/moderate levels of development compared with highly developed countries. ROP screening programs need to use criteria that are appropriate for their local population.

649 citations


Journal ArticleDOI
TL;DR: A previously unappreciated role for TLR9 is revealed in the host response to M. tuberculosis and TLR collaboration in host resistance to a major human pathogen is illustrated.
Abstract: To investigate the role of Toll-like receptor (TLR)9 in the immune response to mycobacteria as well as its cooperation with TLR2, a receptor known to be triggered by several major mycobacterial ligands, we analyzed the resistance of TLR9 − / − as well as TLR2/9 double knockout mice to aerosol infection with Mycobacterium tuberculosis . Infected TLR9 − / − but not TLR2 − / − mice displayed defective mycobacteria-induced interleukin (IL)-12p40 and interferon (IFN)- γ responses in vivo, but in common with TLR2 − / − animals, the TLR9 − / − mice exhibited only minor reductions in acute resistance to low dose pathogen challenge. When compared with either of the single TLR-deficient animals, TLR2/9 − / − mice displayed markedly enhanced susceptibility to infection in association with combined defects in proinflammatory cytokine production in vitro, IFN- γ recall responses ex vivo, and altered pulmonary pathology. Cooperation between TLR9 and TLR2 was also evident at the level of the in vitro response to live M. tuberculosis , where dendritic cells and macrophages from TLR2/9 − / − mice exhibited a greater defect in IL-12 response than the equivalent cell populations from single TLR9-deficient animals. These findings reveal a previously unappreciated role for TLR9 in the host response to M. tuberculosis and illustrate TLR collaboration in host resistance to a major human pathogen.

607 citations


Journal ArticleDOI
TL;DR: An historical review is given of American visceral leishmaniasis (AVL), with particular reference to the eco-epidemiology of the disease in Brazil, and the presence of such an enzootic in a variety of native animals will render the total eradication of AVL unlikely.
Abstract: An historical review is given of American visceral leishmaniasis (AVL), with particular reference to the eco-epidemiology of the disease in Brazil. Following the first records of AVL in this country, in 1934, the sandfly Lutzomyia longipalpis (Lutz and Neiva, 1912) was incriminated as the principal vector. It is now generally accepted, however, that there exist a number of cryptic species under the name of Lu. longipalpis s.l. and that variations in the quantity of the vasodilatory peptide maxadilan in the saliva of flies from different populations of Lu. longipalpis s.l., may account for the variable clinical manifestations of AVL seen in different geographic regions. Distribution of AVL has been shown to extend throughout most of South and Central America, with the domestic dog serving as the principal reservoir of infection for man. However, while one hypothesis suggests that the causative parasite is Leishmania infantum, imported from Europe with the Portuguese and Spanish colonists, the demonstration of a high rate of benign, inapparent infection in foxes in Amazonian Brazil raised an opposing suggestion that the parasite is indigenous to the Americas. Recent reports of similar infections in native marsupials, and possibly rodents, tend to support this view, particularly as Lu. longipalpis is primordially a silvatic sandfly. Although effective control measures in foci of the disease will diminish the number of canine and human infections, the presence of such an enzootic in a variety of native animals will render the total eradication of AVL unlikely.

450 citations


Journal ArticleDOI
TL;DR: Overall, men and women show similar help‐seeking behaviours for sexual problems in this population, and men and girls aged 40–80 years are more likely to seek medical help for these problems.
Abstract: The Global Study of Sexual Attitudes and Behaviors (GSSAB) investigated various aspects of sex and relationships among 27,500 men and women aged 40-80 years. Here, we report help-seeking behaviours for sexual problems in this population. A questionnaire was administered using the accepted survey method in each country. Although almost half of all sexually active respondents had experienced at least one sexual problem, less than 19% of them (18.0% of men and 18.8% of women) had attempted to seek medical help for their problem(s). The most frequent action taken by men and women was to talk to their partner (39%). Only 9% of men and women had been asked about their sexual health by a doctor in a routine visit during the past 3 years. Although sexual problems are highly prevalent, few men and women seek medical help for these problems. Overall, men and women show similar help-seeking behaviours.

319 citations


Journal ArticleDOI
TL;DR: Good evidence is found for a high construct validity of the Medical Outcomes Study's social support scale adapted to Portuguese, when utilized in a cohort study among non-faculty civil servants at a university in Rio de Janeiro, Brazil, supporting its use in future analyses in the Pró-Saúde Study and in similar population groups.
Abstract: This paper evaluates the construct validity of the Medical Outcomes Study's social support scale adapted to Portuguese, when utilized in a cohort study among non-faculty civil servants at a university in Rio de Janeiro, Brazil (Pro-Saude Study). Baseline data were obtained in 1999, when 4,030 participants (92.0% of those eligible) completed a multidimensional self-administered questionnaire at the workplace. From the original scale's five social support dimensions, factor analysis of the data extracted only three dimensions: positive social interaction/affective support; emotional/information support; and material support. We estimated associations between social support dimensions and socio-demographic, health, and well being-related characteristics. We confirmed the hypotheses that less isolated individuals, those with better self-rated health, those who reported more participation in group activities, and those with no evidence of common mental disorders reported better perception of social support. In conclusion, we found good evidence for a high construct validity of this scale, supporting its use in future analyses in the Pro-Saude Study and in similar population groups.

287 citations


Journal ArticleDOI
TL;DR: In this article, a visao compreensiva da complexidade dos fatores de risco and de protecao for o uso de drogas na adolescencia is presented.
Abstract: Este artigo apresenta uma visao compreensiva da complexidade dos fatores de risco e de protecao para o uso de drogas na adolescencia. Discorre sobre a interdependencia dos diversos contextos - individual, familiar, escolar, grupo de pares, midiatico e comunidade de convivencia - propicios tanto ao risco quanto a protecao ao uso das drogas licitas e ilicitas, fornecendo, por ultimo, algumas estrategias de prevencao.

269 citations


Journal ArticleDOI
TL;DR: The authors present a tematica "homens e saude" como questao contemporânea da Saude Coletiva and produto da interface entre as ciencias humanas e a saude: o carater social do adoecimento; a perspectiva de genero como forma particular da relacao saude-sociedade; and a promocao da saude como conceituacao positiva.
Abstract: Apresenta-se a tematica "homens e saude" como questao contemporânea da Saude Coletiva e produto da interface entre as ciencias humanas e a saude: o carater social do adoecimento; a perspectiva de genero como forma particular da relacao saude-sociedade; e a promocao da saude como conceituacao positiva Elabora-se a tematica em torno de tres eixos de aproximacao, sob a perspectiva dos exercicios das masculinidades: saude sexual e reprodutiva; violencia e genero e morbi-mortalidade em homens. Sao apontadas as contribuicoes que estes eixos produzem como esforco empirico para realizar a categoria genero, ao tempo em que revelam novas problematicas para a area de saude: a paternidade, o exercicio interativo da sexualidade, a violencia interpessoal no âmbito da vida privada, a hiper-masculinidade na violencia entre homens, o cuidado de si e o cuidar em saude para os homens. Estas contribuicoes permitirao nao apenas inserir as masculinidades como questao de saude, mas renovar as formas de tratamento de homens e mulheres no campo da saude.

245 citations


Journal ArticleDOI
TL;DR: The aggregate data suggest that point mutations in these candidate genes are likely to contribute to 6% of isolated clefts, particularly those with more severe phenotypes (bilateral cleft of the lip with cleft palate), and the linkage disequilibrium data support a larger, as yet unspecified, role for variants in or near MSX2, JAG2, and SKI.
Abstract: Nonsyndromic or isolated cleft lip with or without cleft palate (CL/P) occurs in wide geographic distribution with an average birth prevalence of 1/700. We used direct sequencing as an approach to study candidate genes for CL/P. We report here the results of sequencing on 20 candidate genes for clefts in 184 cases with CL/P selected with an emphasis on severity and positive family history. Genes were selected based on expression patterns, animal models, and/or role in known human clefting syndromes. For seven genes with identified coding mutations that are potentially etiologic, we performed linkage disequilibrium studies as well in 501 family triads (affected child/mother/father). The recently reported MSX1 P147Q mutation was also studied in an additional 1,098 cleft cases. Selected missense mutations were screened in 1,064 controls from unrelated individuals on the Centre d'Etude du Polymorphisme Humain (CEPH) diversity cell line panel. Our aggregate data suggest that point mutations in these candidate genes are likely to contribute to 6% of isolated clefts, particularly those with more severe phenotypes (bilateral cleft of the lip with cleft palate). Additional cases, possibly due to microdeletions or isodisomy, were also detected and may contribute to clefts as well. Sequence analysis alone suggests that point mutations in FOXE1, GLI2, JAG2, LHX8, MSX1, MSX2, SATB2, SKI, SPRY2, and TBX10 may be rare causes of isolated cleft lip with or without cleft palate, and the linkage disequilibrium data support a larger, as yet unspecified, role for variants in or near MSX2, JAG2, and SKI. This study also illustrates the need to test large numbers of controls to distinguish rare polymorphic variants and prioritize functional studies for rare point mutations.

239 citations


Journal ArticleDOI
TL;DR: It is demonstrated that treatment with benznidazole in the chronic phase of infection prevents the development of severe chronic cardiomyopathy, despite the lack of complete parasite eradication.
Abstract: Chagas' disease, caused by Trypanosoma cruzi infection, is one of the main causes of death due to heart failure in Latin American countries. Benznidazole, the chemotherapeutic agent most often used for the treatment of chagasic patients, is highly toxic and has limited efficacy, especially in the chronic phase of the disease. In the present study we used a mouse model of chronic Chagas' disease to investigate the effects of benznidazole treatment during the chronic phase on disease progression. The hearts of benznidazole-treated mice had decreased parasitism and myocarditis compared to the hearts of untreated chagasic mice. Both groups of Trypanosoma cruzi-infected mice had significant alterations in their electrocardiograms compared to those of the healthy mice. However, untreated mice had significantly higher cardiac conduction disturbances than benznidazole-treated mice, including intraventricular conduction disturbances, atrioventricular blocks, and extrasystoles. The levels of antibodies against T. cruzi antigens (epimastigote extract, P2beta, and trans-sialidase) as well as antibodies against peptides of the second extracellular loops of beta1-adrenergic and M2-muscarinic cardiac receptors were also lower in the sera from benznidazole-treated mice than in the sera from untreated mice. These results demonstrate that treatment with benznidazole in the chronic phase of infection prevents the development of severe chronic cardiomyopathy, despite the lack of complete parasite eradication. In addition, our data highlight the role of parasite persistence in the development of chronic Chagas' disease and reinforce the importance of T. cruzi elimination in order to decrease or prevent the development of severe chagasic cardiomyopathy.

Journal ArticleDOI
TL;DR: The cross-cultural adaptation to Portuguese and the psychometric evaluation of the resilience scale developed by Wagnild & Young showed good results in the semantic equivalence for: general meaning and referential meaning and there was an inverse correlation with the scale that evaluates psychological violence.
Abstract: This study describes the cross-cultural adaptation to Portuguese and the psychometric evaluation of the resilience scale developed by Wagnild & Young. The scale was adapted for a sample of students from public schools in Sao Goncalo, Rio de Janeiro, Brazil. Data from the pilot study (203 students interviewed at two points in time) and from the entire study (977) are presented. The cross-cultural adaptation showed good results in the semantic equivalence for: general meaning (above 90.0%) and referential meaning (above 85.0%). Chronbach alpha was 0.85 in the pilot study and 0.80 in the total sample. Kappa between the two points in time was regular and moderate, and the intraclass correlation coefficient was 0.746 (p = 0.000). Factorial analysis indicated three non-homogeneous factors. Construct validity demonstrated direct and significant correlation with self-esteem, family supervision, life satisfaction, and social support. There was an inverse correlation with the scale that evaluates psychological violence.

Journal ArticleDOI
TL;DR: It is believed that the microbiota present in the midgut of vector insects could have important roles as determinants of parasite survival and development in insect vector hosts and, therefore, contribute to the modulation of vector competence for many important diseases.


Journal ArticleDOI
TL;DR: In this paper, the incorporation of Brazilian elemi, a highly hydrophobic resinous exudate of the botanical family Burseraceae, into gelatin films, using a blend of stearic and palmitic acids to dissolve the elemi and subsequent emulsification of the filmogenic solution using triacetin as plasticizer.

Journal ArticleDOI
15 Jul 2005-Science
TL;DR: A complementary and increasingly important means to improve health equity: the growing ability of some developing countries to undertake health innovation is highlighted.
Abstract: Gross inequities in disease burden between developed and developing countries are now the subject of intense global attention. Public and private donors have marshaled resources and created organizational structures to accelerate the development of new health products and to procure and distribute drugs and vaccines for the poor. Despite these encouraging efforts directed primarily from and funded by industrialized countries, sufficiency and sustainability remain enormous challenges because of the sheer magnitude of the problem. Here we highlight a complementary and increasingly important means to improve health equity: the growing ability of some developing countries to undertake health innovation.

Journal ArticleDOI
TL;DR: Verificaram-se dois niveis de discriminacao, a educacional e a racial, that perpassam a esfera da atencao oferecida pelos servicos de saude a populacao de puerperas do Municipio do Rio de Janeiro.
Abstract: OBJETIVO: Analisar as desigualdades sociais e no acesso e utilizacao dos servicos de saude em relacao a cor da pele em amostra representativa de puerperas que demandaram atencao hospitalar ao parto. METODOS: Trata-se de estudo transversal, realizado no Municipio do Rio de Janeiro, no qual foram amostradas 9.633 puerperas, sendo 5.002 brancas (51,9%), 2.796 pardas (29,0%) e 1.835 negras (19,0%), oriundas de maternidades publicas, conveniadas com o Sistema Unico de Saude e particulares no periodo de 1999 a 2001. Os dados foram coletados de prontuarios medicos e por entrevistas com as maes no pos-parto imediato, aplicando questionarios padronizados. Foram utilizados os testes de chi² para analisar a homogeneidade das proporcoes e t de Student para comparacao de medias. A analise foi estratificada segundo o grau de instrucao materna. RESULTADOS: Observou-se persistente situacao desfavoravel das mulheres de pele preta e parda em relacao as brancas. Nas mulheres pretas e pardas sao maiores as proporcoes de puerperas adolescentes, com baixa escolaridade, sem trabalho remunerado e vivendo sem companheiro. Sofrer agressao fisica, fumar, tentar interromper a gravidez e peregrinar em busca de atencao medica foram mais frequentes nas negras seguidas das pardas e das brancas com baixa escolaridade. O grupo de elevado nivel de escolaridade tem melhores indicadores, mas repete o mesmo padrao. Esse gradiente se mantem, em sentido inverso, quanto a satisfacao com a assistencia prestada no pre-natal e no parto. Constata-se a existencia de duas formas de discriminacao, por nivel educacional e cor da pele. CONCLUSOES: Verificaram-se dois niveis de discriminacao, a educacional e a racial, que perpassam a esfera da atencao oferecida pelos servicos de saude a populacao de puerperas do Municipio do Rio de Janeiro.

Journal ArticleDOI
TL;DR: Results obtained suggest that this technique could be applied as a rapid diagnostic tool in clinical samples in which arbovirus infection is suspected and differential diagnosis is required, avoiding the need to test specimens by separate PCR methods.
Abstract: A new approach was developed for the rapid detection and identification of Brazilian alphaviruses and flaviviruses. The methodology involves the genus-specific detection of Alphavirus and Flavivirus by a duplex reverse transcription-PCR (D-RT-PCR), followed by multiplex nested PCR (M-N-PCR) or nested PCR (N-PCR) assays for species-specific identification. By this protocol, 25 arboviruses were specifically detected and identified. Detection levels between 101.3 and 103.5 50% tissue culture infective doses (TCID50)/ml of Flavivirus and Alphavirus strains were achieved by D-RT-PCR, and levels of <1 TCID50/ml were achieved by M-N-PCR assays. To assess the suitability and clinical application of this methodology, a total of 101 human or animal stored samples were analyzed. Results obtained suggest that this technique could be applied as a rapid diagnostic tool in clinical samples in which arbovirus infection is suspected and differential diagnosis is required, avoiding the need to test specimens by separate PCR methods.


Journal ArticleDOI
TL;DR: It is demonstrated that predominant CD4+ T cell epitopes in persons with resolved HCV infection are preferentially located in the nonstructural proteins and are immunogenic in the context of multiple class II molecules.
Abstract: A vigorous hepatitis C virus (HCV)-specific Th cell response is regarded as essential to the immunological control of HCV viremia. The aim of this study was to comprehensively define the breadth and specificity of dominant HCV-specific CD4(+) T cell epitopes in large cohorts of subjects with chronic and spontaneously resolved HCV viremia. Following in vitro stimulation of PBMC, HCV-specific cell cultures from each subject were screened with an overlapping panel of synthetic 20-mer peptides spanning the entire HCV polyprotein. Of 22 subjects who spontaneously controlled HCV viremia, all recognized at least one of a group of six epitopes situated within the nonstructural (NS) proteins NS3, NS4, and NS5, each of which was detected by >30% of subjects, but most subjects recognized additional, more heterogeneous specificities. In contrast, none of the most frequently targeted epitopes was detected by >5% of persons with chronic infection. The most frequently recognized peptides showed promiscuous binding to multiple HLA-DR molecules in in vitro binding assays and were restricted by different HLA-DR molecules in functional assays in different persons. These data demonstrate that predominant CD4(+) T cell epitopes in persons with resolved HCV infection are preferentially located in the nonstructural proteins and are immunogenic in the context of multiple class II molecules. This comprehensive characterization of CD4(+) T cell epitopes in resolved HCV infection provides important information to facilitate studies of immunopathogenesis and HCV vaccine design and evaluation.

Journal ArticleDOI
01 Sep 2005-Toxicon
TL;DR: The pure compound potentiated the ability of the commercial equine polyvalent antivenom in neutralizing lethal and myotoxic effects of the crude venom and of isolated PLA2s in experimental models.

Journal ArticleDOI
TL;DR: In this article, the authors discuss a discussao dos conceitos de satisfacao do usuario, responsividade, humanizacao, and direitos do paciente, bem como sua pertinencia in pesquisas de avaliacao de servicos e sistemas de saude.
Abstract: O artigo faz uma discussao dos conceitos de "satisfacao do usuario", "responsividade", "humanizacao" e "direitos do paciente". Ressaltam-se suas convergencias e diferencas, bem como sua pertinencia nas pesquisas de avaliacao de servicos e sistemas de saude. Satisfacao e responsividade sao analisados como conceitos operacionais que incorporam a visao do usuario; humanizacao e direitos do paciente referem-se a principios normativos que orientam politicas e programas. Enquanto as pesquisas de satisfacao deram destaque ao lugar dos pacientes nos servicos e sistemas de saude, o conceito de responsividade fortaleceu sua posicao, dando ao paciente o status de um individuo/cidadao, ou seja, de um sujeito de direitos validos universalmente. Esse arcabouco conceitual e metodologico e parte de um paradigma de direitos aplicado tambem na area da avaliacao da qualidade e da assistencia a saude.

Journal ArticleDOI
TL;DR: The surfaceomics approach is particularly amenable to protein expression profiling using small amounts of sample (<107 cells) offering the potential to analyze bacterial surface expression during infection.
Abstract: The identification of the subset of outer membrane proteins exposed on the surface of a bacterial cell (the surfaceome) is critical to understanding the interactions of bacteria with their environments and greatly narrows the search for protective antigens of extracellular pathogens. The surfaceome of Leptospira was investigated by biotin labeling of viable leptospires, affinity capture of the biotinylated proteins, two-dimensional gel electrophoresis, and mass spectrometry (MS). The leptospiral surfaceome was found to be predominantly made up of a small number of already characterized proteins, being in order of relative abundance on the cell surface: LipL32 > LipL21 > LipL41. Of these proteins, only LipL32 had not been previously identified as surface exposed. LipL32 surface exposure was subsequently verified by three independent approaches: surface immunofluorescence, whole-cell enzyme-linked immunosorbent assay (ELISA), and immunoelectron microscopy. Three other proteins, Q8F8Q0 (a putative transmembrane outer membrane protein) and two proteins of 20 kDa and 55 kDa that could not be identified by MS, one of which demonstrated a high degree of labeling potentially representing an additional, as-yet-uncharacterized, surface-exposed protein. Minor labeling of p31(LipL45), GroEL, and FlaB1 was also observed. Expression of the surfaceome constituents remained unchanged under a range of conditions investigated, including temperature and the presence of serum or urine. Immunization of mice with affinity-captured surface components stimulated the production of antibodies that bound surface proteins from heterologous leptospiral strains. The surfaceomics approach is particularly amenable to protein expression profiling using small amounts of sample (<10(7) cells) offering the potential to analyze bacterial surface expression during infection.

Journal ArticleDOI
TL;DR: It is concluded that the birth prevalence rates for both spina bifida and anencephaly decreased as a result of folic acid fortification, without interference of decreasing secular trends.
Abstract: To verify whether the decreasing neural tube defects birth prevalence rates in Chile are due to folic acid fortification or to pre-existing decreasing trends, we performed a population survey using a network of Estudio Colaborativo Latino Americano de Malformaciones Congenitas (ECLAMC, Latin American Collaborative Study of Congenital Malformations) maternity hospitals in Chile, between the years 1982 and 2002. Within each maternity hospital, birth prevalence rates of spina bifida and anencephaly were calculated from two pre-fortification periods (1982-1989 and 1990-2000), and from one fortified period (2001-2002). There was no historical trend for spina bifida birth prevalence rates before folic acid fortification, and there was a 51% (minimum 27%, maximum 66%) decrease in the birth prevalence rates of this anomaly in the fortified period. The relative risks of spina bifida were homogeneous among hospitals in the two period comparisons. There was no historical trend for the birth prevalence of anencephaly comparing the two pre-fortified periods, but the relative risks were heterogeneous among hospitals in this comparison. There was a 42% (minimum 10%, maximum 63%) decrease in the birth prevalence rate of anencephaly in the fortified period as compared with the immediately pre-fortified period, with homogeneous relative risks among hospitals. Within the methodological constraints of this study we conclude that the birth prevalence rates for both spina bifida and anencephaly decreased as a result of folic acid fortification, without interference of decreasing secular trends.

Journal ArticleDOI
TL;DR: Support is provided for the development of an effective recombinant vaccine against hookworm infection in humans by examining the antibody responses of individuals from hookworm endemic areas of Brazil and China against the most abundant L3 secreted antigens, the ancylostoma secreted proteins, ASP‐1 and ASP‐2.
Abstract: The development of a vaccine would provide an important new tool for the control of human hookworm infection. On the basis of successful vaccination of laboratory animals with living irradiated, third-stage hookworm larvae (L3), we examined the antibody responses of individuals from hookworm endemic areas of Brazil and China against the most abundant L3 secreted antigens, the ancylostoma secreted proteins, ASP-1 and ASP-2. Logistic regression was used to investigate the effects of antibody isotype responses to ASPs on the risk of an individual harboring heavy hookworm infection. A significant protective association was observed between increasing anti-ASP-2 IgE levels and the risk of heavy hookworm infection. To confirm that ASP-2 is a protective antigen, laboratory dogs were immunized with recombinant ASP-2 formulated with the GlaxoSmithKline Adjuvant, AS03. Sera obtained from the immunized dogs exhibited high geometric mean antibody titers, immunoprecipitated native ASP-2 from L3 extracts and localized the site of ASP-2 expression to the glandular esophagus and body channels exiting to the cuticle. The sera also exhibited an increased ability to inhibit migration of L3 through tissue in vitro relative to sera from AS03-injected controls. Upon L3 challenge, the ASP-2 vaccinated dogs exhibited significant reductions in fecal egg counts and intestinal hookworm burden. These findings provide strong support for the development of an effective recombinant vaccine against hookworm infection in humans.

Journal ArticleDOI
TL;DR: The aim of this work is to discuss some representative applications of methods that deal with the analysis of spatial patterns of health events, analyzing advantages, disadvantages, and applicability of the proposed models in ecological and health services utilization studies.
Abstract: Studies in which spatial distribution and geographic information systems (GIS) play a central role are becoming more common in the public health literature. However, methods and software to implement such approaches still pose serious limitations, due to unfriendliness and lack of integration. Additionally, most researchers and public health professionals are not familiar with either the techniques or the software. The aim of this work, besides presenting a systematic review of spatial analysis in health, is to discuss some representative applications of methods that deal with the analysis of spatial patterns of health events, analyzing advantages, disadvantages, and applicability of the proposed models in ecological and health services utilization studies.

Journal ArticleDOI
TL;DR: A taxa media de mortalidade masculina per capitais for o Brasil e suas capitais, between 1991 and 2000, was reported to be 119,6/100.000, a 5 vezes higher taxa than a taxa for mulheres.
Abstract: Efetua-se uma reflexao sobre a condicao masculina diante da violencia, situando o tema no campo interdisciplinar da Saude Publica. Usam-se dados do Sistema de Informacao sobre Mortalidade e do Sistema de Autorizacao para Internacao Hospitalar referentes as causas externas para o Brasil e suas capitais, de 1991 a 2000. As populacoes usadas nas taxas foram estimadas pelo IBGE e disponibilizadas na home page do Datasus/MS. Destaca-se que os homens sao as maiores vitimas da violencia. A taxa media de mortalidade masculina por essas causas na decada foi de 119,6/100.000 habitantes, sendo 5 vezes maior que a taxa media observada para as mulheres (24/100.000 habitantes). Dos 15 aos 19 anos, os homens morrem 6.3 vezes mais que as mulheres; dos 20 aos 24 anos suas taxas sao 10.1 vezes maior que a das mulheres. Nos homicidios esse risco e de quase 12 obitos masculinos em relacao a cada morte feminina. Macapa e a capital com maior sobremortalidade masculina: 10,3 mortes masculinas para cada obito feminino. Enfatiza-se que o genero masculino ainda e fortemente configurado por praticas machistas e de risco e que essas praticas sao as mesmas que constituem os homens como maiores vitimas da violencia. No Brasil, essas questoes sao potencializadas pelas intensas desigualdades e outras condicoes adversas a cidadania.

Journal ArticleDOI
TL;DR: In this article, the incorporation of concepts from human geography in health practices, in light of two main authors: Milton Santos ("constitution of territory") and Anthony Giddens ("Constitution of society") is presented.
Abstract: Diagnoses of living conditions and health status, the constitutive elements for the reproduction of social life in various places, are listed and treated as contents disconnected from the territory. The recognition of social dynamics, habits, and customs is highly important for the determination of human health vulnerabilities, which originate in the interactions of social groups in given geographic spaces. The full use of the territory as a strategy for analyzing and intervening in health conditions presupposes the identification of geographic objects, their utilization by the population, and their importance for flows of persons and materials. It is thus necessary to develop methodologies for the recognition (both in the field and through secondary data) of objects and their forms, which are a condition for human action and existence. This article presents an approach to the incorporation of concepts from human geography in health practices, in light of two main authors: Milton Santos ("constitution of territory") and Anthony Giddens ("constitution of society").

Journal ArticleDOI
TL;DR: The results presented here represent the first molecular approach used to infer the natural infection index in both Lutzomyia spp.
Abstract: To identify naturally infected Lutzomyia spp. by Leishmania (Viannia) braziliensis, a PCR multiplex non-isotopic hybridisation assay was developed for the analysis of insect samples collected in distinct areas of the municipality of Rio de Janeiro (Brazil), from March to December 2003. Data from experimental infection indicate that the method can detect one individual infected insect out of ten. Wild sand flies were classified and grouped into pools of 10 specimens each, reaching a total of 40 female groups. Positive results were obtained with pools of Lu. intermedia (5/32) and Lu. migonei (3/5) collected in two areas from the district of Jacarepagua presenting recent cases of human and canine leishmaniasis. Considering eight infected groups (8/40) with at least one positive insect in each, it was possible to infer an infection rate of 2%. This technique permits the synchronous processing of a large number of samples, in order to investigate infection rates in sand fly populations and to identify potential insect vectors. The results presented here represent the first molecular approach used to infer the natural infection index in both Lutzomyia spp. and constitute essential data to the understanding of leishmaniasis ecoepidemiology in endemic areas from Rio de Janeiro.