Chagas disease

We herein describe the synthesis and characterization of nine new 1,3,4-thiadiazolium-2-phenylamine chlorides derived from natural piperine. We evaluate their toxic effects against the different evolutive forms of Trypanosoma cruzi, and the host cell (murine macrophages). The results obtained show that mesoionic hydrochloride MI possesses the best activity profile. Compound MI may be a prototype for use in the development of a new chemotherapeutic agent with high efficiency, which may be employed in the treatment of Chagas' disease.

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The biological behaviour of 23 Trypanosoma cruzi isolates in Swiss mice was compared. Nineteen isolates were obtained from patients in the acute phase of Chagas disease (13), sylvatic reservoir hosts (Didelphis marsupialis) (3), and triatomine bugs (Rhodnius robustus) (3) from four regions of the State of Amazonas (AM). Four isolates were obtained from chronic chagasic patients in the State of Paraná (PR): three autochthones, and one allochthone from the State of Minas Gerais. Only one isolate was unable to infect the mice. The AM and PR isolates showed the largest number of significant differences from each other. The former had lower mean values in the pre-patent (5.4 days) and patent (4.6 days) periods (PP), with the parasitaemia (Pmax) reaching a peak of 9.9 Â 10 4 blood trypomastigotes (BT)/mL of blood by the 7th day following inoculation. The AM isolates also had higher positivity to fresh-blood examination (FBE) (84.1%) compared to haemoculture (HC) (58.7%) and polymerase chain reaction (PCR) (33.3%), in addition to higher mortality (2.9%). The PR isolates had higher values for PP (18.5 days) and Pmax (99.9 Â 10 4 BT/mL) as well as higher positivity to FBE (87.2%), HC (100%), and PCR (83.3%). The correlations between the biological behaviour of the T. cruzi isolates and the clinical and epidemiological characteristics of Chagas disease are discussed.

Long chain fatty acids (LCFA) are needed as a source of metabolic energy, membrane biogenesis, second messengers, modulation of gene expression, and are associated with cell growth, differentiation, apoptosis and inflammatory processes. Lipid hydrolysis in the intestinal lumen releases great quantities of LCFA. Once inside the enterocyte, LCFA can be reversibly bound to two homologous proteins: Intestinal and Liver Fatty Acid Binding Proteins (I-and LFABP). Classical functions proposed are as cytosolic buffers and transporters of hydrophobic ligands, but new studies position them as key components for regulatory systems. The present work was conducted to evaluate FABP's specific roles in the lipid metabolism and cell biology of the enterocyte. For this purpose, we obtained a cellular model of Caco-2 cells with ablated expression of LFABP and analyzed the assimilation and metabolism of LCFA. Knock-down clones showed marked variations in LCFA assimilation rates and differences in oleate distribution among complex lipid species. Cell proliferation and differentiation were also slowed in the clones. In addition, the effect of LCFA in the induction of an inflammatory response in Caco-2 cells was studied, cytokines mRNA levels were increased after LCFA exposure. These results indicate that LFABP plays a specific role in the enterocyte lipid metabolism. Future studies will contribute to asses whether intestinal FABPs are also involved in inflammatory processes triggered by LCFA.

Male and female T. infestans were released on two consecutive nights in the salinas of Cordoba Province, Argentina, when air temperatures during the flying period averaged 28S"C. 136 males (43% of the total released) and 170 females (57%) flew on the first night, and 6 males (18%) and 7 females (27%) on the second. Of these, we recovered 23 males and 14 females within lOOm, and a further female within 200m, all from the first night's release. The remainder appear to have flown more than 100 m and possibly more than 200 m. In support of this conclusion 4 male and 5 female bugs were recovered in an abandoned brick house 550 m from the release point. Since the proportion of bugs apparently flying more than 200 m is considerably greater than that deduced from previous experiments at lower temperatures (Lehane & Schofield, 1981) it is possible that temperature influences not only the proportion of bugs flying but also the distance flown. Flight appears to be affected by wind speed. On the first night, when there was negligible wind, 43% of male and 57% of female bugs flew. On the second night, with winds gusting at 4-5 m/s, only 18% of the male and 27% of the female bugs flew.

Limited access to Chagas disease diagnosis and treatment is a major obstacle to reaching the 2020 World Health Organization milestones of delivering care to all infected and ill patients. Colombia has been identified as a health system in transition, reporting one of the highest levels of health insurance coverage in Latin America. We explore if and how this high level of coverage extends to those with Chagas disease, a traditionally marginalised population. Using a mixed methods approach, we calculate coverage for screening, diagnosis and treatment of Chagas. We then identify supply-side constraints both quantitatively and qualitatively. A review of official registries of tests and treatments for Chagas disease delivered between 2008 and 2014 is compared to estimates of infected people. Using the Flagship Framework, we explore barriers limiting access to care. Screening coverage is estimated at 1.2% of the population at risk. Aetiological treatment with either benznidazol or nifurt...

The drugs against tropical neglected diseases, especially Chagas’ Disease, were launched more than 30 years ago, and the development of resistance requires the discovery of new and more effective chemotherapeutic agents. Trypanosoma cruzi has a redox enzyme called trypanothione reductase which was successfully inhibited for peptide derivatives (McKie et al., Amino Acids, 2001, 20: 145). This work aims at studying the mechanism of inhibition of this enzyme through molecular dynamics simulations and evaluating the behavior of some derivatives when inhibiting this protein. We should affirm that any particular molecular dynamics analysis tools (Hbond pattern, 3-D root-mean-square deviation, solvent accessible surface area, etc.) cannot be used apart from the others to justify completely these peptides inhibitory patterns. Based on our results, we reproduced the experimental data and, moreover, we discriminated against a new site in enzyme aperture, which can assist the development of powerful inhibitors against trypanothione reductase enzyme.

A., ROSALES-ENCINA, J. L., . American trypanosomiasis: In situ and generalized features of parasitism and inflammation kinetics in a murine model. Experimental Parasitology 83, 267-274. Mimicking the natural conditions of mammalian infection, metacyclic trypomastigote forms of a Mexican isolate (Ninoa) of Trypanosoma cruzi were inoculated into mice in order to study inflammation kinetics and parasite clearance at the inoculation site, parasite tropism to different organs, and local inflammatory cell infiltrates. Polymorphonuclear cells were detected at the inoculation site as early as 1 hr after inoculation. Peak cell infiltrate was observed at 24 hr; at 96 hr polymorphonuclear cells had disappeared. Mononuclear cell infiltrates began at 24 hr, peaking at Day 15, and then stared disappearing by Day 30. Antigens and parasites were detected by conventional techniques up to 15 min and thereafter became undetectable. Amplification of the hypervariable region of kinetoplast minicircle DNA by polymerase chain reaction was positive from 24 hr to Day 15, and the reaction became negative on Day 30. Myositis was observed in skeletal muscle from Days 7 to 180, it progressed from slight to severe, with an inflammation process which included macrophages, plasmatic cells, and a few eosinophils, the phenotype of the infiltrating cells included LyT2 / and LyT1 / on Day 30, and both cell populations decreased in parallel on Day 180. Antigen and parasite nests were present from Days 15 to 180; in muscle the earliest time at which minicircle DNA was detected was Day 7 and it was present until Day 180. Myocarditis was also observed; it developed from slight to severe in between Days 7 and 30, then gradually decreased, and cleared up. Mononuclear cell infiltrates in the myocardium were present from Days 7 to 180. Antigen and parasite nests were detected at Days 15 and 30 and disappeared at Day 180, although minicircle DNA was detected until the last day of observation. Both skeletal and heart muscles showed inflammatory reaction foci containing T. cruzi antigen. There was twice the number of foci in heart as in skeletal muscle. This ratio was maintained by Day 30; later skeletal muscle showed persistent inflammation which was practically cleared up in the heart. Parasites or antigen were not detected by Day 180 in both skeletal and cardiac muscle; however, minicircle DNA was amplified, indicating that an small proportion of parasites evaded immune response. According to these data, Mexican Ninoa Strain has a classification as biodeme 3. ᭧

is credited with the discovery of Chagas disease because of his 1909 published findings of the Trypanosoma cruzi parasite isolated in the blood of a Brazilian patient [1]. Following his discovery, reports of Chagas disease from across Latin America were published, classifying these countries as endemic with continual transmission occurring [2]. The United States has long been considered a non-endemic country due to the opinion that transmission between local vector populations and humans is non-existent or infrequent [3]. We recently published an extensive review with published reports of routine human exposure to nocturnal Triatominae vector bites and continual reports of autochthonous transmission to Texas locals over the past 60 years [4]. In the midst of performing this historical literature review, we came across a reference to the original source of the term "kissing bug." Accessing the historical archives that were available online for five different urban newspapers, we searched for newspaper articles that included the key words "kissing bug" and were published between January 1, 1899, and December 31, 1899. What we unearthed was an unexpected "outbreak" of kissing bug assaults that were reported in newspapers across the nation. Ten years before Carlos Chagas described Chagas disease (in 1909), the US experienced a multi-city hysteria caused by the routine, nightly bites of the "kissing bug" that resulted in numerous hospitalizations and even a few deaths. On Tuesday, June 20, 1899, The Washington Post published the first article describing "the bite of a strange bug" [5]. Reporters noted "several victims.. .woke up to find both eyes nearly closed by the swelling.. .the matter is beginning to interest physicians" [5]. During the early days of the epidemic, no one had seen the insect, but only reported that it struck during the night without any initial pain. The afflicted victim would awake in the morning with swelling mostly of the eyelid and lips, and occasionally on the hand, shoulder, or arm [5-9]. Swelling typically subsided within 48 to 72 hours and was accompanied, on occasion, by fever and/or symptoms that resembled poisoning [10-12]. Sadly, several fatalities were reported throughout the continuing epidemic, with one death certificate specifically stating "chief and determining cause of death-sting of a kissing bug" [11,13-16]. Between June and July of 1899, reports of kissing bug victims were rampant across the continental US (Fig 1). More than sixty newspaper articles were published that referenced over 100 cases, with The Washington Post, The New York Times, The Atlanta Constitution, the Boston Daily Globe, and the Chicago Daily Tribune newspapers publishing the majority of the relevant articles. (Of notable interest, patients' names, ages, and residential addresses were published in the newspaper alongside their accounts.) The bug responsible for these attacks was anecdotally referred to as the "kissing bug," "Hobson bug," and "Dorsey Foultz bug" [17]. Despite the ambiguous nature of the newly emerging epidemic, early reports from local entomologists

Two cDNAs, isolated from a Trypanosoma cruzi amastigote library immunoscreened with sera from patients with Chagas disease, encode proteins with sequence homology to eukaryotic components of the cellular sorting and recycling machinery. These proteins, denominated TcAGL, present an N-terminal lectin domain and a C-terminal region containing repetitive amino acids and a poly-glutamine tract. They are products of polymorphic alleles of a single copy gene constitutively expressed during the parasite life cycle. Polyclonal antibodies obtained from mice immunized with the recombinant antigen recognize proteins with apparent molecular weight ranging from 95 to 120 kDa in cell lysates from all three life stages and in various strains of the parasite. Sera from Chagas disease patients recognize the recombinant antigen in ELISA and immunoprecipitation assays but not in Western blot assays under denaturing conditions. Consistent with its proposed role in the glycoprotein secreting pathway, immunofluorescence analyses and expression of a green fluorescent protein-tagged TcAGL protein indicate a sub-cellular localization in the vicinity of the flagellar pocket membrane and the Golgi complex of the parasite. Ó

Background: Triatomines (Hemiptera, Reduviidae) are vectors of Trypanosoma cruzi, the causative agent of Chagas disease, one of the most important vector-borne diseases in Latin America. This study compares the environmental niche spaces of Triatoma brasiliensis and Triatoma melanica using ecological niche modelling and reports findings on DNA barcoding and wing geometric morphometrics as tools for the identification of these species. Methods: We compared the geographic distribution of the species using generalized linear models fitted to elevation and current data on land surface temperature, vegetation cover and rainfall recorded by earth observation satellites for northeastern Brazil. Additionally, we evaluated nucleotide sequence data from the barcode region of the mitochondrial cytochrome c oxidase subunit I (CO1) and wing geometric morphometrics as taxonomic identification tools for T. brasiliensis and T. melanica. The ecological niche models show that the environmental spaces currently occupied by T. brasiliensis and T. melanica are similar although not equivalent, and associated with the caatinga ecosystem. The CO1 sequence analyses based on pair wise genetic distance matrix calculated using Kimura 2-Parameter (K2P) evolutionary model, clearly separate the two species, supporting the barcoding gap. Wing size and shape analyses based on seven landmarks of 72 field specimens confirmed consistent differences between T. brasiliensis and T. melanica. Our results suggest that the separation of the two species should be attributed to a factor that does not include the current environmental conditions. However, as the caatinga is a biome that has existed in the area for at least the last 18,000 years, past conditions might have had an influence in the speciation process. The DNA Barcoding approach may be extended to these members of the subfamily Triatominae.

Chagas disease is a chronic, systemic, parasitic infection caused by the protozoan Trypanosoma cruzi, and was discovered in 1909. The disease affects about 8 million people in Latin America, of whom 30-40% either have or will develop cardiomyopathy, digestive megasyndromes, or both. In the past three decades, the control and management of Chagas disease has undergone several improvements. Large-scale vector control programmes and screening of blood donors have reduced disease incidence and prevalence. Although more effective trypanocidal drugs are needed, treatment with benznidazole (or nifurtimox) is reasonably safe and effective, and is now recommended for a widened range of patients. Improved models for risk stratification are available, and certain guided treatments could halt or reverse disease progression. By contrast, some challenges remain: Chagas disease is becoming an emerging health problem in non-endemic areas because of growing population movements; early detection and ...

Until now, there has been neither an agreed-upon experimental model nor descriptors of the clinical symptoms that occur over the course of acute murine infection. The aim of this work is to use non-invasive methods to evaluate clinical signs in Swiss Webster mice that were experimentally infected with the Y strain of Trypanosoma cruzi during acute phase (Inf group). Infected mice showed evident clinical changes beginning in the second week of infection (wpi): (i) animals in hunched postures, closed eyes, lowered ears, peeling skin, increased piloerection, prostration and social isolation; (ii) significant decrease in the body weight (Inf: 26.2±2.6 g vs. non-infected group (NI) 34.2±2.5 g), chow (1.5±0.3 vs. 6.3±0.5 mg) and water (2.4±0.5 vs. 5.8±0.7 ml) intake; (iii) significant decrease of the spontaneous activity as locomotor parameters: distance (0.64±0.06 vs. 1.8±0.13 m), the velocity (1.9±0.3 vs. 6.7±1.5 cm/s) and exploratory behaviour by the frequency (1.0±0.5 vs.5....

Chagas disease, a chronic systemic parasitosis caused by the Kinetoplastid protozoon Trypanosoma cruzi, is the first cause of cardiac morbidity and mortality in poor rural and suburban areas of Latin America and the largest parasitic disease burden in the continent, now spreading worldwide due to international migrations. A recent change in the scientific paradigm on the pathogenesis of chronic Chagas disease has led to a consensus that all T. cruzi-seropositive patients should receive etiological treatment. This important scientific advance has spurred the rigorous evaluation of the safety and efficacy of currently available drugs (benznidazole and nifurtimox) as well as novel anti-T. cruzi drug candidates in chronic patients, who were previously excluded from such treatment. The first results indicate that benznidazole is effective in inducing a marked and sustained reduction in the circulating parasites' level in the majority of these patients, but adverse effects can lead to treatment discontinuation in 10-20% of cases. Ergosterol biosynthesis inhibitors, such as posaconazole and ravuconazole, are better tolerated but their efficacy at the doses and treatment duration used in the initial studies was significantly lower; such results are probably related to suboptimal exposure and/or treatment duration. Combination therapies are a promising perspective but the lack of validated biomarkers of response to etiological treatment and eventual parasitological cures in chronic patients remains a serious challenge.

Chagas disease represents a serious public health problem in South America. The first line of treatment is Nifurtimox and Benznidazole which generate toxic effects in treated patients. We have recently shown that a number of 5-nitrofuranes possess activity against Trypanosoma cruzi through oxidative stress and inhibition of parasite ergosterol biosynthesis, specifically at the level of squalene epoxidase. Here, we identify new 5-nitrofuranes and the thia-analogues with excellent effects on the viability of T. cruzi and adequate parasite/mammal selectivity indexes. Analysis of the free sterols from parasite incubated, during 120 h, with the compounds showed that some of them accumulated squalene suggesting the squalene epoxidase activity inhibition of the parasite. Nifurtimox was able to accumulate squalene only at lower incubation times. Due to this fact some derivatives were also tested as antifungal agents. Quantitative structure-activity relationship studies were also performed showing relevant features for further new derivatives design. Taken together, the results obtained in the present work point to a more general effect of 5-nitrofuranes and 5-nitrothiophenes in trypanosomatids, opening potential therapeutic possibilities of them for these infectious diseases.

Anti-native DNA antibodies can be detected by indirect immunofluorescence assay with Crithidia luciliae, displaying an annular image due to a kinetoplast containing double stranded DNA. Other structures such as membrane, flagellum and basal corpuscle can be stained as well, showing what is called atypical fluorescent images. As C. luciliae belongs to the Trypanosomatidae family, which include the human pathogens Trypanosoma cruzi and Leishmania spp., it was considered that these atypical images could be caused by cross-reactions. Serological studies for Chagas' disease were performed in 105 serum samples displaying atypical images. Sixty four percent of the samples from non endemic and 78.3% from endemic areas for Chagas' disease showed fluorescence in both, membrane and flagellum (joint image). Fifty samples from normal blood donors and 57 samples from patients with conective tissue diseases were tested with C. luciliae. None of them presented the joint image except for two...

información del artículo Historia del artículo: Recibido el 8 de junio de 2012 Aceptado el 2 de septiembre de 2012 On-line el 25 de octubre de 2012 Palabras clave: Enfermedad de Chagas Diagnóstico Reacción en cadena de la polimerasa Inmunoensayo enzimático Hemaglutinación indirecta Inmunofluorescencia indirecta

Carreira, J. C. A., Jansen, A. M., Meirelles, M. de N., Costa e Silva, F., Lenzi, H. L. 2001. Trypanosoma cruzi in the scent glands of Didelphis marsupialis: The kinetics of colonization. Experimental Parasitology97, 129–140. This study examined the dynamics of colonization of Trypanosoma cruzi in the scent glands of the opossum Didelphis marsupialis following direct inoculation with 105 epimastigotes of isolate G-49 (an opossum-derived strain). One, three, and five days, 1 month, and 1 year after inoculation, scent glands were fixed for analysis using brightfield and electron microscopies. One day after inoculation the parasites, mainly as epimastigotes, were randomly distributed into the lumen. From the third day on, the parasites still in the form of epimastigotes tended to concentrate closer to the epithelium. The flagellates reached the definitive distribution pattern on the fifth day, when they formed huge clusters deep into the foveae. In samples collected 1 month and 1 year after inoculation, the ratio of epimastigotes:trypomastigotes was 1:1, with epimastigotes predominating near the epithelium and trypomastigotes far from it. Our observations suggest that T. cruzi grows continuously in the scent glands and does not depend on adhesion to promote metacyclogenesis. Metacyclogenesis far from the epithelium seems to be an important selective advantage to both host and parasite, since it assures the elimination of the infective forms of the parasite when the host expels the glands' contents, which occurs in frightening situations or at times of stress. The morphological characteristics of infected and noninfected scent glands using transmission and scanning electron microscopies were also described.

A partir del caso de una niña de seis años con diagnóstico confirmado de enfermedad de Chagas aguda, procedente de la localidad de Pozuzo (Oxapampa-Junín) en al selva central del Perú, un área no señalada como endémica en el país, se realizó un estudio ...

Este Artículo aborda la cuestión de la enfermedad de Chagas y como se enfrenta en un contexto migratorio, no endémico por las mujeres que se encuentran afectadas por la enfermedad de Chagas.
Es un capítulo interesante, en tanto aborda desde una aproximación antropológica la cuestión de la enfermedad de chagas de transmisión vertical en un contexto migratorio.
Es un documento que permite mejorar la comprensión dela complejidad de la enfermedad de Chagas

Background: This study identified Trypanosoma cruzi discrete typing units (DTUs) in maternal and infant specimens collected from two hospitals in Bolivia, using conventional genotyping and DTU-specific serotyping. Methods: Specimens from 142 mothers were used, including 24 seronegative and 118 seropositive individuals; 29 women transmitted T. cruzi to their infants. Maternal and infant parasite loads were determined by quantitative real-time PCR. Maternal sera were tested with an in-house parasite lysate ELISA and serotyped by a lineage-specific peptide ELISA, targeting the trypomastigote small surface antigen (TSSA). Trypanosoma cruzi genotypes in infected infants were determined by a triple PCR-RFLP assay. Results: All infant specimens were genotyped as TcV. Maternal parasite loads and absorbance values by the lysate ELISA were significantly higher for transmitters compared with non-transmitters. Among seropositive mothers, 65.3% had positive results by the TSSA II/V/VI peptide ELISA. No significant difference in reactivity to TSSA II/V/VI was observed for transmitters compared with non-transmitters (79.3% vs 60.7%, respectively). Conclusions: Our findings reinforce the difficulty in obtaining sufficient sample numbers and parasite DNA to investigate the interaction between parasite genetics and the risk of congenital transmission and argue for the inclusion of DTU-specific serotyping in prospective studies.

Reyes discuss the development of new tools for the serodiagnosis of Chagas disease (caused by Trypanosoma cruzi) and describe recombinant antigens that have proved to be of great diagnostic potential in distinguishing different sta,~es of the disease. The work is important because different treatment strategies are needed for acute and chronic infection.

The aim of this review is to gather the current knowledge of Trypanosoma cruzi's virulence factors described to date in an integrative way, relating these with the parasite's life cycle and trying to elucidate their importance in each process. Several aspects relevant for the parasite's survival, such as invasion, resistance to oxidative damage, escape from the phagolysosomal vacuole and differentiation, among others, will be discussed. However, there is still a lot to learn about what virulence really means in T. cruzi and which parasite molecules are absolutely required to make T. cruzi one of the most successful pathogens to invade, survive and persist in a mammalian host.

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We report the cloning and kinetic characterization of Trypanosoma cruzi deoxyuridine 5P P-triphosphate nucleotidohydrolase (dUTPase) whose coding sequence was isolated by genetic complementation in Escherichia coli. The deduced amino acid sequence was similar to Leishmania major dUTPase although it exhibits an amino acid insertion which is sensitive to protease inactivation. The catalytically active species of the enzyme is a dimer and a detailed kinetic characterization showed that it is highly speci¢c for dUTP and dUDP. The general observation that dUTPases from the Trypanosomatidae di¡er in sequence, conformation and substrate speci¢city suggests that a di¡erent family of dUTPases exists in certain organisms, which may be exploited as drug targets against infectious diseases. ß 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

O Guia de Vigilância em Saúde (GVS), editado pela Secretaria de Vigilância em Saúde do Ministério da Saúde (SVS/MS), em sua 3ª edição eletrônica, se alinha aos novos desafios e estratégias de vigilância, prevenção e controle das doenças e agravos de importância de Saúde Pública. Esta edição atualiza as recomendações relacionadas às ações de vigilância em saúde presentes na Lista Nacional de Notificação Compulsória de Doenças, Agravos e Eventos de saúde Pública, unificada pela Portaria de Consolidação nº 4, de 28 de setembro de 2017. A publicação do GVS visa disseminar os  procedimentos relativos aos fluxos, prazos, instrumentos, definições de casos suspeitos e confirmados, funcionamento dos sistemas de informação em saúde, condutas, medidas de controle e demais diretrizes técnicas para operacionalização do Sistema Nacional de Vigilância em Saúde. Para a revisão e atualização destes  procedimentos, foram considerados o atual cenário epidemiológico do país, o conhecimento científico disponível e as novas tecnologias incorporadas pelo Sistema Único de Saúde (SUS) às ações de vigilância, prevenção e controle de doenças e eventos de importância para a Saúde Pública. Nesta 3ª edição, passaram por atualizações substanciais os capítulos sobre febre amarela; febre do Nilo Ocidental; sarampo; sífilis congênita; sífilis adquirida e em gestante; rubéola; síndrome da rubéola
congênita; hepatites virais; e infecção pelo HIV e aids. Outras pequenas atualizações foram realizadas nos capítulos de tétano acidental; difteria; caxumba; e varicela. Foram ainda mantidos conteúdos presentes na edição anterior do GVS, conformando um processo de construção coletiva e histórica. Assim, importa agradecer a todos os profissionais, gestores e colaboradores que participaram, em alguma medida, desta
publicação, bem como aos editores, às equipes técnicas da SVS/MS, aos membros de seus comitês técnicos assessores e demais colaboradores, identificados ao final da publicação. A despeito do mérito da contribuição destes profissionais, garante-se a autoria institucional das recomendações contidas neste GVS à SVS/MS, como instância coordenadora do Sistema Nacional de Vigilância em Saúde.
Ressalta-se a dinâmica de atualização do GVS em fluxo contínuo. Portanto, outras edições poderão ser divulgadas com revisão mais ou menos abrangente de conteúdo, à medida que novas evidências e
tecnologias incorporadas indiquem a necessidade de rever as recomendações vigentes para vigilância, prevenção e controle das doenças e agravos de interesse do SUS. Nesse sentido, especialmente aqueles que o utilizam para balizar suas práticas profissionais devem estar atentos às versões eletrônicas que serão divulgadas amplamente pela SVS/MS, particularmente no endereço eletrônico  http://portalms.saude.gov.br/vigilancia-em-saude/publicacoes
Espera-se que o GVS dissemine as informações que possam contribuir para o aprimoramento das práticas da vigilância em saúde, de forma integrada aos serviços de saúde, em todos os municípios do país.

We report the cloning and kinetic characterization of Trypanosoma cruzi deoxyuridine 5P P-triphosphate nucleotidohydrolase (dUTPase) whose coding sequence was isolated by genetic complementation in Escherichia coli. The deduced amino acid sequence was similar to Leishmania major dUTPase although it exhibits an amino acid insertion which is sensitive to protease inactivation. The catalytically active species of the enzyme is a dimer and a detailed kinetic characterization showed that it is highly speci¢c for dUTP and dUDP. The general observation that dUTPases from the Trypanosomatidae di¡er in sequence, conformation and substrate speci¢city suggests that a di¡erent family of dUTPases exists in certain organisms, which may be exploited as drug targets against infectious diseases.

Autonomic dysfunction is common in Chagas disease and diabetes. Patients with either condition complicated by cardiac autonomic dysfunction face increased mortality, but no clinical predictors of autonomic dysfunction exist. Pupillary light reflexes (PLRs) may identify such patients early, allowing for intensified treatment. To evaluate the significance of PLRs, adults were recruited from the outpatient endocrine, cardiology, and surgical clinics at a Bolivian teaching hospital. After testing for Chagas disease and diabetes, participants completed conventional autonomic testing (CAT) evaluating their cardiovascular responses to Valsalva, deep breathing, and orthostatic changes. PLRs were measured using specially designed goggles, then CAT and PLRs were compared as measures of autonomic dysfunction. This study analyzed 163 adults, including 96 with Chagas disease, 35 patients with diabetes, and 32 controls. PLRs were not significantly different between Chagas disease patients and con...

Protozoan infections are very common among tropical countries and have an important impact on public health. Leishmaniasis is the most widely disseminated protozoan infection in the world, while the trypanosomiases are widespread in both Africa and South America. Amebiasis, a less common protozoal infection, is a cause of significant morbidity in some regions. Toxoplasmosis and pneumocystosis (formerly thought to be caused by a protozoan) are worldwide parasitic infections with a very high incidence in immunocompromised patients but are not restricted to them. In the past, most protozoan infections were restricted to specific geographic areas and natural reservoirs. There are cases in which people from other regions may have come in contact with these pathogens. A common situation involves an accidental contamination of a traveler, tourist, soldier, or worker that has contact with a reservoir that contains the infection. Protozoan infections can be transmitted by arthropods, such as sandflies in the case of leishmaniasis or bugs in the case of trypanosomiases. Vertebrates also serve as vectors as in the case of toxoplasmosis and its transmission by domestic cats. The recognition of the clinical symptoms and the dermatologic findings of these diseases, and a knowledge of the geographic distribution of the pathogen, can be critical in making the diagnosis of a protozoan infection. ( J Am Acad Dermatol 2009;60:897-925.) Learning objectives: After completing this learning activity, participants should be able to recognize the significance of protozoan infections worldwide, identify the dermatologic manifestations of protozoan infections, and select the best treatment for the patient with a protozoan infection.