Showing papers by "Oswaldo Cruz Foundation published in 1997"

Immunological control of Trypanosoma cruzi infection and pathogenesis of Chagas' disease.

Abstract: The major goal of studies on immunity to Trypanosoma cruzi is the understanding of immunological mechanisms involved in resistance to this protozoan as well as the pathogenesis of Chagas' disease. Different studies have defined CD8+ T lymphocytes, IFN-gamma and macrophages as important elements controlling parasite replication during the acute phase of infection. In contrast, during the chronic stage of the disease parasite-specific antibodies that fix complement and lyse the blood from trypomastigotes are thought to be the main effector molecules responsible for maintaining latent infection. In both acute and chronic infection with T. cruzi CD4+ Th1 lymphocytes appear to be the main cells responsible for induction of protective immunity. The immunological mechanisms involved in the pathogenesis of Chagas' disease are much more controversial. CD8+ lymphocytes are thought to be the main effector cells responsible for cardiac tissue destruction. Although many experiments suggest the involvement of autoimmunity in the pathogenesis of Chagas' disease, recent studies both in mice and humans indicate a positive association of tissue parasitism, inflammation and severity of pathology induced by T. cruzi. Finally, T. cruzi has emerged as an important opportunistic pathogen in patients infected with HIV and presenting low numbers of CD4+ T lymphocytes. These clinical findings indicate the essential requirement of CD4+ T-helper cells in mediating resistance during chronic Chagas' disease; however, the effector mechanisms that control the reactivation of chronic infection in vivo are not completely defined.

Nematóides do Brasil. Parte V: nematóides de mamíferos

Abstract: A survey of nematode species parasitizing Brazilian mammals is presented, with enough data to provide their specific identification. The tirst section refers to the survey ofthe species, related to 21 superfamilies, 45 families, 160 genera and 495 species that are illustrated and measurement tables are given. The second section is concerned to the catalogue ofhost mammals which includes 34 families, 176 species and their respective parasite nematodes. The identification of these helminths is achieved by means of keys to the superfamilies, families and genera. Specific determination is induced through the figures and tables as above mentioned.

The spectrum of congenital anomalies of the VATER association: An international study

Abstract: The spectrum of the VATER association has been debated ever since its description more than two decades ago. To assess the spectrum of congenital anomalies associated with VATER while minimizing the distortions due to small samples and referral patterns typical of clinical series, we studied infants with VATER association reported to the combined registry of infants with multiple congenital anomalies from 17 birth defects registries worldwide that are part of the International Clearinghouse for Birth Defects Monitoring Systems (ICB-DMS). Among approximately 10 million infants born from 1983 through 1991, the ICB-DMS registered 2,295 infants with 3 or more of 25 unrelated major congenital anomalies of unknown cause. Of these infants, 286 had the VATER association, defined as at least three of the five VATER anomalies (vertebral defects, anal atresia, esophageal atresia, renal defects, and radial-ray limb deficiency), when we expected 219 (P<0.001). Of these 286 infants, 51 had at least four VATER anomalies, and 8 had all five anomalies. We found that preaxial but not other limb anomalies were significantly associated with any combination of the four nonlimb VATER anomalies (P<0.001). Of the 286 infants with VATER association, 214 (74.8%) had additional defects. Genital defects, cardiovascular anomalies, and small intestinal atresias were positively associated with VATER association (P<0.001). Infants with VATER association that included both renal anomalies and anorectal atresia were significantly more likely to have genital defects. Finally, a subset of infants with VATER association also had defects described in other associations, including diaphragmatic defects, oral clefts, bladder exstrophy, omphalocele, and neural tube defects. These results offer evidence for the specificity of the VATER association, suggest the existence of distinct subsets within the association, and raise the question of a common pathway for patterns of VATER and other types of defects in at least a subset of infants with multiple congenital anomalies.

[History and dilemmas in the development of the worker's health field]

Abstract: This article reflects on the theoretical and practical foundations impacting and shaping the field of workers' health in Brazil, as part of the overall field of collective health. By analyzing the various forms of approaching the relationship between work and health, the paper emphasizes its complex and conflicting nature as a central reference for the work process, in keeping with the premises of social medicine in Latin America. This focus underscores the need for interdisciplinary approaches contemplating and even extrapolating the links between areas of knowledge generally ascribed to the field of health. Finally, the paper gives a brief diagnosis of the current situation in this field, where pending questions join those resulting from globalization of the economy and particularly industrial restructuring, in light of which the challenge is raised to broaden the objects of study and intervention to include the implications of outsourcing, increasingly precarious labor conditions, informal labor, and unemployment on the population's health and living conditions.

Glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from Trypanosoma cruzi trypomastigotes initiate the synthesis of proinflammatory cytokines by macrophages.

Abstract: Components of Trypanosoma cruzi able to induce the production of IL-12 and other proinflammatory cytokines by macrophages were identified Murine inflammatory macrophages were cultured with live parasites or with cellular components from different developmental forms of T cruzi (ie, trypomastigotes, amastigotes, metacyclic trypomastigotes, and epimastigotes), and the cytokine levels were measured after 24 and 48 h Our results indicate that live trypomastigotes or live amastigotes (but not live epimastigotes or live metacyclic trypomastigotes) as well as trypomastigote extracts (but not extracts derived from epimastigotes) induce IL-12 and TNF-alpha synthesis by macrophages Such biological activity is enhanced in membrane preparations from trypomastigotes Further enrichment of the trypomastigote-derived monokine-inducing factor was obtained by solvent extraction and hydrophobic-interaction chromatography The resultant purified molecules are a family of closely related glycoconjugates with predominant species at 70 to 80 and 120 to 200 kDa These molecules are composed of carbohydrate chains O-linked to a polypeptide backbone that is anchored to the trypomastigote membrane via a glycosylphosphatidylinositol structure The trypomastigote-derived glycoconjugates are active in inducing cytokine synthesis by macrophages at concentrations of 100 ng/ml These effects are highly potentiated by IFN-gamma Mapping of the glycoconjugate molecules to characterize the structural requirements for macrophage activation suggested that nonsaturated acyl fatty acid chains and periodate-sensitive units from the glycosylphosphatidylinositol anchor are important elements for the infective trypomastigote form to initiate cytokine synthesis by macrophages

Assessment of the efficacy of diethylcarbamazine on adult Wuchereria bancrofti in vivo

Abstract: To assess directly the effect of various doses of diethylcarbamazine (DEC) on adult Wuchereria bancrofti, 31 infected men were randomly assigned to receive an initial single DEC dose of 1 mg/kg (n = 7), 6 mg/kg (n = 10), or 12 mg/kg (n = 14). Beginning 7 d later, the dosage of DEC and duration of treatment were progressively increased for 7–10 weeks. Physical examinations were performed to detect scrotal nodules and the scrotal area was examined by ultrasound (7·5 MHz transducer) to monitor the ‘filaria dance sign’ (FDS), the characteristic pattern of adult worm movement. Of 53 adult worm ‘nests’ that were detected by ultrasound, 22 (41·5%) were DEC-sensitive (FDS became non-detectable and a nodule became palpable at the site); 20 (37·7%) were not sensitive (FDS remained unchanged and detectable and no nodule developed), and 11 (20·8%) showed mixed responses (FDS remained detectable but a palpable nodule developed). All but one sensitive or mixed response occurred within 1 week after the initial single dose. Of 39 ‘nests’ in men who initially received a single 6 or 12 mg/kg dose of DEC, 20 (51·3%) had sensitive responses compared to 2 (14·3%) of 14 ‘nests’ in men who received a single 1 mg/kg dose (P = 0·04). Above 6 mg/kg, the macrofilaricidal effect of DEC did not increase with dose; a significant proportion of adult W. bancrofti were not susceptible to DEC during the study period.

Retrospective study on dengue fatal cases

Abstract: Immunohistochemical procedure (avidin biotin peroxidase complex) was applied in formalin-fixed and paraffin-embedded tissues obtained from 5 fatal cases of dengue infection associated with encephalopathy. Dengue virus antigen was demonstrated in the cytoplasm of phagocytic mononuclear cells from liver, spleen, and lung. Moreover, dengue viral antigens were here, to our knowledge, first demonstrated in the central nervous system (CNS) and numerous immunolabelled cells were found in brain sections from 3 cases. Extended immunohistochemical studies carried out in 1 case showed virus-positive cells mostly located within Virchow Robin space of medium size and small veins, infiltrating the white and grey matter, and often situated close to neurons displaying apparent cytopathic features. Furthermore, immunostaining for CD68 antigens demonstrated that most CD68+ macrophages and dengue antigen-positive cells share similar morphology and localization, suggesting a unique identity for at least part of these cells. Since in dengue fever, virus replicates mostly in cells of macrophage lineage, our results seem to indicate that infiltration of virus-infected macrophages could be one of the pathways by which viruses enter the brain in dengue encephalitis. Whether bone marrow-derived infected macrophages and viral-free particles induce CSN lesions through immune, metabolic, and/or direct viral-induced mechanisms will be essential to better understand the pathogenesis and provide new therapeutic strategies for dengue-associated encephalitis. As the evidence of tissue damage was nonspecific, the detection of virus antigen by immunoperoxidase technique appeared to be highly reliable for dengue diagnosis.

Violencia e saude como um campo interdisciplinar e de acao coletiva

Abstract: While the question of violence and health is a complex one, it opens the door for interdisciplinary collaboration and multi professional efforts. Although this article does not intend to provide any definitive responses, it does endeavor to critique viewpoints that attribute an absolute meaning to the term 'violence'. It warns that this health-care sector runs the epistemological and pratical risk of falling into reductionism when it addresses violence as if it were an epidemic. Furthermore, this sector needs to collaborate with other sectors and wth civil societyu. More than offering answers, the article raises questions within the framework of an interdisciplinary approach encompassing the social sciences, epidemology and psychology.

Rapid increase in bone-marrow eosinophil production and responses to eosinopoietic interleukins triggered by intranasal allergen challenge

Abstract: To define the effects of immunization and exposure to allergen on the eosinophil lineage, we studied blood and bone-marrow eosinophil numbers, serum interleukin (IL)-5 levels, and eosinophil progenitor and precursor responses to IL-3 and IL-5 in ovalbumin-immunized BALB/c mice after intranasal challenge. Increased blood eosinophilia was found in immune relative to nonimmune mice, but the differences between challenged and unchallenged immune animals were not significant. In contrast, significantly increased circulating levels of IL-5 and numbers of bone-marrow eosinophils were found in sensitized animals exposed to allergen, relative to unchallenged, sensitized controls. An allergen-induced increase in IL-3-sensitive progenitors yielding eosinophil-bearing colonies was also found at 2 h after challenge. Furthermore, an eosinophil differentiation assay showed a marked increase in the magnitude of the responses to IL-5 and IL-3 over a 7-day period in bone-marrow cells of sensitized animals, which was detectable at 24 h after allergen challenge, but not at 2 h and not in unchallenged controls. Modulation of the responses of bone-marrow cells to IL-5 is induced by a circulating factor present in challenged immune animals, as shown by in vivo plasma transfer, but is at best only partly blocked by in vivo treatment with the anti-IL-5 antibody TRFK-5. These data indicate that allergen challenge in the airways leads to rapid long-term modifications in bone-marrow eosinophil progenitors and precursors, and that increased responses to eosinopoietins in bone marrow depend on the release, between 2 h and 24 h after challenge, of a circulating factor distinct from IL-5.

A Low-Dose Antimony Treatment in 159 Patients with American Cutaneous Leishmaniasis: Extensive Follow-up Studies (Up to 10 Years)

Abstract: The efficacy of an antimony regimen at the dose of 20 mg/kg/day for a 3-4-week period is well established in the treatment of American cutaneous leishmaniasis. Several drug side effects, however, have been described and the search for more suitable regimens is advisable. In the present paper, the effect of a low dose (5 mg/kg/day for 30 days) of antimony was evaluated in 159 individuals from endemic regions of Rio de Janeiro State, Brazil, an area of Leishmania (V.) braziliensis transmission. Patients presented typical cutaneous lesions and parasites were demonstrated in all cases. One hundred forty-three patients were available for evaluation and of these, 120 (84%) were cured by the end of therapy. Twenty-three patients (16%) were considered treatment failures. Side effects were observed in only six patients (4%). Extensive follow-up (up to 10 years) disclosed no relapses or mucosal lesions. The results show that a low dose of antimony is less toxic, more appropriate, especially in children and elderly people, and has the same final result as that obtained with larger doses.

Glycoconjugates isolated from Trypanosoma cruzi but not from Leishmania species membranes trigger nitric oxide synthesis as well as microbicidal activity in IFN-gamma-primed macrophages.

Abstract: In the present study, we investigated the role of glycosylphosphatidylinositol-anchored mucin-like glycoproteins (GPI-mucins) from Trypanosoma cruzi trypomastigotes in triggering the synthesis of nitric oxide as well as the microbicidal activity in murine macrophages. Our results show that GPI-mucins isolated from trypomastigote membranes are potent inducers of nitric oxide synthesis by IFN-gamma-primed macrophages, even at concentrations as low as 10 ng/ml. Our data also indicate the important role of glycosylphosphatidylinositol anchors from GPI-mucins as the second signal responsible for induction of nitric oxide synthesis by macrophages. To further investigate the role of these parasite molecules in inducing parasiticidal function, we cultured macrophages in the presence or absence of trypomastigote GPI-mucins and/or IFN-gamma and then infected these cells with either Leishmania spp. or T. cruzi. IFN-gamma was sufficient to induce microbial activity in macrophages infected with T. cruzi trypomastigotes. In contrast, killing of different species of Leishmania was further enhanced when macrophages exposed to IFN-gamma were also costimulated with trypomastigote-derived GPI-mucins. Our results also indicate that different glycolipids obtained from Leishmania major or Leishmania donovani (i.e., lipophosphoglycans or glycoinositolphospholipids) were unable to potentiate nitric oxide synthesis and/or microbicidal activity displayed by IFN-gamma-primed macrophages.

Prevalência de sorovares de Salmonella isolados de aves no Brasil

Abstract: Salmonella strains were isolated from ill and shedding birds in several regions of Brazil between 1962 and 1991. Serotyping of 2123 isolates showed 90 serovars pertaining to 14 serogroups. There was a predominance of groups O:9 (40.0%), O:4 (33.3%), O:7 (10.6%) and O:3,10 (6.7%). Major serovar diversity was found to serogroup O:7 that accounted for 22 different types, followed by serogroups O:4, O:3,10 and O:9 with 19, 15 and 10 serotypes respectively. An average of 10.8 serovars was isolated per year. S. Gallinarum, S. Pullorum, S. Typhimurium, S. Heidelberg, S. Enteritidis and S. Infantis were the most frequent serovars found over the 30 years, representing 65% to 67% of the total of isolates. Bacteriological and epidemiological aspects concerning a number of serotypes are discussed.

Cytokine Regulation of Human Immune Response to Schistosoma mansoni: Analysis of the Role of IL‐4, IL‐5 and IL‐10 on Peripheral Blood Mononuclear Cell Responses

Abstract: The role of cytokines on the in vitro proliferative response of peripheral blood mononuclear cells (PBMC) from Schistosoma mansoni infected patients to soluble egg (SEA) and adult worm antigens (SWAP) were evaluated. The results obtained demonstrated that the proliferative response of PBMC from chronic intestinal (INT) patients to SEA and SWAP is increased by the blockage of IL-10 with specific monoclonal antibodies (MAb). The effects of these antibodies were readily reversed by the addition of recombinant IL-10. In contrast, no effect was observed on the PBMC response of acute and hepatosplenic patients (HS) in the presence of anti-IL-10. Anti-IL-4 antibodies decreased the PBMC response of the intestinal (INT) and HS individuals to SEA and SWAP, and the PBMC response of acute patients to SEA but not to SWAP. Addition of anti-IL-5 MAb did not decrease the PBMC response of acute patients to SEA or SWAP. These results suggested that IL-10 has an important role in the modulation of the immune response in chronic asymptomatic patients and that this cytokine may be an important factor in controlling morbidity.

Intralesional therapy of American cutaneous leishmaniasis with pentavalent antimony in Rio de Janeiro, Brazil--an area of Leishmania (V.) braziliensis transmission.

Abstract: Background The drug of choice for leishmaniasis is pentavalent antimony and different regimens are under continuous evaluation. The ideal therapy should be simple, effective, and with no or minor side-effects, in this paper we have studied the efficacy of intralesionally applied antimony in New World cutaneous leishmaniasis. Methods Seventy-four patients from Rio de Janeiro state, Brazil, and presenting with single ulcerative cutaneous lesions mainly located on the trunk or extremities were enrolled in the study. The drug employed was N-methyl glucamine (425 mg of Sbv in each 5 ml ampoule). Each lesion was infiltrated with the drug at the four cardinal points in order to achieve complete blanching. Results Of the 74 patients, 59 (80%) were healed after a 12–week interval. Extensive follow-up (up to 10 years) disclosed no relapses or the development of mucosal lesions. Conclusions The aim of therapy in New World cutaneous leishmaniasis is the healing of the cutaneous lesion and the prevention of late mucosal damage. Both conditions were achieved with the treatment employed with no side-effects and a considerable decrease in costs. In addition, the method is easy to apply in the field.

Delivery by Trypanosoma cruzi of Proteins into the MHC Class I Antigen Processing and Presentation Pathway

Abstract: Class I MHC-restricted T cell responses have been shown to be critical for the development of immune resistance to Trypanosoma cruzi in mice. However, to date, no antigenic targets of this anti-parasite response have been characterized. We have analyzed the characteristics of potential T. cruzi CTL target molecules by expression of the model CTL target molecule chicken OVA in different cellular compartments of T. cruzi. OVA (amino acids 139-385) was expressed as a secretory, cytoplasmic, transmembrane, or glycosylphosphatidylinositol-anchored protein in T. cruzi transfectants. Host cells infected with T. cruzi transfectants that secreted or released OVA, but not those producing cytoplasmic or transmembrane forms of OVA, could process and present OVA peptide via the class I MHC pathway, as indicated by the stimulation of OVA-specific CD8+ T cell hybridomas and the cytolysis of host cells infected with OVA-secreting parasites by OVA-specific CTLs. In addition, infection of mice with OVA-secreting parasites elicited the production of OVA-specific CTLs. These studies demonstrate the ability to target proteins to specific cellular compartments in T. cruzi using either trypanosomal or mammalian signal sequences. Furthermore, these results suggest that proteins secreted or released by T. cruzi in infected cells are a major source of peptides for MHC class I presentation and for the generation of parasite-specific CTL.

Antiplasmodial triterpene from Vernonia brasiliana.

Abstract: The hexane extract from leaves of Vernonia brasiliana (L.) Druce (Compositae) was active in vitro against Plasmodium falciparum and in vivo in mice infected with Plasmodium berghei. This extract was subjected to a bioassay-guided fractionation protocol based on the in vitro model. Lupeol was identified as a compound responsible for the activity, inhibiting the P.falciparum growth by 45% when tested at 25 micrograms/ml. However, this triterpene was inactive in vivo when 15 mg/kg were administered per os during four consecutive days to mice infected with P.berghei. beta-Amyrin and germanicol, isolated from the same fraction that yielded lupeol, were inactive in the in vitro assay.

Processo de vigilância em saúde do trabalhador

Abstract: This paper is part of a broader discussion on the need for more in-depth study of workers' health surveillance practices, which are most often developed empirically, without well-defined theoretical or technical foundations. The paper presents a concept of surveillance in workers' health as a fulcrum for actions in the relationship between the work process and health. It emphasizes the exposure-based perspective involved in the epidemiological approach. Risk situations and effects are placed in spatial and technological context. The model provides an interdisciplinary approach with a technological, social, and epidemiological basis in a three-dimensional structure. A matrix for planning actions in workers' health surveillance is also presented, focusing on the connections between effects, risks, territory, and activities.

Eqüidade e o Sistema Único de Saúde: uma contribuição para debate

Abstract: In this article it is discussed some relevant issues in regard to inequalities in the consumption of health care services and the construction of more equitable health care system in Brazil. The concept of inequalities in health is distinguished from the concept of inequalities in the consumption of health care services. It is argued that the geographical dimension of health care service consumption differs from the social dimension. This implies that a better distribution of financial resources between geographical regions acts at the level of regional inequalities but might not have a positive impact on existing social inequalities. A more equitable system depends on a greater participation on the financing of the system of the richer people. It depends on the solidarity of the different social groups in society. The present situation of great scarcity of financial resources calls for a definition of priorities. Nonetheless, it is argued that the establishment of priorities in the availability of health care services is an ethical approach only if it is assumed to be a transient strategy directed to the construction of a system based in universal access for all those in need.

Cytokine mRNA profile of peripheral blood mononuclear cells isolated from individuals with Trypanosoma cruzi chronic infection.

Abstract: Characterization of immunologic activities during chronic infection with Trypanosoma cruzi is critical for understanding the dynamics of human Chagas' disease. Since cytokine production is mainly regulated by transcription and mRNA stability, quantitative RT-PCR analysis gives an accurate picture of the influences of disease on cytokine profile. Using RT-PCR, the authors analysed the levels of message expression for several cytokines in peripheral blood mononuclear cells (PBMC) freshly isolated from chagasic patients (CP) and non-infected individuals (NI), and in in vitro-stimulated PBMC from CP. Ex vivo analysis showed that mean levels of expression of IL-5, IL-10, IL-13 and IFN gamma were dramatically increased in PBMC from CP, compared to NI. The levels of IL-2 and IL-4 were not significantly different between groups. Analysis of cytokine mRNA production after in vitro culture with parasite-derived antigens (EPI or TRP) or anti-epimastigote antibodies (Id) showed that these two classes of stimuli induced distinct cytokine responses. While EPI or TRP induced higher production of IFN gamma specific message and low IL-10, anti-Id cells produced higher levels of IL-10 and low IFN gamma. The simultaneous presence of antigenic and antibody stimulation in the host during the chronic phase of Chagas' disease could explain the existence of both inflammatory and anti-inflammatory cellular reactivity detected in most patients.

The Indeterminate Phase of Chagas' Disease: Ultrastructural Characterization of Cardiac Changes in the Canine Model

Abstract: The indeterminate phase of Chagas' disease is defined as the prolonged period of clinically silent infection that follows the phase of acute primary infection with Trypanosoma cruzi. The dog is the only experimental animal model in which the indeterminate phase progresses to the late phase of severe, chronic myocarditis. This report describes the cardiac histologic and ultrastructural findings in dogs that survived the acute phase of infection with T. cruzi, becoming clinically and electrocardiographically normal for up to 3.5 years, while maintaining positive serologic test results during this period of time. Most of the myocardium appeared morphologically normal; however, small foci of mild, chronic myocarditis were present, with interstitial edema, mild fibrosis, and infiltration by lymphocytes, macrophages, and plasma cells. No microvascular lesions and no areas of close contact between immune effector cells and endothelial cells or cardiac myocytes were present. These findings were in sharp contrast to those observed in the canine model during the acute infection with T. cruzi. In this model, acute myocyte damage and lesions in the microcirculation, including fibrin microthrombi, were associated with close contacts between immune effector cells and myocytes or endothelial cells. Focally inflamed interstitial tissue showed increased deposition of amorphous and collagenous extracellular matrix as well as evidence of breakdown of collagen. The features of the inflammatory cells in the indeterminate phase of Chagas' disease were interpreted as indicating a self-limited cycle of focal inflammatory changes, with modulation and suppression of cell-mediated immune responses. Thus, we consider the indeterminate phase of Chagas' disease to be a stage of host-parasite equilibrium rather than a process of progressive damage.