In Vitro Antimalarial Activity of Crude Extracts of Phothomorphe peltata and P. umbellata (Piperaceae)

The in vitro antimalarial activity of hexane and methanol extracts of Pothomorphe peltata (L.) Miq. and P. umbellata (L.) Miq. (Piperaceae), two plants used in the Brazilian folk medicine in the treatment of malaria, was assessed against three Plasmodium falciparum strains with different patterns of sensitivity to the standard antimalarial drug chloroquine. Although both fractions had showed considerable activity in the system, methanol extracts of both plants were more effective in inhibiting plasmodial growth in vitro than the hexane ones

Cellular and humoral immune responses against the Plasmodium vivax MSP-1(19) malaria vaccine candidate in individuals living in an endemic area in north-eastern Amazon region of Brazil

Background: Plasmodium vivax merozoite surface protein-1 (MSP-1) is an antigen considered to be one of the leading malaria vaccine candidates. PvMSP-1 is highly immunogenic and evidences suggest that it is target for protective immunity against asexual blood stages of malaria parasites. Thus, this study aims to evaluate the acquired cellular and antibody immune responses against PvMSP-1 in individuals naturally exposed to malaria infections in a malaria-endemic area in the north-eastern Amazon region of Brazil.Methods: the study was carried out in Paragominas, Para State, in the Brazilian Amazon. Blood samples were collected from 35 individuals with uncomplicated malaria. Peripheral blood mononuclear cells were isolated and the cellular proliferation and activation was analysed in presence of 19 kDa fragment of MSP-1 (PvMSP-1(19)) and Plasmodium falciparum PSS1 crude antigen. Antibodies IgE, IgM, IgG and IgG subclass and the levels of TNF, IFN-gamma and IL-10 were measured by enzyme-linked immunosorbent assay.Results: the prevalence of activated CD4(+) was greater than CD8(+) T cells, in both ex-vivo and in 96 h culture in presence of PvMSP-1(19) and PSS1 antigen. A low proliferative response against PvMSP-1(19) and PSS1 crude antigen after 96 h culture was observed. High plasmatic levels of IFN-gamma and IL-10 as well as lower TNF levels were also detected in malaria patients. However, in the 96 h supernatant culture, the dynamics of cytokine responses differed from those depicted on plasma assays; in presence of PvMSP-1(19) stimulus, higher levels of TNF were noted in supernatant 96 h culture of malaria patient's cells while low levels of IFN-gamma and IL-10 were verified. High frequency of malaria patients presenting antibodies against PvMSP-1(19) was evidenced, regardless class or IgG subclass. PvMSP-1(19)-induced antibodies were predominantly on non-cytophilic subclasses.Conclusions: the results presented here shows that PvMSP-1(19) was able to induce a high cellular activation, leading to production of TNF and emphasizes the high immunogenicity of PvMSP-1(19) in naturally exposed individuals and, therefore, its potential as a malaria vaccine candidate.Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Instituto Oswaldo Cruz (FIOCRUZ, Brazil)Fiocruz MS, Inst Oswaldo Cruz, Lab Pesquisas Malaria, BR-21040900 Rio de Janeiro, RJ, BrazilFiocruz MS, Ctr Pesquisa Diagnost & Treinamento Malaria CPD M, Reference Ctr Malaria Extra Amazonian Reg Secreta, BR-21040900 Rio de Janeiro, RJ, BrazilFiocruz MS, Inst Oswaldo Cruz, Lab Biol Mol & Doencas Endem, BR-21040900 Rio de Janeiro, RJ, BrazilUniv São Paulo, Dept Analises Clin & Toxicol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilSVS, Inst Evandro Chagas, Programa Ensaios Clin Malaria, Belem, Para, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilWeb of Scienc

Fixed-Dose Artesunate-Amodiaquine Combination vs Chloroquine for Treatment of Uncomplicated Blood Stage P. vivax Infection in the Brazilian Amazon: An Open-Label Randomized, Controlled Trial

BACKGROUND: Despite increasing evidence of the development of Plasmodium vivax chloroquine (CQ) resistance, there have been no trials comparing its efficacy with that of artemisinin-based combination therapies (ACTs) in Latin America. METHODS: This randomized controlled trial compared the antischizontocidal efficacy and safety of a 3-day supervised treatment of the fixed-dose combination artesunate-amodiaquine Winthrop(R) (ASAQ) versus CQ for treatment of uncomplicated P. vivax infection in Manaus, Brazil. Patients were followed for 42 days. Primary endpoints were adequate clinical and parasitological responses (ACPR) rates at day 28. Genotype-adjustment was performed. RESULTS: From 2012 to 2013, 380 patients were enrolled. In the per-protocol (PP) analysis, adjusted-ACPR was achieved in 100% (165/165) and 93.6% (161/172) of patients in the ASAQ and CQ arm (difference 6.4%, 95% CI 2.7%; 10.1%) at day 28 and in 97.4% (151/155) and 77.7% (129/166), respectively (difference 19.7%, 95% CI 12.9%; 26.5%), at day 42. Apart from ITT D28 assessment, superiority of ASAQ on ACPR was demonstrated. ASAQ presented faster clearance of parasitaemia and fever. Based on CQ blood level measurements, CQ resistance prevalence was estimated at 11.5% (95% CI: 7.5-17.3) up to day 42. At least one emergent adverse event (AE) was recorded for 79/190 (41x6%) in the ASAQ group and for 85/190 (44x7%) in the CQ group. Both treatments had similar safety profiles. CONCLUSIONS: ASAQ exhibited high efficacy against CQ resistant P. vivax and is an adequate alternative in the study area. Studies with an efficacious comparator, longer follow-up and genotype-adjustment can improve CQR characterization

Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial.

There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug.To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19. This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon. - Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days). - Label: Main Outcomes and Measures Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4. Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to high-dosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%). - Label: Conclusions and Relevance The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19

Living and avoiding malaria infection in endemic areas of the amazon basin

Submitted by Sandra Infurna ([email protected]) on 2019-12-03T14:10:40Z No. of bitstreams: 1 HelenaC.Guedes_ClaudioTDRibeiro_etal_IOC_1994.pdf: 122208 bytes, checksum: 8ae61b57516c3652d191151dc3b9a002 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-12-03T14:16:44Z (GMT) No. of bitstreams: 1 HelenaC.Guedes_ClaudioTDRibeiro_etal_IOC_1994.pdf: 122208 bytes, checksum: 8ae61b57516c3652d191151dc3b9a002 (MD5)Made available in DSpace on 2019-12-03T14:16:44Z (GMT). No. of bitstreams: 1 HelenaC.Guedes_ClaudioTDRibeiro_etal_IOC_1994.pdf: 122208 bytes, checksum: 8ae61b57516c3652d191151dc3b9a002 (MD5) Previous issue date: 1994Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil

Autoimmunity, phospholipid-reacting antibodies and malaria immunity

Made available in DSpace on 2015-06-08T14:01:51Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) lr_gomesetal_IOC_2014.pdf: 143511 bytes, checksum: 9aeaea966a032e26cc166f8d5c100d18 (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Brasília, DF, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Brasília, DF, Brasil / Albert Einstein College of Medicine. Department of Pathology. NewYork, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Brasília, DF, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Brasília, DF, Brasil.Several questions regarding the production and functioning of autoantibodies (AAb) during malaria infection remain open. Here we provide an overview of studies conducted in our laboratory that shed some light on the questions of whether antiphospholipid antibodies (aPL) and other AAb associated with autoimmune diseases (AID) can recognize Plasmodia antigens and exert anti-parasite activity; and whether anti-parasite phospholipid antibodies, produced in response to malaria, can inhibit phospholipid-induced inflammatory responses and protect against the pathogenesis of severe malaria. Our work showed that sera from patients with AID containing AAb against dsDNA, ssDNA, nuclear antigens (ANA), actin, cardiolipin (aCL) and erythrocyte membrane antigens recognize plasmodial antigens and can, similarly to monoclonal AAb of several specificities including phospholipid, inhibit the growth of P. falciparum in vitro. However, we did not detect a relationship between the presence of anti-glycosylphosphatidylinositol (GPI) antibodies in the serum and asymptomatic malaria infection, although we did register a relationship between these antibodies and parasitemia levels in infected individuals. Taken together, these results indicate that autoimmune responses mediated by AAb of different specificities, including phospholipid, may have anti-plasmodial activity and protect against malaria, although it is not clear whether anti-parasite phospholipid antibodies can mediate the same effect. The potential effect of anti-parasite phospholipid antibodies in malarious patients that are prone to the development of systemic lupus erythematosus or antiphospholipid syndrome, as well as the (possibly protective?) role of the (pathogenic) aPL on the malaria symptomatology and severity in these individuals, remain open questions

Monoclonal auto-antibodies and sera of autoimmune patients react with Plasmodium falciparum and inhibit its in vitro growth

Graziela Maria Zanini. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento.Submitted by Sandra Infurna ([email protected]) on 2018-04-17T15:10:32Z No. of bitstreams: 1 graziela2_zanini_etal_IOC_2011.pdf: 359196 bytes, checksum: 6ec0b6c731d60f1f1caf1c81ec94a5dd (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2018-04-17T15:19:38Z (GMT) No. of bitstreams: 1 graziela2_zanini_etal_IOC_2011.pdf: 359196 bytes, checksum: 6ec0b6c731d60f1f1caf1c81ec94a5dd (MD5)Made available in DSpace on 2018-04-17T15:19:38Z (GMT). No. of bitstreams: 1 graziela2_zanini_etal_IOC_2011.pdf: 359196 bytes, checksum: 6ec0b6c731d60f1f1caf1c81ec94a5dd (MD5) Previous issue date: 2011Institut Pasteur. Laboratorie de Parasitologie Biomédicale. Paris, France.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Centro de Pesquisa, Diagnóstico e Treinamento em Malária. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Centro de Pesquisa, Diagnóstico e Treinamento em Malária. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Centro de Pesquisa, Diagnóstico e Treinamento em Malária. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil.The relationship between autoimmunity and malaria is not well understood. To determine whether autoimmune responses have a protective role during malaria, we studied the pattern of reactivity to plasmodial antigens of sera from 93 patients with 14 different autoimmune diseases (AID) who were not previously exposed to malaria. Sera from patients with 13 different AID reacted against Plasmodium falciparum by indirect fluorescent antibody test with frequencies varying from 33-100%. In addition, sera from 37 AID patients were tested for reactivity against Plasmodium yoelii 17XNL and the asexual blood stage forms of three different P. falciparum strains. In general, the frequency of reactive sera was higher against young trophozoites than schizonts (p < 0.05 for 2 strains), indicating that the antigenic determinants targeted by the tested AID sera might be more highly expressed by the former stage. The ability of monoclonal auto-antibodies (auto-Ab) to inhibit P. falciparum growth in vitro was also tested. Thirteen of the 18 monoclonal auto-Ab tested (72%), but none of the control monoclonal antibodies, inhibited parasite growth, in some cases by greater than 40%. We conclude that autoimmune responses mediated by auto-Ab may present anti-plasmodial activity

Plasmodium berghei ANKA infection induces thymocyte apoptosis and thymocyte depletion in CBA mice

Submitted by Gentil Jeorgina ([email protected]) on 2012-05-10T14:20:48Z No. of bitstreams: 1 ANKA.pdf: 1292520 bytes, checksum: 5dba12422698e3ed0184fad9c22ea1ca (MD5)Made available in DSpace on 2012-05-10T14:20:48Z (GMT). No. of bitstreams: 1 ANKA.pdf: 1292520 bytes, checksum: 5dba12422698e3ed0184fad9c22ea1ca (MD5) Previous issue date: 2006Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Laboratório de Pesquisas em Malária. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Laboratório de Pesquisas em Malária. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Laboratório de Pesquisas em Malária. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Patologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Patologia. Rio de Janeiro, RJ, Brasil.Immune responses to malaria infections are characterized by strong T and B cell activation, which, in addition of potentially causing immunopathology, are of poor efficacy against the infection. It is possible that the thymus is involved in the origin of immunopathological reactions and a target during malaria infections. This work was developed in an attempt to further clarify these points. We studied the sequential changes in the thymus of CBA mice infected with Plasmodium berghei ANKA, a model in which 60-90% of the infected animals develop cerebral malaria. During the acute phase of infection, different degrees of thymocyte apoptosis were recorded: (1) starry-sky pattern of diffuse apoptosis with maintenance of cortical-medullary structure; (2) intense apoptosis with cortical atrophy, with absence of large cells; (3) severe cortical thymocyte depletion, resulting in cortical-medullary inversion. In the latter, only residual clusters of small thymocytes were observed within the framework of epithelial cells. The intensity of thymus alterations could not be associated with the degree of parasitemia, the expression of clinical signs of cerebral malaria or intensity of brain lesions. The implications of these events for malaria immunity and pathology are discussed