Search

Objective: To compare the clinical outcomes of patients infected with SARS-CoV-2 variants with patients infected with the original strain. Methods: This is a case control study comparing cases of COVID-19 patients infected with SARS-CoV-2 variants of concern identified by genomic sequencing, with a control group of 62 patients randomly selected from a COVID-19 database of patients diagnosed prior to the emergence of these variants. Findings: In the 40 patients infected with variants, the predominant (52.5%) was P.1 variant. The variant group presented more arthralgia (p=0.015), hyporexia (p=0.006), nausea/vomiting (p=0.048), and mental confusion (p=0.029), the last not identified in the control group. There were no significant differences in comorbidities or demographic data between the groups. Severe disease, according to the WHO Clinical Progression Scale, was identified only in those infected with the variants, as well as high-flow oxygen therapy and ICU admission (p=0.05). The two deaths reported in the study were in patients infected with the variants. Conclusions: The worst outcomes were observed in the group infected with SARS-CoV-2 variants, although no significant differences in comorbidities or demographics date were observed between the groups. Objetivo: Comparar los resultados clínicos de los pacientes infectados con variantes del SARS-CoV-2 con los pacientes infectados con la cepa original. Métodos: Se trata de un estudio de casos y controles que comprende casos de pacientes con COVID-19 infectados con variantes de la preocupación por SARS-CoV-2, identificados por secuenciación genómica, con un grupo control de 62 pacientes seleccionados aleatoriamente de una base de datos de pacientes con COVID-19 diagnosticados antes de la aparición de estas variantes de preocupación. Resultados: En los 40 pacientes infectados con las variantes, la forma predominante fue la variante P.1 (52,5%). El grupo infectado con variantes presentó más artralgia (p=0,015), hiporexia (p=0,006), náuseas/vómitos (p=0,048) y confusión mental (p=0,029), no identificándose esta última en el grupo control. No hubo diferencias significativas entre los grupos cuando se compararon las comorbilidades o los datos geográficos. La forma grave de la enfermedad, según la Escala de Progresión de la OMS, se identificó solo en aquellos infectados con formas variantes, así como el uso de oxigenoterapia de alto flujo y el ingreso en la UCI (p = 0,05). Las dos muertes reportadas en el estudio fueron en pacientes infectados con formas variantes del virus. Conclusiones: Los peores resultados se observaron en el grupo infectado con variantes del SARS-CoV-2, aunque no hubo diferencias significativas en las comorbilidades ni en los datos demográficos entre los grupos. Objetivo: Comparar os desfechos clínicos de pacientes infectados com variantes dos SARS-CoV-2 com pacientes infectados com a cepa original. Métodos: Este é um estudo caso controle que compara casos de pacientes com COVID-19 infectados com variantes de preocupação do SARS-CoV-2, identificadas por sequenciamento genômico, com um grupo controle de 62 pacientes selecionados aleatoriamente de um banco de dados de pacientes com COVID-19 diagnosticados previamente ao surgimento dessas variantes de preocupação. Resultados: Nos 40 pacientes infectados com as variantes, a forma predominante foi a variante P.1 (52,5%). O grupo infectado por variantes apresentou mais artralgia (p=0,015), hiporexia (p=0,006), náusea/vômito (p=0,048) e confusão mental (p=0,029), sendo esta última não identificada no grupo controle. Não houve diferenças significativas entre os grupos quando comparados comorbidades ou dados geográficos. Forma grave da doença, de acordo com a Escala de Progressão da OMS, foi identificada somente naqueles infectados com as formas variantes, assim como o uso de oxigenoterapia de alto fluxo e admissão na UTI (p=0,05). As duas mortes reportadas no estudo foram em pacientes infectados com formas variantes do vírus. Conclusões: Os piores desfechos foram observados no grupo infectado com variantes do SARS-CoV-2, apesar de não haver diferenças significativas nas comorbidades ou dados demográficos entre os grupos.

Texto completo: acesso restrito. p. 4460-4467 Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-08-11T13:43:08Z No. of bitstreams: 1 Nívea F. Luz.pdf: 1584833 bytes, checksum: aeb0961f7c6201b1a38868d69549901f (MD5) Rejected by Delba Rosa (delba@ufba.br), reason: Por gentileza, Cite todos os autores; O endereço eletrônico não confere. Grata on 2014-10-09T16:03:14Z (GMT) Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-10-14T11:18:15Z No. of bitstreams: 1 Nívea F. Luz.pdf: 1584833 bytes, checksum: aeb0961f7c6201b1a38868d69549901f (MD5) Approved for entry into archive by Delba Rosa (delba@ufba.br) on 2014-10-14T12:13:10Z (GMT) No. of bitstreams: 1 Nívea F. Luz.pdf: 1584833 bytes, checksum: aeb0961f7c6201b1a38868d69549901f (MD5) Made available in DSpace on 2014-10-14T12:13:10Z (GMT). No. of bitstreams: 1 Nívea F. Luz.pdf: 1584833 bytes, checksum: aeb0961f7c6201b1a38868d69549901f (MD5) Previous issue date: 2012 Visceral leishmaniasis (VL) remains a major public health problem worldwide. This disease is highly associated with chronic inflammation and a lack of the cellular immune responses against Leishmania. It is important to identify major factors driving the successful establishment of the Leishmania infection to develop better tools for the disease control. Heme oxygenase-1 (HO-1) is a key enzyme triggered by cellular stress, and its role in VL has not been investigated. In this study, we evaluated the role of HO-1 in the infection by Leishmania infantum chagasi, the causative agent of VL cases in Brazil. We found that L. chagasi infection or lipophosphoglycan isolated from promastigotes triggered HO-1 production by murine macrophages. Interestingly, cobalt protoporphyrin IX, an HO-1 inductor, increased the parasite burden in both mouse and human-derived macrophages. Upon L. chagasi infection, macrophages from Hmox1 knockout mice presented significantly lower parasite loads when compared with those from wild-type mice. Furthermore, upregulation of HO-1 by cobalt protoporphyrin IX diminished the production of TNF-α and reactive oxygen species by infected murine macrophages and increased Cu/Zn superoxide dismutase expression in human monocytes. Finally, patients with VL presented higher systemic concentrations of HO-1 than healthy individuals, and this increase of HO-1 was reduced after antileishmanial treatment, suggesting that HO-1 is associated with disease susceptibility. Our data argue that HO-1 has a critical role in the L. chagasi infection and is strongly associated with the inflammatory imbalance during VL. Manipulation of HO-1 pathways during VL could serve as an adjunctive therapeutic approach.

11 p. Submitted by Ana Valéria de Jesus Moura (anavaleria_131@hotmail.com) on 2012-03-05T18:37:25Z No. of bitstreams: 1 journal.pntd.0000965.pdf: 1202285 bytes, checksum: 5c2616df5399151d5b3c2dfc7bdb6a25 (MD5) Made available in DSpace on 2012-03-05T18:37:25Z (GMT). No. of bitstreams: 1 journal.pntd.0000965.pdf: 1202285 bytes, checksum: 5c2616df5399151d5b3c2dfc7bdb6a25 (MD5) Previous issue date: 2011-02 Background: Leishmania braziliensis is the main causative agent of cutaneous leishmaniasis in Brazil. Protection against infection is related to development of Th1 responses, but the mechanisms that mediate susceptibility are still poorly understood. Murine models have been the most important tools in understanding the immunopathogenesis of L. major infection and have shown that Th2 responses favor parasite survival. In contrast, L. braziliensis–infected mice develop strong Th1 responses and easily resolve the infection, thus making the study of factors affecting susceptibility to this parasite difficult. Methodology/Principal Findings: Here, we describe an experimental model for the evaluation of the mechanisms mediating susceptibility to L. braziliensis infection. BALB/c mice were inoculated with stationary phase promastigotes of L. braziliensis, isolates LTCP393(R) and LTCP15171(S), which are resistant and susceptible to antimony and nitric oxide (NO), respectively. Mice inoculated with LTCP393(R) presented larger lesions that healed more slowly and contained higher parasite loads than lesions caused by LTCP15171(S). Inflammatory infiltrates in the lesions and production of IFN-c, TNF-a, IL-10 and TGF-b were similar in mice inoculated with either isolate, indicating that these factors did not contribute to the different disease manifestations observed. In contrast, IL-4 production was strongly increased in LTCP393(R)-inoculated animals and also arginase I (Arg I) expression. Moreover, anti-IL-4 monoclonal antibody (mAb) treatment resulted in decreased lesion thickness and parasite burden in animals inoculated with LTCP393(R), but not in those inoculated with LTCP15171(S). Conclusion/Significance: We conclude that the ability of L. braziliensis isolates to induce Th2 responses affects the susceptibility to infection with these isolates and contributes to the increased virulence and severity of disease associated with them. Since these data reflect what happens in human infection, this model could be useful to study the pathogenesis of the L. braziliensis infection, as well as to design new strategies of therapeutic intervention.

BACKGROUND: Nitric oxide (NO) produced in macrophages plays a pivotal role as a leishmanicidal agent. A previous study has demonstrated that 20% of the L. (V.) braziliensis isolated from initial cutaneous lesions of patients from the endemic area of Corte de Pedra, Bahia, Brazil, were NO resistant. Additionally, 5 to 11% of the patients did not respond to three or more antimony treatments" (refractory patients). The aim of this study is to investigate if there is an association between the resistance of L. (V.) braziliensis to NO and nonresponsiveness to antimony therapy and cytokine production. METHODS: We evaluated the in vitro toxicity of NO against the promastigotes stages of L. (V.) braziliensis isolated from responsive and refractory patients, and the infectivity of the amastigote forms of these isolates against human macrophages. The supernatants from Leishmania infected macrophage were used to measure TNF-α and IL-10 levels. RESULTS: Using NaNO2 (pH 5.0) as the NO source, L. (V.) braziliensis isolated from refractory patients were more NO resistant (IC50 = 5.8 ± 4.8) than L. (V.) braziliensis isolated from responsive patients (IC50 = 2.0 ± 1.4). Four isolates were selected to infect human macrophages: NO-susceptible and NO-resistant L. (V.) braziliensis isolated from responsive and refractory patients. NO-resistant L. (V.) braziliensis isolated from refractory patients infected more macrophages stimulated with LPS and IFN-γ at 120 hours than NO-susceptible L. (V.) braziliensis isolated from refractory patients. Also, lower levels of TNF-α were detected in supernatants of macrophages infected with NO-resistant L. (V.) braziliensis as compared to macrophages infected with NO-susceptible L. (V.) braziliensis (p < 0.05 at 2, 24 and 120 hours), while no differences were detected in IL-10 levels. CONCLUSION: These data suggest that NO resistance could be related to the nonresponsiveness to antimony therapy seen in American Tegumentary Leishmaniasis.

Texto completo: acesso restrito. p. 607-613 Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2013-08-27T11:24:37Z No. of bitstreams: 1 1-s2.0-S1567134810001048-main.pdf: 190164 bytes, checksum: 653f3fd37a385fc9938a5a0dd06157ac (MD5) Approved for entry into archive by Rodrigo Meirelles (rodrigomei@ufba.br) on 2013-11-16T12:54:26Z (GMT) No. of bitstreams: 1 1-s2.0-S1567134810001048-main.pdf: 190164 bytes, checksum: 653f3fd37a385fc9938a5a0dd06157ac (MD5) Made available in DSpace on 2013-11-16T12:54:26Z (GMT). No. of bitstreams: 1 1-s2.0-S1567134810001048-main.pdf: 190164 bytes, checksum: 653f3fd37a385fc9938a5a0dd06157ac (MD5) Previous issue date: 2010 Mucosal leishmaniasis (ML) follows localized cutaneous leishmaniasis (CL) caused by Leishmania braziliensis. Proinflammatory responses mediate CL self-healing but are exaggerated in ML. Proinflammatory monocyte chemoattractant protein 1 (MCP-1; encoded by CCL2) is associated with CL. We explore its role in CL/ML through analysis of the regulatory CCL2 −2518 bp promoter polymorphism in CL/ML population samples and families from Brazil. Genotype frequencies were compared among ML/CL cases and control groups using logistic regression and the family-based association test (FBAT). MCP-1 was measured in plasma and macrophages. The GG recessive genotype at CCL2 −2518 bp was more common in patients with ML (N = 67) than in neighborhood control (NC; N = 60) subjects (OR 1.78; 95% CI 1.01–3.14; P = 0.045), than in NC combined with leishmanin skin-test positive (N = 60) controls (OR 4.40; 95% CI 1.42–13.65; P = 0.010), and than in controls combined with CL (N = 60) patients (OR 2.78; 95% CI 1.13–6.85; P = 0.045). No associations were observed for CL compared to any groups. FBAT (91 ML and 223 CL cases in families) confirmed recessive association of ML with allele G (Z = 2.679; P = 0.007). Higher levels of MCP-1 occurred in plasma (P = 0.03) and macrophages (P < 0.0001) from GG compared to AA individuals. These results suggest that high MCP-1 increases risk of ML.

11 p. Submitted by Ana Valéria de Jesus Moura (anavaleria_131@hotmail.com) on 2012-01-03T18:13:34Z No. of bitstreams: 1 1471-2334-10-209.pdf: 831689 bytes, checksum: 81210b7bed68f57e3ff85e018c57b8a5 (MD5) Made available in DSpace on 2012-01-03T18:13:34Z (GMT). No. of bitstreams: 1 1471-2334-10-209.pdf: 831689 bytes, checksum: 81210b7bed68f57e3ff85e018c57b8a5 (MD5) Previous issue date: 2010 Background: Nitric oxide (NO) produced in macrophages plays a pivotal role as a leishmanicidal agent. A previous study has demonstrated that 20% of the L. (V.) braziliensis isolated from initial cutaneous lesions of patients from the endemic area of Corte de Pedra, Bahia, Brazil, were NO resistant. Additionally, 5 to 11% of the patients did not respond to three or more antimony treatments” (refractory patients). The aim of this study is to investigate if there is an association between the resistance of L. (V.) braziliensis to NO and nonresponsiveness to antimony therapy and cytokine production. Methods: We evaluated the in vitro toxicity of NO against the promastigotes stages of L. (V.) braziliensis isolated from responsive and refractory patients, and the infectivity of the amastigote forms of these isolates against human macrophages. The supernatants from Leishmania infected macrophage were used to measure TNF-a and IL-10 levels. Results: Using NaNO2 (pH 5.0) as the NO source, L. (V.) braziliensis isolated from refractory patients were more NO resistant (IC50 = 5.8 ± 4.8) than L. (V.) braziliensis isolated from responsive patients (IC50 = 2.0 ± 1.4). Four isolates were selected to infect human macrophages: NO-susceptible and NO-resistant L. (V.) braziliensis isolated from responsive and refractory patients. NO-resistant L. (V.) braziliensis isolated from refractory patients infected more macrophages stimulated with LPS and IFN-g at 120 hours than NO-susceptible L. (V.) braziliensis isolated from refractory patients. Also, lower levels of TNF-a were detected in supernatants of macrophages infected with NO-resistant L. (V.) braziliensis as compared to macrophages infected with NO-susceptible L. (V.) braziliensis (p < 0.05 at 2, 24 and 120 hours), while no differences were detected in IL-10 levels. Conclusion: These data suggest that NO resistance could be related to the nonresponsiveness to antimony therapy seen in American Tegumentary Leishmaniasis.

BACKGROUND: Nitric oxide (NO•) plays a pivotal role as a leishmanicidal agent in mouse macrophages. NO• resistant Escherichia coli and Mycobacterium tuberculosis have been associated with a severe outcome of these diseases. METHODS: In this study we evaluated the in vitro toxicity of nitric oxide for the promastigote stages of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis parasites, and the infectivity of the amastigote stage for human macrophages. Parasites were isolated from patients with cutaneous, mucosal or disseminated leishmaniasis, and NO• resistance was correlated with clinical presentation. RESULTS: Seventeen isolates of L. (L.) amazonensis or L. (V.) braziliensis promastigotes were killed by up to 8 mM of more of NaNO2 (pH 5.0) and therefore were defined as nitric oxide-susceptible. In contrast, eleven isolates that survived exposure to 16 mM NaNO2 were defined as nitric oxide-resistant. Patients infected with nitric oxide-resistant Leishmania had significantly larger lesions than patients infected with nitric oxide-susceptible isolates. Furthermore, nitric oxide-resistant L. (L.) amazonensis and L. (V.) braziliensis multiplied significantly better in human macrophages than nitric oxide-susceptible isolates. CONCLUSION: These data suggest that nitric oxide-resistance of Leishmania isolates confers a survival benefit for the parasites inside the macrophage, and possibly exacerbates the clinical course of human leishmaniasis.

Texto completo: acesso restrito. p. 478-482 Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2014-01-21T11:51:20Z No. of bitstreams: 1 10.1086-520017.pdf: 284401 bytes, checksum: a82c59fcd9d227388c9c10c70bb4f53d (MD5) Rejected by Flávia Ferreira (flaviaccf@yahoo.com.br), reason: Por favor faça a inclusão dos autores de todos autores do artigo. Grata, on 2014-01-28T12:59:33Z (GMT) Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2014-01-28T16:04:49Z No. of bitstreams: 1 10.1086-520017.pdf: 284401 bytes, checksum: a82c59fcd9d227388c9c10c70bb4f53d (MD5) Approved for entry into archive by Flávia Ferreira (flaviaccf@yahoo.com.br) on 2014-01-30T13:28:59Z (GMT) No. of bitstreams: 1 10.1086-520017.pdf: 284401 bytes, checksum: a82c59fcd9d227388c9c10c70bb4f53d (MD5) Made available in DSpace on 2014-01-30T13:28:59Z (GMT). No. of bitstreams: 1 10.1086-520017.pdf: 284401 bytes, checksum: a82c59fcd9d227388c9c10c70bb4f53d (MD5) Previous issue date: 2007 Cutaneous leishmaniasis affects millions of people worldwide. After observations of atypical lesions in pregnant women at the health centers of Corte de Pedra, Brazil, 9 years of records were reviewed, and 26 pregnant patients were identified. A retrospective case-control study revealed that lesions in pregnant women were much larger than those in nonpregnant patients in an age- and sex-matched group (mean area, 6.08 cm2 vs. 1.46 cm2; P = .008), and many lesions had an exophytic nature. Despite foregoing treatment until after delivery, response to pentavalent antimony therapy was favorable (rate of cure with 1 course of treatment, 85%). High rates of preterm births (10.5%) and stillbirths (10.5%) were reported. Cutaneous leishmaniasis during pregnancy produces distinct lesions and may have adverse fetal effects.

Texto completo: acesso restrito. p. 251-258 Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2014-01-24T15:57:07Z No. of bitstreams: 1 j.1365-3024.2007.00940.x.pdf: 240676 bytes, checksum: fcbb7c920988e7f9f6a2ee087c48d762 (MD5) Approved for entry into archive by Rodrigo Meirelles (rodrigomei@ufba.br) on 2014-09-09T16:14:33Z (GMT) No. of bitstreams: 1 j.1365-3024.2007.00940.x.pdf: 240676 bytes, checksum: fcbb7c920988e7f9f6a2ee087c48d762 (MD5) Made available in DSpace on 2014-09-09T16:14:33Z (GMT). No. of bitstreams: 1 j.1365-3024.2007.00940.x.pdf: 240676 bytes, checksum: fcbb7c920988e7f9f6a2ee087c48d762 (MD5) Previous issue date: 2007 Cutaneous (CL) and mucosal leishmaniasis (ML) are characterized by a predominant type 1 immune response (IFN-γ and TNF-α production) and strong inflammatory response in the lesions with few parasites. This exacerbated type 1 response is more evident in ML as compared to CL. Our main hypothesis is that a differential immune regulation of T cell activation leads to over reactive T cells in ML. In the present study, we investigated immunological factors that could explain the mechanisms behind it by comparing some immune regulatory mechanisms between ML and CL patients: frequency of cells expressing co-stimulatory molecules, apoptotic markers, T cell activation markers; and ability of neutralizing antibodies to IL-2, IL-12 and IL-15 do down-regulate IFN-γ production in leishmania antigen-stimulated peripheral blood mononuclear cells (PBMC). Interestingly, in CL anti-IL-2 and anti-IL-15 significantly suppressed antigen-specific IFN-γ production, while in ML only anti-IL-2 suppressed IFN-γ production. Finally, higher frequency of CD4+ T cells expressing CD28−, CD69+ and CD62Llow were observed in ML as compared to CL. These data indicate that an exacerbated type 1 response in ML is differentially regulated and not appropriately down modulated, with increased frequencies of activated effectors T cells, maintaining the persistent inflammatory response and tissue damage observed in ML.

Texto completo: acesso restrito. p. 1017–1024 Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2014-03-11T15:14:47Z No. of bitstreams: 1 10.1128IAI.00914-06.pdf: 554649 bytes, checksum: e4ffaf2b2ca32eca83ae35e61b28e6e0 (MD5) Approved for entry into archive by Flávia Ferreira (flaviaccf@yahoo.com.br) on 2014-04-09T13:04:35Z (GMT) No. of bitstreams: 1 10.1128IAI.00914-06.pdf: 554649 bytes, checksum: e4ffaf2b2ca32eca83ae35e61b28e6e0 (MD5) Made available in DSpace on 2014-04-09T13:04:35Z (GMT). No. of bitstreams: 1 10.1128IAI.00914-06.pdf: 554649 bytes, checksum: e4ffaf2b2ca32eca83ae35e61b28e6e0 (MD5) Previous issue date: 2007 Leishmania spp. are intracellular protozoa residing in mononuclear phagocytes. Leishmania organisms are susceptible to microbicidal responses generated in response to phagocytosis. Assuming that both phagocyte and parasite populations are heterogeneous, it is advantageous to examine the response of individual cells phagocytosing living parasites. Because Leishmania spp. lose virulence during the raising of transfectants, we developed a method to label live Leishmania chagasi short-term with fluorescent dyes. Up to six parasite divisions were detected by flow cytometry after labeling with carboxyfluorescein diacetate succinimidyl ester (CFSE), dioctadecyl-tetramethylindo carbocyanine perchlorate, or chloromethyl tetramethylrhodamine. Labeled parasites entered mononuclear phagocytes as determined by confocal and time-lapse microscopy. Dihydroethidium (DHE) was used to detect macrophage-derived oxidants generated during phagocytosis. Presumably Leishmania organisms are opsonized with host serum/tissue components such as complement prior to phagocytosis. Therefore, we investigated the effects of opsonization and found that this increased the efficiency of CFSE-labeled parasite entry into monocytes (84.6% ± 8.8% versus 20.2% ± 3.8% monocytes infected; P < 0.001). Opsonization also increased the percentage of phagocytes undergoing a respiratory burst (66.0% ± 6.3% versus 41.0% ± 8.3% of monocytes containing CFSE-labeled parasites; P < 0.001) and the magnitude of oxidant generation by each infected monocyte. Inhibitor data indicated that DHE was oxidized by products of the NADPH oxidase. These data suggest that opsonized serum components such as complement lead to more efficient entry of Leishmania into their target cells but at the same time activate the phagocyte oxidase to generate microbicidal products in infected cells. The parasite must balance these positive and negative survival effects in order to initiate a viable infection.

BACKGROUND: Disseminated leishmaniasis is an emerging infectious disease, mostly due to L. braziliensis, which has clinical and histopathological features distinct from cutaneous leishmaniasis. METHODS: In the current study we evaluated the in vitro production of the cytokines IFN-γ, TNF-α, IL-5 and IL-10 by peripheral blood mononuclear cells (PBMC) from 15 disseminated leishmaniasis and 24 cutaneous leishmaniasis patients upon stimulation with L. braziliensis antigens genotyped as disseminated leishmaniasis or cutaneous leishmaniasis isolates. RESULTS: Regardless of the source of L. braziliensis antigens, PBMC from cutaneous leishmaniasis patients produced significantly higher IFN-γ than PBMC from disseminated leishmaniasis patients. Levels of TNF-α by PBMC from cutaneous leishmaniasis patients were significantly higher than disseminated leishmaniasis patients only when stimulated by genotyped cutaneous leishmaniasis antigens. The levels of IL-5 and IL-10 production by PBMC were very low and similar in PBMCs from both disseminated leishmaniasis and cutaneous leishmaniasis patients. The immune response of each patient evaluated by the two L. braziliensis antigens was assessed in a paired analysis in which we showed that L. braziliensis genotyped as disseminated leishmaniasis isolate was more potent than L. braziliensis genotyped as cutaneous leishmaniasis isolate in triggering IFN-γ and TNF-α production in both diseases and IL-5 only in cutaneous leishmaniasis patients. CONCLUSION: This study provides evidence that antigens prepared from genotypically distinct strains of L. braziliensis induce different degrees of immune response. It also indicates that both parasite and host play a role in the outcome of L. braziliensis infection.

p.1-6 Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2013-08-27T11:36:10Z No. of bitstreams: 1 1471-2334-6-75.pdf: 289112 bytes, checksum: 456a013c7aad83ff1a9b0fa90711a95d (MD5) Approved for entry into archive by Patricia Barroso(pbarroso@ufba.br) on 2013-08-27T17:37:57Z (GMT) No. of bitstreams: 1 1471-2334-6-75.pdf: 289112 bytes, checksum: 456a013c7aad83ff1a9b0fa90711a95d (MD5) Made available in DSpace on 2013-08-27T17:37:57Z (GMT). No. of bitstreams: 1 1471-2334-6-75.pdf: 289112 bytes, checksum: 456a013c7aad83ff1a9b0fa90711a95d (MD5) Previous issue date: 2006 Background: Disseminated leishmaniasis is an emerging infectious disease, mostly due to L. braziliensis, which has clinical and histopathological features distinct from cutaneous leishmaniasis. Methods: In the current study we evaluated the in vitro production of the cytokines IFN-γ, TNF-α, IL-5 and IL-10 by peripheral blood mononuclear cells (PBMC) from 15 disseminated leishmaniasis and 24 cutaneous leishmaniasis patients upon stimulation with L. braziliensis antigens genotyped as disseminated leishmaniasis or cutaneous leishmaniasis isolates. Results: Regardless of the source of L. braziliensis antigens, PBMC from cutaneous leishmaniasis patients produced significantly higher IFN-γ than PBMC from disseminated leishmaniasis patients. Levels of TNF-α by PBMC from cutaneous leishmaniasis patients were significantly higher than disseminated leishmaniasis patients only when stimulated by genotyped cutaneous leishmaniasis antigens. The levels of IL-5 and IL-10 production by PBMC were very low and similar in PBMCs from both disseminated leishmaniasis and cutaneous leishmaniasis patients. The immune response of each patient evaluated by the two L. braziliensis antigens was assessed in a paired analysis in which we showed that L. braziliensis genotyped as disseminated leishmaniasis isolate was more potent than L. braziliensis genotyped as cutaneous leishmaniasis isolate in triggering IFN-γ and TNF-α production in both diseases and IL-5 only in cutaneous leishmaniasis patients. Conclusion: This study provides evidence that antigens prepared from genotypically distinct strains of L. braziliensis induce different degrees of immune response. It also indicates that both parasite and host play a role in the outcome of L. braziliensis infection.

Texto completo:acesso restrito. p. 341-348. Submitted by JURANDI DE SOUZA SILVA (jssufba@hotmail.com) on 2012-12-13T17:47:37Z No. of bitstreams: 1 j.1365-2249.2004.02426.x.pdf: 154075 bytes, checksum: b96d36a6be1a7e1d84e73a6a964ddf6a (MD5) Made available in DSpace on 2012-12-13T17:47:37Z (GMT). No. of bitstreams: 1 j.1365-2249.2004.02426.x.pdf: 154075 bytes, checksum: b96d36a6be1a7e1d84e73a6a964ddf6a (MD5) Previous issue date: 2004 Regulation of the immune response directed against Leishmaniais critical for the establishment of effective control of the disease. It is likely that some types of immune responses directed against Leishmania can lead to more severe clinical forms of leishmaniasis causing a poor control of the pathogen and/or pathology, while others lead to resolution of the infection with little pathology as in cutaneous leishmaniasis. To gain a better understanding of the possible role that subpopulations of T cells, and their associated cytokines have on disease progression and/or protective immune responses to L. braziliensis infection, a detailed study of the frequency of activated and memory T cells, as well as antigen specific, cytokine producing T cells was carried out. Following the determination of cytokine producing mononuclear cell populations in response to total Leishmania antigen (SLA), and to the recombinant antigen LACK, correlation analysis were performed between specific cytokine producing populations to identify models for cellular mechanisms of immunoregulation in human cutaneous leishmaniasis.These studies have shown: (1) a positive correlation between ex vivo CD45RO frequencies and antigen specific cytokine (IFN-gamma or IL-10) producing cells; (2) a negative correlation between ex vivo CD69 expression and the frequency of IFN-gamma producing cells; (3) a positive correlation amongst SLA specific, IFN-gamma or TNF-alpha and IL-10 producing lymphocytes with one another; and (4) a higher frequency of IL-10 producing, parasite specific (anti-SLA or anti-LACK), lymphocytes are correlated with a lower frequency of TNF-alpha producing monocytes, demonstrating an antigen specific delivery of IL-10 inducing negative regulation of monocyte activity.

p. 508–514 Submitted by Ana Valéria de Jesus Moura (anavaleria_131@hotmail.com) on 2011-12-11T17:03:46Z No. of bitstreams: 1 1077.pdf: 1159272 bytes, checksum: 42eaf0f40906bf9b35739de038ee64f2 (MD5) Made available in DSpace on 2011-12-11T17:03:46Z (GMT). No. of bitstreams: 1 1077.pdf: 1159272 bytes, checksum: 42eaf0f40906bf9b35739de038ee64f2 (MD5) Previous issue date: 2004-01 In Corte de Pedra (CP), northeastern Brazil, Leishmania braziliensis causes three distinct forms of American tegumentary leishmaniasis (ATL). To test the hypothesis that strain polymorphism may be involved in this disease spectrum and accurately characterize the parasite population structure in CP, we compared one L. major, two non-CP L. braziliensis, one CP L. amazonensis, and 45 CP L. braziliensis isolates, obtained over a 10-year period from localized cutaneous, mucosal, and disseminated leishmaniasis patients, with randomly amplified polymorphic DNA (RAPD). Electrophoretic profiles were mostly unique across species. All typing protocols revealed polymorphism among the 45 CP L. braziliensis isolates, which displayed eight different RAPD patterns and greater than 80% overall fingerprint identity, attesting to the adequacy of the tools to assess strain variability in CP’s geographically limited population of parasites. The dendrogram based on the sum of RAPD profiles of each isolate unveiled nine discrete typing units clustered into five clades. Global positioning showed extensive overlap of these clades in CP, precluding geographic sequestration as the mechanism of the observed structuralization. Finally, all forms of ATL presented a statistically significant difference in their frequencies among the clades, suggesting that L. braziliensis genotypes may be accompanied by specific disease manifestation after infection.

Texto completo: acesso restrito. p. 101-104 Submitted by Suelen Reis (suelen_suzane@hotmail.com) on 2012-12-17T14:07:20Z No. of bitstreams: 1 101.full.pdf: 157103 bytes, checksum: efc876856ea0c49fcc9a0e237a93cbcd (MD5) Made available in DSpace on 2012-12-17T14:07:21Z (GMT). No. of bitstreams: 1 101.full.pdf: 157103 bytes, checksum: efc876856ea0c49fcc9a0e237a93cbcd (MD5) Previous issue date: 2002-01 High levels of antileishmanial immunoglobulin E (IgE) antibodies are associated with disease activity in visceral leishmaniasis. Herein, we report our observations about the relationship between antileishmanial IgE antibodies and clinical aspects of cutaneous leishmaniasis. This study was carried out with 45 patients (29 male and 16 female), with ages ranging from 11 to 48 years. All subjects were from an area to which leishmaniasis is endemic, Corte de Pedra (Bahia, Brazil), and the duration of the illness was ≤30 days. The patients were classified as positive or negative for IgE serology in enzyme-linked immunosorbent assay with leishmanial antigens. IgE antibodies were detected in 18 patients (optical density, 0.421 ± 0.30; 95% confidence interval, 0.27 to 0.57), and only 3 (17%) had more than one ulcer. In this group the diameter of Montenegro’s reaction was 18 ± 12.2 mm. In the group with negative IgE serology, 11 of 27 patients (48%) presented two or more cutaneous ulcers, and the mean of the skin test result was 9 ± 6.9 mm. There was a positive correlation between IgE antibody levels and Montenegro’s reaction size and an inverse correlation between IgE antileishmanial antibodies and the number of skin ulcers. The presence of antileishmanial IgE antibodies in cutaneous leishmaniasis may be a result of immunoregulatory events with clinical implications.