Forecasting temporal dynamics of cutaneous leishmaniasis in Northeast Brazil.

IntroductionCutaneous leishmaniasis (CL) is a vector-borne disease of increasing importance in northeastern Brazil. It is known that sandflies, which spread the causative parasites, have weather-dependent population dynamics. Routinely-gathered weather data may be useful for anticipating disease risk and planning interventions.Methodology/principal findingsWe fit time series models using meteorological covariates to predict CL cases in a rural region of Bahía, Brazil from 1994 to 2004. We used the models to forecast CL cases for the period 2005 to 2008. Models accounting for meteorological predictors reduced mean squared error in one, two, and three month-ahead forecasts by up to 16% relative to forecasts from a null model accounting only for temporal autocorrelation.SignificanceThese outcomes suggest CL risk in northeastern Brazil might be partially dependent on weather. Responses to forecasted CL epidemics may include bolstering clinical capacity and disease surveillance in at-risk areas. Ecological mechanisms by which weather influences CL risk merit future research attention as public health intervention targets

Early Suppression of Macrophage Gene Expression by Leishmania braziliensis

Leishmania braziliensis is an intracellular parasite that resides mostly in macrophages. Both the parasite genome and the clinical disease manifestations show considerable polymorphism. Clinical syndromes caused by L. braziliensis include localized cutaneous (CL), mucosal (ML), and disseminated leishmaniasis (DL). Our prior studies showed that genetically distinct L. braziliensis clades associate with different clinical types. Herein, we hypothesized that: (1) L. braziliensis induces changes in macrophage gene expression that facilitates infection; (2) infection of macrophages with strains associated with CL (clade B), ML (clade C), or DL (clade A) will differentially affect host cell gene expression, reflecting their different pathogenic mechanisms; and (3) differences between the strains will be reflected by differences in macrophage gene expression after initial exposure to the parasite. Human monocyte derived macrophages were infected with L. braziliensis isolates from clades A, B, or C. Patterns of gene expression were compared using Affymetrix DNA microarrays. Many transcripts were significantly decreased by infection with all isolates. The most dramatically decreased transcripts encoded proteins involved in signaling pathways, apoptosis, or mitochondrial oxidative phosphorylation. Some transcripts encoding stress response proteins were up-regulated. Differences between L. braziliensis clades were observed in the magnitude of change, rather than the identity of transcripts. Isolates from subjects with metastatic disease (ML and DL) induced a greater magnitude of change than isolates from CL. We conclude that L. braziliensis enhances its intracellular survival by inhibiting macrophage pathways leading to microbicidal activity. Parasite strains destined for dissemination may exert a more profound suppression than less invasive L. braziliensis strains that remain near the cutaneous site of inoculation

Geographic Clustering of Leishmaniasis in Northeastern Brazil1

Different forms of this disease are spreading rapidly in distinct geographic clusters in this region

Miltefosine in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania braziliensis in Brazil: A Randomized and Controlled Trial

Cutaneous leishmaniasis (CL) is characterized by skin ulcerations and occurs in rural poor areas of developing countries. It is treated with daily injections of antimony for 20 days, which is associated with irregular use and increasingly lower cure rates. Miltefosine is an oral medication with activity against the agent of CL (Leishmania). We have studied the efficacy and safety of miltefosine compared with antimony in patients with CL caused by Leishmania braziliensis in Bahia, Brazil. A total of 90 patients participated; 60 received miltefosine and 30 were treated with antimony. Six months after treatment, 75% of patients treated with miltefosine were cured, compared with 53% of the patients in the antimony group, a difference considered significant (p = 0.04). We also found that miltefosine was more effective than antimony in adults than in children. The incidence of side effects was similar with both drugs (76.7% vs. 78.3%), but all patients were able to finish the treatments. Our study shows that miltefosine is more effective than antimony for the treatment of CL in Bahia, Brazil and can contribute to the control of this disease due to its activity and easier administration

Differential effects of antigens from L. braziliensis isolates from disseminated and cutaneous leishmaniasis on in vitro cytokine production

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

Differential effects of antigens from L. braziliensis isolates from disseminated and cutaneous leishmaniasis on in vitro cytokine production

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

Enzyme-linked immunosorbent assay for the detection of Bothrops Jararaca Venom

Manoel, Barral Netto. “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”.Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-05-09T18:22:07Z No. of bitstreams: 1 Barral MN Enzyme-linked immunosorbent assay .....pdf: 526126 bytes, checksum: 164bb2224de40d38cc2b2188124b13c9 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-05-09T19:14:21Z (GMT) No. of bitstreams: 1 Barral MN Enzyme-linked immunosorbent assay .....pdf: 526126 bytes, checksum: 164bb2224de40d38cc2b2188124b13c9 (MD5)Made available in DSpace on 2018-05-09T19:14:21Z (GMT). No. of bitstreams: 1 Barral MN Enzyme-linked immunosorbent assay .....pdf: 526126 bytes, checksum: 164bb2224de40d38cc2b2188124b13c9 (MD5) Previous issue date: 1990CNPq's (Conselho National de Desenvolvimento Cientifico e Tecnologico) scientific initiation fellowship . This project was supported by Financiadora de Estudos e Projetos (FINEP).Universidade Federal da Bahia. Hospital Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, BrasilUniversidade Federal da Bahia. Hospital Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, BrasilUniversidade Federal da Bahia. Hospital Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, BrasilUniversidade Federal da Bahia. Hospital Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, BrasilEnzyme-linked immunosorbent assay for the detection of Bothrops jararaca venom. Toxicon 28, 1053-1061, 1990.-This study reports an enzyme-linked immunosorbent assay for detecting Bothrops jararaca venom in fluids, employing the sandwich method with biotin/avidin amplification. The assay exhibits high accuracy in correlating optical densities with venom concentrations (r = 0.98), high reproducibility, low background and limited crossreactivity with venom from other snake genera . Nevertheless, it was unable to distinguish among venoms from different bothropic species. Using this method we evaluated the serum kinetics of Bothrops jararaca venom in C57BL/6 mice. High concentrations were found in serum just 15 min after injection (151 f41 ng/ml; mean±S.D.), followed by a progressive fall (102 f46, 74 f39 and 50±22ng/ml after 1, 3 and 6 hr respectively), being undetectable by 24 hr. Such serum kinetics indicates a pattern of a rapid absorption of venom from the inoculation site, followed by a slow and progressive drop in its serum levels . This ELISA was a reliable tool in the determination of Bothrops jararaca venom levels in mouse serum, and may become useful in other fields of bothropic venom researc

Serum soluble markers in the evaluation of treatment in human visceral leishmaniasis

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-03-26T18:42:12Z No. of bitstreams: 1 Schriefer A Serum Soluble....pdf: 938558 bytes, checksum: 2a23fd655aa0247dcb22e071e2e56851 (MD5)Made available in DSpace on 2014-03-26T18:42:12Z (GMT). No. of bitstreams: 1 Schriefer A Serum Soluble....pdf: 938558 bytes, checksum: 2a23fd655aa0247dcb22e071e2e56851 (MD5) Previous issue date: 1995Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório Integrado de Microbiologia e Imunorregulação. Salvador, BA, BrasilUniversidade Federal da Bahia. Serviço de Imunologia. Hospital Universitário Prof. Edgard Santos. Salvador, BA, BrasilUniversidade Federal da Bahia. Serviço de Imunologia. Hospital Universitário Prof. Edgard Santos. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório Integrado de Microbiologia e Imunorregulação. Salvador, BA, BrasilVisceral leishmaniasis (VL) has a fatal course if not properly treated. Recovery from VL is linked to cellular immune response. Unresponsiveness to antimonial therapy reinforces the importance of determining parameters for treatment assessment. We analysed the pre- and post-treatment serum levels of soluble CD4 (sCD4), sCD8, sIL-2R, soluble intercellular adhesion molecule- I (sICAM- 1) and neopterin in groups of VL patients either responsive or not to standard antimonial therapy. Pretreatment serum levels of all markers except for sICAM-1 were significantly higher in VL patients than in healthy subjects from the same area (P < 0-05). sICAM-1 levels were similar in healthy controls and in VL patients refractory to antimonial therapy (P= 0 25), but significantly higher in patients responsive to treatment (P = 0-02). The comparison of pre- and post-treatment concentrations showed that all markers, except sCD4 and sICAM-1, presented a significant fall (P < 0 05) in patients responsive to antimonial therapy. However, only neopterin presented with levels compatible with those of healthy subjects at the end of treatment (P = 0 30). In refractory patients sICAM-1 presented with post-treatment levels significantly higher than the pretreatment determinations (P=0003), while sCD4 experienced a significant drop (P=0001). All markers displayed clearly distinct behaviour according to the patient's response to therapy. This makes all soluble molecules studied suitable for use as indicators of antimonial therapy response. Additionally the comparison of pretreatment levels of the markers between responders and refractory patients to antimonial therapy showed that serum concentrations of sIL-2R and sICAM-1 significantly differed among these two groups (P= 0 02 in each case), suggesting that they may be used in future as predictors of antimonial therapy response

Clinical and Experimental Immunology

Texto completo: acesso restrito. p.535–540Visceral leishmaniasis (VL) has a fatal course if not properly treated. Recovery from VL is linked to cellular immune response. Unresponsiveness to antimonial therapy reinforces the importance of determining parameters for treatment assessment. We analysed the pre- and post-treatment serum levels of solubleCD4(sCD4).sCD8. SI L-2R, soluble intercellular adhesion molecule-1 (sICAM-1) and neopterin in groups of VL patients either responsive or not to standard antimonial therapy. Pretreatment serum levels of all markers except for sICAM-1 were significantly higher in VL patients than in healthy subjects from the same area (P < 0 05). sICAM-1 levels were similar in healthy controls and in VL patients refractory to antimonial therapy (p = 0 25), but significantly higher in patients responsive to treatment (p = 0.02). The comparison of pre- and post-treatment concentrations showed that all markers, except sCD4 and sICAM-1, presented a significant fall (p < 0. 05) in patients responsive to antimonial therapy. However, only neopterin presented with levels compatible with those of healthy subjects at the end of treatment (p = 0. 30). In refractory patients sICAM-1 presented with post-treatment levels significantly higher than the pretreatment determinations (p = 0.03). while sCD4 experienced a significant drop (p = 0. 01) All markers displayed clearly distinct behaviour according to the patient's response to therapy. This makes all soluble molecules studied suitable for use as indicators of antimonial therapy response. Additionally the comparison of pretreatment levels of the markers between responders and refractory patients to antimonial therapy showed that serum concentrations of sIL-2R and sICAM-1 significantly differed among these two groups (p=0.02 in each case), suggesting that they may be used in future as predictors of antimonial therapy response