Frontiers in parasitology最新文献

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Analysis of insecticides in long-lasting insecticidal nets using X-ray fluorescence spectroscopy and correlation with bioefficacy x射线荧光光谱法分析长效杀虫蚊帐中杀虫剂及其与生物功效的相关性
Frontiers in parasitology Pub Date : 2023-10-11 DOI: 10.3389/fpara.2023.1258429
Melanie Koinari, Nakei Bubun, David Wilson, Evodia Anetul, Lincoln Timinao, Petrina Johnson, Norelle L. Daly, Moses Laman, Tim Freeman, Stephan Karl
{"title":"Analysis of insecticides in long-lasting insecticidal nets using X-ray fluorescence spectroscopy and correlation with bioefficacy","authors":"Melanie Koinari, Nakei Bubun, David Wilson, Evodia Anetul, Lincoln Timinao, Petrina Johnson, Norelle L. Daly, Moses Laman, Tim Freeman, Stephan Karl","doi":"10.3389/fpara.2023.1258429","DOIUrl":"https://doi.org/10.3389/fpara.2023.1258429","url":null,"abstract":"Background Long-lasting insecticidal nets (LLINs) are a key vector control tool used for the prevention of malaria. Active ingredient (AI) measurements in LLINs are essential for evaluating their quality and efficacy. The main aim of the present study was to determine the utility of X-ray fluorescence (XRF) spectroscopy as a suitable field-deployable tool for total AI quantification in LLINs. Methods New and unused LLIN samples containing deltamethrin (PermaNet® 2.0, n = 35) and alpha-cypermethrin (SafeNet®, n = 43) were obtained from batches delivered to Papua New Guinea (PNG) for mass distribution. Insecticides were extracted from the LLINs using a simple extraction technique and quantified using liquid chromatography mass spectrometry (LC-MS). The LC-MS results were correlated with XRF spectroscopy measurements on the same nets. Operators were blinded regarding the type of net. Bioefficacy of the LLIN samples was tested using WHO cone bioassays and test results were correlated with total AI content. Results The results indicate correlation between quantitative XRF and LC-MS. Interestingly, the total AI content was negatively correlated with bioefficacy in PermaNet® 2.0 (especially in recently manufactured nets). In contrast, AI content was positively correlated with bioefficacy in SafeNet®. These results indicate that the chemical content analysis in predelivery inspections does not always predict bioefficacy. Conclusion XRF is a promising field-deployable tool for quantification of both deltamethrin- and alpha-cypermethrin-coated LLINs. Because total AI content is not always a predictor of the efficacy of LLINs to kill mosquitoes, bioefficacy measurements should be included in predelivery inspections.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136062855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Secreted and surface proteome and transcriptome of Opisthorchis felineus 猫科大腹蛇的分泌和表面蛋白质组学及转录组学
Frontiers in parasitology Pub Date : 2023-10-10 DOI: 10.3389/fpara.2023.1195457
Yide Wong, Mark S. Pearson, Olga Fedorova, Vladimir Ivanov, Ekaterina Khmelevskaya, Bemnet Tedla, Buddhika Jayakody Arachchige, Sarah Reed, Matt Field, Thewarach Laha, Alex Loukas, Javier Sotillo
{"title":"Secreted and surface proteome and transcriptome of Opisthorchis felineus","authors":"Yide Wong, Mark S. Pearson, Olga Fedorova, Vladimir Ivanov, Ekaterina Khmelevskaya, Bemnet Tedla, Buddhika Jayakody Arachchige, Sarah Reed, Matt Field, Thewarach Laha, Alex Loukas, Javier Sotillo","doi":"10.3389/fpara.2023.1195457","DOIUrl":"https://doi.org/10.3389/fpara.2023.1195457","url":null,"abstract":"Introduction Opisthorchis felineus , Opisthorchis viverrini , and Clonorchis sinensis are the most medically important species of fish-borne zoonotic trematodes. O. felineus is endemic to the river plains of Western Siberia and Eastern Europe, and it is estimated that more than 1.6 million people could be infected with this parasite. Chronic opisthorchiasis may lead to significant gastrointestinal and hepatobiliary pathology. This study aimed to identify and characterize proteins from the secreted and tegumental proteomes of O. felineus . Methods Adult flukes were collected from experimentally infected hamsters and cultured in vitro in serum-free media. We extracted proteins from different compartments of the O. felineus secretome, including (i) soluble excretory/secretory (ES) products; (ii) secreted 15K-extracellular vesicles (EVs); and (iii) tegument. Results We also generated a transcriptome using long-read sequencing, and when this was combined with high-resolution mass spectrometry, sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) separation, and protein digestion, we identified 686, 894, 389, 324, and 165 proteins from the ES, 15K-EV, and the three sequentially extracted tegument (TEG) protein fractions, respectively. We conducted in-depth gene ontology and protein family analyses on the identified proteins and discussed comparisons against similar proteome data sets acquired for the Southeast Asian liver fluke O. viverrini and the Chinese liver fluke C. sinensis . Discussion The information from this study will form a biologically relevant data set of O. felineus proteins that could be used to develop diagnostic and therapeutic tools to manage the human cost of O. felineus infection and its associated comorbidities.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136295448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An end is in sight: a perspective on PCR as an endpoint for Chagas disease treatment trials 终点在望:PCR作为恰加斯病治疗试验终点的观点
Frontiers in parasitology Pub Date : 2023-10-09 DOI: 10.3389/fpara.2023.1272386
Natasha S. Hochberg, Srinivasa P. S. Rao, Gerhild Angyalosi, Xiaojun Zhao, Leticia Carballo, Caroline Demacq, Sofia Braud-Perez, Daniela Wieser, JP Casas, John Millholland, Debby Ngo
{"title":"An end is in sight: a perspective on PCR as an endpoint for Chagas disease treatment trials","authors":"Natasha S. Hochberg, Srinivasa P. S. Rao, Gerhild Angyalosi, Xiaojun Zhao, Leticia Carballo, Caroline Demacq, Sofia Braud-Perez, Daniela Wieser, JP Casas, John Millholland, Debby Ngo","doi":"10.3389/fpara.2023.1272386","DOIUrl":"https://doi.org/10.3389/fpara.2023.1272386","url":null,"abstract":"Novel therapies for chronic indeterminate Chagas disease (CICD) are needed, but trials are limited by the absence of tests to detect infection and early treatment efficacy. This perspective highlights the shortfalls and strengths of polymerase chain reaction (PCR) as a study endpoint for anti-parasitic drug development. Serologic reversion, the gold standard test of cure, may take decades to occur in adults and therefore is challenging as an endpoint for drug development. Use of PCR as a marker of infection and treatment response has notable limitations due to low parasitemia in CICD, fluctuations in circulating (versus tissue) parasite burden, strain differences, and assay performance. It is, however, rapidly responsive to therapy, and technological advances have improved detection of different strains and may allow for parasite quantification. Until we have more sensitive tests for parasitological clearance, PCR as a measure of treatment failure may be the best available efficacy endpoint to accelerate early development of much-needed novel therapies. Adequately designed clinical studies are needed to correlate PCR clearance with clinical outcomes and to identify novel biomarkers predictive of clinical outcomes in patients with CICD. Public-private partnerships and health authority engagement are paramount to identify feasible trial endpoints and deliver promising new drug candidates for Chagas disease.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135094122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Macrophage metallothioneins participate in the antileishmanial activity of antimonials 巨噬细胞金属硫蛋白参与抗利什曼原虫活性
Frontiers in parasitology Pub Date : 2023-10-04 DOI: 10.3389/fpara.2023.1242727
Deninson Alejandro Vargas, David J. Gregory, Roni Nitzan Koren, Dan Zilberstein, Ashton Trey Belew, Najib M. El-Sayed, María Adelaida Gómez
{"title":"Macrophage metallothioneins participate in the antileishmanial activity of antimonials","authors":"Deninson Alejandro Vargas, David J. Gregory, Roni Nitzan Koren, Dan Zilberstein, Ashton Trey Belew, Najib M. El-Sayed, María Adelaida Gómez","doi":"10.3389/fpara.2023.1242727","DOIUrl":"https://doi.org/10.3389/fpara.2023.1242727","url":null,"abstract":"Host cell functions that participate in the pharmacokinetics and pharmacodynamics (PK/PD) of drugs against intracellular pathogen infections are critical for drug efficacy. In this study, we investigated whether macrophage mechanisms of xenobiotic detoxification contribute to the elimination of intracellular Leishmania upon exposure to pentavalent antimonials (Sb V ). Primary macrophages from patients with cutaneous leishmaniasis (CL) (n=6) were exposed ex vivo to L. V. panamensis infection and Sb V , and transcriptomes were generated. Seven metallothionein (MT) genes, potent scavengers of heavy metals and central elements of the mammalian cell machinery for xenobiotic detoxification, were within the top 20 up-regulated genes. To functionally validate the participation of MTs in drug-mediated killing of intracellular Leishmania , tandem knockdown (KD) of MT2-A and MT1-E, MT1-F, and MT1-X was performed using a pan-MT shRNA approach in THP-1 cells. Parasite survival was unaffected in tandem-KD cells, as a consequence of strong transcriptional upregulation of MTs by infection and Sb V , overcoming the KD effect. Gene silencing of the metal transcription factor-1 (MTF-1) abrogated expression of MT1 and MT2-A genes, but not ZnT-1. Upon exposure to Sb V , intracellular survival of Leishmania in MTF-1 KD cells was significantly enhanced. Results from this study highlight the participation of macrophage MTs in Sb-dependent parasite killing.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135592227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Elucidating Spirocerca lupi spread in the Americas by using phylogenetic and phylogeographic analyses 利用系统发育和系统地理分析阐明lupi螺旋体在美洲的传播
Frontiers in parasitology Pub Date : 2023-09-27 DOI: 10.3389/fpara.2023.1249593
Paula Alfaro-Segura, Joby Robleto-Quesada, Víctor M. Montenegro-Hidalgo, Jose Arturo Molina-Mora, Gad Baneth, Guilherme G. Verocai, Roger I. Rodriguez-Vivas, Alicia Rojas
{"title":"Elucidating Spirocerca lupi spread in the Americas by using phylogenetic and phylogeographic analyses","authors":"Paula Alfaro-Segura, Joby Robleto-Quesada, Víctor M. Montenegro-Hidalgo, Jose Arturo Molina-Mora, Gad Baneth, Guilherme G. Verocai, Roger I. Rodriguez-Vivas, Alicia Rojas","doi":"10.3389/fpara.2023.1249593","DOIUrl":"https://doi.org/10.3389/fpara.2023.1249593","url":null,"abstract":"Spirocerca lupi is a parasitic nematode of domestic and wild canids of the world. This nematode induces esophageal spirocercosis and may eventually lead to carcinomas, aortic aneurisms, and death of the animal. Two genotypes of S. lupi have been described based on specimens from Europe, Asia, Africa, and Oceania, but no profound analysis has been conducted with S. lupi from the Americas. To study this, S. lupi specimens isolated from domestic dogs from Mexico, Costa Rica, and the United States, were molecularly characterized using 18S rDNA and cox 1 fragments. Bayesian inference (BI) phylogenetic trees, Templeton-Crandall-Sing (TCS) haplotype networks and Principal coordinate analysis on nucleotide distances were constructed for each locus separately. In addition, a phylogeographic study using a fragment of the cox 1 gene was used to infer the evolutionary history of the genus. BI cox 1 trees grouped S. lupi from the Americas in genotype 1, together with Israeli specimens, and showed a high nucleotide identity with those worms. In the TCS network, American specimens clustered next to Israeli S. lupi . Furthermore, the 18S rDNA gene fragment separated Costa Rican worms from African, Asian, and European specimens and other species of the family Spiruridae. Interestingly, the phylogeographic analysis suggested that the origin of S. vulpis was in Europe, and it later diverged into S. lupi that spread first to Africa, then to Asia and finally to the Americas. Therefore, we suggest that the worms from the American continent might have originated from Asia by dispersion of infected intermediate, paratenic or definitive hosts.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135580772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unveiling challenges in real-time PCR strategies for detecting treatment failure: observations from clinical trials on chronic Chagas disease 揭示实时PCR检测治疗失败策略的挑战:来自慢性恰加斯病临床试验的观察
Frontiers in parasitology Pub Date : 2023-09-26 DOI: 10.3389/fpara.2023.1260224
Alejandro G. Schijman
{"title":"Unveiling challenges in real-time PCR strategies for detecting treatment failure: observations from clinical trials on chronic Chagas disease","authors":"Alejandro G. Schijman","doi":"10.3389/fpara.2023.1260224","DOIUrl":"https://doi.org/10.3389/fpara.2023.1260224","url":null,"abstract":"Chagas disease (CD) caused by Trypanosoma cruzi remains a Neglected Tropical Disease with limited access to diagnosis and treatment, particularly for chronically infected patients. Clinical trials are underway to improve treatment using new drugs or different regimens, and Real-Time PCR is used to assess the parasitological response as a surrogate biomarker. However, PCR-based strategies have limitations due to the complex nature of T. cruzi infection. The parasite exhibits asynchronous replication, different strains and clones, and diverse tissue tropism, making it challenging to determine optimal timeline points for monitoring treatment response. This mini-review explores factors that affect PCR-based monitoring and summarizes the endpoints used in clinical trials for detecting treatment failure. Serial sampling and cumulative PCR results may improve sensitivity in detecting parasitemia and treatment failure in these trials.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"64 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135719438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Developing inclusive digital health diagnostic for schistosomiasis: a need for guidance via target product profiles 制定包容的血吸虫病数字健康诊断:需要通过目标产品简介提供指导
Frontiers in parasitology Pub Date : 2023-09-26 DOI: 10.3389/fpara.2023.1255848
Adeola Onasanya, Michel Bengtson, Ludo de Goeje, Jo van Engelen, Jan-Carel Diehl, Lisette van Lieshout
{"title":"Developing inclusive digital health diagnostic for schistosomiasis: a need for guidance via target product profiles","authors":"Adeola Onasanya, Michel Bengtson, Ludo de Goeje, Jo van Engelen, Jan-Carel Diehl, Lisette van Lieshout","doi":"10.3389/fpara.2023.1255848","DOIUrl":"https://doi.org/10.3389/fpara.2023.1255848","url":null,"abstract":"Introduction The INSPIRED project aims to develop inclusive Digital Optical Diagnostic Devices (DODDs) for schistosomiasis, to support disease management by enabling rapid diagnostic results, to improve efficient data management to guide decision-making and to provide healthcare workers with critical health information to facilitate follow-up action. Due to the non-availability of Target Product Profiles (TPPs) for guiding the development of digital diagnostics for schistosomiasis, we explored existing diagnostic TPPs. Methods Using a curated open access database (Notion database), we studied a selection of TPPs for diagnosing infectious diseases, focusing on specifications related to digital health products for Neglected Tropical Diseases (NTDs). Results Eighteen TPPs originating from 12 documents, covering 13 specific diseases, were selected and their characteristics were labeled and entered into the database. Further exploration of the database revealed several gaps, including a lack of stakeholder input, sustainability, and TPP availability. Other significant gaps related to digital health platform interconnectivity and data stewardship specifically in relation to digital diagnostics, including DODDs. Discussion These findings reflect two possible scenarios: (1) there is currently no need for digital diagnostic devices for schistosomiasis and, by extension for other NTDs; or (2) those needs are not yet covered by TPPs. Therefore, we recommend that digital health diagnostics are included in the use cases for schistosomiasis control and elimination, at least in the ideal/desirable scenario, as this will guide research and incentivize investment in digital health diagnostics for schistosomiasis.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135718919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chagas disease treatment efficacy markers: experiences from a Phase III study with nifurtimox in children 恰加斯病治疗疗效指标:来自儿童尼福替莫III期研究的经验
Frontiers in parasitology Pub Date : 2023-09-22 DOI: 10.3389/fpara.2023.1229467
Ulrike Grossmann, Maria-Luisa Rodriguez
{"title":"Chagas disease treatment efficacy markers: experiences from a Phase III study with nifurtimox in children","authors":"Ulrike Grossmann, Maria-Luisa Rodriguez","doi":"10.3389/fpara.2023.1229467","DOIUrl":"https://doi.org/10.3389/fpara.2023.1229467","url":null,"abstract":"Determining the success of antitrypanosomal therapy for Chagas disease is challenging, particularly in the chronic phase of the disease, because seropositivity persists for a long time after successful antitrypanosomal treatment and is known to be related to the duration of Trypanosoma cruzi infection. Seroconversion to negative by two or more conventional serologic tests is the currently accepted measure of efficacy, and studies suggest no significant change in seropositivity if left untreated. However, there is no guidance for industry on how to establish the effectiveness of drugs intended for the treatment of Chagas disease. Due to the lack of validated sensitive, specific, easy-to-use markers that allow early monitoring of the efficacy of antitrypanosomal treatment in an efficient manner, we used seroreduction measured by two conventional enzyme-linked immunosorbent assays in addition to the currently accepted criterion for what constitutes a cure, seroconversion to negative, as a surrogate parameter for efficacy in a Phase III pediatric trial with nifurtimox. The measures for confirmation of the antitrypanosomal efficacy of nifurtimox were discussed with US FDA. In this perspective article, we present our experiences obtained from a pediatric study on Chagas disease with an established drug using a surrogate efficacy parameter in addition to the established criterion for a cure.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136061720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Parasitemia and antibody response to benznidazole treatment in a cohort of patients with chronic Chagas disease. 慢性恰加斯病患者的寄生虫血症和对苯并硝唑治疗的抗体反应
Frontiers in parasitology Pub Date : 2023-09-05 eCollection Date: 2023-01-01 DOI: 10.3389/fpara.2023.1235925
Carlos Henrique Valente Moreira, Ana Luiza Bierrenbach, Cesar Augusto Taconeli, Léa Campos de Oliveira-da Silva, Lewis F Buss, Sheila M Keating, Erika Regina Manuli, Noemia Barbosa Carvalho, Cristina Guastini, Sonia Bakkour Coco, José Ângelo Lauletta Lindoso, Lucas Augusto Moyses Franco, Fabio Ghilardi, Flavia Cristina da Silva Sales, Paul Contestable, Clara Di Germanio, Michael P Busch, Ester Cerdeira Sabino
{"title":"Parasitemia and antibody response to benznidazole treatment in a cohort of patients with chronic Chagas disease.","authors":"Carlos Henrique Valente Moreira, Ana Luiza Bierrenbach, Cesar Augusto Taconeli, Léa Campos de Oliveira-da Silva, Lewis F Buss, Sheila M Keating, Erika Regina Manuli, Noemia Barbosa Carvalho, Cristina Guastini, Sonia Bakkour Coco, José Ângelo Lauletta Lindoso, Lucas Augusto Moyses Franco, Fabio Ghilardi, Flavia Cristina da Silva Sales, Paul Contestable, Clara Di Germanio, Michael P Busch, Ester Cerdeira Sabino","doi":"10.3389/fpara.2023.1235925","DOIUrl":"10.3389/fpara.2023.1235925","url":null,"abstract":"<p><strong>Background: </strong>Evaluating the effectiveness of Chagas disease treatment poses challenges due to the lack of biomarkers for disease progression and therapeutic response. In this study, we aimed to assess the clearance of Trypanosoma cruzi (<i>T. cruzi)</i> parasites in a group of benznidazole (BNZ)-treated chronic Chagas disease patients using high-sensitivity quantitative PCR (qPCR) and track <i>T. cruzi</i> antibody levels through a semiquantitative chemiluminescent assay.</p><p><strong>Methods: </strong>A total of 102 <i>T. cruzi</i> seropositive patients with previous PCR-positive results were enrolled in the study. We collected samples 30 days before treatment (T-30d), on the day before initiating BNZ treatment (T0d), and at follow-up visits 60 days (T60d), 6 months (T6M), 12 months (T12M), and 36 months (T36M) after treatment initiation. Treatment efficacy was assessed by testing of serial samples using a target-capture qPCR assay specific to satellite <i>T. cruzi</i> DNA and the ORTHO <i>T. cruzi</i> ELISA Test System for antibody quantitation.</p><p><strong>Results: </strong>Of the enrolled individuals, 87 completed at least 50% of the treatment course, and 86 had PCR results at follow-up visits T6M, T12M, and T36M. PCR results exhibited fluctuations before and after treatment, but levels were significantly lower post-treatment. Only 15 cases consistently tested PCR-negative across all post-treatment visits. Notably, nearly all participants demonstrated a declining antibody trajectory, with patients who tested PCR-negative at T36M exhibiting an earlier and more pronounced decline compared to PCR-positive cases at the same visit.</p><p><strong>Conclusion: </strong>Our study suggests that serial PCR results pose challenges in interpretation. In contrast, serial antibody levels may serve as an ancillary, or even a more reliable indicator of parasite decline following BNZ treatment. Monitoring antibody levels can provide valuable insights into the efficacy of treatment and the persistence of parasites in Chagas disease patients.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":" ","pages":"1235925"},"PeriodicalIF":0.0,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44961581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of broadly-conserved parasitic nematode proteins that activate immunity. 广泛保守的激活免疫的寄生线虫蛋白的鉴定
Frontiers in parasitology Pub Date : 2023-08-08 eCollection Date: 2023-01-01 DOI: 10.3389/fpara.2023.1223942
Bruce A Rosa, Dante S Zarlenga, Valsin M Fournet, Ethiopia Beshah, Dolores E Hill, Alexander Zarlenga, Angela Yee, Xiaowu Liang, Adam D Shandling, Amit Oberai, Joseph F Urban, Makedonka Mitreva
{"title":"Identification of broadly-conserved parasitic nematode proteins that activate immunity.","authors":"Bruce A Rosa, Dante S Zarlenga, Valsin M Fournet, Ethiopia Beshah, Dolores E Hill, Alexander Zarlenga, Angela Yee, Xiaowu Liang, Adam D Shandling, Amit Oberai, Joseph F Urban, Makedonka Mitreva","doi":"10.3389/fpara.2023.1223942","DOIUrl":"10.3389/fpara.2023.1223942","url":null,"abstract":"<p><strong>Introduction: </strong>Soil transmitted nematodes are impediments to human health and agricultural production. Poor anthelmintic efficiencies, the emergence of resistant strains, and the persistence of infective stages highlight the need for more effective control strategies. Parasitic nematodes elicit a Th2-type immune response that most often is not protective. Vaccination has thus far been unsuccessful due to unrealized antigenic characters and unknown mechanisms that nematodes use to circumvent host immunity.</p><p><strong>Methods: </strong>Here, we used a genomics/proteomics approach (including immunoblot experiments from pigs infected with <i>T. suis</i>) to prioritize putative immunogenic excretory/secretory (E/S) proteins conserved across and specific to several gastrointestinal (GI) parasitic nematode species. A cocktail of five recombinant proteins optimized for conserved GI nematode targets was used immunize pigs and test for active antibody responses in both the serum and intestinal ileal fluid of immunized pigs. An antibody-protein array of putative immunogenic proteins was developed from a combined bioinformatic, experimental, and literature-based prioritization of homologous parasite proteins.</p><p><strong>Results: </strong>Screening the array with sera and ileal fluid samples from immunized pigs suggested cross-reactivity among homologous proteins and a general activation of immunity. PCA clustering showed that the overall immune responses were altered by immunization, but no substantial changes were observed following direct worm challenge with either <i>Ascaris suum</i> or <i>Trichuris suis</i>.</p><p><strong>Discussion: </strong>Proteins that activated immunity are potential antigens for immunization and the multi-omics phylum-spanning prioritization database that was created is a valuable resource for identifying target proteins in a wide array of different parasitic nematodes. This research strongly supports future studies using a computational, comparative genomics/proteomics approach to produce an effective parasite vaccine.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":" ","pages":"1223942"},"PeriodicalIF":0.0,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43601863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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