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The performance of Xpert MTB/RIF and MTBDRplus within a Programmatic setting at TB Laboratory in Rio de Janeiro, Brazil. Xpert MTB/RIF 和 MTBDRplus 在巴西里约热内卢结核病实验室计划环境中的性能。
IF 1.8 4区 医学 Q2 PARASITOLOGY Pub Date : 2024-09-13 eCollection Date: 2024-01-01 DOI: 10.1590/0037-8682-0167-2024
Thiago da Silva Santos Malaquias, Eunice Petris Ribeiro, Tatiana Cristina Pereira Dutra, Marina Ricardo, Richard Salvato, Marcela Bhering, Daniella Castanheira Bartholomeu, Elis Regina Dalla-Costa, Miguel Viveiros, Elisangela Costa da Silva, Afrânio Kritski

Background: Few studies in routine settings have confirmed the high accuracy of the Xpert MTB/RIF assay for detecting rifampicin resistance (RR) and the first-line probe assay (FL-LPA) for detecting both RR and isoniazid resistance (INHR).

Methods: The performance of Xpert MTB/RIF and MTBDRplus VER 2.0 LPA was evaluated in 180 Mycobacterium tuberculosis samples collected from January 2018 to December 2019 in Rio de Janeiro, Brazil. The results were compared with those from BACTEC MGIT 960 culture and drug susceptibility testing (DST). Whole-genome sequencing was performed on the samples with discordant results.

Results: The Xpert MTB/RIF assay showed a sensitivity (Se) of 93.3% and a specificity (Sp) of 97.6%, detecting RR. The performance of FL-LPA to identify RIF and INH resistance was, respectively, (Se) 100% and 83.3% and (Sp) 98.8% and 100%. Among 18 clinical isolates with INHR detected by FL-LPA, mutations in the katG gene were observed in 100% of samples, of which only two (11.1%) had mutations in both katG and inhA genes. Overall, the discordant results were identified in 9 (5%) samples. Among the four Xpert RIF-resistant and DST-sensitive, two harbored mutations in rpoB Leu430Pro. Among the four FL-LPA-sensitive and DST-resistant, one had a mutation in inhA 17G>T. FL-LPA showed high accuracy in detecting RR and INHR.

Conclusions: The MTBDRplus test demonstrated excellent performance in detecting RR, and INHR in clinical isolates under routine conditions at a reference laboratory in Rio de Janeiro, Brazil. Incorporating both tests can improve drug-resistant tuberculosis treatment outcomes and monitor the INHR incidence.

背景:很少有常规研究证实Xpert MTB/RIF检测法检测利福平耐药性(RR)和一线探针检测法(FL-LPA)检测RR和异烟肼耐药性(INHR)的准确性很高:对2018年1月至2019年12月在巴西里约热内卢采集的180份结核分枝杆菌样本进行了Xpert MTB/RIF和MTBDRplus VER 2.0 LPA的性能评估。结果与 BACTEC MGIT 960 培养和药敏试验(DST)的结果进行了比较。对结果不一致的样本进行了全基因组测序:Xpert MTB/RIF 检测法检测 RR 的灵敏度(Se)为 93.3%,特异度(Sp)为 97.6%。FL-LPA鉴定RIF和INH耐药性的灵敏度(Se)分别为100%和83.3%,特异度(Sp)分别为98.8%和100%。在通过 FL-LPA 检测出 INHR 的 18 个临床分离株中,100% 的样本都观察到 katG 基因突变,其中只有 2 个样本(11.1%)同时出现 katG 和 inhA 基因突变。总体而言,9 个样本(5%)出现了不一致的结果。在 4 个对 Xpert RIF 抗性和 DST 敏感的样本中,有 2 个样本的 rpoB Leu430Pro 发生了突变。在 4 个对 FL-LPA 敏感且对 DST 敏感的样本中,有 1 个样本的 inhA 17G>T 发生了突变。FL-LPA在检测RR和INHR方面表现出很高的准确性:在巴西里约热内卢的参考实验室,MTBDRplus 检验在常规条件下检测临床分离株中的 RR 和 INHR 方面表现出色。采用这两种检测方法可以提高耐药结核病的治疗效果,并监测 INHR 的发生率。
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引用次数: 0
Molecular detection of multiple arboviruses in the city of Goiânia-Goiás-Brazil. 巴西戈亚尼亚-戈亚斯市多种虫媒病毒的分子检测。
IF 1.8 4区 医学 Q2 PARASITOLOGY Pub Date : 2024-09-06 eCollection Date: 2024-01-01 DOI: 10.1590/0037-8682-0539-2023
Jordana Farias Corrêa, Silvia Maria Salem-Izacc, Elisângela Gomes da Silva, Adriano Roberto Vieira de Sousa, Gabrielly Regis Abrantes, Marina Machado Santos, Juliana Pires Ribeiro, Marco Tulio A Garcia-Zapata, Natália Santana do Nascimento, Carlos Eduardo Anunciação, Sandra Maria Brunini, Elisângela de Paula Silveira-Lacerda

Background: Healthcare systems are currently ill-equipped to diagnose arboviruses rapidly and efficiently or to differentiate between various viruses.

Methods: Utilizing molecular techniques, this study examined arbovirus infections in 459 patients from a public health unit in Goiânia-Goiás, Brazil, a region where arbovirus infection poses a significant public health challenge.

Results: Nearly 60% of the analyzed samples tested positive for at least one arbovirus, and over 10% of the patients were co-infected with more than one virus.

Conclusions: Fast and accurate diagnostic tools are essential for informing public health policy and enhancing epidemiological surveillance.

背景:目前,医疗保健系统还不具备快速有效地诊断虫媒病毒或区分各种病毒的能力:这项研究利用分子技术检测了巴西戈亚尼亚-戈亚斯州公共卫生单位 459 名患者的虫媒病毒感染情况,该地区的虫媒病毒感染对公共卫生构成了重大挑战:结果:近 60% 的分析样本对至少一种虫媒病毒检测呈阳性,超过 10% 的患者合并感染了一种以上的病毒:快速准确的诊断工具对于制定公共卫生政策和加强流行病学监测至关重要。
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引用次数: 0
Trachoma-associated morbidity and mortality in Brazil: an ecological study focusing on hospitalization and mortality data, 2000-2022. 巴西与沙眼相关的发病率和死亡率:2000-2022 年以住院和死亡率数据为重点的生态研究。
IF 1.8 4区 医学 Q2 PARASITOLOGY Pub Date : 2024-09-02 eCollection Date: 2024-01-01 DOI: 10.1590/0037-8682-0158-2024
Adjoane Maurício Silva Maciel, Anderson Fuentes Ferreira, Nádia Maria Girão Saraiva de Almeida, Manuella Maurício Silva Maciel, Taynara Lais Silva, Mirele Coelho Araújo, Roberto da Justa Pires Neto, Alberto Novaes Ramos

Background: Trachoma is the leading infectious cause of blindness worldwide. It is a neglected tropical disease caused by Chlamydia trachomatis. The objective of this study was to analyze the trachoma-associated morbidity and mortality in Brazil from 2000 to 2022. This ecological time-series study was based on secondary data on trachoma obtained from hospital admissions (trachoma as the primary or secondary cause) and death certificates (trachoma as the underlying or associated cause).

Methods: We calculated the sex- and age-standardized rates of hospital admissions and trachoma-specific mortality according to sociodemographic variables and analyzed the spatial distribution.

Results: We identified 141/263,292,807 hospital admissions (primary cause: 83.0%) and 126/27,596,830 death certificates (associated cause: 91.3%) related to trachoma. Trachoma-related sequelae were reported in 8.5% of hospital admissions and 6.3% of death certificates. Trachoma was more common in males (hospital admissions and death certificates), people aged ≥70 years (hospital admissions and death certificates), those with brown skin (hospital admissions and death certificates), and those living in the North (hospital admissions) and Northeast (death certificates) regions of Brazil.

Conclusions: Despite the relatively low rates of trachoma morbidity in Brazil, the associated mortality rates are of concern. The heterogeneous patterns of occurrence in the country in terms of population and territory reinforce the need to evaluate and monitor the available data, despite the low prevalence, in order to achieve and maintain the elimination targets in Brazil in the future.

背景:沙眼是全球致盲的主要传染病因。它是由沙眼衣原体引起的一种被忽视的热带疾病。本研究旨在分析 2000 年至 2022 年巴西与沙眼相关的发病率和死亡率。这项生态时间序列研究基于从入院(沙眼为主要或次要病因)和死亡证明(沙眼为基本或相关病因)中获得的沙眼二级数据:我们根据社会人口变量计算了性别和年龄标准化的入院率和沙眼死亡率,并分析了空间分布:我们确定了 141/263,292,807 例入院病例(主因:83.0%)和 126/27,596,830 例死亡证明(相关原因:91.3%)与沙眼有关。8.5%的住院病例和6.3%的死亡证明与沙眼相关。男性(入院记录和死亡证明)、年龄≥70岁者(入院记录和死亡证明)、棕色皮肤者(入院记录和死亡证明)以及居住在巴西北部(入院记录)和东北部(死亡证明)地区的人更容易患沙眼:尽管巴西的沙眼发病率相对较低,但相关死亡率却令人担忧。尽管发病率较低,但巴西在人口和领土方面的发病模式各不相同,因此有必要对现有数据进行评估和监测,以便在未来实现并维持在巴西消除沙眼的目标。
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引用次数: 0
Acquired thrombotic thrombocytopenic purpura in a patient with plasmodium vivax malaria: A case report. 一名间日疟患者的后天性血栓性血小板减少性紫癜:病例报告。
IF 1.8 4区 医学 Q2 PARASITOLOGY Pub Date : 2024-09-02 eCollection Date: 2024-01-01 DOI: 10.1590/0037-8682-0014-2024
Daren Esteban Araque Gualtero, Diego Augusto Moreno Diaz, Julie Melissa Mogollón, Andrés Felipe Gómez Rueda

Acquired thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening disorder characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ damage. We present the case of a 71-year-old man initially diagnosed with malaria-like symptoms and displaying markers of microangiopathic hemolytic anemia, severe thrombocytopenia, renal injury, and neurological impairment. Despite antimalarial treatment, acquired TTP was suspected. Plasma exchange and immunosuppressive therapy led to clinical improvement, normalizing the platelet count and hemolytic profile. Diagnostic confirmation revealed significantly reduced ADAMTS13 levels. Following the proposed treatment, the patient's ADAMTS13 levels normalized. This case illustrates acquired TTP linked to uncomplicated Plasmodium vivax malaria.

获得性血栓性血小板减少性紫癜(TTP)是一种罕见的危及生命的疾病,其特点是微血管病性溶血性贫血、严重血小板减少和器官损伤。我们介绍了一名 71 岁男性的病例,他最初被诊断为疟疾样症状,并表现出微血管病性溶血性贫血、严重血小板减少、肾损伤和神经功能损害。尽管进行了抗疟治疗,但仍怀疑是获得性 TTP。经过血浆置换和免疫抑制治疗后,患者的临床症状有所改善,血小板计数和溶血情况趋于正常。诊断确认显示 ADAMTS13 水平明显降低。经过建议的治疗,患者的 ADAMTS13 水平恢复正常。本病例说明获得性 TTP 与无并发症的间日疟原虫疟疾有关。
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引用次数: 0
Crusted Scabies. 结痂的疥疮
IF 1.8 4区 医学 Q2 PARASITOLOGY Pub Date : 2024-09-02 eCollection Date: 2024-01-01 DOI: 10.1590/0037-8682-0199-2024
Nurimar Conceição Fernandes, Carolina Piccinini Silva, Gabriel Castro Tavares
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引用次数: 0
Flying to the moon: Impactful accounts of triatomines invasion from the 2nd to the 13th floor of an urban residential building in the municipality of Rio Branco, Acre, Brazil. 飞向月球:巴西阿克里Rio Branco市一栋城市住宅楼2楼至13楼的三蠹入侵情况。
IF 1.8 4区 医学 Q2 PARASITOLOGY Pub Date : 2024-09-02 eCollection Date: 2024-01-01 DOI: 10.1590/0037-8682-0122-2024
Manoella da Silva Moura, Luciana Braga da Silva, Fernanda Portela Madeira, Francisco Warcron Oliveira das Neves, André Luiz Rodrigues Menezes, João Aristeu da Rosa, Jader de Oliveira, Luís Marcelo Aranha Camargo, Mariane Albuquerque Lima Ribeiro, Dionatas Ulises de Oliveira Meneguetti

Background: Vectorial transmission through hematophagous triatomine insects remains the primary mode of Chagas Disease contagion. These insects have become increasingly common in urban environments. Therefore, this study aimed to report an encounter of triatomines with trypanosomatid infection in a vertical residential condominium in Rio Branco, the capital of the state of Acre, in the western Brazilian Amazon.

Methods: Triatomines were collected from residents and sent to the municipality's Entomological Surveillance sector. Trypanosomatid positivity was evaluated using optical microscopy, followed by species and genotype identification using molecular biology techniques.

Results: Twenty-five adult triatomine specimens were collected from two of three condominium buildings invading apartments from the 2nd to 13th floors. Six specimens were identified as Rhodnius sp. and 19 as R. montenegrensis. Among these, molecular tests were conducted on seven specimens, with five testing positive for Trypanosoma cruzi, all belonging to genotype TcI.

Conclusions: These findings underscore the need for further studies to better understand the invasive capacity of these insects in these environments and the mechanisms involved in this process.

背景:通过噬血三蠹昆虫的媒介传播仍然是南美锥虫病的主要传染方式。这些昆虫在城市环境中越来越常见。因此,本研究旨在报告在巴西亚马逊西部阿克里州首府里奥布朗库的一个垂直住宅公寓中发现的三蠹虫感染锥虫病的情况:方法:从居民身上采集三蠹虫,并将其送至市政府昆虫监测部门。使用光学显微镜评估锥虫阳性率,然后使用分子生物学技术鉴定物种和基因型:从三栋公寓楼中的两栋采集到 25 个成虫标本,入侵公寓从 2 楼到 13 楼。6 个标本被鉴定为 Rhodnius sp.,19 个被鉴定为 R. montenegrensis。其中,对 7 个标本进行了分子检测,5 个标本的克鲁斯锥虫检测结果呈阳性,均属于基因型 TcI:这些发现强调了进一步研究的必要性,以便更好地了解这些昆虫在这些环境中的入侵能力以及这一过程的相关机制。
{"title":"Flying to the moon: Impactful accounts of triatomines invasion from the 2nd to the 13th floor of an urban residential building in the municipality of Rio Branco, Acre, Brazil.","authors":"Manoella da Silva Moura, Luciana Braga da Silva, Fernanda Portela Madeira, Francisco Warcron Oliveira das Neves, André Luiz Rodrigues Menezes, João Aristeu da Rosa, Jader de Oliveira, Luís Marcelo Aranha Camargo, Mariane Albuquerque Lima Ribeiro, Dionatas Ulises de Oliveira Meneguetti","doi":"10.1590/0037-8682-0122-2024","DOIUrl":"10.1590/0037-8682-0122-2024","url":null,"abstract":"<p><strong>Background: </strong>Vectorial transmission through hematophagous triatomine insects remains the primary mode of Chagas Disease contagion. These insects have become increasingly common in urban environments. Therefore, this study aimed to report an encounter of triatomines with trypanosomatid infection in a vertical residential condominium in Rio Branco, the capital of the state of Acre, in the western Brazilian Amazon.</p><p><strong>Methods: </strong>Triatomines were collected from residents and sent to the municipality's Entomological Surveillance sector. Trypanosomatid positivity was evaluated using optical microscopy, followed by species and genotype identification using molecular biology techniques.</p><p><strong>Results: </strong>Twenty-five adult triatomine specimens were collected from two of three condominium buildings invading apartments from the 2nd to 13th floors. Six specimens were identified as Rhodnius sp. and 19 as R. montenegrensis. Among these, molecular tests were conducted on seven specimens, with five testing positive for Trypanosoma cruzi, all belonging to genotype TcI.</p><p><strong>Conclusions: </strong>These findings underscore the need for further studies to better understand the invasive capacity of these insects in these environments and the mechanisms involved in this process.</p>","PeriodicalId":21199,"journal":{"name":"Revista da Sociedade Brasileira de Medicina Tropical","volume":"57 ","pages":"e004152024"},"PeriodicalIF":1.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Influence of temperature and precipitation on dengue incidence in Campinas, São Paulo State, Brazil (2013-2022). 气温和降水对巴西圣保罗州坎皮纳斯登革热发病率的影响(2013-2022 年)。
IF 1.8 4区 医学 Q2 PARASITOLOGY Pub Date : 2024-09-02 eCollection Date: 2024-01-01 DOI: 10.1590/0037-8682-0080-2024
Bernardo Geraldini, Igor Cavallini Johansen, Marcelo Justus

Background: Global dengue cases are rising, notably in Brazil.

Methods: By using monthly data, we estimated linear regressions with ARIMA errors to measure the influence of temperature and precipitation on dengue incidence in the city of Campinas, São Paulo State, Brazil.

Results: Findings suggest that a 1°C increase in mean temperature can lead to a cumulative increase of up to 40% in dengue incidence within 2 months. Precipitation shows no significant impact.

Conclusions: Results highlight the importance of temperature on the spread of dengue and potentially other mosquito-borne diseases.

背景:全球登革热病例正在上升,尤其是在巴西:全球登革热病例正在上升,尤其是在巴西:通过使用月度数据,我们估计了带有 ARIMA 误差的线性回归,以衡量气温和降水对巴西圣保罗州坎皮纳斯市登革热发病率的影响:结果:研究结果表明,平均气温每升高 1°C 会导致登革热发病率在 2 个月内累计增加 40%。降水量没有明显影响:结论:研究结果凸显了温度对登革热及其他潜在蚊媒疾病传播的重要性。
{"title":"Influence of temperature and precipitation on dengue incidence in Campinas, São Paulo State, Brazil (2013-2022).","authors":"Bernardo Geraldini, Igor Cavallini Johansen, Marcelo Justus","doi":"10.1590/0037-8682-0080-2024","DOIUrl":"10.1590/0037-8682-0080-2024","url":null,"abstract":"<p><strong>Background: </strong>Global dengue cases are rising, notably in Brazil.</p><p><strong>Methods: </strong>By using monthly data, we estimated linear regressions with ARIMA errors to measure the influence of temperature and precipitation on dengue incidence in the city of Campinas, São Paulo State, Brazil.</p><p><strong>Results: </strong>Findings suggest that a 1°C increase in mean temperature can lead to a cumulative increase of up to 40% in dengue incidence within 2 months. Precipitation shows no significant impact.</p><p><strong>Conclusions: </strong>Results highlight the importance of temperature on the spread of dengue and potentially other mosquito-borne diseases.</p>","PeriodicalId":21199,"journal":{"name":"Revista da Sociedade Brasileira de Medicina Tropical","volume":"57 ","pages":"e007102024"},"PeriodicalIF":1.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Entomological indicators and food sources of triatomines in the Brazilian semi-arid region. 巴西半干旱地区三蠹虫的昆虫学指标和食物来源。
IF 1.8 4区 医学 Q2 PARASITOLOGY Pub Date : 2024-08-16 eCollection Date: 2024-01-01 DOI: 10.1590/0037-8682-0573-2023
Luis Ricardo Soares da Silva, João Paulo Sales Oliveira-Correia, Francisco José de Freitas Araújo, Cleber Galvão, Maria Beatriz Araújo Silva, Jaqueline Bianque de Oliveira

Background: Triatomines are biological vectors of Trypanosoma cruzi, the etiological agent of Chagas Disease (CD) and have various mammalian hosts. This study evaluated the entomological indicators and food sources of triatomines in Petrolina in the semi-arid region of Brazil, where CD is endemic.

Methods: Triatomines were captured indoors and outdoors through an active search and entomological indices (household and natural infections) were calculated. Parasitological analyses were performed through microscopic visualization using Giemsa-stained insect feces, and DNA sequencing was employed to identify food sources from the gut contents of 82 insects (9.05%) that were better preserved.

Results: We captured triatomines (906) in peridomicile (807) and intradomicile (99): Triatoma brasiliensis (84.7%, 767 specimens), Triatoma spp. (8.2%, 74 specimens), T. pseudomaculata (6.5%, 59 specimens), Rhodnius spp. (0.4%, four specimens), R. nasutus (0.1%, one specimen), and T. sordida (0.1%, one specimen). The household infestation index is 11.8%. Thirty-five triatomines were infected (33 T. brasiliensis and two T. pseudomaculata), corresponding to a natural infection index of 3.8%. The identified food sources were human T. pseudomaculata and T. brasiliensis, dogs for T. brasiliensis and rodents (Mus musculus) for T. brasiliensis.

Conclusions: The results reinforce the need to intensify CD diagnosis, surveillance, and control actions, as an increase in entomological indices was recorded. Blood from humans and domestic and synanthropic animals was detected in the infected triatomines, suggesting a risk of CD vector transmission in Petrolina. As CD is a zoonosis, multidisciplinary and intersectoral CD surveillance must be conducted in the context of the One Health.

背景:三蠹虫是南美锥虫病(CD)病原体南美锥虫的生物载体,有多种哺乳动物宿主。本研究评估了南美锥虫病流行的巴西半干旱地区 Petrolina 的昆虫学指标和三蠹虫的食物来源:方法:通过主动搜索在室内和室外捕捉三蠹,并计算昆虫指数(家庭感染和自然感染)。通过显微镜观察吉氏染色的昆虫粪便进行寄生虫学分析,并对保存较好的 82 只昆虫(9.05%)的肠道内容物进行 DNA 测序,以确定其食物来源:结果:我们捕获了906只三蠹昆虫,其中有807只在体外,99只在体内:巴西蝽(84.7%,767 个标本)、蝽属(8.2%,74 个标本)、假蝽(6.5%,59 个标本)、蝽属(0.4%,4 个标本)、鼻蝽(0.1%,1 个标本)和蝽(0.1%,1 个标本)。家庭虫害指数为 11.8%。有 35 只三蝽受到感染(33 只巴西蝽和 2 只假蝽),自然感染指数为 3.8%。已确定的食物来源是人类的假疟原虫和巴西疟原虫,狗是巴西疟原虫的食物来源,啮齿动物(麝)是巴西疟原虫的食物来源:结果表明,由于昆虫学指数的增加,有必要加强 CD 诊断、监测和控制行动。在受感染的三螨中检测到了人类、家畜和同类动物的血液,这表明佩特罗里纳存在着 CD 病媒传播的风险。由于 CD 是一种人畜共患病,因此必须在 "一个健康 "的背景下开展多学科和跨部门的 CD 监测。
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引用次数: 0
Paracoccidioidomycosis: An uncommon cause of discitis in lupus. 副球孢子菌病:狼疮椎间盘炎的罕见病因。
IF 1.8 4区 医学 Q2 PARASITOLOGY Pub Date : 2024-07-29 eCollection Date: 2024-01-01 DOI: 10.1590/0037-8682-0191-2024
Simone Appenzeller, Lilian Lavras Costallat, Marcelo de Carvalho Ramos, Samuel de Oliveira Andrade, Fabiano Reis
{"title":"Paracoccidioidomycosis: An uncommon cause of discitis in lupus.","authors":"Simone Appenzeller, Lilian Lavras Costallat, Marcelo de Carvalho Ramos, Samuel de Oliveira Andrade, Fabiano Reis","doi":"10.1590/0037-8682-0191-2024","DOIUrl":"10.1590/0037-8682-0191-2024","url":null,"abstract":"","PeriodicalId":21199,"journal":{"name":"Revista da Sociedade Brasileira de Medicina Tropical","volume":"57 ","pages":"e00922"},"PeriodicalIF":1.8,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Screening of synthetic 1,2,3-triazolic compounds inspired by SRPIN340 as anti-Trypanosoma cruzi agents. 筛选受 SRPIN340 启发合成的 1,2,3-三唑类化合物作为抗克鲁斯锥虫药物。
IF 1.8 4区 医学 Q2 PARASITOLOGY Pub Date : 2024-07-29 eCollection Date: 2024-01-01 DOI: 10.1590/0037-8682-0585-2023
Fernanda Karoline Vieira da Silva Torchelsen, Tamiles Caroline Pedrosa Fernandes, Sara Maria Ribeiro de Sousa, Policarpo Ademar Sales-Junior, Renata Tupinambá Branquinho, Silvane Maria Fonseca Murta, Róbson Ricardo Teixeira, Vanessa Carla Furtado Mosqueira, Marta de Lana

Background: The current treatments for Chagas disease (CD) include benznidazole and nifurtimox, which have limited efficacy and cause numerous side effects. Triazoles are candidates for new CD treatments due to their ability to eliminate T. cruzi parasites by inhibiting ergosterol synthesis, thereby damaging the cell membranes of the parasite.

Methods: Eleven synthetic analogs of the kinase inhibitor SRPIN340 containing a triazole core (compounds 6A-6K) were screened in vitro against the Tulahuen strain transfected with β-galactosidase, and their IC50, CC50, and selectivity indexes (SI) were calculated. Compounds with an SI > 50 were further evaluated in mice infected with the T. cruzi Y strain by rapid testing.

Results: Eight compounds were active in vitro with IC50 values ranging from 0.5-10.5 µg/mL. The most active compounds, 6E and 6H, had SI values of 125.2 and 69.6, respectively. These compounds also showed in vivo activity, leading to a reduction in parasitemia at doses of 10, 50, and 250 mg/kg/day. At doses of 50 and 250 mg/kg/day, parasitemia was significantly reduced compared to infected untreated animals, with no significant differences between the effects of 6E and 6H.

Conclusions: This study identified two new promising compounds for CD chemotherapy and confirmed their activity against T. cruzi.

背景:目前治疗南美锥虫病(CD)的药物包括苯并咪唑和硝呋太尔制霉素,这两种药物的疗效有限,而且副作用很大。三唑类药物能够通过抑制麦角甾醇的合成,从而破坏寄生虫的细胞膜,从而消灭南美锥虫病寄生虫,因此是治疗南美锥虫病的新药:方法:针对转染有β-半乳糖苷酶的Tulahuen菌株,体外筛选了含有三唑核心的激酶抑制剂SRPIN340的11种合成类似物(化合物6A-6K),并计算了它们的IC50、CC50和选择性指数(SI)。通过快速测试,对 SI > 50 的化合物在小鼠感染 T. cruzi Y 株后进行了进一步评估:结果:8 个化合物在体外具有活性,IC50 值在 0.5-10.5 µg/mL 之间。活性最强的化合物 6E 和 6H 的 SI 值分别为 125.2 和 69.6。这些化合物还显示出体内活性,在剂量为 10、50 和 250 毫克/千克/天时可降低寄生虫血症。在 50 和 250 毫克/千克/天的剂量下,寄生虫血症与未受感染的动物相比明显减少,6E 和 6H 的效果没有显著差异:这项研究发现了两种有希望用于CD化疗的新化合物,并证实了它们对T. cruzi的活性。
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引用次数: 0
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