Current Treatment of Chagas Disease

Álvarez-Hernández, Diego-Abelardo; Castro-Rico, Zaira-Leticia; García-Rodríguez-Arana, Rodolfo; González-Chávez, A.-M.; González-Chávez, Mario-Andrés; Martínez-Juárez, Luis-Alberto; Ferreira, Claudia; Vázquez-López, Rosalino

doi:10.1007/s40506-020-00238-1

Cited by 5 publications

(11 citation statements)

References 41 publications

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“…Nifurtimox is also contraindicated in case of neurological or psychiatric disorders. 2 , 25 Their cure rate ranges from 70% to 80% when administered during the acute stage of the disease; meanwhile, it ranges from 6% to 10% when administered during the chronic stage. 25 In our review, about 3 out of 10 patients were at the acute stage of the disease, and 7 out of 10 at the chronic stage.…”

Section: Discussionmentioning

confidence: 99%

“…2 , 25 Their cure rate ranges from 70% to 80% when administered during the acute stage of the disease; meanwhile, it ranges from 6% to 10% when administered during the chronic stage. 25 In our review, about 3 out of 10 patients were at the acute stage of the disease, and 7 out of 10 at the chronic stage. From the patients at the chronic stage of the disease, 1 out of 10 remained in the chronic indeterminate stage, and 5 out of 10 developed the chronic determinate stage.…”

Section: Discussionmentioning

confidence: 99%

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A systematic review of historical and current trends in Chagas disease

Álvarez-Hernández

García-Rodríguez-Arana

Ortiz-Hernández

et al. 2021

Therapeutic Advances in Infection

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Introduction: Chagas disease (CD) is caused by Trypanosoma cruzi. When acquired, the disease develops in stages. For diagnosis, laboratory confirmation is required, and an extensive assessment of the patient’s health should be performed. Treatment consists of the administration of trypanocidal drugs, which may cause severe adverse effects. The objective of our systematic review was to analyze data contained in the CD published case reports to understand the challenges that patients and clinicians face worldwide. Materials and methods: We performed a systematic review following the PRISMA guidance. PubMed database was explored using the terms ‘American trypanosomiasis’ or ‘Chagas disease’. Results were limited to human case reports written in English or Spanish. A total of 258 reports (322 patients) were included in the analysis. Metadata was obtained from each article. Following this, it was analyzed to obtain descriptive measures. Results: From the sample, 56.2% were males and 43.8% were females. Most cases were from endemic countries (85.4%). The most common clinical manifestations were fever during the acute stage (70.0%), dyspnea during the chronic stage in its cardiac form (53.7%), and constipation during the chronic stage in its digestive form (73.7%). Most patients were diagnosed in the chronic stage (72.0%). Treatment was administered in 56.2% of cases. The mortality rate for the acute stage cases was 24.4%, while for the chronic stage this was 28.4%. Discussion: CD is a parasitic disease endemic to Latin America, with increasing importance due to human and vector migration. In this review, we report reasons for delays in diagnosis and treatment, and trends in medical practices. Community awareness must be increased to improve CD’s diagnoses; health professionals should be appropriately trained to detect and treat infected individuals. Furthermore, public health policies are needed to increase the availability of screening and diagnostic tools, trypanocidal drugs, and, eventually, vaccines.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A systematic review of historical and current trends in Chagas disease

Álvarez-Hernández

García-Rodríguez-Arana

Ortiz-Hernández

et al. 2021

Therapeutic Advances in Infection

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“…Como dito anteriormente, a HAS constitui-se como uma das principais complicações cardiovasculares da doença de Chagas . A fisiopatologia da tripanossomíase que envolve o comprometimento cardíaco se inicia com uma miocardite durante a fase aguda da doença (Álvarez-Hernández et al, 2020). Posteriormente, em alguns casos o paciente pode evoluir clinicamente com uma miocardite crônica fibrosante, com características de baixa intensidade e persistente, induzindo Research, Society and Development, v. 11, n. 15, e81111537133, 2022 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v11i15.37133 o dano miocárdico e resultando, de forma tardia, a cardiomiopatia chagásica crônica (de Oliveira Vieira et al, 2021;.…”

Section: Discussionunclassified

A relação entre a doença de Chagas e a hipertensão arterial sistêmica: revisão integrativa

Neto

Faria

Machado

et al. 2022

RSD

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A doença de Chagas é uma infecção causada pelo protozoário Trypanosoma cruzi. Essa patologia apresenta curso clínico bifásico, dividido em agudo e crônico, no qual o segundo é responsável por 10 a 30% das complicações cardíacas associadas, sendo que dentre as principais formas de comprometimento cardiovascular, vale destacar a ocorrência da Hipertensão Arterial Sistêmica (HAS). Portanto, o objetivo deste estudo foi revisar a literatura acerca das principais características que envolvem a relação entre a doença de Chagas e a HAS. Para isso, foi realizada uma busca por estudos nas seguintes bases de dados bibliográficos: PubMed, STM (Science Translational Medicine) e SciELO (Scientific Eletronic Library Online), durante o período de setembro a outubro de 2022. Dentre os resultados apresentados, do total de 195 estudos encontrados nas bases de dados citadas, apenas 30 foram usados como fontes para esta revisão, sendo 7 artigos originais e 23 de revisão. Os dados referentes a cada um dos trabalhos estão expostos no Quadro 1, elaborado pelos autores. Dessa forma, embora a literatura atual tenha poucos estudos relacionados a esta temática, duas hipóteses puderam ser levantadas: a primeira classifica a HAS um fator de risco para a doença de Chagas, e a segunda a considera para pacientes chagásicos que possuem predisposição para doenças cardiovasculares. No entanto, ambas a denominam como complicação da tripanossomíase.

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“…The drugs cannot be administrated during pregnancy and in patients with hepatic or kidney disease. Nifurtimox is also contraindicated in neurological or psychiatric disorders 8 . The biggest problem however, is that while the efficacy in the acute stage of the disease ranges from 70 to 80%, it drops dramatically to 6–10% cure rate in the chronic stage 8 .…”

Section: Introductionmentioning

confidence: 99%

“…Nifurtimox is also contraindicated in neurological or psychiatric disorders 8 . The biggest problem however, is that while the efficacy in the acute stage of the disease ranges from 70 to 80%, it drops dramatically to 6–10% cure rate in the chronic stage 8 . Furthermore, adverse effects of a required long-term treatment frequently lead to discontinuation and treatment failure.…”

Section: Introductionmentioning

confidence: 99%

Small molecule mediated inhibition of protein cargo recognition by peroxisomal transport receptor PEX5 is toxic to Trypanosoma

Napolitano

Softley

Blat

et al. 2022

Sci Rep

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Trypanosomiases are life-threatening infections of humans and livestock, and novel effective therapeutic approaches are needed. Trypanosoma compartmentalize glycolysis into specialized organelles termed glycosomes. Most of the trypanosomal glycolytic enzymes harbor a peroxisomal targeting signal-1 (PTS1) which is recognized by the soluble receptor PEX5 to facilitate docking and translocation of the cargo into the glycosomal lumen. Given its pivotal role in the glycosomal protein import, the PEX5–PTS1 interaction represents a potential target to inhibit import of glycolytic enzymes and thus kill the parasite. We developed a fluorescence polarization (FP)-based assay for monitoring the PEX5–PTS1 interaction and performed a High Throughput Screening (HTS) campaign to identify small molecule inhibitors of the interaction. Six of the identified hits passed orthogonal selection criteria and were found to inhibit parasite growth in cell culture. Our results validate PEX5 as a target for small molecule inhibitors and provide scaffolds suitable for further pre-clinical development of novel trypanocidal compounds.

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Current Treatment of Chagas Disease

Cited by 5 publications

References 41 publications

A systematic review of historical and current trends in Chagas disease

A systematic review of historical and current trends in Chagas disease

A relação entre a doença de Chagas e a hipertensão arterial sistêmica: revisão integrativa

Small molecule mediated inhibition of protein cargo recognition by peroxisomal transport receptor PEX5 is toxic to Trypanosoma

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