System-based insights into parasitological and clinical treatment failure in Chagas disease
ABSTRACT Infectious disease treatment success requires symptom resolution (clinical treatment success), which often but not always involves pathogen clearance. Both of these treatment goals face disease-specific and general challenges. In this review, we summarize the current state of knowledge in m...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2025-02-01
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| Series: | mSystems |
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| Online Access: | https://journals.asm.org/doi/10.1128/msystems.00038-24 |
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| author | Luis Ernst Giovana C. Macedo Laura-Isobel McCall |
| author_facet | Luis Ernst Giovana C. Macedo Laura-Isobel McCall |
| author_sort | Luis Ernst |
| collection | DOAJ |
| description | ABSTRACT Infectious disease treatment success requires symptom resolution (clinical treatment success), which often but not always involves pathogen clearance. Both of these treatment goals face disease-specific and general challenges. In this review, we summarize the current state of knowledge in mechanisms of clinical and parasitological treatment failure in the context of Chagas disease, a neglected tropical disease causing cardiac and gastrointestinal symptoms. Parasite drug resistance and persistence, drug pharmacokinetics and dynamics, as well as persistently altered host immune responses and tissue damage are the most common reasons for Chagas disease treatment failure. We discuss the therapeutics that failed before regulatory approval, limitations of current therapeutic options and new treatment strategies to overcome persistent parasites, inflammatory responses, and metabolic alterations. Large-scale omics analyses were critical in generating these insights and will continue to play a prominent role in addressing the challenges still facing Chagas disease drug treatment. |
| format | Article |
| id | doaj-art-8fd3a9d7d51e46198478e04fec8ec4a7 |
| institution | DOAJ |
| issn | 2379-5077 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSystems |
| spelling | doaj-art-8fd3a9d7d51e46198478e04fec8ec4a72025-08-20T03:16:22ZengAmerican Society for MicrobiologymSystems2379-50772025-02-0110210.1128/msystems.00038-24System-based insights into parasitological and clinical treatment failure in Chagas diseaseLuis Ernst0Giovana C. Macedo1Laura-Isobel McCall2Department of Chemistry and Biochemistry, San Diego State University, San Diego, California, USADepartment of Chemistry and Biochemistry, San Diego State University, San Diego, California, USADepartment of Chemistry and Biochemistry, San Diego State University, San Diego, California, USAABSTRACT Infectious disease treatment success requires symptom resolution (clinical treatment success), which often but not always involves pathogen clearance. Both of these treatment goals face disease-specific and general challenges. In this review, we summarize the current state of knowledge in mechanisms of clinical and parasitological treatment failure in the context of Chagas disease, a neglected tropical disease causing cardiac and gastrointestinal symptoms. Parasite drug resistance and persistence, drug pharmacokinetics and dynamics, as well as persistently altered host immune responses and tissue damage are the most common reasons for Chagas disease treatment failure. We discuss the therapeutics that failed before regulatory approval, limitations of current therapeutic options and new treatment strategies to overcome persistent parasites, inflammatory responses, and metabolic alterations. Large-scale omics analyses were critical in generating these insights and will continue to play a prominent role in addressing the challenges still facing Chagas disease drug treatment.https://journals.asm.org/doi/10.1128/msystems.00038-24drug developmentantiparasitic treatmenttreatment failureChagas diseaseTrypanosoma cruzidrug resistance |
| spellingShingle | Luis Ernst Giovana C. Macedo Laura-Isobel McCall System-based insights into parasitological and clinical treatment failure in Chagas disease mSystems drug development antiparasitic treatment treatment failure Chagas disease Trypanosoma cruzi drug resistance |
| title | System-based insights into parasitological and clinical treatment failure in Chagas disease |
| title_full | System-based insights into parasitological and clinical treatment failure in Chagas disease |
| title_fullStr | System-based insights into parasitological and clinical treatment failure in Chagas disease |
| title_full_unstemmed | System-based insights into parasitological and clinical treatment failure in Chagas disease |
| title_short | System-based insights into parasitological and clinical treatment failure in Chagas disease |
| title_sort | system based insights into parasitological and clinical treatment failure in chagas disease |
| topic | drug development antiparasitic treatment treatment failure Chagas disease Trypanosoma cruzi drug resistance |
| url | https://journals.asm.org/doi/10.1128/msystems.00038-24 |
| work_keys_str_mv | AT luisernst systembasedinsightsintoparasitologicalandclinicaltreatmentfailureinchagasdisease AT giovanacmacedo systembasedinsightsintoparasitologicalandclinicaltreatmentfailureinchagasdisease AT lauraisobelmccall systembasedinsightsintoparasitologicalandclinicaltreatmentfailureinchagasdisease |