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Markers of Triclabendazole Resistant Fascioliasis in the Highlands of Peru

Award Number: R01AI146353
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/20/2019
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Markers of Triclabendazole Resistant Fascioliasis in the Highlands of Peru - PROJECT SUMMARY/ABSTRACT Fascioliasis is a global food-borne trematode infection targeted by WHO as an important neglected tropical disease due to its high impact in human and livestock populations around the world. Triclabendazole is the only drug recommended for treatment, but drug resistance is widespread in livestock and is an emerging problem among infected humans. The mechanisms of triclabendazole resistance are not known and there are no reliable markers that predict the susceptibility phenotype among infected subjects. Targeted evaluation of specific candidate genes has yielded inconsistent results, likely due to the complexity of genotype-phenotype relationships. The current proposal will use a genome-wide association approach to identify genetic variants that are associated with triclabendazole resistance by analyzing the genomes of a large number of Fasciola parasites infecting animals, including susceptible and triclabendazole-resistant isolates. The resistance-associated loci will be validated using human-infecting parasites because we hypothesize that, due to the zoonotic nature of F. hepatica, the variants contributing to resistance in animal and human hosts are conserved. Lastly, the current grant will evaluate the transcriptional response of different stages of Fasciola exposed to various doses of triclabendazole to uncover the mechanisms that induce resistance to triclabendazole. This is a well-rounded proposal that upon completion will provide a mechanistic understanding of the biological processes that determine the triclabendazole resistance phenotype and a set of reliable genetic markers that distinguish between resistant and susceptible Fasciola parasites. In the long term, the results of this study may allow the creation of diagnostic tools for early identification of TCBZ-R, to direct treatment of infected subjects, and provide guidance for stewardship and control strategies. Identifying and restoring altered pathways may also help overcome resistance and make TCBZ effective again. In addition, we will set-up of a model to study other trematode parasites with complex lifecycles.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$18,953 )
2026	2022	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	4	1/27/2026	NON-COMPETING CONTINUATION	-$18,953
														Subtotal = -$18,953

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	4	8/21/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $483,573 )
2022	2022	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	4	7/26/2022	NON-COMPETING CONTINUATION	$483,573
														Subtotal = $483,573

Issue Date FY: 2021 ( Subtotal = $487,857 )
2021	2021	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	3	7/7/2021	NON-COMPETING CONTINUATION	$487,857
														Subtotal = $487,857

Issue Date FY: 2020 ( Subtotal = $497,882 )
2020	2020	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	2	6/25/2020	NON-COMPETING CONTINUATION	$497,882
														Subtotal = $497,882

Issue Date FY: 2019 ( Subtotal = $533,713 )
2019	2019	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	1	8/20/2019	NEW	$533,713
														Subtotal = $533,713

Grand Total All Awards = $1,984,072

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Markers of Triclabendazole Resistant Fascioliasis in the Highlands of Peru

Award Number: R01AI146353

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/20/2019

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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