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Parasite polymorphism and host immune response in cutaneous leishmaniasis outcome

Award Number: R01AI136862
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: 03/20/2018
PERIOD OF PERFORMANCE END DATE: 02/29/2024

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Parasite polymorphism and host immune response in cutaneous leishmaniasis outcome - Summary Leishmania braziliensis infection may cause a high spectrum of clinical manifestation, including the more prevalent form, cutaneous leishmaniasis (CL). Inflammatory response is a hallmark of CL and high levels of TNF, presence of CD8+ T cells and mononuclear phagocytes are associated with skin ulcer development in these individuals. In our endemic area we have been able to identify individuals with a non-ulcerated lesion (papule), with regional lymphadenopathy and positive Leishmania skin test. These individuals report less than 15 days of disease evolution and are considered to have early CL (ECL). Our preliminary data shows that ECL patients have more parasites than CL ones and are able to mount inflammatory response to Leishmania antigen in in-vitro assays. A major problem in areas of L. braziliensis transmission regards therapeutic failure. Studies from our group and others show that up to 30% of CL (with ulcerated lesion) patients fail treatment with pentavalent antimony, drug of choice of Brazilian Minister of Health to treat leishmaniasis. The early treatment of the majority of infectious disease benefits the patients, decreasing time to cure and relapses. However, we have been reporting that in ECL the therapeutic failure is up to 70%. Interestingly, our preliminary data show genetic differences between most parasites isolated from ECL and those from CL. Our main hypothesis is that high rates of therapeutic failure in ECL is associated with drug resistance and lack of regulation of inflammatory due to high amounts of Leishmania, thus contributing to ulcer development. To investigate the mechanisms associated with therapeutic failure we will establish a cohort of ECL and CL individuals admitted in the health post of our endemic area. In the Aim 1 of the present proposal we intend to assess parasite genetic polymorphism and resistance to leishmanicidal drugs, and quantify host and Leishmania genes associated with therapeutic failure. In Aim 2 we will investigate immune mechanisms involved of therapeutic failure. For that we will determine the contribution of cells, soluble factors, cell receptors and regulatory mechanisms in ECL and CL before and during therapy. In Aim 3 we will study the ability of eicosanoids metabolites of Omega-3 fatty acids (DHA, EPA and Resolvins) to regulate inflammatory response in ECL and CL. The early identification of individuals that will fail treatment will allow the early use of another choice of therapy.


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: 2025 ( Subtotal = $0 )
2025	2022	FUNDACAO DE APOIO A PESQUISA E A EXTENSAO	RUA PROFESSOR EDGARD MATA 001	SALVADOR				BRA	Allergy and Infectious Diseases Research	000	5	1/7/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $118,530 )
2022	2022	FUNDACAO DE APOIO A PESQUISA E A EXTENSAO FAPEX	AV. MANOEL DIAS DA SILVA 1.784 ED. COM. PITUBA TRADE	SALVADOR	BA			BRA	Allergy and Infectious Diseases Research	000	5	3/2/2022	NON-COMPETING CONTINUATION	$118,530
														Subtotal = $118,530

Issue Date FY: 2021 ( Subtotal = $118,530 )
2021	2021	FUNDACAO DE APOIO A PESQUISA E A EXTENSAO - FAPEX.	RUA CAETANO MOURA 140	SALVADOR	BA			BRA	Allergy and Infectious Diseases Research	000	4	3/24/2021	NON-COMPETING CONTINUATION	$118,530
														Subtotal = $118,530

Issue Date FY: 2020 ( Subtotal = $118,530 )
2020	2020	FUNDACAO DE APOIO A PESQUISA E A EXTENSAO - FAPEX.	RUA CAETANO MOURA 140	SALVADOR	BA	40210-340		BRA	Allergy and Infectious Diseases Research	000	3	1/31/2020	NON-COMPETING CONTINUATION	$118,530
														Subtotal = $118,530

Issue Date FY: 2019 ( Subtotal = $118,530 )
2019	2019	FUNDACAO DE APOIO A PESQUISA E A EXTENSAO - FAPEX.	RUA CAETANO MOURA 140	SALVADOR	BA	40210-340		BRA	Allergy and Infectious Diseases Research	002	2	2/20/2019	NON-COMPETING CONTINUATION	$118,530
2019	2018	FUNDACAO DE APOIO A PESQUISA E A EXTENSAO - FAPEX.	RUA CAETANO MOURA 140	SALVADOR	BA	40210-340		BRA	Allergy and Infectious Diseases Research	000	1	12/19/2018	NEW	-$118,530
2019	2018	FUNDACAO DE APOIO A PESQUISA E A EXTENSAO - FAPEX.	RUA CAETANO MOURA 140	SALVADOR	BA	40210-340		BRA	Allergy and Infectious Diseases Research	001	1	1/7/2019	NEW	$118,530
														Subtotal = $118,530

Issue Date FY: 2018 ( Subtotal = $118,530 )
2018	2018	FUNDACAO DE APOIO A PESQUISA E A EXTENSAO - FAPEX.	RUA CAETANO MOURA 140	SALVADOR	BA	40210-340		BRA	Allergy and Infectious Diseases Research	000	1	3/20/2018	NEW	$118,530
														Subtotal = $118,530

Grand Total All Awards = $592,650

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Parasite polymorphism and host immune response in cutaneous leishmaniasis outcome

Award Number: R01AI136862

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: 03/20/2018

PERIOD OF PERFORMANCE END DATE: 02/29/2024

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