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Determining the relationship between parasite genetics and pathogen burden in Trypanosoma cruzi infected hosts

Award Number: R21AI202296
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: 09/03/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Determining the relationship between parasite genetics and pathogen burden in Trypanosoma cruzi infected hosts - Project Summary/Abstract There are many unanswered questions concerning the relationship between T. cruzi and the development of clinical Chagas disease. For example, it is often stated that ~30% of T. cruzi infected humans develop clinical Chagas disease but the reasons that most do not is not known. Also, it is not clear why T. cruzi persists for the life of many hosts, despite a vigorous anti-parasite immune response, but is completely resolved in a select few. It is likely that both host and parasite factors contribute to these variable infection outcomes. One limitation in addressing these gaps in knowledge has been the lack of methods to accurately and sensitively quantify parasite burden over time in hosts. We have recently established protocols that allow for sensitive and precise quantification of the relative T. cruzi burden in essentially any infected host and have shown that the stable parasite load can vary between hosts by over 1 million-fold. Additionally, we have isolated over 400 parasite lines from non-human primates that exhibit these wide ranges of parasite burden. The primary goal of this study will be to determine the relationship between parasite burden in hosts and the genetics of the T. cruzi population in those hosts – in short, does parasite genetics largely or partially determine the parasite load in a host? To achieve this goal, we will apply low-coverage whole-genome sequencing (lcWGS) of T. cruzi isolates freshly obtained from multiple colonies of non-human primates whose parasite burden has been precisely determined. In addition, these studies are expected to allow us to begin to address other important questions about the populations genomics of T. cruzi, including: Are distinct populations of parasites circulating in locations separated by 100 miles or more and do the genetics of these parasite population shift significantly over time?; Are distinct parasite populations circulating in different host species in the same facility?; How diverse are the parasite populations in an individual and do these populations change over time and with and without treatment?. Collectively, we expect the completion of this study to provide answers to long-standing questions on one of the major and long-debated variables that impact the development of clinical disease in T. cruzi infection – that of the genetics of the infecting parasite population. These studies are also expected to establish lcWGS as an essential tool for parasite population genomics, including that of T. cruzi, and to provide the means to better understand the dynamics of T. cruzi transmission in different settings and over time.


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 = $228,000 )
2026	2026	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	1	9/3/2026	NEW	$228,000
														Subtotal = $228,000

Grand Total All Awards = $228,000

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Determining the relationship between parasite genetics and pathogen burden in Trypanosoma cruzi infected hosts

Award Number: R21AI202296

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: 09/03/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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