{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:36:09Z","timestamp":1787567769653,"version":"build-2736575974"},"reference-count":32,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03 AI166504"],"award-info":[{"award-number":["R03 AI166504"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1UL1TR003163"],"award-info":[{"award-number":["1UL1TR003163"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Infection with the protozoan parasite\n                    <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                    is generally well-controlled by host immune responses, but appears to be rarely eliminated. The resulting persistent, low-level infection results in cumulative tissue damage with the greatest impact generally in the heart in the form of chagasic cardiomyopathy. The relative success in immune control of\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    infection usually averts acute phase death but has the negative consequence that the low-level presence of\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    in hosts is challenging to detect unequivocally. Thus, it is difficult to identify those who are actively infected and, as well, problematic to gauge the impact of treatment, particularly in the evaluation of the relative efficacy of new drugs. In this study, we employ DNA fragmentation and high numbers of replicate PCR reaction (\u2018deep-sampling\u2019) and to extend the quantitative range of detecting\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    in blood by at least three orders of magnitude relative to current protocols. When combined with sampling blood at multiple time points, deep sampling of fragmented DNA allowed for detection of\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    in all infected hosts in multiple host species, including humans, macaques, and dogs. In addition, we provide evidence for a number of characteristics not previously rigorously quantified in the population of hosts with naturally acquired\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    infection, including, a &gt;6 log variation between chronically infected individuals in the stable parasite levels, a continuing decline in parasite load during the second and third years of infection in some hosts, and the potential for parasite load to change dramatically when health conditions change. Although requiring strict adherence to contamination\u2013prevention protocols and significant resources, deep-sampling PCR provides an important new tool for assessing therapies and for addressing long-standing questions in\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    infection and Chagas disease.\n                  <\/jats:p>","DOI":"10.7554\/elife.104547","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T07:25:17Z","timestamp":1738740317000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.104547","source":"Crossref","is-referenced-by-count":3,"title":["Serial \u2018deep-sampling\u2019 PCR of fragmented DNA reveals the wide range of Trypanosoma cruzi burden among chronically infected human, macaque, and canine hosts, and allows accurate monitoring of parasite load following treatment"],"prefix":"10.7554","volume":"14","author":[{"given":"Brooke E","family":"White","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00te3t702","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Tropical and Emerging Global Disease","place":["Athens, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Carolyn L","family":"Hodo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"Michale E. Keeling Center for Comparative Medicine and Research, The University of Texas MD Anderson Cancer Center","place":["Bastrop, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Sarah","family":"Hamer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01f5ytq51","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University","place":["College Station, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"resources","vocabulary":"credit"}]},{"given":"Ashley B","family":"Saunders","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01f5ytq51","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University","place":["College Station, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"resources","vocabulary":"credit"}]},{"given":"Susana A","family":"Laucella","sequence":"additional","affiliation":[{"name":"Research Department, Instituto Nacional de Parasitolog\u00eda \"Dr. Mario Fatala Chaben\", Buenos Aires, Argentina. Chagas Disease Unit, Hospital Interzonal General de Agudos Eva Per\u00f3n","place":["Buenos Aires, Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"resources","vocabulary":"credit"}]},{"given":"Daniel B","family":"Hall","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00te3t702","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Statistics, University of Georgia","place":["Athens, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9589-5243","authenticated-orcid":true,"given":"Rick L","family":"Tarleton","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00te3t702","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Tropical and Emerging Global Disease","place":["Athens, United States"]},{"id":[{"id":"https:\/\/ror.org\/00te3t702","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cellular Biology, University of Georgia","place":["Athens, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abb7656","type":"journal-article","article-title":"A modified drug regimen clears active and dormant trypanosomes in mouse models of Chagas disease","volume":"12","author":"Bustamante","year":"2020","journal-title":"Science Translational Medicine"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0010688","type":"journal-article","article-title":"Prophylactic low-dose, bi-weekly benznidazole treatment fails to prevent Trypanosoma cruzi infection in dogs under intense transmission pressure","volume":"16","author":"Bustamante","year":"2022","journal-title":"PLOS Neglected Tropical Diseases"},{"key":"bib3","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00132-23","type":"journal-article","article-title":"Frequency variation and dose modification of benznidazole administration for the treatment of trypanosoma cruzi infection in mice, dogs, and nonhuman primates","volume":"67","author":"Bustamante","year":"2023","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"bib4","first-page":"155","type":"journal-article","article-title":"Pitfalls of quantitative real-time reverse-transcription polymerase chain reaction","volume":"15","author":"Bustin","year":"2004","journal-title":"Journal of Biomolecular Techniques"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1093\/jac\/dkab054","type":"journal-article","article-title":"Reduced trypanosoma cruzi-specific humoral response and enhanced T cell immunity after treatment interruption with benznidazole in chronic Chagas disease","volume":"76","author":"Castro Eiro","year":"2021","journal-title":"The Journal of Antimicrobial Chemotherapy"},{"key":"bib6","type":"conference-paper","article-title":"Chemotherapy of Chagas\u2019 Infection in Man","author":"Cerisola","year":"1977","unstructured":"Cerisola JA. 1977. 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