The importance of persistence and dormancy in Trypanosoma cruzi infection and Chagas disease
Trypanosoma cruzi typically establishes a life-long infection in its mammalian hosts, causing the destruction of muscle tissues and ultimately resulting in potentially fatal Chagas disease. In this review, we consider the array of avoidance mechanisms that allow for T. cruzi persistence, many of which are unconventional among protozoan pathogens but which collectively are highly effective in the face of otherwise potent host immune responses. We also reflect on the phenomenon of dormancy in T. cruzi amastigotes, which is likely not involved in the long-term persistence of infection. Lastly, we consider how these phenomena of persistence and dormancy complicate the effectiveness of potential therapeutic interventions to prevent Chagas disease.
Molly E Bunkofske, Fernando J Sanchez-Valdez, Rick L Tarleton. Curr Opin Microbiol. 2025 Jun 5:86:102615. doi: 10.1016/j.mib.2025.102615.
In the News: Rick Tarleton
Researchers secure funding to advance Chagas disease research (News-Medical.net)
Investigators are studying Chagas disease with a One Health approach (DVM360)
UGA and Texas A&M Researchers tackle Chagas disease in dogs and humans (WUGA)
Countable Labs Launches Single-Molecule DNA Counting System, PCR Application (GenomeWeb)
Scientists use ‘One Health’ model to fight Chagas disease
Supported by almost $4 million in new funding, researchers at the University of Georgia and Texas A&M are using improved detection and treatment methods to understand Chagas disease, a serious, often overlooked illness affecting both dogs and humans.
A team of researchers at the University of Georgia and Texas A&M University has received more than $4 million from federal and nongovernmental organizations to support research on Chagas disease.
The research will consist of multiple projects focused on the disease’s prevalence, diagnostics to detect the parasite that causes the disease, and treatment protocols to prevent infection and disease in dogs. The ultimate goal is to use the findings to help people as well.
Funded by a $3 million grant from the National Institutes of Health, UGA’s Rick Tarleton will co-lead a project focused on strategies to detect, treat and monitor treatment outcomes in dogs in Texas. The goal is to establish the best practices that prevent the development of cardiac disease, one severe potential side effect of Chagas disease, and to establish resistance to possible future infection.
The researchers will work with dogs that were naturally infected with Chagas disease. Because the disease presents similarly in dogs as in humans, dogs are a good model for examining the effectiveness of the treatment.
“There are a number of important questions related to treatment efficacy and the protection that cured subjects have from future infection that cannot be easily addressed in humans but can be in these dog populations that are under intense transmission pressure in Texas,” said Tarleton, Regents Professor in UGA’s Franklin College of Arts and Sciences.
A growing threat to dog, human health
Tens of millions of people across the Americas have Chagas disease.
Chagas disease is a largely neglected disease. The parasite that causes it, Trypanosoma cruzi, is spread by blood-sucking insects known as kissing bugs, which can be found throughout North, Central and South America.
The disease, which commonly develops in humans and dogs, as well as many other mammals, often goes unnoticed in early stages. But a chronic infection can lead to serious heart and digestive system problems, making early diagnosis and prompt treatment important.
Although most human cases of Chagas disease are reported from South and Central America and Mexico, the parasite and its insect vector are found in abundance in the southern United States. Outdoor pets — particularly working dogs — face especially high risks of infection.
“These areas we are working in have 20% to 30% rates of new infections per year,” Tarleton said. “Those tend to be severe infections where the dogs either die or develop a disease that makes them unable to work.”
Texas has become a hotspot of kissing bugs.
“Unfortunately, Texas has emerged as a hotspot of infected kissing bugs, infected wildlife and infected dogs across the landscape,” said Dr. Sarah Hamer, a professor in the Texas A&M College of Veterinary Medicine and a primary investigator on the projects.
“These projects will advance Chagas disease research to understand the process of natural infections, disease and effect of treatments,” Hamer said. “These projects combine many aspects of biomedical research. We’re conducting field and laboratory research, treating dogs, measuring clinical outcomes and studying ecological factors. It’s truly a ‘One Health’ approach.”
A One Health approach to Chagas disease research
Diagnosing Chagas is complicated — in both people and canines. False negatives aren’t unheard of, leading people to not know they or their pets are infected. And that delays treatment.
Even when the disease is diagnosed promptly, treating the condition can be challenging.
The go-to medications used to treat Chagas, as currently applied, are not reliably effective. But they’re currently the only treatment option. Tarleton’s previous work in mice and other species show that their effectiveness can be improved by altering the dosing regimen.
To address these issues, the researchers will track infected canines using a combination approach with sensitive tests to detect both the parasite DNA and the body’s response to infection. The team will simultaneously test a revised dosing strategy for the current antiparasitic treatment, providing fewer but high-level doses and extending the administration period to improve effectiveness.
Recording health information from such a large population of dogs will hopefully help us understand why the disease develops in different ways.” —Dr. Sarah Hamer, Texas A&M
“The drug we’re using is an existing treatment for Chagas disease in humans,” said Dr. Ashley Saunders, a professor in the Texas A&M College of Veterinary Medicine and a primary investigator on the projects. “But Dr. Tarleton has shown that the parasites aren’t susceptible to this drug when they’re dormant. By changing the drug delivery protocol to dosing over a longer period of time, when the dormant parasites become active again, they are killed by the drug.”
In a related study funded by the United States Department of Homeland Security, the researchers will also monitor DHS-owned working dogs that are often trained in areas where Chagas disease is prevalent. The goal is to understand how the dogs are exposed to the disease as well as the impacts it can have on the canines’ heart health, as well as to develop monitoring and treatment strategies for these working dogs.
“One of the reasons that monitoring dogs is so helpful is because Chagas disease can produce so many different subsets of health problems,” Saunders said. “Some dogs end up with a heart abnormality, but a large number continue living and working happily for many years. Others will die quite suddenly, before anyone knew they had the disease.”
“Recording health information from such a large population of dogs will hopefully help us understand why the disease develops in different ways,” Hamer said.
Advancing canine Chagas disease management
With continued support from the American Kennel Club Canine Health Foundation, the team will treat and monitor individual pet dogs brought to Texas A&M’s Small Animal Teaching Hospital while developing a staging system for Chagas disease in dogs.
“The staging system we develop will help us to categorize the severity of disease, making it easier to determine which dogs will benefit most from drug treatment,” Saunders said. “This scoring system will work hand-in-hand with our improved diagnostic and treatment plan.”
This story was originally published at UGA Today: https://news.uga.edu/scientists-use-one-health-model-to-fight-chagas-disease/
Serial ‘deep-sampling’ 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
Infection with the protozoan parasite Trypanosoma cruzi 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 T. cruzi infection usually averts acute phase death but has the negative consequence that the low-level presence of T. cruzi 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 (‘deep-sampling’) and to extend the quantitative range of detecting T. cruzi 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 T. cruzi 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 T. cruzi infection, including, a >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-prevention protocols and significant resources, deep-sampling PCR provides an important new tool for assessing therapies and for addressing long-standing questions in T. cruzi infection and Chagas disease.
Brooke E White, Carolyn L Hodo, Sarah Hamer, Ashley B Saunders, Susana A Laucella, Daniel B Hall, Rick L Tarleton. Elife. 2025 Apr 15:14:RP104547. doi: 10.7554/eLife.104547.
Domestic Dog Infection with Trypanosoma cruzi from Northern and Southern Regions of Mexico
Background: Chagas disease or American trypanosomiasis, caused by Trypanosoma cruzi and vectored by triatomines, affects millions of people worldwide. In endemic countries including Mexico, infections in domestic animals, such as dogs, may affect the risk of human disease when they serve as a source of infection to vectors that subsequently infect humans. Materials and Methods: We conducted a cross-sectional study of 296 dogs from two cities near the northern and southern borders of Mexico: Reynosa, Tamaulipas, and Tuxtla Gutierrez, Chiapas. Infection was measured based on testing of blood using T. cruzi quantitative PCR (qPCR) and up to three antibody detection assays. The StatPak immunochromatographic assay was used to screen samples and the indirect fluorescent antibody (IFA) and multiplex microsphere immunoassay (MIA) tests were used as secondary tests on all samples that screened positive and a subset of negatives. Serologic positivity was defined based on reactivity on at least two independent tests. Results: Of the 280 samples tested for parasite DNA, two (0.7%) were positive, one of which (0.4%) was confirmed as T. cruzi discrete typing unit TcIV. Overall, 72 (24.3%) samples were reactive for T. cruzi antibodies via StatPak of which 8 were also positive using MIA and 2 were also positive using IFA (including one of the PCR-positive dogs). Overall, nine dogs (3.4%) met study criteria of positivity based on either/both serology or PCR tests. Positive dogs were found in both regions of Mexico; five (2.7%) from Reynosa and four (3.6%) from Tuxtla Gutierrez. We found no association between infection status and state of origin, sex, age group, breed group, neighborhood, and whether other pets lived in the home. Conclusion: Our results re-emphasize dogs’ utility as sentinels for T. cruzi in Mexico and underscore the need for improved veterinary diagnostic tests and parasite surveillance at the household level in endemic countries.
Edward Davila, Nadia A Fernandez-Santos, José Guillermo Estrada-Franco, Lihua Wei, Doireyner Daniel Velázquez-Ramírez, Rosario García-Miranda, Cesar Irecta Nájera, Raúl Cruz-Cadena, Carlos Guichard-Romero, Carlos Rodriguez, Rick Tarleton, Mario A Rodríguez-Pérez, Héctor Ochoa-Díaz-López, Gabriel L Hamer, Sarah A Hamer. Vector Borne Zoonotic Dis. 2024 Jul 1. doi: 10.1089/vbz.2023.0110
People, Parasites, and Pooches – People, Parasites, & Plagues podcast with Rick Tarleton
Rick Tarleton, Regents’ Professor in Franklin College‘s Department of Cellular Biology and member of CTEGD, is the featured guest on this episode of People, Parasites, and Plagues. Listen as he discusses his work with Trypanosoma cruzi and Chagas Disease, what transmission looks like here in the U.S., and the important research being done in this area.
The Unfortunate Abundance of Trypanosoma cruzi in Naturally Infected Dogs and Monkeys Provides Unique Opportunities to Advance Solutions for Chagas Disease
Trypanosoma cruzi, the protozoan parasite and cause of Chagas disease, is widely distributed in many vertebrate and triatomine species throughout North, Central, and South America. Variations in housing quality largely determines human infection risk in the Americas. However, the southern U.S. contains widespread, infected triatomine vectors and captive species and domesticated animals with active T. cruzi infection or at high risk of becoming infected and developing Chagas disease. There is a critical need for better detection and intervention strategies, principally focused on human infection throughout the Americas, but mainly in the U.S., for high-value dogs employed in government and other work. In addition to this economic impact, the concentration of largely unavoidable T. cruzi infections in U.S. dogs provides an incomparable opportunity to answer questions related to T. cruzi infection and Chagas disease that are impossible or unethical to address in humans. As the course of T. cruzi infection and Chagas disease, the immune response to infection, and the response to therapeutics are highly similar across the range of mammalian host species, information obtained from studies in other species can directly inform researchers on how to best detect, manage, and treat T. cruzi infection and Chagas disease in humans.
Rick L. Tarleton, Ashley B. Saunders, Bruno Lococo, Maria Gabriela Alvarez Gianni, Susana Laucella, Carolyn L. Hodo, Gregory K. Wilkerson, Sarah A. Hamer. Zoonoses. 2024. Vol. 4(1). DOI: 10.15212/ZOONOSES-2024-0005
Positive clinical outcome using a modified dosing regimen of benznidazole in dogs at high risk for infection or acutely infected with Trypanosoma cruzi
Trypanosoma cruzi infection in dogs can cause heart failure and sudden death with few treatment options available. A litter of 4 dogs living in a T cruzi endemic area were randomized to prophylaxis and nonprophylaxis groups as part of a study evaluating a modified benznidazole dosing regimen administered twice weekly to prevent T cruzi infection during a vector transmission season. The 2 dogs that received prophylaxis remained healthy without T cruzi infection or cardiac disease for >2 years. One dog that did not receive prophylaxis died unexpectedly with acute T cruzi-induced pancarditis, and the second dog tested positive for T cruzi and developed complex arrhythmias with markedly increased cardiac troponin I and improved with a higher benznidazole treatment dose. Although the small sample size precludes definitive conclusions, we describe the potential clinical benefit of prophylactic and early treatment with modified benznidazole dosing regimens for dogs with T cruzi infection.
Sukjung Lim, Stephanie Collins, Sarah A Hamer, Rick L Tarleton, Ashley B Saunders. J Vet Intern Med. 2024 Mar 18. doi: 10.1111/jvim.17028.
Chagas disease research in the news
DDN Dialogues
Rick Tarleton was recently interviewed for the Drug Discovery News podcast. Listen as he talks about his research into new drug treatments for Chagas disease.
A written transcript is available on DDN’s website.
KFF Health News
Rick Tarleton, along with Drew Etheridge‘s lab, was featured in a KFF Health News story about Chagas disease that has been picked up by a number of media outlets.
KFF Health News (Spanish translation)