Chronic Chagas Disease—the Potential Role of Reinfections in Cardiomyopathy Pathogenesis

Freites, Christian Olivo; Sy, Hendrik; Gharamti, Amal; Higuita, Nelson Iván Agudelo; Franco‐Paredes, Carlos; Suárez, José Antonio; Henao-Martínez, Andrés F

doi:10.1007/s11897-022-00568-9

Cited by 14 publications

(4 citation statements)

References 85 publications

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“…9 This rate suggests a possible role for reinfections in cardiomyopathy risk among patients with the indeterminate form in endemic countries. 21 The annual mortality rate for CCC was 2.7% during those 5 years, significantly lower than that recently reported by a meta-analysis performed in endemic countries of 7.9%, 10 which can partially be explained by the higher mean LVEF encountered in our study (53% versus 38%) and the inclusion of old studies in patients with more severe cardiomyopathy in the meta-analysis above. In addition, advanced cardiac disease requires access to high-technology healthcare, including multidisciplinary assessments, implantable cardiac devices, and heart transplantation.…”

Section: Discussioncontrasting

confidence: 65%

Clinical Characteristics and Outcomes of Chagas Disease in the United States: A Multicenter Retrospective Analysis

Henao-Martínez,

Olivo-Freites,

Higuita

et al. 2023

The American Journal of Tropical Medicine and Hygiene

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Chagas disease affects approximately 300,000 patients in the United States. We evaluated a multicenter U.S.-based network to obtain clinical characteristics and outcomes of chronic Chagas disease by disease forms. This was a U.S.-based, multicenter, population-based, retrospective cohort study. We queried TriNetX, a global research network, to identify patients with dual-positive IgG serology for Trypanosoma cruzi. We captured outcomes of interest for up to 5 years. We found 429 patients with evidence of dual-positive T. cruzi IgG out of 19,831 patients with an available test result from 31 U.S. medical centers. The positive proportion for those tested was 2.2%, up to 4.6% among Hispanics. We found a prevalence of a positive Chagas serology of 0.02% among Hispanics. Cardiomyopathy risk reached an annual rate of 1.3% during the initial 5 years of follow-up among patients with the indeterminate form. We found no new events for pulmonary embolism, sudden death, or left ventricular aneurysms at 5 years. Annual risks for arrhythmias and stroke for chronic Chagas cardiomyopathy (CCC) were 1.6% and 0.8%, respectively. The yearly mortality and hospitalization rates for CCC were 2.7% and 17.1%, respectively. Only 13 patients had a documented antitrypanosomal therapy course within 6 months after diagnosis. Of those receiving treatment, 10 patients received benznidazole and three nifurtimox. Chagas disease screening in patients from endemic areas living in the United States remains crucial. Chronic Chagas cardiomyopathy carries a considerable disease burden, translating into increased morbidity and mortality and an enlarging medical health service utilization.

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Section: Discussioncontrasting

confidence: 65%

Clinical Characteristics and Outcomes of Chagas Disease in the United States: A Multicenter Retrospective Analysis

Henao-Martínez,

Olivo-Freites,

Higuita

et al. 2023

The American Journal of Tropical Medicine and Hygiene

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“…In contrast, an excessive pro-inflammatory response can result in cardiac pathology ( 42 ). An ineffective immunological response can exacerbate the parasitic burden and incite an overwhelming inflammatory response, leading to tissue damage ( 43 ). Conversely, in the case of an effective immune response, the parasitic load and the inflammatory consequences are minimized ( 44 ).…”

Section: Discussionmentioning

confidence: 99%

Signatures of CD4+ T and B cells are associated with distinct stages of chronic chagasic cardiomyopathy

Vale,

Almeida,

Rimkute

et al. 2024

Front. Immunol.

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IntroductionChagas disease is a neglected parasitic disease caused by Trypanosoma cruzi. While most patients are asymptomatic, around 30% develop Chronic Chagasic Cardiomyopathy (CCC).MethodsHere, we employed high-dimensional flow cytometry to analyze CD4+ T and B cell compartments in patients during the chronic phase of Chagas disease, presenting the asymptomatic and mild or moderate/severe cardiac clinical forms.ResultsEffector CD27-CD4+ T cells were expanded in both CCC groups, and only mild CCC patients showed higher frequencies of effector memory and T follicular helper (Tfh) cells than healthy donors (CTL) and asymptomatic patients. Unsupervised analysis confirmed these findings and further revealed the expansion of a specific subpopulation composed of Tfh, transitional, and central memory CD4+ T cells bearing a phenotype associated with strong activation, differentiation, and exhaustion in patients with mild but not moderate/severe CCC. In contrast, patients with mild and moderate/severe CCC had lower frequencies of CD4+ T cells expressing lower levels of activation markers, suggesting resting status, than CTL. Regarding the B cell compartment, no alterations were found in naïve CD21-, memory cells expressing IgM or IgD, marginal zone, and plasma cells in patients with Chagas disease. However, expansion of class-switched activated and atypical memory B cells was observed in all clinical forms, and more substantially in mild CCC patients.DiscussionTaken together, our results showed that T. cruzi infection triggers changes in CD4+ T and B cell compartments that are more pronounced in the mild CCC clinical form, suggesting an orchestrated cellular communication during Chagas disease.ConclusionOverall, these findings reinforce the heterogeneity and complexity of the immune response in patients with chronic Chagas disease and may provide new insights into disease pathology and potential markers to guide clinical decisions.

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“…Data reported by other groups using less virulent strains demonstrated that, while some immunization protocols protected mice from rechallenge, T. cruzi infection alone did not ( Bustamante and Tarleton, 2015 ; Chowdhury et al., 2020 ; Mann et al., 2020 ; Ward et al., 2022 ). The effectiveness of our immunization protocol in protecting against re-challenges is highly relevant because, in the context of natural human infections, re-infections are frequent and associated with the risk of chronic manifestations of the disease ( Monje-Rumi et al., 2015 ; Tomasini et al., 2017 ; Prescilla-Ledezma et al., 2021 ; Olivo Freites et al., 2022 ; Hakim et al., 2023 ). Complementary, after immunosuppression, TcTASV-vaccinated and infected mice quickly recovered from the reactivation of the infection, controlling parasitemia to undetectable levels without mortality, while mortality and extremely high levels of parasitemia were detected in control-vaccinated and infected mice.…”

Section: Discussionmentioning

confidence: 99%

Vaccination with parasite-specific TcTASV proteins combined with recombinant baculovirus as a delivery platform protects against acute and chronic Trypanosoma cruzi infection

Masip,

Caeiro,

Cosenza

et al. 2024

Front. Cell. Infect. Microbiol.

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Chagas’ is a neglected disease caused by the eukaryotic kinetoplastid parasite, Trypanosoma cruzi. Currently, approximately 8 million people are infected worldwide, most of whom are in the chronic phase of the disease, which involves cardiac, digestive, or neurologic manifestations. There is an urgent need for a vaccine because treatments are only effective in the initial phase of infection, which is generally underdiagnosed. The selection and combination of antigens, adjuvants, and delivery platforms for vaccine formulations should be designed to trigger mixed humoral and cellular immune responses, considering that T. cruzi has a complex life cycle with both intracellular and bloodstream circulating parasite stages in vertebrate hosts. Here, we report the effectiveness of vaccination with a T. cruzi-specific protein family (TcTASV), employing both recombinant proteins with aluminum hydroxide and a recombinant baculovirus displaying a TcTASV antigen at the capsid. Vaccination stimulated immunological responses by producing lytic antibodies and antigen-specific CD4+ and CD8+ IFNɣ secreting lymphocytes. More than 90% of vaccinated animals survived after lethal challenges with T. cruzi, whereas all control mice died before 30 days post-infection. Vaccination also induced a strong decrease in chronic tissue parasitism and generated immunological memory that allowed vaccinated and infected animals to control both the reactivation of the infection after immunosuppression and a second challenge with T. cruzi. Interestingly, inoculation with wild-type baculovirus partially protected the mice against T. cruzi. In brief, we demonstrated for the first time that the combination of the baculovirus platform and the TcTASV family provides effective protection against Trypanosoma cruzi, which is a promising vaccine for Chagas disease.

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Chronic Chagas Disease—the Potential Role of Reinfections in Cardiomyopathy Pathogenesis

Cited by 14 publications

References 85 publications

Clinical Characteristics and Outcomes of Chagas Disease in the United States: A Multicenter Retrospective Analysis

Clinical Characteristics and Outcomes of Chagas Disease in the United States: A Multicenter Retrospective Analysis

Signatures of CD4+ T and B cells are associated with distinct stages of chronic chagasic cardiomyopathy

Vaccination with parasite-specific TcTASV proteins combined with recombinant baculovirus as a delivery platform protects against acute and chronic Trypanosoma cruzi infection

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