Introduction
Chagas disease (CD), also known as American trypanosomiasis, is caused by the parasite Trypanosoma cruzi. It is prevalent in areas belonging to South and Central America, but in the global scenario, the disease ranks third among parasitic diseases (World Health Organization, ). Currently, it is estimated that around 10 million people are infected worldwide, especially in Latin America, where the disease is endemic and is the leading cause of non-ischemic heart disease (Pan American Health Organization, ). T. cruzi is mainly transmitted by kissing bugs hematophagous insects belonging to the subfamily Triatominae. Thus, CD stands out as a public health problem in Latin America and other continents, mainly in North America and Europe. This spread is due to the immigration of infected individuals and the expansion of the insect vector in border areas, in addition to the failure to control clinical procedures such as blood transfusions and organ transplants (Nunes et al., ). Another form of transmission is the congenital form. Congenital infection with T. cruzi has become the primary mode of CD transmission in non-endemic countries where pregnant women are not regularly screened for the infection (Antinori et al., ). At the maternal-fetal interface, a complex interaction takes place between the parasite and host cells when bloodstream trypomastigotes engage with the syncytiotrophoblasts (SYNs) (Blaszkowska and Goralska, ; Silberstein et al.). RNA sequencing, complete transcriptome analysis, and 3D-cultured placental trophoblasts were used to describe the SYN response to T. cruzi and validate their crucial function as immunological sensors of parasite infection. Knowledge of the placenta's immunological environment, particularly the role of SYNs and the regulation of innate immunity, may aid in creating novel treatments to lower the risk of congenital CD. Both the acute and chronic phases of maternal infection can result in this kind of infection; moreover, pregnant women with greater parasitemia have higher transmission rates (Silberstein et al.).
Diagnosis
The diagnosis of CD is fraught with significant challenges, primarily due to cross-reactivity in serological tests with other pathogens, such as Leishmania spp. and Trypanosoma rangeli (Ascanio et al.). This Research Topic is particularly problematic in situations like blood or organ donation, where inaccurate results can compromise patient safety. In the chronic phase, the use of multiple assays becomes necessary to confirm the diagnosis, tests that encompass a variety of approaches, each with its specific characteristics (World Health Organization, ). In response to this complex scenario, numerous researchers have intensified their efforts to develop and test new antigens, such as recombinant proteins. These recombinant antigens offer several advantages, including increased sensitivity and specificity. Despite being in smaller quantities, recombinant multiepitope proteins have also shown improved diagnostic performance, significantly enhancing diagnostic accuracy and providing a reassuring outlook for the future of CD diagnosis (Resende et al.). Among the serological tests, ELISA (Enzyme-Linked Immunosorbent Assay) is widely used to detect antibodies against T. cruzi and is considered one of the most sensitive and specific methods available. Another option is the RDT (Rapid Diagnostic Test), which provides results quickly, making it especially useful in areas with limited resources. In addition to molecular methods, where PCR (Polymerase Chain Reaction) detects T. cruzi DNA in blood samples, RDT is especially effective in acute cases and patients with high parasitemia (Ascanio et al.).
Treatment
Despite the availability of some drugs in the clinic, these therapies have significant limitations. The toxicity associated with available medications, especially nifurtimox and benznidazole, often limits treatment adherence, given the adverse effects of continued use (Ferri et al.; Gonzaga et al.). Although such treatment shows results in the acute phase of the disease, its effectiveness in the chronic phase is considered limited. In addition to controlling parasitemia, no molecules are available in the industry that act to reverse the damage already caused by cardiac or hepatic complications in advanced stages (Altcheh et al., ). Many studies attempt to reduce this damage caused by the current treatment available for the disease. Some studies look for molecules acquired from natural compounds, such as those found in hawthorn extract (Crataegus oxyacantha), which can inhibit the Epac-Rap1b pathway, reducing invasion levels comparable to no treatment (Ferri et al.). Among the natural compounds found easily in different environments, both in the gut of the insect and in the bloodstream of the mammalian host, others are acquired naturally from the diet (Dick et al., ). The parasite finds competition for these nutrients in the mammalian host's bloodstream environment and within the insect vector's gut. The intestinal microbiota of the vector competes with T. cruzi for essential nutrients, such as sugars, amino acids, and Fe, all crucial elements for the energy metabolism of the protozoan (VillacÃs et al.). This competition can limit the availability of Fe in the environment, impairing processes such as cellular respiration, which may influence the growth of the parasite, compromising the glycolytic and oxidative metabolism of the protozoan (Orantes et al., ).
As previously presented, the urgent need for new therapeutic targets for CD is underscored by the limited therapeutic arsenal. This pressing need necessitates the development of more effective and less toxic approaches that consider different disease mechanisms. Therefore, the proposed new targets offer promising approaches for their use alone or in combination with existing therapies.
Statements
Author contributions
GF: Writing – original draft, Writing – review & editing. AV: Writing – original draft, Writing – review & editing. CD: Writing – original draft, Writing – review & editing.
Funding
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Financial support was received from Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro/FAPERJ (grant E-26/202.732/2024 to Giovanna Frechiani; grant E-26/210.336/2024 to Claudia F. Dick), and from Financier of Studies and Projects/FINEP (grant 01.17.0058.03 to Adalberto Vieyra).
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1
AltchehJ.CastroL.DibJ. C.GrossmanU.HuangE.Moscatelliet al. (2021). Prospective, historically controlled study to evaluate the efficacy and safety of a new pediatric formulation of nifurtimox in children aged 0 to 17 years with Chagas disease one year after treatment (Chico). PLoS Negl. Trop. Dis. 15, 1–18. 10.1371/journal.pntd.0008912
2
AntinoriS.GalimbertiL.BiancoR.GrandeR.GalliM.CorbellinoM. (2017). Chagas disease in Europe: a review for the internist in the globalized world. Eur. J. Intern. Med. 43, 6–15. 10.1016/j.ejim.2017.05.001
3
BlaszkowskaJ.GoralskaK. (2014). Parasites and fungi as a threat for prenatal and postnatal human development. Ann. Parasitol.60, 225–222.
4
DickC. F.GuimarãesL. N.Carvalho-KellyL. F.CortesA. L.MorcilloL. S. L.SampaioL. S.et al. (2020). A ferric reductase of Trypanosoma cruzi (TcFR) is involved in iron metabolism in the parasite. Exp. Parasitol.217:107962. 10.1016/j.exppara.2020.107962
5
NunesM. C. P.BeatonA.AcquatellaH.BernC.BolgerA. F.EcheverrÃaL. E.et al. (2018). Chagas cardiomyopathy: an update of current clinical knowledge and management: a scientific statement from the American Heart Association. Circulation138, e169–e209. 10.1161/CIR.0000000000000599
6
OrantesL. C.MonroyC.DornP. L.StevensL.RizzoD. M.MorrisseyL.et al. (2018). Uncovering vector, parasite, blood meal and microbiome patterns from mixed-DNA specimens of the Chagas disease vector Triatoma dimidiata. PLoS Negl. Trop. Dis.12:e0006730. 10.1371/journal.pntd.0006730
7
Pan American Health Organization (2023). Chagas Disease. Available at: https://www.paho.org/en/topics/chagas-disease (accessed November 23, 2024).
8
World Health Organization (2023). World Chagas Disease Day 2023 to Focus on Integrating Universal Care and Surveillance at the Primary Care Level. Available at: https://www.who.int/news/item/14-04-2023-world-chagas-disease-day-2023-to-focus-on-integrating-universal-care-and-surveillance-at-the-primary-care-level (accessed November 23, 2024).
Summary
Keywords
trypanosomatids, new therapeutic strategies, Chagas disease diagnosis, Chagas disease, Trypanosoma cruzi
Citation
Frechiani G, Vieyra A and Dick CF (2024) Editorial: Recent advances in the prevention, diagnosis and treatment of Chagas disease. Front. Microbiol. 15:1537105. doi: 10.3389/fmicb.2024.1537105
Received
29 November 2024
Accepted
03 December 2024
Published
20 December 2024
Volume
15 - 2024
Edited and reviewed by
Axel Cloeckaert, Institut National de recherche pour l'agriculture, l'alimentation et l'environnement (INRAE), France
Updates
Copyright
© 2024 Frechiani, Vieyra and Dick.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Claudia F. Dick claudiadick@biof.ufrj.br
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.