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Jorge Vásconez-González1
Camila Miño2
Camila Salazar-Santoliva1
Melissa Villavicencio-Gomezjurado1
Esteban Ortiz-Prado1*- 1One Health Research Group, Faculty of Health Science, Universidad de Las Américas, Quito, Ecuador
- 2Department of Public Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
Introduction
Chagas disease (CD) is endemic in 21 countries in Latin America, affecting around 30,000 people annually and putting approximately 70 million individuals at risk (1, 2). Factors such as poverty, inadequate housing, and insufficient health infrastructure contribute to its high prevalence within the region (1, 3). Stroke, on the other hand, impacts more than 15 million people globally each year, causing 5 million deaths and leaving another 5 million permanently disabled (4). This number is expected to increase by 2025. By 2050, 77.6% of disability-adjusted life years (DALYs) will be caused by non-communicable diseases (5). The relationship between Chagas disease and stroke has been poorly studied, but both conditions pose significant public health challenges due to their high morbidity and mortality rates in Latin America. For instance, in this region alone, Chagas disease accounts for 662,000 disability-adjusted life years (DALYs), while stroke contributes to 20 million DALYs (6–8).
The complex relationship between these two pathologies must be analyzed together because, although complications of Chagas disease such as megacolon, megaesophagus, and cardiomegaly are well-documented (9–13), the link between CD and stroke has not received adequate attention. Oliveira-Filho outlines mechanisms through which CD can lead to cardioembolic stroke, including chronic inflammation, activation of the coagulation system, cardioembolism, microembolism, and watershed infarcts from low cardiac output states (14). Additionally, patients with CD can experience non-embolic strokes due to small vessel disease, atherosclerosis, and cryptogenic causes (15).
The mechanisms by which a parasitic infection like Chagas disease increases the risk of developing a stroke are not entirely clear. However, several proposed mechanisms exist (Figure 1). Carod-Artal et al. found that approximately 40% of Chagas disease (CD) patients with ischemic stroke have an apical aneurysm of the left ventricle (16). Additionally, 70% of these patients exhibit electrocardiogram abnormalities, with right bundle branch block present in 35% of cases, left anterior fascicular block in 17%, and atrial fibrillation in 15% (16). This may be one of the primary reasons why Chagas disease can increase the risk of developing a stroke. Furthermore, family history is also significant, as 32.7% of CD patients who suffer a stroke have relatives with Chagas disease. Special caution is necessary in managing these patients to prevent stroke (17).
Figure 1
Figure 1. Main risk factors and mechanism of stroke in CD. Created with BioRender.com.
In some areas where Chagas disease (CD) is highly prevalent, stroke could be the first manifestation of CD, particularly in patients with left ventricular dysfunction. In regions like Brazil, 40% of patients diagnosed with CD have been identified after suffering a stroke (18). About 38.4% of patients with Chagas-related stroke have asymptomatic T. cruzi infection, which can lead to small and large vessel infarctions (19). Asymptomatic patients may also present with apical aneurysm, left atrial dilation, and left ventricular hypokinesia, increasing the risk of cardioembolism. With the aging population, cerebrovascular complications in CD patients are expected to rise (16).
Cerqueira-Silva et al. conducted a study involving 210 patients with heart failure and CD and 194 patients with heart failure without CD. They found that the incidence of stroke was 20.2 per 1,000 patient-years in the CD group and 13.9 per 1,000 patient-years in those without CD. Additionally, it was revealed that Chagas disease is an independent predictor of first ischemic stroke (HR 2.54, 95% CI: 1.01–6.42) (20). In a study conducted in Brazil comparing 329 patients with Chagas cardiomyopathy to 461 patients with non-Chagas cardiomyopathy, the mean age was 58.3 years. It was observed that strokes were more frequent in the group with CD compared to the infection-free group (17.3% versus 11.1%; p < 0.01). Additionally, Chagas patients who experienced a stroke had a very high frequency of individuals without any vascular risk factors (40.4%; OR, 4.8) (21).
In Colombia, a case-control study involving 82 cases (mean age 66.6) and 102 controls (mean age 61.9) revealed that T. cruzi infection was more frequent and statistically significant in stroke cases (24.4%) compared to controls (1.9%) (p < 0.00001). Even after excluding Chagas patients with cardiac abnormalities, the significance remained (p < 0.05) (22). In a case-control study in Brazil, T. cruzi infection was significantly more common in 101 consecutive cases of acute stroke than in 100 cases of acute coronary syndrome (14% vs. 2%; p = 0.002) (23).
Whether stroke is diagnosed first and then CD identified, or vice versa, it is crucial to note that having Chagas disease significantly increases the risk in stroke patients (24). Lima-Coste et al. followed 1,398 patients over ten years and found that the risk of death from stroke in CD patients was twice that of uninfected individuals (adjusted hazard ratio, 2.36; 95% CI, 1.25 to 4.44) (24). In this study, elevated levels of type B natriuretic peptide in these patients were determined to be predictors of mortality, especially when combined with atrial fibrillation, which increased the risk of death by 11.49% (24). It is estimated that more than 60% of stroke patients with Chagas disease living in endemic regions have a family history of the infection, compared to only 16% of stroke patients without Chagas disease. In addition to having relatives with Chagas disease and having lived in an adobe house during childhood, these social variables are associated with Chagas-related strokes (p < 0.001) (25).
Additionally, it has been reported that both chronic heart disease and gastrointestinal forms of CD can coexist in patients who have experienced a Chagas-related stroke. Chronic intestinal CD has been identified in 20% of these patients, with 8% having megaesophagus, 8% with megacolon, and 4% with both conditions (25). Regarding heart disease, left ventricular dysfunction has been observed in 65% of stroke patients, apical aneurysm in 40%, and left ventricular dilation in 23% (25).
Call for action
The information about this not-so-rare link is vital for understanding that a parasitic disease like Chagas disease can leave severe sequelae that significantly increase the risk of stroke. Therefore, it is crucial to improve screening campaigns and identify risk factors. Given the above, diagnosing CD in stroke patients, particularly those from endemic areas or with relevant travel histories, is essential.
Educational programs for both the public and healthcare providers are crucial, as awareness of the stroke risk in Chagas patients is only 5% (18).
Moreover, diagnostic campaigns are needed, as less than 10% of infected individuals are aware of their condition. Early detection of CD can lead to a 100% cure rate, while untreated cases may result in severe, often irreversible complications affecting various systems (26).
Raising awareness, enhancing detection efforts, and providing comprehensive education can prevent many stroke cases related to Chagas disease and improve overall patient outcomes. As shown in Table 1.
Table 1
Table 1. Recommendations for the management of chagasic stroke.
Further research should focus on developing better treatment regimens and creating a multicenter database on Chagas patients (16, 22). Clinical settings need standard diagnostic procedures and effective treatment strategies, particularly in endemic regions (16, 24). Public health initiatives must include integrated vector control protocols and active screening programs for T. cruzi (16, 22, 24). Coordination between national and international stakeholders and community involvement in preventive measures are also essential (23, 24). By implementing these recommendations, we can significantly reduce the burden of Chagas-related strokes and enhance patient care.
Author contributions
EO-P: Investigation, Supervision, Validation, Writing – review & editing. JV-G: Conceptualization, Investigation, Methodology, Writing – original draft, Writing – review & editing. CM: Data curation, Investigation, Writing – original draft. CS-S: Writing – review & editing. MV-G: Investigation, Methodology, Validation, Writing – review & editing.
Funding
The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
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
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References
1. Vásconez-González J, Izquierdo-Condoy JS, Fernandez-Naranjo R, Gamez-Rivera E, Tello-De-la-Torre A, Guerrero-Castillo GS, et al. Severe Chagas disease in Ecuador: a countrywide geodemographic epidemiological analysis from 2011 to 2021. Front Public Health. (2023) 11:1172955. doi: 10.3389/fpubh.2023.1172955
2. Stanaway JD, Roth G. The burden of Chagas disease: estimates and challenges. Glob Heart. (2015) 10:139–44. doi: 10.1016/j.gheart.2015.06.001
3. PAHO. Chagas Disease - PAHO/WHO | Pan American Health Organization. Pan Am Health Organ World Health Organization. (2024). Available at: https://www.paho.org/en/topics/chagas-disease (accessed June 1, 2024).
4. WHO EMRO. Stroke, Cerebrovascular accident | Health topics. In: World Health Organ - Reg Off East Mediterr. (2024). Available at: http://www.emro.who.int/health-topics/stroke-cerebrovascular-accident/index.html (accessed July 27, 2024).
5. Safiri S, Karamzad N, Singh K, Carson-Chahhoud K, Adams C, Nejadghaderi SA, et al. Burden of ischemic heart disease and its attributable risk factors in 204 countries and territories, 1990–2019. Eur J Prev Cardiol. (2022) 29:420–31. doi: 10.1093/eurjpc/zwab213
6. Bonney KM. Chagas disease in the 21st century: a public health success or an emerging threat? Parasite. (2014) 21:11. doi: 10.1051/parasite/2014012
7. Donkor ES. Stroke in the 21st century: a snapshot of the burden, epidemiology, and quality of life. Stroke Res Treat. (2018) 2018:3238165. doi: 10.1155/2018/3238165
8. Sousa AS de, Vermeij D, Ramos AN, Luquetti AO. Chagas disease. Lancet. (2024) 403:203–18. doi: 10.1016/S0140-6736(23)01787-7
9. Bonney KM, Luthringer DJ, Kim SA, Garg NJ, Engman DM. Pathology and pathogenesis of Chagas heart disease. Annu Rev Pathol. (2019) 14:421–47. doi: 10.1146/annurev-pathol-020117-043711
10. da Silveira ABM, Lemos EM, Adad SJ, Correa-Oliveira R, Furness JB, D'Avila Reis D. Megacolon in Chagas disease: a study of inflammatory cells, enteric nerves, and glial cells. Hum Pathol. (2007) 38:1256–64. doi: 10.1016/j.humpath.2007.01.020
11. Montalvo-Ocotoxtle IG, Rojas-Velasco G, Rodríguez-Morales O, Arce-Fonseca M, Baeza-Herrera LA, Arzate-Ramírez A, et al. Chagas heart disease: beyond a single complication, from asymptomatic disease to heart failure. J Clin Med. (2022) 11:7262. doi: 10.3390/jcm11247262
12. Teixeira ARL, Nitz N, Guimaro MC, Gomes C. Chagas disease. Postgrad Med J. (2006) 82:788–98. doi: 10.1136/pgmj.2006.047357
13. Matsuda NM, Miller SM, Evora PRB. The chronic gastrointestinal manifestations of Chagas disease. Clinics. (2009) 64:1219–24. doi: 10.1590/S1807-59322009001200013
14. Oliveira-Filho J. Stroke and brain atrophy in chronic Chagas disease patients: a new theory proposition. Dement Neuropsychol. (2009) 3:22–6. doi: 10.1590/S1980-57642009DN30100005
15. Lage TAR, Tupinambás JT, de Pádua LB, Ferreira M, Ferreira AC, Teixeira AL, et al. (2021). Stroke in Chagas disease: from pathophysiology to clinical practice. Rev Soc Bras Med Trop. 55:e0575. doi: 10.1590/0037-8682-0575-2021
16. Carod-Artal FJ. Policy implications of the changing epidemiology of chagas disease and stroke. Stroke. (2013) 44:2356–60. doi: 10.1161/STROKEAHA.113.000738
17. Carod-Artal FJ, Ribeiro L da S, Vargas AP. Awareness of stroke risk in chagasic stroke patients. J Neurol Sci. (2007) 263:35–9. doi: 10.1016/j.jns.2007.05.022
18. Carod-Artal FJ. Stroke: a neglected complication of American trypanosomiasis (Chagas' disease). Trans R Soc Trop Med Hyg. (2007) 101:1075–80. doi: 10.1016/j.trstmh.2007.06.007
19. Carod-Artal FJ, Vargas AP, Falcao T. Stroke in asymptomatic trypanosoma cruzi-infected patients. Cerebrovasc Dis. (2010) 31:24–8. doi: 10.1159/000320248
20. Cerqueira-Silva T, Gonçalves BM, Pereira CB, Porto LM, Marques ME, Santos LS, et al. Chagas disease is an independent predictor of stroke and death in a cohort of heart failure patients. Int J Stroke. (2022) 17:180–8. doi: 10.1177/17474930211006284
21. Matta JAM da, Roque Aras J, Macedo CRB de, Cruz CG da, Netto EM. Stroke correlates in Chagasic and non-Chagasic cardiomyopathies. PLoS ONE. (2012) 7:e35116. doi: 10.1371/journal.pone.0035116
22. Leon-Sarmiento FE, Mendoza E, Torres-Hillera M, Pinto N, Prada J, Silva CA, et al. Trypanosoma cruzi-associated cerebrovascular disease: a case-control study in Eastern Colombia. J Neurol Sci. (2004) 217:61–4. doi: 10.1016/j.jns.2003.08.015
23. Paixão LC, Ribeiro AL, Valacio RA, Teixeira AL. Chagas disease: independent risk factor for stroke. Stroke. (2009) 40:3691–4. doi: 10.1161/STROKEAHA.109.560854
24. Lima-Costa MF, Matos DL, Ribeiro ALP. Chagas disease predicts 10-year stroke mortality in community-dwelling elderly. Stroke. (2010) 41:2477–82. doi: 10.1161/STROKEAHA.110.588061
25. Carod-Artal FJ, Gascon J. Chagas disease and stroke. Lancet Neurol. (2010) 9:533–42. doi: 10.1016/S1474-4422(10)70042-9
26. PAHO. Less than 10% of people with Chagas receive a diagnosis - PAHO/WHO | Pan American Health Organization. In: Pan Am Health Organ World Health Organization. (2023). Available at: https://www.paho.org/en/news/13-4-2023-less-10-people-chagas-receive-diagnosis (accessed June 1, 2024).
27. Tarleton RL. Chagas disease impact and opportunities: beyond the historical dogma. In: The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: National Academies Press (US) (2011). Available at: https://www.ncbi.nlm.nih.gov/books/NBK62523/ (accessed July 5, 2024).
28. Branquinha MH, Sangenito LS, Oliveira SSC, d'Avila-Levy CM, Santos ALS. Chagas disease control—many approaches to prospect. Trop Med Infect Dis. (2023) 8:395. doi: 10.3390/tropicalmed8080395
Keywords: Chagas disease, stroke, public health, Trypanosoma cruzi, cerebrovascular accident
Citation: Vásconez-González J, Miño C, Salazar-Santoliva C, Villavicencio-Gomezjurado M and Ortiz-Prado E (2024) Chagas disease as an underrecognized cause of stroke: implications for public health. Front. Med. 11:1473425. doi: 10.3389/fmed.2024.1473425
Received: 19 August 2024; Accepted: 04 November 2024;
Published: 22 November 2024.
Edited by:
Sam Donta, Falmouth Hospital, United StatesReviewed by:
Julio A. Urbina, Instituto Venezolano de Investigaciones Cientificas, VenezuelaCopyright © 2024 Vásconez-González, Miño, Salazar-Santoliva, Villavicencio-Gomezjurado and Ortiz-Prado. 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: Esteban Ortiz-Prado, ZS5vcnRpenByYWRvQGdtYWlsLmNvbQ==