The Role of Immunogenetics in the Host–Parasite Interaction of Chagas Disease: Implications for Personalized Medicine

Hassnain, Muhammad; Bukhari, Syeda Mahnoor; Bibi, Tahira; Waheed, Syeda Fakhra; Botelho, Monica C.; Ahmad, Waqas

doi:10.3390/tropicalmed11010002

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The Role of Immunogenetics in the Host–Parasite Interaction of Chagas Disease: Implications for Personalized Medicine

by

Muhammad Hassnain

¹

,

Syeda Mahnoor Bukhari

²,

Tahira Bibi

³,

Syeda Fakhra Waheed

⁴,

Monica C. Botelho

^5,6,* and

Waqas Ahmad

^7,*

¹

University of Veterinary and Animal Sciences, Lahore, Sub-Campus, Narowal 51600, Pakistan

²

Department of Chemistry, The Women University, Multan 06009, Pakistan

³

Department of Botany, Sardar Bahadur Khan Women’s University, Quetta 87300, Balochistan, Pakistan

⁴

Department of Veterinary Science, Faculty of Veterinary and Animal Sciences, Azad Jammu and Kashmir University of Bhimber, Bhimber 10040, Pakistan

⁵

Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal

⁶

Department of Health Promotion and Chronic Diseases, INSA—National Institute of Health Dr. Ricardo Jorge, 4000-055 Porto, Portugal

⁷

Department of Clinical Sciences, University of Veterinary and Animal Sciences, Lahore, Sub-Campus, Narowal 51600, Pakistan

^*

Authors to whom correspondence should be addressed.

Trop. Med. Infect. Dis. 2026, 11(1), 2; https://doi.org/10.3390/tropicalmed11010002 (registering DOI)

Submission received: 19 August 2025 / Accepted: 17 December 2025 / Published: 19 December 2025

(This article belongs to the Special Issue Advances in Parasitic Neglected Tropical Diseases)

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Abstract

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, continues to be a significant global health issue, especially in Latin America, with increasing international prevalence due to migration. Despite advancements in diagnosis and treatment, it remains a neglected tropical disease characterized by significant morbidity and mortality, mainly influenced by the complex interaction between parasite diversity and host immune responses. Importantly, the remarkable genetic diversity of T. cruzi lineages also contributes to clinical heterogeneity, influencing immune evasion, therapeutic responses, and vaccine feasibility. This review analyzes the impact of immunogenetics on host–parasite interactions in Chagas disease and explores its implications for personalized therapy approaches. Recent research, particularly over the last decade, has indicated that processes including antigenic variation, extracellular vesicle-mediated regulation, and disruption of host signaling pathways facilitate parasite persistence. Host genetic variables significantly influence susceptibility, disease development, and treatment outcomes, including changes in Human Leukocyte Antigen (HLA) genes, cytokine gene polymorphisms, and immunogenetic determinants of cardiac pathology. These findings underscore the potential of immunogenetic markers as tools for prognosis and as targets for personalized therapies. However, there are still considerable research deficiencies. Inadequate comprehension of gene–environment interactions, lack of representation of varied populations, and inconsistencies in study design limit the use of immunogenetic findings in therapeutic settings. At present, the concept of personalized medicine in Chagas disease remains largely aspirational, better understood as a framework for precision public health or stratified interventions guided by host immunogenetic and parasite lineage data. Addressing these issues necessitates comprehensive genomic research, mechanistic investigations of host–parasite interactions, and clinical validation of genetic markers. This study emphasizes the necessity of incorporating immunogenetics into personalized patient management strategies based on existing evidence. This integration has the potential to improve diagnosis, enhance treatment efficacy, and inform preventive interventions, thereby advancing personalized therapy for Chagas disease.

Keywords: Chagas disease; T. cruzi; immunogenetics; host–parasite interaction; personalized medicine; immune response; genetic polymorphisms

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MDPI and ACS Style

Hassnain, M.; Bukhari, S.M.; Bibi, T.; Waheed, S.F.; Botelho, M.C.; Ahmad, W. The Role of Immunogenetics in the Host–Parasite Interaction of Chagas Disease: Implications for Personalized Medicine. Trop. Med. Infect. Dis. 2026, 11, 2. https://doi.org/10.3390/tropicalmed11010002

AMA Style

Hassnain M, Bukhari SM, Bibi T, Waheed SF, Botelho MC, Ahmad W. The Role of Immunogenetics in the Host–Parasite Interaction of Chagas Disease: Implications for Personalized Medicine. Tropical Medicine and Infectious Disease. 2026; 11(1):2. https://doi.org/10.3390/tropicalmed11010002

Chicago/Turabian Style

Hassnain, Muhammad, Syeda Mahnoor Bukhari, Tahira Bibi, Syeda Fakhra Waheed, Monica C. Botelho, and Waqas Ahmad. 2026. "The Role of Immunogenetics in the Host–Parasite Interaction of Chagas Disease: Implications for Personalized Medicine" Tropical Medicine and Infectious Disease 11, no. 1: 2. https://doi.org/10.3390/tropicalmed11010002

APA Style

Hassnain, M., Bukhari, S. M., Bibi, T., Waheed, S. F., Botelho, M. C., & Ahmad, W. (2026). The Role of Immunogenetics in the Host–Parasite Interaction of Chagas Disease: Implications for Personalized Medicine. Tropical Medicine and Infectious Disease, 11(1), 2. https://doi.org/10.3390/tropicalmed11010002

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The Role of Immunogenetics in the Host–Parasite Interaction of Chagas Disease: Implications for Personalized Medicine

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