HOST-PARASITE GENOMIC INTERACTIONS IN LEISHMANIASIS: EMERGING DIAGNOSTIC BIOMARKERS AND PREDICTIVE GENE SIGNATURES
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Objective: This review aims to explore the genetic underpinnings of Leishmaniasis, focusing on host-parasite genomic interactions and their implications for diagnostics, treatment, and control. Method: The study synthesizes recent advancements in host-parasite genomics, highlighting genetic polymorphisms in the host's immune response and parasite-mediated virulence determinants, identified through high-throughput sequencing and multi-omics analyses. Results: Key findings include the identification of genetic markers associated with immune responses and disease severity, as well as parasite traits influencing tissue tropism and survival. Co-regulated gene networks have been revealed, underscoring the dynamic interplay between host immunity and parasite adaptability. Novelty: The review identifies the potential for genomic biomarkers to differentiate asymptomatic carriers from active cases, predict treatment failure, and enable personalized treatment strategies. Furthermore, it discusses the prospects of genomic insights in developing targeted vaccines and enhancing control programs for leishmaniasis. This work contributes to precision medicine and the future control of leishmaniasis through the application of genomic biomarkers.
F. Afrin, I. Khan, and H. A. Hemeg, "Leishmania-host interactions—an epigenetic paradigm," Front. Immunol., vol. 10, p. 492, 2019.
J. Swann, et al., "Systems analysis of host–parasite interactions," Wiley Interdiscip. Rev. Syst. Biol. Med., vol. 7, no. 6, pp. 381-400, 2015.
Z. N. Omondi, et al., "Host–Parasite interactions: Regulation of Leishmania infection in sand fly," Acta Parasitol., vol. 67, no. 2, pp. 606-618, 2022.
P. Kaye and P. Scott, "Leishmaniasis: complexity at the host–pathogen interface," Nat. Rev. Microbiol., vol. 9, no. 8, pp. 604-615, 2011.
C. Karimkhani, et al., "Global burden of cutaneous leishmaniasis: a cross-sectional analysis from the Global Burden of Disease Study 2013," Lancet Infect. Dis., vol. 16, no. 5, pp. 584-591, 2016.
C. J. Scheufele, R. L. Giesey, and G. R. Delost, "The global, regional, and national burden of leishmaniasis: An ecologic analysis from the Global Burden of Disease Study 1990-2017," J. Am. Acad. Dermatol., vol. 84, no. 4, pp. 1203-1205, 2021.
F. Bailey, et al., "A new perspective on cutaneous leishmaniasis—Implications for global prevalence and burden of disease estimates," PLoS Negl. Trop. Dis., vol. 11, no. 8, p. e0005739, 2017.
J. M. T. Bezerra, et al., "Burden of leishmaniasis in Brazil and federated units, 1990-2016: Findings from Global Burden of Disease Study 2016," PLoS Negl. Trop. Dis., vol. 12, no. 9, p. e0006697, 2018.
C. Medina and F. J. López-Baena, "Host-Pathogen Interactions," Methods in, 2018.
A. Rausell and A. Telenti, "Genomics of host–pathogen interactions," Curr. Opin. Immunol., vol. 30, pp. 32-38, 2014.
H. Yu, et al., "A new framework for host-pathogen interaction research," Front. Immunol., vol. 13, p. 1066733, 2022.
A. Llanes, C. M. Restrepo, and R. Lleonart, "Unraveling the genome diversity of Leishmania parasites using next-generation DNA sequencing strategies," Life, vol. 15, no. 10, p. 1590, 2025.
S. Khandibharad and S. Singh, "Epigenetic landscape of Leishmania-host interactions," Epigenomics, pp. 1-16, 2025.
P. Kaye and P. Scott, "Leishmaniasis: complexity at the host–pathogen interface," Nat. Rev. Microbiol., vol. 9, no. 8, pp. 604-615, 2011.
M. A. Gómez, et al., "Innate biosignature of treatment failure in human cutaneous leishmaniasis," Nat. Commun., vol. 16, no. 1, p. 3235, 2025.
L. G. Gardinassi, et al., "Blood transcriptional profiling reveals immunological signatures of distinct states of infection of humans with Leishmania infantum," PLoS Negl. Trop. Dis., vol. 10, no. 11, p. e0005123, 2016.
A. Diotallevi, et al., "Transcriptional signatures in human macrophage-like cells infected by Leishmania infantum, Leishmania major and Leishmania tropica," PLoS Negl. Trop. Dis., vol. 18, no. 4, p. e0012085, 2024.
E. Ontoria, et al., "Transcriptional profiling of immune-related genes in Leishmania infantum-infected mice: identification of potential biomarkers of infection and progression of disease," Front. Cell. Infect. Microbiol., vol. 8, p. 197, 2018.
L. G. Gardinassi, et al., "Blood transcriptional profiling reveals immunological signatures of distinct states of infection of humans with Leishmania infantum," PLoS Negl. Trop. Dis., vol. 10, no. 11, p. e0005123, 2016.
C. R. Sanz, et al., "Modulation of host immune response during Leishmania infantum natural infection: A whole-transcriptome analysis of the popliteal lymph nodes in dogs," Front. Immunol., vol. 12, p. 794627, 2022.
D. N. Hupalo, M. Bradic, and J. M. Carlton, "The impact of genomics on population genetics of parasitic diseases," Curr. Opin. Microbiol., vol. 23, pp. 49-54, 2015.
C. A. Grace, et al., "Parasite genotype is a major predictor of mortality from visceral leishmaniasis," MBio, vol. 13, no. 6, p. e02068-22, 2022.
C. A. Grace, et al., "Parasite genotype is a major predictor of mortality from visceral leishmaniasis," MBio, vol. 13, no. 6, p. e02068-22, 2022.
P. Anuntasomboon, et al., "Genome alteration of Leishmania orientalis under Amphotericin B inhibiting conditions," PLoS Negl. Trop. Dis., vol. 18, no. 12, p. e0012716, 2024.
A. M. M. Santi and S. M. F. Murta, "Impact of genetic diversity and genome plasticity of Leishmania spp. in treatment and the search for novel chemotherapeutic targets," Front. Cell. Infect. Microbiol., vol. 12, p. 826287, 2022.
X. Roca-Geronès, et al., "Genetic variability in Leishmaniasis-causing Leishmania infantum in humans and dogs from North-East Spain," Animals, vol. 14, no. 12, p. 1796, 2024.
V. Chaparro, et al., "Transcriptional profiling of macrophages reveals distinct parasite stage-driven signatures during early infection by Leishmania donovani," Sci. Rep., vol. 12, no. 1, p. 6369, 2022.
S. R. Maruyama, et al., "Insight into the long noncoding RNA and mRNA coexpression profile in the human blood transcriptome upon Leishmania infantum infection," Front. Immunol., vol. 13, p. 784463, 2022.
S. Mehrotra, et al., "Advances and challenges in the diagnosis of leishmaniasis," Mol. Diagn. Ther., vol. 29, no. 2, pp. 195-212, 2025.
J. Martí-Carreras, et al., "Identification of Leishmania infantum epidemiology, drug resistance and pathogenicity biomarkers with nanopore sequencing," Microorganisms, vol. 10, no. 11, p. 2256, 2022.
M. Leroux, et al., "Fatty acid composition and metabolism in Leishmania parasite species: potential biomarkers or drug targets for leishmaniasis?," Int. J. Mol. Sci., vol. 24, no. 5, p. 4702, 2023.
M. Carrasco, et al., "Drug-Resistance Biomarkers in Leishmania infantum through Nanopore-Based Detection of Aneuploidy and Gene Copy Number Variations with LeishGenApp," bioRxiv, 2025.
E. A. Ozturk and A. Caner, "Liquid biopsy for promising non-invasive diagnostic biomarkers in parasitic infections," Acta Parasitologica, vol. 67, no. 1, pp. 1-17, 2022.
S. S. I. Bamarni and M. B. Said, "Genomic approaches in parasitic diagnosis," in Omics Approaches in Veterinary Parasitology, CRC Press, 2024, pp. 47-61.
A. Efstathiou and D. Smirlis, "Leishmania protein kinases: important regulators of the parasite life cycle and molecular targets for treating leishmaniasis," Microorganisms, vol. 9, no. 4, p. 691, 2021.
S. Mehrotra, et al., "Advances and challenges in the diagnosis of leishmaniasis," Mol. Diagn. Ther., vol. 29, no. 2, pp. 195-212, 2025.
M. A. Gómez, et al., "Innate biosignature of treatment failure in human cutaneous leishmaniasis," Nat. Commun., vol. 16, no. 1, p. 3235, 2025.
M. A. Gómez, et al., "Innate biosignature of treatment failure in human cutaneous leishmaniasis," Nat. Commun., vol. 16, no. 1, p. 3235, 2025.
S. Lima, et al., "Biomarkers of the early response to treatment of visceral leishmaniasis: a prospective cohort study," Parasite Immunol., vol. 43, no. 1, p. e12797, 2021.
E. Harigua-Souiai, et al., "Lesionia: a digital data management system to enhance collaborative management of epidemiological and clinical data of cutaneous leishmaniases patients," BMC Res. Notes, vol. 18, no. 1, p. 160, 2025.
H. Silva, et al., "Autochthonous Leishmaniasis caused by Leishmania tropica, identified by using whole-genome sequencing, Sri Lanka," Emerg. Infect. Dis., vol. 30, no. 9, pp. 1872-1880, 2024.
O. A. Pilling, et al., "Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies," PLoS Pathog., vol. 19, no. 3, p. e1011230, 2023.
O. A. Pilling, "Selective Whole Genome Amplification (SWGA) Reveals Population Genomics of Leishmania braziliensis Directly from Patient Skin Biopsies," Ph.D. dissertation, Univ. of Pennsylvania, 2024.
C. M. C. Catta-Preta, et al., "Single-cell atlas of Leishmania development in sandflies reveals the heterogeneity of transmitted parasites and their role in infection," Proc. Natl. Acad. Sci., vol. 121, no. 52, p. e2406776121, 2024.
A. Vafadar, et al., "Meta-analysis of microarray data to identify potential signature genes and MiRNAs associated with the pathogenesis of asthma," J. Transl. Med., vol. 23, no. 1, p. 796, 2025.
B. J. Maguire, "From Scoping to Scaling: Collaborative Individual Patient Data Platforms for Neglected Infectious Diseases," Ph.D. dissertation, Queen Margaret Univ., 2025.
H. J. C. de Vries and H. D. Schallig, "Cutaneous leishmaniasis: a 2022 updated narrative review into diagnosis and management developments," Am. J. Clin. Dermatol., vol. 23, no. 6, pp. 823-840, 2022.
E. Abbasi, "A Perspective on Human Leishmaniasis and Novel Therapeutic Methods for Diagnosis, Prevention and Treatment," Pediatr. Infect. Dis. J., 2025.
D. M. de Avelar, C. C. Santos, and A. F. Faioli, "Developments in Leishmaniasis diagnosis: A patent landscape from 2010 to 2022," PLoS Glob. Public Health, vol. 3, no. 11, p. e0002557, 2023
K. Boch, et al., "Evaluation of clinical and laboratory characteristics of patients with cutaneous sarcoidosis: A single-center retrospective cohort study," Front. Med., vol. 9, p. 980507, 2022.
L. R. Ribeiro, et al., "Safety profile of miltefosine in the treatment of cutaneous leishmaniasis," PLoS One, vol. 19, no. 12, p. e0315710, 2024.
G. Panditrao, P. Ganguli, and R. R. Sarkar, "Delineating infection strategies of Leishmania donovani secretory proteins in human through host–pathogen protein interactome prediction," Pathogens Dis., vol. 79, no. 8, p. ftab051, 2021.
F. Caixeta, et al., "Expression of Network Medicine-Predicted Genes in Human Macrophages Infected with Leishmania major," Int. J. Mol. Sci., vol. 25, no. 22, p. 12084, 2024.
M. Safaei, et al., "Determination of key hub genes in Leishmaniasis as potential factors in diagnosis and treatment based on a bioinformatics study," Sci. Rep., vol. 14, no. 1, p. 22537, 2024.
L. N. Ondari, "Metabolomic Analysis of Trypanosoma Congolense and Leishmania Mexicana Treated with Selected Antiparasitic Drugs and in Silico Modelling of Potential Drug Targets," 2022.
G. Panditrao, P. Ganguli, and R. R. Sarkar, "Delineating infection strategies of Leishmania donovani secretory proteins in human through host–pathogen protein interactome prediction," Pathogens Dis., vol. 79, no. 8, p. ftab051, 2021.
M. Aminzadeh, et al., "Unraveling Leishmania major Metacyclogenesis: A Comprehensive Analysis of Transcriptomic and Metabolomic Profiles," Iran. Biomed. J., vol. 29, no. 1-2, p. 68, 2024.
E. Abbasi, "Advancing insights into visceral leishmaniasis: challenges, innovations, and future directions in global disease management," Innovations Global Disease Management, 2025.
S. Mann, et al., "A review of leishmaniasis: current knowledge and future directions," Curr. Trop. Med. Rep., vol. 8, no. 2, pp. 121-132, 2021.
D. Sereno, et al., "Mapping unconventional Leishmania in human and animal leishmaniasis: A scoping review protocol on pathogen diversity, geographic distribution and knowledge gaps," PLoS One, vol. 20, no. 9, p. e0332874, 2025.
C. Cosma, et al., "Leishmaniasis in humans and animals: A One Health approach for surveillance, prevention and control in a changing world," Trop. Med. Infect. Dis., vol. 9, no. 11, p. 258, 2024.
S. Mehrotra, et al., "Advances and challenges in the diagnosis of leishmaniasis," Mol. Diagn. Ther., vol. 29, no. 2, pp. 195-212, 2025.
N. Singh and A. Sharma, "India should invest in the expansion of genomic epidemiology for vector-borne diseases filariasis, malaria and visceral leishmaniasis that are targeted for elimination," IJID Regions, vol. 13, p. 100453, 2024.
S. Mehrotra, et al., "Advances and challenges in the diagnosis of leishmaniasis," Mol. Diagn. Ther., vol. 29, no. 2, pp. 195-212, 2025.
O. Daoui, et al., "Genome sequencing of Leishmania tropica in tissues of Moroccan patients reveals microfocal transmission underlain by (pseudo) clonal and sexual reproduction," J. Infect. Dis., 2025, doi: 10.1093/infdis/jiaf485.
R. M. Kobialka, et al., "Portable smartphone-based molecular test for rapid detection of Leishmania spp.," Infect., vol. 52, no. 4, pp. 1315-1324, 2024.
A. J. Roberts, et al., "A panel of recombinant Leishmania donovani cell surface and secreted proteins identifies LdBPK_323600.1 as a serological marker of symptomatic infection," MBio, vol. 15, no. 5, p. e00859-24, 2024.
Copyright (c) 2025 Zainab Khamees Abbas, Muntaha Maddah Al Alouci, Osama A Mohsein

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