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Their role is increasingly relevant for neglected tropical diseases (NTDs), where traditional trial approaches may be slow, costly, or unfeasible. This review explores the scientific, ethical and translational dimensions of CHIMs, with a focus on the recently developed\n                      <jats:italic>Leishmania major<\/jats:italic>\n                      CHIM for cutaneous leishmaniasis (CL).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A narrative synthesis of peer\u2010reviewed literature and regulatory guidance documents published over the past two decades was conducted, with additional insights drawn from original fieldwork and the first\u2010in\u2010human sand fly\u2010transmitted CHIM for CL. Considerations included CHIM design principles, immunological outcomes, safety considerations and translational utility, including integration with omics and early phase trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CHIMs provide early efficacy data, help identify immune correlates of protection and facilitate the prioritisation of vaccine candidates. The\n                      <jats:italic>Leishmania major<\/jats:italic>\n                      CHIM demonstrated safety, high participant acceptability and revealed insights into lesion kinetics and host\u2013parasite interactions. Ethical and regulatory frameworks remain heterogeneous across regions, limiting scalability. Barriers to CHIM deployment in low\u2010 and middle\u2010income countries include infrastructure, governance and community engagement challenges.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CHIMs represent a critical translational tool for NTD vaccine research. Lessons from the CL CHIM underscore the potential and challenges of broader implementation. Harmonised regulation, ethical innovation and global collaboration will be essential for future impact.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/eci.70160","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T17:19:13Z","timestamp":1765991953000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Harnessing controlled human infection models to accelerate vaccine development for neglected tropical diseases: Lessons from leishmaniasis"],"prefix":"10.1111","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9701-5767","authenticated-orcid":false,"given":"Vivak","family":"Parkash","sequence":"first","affiliation":[{"name":"Division of Clinical Medicine, School of Medicine and Population Health The University of Sheffield  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"Ending the neglect to attain the Sustainable Development Goals: A road map for neglected tropical diseases 2021\u20132030.https:\/\/www.who.int\/publications\/i\/item\/9789240010352"},{"key":"e_1_2_12_3_1","article-title":"Neglected disease research and development: reflecting on a decade of global investment","author":"Chapman N","year":"2017","journal-title":"Policy Cures Research"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/14760584.2021.1991795"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0011394"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00068-7"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac820"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf1517"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105424"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03146-9"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc1076"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(24)00025-9"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0325149"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00392-15"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0759-x"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.223"},{"key":"e_1_2_12_17_1","unstructured":"Investigating Immune Responses to Aerosol BCG Challenge in Healthy UK Adults. 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