Study Finds Safe, Effective Way of Infecting Participants With the Parasite Causing Leishmaniasis

This breakthrough can be significant in the development for a vaccine and other preventative measures to protect individuals from leishmaniasis.

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About the Trial

Trial Name: A Clinical Study to Develop a Controlled Human Infection Model Using Leishmania Major-infected Sand Flies (LEISHChallenge)

ClinicalTrials.gov ID: NCT04512742

Sponsor: University of York

Completion Date: November 1, 2023

According to findings published in Nature Medicine, investigators have developed a new, safe, and effective method of infecting volunteers with the parasite that causes leishmaniasis. This allows the investigators to measure the body’s immune response and lays out a foundation, allowing for the vaccine development and for testing new preventative measures to protect individuals from the tropical disease.¹

Leishmaniasis is caused by infection with microscopic Leishmania parasites that are transmitted into the skin via a bite from an infected sand fly. According to evidence, the disease affects over 1 million people per year, with the majority developing an ulcer at the site of infection which is slow to heal. Experts note that although the ulcer does eventually heal, the scar can have significant impacts on quality of life, notably in women, children, and individuals who have the infection on their face.¹

Currently, no vaccines or drugs are available to prevent individuals from becoming infected with leishmaniasis. This is notably because of difficulties and costs that are associated with conducting clinical trials in countries where the infection is most common.¹

This study, which was conducted from January 24, 2022, to August 12, 2022, exposed 14 participants to L. major-infected Phlebotomus duboscq. The primary objective of the study is to demonstrate effectiveness of lesion development—or take rate—and safety, which was defined as the absence of cutaneous leishmaniasis lesion at 12 months. Secondary and exploratory objectives include the rate of lesion development, parasite load, and the analysis of local immune responses via immunohistology and spatial transcriptomics.²

The investigators estimated that an overall take rate for cutaneous leishmaniasis development of approximately 64% (n = 9). According to the findings, 2 of 10 participants had 1 and 1 of 10 participants had 2 lesion recurrences about 4 to 8 months after biopsy. These participants had their lesions successfully treated with cryotherapy. Additionally, all participants were lesion-free on or beyond their 12-month follow-up.²

“Research on skin diseases that affect people in the UK and in developing countries is a priority at the Medical School,” said clinical lead Alison Layton, MBChB, FRCP, professor at Hull York Medical School Centre for Skin Research, University of York, in a news release. “This study, which demonstrates that this infection model is safe and well tolerated by participants, exemplifies our global approach to skin health and has the potential to impact the lives of many millions worldwide.”¹

According to the investigators, there were no grade 3 or serious adverse events (AEs) recorded, and there were none reported during the biting phase of the study. One participant had a grade 1 AE (oozing from a scar), and 2 had reported experiencing a grade 2 AE (infections at wound site). Additionally, wound infections were often associated with itch and scratching, but there was no evidence of cellulitis. Full blood count, liver function tests, urea and electrolytes, and C-reactive protein were taken in all participants at both baseline and follow-up, with no significant differences observed. A minimal inflammatory response was noted, and any changes observed within the prior parameters remained within a normal range and were considered to not be clinically relevant.²

The investigators note that this is the first comprehensive map for immune cell distribution and cytokine/chemokine expression in cutaneous leishmaniasis in human lesions. This study can lead to further opportunities and research to determine or develop a vaccine candidate based on human efficacy data, according to the investigators.²

“This is a landmark study that now provides a new approach to test vaccines and preventative measures for leishmaniasis in a rapid and cost-effective way. It also allows us to learn more about how our immune system fights the infection,” explained lead investigator Paul Kaye, PhD, FRCPath, FMedSci, professor at Hull York Medical School at the University of York, in the news release. “Thanks to the generosity of the volunteers that took part in our study, we are now well-positioned to bring new hope to those that are affected by this disease.”¹

References

1. University of York. York researchers make breakthrough in bid to develop vaccines and drugs for neglected tropical disease. News release. August 2, 2024. Accessed August 5, 2024. https://www.eurekalert.org/news-releases/1053333

2. Parkash, V, Ashwin, H, Dey, S, et al. Safety and reactogenicity of a controlled human infection model of sand fly-transmitted cutaneous leishmaniasis. Nat Med (2024) doi:10.1038/s41591-024-03146-9