LEISH_Challenge
Research type
Research Study
Full title
A clinical study to develop a controlled human infection model using Leishmania major-infected sand flies
IRAS ID
286420
Contact name
Charles Lacey
Contact email
Sponsor organisation
University of York
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 6 months, days
Research summary
Summary of Research: The disease leishmaniasis mainly occurs in hot and tropical countries, affects millions of people and causes around 20,000 deaths across the world every year. Leishmaniasis is caused by the Leishmania parasite and is transmitted by sand flies. The parasite is tiny and not visible to the naked eye, whereas the sand fly is visible but small and inconspicuous.
There are different types of leishmaniasis which can affect the skin (cutaneous leishmaniasis) or the internal organs of the body (visceral leishmaniasis). Some of the milder forms will produce skin problems which will be localised, whilst other forms of leishmaniasis will cause widespread skin changes. The skin lesions of cutaneous leishmaniasis can be disfiguring if left untreated.
We do have some treatments for leishmaniasis but many of them are not easy to use or don’t work well. Therefore, we need new treatments and would like to find vaccines that prevent or work against leishmaniasis.
A solution being adopted for other diseases, which we now wish to adopt for leishmaniasis is to develop a ‘Controlled human infection model’ (CHIM). These models involve deliberate exposure of individuals to an infection, in order to better understand how the disease works and to test potential vaccines and treatments. They have contributed knowledge that has led to advances in the development of treatments.
This is study builds on an our initial successful study, FLYBITE, where we used uninfected (disease-free) sand flies to test the safety aspects and ensure that sand flies were able to bite human participants in a controlled environment. We observed no major adverse effects and it was well tolerated by participants. We therefore wish to proceed to a study using sand flies infected with a form of leishmaniasis that causes localised skin disease and is treatable, on the pathway to assessing future vaccines.Summary of Results: Cutaneous leishmaniasis is a skin disease caused by a tiny parasite called Leishmania, which is spread to humans through the bite of infected sand flies. It causes skin sores that can take a long time to heal and may leave scars. There is no approved vaccine to prevent it.
In this study, researchers set up a Controlled Human Infection Model (CHIM) for cutaneous leishmaniasis. This means they carefully and safely infected healthy volunteers in a clinical setting in order to study the disease and help test future vaccines. This kind of research is already used for other diseases such as malaria and influenza.
The study involved 14 healthy adult volunteers who had never been exposed to the parasite. The volunteers were bitten by laboratory-bred sand flies that were infected by the Leishmania major parasite, which causes a milder form of the disease and is not life-threatening.
The researchers closely monitored the volunteers over time to see if they developed any sores (called “lesions”) and to assess how their bodies responded. They also ensured early treatment if needed.
Key results:
9 out of 14 people (64%) developed skin lesions. However, we know that when a participant received a definite bite as judged by the researchers, 100% of participants developed a lesion. This is important because it means the infection model works and could be used to test vaccines.
The lesions were small and treated by removing a small piece of skin (a biopsy), which cleared the infection in most cases.
3 people had mild recurrences months later but were treated successfully with freezing therapy (cryotherapy).
No one had serious side effects, and all participants were completely healed after 12 months.
In addition to showing that the model is safe, the researchers also studied the immune response in the skin sores using advanced lab techniques. This gives scientists new insights into how the body fights off this parasite, and how the skin behaves when infected.This new model provides a safe and ethical way to test how well new vaccines work before trying them in larger groups. It could help speed up the development of vaccines for cutaneous leishmaniasis, especially for use in the parts of the world where the disease is common.
For more details, the full study is available at:
https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fwww.nature.com%252Farticles%252Fs41591-024-03146-9%2FNBTI%2F6tC9AQ%2FAQ%2F381bfc3d-5bb0-48d8-b9ad-fedcce587740%2F2%2FJJ_Fwsd_Ia&data=05%7C02%7Champshirea.rec%40hra.nhs.uk%7Cf354e2cf2d414db5db5e08dda439724c%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638847288849078094%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=jirPaV9AOxO2tYNLxKJ6%2B1OH%2BYmVaXiExeI2pqsngpU%3D&reserved=0REC name
South Central - Hampshire A Research Ethics Committee
REC reference
20/SC/0348
Date of REC Opinion
8 Dec 2020
REC opinion
Further Information Favourable Opinion