The Project

How we aim to lay the foundation blocks that will drive a new way of conducting research into leishmaniasis

Background

The leishmaniasis are parasitic diseases caused by one of several species of single cell parasites (Leishmania) that are transmitted to humans by the bite of infected phlebotamine sand flies. These diseases affect over 150 million people across 98 countries worldwide, including many low and middle income countries (LMICs). Some forms of leishmaniasis are fatal, whereas other are very stigmatising and affect quality of life, particularly in children and women. Few drugs are available for patients with leishmaniasis and no vaccines are currently registered for use in preventing or treating these diseases. Importantly, the drugs that we do have are not universally effective and often have significant side effects.

Sometimes patients even in the same geographical area will respond quite differently to therapy, and for some drugs effectiveness may vary widely between different countries. In order to make the best use of current and future drugs for the leishmaniasis, we need to understand more about why this is the case, and use that information to select appropriate drugs or drug combination for use in different settings.

Using the appropriate treatment would save costs in health care, minimise the patient suffering that results from administering ineffective treatments, and reduce the economic burden of disease on patients, their families and communities.

WHO endemicity maps:

Cutaneous leishmaniasis:

Cutaneous leishmaniasis:

Visceral leishmaniasis

Visceral leishmaniasis

This project:

An overview of the project is provided in the following figure:

Workflow for sample analysis and data integration in LeishPathNet. Blue boxes represent the digital pathology infrastructure; red boxes represent work to be initiated in this Award; Data integration and links to other databases represent future developments

To maximise the value of clinical samples taken for research or diagnostic purposes, we need to:

  1. develop standardised approaches to sample collection and collection of patient meta-data;
  2. develop tools for multiparameter and multidimensional phenotyping;
  3. provide access to whole slide images via a searchable database;
  4. provide an online forum for discussion of disease pathology and training;
  5. allow local image analysis to facilitate the development of new tools (e.g. machine or deep learning) for identifying novel phenotypic traits; and
  6. provide access to locally held tissues samples for further interrogation by collaborating researchers.

Our Foundation Award has allowed us to develop this beta test site, to develop and pilot a standardised case record form for tegumentary leishmaniasis in India, Sri Lanka and Brazil, to collect a training set of clinical samples from patients pre- and post-treatment, and to begin to develop new molecular approaches to tissue analysis.  We are providing access to WSIs via the Zeiss Zen Browser platform, which also contains standard analytic and mark-up tools.  Working with Zeiss, we are developing further search strategies for extracting images based on searches of the meta-data held in the CRFs (see SLIDES).  In addition to this “laboratory” research, we are also conducting a health economics analysis of the potential research and clinical impact of digital pathology, to support funding and health care decision making processes.

Our Foundation Award does not currently support opening our tissue banks to the research community, but this is a long term ambition for future funding. We would value any suggestions for novel immune pathways that might be interrogated at the tissue level across the spectrum of tegumentary leishmaniasis caused by L. donovani and L. braziliensis.

To foster a One-Health (http://www.who.int/features/qa/one-health/en/) and 3Rs approach (https://www.nc3rs.org.uk/the-3rs), we have also included capacity in LeishPathNet to host data from pre-clinical models of leishmaniasis.  The associated meta-data also indicates the availability of samples (paraffin / cryo blocks, RNA, transcriptomic data from multiple tissues) that could be available for future collaborative research, with considerable 3Rs impact.

More about the project