Identifying genetic causes leading to Keratitis infection in UK patients

Brief Lay background

Acanthamoebae are found worldwide amongst a wide range of microbial environmental habitats including fresh water bodies, swimming pools and domestic water supply. Acanthamoebae exist in two life cycle stages: a free-living trophozoite and a dormant cyst which, because its cell wall has two layers, is environmentally resistant. Both can cause opportunistic infections in humans, the most common of which is Acanthamoeba keratitis (AK), a painful infection of the cornea, the clear window at the front of the eye.

AK is being increasingly diagnosed in the UK, almost always associated with the incorrect use of contact lenses. AK can be difficult to diagnose because it is relatively rare, and signs and symptoms overlap with other causes which are usually ruled out first. Delay in diagnosis adds to a second issue which is that AK is difficult to treat; this is not only because of the location of the parasite, but also because the drugs used for treatment are not very effective against the cyst stage. Very little is known about the different types of Acanthamoeba, nor about how these types vary in response to treatment with the drugs used to treat AK.

What problem/knowledge gap does it help address

The numbers of positive diagnoses in the researchers’ reference laboratory averaged approximately five positive samples each month in 2019. The team has described at least six different species of Acanthamoeba among isolates from UK patients based on differences in cyst size and shape. Using genetic methods, other researchers have shown that such descriptions alone are not sufficient to classify Acanthamoeba. Despite this, there are currently no published reports on variation among UK Acanthamoeba and very few large-scale studies of AK patients anywhere.

Aim of the research project

To determine whether different types of isolates respond differently to drugs used to prevent or treat Acanthamoeba infection.

Key procedures/objectives

1. Identify the range of UK Acanthamoeba.
2. Identify genomic determinants to assess relevance to clinical features such as virulence or drug susceptibility.
3. Establish which drugs are most effective in managing infections and treating the different AK types.

Potential impact on people with sight loss

This study will provide new, comprehensive understanding of variation occurring among Acanthamoeba from UK keratitis patients, and new estimates of drug susceptibility. Results from the project will improve identification and genetic characterisation, and thus contribute to better diagnostic guidelines for AK in the UK.

These newly detailed descriptions will be linked wherever possible to information on disease severity received from doctors treating AK patients, allowing better future decisions about how to manage AK infections of the different types.