Parasite genetic variation and systemic immune responses are not associated with different clinical presentations of cutaneous leishmaniasis caused by Leishmania aethiopica

Cutaneous leishmaniasis (CL) is a neglected tropical skin disease, caused by the protozoan parasite Leishmania (L.). It is endemic to 90 countries and causes >200,000 new infections each year. In Ethiopia, CL is mainly caused by L. aethiopica and can present in different clinical forms: localised cutaneous leishmaniasis (LCL); mucocutaneous leishmaniasis (MCL), where the mucosa of the nose and/or the mouth are affected; and diffuse CL (DCL), characterised by non-ulcerating nodules. Persistent forms of LCL, as well as MCL and DCL, require treatment but are difficult to treat successfully and can lead to permanent disfigurement, social stigmatisation, and a mental health burden. The mechanisms behind the development of these different presentations of CL are not clearly understood, and both parasite and host factors could be involved. Here we analysed the whole genome sequence data for 48 clinical parasite isolates and show that parasites from CL cases with different presentations in a single Ethiopian setting are from the same genetic population. Furthermore, we did not identify any individual genetic variants significantly associated with disease presentation. We also measured plasma chemokine and cytokine levels of 129 CL patients presenting with different forms of CL. None of the cytokine or chemokine levels measured were significantly different between the different clinical presentations of CL. We also compared those with healthy nonendemic controls: our results show a chemokine but not a cytokine immune signature in patients with CL as compared to healthy nonendemic controls.