Early reduction in PD-L1 expression predicts faster treatment response in human cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) is caused by Leishmania donovani in Sri Lanka. Pentavalent antimonials (e.g., sodium stibogluconate [SSG]) remain first-line drugs for CL with no new effective treatments emerging. We studied whole blood and lesion transcriptomes from Sri Lankan patients with CL at presentation and during SSG treatment. From lesions but not whole blood, we identified differential expression of immune-related genes, including immune checkpoint molecules, after onset of treatment. Using spatial profiling and RNA-FISH, we confirmed reduced expression of programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) proteins on treatment in lesions of a second validation cohort and further demonstrated significantly higher expression of these checkpoint molecules on parasite-infected compared with noninfected lesional CD68+ monocytes and macrophages. Crucially, early reduction in PD-L1 but not IDO1 expression was predictive of rate of clinical cure (HR = 4.88) and occurred in parallel with reduction in parasite load. Our data support a model whereby the initial anti-leishmanial activity of antimonial drugs alleviates checkpoint inhibition on T cells, facilitating immune-drug synergism and clinical cure. Our findings demonstrate that PD-L1 expression can be used as a predictor of rapidity of clinical response to SSG treatment in Sri Lanka and support further evaluation of PD-L1 as a host-directed therapeutic in leishmaniasis.

Imprint cytology: a useful screening test for diagnosis of Helicobacter pylori in resource poor settings.

OBJECTIVE: The study aimed to compare the usefulness of two staining methods for imprint cytology for diagnosis of Helicobacter pylori infection. Gastric biopsy specimens (from dyspeptic patients attending routine upper gastrointestinal endoscopy) were placed on glass slides to obtain imprints. The imprints were stained with Toluidine blue and Giemsa stains separately and observed under ×400 magnification using a light microscope. Imprinted biopsies were sectioned and stained with H & E stain and Giemsa stain for histological analysis. Diagnosis of H. pylori infection in both imprint and histological sections were confirmed by a consultant pathologist. The sensitivity, specificity, positive predictive value and negative predictive value of each stain were calculated and benchmarked against histological diagnosis. RESULTS: Of the 55 dyspeptic patients enrolled in the study, 5 were positive for H. pylori by Toluidine blue stain and 4 by Giemsa stain. The sensitivity of Toluidine blue stain (57.1%) was higher than Giemsa stain (42.9%) while the specificity of both stains was equal (97.9%). Giemsa stain gave a better discrimination for identification of H. pylori bacteria among the mucosal background. Imprint cytology is a rapid, simple and cost effective diagnosis method that can supplement histological diagnosis.