Transcriptional Blood Signatures for Active and Amphotericin B Treated Visceral Leishmaniasis in India

• DOI: 10.1101/554022
• Publication Date: 2019-02-18T22:06:38Z
• Authors: Michaela Fakiola; Om-Prakash Singh; Genevieve Syn; Toolika Singh; Bhawana Singh; Jaya Chakravarty; Shyam Sundar; Jenefer M. Blackwell
• Keywords: QuantiFERON; CXCL9

Abstract Amphotericin B provides improved therapy for visceral leishmaniasis (VL) caused by Leishmania donovani , with single dose liposomal-encapsulated Ambisome providing the best cure rates. The VL elimination program aims to reduce incidence rate in Indian subcontinent <1/10,000 population/year. Ability predict which asymptomatic individuals (e.g. anti-leishmanial IgG and/or Leishmania-specific modified Quantiferon positive) will progress clinical would help monitoring disease outbreaks. Here we examined whole blood transcriptional profiles associated infection, active disease, and treated cases. Two independent microarray experiments were performed, analysis focussed primarily on differentially expressed genes (DEGs) concordant across both experiments. No DEGs identified or positive groups compared negative healthy endemic controls. We therefore concentrated comparing from cases all controls, examining differences transcriptome following different regimens of drug treatment. In these comparisons 6 major themes emerged: (i) expression enrichment gene sets erythrocyte function cases; (ii) strong evidence involved cell cycle controls; (iii) identification IFNG encoding interferon-γ as hub patterns controls (iv) interleukin signalling (IL-1/3/4/6/7/8) a prominent role CXCL10/9/11 chemokine pathways (v) novel Aryl Hydrocarbon Receptor significant canonical pathway when (vi) global profiling support more effective at day 30 post-treatment liposomal encapsulated amphotericin multi-dose non-liposomal treatment over days. Author Summary Visceral (VL), also known kala-azar, is potentially fatal intracellular parasites species complex. serious public health problem rural India, causing high morbidity mortality, well costs local national budgets. Ambisome, now affordable through WHO-negotiated price reductions, By assessing immune responses people infected L. but status, can determine requirements development individuals, example antibody levels, VL. This this study looked try understand about VL, B. signatures aid our understanding pathogenesis provide targets therapeutic intervention future.