School Of Basic And Applied Sciences

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    An Insight Into Systemic Immune Response in Leishmania donovani Mediated Atypical Cutaneous Leishmaniasis in the New Endemic State of Himachal Pradesh, India
    (Frontiers Media S.A., 2022-01-04T00:00:00) Thakur, Lovlesh; Madaan, Priyanka; Jain, Aklank; Shankar, Vinay; Negi, Ajeet; Chauhan, Shashi Bhushan; Sundar, Shyam; Singh, Om Prakash; Jain, Manju
    Leishmaniasis continues to afflict known and newer endemic sites despite global efforts towards its control and elimination. In this regard, the emergence of newer endemic sites with unusual disease formats is recognized wherein Leishmania donovani complex classically known to cause visceral disease is demonstrated to cause cutaneous manifestation. In this context, atypical cutaneous leishmaniasis (CL) cases caused by L. donovani genetic variants from the newer endemic state of Himachal Pradesh (HP) in India are beginning to be understood in terms of parasite determinants. The atypical CL manifestation further needs to be explored to define host immune correlates with a possible role in driving the unusual disease progression. In the given study, we performed comprehensive systemic-immune profiling of the atypical CL patients from the study area in HP, India, in comparison with the classical visceral leishmaniasis (VL) patients from the northeast region of India. The systemic immune response was studied using ELISA-based assessment of Th1, Th2, Th17, Treg, and Th22 specific plasma cytokine expression pattern and parasite-specific total serum IgG/IgG subclasses. The specified immune correlates are known to exhibit heterogeneous association with the different infecting parasite species, infection load, and co-lateral host immunopathology in classical CL and VL. In the atypical CL patient group, altered expression of IL-10 emerged as the key finding that could potentially fine-tune the Th1/Th17/Th22 effector cytokine axis towards a localized cutaneous manifestation. A reduced expression of IL-10 along with a high IFN-?/IL-10 ratio as a readout of effective parasite killing defined atypical cutaneous outcome. In contrast, high circulatory IL-10 levels and a depressed IFN-?/IL-10 ratio were seen in classical VL patients in line with an ineffective parasite-killing cytokine response. Overall,�the study highlights new knowledge on host immune correlates in terms of cytokine expression pattern and IgG subclasses that underline atypical disease manifestation such that L. donovani, a generally visceralizing parasite species cause skin localized cutaneous lesions. Copyright � 2022 Thakur, Madaan, Jain, Shankar, Negi, Chauhan, Sundar, Singh and Jain.
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    Leishmania donovani persistence and circulation causing cutaneous leishmaniasis in unusual-foci of Nepal
    (Nature Research, 2023-07-29T00:00:00) Rai, Tinmaya; Shrestha, Srijan; Prajapati, Sabita; Bastola, Anup; Parajuli, Niraj; Ghimire, Pragya Gautam; Bhandari, Parmananda; Pandey, Kishor; Jain, Manju; Matlashewski, Greg; Bras-Goncalves, Rachel; Manandhar, Krishna Das
    Cutaneous leishmaniasis cases have increased dramatically in recent years in Nepal. The study offers molecular identification of the Leishmania species using 40 patient�s aspiration biopsy samples, targeting markers kinetoplast minicircle DNA (kDNA) and internal transcribed spacer-1 (ITS1). Among molecularly diagnosed 22 cutaneous leishmaniasis cases, L. donovani complex was identified in 13 instances and L. major in 9 cases. The ITS1 PCR was positive in 12 of the positive nested- kDNA PCR cases (12/22), confirming L. donovani complex in seven of the cases and L. major in five of the cases. In addition, the study conclude that concurrent occurrence of atypical cutaneous infections caused by L. donovani parasite in 59.1% of cases and typical cutaneous infections caused by L. major parasite in 40.9% of cases. A Phylogentic analaysis showed that the detected L. donovani species present null genetic distances from seven references of L. donovani, but slight differences between ITS1 sequences and not grouped into a significant monophyletic cluster. � 2023, The Author(s).