Browsing by Author "Santhanam Sundar"

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Advances and Challenges in the Diagnosis of Leishmaniasis
(Adis, 2025) Sanjana Mehrotra; Rahul Tiwari; Rajiv Kumar; Santhanam Sundar
Leishmaniasis remains a significant public health challenge, particularly in endemic regions with limited resources. Traditional diagnostic methods, including microscopy, culture, and serology, though widely utilized, often suffer from limitations such as variable sensitivity, time delays, and the need for specialized infrastructure. Some of these limitations have been addressed with the emergence of molecular diagnostic techniques. Quantitative PCR (q-PCR), loop-mediated isothermal amplification (LAMP), and recombinase polymerase amplification (RPA) assays have improved the diagnostic sensitivity and specificity, enabling species identification and detection of asymptomatic infections. Further, nanodiagnostics and portable sequencing technologies such as the MinION™, along with lab-on-chip platforms, are revolutionizing the diagnostic landscape of leishmaniasis by offering point-of-care (POC) options for remote settings and field-based diagnosis. This review provides an in-depth analysis of these cutting-edge advances, discusses their application in resource-constrained settings, and evaluates their potential to reshape the future of leishmaniasis diagnosis and management. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2025.
Amine-Functionalized Graphene Quantum Dots Conjugated with Amphotericin B: Synthesis, Characterization, and In Vitro Evaluation for Visceral Leishmaniasis Treatment
(American Chemical Society, 2025) Prasoon Madhukar; Rashmi Kesarwani; Sundaram Pandey; Vishal K. Singh; Mallikarjuna Rao Gedda; Omprakash Singh; Mohammad R. Shaz; Rajiv Kumar; Santhanam Sundar
Visceral Leishmaniasis (VL) is a life-threatening parasitic disease primarily affecting populations in resource-limited, endemic regions. Existing treatments for VL face limitations such as toxicity, high costs, and suboptimal efficacy in specific patient groups. Given the lack of a vaccine, chemotherapy remains the only option, emphasizing the urgent need for safer and more effective treatments. Nanotechnology offers promising avenues to overcome these challenges. This study introduces a novel approach involving amine-functionalized graphene quantum dots (fGQDs) conjugated with Amphotericin B (fGQDAmB) to enhance targeted drug delivery to Leishmania-infected macrophages. This novel approach, which could lead to a safer and more effective treatment for VL, is a significant contribution to the field. Structural characterization by XRD and FTIR confirmed successful GQD synthesis and functionalization, while cellular assays demonstrated significantly higher macrophage uptake and enhanced antileishmanial efficacy. fGQDAmB demonstrated approximately 4.2-fold greater potency against intracellular amastigotes and 2-fold higher efficacy against promastigotes, while also exhibiting reduced cytotoxicity compared to conventional AmB. The safety and effectiveness of fGQDAmB were further validated through hemolysis assay, providing reassurance and confidence about its potential use and instilling confidence in the potential of Quantum Dot-based Nanomedicine formulations. © 2025 The Authors. Published by American Chemical Society.
Anti-leishmanial therapies: overcoming current challenges with emerging therapies
(Taylor and Francis Ltd., 2025) Santhanam Sundar; Prasoon Madhukar; Rajiv Kumar
Introduction: Leishmaniasis, including visceral, cutaneous, and mucocutaneous forms, present a major health challenge in tropical regions. Current antileishmanial medications has significant limitations, creating a critical need for novel therapies that are safe and cost-effective with a shorter duration of treatment. Areas Covered: This review explores the critical aspects of existing antileishmanial therapy and targets for future therapeutic developments. It emphasizes the need for new treatment options due to drug resistance, low success rates, toxicity, and high prices associated with current medications. The different forms of leishmaniasis, their clinical manifestations, the challenges associated with their treatment and emerging treatment options are explored in detail. Expert Opinion: The first anti-leishmanial drug pentavalent antimony (SbV) was invented more than 100 years back. Since then, this compound has been used for all forms of leishmaniasis worldwide. For more than 70–80 years after discovery of SbV, no new antileishmanial drugs were developed, reflecting the lack of interest from academia or pharma industry. All three new treatments (Amphotericin-B, paromomycin and miltefosine) which underwent the clinical trials were repurposed drugs. The current pipeline for antileishmanial drugs is empty, with LXE 408 being the only potential drug reaching phase II clinical trial. © 2025 Informa UK Limited, trading as Taylor & Francis Group.
Characterization of differentially regulated carboxypeptidase (metallopeptidase M32) protein in Miltefosine resistant Leishmania donovani parasites
(Elsevier B.V., 2025) Krishan Amith Kumar; Sneha Banerjee; Hemalatha Sanivarapu; Jalaja Veronica; Madhulika Namdeo; Anjali Anand; Santhanam Sundar; Musti J. Swamy; Radheshyam S. Maurya
Introduction: Carboxypeptidase, a member of the metallopeptidase M32 family, catalyses the C-terminal hydrolysis of a variety of peptides and proteins in the presence of metal ions. Objective: To characterize Leishmania donovani carboxypeptidase (LdCP) in miltefosine (MIL) drug-resistant parasites. Methods: We performed the MTT assay and cell cycle analysis to confirm the MIL resistance of clinical isolates. LdCP gene was cloned and expressed in E. coli Artic strain. The purified LdCP protein was used for antibody generation and biochemical characterization. Results: MTT assay and cell cycle analysis revealed that all three isolates exhibit MIL resistance. LdCP constitutively expressed in both promastigote and amastigote stages of parasites, and its activity increased 2–3 fold in MIL-resistant parasites. LdCP has high α-helical content at physiological pH and temperature. The protein is quite thermostable with a Tm of 63 °C and susceptible to chemical denaturation, with 50 % unfolding induced by 3.59 M urea or 0.31 M guanidine hydrochloride (GdmCl). LC-MS/MS study reveals that LdCP interacts with membrane-associated proteins that have ATP binding sites and involved in protein phosphorylation. Conclusion: To our knowledge, this is the first study to characterize the carboxypeptidase of L. donovani that appears to contribute to the development of MIL resistance parasites. © 2024 Elsevier B.V.
Characterization techniques for mesoporous silicon nanoparticles
(Elsevier, 2025) Prasoon Madhukar; Shambhavi Kashyap; Priya Maurya; Santhanam Sundar
The characterization of mesoporous silicon nanoparticles (MSNs) is essential for understanding their unique properties and potential applications. It helps us to gain an insight into the morphology, structure, and surface characteristics of these particles, which aids in the development of novel technologies and materials. Characterization additionally enables us to tailor the synthesis and processing of these nanoparticles for particular purposes. MSNs typically have pore size ranges of the order of 2–6 nm and particle sizes in the range of 50–300 nm. The MSNs’ high surface area and pore volumes, which result from their controlled structure and morphology at both the nanometer and micrometer scales, allow for a high cargo-carrying capacity. By employing various types of templates and altering the reaction settings, the pore size of the mesoporous material for such an application can be adjusted. Various techniques have been developed to characterize these nanoparticles, including electron microscopy, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy, and surface area analysis using nitrogen adsorption-desorption analysis. Each technique provides different information about the morphology, structure, and surface properties of the nanoparticles. This chapter aims to review the different characterization techniques for mesoporous silicon nanoparticles, highlighting their strengths and limitations. © 2026 Elsevier Inc. All rights reserved.
Etiology of Acute Encephalitis Syndrome in Adults in a Tertiary Care Center in Eastern Uttar Pradesh
(American Society of Tropical Medicine and Hygiene, 2025) Tulika Kumari Rai; Jaya Chakravarty; Shubham Kashyap; Sumeet Chatterjee; Vishwa Deepak Tiwari; Urvashi Geeta Rai; Mayank Gangwar; Santhanam Sundar; Gopal Nath
Seasonal outbreaks of acute encephalitis syndrome (AES) with high case fatality rates have been commonly reported among adults in India. With an increase in Japanese encephalitis virus (JEV) vaccination, the etiology of AES is also changing. However, most studies on AES in India have focused only on children and on JEV. This study was conducted in the Department of Medicine, Institute of Medical Sciences, Banaras Hindu University between 2020 and 2022 to determine the etiology of AES in adults. Blood and cerebrospinal fluid (CSF) were collected from patients 18 years or older with fever and altered sensorium for #15 days. We did IgM ELISA for dengue, chikungunya, West Nile virus, scrub typhus, leptospirosis from serum, CSF-IgM for JEV, and CSF–polymerase chain reaction for herpes simplex virus 1 and 2, varicella-zoster virus, enterovirus, and cartridge-based nucleic acid amplification test (CBNAAT) for tuberculous meningitis (TBM). The most common cause of AES identified in our study was TBM (16.7%), followed by leptospirosis (15.1%) and scrub typhus (11.9%). The high occurrence of TBM in our study highlights the importance of CSF-CBNAAT for all AES patients. As leptospirosis and scrub typhus are easily treatable, early detection and treatment of these infections should be recommended. © © 2025 American Society of Tropical Medicine and Hygiene.
Navigating the Roadblocks: Progress and Challenges in Cell-Based Therapies for Human Immunodeficiency Virus
(John Wiley and Sons Inc, 2025) Lakshay Chhabra; Rajeev Kumar Pandey; Rajiv Kumar; Santhanam Sundar; Sanjana Mehrotra
Cell-based therapies represent a major advancement in the treatment and management of HIV/AIDS, with a goal to overcome the limitations of traditional antiretroviral therapy (ART). These innovative approaches not only promise a functional cure by reconstructing the immune landscape but also address the persistent viral reservoirs. For example, stem cell therapies have emerged from the foundational success of allogeneic hematopoietic stem cell transplantation in curing HIV infection in a limited number of cases. B cell therapies make use of genetically modified B cells constitutively expressing broadly neutralizing antibodies (bNAbs) against target viral particles and infected cells. Adoptive cell transfer (ACT), including TCR-T therapy, CAR-T cells, NK-CAR cells, and DC-based therapy, is adapted from cancer immunotherapy and repurposed for HIV eradication. In this review, we summarize the mechanisms through which these engineered cells recognize and destroy HIV-infected cells, the modification strategies, and their role in sustaining remission in the absence of ART. The review also addresses the challenges to cell-based therapies against HIV and discusses the recent advancements aimed at overcoming them. © 2024 Wiley Periodicals LLC.
Patient insights research exploring disease awareness, patient life experience, and current management of visceral leishmaniasis in Bihar, India
(Public Library of Science, 2025) Santhanam Sundar; Fabiana Piovesan Alves; Koert Ritmeijer; Margriet Leontine den Boer; Colin Forsyth; Bethan Hughes; Clare Zamble; Kirsten Carter; Gerhild Angyalosi
Background Visceral leishmaniasis (VL) is a vector-borne disease caused by Leishmania parasites and transmitted by sand fly bites, targeted for elimination in India. VL primarily affects rural, low-income populations with limited health care access. In South Asia, few studies have explored patients’ perspectives, diagnoses, and treatment experiences; particularly lacking an understanding about the patients’ life experiences outside of clinical research settings. Methodology/principal findings A qualitative study was conducted in Bihar, India, using moderator-facilitated, protocol-defined discussion. Eighteen adult patients and 12 caregivers of children diagnosed with and treated for VL within the last 12 months were identified by self-report. Mean time from symptom onset to diagnosis was 13.8 days. Challenges of the early patient life experience included lack of urgency by health care professionals, delayed diagnosis, and no guar-antee of treatment at the location of their VL diagnosis (63% had to switch to a different center for treatment, at times delaying treatment). Key barriers identified in previous studies that were re-confirmed in this study include out-of-pocket financial burden, absence from work/home duties, and long-distance travel to hospitals. Patients and caregivers (n = 29/30) expressed a preference for a potential oral treatment that could be taken close to home. Conclusions/significance This study reveals new insights about the patient life experience and reconfirms previous research indicating that access to care for patients with VL in the Bihar area remains a challenge. Although most patients with VL seek care early, diagnosis often requires multiple visits to a health care facility. Despite access to therapy in public hospi-tals, some patients reported a preference for private care. Even if diagnosis takes place in a government-funded public setting, some patients reported needing to move from the location of diagnosis to another center to receive therapy, creating an additional burden for patients. As a potential alternative to current parenteral treatment, adult patients and caregivers of pediatric patients expressed interest in a potential oral therapy because it may reduce barriers to access care. © 2025 Sundar et al.
Synthesis of porous silicon–based nanoparticles
(Elsevier, 2025) Prasoon Madhukar; Sarita Singh; Santhanam Sundar
The synthesis of porous silicon–based nanoparticles (NPs) is an important topic in the fields of nanotechnology and materials science. Porous silicon–based NPs have unique properties, including high surface area, biocompatibility, and tunable pore size, which make them useful for a variety of applications, such as drug delivery, biosensing, and energy storage. Therefore understanding the different methods for synthesizing these NPs is crucial for researchers and engineers who work in these fields. Some of the tradition methods for the synthesis of these particles are laser ablation, chemical or electrochemical reduction, chemical or physical deposition, and hydrothermal synthesis. These techniques have some drawbacks, including the use of dangerous chemicals, high temperatures and vacuums, and requirement of complicated equipments. In the current chapter, several methods for the synthesis of porous silicon–based NPs, such as metal-aided chemical etching, electrochemical etching, magnesium isothermic reduction, chemical vapor deposition, selective dealloying, and other synthetic methods, have been thoroughly discussed, and it has been clearly demonstrated that the structural parameters, such as pore size, particle size, and specific surface area, can be regulated by changing the synthesis conditions. © 2026 Elsevier Inc. All rights reserved.
The circulating plasma microRNA signature in human visceral leishmaniasis
(American Society for Microbiology, 2025) Ritirupa Roy; Cinthia L. Hudachek; Shashi Bhushan Chauhan; Shashi Kumar; Awnish Kumar; Bayan Sudan Zhanbolat; Madhukar Rai; Rajiv Kumar; Santhanam Sundar; Mary E. Wilson
Visceral leishmaniasis (VL) is a vector-borne disease caused by the obligate intracellular protozoan Leishmania donovani in India. VL can be complicated by post-kala-azar dermal leishmaniasis (PKDL), a macular or nodular rash that develops in 10%-20% of patients after treatment of VL in India. Patients with PKDL are infectious to sand flies,promoting further transmission of the parasite. MicroRNAs (miRNAs) are 18-25 nt, non-coding RNAs that simultaneously regulate the expression of several or many target transcripts. This study was based on the hypothesis that the host response to L. donovani is modifiedby distinct sets of miRNAs in VL or PKDL and that these might differfrom healthy controls. We investigated this hypothesis using a NanoString panel to profilethe miRNAs expressed in the plasma of patients with VL or PKDL diagnosed at a hospital in Bihar, India. We compared these to plasma microRNAs of healthy control individuals from the same endemic villages. miRNAs hsa-miR-223-3p, hsa-miR-191-5p, hsa-miR-23a-3p, and hsa-1285-5p were significantlyhigher in the plasma samples from patients with VL compared to either PKDL or endemic controls. Prediction programs highlighted potential mRNA targeted by these miRNAs, among which we verifiedthe down-modulation of several transcripts belonging to the NFκB and NLRP3 inflammasomepathways in circulating leukocytes of VL patients. By contrast, miRNA patterns in subjects with PKDL were similar to control subjects, possibly suggesting that the pathogenic immune response during PKDL is primarily localized in the skin. © 2025 American Society for Microbiology. All rights reserved.
The development of a global research agenda and individual participant data platform for visceral leishmaniasis: challenges and future opportunities
(BioMed Central Ltd, 2025) Sauman Singh-Phulgenda; Prabin Dahal; Brittany J. Maguire; Jorge Alvar; Fabiana Piovesan Alves; Mitali Chatterjee; Carlos Henrique Nery Costa; Simon L. Croft; Philippe Jean Jean Guérin; Dinesh K. Mondal; Ahmed Mudawi Musa; Krishna Pandey; Koert Ritmeijer; G. A.s. Romero; Santhanam Sundar
Background: Visceral leishmaniasis (VL) is one of the neglected tropical diseases (NTDs) listed by the World Health Organization (WHO). The disease is currently in the elimination phase in the Indian subcontinent (ISC) and being targeted for elimination by 2030 in East Africa (EA). Maintaining the necessary financial and political commitments to achieve and sustain the current elimination efforts remains challenging. As with other NTDs, VL research is constrained by limited funding, and drug development has relied largely on partnerships between not-for-profit organisations and the pharmaceutical industry. Conducting robust clinical studies remains difficult, and therapeutic innovations have been limited. However, re-use of existing data offers an untapped opportunity to generate new evidence. Methods: We describe the process of developing a global VL research agenda and the establishment of an individual participant data (IPD) platform at the Infectious Diseases Data Observatory (IDDO). Key steps included a systematic scoping review of VL clinical trials, consultations with the Scientific Advisory Committee, expert and public reviews, and implementation of an equitable governance framework to harmonise and share IPD. Results: The VL research agenda, finalised in 2019, identified priority methodological and clinical questions suited to IPD analyses. The IDDO VL platform currently hosts harmonised data from nearly 15,000 patients across more than 50 studies (VL and post-kala-azar dermal leishmaniasis, PKDL). The platform is an inclusive resource guided by an equitable governance framework and provides a critical asset to support new evidence generation and can serve as a historical data to support accelerated drug development. Conclusions: The development of a global VL research agenda has provided an inventory of priority research questions of public health importance. A shared IPD platform aligned with this agenda was developed to complement ongoing global efforts. In addition, such a platform can accelerate secondary evidence generation, support methodological innovation and inform future trial designs and policy. Sustained collaboration and investment are needed to maximise the scientific and public health value of data re-use in VL and PKDL. © The Author(s) 2025.
The story of elimination of visceral leishmaniasis (kala-azar) in India—Challenges towards sustainment
(Public Library of Science, 2025) Santhanam Sundar
The earliest record of visceral leishmaniasis (kala-azar, KA, VL) dates back two centuries from Jessore (now in Bangladesh), with 0.75 million deaths in 3 years. In the 1950s, there was extensive insecticide dichlorodiphenyltrichloroethane (DDT) spray under the aegis of the National Malaria Eradication Program. As a corollary benefit, there was a sharp decline in the incidence of VL due to the reduced prevalence of the vector to extremely low levels, resulting in substantial decreases in the number of KA cases. In the early 1970s, a surge in the number of cases was noted, and since then, it has taken the shape of the current epidemic. In 1990–91, the National Kala-azar Control Program was launched in India, though without much impact due to the diminishing efficacy of treatment with pentavalent antimonial. This was followed by the introduction of highly effective amphotericin B deoxycholate. In 2005, the Kala-azar Elimination Program (KAEP) was launched jointly by India, Bangladesh, and Nepal, with treatment initially with oral miltefosine, succeeded later by single-dose liposomal amphotericin B (AmBisome), and in 2023, India achieved the goal of kala-azar elimination, defined as an incidence below 1 per 10,000 at sub-district (block) level. Patients with post kala-azar dermal leishmaniasis, HIV-VL coinfection, and undiagnosed/untreated VL patients are the human sources for the vector. They may herald an outbreak resulting in the commencement of a new epidemic. Active case detection, early diagnosis, and prompt, complete treatment are required to prevent fresh transmission. Periodic updates of health personnel, community awareness, and continued availability of the theragnostics are important steps for early detection and containment of an outbreak. © 2025 Shyam Sundar.