Biology subjects

Roy, L.

Publications and source records attributed to Roy, L..

3 recordsLinked to original sources

bioRxiv2025

Unravelling the distribution of vectors of major vector-borne diseases in Koshi Province of Nepal: A concern of expansion in diverse geo-ecological and climatic regions

BackgroundVector-borne diseases, being major public health concerns, are either slated for elimination or projected for control in Nepal. One of the major challenges in controlling these VBDs is to halt their emergence and expansion in diverse geo-ecological and climatic regions. In this study, we collected vectors of major VBDs to understand their distribution, diversity, and association with ecological variances. Methodology/Principal findingsA descriptive cross-sectional survey was conducted to collect the vectors in five districts situated at altitudes of up to 98 - 1,274 meters in Koshi Province, Eastern Nepal, representing three distinct geo-ecological and climatic regions: mountain, hills and lowlands during May and June 2023. Adult vectors were captured using CDC miniature light traps, BG sentinel traps, and manual aspirators. Association of vectors abundance in function of the geo-ecological and climatic variables was assessed in two vector species (Culex quinquefasciatus and Phlebotomus argentipes). We found the malaria vector Anopheles annularis, the lymphatic filariasis vector Cu. quinquefasciatus and visceral leishmaniasis vector Ph. argentipes from all three geo-ecological regions. The other vectors of the malaria parasite, An. pseudowillmori and An. willmori, and Japanese encephalitis vector Cu. tritaeniorhynchus were recorded from hilly districts only. Mean temperature and rainfall had positive effect on Cu. quinquefasciatus density and deleterious on Ph. argentipes. Culex quinquefasciatus and Ph. argentipes were captured in high abundance per household in hills (IRR = 1.23 and IRR = 13.00, respectively) and mountain (IRR = 1.96 and IRR = 4.00, respectively) as compared to lowland. ConclusionTwo major vectors, Cu. quinquefasciatus and Ph. argentipes were indiscriminately present in all geo-ecological regions. Climatic variables favour vectors survival, distribution and growth in diverse altitudes, including areas previously impervious to the vectors and VBDs. Our findings alert the VBD control program and suggest regular monitoring, strengthening the existing surveillance system and evidence-based planning and implementation of vector control interventions in wider geo-ecological regions to prevent the disease transmission. Authors SummaryThe Government of Nepal is committed to eliminate and control major vector-borne diseases: malaria, visceral leishmaniasis, lymphatic filariasis, Japanese encephalitis and dengue as a public health problem by 2030. These diseases, once endemic to lowlands with tropical and subtropical climates only, have been spread to a wide geography, including hills and mountains. These high-altitude areas were considered unsuitable for the existence of vectors and transmission of pathogens. Considering the impact of climate change on founding a favorable environment for the establishment of viable populations of vectors for pathogens transmission and thus threatening all the efforts of VBDs control and elimination, we conducted a cross-sectional survey to explore the diversity of vectors in varied geo-ecological regions. We collected vectors from five districts situated at different altitudes and having fairly diverse geography. Major vectors of responsible of transmission of pathogens causing VL and LF were abundantly present in all geo-ecological regions, while vectors of malarial parasites and dengue virus were sparsely present in fewer areas. This study also examined the feasibility of the integrated vector survey in favour of maximising the available resources for entomological investigations. Further, this study provides updated information on the diversity of the vectors in the areas having cases of VBDs and suggests authorities for regular monitoring, strengthening the existing surveillance system and evidence-based planning and implementation of vector control interventions to prevent the disease transmission in wider geo-ecological regions.

zoology↗

bioRxiv2024

In Silico designed cell-penetrating anti-cancer peptide specifically inhibits VEGF-A expression

Vascular Endothelial Growth Factor-A (VEGF-A), a pluripotent cytokine and angiogenic growth factor mediates the switch to an angiogenic phenotype in cancer cells. The interaction of VEGF-A protein with the VEGF receptors (VEGFR-1and VEGFR-2) starts downstream effect that promotes angiogenesis by mediating migration and increasing the permeability of endothelial cells. A cis-regulatory elements consisting of a polypurine/polypyrimidine (pPu/pPy) tract in the proximal 36-bp region (-85 to -50), can participate in the formation of a stable higher order G-quadruplex structure (G4) which is essential for VEGF promoter activity. During cancer progression the VEGF-A G4 succumbs to cellular pressure and fails to maintain the stable structure. This shifts the balance to form duplex structure thereby increasing the rate of transcription. Earlier research has tried to develop small-molecule ligands to target and stabilize G4, however they either lack specificity or non-toxicity. Peptide on the other hand are very less studied. Here we used bioinformatics in-silico tool to develop peptides which can successfully bind and stabilize the VEGF-A G4 while reducing its gene expression. This further alters the expression fate of the VEGF-A signalling cascade and prevents angiogenesis in cancer cells. We used high resolution Nuclear magnetic resonance and molecular dynamics simulation to map the chemistry of the interaction while the qPCR and western blot allowed us to check the expression pattern of the molecules of VEGF-A signalling cascade. In this investigation, we navigate the complex interplay between peptides and quadruplex structures, unravelling valuable insights that can enhance the crafting of pharmacophores directed at the dynamic quadruplex structure. The outcomes of our study are promising, paving the way for progress in the realms of research, characterization, and optimization of peptides binding to G-quadruplexes, with potential implications for therapeutic applications.

biophysics↗

bioRxiv2022

Status of susceptibility of the visceral leishmaniasis vector, Phlebotomus argentipes (Diptera: Psychodidae: Phlebotominae), to insecticides used for vector control in Nepal

BackgroundVisceral leishmaniasis (VL) is targeted for elimination as a public health problem in Nepal by 2023. For nearly three decades, the core vector control intervention in Nepal has been indoor residual spraying (IRS) with pyrethroids. Considering the long-term use of pyrethroids and possible development of resistance of the vector Phlebotomus argentipes sand flies, we monitored susceptibility status of their field populations to the insecticides of different classes, in villages with and without IRS activities in recent years. Methodology/Principal findingsSand flies were collected from villages with and without IRS in five VL endemic districts from August 2019 to November 2020. The WHO susceptibility test procedure was adopted using filter papers impregnated at the discriminating concentrations of insecticides of the following classes: pyrethroids (alpha-cypermethrin 0.05%, deltamethrin 0.05% and lambda-cyhalothrin 0.05%), carbamates (bendiocarb 0.1%) and organophosphates (malathion 5%). Pyrethroid resistance intensity bioassays with papers impregnated with 5x of the discriminating concentrations, piperonyl butoxide (PBO) synergist-pyrethroid bioassays and DDT cross resistance bioassays were also performed. In the IRS villages, the vector sand flies were resistant (mortality rate <90%) to alpha-cypermethrin and possibly resistant (mortality rate 90-97%) to deltamethrin and lambda-cyhalothrin, while susceptibility to these insecticides was variable in the non-IRS villages. The vector was fully susceptible to bendiocarb and malathion in all villages. A delayed knockdown time (KDT50) with pyrethroids was observed in all villages. The pyrethroid resistance intensity was low, and the susceptibility improved at 5x of the discriminating concentrations. Enhanced pyrethroid susceptibility after pre-exposure to PBO and the DDT-pyrethroid cross-resistance were evident. Conclusions/SignificanceOur investigation showed that P. argentipes sand flies have emerged with pyrethroid resistance, suggesting the need to switch to alternative classes of insecticides such as organophosphates for IRS. We strongly recommend for the regular and systematic monitoring of insecticide resistance in sand flies to optimize the efficiency of vector control interventions to sustain VL elimination efforts in Nepal. Author summaryVisceral leishmaniasis (VL), transmitted by P. argentipes sand flies, is endemic in South-East Asian countries such as Bangladesh, India and Nepal, and is on the verge of elimination as a public health problem in Nepal by 2023. As part of the WHO Global Vector Control Response, entomological surveillance including insecticide resistance monitoring is one of the four main pillars of this strategy. In the early 1990s, the historical use of DDT for sand fly vector control was replaced with deltamethrin or alpha-cypermethrin, which have now been in use for almost three decades in Nepal. Suspecting that this long-term use of pyrethroids might have selected resistance in sand fly populations which would jeopardize control efforts, we conducted the first comprehensive survey to generate contemporary evidence of insecticide resistance in Nepal. For this, we performed WHO susceptibility tests in five VL endemic districts and found strong evidence of pyrethroid resistance in vector populations from the areas receiving IRS. Resistance mechanisms involved would probably be kdr mutations and monooxygenase. This study also endorses regular insecticide resistance monitoring to inform evidence-based decisions on insecticide use for vector control and to maintain the effectiveness of vector control measures as a core intervention in the fight against VL.

zoology↗