Publications by authors named "Krishna Das Manandhar"

Article Synopsis
  • Dengue virus (DENV), a major mosquito-borne threat, is prevalent in Nepal with limited knowledge on its evolution or immunity levels in the population.
  • A study of 49 patients during the 2017 dengue season revealed 43% tested positive for DENV NS1 antigen, indicating DENV2 as the dominant strain, with significant presence of neutralizing antibodies across various serotypes.
  • The findings highlight the need for enhanced local monitoring of DENV genotypes and immunity to better control future outbreaks in Nepal.
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Background: The 4 serotypes of dengue virus (DENV1-4) can each cause potentially deadly dengue disease, and are spreading globally from tropical and subtropical areas to more temperate ones. Nepal provides a microcosm of this global phenomenon, having met each of these grim benchmarks. To better understand DENV transmission dynamics and spread into new areas, we chose to study dengue in Nepal and, in so doing, to build the onsite infrastructure needed to manage future, larger studies.

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Article Synopsis
  • A patient with fever was referred to a hospital in Kathmandu, Nepal, for infectious disease treatment.
  • Metagenomic sequencing of the patient's serum revealed a nearly complete genome of HIV-1.
  • This genome was different from previous HIV-1 genomes found in Nepal and showed a 92.48% nucleotide identity with an HIV-1 subtype C isolate from India.
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Circulating plasma miRNAs have emerged as potential early predictors of glucometabolic disorders. However, their biomarker potential remains unvalidated in populations with diverse genetic backgrounds, races, and ethnicities. This study aims to validate the biomarker potential of plasma miR-9, miR-29a, miR-192, and miR-375 for early detection of prediabetes and type 2 diabetes mellitus (T2DM) in Nepali populations that represent distinct genetic backgrounds, races, and ethnicities.

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Unlabelled: Acute encephalitis syndrome (AES) causes significant morbidity and mortality worldwide. In Nepal, Japanese encephalitis virus (JEV) accounts for ~5-20% of AES cases, but ~75% of AES cases are of unknown etiology. We identified a gemykibivirus in CSF collected in 2020 from an 8-year-old male patient with AES using metagenomic next-generation sequencing.

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Background: The 4 serotypes of dengue virus (DENV1-4) can each cause potentially deadly dengue disease, and are spreading globally from tropical and subtropical areas to more temperate ones. Nepal provides a microcosm of this global phenomenon, having met each of these grim benchmarks. To better understand DENV transmission dynamics and spread into new areas, we chose to study dengue in Nepal and, in so doing, to build the onsite infrastructure needed to manage future, larger studies.

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Article Synopsis
  • - Dengue virus (DENV), a mosquito-borne virus affecting nearly half of the global population, has been present in Nepal since 2006, with little understanding of its evolution or the local immunity levels.
  • - A study of 49 patients during the 2017 dengue season revealed that 43% tested positive for DENV, with DENV2 identified as the dominant serotype, while also showing significant presence of neutralizing antibodies in the population.
  • - Findings indicate that a substantial portion of the population had prior exposure to multiple DENV serotypes, highlighting the necessity for improved local monitoring of DENV and community immunity to better control future outbreaks in Nepal.
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Acute Encephalitis Syndrome (AES) causes significant morbidity and mortality worldwide. In Nepal, Japanese encephalitis virus (JEV) accounts for ~ 5-20% of AES cases, but ~75% of AES cases are of unknown etiology. We identified a gemykibivirus in CSF collected in 2020 from a male child with AES using metagenomic next-generation sequencing.

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 ATP-binding cassette transporter A1 (ABCA1) encoded by ABCA1 gene is one of the important protein involved in lipid metabolism. The effect of statin therapy on dyslipidemia varies among individuals and it may be due to different genetic polymorphism. The R219K polymorphism of ABCA1 gene is found to have a significant role in the response of statin.

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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.

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Article Synopsis
  • Nepal experiences cyclic outbreaks of dengue every three years, with significant growth in cases since 2019 and the virus spreading to previously unaffected temperate regions.
  • This research analyzed 61 suspected dengue cases from 2017-2018, revealing co-circulation of three serotypes in 2017 and only DENV-2 in 2018, while using phylogenetic methods to identify genotypes.
  • Findings suggest genetic drift influenced by climate change, indicating dengue's expansion into new populations and emphasizing the importance of specific clinical markers for diagnosis.
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Objectives: Scrub typhus is an emerging infectious disease in Asia caused by Orientia tsutsugamushi (Ot). From Nepal, only scant data on the genetic epidemiology of this agent is available, and determinants of immunoregulation are poorly understood.

Methods: Patients (n = 238) referred to the National Public Health Laboratory (Kathmandu, Nepal) from all over Nepal for suspected scrub typhus were enrolled upon positive immunoglobulin (Ig)M testing between July and October 2015.

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The Tibetan plateau and high mountain ranges of Nepal are one of the challenging geographical regions inhabited by modern humans. While much of the ethnographic and population-based genetic studies were carried out to investigate the Tibetan and Sherpa highlanders, little is known about the demographic processes that enabled the colonization of the hilly areas of Nepal. Thus, the present study aimed to investigate the past demographic events that shaped the extant Nepalese genetic diversity using mitochondrial DNA (mtDNA) variations from ethnic Nepalese groups.

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Chitosan-functionalized pyridine-based thiosemicarbazones and their copper(II) complexes have been found to own a substantial antiproliferative activity against the tumorigenic Madin Darby canine kidney (MDCK) and MCF-7 cancer cell lines. In the current study, chitosan oligosaccharide (CS) (87% DDA, M < 3000 Da) and crab shell chitosan (CCS) (67% DDA, 350 kDa) were functionalized as chitosan pyridine-2-thiosemicarbazones and chitosan 2-acetyl pyridine-2-thiosemicarbazones, and their copper(II) complexes were synthesized. The formation of chitosan thiosemicarbazones and their NNS tridentate behavior to give the square planar copper(II) chitosan thiosemicarbazone complexes were established by spectroscopic studies, powder X-ray diffraction, elemental analysis, and magnetic moment measurements.

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Background: Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen frequently causing healthcare-associated infections. The apocalyptic rise of antimicrobial resistance has rekindled interest in age-old phage therapy that uses phages (viruses that infect bacteria) to kill the targeted pathogenic bacteria. Because of its specificity, phages are often considered as potential personalized therapeutic candidate for treating bacterial infections.

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Article Synopsis
  • The Asiatic wild water buffalo, an endangered species in Nepal's Koshi Tappu Wildlife Reserve, was translocated to Chitwan National Park, where it faces gastrointestinal (GI) parasite threats that impact animal health.
  • A coprological survey in 2020 revealed nine types of GI parasites in wild water buffalo dung, with Entamoeba spp. being the most prevalent, confirmed through DNA analysis as Entamoeba bovis.
  • This study marks the first molecular detection of E. bovis in wild water buffaloes in Nepal, indicating a need for further research on parasite prevalence in natural habitats.
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Article Synopsis
  • Dengue virus (DENV) is a major neglected tropical disease affecting up to half of the global population, and vaccination could potentially cause severe outcomes in those with no prior exposure.
  • * Recent studies show that Nepal has a relatively naive population regarding DENV, with the first infection documented in 2004 and an increasing prevalence.
  • * Research involving 112 Nepali patients revealed evidence of DENV infections predominantly of serotypes 1-3, suggesting cross-border introduction from India, prompting a need for further investigation into the DENV situation in Nepal.
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Aim: To analyze the serology and molecular markers of the hepatitis B-infected patients from the tertiary care hospital at Kathmandu in Nepal.

Methods: A total of 399 blood samples of patients from Sukraraj Tropical and Infectious Disease Hospital, Teku, Kathmandu, were collected. Samples were tested for HBsAg, HBeAg, and IgM anti-HBc using ELISA method.

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The diagnosis of cutaneous leishmaniasis is mostly confirmed by the identification of parasite in a skin smear or biopsy. However, this method may not always be sensitive enough to detect the disease when parasitic load is low. Molecular test such as polymerase chain reactions can be useful in such circumstances.

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Dengue virus (DENV) infection is endemic in Nepal. Although infection rates are reported annually, little information is available about the circulating viral serotypes and genotypes. Here, we report the results of a multicentre cross-sectional study of DENV serotypes and genotypes sampled from individuals with suspected DENV infection in Nepal in 2017.

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Objective: CD4 T lymphocytes are the most widely used cellular markers to assess the course of HIV infection, clinical staging and, monitoring the effect of antiretroviral therapy. The regional reference range for Eastern, Central and Western development region of Nepal had already been established whereas the same was still lacking in Mid-western and Far-western development region. The objective of this study was to establish reference range of CD4 T lymphocyte in the remaining two development regions and finally the national reference range using data from previous study.

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Background: Influenza is a highly contagious viral respiratory infection caused by influenza viruses whose epidemic and pandemic have resulted in significant morbidity and mortality. The annual epidemic of influenza results in an estimated 3-5 million cases of severe illness and about 290000-650000 deaths globally. The vaccination program has been successful to control the epidemic however, it further needs improvement.

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Article Synopsis
  • * His diagnosis was confirmed through histological microscopy, nested PCR, and a positive blood test, revealing the presence of Leishmania donovani complex.
  • * The patient responded well to treatment, and the lesions healed over six months, marking the first recorded case of cutaneous leishmaniasis in a non-endemic, high-altitude area in Nepal, potentially linked to rising temperatures affecting disease vector habitats.
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Background: The UniCel® DxH-800 is an automated cell counter widely used in laboratories. However, the effects of increased nucleated red blood cells (NRBCs) on the lymphocyte counts obtained using the UniCel DxH-800 have not been fully elucidated.

Objective: The study's objective was to compare lymphocyte counts obtained using the DxH-800 and those obtained using flow cytometry in various ranges of NRBCs.

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Article Synopsis
  • - Visceral Leishmaniasis (VL), caused by the Leishmania donovani parasite transmitted by sandflies, is becoming a concern as it spreads to previously unaffected high-altitude regions in Nepal, threatening elimination efforts.
  • - An exploratory study showed a significant decrease in VL cases in program districts, while cases have increased in non-program districts over the past decade, highlighting a concerning trend.
  • - Molecular testing confirmed the presence of L. donovani in some patients from non-program districts, indicating that VL may be emerging as a new threat in these areas, emphasizing the need for attention and resources.
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