MyMedR

Displaying all 6 publications

Abstract:

Sort:

Fulltext Surveillance of norovirus among children with diarrhea in four major hospitals in Bhutan: Replacement of GII.21 by GII.3 as a dominant genotype

Wangchuk S, Matsumoto T, Iha H, Ahmed K

PLoS One, 2017;12(9):e0184826.
PMID: 28910371 DOI: 10.1371/journal.pone.0184826

BACKGROUND: Diarrhea is a major cause of morbidity and mortality among Bhutanese children. The etiology of diarrhea is not well known due to the challenges of conducting routine surveillance with Bhutan's modest research facilities. Establishing an etiology is crucial toward generating evidence that will contribute to policy discussions on a diarrheal disease control program. Our previous study, during 2010-2012, revealed that norovirus (NoV) is an important cause of diarrhea among Bhutanese children, and that GII.21 was the major genotype circulating at that time. In other countries, GII.4 is the major genotype responsible for NoV infections. In this update report, we provide new prevalence data to describe the progression of the transformation and distribution of the NoV genotype among Bhutanese children.
METHODS: From June 2013 through May 2014, diarrheal stool samples were collected at one national referral hospital in Thimphu, two regional referral hospitals in the eastern and central regions, and one general hospital in the western region of Bhutan. NoV was detected by reverse transcription-polymerase chain reaction (RT-PCR), by amplifying the capsid gene. The RT-PCR results were confirmed by nucleotide sequencing of the amplicons.
RESULTS: The proportion of NoV-positive stool samples was 23.6% (147/623), of which 76.9% were NoV GII and the remainders were NoV GI. The median age of infected children was 15.5 months, with a fairly balanced female: male ratio. NoV GII was most prevalent in the colder months (late November-mid April) and NoV GI had the highest prevalence in the summer (mid April-late September). Nucleotide sequencing was successful in 99 samples of GII strains. The most common genotypes were GII.3 (42.6%), GII.4 Sydney 2012 (15.8%), and GII.4 unassigned (11.9%). No GII.21 was found in any child in the present study. Phylogenetic analysis showed that GII.3 strains in the present study belonged to an independent cluster in lineage B. These strains shared an ancestor with those from different countries and Bhutanese strains circulating during 2010.
CONCLUSION: NoV remains an important cause of diarrhea among Bhutanese children. Genotype GII.3 from a single ancestor strain has spread, replacing the previously circulating GII.21. Current NoV genotypes are similar to the strains circulating worldwide but are primarily related to those in neighboring countries. NoV GII is prevalent during the cold season, while GI is prevalent during the summer. To develop a NoV infection control policy, further studies are needed.
Fulltext An outbreak of gastroenteritis by emerging norovirus GII.2[P16] in a kindergarten in Kota Kinabalu, Malaysian Borneo

Ahmed K, Dony JJF, Mori D, Haw LY, Giloi N, Jeffree MS, et al.

Sci Rep, 2020 04 28;10(1):7137.
PMID: 32346119 DOI: 10.1038/s41598-020-64148-4

Outbreaks of diarrhea in kindergartens are underreported and frequently go unnoticed in developing countries. To better understand the etiology this study was performed during an outbreak of diarrhea in a kindergarten in Sabah, Malaysia. Outbreak investigation was performed according to the standard procedures. In this outbreak a total of 34 (36.5%) children and 4 (30.8%) teachers suffered from gastroenteritis. Stool samples from seven children and 13 teachers were tested for rotavirus and norovirus. During the investigation stool samples were collected and sent in cold chain to the laboratory. The samples were subjected to rotavirus enzyme linked immunosorbent assay, and reverse transcription PCR for norovirus. All samples were negative for rotavirus but positive for norovirus. To determine the genogroup and genotype of norovirus, nucleotide sequencing of the amplicons was performed. All norovirus from the outbreak was of genotype GII.2[16]. To determine the relatedness of the strains phylogenetic analysis was done using neighbor-joining method. Phylogenetically these strains were highly related to GII.2[P16] noroviruses from China and Japan. This study provided evidence that a diarrheal outbreak in a kindergarten was caused by GII.2[P16] norovirus which is an emerging strain in East Asia and Europe.
Human-porcine reassortant rotavirus generated by multiple reassortment events in a Sri Lankan child with diarrhea

Yahiro T, Takaki M, Chandrasena TGAN, Rajindrajith S, Iha H, Ahmed K

Infect Genet Evol, 2018 11;65:170-186.
PMID: 30055329 DOI: 10.1016/j.meegid.2018.07.014

A human-porcine reassortant rotavirus, strain R1207, was identified from 74 group A rotaviruses detected in 197 (37.6%) stool samples collected from patients who attended a tertiary care hospital in Ragama, Sri Lanka. This is the first report of a human-porcine reassortant rotavirus in Sri Lanka. The patient was a 12-month-old boy who had been hospitalized with fever and acute diarrhea with a duration of 6 days. The family had pigs at home before the birth of this boy. However, the neighbors still practice pig farming. The genotype constellation of R1207 was G4-P[6]-I1-R1-C1-M1-A1-N1-T1-E1-H1. This is based on the assignment of all the eleven gene segments a full genome-based genotyping system. R1207 showed a 4-2-3-2 genomic electrophoretic migration pattern, which is characteristic of group A rotaviruses. Our analyses revealed that five (NSP2, NSP4, VP1, VP2, and VP7) of the 11 genes were closely related to the respective genes of porcine strains. Although the remaining six genes (NSP1, NSP3, NSP5, VP3, VP4, and VP6) were related to human strains, with the exception of the gene sequence of NSP1, all of these human strains were human-porcine reassortants. With a genogroup 1 genetic backbone, this strain was possibly formed via multiple genetic reassortments. We do not know whether this strain is circulating in pigs, as no data are available on porcine rotaviruses in Sri Lanka. Surveillance should be strengthened to determine the epidemiology of this genotype of rotavirus in Sri Lanka and to assess whether the infection was limited or sustained by ongoing human-to-human transmission.
Increased serum vascular endothelial growth factor is associated with acute viral encephalitis in Bangladeshi children

Mori D, Khanam W, Sheikh RA, Tabib SMSB, Ikebe E, Hossain MM, et al.

Sci Rep, 2017 Nov 23;7(1):16181.
PMID: 29170534 DOI: 10.1038/s41598-017-16474-3

Encephalitis causes significant global morbidity and mortality. A large number of viruses cause encephalitis, and their geographic and temporal distributions vary. In many encephalitis cases, the virus cannot be detected, even after extensive testing. This is one challenge in management of the encephalitis patient. Since cytokines are pivotal in any form of inflammation and vary according to the nature of the inflammation, we hypothesized cytokine levels would allow us to discriminate between encephalitis caused by viruses and other aetiologies. This pilot study was conducted in a tertiary care hospital in Dhaka, Bangladesh. Viral detection was performed by polymerase chain reaction using patient cerebrospinal fluid. Acute phase reactants and cytokines were detected in patient serum. Of the 29 biomarkers assessed using the Wilcoxon rank-sum test, only vascular endothelial growth factor (VEGF) was significantly higher (P = 0.0015) in viral-positive compared with virus-negative encephalitis patients. The area under the curve (AUC) for VEGF was 0.82 (95% confidence interval: 0.66-0.98). Serum VEGF may discriminate between virus-positive and virus-negative encephalitis. Further study will be needed to confirm these findings.
Fulltext IMiD/CELMoD-induced growth suppression of adult T-cell leukemia/lymphoma cells via cereblon through downregulation of target proteins and their downstream effectors

Wang Y, Shimosaki S, Ikebe E, Iha H, Yamamoto JI, Fife N, et al.

Front Oncol, 2023;13:1272528.
PMID: 38344143 DOI: 10.3389/fonc.2023.1272528

Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell neoplasia associated with human T-cell leukemia virus type 1 (HTLV-1) infection and has an extremely poor prognosis. Lenalidomide (LEN; a second-generation immunomodulatory drug [IMiD]) has been employed as an additional therapeutic option for ATL since 2017, but its mechanism of action has not been fully proven, and recent studies reported emerging concerns about the development of second primary malignancies in patients treated with long-term IMiD therapy. Our purpose in this study was to elucidate the IMiD-mediated anti-ATL mechanisms. Thirteen ATL-related cell lines were divided into LEN-sensitive or LEN-resistant groups. CRBN knockdown (KD) led to a loss of LEN efficacy and IKZF2-KD-induced LEN efficacy in resistant cells. DNA microarray analysis demonstrated distinct transcriptional alteration after LEN treatment between LEN-sensitive and LEN-resistant ATL cell lines. Oral treatment of LEN for ATL cell-transplanted severe combined immunodeficiency (SCID) mice also indicated clear suppressive effects on tumor growth. Finally, a novel cereblon modulator (CELMoD), iberdomide (IBE), exhibited a broader and deeper spectrum of growth suppression to ATL cells with efficient IKZF2 degradation, which was not observed in other IMiD treatments. Based on these findings, our study strongly supports the novel therapeutic advantages of IBE against aggressive and relapsed ATL.
Fulltext Complete Sequences of the Human T-Cell Leukemia Virus Type 1 Proviral Genomes from Newly Established Adult T-Cell Leukemia Cell Lines in Oita Prefecture, Japan

Fukumoto T, Ikebe E, Ogata M, Kohno K, Kuramitsu M, Sato Y, et al.

Genome Announc, 2018 Jun 21;6(25).
PMID: 29930027 DOI: 10.1128/genomeA.00090-18

We report two complete proviral genome sequences of human T-cell leukemia virus type 1 (HTLV-1) isolated from the peripheral blood specimens of acute type adult T-cell leukemia (ATL) patients in Oita Prefecture, Japan.