Molecular epidemiology of dengue fever outbreaks in Bhutan, 2016-2017

Zangmo, Sangay; Darnal, Jit Bdr.; Tsheten,; Gyeltshen, Sonam; Thapa, Binay; Rodpradit, Prinyada; Chinnawirotpisan, Piyawan; Manasatienkij, Wudtichai; Macareo, Louis; Fernandez, Stefan; Wangchuk, Sonam; Klungthong, Chonticha

doi:10.1371/journal.pntd.0008165

Cited by 8 publications

(5 citation statements)

References 25 publications

(38 reference statements)

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“…Only four DENV1 envelope sequences from Bangladesh were deposited in the NCBI database before 2012, and these were also genotype V [ 48 ]. Evidence of DENV1 genotype V circulation was also reported for Bhutan, Nepal, Brazil, and Senegal [ 49 , 50 , 51 , 52 ]. In India, however, genotype V and I were co-circulating [ 53 , 54 ].…”

Section: Discussionmentioning

confidence: 69%

Genetic Analysis of Dengue Virus in Severe and Non-Severe Cases in Dhaka, Bangladesh, in 2018–2022

Rahim

Hasan

Phadungsombat

et al. 2023

Viruses

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Dengue virus (DENV) infections have unpredictable clinical outcomes, ranging from asymptomatic or minor febrile illness to severe and fatal disease. The severity of dengue infection is at least partly related to the replacement of circulating DENV serotypes and/or genotypes. To describe clinical profiles of patients and the viral sequence diversity corresponding to non-severe and severe cases, we collected patient samples from 2018 to 2022 at Evercare Hospital Dhaka, Bangladesh. Serotyping of 495 cases and sequencing of 179 cases showed that the dominant serotype of DENV shifted from DENV2 in 2017 and 2018 to DENV3 in 2019. DENV3 persisted as the only representative serotype until 2022. Co-circulation of clades B and C of the DENV2 cosmopolitan genotype in 2017 was replaced by circulation of clade C alone in 2018 with all clones disappearing thereafter. DENV3 genotype I was first detected in 2017 and was the only genotype in circulation until 2022. We observed a high incidence of severe cases in 2019 when the DENV3 genotype I became the only virus in circulation. Phylogenetic analysis revealed clusters of severe cases in several different subclades of DENV3 genotype I. Thus, these serotype and genotype changes in DENV may explain the large dengue outbreaks and increased severity of the disease in 2019.

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Section: Discussionmentioning

confidence: 69%

Genetic Analysis of Dengue Virus in Severe and Non-Severe Cases in Dhaka, Bangladesh, in 2018–2022

Rahim

Hasan

Phadungsombat

et al. 2023

Viruses

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“…Moreover, In 2017, studies conducted in the country revealed that DENV-2 and 3 were dominant in the southern region, while DENV-1 and 2 were prevalent in the northern region (Agarwal et al, 2019;Ganeshkumar et al, 2018;Gupta & Ballani, 2014). Recently, the shifting of predominant serotypes also observed in Thailand (from DENV-2 and DENV-4 to DENV-3), (Hamel et al, 2019) Sri Lanka (from DENV-1 to DENV-2) (Ali et al, 2018), Myanmar (from predominant serotype 1 to co-dominant serotypes 1, 2, and 4) (Oo et al, 2017), Indonesia, Bhutan (from DENV-3 to DENV-1), and in Nepal (Kusmintarsih et al, 2018;Prajapati et al, 2020;Zangmo et al, 2020) .…”

Section: Discussionmentioning

confidence: 90%

Comparative Phylogenetic Analysis and Transcriptomic Profiling of Dengue (DENV-3 genotype I) Outbreak in 2021 in Bangladesh

Sarkar

Rahman²,

Islam

et al. 2022

Preprint

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Objectives: The lack of a dengue disease animal model and the complex immune interaction in dengue infection hinders the study of host response and immunopathogenesis. The development of next-generation sequencing (NGS) technology allowed the researchers to study the transcriptomic profiles of human in-depth. We, therefore, implicated phylodynamic and transcriptomic approaches through NGS technology to know the origin of dengue virus (DENV) and their host response in infected patients with dengue fever. Methods: To determine the whole genome sequences of the dengue virus and their transcriptomic profiles, RNA was extracted from the serum samples of 3 healthy, and 21 dengue patients. These samples were custom performed at phylogenetic, phylodynamic, differential express gene (DEG), and gene ontology (GO) using respective bioinformatics tools. Results: The whole genome sequence analysis revealed that the total number of nucleotide ranges on these serum RNA samples were in between 10647 and 10707. Phylogenetic tree analysis showed that these strains were belonged to DENV-3 genotype I. Phylodynamic analysis showed that the 2021 epidemic isolates were clade shifted and maintained as a new clade in compared to 2019 epidemic. Transcriptome analysis mapped a total of 19267 expressed genes. Of them, there were higher expression of genes in dengue-positive samples (n = 17375) with a count of 6953 unique genes in comparison to healthy controls (n = 12314) with a count of 1892 unique genes. A total of 2686 DEGs were identified in a host factor-independent manner in dengue patients with a q-value < 0.05. DESeq2 plot counts function of the top 24 genes with the smallest q-values of differential gene expression of RNA-seq data showed that 11 genes were upregulated, whereas 13 genes were downregulated. GO analysis showed a significant upregulation (p = <0.001) in a process of multicellular organismal, nervous system, sensory perception of chemical stimulus, and G protein-coupled receptor signalling pathways in the dengue patients. However, there were a significant downregulation (p = < 0.001) of intracellular component, cellular anatomical entity, and protein-containing complex in dengue patients. Most importantly, there was significant increase of a classes of immunity protein (Cytokines especially TGF-beta;1, chemokines, inflammasome, and factors for blood coagulations) in dengue patients in compared to the healthy controls, with increased GO of immune system process. In addition, upregulation of toll receptor (TLR) signalling pathways were also initiated in the patients infected with dengue virus. These TLR pathways were particularly involved for the activation of innate in couple with adaptive immune system that probably involved the rapid elimination of dengue virus infected cells. These differentially expressed genes could be further investigated for target based prophylactic interventions for dengue. Conclusion: This is a first report to document the complete genomic features of dengue, and differentially expressed genes in patients with dengue virus in Bangladesh. These genes may have diagnostic and therapeutic values for dengue infection. Continual genomic surveillance is required to further investigate the shift in dominant genotypes in relation to viral pathogenesis.

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“…DENV-2 was the predominant serotype in 2004, while DENV-2 and 3 predominated in 2005 and 2006 [ 16 ]. A serotype shift with predominant DENV-1 was reported in 2013–2014, and DENV-1 and 2 in 2016–2017 [ 15 , 39 ]. After an absence of more than a decade, DENV-3 re-emerged and predominated in the current outbreak.…”

Section: Discussionmentioning

confidence: 99%

“…Further, DENV-3 is often associated with intense force of transmission [ 43 ]. Previous outbreaks in Bhutan have been linked to the importation of dengue virus from neighboring countries in the South-East Asia region [ 16 , 39 ]. As the surveillance system did not capture information on the travel history of the dengue patients, the source that triggered this large epidemic could not be established.…”

Section: Discussionmentioning

confidence: 99%

Epidemiological Analysis of the 2019 Dengue Epidemic in Bhutan

Tsheten

McLure

Clements

et al. 2021

IJERPH

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Bhutan experienced its largest and first nation-wide dengue epidemic in 2019. The cases in 2019 were greater than the total number of cases in all the previous years. This study aimed to characterize the spatiotemporal patterns and effective reproduction number of this explosive epidemic. Weekly notified dengue cases were extracted from the National Early Warning, Alert, Response and Surveillance (NEWARS) database to describe the spatial and temporal patterns of the epidemic. The time-varying, temperature-adjusted cohort effective reproduction number was estimated over the course of the epidemic. The dengue epidemic occurred between 29 April and 8 December 2019 over 32 weeks, and included 5935 cases. During the epidemic, dengue expanded from six to 44 subdistricts. The effective reproduction number was <3 for most of the epidemic period, except for a ≈1 month period of explosive growth, coinciding with the monsoon season and school vacations, when the effective reproduction number peaked >30 and after which the effective reproduction number declined steadily. Interventions were only initiated 6 weeks after the end of the period of explosive growth. This finding highlights the need to reinforce the national preparedness plan for outbreak response, and to enable the early detection of cases and timely response.

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Molecular epidemiology of dengue fever outbreaks in Bhutan, 2016-2017

Cited by 8 publications

References 25 publications

Genetic Analysis of Dengue Virus in Severe and Non-Severe Cases in Dhaka, Bangladesh, in 2018–2022

Genetic Analysis of Dengue Virus in Severe and Non-Severe Cases in Dhaka, Bangladesh, in 2018–2022

Comparative Phylogenetic Analysis and Transcriptomic Profiling of Dengue (DENV-3 genotype I) Outbreak in 2021 in Bangladesh

Epidemiological Analysis of the 2019 Dengue Epidemic in Bhutan

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