Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Rahim R

PROVIDER: S-EPMC10222234 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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

Rahim Rummana R Hasan Abu A Phadungsombat Juthamas J Hasan Nazmul N Ara Nikhat N Biswas Suma Mita SM Nakayama Emi E EE Rahman Mizanur M Shioda Tatsuo T

Viruses 20230510 5

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 49 ...[more]

PMID: 37243230

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Project description:Acute arboviral infections like dengue have a significant negative socioeconomic and health impact on many tropical and subtropical areas of the world. About 3.9 billion Individuals are at risk of contracting the dengue virus and Asia bears the brunt of that load. Bangladesh, like other south-east Asian countries faced a massive outbreak of dengue in 2019. This cross sectional study was done in three tertiary care centers in Dhaka, Bangladesh during this worst outbreak of dengue. The study was conducted from 1st July to 31st December, 2019 with an aim to describe the clinical and laboratory variations among severe dengue cases and to conduct a serotype survey. This might help to understand the future changes in the clinical or serological profile of the circulating dengue virus. The study enrolled 1978 participants who were grouped into group B (Patients with warning signs or risk factors who should be admitted for close observation as they approach critical phase) and C (Patients having severe plasma leakage leading to dengue shock and/or fluid accumulation with respiratory distress, severe organ impairment and severe metabolic abnormalities) according to national guidelines. Furthermore, 81 samples were serotyped using Qiagen One step RT-PCR kit (Cat. No: 210212). In addition sequencing (ABI sequencing platform) of partial C-prM gene of five DENV-3 isolates were done and analyzed (BLAST tool of NCBI) for phylogenetics (MEGA6 software package). Among the 1978 enrolled participants group B and C patients were 1580 (80%) and 398 (20%) respectively. The median (IQR) age of the patients were 26(11 to 41). Maximum proportion of the enrolled were male (72.3%) (p = 0.0002). Most common co- morbidities were hypertension (90; 4.5%) and DM (70; 3.5%). Group C patients more commonly presented with vomiting (p 0.133), diarrhea (p<0.0001) and abdominal pain (p 0.0203). The common mode of bleeding was melaena (12%). Thirteen (0.7%) patients succumbed to death, 12 of them belonged to group B who mostly presented with GI manifestations (99.9%) and melaena (12%). Only 5.6% of the cases were secondarily infected. In group C cases low hemoglobin and hematocrit was observed with high AST (p 0.004, 0.006 and 0.0016 respectively). Fluid requirement was also more in the same group (p<0.0001). Group B patients had a higher platelet requirement (p = 0.0070). Twelve patients (0.7%) required ICU. The management profile of these cases are showcased here which highlights minimal use of antibiotics and no application of steroids, which abides by the current national protocol. Furthermore, 81 samples from enrolled participants were serotyped and majority (79%) yielded DENV-3, followed by DENV 2 & 3 co-infection (13.6%) and DENV-2 alone (7.4%). Following phylogenetic analysis DENV-3 and DENV2 were deemed to be of genotype I and cosmopolitan variety respectively. This study presents the first instance of heterogeneous co-infection with several serotypes since 2000 in Bangladesh. It also gives an overview of serotype prevalence, management evaluation and clinical results that promises to navigate future control planning.

Project description:BackgroundDengue virus (DENV) activity has been reported in Dhaka, Bangladesh since the early 1960s with the greatest burden of dengue fever and dengue hemorrhagic fever cases observed in 2000. Since this time, the intensity of dengue activity has varied from year to year, and its determining factors remained relatively unknown. In light of such gaps in knowledge, the main objectives of this study were to determine the magnitude of seroprevalence and seroconversion among the surveyed population, and establish the individual/household level risk factors for the presence of DENV antibodies among all age groups of target populations in the city of Dhaka.Methodology/principal findingsConsidering the lack of fine scale investigations on the factors driving dengue activity in Bangladesh, a prospective cohort study involving serological surveys was undertaken with participant interviews and blood donation across the city of Dhaka in 2012. Study participants were recruited from 12 of 90 wards and blood samples were collected during both the pre-monsoon (n = 1125) and post-monsoon (n = 600) seasons of 2012. The findings revealed that the seroprevalence in all pre-monsoon samples was 80.0% (900/1125) while the seropositivity in the pre-monsoon samples that had paired post-monsoon samples was 83.3% (503/600). Of the 97 paired samples that were negative at the pre-monsoon time point, 56 were positive at the post-monsoon time point. This resulted in a seroprevalence of 93.2% (559/600) among individuals tested during the post-monsoon period. Seroprevalence trended higher with age with children exhibiting a lower seropositivity as compared to adults. Results from this study also indicated that DENV strains were the only flaviviruses circulating in Dhaka in 2012. A multivariate analysis revealed that age, possession of indoor potted plants, and types of mosquito control measures were significant factors associated with DENV seroprevalence; while attendance in public/mass gatherings, and use of mosquito control measures were significantly associated with DENV seroconversion after adjusting for all other variables.Conclusions/significanceOur study suggests that there is a high level of endemic dengue virus circulation in the city of Dhaka which has resulted in significant DENV seroprevalence among its residents. Seropositivity increased with age, however, a substantial proportion of children are at risk for DENV infections. Our serological analysis also documents considerable DENV seroconversion among study participants which indicates that a large proportion of the population in the city of Dhaka were newly exposed to DENV during the study period (pre-and post-monsoon 2012). High levels of seroconversion suggest that there was an intense circulation of DENV in 2012 and this may have resulted in a significant risk for viral associated illness. Findings of our study further indicated that home-based interventions, such as removing indoor potted plants and increased bed net use, in addition to vector control measures in public parks, would reduce exposure to DENV and further decrease risk of viral associated disease.

Project description:BackgroundDengue virus (DENV) infection is one of the biggest challenges for human health in the world. In addition, a secondary DENV infection sometimes causes dengue hemorrhagic fever (DHF), which frequently leads to death. For this reason, accurate diagnosis record management is useful for prediction of DHF. Therefore, the demand for DENV rapid diagnosis tests (RDTs) is increasing because these tests are easy and rapid to use. However, commercially available RDTs often show low sensitivity for DENV and cross-reactivity against other flaviviruses, especially Zika virus (ZIKV).MethodsWe developed two types of novel DENV non-structural protein 1 (NS1) detection RDTs, designated TKK-1st and TKK-2nd kits. Specificities of the monoclonal antibodies (MAbs) used in these kits were confirmed by enzyme-linked immuno-sorbent assay (ELISA), dot blot, and western blot using recombinant NS1 proteins and synthetic peptides. For evaluation of sensitivity, specificity, and cross-reactivity of the novel DENV NS1 RDTs, we first used cultured DENV and other flaviviruses, ZIKV and Japanese encephalitis virus (JEV). We then used clinical specimens obtained in Bangladesh in 2017 for further evaluation of kit sensitivity and specificity in comparison with commercially available RDTs. In addition, RNA extracted from sera were used for viral genome sequencing and genotyping.ResultsEpitopes of three out of four MAbs used in the two novel RDTs were located in amino acid positions 100 to 122 in the NS1 protein, a region that shows low levels of homology with other flaviviruses. Our new kits showed high levels of sensitivity against various serotypes and genotypes of DENV and exhibited high levels of specificity without cross-reactivity against ZIKV and JEV. In clinical specimens, our RDTs showed sensitivities of 96.0% (145/151, TKK-1st kit) and 96.7% (146/151, TKK-2nd kit), and specificities of 98.0% (98/100, TKK-1st kit and TKK-2nd kit). On the other hand, in the case of the commercially available SD Bioline RDT, sensitivity was 83.4% (126/151) and specificity was 99.0% (99/100) against the same clinical specimens.ConclusionsOur novel DENV NS1-targeting RDTs demonstrated high levels of sensitivity and lacked cross-reactivity against ZIKV and JEV compared with commercially available RDTs.

Project description:Dengue, the most important mosquito-borne viral disease of humans is a recurring global health problem. In Bangladesh, dengue outbreaks are on the increase despite the efforts of government and it is not clear what the understanding of the general Dhaka population towards dengue fever is. Knowledge, attitude and practice (KAP) studies are essential guides in public health interventions. Hence, using KAP, this study aims to assess patient-perspectives with regards to factors associated with dengue, as well as investigate the associated factors between the two corporations in Dhaka. A Hospital-based cross-sectional study of 242 fever patients from two city-corporations in Dhaka (Dhaka North City Corporations, DNCC (n = 91, 37.6%) and Dhaka South City Corporation, DSCC (n = 151, 62.4%) was conducted using pre-tested KAP items. Wilcoxon's Rank Sum was used to determine the KAP by DNCC, DSCC and both corporations and multivariate Poisson regression analyses. The two corporations were analysed separately due to the differences in income distribution, concentration of slums, hospitals and clinics. The study found that more than half of the study population were knowledgeable about dengue (mean percentage scores was 52%), possess an appropriate and acceptable attitude towards the disease (69.2%), and about two thirds of the respondents (71.4%) engaged in practices towards its prevention. After adjusting for the potential cofounders, the factors associated with KAP about dengue fever varied between DNCC and DSCC; with duration of residency and use of mosquito nets were associated with knowledge in the north while income class and age were associated with knowledge and attitude in the south. In the pooled analysis (combining both corporations), knowledge of dengue was associated with good practice towards dengue fever among the respondents. The duration of residence in Dhaka (10+ years), not using mosquito nets and length of time spent in the hospital (7+ days) due to dengue, and decreased knowledge (Adjusted coefficient (β) = -0.01, 95%CI: -0.02, -0.01) were associated with attitude towards dengue in DNCC. On the other hand, middle-high income class, age (40+ years) and increased knowledge were associated with practice towards dengue in DSCC (β = 0.02, 95%CI: 0.01, 0.03). Efforts to increase knowledge about dengue fever through education by the administrations of both corporations would benefit from targeting these high-risk groups for a more sustainable outcome.

Dataset Information

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

Publications

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

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