Detection of genotype-1 of dengue virus serotype 3 for the first time and complete genome analysis of dengue viruses during the 2018 epidemic in Mandalay, Upper Myanmar.

Mya Myat Ngwe Tun,Hlaing Myat Thu,Takeshi Nabeshima,Kouichi Morita,Su Su Myaing,Kyaw Ko Ko Htet,Thein Thein Htwe,Aung Min Soe,Thidar Aung,Tu Tu Mar,Ei Phyu Lwin,Aung Kyaw Kyaw,Khine Mya Nwe,Thet Htoo Aung,Kyaw Zin Thant

doi:10.1371/journal.pone.0251314

Abstract

BackgroundDengue (DEN) is a neglected tropical disease, and surveillance of dengue virus (DENV) serotypes and genotypes is critical for the early detection of outbreaks. Risk factors for outbreaks include the emergence of new genotypes and serotype shifting.Methodology and principal findingsTo understand the genomic and viral characteristics of DENV-infected patients, we conducted a cross-sectional descriptive study among pediatric patients admitted at the 550-bedded Mandalay Children Hospital during the 2018 DEN endemic season. We conducted virus isolation, serological tests, viremia level measurement, and whole-genome sequencing. Among the 202 serum samples, we detected 85 samples with DENV (46 DENV-1, 10 DENV-3, 26 DENV-4 and three multiple serotype co-infections) via reverse transcription quantitative/real-time PCR (RT-qPCR), and we obtained 49 DENV isolates (31 DENV-1, 10 DENV-3 and 8 DEN-4). We did not detect DENV-2 in this study. The viral genome levels in serum did not differ significantly among virus serotypes, infection status (primary versus secondary) and disease severity. Based on the phylogenetic analysis, we identified DENV-1 genotype-1, DENV-4 genotype-1 and DENV-3 genotype-3 and genotype-1 which was detected for the first time. Next-generation sequencing analysis revealed greater frequencies of nonsynonymous and synonymous mutations per gene in the nonstructural genes. Moreover, mutation rates were also higher among DENV-1.Conclusion/SignificanceIn conclusion, there was an increasing trend of DENV-3 cases during DENV endemic season in 2018 with the first detection of the genotype 1. However, DENV-1 has remained the predominant serotype in this study area since 2013, and we identified stop codon mutations in the DENV-1 genome. This report is the first to feature a complete genome analysis of the strains of DENV-3 and DENV-4 circulating among pediatric patients in Myanmar. This study highlighted the importance of annual surveillance for a better understanding of the molecular epidemiology of DENVs.

Highlights

Dengue (DEN) is a neglected tropical disease that still constitutes a major public health problem in low-resource countries
Based on the phylogenetic analysis, we identified dengue virus (DENV)-1 genotype-1, DENV-4 genotype-1 and DENV-3 genotype-3 and genotype-1 which was detected for the first time
Of 202 patients with serum samples screened by CareUs DENV Combo test kits, 109/202 (53.9%) children were positive for NS-1 Ag, 90/202 (44.6%) cases for AntiDENV IgM and 103/202 (50.9%) for anti-DENV IgG

Summary

Introduction

Dengue (DEN) is a neglected tropical disease that still constitutes a major public health problem in low-resource countries. DENV infection is endemic in more than 128 countries, including Myanmar. The incidence of DEN cases is increasing, and the virus has spread to new areas worldwide. According to estimates from one mathematical model of DENV infection, about 390 million people (95% confidence interval; 284–528 million) contract DEN [2]. During the past two decades the number of reported cases has increased eightfold worldwide. According to the WHO report, the total number of DEN cases increased from 505,430 cases in 2000 to 4.2 million in 2019. Dengue (DEN) is a neglected tropical disease, and surveillance of dengue virus (DENV) serotypes and genotypes is critical for the early detection of outbreaks. Risk factors for outbreaks include the emergence of new genotypes and serotype shifting

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Discussion

Conclusion