Abstract

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. Of the 50 patients sampled, 40 were serologically positive for DENV NS1, 29 for anti-DENV IgM, 21 for anti-DENV IgG and 14 were positive by qRT-PCR. The three serotypes DENV-1, 2 and 3 were detected and there was no DENV-4. Positive samples from serotyping were subjected to PCR amplification by envelope (E) gene specific primer and subsequent bidirectional sequencing of 5 samples. A time to most recent common ancestor phylogenetic tree was constructed from the new sequences obtained here together with historical DENV-1 and DENV-2 E gene sequences. The DENV-1 isolates (n = 2) from Nepalese individuals were closely related to Indian genotype V, whereas DENV-2 isolates (n = 3) belonged to Cosmopolitan genotype IVa, which is closely related to Indonesian isolates. Historical DENV isolates obtained between 2004 and 2013 clustered with Cosmopolitan IVb, Cosmopolitan IVa, and Asian II genotypes. All Nepalese isolates had different lineages with distinct ancestries. With the exception of isolates obtained in 2004, all other previously published isolates had ancestry to geographically distant part of the world. Molecular analysis revealed dengue epidemics to be comprised of different genotypes of serotype 1 and 2 raising concerns on potential role of different genotypes causing Dengue hemorrhagic fever. Also, our result indicated spread of DENV-2 in non-endemic area such as hilly region of Nepal which was considered to be free of dengue due to high altitude and cold weather.

Highlights

  • Dengue virus (DENV) is transmitted by Aedes spp. mosquitoes and causes an estimated 390 million infections annually [1]

  • This hospital-based study enrolled 50 patients with suspected DENV infection seen at six hospitals in Nepal: Sukraraj Tropical and Infectious Disease Hospital (STIDH) (n = 27); Chitwan Medical College and Teaching Hospital (CMC) (n = 14); UCMS (n = 2); and the three hospitals from Butwal (n = 7)

  • We found that DENV-1 and DENV-3 were circulating in the lower belts of Terai, whereas DENV-2 had spread to hill districts such as Dhading

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Summary

Introduction

Dengue virus (DENV) is transmitted by Aedes spp. mosquitoes and causes an estimated 390 million infections annually [1]. DENV exists as four serotypes that are further divided into distinct genotypes with sequence divergence not greater than 6% within the chosen genome region [4]. DENV infection was first detected in Nepal in a Japanese traveler in 2004 [6]; this was reported as serotype 2 and cosmopolitan genotype IVb (referred to as genotype 1 in Takasaki et al.) [7]. The report of DENV infection in Nepal in 2006 indicated that all four serotypes were circulating [8] in nine districts of the lowland Terai region, but sequence information was unavailable at that time. Sporadic DENV outbreaks have been reported annually, with major outbreaks occurring in 3-year cycles with a shift in dominant serotype and genotype: DENV-1 genotype V in 2010 [9], DENV-2 Cosmopolitan IVa and Asian II genotypes in 2013 [10] and DENV-1 of unknown genotype in 2016 [11]

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