Phylogenetic Analysis of the Dengue Virus Strains Causing the 2019 Dengue Fever Outbreak in Hainan, China

Abstract

Dengue virus is an arthropod-borne pathogen that is transmitted to humans primarily by Aedes spp. mosquitos, causing the acute infectious disease, dengue fever (DF). Until 2019, no dengue outbreak had been reported in Hainan Province for over 20 years. However, in early September of 2019, an increasing number of infected cases appeared and the DF outbreak lasted for over one month in Haikou City, Hainan Province. In our study, we collected 97 plasma samples from DF patients at three hospitals, as well as 1585 mosquito larvae samples from puddles in different areas of Haikou. There were 49 (50.5%) plasma samples found to be strongly positive and 9 (9.3%) plasma samples were weakly positive against the NS1 antigen. We discovered DENV both in the patient's plasma samples and mosquito larvae samples, and isolated the virus from C6/36 cells inoculated with the acute phase serum of patients. Phylogenetic analysis revealed that the new strains were the most closely related to the epidemic strain in the southern regions of China, belonging to lineage IV, genotype I, DENV-1. Compared to the seven closest strains from neighboring countries and provinces, a total of 18 amino acid mutations occurred in the coding sequences (CDS) of the new isolated strain, DENV1 HMU-HKU-2. Our data shows that dengue virus is re-emerged in Hainan, and pose new threats for public health. Thus regular molecular epidemiological surveillance is necessary for control and prevention of DENV transmission.

Association of virome dynamics with mosquito species and environmental factors

“…albopictus are important vectors of dengue fever [ 40 ]. We did not detect the dengue virus in the two mosquito species, although 264 dengue fever cases were reported, and the outbreak lasted for over one month in 2019 in Hainan Island [ 19 ]. A similar result was reported previously, in which pathogenic arboviruses were not detected in field-caught mosquitoes using large-scale virome sequencing [ 9 ].…”

“…Tropical islands are hotspots for the emergence of mosquito-borne viruses due to sylvatic spillover events resulting from increases in commerce, travel, and urbanization [ 18 ]. In fact, mosquito-borne infectious diseases, such as malaria, dengue fever, and filariasis, were historically prevalent in Hainan Island [ 17 , 19 ]. Therefore, virome characterization and surveillance of mosquitoes in Hainan Island could provide important cues for the prevention of pathogen transmission and early warning programs for preexisting arboviruses.…”

A Serotype-Specific and Multiplex PCR Method for Whole-Genome Sequencing of Dengue Virus Directly from Clinical Samples

“…DENVs are known for their genetic diversity within serotype groups and geographical regions ( 1 , 16 ). Currently, consolidation and urban circulation of DENV are rare in mainland China ( 17 , 39 – 43 ). Due to the abundance of rainfall in summer and the wide distribution of Aedes albopictus , DENV outbreaks in mainland China are usually caused by imported strains.…”

The epidemiology and evolutionary dynamics of massive dengue outbreak in China, 2019

“…Additionally, the number of provinces affected by the disease significantly increased ( Yue et al, 2022 ). The southern province of Hainan reported its first dengue outbreak after disappearing for over 20 years ( Du et al, 2021 ). Dengue viruses are diverse, but there is no systematic study analyzing the genetic diversity of the viruses from outbreak provinces.…”