Dengue Virus in Sub-tropical Northern and Central Viet Nam: Population Immunity and Climate Shape Patterns of Viral Invasion and Maintenance

Abstract

Dengue virus transmission occurs in both epidemic and endemic cycles across tropical and sub-tropical regions of the world. Incidence is particularly high in much of Southeast Asia, where hyperendemic transmission plagues both urban and rural populations. However, endemicity has not been established in some areas with climates that may not support year-round viral transmission. An understanding of how dengue viruses (DENV) enter these environments and whether the viruses persist in inapparent local transmission cycles is central to understanding how dengue emerges in areas at the margins of endemic transmission. Dengue is highly endemic in tropical southern Vietnam, while increasingly large seasonal epidemics have occurred in northern Viet Nam over the last decade. We have investigated the spread of DENV-1 throughout Vietnam to determine the routes by which the virus enters northern and central regions of the country. Phylogeographic analysis of 1,765 envelope (E) gene sequences from Southeast Asia revealed frequent movement of DENV between neighboring human populations and strong local clustering of viral lineages. Long-distance migration of DENV between human population centers also occurred regularly and on short time-scales, indicating human-mediated viral invasion into northern Vietnam. Human populations in southern Vietnam were found to be the primary source of DENV circulating throughout the country, while central and northern Vietnam acted as sink populations, likely due to reduced connectedness to other populations in the case of the central regions and to the influence of temperature variability on DENV replication and vector survival and competence in the north. Finally, phylogeographic analyses suggested that viral movement follows a gravity model and indicates that population immunity and physical and economic connections between populations may play important roles in shaping patterns of DENV transmission.

Synchrony of Dengue Incidence in Ho Chi Minh City and Bangkok

“…In particular, the importance of local environment in shaping temporal and spatial patterns is not known. Human movement has been implicated in both local and regional dispersion in epidemics in a number of locations; however, population immunity and climatic factors may also have a major role [6]. Comparisons in the dengue experiences across locations can provide insights to disentangle these factors.…”

“…Previous work using case data has focused on the spread of dengue within urban or rural communities [7–9] or the dispersion of the virus across a country [6]. These studies have demonstrated micro-scale spatial dependence between cases at distances of under one kilometer in both rural Northern Thailand and Bangkok suggesting focal transmission in these settings but also waves of dengue incidence coming out of Bangkok [7, 8, 10].…”

“…Phylogenetic studies have found a rate of viral movement between Ho Chi Minh City and surrounding rural communities [11, 12]. On a broader scale, phylogenetic studies have also suggested that Thailand may act as a source of virus for the region, however, these studies suffer from limited availability of sequences and time periods where sequences are available often do not overlap between countries [6, 11]. Ho Chi Minh City and Bangkok are separated by a 90-minute flight (750 km) and are two of the largest and most important regional centers, acting as major trade and airline hubs.…”

The Epidemiological Characteristics and Dynamic Transmission of Dengue in China, 2013

“…Aware of the importance of air travel in dengue transmission, researchers developed simple models to estimate the importing risk of dengue or even the possible origin of importation in Europe [13, 14]. In Asia, because of the reintroductions of dengue viruses from Southern Vietnam where dengue is endemic, Northern Vietnam had dengue epidemics occurred frequently [15]. At finer spatial scales (regional, intra-urban, neighborhood), population movements associated with work and recreation are important for dengue transmission [6], and house-to-house human movements may shape spatial patterns of dengue incidence, causing significant heterogeneity in dengue incidence [16].…”

Whole genome sequencing and genetic variations in several dengue virus type 1 strains from unusual dengue epidemic of 2017 in Vietnam

“…In this ourbreak in Hanoi, the number of cases was 70 times higher compared to the same period in 2016, with nearly 37,651 people infected and seven deaths [25].. DENV-1 accounted for the largest proportion of detected viruses in the 2017 epidemic besides types 2, 3, and 4 [26]. Previous genetic studies in Vietnam on this virus involved only analysis of the E-gene sequence [27][28][29][30]. Thus, not much information is available on the genetic diversity of the whole DENV-1 genome over time and the genetic diversity of the DENV resulting due to synonymous and non-synonymous mutations that make the DENV adaptable under selective pressure.…”