Genetic Diversity and Dispersal of DENGUE Virus among Three Main Island Groups of the Philippines during 2015-2017

Abstract

Dengue has been one of the major public health concerns in the Philippines for more than a century. The annual dengue case burden has been increasing in recent years, exceeding 200,000 in 2015 and 2019. However, there is limited information on the molecular epidemiology of dengue in the Philippines. We, therefore, conducted a study to understand the genetic composition and dispersal of DENV in the Philippines from 2015 to 2017 under UNITEDengue. Our analyses included 377 envelope (E) gene sequences of all 4 serotypes obtained from infections in 3 main island groups (Luzon, Visayas, and Mindanao) of the Philippines. The findings showed that the overall diversity of DENV was generally low. DENV-1 was relatively more diverse than the other serotypes. Virus dispersal was evident among the three main island groups, but each island group demonstrated a distinct genotype composition. These observations suggested that the intensity of virus dispersal was not substantive enough to maintain a uniform heterogeneity among island groups so that each island group behaved as an independent epidemiological unit. The analyses suggested Luzon as one of the major sources of DENV emergence and CAR, Calabarzon, and CARAGA as important hubs of virus dispersal in the Philippines. Our findings highlight the importance of virus surveillance and molecular epidemiological analyses to gain deep insights into virus diversity, lineage dominance, and dispersal patterns that could assist in understanding the epidemiology and transmission risk of dengue in endemic regions.

Keywords: dengue virus; evolution; genetic diversity; molecular epidemiology; phylogeography.

Figure 1

Dengue cases and DENV serotypes in the Philippines from 2015 to 2017: (a) monthly distribution of cases in the Philippines (overall) and three main island groups; (b) monthly proportion of DENV serotypes in the Philippines.

Figure 2

The genotype composition of DENV serotypes in three island groups, namely Luzon, Visayas, and Mindanao. The nomenclature of clades is as per the phylogenetic analyses illustrated in Figures S1–S4. Each color represents a genetically distinguishable clade as named in the legend. Numbers in parentheses indicate the number of sequences analyzed.

Figure 3

The network of DENV dispersal among different regions in the Philippines. The dispersal patterns were inferred by using the Bayesian Stochastic Search Variable Selection (BSSVS) procedure in BEAST 1.7.4 [30]. The analysis included 377 E gene sequences reported from 17 administrative regions. Sequences were categorized into 17 discrete states based on case locations in 17 administrative regions. The latitude and longitude of the center of each region were used to define the geo-position of each discrete state. Any link supported by Bayes factor (BF) >3 was considered significant. Only significant links are shown in the figures. The branch color indicates the BF values (highest in red and lowest in green). The BF values of each link are given in Table S2. The regions marked with red stars are the locations with maximum number of links.

Figure 4

Root state posterior probability analysis for each serotype. The root state posterior probability value of each discrete location (region) was extracted from the annotated maximum clade credibility tree for (a) DENV-1, (b) DENV-2, (c) DENV-3, and (d) DENV-4 via FigTree v. 1.4.4 “http://tree.bio.ed.ac.uk/software/figtree/ (accessed on 1 March 2023)” to determine the most probable location of origin of virus lineages.