Air travel is associated with intracontinental spread of dengue virus serotypes 1-3 in Brazil

Abstract

Dengue virus and its four serotypes (DENV-1 to DENV-4) infect 390 million people and are implicated in at least 25,000 deaths annually, with the largest disease burden in tropical and subtropical regions. We investigated the spatial dynamics of DENV-1, DENV-2 and DENV-3 in Brazil by applying a statistical framework to complete genome sequences. For all three serotypes, we estimated that the introduction of new lineages occurred within 7 to 10-year intervals. New lineages were most likely to be imported from the Caribbean region to the North and Northeast regions of Brazil, and then to disperse at a rate of approximately 0.5 km/day. Joint statistical analysis of evolutionary, epidemiological and ecological data indicates that aerial transportation of humans and/or vector mosquitoes, rather than Aedes aegypti infestation rates or geographical distances, determine dengue virus spread in Brazil.

Figure 1. Temporal-scaled phylogeographic DENV-1 tree.

Each branch is colored according to the most probable location as inferred using a discrete phylogeographic diffusion model. Geographic locations considered are shown in the left. Phylogenetic posterior probabilities percentages are shown next to relevant nodes along with the location-state posterior support. The number of sequences falling in Brazilian monophyletic lineages (highlighted in grey) is shown in brackets. For each lineage, the mean estimated time of the most recent common ancestor (tMRCA) and respective 95% Bayesian credible intervals (BCI) are shown in a black box.

Figure 2. Temporal-scaled phylogeographic DENV-2 tree.

Each branch is colored according to the most probable location as inferred using a discrete phylogeographic diffusion model. Geographic locations considered are shown in the left. Phylogenetic posterior probabilities percentages are shown next to relevant nodes along with the location-state posterior support. The number of sequences falling in Brazilian monophyletic lineages (highlighted in grey) is shown in brackets. For each lineage, the mean estimated time of the most recent common ancestor (tMRCA) and respective 95% Bayesian credible intervals (BCI) are shown in a black box.

Figure 3. Temporal-scaled phylogeographic DENV-3 tree.

Each branch is colored according to the most probable location as inferred using a discrete phylogeographic diffusion model. Geographic locations considered are shown in the left. Phylogenetic posterior probabilities percentages are shown next to relevant nodes along with the location-state posterior support. The number of sequences falling in Brazilian monophyletic lineages (highlighted in grey) is shown in brackets. For each lineage, the mean estimated time of the most recent common ancestor (tMRCA) and respective 95% Bayesian credible intervals (BCI) are shown in a black box.

Figure 4. Population dynamics of DENV-1, DENV-2 and DENV-3 circulating lineages in Brazil.

Panel A shows the proportion of federal states (total of 27) where each DENV serotype was molecularly confirmed from 2002 to 2012. Panels B, C and D depict changes in effective population size (Ne) over time (dashed lines) respectively for DENV-1, DENV-2 and DENV-3 viral lineages circulating in Brazil. Mean estimates of Ne (tick dashed line) are shown along with respective uncertainty intervals (thin dashed lines). In panels B–D, filled line shows the yearly counts of federal states where each serotype was detected. The temporal period highlighted in grey corresponds to the time-span for which epidemiological information on serotype-specific state counts was available (2002 to 2012). Data on yearly state counts was available from the Ministry of Health of Brazil , .

Figure 5. Snapshots of Dengue virus (DENV) lineages spatiotemporal spread.

Geographic dispersion of DENV-1 lineage I in 1999 (a1), 2001(a2), 2005 (a3), and 2008 (a4). DENV-1 lineage II: years of 1989 (b1), 1993 (b2), 1995 (b3), and 1997–2001 (b4). DENV-2 lineage I: years of 1992 (c1), 1994–1996 (c2), 1998 (c3), and 2000–2005 (c4). DENV-2 lineage II (d); DENV-2 lineage III (e); DENV-3 lineage II: years of 1998 (f1), 2000 (f2), 2002 (f3), 2004 (f4), 2006 (f5) and 2008 (f6).

Figure 6. Predictors of DENV spatial dispersal. For each potential predictor, respective Bayes factor support and conditional effect sizes (cES) are shown.

Circles and bars indicate respectively the mean and 95% Bayesian credible intervals of the estimated cES, respectively. Only predictors that obtained a Bayes factor support above 3 are considered significant (highlighted in bold).