Introduction of New Dengue Virus Lineages of Multiple Serotypes after COVID-19 Pandemic, Nicaragua, 2022

Abstract

Major dengue epidemics throughout Nicaragua's history have been dominated by 1 of 4 dengue virus serotypes (DENV-1-4). To examine serotypes during the dengue epidemic in Nicaragua in 2022, we performed real-time genomic surveillance in-country and documented cocirculation of all 4 serotypes. We observed a shift toward co-dominance of DENV-1 and DENV-4 over previously dominant DENV-2. By analyzing 135 new full-length DENV sequences, we found that introductions underlay the resurgence: DENV-1 clustered with viruses from Ecuador in 2014 rather than those previously seen in Nicaragua; DENV-3, which last circulated locally in 2014, grouped instead with Southeast Asia strains expanding into Florida and Cuba in 2022; and new DENV-4 strains clustered within a South America lineage spreading to Florida in 2022. In contrast, DENV-2 persisted from the formerly dominant Nicaragua clade. We posit that the resurgence emerged from travel after the COVID-19 pandemic and that the resultant intensifying hyperendemicity could affect future dengue immunity and severity.

Keywords: Nicaragua; dengue; dengue virus; genome; neglected disease; parasites; serotypes; vector-borne infections; viruses.

Figure 1

DENV serotypes 1–4 circulation in Nicaragua during 1998–2022. Data on dengue cases with serotype information available were obtained from the Nicaraguan Dengue Surveillance Program; many more cases were confirmed via serology that are not included here because the serotype is unknown. A) Total dengue cases by serotype and year. B) Percentage of circulating dengue cases by serotype and year. C) Case count of each serotype identified by real-time reverse transcription PCR over time during January–December 2022. DENV, dengue virus.

Figure 4

Dengue virus (DENV) serotype 3 maximum clade credibility tree, generated from 131 DENV-3 nucleotide sequences, showing emergence over time. Sequences are labeled by country of sample origin, indicated by colored circles, and include Nicaraguan sequences (red) and publicly available sequences, as indicated. Nicaragua clades are indicated with square brackets labeled by year(s) of detection. The estimated time to most recent common ancestor (95% high probability density) is indicated at the nodes leading to Nicaraguan clades. Genotypes are identified in the vertical bar to the right. Posterior node probabilities are indicated at major nodes.

Figure 2

Dengue virus (DENV) serotype 1 maximum clade credibility tree, generated from 130 DENV-1 nucleotide sequences, showing emergence over time. Sequences are labeled by country of sample origin, indicated by colored circles, and include Nicaragua sequences (red) and publicly available sequences. DENV-1 genotypes are identified in the vertical bar to the right. Two Nicaragua clades, DV1-NI-1 and DV1-NI-2, are indicated with square brackets. The time to most recent common ancestor (95% high probability density range) is indicated at the nodes leading to Nicaragua clades. Posterior node probabilities are indicated at major nodes.

Figure 3

Time-scaled dengue virus (DENV) serotype 2 maximum clade credibility tree, generated from 136 DENV-2 nucleotide sequences, showing emergence over time. Sequences are labeled by country of sample origin, indicated by colored circles, and include Nicaragua sequences (red) and publicly available sequences, as indicated. Nicaragua clades are indicated with square brackets labeled by year(s) of detection, including the DV-NI-3 clade. The time to most recent common ancestor (95% high probability density) is indicated at the nodes leading to Nicaragua clades. Genotypes are identified by vertical bar to the right. Posterior node probabilities are indicated at major nodes.

Figure 5

Dengue virus (DENV) serotype 4 maximum clade credibility tree, generated from 115 DENV-4 nucleotide sequences, showing emergence over time. Sequences are labeled by country of sample origin, indicated by colored circles, and include Nicaragua sequences (red) and publicly available sequences, as indicated. Nicaragua clades are indicated with square brackets labeled by year of detection. The time to most recent common ancestor (95% high probability density) is indicated at the nodes leading to Nicaragua clades. Genotypes are identified in the vertical bar to the right. Posterior node probabilities are indicated at major nodes.