Phylodynamics of dengue virus 2 in Nicaragua leading up to the 2019 epidemic reveals a role for lineage turnover.

BACKGROUND: Dengue is a mosquito-borne viral disease posing a significant threat to public health. Dengue virus (DENV) evolution is often characterized by lineage turnover, which, along with ecological and immunological factors, has been linked to changes in dengue phenotype affecting epidemic dynamics. Utilizing epidemiologic and virologic data from long-term population-based studies (the Nicaraguan Pediatric Dengue Cohort Study and Nicaraguan Dengue Hospital-based Study), we describe a lineage turnover of DENV serotype 2 (DENV-2) prior to a large dengue epidemic in 2019. Prior to this epidemic, Nicaragua had experienced relatively low levels of DENV transmission from 2014 to 2019, a period dominated by chikungunya in 2014/15 and Zika in 2016. RESULTS: Our phylogenetic analyses confirmed that all Nicaraguan DENV-2 isolates from 2018 to 2019 formed their own clade within the Nicaraguan lineage of the Asian/American genotype. The emergence of the new DENV-2 lineage reflects a replacement of the formerly dominant clade presiding from 2005 to 2009, a lineage turnover marked by several shared derived amino acid substitutions throughout the genome. To elucidate evolutionary drivers of lineage turnover, we performed selection pressure analysis and reconstructed the demographic history of DENV-2. We found evidence of adaptive evolution by natural selection at the codon level as well as in branch formation. CONCLUSIONS: The timing of its emergence, along with a statistical signal of adaptive evolution and distinctive amino acid substitutions, the latest in the NS5 gene, suggest that this lineage may have increased fitness relative to the prior dominant DENV-2 strains. This may have contributed to the intensity of the 2019 DENV-2 epidemic, in addition to previously identified immunological factors associated with pre-existing Zika virus immunity.

Validity of Self-Reported Mosquito Bites to Assess Household Mosquito Abundance in Six Communities of Esmeraldas Province, Ecuador.

Mosquito-borne diseases are a global burden; however, current methods of evaluating human-mosquito contact rates are expensive and time consuming. Validated surveys of self-reported mosquito bites may be an inexpensive way to determine mosquito presence and bite exposure level in an area, but this remains untested. In this study, a survey of self-reported mosquito bites was validated against household mosquito abundance from six communities in Esmeraldas, Ecuador. From February 2021 to July 2022, households were interviewed monthly, and five questions were used to ask participants how often they were bitten by mosquitoes at different times during the day. At the same time, adult mosquitoes were collected using a Prokopack aspirator. Species were identified and counted. Survey responses were compared with the total number of mosquitoes found in the home using negative binomial regression. More frequent self-reported mosquito bites were significantly associated with higher numbers of collected adult mosquitoes. These associations were driven by the prevalence of the dominant genera, Culex. These results suggest that surveys of perceived mosquito bites relate to actual mosquito presence, making them a potentially useful tool for determining the impact of vector-control interventions on community perceptions of risk but less useful for assessing the risk of nondominant species such as Aedes aegypti. Further work is needed to examine the robustness of these results in other contexts.

Evolution and epidemiologic dynamics of dengue virus in Nicaragua during the emergence of chikungunya and Zika viruses.

Arthropod-borne viruses (arboviruses) comprise a significant and ongoing threat to human health, infecting hundreds of millions annually. Three such arboviruses include circumtropical dengue, Zika, and chikungunya viruses, exhibiting continuous emergence primarily via Aedes mosquito vectors. Nicaragua has experienced endemic dengue virus (DENV) transmission involving multiple serotypes since 1985, with chikungunya virus (CHIKV) reported in 2014-2015, followed by Zika virus (ZIKV) first reported in 2016. In order to identify patterns of genetic variation and selection pressures shaping the evolution of co-circulating DENV serotypes in light of the arrival of CHIKV and ZIKV, we employed whole-genome sequencing on an Illumina MiSeq platform of random-amplified total RNA libraries to characterize 42 DENV low-passage isolates, derived from viremic patients in Nicaragua between 2013 and 2016. Our approach also revealed clinically undetected co-infections with CHIKV. Of the three DENV serotypes (1, 2, and 3) co-circulating during our study, we uncovered distinct patterns of evolution using comparative phylogenetic inference. DENV-1 genetic variation was structured into two distinct co-circulating lineages with no evidence of positive selection in the origins of either lineage, suggesting they are equally fit. In contrast, the evolutionary history of DENV-2 was marked by positive selection, and a unique, divergent lineage correlated with high epidemic potential emerged in 2015 to drive an outbreak in 2016. DENV-3 genetic variation remained unstructured into lineages throughout the period of study. Thus, this study reveals insights into evolutionary and epidemiologic trends exhibited during the circulation of multiple arboviruses in Nicaragua.