Dengue in Latin America: Systematic Review of Molecular Epidemiological Trends

<div><p>Dengue, the predominant arthropod-borne viral disease affecting humans, is caused by one of four distinct serotypes (DENV-1, -2, -3 or -4). A literature analysis and review was undertaken to describe the molecular epidemiological trends in dengue disease and the knowledge generated in specific molecular topics in Latin America, including the Caribbean islands, from 2000 to 2013 in the context of regional trends in order to identify gaps in molecular epidemiological knowledge and future research needs. Searches of literature published between 1 January 2000 and 30 November 2013 were conducted using specific search strategies for each electronic database that was reviewed. A total of 396 relevant citations were identified, 57 of which fulfilled the inclusion criteria. All four dengue virus serotypes were present and co-circulated in many countries over the review period (with the predominance of individual serotypes varying by country and year). The number of countries in which more than one serotype circulated steadily increased during the period under review. Molecular epidemiology data were found for Argentina, Bolivia, Brazil, the Caribbean region, Colombia, Ecuador, Mexico and Central America, Paraguay, Peru and Venezuela. Distinct lineages with different dynamics were found in each country, with co-existence, extinction and replacement of lineages occurring over the review period. Despite some gaps in the literature limiting the possibility for comparison, our review has described the molecular epidemiological trends of dengue infection. However, several gaps in molecular epidemiological information across Latin America and the Caribbean were identified that provide avenues for future research; in particular, sequence determination of the dengue virus genome is important for more precise phylogenetic classification and correlation with clinical outcome and disease severity.</p></div

Distribution of DENV genotypes in the Americas region (2002–13).

<p>The maps show the reported DENV genotypes by country between 2002 and 2013. The balloons indicate the country where the DENV was isolated, and the colour the genotypes determined. The maps were generated using ArcGIS 10.0 (<a href="http://www.strath.ac.uk/is/software/arcgis100-windows/" target="_blank">http://www.strath.ac.uk/is/software/arcgis100-windows/</a>) and modified proportionally to fit in the figure (the bar at the bottom of the panel represents 1,000 km).</p

Circulating serotypes in the region, according to country for 2000–13 [27].

<p>Circulating serotypes in the region, according to country for 2000–13 [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005224#pntd.0005224.ref027" target="_blank">27</a>].</p

The Latin American region.

<p>The strict definition of ‘Latin America’ is the region of the Americas where Latin languages are spoken (Spanish, Portuguese and French). These countries have more in common with each other, sharing elements of historical experience, language and culture, than they do with North America. Nevertheless, Latin America is a diverse group of countries, with varied landscapes, peoples and cultures. However, for the purposes of this review, we included all countries within the Caribbean and Central and South America, and did not exclude countries located in the same region that speak other European languages, such as Belize, Guyana and the smaller Caribbean island nations. Colour code: Black: Brazil and Southern Cone; Dark Grey: Haiti and Latin Caribbean; Mid Grey: Mexico and Central America; Light Grey: Andean countries.</p

Result of literature search and evaluation of identified studies according to the preferred reporting items of systematic reviews and meta-analyses (PRISMA).

<p>All references identified in the on-line database searches were assigned a unique identification number. Following the removal of duplicates and articles that did not satisfy the inclusion criteria from review of the titles and abstracts, the full papers of the first selection of references were retrieved either electronically or in paper form. A further selection was made based on review of the full text of the articles.</p

Dengue fatal case confirmation by any of the NS1 capture tests per tissues per case.

<p>*Positive/total analyzed (%), +: positive sample, −: negative sample, NA: not available.</p

NS1 antigen capture tests analysis in tissues from dengue fatal cases (<i>n = </i>23).

<p>NS1 antigen capture tests analysis in tissues from dengue fatal cases (<i>n = </i>23).</p

NS1 antigen capture tests applied to tissues (<i>n = </i>74) from confirmed dengue fatal cases (<i>n = </i>23).

<p>*Total positive /total tested (%), ND: not done, NA: not available.</p

Twenty Years of DENV-2 Activity in Brazil: Molecular Characterization and Phylogeny of Strains Isolated from 1990 to 2010

<div><p>In Brazil, dengue has been a major public health problem since its introduction in the 1980s. Phylogenetic studies constitute a valuable tool to monitor the introduction and spread of viruses as well as to predict the potential epidemiological consequences of such events. Aiming to perform the molecular characterization and phylogenetic analysis of DENV-2 during twenty years of viral activity in the country, viral strains isolated from patients presenting different disease manifestations (<i>n</i> = 34), representing six states of the country, from 1990 to 2010, were sequenced. Partial genome sequencing (genes C/prM/M/E) was performed in 25 DENV-2 strains and full-length genome sequencing (coding region) was performed in 9 strains. The percentage of similarity among the DENV-2 strains in this study and reference strains available in Genbank identified two groups epidemiologically distinct: one represented by strains isolated from 1990 to 2003 and one from strains isolated from 2007 to 2010. No consistent differences were observed on the E gene from strains isolated from cases with different clinical manifestations analyzed, suggesting that if the disease severity has a genetic origin, it is not only due to the differences observed on the E gene. The results obtained by the DENV-2 full-length genome sequencing did not point out consistent differences related to a more severe disease either. The analysis based on the partial and/or complete genome sequencing has characterized the Brazilian DENV-2 strains as belonging to the Southeast Asian genotype, however a distinction of two Lineages within this genotype has been identified. It was established that strains circulating prior DENV-2 emergence (1990–2003) belong to Southeast Asian genotype, Lineage I and strains isolated after DENV-2 emergence in 2007 belong to Southeast Asian genotype, Lineage II. Furthermore, all DENV-2 strains analyzed presented an asparagine (N) in E₃₉₀, previously identified as a probable genetic marker of virulence observed in DHF strains from Asian origin. The percentage of identity of the latter with the Dominican Republic strain isolated in 2001 combined to the percentage of divergence with the strains first introduced in the country in the 1990s suggests that those viruses did not evolve locally but were due to a new viral Lineage introduction in the country from the Caribbean.</p> </div

Primers used for amplification of the partial and complete genes (coding region) from Brazilian DENV-2.

<p>Primers used for amplification of the partial and complete genes (coding region) from Brazilian DENV-2.</p