What is the clinical evidence from this study?

Study design: Observational. Population: Acute hemorrhagic conjunctivitis (AHC) (n=159). Intervention: Coxsackievirus A24v (CVA24v). Primary outcome: Nucleotide substitution rate and transmission routes.

What does this research mean for the field?

Coxsackievirus A24 variant strains causing outbreaks in Cuba evolved through repeated introductions of genotypes GIII and GIV originating in Asia, with nucleotide substitution rates peaking during pandemics. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To characterize the long-term molecular evolution, substitution rates, and global transmission pathways of coxsackievirus A24 variant associated with acute hemorrhagic conjunctivitis epidemics.

August 13, 2020Scientific ReportsOpen Access

Molecular evolution of coxsackievirus A24v in Cuba over 23-years, 1986–2009

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Key result

Cuban CVA24v strains evolve rapidly with repeated pandemic introductions from Asia.

n=159

Why the study?

Coxsackievirus A24 variant is a major cause of acute hemorrhagic conjunctivitis outbreaks worldwide, but its evolutionary and transmission dynamics remain unclear.

Key Points

To characterize the long-term molecular evolution, substitution rates, and global transmission pathways of coxsackievirus A24 variant associated with acute hemorrhagic conjunctivitis epidemics.
Analyzed and compared the 3C and partial VP1 gene sequences of CVA24v isolates from five epidemic outbreaks between 1986 and 2009 in Cuba alongside global reference strains.
Conducted molecular clock and phylogeographic analyses to estimate evolutionary substitution rates and reconstruct worldwide viral dissemination networks.
Identified repeated introductions of two distinct genotypes (GIII and GIV) that co-evolved with stable population sizes over time and emerged roughly two years prior to outbreak detection.
Determined peak pandemic nucleotide substitution rates of 4.39 × 10⁻³ substitutions per site per year for the 3C region and 5.80 × 10⁻³ substitutions per site per year for the VP1 region.
Identified 25 and 19 viral transmission routes based on 3C and VP1 regions, respectively, tracing pandemic origins primarily to Asia and establishing China and Brazil as primary global dispersal hubs.

Study Design

Type

Observational (n=159)

Structured PICO

Population

159 coxsackievirus A24v strains isolated from patients with acute hemorrhagic conjunctivitis during five major outbreaks in Cuba between 1986 and 2009.

Outcome

Evolutionary and transmission dynamics based on 3C and partial VP1 gene regions

The study provides novel insights into the epidemiological and evolutionary dynamics of the coxsackievirus A24 variant, identifying Asia as a common origin and China and Brazil as major hubs for global dispersal.

Limitations

Sanger methodology used for sequencing might have resulted in an underestimation of the genetic diversity
Analysis was performed only on partial and not complete genomes
Few availability of the CVA24v sequences from all affected regions and pandemic periods
Intrinsic limitations of the phylogenetic analysis and software

Implication

Highlights need for monitoring Asian CVA24v imports; leaves open impact on outbreak control and requires prospective validation.

Abstract

Coxsackievirus A24 variant (CVA24v) is a major causative agent of acute hemorrhagic conjunctivitis outbreaks worldwide, yet the evolutionary and transmission dynamics of the virus remain unclear. To address this, we analyzed and compared the 3C and partial VP1 gene regions of CVA24v isolates obtained from five outbreaks in Cuba between 1986 and 2009 and strains isolated worldwide. Here we show that Cuban strains were homologous to those isolated in Africa, the Americas and Asia during the same time period. Two genotypes of CVA24v (GIII and GIV) were repeatedly introduced into Cuba and they arose about two years before the epidemic was detected. The two genotypes co-evolved with a population size that is stable over time. However, nucleotide substitution rates peaked during pandemics with 4.39 × 10−3 and 5.80 × 10−3 substitutions per site per year for the 3C and VP1 region, respectively. The phylogeographic analysis identified 25 and 19 viral transmission routes based on 3C and VP1 regions, respectively. Pandemic viruses usually originated in Asia, and both China and Brazil were the major hub for the global dispersal of the virus. Together, these data provide novel insight into the epidemiological dynamics of this virus and possibly other pandemic viruses.

Discussion

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Published by Scientific Reports · CC BY

Cite This Study

Fonseca et al. (2020) conducted an observational in Acute hemorrhagic conjunctivitis (AHC) (n=159). Coxsackievirus A24v (CVA24v) was evaluated on Nucleotide substitution rate and transmission routes. Cuban CVA24v strains evolved with nucleotide substitution rates of 4.39 × 10−3 (3C) and 5.80 × 10−3 (VP1) per site per year, with pandemic viruses repeatedly introduced from Asia.

synapsesocial.com/papers/6aa8a39136a75cb63eb5c898 https://doi.org/10.1038/s41598-020-70436-w

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Implication

Highlights need for monitoring Asian CVA24v imports; leaves open impact on outbreak control and requires prospective validation.

Molecular evolution of coxsackievirus A24v in Cuba over 23-years, 1986–2009

Key Points

Study Design

Structured PICO

Limitations

Implication

Abstract

Discussion

Figures from the paper

Cite This Study

Molecular evolution of coxsackievirus A24v in Cuba over 23-years, 1986–2009

Key Points

Study Design

Structured PICO

Limitations

Implication

Abstract

Discussion

Figures from the paper

Cite This Study

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