Summary
Recent findings highlight a critical flaw in routine dengue surveillance: sylvatic dengue virus 2 (DENV-2) infections are being misclassified as “Undetermined Serotype” by commercial molecular serotyping assays. This misclassification stems from the noninclusion of sylvatic DENV-2 strains in current diagnostic panels, masking the true viral diversity circulating in populations. The consequence is a blind spot in dengue surveillance that can hinder public health responses and hinder understanding of sylvatic contributions to human dengue infections.
Context and Evidence
Suppiah and colleagues have demonstrated that DENV-2 positive samples can be misidentified as Undetermined Serotype when using widely available molecular serotyping assays. This finding echoes prior notifications in Senegal, West Africa, where sylvatic DENV-2 strains failed to be captured by existing tools. The lack of representation for sylvatic lineages in commercial tests means that a meaningful portion of dengue-positive samples may be misclassified, distorting the picture of circulating serotypes and impeding real-time monitoring of viral evolution.
Implications for Surveillance
The misclassification of sylvatic DENV-2 has several implications for public health surveillance. First, it obscures the true prevalence of sylvatic lineages among reported dengue infections, potentially underestimating spillover events from non-urban reservoirs. Second, when surveillance data are relied upon to guide vaccine and therapeutic strategies, gaps in serotype resolution may misinform risk assessments for outbreaks and outbreaks of unusual serotype patterns. Third, routine RT-qPCR workflows that do not account for sylvatic diversity risk perpetuating a cycle of misclassification, delaying detection of shifts in viral populations that could signal emerging transmission dynamics.
Recommendations for Tool Improvement
To address these gaps, researchers and public health laboratories should consider:
- Expanding multiplex assays to include both urban and sylvatic DENV-2 targets, ensuring broader coverage of circulating lineages.
- Regularly updating primer and probe sets to reflect genetic diversity observed in sylvatic reservoirs and recent human infections.
- Collaborative validation across laboratories and regions to harmonize detection capabilities and reporting formats.
- Incorporating genomic surveillance components to confirm serotype assignment and track lineage movements in near real time.
- Transparent reporting of assay limitations and ongoing efforts to refine diagnostic tools, with open access sharing of updated protocols.
Strategic Benefits of Updated Assays
Adopting multiplex assays that detect both urban and sylvatic DENV-2 could enhance the granularity of dengue surveillance. Real-time monitoring of sylvatic lineages among reported infections would provide critical insights into the ecology of dengue transmission, the risk of spillover, and the effectiveness of control strategies in different settings. This approach aligns with a broader shift toward precision surveillance, where nuanced serotype and lineage information informs targeted interventions, vaccine development, and public health preparedness.
Open Access and Collaboration
The discussed developments underscore the importance of open access and shared methodologies. When diagnostic tools are openly available, researchers worldwide can rapidly validate, adapt, and implement improvements that reflect evolving viral genetics. This collaborative stance is essential for maintaining robust dengue surveillance in the face of genetic diversification and changing transmission landscapes.
Conclusion
The systematic misclassification of sylvatic DENV-2 as Undetermined Serotype represents a significant gap in dengue diagnostics and surveillance. Updating molecular serotyping tools to include sylvatic strains, and developing inclusive multiplex assays, will enable more accurate detection and real-time insight into the prevalence of sylvatic lineages. Such enhancements are critical for informed public health action, better surveillance data integrity, and resilient responses to dengue’s evolving epidemiology.
