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La evidencia genómica vincula los casos de dengue en humanos con serotipos indeterminados a linajes silvestres
Jeyanthi Suppiah1, Murni Maya Sari Zulkifli2, Amir Hussin Adiee2
1Virology Unit, Infectious Disease Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, Shah Alam, Selangor, Malaysia. jeyanthi@moh.gov.my.
Tropical medicine and health
|August 24, 2025
Resumen
El virus del dengue silvático (DENV2) se ha extendido a los humanos en Malasia, causando enfermedades graves. Los diagnósticos estándar no detectaron estas infecciones debido a las diferencias genéticas del virus, lo que pone de relieve la necesidad de mejorar la vigilancia.
Área de la Ciencia:
- Virología
- Epidemiología
- La genómica
Sus antecedentes:
- Los virus del dengue silvático (DENV) se mantienen en los ciclos forestales y rara vez infectan a los humanos.
- Los derrames esporádicos de DENV ocurren en el sudeste asiático, pero a menudo se pasan por alto debido a la divergencia genética de las cepas urbanas.
- La vigilancia de rutina en Malasia (2024-2025) identificó casos de dengue con serotipos no detectables por RT-PCR comercial, lo que sugiere un posible origen silvestre.
Objetivo del estudio:
- Investigar los casos de dengue con serotipos no detectables en Malasia.
- Determinar el origen y las características genéticas de estas inusuales cepas DENV.
- Evaluar los desafíos de diagnóstico planteados por el DENV silvático genéticamente divergente.
Principales métodos:
- Se realizaron análisis clínicos, serológicos, moleculares y filogenéticos en 22 pacientes.
- El antígeno NS1 y la RT-PCR de amplio alcance confirmaron la infección aguda por dengue.
- Las muestras seleccionadas se sometieron a secuenciación para la determinación del linaje y el análisis comparativo de aminoácidos.
Principales resultados:
- La mayoría de los pacientes presentaron dengue grave, con alta positividad del antígeno NS1 y predominantemente infecciones primarias.
- La secuenciación identificó DENV2 silvático en ocho de las nueve muestras analizadas, con una DENV3 divergente.
- Las mutaciones únicas de aminoácidos en las cepas DENV2 silváticas de Malasia (por ejemplo, V270 en el gen M, R844 en el gen NS1) los diferenciaron de los linajes silváticos urbanos e históricos.
- El análisis filogenético reveló un clado silvático DENV2 de Malasia distinto.
Conclusiones:
- Este estudio proporciona la primera evidencia genómica de la propagación del DENV2 silvático en humanos en Malasia.
- La divergencia genética del DENV2 silvático probablemente condujo a su subdetección por ensayos de diagnóstico estándar.
- Las herramientas de vigilancia mejoradas y la comprensión del ciclo silvestre son cruciales para la epidemiología del dengue.
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