Dengue, zika, chikungunya y el desarrollo de vacunas / Dengue, zika, chikungunya and the development of vaccines

Dengue (DENV), zika (ZIKV) y chikungunya (CHIKV), tres arbovirosis transmitidas por mosquitos Aedes, se han propagado en las últimas décadas en zonas tropicales y subtropicales húmedas. El dengue es epidémico en áreas subtropicales de la Argentina. Después de la infección por DENV hay inmunidad duradera contra el serotipo infectante, pero aumenta el riesgo de enfermedad grave por los otros tres. La vacuna recombinante tetravalente, Dengvaxia® previene el dengue grave y la hospitalización en sujetos seropositivos. En 2017 se aprobó Dengvaxia en Argentina, para edades de 9 a 45 años, sin incluirla en el calendario nacional de vacunación. Otras dos vacunas se hallan en evaluación Fase III: la desarrollada por NIAID/ Instituto Butantan y la vacuna Takeda. ZIKV, virus asociado a microcefalia en recién nacidos en Brasil, circula desde 2016 en Argentina. Aún no existe vacuna de actividad comprobada contra ZIKV ni tratamiento eficaz. No se registró circulación activa de CHIKV en Argentina en 2017. Los brotes de fiebre CHIKV tienen una complicación: el desarrollo de reumatismo crónico post-enfermedad. No existen vacunas aprobadas para humanos ni terapias antivirales efectivas. La gravedad de estas virosis contribuyó a un rápido progreso en el conocimiento de los procesos de infección y de la respuesta inmune. Pero sus vectores, Aedes aegypti y A. albopictus, continúan expandiéndose, lo que indica que la vacuna será el medio más efectivo para el control. Se resume aquí información sobre estas arbovirosis en Argentina y Brasil, y se describen avances en el desarrollo y la evaluación de vacunas.

Dengue (DENV), zika (ZIKV) and chikungunya (CHIKV), three arbovirosis transmitted by Aedes mosquitoes, have spread in recent decades in humid tropical and subtropical zones. Dengue is epidemic in subtropical areas of Argentina. DENV infection confers lasting immunity against the infecting serotype but increases the risk of serious disease upon reinfection by any of the other three. The recombinant tetravalent vaccine Dengvaxia® prevents severe dengue and hospitalization in seropositive subjects. In 2017, Dengvaxia was approved in Argentina, for ages 9 to 45, but is not included in the national vaccination calendar. Two other vaccines are in Phase III evaluation: one developed by NIAID / Instituto Butantan and the other by Takeda.ZIKV, a virus associated with microcephaly in newborns in Brazil, circulates since 2016 in Argentina. There is still not effective treatment nor vaccine with proven activity against ZIKV. There has been no active circulation of CHIKV in Argentina in 2017. Outbreaks of CHIKV fever have a complication: the development of chronic post-disease rheumatism. There are not approved vaccines for humans nor effective antiviral therapies. The seriousness of these virosis has contributed to a rapid progress in the knowledge of the infection processes and the immune response. For now, Aedes aegypti and A. albopictus vectors continue to expand, suggesting that the vaccine will be the most effective means of controlling these viruses. Here we summarize information about these arbovirosis in Argentina and Brazil and describe advances in the development and evaluation of vaccines.

SAGE recommends introduction of dengue vaccine in geographic set-tings with high endemicity

The Strategic Advisory Group of Experts [SAGE] on immunization recently reviewed the evidence generated from two large Phase 3 clinical trials, one conducted in Asia and the other in Latin America. On the basis of currently available evidence, SAGE recommended that the countries may consider introduction of dengue vaccine [CYD-TDV] only in in geographic settings with high endemicity [seroprevalence is greater than 70% or more in targeted age group or other suitable epidemiologic marker]

Designing a vaccination strategy against dengue / Modelos para implementar a vacinação contra dengue

In this work we propose a mathematical approach to estimate the dengue force of infection, the average age of dengue first infection, the optimum age to vaccinate children against dengue in a routine fashion and the optimum age interval to introduce the dengue vaccine in a mass vaccination campaign. The model is based on previously published models for vaccination against other childhood infections, which resulted in actual vaccination programmes in Brazil. The model was applied for three areas of distinct levels of endemicity of the city of Recife in Northeastern State of Pernambuco, Brazil. Our results point to an optimal age to introduce the dengue vaccine in the routine immunization programme at two years of age and an age interval to introduce a mass vaccination between three and 14 years of age.

Neste trabalho propomos um modelo matemático para a estimativa da força de infecção, da idade média de primo-infecção, da idade ótima para vacinação de rotina e do intervalo ótimo de cobertura vacina em uma campanha para a introdução da vacina contra a dengue. O modelo baseia-se em publicações anteriores de desenhos de estratégias de vacinação contra outras infecções e que resultaram em estratégias de vacinação no Brasil. O modelo foi aplicado em três áreas com níveis endêmicos de dengue distintos na cidade de Recife, Pernambuco. Nossos resultados apontam para uma idade ótima de vacinação na rotina de dois anos de idade e para um intervalo de vacinação em campanha entre três e 14 anos.