[Observations on the dengue vaccination strategy in Argentina]. / Observaciones sobre la estrategia de vacunación contra el dengue en Argentina.

A new dengue vaccine has recently been licensed in Argentina, with the Argentine government planning to acquire it in order to develop a vaccination strategy. As the disease is gradually following a path to endemicity in some regions of the country, the incorporation of these vaccines will have the potential to tackle the growing incidence of the disease and to reduce the disease burden. However, the establishment of the vaccination programme may also be susceptible of threats related to the epidemiological shift of the disease. Selecting a specific age group for the vaccine may result in a change in the peak incidence to other age groups more susceptible to severe forms of the disease, such as children or the elderly. Furthermore, the perception of protection following vaccine introduction in one jurisdiction may reduce adherence to vector control activities, increasing the risk of virus introduction and transmission in other areas not prioritised by the vaccination strategy, and the risk of other arboviral diseases such as Zika and chikungunya fever. These and other potential limitations to be considered prior to the implementation of vaccination programmes are discussed in this article, with a series of recommendations on how to address these concerns. These recommendations can help decision makers and public health practitioners at this early stage of the vaccination programme development.

Una nueva vacuna contra el dengue ha sido recientemente aprobada en Argentina, y el gobierno argentino se encuentra planificando su adquisición para desarrollar una estrategia de vacunación. Mientras la enfermedad se está dirigiendo gradualmente hacia la endemicidad en algunas regiones del país, la incorporación de estas vacunas tendrá el potencial de atacar la creciente incidencia de la enfermedad y de reducir su carga. Sin embargo, el establecimiento de un programa de vacunación puede también ser susceptible de amenazas relacionadas con el cambio epidemiológico de la enfermedad. La selección de un grupo de edad específico para la vacunación puede resultar en un cambio en el pico de la incidencia hacia otros grupos de edad más vulnerables a las formas graves de la enfermedad, como los niños o los ancianos. Además, la percepción de protección luego de la introducción de la vacuna en una jurisdicción puede reducir la adherencia a las actividades de control del vector, incrementando el riesgo de introducción y transmisión del virus en otras áreas no priorizadas por la estrategia de vacunación, y aumentando el riesgo de otras arbovirosis como las fiebres Zika y chikungunya. Estas y otras potenciales limitaciones para ser consideradas antes de la implementación de los programas de vacunación son discutidas en este artículo, en conjunto con una serie de recomendaciones sobre cómo abordar estas preocupaciones. Estas recomendaciones pueden resultar de utilidad para los tomadores de decisión y actores sanitarios, en esta etapa temprana del desarrollo de un programa de vacunación.

Observaciones sobre la estrategia de vacunación contra el dengue en Argentina / Observations on the dengue vaccination strategy in Argentina

Resumen Una nueva vacuna contra el dengue ha sido reciente mente aprobada en Argentina, y el gobierno argentino se encuentra planificando su adquisición para desarrollar una estrategia de vacunación. Mientras la enfermedad se está dirigiendo gradualmente hacia la endemicidad en algunas regiones del país, la incorporación de estas vacunas tendrá el potencial de atacar la creciente inci dencia de la enfermedad y de reducir su carga. Sin em bargo, el establecimiento de un programa de vacunación puede también ser susceptible de amenazas relaciona das con el cambio epidemiológico de la enfermedad. La selección de un grupo de edad específico para la vacunación puede resultar en un cambio en el pico de la incidencia hacia otros grupos de edad más vulnerables a las formas graves de la enfermedad, como los niños o los ancianos. Además, la percepción de protección lue go de la introducción de la vacuna en una jurisdicción puede reducir la adherencia a las actividades de control del vector, incrementando el riesgo de introducción y transmisión del virus en otras áreas no priorizadas por la estrategia de vacunación, y aumentando el riesgo de otras arbovirosis como las fiebres Zika y chikungunya. Estas y otras potenciales limitaciones para ser conside radas antes de la implementación de los programas de vacunación son discutidas en este artículo, en conjunto con una serie de recomendaciones sobre cómo abordar estas preocupaciones. Estas recomendaciones pueden resultar de utilidad para los tomadores de decisión y actores sanitarios, en esta etapa temprana del desarrollo de un programa de vacunación.

Abstract A new dengue vaccine has recently been licensed in Argentina, with the Argentine government planning to acquire it in order to develop a vaccination strategy. As the disease is gradually following a path to endemicity in some regions of the country, the incorporation of these vaccines will have the potential to tackle the grow ing incidence of the disease and to reduce the disease burden. However, the establishment of the vaccination programme may also be susceptible of threats related to the epidemiological shift of the disease. Selecting a specific age group for the vaccine may result in a change in the peak incidence to other age groups more suscep tible to severe forms of the disease, such as children or the elderly. Furthermore, the perception of protection following vaccine introduction in one jurisdiction may reduce adherence to vector control activities, increasing the risk of virus introduction and transmission in other areas not prioritised by the vaccination strategy, and the risk of other arboviral diseases such as Zika and chikun gunya fever. These and other potential limitations to be considered prior to the implementation of vaccination programmes are discussed in this article, with a series of recommendations on how to address these concerns. These recommendations can help decision makers and public health practitioners at this early stage of the vac cination programme development.

Acceptability of a hypothetical dengue vaccine and the potential impact of dengue vaccination on personal vector control behavior: a qualitative study in Fortaleza, Brazil.

BACKGROUND: Dengue is the most rapidly spreading viral vector-borne disease in the world. Promising new dengue vaccines have contributed to a growing consensus that effective dengue control will require integrated strategies of vaccination and vector control. In this qualitative study, we explored the perspectives of residents of Fortaleza, Brazil on acceptability of a hypothetical safe and effective dengue vaccine, specific drivers of dengue vaccine acceptance or hesitance, and the expected impact of dengue vaccination on their personal vector control practices. METHODS: A total of 43 in-depth interviews were conducted from April to June 2022 with Fortaleza residents from a diverse range of educational and professional backgrounds, with and without recent personal experiences of symptomatic dengue infections. Data were analyzed using the principles of inductive grounded theory methodology. RESULTS: Our findings indicate that knowledge of dengue transmission, symptoms, and prevention methods was strong across respondents. Respondents described willingness to accept a hypothetical dengue vaccine for themselves and their children, while emphasizing that the vaccine must be demonstrably safe and effective. Respondents expressed diverse perspectives on how receiving a safe and effective dengue vaccine might influence their personal vector control behaviors, relating these behaviors to their perception of risk from other Aedes mosquito-carried infections and beliefs about the role of vector control in maintaining household cleanliness. CONCLUSIONS: Our study findings provide community-level perspectives on dengue vaccination and its potential impact on personal vector control behavior for policymakers and program managers in Fortaleza to consider as new dengue vaccines become available. With the introduction of any new dengue vaccine, community perspectives and emerging concerns that may drive vaccine hesitancy should be continuously sought out. Improved urban infrastructure and efforts to engage individuals and communities in vector control may be needed to optimize the impact of future dengue vaccinations and prevent rising cases of other arboviruses such as Zika and chikungunya.

Vaccination coverage and adherence to a dengue vaccination program in the state of Paraná, Brazil.

The success of vaccination programs depends on the level of acceptance of the vaccine to achieve high vaccine coverage rates (VCR). Vaccine hesitancy is a challenge, especially concerning new vaccines. Dengue vaccine, Dengvaxia®, was licensed in Brazil in 2015 and implemented, in a pioneering publicly-funded initiative in the state of Paraná, between 2016 and 2018. The vaccination program took place in five phases in the 30 municipalities most affected by dengue in the state, targeting individuals from nine to 44 years-old in two cities and from 15 to 27 years-old in the other 28 municipalities, totaling a target population of 500,000 individuals. A cross-sectional descriptive study was carried out to assess VCR and adherence to the dengue vaccine in this program. VCR, dropout ratio (DR), and compliance with the vaccination schedule (CVS) were analyzed by sex, age group, and municipality size. A total of 302,603 individuals (60.5%) received ≥ 1 dose, 44.2% received ≥ 2 doses, and 28.6% 3 doses. The DR was 52.8%. Among individuals who started vaccination, 40.6% achieved CVS. The highest VCR, highest CVS, and lowest DR occurred in the age group from 9 to 14 years old and from 28 to 44 years old and in smaller municipalities. A greater proportion of men started vaccination (male 64.0%; female 57.1%) however, the DR was higher in men (male 55.4%; female 49.9%), and a higher percentage of women completed the vaccination schedule according to the recommendations (CVS male 37.8%; female 43.6%). Differences were noted in the CVS according to the initial phase of the program (first phase 50.8%; second phase 18.8%). The heterogeneity in vaccine uptake and compliance according to sex, age, and municipality size suggests the need for differentiated strategies to address challenges with new and multiple-dose vaccines.

Eficacia y seguridad de la vacuna contra el dengue / Efficacy and safety of dengue vaccine

El dengue es un problema creciente para la salud pública mundial. En Argentina, los casos se han ido incrementado en los últimos años. La vacuna Dengvaxia (CYD-TDV) fue aprobada por la Agencia Nacional de Medicamentos, Alimentos y Tecnología (ANMAT) en 2017, y actualmente está indicada para personas entre los 9 y 45 años de edad que residan enzonas endémicas. A partir de la consulta de una paciente sobre la posibilidad de vacunarse contra el dengue, la autora se plantea la pertinencia de su indicación, teniendo en cuenta la eficacia y seguridad de la vacuna. Luego de una búsqueda rápida se encontró evidencia que señala que la vacuna contra el dengue CYD-TDV mostró poca eficacia en comparación con otras vacunas disponibles en el mercado, siendo más segura y eficaz en personas que ya han sido infectadas anteriormente por el virus del dengue (sujetos seropositivos). En cambio, se observó un aumento del riesgo de dengue grave en los infectados por vez primera tras la vacunación (sujetos seronegativos). Se concluye que la estrategia recomendada consiste en vacunar únicamente a las personas que hayan tenido infección por dengue con anterioridad, consistiendo en una buena práctica la toma de decisiones compartidas con cada paciente. (AU)

Dengue is a growing problem for global public health. In Argentina, cases have been increasing in recent years. The Dengvaxia vaccine (CYD-TDV) was approved by the National Agency for Medicines, Food and Technology in 2017, and it is currently indicated for people between 9 and 45 years of age who reside in endemic areas. Based on the consultation of a patient about the possibility of being vaccinated against dengue, the author considers the relevance of its indication, taking into account the efficacy and safety of the vaccine. After a quick search, evidence was found that indicates that the CYD-TDV dengue vaccine showed little efficacy compared to other vaccines available on the market, being safer and more effective in people who have already been previously infected by the dengue virus (seropositive subjects). In contrast, an increased risk of severe dengue was observed in those infected for the first time after vaccination (seronegative subjects). It is concluded that the recommended strategy consists of vaccinating only people who have had dengue infection before, making shared decisions with each patient a good practice. (AU)

Transcutaneous Administration of Dengue Vaccines.

In the present study, we evaluated the immunological responses induced by dengue vaccines under experimental conditions after delivery via a transcutaneous (TC) route. Vaccines against type 2 Dengue virus particles (DENV2 New Guinea C (NGC) strain) combined with enterotoxigenic Escherichia coli (ETEC) heat-labile toxin (LT) were administered to BALB/c mice in a three-dose immunization regimen via the TC route. As a control for the parenteral administration route, other mouse groups were immunized with the same vaccine formulation via the intradermic (ID) route. Our results showed that mice vaccinated either via the TC or ID routes developed similar protective immunity, as measured after lethal challenges with the DENV2 NGC strain. Notably, the vaccine delivered through the TC route induced lower serum antibody (IgG) responses with regard to ID-immunized mice, particularly after the third dose. The protective immunity elicited in TC-immunized mice was attributed to different antigen-specific antibody properties, such as epitope specificity and IgG subclass responses, and cellular immune responses, as determined by cytokine secretion profiles. Altogether, the results of the present study demonstrate the immunogenicity and protective properties of a dengue vaccine delivered through the TC route and offer perspectives for future clinical applications.

Designing effective control of dengue with combined interventions.

Viruses transmitted by Aedes mosquitoes, such as dengue, Zika, and chikungunya, have expanding ranges and seem unabated by current vector control programs. Effective control of these pathogens likely requires integrated approaches. We evaluated dengue management options in an endemic setting that combine novel vector control and vaccination using an agent-based model for Yucatán, Mexico, fit to 37 y of data. Our intervention models are informed by targeted indoor residual spraying (TIRS) experiments; trial outcomes and World Health Organization (WHO) testing guidance for the only licensed dengue vaccine, CYD-TDV; and preliminary results for in-development vaccines. We evaluated several implementation options, including varying coverage levels; staggered introductions; and a one-time, large-scale vaccination campaign. We found that CYD-TDV and TIRS interfere: while the combination outperforms either alone, performance is lower than estimated from their separate benefits. The conventional model hypothesized for in-development vaccines, however, performs synergistically with TIRS, amplifying effectiveness well beyond their independent impacts. If the preliminary performance by either of the in-development vaccines is upheld, a one-time, large-scale campaign followed by routine vaccination alongside aggressive new vector control could enable short-term elimination, with nearly all cases avoided for a decade despite continuous dengue reintroductions. If elimination is impracticable due to resource limitations, less ambitious implementations of this combination still produce amplified, longer-lasting effectiveness over single-approach interventions.

A Dengue Vaccine: Will It be Accepted and Is It Feasible? Lessons from Barranquilla, Colombia, and Merida, Venezuela.

With one vaccine on the market and others in clinical trials, policy makers in dengue endemic regions face the decision of whether to introduce a dengue vaccine in their communities. The World Health Organization (WHO) recommends that individualized assessments be conducted before any vaccine introduction to evaluate disease burden and the strength of current vaccination programs. This study seeks to aid in that decision-making process by examining the acceptability and feasibility of dengue vaccine introduction in Barranquilla, Colombia, and Merida, Venezuela. Surveys were administered February-June of 2018 for three groups: patients (n = 351), health professionals (n = 197), and government officials (n = 26). In Barranquilla, most respondents reported dengue to be a moderate-severe problem, that a dengue vaccine would be useful in their communities, and that their current vaccination programs could handle the addition of a new vaccine. In Venezuela, respondents were less likely to view dengue as a major concern and listed multiple barriers to not just dengue vaccine introduction, but to providing current vaccines as well. Further work is needed in Colombia to more objectively assess the country's readiness as a whole for a future dengue vaccine. As political and social unrest continues in Venezuela, however, future initiatives should focus on trust and capacity building. This study can serve as a framework for future assessments of the acceptability and feasibility of a dengue vaccine in both targeted areas and on larger scales.

Biological view of vaccination described by mathematical modellings: from rubella to dengue vaccines.

The only rubella vaccine available in North America is the RA27/3 strain (isolated from the kidney of a rubella-infected fetus and attenuated) licensed in 1979, which substituted HPV77/DE5 strain vaccine due to concerns about waning immunity. The first dengue vaccine (Dengvaxia CYDTDV) was first registered in Mexico in December, 2015, which is a live recombinant tetravalent dengue vaccine. Rubella vaccine was applied since 1969, but tetravalent dengue vaccine is being used in large scale nowadays. In the past, based on unavailable information regarded to rubella vaccine, mathematical models were used to design vaccination schemes in order to avoid congenital rubella syndrome (CRS). Currently, knowing that vaccine does not result in CRS, rubella vaccination is modelled as usual childhood infection. This experience of updated biological knowledge that influenced mathematical modellings of rubella vaccination is taken into account to reflect about the tetravalent dengue vaccine. We also address a discussion about the security of vaccination strategies.

Systematic review of dengue vaccine efficacy.

BACKGROUND: Dengue is an arbovirus that has rapidly spread worldwide, and the incidence of dengue has greatly increased in recent decades. The actual numbers of dengue cases are underreported, and many cases are not classified correctly. Recent estimates indicate that 390 million dengue infections occur per year (95% CI, 284-528 million), of which 96 million (67-136 million) are symptomatic infections of any severity. One of the goals of the World Health Organization is to reduce dengue mortality by 50% by the year 2020. The use of a vaccine can be an important strategy to achieve this goal. Vaccines for dengue are in various stages of development; in Brazil, only one commercial formulation is available (CYD-TDV), which was developed by Sanofi Pasteur. METHODS: To evaluate the efficacy of Dengue vaccine, a systematic review with a meta-analysis was conducted using randomized controlled clinical trials published between 2000 and 2017 that were identified in the MEDLINE databases via PubMed, LILACS, Cochrane Library, and EMBASE. The selection was performed by two reviewers independently, with disagreements resolved by a third reviewer. RESULTS: Seven clinical trials were included, with a total of 36,371 participants (66,511 person-years) between the ages of 2 and 45 years. The meta-analysis using the random-effects model estimated the efficacy of the vaccine at 44%, with a range from 25 to 59% and high heterogeneity (I2 = 80.1%). The serotype-stratified meta-analysis was homogeneous, except for serotype 2, with the heterogeneity of 64.5%. Most of the vaccinated individuals had previous immunity for at least one serotype, which generated safety concerns in individuals without previous immunity. CONCLUSIONS: Compared with other commercially available vaccines, the dengue vaccine showed poor efficacy.

Systematic review of health economic evaluation studies of dengue vaccines.

OBJECTIVES: To review the literature on economic evaluation of dengue vaccination to produce evidence to support a local cost-effectiveness study and to subsidize the decision to introduce a dengue vaccine in the Brazilian National Immunization Program. METHODS: We systematically searched multiple databases (MEDLINE (via PubMed), EMBASE, SCOPUS, NHS Economic Evaluation Database (NHS EED), HTA Database (via Centre for Reviews and Dissemination - CRD) and LILACS), selecting full HEEs of dengue vaccine. Two independent reviewers screened articles for relevance and extracted the data. The methodology for the quality reporting was assessed using CHEERS checklist. We performed a qualitative narrative synthesis. RESULTS: Thirteen studies conducted in Asian and Latin America countries were reviewed. All studies were favorable to the incorporation of the vaccine. However, the assumptions and values assumed for vaccine efficacy, safety and duration of protection, as well as the choice of the study population and the type of model used in the analyses, associated to an insufficient reporting of the methodological steps, affect the validity of the studies' results. The quality reporting appraisal showed that the majority (8/13) of the studies reported less than 55% of the CHEERS checklists' items. CONCLUSIONS: This systematic review shows that the economic evaluation of dengue vaccination did not adhere to key recommended general methods for economic evaluation. The presented cost-effectiveness results should not be transferred to other countries. It is recommended to conduct studies with local epidemiological and cost data, as well as assumptions about vaccination that reflect the results observed in clinical trials.

A multi-country study of dengue vaccination strategies with Dengvaxia and a future vaccine candidate in three dengue-endemic countries: Vietnam, Thailand, and Colombia.

BACKGROUND: The dengue vaccination era began when Dengvaxia (CYD-TDV) became available in 2016. In addition, several second-generation vaccine candidates are currently in phase 3 trials, suggesting that a broader availability of dengue vaccines may be possible in the near future. Advancing on the recent WHO-SAGE recommendations for the safe and effective use of CYD-TDV at the regional level on average, this study investigates the vaccination impacts and cost-effectiveness of CYD-TDV and of a hypothetical new vaccine candidate (NVC) in a country-specific manner for three endemic countries: Vietnam, Thailand, and Colombia. METHODS: The vaccination impacts of CYD-TDV and NVC were derived by fitting the empirical seroprevalence rates of 9 year olds into an individual-based meta-population transmission model, previously used for the WHO-SAGE working group. The disability-adjusted life years were estimated by applying country-specific parametric values. The cost-effectiveness analyses of four intervention strategies in combination with routine and catch-up campaigns were compared for both vaccines to inform decision makers regarding the most suitable immunization program in each of the three countries. RESULTS AND CONCLUSION: Both CYD-TDV and NVC could be cost-effective at the DALY threshold cost of $2000 depending upon vaccination costs. With CYD-TDV, targeting 9 year olds in routine vaccination programs and 10-29 year olds as a one-off catch-up campaign was the most cost-effective strategy in all three countries. With NVC, while the most cost-effective strategy was to vaccinate 9-29 and 9-18 year olds in Vietnam and Thailand respectively, vaccinating younger age cohorts between 1 and 5 years old in Colombia was more cost-effective than other strategies. Given that three countries will soon face decisions regarding whether and how to incorporate CYD-TDV or future dengue vaccines into their budget-constrained national immunization programs, the current study outcomes can be used to help decision makers understand the expected impacts and cost-effectiveness of such vaccines.

Dinámica de la respuesta inmune en la infección por virus del dengue / Dynamics of the immune response in dengue virus infection

La infección por virus del dengue se ha incrementado enormemente en las últimas décadas. El desarrollo de vacunas constituye una estrategia fundamental en el control de la enfermedad. Sin embargo, el sistema inmune juega un papel fundamental en la aparición de formas graves, de ahí que sea importante comprender la inmunopatogenia de la enfermedad, propósito al que coadyuva esta revisión. Se explica como el virus entra a las células huésped mediado por receptores relacionados con el sistema inmune. La presencia de anticuerpos heterólogos no neutralizantes amplifica la infección viral. Durante la respuesta inmune se producen citocinas proinflamatorias, lo que unido a la acción de los anticuerpos heterólogos, el sistema de complemento y la acción de poblaciones celulares inducen el daño endotelial y los trastornos de la coagulación característicos de esta enfermedad. Finalmente basado en los signos de alarma que han sido asociados con las formas graves, la OMS emitió una nueva clasificación que orienta hacia un diagnóstico oportuno.

Dengue virus infection has noticeably increased in recent decades. Vaccines development constitutes an essential strategy in the disease control. The immune system, however, plays an essential role in the appearance of severe forms, reason which provides a great importance to understanding the disease immuno-pathogenesis; this review contributes to this purpose. It is explained how the virus enters host cells mediated by receptors related to the immune system. The presence of non-neutralizing heterologous antibodies amplifies the viral infection. During the immune response, inflammatory cytokines are produced, which, together with the action of heterologous antibodies, the complement system and the action of cell populations, induce endothelial damage and the characteristic coagulation disorders of this disease. Finally, based on the warning signs associated with severe forms, the WHO issued a new classification which guides towards an opportune diagnosis.

Estimation of expected dengue seroprevalence from passive epidemiological surveillance systems in selected areas of Argentina: A proxy to evaluate the applicability of dengue vaccination.

BACKGROUND: Current recommendations about dengue vaccination by the World Health Organization depend on seroprevalence levels and serological status in populations and individuals. However, seroprevalence estimation may be difficult due to a diversity of factors. Thus, estimation through models using data from epidemiological surveillance systems could be an alternative procedure to achieve this goal. OBJECTIVE: To estimate the expected dengue seroprevalence in children of selected areas in Argentina, using a simple model based on data from passive epidemiological surveillance systems. METHODS: A Markov model using a simulated cohort of individuals from age 0 to 9 years was developed. Parameters regarding the reported annual incidence of dengue, proportion of inapparent cases, and expansion factors for outpatient and hospitalized cases were considered as transition probabilities. The proportion of immune population at 9 years of age was taken as a proxy of the expected seroprevalence, considering this age as targeted for vaccination. The model was used to evaluate the expected seroprevalence in Misiones and Salta provinces and in Buenos Aires city, three settings showing different climatic favorability for dengue. RESULTS: The estimates of the seroprevalence for the group of 9-year-old children for Misiones was 79% (95%CI:46-100%), and for Salta 22% (95%CI:14-30%), both located in northeastern and northwestern Argentina, respectively. Buenos Aires city, from central Argentina, showed a likely seroprevalence of 7% (95%CI: 3-11%). According to the deterministic sensitivity analyses, the parameter showing the highest influence on these results was the probability of inapparent cases. CONCLUSIONS: This model allowed the estimation of dengue seroprevalence in settings where this information is not available. Particularly for Misiones, the expected seroprevalence was higher than 70% in a wide range of scenarios, thus in this province a vaccination strategy directed to seropositive children of >9 years should be analyzed, including further considerations as safety, cost-effectiveness, and budget impact.

Razones para recomendar la vacunación contra el dengue en Isla de Pascua: Opinión del Comité de Inmunizaciones de la Sociedad Chilena de Infectología / Reasons to recommend vaccination against dengue in Easter Island: Immunization Advisory Committee of Sociedad Chilena de Infectología

Dengue was first diagnosed on Easter Island on year 2002 and thereafter recurrent outbreaks have occurred involving different serotypes of dengue virus. Its vector, Aedes aegypti has not been eliminated despite the small size of the island. Conditions at the local hospital preclude adequate management of severe and hemorrhagic cases due to the absence of a Critical Care Unit as well as no availability of platelets, or plasma units for transfusion. Besides, transfer, of severely affected patients to continental Chile is cumbersome, slow and expensive. In this scenario, it is advisable to implement selective vaccination of Easter Island habitants with an available quadrivalent attenuated dengue vaccine with the aim to reduce hemorrhagic and severe dengue cases. This strategy should not replace permanent efforts to control waste disposal sites, water sources, maintain vector surveillance and increase education of the population.

El dengue surgió el año 2002 en Isla de Pascua y se ha presentado en brotes intercurrentes desde entonces con aparición de diferentes serotipos. El vector Aedes aegypti no ha logrado ser eliminado a pesar del pequeño tamaño de la isla y las condiciones del hospital local no permiten el manejo de casos graves por ausencia de una unidad de cuidados intensivos y disponibilidad de transfusiones de plaquetas o plasma fresco congelado. Además, el traslado de pacientes graves hacia el continente no es inmediato y es muy costoso. En este escenario, es aconsejable vacunar selectivamente a la población residente con la vacuna cuadrivalente atenuada para disminuir la probabilidad de dengue grave. Esta estrategia no debe reemplazar los esfuerzos para el control de basurales, fuentes de agua, vigilancia del vector y educación de la población.

Las vacunas contra el dengue ¿una realidad para la Argentina? / Dengue vaccines. A reality for Argentina?

Los brotes de dengue se suceden anualmente en Argentina desde el año 1998. Existen vacunas contra esta enfermedad en distintos grados de desarrollo que han sido probadas en países endémicos. La más avanzada hasta el momento fue autorizada para su comercialización en tres países de América Latina, para niños mayores de 9 años. En este artículo se discuten los beneficios e inconvenientes de las vacunas, así como los desafíos para la implementación de una estrategia de vacunación. Asimismo, se plantea la necesidad de una estratificación de riesgo con nuevos criterios y visión multidisciplinaria como un camino posible para evaluar la pertinencia de un programa de vacunación en las áreas con mayor riesgo de transmisión, y/o en individuos con mayor riesgo de dengue grave. Se sugiere también que la definición del estatus de endemicidad debe tomar en cuenta a las realidades locales. Por último, este artículo propone una discusión amplia de las evidencias, impacto esperado y aspectos instrumentales que estarían involucrados en la incorporación de una vacuna contra el dengue, ya en mercado o en desarrollo, en el programa nacional de inmunizaciones, y especialmente a qué subpoblaciones debería ser dirigida para que la estrategia de inmunización sea costo-efectiva.

Dengue outbreaks have occurred yearly in Argentina since 1998. A number of candidate vaccines have been tested in endemic countries. The most advanced one was licensed in three countries of Latin America for children over 9 years of age. In the present article the benefits and drawbacks of these vaccines as well as the challenges for the implementation of a vaccination strategy in Argentina are discussed. Furthermore, a risk stratification strategy with new criteria and a multidisciplinary vision is suggested as a possible path for the assessment of the pertinence of a vaccination program in areas showing the highest risk of dengue transmission and/or for people at the greatest risk of developing severe dengue. It is also suggested that the definition regarding the status of endemicity should take into account the local realities. Finally, this paper proposes a broad discussion on the evidences, the expected impact and instrumental aspects that would be involved in the incorporation of a dengue vaccine, marketed or in development, into the national immunization program, and especially which subpopulation should be targeted for the immunization strategy to be cost-effective.

[Dengue vaccines. A reality for Argentina?]. / Las vacunas contra el dengue ¿Una realidad para la Argentina?

Dengue outbreaks have occurred yearly in Argentina since 1998. A number of candidate vaccines have been tested in endemic countries. The most advanced one was licensed in three countries of Latin America for children over 9 years of age. In the present article the benefits and drawbacks of these vaccines as well as the challenges for the implementation of a vaccination strategy in Argentina are discussed. Furthermore, a risk stratification strategy with new criteria and a multidisciplinary vision is suggested as a possible path for the assessment of the pertinence of a vaccination program in areas showing the highest risk of dengue transmission and/or for people at the greatest risk of developing severe dengue. It is also suggested that the definition regarding the status of endemicity should take into account the local realities. Finally, this paper proposes a broad discussion on the evidences, the expected impact and instrumental aspects that would be involved in the incorporation of a dengue vaccine, marketed or in development, into the national immunization program, and especially which subpopulation should be targeted for the immunization strategy to be cost-effective.

Cost-utility analysis of dengue vaccination in a country with heterogeneous risk of dengue transmission.

BACKGROUND: Dengue is one of the most important vector-borne diseases worldwide, and annually, nearly 390 million people are infected and 500,000 patients are hospitalized for severe dengue. Argentina has great variability in the risk of dengue transmission due to eco-climatic reasons. Currently no vaccines are available for dengue even though several vaccines are under development. OBJECTIVE: The aim of this study was to estimate the cost-effectiveness of a dengue vaccine in a country with heterogeneous risk of dengue transmission like Argentina. METHODS: The analysis was carried out from a societal perspective using a Markov model that included both vaccine and disease parameters. Utility was measured as disability adjusted life years (DALYs) averted, and the incremental cost-effectiveness ratio (ICER) of the vaccination was expressed in 2014 American dollars (US$) per DALY averted. One-way and probabilistic sensitivity analyses were performed to evaluate uncertainty in model outcomes, and a threshold analysis was conducted to estimate the highest possible price of the vaccine. RESULTS: The ICER of the vaccination program was found to be US$ 5714 per DALY averted. This value is lower than 3 times the per capita GDP of Argentina (US$ 38,619 in 2014); 54.9% of the simulations were below this value. If a vaccination program would be implemented the maximum vaccine price per dose has to be US$1.49 for a vaccination at national level or US$28.72 for a targeted vaccination in high transmission areas. CONCLUSIONS: These results demonstrate that vaccination against dengue would be cost-effective in Argentina, especially if carried out in predetermined regions at high risk of dengue transmission. However, these results should be interpreted with caution because the probabilistic sensitivity analysis showed that there was considerable uncertainty around the ICER value. The influence of variations in vaccine efficacy, cost and other important parameters are discussed in the text.