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Keyword: dengue

This article was originally published on the Dengue Vaccine Initiative website and is cross-posted here with permission. IVAC is a member of the Dengue Vaccine Initiative (DVI). 

On December 9 2015, Mexico approved Sanofi Pasteur’s dengue vaccine marking the first time a dengue vaccine has been licensed for use in a country. Called Dengvaxia® and developed by the French pharmaceutical company, Sanofi Pasteur, the vaccine was approved for people aged 9 to 45 years in areas that are highly endemic, with a dengue seroprevalence of more than 60 percent.

The Dengue Vaccine Initiative (DVI) views Mexico’s licensure of Dengvaxia® as an important milestone in the fight against dengue. Recent studies have demonstrated that in children and adolescents aged 9 years and above, Dengvaxia® reduces dengue cases overall by approximately 65 percent; dengue cases requiring hospitalization by 81 percent; and severe dengue cases by 93 percent. The vaccine’s efficacy was most apparent in individuals with evidence of prior dengue virus exposure. In children below the age of 9 years and in those with no evidence of prior dengue, the vaccine’s efficacy was substantially lower. There was also an increased risk of cases requiring hospitalization during the third year after vaccine initiation in children under 9.

These results suggest that Dengvaxia® may have significant public health impact in reducing dengue disease burden for people 9 years of age and older, especially in areas with existing high infection rates of dengue. Questions remain regarding Dengvaxia®, including duration of protection, price, and impact on overall dengue virus transmission given that the youngest age groups will not be vaccinated. These and other issues will have to be closely followed in order to ascertain the ultimate impact of this vaccine.

Dengue, also known as “breakbone fever,” is caused by a virus transmitted by Aedes mosquitoes, the same mosquitoes that can transmit chikungunya and Zika virus. Dengue virus causes approximately 400 million infections globally each year. In the Americas alone, dengue’s economic burden has been estimated to cost $2.1 billion dollars a year.

DVI believes that this first vaccine licensure in a dengue-endemic country may pave the way for other countries considering new technologies to fight dengue, but stresses that the decision to introduce a dengue vaccine should follow scientific evidence. Following registration, ministries of health will still face important decisions about whether and how to introduce the vaccine into national programs. These decisions may vary according to the specific demographic characteristics, dengue epidemiology and the capacity of public health systems of each country. Therefore, DVI continues to strongly support increasing efforts to improve endemic countries’ access to the evidence needed to inform vaccine introduction decisions.

DVI also welcomes the decision by Mexico as an opportunity to increase our understanding of the questions raised above, as well as the effectiveness of the vaccine in field conditions. DVI recognizes the importance of effective integration of dengue prevention and control strategies, notably vaccination and vector-control approaches, to comprehensively reduce dengue. DVI also encourages the global health community to facilitate and support mechanisms for regional knowledge transfers and information sharing among endemic countries to collectively fight dengue and other vector-borne diseases that are also on the rise. We hope this development spurs other vaccine candidates currently in clinical development to continue to progress in the pipeline.

About the Dengue Vaccine Initiative
The Dengue Vaccine Initiative is an international consortium of the International Vaccine Institute, the World Health Organization Initiative for Vaccine Research, the International Vaccine Access Center at the Johns Hopkins University Bloomberg School of Public Health and the Sabin Vaccine Institute that specializes in research, health economics, policy and advocacy to equip countries with objective information and scientific evidence to fight dengue fever. The Initiative is supported by the Bill & Melinda Gates Foundation.

By Dagna Constenla, Gatien de Broucker, Jorge Martin del Campo and Alexandra Greenberg, IVAC at Johns Hopkins University

This article was originally published on the Dengue Vaccine Initiative's blog and is cross-posted here with permission. IVAC is a member of the Dengue Vaccine Initiative (DVI). 

The successful introduction of a vaccine in affected countries depends heavily on issues such as supply constraints, potential demand, and the impact of policy decisions on future demand and supply. Strategic demand forecasts (SDFs) play a central role in enabling vaccine suppliers, donors, and country-level stakeholders to make informed decisions about vaccine supply, financing, and adoption. In recent years, Accelerated Development and Introduction Plans (ADIPs) have used strategic demand forecasts to adjust market forces for the purpose of accelerating access to new vaccines in countries where they are needed the most.

Our team at the International Vaccine Access Center at Johns Hopkins University has developed several models to estimate the potential demand of dengue vaccine and the costs associated with dengue introduction programs, enabling vaccine suppliers, donors, and country-level stakeholders to make informed decisions about vaccine supply, financing, and adoption. These models have been developed with specific price and coverage assumptions for a variety of target ages and regions.

For the next phase of our project, we will quantify the potential demand for dengue vaccines in Latin America, specifically Mexico, Colombia, Honduras, Paraguay, El Salvador and Peru, taking into account the different scenarios envisioned by each country. Using advanced economic modeling, we aim to determine which factors would drive dengue vaccine demand in these countries.

Building off of our team’s current work on a similar model in Brazil, our team will develop SDF models in collaboration with the Ministries of Health in Mexico, Colombia, Honduras, Paraguay, El Salvador and Peru. While we already have access to relevant information in some of the countries in the region, this collaborative work is essential to ensure that the outputs of the model are relevant and integrated in the decision-making process for each country of interest.

Approaching six different countries at the same time brings many challenges in forecasting the potential demand of the vaccine. Each country has unique characteristics that impact the way vaccine introduction decisions are made. Differing geographical specificities, population demographics, health systems and political infrastructure within countries are good examples.

While strategic demand forecasts can be powerful communication tools, they have certain limitations. SDF depends on the availability of vital pieces of information from stakeholders, namely in-country policy makers, industry, and global donors. Getting information from one stakeholder can be hard without the ability to rely on credible information from other relevant players. All stakeholders must participate with equal commitment towards providing timely and accurate data for the results of strategic demand forecasts to be valid. The lack of reliable information can also make it difficult to verify or test key assumptions made by disease modelers.

In addition to the potential absence of consistent and reliable information, it can be challenging to generalize across developing countries. Significant differences in low- and middle-income countries can make operating conditions vastly divergent on the ground, thereby making broad-based assumptions and generalizations ineffective. Economic and political conditions – such as the unequal distribution of resources and infrastructure, limited budgets, inadequate healthcare policies, and divergent political priorities – can vary substantially between countries, even within the same sub-region.

Lastly, unequal financial commitment from international and local donors makes it difficult to determine the price funders would be willing and able to pay for a vaccine. This is an especially crucial piece of information for low-income countries, which would be unable to introduce a new vaccine without significant support from outside funders. Without this vital information it is challenging to estimate the potential demand for a vaccine in any given market.

So far we are having fruitful discussions with highly positioned local stakeholders in each country including program heads, government officials and representatives at the national and state levels. Their response has surpassed our expectations: they are themselves working to engage new key actors in this discussion. Stakeholders are driven and committed to understanding this disease and to ensuring that a vaccine is introduced in the most efficient and beneficial way for every country.

This research will be critical for laying the groundwork so that countries in the Americas can establish a viable vaccine introduction plan, which can be immediately implemented following the introduction of a dengue vaccine.

By Rebecca Van Roy, Communications Officer, Vaccine Advocacy and Education at Sabin Vaccine Institute

This article was originally published on the Dengue Vaccine Initiative's blog and is cross-posted here with permission. IVAC is a member of the Dengue Vaccine Initiative. (DVI) 

Earlier this year, DVI convened the Americas Dengue Prevention Board along with scientists, global health experts, mathematical modelers and representatives of dengue vaccine manufacturers to discuss updates in dengue vaccines and vaccine introduction. Held in Bogota at the Colombian National Institute of Health (Institituto Nacional de Salud – INS), the meeting was instrumental given the new available clinical trial data, particularly the results of the first Phase 3 trials ever completed for a dengue vaccine candidate. These results demonstrated that a safe and effective dengue vaccine is feasible

A mosquito that costs over $2 billion

Dengue, caused by a small mosquito with black and white striped legs, is the most widespread vector-borne disease in the Americas. In 2013, cases and deaths nearly doubled those of previous years in the region. The southern cone reported the highest incidence rate of cases, but the Andean region reported the highest number of severe cases. The burden of dengue in the Americas has been estimated at more than $2 billion dollars, from hospitalization costs to loss of productivity, representing a significant threat to the wellbeing of the region.

A safe and effective vaccine can help reduce this threat. While the decision to introduce a dengue vaccine can only be driven at the country level, such decisions must be based on sound evidence. DVI Dengue Prevention Board Meetings seek to share and update existing dengue knowledge and identify gaps to ensure countries have scientific, objective data to make informed public health decisions proactively, before a vaccine becomes available.

An open forum to share dengue knowledge –-and its gaps

With this objective in mind, the meeting offered an open forum where participants revisited the minimum requirements for successfully launching a dengue vaccination program among other crucial dengue topics.

On the first day, they reviewed the status of dengue vaccine development with representatives of the manufacturers of the five vaccines in clinical trial (Butantan/NIH, GSK/Fiocruz/Walter Reed, Merck, Sanofi Pasteur and Takeda). They also discussed the applications of mathematical modeling for predicting the impacts of dengue vaccination.

On the second day, country representatives presented the current dengue situation in their homeland and perspectives on dengue vaccine introduction and use.

Finally, the meeting broke into groups to assess considerations for vaccine introduction. The Board then met separately to draw conclusions. The meeting ended with the closing remarks of the Colombian Ministry of Health, who highlighted the spread of dengue and the urgent need to stop it. 

Board Conclusions

The Board noted the critical importance of linked disease surveillance and vaccination registries to monitor coverage and vaccine effectiveness, as well as monitoring for vaccine safety. They also urged the standardization of age groups and case definitions of dengue disease across countries in the region to enable comparisons. They called for further analyses to understand how a limited supply of vaccine might best be utilized in the first year(s) of vaccine introduction. They affirmed the importance of the Pan-American Health Organization (PAHO) for supporting vaccine introductions, particularly through activities such as issuing recommendations for laboratory-based disease surveillance in the region, with an aim of standardizing the diagnostic tests.

The table below summarizes these conclusions. For more detail we encourage you to read the full report here: “Development of Dengue Vaccines: A Review of the Status and Future Considerations.


About Dengue Prevention Boards

In 2007, PDVI (Pediatric Dengue Vaccine Initiative—DVI’s precursor) established two regional Dengue Prevention Boards (DPBs) — one for Asia and one for the Americas. Members of the boards include medical and public health experts, opinion leaders and policy makers from countries in their respective regions. They meet once a year to advise on dengue surveillance, diagnostics, vaccine introduction and communications.

All reports on DPB meetings are published in the DVI website to inform dengue and global health stakeholders.

By Dr. Dagna Constenla and Samantha Clark

For many people throughout the world, the bite of a mosquito is nothing more than a common annoyance. But for individuals living in dengue endemic countries such an annoyance can quickly turn into a life threatening condition. Patients who get sick with dengue fever often experience excruciating headaches, skin rash, and debilitating muscle and joint pains. In severe cases, it can lead to circulatory failure, shock, coma, and death. Though early and effective treatment can ease symptoms, there is no specific cure available for dengue. Efforts to control dengue through preventing mosquito bites and breeding have proven to be largely ineffective due to the mosquito’s tendency to feed throughout the day and ability to breed in even small bits of stagnant water. 


The good news is a vaccine is forthcoming. After more than 60 years, the development of dengue vaccines has accelerated dramatically. Today, several vaccines are in various stages of advanced development, with clinical trials currently underway on five candidate vaccines. While it is difficult to predict the introduction date of a new dengue vaccine, it is expected that one will be available by 2017.

Unlike a new iteration of an existing vaccine, this is uncharted territory. Even if a dengue vaccine is successfully developed, a number of issues remain. How do we predict its use? Its costs? Its cost-effectiveness and affordability? How will countries introduce it?

Perhaps the greatest challenge facing countries will be how to finance the addition of a dengue vaccine to the national vaccine schedule. Vaccine price, availability of funding, and ability to negotiate pricing will all play a critical role in the ability of a country to finance a dengue vaccine. In the Americas, one of the regions where dengue is endemic, a key mechanism for introducing new vaccines has been PAHO’s Revolving Fund. This, along with other options such as pooled procurement, regional and domestic taxes, and low interest multilateral loans are all potential sources of funding.

These and other funding topics will be on the agenda at a workshop starting today and hosted by IVAC, a core partner in the Dengue Vaccine Initiative, in partnership with the International Vaccine Institute, the Sabin Vaccine Institute and the Pan-American Health Organization. The dengue finance workshop will bring together more than 30 experts from the Latin America and Caribbean region, including academics, representatives from bilateral organizations, international public health agencies, nonprofit organizations, international financial institutions, and government agencies. They will convene in Washington, D.C. on July 22-23, 2013 to discuss the challenge of vaccine finance in countries throughout the region.

This workshop will be critical to laying the groundwork for countries to establish a viable financing plan that can be immediately implemented following the introduction of a dengue vaccine. Stay tuned to the IVAC website for more information following the workshop.


Dagna Constenla, PhD, is the Director of Economics & Finance at IVAC. Samantha Clark is a Health Economist at IVAC.

By Dr. Dagna Constenla

Dengue is a painful and debilitating mosquito-borne virus affecting millions of people worldwide every year. Prior to 1970, the disease was endemic in just nine countries. Today it is endemic in more than 100 countries, and WHO estimates that 2.5 billion people are at risk of infection each year.

Dengue Costing Guidelines

Costing Dengue Cases and Outbreaks: A Guide to Current Practices and Procedures

As the global burden of dengue grows, so too does the realization of just how little we know about the health and economic toll of the disease. At the same time, the prospect of a licensed vaccine is growing near, and dengue-endemic countries will have to begin to consider whether or not to introduce the vaccine. An important question they must ask when weighing the costs against the benefits of vaccine introduction is, “how much does dengue cost?”

In response to the growing need to answer that question and lay the groundwork for vaccine decision making by endemic countries, the International Vaccine Access Center, as part of its work on the Dengue Vaccine Initiative (DVI), convened an expert panel in March 2012 to discuss and develop a standardized methodology for estimating costs of dengue in the Americas. The resulting guidelines, Costing Dengue Cases and Outbreaks: A Guide to Current Practices and Procedures, published late last month, aim to ensure robust assessment of the economic burden of dengue infections and to make the results of future dengue cost studies more comparable among Latin American countries. 

The guidelines highlight the many considerations that need to be taken into account when doing analysis to understand the overall economic burden borne by a community as a result of dengue, from understanding the health care system where the study is being conducted to determining the definition of a dengue outbreak. The expert panel concluded that, while there is no single theoretically correct approach to costing dengue, experts generally adhered to certain principles including:

  • The adoption of a societal (broad rather than individual) perspective;
  • The inclusion of all relevant costs and effects (direct medical and non-medical costs of treating a case of dengue, productivity loss of patient and caregiver, etc);
  • The use of an adequate sample size, and;
  • The optimal collection and valuation of unit cost data for use in multi-country settings (making sure that data collected from a variety of countries and settings is collected well and able to be compared).

Creation of these guidelines was just one piece of IVAC’s work on dengue. This spring we plan to convene leaders from Latin America to tackle another key challenge in dengue vaccine introduction – financing. We are also tasked, through the DVI, with linking epidemiologic and economic modeling to create a strategic demand forecast for dengue vaccines.

It is important to note that estimation of dengue costs is a new area in which there is little published literature and in which few of the guideline authors had practical experience. Dengue financing is also an area that experts are just now beginning to address. It is our hope that our work will spur further discussion and research that will help position countries to make well-informed decisions about vaccine introduction. We welcome your thoughts on the guidelines and other dengue costing and financing issues here, or via email to

Dagna Constenla, PhD, is the Director of Economics & Finance at IVAC.