Point/Counter

Are there sufficient data to implement wide-scale dengue vaccination in endemic countries?

As a leading cause of serious illness and death among Latin American and Asian children and with more than 40% of the world’s population at risk for the disease, dengue is one of the most widespread infectious diseases globally.

Dengue incidence has increased 30-fold during the past 50 years, according to WHO. Before 1970, nine countries had experienced severe dengue epidemics. Since then, dengue has become endemic in more than 100 countries in Africa, North America, the Eastern Mediterranean, Southeast Asia, South America and the Western Pacific. Although dengue control efforts have primarily relied on vector control and disease surveillance, the development and implementation of an effective vaccine remains key to eliminating dengue.

In this Point/Counter, two clinicians debate whether there are sufficient data – including effective disease surveillance and reporting – and adequate resources to implement wide-scale dengue vaccination in endemic countries.

Are there sufficient data to implement wide-scale dengue vaccination in endemic countries?

POINT

Successful vaccination implementation is feasible in endemic countries but comes with significant complications.

It is complicated to try to put all the countries in one category because there are different types of countries within the title ‘endemic.’ In the Americas alone, there are significant differences between Columbia, Brazil and Mexico compared with smaller countries in Central America and even some of the Caribbean islands.

The difficulty we have been trying to address, specifically here in Mexico, is that dengue is a disease that has regional differences within countries; to determine vaccine efficacy in a particular country, you have to define geographical areas that are at risk or communities in which the majority of transmission occurs.

For instance, there are communities within endemic areas that are not necessarily where people transmit and catch dengue. There are hubs — transportation hubs, commercial hubs, educational hubs — in which people from different communities travel and where dengue is transmitted and exchanged.

Additionally, we cannot simply say, ‘Let’s incorporate the dengue vaccine and make it part of a universal vaccine.’ The process is not that straight forward. In Mexico, for instance, 26 out of 32 states are endemic with sustained person-to-person transmission through the vector; however, there are parts within states that do not have the vector due to the altitude.
Countries would have to decide whether to use the dengue vaccine only in the communities that lie within the boundaries of mosquito habitats or include other communities that experience a flow of individuals in one of the two directions.

Also, in Mexico, there are different epidemiological profiles in different areas of the country. While most of the country experiences a peak in dengue cases during childhood from first disease exposure, there are some states with patients that experience a second peak in dengue cases around 40 years of age.

Another obstacle to effective dengue vaccine implementation is the distribution of the virus. As we have seen with the Sanofi vaccine, the level of protection varies against each of the four dengue viruses, and Mexico does not have a homogenous circulation of the viruses.

In the case of Mexico, we have realized that we have to be very careful in how to define the geographical area, the levels of dengue transmission, the epidemiological profiles, the virological profiles that we are facing, as well as the flow of people around dengue-transmitting communities, in order to decide how widespread we need to implement the vaccine.

Miguel Betancourt Cravioto, MD, MSc, DrPH, is the director of global solutions at the Carlos Slim Foundation in Mexico City. Disclosure: Betancourt Cravioto reports no relevant financial disclosures.

COUNTER

We need more evidence to know exactly what challenges endemic countries may face when implementing dengue vaccine.

Vaccine implementation is evidence-based. A vaccine schedule needs to be determined — will the vaccine be given in the first year of life, the second year of life? Is catch-up immunization needed? None of these variables have been figured out for a dengue vaccine. Demonstration projects, which examine feasibility and disease prevention need to be conducted.

Ideally, if we had the perfect vaccine that worked in the first year of life, it could be added into the Expanded Program for Immunization, administered during pre-existing immunization visits and successfully integrated into vaccination programs in endemic countries.

However, if the dengue vaccine turns out to be similar to the tetravalent vaccine from Sanofi Pasteur (CYD-TDV), which is administered in the second year of life or after maternal antibodies have disappeared, it will be more difficult to implement in endemic countries. This is because many countries do not have existing routine immunization visits that match a schedule when CYD-TDV should be administered.

Based on our understanding of the epidemiology of dengue virus transmission, catch-up immunization will likely be necessary for successful dengue vaccine implementation. This brings up the question: How can we reach children in older age groups (eg, ages 2 to 10 years) to vaccinate them? School-based vaccination systems and mass vaccination strategies are possible options.

There have been well-documented demonstration projects conducted in Taiwan, Indonesia and China that addressed operational issues related to the introduction of new vaccines in an existing infrastructure, for example, hepatitis B vaccine and the administration of the birth dose. This will likely need to happen for a dengue vaccine once we have one and know how it performs.

Currently, we have one promising vaccine candidate that has not progressed past controlled efficacy trials, and thus, how it would be used in a community-based program has yet to be determined. This needs to be determined so we can assess feasibility operational issues and disease prevention.

Harold S. Margolis, MD, is the chief of the dengue branch of the CDC, San Juan, Puerto Rico. Disclosure: Margolis reports no relevant financial disclosures.