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Dr. Anavaj Sakuntabhai (Institut Pasteur): genetic susceptibility to dengue

Dr. Anavaj Sakuntabhai

Institut Pasteur

Functional Genetics of Infectious Diseases

In the age of the 24 hour news-cycle we are all witness to almost continous coverage of dengue outbreaks across South East Asia and Latin America: outside of the obvious regional and climatic vector-disease ditribution, what role does host genetics play in these outbreaks and their severity?

We have published two articles. The first one was based on a study in Cuba, which showed that African ancestry has variants of genes which confer resistance to dengue disease. The other study from Thailand demonstrated that North East Asians and South East Asians are more susceptible to dengue and severe dengue than South Asians. We also identified the genes and pathways involved. We also demonstrated that people who got dengue infection without symptoms could transmit the virus to mosquitoes. This finding is important because these people were not under any surveillance systems and these are the majority of cases of infection (estimated at about 75%). They can travel and spread the virus to uninfected regions.

Which patient popultaion is in your opinion most suceptible to dengue and why?

In my opinion, it would be South East Asians, for two main reasons: firstly, from epidemiological data we know that we have more severe dengue in this region and secondly, we have also confirmed this with our human genetic study.

Moving from the Tropics to Europe, we have seen a very successful dengue outbreak management programme on the island of Madeira, Portugal. What are the key factors affecting dengue transmission and disease dynamics?

The keys factors affecting dengue transmission and disease dynamics are to be found within mosquitoes and humans. We tend to ignore that humans are one of major factors for dengue transmission. Our group demonstrated that people could have a dengue infection without symptoms and can still transmit this virus to mosquitoes. Most research on dengue transmission and control only focused on mosquitoes. Therefore, we also need to focus on why some humans are better at transmitting the virus to mosquitoes.

How do you anticpate that your work will translate into new tools? What will these new tools look like and what will they try to do?

From our study of immune response in asymptomatic dengue infection, we found that cellular immunity is important in clearing the virus without development of the disease. All dengue vaccine candidates, as well as the current vaccine, focused on induction of antibodies, not cellular immunity. Some antibodies against the dengue virus at the intermediate level have been shown to enhance the severity of subsequent infection. Therefore, we hypothesize that a dengue vaccine which induces cellular immunity will be more efficient and safer than the ones which induce antibodies. It has been shown in the mouse model that cellular immunity can also minimize the effect of antibody-dependent enhancement.

How will your work affect dengue control strategies? Will this be different in different regions and if so how so?

Dengue control strategy has been focused on the reduction of mosquito density, which has been proved inefficient. We therefore propose a new strategy to focus on both humans and mosquitoes. Our current research is trying to find factors in humans, which modulate the viral transmission. We are working towards the development of a next generation dengue vaccine, which can both reduce the severity of the disease and minimize transmission.

We are all aware of the WHO's position on the need for an integrated approach to combatting dengue. From your genetics and transmission perspective, what 'other' disciplines need to get involved and how?

Again, we need to look wider than just mosquitoes for controlling dengue. Human factor is one; the other important factor is environment including urbanization, garbage management etc. These factors could be the most important and are manageable.

As you know we are driving a World Dengue Day petition that will be aiming for the United Nations to ratify a galvinising day for all involved in the fight against dengue: do you support this and why do you think we need such a day?

I definitely support this initiative. We need to make people aware of this virus. It is not as scary as Ebola. It does not cause high mortality rates. However, it can have tremendous impact and burden on an individual’s life, including the work ability of patients, their families, parents... It has a significant effect on the economy of countries. And most importantly, it is spreading to uninfected areas.


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