DW: In 2016, the Philippines launched the world's first public dengue vaccine program with the dengue vaccine Dengvaxia from Sanofi Pasteur. Over 800,000 children have already been vaccinated. In December last year, the French pharmaceutical company itself warned that vaccination in children who had not previously been infected by the dengue virus, can lead to serious health risks. As a result, the Philippine Ministry of Health stopped the mass vaccination program. Now, three out of a total of 14 examined deaths have been linked to the controversial vaccine. Mr. Schmidt-Chanasit, what's the danger of the vaccine?

Schmidt-Chanasit: The vaccine itself has no side effects. That means after the injection, nothing bad happens. However, if you vaccinate children who have not previously had dengue fever infections, severe hemorrhagic dengue fever can occur.

The phenomenon behind it is called Antibody-dependent enhancement. After vaccination, the immune system develops antibodies. An infection with the dengue virus results in the binding of the previously formed antibodies to the virus, which prevents the immune system from blocking it.

The virus can now easily multiply and trigger hemorrhagic dengue fever. This mechanism of antibody-dependent enhancement occurs not only after vaccination, but also in natural infections with a new type of virus. In the end, this means that the vaccine provokes severe health risks without directly causing them.

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So not every dengue virus is the same?

There are four different serotypes of the dengue virus, which means that you can get infected with dengue four times. After the first infection with a dengue virus, the immune system reacts normally by creating antibodies, and usually symptoms can be treated quite well.

But these antibodies can become confused if confronted with another type of the virus later, which leads to hemorrhagic fever. This creates a vaccine gap. Furthermore, the vaccine does not protect equally well against all four virus types. The protection against re-infection by Dengvaxia is 60 percent. For the types 2 and 3, the vaccine is worse, sometimes only 30 percent.

All four virus types occur worldwide, also in the Philippines. But their frequency varies from year to year, from month to month. This is a very complex network. Of course, humans develop immunity to the currently circulating virus type, resulting in a gap for another type.

More than 800,000 children have been vaccinated with Sanofi's Dengvaxia. Why have doctors not previously checked if they've already had a viral infection?

That would be very time-consuming with such a comprehensive vaccination program. A specific diagnosis of dengue infections is not that easy. The WHO also made clear that the vaccine should only be used in areas where at least 70 percent of people have already experienced a dengue virus infection.

If this isn't closely regulated and even children, who have not previously been infected by dengue, receive the vaccination, serious health problems can arise. In addition, Dengvaxia must be given three times, to guarantee a real protection. Of course, it would be much easier and cheaper to prescribe a vaccine only once.

Are there any ways to handle these vaccine gaps that occur with Dengvaxia?

Not much can be done about this vaccine now. The existence of gaps in certain serotypes and the antibody-dependent-enhancement phenomenon were already known from Phase III studies. However, these studies were conducted for a very limited period of time and even in countries where not all virus types circulated simultaneously. Here, we have to wait for long-term results.

Takeda Pharmaceuticals or the Butantan Institute in Brazil are developing additional vaccine candidates that are being tested in phase III trials now. It is still unclear whether they will provide sufficient protection even for children previously infected with dengue virus. The results are still pending.

The vaccine program in the Philippines was the first large-scale Dengvaxia vaccine program worldwide. Do you think that other countries like Brazil could also stop vaccination programs? 

The vaccine program in the Philippines was also done to study the long-term effects of the vaccine. You can only see certain effects if you vaccinate widely and many people.

Then each country has to decide on the limits for itself - whether the vaccine is clearly related to three deaths, or fourteen or twenty. Each country determines individually how to deal with such vaccination programs.

So far, no similar cases are known in Brazil or other countries?

Not to that extent. But we also have to be careful, because structures and health reporting systems in other countries are very different and not comparable with the German system. Certain cases can be overseen, that's what we observed with Zika.

And the reporting systems in Brazil are not as good as ours. The investigation into vaccine-related deaths also takes some time in itself. So far, I have not heard anything about Brazil.

Dr. Jonas Schmidt-Chanasit is a professor of virology at the Bernhard Nocht Institute for Tropical Medicine in Hamburg. He works with the World Health Organization to fight vector transmitted hemorrhagic fevers.