Dengue

In tropical and subtropical countries, the virus causing dengue is spiking. Close to an historic high of over 6 million cases and more than 7,000 dengue-related deaths were reported in over 80 countries and territories in 2023. Most places in Europe remain too cool to favour the mosquito or the virus, but imported dengue cases have been rising in the European region and the impact of climate change appears to be shifting the picture. 

To find out more about dengue and the family of viruses it belongs to, called arboviruses, Alice Allan speaks to Marc-Alain Widdowson, high threat pathogens technical lead at the WHO Regional Office for Europe and medical entomologist Luca Facchinelli. To learn more about Italy’s work on dengue prevention and communication, she speaks to Flavia Riccardo, an epidemiologist in the Infectious Disease Department of the Italian National Institute of Health, and her colleague from the Institute’s press office, Pier David Malloni. 

Transcript

Alice Allan: For most of us in Europe, mosquitoes are an irritation -- they give us itchy bites and disrupt our sleep.  

But for millions around the world, mosquitoes are the vector that expose them to serious health threats. The most infamous of course is malaria – a parasitic disease which kills over 600,000 people a year globally. But the virus causing dengue – long endemic in tropical and subtropical regions - is also spiking, resulting in close to an historic high of over 6 million cases and more than 7,000 dengue-related deaths reported in over 80 countries and territories in 2023. Most places in Europe remain too cool to favour the mosquito or the virus. But imported dengue cases have been rising in the European region and the impact of climate change appears to be shifting the picture. 

To find out more about dengue and the family of viruses it belongs to, called arboviruses, I spoke to Marc-Alain Widdowson, high threat pathogens technical lead at the  WHO Regional Office for Europe. 

Can you give me the definition of an arbovirus?

Marc-Alain Widdowson: The AR is arthropod. So basically insects. And bio just means borne.

So the viruses that are borne, spread, carried by insects. And there's a whole host of these, some of which some people have heard of. Dengue is one that we've been talking about a lot recently. Zika is another one. There's other ones which are less known like Chikungunya, O’Nyong Nyong fever.

There's also Japanese encephalitis, and others which people may be aware of like West Nile virus, which was another arbovirus that affected Europe. But there are lots of these, out there. Some of them are actually quite deadly. So there's some in the eastern part of Europe called Crimean Congo haemorrhagic fever virus, and they're spread not by mosquitoes but by ticks. So a whole host of these viruses in different types of insects.

AA: Do arboviruses affect the human body in similar ways.

MAW: The fundamental thing is like a viral fever. So that's most cases of most arboviruses, and there are lots of caveats, but just cause a kind of mild fever, rash, aching bones, joints that hurt, in fact, some of the disease of break bone fever because it's really thought to be so painful to the bones, the bones themselves seem to hurt, but usually self-limited.

So let's just take one of these again, dengue, you know, 70 to 80 percent of infections with dengue are asymptomatic. You may get it and have hardly anything. A lot of these other viruses also cause kind of haemorrhagic fever. So you get the fever, so dengue is an example, but in some cases, we don't always know why you get a much more severe disease where it affects your blood and your clotting, and that's a haemorrhagic fever. And that's when you start to bleed. You know, it's not dissimilar to Ebola and it's also very serious. And there are a few arboviruses that do that. 

We don't fully understand why some people get severe disease, but there are some things that we know a bit about. So for instance, dengue is really interesting because there are four types of dengue virus and the serotype 1, 2, 3, 4, if you get one of those serotypes, and then you get immune to that and you throw it off and you're fine, no problem.

 If you get a second serotype after that, you actually much more likely to get severe disease. Now it's curious because most people think of diseases like if you get it once you're less likely to get it bad again. But actually, dengue is actually the opposite almost, because the antibodies that you make at the first infection are actually traitors to your body.

What they tend to do, these particular antibodies, is that they take the new infection that you've had and they kind of take, take the hand of the virus and they take the hand of your cells and put them together. So there are cells in your body that actually Act as matchmakers, if you will, vicious matchmakers and help the new infection get introduced into your body. And that's the antibodies that were raised by the first infection. 

 AA: Where are most of these arboviruses endemic?

MAW: It's kind of shifting. Very crudely, most of these other viruses mostly are in the kind of tropical subtropical areas. Dengue, for instance, was Asia and Latin America, but increasingly more in Africa. These are the ones that spread by mosquitoes. But those boundaries no longer really count for much anymore.

There are other viruses spread by ticks, like this Crimea Congo fever, haemorrhagic fever I mentioned. They tend to be in Turkey and Iran and, the Central Asian Republics and Russia. 

But generally the ones that we think about, the dengue, the chikungunya, the West Nile, a lot of that is in the tropical zones, but they spill over. And increasingly we're seeing, what we call autochthonous cases, which basically means cases of, for instance, dengue in people that haven't travelled.

So, all countries, you know, around Europe get people who've been on travel, been to Thailand or been somewhere exotic and they've got an infection and they come back and they don't feel well and they're diagnosed with dengue. Now those are imported cases which aren't a real public health risk, but then these cases can cause, cases in people who haven't travelled.

 These are autochthonous cases and we're seeing more and more of these autochthonous cases. So tropical areas is that kind of traditional, area of where these viruses and their vectors live, but their vectors are spreading, to the temperate zones.

AA: Medical entomologist Luca Facchinelli is a project manager working for the Liverpool School of Tropical Medicine.. He's worked a lot with the two species of mosquito that are vectors for dengue, aedes aegyptae and aedes albopictus. 

Luca Facchinelli: I remember I was with a colleague and we were trying to, um, measure the, the number of mosquitoes that were coming to bite us.

And there were no clues about, uh, arboviral transmission in Italy at that time. So, so it was allowed to collect mosquitoes coming, coming to you. 

AA: And, so you're literally encouraging these mosquitoes to bite you?

LF: You sit in an area that you are to measure how many females are host seeking and come to you and the other, the other, the colleague is looking around you with an aspirator and collects the mosquitoes that land on your skin. And there were all these males like flying around me. Because they, the males wait for the females to come to the host and then they, they grab them and they inseminate them and I was amazed, we captured more than 50 females in 15 minutes, it was a nightmare. And I realized then that there were areas in the city with vegetation, where the population is so high, that it is almost impossible to stay outside without skin repellents.

AA: Oh, I'm itching now just thinking about it. 

LF:  We link mosquitoes usually to, pests that bite at night and wake up at night, but these are a bit different because they are daylight mosquitoes. So they are active during the day. So they are usually aggressive. So if we move and we try to react to their presence, they immediately fly away and try to bite again us, so the same host, or they go to a different host in the same house, so they need many different bites to complete a blood meal that is needed to develop the eggs.

So this can increase the chances for if they are infected with an arbovirus to infect more than one person because they bite different people.

AA: Where are these mosquitoes generally found in Europe?

LF: So, Aedes Albopictus is present in Southern Europe. It, it was found first in 1979 in Albania, and then in the, in the nineties, beginning of the nineties in Italy. And it's spread through, uh, southern France, Spain, and we find it in some areas in Switzerland, and, and we found also some population in Germany. So it is still spreading. It is different from Aedes Aegyptae because its eggs are able to withstand the winter months. So it was able to spread in the temperate areas. Aedes Aegyptae we can find it in some spots in Southern Europe in Madeira Island in Portugal, and on the coasts of the Black Sea, Turkey and Brazil. In the Sochi, uh, area. 

So albopictus,  we can find it in the city where we have some green areas, some vegetation, but it also enters houses and it bites indoors. In Rome, it's pretty common. This is not trivial because, a mosquito that enters indoor, so inside houses, comes in close contact with humans. And so there is an increased probability that it bites humans and increases the chance for viral transmission.  

AA: Back to Marc Alain Widdowson to find out more about the rare, but rising cases of locally acquired, or autochthonous cases seen in Europe. 

MAW: We have a bunch of autochthonous cases reported from Italy, France  Spain but there's actually very little detail in many of them as to how they got infected. Did they have a specific contact, or were they close to someone who'd been diagnosed with dengue? So we don't see autochthonous cases in the winter, even though they're imported cases. So that tells us that it's not human to human. And there's something in between that isn't around in the winter, and that's the mosquito. But in the summer, there's the mosquito there. And so what happens is someone who's got dengue, whether they know it or not, lands in Paris, and gets bit by an aedes albopictus, which is one of the transmitting mosquitoes and that, that mosquito then flies a little bit and bites someone else and then it transmits the virus. it tends to happen in the summer because that's when the mosquitoes that can do this are around.

 Like I said, many cases of dengue, you remember, are mild, so, people may not even know they have dengue before they're transmitting it. 

AA: If somebody does, develop severe dengue what sort of treatments are you talking about?

MAW: I'm not a clinician, but most of it symptomatic. So if you get this haemorrhagic thing where you're losing blood and your whole fluid balances off kilter, um, then a lot of it is just aggressive fluid therapy. Most of it is just making sure that your body is supported while it heals itself, , from the episode.

AA: Unfortunately, vaccination against dengue isn’t straightforward. There are specific recommendations and limitations for use of vaccines related to age, certain health conditions, reaction to previous doses and other criteria, and these interactions and contraindications have to be considered before immunization. In places where dengue presents a big public health problem, WHO recommends that countries consider introducing vaccination into their routine immunization programmes. Elsewhere, where dengue transmission is low, pre-vaccination screening can be needed.

And of course, depending on the location, the mosquitos that carry dengue can transmit other important viruses. Outside Europe these include yellow fever and Zika viruses and in our region, chikungunya. This is why experts say an integrated strategy to control the disease is needed, including controlling mosquito populations, management cases of dengue, community education, and community engagement.

AA: What's the picture currently around cases of dengue in WHO European countries.

MAW: Yeah. So, so this is actually what we're doing right at the moment is trying to understand which countries are at risk of having autochthonous dengue. We want to improve surveillance in countries which we may not previously have known much about.

So the countries that tend to be affected, there's two criteria that need to be fulfilled. One is they need to have the vector. Therefore, you know, we don't see much dengue in Sweden, other than in imported cases. Um, the second thing is the temperature sensitivity. Now this is actually separate from the vector and it's something that isn't often fully appreciated is that the virus has its own sensitivity. So even if you have the vector in a country, the fact that the virus appears doesn't mean that the vector will suddenly pick it up and will start spreading it like crazy. If the temperature is not right for the virus, then the vector can be there, but it won't replicate 

We've identified just about 30 different countries, along the south, the Mediterranean coast, but stretching all the way into the Caucasus and even further that have You know, potentially, at least, the vectors and the temperature, , but we don't get many reports of autochthonous, dengue at all from most countries. The cases that we get the most from are from Italy, from France, um, from Spain, in the past, Croatia, , had a couple of cases, but that's about it in terms of actual cases of autochthonous cases.

AA: Okay. Is there a sense that if so much of dengue is asymptomatic, that dengue could be out there, but people are not reporting it because they're not feeling the symptoms?

MAW: Yeah, no, I think they could be. And I think that's either that or they are feeling it, but countries don't have the laboratory capacity to be able to, diagnose it. So they may think, oh, you just got flu or you just got some other, you know, infection. And then of course it passes and nobody knows what it was.

When the person has an infection, it leaves a mark in the body in the sense that you usually have an antibody trace of it. So one of the things that we're trying to do is to, to look at serology to sort of see if countries have done any serologic works are looking at antibodies, which would be a marker of past infection.

AA: With climate change summers getting hotter are parts of Europe going to see many more mosquitoes?

MAW: It's not entirely straightforward because I've talked about temperature and that certainly is a major factor, but there's also humidity. I mean, these mosquitoes need. humidity to replicate. So if things get drier and hotter, you're not going to get mosquitoes. So just like you don't get mosquitoes in Sweden, nor do you get them in the Sahara.

If things get drier, then we don't know how that will affect exactly the spread of mosquitoes. So it could be worse. It could be, it could be better. Uh, it's unclear and we need to sort of have. Better predictions. We know things bad are happening, but we don't quite know what they're going to look like in 20 years, 30 years time.

AA: Could it ever become a pandemic and be really global?

MAW: It depends a little bit what we mean by pandemic. I don't think mosquitoes will be able to live genuinely in the whole world. In that sense, no. But a spreading ecosystem, a spreading, zone, territory, that, yes. And affecting most continents in the world, that, yes. Affecting temperate regions of the world. That yes, though, again, to a lesser degree. We worry a lot in, in Europe about dengue and we should, but the bottom line is that even in a near medium future where dengue is endemic, even if you get it bad, in Europe you’re generally going to be treated okay. So yes, it's scary. We don't want dengue and yes, we should do everything we can to avoid it. But the real burden, is in places where people are getting repeatedly infected, getting severe disease, don't have the clinical care to be able to deal with it, et cetera.

AA: Flavia Riccardo is a medical epidemiologist from the National Institute of Health in Italy. She started her career in a parasitology lab before becoming an infectious disease physician. Working on complex emergencies in different areas of the world drew her to epidemiology. I asked her to explain Italy's experience with dengue.

Flavia Riccardo: So when we talk about locally acquired dengue cases in Italy, uh, we've identified those to date only three times. The first time was in 2020 with a small cluster in a rural area in the northeast of Italy. And more recently in 2023 with cases occurring in localized clusters in northern central Italy.

Now there is a relatively widespread climate suitability for dengue transmission. So the reason why it's one area on the other is actually quite likely due to chance. So we have the contact between a mosquito and maybe a returning traveller who has an ongoing viral infection. that coming together can begin a local transmission chain.

AA: So, what are you learning from other countries in the region or globally about dengue. 

FR: Well, exchanges have taken place, especially in countries in Europe, that are experiencing similar transmission events as Italy. And the lessons learned for us are very valuable, because it allows us to compare approaches, and understand how best to mitigate the impact of local transmission, also looking forward in time. Thinking of a time where we might be seeing more of this,  and at the same time Italy shares all data on both  imported and locally acquired confirmed dengue infections through a dashboard that is available online and that during the transmission season is updated every week.

So Italy has developed a national arbovirus response plan,  with measures in place to prepare and respond to dengue transmission,  both  imported and locally acquired. And this includes actions such as enhanced surveillance, case detection throughout the year. We also have focused prevention measures around imported cases of infection. So, looking at  behavioral and vector control. And in case of local transmission, there is a rapid active case investigation, proximity vector monitoring control, and also safety measures that are activated for the safety of transfusions and transplants in the area where this transmission is occurring. 

The man with the delicate task of sensitizing, the public to this changing epidemiology without causing undue alarm is Pier David Malloni. He works closely with researchers and epidemiologists like Flavia Riccardo in the press office of the National Institute of Health to effectively disseminate the results of surveillance on dengue. 

 How do you prepare the public for a problem which hasn't really arrived yet?

 Pier David Malloni: From the communication point of view, it's better that you prepare the population to what can happen because otherwise, they can say why you didn't tell us that before? You knew that and you didn't tell us.

I think that, both last year and at the moment this year, the main communication problem in dengue is like, let's say, fine tuning the attention of the public.   We issued a very general FAQ about dengue, telling that at the moment the situation is not worrying, but that there is the possibility that the cases will rise.

AA: Pier David's top tips to decrease your likelihood of being bitten by a mosquito, are simple.  Wear clothing that covers most of your body. Use a commercially available mosquito repellent. And remember to follow the instructions on how to use it. And remove standing water from your home in places like flowerpots, for example, as that's where mosquitoes might breed.

How in your communication are you able to explain the why, why is it worth doing this?

PDM: I'm used to start with numbers. So we will start a weekly bulletin with the number of cases, which is good because it attracts a lot the attention of especially of journalists. So to catch the attention, the numbers are always a good thing.

But we are planning to every week also to give some advice about the situation and about who have to be more worried about it. You know this is, at the moment, a local problem, which happens in small communities or in very specific communities. And in these communities for example, the local newspapers are a very powerful way carry message of sometimes wrong message. So you cannot forget this part, even because you are talking a lot to elderly people, which is not used to social media, but they always go to the bar and read the newspaper.

 We and the Ministry of Health, we are proceeding in parallel. The Ministry of Health is more focused on traveling people. They have prepared some materials for that is in the airport. Some visuals, explaining the risks and what to do. Now, we are more focused on the people here. 

 We already have this situation with the West Nile virus which now is endemic here in Italy and  in every season. So until last year, I was preparing for the West Nile season, but now probably , we don't know, we hope that this will not be the West Nile and dengue season, but we can use the experience of West Nile. We have very good surveillance, both in animals and in people. So we probably will use this lesson to adjust it to dengue, but I think we are prepared for that.

AA: Because of the global eightfold increase of dengue, WHO has issued a grade three global emergency grading. There's a huge amount of work being done in countries where dengue is endemic, but the WHO Regional Office for Europe is also taking action.

Back to Marc-Alain Widdowson.

MAW: We've got about five or six different pillars of things that we're doing. One is to understand who's at risk of maybe having dengue. So some countries we know, like I said, France and Italy, they have autochthonous cases, but other areas we don't. So we're doing a risk assessment to see if they have the vector and the temperature and serology and come up with the countries that we think are at risk.

And then to establish surveillance. The second is to look at laboratory capacity to make sure that they have the laboratory capacity necessary to diagnose it.

Third is, actually looking at, some training on clinicals. If they do get a severe case, how to support countries to deal with that. And then another big piece is the forecasting piece. Where do we expect this to go?