Dengue fever outbreak grips Brazil

Brazil is in the midst of a huge outbreak of dengue fever, with public health experts anticipating a surge in cases across Latin America. To find out more, we put in a call to James Whitehorn who is a consultant in microbiology and infectious diseases at Guy's and St Thomas' NHS Foundation Trust. Jamie has spent a large part of his professional career studying this particular virus…

James - Dengue is a viral infection that is increasing in incidence around the world for a number of reasons. But what's been particularly striking is in Brazil where the case numbers are three or four times higher than they were this time last year. That's happening for a number of reasons; one of the reasons that's happening is due to the El Nino effect, which is causing increased rain and more water which promotes more breeding of mosquitoes which are the vectors that transmit dengue. And because of warmer weather and more wet weather, there's more breeding of mosquitoes and therefore more vectors that can transmit dengue. There are four types of dengue virus: 1, 2, 3, and 4. They circulate within populations over a period of time, but there's been a recent reemergence of dengue 3 in Brazil as well. Lots of people haven't been exposed to that particular strain of dengue before and they're being exposed to that as well as the increased numbers of mosquitoes, which is leading to increased transmission.

Chris - Because when people catch a different type of dengue to one they've had before, there's a chance of getting more severely ill paradoxically than if you'd never had dengue, isn't there?

James - Yeah, that's absolutely right. If you get one infection with one of those strains, you have lasting immunity to that. You have brief cross protective immunity to the other strains, but once that cross protective immunity wanes, you do become at increased risk of more severe disease. So having a secondary infection with a different serotype is a recognised risk factor for a more severe disease course.

Chris - Do we know why that happens?

James - The best explanation for this phenomenon is called antibody dependent enhancement. What happens is that the antibodies that were produced when you were originally infected with dengue bind to the new infecting strain, but they don't neutralise that. These antibody viral complexes are then taken up into cells and that leads to a higher viral load in the patient who's been reinfected with dengue with a different strain.

Chris - Luckily, though, there are vaccines. Are they effective?

James - There are two vaccines that are currently licensed for dengue. There is one which was developed by Sanofi Pasteur which was the original one which was licensed, and there's more recently been the Takeda vaccine. They are effective, but there are a number of caveats that need to be taken on board with that. The Sanofi Pasteur vaccine, when it was originally used, seemed to be associated with an increased risk of severe disease and hospitalisation. When that was looked at in more detail, it seems that patients who were given that vaccine who hadn't had dengue before were more at risk of getting severe disease. Those safety issues aren't the case for the Takeda vaccine: you can give it to patients who've not had dengue before. It seems, although there needs to be ongoing work looking at long-term follow-up data, it seems to be safe and effective. In Brazil, they're using the Takeda vaccine to try and help control this current outbreak of dengue.

Chris - And if someone doesn't get vaccinated in time and does get it, what happens to them?

James - In most cases of dengue, a self-limiting but quite unpleasant infection. You get a high fever, rashes, you get headache, lots of body pains, lots of aches, and you can be very, very unwell for quite a few days. Some patients do go on to get a more complicated disease course. You see in that situation things like dengue shock when you get leakage from the blood vessels and you can get low blood pressure, high pulse, and you need fluid resuscitation. Some patients can go on to get hemorrhagic complications, so they can get bleeding manifestations from the GI tract or from other parts of the body as well.

Chris - So you really want to avoid catching this, don't you. If you can't have a vaccine, Is controlling the thing that makes the disease spread, mosquitoes, Is that an option?

James - Yes, they are doing that. That's the mainstay of taking control really prior to these vaccines being released. In Brazil, actually, they're using the army to try and remove the breeding habitats, the mosquitoes, from peoples' houses and things like that. One of the issues is that mosquitoes breed in standing water that people may have in their homes or around their homes. The main vector of dengue is the Aedes aegypti mosquito, which is very, very domesticated. If you can remove water from plants, etc. in the house, that can reduce the risk of transmission and reduce the burden of mosquitoes. Also, you can spray houses and things like that. That's done widely throughout the world where dengue is transmitted. There's been some really exciting and encouraging work looking at biological control of the disease vector. There's a bacteria called Wolbachia which can be introduced into Aedes mosquitoes and they don't naturally have that bacteria. When that bacteria is introduced, it can then become sustained in the mosquito population and seems to block their ability to transmit dengue. Though the mosquitoes that are infected with Wolbachia will bite people who've got dengue, they won't be able to generate an infection and become infectious themselves. That's been some very encouraging work done from a big cluster randomised trial in Indonesia that was published a couple of years ago, which showed that it reduced the dengue incidence by 70% in areas of the city where this approach to vector control was used.

Chris - I suspect that many people listening to this who don't live in Brazil might well be in Europe or travelling to Europe. Are we at risk here? Could we see these sorts of diseases as the mosquitoes move them, taking the disease with them, and placing us at risk in countries where we were previously pretty complacent and thought we were beyond harm?

James - That's a really good question. I think there has been transmission of dengue in European countries, but there have been relatively small clusters of cases. In France and Italy and small transmission events in those settings, there's been a number of climate change predictive models. Looking at the more extreme versions of those predictions, it is likely that dengue transmission will occur more widely in Europe over the next hundred years. But at the moment, I think we're not seeing anything beyond these relatively isolated clusters of cases.