August 2008

What is dengue fever?

Gubler: Dengue [pronounced DEN-ghee] fever is a flu-like illness without the upper respiratory symptoms. It is caused by a virus that is transmitted by common mosquitoes. Mosquitoes are all over the world but several things are needed to contract the disease: susceptible human beings, competent mosquito vectors (carriers), and a particular virus transmitted by the mosquito.

Dengue fever is caused by four distinct viruses; but, they are very closely related to each other. The illness is the same; the mosquito vector is the same; and the host is the same. A person living in a tropical area where there are disease-carrying mosquitoes can have four separate types of infections in his or her lifetime.

We usually hear about the disease in the tropics because that is where it thrives. But dengue arrived in the United States some 300 years ago. Fortunately, we eliminated dengue along with malaria and yellow fever more than 50 years ago. We eliminated it, not by eliminating the mosquitoes, they’re still here, but by improving our living standards, with better housing, hot water systems, medical care, mosquito control—essentially good public health. In recent years, we have seen a dramatic increase in dengue fever worldwide. America is vulnerable since the more dengue occurs in tropical, tourist, and business destinations, the more likely it will be imported into the USA.

We have two mosquitoes in the USA that can transmit dengue. The mosquito that is a very efficient epidemic vector, Aedes aegypti, is mostly localized in south Texas, south Florida and some areas in Arizona. Interestingly in the desert, by turning places like Tucson into tropical oases, we made a good home for the mosquitoes.

Is Dengue fever a serious health concern?

Gubler: In terms of health, it is serious because it causes an acute prostration febrile illness, in other words, a fever illness that causes people to be laid up for probably a good week to six weeks, depending on the individual and the particular infection. There are no permanent, lasting effects associated with it. A small percentage of patients develop a severe form of the disease. Some patients will have a viral encephalitis-like illness (affecting the brain) or internal bleeding. The severe form spans a spectrum of conditions.

Dengue fever can have a tremendous economic impact on populations when it causes a major epidemic affecting thousands of cases. When that happens, essentially the community and the medical system shut down. It puts a big overload on the hospitals and clinics.

All in all, dengue fever is a very important disease. From the economic impact standpoint, its impact can be measured by what we call “disability adjusted life years.” The impact is of the same order of magnitude as many of the important infectious diseases we hear about on a daily basis.

What are the major drivers for this disease?

Gubler: The major driver is urbanization. As the cities of the tropical developing world have grown, the mosquito vector that has been there for many years has expanded. All of a sudden, you have large human populations living in intimate contact with the mosquito populations. If the virus is not already there, it could be introduced. But, the disease is there in most of these cities so you have constant transmission, which increases the possibility of genetic change in the virus, which then increases the probability of an epidemic strain emerging.

If the major driver is urbanization, it becomes more acute when there is a lack of effective mosquito control. Combine that with modern transportation and you have a formula for potential disaster. Up until the 1960s most of travel was by boat. It took us weeks to get across the ocean. Beginning in the 1960s, but accelerating in the 1970s and 1980s, people began to travel mostly by airplane. In the 1980s and 1990s, we began to move most of our commodities by plane. Modern transportation has become a new major driver that helps spread the virus to urban centers around the world.

Is dengue fever confined to the tropical regions?

Gubler: Yes, it is mostly confined to tropical regions. Sub-tropical regions, like Texas and Florida, can be susceptible. Here in the United States, we are lucky, for several reasons. First, we eliminated the diseases in the 1950s and 1960s through improved living standards—by better public health.

Furthermore, our population density is not that great in those areas of the USA where there are mosquitoes. So you have the combination of better public health, lower mosquito populations, and lower human populations, which results lesser risk of human-mosquito contact. Even though we have many viruses imported into the USA from tropical areas, the amount of local transmission is very limited and sporadic.

Does the virus mutate quickly or has it remained the same over time?

Gubler: Luckily, dengue does not mutate as fast as the avian influenza, but it does mutate. As we have learned more about the viruses in the last 10-15 years, we’ve been able to use new technologies to study the genetic changes that occur in the viruses. We are finding genetic changes, or mutations, as you call them, which influence the epidemic potential of these viruses. So, it does not change as fast as flu, but it does change. It is not a static or monolithic organism, and we do see that there is genetic change that influences epidemic transmission.

As tropical cities grow and human populations get larger, and we have all four serotypes (groups) co-circulating in those cities, transmission increases. This increases the possibility of genetic change in the virus, which then increases the probability of a new strain being selected that has greater fitness and greater epidemic potential.

Does dengue fever have the potential to adapt to colder climates?

Gubler: Probably not. We have had major epidemics of yellow fever and dengue in the USA, as far north as Philadelphia and Boston. The reason this happened is that during the summer months it was warm enough to transmit tropical diseases. If you have diseases introduced into an area where the mosquito occurs, you can have transmission.

In the old days, the mosquito was found in the Gulf Coast states, but every summer it would migrate up the rivers or the coast in boats and re-infest port cities on the rivers or the ocean. Every summer, there would be populations of mosquitoes breeding in these cities. That could happen today, but our northern cities now do not have the conditions that allow mosquitoes to breed.

Mosquitoes breed primarily in stored water containers. In the old days, we did not have piped-water systems. We stored water, which was ideal for the mosquitoes. Today, not only do we have piped-water systems, we also have good sewer systems. There are very few places for the mosquito to breed. Even if they are introduced to new places, they do not become established.

Have there been pandemics of dengue fever?

Gubler: Well, a pandemic is defined as a global epidemic. We are in the middle of one right now. It began in the 1950s, and it has been getting progressively worse for 50 years. I do not know how much worse it is going to get, but I think most of the whole tropical world has been infected. Most of the four serotypes occur in all the urban tropical cities. I do not expect to see epidemics in the USA because the one vector that we have here that has widespread distribution is a very inefficient epidemic vector. It can transmit but sporadically.

The current pandemic is pretty bad because it is all over the tropical world. There have been pandemics of this disease in the past, as well. In the 1800s, these diseases would move from region to region in sailing boats; they would actually breed in the stored water on the boats, and that is how the mosquito was introduced into new areas. The mosquitoes they were transporting were being transmitted among the ship’s crew and when they went on shore, they introduced the virus to the mosquito population that lived there.

Those pandemics were not nearly as bad as the current one, and the reason is that the cities today are much larger. We have a much larger population. We have jet airplanes as opposed to boats. So, the pandemics we experience now are far worse than anything we have experienced in the past.

These same factors will influence pandemic influenza if it occurs in the future. You have something like two billion people a year getting on airplanes and flying somewhere, so you have the mechanisms not only for dengue, but also for other diseases like influenza to spread rapidly.

Is there a vaccine or other preventative measures for dengue?

Gubler: There is no vaccine. There is no drug. There is a lot of progress in both areas, and I am going to come back to that. There are very effective methods of controlling and preventing the disease, and that is simply by controlling the mosquito. The mosquito is a highly domesticated insect that lives in intimate association with humans. It prefers to live in a house; it prefers to breed in a house; it prefers to rest in the house. So, if you eliminate stored-water containers in the environment, you can greatly reduce the population of mosquitoes, and therefore greatly reduce the probability of transmission. That is what we have not done adequately in most parts of the tropical world. Many places do not do good mosquito control, mainly because it is too hard. The Gates Foundation has funded a program called The Pediatric Dengue Vaccine Initiative, which focuses on helping companies that are developing a dengue vaccine and eventually distributing it to at-risk populations. That program has great potential.

We have a whole generation of people in the world today that have been raised since the 1960s to believe that basically, they do not have a major role to play in their health destinies. There are drugs; there are vaccines. We do not even teach hygiene in our schools anymore. One of the most effective ways of preventing diseases like influenza is washing your hands. It is too easy now. You get sick, you go to the doctor; you get a drug; you get an antibiotic. In the tropics, you get an injection. You get better, so there is no responsibility by people.

We live in a crisis-oriented society—we do not do anything until there is a crisis. We wait for the epidemic to occur, and then we try to respond to it. People could very easily help public health officials with this disease if they would control disease in their own domestic environment. But, many will not do it; they believe it is the government’s responsibility to do that.

Researchers started working on a vaccine 30 years ago, in the late 1970s. It is a very complex problem because there are four viruses. You have to immunize against all four simultaneously, and that is what makes it so difficult. They have made very good progress, though. We have probably at least five good vaccine candidates in the pipeline. In the next couple of years, there will probably be several of them that will undergo efficacy trials in the human population. And, the best guess is that probably in five to seven years, we may have a vaccine. But, we have been saying that for 30 years, so …

The other area where there is a lot of progress is an antiviral drug that will inhibit virus replication in the human body. The Novartis Institute of Tropical Diseases has focused exclusively on dengue and tuberculosis in developing an antiviral drug. They have a good candidate that is probably going into clinical trials next year and it looks very promising.

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