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The Devil's Disease: Dengue Fever

Dung Hoang

The Devil's Disease: Dengue Fever (continued)

Even so, Dimopoulos believes it will take a combination of strategies to solve the dengue problem. One of those strategies comes from neither the human nor the mosquito side. Derek Cummings, PhD, an assistant professor of Epidemiology and International Health, comes down on the side of algorithms.

Using self-designed computer models, Cummings crunches and analyzes dengue numbers based on data kept by the government in Thailand going back 40 years.

“The task is to try to understand what’s driving the dynamics of a dengue pathogen spreading through the population,” says Cummings. “Ultimately, what you want to do is understand how you can control it. If I have a model that captures the features of the epidemiology I can start to test ideas.”

For instance, he says, if he knew of a vaccine that performed in a certain way, he could build a mathematical model that captures the basic dynamics of how the incidence of dengue cycles through a population. He could then hypothesize as to how much of an impact that vaccine might have, or what is the best age to use it—at what time and in what place—to minimize transmission.

Cummings splits his time between computer modeling in Baltimore and field studies in Thailand. There he works with the Ministry of Public Health and with the U.S. Army’s Armed Forces Research Institute of Medical Sciences, which partners with the Royal Thai Army.

Among the records he reviews are longitudinal studies of dengue involving schoolchildren. Blood tests show which children have serological evidence of dengue. Analyzing data going back three decades, Cummings discovered that in Bangkok the incidence of dengue showed a much larger peak than normal every two to four years.

“It’s thought to be driven by the cycling of immunity in the population,” he says, using the predator-prey model to illustrate. “You have foxes and rabbits. The fox eats the rabbits, the rabbit population goes down. So then the fox population crashes. Because foxes have disappeared, the rabbits begin to grow and then the foxes return.”

A large dengue outbreak immunizes people to a specific serotype. When that serotype shows up again the next year, not as many people are infected. Cummings also found a shift in the age group most affected by dengue. Historically in Thailand, 7- to 9-year-olds have shown the highest incidence. Surprisingly, surveillance data shows that the mean age of dengue cases is now 18.  Cummings used a dengue transmission model to determine the cause of this shift. The model considered factors such as climate, socioeconomic indices and demography. Cummings says the most plausible explanation is that changes in population structure have altered dengue transmission to reduce the rate at which people become infected. The results were published last fall in the journal PLoS Medicine.

The results are classic for a developing country, says Cummings. “From the 1960s to today, Thailand went through some pretty dramatic changes in its population structure. What that means for dengue transmission is that the number of kids being born who are completely naïve to dengue and can be infected by any serotype is proportionally less than used to be because birth rates are down. Older people have immunity because they had it when they were kids,” he says. “It makes it less likely that a mosquito that’s bitten someone infectious will go and bite a naïve kid. As a population, Thailand has hung onto its immunity longer because of lower death and birth rates.”

Because the only treatment for dengue is supportive care, efficient case management of the disease can mean the difference between a patient surviving the severest form of dengue or dying. “Thailand really does case management well,” says Cummings, “but the doctors who learn to manage dengue cases are pediatricians.” Because of his study, Thai health officials recognize the need to train regular internists in dengue care.

Cummings has also identified patterns in which dengue epidemics spread through Thailand. “It appears to peak first in the center of the country in Bangkok,” he says. “Then there is a lag as the pathogen moves north and south. It sort of appears as a traveling wave moving out into the country.

“I’m interested in what drives those waves,” says Cummings. “If you can understand that, you might understand what’s really driving transmission to a particular location. You then might understand how best to allocate resources to reduce incidence of dengue in the country.”

While computer models can help analyze data and lead to an understanding of transmission dynamics, he says, sometimes it takes old-fashioned, face-to-face detective work to get a fuller picture.

“There’s a lot of interest in investigating people’s behaviors during outbreaks,” says Cummings. “You try to understand who interacts with who. You ask people over the course of 24 hours who they talked to in the morning, how old were they, how often do you see them. If you find one person who’s infected, how much more likely are you to find another infected person right around them, defining the spatial scale of transmission?”

In the Nile valley two millennia ago, people knew nothing of transmission waves or spatial scales or disease dynamics. Slowly, across most of those 2,000 years, scientific knowledge based on the accumulation of incremental advances in research has struggled to outpace ancient legends of evil spirits. But when circumstance triggered a new life for dengue, it also sparked a new urgency to come to grips at last with this complex virus. With the fight fully engaged comes the question: how close are we to winning?

“That’s a tough question,” says Cummings. “I think we know a lot about dengue. But there are still basic things we don’t know. It’s incremental. The thing I’m proud of at the end of a year is if I can explain something new that could potentially be important in designing control measures to reduce incidence.”

Ultimately, just as a victim of dengue has but one course to follow, so goes the course for science. Says Cummings: “You have to be patient.”

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  • Ifelayo

    Hyattsville, MD 07/09/2010 08:51:20 AM

    I like this display of a combination of efforts to fight an old scourge! With patient persistence following these tracks, we should overcome Dengue and hopefully Malaria too...

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