Over the last 40 years, the average age of someone infected with dengue in Thailand climbed from about 8 years old to early adulthood, or 24 years old.
The question is, Why?
Researchers have theorized that better detection methods, or interventions that reduce the likelihood of humans being bit by mosquitoes – such as using window screens, or spraying mosquitos with insecticide – may have played a role.
But new research published in the journal PNAS, led by researchers from the University of Florida, paints a different story. Using modeling and statistical analyses, the research team showed that most of the reason for the age shift in dengue cases to older individuals could be traced to change demographics — the natural ebb and flow of the age structure of a population of people. But other factors also played a role.
“We evaluated many different factors that could be creating the age shift. The key driver is Thailand’s changing demographics,” says first author Angkana Huang, who was a Ph.D. student in biology at the University of Florida when she performed the study, and who is now a postdoctoral researcher at the University of Cambridge. UF biology professor Derek Cummings was Huang’s advisor and is senior author of the paper. Cummings is a faculty member in the UF College of Liberal Arts and Sciences Department of Biology and the UF Emerging Pathogens Institute, he also directs the UF Infectious Disease Dynamics lab.
Driving causes
The team built a collection of nested models that considered possible explanatory factors such as changing infection rates, changing symptoms that could lead to better detection in adults and the elderly, changes in surveillance that could lead to differences in cases being detected based on age, and changes in the susceptibility that affects the intensity of transmission. When infection rates fall, people experience longer time spans between infections. The model was based on case data reported across Thailand’s provinces.
The main take-away message from the new work is that the shift away from children bearing the burden of dengue cases is directly attributable to the country’s shifting population demographics. Declining birth rates and increasing life spans has changed the distribution of immunity in the population, changing the risk faced by individuals who have not yet been infected by dengue.
“Older individuals who are immune can absorb potentially infectious bites from mosquitos that would have otherwise bitten younger individuals who are more likely to be susceptible. As the Thai population has aged, there are proportionally more older individuals, providing more protection to younger individuals,” Cummings said.
The researchers also considered other factors, such as changes in how dengue is detected within the Thai population.
“Though we found a small role for changes in surveillance, our models suggest that the demographic shift of the humans explains almost all of the change in the age of dengue cases that has been observed,” Huang said.
Implications for the elderly, and vaccines
Dengue is a complex disease to detect in part because there are 4 serotypes, these are genetically distinct but related dengue viruses that compete for hosts. When someone is infected for the first time, they develop antibodies against the dengue virus, but they are then also more likely to experience severe disease in a later, second infection.
“The general belief is that once you are infected with two serotypes, your immunity starts to become quite broad, so when you go to your third infection you may not become that symptomatic,” Huang said.
In addition to finding that the mean age for dengue cases had shifted to the mid-twenties, the team also found an increasing chance of infections being reported as people age.
Huang explained that as individuals become infected in older age, they may have developed other conditions or diseases that change their clinical profile and symptoms, possibly making them more detectable. But this could reflect their healthcare seeking behaviors, and lead to older people being more reported than other age groups.
Whether infections in the elderly are truly more severe, or if they are simply being detected more is not clear from this study. But the trend of elderly people experiencing more dengue cases in Thailand has implications for other global areas where dengue is endemic.
“The age structure of Thailand is changing, but we are also trending globally toward having more and more older individuals,” Huang said.
This means that areas such as Africa, Asia, and Latin America where dengue is endemic and populations are aging, could benefit from the new findings. For example, their health care systems could begin planning training and education programs to foster clinical awareness of dengue in older individuals.
“We may also need more studies to understand symptoms and complications in adult dengue infections, as our knowledge in treating dengue in children may not be totally applicable to older infected individuals,” Huang said.
Though the study focuses on Thailand, it’s findings are useful elsewhere too.
“These demographic changes are occurring in lots of regions where dengue is endemic and they are predictable at multi-year time scales. There is a big opportunity to project some broad trends in dengue in many locations—years in advance,” said Cummings.
The new study also found that the declining transmission intensity in Thailand translates to timing changes for when people become infected. This in turn alters expected immunity based on historic data and increases the variability of being exposed to specific dengue strains.
But the team found little evidence that the fundamentals of dengue transmission have changed, such as the rate at which people are bitten by mosquitoes.
“It’s counter-intuitive that these trends are not really about contact with mosquitoes,” Huang said.
Thailand has urbanized over the past 30 years, she noted. People are more likely to have piped water and mosquito control now than in decades past.
“But interventions have mattered less than one would have hoped over time,” Huang said. It suggests that vector control to reduce dengue is extremely challenging. “What this paper shows is that the overwhelming thing that matters is susceptibility. Which might mean that what we need is a really good vaccine to have the biggest public health impact.”
By: DeLene Beeland