Study examines dengue infection and immunity among children

Dengue fever, a mosquito-borne viral infection, is now endemic to more than 100 countries, and the severe form of the disease is a leading cause of death among children in some Latin American and Asian nations.

Understanding the complex patterns of dengue infection and immunity is difficult because little is known about individual infection history. A University of Florida team, along with colleagues in Nicaragua and the U.S., combined a prospective cohort study of children in Nicaragua with epidemiological surveillance data in the nation to infer the complete exposure history at the individual level for each participant in the cohort. Their findings appear in the journal Nature Communications.

Many people infected by dengue may have mild symptoms or not even know they have been infected. Those who develop general dengue disease may experience fever, headache, joint muscle pain, rash and fatigue. Rarely, patients may develop severe dengue, or hemorrhagic fever, which can be life threatening.

Dengue is caused by one of four closely-related virus serotypes. It is widely accepted that infection with one serotype provides lifetime immunity against that serotype. However, cross-immunity against the other serotypes may be brief and infection by another serotype can put patients at risk for developing severe dengue, a phenomenon known as the antibody-dependent enhancement effect, or ADE. ADE is well known for the risk of severe dengue fever, however, the UF-led research is the first to demonstrate ADE for the risk of infection.

“By dissecting the risk of dengue disease into the risk of infection and the risk of general dengue disease given infection, we found the antibody-dependent enhancement effect applies to the risk of infection as well, but not to the risk of general dengue disease given infection,” said Yang Yang, Ph.D., an associate professor in the department of biostatistics at the UF College of Public Health and Health Professions and the College of Medicine.

The pediatric cohort study, led by scientists at University of California, Berkeley, University of Michigan and Nicaragua Ministry of Health, followed more than 5,000 children between the ages of 2 to 9 living in Managua, Nicaragua, since 2004. Along with these scientists, the UF team further found that after controlling for age, one prior infection is associated with a 54 percent lower risk of dengue infection, while two or more previous dengue infections are associated with a 91 percent higher risk of a new dengue infection.

Children older than 8 had a higher risk of dengue infection than younger children.

“Even after controlling for the number of prior infections and time since most recent infection, older children are still subject to more risks of both infection and subsequent disease than younger children,” Yang said. “The higher risk of infection for older children is probably due to higher mobility, but other unknown factors could have contributed as well.”

The researchers also evaluated infection risk associated with living conditions. They found that home ownership was associated with a 20 percent lower risk of infection. Having one to four electric fans in the house was associated with a 32 percent lower risk of infection, and a 45 percent reduced risk with five or more fans.

“Our study is not a clinical study designed for the preventive effect of electric fans, and thus no causal relationship can be claimed,” Yang said. “However, we do hope our finding in this regard will interest people to perform more rigid epidemiological evaluation for the utility of electric fans, through either randomization trials or case-control studies.”

In addition to Yang, UF research team members included Tim Tsang, Ph.D., Samson Ghebremariam, Ph.D., Diana Patricia Rojas, Ph.D., and Ira Longini, Ph.D.