Predicting progression to life-threatening dengue fever

Australian and Indonesian scientists have discovered cell populations in blood which clearly indicate whether a person infected with dengue fever is likely to progress to life-threatening severe disease or not. Their work has been published in the Journal of Biomedical Science.

About half of the world’s population is at risk of dengue fever — with almost 400 million annual cases — and more will be at risk as global warming enables the spread of mosquito strains that carry the virus. But until now, there has been no accurate way to predict which patients will progress to severe dengue fever. The new finding uses immune cells to grade potential severity, paving the way for improved patient management, health system savings and the development of a biomarker test.

The research team is being led by Professor Diana Hansen, from the Monash Biomedicine Discovery Institute. Her team found that during a second dengue virus infection (secondary infections are usually more severe), one group of people had a T cell response which reduced its impact.

“These type of immune system cells get called into action by what’s called the adaptive immune system,” Hansen said. “That’s a very targeted response, specific to the pathogen, helping you get less sick.

“The other group, who didn’t have this specific response, have instead an innate immune system response, characterised by a strong inflammatory attack to control the virus. Those people get really sick, likely needing hospital care.

Hansen said identifying the cell types and their subtypes wasn’t easy, stating, “It’s a bit like trying to identify which particular fruit is causing a scent in a blended fruit salad — is it the mango or the pineapple? We used a technique called mass cytometry, which tags cell types with rare earth metals, to identify specific cell types within complex blood samples, so we could ‘unblend’ the mix.”

Hansen’s team is confident that the results will enable them to develop a biomarker test, like a COVID rapid antigen test, for dengue fever. This should take some of the burden off health facilities in areas prone to dengue fever, which are often overwhelmed with patients who are admitted for observation.

“This will enable doctors to triage patients at an early stage, instead of referring all those diagnosed with dengue virus disease on to hospital,” Hansen said.

Hansen noted that dengue virus is one of tropical medicine’s big challenges, as there is no highly effective vaccine and no available treatment for severe cases. She said her team is “beginning a second clinical study in an endemic area of Indonesia, to obtain more specificity in profiling particular cells predicting progression to severe dengue, to get a step closer to the development of a test for patients at the onset of fever”.

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