Dengue fever, commonly known as breakbone fever, is transmitted by mosquitoes which carry the dengue virus. Dengue typically manifests itself after an incubation period of four to ten days through high fever, acute headaches, nausea, body ache and rashes. The World Health Organisation (WHO) estimates that as many as 390 million dengue infections occur yearly and that number continues to increase. In severe dengue cases, patients may experience haemorrhagic symptoms and organ failure that could lead to shock and death.

As of 7 October this year, 74,641 cases of confirmed dengue cases were reported in Malaysia. From this figure, 159 deaths were recorded. This is a genuine cause for concern and initiatives such as the “Search and Destroy Aedes Rangers” (Sedar) programme have been launched to raise public awareness and encourage steps to prevent dengue. Recently, however, a team of scientists has found that prevention may no longer be enough to curb dengue, especially for people infected with the virus for the second time.

Antibody-dependent enhancement (ADE)

The dengue virus is mainly transmitted via female mosquitoes of the species, Aedes aegypti.
The dengue virus is mainly transmitted via female mosquitoes of the species, Aedes aegypti.

Science journal has recently published a study by a team of American and Nicaraguan scientists, who discovered that severe dengue may occur due to antibody-dependent enhancement, or ADE.

In the study, 6,600 children with the disease were monitored over a course of 12 years in Nicaragua. The researchers took blood samples from the children every year which were later analysed for dengue-binding antibody levels. What they found shocked them: children infected for the second time were found to be prone to severe forms of dengue when antibodies in their blood were present at specific levels.

Three different statistical approaches were used to test why some children developed severe dengue the second time they were infected. Eva Harris, lead researcher of the study from the University of California, said, “Amazingly not only do we find that there is a specific titre of antibody that is predictive of severe disease, but all the three methods came to the exact same range of titres.” The findings showed that children with intermediate antibody levels are 7.64 times more likely to develop dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS). On the other hand, children with high or low antibody levels were not affected.

Further research needed

Harris notes that one of the main problems in previous studies is that antibody-dependent enhancement had been observed with many viruses inside test tubes but “it's been unclear how these experiments translate to dengue in humans.”

Nikos Vasilakis, an associate professor of pathology at the University of Texas Medical Branch, commended the study for demonstrating ADE in people (in vivo).

“This paper, what it does, it shows for the first time the narrow range of antibody concentrations… that actually produces enhancement of disease in vivo,” said Vasilakis.

Despite the mounting new evidence, many researchers in the field remain sceptical and demand further proof.

Dengue antibodies have been found to trigger life-threatening infections among humans.
Dengue antibodies have been found to trigger life-threatening infections among humans.

Timothy Endy, a dengue researcher from the State University of New York Upstate Medical University, highlights the fact that Harris’s investigation failed to distinguish between binding and neutralising antibodies or different serotypes. He claims that associating ADE with certain levels of dengue antibodies is considered too “simplistic” and that “ADE is still a theory that invites rigorous science and investigation.”

Nevertheless, the observations made in the study may prove useful for vaccine trials and assessments for both dengue and Zika viruses. Vaccine experts from the WHO advise that the vaccine — Dengvaxia — should only be administered to children who have been infected with dengue at least once in areas with high dengue activity. MIMS

Read more:
After Kedah’s spike in cases, MOH Malaysia warns of rising dengue threat
Singapore revisits unconventional method to track dengue infections
Life expectancy and spread of infectious diseases in Malaysia – a paradoxical increase