A recent study, published in Journal of Virological Methods, suggests and evaluates a modification to a currently used lab-based diagnostic test for dengue. The improved test has shown it can reduce the likelihood of false negatives and increase identification of a specific type of the virus.
The research, which was led by i-sense researchers at UCL, in collaboration with researchers at UCLH, the NHS, and the Oswaldo Cruz Institute in Brazil, harnesses technological advances to update an existing test and improve its sensitivity.
What is dengue fever?
Dengue is a viral infection that is transferred by mosquitos and affects between 50 to 100 million people worldwide each year. The virus presents as fever or flu-like symptoms, and although in majority of cases will pass with no lasting effects, in a very few severe cases it can be life threatening.
To date, there is no specific treatment available or universally recommended vaccine for dengue, and diagnosis is usually based on clinical evaluation of symptoms and risk factors (such as travel history).
Why is identifying the virus important?
“Globalisation has widespread implications for disease transmission, and today, even those countries that do not have endemic dengue, are seeing rising numbers of cases imported by returning travellers,” says Consultant Virologist at University College London Hospital, Dr Eleni Nastouli.
“Good diagnostic tools are important to identifying cases and all types of dengue in order to get a better epidemiological picture of the disease.”
In most countries that are affected by dengue, there are four types of the virus that can circulate at the same time. This means that once infected, an individual will have life-long immunity to one particular type of the virus, but may still be susceptible to the other three types. Prior infection with one of the types can predispose an individual to a more serious episode upon subsequent infections.
Although identifying the strain of the virus is not immediately important, understanding whether a predominant strain has been replaced is important in identifying the potential risk of a more severe, secondary infection.
How has the test been modified to improve diagnosis?
A widely used diagnostic test for dengue is a lab-based test published by Drosten and colleagues in 2002, which is a pan-serotype molecular test. The study used this test on 32 samples across Europe (21 samples) and Brazil (11 samples) and found that it failed to detect one of the four types of dengue, known as serotype 4. Although serotype 4 causes a minority of infections, assays that cannot detect this type may lead to missed diagnosis opportunities, and cause the burden of dengue to be underestimated.
“While we found that the minor groove binder modification improved the detection of serotype 4 substantially, we were pleased to also find that it did not weaken the detection of other types, but instead appeared to have an overall improvement,” says lead author and Postdoctoral Research Associate in the i-sense McKendry group at UCL, Dr Eleanor Gray.
Of the 32 samples, the original version of the assay failed to detect eight of the samples that the minor groove binder-modified version detected, of which six out of seven belonged to serotype 4.
In light of this, it would be simple for laboratories that use the original version of the assay to detect dengue to change to the modified version described in this paper, to avoid false-negative results from dengue infections caused by dengue serotype 4.
