Dengue virus is evolving, say virologists

Virology experts have pointed out that the aggravated presentation and severity of dengue in the State may be possibly due to antibody-dependent enhancement.

While larger studies will be required to ascertain this theory and the possibility of an increased viral virulence, the evolutionary dynamics of the dengue virus circulating in Kerala have been changing since 2008 and whenever a new serotype is introduced in a locality, a deluge of cases should be expected, they say.

All four serotypes of the virus have been circulating in the State, DENV-1 and -3 being the most common.

“The serotype and genotype shifts occurring in circulating dengue viral strains in a locality are important causes for enhanced severity of dengue outbreaks,’’ says E. Sreekumar, virology expert at the Rajiv Gandhi Centre for Biotechnology (RGCB), in his research paper on dengue lineage shifts, which appeared in the latest issue of

Virology Journal .

“We are living in a hyper endemic area for dengue and during previous dengue outbreaks in the State, we have had a significant number of patients with concurrent infections involving multiple serotypes. For example, in a dengue outbreak that occurred in the Ernakulam General Hospital in 2008-09, we have found co-infection with two or more serotypes of dengue virus in the same patient. We have also found that certain DENV-1 strains that are possibly introduced from neighbouring countries are also circulating here,” says Dr. Sreekumar

Pre-existing immunity

The severity of dengue infection could be attributed to not just the change in virus’s genotype but also to the pre-existing immunity to dengue in a population, he points out.

A majority of dengue infections in the community presents as sub-clinical or mild infections and may often be taken for simple viral fever.

But these would have created antibodies to that particular dengue serotype in the community. “People who are infected a second time with a different type of the dengue virus may have a different immune response wherein the clinical symptoms of dengue might worsen and the person will have severe disease. This is called “antibody-dependent enhancement,” he says.

Testing for pre-existing antibodies (IgG) can reveal if a person is having a primary or second infection with dengue, while the presence of IgM antibodies indicates a recent infection.

Thus if a patient’s blood test reveals the presence of both IgG and IgM antibodies, it gives a certain indication whether he is being afflicted by dengue for the first time.

In clinical practice, confirmation of the presence of IgG cannot be taken as a fool-proof test to predict that a person’s current dengue infection could turn severe, clinicians point out.

“We do test seriously ill patients for IgM and IgG but we rely more on clinical assessment and close monitoring of the patient rather than lab tests. There are occasions when even a first infection could be serious,” a senior doctor at MCH says.

Dengue virus is an RNA virus, which is constantly evolving. In fact, it is its capacity to evolve and adapt through genetic changes that has made it such a successful pathogen, says Dr. Sreekumar.

Since 2008, various studies at the RGCB has shown how new strains of the dengue virus are being introduced in the State through cross-border transmission and how genotype changes and even subtle changes in lineages have been happening.

The dengue virus strain circulating in Kerala is generally benign, while the Tamil Nadu strain seems to be more severe in presentation. Thus the possibility that those living near Tamil Nadu border districts may develop a much serious form of dengue cannot be discounted.

It was a string of paediatric cases of dengue from the border areas of Karakonam and Parassala in May, with unusual clinical presentations and higher mortality reported by the SAT hospital, which prompted the Health Department to seek the help of RGCB .

The RGCB is studying 600 blood samples collected from Tamil Nadu border areas and initial reports has suggested that about 50 per cent of the samples are indeed dengue and that the predominant serotype in circulation now is DENV 1.

Any speculation about increased virulence of dengue virus can only be validated after completing the gene sequencing and then correlating it with the patient’s clinical history, R. Radhakrishnan, Head, Laboratory Medicine, RGCB, says.