New sub-strains of the dengue virus are appearing in Sri Lanka, affecting more people and causing more severe cases of disease, say epidemiologists online this month in Emerging Infectious Diseases. Experts see signs from around the world suggesting the phenomenon is widespread, but caution evidence is "circumstantial".

 

“The most striking feature of the epidemiology of dengue in Sri Lanka is the abrupt, stepwise increase in the number of severe disease cases in 1989 and again in 2000,” write Nalaka Kanakaratne and colleagues. These patterns are likely down to genetic changes in the circulating strain of dengue virus, they say.

 

About 40% of the world’s population is at risk from dengue, a mosquito-borne infection that causes flu-like symptoms. Although there is no treatment for the viral disease, most people who become infected recover fully. But others develop dengue haemorrhagic fever, a life-threatening complication caused by circulatory failure.

 

There are four dengue viruses, known as serotypes, circulating around the world. These are different but closely related. Past outbreaks of severe disease in South America have been associated with genetic changes in the serotypes circulating on the continent. Recent reports from countries in the region suggest the number of dengue cases is rising rapidly, prompting fears that a new sub-strain with the potential to start an epidemic may have evolved.

 

Patterns of dengue in the Sri Lankan population have been changing over the past two decades, according to the authors. Regular epidemics affecting a relatively small number of people occurred during the 1990s. But since 2000, outbreaks have become larger in scale and have affected more people, with particularly severe epidemics reported in 2002 and 2004, explain Kanakaratne and colleagues.

 

To see if changes in the circulating strains of dengue virus were behind the new disease patterns, the researchers analysed nearly 4000 samples of blood serum collected from patients with suspected dengue fever from 2003 to 2006. They also looked at public health records about dengue infections on the island from 1996–2005.

 

Genetic analysis of the viruses revealed that all strains of the dengue 3 virus (DENV-3) circulating in Sri Lanka belonged to a single group, known as DENV-3 genotype III. In 1989, and again in 2000, a sudden increase in the number of dengue cases was reported on the island. On both occasions, this upsurge coincided with a new DENV-3 sub-strain, or viral clade, arriving and replacing the existing one.

 

Evidence suggests that these new viral clades have a capacity to multiply and spread faster than the ones they replaced, note the authors.

 

Although the emergence of more virulent clades of dengue virus has been well documented in Asia and the Americas, the evidence-base used to substantiate these claims is lacking, says Scott Weaver, from The University of Texas Medical Branch in Texas, USA. “It’s hard to prove what’s going on,” he told EHTF News. “With so much research going on that points to this replacement theory, it is likely to be right.”

 

But there are no good animal models to study dengue virus infection, Weaver points out. So scientists can’t determine objectively whether different clades of the virus are associated with different health outcomes.

 

The presumption that some strains are more virulent and affect more people than others is based on viral genetics, according to Weaver. In reality, there are other factors that can influence human infection, and these factors are difficult to rule out, he says.

 

They include weather patterns, which can influence mosquito numbers, temperature, which can alter mosquitoes’ ability to transmit the virus, as well as human immunity. Different people have different levels of immune protection to the dengue viruses, Weaver explains.

 

In some countries, the data collected to help draw these conclusions may also be biased. “Most countries don’t have systematic surveillance,” says Weaver. “So only the people that present to hospital and clinics end up being counted.” This means that data are incomplete as they are collected from only a part of the community.

 

A better method to uncover the identity of circulating dengue viruses would be to collect a lot of mosquitoes and see what virus clades they are carrying. But this is expensive, he admits.

 

Meanwhile the evolution of DENV-3 may be continuing in Sri Lanka, according to Kanakaratne et al. “The DENV-3 strains from Sri Lanka isolated in 2003 and 2004 form a new, distinct clade that is closely related [to]… the DENV-3… viruses that were isolated in the 1990s,” they write. This clade was first spotted in 1993, suggesting it has come from strains that have been in Sri Lanka for some time.

 

“There is no reason to suggest things won't get worse until a vaccine against dengue becomes available,” says Weaver.