Feverish Fight to Stop Disease

(April 28th, 2014) Dengue fever might mostly sicken people in Asia and Latin America but Europe can help out, keeping infections at bay or prevent them altogether. DengueTools, hosted at Umeå University, develops and identifies methods to monitor and diagnose the disease.

Dengue fever might be relatively unknown in Europe but worldwide the disease affects 230 million people each year and is fatal in around 25,000 cases. Transmitted by bites from Aedes mosquitoes infected with the dengue virus, it is characterised by fever, joint aches and muscle pain. The disease can progress to a more severe infection, dengue haemorrhagic fever (DHF), causing high fever, organ impairment, severe bleeding, persistent vomiting and severe abdominal pain. Due to the lack of a vaccine, the best defence against the spread of the disease is to limit the number of infections. Currently, DHF is the leading cause of hospitalisation and death in children in Asian and Latin American countries. But it’s coming closer and closer to Europe…

Thus, the European Commission is funding three consortia in order to further understand the risk of dengue fever. “The aims of all three consortia overlap or complement each other,” says Raman Preet of Umeå University, Sweden, scientific project manager for one of the consortia, DengueTools. Hosted and led by a team at Umeå University, DengueTools involves experts from 14 institutions worldwide and aims to investigate the potential spread of dengue fever around the world, particularly into Europe. "DengueTools places particular emphasis on dengue risk maps under different climate and future scenarios, influenced by global human mobility. Further, DengueTools plans to look at clinical and virological parameters that may contribute to improved surveillance systems."

At the heart of the project is the development of novel, quick and cost-effective methods of diagnosis. Current diagnosis relies on techniques such as ELISA, viral culture and quantitative PCR (qPCR). However, these methods are costly and time-consuming and therefore not suitable for rapid diagnosis. The DengueTools consortium has developed a method of nucleic acid amplification, which takes place in a single tube and at a constant temperature of 60-65°C. Validation of this method demonstrated a detection rate of 97.7% when used in combination with ELISA tests, a remarkable increase compared to 70.8% when using ELISA alone. Additionally, the researchers have also identified methods to increase the sensitivity of qPCR, using low levels of template DNA, which will allow earlier identification of viral DNA present in a patient sample.

Identifying methods to prevent the infection of children is another aim of DengueTools. “This aspect is unique to DengueTools, of the three dengue consortia,” says Ms Preet. “In many endemic countries, children are the most affected group, in terms of both incidence and severity of dengue. Effective control strategies to protect children are lacking. Children spend a substantial amount of their time at schools, and Aedes mosquitoes bite mainly during the day.” A clinical trial is currently underway in ten schools in Thailand to investigate the preventative capability of insecticide-treated fabrics used in school uniforms. Although the investigation is ongoing, mathematical models predict that the method is likely to be effective, giving success rates of up to 55% in the most optimistic simulation scenarios.

The final research area of the consortium focuses on the threat of this disease spreading into Europe. So far, the work has focussed on modelling the spread of disease and developing methods for determining the source country of current outbreaks and the likely risk of infection in travellers. For example, using mathematical modelling, DengueTools researchers predict that the risk of infection in Thailand is 0.2% if a traveller stays for no more than 7 days. However, if the traveller remains in the country for up to 30 days, the risk of infection rises to 0.81%. Other work has focussed on the use of genetic sequencing to identify the country of origin of a strain of dengue causing an outbreak in Angola, West Africa.

This project aims to make a difference by “assessing the risk of spread of dengue in uninfected areas like Europe and spreading awareness regarding this disease,” says Ms Preet. She continues, “The project has completed 31 months and the objectives aligned for this time frame were all achieved.”

Amy-Leigh Johnson

Picture: DengueTools

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