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FocusDx Simplexa Dengue Test Outperforms Three Other Molecular Assays in Clinical Evaluation

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NEW YORK (GenomeWeb) — Researchers in Martinique recently compared four dengue virus detection kits to a hemi-nested RT-PCR test used for routine dengue diagnosis, finding that the Simplexa Dengue assay produced by Focus Diagnostics, a Quest Diagnostics subsidiary, was the most specific and sensitive.

The study, published online this week in Virology Journal, was done by a group at the University Hospital in Fort-de-France, Martinique. It compared four commercially available kits — the Focus test and assays from Altona Diagnostics, Shanghai ZJ Bio-Tech, and Genome Diagnostics — to a gold-standard RT-PCR protocol.

The results showed Simplexa Dengue was about 93 percent sensitive with clinical samples obtained between one and seven days after fever onset, had significantly higher sensitivity than the other three kits, and its performance and genotyping agreed with the hemi-nested gold-standard assay.

The authors also verified the Simplexa Dengue assay did not cross-react with Chikungunya virus. This could be a benefit in light of current outbreaks in the Caribbean, where both dengue and Chikungunya are endemic.

Martinique experienced four major dengue outbreaks between 2000 and 2010. These outbreaks resulted in a total of approximately 100,000 symptomatic cases, or about one quarter of the island's population.

In a study published earlier this year in The American Journal of Tropical Medicine and Hygiene, researchers, some of whom also authored the recent kit evaluation, compared records of clinical presentation to serotype in samples from these outbreaks.

They used 715 archived patient samples obtained between 2005 and 2010, and a hemi-nested RT-PCR assay with both dengue virus generic and serotype-specific primers. All four serotypes were represented, and each epidemic was characterized by the predominance of one or two serotypes: DENV-3 in 2001 (26,000 cases), co-epidemic DENV-2 and -4 in 2005 (14,500 cases), DENV-2 in 2007 (18,000 cases), and co-epidemic DENV-1 and -4 in 2010 (42,000 cases), according to the study.

Now, in the Virology Journal article, the researchers explained that the presence of all serovars in Martinique means the ideal molecular kit should be able to detect all four to be clinically useful in managing an outbreak.

The authors also argued that non-molecular diagnostic methods have limitations. ELISA assays for immunoglobulin M do not detect dengue in early stages of the disease or in secondary dengue, while assays for dengue NS1 antigen have limited sensitivity, they noted. Virus isolation from sera is "useless for patient management" because it requires several days to get results. Thus, molecular methods are ideal for fast detection of dengue in the acute phase.

In comparing the four molecular kits, the researchers found that one unique aspect of the Focus kit was that it also yielded genotype information, revealing which of the four serotypes was detected.

This feature of the Simplexa Dengue assay seems to appeal to the clinical market, according to Focus.

Michelle Tabb, vice president of research and development at Focus, told PCR Insider in an email this week that the company is "continuing to see strong interest in the assay because it is able to detect and subtype the dengue virus serotypes 1 through 4." She added that "this is the second publication demonstrating favorable performance of our assay in recent months."

Last month, a study in Indonesia was the first to validate Simplexa Dengue in a clinical setting, as covered in PCR Insider.

At that time, Mona Gross, marketing manager for the Simplexa line at Focus, explained the dengue test is "a relatively new product," and studies showing its utility in the clinical setting "could potentially help us to get more visibility and business."

Gross explained that outside the US, Focus works with partners in each country to promote and market its tests. She noted that Thailand had done a lot of work with Focus using this particular kit in its public health labs, and Brazil, where Simplexa Dengue was approved for use in 2011, had also shown a lot of interest in the product, but was not yet using it routinely.

Tabb told PCR Insider that the Caribbean is "a key area where our tests would be clinically useful, not only for dengue but for the Chikungunya virus, which is also spreading in this region."

Early symptoms of Chikungunya and dengue fever can have similar presentations. Chikungunya is rarely fatal, but Dengue can be, so reliable diagnosis is necessary for appropriate treatment.

Focus is also in the process of developing and commercializing reagents for molecular detection of Chikungunya to complement the Simplexa Dengue test, which Focus said would make it the only US commercial clinical laboratory to provide antibody and molecular testing for the virus. More than 1,000 Chikungunya cases have been reported to a national surveillance system for arthropod-borne diseases so far this year, compared to an average of 28 per year between 2006 and 2013, according to the US Centers for Disease Control and Prevention.

The Martinique study authors now hope to evaluate combining automated extraction with the Simplexa Dengue kit in multicenter and prospective studies, in the context of clinical management during dengue outbreaks.

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