Getting the right test, at the right time, to the right population is key to effective dengue control

Five years ago, Honduran Yensi Flores experienced the worst dengue epidemic she had ever known. Her determination to help her countrymen led to GlowDx – a new type of dengue test.

In 2011, Yensi saw family and friends hospitalized with dengue-like symptoms. Initially misdiagnosed, they didn’t receive the immediate dengue treatment they needed, putting their lives at risk.

Yensi was, at that time, managing the Molecular Diagnostics Lab of the biggest private laboratory firm in Honduras. Her personal experience made her determined to find a way to ensure all Hondurans could get a quick and accurate diagnosis whenever they were suffering from symptoms which could indicate the disease: fever, body pain, diarrhea and other flu-like symptoms.

Yensi was, at that time, managing the Molecular Diagnostics Lab of the biggest private laboratory firm in Honduras. Her personal experience made her determined to find a way to ensure all Hondurans could get a quick and accurate diagnosis whenever they were suffering from symptoms which could indicate the disease: fever, body pain, diarrhea and other flu-like or even menstruation-like symptoms.

Dengue diagnostics in Honduras

In Honduras, dengue is generally diagnosed by a combination of symptoms and a blood platelet count. But the diagnosis is not conclusive since there are other things that may cause the same symptoms: flu, a bacterial infection, menstruation or one of the three other arbovirus infections circulating (chikungunya or Zika).

Scared and aware that the weak public health system was often oversaturated and unable to meet the population needs; people with dengue-like symptoms often turn to the private alternative. Most of them go to a lab for a blood platelet count to diagnose their symptoms themselves. After all, lab tests don’t need a prescription and self-diagnosis cost significantly less than an initial $25 trip to the doctor, $10 lab test, $25 follow-up with the doctor and so on for medication.

Without a specific diagnostic, or even a doctor in the loop, misdiagnosis is commonplace. After all, symptoms are only suggestive of dengue, but don’t establish a definitive diagnosis. And a low platelet count symptom is not always present.

So, if a patient’s shows a reduction in platelet levels, doctors and/or self-treating patients may assume dengue – whether or not it really is. On the other hand, if they don’t assume dengue, they assume another infection and might purchase aspirin, antibiotics or painkillers (including steroids) from their local pharmacy to treat their ‘infection’ – again without needing a prescription. This can be dangerous.

“If they do have dengue and take aspirin, they might develop hemorrhagic fever,” says Yensi. “If they take steroids, they might harm their liver. If they take antibiotics, they can build antibiotic resistance.”

Dengue disease phases and potential complications. Image via antimicrobe.org

A devious disease

Moreover, dengue is a deceitful disease; its critical phase begins just when you think you are getting better.

Usually, symptoms are very bad during the disease onset: fever, muscular pain, headache, migraines. During this time people tend to suspect dengue or the flu. These symptoms generally disappear within three or four days. People begin to feel better and think they’re recovering.

But hemorrhagic fever may appear between days four and seven after the initial onset of symptoms. A patient that isn’t being monitored will be caught by surprise. The journey to or wait in the hospital might take too long. The treatment they receive for hemorrhagic fever may be too late.

The clinical course of dengue, showing the three distinct phases. Image via nature.com

What good diagnostics would mean

An early reliable dengue diagnosis would ensure that people with dengue get the right follow-up and that positive cases at risk of hemorrhage are taken to the hospital, where they can be monitored to prevent and control hemorrhagic shock – saving living lives. “Doctors will have a clear scenario of the treatment course and people with a positive dengue diagnosis will seek adequate care, avoiding any neglect towards the disease” adds Yensi.

A timely and correct dengue diagnosis also means infected people can be isolated. “Dengue would not spread and Honduras would avoid the dengue epidemics that occur every four or five years,” says Yensi. “It’s people that spread the disease – not the mosquitoes that never travel further than 100 meters from where they were born.”

In addition, accurate diagnostics would also help authorities with resource planning (including for fumigation programs, allocation of medicines and hospital resources) and reduce the over expenses caused by many false-positives (patients negative for dengue but with symptoms and low platelet levels). Finally, they are key for assessing the impact of interventions such as a dengue vaccination program.

A search for a solution

For two years, Yensi searched for a company to provide a dengue molecular diagnostic. It would be more effective than traditional immunoassays, which can only give results after the critical period of the disease has passed. Yensi didn’t find anything, the region nor the disease was of interest for many companies, despite the clear demand.

An MSc in molecular biology at University College Cork helped Yensi learn the principles of molecular assays. “I realized the project was feasible and that with the technology in place we could achieve much more than just a traditional molecular essay, which limits reach and impact because of the cost of reagents and the cost of equipment needed to run the test,” Yensi says. “Now, I could create a molecular assay that will be inexpensive, mobile and not rely on specialized equipment or personal.”

With the idea in mind, Yensi met Blaine Doyle, a young biotechnologist with all the enthusiasm to develop the new diagnostic: “He was intrigued and he just knew how to move it forward.”

GlowDx is born

In less than a week, Blaine set up their company and signed into IndieBio, from where they obtained their seed funding. In less than a year, Blaine turned Yensi’s rough idea for local small-scale production that was going to take around 10 years to bring to life into GlowDx. An Irish start-up that would launch diagnostic tests within three years.

#IBYE Impact! Blaine Doyle of @GlowDx #TeamKilkenny @LEOKilkenny #DrivetheDream pic.twitter.com/I95UPdNRWu

— IBYE (@ibye_2016) November 18, 2015

Over the years, GlowDx has built on its technology while adapting its approach. Some components are now at the proof of concept while other are still being refined to guarantee the specificity and sensitivity required for a high-quality diagnostic test.

“We have evolved from a diagnostics approach that glowed to indicate dengue to a robust solution that will be cost-effective, simple and reliable,” says Yensi.

Annnnnnd we are in the final tomorrow!
Congrats to @DesktopGenetics!@liaonet @indbio @CorkBIC #SXSW2016 #irelandatsxsw #IrelandOn6thSt

— GlowDx (@GlowDx) March 13, 2016

That robust solution also includes a small portable hardware unit, some software for reading and interpreting the results and networking that will allow the results to be shared automatically.

Plans for the future

GlowDx plans to launch the final solution in 2018, but not before ensuring the technology meets Yensi’s original aim of developing a simple test that is suitable for low-resource settings. “We visited major hospitals as well as urban and rural clinics in Honduras where we developed links with epidemiologists, clinicians, and other health personnel,” says Yensi. “They’ve guided us in the development of a tailored solution that could be used by non-specialists in rural clinics.

”The company is also currently working on is a way to share results automatically, feeding local health authority’s heat maps of dengue cases. “This information is crucial for the local health community, for helping plan dengue prevention initiatives,” states Yensi. “The spread of dengue and other arbovirus infections can be prevented. Education and awareness campaigns before an epidemic arises can save lives and alleviate the heavy economic burden of these diseases.”

The company is also currently working on is a way to share results automatically, feeding local health authority’s heat maps of dengue cases. “This information is crucial for the local health community, for helping plan dengue prevention initiatives,” states Yensi.

“The spread of dengue and other arbovirus infections can be prevented. Education and awareness campaigns before an epidemic arises can save lives and alleviate the heavy economic burden of these diseases.”We look forward to learning more about GlowDx as its novel approach to dengue diagnostics comes to life.

We look forward to learning more about GlowDx as its novel approach to dengue diagnostics comes to life.

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