Community projects add vaccine to anti-dengue arsenal

Break Dengue Community Action Prize results – One prize, two awards

In 2016 Break Dengue launched the Community Action Prize – a competition which rewards the best grassroots initiatives that combat dengue in an innovative way while integrating dengue vaccines as part of a holistic plan.

67 submissions from NGOs, healthcare professionals, vector control specialists and active community members entered the competition. Participants proposed ideas on how to educate communities on the dengue risk, help implement prevention measures and address community-level drivers and barriers for dengue vaccine integration.

Out of the 67 submissions, 15 finalists were selected and sent to the jury for deliberation. You can find the full list at the end of the article.

After careful analysis, we are excited to announce the winning initiative – Integrate vaccine aspects in “Implementing integrated vector management for dengue control”. This project is based in Phnom Penh, Cambodia and the jury was impressed by the initiative’s strategy to integrate a dengue vaccine within a proven, established platform initially focused on vector control. The results were unveiled today, at the ISNTD festival in London.

How will the initiative help combat dengue?

The project has an integrated approach to fighting dengue. It will first be implemented in the province of Kampong Cham, an area which suffers one of the highest dengue incidence rates in Cambodia. The initiative will be further implemented at the national level, through sustained efforts for governmental collaboration.

The Break Dengue Community Action Prize will allow the winning team to make a real difference in the fight against dengue by building on a successful vector control platform to establish a robust vaccine integration program at the community level. This will help to raise vaccine awareness with the support of Community Health Workers and the implementation of a COMBI (Communication for Behavioral Impact) program. In this way health educational messages are being developed with community members’ input (to ensure cultural resonance) and disseminated via a tuk-tuk driving through villages. These efforts will be scaled to the national level by leveraging the initiative’s strong relationship with the Cambodian Ministry of Health as it revises its National Dengue Strategic Plan for 2017-2020 to integrate dengue vaccines.

The jury recognized the scalability and potential for impact of this initiative’s integrated methodology. The submitting team’s strong presence at the ground level and a collaborative approach with the Cambodian Ministry of Health leaves it well positioned for success.

Special award for a systematic approach to vaccine integration

Break Dengue wishes to reward another initiative which submitted a strong scientific methodology for analyzing the vaccine integration options in the overall Colombian strategy to fight dengue.

The initiative – “Evaluation of Introduction of Dengue Vaccine in Colombia” – submitted by the George Washington University in USA, proposes surveying patients, practitioners, and public health officials to evaluate the feasibility and acceptability of introducing a dengue vaccine into Colombia.

The initiators plan to focus on elements vital for dengue vaccine dissemination such as: evaluation of budget for dengue vaccination nationwide, capacity for immunization monitoring, capacity for cold chain and logistics, vaccine demand, and vaccine acceptability.

These are the first steps in developing a systematic, science-based approach to dengue vaccine implementation. The jury views this to be an initiative of the highest distinction which has the potential to complement strategies to build an integrated approach to dengue control around the world.

Ambitious targets – now what?

The Break Dengue team will not only support the winning initiatives, but it commits to supporting the finalists through various activities – from editorial coverage to looking at how they can be included in the constantly-growing Break Dengue ecosystem.

Acknowledgments

We would like to congratulate all the 67 applicants, as well as the 15 finalists of the competition:

Creativity beats dengue. Break Dengue participates at this year’s ISNTD festival

Break Dengue is proud to be one of the patrons in this year’s ISNTD Festival.

On the 23rd of February representatives from creative industries will come together in London to try and find innovative solutions for global health. New media, film, theater, radio, photography, documentary, e-health, social media and digital marketing are just some of the industries present at the festival.

Together we can find dengue

Break Dengue presented three challenges to be tackled by the festival participants:

Communication & increasing awareness of dengue burden and risks at global level;
Generating better data about dengue, dengue surveillance and creation of a Dengue Barometer;
Building ambassadors and mobilizing the scientific community.

We are committed to implementing the most scalable and sustainable idea on how to communicate the dengue risk, develop the prediction tool and build a strong scientific community. We will carefully analyse all submissions per each challenge and offer a symbolic prize to the best ideas.

Follow our Twitter account on the day for live updates and this blog to find out more about the hackathon ideas.

Fighting dengue with data creativity

As part of the festival, a series of speakers will talk about innovative solutions for global health. Some of the participants include representatives from Bill & Melinda Gates Foundation, BBC Media Action, MTV Staying Alive Foundation, The Leprosy Mission England & Wales etc.

Nicholas Brooke, CEO for Break Dengue and the Synergist will talk about ways of fighting dengue with an innovative platform and data collaboration tool.

Find out here more about the event.

Fight Dengue app: tackling dengue at the source

Data on where people have been in the days leading up to their diagnosis promises to provide a novel source of insight on the source of infections. But accessing that data isn’t as easy as you might expect, as the Fight Dengue app’s creator explains.

“If there’s a mosquito outbreak near where we live, I want to know so I can ensure my kids put on extra protection before they go to school,” says Steve Barnes, CEO of Access Devices Asia and inventor of the Fight Dengue application.

Steve and his family live in Malaysia, where dengue cases and deaths have been growing year on year. “So much more could be done,” says Steve. “People don’t understand that they need to be quarantined for a week if they’re infected. A lot more education is needed.”

Working in IT, Steve is more than familiar with the term Big Data and how the technology giants are gathering loads of data to build a big picture of the world around us. But Steve wasn’t interested in the big picture; he just wanted to know about the things that are important to him.

“I’m not interested in the broad brush strokes,” says Steve. “I want to know where dengue is and where it has come from so I can protect my family.”

Unable to find a tool that would let him know when there was mosquito activity nearby; Steve decided to develop his own web app: Fight Dengue.

Combining official and informal data sources

Steve’s Fight Dengue app marks active dengue cases with red spots, then uses green heat maps to mark bites and blue heat maps to mark breeding grounds.

Case information is sourced from official case data feeds supplied by the Ministries of Health of Malaysia and Singapore. Information on mosquito activity and breeding grounds are crowdsourced: users use the app to report breeding grounds or bites. Users can also use the app to check on dengue and mosquito activity in their local area and to share local cases on social media.

“The app lets people know whether their area is safe or if they need to take extra precautions because there is a dengue outbreak nearby,” say Steve. “I use it to see if there are cases near my home and my kids’ school.”

To date, more than a thousand users have downloaded the app.

But knowing where the dengue cases and mosquitos are is only half the battle.

Where’s the source of infection?

“We also need to know where people are being infected,” adds Steve. “Three of his wife’s school friends were diagnosed with dengue a few days after meeting in the park. There’s a high chance that the park was the dengue source.”

Combining accurate data on the locations of each infected person in the days preceding diagnosis could help to identify potential sources of infection; it could be overlaid to identify common locations.

“If we know where the infection started then we can narrow down the sources of dengue,” says Steve. “Identifying the source of infection will have a dramatic effect on the number of future cases. It doesn’t require a huge amount of data or processing power.”

Steve would like to see doctors ask their patients to install the Fight Dengue app and anonymously submit data on where they’ve been for the last 15 days at the point of diagnosis. There are a number of different ways this could be done:

By using the app to collect the data on where a person goes and upload the information if they become infected. For that to work, everybody would need to install the app in case they become infected.
By using location data gathered by an infected person’s mobile service provider as the source of where they have been, but that lacks accuracy and there’s much red tape to cut through.
By using location data gathered by Google but, although Google probably has much of the data needed, it doesn’t provide an easily accessible API (programming interface) that would allow Steve to do this.

“When someone is diagnosed with dengue, we could immediately compare the previous location data of this patient,” says Steve. “If we could locate the source of the infection, resources could be used more effectively to resolve the problem.”

For now, without that all-important local data, Steve simply plans to simply keep the app running and, whenever there is mosquito of dengue activity near to where he lives, to ensure his family is adequately protected and print off the map and share a copy with local schools.

Meanwhile, our Dengue Track here at Break Dengue has also been crowdsourcing dengue data and translating it into meaningful and actionable information, alerting people when they may be at risk. “I think it’s a great tool,” comments Steve. “It has a nice novel way of crowdsourcing additional data from the users and a huge selection of educational material, which is so valuable.”

With so much data being gathered, how are you using the figures to help your local fight against dengue?

New dengue treatments needed to fight Asian tiger mosquito

New dengue treatments are required to keep up with the evolving dengue threat, which some fear could hit Europe and the US. As the Asian tiger mosquito spreads the disease to colder climes, the co-founders of Effecta Pharma explain their efforts to tackle the problem today.

The extent to which dengue infection has advanced over the past few decades has been phenomenal. Most of this spread has been down to the Aedes aegypti mosquito. This primary dengue vector thrives in tropical and sub-tropical climates but struggles to survive in cooler temperatures.

While we’ve previously raised concerns about how climate change might allow this vector to spread further afield in the future, we haven’t considered the threat from its cousin and secondary dengue vector: Aedes albopictus.

Aedes Albopictus: partner in crime

Also known as the ‘Asian tiger mosquito’, Aedes albopictus, though native to the same regions as its cousin, has successfully adapted to thrive in cooler, more temperate regions. Here it hibernates over the winter months and can even tolerate snow and freezing temperatures.

According to the European Centre for Disease Control (ECDC), the Asian tiger mosquito has already reached more than 25 countries in Europe, largely because of international trade and infected travellers returning home from endemic regions: “The presence of Aedes albopictus in Europe and the increasing number of overseas travellers may increase the risk of dengue outbreaks in Europe”.

ECDC believes climate change could further increase the distribution of the Asian tiger mosquito and enhance the risk of dengue in temperate regions. This is confirmed by a recent eLIFE study that highlighted the mosquito’s potential to spread across Europe and the Americas.

Image showing the needs for new dengue treatments as the risks of mosquito-borne disease spreads to new countries.

Images via elifesciences.org

The maps in figure 1 show the study’s predictions on the probability that Aedes albopictus will appear in Europe (A) and the United States (B) – red being 100%. It notes that these are “regions in which Aedes albopictus is rapidly expanding its range”.

“Dengue has and will continue to spread to the West and become a significant problem in the future,” says Dr. Paul Edwards, co-founder of Effecta Pharma, a UK-based biotechnology company dedicated to the discovery and development of novel medicines to treat viral diseases.

Effecta is focussed on developing antivirals for treating dengue and other flaviviruses (a genus of virus that also includes the West Nile virus, Yellow fever, and Zika virus).

A new treatment?

Dr. Edwards believes that given the time it takes to discover and develop new drugs, now is the time for the West to act so that a treatment is in trials or ready on the market for when those epidemics happen. Any novel treatments developed would not only stop dengue becoming endemic in Europe and North America, they would also help in the fight against dengue in the warmer regions where it is already endemic.

“Currently, there are no therapeutics for dengue virus infection on the market,” says Dr. Helmuth van Es, co-founder of Effecta Pharma. “There is a real need for an effective and safe treatment.”
Effecta’s dengue drug discovery program aims to identify a safe and effective drug that can be used to treat dengue, possibly in combination with other classes of dengue antiviral drugs. “We’re looking to treat all dengue serotypes within five days of onset of symptoms,” says Dr van Es.

The team at Effecta are also hoping to develop a ‘direct acting antiviral’ pill that the local population could take in the first few weeks of an outbreak, to protect themselves against the virus. Although this hasn’t yet been proven in practice, Effecta has spoken with experts in the field and these researchers believe that the potential for developing this type of proactive treatment is there.

Early stages of a new dengue treatment

Effecta is still in the early stages of drug discovery in this area and is currently seeking partnerships and funds to take it to the next stage.

A collaboration with the European Lead Factory (ELF) has produced some potential ‘hit compounds’ (hits from a high throughput screen (HTS) that have been evaluated as promising lead compounds – chemical compounds that show pharmacological or biological activity likely to be therapeutically useful). It’s still early days, but Effecta is hoping these chemical starting points will result in preclinical candidate drugs that will one day be tested in a clinical proof of concept study in patients

In parallel, Effecta’s dengue drug discovery program has also been studying the dengue virus NS5 protein that studies have shown plays a key role in the virus being able to replicate itself. Understanding the structure of this protein is critical to identifying a chemical compound that can act on it. Effecta has been looking for ‘pockets’ that a drug could bind to in order to hinder this replication and, in doing so, produce an antiviral effect. This phase was funded by the Wellcome Trust. Now almost complete, it resulted in additional chemical starting points for drug discovery and development.

As dengue continues to spread across the global – with global trade, climate change and the evolution of the Asian tiger mosquito giving it a further boost – are we doing enough to combat the disease? The development of new drugs today and new dengue treatments for tomorrow are critical to combating the ever-evolving threat posed by dengue and its vectors.

—

Click below to begin mapping dengue from your smartphone.

Dengue Track

Break Dengue award for creative prediction models

We are excited to have been part of the data hackathon organised by DengueHack.org on November 25th and 26th in Brussels.

We feel very fortunate that over 60 participants chose to spend their Saturday browsing through our datasets to tackle problems related to dengue. Everyone showed creativity and two teams were awarded the 2 * €500 prize.

During 36 hours data scientists, programmers and designers used a high variety of data to help build a model that would identify outbreaks sooner, predict future outbreaks, educate the public or determine new factors that could influence the dengue virus spread. We are very happy to reward the most actionable, scalable and sustainable ideas to break dengue!

10 teams were spontaneously formed, each one of them bringing a fresh perspective in the area. From analyzing Twitter streams and big data from the news, to looking at demographic and vegetation data, the teams proved to be not only determined in the fight against dengue, but also creative and technically competent.

The Break Dengue team decided to offer a €1000 prize to be split between two teams that fulfilled certain criteria put together by our jury. The winning ideas were asked to be actionable, scalable and sustainable. They were also supposed to combine at least two types of data: traditional data (like number of dengue cases), nonconformist data (like crowd surveillance or social media data) and “surprise” data (any type of data that is usually not used in the epidemiological conversation).

After careful consideration, our team picked two winning teams:

1.The Cube

This team focused on analysing the media and keywords used in communication, as well as on trends in social media and traditional media, using data mining techniques. Our jury considered this was a fresh idea that could support the “traditional” prediction tools created today, which only use traditional datasets;

2. Explodata

This team focused on trying to predict dengue, by analysing the presence of mosquitos in addition to other types of traditional data. The novelty of the approach included a look at the link between deforestation rates and dengue outbreaks.

The efforts from this Hackathon will not stop here. We will continue working with the data scientist community to follow up on these projects and ideas.

We would like to thank everyone who participated and helped make this contest a success. Special thanks go to John Snow Labs, our healthcare data partner.

We look forward to the upcoming hackathons and prizes in 2017! Stay tuned.

Global health threats vs Microsoft’s tech know-how

Image of the tools usf in Projact Peminition, by Microsoft, fighting global health threats like dengue and Zika.

Images courtesy of Microsoft

Global health threats are on the rise, due in part to the widening reach of the world’s deadliest creature…the mosquito. Mosquitoes spread deadly diseases such as dengue, Zika, and malaria just to name a few, and Project Premonition aims to give dengue outbreak prevention a jump start that we could have only dreamed of just a few years ago. Microsoft takes its own technology know-how to the fight against dengue and other global health threats.

Wouldn’t it be great if you had a heads-up that dengue is heading your way? Or that the dengue you’re currently fighting is changing tack?

That is exactly what Microsoft’s Project Promotion is aiming to give communities around the world. The Microsoft Research team shared their ambitions in a blog post on Microsoft’s site last year: “Project Premonition could eventually allow health officials to get a jump start on preventing outbreaks of a disease like dengue fever or avian flu before it occurs, whether or not it is a disease spread by mosquitoes.”

The three key elements to Project Premonition all leverage the computer giant’s latest technology advances:

Smart insect traps use machine learning to distinguish disease vectors from other flying insects.
Smart drones use machine vision and learning to identify mosquito hot spots where smart traps could be placed.
Genetic sequencing uses advanced analytics to take a closer look at any vectors caught in the traps.

The smart trap

Let’s start by taking a closer look at Microsoft’s traps. Unlike most traps that simply catch any insects passing through, Microsoft’s smart trap intelligently checks out what it has caught before deciding whether to keep hold of it or set it free.

The Microsoft research team reports in its post that the trap “is designed to only collect the type of mosquito an entomologist wants to track, instead of a hodgepodge of mosquitoes, flies, moths and other critters that scientists then need to manually sort through.”

How does it do that? By analyzing the wing movements of the little creature. If the insect looks like a ‘mosquito of interest’, the trap shuts its door.

That intelligence relies on some very advanced technologies: machine learning in particular. Machine learning is not only critical for the initial training each trap needs, it also helps ensure each trap continues to learn from its mistakes once deployed in the field.

Mosquito traps were deployed in Houston, Texas, last summer to gather the insects and the data needed for the training. Microsoft explains how, to recognize which mosquito it’s supposed to catch, the trap “needs what experts call training data: Lots and lots of examples of mosquitoes and other bugs flying into the traps. […] That data can then be used to build an algorithm that uses machine learning to help the trap learn to correctly identify the mosquito it should be capturing.”

Building a clearer picture

But the traps do more than simply catch potential vectors. They also record when the insect was trapped and the local weather conditions at that time, wirelessly downloading that information to the Microsoft cloud for scientists to then explore.

“That could help scientists understand the specifics of how a virus is spreading, such as what type of mosquito is infecting people and whether those mosquitoes are more likely to feed at night or when temperatures reach a certain point,” according to Microsoft.

The smart drone

In addition to the smart traps, Microsoft is also developing technology to make drones smarter. With these advances, Microsoft hopes drones will one day be able to autonomously (on their own without human input) place the smart traps in mosquito hotspots.

Again, these smart machines will rely on some of the latest technological advances: computer vision technology and machine learning.

Together these technologies could allow the drones to seek out remote areas where mosquitos are gathering. The team also hopes to train the drones to place the smart traps in suitable locations in these areas and pick them up again.

“Using drones instead of people [hiking for several hours] could be another way to save time and money,” Microsoft says.

The Asian tiger mosquito has adapted to colder climates, raising the risk of dengue spreading into new regions of the world.

Cutting-edge molecular biology

The third part of the solution is all about examining the mosquitos caught by the traps. Not just at the microscopic level, but right down to their genes.

A view on how the mosquitos, or even the pathogens, are evolving would be invaluable on so many levels. We’ve recently looked at how Aedes albopictus, also known as the Asian tiger mosquito has adapted to colder climates, raising the risk of dengue spreading into new regions of the world. Any warning on further changes in the vector’s DNA could be a crucial warning of its potential to survive in new environments.

On another level, visibility on any evolution in the dengue virus itself is going to be critical to programs developing therapeutic antivirals for treating the disease or vaccines for its prevention.

So, what elements of its technology know-how is Microsoft using for this analysis?

“The latest advances in both computer science and molecular biology are making it more practical for researchers to cull through the ‘soup’ of mosquitoes and the blood they fed on to figure out what viruses and microbes might be lurking there,” Microsoft reveals.

The ‘soup’ is being used to identify the species of mosquitoes collected, the animals they have bitten and the pathogens they may have encountered. New algorithms are needed to compare its contents with reference genomic (DNA) and protein databases to help scientist identify viruses and whether they are evolving. Microsoft recently shared news on a separate project aimed at accelerating genomic sequencing.

Global health threats at the crossroads of technology and society

It’s great to hear about how one of the technology giants is taking its own technology advances to the fight against dengue and other global health threats.

“Microsoft is driven to find innovative solutions to pressing societal problems that intersect with technology. With this project, we believe there is the opportunity to revolutionize disease monitoring in a safe and efficient manner. Our hope is that by combining custom-built traps with drones and the power of the cloud, we’ll be able to collect and analyse a plethora of previously unavailable data on a number of vector-borne diseases,” Ethan Jackson, a researcher in The Research in Software Engineering (RiSE) Group at Microsoft Research focusing on formal methods for safe cyber-physical systems (CPS) who is leading Project Premonition.

We’ll be keeping a close eye on the progress being made by this truly innovative project. Stay tuned…

—

Inside GlowDx: A personal journey into dengue diagnostics

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.

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.”

Image showing the dengue disease phases and potential complications.

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.

Image showing the clinical course of dengue, showing the three distinct phases.

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_ie) 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.

—

Dengue diagnostics: a vital tool for disease control

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

When a parent presents their child at a clinic with a high fever, clinicians often find it hard to determine the cause based on the symptoms alone. After all, it could be malaria, dengue, Zika, chikungunya or one of a host of other possibilities.

“Whenever it’s rainy season and there’s a dengue outbreak, emergency rooms are full of anxious parents with children with a fever,” states Professor Rosanna Peeling, Professor and Chair of Diagnostics Research at the London School of Hygiene and Tropical Medicine (LSHTM) and Director of the International Diagnostics Centre (IDC). “For them, efficient and accurate dengue diagnostics are very important for early confirmation of dengue as it can quickly progress to severe dengue in children.”

More than that, diagnostics also have a vital role to play in identifying infectious diseases that have the potential to become an epidemic – including dengue. Diagnostics not only helps with quickly identifying the cause of the outbreak; it also allows the impact of any interventions to be assessed.

Getting it right

The dengue diagnostics available for detecting and confirming the disease are wide-ranging. At one end of the spectrum are reliable, but time-consuming, laboratory tests; at the other are rapid testing kits that can be used in the field but vary substantially in their accuracy.

In developing countries, clinicians seldom have access to laboratory tests. Instead, they rely on the rapid tests, which are often sold and used without evidence that they work.

“Dengue and malaria diagnostics are not regulated in most countries in terms of their quality and safety,” states Professor Peeling. “There is a real need for the global community to share information on the latest diagnostics, how well they work, and what they should be used for.”

But it’s not just the effectiveness of the tests that is a concern; it’s also how and when the tests are used since the presence of the dengue virus in the patient’s blood becomes harder to detect over time. From day six onwards, diagnostic tests should be used to look for antibodies rather than the virus in the patient’s blood.

“People shed the virus in the first five days from the onset of fever,” states Professor Peeling. “We have shown that no matter how good the test is for detecting the virus, they can only really be used in the very early phase of infection since sensitivity drops down to as low as 30 percent from day six onwards. We need the right test, at the right time, for the right population.”

Understanding dengue diagnostics

In its 2009 report, Dengue: Guidelines for diagnosis, treatment, prevention and control, the World Health Organization devotes a whole chapter to dengue diagnosis; it describes in some detail the timeline for the evolution of the virus, the body’s response from the onset of fever and the role of diagnostics as time progresses.

In their early stages, dengue infections can be diagnosed by identifying dengue antigens (foreign bodies that cause the immune system to react) in the patient’s blood: isolating the virus itself or by detecting its genes (DNA/RNA) or its proteins (NS1). In their later stages, when the virus has disappeared from the patient’s blood, dengue infections can be diagnosed by detecting dengue antibodies (IgM and IgG) in the patient’s blood. The patient’s immune system will have produced these in response to the virus.

Image via WHO http://www.who.int/tdr/publications/documents/dengue-diagnosis.pdf

The report also compares the various dengue diagnostic methods available back in 2009, along with their advantages and disadvantages. It also notes: “Unfortunately, an ideal diagnostic test that permits early and rapid diagnosis, is affordable for different health systems, is easy to perform, and has a robust performance, is not yet available.”

Where we are today

Traditionally, confirmation of an acute dengue infection has required detection of IgM antibodies or detection of a four-fold rise in the concentration of IgG antibodies in paired specimens of the patient’s blood – one collected during the acute disease and once the patient is recovering.

An article published in the Nature Research Journal last year discussed the viability of rapid test kits that can be used outside of the laboratory for detecting the virus’ NS1 protein. In many cases, it notes, “the infection status of patients limit the sensitivity and reliability of these tests and laboratory confirmation is often required.” And so in dengue endemic areas, a test that takes several hours and requires specialized personnel and laboratory facility remain the norm.

And so it seems clinicians caring for patients with high fevers continue to contend with delayed results that are of limited value.

We can, however, expect this to change soon. The urgent need for rapid, accurate and affordable diagnostics has accelerated with the WHO declaring the Zika outbreak a health emergency of international concern. With dengue, Zika and chikungunya all displaying similar symptoms, developing tests that can be used outside of a laboratory and are sufficiently sensitive to identify which of these three diseases is the cause of a patient’s fever is now a top priority.

New dengue diagnostics possibilities

New diagnostics are emerging, specifically, diagnostics that combine virus or antigen detection with detection of IgM antibodies. A recent publication by Hunsperger et al in the Journal of Infectious Diseases showed that if we combine the detection of dengue virus or NS1 proteins with a test for IgM antibodies using a single sample collected during the first 10 days of illness, we can accurately identify more that 90 percent of primary and secondary dengue infections.

Professor Peeling comments: “Recent advances in diagnostics will be incorporated in the new WHO guidelines for dengue, Zika, and chikungunya, which can cause outbreaks in the same population.”

The US Centers for Disease Control and Prevention (CDC) have already done quite a bit of work in this area, sharing their findings.

New diagnostics products

There are a number of companies working on products in this area. Towards the end of 2015, we published an article about an innovative rapid test from start-up BluSense Diagnostics.

Catching up with Dr. Marco Donolato, the company’s Chief Scientific Officer, he told us how the company is about to embark on testing of its prototype for detecting the NS1 and that it is also expanding the biomarkers its technology can detect. “We are now also working on detecting the antibodies IgG and IgM and will be testing that in the field during November,” states Dr. Donolato.

With such good progress, BluSense Diagnostics has been awarded a substantial grant by the US Agency for International Development (USAID) for developing its technology as a diagnostic for Zika. Dr. Donolato adds: “We have seen that we can detect Zika in NS1 and we hope to finalize our product for both dengue and Zika next year.”

To get there the company must ensure its technology meets the performance requirements set out by WHO and gain ISO certification as a manufacturer of medical devices, which it hopes to achieve by February.

Also in the pipeline is a new rapid test kit that’s being developed by GlowDX – Break Dengue will have a feature interview with the company next month.

Diagnostics is clearly taking some great steps forward in the helping clinicians treat dengue. More than that, it may well also have a critical role to play in dengue vaccination programs too. Look out for future discussions to learn why.

—

Community health projects in line for dengue funding

€10,000 in funding for projects and ideas that integrate vaccine into anti-dengue strategy

Community health projects can help societies to embrace new tools in a way that ensures buy-in from local people.

That is why we have launched the €10,000 Break Dengue Community Action Prize to support projects that make the most of public health interventions. This community-centric approach will back a project or initiative that can integrate vaccination into the anti-dengue arsenal.

We are looking for pilot initiatives or simply ideas to design and test new approaches to integrating a dengue vaccine as part of a holistic plan to combat dengue. These ideas or initiatives should ideally identify, understand and address community-level drivers and barriers for dengue vaccine integration, its sustained uptake, and/or compliance.

Grassroots campaigns

Community-driven initiatives are more likely to be successful because they answer an unmet need and are presented in a way that resonates with the target audience. They can create awareness of health challenges – and solutions – by developing publicity campaigns designed by communities.

The role of community health projects was highlighted at ASEAN Dengue Day 2016 and the Aid and International Development Forum (AIDF) in Bangkok earlier this year.

“Dengue prevention and control is a shared responsibility which needs collective action from all stakeholders to work together and enhance cooperation as one community,” said the Bangkok Call for Action released on the occasion of the 6^th ASEAN Dengue Day, held under the theme, ‘Community Empowerment: A Sustainable Success to Fight Dengue’.

For this approach to be effective, identifying the key actors in the communities is essential. “This is very context specific. Some may believe more in religious figures. For other, the village chief is more acceptable to them,” says Muhammad Shafique, Regional Behaviour Change Communication Specialist at the Malaria Consortium.

Image of the Aedes moqsuito. Public health organizations are uniting to stop the disease it spreads.

Community health projects could improve dengue vaccine uptake

Nevertheless, research shows that the most trusted figures are community healthcare workers (CHW). In India, for instance, CHW help to strengthen the immunization programs and reduce the burden of vaccine-preventable diseases, according to a study from the University of Pittsburgh.

Examples from the field

Communities have been mobilized to:

improve disease surveillance in India
encourage vector control in Laos and Cambodia
raise disease awareness in Thailand
rid Malaysia of mosquito breeding sites,
unite the Virgin Islands against dengue

Modern approaches to community health include ‘positive deviance’ – highlighting examples of healthy behavior from within communities.

Similarly, community role models can help to reassure a local population that taking action to stay healthy is in keeping with their core identity. For example, this Australian project sought to reassure people that vaccination is compatible with their strong communitarian values.

It saw real parents step up to tell their friends and neighbors that their children are vaccinated – helping to normalize the behavior in an area where alternative health practices were common.

So whether it is through education, role modeling or health service delivery, community projects can play a vital role in the fight against dengue.

—

Controlling mosquito populations with toxic sugar

Image of the world's deadliest creature. The mosquito.

Images courtesy of Professor Gunter Müller

Controlling mosquito populations is becoming an ongoing battle in much of the world. Like any other living thing, mosquitoes need the energy to survive. They need it to fly, to reproduce … to live. Many people think that all mosquitoes bite humans and that our blood is their main source of food.

But did you know that it’s only female mosquitoes that bite us? And that she uses the protein in our blood to help her eggs develop – not as a source of energy? The main source of energy for mosquitoes – male and female alike – is actually sugars derived from plant nectar, fruit juices, and other natural juices.

So, what does this have to do with vector control?

More than a decade ago, Professor Gunter Müller and Professor Yosef Schlein from the Department of Microbiology and Molecular genetics, IMRIC, Kuvin Center for the Study of Infectious and tropical Diseases, Faculty of Medicine, Hebrew University of Jerusalem in Israel (HUJI) came up with an elegant vector control solution based on the simple fact that mosquitoes require sugar for survival.

Amy Junnila, an entomologist at HUJI, explains one of the key benefits of this approach: “While current insecticide-based vector control solutions use environmentally toxic materials to which mosquitos develop resistance, this solution overcomes resistance because there’s no repeated exposure.”

There are currently three teams working on the project: a team – including the principal investigator – from the Hebrew University, a group from the University of Miami and researchers at the University of Bamako in Mali.

The right formulation

The attractive toxic sugar bait, or ATSB as it is more widely known, has three main components: something attractive to entice the mosquito, an oral toxin to kill it and a feeding stimulant to compel the mosquito to eat and digest the toxin.

Finding a suitable attractant wasn’t easy. After all, it needed to be more enticing than the natural flowers and vegetation that mosquitoes would normally gravitate towards. Attractants suited different ecologies. “Local fruits and seedpods ripen in buckets worked very well in Mali,” says Amy.

The team tested various flower scents, fruit juices, wine and seed pods. Whilst many were similar in their effectiveness, they needed something that was commercially available. That way they would be able to scale the solution up for mass production. They settled on using nectarine juice.

Is public health headed for an ‘analytics revolution’?

The oral insecticide chosen was garlic oil. Not only had it been used against other pests; it was a food additive and, as such, poses little risk and requires little regulation.

“We started out with Spinosad because it’s a good, low-risk insecticide with low toxicity to mammals,” says Amy. “But it would have been too expensive for many regions. We also looked at boric acid and Dinotefuran.”

For the feeding stimulant, the team chose sugar.

How the ATSB works

The ATSB is sprayed on non-flowering vegetation. It works by first attracting the mosquitoes then providing sugar to entice them to feed and the oral toxin to eliminate them.

“By not spraying it on the attractive blossoms that bees and other insects feed on for their sugar we have reduced its impact on those populations.”

Not poisonous to mammals or other animals, the ATSB can also be used within a portable bait station. The station looks like a water bottle with a sock around it. Mosquitoes are attracted to and feed on the ATSB-soaked sock.

“You could hang the bait station around the yard for the mosquitoes to come and feed on,” says Amy. “Putting a wire mesh around it ensures bees and butterflies can’t reach it.”

Image aof a mosquito trap intended at controlling mosquito populations.

Image courtesy of Professor Gunter Müller

Extensive testing

HUJI first tested the ATSB approach in Israel against a number of mosquito species. Since mosquitoes in Israel don’t carry disease, the testing focused on the ATSB’s effectiveness in eradicating mosquitoes. “We added different food dyes to the ATSB to allow us to see which mosquitoes had fed from which ATSB,” says Amy.

Image courtesy of Professor Gunter Müller

Testing found the solution to be particularly effective against more mature insects, which, incidentally, are the age group most likely to carry and transmit disease.

Funding from the Bill and Melinda Gates Foundation allowed testing to move to Mali in Africa, where it focused on the ATSB’s effectiveness in eradicating disease-carrying mosquitoes. In Mali, the ATSB solution sprayed onto vegetation near breeding sites reduced local vector densities by 90%.

“We’re also testing the ATSB against different vectors,” says Amy. “We’re testing it against the Asian tiger mosquito because it’s such a nasty invasive mosquito species that’s so difficult to get rid of.” As well as dengue, the Asian tiger mosquito – Aedes albopictus – also transmits the chikungunya virus and heartworm in dogs.

More than that, the ATSB was also found to be effective against the sand fly, which also carries disease.

With the potential to help in the fight against a wide number of vectors and diseases, it certainly sounds like the ATSB will be a very welcome addition to the integrated vector management toolbox.

—