Active surveillance: understanding the burden of dengue

Image of a wall with messages in Mexico for active surveillance for dengue

Painted wall near Mexico City instructs residents about dengue. Photo courtesy of Professor Eduardo Undurraga.

We don’t yet have a clear picture of the true burden of dengue. It could be 58 million cases a year. It could be double that number. It could be half that number. We just don’t know. But understanding the true burden of the disease is critical – both for developing local dengue control and prevention strategies and for encouraging investment in technologies to help the global fight against the disease.

For dengue, as with all reportable diseases, public health systems are only able to report the cases that come to their attention – an approach to monitoring cases known as passive surveillance.

“Reported dengue case numbers depend on patients going to a health facility, those patients being diagnosed either clinically or through laboratory tests, and the healthcare providers reporting those cases to health authorities,” says Donald Shepard, Professor at the Schneider Institutes for Health Policy at Brandeis University in Massachusetts.

While those reported numbers are invaluable for public health– for comparing dengue over time and guiding responses – they aren’t always enough. When public health authorities are making decisions about deploying dengue prevention and control interventions, they need to understand the true burden of dengue. Professor Shepard explains: “To know the health benefits of a dengue control measure, you need an accurate picture of case numbers. With every dengue case avoided, the health system usually saves costs, and the well-being of the person who would otherwise have been sick is preserved.”

A true picture isn’t easy to come by

But figuring out the true number of dengue cases across a country is both time-consuming and costly. It requires active surveillance – where the health system carefully gathers information on the illnesses experienced by people across the country. Active surveillance for every case for every disease would be an extraordinary effort for a health system and a huge burden for patients.

“An extreme version of active surveillance throughout a country would literally require the country’s health system to telephone or visit every resident every week to ask if they had been ill in the last week,” says Professor Shepard. “If they had been ill, they would be asked to attend a clinic where they would give a sample of blood for testing. That would clearly be infeasible on a national level.”

Building a clearer picture

One answer to understanding the true burden of dengue lies in comparing existing passive surveillance data with data from any active surveillance undertaken in the same region. By doing this can you understand what percentage of dengue cases are reported and, from that, have a more accurate estimate of the true burden of the disease.

Take the Philippines as an example, where the government needed reliable estimates to inform dengue control measures. In 2012, the Armed Forces Research Institute of Medical Sciences (AFRIMS) and the Philippines AFRIMS Virology Research Unit (PAVRU), hosting Prof. Shepard and colleagues, described their ongoing cohort study on dengue in 1,008 adults and children in the Punta Princesa area of Cebu City in the Philippines.

Image of Active surveillance workshop for dengue in the Philippines.

Professor Shepard (front center) and other dengue experts meet in Cebu, Philippines, 2012.

The teams concluded that collaboration on a related study would be a valuable scientific contribution and feasible to implement. Subsequently, the related study was initiated with Professor Shepard as the principal investigator. Its goal was to estimate the burden of dengue in the Philippines using the active surveillance data gathered during the first study.

Professor Shepard explains: “We compared the active surveillance data of dengue infections from the Punta Princesa study with reported dengue episodes based on passive surveillance data from the Cebu City Health Department (CCHD).”

The study found the reporting rate of dengue in Cebu City to be just 21% or, expressed another way, the expansion factor of dengue to be 4.7. In essence, for every dengue case reported, there were between four and five actual cases.

Active surveillance from trials

Dengue vaccine trials provide another opportunity for gathering active surveillance data. Whenever a company tests a dengue vaccine or drug, it needs to capture and very precisely describe each illness to measure the effectiveness of its product.

A study into symptomatic dengue in five southeast Asian countries used the active surveillance data from Sanofi Pasteur’s vaccine trials to establish the dengue expansion factors for Indonesia, Malaysia, Thailand, the Philippines, and Vietnam. The study found it ranged from 0.5 to 31.7.

“Expansion factors vary from country to country, within a country, and may also vary by year,” says Professor Shepard. “The more active surveillance data becomes available, the greater our understanding of what the expansion factors are and how they vary.”

There are also other ways to estimate expansion factors. They can, for instance, also be estimated by analyzing overlap between two independent samples of dengue cases using a technique known as ‘capture-recapture’.

But many countries have no active surveillance data nor independent samples. They can only make generalizations on expansion factors from neighboring countries. And even when countries do have data available, it’s generally limited; they have to make generalizations on expansion rates across regions.

Turning up the volume on dengue

Reporting rates and expansion factors also have another role to play: they’re helping the world understand how devastating the global of dengue is.

The GBD (global burden of disease) collaborators at the University of Washington publish estimates on the burden of hundreds of diseases worldwide – including dengue. “As better data have become available, GBD estimates on the numbers of dengue deaths and cases have been rising steadily,” says Professor Shepard.

Image of students involved with active dengue surveillance in Mexico

Camino Verde (Green Way) participants exhibit mural near Acapulco, Mexico. Photo courtesy of Professor Eduardo Undurraga.

The rising estimates have helped to strengthen interest and investment in new approaches and technologies for fighting the dengue. Companies, governments, and donors are committing more time, money and resources.

But considerable uncertainty remains around current estimates. Professor Shepard discusses the figures he shared when we spoke with him last year on estimating the true cost of dengue: “We estimated 58 million annual episodes of dengue at a global annual cost of $8,9 billion. But economists’ confidence around that number is quite wide: the minimum could be less than half, or the maximum could be more than twice that number.”

Active surveillance is key to improving estimates not only on the burden of dengue but also on other diseases. After all, many of the uncertainties about the burden of dengue also apply to Zika since the same mosquito transmits both diseases.

“With Zika there is even less information on infections and, as such, even more, uncertainty. Applying what we have learned about dengue can help us understand the burden of and develop control strategies for other public health threats – in particular, the other diseases spread by the same species of mosquito, such as Zika and Chikungunya,” concludes Professor Shepard.

With many cases of dengue and Zika remaining undiagnosed, modern crowdsourcing tools are adding to the picture by allowing individuals to report cases themselves. Dengue Track, for example, combines information on dengue cases reported by users with statistics from larger national databases to create a real-time map of outbreaks and provide information to travelers, organizations and local communities. The same tool could be just as effective in mapping other mosquito-borne diseases, turning big data into actionable information.

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The more data we collect, the more accurate the system will be. Report dengue activity to near you to Dengue Track.

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Urbanization and globalization: spreading dengue around the globe

Half a century ago, dengue was under control; DDT and spraying kept Aedes aegypti mosquitoes at bay. In stark contrast, dengue is now a serious global health threat. Over the past four decades, dengue’s global threat has grown as urbanization and globalization have helped the Aedes aegypti mosquito spread the disease around the world.

We spoke with Professor Duane Gubler, Founding Director, Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, about the global trends over recent decades that have taken dengue from being a controlled disease to the growing global health problem we see today.

Complacency, urbanization, and globalization

Fifty years ago, every house in an affected area would be inspected for mosquito breeding and sprayed with DDT to eliminate the Aedes aegypti mosquito. It was a quick and cost-effective method for preventing outbreaks of dengue and other mosquito-borne diseases. Developed in the 1940s, DDT was the first modern synthetic insecticide. It could be sprayed both inside and outside of homes and other buildings, making it an ideal control tool.

“In the 1970s, we became complacent,” says Professor Gubler. “Dengue was not thought to be a global health problem. Interest in the disease decreased, along with the resources that went into managing it.”

But it’s not only our complacency that has led to dengue’s global threat becoming what it is today. Urbanization has also had a major role to play. Cities have grown bigger over recent decades. With that, they’ve become overcrowded. Housing is poor. Water and waste management are inadequate. Cities are now an ideal habitat for Aedes mosquitoes to thrive.

“It’s difficult to inspect and treat every house in large overcrowded cities,” says Professor Gubler. “Over the years, spraying techniques have evolved to spraying small droplets of insecticide into the air and hoping they impact a flying or resting mosquito – rather than targeted spraying of surfaces where mosquitoes rest before and after feeding and egg laying.”

In addition, growing cities mean more people are traveling between them and surrounding rural communities. These travelers are helping the Aedes aegypti mosquito (which can only fly a few hundred meters under its own power) spread further afield.

Add to that globalization. Nowadays, we travel across the globe more than ever before – unsuspectingly introducing dengue viruses and Aedes aegypti to new regions of the world.

New solutions required

But it’s not just complacency, urbanization and globalization that have been helping the Aedes aegypti mosquito reach and establish itself in new locations. The mosquito has also built up resistance to DDT and the other insecticides that were keeping dengue under control.

“We desperately need a new insecticide, a new compound that can be sprayed both outdoors and indoors to control mosquito populations,” says Professor Gubler. “An insecticide that is safe and people can use themselves would be tremendous.”

A new insecticide solution will require multiple compounds that can be alternated to minimize the risk of the mosquitoes developing resistance. But developing new insecticides is an expensive process, increasing the economic risk for chemical companies and consequently, reducing the number of companies willing to invest their time and resources.

As such, partnerships are key to developing novel solutions since they reduce the risk for private sector companies but providing them with some of the resources needed. Private sector companies might establish partnerships with governments or charitable organizations, for example.

“The Gates Foundation has funded research at the Liverpool School of Tropical Medicine to help move development of new insecticides forward,” says Professor Gubler. “There are new compounds under development.”

However, a sustainable approach to tackling dengue will need to go beyond controlling the Aedes aegypti mosquito; it will also require increasing people’s immunity to the disease itself.

“Vaccines are important,” says Professor Gubler. “They give us a critical new tool alongside new insecticides and novel solutions such as Wolbachia bacteria and friendly mosquitoes.”

While the Sanofi dengue vaccine is available today, there are a number of vaccines in development in the dengue vaccine pipeline from companies such as Takeda, Merck, and others.

Community action

With local government resources already stretched, Professor Gubler is keen to emphasize the role individuals have to play in tackling dengue: “No government has the resources to reach every house in our growing cities. Bringing the community into the process is key.”

He highlights the success of the community-based programs run by Rotary International in cities such as Manilla and Bangkok since the 1970s. “In 1998, Rotary International helped prevent a dengue outbreak in Purwokerto in Indonesia,” says Professor Gubler. “There were very few cases that year while neighboring cities suffered badly.”

The successful fight against dengue in Purwokerto involved partnerships between the local government, the Rotary Club, local communities and municipal health services – a then novel, approach documented in a World Health Organization case study. More recently, a community-based program in Nicaragua was also successful in reducing dengue transmission.

Sadly, community-based programs have not always had the impact expected, often because of a lack of support from local authorities. “Over the years, I have seen ministries of health fail to provide local communities with the expertise and guidance they need,” says Professor Gubler. “Fighting dengue requires a strong partnership between local authorities and local communities – and also NGOs, such as Rotary International.”

One thing is clear – we cannot afford to get complacent about dengue’s global threat again. Even with vaccines added to our toolbox, we must continue our efforts controlling mosquito populations.

As Professor Gubler says: “Urbanization and globalization mean the risk of dengue is now higher than ever before. While increasing dengue immunity is important, we must also continue to focus on decreasing mosquito populations.”

Tell us about the steps your community is taking to eliminate mosquitoes from your community and to stop dengue from spreading.

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Dengue in Cairns: reducing local transmission despite imported cases

Lying in the northernmost region of Queensland in North East Australia, the city of Cairns is no stranger to dengue. This gateway to the Great Barrier Reef has seen almost 40 outbreaks and more than two thousand cases since 2000, including more than 900 cases during a dengue epidemic in 2008. While imported cases have been on the rise during the past decade, local transmission of dengue in Cairns has been on the decline. We explore why.

A growing year-round challenge

“Our dengue season here in Cairns coincides with our wet summer season and typically runs from December to May,” says Mr. Joe Davis, Director of Medical Entomology at Cairns Public Health Services and Manager of the Cairns Dengue Action Response Team (DART). “Even during the winter, it’s still warm enough for mosquitoes to mature – but the lifecycle is slower, which means there are fewer mosquitoes around and so less transmission.”

Throughout the year, travelers import dengue into Cairns from dengue-endemic countries across South East Asia through being infected themselves. And with growth and development in nearby South East Asian countries, fly in-fly out workers based in Australia are also at risk of importing the virus.

With that in mind, it’s hardly surprising that imported cases of dengue in Cairns have been rising over the past couple of decades. “In the early 2000s there would have been five to ten imported cases each year,” says Mr. Davis. “In 2015, that number rose to more than 80.”

DART: flying into action

Despite an increase in dengue cases imported into Cairns, local transmission has decreased thanks to effective treatments and methodologies. Whenever a potential case arises, Mr. Davis’ DART team is quickly called into action, quashing any outbreak.

Is low-cost travel spurring dengue outbreaks?

Dengue is a notifiable disease in Queensland. Any doctor suspecting dengue must notify the Cairns public health unit, which notifies the DART team. The team’s rapid response starts at the patient’s residence. “We target our application of pesticides where the Aedes aegypti mosquito likes to rest – under sofas and tables, in dark hiding places and amongst laundry,” says Mr. Davis. “We also treat any containers in the back yard and within a sufficient buffer zone around the property.”

The team also treats any places the patient has visited since their symptoms first appeared in the same way. These additional properties can significantly increase the number of response areas.

Expanding as needed

If the dengue case is locally-acquired, the team increases that buffer zone significantly – to as much as an entire suburb. Mr. Davis explains why: “With locally-acquired dengue, we know there is local dengue transmission in that area. That means the imported dengue has infected local mosquitoes and we are likely to have more cases.”

If the number of dengue cases does start to rise, the DART team can expand quickly – from a core team of ten up to the required number of vector control officers, depending on the size of the outbreak.

The team also expands at the start of each wet season. Additional staff is brought in to help with preventative measures.

Dengue in Cairns a proactive approach to control

Indeed, the team doesn’t rest during the winter or during periods when there is no transmission; it continues its focus on prevention, which includes visiting properties known to be at high risk for the Aedes aegypti mosquito. “We visit people who routinely keep a lot of stuff in their yard, along with car wreckers’ and tire yards, to make sure there are no mosquitoes there,” says Mr. Davis.

Mr. Davis and his team also take a proactive approach to suppressing Aedes aegypti mosquito populations; they visit places at risk for imported cases, such as backpackers’ accommodation. Here they put up posters, treat common areas with pesticides, and check and treat any empty containers that are lying around.

During the wet season, the team visits monthly; during the dry season, they visit once or twice throughout the season.

Wolbachia mosquitoes

Cairns has had a new tool help it in its fight against dengue: the Wolbachia mosquito we wrote about earlier this year in ‘Learn how Wolbachia bacteria are reducing the impact of dengue’. Wolbachia mosquitoes are mosquitoes infected with Wolbachia bacteria, which reduce the dengue virus’ ability to replicate and the mosquitoes’ ability to transmit dengue.

“We have had no dengue outbreaks in any suburb with Wolbachia mosquitoes,” says Mr. Davis, “And that’s in spite of local transmission in other suburbs in our region.”

The Eliminate Dengue Program began releasing Wolbachia bacteria-infected mosquitoes in Cairns in 2011, initially in two suburbs – including Parramatta Park. Historically, Parramatta Park was a hot spot for dengue outbreaks because of the age and style of its housing and the leafy vegetation that grows there. But the Parramatta Park area where Eliminate Dengue released Wolbachia mosquitoes has not seen any dengue outbreaks since 2011.

In 2012, Eliminate Dengue expanded the initial two suburbs to four, then added further suburbs into the release program in the following years. By last season, the program had covered all Cairns suburbs with historical local dengue transmission. “Every time Eliminate Dengue releases Wolbachia mosquitoes into an area, local dengue outbreaks cease in that area,” says Mr. Davis.

By the time the 2017/2018 dengue season begins, Eliminate Dengue will have completed its Wolbachia mosquito releases in all of Cairns’ suburbs. It could be a monumental year for the city, as Mr. Davis says: “It will be interesting to see if we have any dengue outbreaks at all this coming summer.”

Even with the Wolbachia mosquitoes on its side, Mr. Davis knows his team cannot be complacent. It must continue to respond to imported dengue cases and proactively prevent dengue outbreaks. “I will be interested to see how the Wolbachia approach will complement our services and how it will shift our focus,” Mr. Davis concludes.

Share your news on how your community is taking the fight to dengue. What initiatives do you have in place and what impact are they having?

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Dengue outbreaks in Argentina: how ‘healthy blocks’ are building dengue-free neighborhoods

Dengue outbreaks in Argentina have prompted authorities to engage communities in local mosquito control.

Image of a poster used in an Argentina Dengue Campaign

Image by Ivan Pawluk

After major outbreaks in 1998, 2009 and 2016, the people of Argentina are all too familiar with dengue fever. The 2016 outbreak saw 7,000 cases reported in Buenos Aires and inspired the government to take action.

Authorities turned to experts including Nicolás Schweigmann – an Argentinian CONICET researcher, Buenos Aires University teacher and TED speaker. When I met him in Buenos Aires I was struck by the concept of ‘healthy blocks’: neighborhoods where the local community is aware of dengue fever and taking collective action to control mosquitoes.

Managing dengue outbreaks in Argentina

“The real problem with dengue is the fact that people don’t know how to avoid it,” he says. “People here buy sprays to kill the adult mosquito, but once they are adult mosquitoes, it is already too late and they are already too numerous. You have to stop the larvae reaching the adult stage.” He adds that the general public is misinformed about how to avoid the dengue fever: “Prevention is the key.”

Nicolás and his collaborators found that the mosquito that spreads dengue (Aedes aegypti) tends not to travel far. In fact, research suggests that, in cities, they only travel about 20m to 40m – around the length of a city block. He believes that the reason could be that mosquito might not be as competitive as would be outside the urban environment.

For mosquitoes, cities can be great places to thrive: they can eat fruit or flowers; females can drink blood by biting city-welling humans; and, after fertilization, they can lay eggs in water tanks, flower vases and drains which contain stagnant water. “Removing these factors would be a critical step in breaking the grub mosquito cycle,” Nicolás says.

This is how the ‘Healthy Blocks’ action plan was created. A big communication campaign was rolled out in 2016, urging citizens to join forces against dengue. They formed neighborhood groups to ensure that there were no mosquito eggs in water tanks in their local area. A block free of mosquito eggs is a block free of dengue.

The Health Blocks concept is also being applied to hospitals and schools, where egg-laying areas are being mapped and eliminated. A communication campaign is visible on the street, in airports, on the internet, and especially at bus stations. Cordoba is the perfect example of a city where the dengue campaign can be seen everywhere.

As part of the same campaign, the government together with UNICEF, Red Cross and University of Buenos Aires mosquito researchers (Nicolás Schweigmann and Sylvia Fischer) have created a social collaboration to prevent Dengue.

Map showing the most endemic countries for dengue.

Image via Malaria Consortium

Looking at the last three dengue outbreaks, the impact of illness has grown exponentially. The 2016 outbreak was a big one. Besides the 7,000 cases in Buenos Aires, it was by far the worst in Misiones and the rest of Northeast. In El Dorado, up to 80% of the population was sick, according to unofficial estimates.

Could a vaccine help?

For Nicolás, Healthy Blocks are a more appropriate solution than the vaccine: “The same mosquito (Aedes aegypti ) can cause Zika, dengue, chikunguña, Mayaro or urban yellow fever,” he says. “The dengue vaccine will not protect you from all these illnesses, but if you stop the mosquito reaching adulthood you can avoid all five diseases.”

Although dengue receives more media coverage than Zika in Argentina, there are already Zika cases here. Late last year the first girl with microcephaly died in Tucumán. “The worst of Zika is still to come in Argentina: a man that has Zika can be infectious for five or six months and transmit it sexually,” says Nicolás. “Even Europe could be affected in future.”

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Pacific dengue outbreak: How Vanuatu Red Cross and IFRC are helping island communities fight back

Vanuatu dengue outbreak gets help from the Red Cross Society.

Photo courtesy of Vanuatu Red Cross Society

The Pacific Island nation of Vanuatu is no stranger to dengue; the country has experienced five major dengue outbreaks since 1970. In January this year, local authorities called on the Vanuatu Red Cross Society (VRCS) to help curb what was turning into a very significant new outbreak. The Vanuatu Red Cross Society’s ongoing health education, awareness raising, and community mobilization operations have reached thousands of islanders.

Vanuatu’s rainy season spans November to April. During this six-month period, islanders and tourists alike risk being bitten by the Aedes aegypti mosquito that has made this group of around 80 tropical islands, home. A dengue outbreak had not occurred in Vanuatu since June 2014 – when 300 cases were reported.

At the beginning of the 2016 wet season, on 11th November, Vanuatu recorded its first new case of dengue for more than two years. Within weeks, case numbers began rising rapidly.

As of 1st April, the number of suspected dengue cases reported had reached 2238, including 90 hospitalizations, according to the Vanuatu Ministry of Health. A total of 446 cases have been confirmed, 90 of them severe.

Springing into action to combat dengue in Vanuatu

In December 2016, the local Ministry of Health established a National Dengue Task Force (NDTF) and began an Emergency Rapid Response to tackle the outbreak. Its plans included heightening dengue awareness, reducing breeding sites and distributing educational and communication materials, amongst other things. In January, it called out to the IFRC and Vanuatu Red Cross for assistance.

“The International Federation of Red Cross and Red Crescent Societies (IFRC) provided technical support during the design phase of the dengue Emergency Rapid Response,” says IFRC health worker Angus Walker. “It also released emergency funds of 81,000 Swiss francs to support a three-month operation lasting from January 21st until April 26th.”

Working closely with the Ministry of Health, the Red Cross began by conducting a survey to assess the knowledge, attitudes, and practices of community members in provincial locations. It would use the information gathered, along with other assessment information, to inform its response and help it to plan accordingly.

Health Assistant Denny Manvoi conducts a (dengue) KAP assessment in Vanuatu.

Health Assistant Denny Manvoi conducts a KAP assessment. Photo courtesy of Vanuatu Red Cross Society

“We asked a wide range of questions, including what people would do if a family member displayed dengue symptoms,” says Vanuatu Red Cross health coordinator Sandrine

“We asked a wide range of questions, including what people would do if a family member displayed dengue symptoms,” says Vanuatu Red Cross health coordinator Sandrine Benjimen. “We discovered that people tend to delay treatment or turn to herbal remedies when dengue symptoms are present.”

These behaviors can lead to complications, especially if the dengue progresses to its severe form. Given this, the Red Cross developed key messages aimed at encouraging people to seek medical advice early.

Awareness and education crucial to changing behavior

The Red Cross response is supported by Vanuatu Red Cross volunteers and health team. Thirty-five volunteers are currently active in two provincial locations, mobilizing communities, including schools, and disseminating relevant information.

Sandrine and Red Cross health assistant Denny Manvoi conducted several workshops in dengue hotspots to train volunteers ahead of a dengue awareness and response campaign. Volunteers were given copies of the IFRC ZDC (Zika, dengue, and chikungunya) Prevention Toolkit, which had been adapted to focus on dengue and translated into Vanuatu’s local language – Bislama.

Health Coordinator, Sandrine Benjimen conducts a dengue awareness workshop in Vanuatu.

Health Coordinator, Sandrine Benjimen conducts an awareness workshop. Photo courtesy of Angus Walker/IFRC

The three-month dengue campaign began shortly afterward. “We printed 4,000 pamphlets and 200 posters,” says Sandrine. “These explain dengue symptoms and when to get treatment. They also tell people how they can help stop the spread of dengue. Disseminating factual information, along with other activities, is an important part of changing people’s behavior.”

Before initiating the campaign, the Vanuatu Red Cross worked closely with local community leaders and church elders to gain their support, which would be vital for ensuring the campaign had the full backing of the local community.

After all, the awareness campaign is very people oriented, involving door-to-door visits to speak with families and working with schools.

Red Cross volunteers in Vanuatu in a school teaching students about dengue.

Volunteers working with students to educate them about dengue. Photo courtesy of Angus Walker/IFRC

“We’re working in schools to educate students on dengue, teaching them about the mosquito life cycle, disease transmission, larval habitats, and control measures,” Sandrine says. “The ZDC Toolkit also provides a range of games and activities that help to make the learning fun and interactive.”

Broadening reach

Roads on some of the dengue-infected islands are more than 100 kilometers long and virtually impassable during the rainy season. Needing an effective way to reach remote communities, the Red Cross turned to social media, the local press, radio, and text messaging.

Example of the Red Cross sms dengue alert in vanuatu.

Image via Vanuatu Red Cross Society

“We began our Digicel SMS communication campaign by surveying 250 people in the two provincial hotspots,” says Sandrine. “Then, on 13th March, we initiated a four-week campaign sending SMS messages in Bislama to 8,500 recipients to raise awareness of dengue symptoms, treatment, and prevention.”

To enable two-way communication, some of the messages also included a phone number that people could ring for further advice.

Additional strategies

The ZDC Toolkit also includes another important activity: environmental mapping. Conducted by community members and school students, with the support of Red Cross volunteers, environmental mapping identifies mosquito breeding areas as part of the community mobilization process. Based on this information, communities and students can then develop and implement action plans.

The Red Cross dengue campaign aims to reach 26,000 people, including 1,250 families in two dengue hotspots. It will run until the end of April, despite dengue numbers falling significantly over recent weeks.

“Our strategy is to work with the community to not only curb the current outbreak but also to ensure the community is better equipped to prevent future dengue outbreaks,” says Sandrine. “The end of the wet season can create more mosquito breeding sites because water that is usually flushed by heavy rain can stagnate. It’s important that people don’t become complacent when the rains become less frequent.”

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Dengue update: Solomon Islands

The nearby Solomon Islands have also been fighting a significant dengue outbreak, which began in October 2016.

As of 5th March, there were more than 11,500 suspected cases of dengue reported, according to the Solomon Islands Ministry of Health and Medical Services. These included 774 hospitalizations and 12 deaths.

Around 28% of reported cases were tested, and 44% of those were confirmed as dengue.

Fortunately, the number of cases is starting to decrease, indicating a possible slowdown in the outbreak.

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Is there a dengue outbreak in your area? Tell us how awareness, education, and mobilization are helping your community fight this deadly disease.

The dengue vaccine pipeline: what’s next?

The dengue vaccine pipeline continues to develop steadily. We last took a look at the state of dengue vaccine development back in October 2014. Since then, Sanofi Pasteur’s CYD-TDV has been licensed, trademarked as Dengvaxia®, and two vaccine candidates – one developed by Takeda and another by the National Institute of Allergy and Infectious Diseases (NIAID) and Instituto Butantan – have entered phase III trials.

We spoke with In-Kyu Yoon, Deputy Director General of Science at the International Vaccine Institute (IVI) and Director of the Global Dengue + Aedes-Transmitted Diseases Consortium (GDAC), to learn more about where the dengue vaccine pipeline stands today.

The dengue vaccine pipeline in 2017

Phase III trials

Formerly known as DENVax, Takeda’s TDV (or TAK-003) is given in two doses 90 days apart and targets all four dengue serotypes. Takeda has completed phase II trials in Puerto Rico, Colombia, Singapore and Thailand to test the safety and immune response of the candidate vaccine. These were followed by further phase II trials in the Dominican Republic, Panama, and the Philippines to refine the dosing. A phase III trial, aimed at testing its ability to provide the desired protection, began in Asia and Latin America last September.

Developed by the US-government funded NIAID (part of the United States National Institutes of Health (US NIH)), TV003/TV005 also targets all four dengue serotypes, but, unlike TDV, is intended to be given as a single dose. TV005 and TV003 are variations of the same vaccine except that the former has 10 times more dengue serotype 2 component than the latter. NIAID has licensed TV003/TV005 to several manufacturers for further development. These include Instituto Butantan in Brazil; VaBiotech in Vietnam; Panacea Biotec, Serum Institute of India and Indian Immunologicals in India; Medigen Biotech in Taiwan; and Merck. Instituto Butantan began a large phase III trial across Brazil in February 2016, while the other manufacturers are still in the preclinical stage.

Phase II trials

NIAID has also sponsored phase II trials of TV003/TV005 in countries such as Thailand and Bangladesh.

The vaccine candidate TDENV-PIV emerged from a collaboration between GlaxoSmithKline (GSK), Walter Reed Army Institute of Research (WRAIR) and Fiocruz. TDENV-PIV is a purified inactivated vaccine (meaning it is made up of dead purified components of the dengue virus). From the knowledge gained from this collaboration, GSK is developing its DPIV vaccine candidate, which has not yet reached clinical trials. Like TDV, TDENV-PIV is given in two doses, which are four weeks – as opposed to 90 days – apart. Having completed phase I trials in the US and Puerto Rico, the collaboration is currently evaluating and refining TDENV-PIV in a phase II trial in the US.

Phase I trials

Merck’s V180 was again designed to protect against all four dengue serotypes. Phase I trials in the US and Australia tested different doses of the vaccine candidate in combination with different ‘adjuvants’ – substances that help to boost the body’s immune reaction.

Also in phase I, TVDV was developed by the U.S. Naval Medical Research Center (NMRC) and has been evaluated in combination with an adjuvant in a phase I trial. While TVDV targets all four dengue serotypes, an earlier phase I trial evaluated its DENV-1 component, which is known as D1ME100.

Other evaluations

In addition to the clinical trials mentioned above, other trials are testing vaccines in combination to glean more information on how our bodies respond to dengue infection and vaccines, along with how the vaccines complement each other. The vaccines in the examples below are combined using a ‘prime-boost strategy’, which primes the body’s immune system with a first vaccine before boosting its immune response with a second.

Firstly, WRAIR is testing TDENV-PIV with an adjuvant in combination with TDENV-LAV. TDENV-PIV is a purified inactivated vaccine while TDENV-LAV is a live attenuated vaccine (meaning it is made up of a weakened live dengue virus).

See the global cost of dengue

Secondly, a collaboration between NIAID and Merck is testing a combination of the vaccine candidates TV005 and V180 in a phase II trial.

Pre-clinical developments

Before we finish, it’s worth noting that there a lot of other dengue vaccine approaches currently in pre-clinical development. Three, in particular, are probably worth a quick mention. The first approach is based on dengue virus-like particles (or VLPs). These vaccine candidates use structures that look similar to dengue virus to induce an immune response. The second approach is based on virus vectors. These vaccine candidates use a modified virus to carry parts of the dengue vaccine to stimulate an immune response.

The third approach focuses on the non-structural protein-1 (NS1 protein), a distinct protein within the dengue virus that researchers believe may play a fundamental role in bringing about vascular leakage in people with severe dengue. These vaccine candidates aim to induce an immune response that protects against the potentially lethal DENV-induced vascular leakage.

It’s heartening to see that the dengue vaccine pipeline continues to evolve, making great steps forward in developing a variety of vaccines to combat this terrible disease.

Could a shift in vaccine confidence towards other vaccines affect dengue vaccination rates?

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Oxitec’s ‘friendly mosquitoes’ now protect thousands from dengue

Image of oxitec's mosquito pupae emerging.

Photo courtesy of Oxitec

‘Friendly Mosquitoes’ from Oxitec are now protecting more than 60,000 people from the ‘dengue mosquito‘. The genetically modified male Aedes aegypti mate with wild females, passing a self-limiting gene on to offspring. The youngsters die before they reach maturity and before they’re able to spread the dengue virus.

It’s just over a year since we last spoke to Oxitec. At that time, its mosquito control solution was moving from field trials to operational use in Piracicaba, Brazil, having suppressed more than 90% of the wild Aedes aegypti population in several trials. Since then, the company has been focusing on commercializing and expanding projects with its technology.

We spoke to Oxitec’s CEO Hadyn Parry, who began by telling us why Oxitec’s mosquito control solution is affectionately known as Friendly™ Aedes: “We take some of our mosquitoes when we visit communities and ask people to put their hand in the cage.

The press in Brazil and Panama began to call it the friendly mosquito because, being males, they don’t bite. They’re friendly!”

Oxitec mosquitoes: trials to operations

Oxitec began rolling out its technology on an operational basis last July, within the São Judas district of Piracicaba and the Cayman Islands. It then began to release further Friendly™ Aedes in ten additional downtown neighborhoods of Piracicaba during August and September.

With scale-up, Oxitec needed to make sure its technology could produce large numbers of healthy mosquitoes cost-effectively. To do that, biological engineers adapted equipment within Oxitec’s breeding facilities and quality processes were stepped up.

“Quality control is vital for scaling our operations,” states Parry. “We need to ensure the large numbers of insects we breed in our mosquito factories are fit and strong.”

Image of an Oxitec researcher inspects mosquitoes.

Photo courtesy of Oxitec

The operational solution also needed a tool to automatically calculate exactly where and how many mosquitoes should be released. “You may have high mosquito population levels in one area of town and low population in another,” explains Parry. “You need a monitoring system that will allow you to release the right number of mosquitoes.”

The system is both precise and easy to use, so it can be shared with any customers wanting their own mosquito factories.

Factories across the globe

Currently only Oxitec has mosquito factories: a large factory in Piracicaba; a small factory in the Cayman Islands; factories in Florida and India that will breed mosquitoes for trials; and a development factory in the UK where new cages and rearing systems are developed, and eggs are produced in the factory in the Cayman Islands.

Image of Oxitec researchers in a lab storage facility.

Photo courtesy of Oxitec

“In our next phase, we’re going to be ramping up production in our large factory in Brazil, which has the capacity to produce 60 million mosquitoes per week,” says Parry. A weekly output of 60 million mosquitoes could protect anything from around 300,000 people in a region with poor mosquito control.

Once you have significantly reduced the population of wild mosquitoes, the only female mosquitoes around are those arriving on buses and boats. You then only need to do a very low-level release across the area, meaning 60 million mosquitoes could protect up to two million people – or even three million within an integrated vector control program.

“Within a physically separated island you might be able to actually eliminate mosquitoes altogether,” ponders Parry. “You’d only need to release genetically engineered mosquitoes around airports or marinas to control mosquitoes returning by boat or plane since Aedes mosquitoes can’t fly very far.”

Next stop: India and the USA

Oxitec is currently running early stage regulatory trials in Florida and Dawalwadi in India. In Florida, a referendum saw 31 out of 33 districts voting in support of the trial. In India, a second mosquito factory is being built so that breeding can be quickly scaled up once Oxitec gains regulatory approval.

“Our technology needs to gain regulatory approval in every country where it is deployed,” says Parry. “Each country has its own process: some ask for data from earlier trials then give permission for trials; others allow small trials, then bigger trials before if all is well, we gain regulatory approval to commercialize it.”

With a pipeline of countries looking to trial the friendly mosquitoes, Oxitec must manage its resources carefully, as Parry explains: “We have to balance between how many people we have and how much we can do at any one time. Demands on resources also depend on countries’ regulatory systems and what we need to do to bring the product to them.”

Battling Zika together

Parry agrees that Friendly™ Aedes could be deployed as part of an integrated vector control program alongside other interventions such as insecticides or potentially Wolbachia mosquitos [insert link] in the fight against Zika and chikungunya as well as dengue: “You could, in theory, combine the technologies one day if both solutions pan out: using Oxitec’s Friendly™ Aedes to bring down the wild population and then the Wolbachia mosquitoes to rebuild it.”

Both solutions are already proving to be key weapons in the fight against Zika. Last March, the World Health Organization (WHO) recommended “carefully planned pilot deployment under operational conditions accompanied by rigorous independent monitoring and evaluation.”

Tell us about the novel solutions that you’ve experienced as your community battles dengue.

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Learn how Wolbachia bacteria are reducing the impact of dengue

Wolbachia bacteria are helping the Eliminate Dengue Program fight the disease: reducing the virus’ ability to replicate and the mosquitoes’ ability to transmit it. This unique approach is both cost-effective and self-sustaining; with community buy-in and participation critical to its long-term success.

The Eliminate Dengue Program has developed a totally natural approach to fighting dengue: it halts transmission of the dengue virus by using Wolbachia bacteria to stop the virus from replicating within Aedes aegypti mosquitoes.

How does the Eliminate Dengue approach work?

The dengue transmission cycle is quite simple:
1. A healthy mosquito contracts the virus by biting an infected person.
2. The virus matures (replicates) inside the mosquito over a short incubation period.
3. At the end of this period, anyone bitten by the infected mosquito contracts dengue.
4. The virus matures (replicates) inside the person over a short incubation period.
5. A healthy mosquito contracts the virus by biting an infected person.

https://youtu.be/1ErcwogWbIA

However, when a mosquito with Wolbachia bites a person infected with dengue, the virus inside it does not thrive. It must fight the Wolbachia bacteria for the resources it needs to mature – with the bacteria inevitably coming out on top.

“The mosquitoes with Wolbachia can still catch dengue,” explains Shane Fairlie, Global Communications and Engagement Manager for the Eliminate Dengue Program. “But they can’t pass it onto humans.”

Image of a scientist from Eliminate Dengue posing for a photo.

Image courtesy of Eliminate Dengue

In the early days, microscopic injection techniques were used first to transfer Wolbachia bacteria from fruit fly into Aedes aegypti mosquitoes. Today, Eliminate Dengue researchers rear colonies of mosquitoes with Wolbachia in the lab. The bacteria are naturally passed down from one mosquito generation to the next.

When researchers release a small number of Wolbachia bacteria-infected mosquitoes into a local community, they breed with the wild mosquitoes, passing on the bacteria. After between two and three months, the majority of the mosquitoes in that community have the Wolbachia and the Eliminate Dengue team stops releasing. The local community continues to host strategically-placed mosquito traps. Since the method is self-sustaining, there’s never any need for further Wolbachia mosquitoes to be released, making the approach cost effective.

The research team returns every few weeks or few months to check the traps. “After we leave the area, our only task is to periodically check traps to ensure the Wolbachia levels in the mosquito population are still high,” says Fairlie. “Volunteers in the local community look after the traps, so there’s no real on-going cost”

Wolbachia bacteria: grounded in research

The not-for-profit international collaboration behind the program is led by Melbourne’s Monash University. Led by Professor Scott O’Neill, Director of the university’s Institute of Vector-Borne Disease, Eliminate Dengue’s approach is based on years of laboratory research and extensive small-scale field trials.

Professor O’Neill has been working with Wolbachia for more than 20 years. His early research involved engineering Wolbachia to carry genes that reduce the mosquitoes’ ability to transmit viruses into a mosquito population.

Image od a scientist studying the wolbachia bacteria.

Image courtesy of Eliminate Dengue

After trying a number of different approaches, some unique traits came to light. “While putting Wolbachia into the mosquitoes, we discovered the bacteria’s ability to block transmission of the dengue virus,” states Professor O’Neill. The bacteria no longer needed to be genetically engineered; putting the Wolbachia into the mosquitoes was enough to greatly reduce the viruses’ ability to replicate.

Funding from a Bill and Melinda Gates Foundation initiative gave the research a welcome boost in 2005. A further six years of research allowed the team to refine their approach and gain support from local governments and communities.

Open field trials began in 2011 and have now been conducted in Australia, Colombia, Vietnam, Brazil and Indonesia. These projects have shown this is a feasible approach to fighting dengue. “Mathematical models and our observational data show sufficient reduction to have a very large impact on transmission,” says Professor O’Neill.

Communities at its core

Local community engagement is a key of the program’s success: each project puts a significant amount of resource into gaining buy-in from the local community before releasing the mosquitoes with Wolbachia; and also into encouraging the community’s participation that is critical to sustaining each project.

“You can have a great approach that works in the lab from a technical perspective, but without it being effective in the field and community acceptance, it’s going to struggle to be sustainable,” adds Fairlie. In fact, the approach depends on communities taking the lead once the release phase is complete. Local volunteers are more than happy to host mosquito traps at their home

Eliminate Dengue uses local community engagement experts to help build community support in the months – even years – leading up to their field trials: sharing information, answering questions and listening to community concerns. Community members are invited to see how mosquitoes with Wolbachia are reared in the Eliminate Dengue laboratory. School children learn about different types of mosquito breeding sites.

image of students releasing wolbacj-hia infected mosquitoes to fight dengue in Australia.

Image courtesy of Eliminate Dengue

Toni Salgado, a volunteer in Rio de Janeiro, Brazil, shares his experience: “There was some hesitation in the beginning, in 2012, when the scientists first came here. But then we had meetings in which they explained to the community why this release was needed and residents agreed to participate. I am now proud to be part of it.”

The program also puts a great deal of time and effort into encouraging community participation. Local residents – including school children – grow and release their own Wolbachia mosquitoes as part of the project. “It is quite a good feeling knowing that just a minute of my time each fortnight is enough to benefit my neighborhood, and, potentially, others around the world. Even the busiest person could do this, and, in fact, we don’t have time not to because dengue outbreaks can be a huge burden on our community,” Doreen Ross, volunteer in Townsville, Australia.

Looking ahead in 2017

2017 is going to be a very important year for the Eliminate Dengue Program: significant new funding received last October means it can scale up its field trials this year. “We’re about to embark on a large-scale trial in the Columbian state of Antioquia, covering an area with more than 2 million residents over the next two years,” says Fairlie.

Other large-scale deployments on the horizon include an expansion into parts of Rio de Janeiro and Niteroi in Brazil that will reach a population of more than 2.5 million people over the next two years. In Indonesia, a large-scale efficacy study over the next two to three years across the city of Yogyakarta will rigorously evaluate the impact of Wolbachia bacteria on the transmission of dengue and other mosquito-borne diseases.

The program is also working to further reduce the cost of their approach, as Professor O’Neill explains: “Resources are limited in many countries suffering from dengue. We want to reduce the cost of deployment to less than a dollar per person.”

The team expects the approach will have a very significant impact in the long term. They see it as a complementary tool, supporting other initiatives in an Integrated Vector Management approach to fighting vector-borne diseases. “The Wolbachia mosquitoes should enhance the effectiveness of the dengue vaccine and the vaccine should enhance the effectiveness of the Wolbachia mosquitoes,” concludes Professor O’Neill.

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Break Dengue given ASAP Award for CSR

Every year, ASAP, a world leading professional association dedicated to the practice of alliance management, partnering, and business collaboration, chooses to highlight outstanding accomplishments of innovative partnerships at the Global Alliance Summit.

This year, 10 nominees competed in four categories for the Alliance Excellence Awards: Individual Alliance Excellence, Innovative Best Alliance Practice, Alliance Program Excellence, and Alliance for Corporate Social Responsibility.

We are thrilled to share that Break Dengue won the prize in the Corporate Social Responsibility category. The Alliances for Corporate Social Responsibility Award is for partnerships making a profound, measurable, and positive social impact.

Special recognition goes to the Break Dengue partners that made this result possible:

We are all winners

We are proud to have been considered together among the two other sound initiatives that had a strong, relevant and diverse impact:

Bayer and Drugs for Neglected Diseases Initiative (DNDi), an alliance focusing on developing a drug to dramatically reduce treatment time and increase effectiveness for River Blindness, a disease affecting 25 million people in 31 African countries.

Dimension Data and Cisco Systems Inc, an alliance developing advanced tracking technology that helps reduce the number of rhinos being poached in South Africa’s Kruger National Park.

Break Dengue is committed to advancing the shared-value approach for addressing dengue fever – the fastest-growing mosquito-borne viral infection in the world today. Our partners continue to grow, co-creating solutions for tracking and predicting disease epidemics, educating the populations at risk on prevention models, as well as growing and enabling support to the scientific community. In addition to dengue, we are optimistic that down the road the platform our collaborations produced could be extended even further to lessen the impact other diseases.

To get involved in the project please contact us.
You can also follow our activity on the blog, Facebook, Twitter and LinkedIn.

Watch our documentary and see how dengue affects the lives of its victims long after the fever passes.

Together we are stronger. The shared value approach and Break Dengue

Break Dengue team members will be joining the Global Alliance Summit on Feb 28 – March 2 in San Diego, California to explore key questions surrounding topics on successful partnerships.

The event organized by ASAP, a leading global professional association dedicated to the practice of alliance management, partnering, and business collaboration. The conference is features key speakers from around the world including our own Aaron Hoyles and Dr. Lode Dewulf.

Illustrating the power of shared value

Dengue has become the fastest growing mosquito-borne viral infection in the world today, resulting in an estimated 390 million infections every year. The global dengue effects are real, and despite increasing global health risks remain largely ignored.

In 2012, we created a response. Our founders set out to launch a collaborative, pre-competitive multi-stakeholder shared value partnership model to address the growing concerns surrounding the increasing global health burden of dengue fever – Break Dengue.

Our speakers will talk about this model and its challenges in a dedicated session – “Collective Impact Partnerships – Why, How, and What?”

Shared value and collective impact – what is it?
What are the key success factors for a shared value partnership to thrive and deliver greater impact?
How do you develop a sustainable plan for such an approach?
What does it look like in practice?

About the presenters

Aaron Hoyles is Program Manager of Break Dengue, a collective impact partnership initiative at The Synergist. Prior to joining The Synergist, Aaron worked as a management consultant for organizations of all sizes, including Allstate in the U.S. and startup Hub-Grade in France. Aaron began his career in the U.S. Navy. Aaron has a BA in Philosophy from DePaul University in the U.S. and an MBA in International Business from EMLYON Business School in France.

Lode Dewulf is a physician with a passion for patient perspectives and understanding. When he studied and practiced medicine in Belgium and South Africa, he quickly realized that good education about health and disease was at least as important as good medicines to help patients achieve the best outcomes. To have a broader impact he then joined the pharmaceutical industry in 1989 and worked to provide education surrounding certain diseases and new treatment options. Ten years later, when the internet opened new possibilities to provide quality medical information, he took a one-year sabbatical leave to co-found PlanetMedica, the first Healthcare internet portal in Europe. He now has almost 25 years of pharmaceutical medical experience around the world and currently works as Chief Patient Affairs Officer at UCB, Belgium.

Download to the Full Conference Agenda and learn more about the Global Alliance Summit on the official website.

More good news

Break Dengue was shortlisted for the ASAP awards – the “Alliance for Corporate Social Responsibility” category.
We are honored to receive this nomination and we wish best of luck to all the other participants. Special recognition goes to our partners that made this nomination possible:

About Break Dengue

Break Dengue is creating a global, neutral and fertile ecosystem to address the issue of dengue, connecting different initiatives around the world so that together they can together make a bigger impact. Break Dengue is an open platform to all: scientists, health-care providers, patients and relatives, journalists, industry and anyone concerned about the problem of dengue. Focus areas include healthcare, technology, disease surveillance, vector control, vaccines, education.