Learn more about mosquito bites and how saliva gives dengue a hand

Mosquito bites and how saliva gives dengue a hand

When mosquitoes bite, the effect may be much more than just skin deep. Researchers at the Baylor College of Medicine in Houston, Texas, found mosquito bites can meddle with our immune systems for days, right down to our bone marrow. Mosquito saliva helps dengue replicate and spread around our bodies. Their findings might mean we need to rethink how we prevent, diagnose and treat dengue and other mosquito-borne diseases.

“We realized we knew little about what happens inside us after a mosquito with dengue bites,” Professor Rebecca Rico-Hesse, a virologist at Baylor College of Medicine, told us. “So, we developed a model to show how dengue fever behaves inside a human, using ‘humanized’ mice.”

Only humans can catch dengue; mice and other animals can’t. So, to study what happens after a bite from a mosquito infected with dengue, the team implanted specific human stem cells (the ones that make our immune system) into a group of mice. These mice were now primed and ready to catch the virus.

But only some of them caught dengue when the researcher injected the virus into them. “We decided to take a more natural approach to dengue transmission and let infected mosquitoes bite the mice,” said Professor Rico-Hesse. “That changed everything.”

Mosquitoes courtesy of Baylor College of Medicine

When bitten by mosquitoes, the mice had a higher infection rate, worse rash, and lower platelet levels. They had pretty much more of all the things that are the normal signs of dengue fever, and the virus remained in their blood for longer.

Examining the bite

Seeing mosquito bites were far better at passing on dengue than a syringe, the team realized they had never actually studied how a mosquito bite alone affects us. What they found was totally unexpected: mosquito bites actually change our immune system.

“We saw changes in immune system cells seven days after a mosquito bite, sometimes right down to the cells in the bone marrow,” said Professor Rico-Hesse. “If mosquitoes are constantly biting us, they are constantly affecting our immune system.”

So how does this happen?

When a mosquito bites, it injects saliva first to make it easier to draw blood. That saliva “probably contains more than 100 active proteins,” according to Professor Rico-Hesse. “These proteins don’t just affect us locally area around the bite; they also attract and affect our immune system cells.”

Are mosquito bites giving the dengue virus a ride?

Add the dengue virus, and you can see how the mosquito saliva is giving dengue a helping hand. The proteins in the saliva attract our immune system cells, which then take the dengue virus down into our bone marrow.

But the immune system cells in our bone marrow aren’t so good at fighting antigens (foreign bodies such as infections or viruses). The virus can spread virtually unchallenged into the new immune system cells our bone marrow is tasked with forming. Our bone marrow is effectively “serving as a sanctuary for the virus to replicate.”

Even more concerning is that you can’t necessarily detect dengue in a blood sample when the virus is busy replicating deep down in our bone marrow.

Learn how the CDC is fighting the spread of dengue in the USA

And that’s not all. After the bone marrow has finished forming new immune system cells, these are sent out to different tissues to do their work. Some make their way back out to our skin seven days after the initial mosquito bite. Another mosquito could then come and bite us and become infected with the dengue virus – without us even knowing we have dengue.

We have a problem

In a nutshell, this means a person showing no signs of dengue in a blood sample could still be contagious to a mosquito. “If we have people walking around with dengue in their bone marrow when they don’t even realize they’re infectious, then we have a problem,” says Professor Rico-Hesse.

“If it turns out that the very core of our immune systems is getting infected with dengue, then we need other types of cells to detect the infected immune system cells,” she continues. “And we need a therapeutic that can get rid of the virus inside immune system cells, right down to the bone marrow.”

Professor Rico-Hesse and her team are next planning to investigate what happens inside us at a cellular level if the mosquito is a vector for not only dengue but also Zika and chikungunya. She explains: “We have to repeat our research with these three viruses and look for similarities and differences in how mosquito saliva affects dengue transmission and distribution to the tissues in the human host.”

The team’s findings could completely transform our understanding of dengue, dengue transmission and what we need to do to prevent this terrible disease.

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Dengue in Africa: Why we urgently need to wake up to the public health threat on the continent

Dengue is no stranger to West Africa. The potentially deadly virus might even be endemic in many countries in the region. The problem is, nobody knows the real status of dengue in Africa. And with the numbers not understood, dengue does not feature highly among governments’ health priorities. We spoke with Justin Stoler from the University of Miami’s Departments of Geography and Regional Studies and of Public Health Sciences to find out more. He has spent many years investigating dengue fever, particularly in West Africa.

Despite the almost certain presence of dengue in Africa, the true burden of the disease is unknown, as highlighted by the World Health Organization in its Global Strategy for Dengue Prevention and Control 2012-2020:

The strategy goes on to note that an article, “Dengue virus infection in Africa” published in Emerging Infectious Diseases in 2011 reported:

“During 1960-2010, a total of 22 countries in Africa reported sporadic cases or outbreaks of dengue; 12 other countries in Africa reported dengue only in travelers.”

The article maps the presence of both dengue in Africa and Aedes aegypti across the continent, with brown indicating the 34 countries where dengue is present, light brown indicating the 13 countries with Aedes aegypti but no dengue, and white indicating countries with no data available.

Image showing dengue activity in countries in Africa.

Dengue and Aedes aegypti mosquitoes in Africa

Of the countries that make up West Africa (Benin, Burkina Faso, Cape Verde, Ivory Coast, Gambia, Ghana, Guinea, Guinea-Bissau, Liberia, Mali, Mauritania, Niger, Nigeria, Senegal, Sierra Leone, Togo and Saint Helena, Ascension and Tristan da Cunha), around half reported the presence of dengue, with the remaining reporting the presence of Aedes aegypti.

Just last year, we reported on a major dengue outbreak in Burkina Faso and the World Health Organization’s Disease Outbreak News reported a dengue outbreak in the Ivory Coast.

“The landscapes of West Africa certainly support Aedes aegypti,” says Stoler. “The mosquito has been present for most of the 20th Century; it would seem almost impossible for dengue not to be circulating at some level – but nobody had really studied it.”

Fevers misdiagnosed as malaria

Worse still, whenever someone in sub-Saharan Africa [which includes West Africa] has the high fever that could indicate dengue, they’re all too often diagnosed with malaria. Why? Because the two diseases present similarly, and limited health care resources do not stretch to confirming the actual illnesses in the lab.

Stoler explained how malaria, which affects more than 200 million Africans each year, has been “institutionalized as the disease that you have when you have fever and headaches.
People are presumptively diagnosed with malaria and given antimalarials all the time, even when the parasite is not circulating.”

This misdiagnosis is still commonplace despite, the burden of malaria falling 20% in the region between 2010 and 2016, according to the WHO Malaria Report. “Research over the last five years has shown that only 10 to 20% of febrile children actually have malaria, yet many more are presumptively diagnosed with it,” says Stoler. “Other infections, including dengue, are being missed.”

Previous dengue exposure uncovered

Given that Aedes was known to be circulating in West Africa, Stoler wanted to find out what viral diseases the mosquitoes were actually transmitting – including dengue.

In his early research into dengue in West Africa (conducted in collaboration with Gordon Awandare, Director of the West African Center for the Cell Biology of Infectious Pathogens [WACCBIP] at the University of Ghana), Stoler found that in many parts of sub-Saharan Africa “up to a third of patients suffering from acute fever do not receive a correct diagnosis of their infection.” He concluded that “the true burden of diseases such as typhoid, influenza and dengue fever are likely understated.”

Read about the impact of climate change on dengue

These conclusions came from analyzing samples from 218 feverish children in Ghana, all of whom had laboratory-confirmed malaria. The samples revealed previous exposure to dengue in 21.6% of samples and recent exposure in 3.2% – but no current infections.

Suspected malaria found to be dengue

But the laboratory had also confirmed that some patients with a high fever did not have malaria. The researchers became convinced that there was a real possibility these patients might have dengue.

Stoler and Awandare continued their research, this time analyzing blood samples from 166 Ghanaian children attending hospital with acute fever and suspected malaria. Their analysis found two children suspected of having malaria had, in reality, a strain of the dengue virus closely related to the DENV-2 serotype isolated in a 2016 outbreak in nearby Burkina Faso.

The study was the first to isolate the dengue virus in feverish children with suspected malaria, concluding: “This DENV-2 strain may soon become regionally endemic [in West Africa] if it has not already.”

Stoler expanded on this during our interview, saying: “This virus strain has most likely been migrating throughout West Africa, following local population movements. But we don’t quite know the extent to which this – or any – strain of dengue is already endemic because dengue isn’t generally considered in Africa when people have an acute fever.”

Dengue in Africa: attention needed

The receding burden of malaria is one of four global health trends that Stoler firmly believes indicate we must give urgent attention to the spread of dengue in Africa, the others being climate change, emerging pesticide resistance and the delayed promise of a dengue vaccine.

“The decline in malaria transmission in many endemic areas of Africa over recent years means there is an urgent need for physicians to diagnose acute fevers accurately,” says Stoler.

The search is on for diagnostic solutions that allow physicians to test for multiple pathogens at the same time. “That’s the type of thing we are experimenting with,” says Stoler. “We are piloting a customized card that can test for dozens of different infections, all with one blood sample.”

While new diagnostics will be important for identifying infections beyond malaria, with dengue being one of the primary suspects, there is also an urgent need for re-education – not only of the public but also of the “entire medical establishment,” as Stoler puts it. “There are other possibilities they need to be considering in their diagnosis.”

The immediate challenges are two-fold: convincing the medical establishment that misdiagnosis is, in fact, a problem, and persuading national governments that dengue demands their attention.

“We have held dissemination meetings with the top hierarchy of the Ghana Health Service, and I believe they are taking the threat very seriously. So, we expect to see an increased and more coordinated surveillance program soon,” says Awandare.

If you have experience with dengue in Africa, we’d love to hear your story. Or maybe you were diagnosed with malaria but suspected your fever was actually dengue or another infectious disease.

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The impact of climate change on dengue, and why we can’t ignore it

The impact of climate change on dengue is taking its toll on public health, and the 2018 global heat wave has given the world a taste of what may lay in store. Our recent update on dengue fever in the Asia Pacific reveals how some have attributed the unusual 2018 climate – with its unseasonably wet and warm weather and early monsoons – to dengue outbreaks in the region. With the world already feeling the effects of global warming, what impact will climate change have on dengue around the globe by the end of this century?

Vladimir Kendrovski, technical officer for climate change and health for the World Health Organization (WHO) regional office for Europe, recently told Deutsche Welle that in a climate change scenario, extreme heatwaves might occur “as often as every two years in the second half of the 21st century”.

And climate change increases risks to human health. Universities around the world are looking into the many ways global heatwaves could affect our well-being, including the impact of climate change on the spread of the dengue virus and its vector, the mosquito.

Our own investigation took us to the University of East Anglia in the UK and the University of Miami in Florida.

Dengue cases up by 7.8 million

The UK researchers we spoke with have built a statistical model to predict how global heatwaves could impact on human health.

“We know limiting global warming benefits human health,” says Felipe Colón-González, a senior research associate at the university’s School of Environmental Sciences. “Before our research, little was known amount the size of those benefits. We wanted to quantify those benefits, so we built a statistical model.”

The team trained their model using historical dengue, climate and population data from across Brazil, Colombia, and Mexico. Once prepared, it revealed how many dengue cases Latin America can expect by 2100 if we continue on the current trajectory and global warming increases by 3.7°C above pre-industrial levels.

Their findings were truly eye-opening: doing nothing to limit global warming could lead, by 2100, to a dengue case rate 281% of the 4.5 million we currently see in Latin America. “That’s about 7.8 million more dengue cases than we see today,” says Colón-González.

The rise in dengue cases is the result of a combination of two factors: global warming increases both the length of the dengue transmission season (as we have been seeing in Asia this year) and the number of geographical areas where the climate is suitable for dengue.

The team’s model also offered some somewhat better news. It revealed that Latin America would see fewer dengue cases if we limit global warming to the goals set by the UN Paris Climate Agreement – well below 2°C and to aim to limit any increase to 1.5°C.

Limiting climate change to 2°C would still lead to a less significant increase in dengue cases in Latin America, dropping by 2.8 million to 5.0 million additional dengue cases compared to today. Limiting it even further, to 1.5°C, could mean an even greater reduction in the increase dengue cases, with 4.5 million extra cases.

Colón-González is in no doubt that curbing global heatwaves alone would not be enough to combat dengue. “Limiting global warming helps limit the temporal and spatial spread of diseases like dengue,” says Colón-González. “But limiting climate change alone is not going to help totally control the number of cases. We have to do much more.”

Dengue hitches a lift with migrating farmers

The Miami researchers, as part of their wider studies into the impacts of climate change on human health, have identified some novel ways global warming could increase the risk of dengue.

Justin Stoler, associate professor in the university’s Department of Geography and Regional Studies and Department of Public Health Sciences has spent many years investigating dengue fever, particularly in West Africa. He believes climate change is one of four global health trends that demand we give urgent attention to the spread of dengue in Africa, the others being the receding burden of malaria, emerging pesticide resistance and the delayed promise of a dengue vaccine.

Read: Dengue in the USA: Avoiding larger outbreaks and the wider spread of vector-borne disease

Stoler is aware of on-going research into how interactions between the environment, vector, and virus influence how the virus replicates, mosquito survives and disease spreads. He puts this into a global warming context by explaining how climate change could potentially accelerate the paradoxical effect of the chemicals used to control mosquitoes.

“Various species – pollinators or other organisms – are part of the ecological web that could potentially keep mosquito numbers in check,” says Stoler. “The use of pesticides is already wiping out some of these organisms, meaning any new mosquitoes introduced could potentially survive. Climate change is only going to add to the pressure on the various species and their potential to crowd out mosquitoes.”

In his second example, Stoler discusses how, during his own research, he has witnessed climate change driving migration and pushing pathogens around the world. “Dengue’s movement throughout West Africa may be linked to people leaving drier, inland areas where the Sahara Desert is expanding,” he says. “There’s a lot of circular migration in and out of the big coastal cities in West Africa.”

He explains how Ghana’s capital, Accra, has grown dramatically, continually absorbing people from Northern areas where people’s farms are failing due to irregular rainfall and longer dry seasons, while migrants, at the same time, usually maintain close ties with their home communities. “When people are on the move, pathogens hitch a ride,” says Stoler.

If you’ve been looking into the potential impact of climate change, or maybe this year’s global heatwave has affected dengue in your local area. Whatever your story, we’d love to hear it. Please get in touch.

Tell us whether climate change means you’ve had to step up the fight against dengue in your community this year.

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Join the effort to map dengue fever. Click below to report dengue near you to Dengue Track.

Dengue fever in the Asia Pacific region: A look at trends in 2018

Dengue fever in the Asia Pacific continues to threaten the quality of public health in the region. Increasing populations and warmer climates are among the factors facilitating the spread of the of the mosquito-borne disease worldwide. In recent years, the Asia Pacific region has seen outbreaks increase alongside the burden of dengue. The World Health Organization reports the dengue serotype 2 has been widespread across the region since the start of 2017.

Let’s take a closer look at the dengue trends across the region in the first half of 2018.

Dengue activity across the Asia Pacific

Across the Asia Pacific region, countries are feeling the effects of this year’s unusual climate. For some countries, recent months have been unseasonably wet and warm; for others, monsoons have arrived early.

Thailand

Thailand is experiencing its largest dengue epidemic in more than two decades, with a record number of people infected, according to The Samui Times. With the country now in the middle of its May to September rainy season, health officials are blaming the unseasonably wet and warm weather due to climate change for making the situation particularly bad this year.

Thailand’s Bureau of Epidemiology reported a total of 22,564 cases as of 23rd July. It notes that most of the cases were in age groups 15-24 years old (24.64%), 10-14 years old (22.38%) and 25-34 years old (12.07%). The highest incidence rates were found in students (51.2%) and general laborers (16.7%).

Bangladesh

Now in the middle of its June to September monsoon – and peak transmission – season, Bangladesh’s capital city is bracing itself for another spike in dengue. The incidence of dengue in the capital suddenly increased in July. 93 dengue patients were admitted to hospitals during the first four days of the month after a total of 250 dengue patients were admitted to hospitals throughout June. Dhaka has had 992 confirmed dengue cases as of the end of July of this year. Dhaka also reports eight deaths of dengue in 2018.

The Philippines

Nationwide, the Philippines saw 53,039 cases as of 7th July 2018, with 289 deaths, according to the Philippine Information Agency. Most of those affected were between the ages of 10 and 14 years. During the first seven days of July, only 412 cases were reported, an 87% drop compared to the same period last year.

Meanwhile, health officials in the Pangasinan province reported a significant increase in dengue fever cases during the first five-plus months of 2018. The Pangasinan Provincial Health Office (PHO) recorded 1,398 dengue cases as of 11th June, compared with just 592 cases during the same period last year – a 136% rise. Fatalities have also risen, to six in the first five-plus months of 2018 from four during the same period in 2017.

The Aklan region is also reporting a rise in the first six-plus months of 2018 with 696 cases, compared to 536 cases in the same period last year. Youth and young children are most affected by dengue fever in the country with the biggest age group of patients suffering from dengue infections (35%) aged 11 to 20 years.

Malaysia

Nationwide, Malaysia has succeeded in reducing the number of dengue cases and deaths for two consecutive years. The country saw a 16% drop in cases and a 29% fall in deaths in 2016, followed by a 17% fall in cases and 25% in deaths in 2017. The first six months of 2018 looked equally positive with 17,291 fewer cases (a 34.8% fall), and 110 fewer deaths reported compared to the same period in 2017.

The Penang region in northwest Malaysia is not following the same trend. The New Straits Times reports that the region recorded 2,528 dengue cases between January and July this year, an increase of 74.95% compared to last year.

Laos

In Laos, 12 people died in the first six months of this year as a result of dengue fever. The more than 2,426 cases of dengue doubled the number of cases during the same period last year. The country, where the peak transmission runs from May to October, recorded 5,584 dengue cases including 14 fatalities throughout 2017.

Dengue in the Western Pacific

Islands across the Pacific Ocean are experiencing significant dengue outbreaks with more than 39,000 cases reported over the past 18 months, the WHO revealed in a radio interview in June (Click below to hear the broadcast). Serotype 2, which has not been seen in some countries for nearly two decades, is widespread, prompting fears that the virus could spread rapidly. Serotypes 1 and 4 are also in circulation.

Wallis and Futuna

Northeast of Fiji, on 17th July the French Territory of the Wallis and Futuna Islands reported 203 cases and 23 hospitalizations since September 2017, according to a recent WHO report. The highest cases numbers were in age groups 15-20 years old (44), 10-15 years old (42) and 5-10 years old (22). Of those cases, 16 were imported from outside the territory, from New Caledonia and Vanuatu.

Kiribati

The Republic of Kiribati, which comprises 33 coral atolls and isles stretching along the equator, is experiencing an ongoing dengue outbreak. As of 16th July, 1,435 cases had been reported including 32 hospitalizations and two deaths. A recent report from the WHO shows the weekly number of dengue cases is decreasing from peaks.

Read how artificial intelligence is predicting dengue outbreaks and outcomes

The World Mosquito Program is working with the Kiribati government to bring its Wolbachia-infected mosquitoes to the republic in a project funded and supported by the Australian Government’s innovation change. In July, the WMP announced that it had commenced releases of mosquitoes with Wolbachia in Kiribati, Fiji, and Vanuatu.

New Caledonia

New Caledonia declared a dengue epidemic back in February of this year. As of 1st June, the WHO reported 1,257 confirmed cases since January including 112 hospitalizations, and two fatalities. The dengue epidemic in 2017 claimed 11 lives and affected over 4,500 people.

American Samoa

The American Samoa dengue outbreak has been ongoing since March 2017, with a total of 978 confirmed cases since the start of the outbreak. Since 24th June, American Samoa has continued to see a decline in the ratio of samples that test positive for dengue.

Are you currently in the Asia Pacific region? If so we’d like to know how climate change is impacting your community’s approach to stepping up the fight against dengue this year.

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https://www.breakdengue.org/global-dengue-day/

Emerging technology combating dengue: Big data and drones join the fight

We recently looked at Artificial Intelligence predicting dengue alongside and how smart machines are being employed to help control outbreaks of this disease. However, there are other emerging technologies are also becoming increasingly important in the fight – including big data and drones. Let’s take a look at some initiatives using emerging technology to fight dengue.

Big data versus dengue

Big data, in a nutshell, is a term for large and complex sets of data – generally gathered from a combination of different sources – that are too much for traditional data-processing software to analyze. Big data is important because it can help you solve problems you wouldn’t have been able to tackle before, thanks to the unique understanding or near real-time insights that specialist ‘advanced analytics’ software can provide.

The greater the volume and variety of data, the more accurate the insights because the diversity of the data sources helps to correct any errors in any individual source. Our own Dengue Track initiative, for instance, combines official data, the results of internet queries, social media messages, crowd-sourced surveillance and data from diagnostics. By analyzing these together, Dengue track not only informs health authorities of impending risks but also lets individuals know when they are at risk.

Click to sign the petition for a World Dengue Day

Other initiatives use a wide variety of structured and unstructured sources, from traditional data sources such as climatic factors and population density to modern social media posts and mobile phone records:

• In 2014, researchers at the Harvard T.H. Chan School of Public Health (HSPH) in Boston combined phone records of around 40 million Pakistani subscribers (representing 22 percent of the country’s population) with climate data to predict the spread of dengue. They matched the trajectory of the dengue virus in the 2013 epidemic to the traveling pattern of mobile users and found that mobile tracking could fairly accurately predict instances of dengue.

• In the same year, a team comprising Malaysia’s Teradata, Multimedia University (MMU) and Ministry of Health won the Big Data App challenge with a dengue prediction index. They combined atmospheric, altitude, construction, weather (rainfall, wind velocity and direction, min/max temperature and solar radiation, humidity, and thunderstorms) with dengue statistics for their index for Malaysia. The index predicted outbreaks with 80 percent success rate, which decreased dengue-related deaths by 40 percent from 2016 to 2017.

• A big data project by the Software Engineering Research Group at Paulista University in Brazil uses data gleaned from social networks, text mining, and machine learning to identify patterns in dengue outbreaks and, from that, probable dengue outbreaks in a particular region of Brazil. It showed that combining this unstructured data with structured data from traditional sources could help predict future behaviors and, thus, help with prevention.

• A big data analytics study by the Department of Information System at the Universiti Tenaga Nasional in Malaysia proposed big data analytics modeling techniques to determine and predict how long dengue patients would be hospitalized. Its finding may improve resource planning and assist with expectations around patients’ length of stay.

• The European Commission is running a competition to build an early warning system for epidemics. Applicants are invited to demonstrate a “reliable, cost-effective and scalable early warning system prototype to forecast and monitor vector-borne diseases” by integrating big data from a variety of sources. The competition opened in April and runs until September 2020.

Drones versus dengue

Drone is a common name for an unmanned aerial vehicle or UAV. It’s a small aircraft that flies without a human pilot on board; instead, a ground-based controller flies it using a two-way communications system.

Engineers are using drones with cameras on board to inspect places that are either hazardous or difficult to reach. This saves a great deal of time and expense, allowing places that would not otherwise be inspected to be checked out – as in the following examples:

Dengue awareness image showing why dengue is spreading.

Image courtesy of Malaria Consortium

• If tests show the quality of images to be satisfactory, Siliguri in West Bengal will use a drone to take pictures of stagnant water on terraces of buildings. It will, hopefully, help identify where dengue larvae need to be eliminated from high-rise buildings.

• Also in West Bengal, Kolkata is also planning to use drones to identify Aedes aegypti breeding grounds. While it will mainly survey the rooftops of high-rise buildings (including those under construction), it will also look at bridges and flyovers.

• In Guatemala, public authorities are deploying drones to collect aerial images of potential breeding sites near rural villages, including cisterns, pots and buckets, old tires, flower pots, and unused fountains. These images will be analyzed to target larvicide applications. The collaboration with the Universidad del Valle de Guatemala will monitor public perception of the use of this technology.

• A similar project in Trinamul in West Bengal encountered resistance, with people concerned about privacy – for both individuals and important establishments. Some councilors opposed to their use have questioned whether permission is needed to fly the drones.

Future drone use:

• Officials in Placer County in California are planning to experiment with using the drones to apply larvicide this summer, after successfully using the technology to photograph larvae in standing water.

• A joint UNICEF and Vanuatu project plans to use drones to deliver vaccines along with the nation’s chain of 83 tiny, remote volcanic islands, which span a 1600 km atoll. Currently, nine-seater puddle-jumper planes hop from island to island, landing on grass airstrips in an approach that is slow and inefficient, and frequently faces delays.

Emerging technologies continue to add to the toolbox as we step up the fight against dengue. Share your stories of how you are turning to modern technologies in your own battle against the disease.

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Help us map dengue so that experts better understand this disease. Click below to report dengue activity near you to Dengue Track.

Artificial Intelligence: predicting dengue outbreaks and outcomes

Technology is becoming increasingly important in the fight against dengue. Our own Dengue Track initiative is translating data from a variety of sources to create useful alerts when people may be at risk. Under the covers, it uses big data methodologies to generate its meaningful information. Other emerging technologies, including Artificial Intelligence (AI), may also soon also play a critical role in combatting the disease. Let’s explore AI and dengue: how smart machines are taking the fight to this deadly disease.

AI is based on the idea that computers can perform tasks that require some intelligence – that need them to be ‘smart’, in other words. These days, AI tends to be about creating machines that mimic human intelligence: how we learn, carry out tasks and make decisions.

Machine learning is a specific type of AI that mimics how humans learn. Give machine-learning computers relevant data, tell them about it and they will acquire new knowledge. These smart computers apply step-by-step instructions known as ‘algorithms’ to the data to create a digital ‘model’ of the real-world problem they are trying to solve. They reuse this model to solve similar problems time and again, improving it with experience.

Back in 2016, we asked whether AI was the key to dengue prevention. Today, AI technologies are being used to help smart machines learn how to predict dengue outbreaks, predict how individual dengue cases might develop and guide drug discovery.

Let’s start by looking at how AI is helping to predict dengue outbreaks.

Artificial Intelligence predicting dengue outbreaks

When it comes to Artificial Intelligence predicting dengue outbreaks, it begins with the smart computer digesting and analyzing vast amounts of relevant data, about the environment and patient outcomes in dengue-endemic regions, for example. The computer then deciphers and learns which conditions are most likely to result in an outbreak, and from that estimates the dengue risk for any particular local scenario, as we can see in these examples:

• Aime Inc has developed a tool for providing real-time predictions on the locations and timing of dengue outbreaks. The result of 2.5 years of research, it worked with “up to 84% accuracy” in trials in Penang. Aime now has contracts in Rio de Janeiro, Manila and Kuala Lumpur.

“The predictive platform can warn of possible outbreaks three months in advance and pinpoint them to within a 400m radius.”

• A study in China developed a model based on climate factors (including mean temperature, relative humidity, and rainfall), search query data from China’s Baidu internet search engine, dengue case data and human population data to develop an AI dengue prediction model.

“The epidemics during the last 12 weeks and the peak of the 2014 large outbreak were accurately forecasted.”

• A team in Manila developed a model that can predict the number of cases per 1,000 residents at locations throughout the city based on land use and rainfall levels.

“The computer learns over many iterations how to fine-tune its model to predict dengue occurrence from local conditions with increasing accuracy.”

• A study in India is looking to design a new model by combining various diverse machine learning models.

“As there are some prediction models are developed for dengue fever predication. The discipline is in its infancy and much work has to be done, so more research work is needed.”

• Researchers in Colombia are exploring using data about the pattern of dengue and chikungunya outbreaks to develop machine-learning models to predict disease spread.

“The development of computational models to forecast the number of cases based on available epidemiological data would benefit public surveillance systems to take effective actions regarding the prevention and mitigation of these events.”

AI predicting dengue outcomes

One second possible way machine learning could help the fight against dengue is by predicting which dengue cases are likely to evolve into something more severe. Here, researchers have been looking for any genes that might mean a patient is at higher risk.

Read more on, ‘Advances in using Internet searches to track dengue‘

To build an AI model to estimate patients’ risk of ultimately developing severe dengue, a study by Stanford University in California fed their computer with vast volumes of health records from patients who had contracted dengue. They combined this with data on gene expression from the US National Center for Biotechnology Information (information on our how bodies convert DNA instructions into something they can use to fight the infection).

While the scientists have identified several important genes and their parts (gene features) linked to the risk of developing severe dengue, they still have more work to do:

“In a real-world diagnostic situation, the relative proportion of patients who will develop severe dengue would be much lower than in our study. […] The machine learning algorithms will likely need tweaking before deployment as a diagnostic tool.”

AI and dengue drug discovery

Our third example of AI helping the fight against dengue is all about treating dengue. Scientists have turned to machine learning to help in the early stages of developing an antiviral drug for treating dengue infection.

During its lifecycle, the dengue virus produces a single protein that goes on to create all the viral proteins it needs to do its work inside an infected cell, according to an article in Atlas of Science. Before they can look for potential new treatments to combat this, the scientists needed to identify where new drugs could attach to these proteins.

After building a machine-learning algorithm and feeding it with published experimental data and molecule descriptions they were able to “characterize novel sites in the protein complex as susceptible targets or anchor points for drugs against all four serotypes of dengue virus.”

In other words, they used machine learning to find new places for potential future dengue treatments to latch onto and impede the dengue virus, stopping it in its tracks.

With so many stories of AI helping the fight against dengue, we’d love to hear your stories of how you are engaging modern technologies in your own battle against the disease.

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Help reduce the impact of dengue in your area. Click below to create a record of dengue in your neighborhood.

Dengue in the USA: Avoiding larger outbreaks and the wider spread of vector-borne disease

Dengue in the USA is mainly confined to its overseas territories, Puerto Rico and American Samoa in particular. The US mainland does, however, occasionally experience dengue outbreaks in its more subtropical parts – including Florida and the Gulf of Mexico. What more needs to be done to minimize the risk of dengue in the USA? We spoke with Dr. Ronald Rosenberg, Associate Director for Science at the Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (CDC) and lead author of Vital Signs: Trends in Reported Vector-borne Disease Cases – United States and Territories, 2004–2016.

Dengue’s primary vector, Aedes aegypti, is established across large parts of the US, both in the overseas territories and the mainland. Despite this, the US mainland is largely free of dengue. Occasional outbreaks linked to imported cases from endemic countries typically infect fewer than 50 people.

It’s easy to see how dengue reaches the regions where outbreaks occur. In southern Texas and the other states bordering Mexico, for instance, large numbers of people travel back and forth across the border, providing “many opportunities for introducing dengue,” according to Dr. Rosenberg. Meanwhile, southern Florida, especially Miami, is an enormous air hub for Latin America and the Caribbean, “so we have large numbers of people traveling to and from places where dengue is endemic,” he adds.

The picture is very different in some of the US territories. “Puerto Rico is our main concern when it comes to dengue,” says Dr. Rosenberg. “All four dengue viruses, as well as chikungunya and Zika, are endemic.”

Reducing risks of dengue in the USA

We asked Dr. Rosenberg whether he expects outbreaks of dengue in the USA to increase on the mainland. He foresees some transmission to continue in areas that have already seen outbreaks but is very concerned that future outbreaks could be larger: “If weeks go by without a dengue outbreak being detected, we could have an epidemic in mainland US. Thus far, local authorities have identified them pretty rapidly.”

Florida, Texas and other places susceptible to dengue introduction have excellent dengue surveillance and vector control operations. “They have a lot of nuisance mosquitoes and good nuisance mosquito surveillance and control operations, which also control vector mosquitoes,” says to Dr. Rosenberg.

Other parts of the US, he feels, need better surveillance and “badly need better vector control”, which is “too fragmented”. In the US, vector control departments exist at city or county level, not often at the state level. “Vector control operations in one town could be really good, but then a nearby town may have no vector control operations at all,” says Dr. Rosenberg.

Networking operations

To increase communications, enhance information sharing and develop best practices, the CDC is building a network of vector control officials. Dr. Rosenberg would like to see this network be as good as the US’s excellent network of state laboratories, which is very effective in diagnosing cases of dengue and other diseases. Every lab in the US’s Laboratory Response Network is kept up to date with the best tests needed to detect dengue, or another disease, outbreak.

On the surveillance side, the CDC is mapping Aedes aegypti, along with Aedes albopictus, populations with the help of the network it’s building. “During the 2016 Zika outbreak, we found many mosquito operations didn’t know they had Aedes aegypti in their area,” says Dr. Rosenberg. “We asked them to look for where Aedes aegypti can actually be found. We then built on that by modeling where we think it could be found.”

The CDC used that information to build and publish maps of the potential range of Aedes aegypti and Aedes albopictus populations in the US:

Nevertheless, Dr. Rosenberg would still like to know more precisely where Aedes aegypti is. “We will continue monitoring so we know if it’s spreading,” he says.

Improving know-how

The CDC is also providing training to ensure those involved in dengue surveillance and control have a good understanding of Aedes aegypti and how to respond if there is a disease outbreak.

Take insecticide resistance, for instance; it’s a big problem in the US and significantly hinders vector-borne disease control efforts. Again, during the Zika outbreak, the CDC found many US mosquito control operations had never done any insecticide testing. “If there’s an outbreak of disease and vector control operations spray areas where the mosquitoes are resistant to the insecticide, they’re wasting time and money – and not controlling the outbreak,” says Dr. Rosenberg.

The CDC is now working with mosquito control organizations to build a robust network of well-trained mosquito control operatives who can test for insecticide resistance. “We want them to have the equipment and strategies for responding to an outbreak, or even just to suppress Aedes aegypti populations as a preventative measure,” says Dr. Rosenberg.

The network is also improving operatives’ public relations skills because, as Dr. Rosenberg points out, “Aedes aegypti breeds around people’s houses and containers, so you need the community to help with depriving it of a place to reproduce”.

More research needed

Dr. Rosenberg agrees that the US needs better tools for suppressing Aedes aegypti: “There are more innovative methods on the horizon. We’d certainly like to see more results from the various sterile insect technique releases like Wolbachia bacteria and irradiated males, or the RIDL(Release of Insects carrying Dominant Lethals) technique.”

He would also like to see more research on epidemiology modeling. He nevertheless acknowledges that the dynamics of the transmission of vector-borne diseases are very difficult to model: “You don’t know with much certainty where the mosquito is going and how far it will fly, and you don’t know if it’s going to bite somebody who has dengue.”

While models could be very helpful, they are always limited by the accuracy and the completeness of the information put into them. “Responding to an outbreak requires precise models, and that requires more research into the biology and habits of Aedes aegypti,” he says.

Finally, Dr. Rosenberg shares his thoughts on how dengue in the USA is intimately linked to the global dengue problem. “We’re not going to remove the threat of dengue in the USA, even if it is limited until we reduce dengue transmission in Latin America, South East Asia, and Africa,” he says. “After all, you can get on an airplane any place in the world feeling perfectly fine, then get off the airplane with dengue having been bitten by a mosquito.”

Is low-cost travel spurring dengue outbreaks?

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What are the benefits of dengue vaccination?

Life is full of decisions. But no decision is ever black or white. Each has an upside and a downside. Every health decision – medical treatment, surgery and preventative measure – has its benefits and its risk. We spoke with Professor Tikki Pang (Pangestu), Visiting Professor at the Lee Kuan Yew School of Public Policy in the National University of Singapore, about weighing up the cost and benefits of dengue vaccination.

Dengue vaccination is around 66% effective at protecting against the disease when used in appropriate populations, according to Professor Pang. While you may think this is low, the public health and economic benefits these levels of protection deliver can be considerable.

Professor Pang uses Malaysia, which has about 100,000 dengue cases each year, as an example: “The cost savings from protecting 66,000 people can be very, very significant. Fewer people need to be cared for in hospital.”

The benefit also extends to specific industries. “A country suffering from an epidemic of dengue will see a drop in the number of tourists visiting,” says Professor Pang. “The vaccine can alleviate that loss of income.”

The real benefits of dengue vaccination

The vaccine also benefits individuals, giving “an enhanced sense of security and safety,” according to the Professor. He adds: “The protection means you don’t need to take any time off work, which is particularly important for people who don’t have paid medical leave.”

Professor Pang speaks from experience. “When I had dengue, it knocked me out for about two weeks. I couldn’t function,” he says.

And if someone is not infected, their immediate family will also be less at risk of getting sick. The actual benefit of dengue vaccination is, therefore, in reality, much greater than its 66% efficiency would suggest.

“Dengue vaccination cuts the total number of people likely to get infected,” says Professor Pang. “Researchers have modeled the tremendous impact vaccination has on reducing the overall number of cases.”

A sensitive balance

Professor Pang was keen to highlight that while “no new drug is completely free of risks”, the dengue vaccine had been studied on 30,000 people in 10 countries. This research, he said, found the dengue vaccine only caused minor side-effects such as a rash, slight fever or some pain at the injection site, adding “There are no very serious risks such as bleeding or going into shock.”

When it comes to deciding whether to adopt the dengue vaccine, countries must analyze the benefits and weigh them against the costs. “It can be a sensitive subject because it’s balancing the risk to the individual against the benefit of protecting the whole population,” says Professor Pang. “Research has shown the dengue vaccine is very cost effective in terms of how much it will cost and how much benefit it will bring populations receiving it”.

He is referring to the wealth of research on the topic. “Modelling studies have shown dengue vaccination to be both effective in reducing the number of people who get sick and cutting healthcare costs,” says Professor Pang.

Opposing views

The government in the Philippines suspended its dengue vaccine program following the dengue vaccine scare in the country. This followed concerns related to vaccinating people who had never before been infected with any dengue virus. Professor Pang believes the decision to scrap dengue immunization is “really unwarranted”.

“Only a very small percentage of the population – around 1% of children not previously exposed to dengue – got a little bit of the severe form of the disease,” says Professor Pang, who believes there were no deaths as a result of the vaccine. “It was nothing serious and well managed. All the children recovered well.”

The media did not agree with headlines stating that children had died because of the dengue vaccine. The Professor believes these headlines were “utter nonsense”. He is convinced the reported deaths had nothing to do with the vaccine; rather the children had other serious diseases that were not known when they received their vaccinations.

In fact, he is frustrated with the media for “sensationalizing the issue” but, at the same time, acknowledges the situation is quite complicated with lots of domestic political factors at play.

Brazil, meanwhile, is continuing with its vaccine program. With one million cases of dengue a year, even just 60% vaccine effectiveness means 600,000 people are protected. “Brazil has very good risk communication and a very responsible media,” says Professor Pang.

‘Point of care’ tests

Recent World Health Organization recommendations suggest using the vaccine “when a point of care test becomes available” and “in areas where there is a very high level of dengue”.

The Professor is concerned that point of care testing may not be feasible in some countries because it is impractical, more specifically time-consuming and very expensive.

His ideal scenario would be to have a very easy-to-use, fast, cost-efficient and reliable point of care test that uses a finger prick, costs one US dollar and where results are within an hour or 30 minutes.

“We are far from that situation,” says Professor Pang. He explains that before even giving the vaccine, you have to withdraw blood from children, which is not trivial. The wait for the test results could then be as much as a week. After that, the children would need to come back for three more injections.

Endemic dengue

Professor Pang says the recommendation for using the vaccine in areas where dengue levels are high “makes perfect sense”. He comments that the WHO recommendation has always been to consider the dengue vaccine in areas where the percentage of people who have already had dengue is greater than 70%.

“In Philippines, Indonesia, Thailand, and Malaysia, 90% of the population would have been exposed to dengue by the age of 15,” says Professor Pang. “At the age of nine, it’s probably closer to 70 or 80%.”

Singapore, notes Professor Pang, is an exception. With the virus not circulating at such high levels, he agrees the dengue vaccine is not justified but believes it may still be useful for travelers going from Singapore to Indonesia or the Philippines, for instance – particularly if they have young children.

Improving communication

Professor Pang suggested some potential actions he believes would help. The first is improving risk communication, awareness, and education around the current vaccine. “You need to communicate the issue of risk very clearly, to explain it’s much riskier for your kid to get dengue than the vaccine.”

The second is managing the expectations of countries waiting for newer dengue fever vaccine pipeline products. Professor Pang believes it will be at least another two or three years before another vaccine is ready. “The studies are still ongoing,” he says. “They have to analyze their data, publish their results in an independently reviewed journal and then they have to submit their dengue vaccine for regulatory approval.”

He also feels these potential dengue vaccines are actually quite similar to the currently available vaccine: “There’s nothing particularly different or revolutionary about these two new vaccines.”

To conclude, Professor Pang shared his advice for governments – many of whom he sees as “sitting on the fence” when it comes to using the vaccine for public health issues. He suggests they should follow the example of Brazil: “The Brazilians adopted the dengue vaccine because they understood the magnitude of the public health problem”.

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Dengue in Reunion: Increasing the risk of dengue in France

The French island of Reunion is currently facing an unprecedented number of dengue cases– a more than 30-fold increase on 2017. The primary vector, Aedes albopictus, is also established in some European countries, including southern France. The mere presence of these mosquitoes makes the threat of dengue in Europe real, as we discussed earlier this year. With thousands of tourists traveling from France to Réunion each year, can we expect to see dengue in France sometime soon?

It’s not unusual to see outbreaks of dengue in Reunion, a French overseas territory situated east of Madagascar and southwest of Mauritius in the Indian Ocean. The island typically sees between 10 and 250 dengue cases each year. While major outbreaks are rare, one in the summer of 1997/8 is thought to have infected 30% of the population.

A table showing the outbreaks of dengue in Reunion from 2004 to 2017.

Image source: ECDC

[While both Aedes albopictus and Aedes aegypti mosquitos live on the island, Aedes albopictus is dominant and believed to be the main dengue vector. Local dengue transmission typically consists of a mix of the DENV-1, DENV-2 and DENV-3 serotypes with DENV-2 currently dominating. In 2016, it was DENV-1. Before that, in 2014, it was DENV-2.

Dengue in Reunion – rising case numbers

Case numbers of dengue in Réunion have risen sharply since the beginning of 2018. Numbers had grown to 1,816 autochthonous cases (all DENV-2) by 23rd April, including 50 hospitalizations, according to the World Health Organization.

Just a few weeks later, on 16th May, the French Public Health authority reported 2,980 cases of biologically confirmed or probable dengue in Reunion for 2018. This included 1,407 cases during April alone, 356 of them during the last week of April. It noted a further 388 cases during the first week of May.

Though not fully understood, possible causes of the outbreak include:

• A significant proportion of the local population had not previously been exposed to dengue.
• A high proportion of cases were asymptomatic, allowing the virus to spread unnoticed until now.
• Tropical cyclones Berguitta and Dumazile providing a suitable environment for the mosquitoes to thrive while hampering vector control activities.

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There is one other possible explanation – that Aedes albopictus has mutated locally in Réunion. While there is no evidence of this as yet, further investigations are needed.

A long but quiet 2017

Transmission patterns for dengue in Réunion during 2017 were far from normal; this might also be significant.

Reunion’s mosquito populations are at their most dense during the humid season: from December to April. While the mosquitoes can remain active throughout the year, dengue transmission typically finishes after July – the beginning of the southern-hemisphere winter, according to the European Centre for Disease Prevention and Control (ECDC).

But 2017 was very different. While dengue case numbers were an extremely low number (103 in total), transmission continued throughout the year – even during winter months.

With winter fast approaching, weather conditions are suiting the mosquitoes again this year, just like they did in 2017. If the virus persists during the 2018 winter months, the island is at risk of an epidemic during its 2018/2019 summer.

What does this mean for Europe?

Reunion is a popular tourist destination, meaning a large number of people travel not only to but also from it each year. In fact, an average of 500,000 people travels from Reunion to Europe every year, mostly to mainland France. Peak travel periods are from December to January and July to August.

The current outbreak increases the likelihood of dengue in Europe, notably in France. Infected travelers could bring dengue to areas where mosquitoes, Aedes albopictus in particular, are already established. This includes France, which reported one dengue case imported from Reunion in 2016.

Map indication the whereabouts of the dengue mosquitoes in Europe in 2018.

Image via ECDC

With the summer imminent and temperatures on the rise, France’s mosquito populations will likely grow in the coming weeks and continue to do so until early autumn. This increases the risk of local dengue transmission – and potentially an outbreak – if an infected traveler were to return to France having contracted dengue in Réunion.

The ECDC has highlighted the importance of early detection, particularly during the warm summer months and in southern Europe, to prevent the disease from becoming established. It advises any locally transmitted dengue should trigger investigations to “assess the potential for onward transmission and guide vector control measures.”

If you’ve been lucky enough to travel to Reunion but unfortunate enough to experience dengue, get in touch. We’d love to hear your story.

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Dengue Prize: one year on

It’s one year since we unveiled the winners of our first Break Dengue Community Action Prize. The initiative sought to reward promising research with the potential to reduce the burden of dengue. In particular, the prize recognized academic projects that engaged communities in rising to the shared challenge of dengue fever.

We were pleased to present prizes to two winners and both have made important progress in the 12 months that followed. Dr. Aileen Chang, an Assistant Professor of Medicine at George Washington University Medical School in Washington DC, was one of the recipients. She has been working with NGOs and government officials on fighting dengue in Colombia to assess feasibility and acceptability of introducing dengue vaccines to Colombia.

Dr. Chang’s team has developed a robust survey which has been deployed in three areas of Colombia where dengue is endemic. The researchers are now analyzing the data and look forward to sharing their findings with the academic community. They are also conducting surveys in Venezuela using a similar survey tool.

Image showing how to reduce the dengue burden through traditional vector control methods.

Image courtesy of Malaria Consortium

The other winner, Dr. John Hustedt, an epidemiologist at the Malaria Consortium in Cambodia, has also completed work supported by the Break Dengue Prize. Their vector control initiative focused on the role of community health workers and the use of guppy fish to tackle mosquitoes in villages. It also presented opportunities to engage with healthcare workers and villagers on other dengue prevention tools, including vaccination.

The project raised awareness of dengue in Cambodia, vector control and identified some of the benefits and challenges of integrating guppy fish into dengue prevention strategies. Results of the project are being published in peer-reviewed journalist and will be presented at scientific conferences.

We are delighted to see the Break Dengue Prize translating into real results for dengue researchers in Asia and Latin America.

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