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EU green-lights first vaccine for prevention of dengue

Image of a woman being vaccinated against dengue for a story about, the EU decision to green light the dengue vaccine.

The decision focuses on overseas territories – but climate change could bring mosquito-borne diseases to northern Europe

The European Medicines Agency – the EU drug watchdog – has paved the way for the approval of the first vaccine for prevention of dengue. The EMA’s influential Committee for Medical Products for Human Use (CHMP) recommended that Dengvaxia be granted a marketing authorization. The European Commission has the final say but this is usually a formality for medicines and vaccines given the green light by key EMA experts.

‘Dengue is by far the most common mosquito-borne viral disease affecting people worldwide…’

‘Dengue is by far the most common mosquito-borne viral disease affecting people worldwide (mainly in tropical areas); tens of millions of cases occur each year resulting in approximately 20,000-25,000 deaths, mainly in children,’ the EMA said, announcing its decision.

The regulator said that while most people affected by one of the four strains of dengue virus recover well, around 2% suffer severe dengue which can be lethal. There is currently no specific treatment for dengue and, until the development of the first vaccine against dengue, prevention has been limited to the environmental management of mosquitoes.

Chart showing the estimated cost of dengue fever to public health.

The dengue vaccine recommendation excludes the EU mainland and territories outside tropical areas. ‘A number of EU territories, mainly overseas, are situated in endemic areas, and these territories could benefit from this vaccine,’ the regulator said.

Dengue in Europe is nothing new. In fact, outbreaks of the disease have been recorded on the continent for almost a century, but most cases have been reported in tropical outposts such as Reunion Island and Madeira. However, both Spain and France recorded locally transmitted dengue cases in 2018. And climate modeling research suggests that global warming could make mainland Europe more hospitable to mosquitoes, raising the risk of dengue outbreaks to northern cities including Berlin and Stockholm.

Shot in the arm

The decision is a shot in the arm for the vaccine which had faced political challenges in the Philippines. The first public dengue vaccination program was introduced by a Manila government, only for its successor to suspend the initiative.

The controversy in the Philippines stems from the public and political response to data released by the vaccine’s manufacturer, Sanofi Pasteur, in late 2017 showing that the vaccine is best suited to people who have had prior dengue infections. This is because a second dengue infection can be worse than a first infection and the body responds to the vaccine as though it were the first infection. As a result, the WHO updated its advice on the vaccine, recommending that it be used in endemic areas and for people who have had already been exposed to the dengue virus.

The EMA’s CHMP also recommended limiting the use of the vaccine to individuals with prior dengue virus infection, for whom laboratory confirmation of the previous infection is available before vaccination. ‘In people who have never had dengue, there is an increased risk of clinically severe dengue disease leading to hospitalization when vaccinees are subsequently infected with dengue virus,’ it said.

‘In addition, because there are no safety, immunogenicity or efficacy data to support the vaccination of individuals living in non-endemic areas and traveling to endemic areas, vaccination of these individuals is not recommended.’

Image and text explaining basics on dengue fever and symptoms.

In their decision to recommend approval of the vaccine, EMA experts pointed to 31 clinical studies in dengue-endemic areas, mostly in Latin America and the Asia Pacific. These trials included over 41,000 participants aged 9 months to 60 years receiving at least one dose of the vaccine.

‘The overall available data demonstrate that for people between 9 and 45 years of age, the vaccine has positive effects in preventing symptomatic and severe dengue disease in people who have had previous dengue infection and live in endemic areas.’

Dengvaxia, the first vaccine for the prevention of dengue fever. Several other dengue vaccines, currently in the dengue vaccine pipeline are expected to be available in the years to come.

Help create an international day focused on dengue fever and the prevention of this disease. Sign our joint petition for a World Dengue Day, below.

World Dengue Day

Learn why a day dedicated to dengue awareness day is long overdue

Image of an Aedes mosquito with tex promoting a dengue awareness day.
Dengue fever is a global concern – we urge the United Nations to designate a World Dengue Day at its General Assembly in September 2019

Break Dengue and The International Society for Neglected Tropical Diseases (ISNTD) have joined forces to advance a global collective, Dengue VOICE, with the clear goal of reducing the burden of dengue around the world. Together, we are devising action plans and collaborations to contribute to the fight against dengue in communities and countries where dengue is a public health concern.

2,976,800,000 people in 150 countries are at risk of dengue. However, the real burden of dengue is not appreciated, slowing down efforts to fight it. By designating a World Dengue Day, the UN can help to raise awareness of dengue and share the ambitious work being done around the world to fight the disease.

Effective advocacy needs to happen at the grass-roots level, and Dengue VOICE is an important step towards the WHO objective of reducing dengue morbidity and mortality by 25% and 50% respectively, by 2020. We want the tool to empower communities and raise awareness among leaders and health authorities to break dengue.
Chart showing the estimated cost of dengue fever to public health.
Dengue VOICE is made up of HCPs, NGOs, experts, prevention champions and advocates, all of us that share the vision, the knowledge and the experience to be the strongest VOICE against dengue.

Find out more about World Dengue Day and add your voice to our call

One of the concrete outputs of this year’s Dengue VOICE collaboration is a letter will be presented to the 74th United Nations General Assembly in Sept 2019 – the letter is a consolidated request to create an international dengue awareness day, a World Dengue Day to serve as a rallying point to connect and focus the dengue prevention efforts worldwide.

More than 100 people have already signed the petition, including WHO employees, a member of the Australian parliament and growing numbers of people affected by dengue from across the globe.

Dengue in Africa: Read about the public health threat on the continent

We are partnering with communities and organizations worldwide that have been affected by Dengue such as Thailand, where we’re bringing the petition directly to Bangkok neighborhoods by sponsoring a local Dengue Day led by Break Dengue volunteers.

Given the scale and scope of dengue, we need everyone to add their voice to our effort so that we can collectively build on this momentum to meet the WHO objective of reducing the burden of dengue.

It’s time for a World Dengue Day. Please, click below to support our request for a dedicated, international dengue awareness day.

Thank you!

Add your name to the petition asking for a World Dengue Day

World Dengue Day

ASEAN Dengue Day is great – but it’s time to go global

Logo from ASEAN Dengue Day 2018

The annual awareness day brings Asian countries together to combat dengue fever. But dengue is a global challenge that demands a global response.

ASEAN Dengue Day marks an annual drive to bring together experts, policymakers, and the public to share solutions to the global problem of dengue fever. This year’s theme – One ASEAN Community Against Dengue – reflects the need to join forces against a major public health threat.

A series of events, including regional conferences in Singapore and Malaysia, will put dengue in the spotlight. As dengue is the most rapidly spreading mosquito-borne viral in the Asian region, it makes sense for governments to share resources, expertise, and experience. In a region where resources can be scarce, there is also great efficiency in pooling efforts in order to avoid wasteful duplication.

This is the 10th ASEAN Dengue Day and the experience to date has shown what is possible when governments, academics, and NGOs collaborate. Although the threat of dengue has grown over the past decade, knowledge-sharing and capacity-building in the ASEAN region have blossomed.

Going global with dengue awareness

The ASEAN region faces a major dengue problem – but it is not alone. The mosquitoes that spread dengue fever know no borders and need no visas. The Americas, the Indian subcontinent – and even some EU territories – are at risk of dengue outbreaks.

Click here to join ISNTD and Break Dengue in support for a Global Dengue Day

There are 390 million cases of dengue in over 100 countries each year. The World Health Organization estimates that 40% of the world’s population is now at risk from the disease. This is why we need to make sure that the control of one of the fastest growing neglected tropical diseases remains a priority for all nations in all regions.

Building on the success of ASEAN Dengue Day, the International Society for Neglected Tropical Diseases (ISNTD) and Break Dengue (BD) have joined forces to call for a Global Dengue Day.

We share the WHO’s goal of reducing dengue morbidity and mortality by 25% and 50% respectively by 2020 but believe we need to significantly step up our efforts to raise awareness of the disease and of all available solutions.

You can add your voice to the chorus of experts, academics, NGOs and citizens urging the UN to act. Sign the open letter and together we can hope to celebrate a Global Dengue Day – and the reduction of the burden of dengue.

Wanted: a simple test for diagnosing dengue

Image of a worker in a lab with text reading, 'Wanted: a simple test for diagnosing dengue'

Diagnosing dengue has become a major research focus follow calls from the WHO for point-of-care testing to be used prior to dengue vaccination.

The World Health Organisation’s Strategic Advisory Group of Experts (SAGE) on immunization has proposed that people be tested to see if they have had dengue in the past before they are given the dengue vaccine.

At its April 2018 meeting, SAGE noted second infections with a dengue virus can be worse than first infections, and that the best candidates for vaccination are those who have had a previous infection. The group suggests that the vaccine is of most value to public health, and least risk to individuals, in countries where dengue fever is endemic.

The call for a simple point-of-care test has injected new urgency into research on tools for diagnosing dengue that is rapid, inexpensive, accurate and mass produced. Today, such a test does not exist. Several are in development but some estimates suggest it could be two to three years before a suitable product hits the market.

At present, there is no straightforward way of diagnosing dengue. Lab-based tests are slow and mobile diagnostic kits are not yet accurate enough to determine whether patients have had dengue.

Tests that reveal whether a patient has a dengue virus now are no use: what’s needed is a simple pin-prick blood testing kit capable of diagnosing dengue in a matter of minutes. Patients requesting vaccination could then await the results and, depending on the outcome, have the first of their dengue vaccines.

Where are we now?

The London School of Hygiene and Tropical Medicine published a detailed report last year on the dengue diagnostics landscape. It highlights the major drawbacks with currently-available options, ranging from complexity and cost to speed and accuracy.

One of the most promising technologies comes from BluSense diagnostics – a start-up featured on Break Dengue in 2015 and 2016. They have used Blu-Ray technology to develop a portable diagnostic kit that quickly and accurately detects one of the biomarkers for dengue fever (NS1) based on a simple pinprick of blood.

According to Dr. Marco Donolato, formerly researcher at the Technical University of Denmark and now Chief Scientific Officer at BluSense Diagnostics, and one of the authors of the Nature Scientific Reports paper on diagnosing dengue says the technology is a ‘cheap and easy to use system, as simple to manipulate as a standard Blu-ray disc player.’

Since the publication of the 2015 paper, the company has attracted strong interest from the research community and funding agencies. BlueSense won the Malaysian Colussus Inno 2017 for entrepreneurship in a competitive field of more than 1,800 projects worldwide.

Diagnosing dengue and the race against time

The company plans to begin a feasibility project in Kuala Lumpur in July. This community study will be used to evaluate BluSense technology in diagnosing past dengue infections among 500 people of different age groups, mostly children.

‘We expect to have initial results by October this year,’ says company founder and CEO Filippo Bosco. ‘If the study goes well, we shall have a product ready for on-field validation early in 2019.’

The road from a high-tech idea to clinics in dengue-endemic countries is long but BluSense has been quietly working away for years – long before the WHO SAGE committee statement relating to dengue vaccination. While others will now invest in the field, BluSense appears as likely as any to reach the market next year.

‘Our goals are to have a point-of-care test that, in less than 10 minutes, will give a clear answer on the vaccinability of a person,’ Bosco told Break Dengue. ‘This would not require phlebotomy [drawing of blood using a syringe] but will be done via a single capillary finger prick requiring only 10 uL of blood. The current status of the technology is very promising, but we won’t have any final feasibility data before after the summer.’

Gene editing tech

There are other high-tech solutions in the pipeline that could ultimately make diagnosing dengue quick and easy. A ground-breaking gene-editing technology – known as CRISPR – has sparked a biotech revolution that is expected to translate into dozens of new gene therapies over the coming decade.

However, fixing faulty genes is not its only applications. Companies such as Mammoth Biosciences are looking at the power of this technology to detect tiny fragments of genetic material circulating in the blood. These could include stray copies of dengue viruses left behind by a mosquito (or even mutations in cancer cells shed by a tumor).

This would spark a diagnostics revolution. Not only could it be used to find genetic material in the blood, it may even be powerful enough to detect them in urine or saliva. Mammoth Biosciences envisages developing simple paper strips that would change color when dipped in urine, saliva or a spot of blood. This would make point-of-care testing even easier – provided high levels of accuracy and speed could be achieved.

For now, that still appears to be several years away from clinics. In the near term, it appears BluSense or something similar will emerge as the next breakthrough in dengue diagnostics – potentially unlocking the potential of the first dengue vaccine in the process.

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

Dengue Track

Dengue in Colombia: is it ready for the vaccine?

Image of some of the health experts fighting dengue in Colombia pictured in a lab.

Dengue in Colombia is not a new phenomenon. In fact, more than half of Colombia’s 25 million population is at risk of dengue fever. A new research project aims to explore whether the Latin American nation is ready to embrace the dengue vaccine.

Dengue is endemic in Colombia. Most Colombians live in areas where mosquito-borne illnesses are a daily threat. The country’s largest recorded outbreak came in 2010 when more than 157,000 cases were reported, and it has been hit hard in recent years by Zika outbreaks.

As an expert in arboviruses that cause Zika, chikungunya and dengue fever, Dr. Aileen Chang, frequently travels to Colombia. Dr. Chang is an Assistant Professor of Medicine at George Washington University Medical School in Washington DC and works with NGOs and government officials on health projects.

Image of Dr. Chang pictured with Aaron Hoyles from Break Dengue.

Dr. Aileen Chang fighting dengue in Colombia pictured here with Break Dengue’s Aaron Hoyles

‘I’ve treated patients affected by arboviruses for several years and studied Zika and chikungunya in Colombia to understand how to prevent and treat these infections,’ she told Break Dengue.

Now, inspired by the Break Dengue Community Action Prize, Dr. Chang has dengue in her sights. ‘A collaborator in Colombia in Colombia encouraged me to apply for the prize so that we could launch an initiative targeting dengue prevention.’

Having discussed dengue vaccination with colleagues on the ground in Colombia, Dr. Chang found the vaccine was in very limited use. In fact, awareness of its existence was very low. ‘We wanted to do a more scientific study of the feasibility and acceptability of introducing dengue vaccines to Colombia.’

Dr. Chang’s team won $10,000 through the Break Dengue prize and will begin developing a detailed questionnaire in the coming months. The plan is to survey patients, health professionals and to engage with public health administrators to understand whether Colombia has the appetite and resources to introduce a vaccine program in endemic areas, like the dengue immunization program launched by Parana State in Brazil last year. It will include questions on disease awareness, demand for vaccination and acceptability of the vaccine.

‘We want the survey to be robust and culturally resonant so we are drawing on the WHO vaccine preparedness document, and we will test the questions to ensure the translation is suitable for the audience,’ explains Dr. Chang. ‘After that, we will introduce it in three areas of Colombia with the highest levels of mosquito-borne illnesses.’

Dr. Chang’s links to the Universidad El Bosque, Fundacion Santa Fe, and Colombian government will provide access to officials who can help answer key questions about the feasibility of vaccine introduction. ‘We have particularly strong contacts in the Atlantico Department along the northern coast and have a large team of people based in Colombia,’ she explains.

Fighting dengue in Colombia integrating vaccination

The challenges for a low-resource country, albeit a fast-growing one, is to find the resources required to procure a vaccine, develop infrastructure for vaccine delivery and disease monitoring, as well as cold-chain, logistics and training health professionals.

Colombia’s health service is funded through a mix of public and private health insurers. Employees in the public service are entitled to publicly-funded care while others can – if they have the money – purchase private health insurance policies giving them access to multipurpose clinics.

This makes rolling out vaccination a complex prospect in Colombia, a country experiencing steady economic growth but with significant income inequality challenges.

‘There is a real divide between rich and poor,’ explains Dr. Chang. ‘The poorer areas are worst-hit by outbreaks of arboviral diseases, due to unplanned urbanization and water supply issues which provide mosquito breeding sites.’

She says that the gap between the haves and have-nots is widening because diseases like dengue and chikungunya are disproportionately affecting low-income households without access to healthcare. ‘People who have previously had one arboviral disease are at a higher risk of subsequent mosquito-borne infections. And if you develop an illness you may be unable to work for a significant period, reducing your earning capacity.’

However, Dr. Chang says that her Colombian partners are keen to embrace new technologies and to build research capacity in their country. ‘There is a big push in Colombia to do more research,’ she says. ‘Academic institutions are particularly keen to work with partners in the US and local health ministers have reached out to our group asking for support in developing evidence-based responses to the challenges they face.’

Dr. Chang’s project on dengue vaccination could be a step in the right direction. Any measures that effectively curb the impact of arboviruses in developing countries can help break the cycle of poverty and ill-health.

Click below to boost dengue surveillance near you and report your local dengue activity to Dengue Track.

https://www.breakdengue.org/dengue-track/about/

Dengue vaccine scare: business-as-usual in Brazil as Philippines freaks out

Image of an arm getting a shot with text reading, 'dengue vaccine scare: business-as-usual in Brazil as Philippines freaks out.'

World Immunization Week and vaccine confidence

The dengue vaccine scare that erupted last November prompted a fierce political and public reaction in the Philippines – yet another dengue immunization program in a Brazilian state has been unaffected. A leading vaccine confidence expert has drawn contrasts between outrage in Manila and relative calm in Parana state.

Vaccine scare stories are as old as vaccination itself. Public health experts shudder at the painful memory of the MMR vaccine catastrophe where a now-disgraced former doctor falsely linked the vaccine to developmental problems in children. Vaccination rates fell and measles outbreaks followed.

More recently, HPV vaccines – which prevent several cancers, including cervical cancer – are in the firing line. Concerns were raised that a small number of teenagers who had the shot later suffered chronic fatigue syndrome. This was not, initially, an unreasonable worry: parents naturally want to protect their kids from cancer but are equally careful to protect them from any side effects of medication or vaccines.

The issue was thoroughly investigated by the best experts in the world. They found that the rate of chronic fatigue symptoms in teenagers was the same before – and after – the vaccine was introduced. Yes, some adolescents were ill but it was not related to the HPV shot.

While vaccines are among the safest and most effective public health interventions in history, the public remains wary of an injection given to otherwise healthy people. And, when we make decisions for others – such as our kids or elderly relatives – the pressure to get it right is particularly acute.

So, the public is somewhat primed to overreact at the first whiff of a safety issue with any vaccine.

Suspension of a vaccine program

In late November 2017, dengue vaccine-maker, Sanofi Pasteur publicly shared data showing that people with prior dengue infections were best-suited to the dengue vaccine. There are four types of dengue and a second infection is often worse than the first. Because the body responds to vaccination in the same way as it would to an initial infection, it may not be advisable to vaccinate those who have never been infected by dengue.
Read why a second dengue infection is often worse than the first

In Parana, Brazil, where a public vaccination campaign had run for more than a year, authorities updated the vaccine’s label and got on with the job. In the Philippines, all hell broke loose. The government swiftly suspended the vaccination program and blamed its political predecessor for introducing the scheme in the first place.

‘The Philippines made headlines with public outrage and a suspension of the vaccine program, as well as threats to sue the manufacturer,’ says Dr. Heidi Larson of the Vaccine Confidence Project. ‘Brazil has stood by scientific evidence and, recognizing that the vaccine still has benefits although it carries some risk, it is facing this risk with resolve.’

Larson runs the Vaccine Confidence Index – a 67-country survey of attitudes to vaccination. She is a world-renowned expert on the factors that influence public perceptions, attitudes, and actions on vaccination. Larson told Break Dengue that the dengue vaccine scare has prompted her team to rerun their vaccine confidence survey in the Philippines.

‘One of the main things about the dengue vaccine story is that, compared to Brazil, the Philippines was much more fertile ground [for a vaccine scare],’ she said. ‘We look at some of the factors that can predict problems with vaccine confidence. They include low levels of underlying social trust, low trust in the political or health system, previous issues with vaccines – the kinds of things that historically have been amplifiers.’

Political issues have been part of the problem in the Philippines with the government keen to prosecute their rivals and criticise big business.

‘You have to appreciate the position politicians and leaders are in when faced with serious dengue outbreaks,’ notes Larson. ‘Dengue can have a real health impact and cause stresses on the overall health system. The vaccine was a source of hope but, for now, that opportunity seems to be lost in the Philippines.’

Spill-over effect

Now, the situation has taken another turn: the Philippines is suffering a measles outbreak. Spill-over from one vaccine panic to another is not uncommon.

‘There’s always a risk that anxiety or a loss of confidence in the system can have a knock-on effect,’ says Larson. The MMR scare somewhat dented uptake of other vaccines; a case of fraud in China that involved reselling out-of-date vaccines undermined confidence in pharmacies and immunization generally. ‘This creates a generalized anxiety about vaccines. People wonder whether they are safe, whether the system is reliable, and may not be sure which vaccines were involved.’

Measles outbreaks are, unfortunately, occurring in many countries around the world despite the availability of a cheap, safe and effective vaccine. However, the Philippines epidemic appears to be linked to the dengue vaccine scare.

‘The people I’m in touch with on the ground feel that some of the reasons that people are refusing vaccines are linked to a general anxiety following dengue vaccine,’ Larson says. ‘The outbreaks are in areas where the dengue vaccine was given.’

How did the dengue vaccine scare affect Brazil?

Given the reaction of authorities in the Philippines, it is somewhat surprising that other governments were not affected by contagion from the panic. Information spreads quickly online so the public and politicians in Parana, Brazil, will have been aware of events in Manila.

‘There are other contextual issues that can shape how a society reacts,’ explains Larson. ‘Brazil has been through so much with Zika and yellow fever that they may have had panic fatigue. I think there is a threshold for public anxiety. There is only so much any country and any public can take.’

For now, it appears unlikely that people in the Philippines will have the option of getting the dengue vaccine. However, if public dengue immunization programs elsewhere deliver a clear reduction in dengue death rates – and reduced spending on hospitalization – then public opinion may turn. For the Philippines, this is unlikely to occur any time soon.

Are you a dengue expert? Click here to join Dengue Lab and contribute to the discussion around this disease.

Dengue is different: why the dengue vaccine is still needed

Text over a blurred image about the dengue vaccine and why it is still needed.

The unique characteristics of dengue fever mean the dengue vaccine is different to other vaccines, according to an expert from The Philippines

Most vaccines are given to infants before they are exposed to a disease-causing virus or bacteria. Dengue is different. Because the disease can be caused by four types of virus, people who have already been exposed to a first infection are good candidates for the vaccine.

‘The breakthrough dengue vaccine does not work like a traditional vaccine,’ says Dr. Edsel Maurice Salvana. ‘Instead, it is meant to reduce the risk of severe dengue infection. And it does this very well.’

In the wake of a political and media storm in the Philippines, Dr. Salvana has been calmly injecting a dose of science into the public discussion. As Director of the Institute of Molecular Biology at the National Institutes of Health and a practicing physician who sees dengue fever on a daily basis, he has urged the public to take a balanced view of why the dengue vaccine is still needed – provided it is used appropriately.

The trouble began in late November when Sanofi Pasteur publicly shared data showing that people with prior dengue infections were best-suited to the dengue vaccine. There are four types of dengue and a second infection is often worse than the first. Because the body responds to vaccination in the same way as it would to an initial infection, it may not be advisable to vaccinate those who have never been infected by dengue.

Read why a second dengue infection is often worse than the first

The dengue immunization program introduced by the previous government in Manila has now been suspended by their successors. This has led to considerable public consternation, damaging the perception of the dengue vaccine – and potentially harming how the public views others vaccines too.

As a TED fellow and frequent media contributor, Dr. Salvana is more media savvy than most epidemiologists. He has been popping up on CNN, publishing opinion pieces on Esquire magazine and using Facebook to directly appeal to the public, lawmakers, regulators, and industry to make the most of a life-saving vaccine.

Amid the online chatter about whether the dengue vaccine is still needed, is there a risk that people are losing sight of the impact of dengue fever? ‘Certainly,’ Dr. Salvana told Break Dengue. ‘Many people cannot believe that the seroprevalence of dengue infection in our country is so high – it’s more than 90% at 11 years old.’

This means that most people have been exposed to dengue and are thus good candidates for the vaccine – provided they can show this, either through dengue diagnostics testing or medical records.

‘The panic has severely impacted the vaccine in our country, and this is despite the fact that the other 18 countries that approved the vaccine continue to use it, and Singapore even approved after the label change,’ he says. ‘It has also lowered uptake of other vaccines, and this is truly tragic.’

Dr. Salvana says people who have already had some doses of the vaccine but not completed the three-dose course should complete the series. He is calling on authorities to lift the temporary suspension which prevents the vaccine from being used.

infographic showing the economic cost of dengue.

Image courtesy of Malaria Consortium.

In the meantime, he is also offered some context for the public on how the dengue vaccine could be used in future. ‘[With the vaccine] there is a 90% decreased risk of hospitalized with severe dengue and an 80% decreased risk of hospitalization in those with previous dengue infection,’ he says.

He argues that the public and decision-makers will need to weigh the certain benefits of dengue vaccination against any risk that it may pose for the small number of people in dengue-endemic areas who have never hard dengue.

Dr. Salvana’s view chimes with others outside the Philippines who argue that Manila must not throw the baby out with the bathwater. Dr. Heidi Larson, Director of the Vaccine Confidence Project at the London School of Hygiene and Tropical Medicine, has drawn a contract between the air of panic in the Philippines and the more sanguine reaction in Brazil.

‘The Philippines made headlines with public outrage and a suspension of the vaccine program, as well as threats to sue the manufacturer,’ Larson wrote on her influential blog. ‘Brazil has stood by scientific evidence and, recognizing that the vaccine still has benefits although it carries some risk, it is facing this risk with resolve.’

Meanwhile, the WHO has updated a Questions and Answers document on the vaccine. Pending a review of data, it recommends vaccination only in individuals with a documented past dengue infection, either by a diagnostic test or by a documented medical history of past dengue illness. The Organisation will update its official position paper in April. ‘Meanwhile, WHO encourages the development of a rapid diagnostic assay to determine past dengue infection.’

 

Disease surveillance: researcher explains how you can help

Blurred image with text reading, disease surveillance: researcher explains how you can help

We speak to Mauricio Santillana, Boston Children’s Hospital and Harvard University, about his new paper on the use of Google searches in disease surveillance. Not only are search engines a vital tool for fighting dengue, they connect the community in a novel way, opening the door to crowd-sourced real-time outbreak monitoring.

What was already known, and what question(s) were you attempting to answer?

Multiple previous studies have explored the utility of using information from Internet searches to track disease activity in a given location. Google Flu Trends (GFT) is one of the earliest attempts aimed at tracking flu activity in the USA and other countries using flu-related Google search activity in the population. Unfortunately, GFT was shown to poorly track flu activity on multiple occasions and was discontinued in 2015. An array of studies has emerged, attempting to revisit the idea of using Internet searches to track diseases. In a recent study, our team introduced a methodology that leads to accurate tracking of flu in the USA at the national level using Internet search data.

Most of the previous research studying disease tracking with Internet search information has been conducted in developed and wealthy countries where internet penetration is high and healthcare-based disease surveillance systems have been in place for multiple decades. However, few studies have investigated the capabilities of using these novel methodologies to track neglected tropical diseases in less developed countries; similarly, the limitations of these methodologies, and how the tracking accuracy relates to the underlying characteristics of a country, such as Internet penetration and disease prevalence, are investigated by very few studies.

Read about the hidden economic cost of dengue

In this research, we studied the potential of using dengue-related Google search activity to track real-time dengue activity in five very distinct countries/states around the world: Mexico, Brazil, Thailand, Singapore, Taiwan. Specifically, we studied the capabilities and limitations of using Internet search activity to track dengue in less developed countries, as well as how the tracking accuracy relates to the underlying characteristics of a country.

What is the most important finding of your study?

By extending our methodology ARGO (AutoRegression with Google search queries), initially introduced for flu surveillance, to track dengue in these five countries/states, we show that:

(i) the lessons learned to track influenza in data-rich environments, like the United States, can be effectively used to develop methodologies to track an often-neglected tropical disease, dengue, in data-poor environments;

(ii) even in countries where traditional health care-based disease surveillance systems are lacking, properly developed methods using Internet searches of those countries can give accurate tracking of dengue;

(iii) our ARGO method significantly improves the tracking of dengue, which is particularly important for countries with less advanced clinical based disease surveillance systems, and

(iv) dengue-tracking methods based on Internet searches perform best in dengue-endemic areas with a high number of yearly cases and with sustained seasonal incidence.

What are the larger implications of your findings?

Previous inaccuracies of disease tracking systems such as Google Flu Trends and Google Dengue Trends led many public health officials to question the capabilities of big data approaches in tracking epidemic outbreaks. We show in our study that despite the discontinuation of Google Flu Trends and Google Dengue Trends, it is still meaningful to formulate, develop, and refine robust methodologies that are capable of extracting disease-related information from data sources not designed to do so.

In short, we have shown that information from Internet search engines can be used effectively to track mosquito-borne diseases with proper and rigorous statistical methods (i.e., analytics). This is particularly useful for less developed countries, where traditional clinical-based reporting systems are often delayed or missing. This alternative way of tracking disease can be used to alert governments and hospitals when elevated dengue incidence is anticipated, and provide safety information for travelers.

Based on your findings, what are the next steps for this research?

Future work should include investigating the feasibility of applying our methodology to other countries, finer spatial and temporal resolutions, as well as to other infectious diseases.

In a nutshell, what’s the most exciting aspect of the study?

The wide availability of Internet throughout the globe provides the potential for alternatives for reliably tracking dengue and other infectious diseases faster than traditional clinical-based systems. Such a development would be particularly useful for less developed countries, but proper and rigorous statistical methods are needed for the potential to be realized.

Click below to report dengue activity in your area.

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Surge in dengue fever publications

Image showing various publications and the text, 'surge in dengue fever publications'

The number of dengue fever publications has grown strongly since 1960.

According to an analysis of PubMed, performed by Break Dengue, just five search results were returned for ‘dengue fever’ in the year 1960. This rose gently until the late 1990s when the graph turned upwards. After that, growth was exponential. In 2015, more than 1,500 papers were published on dengue fever.

This reflects the strong growth in academic and public health interest in dengue fever, as well as increased research funding for this serious disease. The trend follows a growth in the number of cases of dengue worldwide – and reflects the urgent need to contain its spread.

Image of a chart showing the surge in dengue fever publications in recent years.

Dengue fever publications: highlights from 2017

This year has seen several notable dengue publications on topics ranging from mosquito control and dengue treatment to disease surveillance and the burden of disease including the economic cost of dengue.

1. Lancet Infectious Diseases published a study by Castro, Wilson, and Bloom – all from Harvard – on the large and growing burden of dengue fever. The paper explores not only the number of cases but the economic impact of outbreaks.

2. A study published in BMC Infectious Diseases looked at early warning signals for dengue outbreaks in Colombia using a mix of climate and other data. Colombia faces a range of competing, health challenges. An early warning system would help decision-makers to prioritize how they use resources and getting better value for money.

3. A paper by experts in Taiwan explores the role of public transport in the spread of dengue in urban settings. The authors look at metro passenger numbers and how this relates to dengue outbreaks. They found that large flows of passengers through metro stations can dramatically increase the risk of dengue in the neighborhood.

4. The disease burden of dengue in the Philippines is the focus of a study published in the American Journal of Tropical Medicine and Hygiene. The authors aim to address the underreporting of cases in order to get a more accurate estimate of the trust burden of disease. We will have an interview feature on this topic in the coming weeks.

5. Looking ahead, an important publication is due for a release this coming summer examining the role of search engines in tracking dengue. While this paper remains under embargo, we can whet your appetite by saying that it looks at the potential of combining search engine data with official clinical information in five countries. Watch this space.

What is clear is that the commitment among academics and funding agencies to understanding dengue fever is stronger than ever. So too is the level of diversity we see in the kinds of papers being published. No longer are dengue fever publications the exclusive domain of mosquito experts and biochemists, economists and mathematical modelers have entered the fray.

The big question is whether the growth in knowledge from multiple disciplines can be translated into strategies that improve our power to break dengue.

Double dengue: why a second dengue infection is worse than the first – and what it means for vaccination

Text, reading Double dengue: why a second dengue infection is worse than the first – and what it means for vaccination over a blurred image of the dengue virus.

The impact of a second dengue infection can be amplified due to antibodies produced to fight off an earlier infection. That’s why dengue vaccination may be best for those who have already recovered from the disease.

‘Antibody enhancement’ may sound like technical medical jargon but the immunological theory is having its day in the sun. It is the idea that explains why the first brush with a dengue virus is less serious than the second.

‘There are thousands of dengue cases across the world each year, making dengue viruses one of the most important mosquito-borne pathogens,’ explains Professor Pratit Samdani, a renowned dengue expert in Mumbai, India. ‘There are four types of dengue – known as DEN I, DEN II, DEN III and DEN IV – and while infection with one virus will make you seriously ill, the symptoms can become potentially fatal when infected subsequently with a different strain.’

The science behind this phenomenon is fascinating. It turns out that natural proteins called antibodies, produced by the body to fight infection, help defeat the first dengue virus but leave us susceptible if we are later hit with another dengue virus.

‘Whenever one gets an infection you get antibodies,’ says Prof Samdani. ‘In dengue, these antibodies let the second virus enter the cells easily, increasing the risk of dengue hemorrhagic fever! This is because of a phenomenon called antibody-dependent enhancement.’

This explanation is supported by most experts in the field, including Prof Tikki Pang at the University of Singapore’s Lee Kuan Yew School of Public Policy. ‘Instead of protecting the individual during a second dengue infection with a different dengue serotype, it enhances virus replication and causes more severe disease,’ he says.

Who should have the dengue vaccine?

The impact of a second dengue infection has been in the news this month after Sanofi Pasteur, the company that developed the world’s first dengue vaccine, shared new data on the impact of prior dengue infection.

The company has found that the vaccine protects against disease in those who had been infected before vaccination. For those who have never been infected, vaccination may not be advisable as the body responds in the same way as it would to an initial infection. Thus, a second dengue infection could be more severe.

‘Ideally, people should do a diagnostic test first to determine if they have ever been exposed to dengue, but this is not always possible,’ says Prof Pang. ‘Instead, a good knowledge of a previous history of dengue infection and physicians’ acumen and experience are important.’

While most people in endemic areas have been infected by the time they reach adolescence, many cases are mild or ‘silent’ – which serious or lasting symptoms.

Image and text explaining basics on dengue fever and symptoms.

‘In endemic areas, people who have never been infected by dengue are in the minority – in most endemic countries 90% are infected by the time they reach adolescence, without necessarily becoming ill,’ says Prof Pang. ‘The vaccine is still very safe and not all of those who are facing the risk of a second infection, develop a severe form of the disease. Actually, the vast majority don’t.’

Better diagnostics and surveillance needed

The new data on how best to use the vaccine has caused confusion in some quarters. In the Philippines, for example, a pioneering immunization campaign has been put on hold and a political row is brewing.

ADVA – the Asian Dengue Vaccine Advocacy group – released a statement explaining the science and calling for calm. ‘This outcome should not cause undue panic among individuals who have already received the dengue vaccine,’ it said. ‘Seropositive individuals would benefit from receiving the vaccine.’

The group said serological pretesting would help doctors to determine whether patients were suitable candidates for the vaccine, adding that an ‘appropriate, cheap’ test should be made universally available.

The furor over the dengue vaccine has sparked concerns that vaccine uptake and development might be harmed by negative headlines.

‘Once you cut through the noise, what is most apparent is that the global dengue community – particularly in areas of high endemicity – urgently need better dengue diagnostics and disease surveillance reporting,’ said Kamran Rafiq, International Society for Neglected Tropical Diseases.

‘This news could potentially mean delays in the global vaccine development pipeline by forcing longer waits for safety issues to be cleared, underlining the pressing need to differentiate between seropositive and seronegative patients.’