- by Gary Finnegan

Malaria campaigners take on dengue fight

Image showing the vast spread of dengue on a world map, produced by Malaria Consortium.

Dengue is one of the fastest growing infectious diseases in the world. The disease burden has grown from 15,000 cases per year in the 1960s to over 390 million today

Commitment of veteran malaria campaigners to tackle dengue is a sign of how serious global public health advocates take the disease

Leading global health organization Malaria Consortium is hosting a roundtable in London this week and launching a new report in an effort to put dengue fever on the political agenda. The move marks the latest initiative by the not-for-profit group to raise awareness of dengue among Westminster politicians and the influential global health policy community in London.

Malaria Consortium has deep experience in disease surveillance, prevention and treatment of mosquito-related diseases, and has a network of staff running programs in 12 African and Southeast Asian countries. As both malaria and dengue are spread by mosquitoes, the group starts from a position of strength.

However, there are some significant differences between the two diseases. For a start, the geographical spread of the mosquitoes that spread malaria are limited to warm and humid climates. The dengue mosquito, in contrast, has the potential to invade new areas and are spreading fast around the world. Their eggs can withstand dry conditions and the diseases are even extending into temperate regions, including Europe.

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The time of transmission is different too. Mosquitoes transmitting dengue usually bite during the daytime, while malaria vectors bite during the night. This means that insecticide-treated nets (ITNs) which are used to fight malaria would have limited effect for a large proportion of the population who have daytime activities.

There are also habitat differences: dengue vectors, especially Aedes aegypti, are widespread in urban areas and breed mainly in water containers and discarded items. Another invasive dengue mosquito, Ae. albopictus (the so-called Asian tiger mosquito) that breeds in natural habitats such as tree holes, was previously considered a rural vector; it is now adapted well to urban environments with larvae breeding in artificial containers and has become an important and sometimes sole vector in urban areas.

Urbanization boosts dengue

Urban areas are unsuitable for breeding of the Anopheles vector in most African countries, although in Asia some malaria vectors are adapted to urban environments. In contrast, urban areas usually create suitable breeding conditions for mosquitoes that transmit dengue.

Increasing community awareness to participate in vector control and prevention of mosquito breeding would help in tackling both diseases.

While the dengue problem is growing, Malaria Consortium experts see great scope for improvement. In the field of diagnostics, for example, malaria diagnostic tools are well developed and in widespread use, including rapid diagnostic tests (RDTs) that can be used even at community levels.

In contrast, while there is a range of laboratory-based diagnostic techniques for dengue diagnosis, the lack of standardization and quality control measures for these techniques is a major concern. Some tests (e.g. nucleic acid detection) are very important but are often not feasible because of their cost and complexity, according to Malaria Consortium. Some antigen detection assays are credible candidates, but further improvement and evaluation is required.

Image and quote from Dr Jeffrey Hii. The quote reads, “It is essential that an accurate, rapid and affordable diagnostic test that covers the first seven days of dengue infection..." -Dr. Jeffrey Hii

Dr. Jeffrey Hii, Senior Malaria Consortium Vector Control Specialist

“It is essential that an accurate, rapid and affordable diagnostic test that covers the first seven days of dengue infection, and that can be used in peripheral and remote settings on a single acute sample, be developed,” says Dr. Jeffrey Hii, Senior Malaria Consortium Vector Control Specialist. “Due to high costs, a high range of false positivity from 0% to 31% with dengue RDTs, and the need for a quality-assured laboratory and strong health system support, diagnostic tools for dengue are still not widely available for use especially at peripheral levels.”

As a result, the disease is under-reported and it is not as easy to detect and respond to outbreaks. The distribution of dengue, especially in Africa, is still poorly understood making appropriate targeting of interventions challenging.

Treatment and vaccines

“When we compare treatment for both diseases, it is yet another story. Artemisinin-based combination therapy is available and widely recommended for malaria; there are currently no approved or registered anti-viral drugs for dengue,” Dr. Hii says.

Malaria vaccines are in an advanced stage of clinical testing; a Phase 3 trial of malaria vaccine RTS,S/ASO1 enrolled 15,460 infants and young children in seven countries in sub-Saharan Africa achieved vaccine efficacy of 27 percent in infants (who received four doses) and 35 percent among children aged 5-17 months who received four doses.

The first dengue vaccine, Dengvaxia (CYD-TDV) by Sanofi Pasteur, was first registered in Mexico in December 2015, followed by the Philippines in 2016. CYD-TDV is a live recombinant tetravalent dengue vaccine that has been evaluated as a 3-dose series on a 0/6/12 month schedule in Phase III clinical studies with an overall vaccine efficacy of 65.5 percent participants aged nine years and over (Hadinegoro SR et al. 2015). It has been since been registered for use in individuals 9-45 years living in endemic areas.

Neglected disease

Malaria Consortium is stepping up its work in this area but has, in fact, been active for several years. “Dengue is and has been a focus area for Malaria Consortium for some time,” says Dr. Giuseppina Ortu. “Our organization supports integrated vector control activities for insect vector-borne diseases in its core areas of work, depending on needs and disease burden. Although Malaria Consortium has a strong record on malaria, interest in dengue has been growing not only as part of our integrated vector management approach but also as part of Malaria Consortium’s neglected tropical diseases (NTDs) agenda.”

Dengue is one of the 17 recognized neglected tropical diseases but even within NTD circles, it has been one of the least prominent. Yet it has been one of the major causes of recent disease outbreaks not only in Asia but even in Europe. National Institutes of Health (NIH) has even included dengue as one of the current bioterrorism threats. “There is an urgency to address this disease now, understand these outbreaks and implement differential diagnosis for non-malaria cases, especially in Africa where the dengue burden is still not completely understood,” Dr Ortu adds.

“We are committed to extending our work on dengue and possibly to integrate future malaria projects with dengue prevention, control and management…”

So what is Malaria Consortium doing on the ground to tackle dengue? The NGO has been working with governments in assessing dengue surveillance systems as a first step to evaluate needs and challenges in the management of the disease. In Cambodia, Malaria Consortium is currently evaluating alternative methods of vector control such as the use of guppy fish (released in water containers to eat mosquito larvae) in reducing dengue transmission.

Increasing resistance to temephos (an organophosphate larvicide) and the high cost of Bacillus thuringiensis serotype israelensis (a group of bacteria used as biological control agents for larvae stages) to kill mosquitos in standing water in Cambodia, have raised the need to pilot new affordable vector control strategies, such as the one Malaria Consortium is currently testing. Alongside this study, Malaria Consortium is surveying knowledge, attitudes, and practices to determine the feasibility of such interventions in Cambodia.

“We are committed to extending our work on dengue and possibly to integrate future malaria projects with dengue prevention, control, and management,” says Dr. Ortu.

Advocacy work

Overall, while the malaria distribution map is shrinking, dengue is a rapidly expanding disease. Despite an estimated 390 million cases and roughly 12,500 deaths every year, dengue has not received the enough attention given its public health significance. Disease advocacy is a big part of fighting dengue, according to Malaria Consortium.

Great progress has been made in tackling other diseases, including malaria, following the increased attention and mobilization of resources unleashed by the Millennium Development Goals. Tackling dengue poses different challenges. To be successful, we need a similar global mobilizing of resources. Malaria Consortium is working to raise awareness of dengue among policymakers, both in the UK and in endemic countries.

At its policy roundtable event in London this week, it will launch a new report which it hopes will put dengue on the radar of policymakers and aid agencies.

“We hope that our latest report, and this roundtable discussion, will help to stimulate debate around the key issues involved in the fight against dengue, and raise awareness of the huge impact it is having around the world,” says Dr. James Tibenderana, Malaria Consortium Technical Director. “The UK is already a world leader in the fight against infectious diseases, including a range of NTDs, but even as one of those diseases classified as ‘neglected’, dengue receives little funding or attention.”

The new report will highlight areas where action can be taken to reduce the spread of dengue and control outbreaks when they occur. “Globally there needs to be a shift from responding to isolated outbreaks of dengue on an ad-hoc basis to a focus on developing long-term, integrated programming, including community-level initiatives leading to sustainable behavior change,” Dr. Tibenderana says. “This can be done by empowering communities with the essential knowledge and skills concerning hygiene and environmental sanitation, and training and engaging community health volunteers to better identify and refer suspected dengue cases, and improving community-based disease surveillance.”

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