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Discovery & Development Drug Discovery

The Dangers of Dengue

Credit: Luke Duggleby-DNDi

Did you know that dengue is the most rapidly increasing mosquito borne infection worldwide? In the last few months, countries on almost every continent have faced large outbreaks. Peru is now experiencing its worst dengue crisis on record, while Bolivia, Bangladesh, Nepal and Pakistan went through devastating outbreaks in recent months. In 2022, hospitalizations were several times higher than hospitalizations for COVID-19 in many endemic countries. Worse still, the incidence of dengue further increased in early 2023.

When I started my career as a medical doctor, I witnessed the devastating impact dengue had on patients firsthand, and for the last 20 years I’ve dedicated myself to finding a treatment for the disease. Although the majority of dengue infections cause asymptomatic or mild illness, a proportion of infected individuals develop serious complications, including plasma leakage, which can lead to shock, bleeding manifestations, organ dysfunction, and, in some cases, death.

The lack of treatment options for dengue is a major cause for concern because climate change and rapid urbanization are causing the disease to spread further and faster. In 2019, dengue was named one of the top ten threats to global health by the World Health Organization. In fact, dengue incidence has increased eightfold over the past three decades, while the age standardized disability adjusted life years (DALYs) increased by 107.6 percent. Unfortunately, dengue is mostly endemic in low- and middle-income countries and there is little financial incentive for commercially driven pharmaceutical research. Moreover, four serotypes of dengue exist, which makes the development of treatments and vaccines even more difficult. 

Despite these challenges, progress has been made; thanks to a better understanding of disease pathogenesis and clinical progression, doctors have managed to decrease casualties through strict monitoring and careful fluid management. Currently, all patients with suspected dengue are monitored at least once a day in outpatient facilities or primary healthcare settings; daily blood samples and blood counts allow us to detect lowering platelets and rising haematocrits, which is suggestive of plasma leakage.

Credit: Luke Duggleby-DNDi

Patients suspected of having fluid leakage or who develop any of the dengue warning signs – mucosal bleeding, persistent vomiting, and abdominal pain – are admitted to hospital. And those at risk of developing severe disease, such as pregnant women, those with comorbidities (for example, diabetes, obesity, and hypertension), and the elderly, need to be monitored several times a day. This comprehensive approach has reduced the case fatality rates of hospitalized patients from around 5–10 percent in the 1980s and 1990, to below 0.1 percent in many countries today, such as Thailand, South East Asia, and Indonesia. But these monitoring measures are only feasible when patient numbers are low; in large outbreaks, such efforts are unsustainable.

Vector control efforts have been made in numerous countries; for example, using fogging to reduce the number of Aedes mosquitoes that carry the disease. Though novel techniques, such as the World Mosquito Program’s Wolbachia method, are likely to improve results, this approach alone is not enough. Several dengue vaccines have also been developed, but they are not equally effective against all serotypes of the disease For example, the TAK-003 vaccine looks promising and is currently being registered in multiple territories; however, it shows less efficacy against dengue serotype 3 in “dengue naïve” individuals. 

According to some predictions, the number of people at risk of dengue will reach 60 percent of the world’s population by 2080, partially linked to rising temperatures instigated by climate change that allow Aedes mosquito larvae to mature earlier, increasing biting frequency and transmission correspondingly. I have seen many experts disregard the impact of mild dengue. But dengue, even in its so-called “mild” form, presents huge economic repercussions. The estimated cost in India alone in 2016 was the equivalent of around $5.71 billion,making a disease with one of the largest enormous economic tolls. Dengue is no longer affecting only historically endemic countries, but also new geographical locations including high-income countries previously unaffected by the disease. Notably, both France and Spain experienced unprecedented locally transmitted dengue outbreaks in 2022. 

Similar to the global effort against COVID-19, we must use multiple strategies, join hands, and invest in research to develop therapeutics for dengue – the disease the world can no longer afford to neglect.

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About the Author
Neelika Malavige

Head of Dengue Global Programme at the Drugs for Neglected Diseases initiative

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