In October 2023, I planned a trip to Thailand and Vietnam and, as any good traveller would do, I checked the vaccination requirements and health risks on the NaTHNaC website before going. While I had read a brief section on dengue fever, it seemed rare that I would get a severe case if at all and as there was no vaccine to take, I did not feel the need to be concerned. With the knowledge that I was up to date with all my (available) travel vaccinations and as I was travelling to a low-risk malaria area, I did not anticipate returning home early and spending the night in A&E. I was initially diagnosed with malaria in the UK, but following a second examination and test, the UK NHS diagnosed me with dengue fever.
Dengue fever is the most prevalent mosquito transmitted viral infection worldwide, with more than 3.9 billion people in over 129 countries at risk of contracting the disease. The global burden has risen significantly, with a ten-fold increase in the incidence rate in the past 20 years, and will continue to rise without additional action. It is also likely that this burden is underestimated given the lack of surveillance in most countries and the high proportion of asymptomatic patients. It is a common misconception that dengue is only prevalent in tropical climates. Due to climate change, it is becoming a growing concern in all regions in the world, with Italy, Spain and France experiencing local outbreaks in 2023.
So, what is dengue fever and how can we reduce the burden? In short, dengue (or break-bone fever) is a viral infection with four different serotypes that is transmitted by mosquitos. Many individuals who are infected are symptom free, with those who do have symptoms experiencing a high fever, headache, body aches, nausea and a rash. A small proportion of people develop severe dengue which, if left untreated, can be fatal. It didn’t reassure me to find that there is currently no specific treatment available for dengue fever, with hospital admission and symptom management being the norm for patients with moderate to severe disease. This means, should cases continue to rise, countries could expect a significant burden on struggling health systems.
Current advice to protect against dengue is to reduce the risk of mosquito bites. The development of a vaccine is complicated by what is known as antibody-dependent enhancement (ADE). ADE refers to previously infected individuals with one type of dengue serotype, having a higher risk of severe dengue if they are infected a second time with a different serotype. In other words, individuals who have already had dengue do not necessarily have immunity against other serotypes and are at risk of more severe illness.
ADE presents a major challenge for use of dengue vaccines in individuals with no prior dengue infection. Currently, one dengue vaccine has been licensed (dengvaxia by Sanofi Pasteur) with approximately five others in clinical development. Dengvaxia was approved in 19 countries, with the WHO recommending the vaccine only be used in dengue immune individuals to prevent re-infection. At the time of publishing, the WHO acknowledged a pre-vaccination screening strategy is needed to support wider rollout of this vaccine, which requires economic evaluation. Recent results published by Takeda using their long-term follow up data from a phase 3 trial suggest that the dengue vaccine could potentially be used in individuals who have not previously been infected. The results, published this month, demonstrate long-term efficacy and safety against all four serotypes in previously exposed individuals and against two serotypes (DENV-1 and DENV-2) in individuals who have not previously been infected. However, the authors acknowledged that it remains difficult to generate robust serotype-level data.
While these results are promising, more needs to be done globally to prevent further increases in transmission and subsequent cases and deaths. Better surveillance is needed to understand epidemiological patterns, openness in data sharing to improve vaccine development and additional economic analysis to understand the cost-effective impacts of preventative strategies.
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