New Year, New V
I have flown straight into back-to-back Philippine Typhoons, hearing frequent reports of floods and landslides. Looking forward to 2016, there is cautious optimism amongst scientists and clinicians for combating an altogether different geographical hazard across this region of tropics, with the potential rollout of a vaccine for Dengue Virus!
A drop in platelets, circulatory arrest, impaired consciousness, liver failure, Haemorrhagic fever, localised outbreaks and no approved medicine.
You might think we’re talking about Ebola virus. The clinical picture for the more severe grade of Dengue Haemorrhagic Fever is not too dissimilar, but the geographical spread is rife between the Tropic of Capricorn and Tropic of Cancer. Altogether, there are an estimated 100 million dengue virus cases per year.
The pathogenesis is complex, with evidence supporting two mechanisms. Firstly, there is ‘Antibody-dependant enhancement’ whereby antibodies against one dengue serotype from a previous infection augment the entry of a second dengue virus into macrophages, which ultimately leads to a more severe infection. Secondly, there are four different virus strains of Dengue Virus, with differences in their clinical presentation. In South East Asia, inclusive of the Philippines, there is an increased virulence of dengue-2-virus.
The pathogenic profile makes Dengue Virus a tough nut to crack in terms of developing a successful vaccine – especially with the nature of overlapping strain coverage – and with over a decade in the pipeline, the approval of the Sanofi-Pasteur CYD-TDV vaccine has been a long time coming. Mexico is the first and only country to approve the commercial rollout of the Dengue Vaccine so far. At present, it is unclear whether other endemic countries will follow suit.
And even so… will it work?
As Dr Simmons describes, this ‘Live-Attenuated’ candidate vaccine walks a tightrope. Two large, phase III, paediatric trials across South America and South East Asia demonstrated a 67 – 80% reduction in dengue hospitalisations, and continued surveillance is demonstrating a benefit to 9 – 16 year olds. Annoyingly, the candidate vaccine showed an efficacy of 50% or less against Dengue-2-Virus which generally appears the most virulent. The safety profile, however, particularly amongst the very young (2 – 5 and up to 9 year-old children), has much needed room for improvement and to some extent may even increase the risk of dengue-associated hospitalisation. Endemic countries will have a difficult decision to make if much of their case burden is in children below 9 years old.
In the future, perhaps as a clinician practising in tropical endemic regions like the Philippines, either in short or long stints; I would love to be in the position where I can offer patients and community members more than fluid replacement therapy and supportive care in the face of severe Dengue Haemorrhagic Fever of Dengue Shock Syndrome. I hope CYD-TDV or other candidate vaccines for this complex virus come to represent one such effective option. For now, all I can do is eagerly watch the story unfold from the sidelines. Let’s see what the New Year brings.