The commercial roll-out of the world’s first dengue vaccine is in sight, but tropical disease experts are already questioning the breakthrough vaccine’s drawbacks. Often known as “breakbone fever”, with symptoms of excruciating joint pain, high fevers, and, in severe cases, internal bleeding – dengue is carried by mosquitos.
As global warming accelerates the spread of tropical diseases around the world, dengue is on the march. Malaysia has registered an alarming escalation of dengue cases, leaving more than 130 dengue patients dead this year. And in recent weeks, dengue has erupted in Japan for the first time in more than 70 years, with more than 133 cases so far.
Scientists around the world have spent decades working on ways to limit the fast-spreading disease that kills an estimated 20,000 people every year, and leaves many thousands more ill.
A British firm, Oxitec, in July began breeding genetically-engineered mosquitos in special-purpose factory in Brazil, with hopes of winning government contracts for the insects’ release. Meanwhile, Australian scientists are working with carefully-bred non-dengue carrying mosquitos in Vietnam, Indonesia and Australia.
At the same time, the French pharmaceutical company Sanofi Pasteur is pushing forward with its dengue vaccine. Confident of success, Sanofi began producing the vaccine last year, well before the release of final trials results, and the firm expects to begin distribution next year, following regulatory approval. With a production capacity of 100 million doses per year, there’s little doubt Sanofi expects the vaccine to do well commercially. Financial analysts have already begun suggesting the vaccine’s sales might be worth US$1 billion a year.
Yet many in the dengue world have delayed popping the champagne. One government minister in Singapore, environment and water resources minister Vivian Balakrishnan, in August declared the vaccine was simply “not good enough”, following the vaccine’s first large-scale trial which suggested it provided little protection against one of the four dengue viruses.
Dr Cameron Simmons, a professor of infectious diseases who holds positions at both Melbourne and Oxford universities, has concerns about the vaccine. “From my perspective, the interesting result (from the Sanofi trials) is a reduction in hospitalisations and severe disease,” he told the Edge Review.
Yet he noted the vaccine didn’t work equally well with all age groups, performing poorly in younger children. Similarly, from the trials results, it doesn’t seem the vaccine will work well with Europeans or others from nations that are dengue-free. “There’s a strong sense that the vaccine is reliant on a person having had some sort of dengue virus exposure in the past,” Dr Simmons noted. “That tells us this is a vaccine that’s probably not going to work in travellers from non-dengue endemic countries.”
As it stands, the Sanofi vaccine requires three doses over 12 months, a regime that many see as difficult. “In the trials it was very easy to make sure everyone got their three doses,” Dr Simmons said. “In the real world, it’s much harder. People missing doses – that would be very common. And we don’t know how the vaccine performs without a full program of vaccinations.”
Earlier this month Sanofi published the results of its last phase III trial, which provided information on the protection the vaccine provided against each of the dengue viruses. Conducted in five countries in Latin America, the trial included 20,875 children between the ages of 9 and 16, and demonstrated a 60.8 per cent reduction in dengue cases and protection against all four serotypes.
This was a marginally better result than Sanofi’s first phase III trial in Asia, published earlier this year, which had fewer participants, and covered slightly younger children, and a final efficacy rate of 57 per cent (and with the shortfall in protection against at least one serotype).
Alain Bernal, Sanofi’s vice-president of global communications, said that it was not unusual to see lower efficacy of vaccines (for example, meningitis and influenza vaccines) in very young children. “Furthermore, it is important to remember that there is currently no vaccine available at all so these findings remain a major public health advance,” he added.
The three-dose regime, he explained, had been chosen to provide a balanced immune response against all four dengue virus serotypes.
There are also questions about the length of protection provided by the vaccine. Time will tell whether booster shots will be required, so adding to expense and logistical difficulties.
Drawbacks notwithstanding, Sanofi is keen to kick-start its dengue vaccine rollout. With a Japanese firm hard on its heels (pharmaceutical firm Takeda expects to begin final trials of its own dengue vaccine next year, following its success in earlier trials), time is of the essence.