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new analysis adds to concerns about the only vaccine available to protect against dengue, a nasty mosquito-spread disease colloquially called “breakbone fever” because of the painful achiness its sufferers endure.

The study, published in the journal Science, suggests the vaccine should really only be used in places where there is a lot of dengue activity and where most children who receive it will have already had at least one bout of the disease.

That’s because data from the studies used to approve the vaccine — called Dengvaxia, and produced by Sanofi Pasteur — showed a higher rate of hospitalizations for dengue three years after vaccination in young children who got the vaccine when compared to children who were unvaccinated.

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The increased risk, the study authors and others have said, appears to be for children who had had no previous dengue infections when they were vaccinated — in scientific terms, children who were seronegative.

“Our current estimates indicate that in all but the highest-transmission settings, use of this vaccine may lead to an increase in the risk of hospitalization for dengue in seronegative recipients even if the overall impact of vaccination is positive,” wrote the authors, from Imperial College London, Johns Hopkins Bloomberg School of Public Health, and the University of Florida.

“We predict routine vaccination will cause, at most, moderate … reductions in disease incidence, so it is important to set realistic expectations of impact for the policy makers and populations of countries likely to implement such policies.”

There are four different dengue viruses, named dengue 1 through dengue 4. Once you’ve been infected with one virus, it’s generally assumed you cannot contract that type again. But immunity to one of the viruses does not protect against the others.

In fact, having had one type of dengue increases your risk of having severe illness if you have a second infection. The most severe form of dengue — dengue hemorrhagic fever — can be fatal.

There has always been a concern that a dengue vaccine would increase the risk of severe disease, not lower it. And the studies Sanofi did to support its licensure bid for Dengvaxia seem to suggest that may be the case in young children who have not yet had dengue. The increased hospitalizations occurred in children between the ages of 2 and 5.

The vaccine is licensed for use in children 9 and older. Six countries have approved the vaccine: Brazil, El Salvador, Paraguay, Costa Rica, Mexico, and the Philippines, which earlier this year started using the product.

The World Health Organizations vaccine experts — known as the Strategic Advisory Group of Experts on Immunization — recommended earlier this year that if countries approve the vaccine, they should only use it in places where there is substantial dengue activity.

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Countries that want to use the vaccine should do studies in areas where they want to roll it out, ideally limiting its use to places where at least 70 percent of would-be recipients have had at least one dengue infection already, although prior infection rates of 50 to 70 percent would also be acceptable, the committee said.

Dr. Scott Halstead, a dengue expert who first flagged this problem, doesn’t think that position is safe enough.

“I do not believe … anybody should be going forward using this vaccine without testing the individual recipient to be sure they’re already seropositive. Because that’s the group that can benefit from this vaccine,” Halstead, a former US Army scientist who is semi-retired, told STAT.

Neil Ferguson, an infectious diseases modeling expert at Imperial College who is first author of the Science paper, agreed that would be the best way to use this vaccine.

Ferguson said a cheap, rapid test could be developed to check the status of each child due to get the vaccine. Children who had not yet had dengue would not be given the vaccine. And children who had already had a bout of dengue would only need one dose, not the three that Sanofi recommends — which would actually save money, Ferguson said.

Dr. Cesar Mascareñas, Sanofi’s global medical head for dengue, said the company is following the WHO’s position on when and how the vaccine should be used.

Mascareñas noted there is no sign the problem seen in the younger children happens when the vaccine is given to children 9 years and older. And he said the data on the younger children is not conclusive.

He also stressed that it is important to consider that the vaccine is the only medical tool against dengue, which the WHO suggests may infect nearly 400 million people a year.

There is no cure for dengue. Severe cases are treated with what’s known as supportive care — therapies that ameliorate the symptoms until the patient’s immune system can quell the disease.

The research was not funded by any one organization; the authors receive funding from a number of sources, including the UK Medical Research Council, the National Institutes of Health, and the Bill and Melinda Gates Foundation.

The six authors disclosed that three among them — including Ferguson — had advised Sanofi Pasteur on the implications of their findings, but had not taken payment for doing so.

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