Disarming dengue

Disarming dengue

Being the national coordinator for the ongoing dengue vaccine efficacy trials in the Philippines, Dr Maria Rosario Capeding is a paediatrician who is very familiar with dengue.

But this familiarity did not help ease her anxiety when her 21-year-old son, Juhani, came down with it a year ago.

"He was a first year medical student, and he was also worried about his studies. He felt weak and helpless," she says in an e-mail.

It started when Juhani fell sick with a high fever and headaches. A tourniquet test - a useful screening test for dengue - that was done on the second day came back negative.

However, because of his persistent fever, Dr Capeding had to be sure.

She ordered a complete blood count and some specific blood tests for dengue for Juhani on the third day.

He was confirmed to have dengue type 3.

But when Juhani's high fever lasted for more than a week than the average four to five days, and his platelet counts dropped, Dr Capeding was fearful and apprehensive that he might have potentially fatal bleeding.

"I know that dengue can simply be managed by fluid replacement and this is easy for me to say during my lectures to physicians. I realised that the reality is different, especially when it is your child who is sick," says Dr Capeding.

Dr Capeding's story may not be typical (how many of the estimated 220 million people infected with the dengue virus every year have relatives who are doctors or dengue researchers?) but it contains many lessons about dengue prevention and treatment.

Without a working vaccine, we cannot actually protect ourselves from dengue.

The best way to decrease the risk of getting infected is to reduce our chances of getting bitten by a mosquito by destroying mosquito-breeding sites.

And without specific treatment, doctors can only manage their patients' symptoms and help their patients stay strong enough to fight the virus from within.

But most of all, Dr Capeding's story highlighted the emotional cost that comes with dengue.

Although she knew that a dengue vaccine is still years away, she couldn't help but wish it was available earlier.

Perhaps, this episode could have been prevented.

Vaccine in progress

A vaccine in progress

The search for a viable dengue vaccine has been going on for more than 60 years. Due to the unique characteristics of the dengue viruses and the disease in humans, it had been difficult to develop a vaccine that is effective and safe.

As there are four types of dengue viruses that can cause the disease, developing a vaccine that will help the body produce antibodies against all four is technically challenging.

On top of that, when a person's immune system has developed antibodies against one type of dengue virus, it may respond more aggressively when he is infected by another type of virus and result in more complications.

This is why scientists also had to make sure that after vaccination, the antibodies developed against the four types of viruses would be individually strong enough to fight off each of the viruses without triggering those reactions.

Making things even more difficult is the fact that dengue is a human disease. Animals do not get sick when they are exposed to the virus.

"We don't have an animal model for the disease. Tests on rodents and primates can only show whether our vaccine can elicit antibodies," says Sanofi-Pasteur's global department of research and development associate vice-president Jean Lang. As such, scientists can only predict the viability, and not the efficacy or effectiveness, of the vaccine before it is tested in humans.

The clinical trials to test the efficacy and effectiveness of several candidate vaccines are already under way, and a candidate vaccine by the company is one of them.

However, since October last year, the company's candidate vaccine is the first to enter phase III clinical trials, the last scientific hurdle for the vaccine to prove its worth before health regulatory bodies can decide to approve its use in their respective countries.

These trials are currently ongoing in six countries from South East Asia (including Malaysia), six from Latin America, the United States, and Australia.

The vaccine is (simplistically) a concoction of four different, weakened, viruses that each contain a DNA backbone of a Yellow Fever virus that is inserted with a gene that codes for the membrane and envelope of one of the four dengue viruses.

"So far, there is promising data ... and we are hopefully optimistic," says Lang.

Published results from Phase I studies funded by Sanofi Pasteur, one in the US and another in the Philippines, have suggested that the vaccine is safe and able to elicit an immune response from almost all adult participants and more than 80% in children and adolescents when given in three doses within a year respectively.

Phase II results from an efficacy study in Thailand is expected to be available by the end of year 2012.

Glimpse into the future

A glimpse into the future

While the vaccine is found to be able to elicit immune responses from adults, adolescents, and children, it is currently tested in children.

The reason behind this strategy is to vaccinate people before they are exposed to the virus, says Lang. "In Thailand, most of the children are exposed before they are 12. That is why we vaccinate those who are between four and 11 years old," he explains.

Although estimated statistics show that worldwide, children are still more likely to experience serious complications of dengue like dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS), the age groups that are most affected by the disease differ in different countries.

In most of Asia, for instance, more young children are affected by dengue compared to adults.

In Malaysia, however, the incidence of dengue infections is highest in the working and school-going age groups that are above 15 years of age.

Also, since year 2000, more people above 15 years old die from dengue compared to those who are younger.

If all goes well, a vaccine may be available by the end of 2014, says Lang, who also revealed that a production plant is already being built to produce the vaccines once it is approved.

"The critical question is how is the vaccine going to be rolled out, and what is the vaccination process?" he notes.

The target population, age group and location of vaccination (whether in schools, or made available to the public in health centres) is up to the various health authorities to decide based on their health delivery system and the disease pattern of dengue in their countries.

In year 2009, a scientific forum called Dengue v2V (vaccine to vaccination) was formed to ensure that future dengue vaccines, once licensed, are readily introduced into the vaccination programmes of countries with the highest burden of disease.

"Hopefully, when the vaccine is rolled out, it will not be too pricey so that it can be made available to the general population," says Dengue v2V chairman Professor Emeritus Lam Sai Kit.

A vaccine is of no use if people could not afford it, he adds.

Cost-effectiveness studies done so far had projected that millions can be saved in terms of treatment and hospitalisation costs.

But even greater would be productive time of patients and caregivers saved through less illness and fewer fatalities, says Donald S. Shepard, PhD, a researcher from the Brandeis University Schneider Institute for Health Policy who had done some of the studies.

That being said, a vaccine is not a replacement to all the ongoing efforts to prevent dengue infections.

A vaccine may confer protection to those who will be vaccinated in the future, but it may take months and years for it to have an impact on the general population.

Also, there are also other diseases, like chikungunya, that are transmitted by the Aedes mosquitoes.

That is why vector control and community efforts to reduce the numbers of the Aedes mosquito and aid in the early detection of dengue must continue.

Even so, the possibility of a vaccine has given renewed hope for those involved in dengue prevention and control.

With a working vaccine, the eradication of dengue may still be decades away.

But without one, it would have been impossible.

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