In the last 50 years, dengue has spread from being present in a handful of countries to being endemic in 128 countries, where about 4 billion people live, reports the Geneva-based World Health Organization (WHO).
Each year an estimated 390 million dengue infections occur around the world, according to website of Eliminate Dengue Program. Of these, 500,000 develop into dengue hemorrhagic fever, a more severe form of the disease, and dengue results in up to 25,000 deaths annually worldwide
“Dengue is the world’s most important viral disease transmitted by mosquitoes,” declares Dr. Duane Gubler, health administrator of the US Centers for Disease Control and Prevention. “The mosquitoes become infected when they feed on someone who has the virus.”
Dengue comes from the Swahili word which means “a sudden overtaking by a spirit.” Also known as “break-bone fever,” it is caused by four distinct virus serotypes (varieties recognized as distinct by the immune system) and is a distant cousin of yellow fever.
Like death and taxes, dengue exempts no one: fat or thin, ugly or beautiful, rich or poor, educated and illiterate. Children, who are exposed in open areas while playing, are more prone although adults are not spared.
I had a friend, a lawyer and a staff of a former senator. He was based in Manila but at one time he went to Baguio, where he contracted dengue. A few days after bitten, he suffered high fever, severe headache, and pain behind the eyes. There was also an outbreak of rashes in some parts of his body.
From Baguio, he was brought to Manila. But it was already too late; he suffered hemorrhage in the liver and died three weeks after being confined in one of the well-known hospitals in Makati City.
Even doctors die from it, too! There was a case of a lady physician whose daughter suffered from dengue. Unknowingly, a mosquito which bit her daughter had bitten the doctor. A few days after the daughter died, as a result of dengue, the doctor also showed manifestations of having dengue. She also died of the same disease.
In 2000, my very first article on dengue came out in the Asian edition of Reader’s Digest. Most of the doctors I interviewed for the feature said a dengue vaccine is very difficult to produce as there are four distinct strains of dengue.
Here’s a better explanation from Dr. Richard T. Mata, a pediatrician from Panabo City: “The vaccine must cover for all four strains because if there is a strain not included, it can become a dangerous vaccine that may give potential harm than good.”
And what seemed to be a breakthrough, a dengue vaccine was introduced in May. The world’s first dengue vaccine for human use was approved in three countries, including the Philippines, according to Sanofi Pasteur, the vaccines division of France’s Sanofi. (The two other countries are Brazil and Mexico.)
“Approval of the first dengue vaccine in Asia, which bears 70% of global disease burden, is a major milestone in dengue prevention and public health,” pointed out Olivier Charmeil, president and chief executive officer of Sanofi Pasteur in a press statement.
The vaccine has undergone testing on more than 29,000 patients worldwide. The Philippines reportedly participated in all three phases of the clinical development of the vaccine called Dengvaxia®. The New England Journal of Medicine published the pooled efficacy and integrated safety analyses from the 25-month Phase III efficacy studies and the ongoing long-term studies.
But there’s a big but. “Dengvaxia is not for children below 9 years old because there were findings that those given had more chances to be hospitalized of dengue than those not given,” said a report.
The dengue vaccine is not also recommended to people aged above 45. A study conducted in Australia showed that people aged 46 to 50 had a very low antibody response to the vaccine. This means that “it is likely to be less effective at protecting people in this age group from dengue.”
“Primum non nocere” (First, do no harm), so goes the cardinal rule which physicians follow. This rule, according to Dr. Rafael R. Castillo, editor-in-chief of Health and Lifestyle, must be observed in connection with the government’s dengue vaccination program.
Last year, Professor Scott B. Halstead, an acknowledged figure in dengue research in the past 50 years, published an article claiming that the dengue vaccine may even enhance the development of dengue rather than prevent it.
“The vaccine appears to cause antibody-dependent enhancement or ADE, a phenomenon whereby the dengue vaccine literally predisposes the dengue-naïve recipients of the vaccine for a more severe clinical expression of the disease,” explained Dr. Castillo in his editorial piece.
“Dr. Halstead was the first to identify this phenomenon, and he explained that in ADE, infection with one of the four strains of the dengue virus produces antibodies to that strain and cross-reactive antibodies to the other dengue strains.”
Here’s what Dr. Halstead said: “Over time, you make and keep protective levels of antibody from the initial infection, but you lose the cross-reactive antibodies. That allows a second dengue infection to cause severe illness, including dengue hemorrhagic fever.”
Alarmed by the program initiated by the Department of Health to vaccinate one million children against the dengue virus, doctors and health advocates, led by Dr. Antonio L. Dans, Dr. Leonila F. Dans, and Anthony C Leachon, submitted a position paper to the Congress Committee on Health and Senate Blue Ribbon Committee.
“There is a lingering uncertainty about the long-term safety of this new vaccine against dengue fever,” the position paper said.
“Evidence from the manufacturer’s trial shows that there may be a paradoxical increase in the incidence of severe dengue beginning a few years after children are vaccinated, and possibly continuing for the rest of their lives. This danger especially applies to children who have never had dengue fever before,” the position paper explained.
Clinical trials were conducted to assess the danger of dengue vaccine. Sadly, the danger has been confirmed. “A trial that included Filipinos showed that the incidence of severe dengue increased up to five times more, three years after children were vaccinated,” Dr. Dans, an epidemiologist from the University of the Philippines College of Medicine, was quoted as saying by the Health and Lifestyle.
The position paper reported: “In one study involving Asian children aged 2-14 years, vaccination increased the incidence of severe dengue by 400% on the third year of vaccination.”
The authors of the aforementioned study concluded that the reasons for the rise in dengue need further investigation. “We agree,” the doctors said. “Until these trials are completed, we recommend, as many other groups have, that children should be tested for past dengue infection before vaccination.”
The position paper also observed that the cost-effective study assessing potential use in the Philippines was funded by the manufacturer instead of an independent body. “The study was biased in that there were clear measures to minimize expenses (it did not account for the potential cost of increased disease severity arising from the vaccine) and maximize savings (effectivity was assumed to last 10 years when it is clear that protection wanes by the third year). These strategies make the vaccine seem highly cost-effective,” the paper said.
According to the position paper, in terms of easing the dengue burden in the country, the current program is not a feasible strategy. It gave this bit of information: “The program cost the Philippine government P3.58 billion, for just one million children in only three regions, representing a mere 1% of the population. Scale-up this program, even for the lowest quintile of wealth, is simply not a viable option for the country.”
Because the program was done hurriedly, the community was “inadequately prepared” for the implementation. From the time the Formulary Executive Committee issues guidance, some 12-18 months is allotted to prepare health workers and communities to introduce a new vaccine.
“Administrative orders and guidelines needs to be issued to local government units. Field manuals need to be produced and translated into dialects. Health workers need to be trained to give the vaccine and answer questions from parents and children. Referral systems for adverse events need to be activated and tested, a research protocol for monitoring on adverse events should be in place,” the position paper explained.
And these were done only in a matter of 26 days. “Many parents, teachers and health care workers claim they were never fully informed about the benefits and potential side effects of the vaccine,” the paper said.
To proceed or not to proceed – that is the question.
“I am not against it having been registered for Phase IV but it should have been physician-supervised like most drugs launched in Phase IV trials,” says Dr. Teodoro Javier Herbosa, former undersecretary of health. “Up to this point, I consider dengue vaccine as experimental and therefore should never have been implemented as a school-based program without having completed 5-6 years of Phase IV implementation.”
Dr. Mata echoes the same concern. “I am not against Dengvaxia,” he says. “They could have started low profile in private sectors and allow more good feedback. And probably further research on safety for less than 9 years old, just to satisfy the doctors who are meticulous.”
The well-designed critical trial will end by 2017 yet. By that time, a solid data can be provided “whether or not we can prevent more deaths and severe dengue with vaccination than without it.”
The dengue virus is transmitted to humans through the bite of infected Aedes aegypti and Aedes albopictus mosquitoes. Most Aedes mosquitoes are found indoors than outdoors. The Aedes aegypti prefers to rest in shaded places while Aedes albopictus prefer to rest in shrubs and trees.
When the dengue-carrying mosquito gorges on the blood of an infected human, the virus enters the insect’s salivary gland, where it incubates for eight to ten days. After that, the mosquito can pass the virus on to the next person it bites.
