“Please, our son needs help!” pleaded Rina as she carried her son Noel to the hospital. The nurses, who were having lunch that hot Friday afternoon, immediately quit eating and tried to calm the mother of the 9-year-old boy from Bansalan, Davao del Sur.
“What happened,” one of the nurses asked. Rina then shared this story: Five days earlier, Noel had a fever and was complaining of abdominal pain. The parents thought it was due to some kind of “wind” because the child had not eaten. The fever, however, was on-and-off for four days.
Despite the medications they have given to the boy, their son’s condition was getting worse. That was when the parents decided to bring the boy to the hospital. By this time, Noel’s breathing was rapid and the pulse was beating fast. His skin was cold and clammy. Chest X-rays showed the boy having an abnormal build-up of fluid in the lungs. He was breathing difficulty. Doctors told the parents that their son was in a state of shock. The boy was immediately brought to the emergency department. Inside the intensive care unit, the boy started bleeding profusely despite the blood transfusion done by the doctors.
Early Sunday, at about three o’clock, Noel died.
Out of 211,000 suspected dengue cases last year, more than 1,000 people – mostly children – died from the mosquito-viral disease, according to the records released by the Department of Health (DOH).
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.
Actually, there are two kinds of diseases caused by dengue virus. There’s the classical dengue known for more than 200 years. The other new entity, dengue hemorrhagic fev er – also called as Philippine, Thai, or Southeast Asian hemorrhagic fever or dengue sh ock syndrome – emerged in 1953 in Manila and in 1958 in Bangkok.
One of the most cost-effective ways to reduce the spread of dengue is through a vaccine. “Many biotechnological approaches have been used in attempts to develop dengue vaccines candidates, including live attenuated vaccines, infectious clone-derived vaccines, recombinant live vector systems, subunit vaccines, and nucleic acid vaccines,” pointed out the “State of the World’s Vaccines and Immunization” in 2002.
There are several reasons why dengue vaccine is very hard to produce. One of these is that dengue has four distinct strains. “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,” explained Dr. Richard T. Mata, a pediatrician from Panabo City.
In 2002, Professor Natth Bhamarapravati, chief scientist of the dengue research team at Bangkok’s Mahidol University was reported to have spent already 12 years of his life trying to develop the dengue vaccine. There were other medical researchers doing the same thing.
Last year, what seemed to be a breakthrough, a dengue vaccine was introduced. 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 were 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,” said Olivier Charmeil, president and chief executive officer of Sanofi Pasteur in a press statement.
The vaccine reportedly has undergone testing on more than 29,000 patients worldwide. The Philippines 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 hitch. “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 press release.
The dengue vaccine is also not 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.
Two years ago, 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,” he added.
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.”
In December 2015, the Philippines was the first country in Asia to approve the use of dengue vaccine for people aged 9 to 45. The health department approved the procurement of Dengvaxia intended for one million public school children in areas reported to have the highest incidence of dengue.
Alarmed by the said program, 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 document 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.”
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,” Dr. Teodoro Javier Herbosa, former undersecretary of health, said at that time. “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 echoed the same concern. “I am not against Dengvaxia,” he said. “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.”
Last November 29, the dengue vaccine made headlines when Sanofi Pasteur announced that, based from six years of clinical data, it poses more risks for people who have not been infected by the dengue virus before immunization.
“The analysis confirmed that Dengvaxia provides persistent protective benefit against dengue fever in those who had prior infection. For those not previously infected by dengue virus, however, the analysis found that in the longer term, more cases of severe disease could occur following vaccination upon a subsequent dengue infection,” Sanofi said in a press statement.
“Vaccination should only be recommended when the potential benefits outweigh the potential risks (in countries with high burden of dengue disease),” it added. “For individuals who have not been previously infected by dengue virus, vaccination should not be recommended.”
Aside from the Philippines, 10 other countries have approved the commercial release of the dengue vaccine; these are: Brazil, Costa Rica, El Salvador, Guatemala, Mexico, Paraguay, Peru, Indonesia, Singapore and Thailand.
Immediately after the announcement, the government suspended the dengue immunization program for public school children. But the hitch is that more than 700,000 children were already given the vaccine.
Health Secretary Francisco Duque III told the press that so far no cases of “severe dengue infection” have been monitored among those that were given the vaccine. It takes about five years for such severe dengue cases to become evident, some reports said.
In another news briefing, Dr. Eric Tayag, DOH spokesman said the health department “is prepared for a worst-case scenario.” He added that those who had been vaccinated “are being followed up for adverse effects.”
Since dengue vaccine is still in a limbo, there’s a better way to treat dengue. That is through water. “Dengue is a water-borne disease and so the best possible solution to it might be in water, too. It’s simply water-in versus water-out issue,” said Dr. Mata.
“When the mosquito bites you, the dengue virus will enter your blood vessels and it will cause plasma leakage, or what I call as butas ang mga ugat. It’s like you have thousands of pinpoint holes in your blood vessels that causes it to leak with water that will cause dehydration,” he explained.
“Para kang supot na may tubig na may butas butas,” he further said. “It’s like a secret diarrhea. And that’s why it’s dangerous because you cannot see the fluids that comes out of the vessels unlike in loose bowel movement where it’s obvious. So, it’s easy to estimate the needed amount of hydration in diarrhea than that of dengue. All the worst if you don’t even know its dehydration.”
Dr. Mata said dehydration causes shock, “dahil naubos na ang tubig, wala ng pressure. Kaya nga tinawag na dengue shock.”
Dehydration also causes intestinal ulcer that causes bleeding. “And because the platelets are low, the bleeding becomes severe,” Dr. Mata said. “But if there was no dehydration, there will be no ulcer and thus no bleeding – even if the platelets are low. So, it still boils down to dehydration.”
Dehydration also causes kidney failure, which result from the decrease in urine output. “This causes the water to be retained in the lungs thereby creating congestion that can kill the patients,” he said.
Many people believe congestion is caused by over hydration. “But the truth is, it is caused by kidney failure due to dehydration,” he said. “That’s ironic, right?”
Dr. Mata suggested that doctors should focus on improving the knowledge and the management on hydration. By doing so, he said, “we will save thousands of patients from those complications of dehydration and even from dying.”
If only the scientists got it right from the start, it should have been called dengue dehydration fever and not dengue hemorrhagic fever. “Imagine how many people we could have saved by proper understanding,” he pointed out.
“So how will you know if you are well-hydrated,” he asked. “Ang ihi ng ihi wagi! Dengue patients must be well-hydrated with Oresol and dextrose. If the patients are well hydrated, they will always urinate. With an almost clear color (of the urine)!
“Those who urinate small with longer intervals and with dark colored urine are in danger of severity. The good news is that the quality of the urine can warn us before the blood pressure drops and thus can be hydrated early and save the patient,” Dr. Mata concluded.
