The Dengue Vaccine Dilemma


In the practice of Medicine, there are a lot of controversies with no clear answers yet as to which direction the doctor or healthcare provider should go. When faced with such a dilemma, there is only one cardinal rule which the physician follows—“Primum non nocere” (First, do no harm).

This cardinal rule comes to mind again with the current controversy whether or not to continue the government’s dengue vaccination program.

Health experts formed by the Department of Health (DOH) are divided whether to administer the vaccine to all nine-year-old and older school children or not.

Professor Scott B. Halstead, who is the acknowledged leading figure in dengue research in the past 50 years, warned that the vaccine may even be worse than an actual dengue infection, “because it has all different antibodies that wane over time.”

The controversy even becomes more complicated as some members of Congress threaten to block the passage of the 2017 budget of the DOH because of the exclusion of the vaccine from their current active programs.

Doctors and health advocates, led by Dr. Tony Dans, Dr. Mercy Fabros, and Dr. Tony Leachon, appealed to the legislators to consider the unresolved efficacy and safety issues of the vaccine, which may cause a more complicated dengue problem in the future if the vaccination program is fully implemented as initially planned.

Even the experts agree that there are still unfilled “knowledge gaps” on the vaccine’s long-term safety, particularly on Year 3 after its administration. Based on the original paper of the clinical investigators of the vaccine published in the New England Journal of Medicine (NEJM), even the authors acknowledged that they still do not have the complete answers to the unresolved questions. They stressed the need to continue monitoring cases and do further studies to provide the answers that can increase our confidence on the safety of the vaccine.

In an article published this year by the Center for Infectious Disease Research and Policy, Dr. Halstead reiterated the serious concern on the vaccine—that it 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-naive recipients of the vaccine for a more severe clinical expression of the disease. 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.

“Over time, you make and keep protective levels of antibody from the initial infection, but you lose the cross-reactive antibodies,” added Dr. Halstead. “That allows a second dengue infection to cause severe illness, including dengue hemorrhagic fever.”

This adverse effect can be deduced from the Cuban experience. In 1977, Cubans were a dengue-naive population, before dengue 1 infections were reported. After around 20 years, in 1997, there was an outbreak of dengue 2 in the city of Santiago, and hospital admissions for dengue were reported to be eightfold higher in patients previously infected with dengue 1.

The problem with any adverse effect of the vaccine is that it would only be seen many years later. A long dengue-free interval is also not reassuring. “The longer interval (between infection with different dengue strains), the more severe the disease,” warned Dr. Hallstead.

A similar phenomenon has also been observed in mothers who’ve had two or more dengue infections. Cross-reactive antibodies are transferred to their babies, devoid of T cells, which are important in the immune response. What happens is that their children can have a more serious dengue infection once they get the virus.

According to Dr. Halstead, immunization with dengue vaccine can serve as the initial viral exposure in seronegative individuals—very similar to the mother-and-baby transmission—which can trigger the ADE phenomenon years following immunization.

We’ve decided to make the dengue controversy as our cover story for this issue of H&L; and we hope our legislators would be enlightened not to pressure DOH into continuing and expanding the dengue vaccination program. Spending PhP 3 billion pesos for a potentially harmful vaccine may not exactly fit the description of a sound preventive public health strategy.

RAFAEL R. CASTILLO, MD
Editor-in-Chief
rafael.castillo@fame.ph

October 2016 Health and Lifestyle

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