Dengue is a viral infection that is transmitted by the Aedes mosquito for which there is no specific treatment.
Early detection and access to proper medical care lowers fatality rates, particularly in severe dengue. Dengue prevention and control depends on effective mosquito control measures.
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| An elementary student grimaces as a nurse administers an anti-dengue vaccine at Parang Elementary School in Marikina, west of Manila on April 4, 2016.The Philippines began injecting up to one million school children with the worlds first vaccine for dengue fever, a mosquito-borne viral infection that is a leading cause of serious illness and death among children in some Asian and Latin American countries. / AFP PHOTO / NOEL CELIS |
Despite public health measures, the incidence of dengue has increased markedly in the last two years, with a daily average of 331 cases and just under one death in 2015.
The data for 2016 is still gloomy, with a daily average of 378 cases and just under one death.
Starting from 2010, there has been upward trend when it comes to the incidence and deaths resulting from dengue, with the only exception being 2011, where there were 19,884 cases, with 36 deaths.
Dengue vaccine development
The clinical trials of new medicines and treatment undergo three phases before they can be licensed for human use.
Phase I involves the testing in a small group of people to evaluate its safety, determine a safe dose, and identify its side effects.
Phase II involves testing in a larger group of people to evaluate its effectiveness and its safety.
Phase III involves large groups of people to confirm its effectiveness and side effects; compare it to existing treatments, if any; and collect more information about its safety.
After the new medicine or treatment has been licensed and marketed, Phase IV studies involve the collection of information of the effect of the medicine or treatment in various populations and side effects with long-term use.
Three of the dengue vaccine formulations are live recombinant vaccines (by Sanofi Pasteur, Takeda and the United States National Institutes of Health); one is a purified inactivated vaccine (GlaxoSmithKline/Fiocruz/Walter Reed); one is a recombinant subunit protein vaccine (Merck & Co); and the other is a plasmid DNA vaccine (US Naval Medical Research Center).
Since last December, the Sanofi Pasteur CYD-TDV vaccine has been licensed for use in Mexico, Brazil, El Salvador and the Philippines in the nine-to-45 years or nine-to-60 years age groups.
There are other candidate vaccines at various phases of development, of which the one from the Butantan institute/US National Institutes of Health is in Phase III of clinical trials, with the rest in Phases II and I. (Source: www.denguevaccines.org/winter-newsletter-2016. Accessed Apr 28.)
The time from Phase III to licensing is about three to five years. In other words, the next dengue vaccine licensed for use will be available in about three to five years.
WHO SAGE statement
The World Health Organization (WHO) has a Strategic Advisory Group of Experts (SAGE), which comprises experts who advise WHO on the optimal use of vaccines through an evidence-based review process.
SAGE reviewed the data from two large Phase III trials in Asia and Latin America, the former in nine- to 14-year-olds in five Asian countries, including Malaysia, and the latter in nine- to 16-year-olds in five Latin American countries.
They issued a statement on Apr 15: “Vaccine efficacy over 25 months from the first vaccine dose among nine- to 16-year-olds, using data pooled from both trials, was 65.6%. The sub-group benefit profile is complex: vaccine efficacy varied by infecting virus (higher protection against DENV 3 and 4 than DENV 1 and 2); age (higher protection in older children) and disease severity (higher protection against hospitalised and severe dengue) and serostatus at the time of vaccination (higher protection in participants who had already been exposed to dengue virus).”
The statement went on: “SAGE considered the results of a comparative mathematical modelling evaluation of the potential public health impact of CYD-TDV introduction done by seven different groups. There was agreement across the different models that in high transmission settings, the introduction of routine CYD-TDV vaccination in early adolescence could reduce dengue hospitalisations by 10-30% over a period of 30 years, representing a substantial public health benefit.”
SAGE recommended that countries consider introduction of CYD-TDV only in geographic settings (national or subnational) where dengue is highly prevalent, which is the case with Malaysia.
Waiting for a decision
The safety profile of CYD-TDV to-date has been benign. In the Asian study, 1% of vaccine recipients and 1% in the control group had serious adverse events that happened within 28 days of vaccination.
These events were mainly infections and injuries.
The dengue vaccine will not do away with the need for mosquito control as it is not a magic bullet.
What are the benefits of the vaccine? Phase III trials reported a marked reduction in hospitalisations for dengue and severe dengue, as well as dengue infections.
The Health Ministry has been studying the dengue vaccine for more than a year, surpassing considerably its KPI (key performance indicator) for time taken for decision-making.
What the studies are is not known to the medical community.
Clinicians who have to manage the marked increase in disease burden wonder if, and when, the dengue vaccine, which is a potential game changer, will be available for use, or whether the public have to wait for the perfect vaccine.
Whether the next vaccine in the pipeline, which will be in three to five years’ time, will be the perfect vaccine is still unknown.
It is pertinent to note that less than perfect vaccines are licensed for use, e.g. typhoid vaccine, which has a protective efficacy of 70% 1.5 years after vaccination and 50% after three years.
The Philippines licensed the dengue vaccine last December and launched the world’s first public dengue vaccination programme on Apr 4.
What will be the Health Ministry’s decision? It is anybody’s guess.
What is certain, however, is that, based on current data, dengue cases and deaths will continue to afflict the population.
