Rejoinder on the dengue vaccine issue

On the same day that our column came out last week (“A second thought on the dengue vaccine,” 4/16/16), the Strategic Advisory Group of Experts (SAGE) on immunization of the World Health Organization (WHO) came out with its recommendations based on its members’ consensus during its meeting in Geneva a few days earlier on April 12-14.

“WHO acknowledges that the dengue vaccination effort that is ongoing in the Philippines is consistent with the recommendations made by the WHO expert group. The effort focuses on three regions that have particularly high transmission,” said WHO country representative Gundo Weiler during a press briefing at the Department of Health (DOH).

In its recommendations, SAGE stated that Dengvaxia (CYD-TDV), the first approved vaccine for dengue, may be considered for use in geographic settings with high endemicity, as indicated by a seroprevalence of approximately 70 percent (range of 50 to 90 percent) or greater in the age group targeted for vaccination.

Weiler explained that SAGE evaluated the safety of the vaccine, its efficacy and its potential impact based on the pooled results of clinical trials done in Asian and Latin American countries, using “different epidemiological settings based on mathematical modeling.”

Substantial health impact

The bottom line is that SAGE believes that introducing dengue vaccination in high transmission settings can have a substantial public health impact especially reducing severe dengue cases and the need for hospitalization.

Health Secretary Janette Garin must have heaved a sigh of relief following the endorsement from the WHO country representative of its seemingly rushed dengue immunization program, which was rolled out amid concerns from various health advocates that I also shared.

And many of these concerns have not really been answered by the SAGE recommendations, which are general statements on how the vaccine’s overall effects could translate into an actual public health benefit. The final decision whether a dengue vaccination program should be implemented or not must be based on country- and region-specific factors, as guided by pertinent and updated research data.

In its preliminary report (final report of its meeting is expected in July 2016), SAGE specifically states that “the target age for routine vaccination should be defined by each country based on an assessment of dengue endemicity and programmatic feasibility of targeting particular ages. For highly endemic settings (e.g. seroprevalence at 9 years of age of approximately 90 percent or greater), vaccination at 9 years of age is projected to maximize impact. In settings where seroprevalence at 9 years of age is below 90 percent (but above 50 percent), vaccination at 11-14 years of age is preferable.”

There’s no question that dengue fever is endemic in various parts of the country. But since the effectiveness and safety of the vaccine are linked to specific seroprevalence data, we must make sure that we have reliable updated data per region and this must be age-stratified. I tried to look for these data in the literatures and could not find any published updated reports. There were only four seroprevalence reports published in 2005, 2006, 2009 and 2010 with the actual studies done several years earlier.

In all these reports (including the last one which was funded by the vaccine manufacturer), the seroprevalences were not age-stratified and all seroprevalences were less than 90 percent but more than 50 percent. If these were the bases for the dengue immunization program, then it should have been limited to the 11-14 years age group based on the SAGE recommendations. But in the first place, are these data valid bases considering that they’re not updated (6-10 years old) and they’re not age-stratified?

I hope that the DOH has, as its basis for the decision to immediately execute the dengue vaccination program, updated seroprevalence data on dengue in the regions where the program is being implemented. If the decision was merely based on assumptions of high endemicity or transmission rates,  or data from the old studies, this may not be a good idea.

Dengue control

Secretary Garin should allocate part of the DOH’s budget for the dengue control program in conducting national and regional studies that can fill in the blinding gaps on vital epidemiological information that are needed to guide her and her department before making crucial decisions on cost-effective programs.

Unless we have comprehensive and continually updated data on national and regional age-stratified seroprevalence rates and sex distribution data, targeting specific segments of the populations—wherein interventions such as a dengue immunization program would be most cost-effective—is impossible to make.

Speaking of cost effectiveness, I’m sure the SAGE could also recommend an ideal price of the three-dosed vaccination so it could be considered cost-effective or worth the money the government will spend for it.

Renegotiate

If the SAGE-recommended cost is lower than the cost at which DOH got it from the vaccine manufacturer (Sanofi Pasteur), they should renegotiate for a lower price of the vaccine to match or preferably be lower than the ceiling cost recommended by the expert body. I’m sure once the other vaccines that are already in late-stage clinical development become available, the prices of the dengue vaccine will dramatically drop.

During the DOH-WHO press conference on Monday this week, Secretary Garin said: “We know there will be hindrances when it comes to implementing (health) programs, especially if it is a good program. We decided to take all the punches because we know that’s part of good governance.”

I found the statement a little odd, seemingly insinuating that expressions of valid concerns by health advocates are being taken as mere flippant objections to prevent the DOH from implementing a good program. I am giving the good secretary the benefit of a doubt, and I’m pretending not to have read any news report stating that.