Philippines Halts Major Dengue Vaccination Program Because Vaccine May Increase Risk of Severe Disease

A panel of experts from the Philippines Department of Health finds that Sanofi Pasteur's dengue fever vaccine, Dengvaxia (CYD-TDV), may be connected with 3 deaths.

Dengue is a mosquito-borne virus once known as dengue hemorrhagic fever, which causes severe flu-like illness. Once infected with 1 of the 4 serotypes of the virus, an individual gains immunity to that serotype, though only partial and temporary immunity to the other serotypes. Repeat infections can lead to severe dengue, a more serious illness with complications. While only 9 countries experienced severe outbreaks of dengue prior to 1970, according to the World Health Organization (WHO), today nearly half of the world’s population is at risk of dengue. The disease is now widespread in the tropics and endemic in more than 100 countries in Africa, the Americas, Eastern Mediterranean, Southeast Asia, and Western Pacific regions, affecting mostly urban and semi-urban settings. While health officials say dengue cases are often unreported or misclassified, in a 2013 study published in the journal Nature researchers estimated that there are 390 million dengue infections worldwide each year.

In 2016, following 2 decades of clinical trials, Sanofi Pasteur gained WHO approval for Dengvaxia, the pharmaceutical company’s live recombinant tetravalent vaccine for Dengue fever. WHO recommends that the vaccine is administered in 3 doses to individuals between the ages of 9 and 45 who are living in dengue-endemic regions, particularly in settings with a high burden of disease. In November of 2017, Sanofi requested new labeling of the vaccine due to findings of “differences in vaccine performance based on prior dengue infection.” Analysis of a long-term clinical trial found that Dengvaxia vaccination may increase the risk of severe disease in individuals who had never been exposed to the virus.

The news from Sanofi has alarmed health officials in the Philippines, a country that has—along with Brazil— taken part in a subnational program for Dengvaxia vaccination targeting about 1 million individuals. The Philippine Health Ministry soon halted the vaccination program, and in December 2017, the Public Attorney’s Office (PAO) of the Philippines announced that 2 children had died from severe dengue following Dengvaxia vaccination. Now, a panel of experts convened by the country’s Department of Health (DOH) has looked at the deaths of 14 vaccine recipients and found that Dengvaxia may be connected to 3 deaths. PAO has announced that they will be suing Sanofi for the death of Anjielica Pestilos, 1 of more than 800,000 children in the Philippines who received the vaccine.

At issue is the child’s health prior to vaccination, Philippines officials report. She had no previous exposure to dengue and suffered from severe systemic lupus erythematosus, and PAO officials say the pre-existing condition was revealed prior to vaccination. At a recent news conference, PAO forensic expert Erwin Erfe described the child’s condition at death, saying she had, “so much bleeding from her lungs, her liver, her heart, her stomach were from a viscerotropic-like disease which was caused by the injection of Dengvaxia.” The PAO wants Sanofi, several former and current health ministry officials, and the vaccine’s domestic distributor declared jointly liable for the death of Pestilos.

“In Dengvaxia clinical trials conducted over more than a decade and over one million doses of the vaccine administered, no deaths causally related to the vaccine have been reported to us,” Sanofi shared in a recent statement. The company’s global medical head, Su-Peing Ng, MB, BS, noted the complexities of this virus and the introduction of the first dengue vaccine. “These findings highlight the complex nature of dengue infection. We are working with health authorities to ensure that prescribers, vaccinators, and patients are fully informed of the new findings, with the goal of enhancing the impact of Dengvaxia in dengue-endemic countries.”