Three deaths in Philippines linked to Dengvaxia vaccine

The Philippines Department of Health announced that a “causal association” has been found between three pediatric deaths and the dengue vaccine, Dengvaxia.

Two of these deaths may have been caused by vaccine failure, according to a Department of Health (DOH) press release.

The deaths were investigated by members of a Dengue Investigative Task Force (DITF) that was created by the Philippine General Hospital (PHG) in response to concerns over the safety of Dengvaxia (Sanofi Pasteur) — the only licensed dengue vaccine approved for use by 19 regulatory authorities in endemic areas. Concerns arose in December after Sanofi Pasteur released data showing Dengvaxia is effective in patients who had a prior dengue infection but may cause more severe disease in nonimmune patients who become infected after vaccination. In light of these data, the Philippines DOH suspended an immunization program that used the vaccine to prevent dengue virus infection, which is endemic in the country. During the immunization program, more than 830,000 children received at least one dose of Dengvaxia, according to the DOH.

Scott B. Halstead, MD, an adjunct professor in the department of preventive medicine and biometrics, Uniformed Services of the University of Health Sciences in Bethesda, Maryland, previously told Infectious Disease News that the live, recombinant vaccine may have triggered antibody-dependent enhancement (ADE) in vaccine recipients with no prior infection. ADE, he said, occurs when a patient who has recovered from infection with one type of dengue virus develops antibodies that can react with other dengue viruses, making subsequent infections with dengue more severe and potentially fatal.

In addition to the three deaths with “casual association,” the PHG DITF report included information on 11 other children who died after Dengvaxia vaccination. Three of these deaths were considered “coincidental” and two had inadequate information. A temporal association was established in the remaining six children — all of whom died within 30 days of receiving the vaccine.

“These results strengthen our decision to suspend the Dengue Immunization Program as Dengvaxia is not fit for a mass immunization program that does not screen for prior dengue infection and comorbidities of children before the administration of the vaccine,” the release said. “In this light, the DOH will now hand over the PGH DITF report and the National Expert Panel reports to the Department of Justice so that they may use them in the fulfillment of their mandate to investigate and prosecute those who are possibly accountable.”

A spokesperson for Sanofi Pasteur told Infectious Disease News “there are no safety or quality concerns about the Dengvaxia vaccine,” and the report shows “no evidence directly linking the Dengvaxia vaccine to any of the 14 deaths.”

“Sanofi Pasteur has always followed the highest ethical standards and should there be any case of injury due to dengue that has been demonstrated by credible scientific evidence to be causally related to vaccination, we will assume responsibility,” the company spokesperson said.

Sanofi Pasteur had previously agreed to refund the Philippines for unused doses of the vaccine. However, it recently declined the DOH’s request to refund the government for used doses and to financially support an indemnification fund.

“When Sanofi Pasteur agreed to reimburse the Philippine government for unused doses of Dengvaxia, we did so to show our continued commitment to cooperate with the Department of Health in ensuring the best possible health outcomes for the people of the Philippines. This decision was not due to any safety or quality concerns about the Dengvaxia vaccine,” the spokesperson said. “Agreeing to refund the used doses of Dengvaxia would imply that the vaccine is ineffective, which is not the case. The data remains quite clear that, in absolute terms, dengue vaccination in the Philippines will provide a net reduction in dengue disease, including severe dengue and, thereby, reduce the overall public health burden associated with this disease.”

If the DOH decides to reinstate the immunization program with Dengvaxia after a complete review of data, Sanofi Pasteur said it would be willing to provide new doses free of charge so that people can complete the 3-dose series. – by Stephanie Viguers

Reference:

Republic of the Philippines Department of Health. Results of the Investigation of the Philippine General Hospital Dengue Investigative Task Force (PGH - DITF). http://www.doh.gov.ph/node/12849. Accessed February 2, 2018.

Disclosure: Halstead reports no relevant financial disclosures.

The Philippines Department of Health announced that a “causal association” has been found between three pediatric deaths and the dengue vaccine, Dengvaxia.

Two of these deaths may have been caused by vaccine failure, according to a Department of Health (DOH) press release.

The deaths were investigated by members of a Dengue Investigative Task Force (DITF) that was created by the Philippine General Hospital (PHG) in response to concerns over the safety of Dengvaxia (Sanofi Pasteur) — the only licensed dengue vaccine approved for use by 19 regulatory authorities in endemic areas. Concerns arose in December after Sanofi Pasteur released data showing Dengvaxia is effective in patients who had a prior dengue infection but may cause more severe disease in nonimmune patients who become infected after vaccination. In light of these data, the Philippines DOH suspended an immunization program that used the vaccine to prevent dengue virus infection, which is endemic in the country. During the immunization program, more than 830,000 children received at least one dose of Dengvaxia, according to the DOH.

Scott B. Halstead, MD, an adjunct professor in the department of preventive medicine and biometrics, Uniformed Services of the University of Health Sciences in Bethesda, Maryland, previously told Infectious Disease News that the live, recombinant vaccine may have triggered antibody-dependent enhancement (ADE) in vaccine recipients with no prior infection. ADE, he said, occurs when a patient who has recovered from infection with one type of dengue virus develops antibodies that can react with other dengue viruses, making subsequent infections with dengue more severe and potentially fatal.

In addition to the three deaths with “casual association,” the PHG DITF report included information on 11 other children who died after Dengvaxia vaccination. Three of these deaths were considered “coincidental” and two had inadequate information. A temporal association was established in the remaining six children — all of whom died within 30 days of receiving the vaccine.

“These results strengthen our decision to suspend the Dengue Immunization Program as Dengvaxia is not fit for a mass immunization program that does not screen for prior dengue infection and comorbidities of children before the administration of the vaccine,” the release said. “In this light, the DOH will now hand over the PGH DITF report and the National Expert Panel reports to the Department of Justice so that they may use them in the fulfillment of their mandate to investigate and prosecute those who are possibly accountable.”

A spokesperson for Sanofi Pasteur told Infectious Disease News “there are no safety or quality concerns about the Dengvaxia vaccine,” and the report shows “no evidence directly linking the Dengvaxia vaccine to any of the 14 deaths.”

“Sanofi Pasteur has always followed the highest ethical standards and should there be any case of injury due to dengue that has been demonstrated by credible scientific evidence to be causally related to vaccination, we will assume responsibility,” the company spokesperson said.

Sanofi Pasteur had previously agreed to refund the Philippines for unused doses of the vaccine. However, it recently declined the DOH’s request to refund the government for used doses and to financially support an indemnification fund.

“When Sanofi Pasteur agreed to reimburse the Philippine government for unused doses of Dengvaxia, we did so to show our continued commitment to cooperate with the Department of Health in ensuring the best possible health outcomes for the people of the Philippines. This decision was not due to any safety or quality concerns about the Dengvaxia vaccine,” the spokesperson said. “Agreeing to refund the used doses of Dengvaxia would imply that the vaccine is ineffective, which is not the case. The data remains quite clear that, in absolute terms, dengue vaccination in the Philippines will provide a net reduction in dengue disease, including severe dengue and, thereby, reduce the overall public health burden associated with this disease.”

If the DOH decides to reinstate the immunization program with Dengvaxia after a complete review of data, Sanofi Pasteur said it would be willing to provide new doses free of charge so that people can complete the 3-dose series. – by Stephanie Viguers

Reference:

Republic of the Philippines Department of Health. Results of the Investigation of the Philippine General Hospital Dengue Investigative Task Force (PGH - DITF). http://www.doh.gov.ph/node/12849. Accessed February 2, 2018.

Disclosure: Halstead reports no relevant financial disclosures.