In the Journals

Dengvaxia increases risk for dengue virus in low-transmission areas

The dengue virus vaccine Dengvaxia, now available in six countries, may increase disease severity in locations with lower infection rates and in younger children, according to recent study findings published in Science.

“If someone has never been exposed to dengue, [Dengvaxia] seems to act like a silent infection,” Neil M. Ferguson, DPhil, director of the MRC Centre for Outbreak Analysis and Modeling at Imperial College London, said in a press release. “The initial exposure to the virus from the vaccine primes the immune system, so when they are infected again, the symptoms are more likely to be severe.”

Neil Ferguson, MD
Neil M. Ferguson

To expose the benefits and risks from Dengvaxia (CYD-TDV, Sanofi Pasteur), a recombinant chimeric live-attenuated dengue virus vaccine, Ferguson and colleagues developed mathematical models of the four dengue virus serotypes’ transmission and applied it to efficacy data available from two clinical trials. One trial, held in Southeast Asia, included an estimated 10,000 children aged 2 to 14 years; the other trial in Latin America included about 21,000 children aged 9 to 16 years.

Both trials reported CYD-TDV had an efficacy rate of about 60% against symptomatic dengue as well as increased protection against severe dengue and serotype variation efficacy. Ferguson and colleagues wrote, however, that both trials demonstrated a higher efficacy for children who were seropositive for dengue at vaccination, but low efficacy in patients who were seronegative at vaccination.

The researchers simulated the effect of vaccination at 80% coverage to fit their model’s prediction rates with those of the clinical trials. While the “poorest aspect of model fit is to the sevenfold greater incidence in hospitalization with dengue” seen among children aged 2 to 5 years who were vaccinated vs. controls during follow-up in Southeast Asia, the model predicted near precise measurements to the trials. Data analysis showed that positive and negative impact on occurrence of symptomatic dengue and hospitalized dengue were dependent on time lapse, prior exposure, age at exposure and location.

“Our model refines estimates of which places would see a decline in dengue incidence with large-scale vaccination programs, and which places should not implement programs at this point in time,” Ferguson said in the release. “These results present the first published, independent predictions of the potential impact of vaccination that take account of recent data showing that the vaccine can increase the risk of severe dengue disease in young children.” – by Kate Sherrer

Disclosure: The researchers report no relevant financial disclosures.

The dengue virus vaccine Dengvaxia, now available in six countries, may increase disease severity in locations with lower infection rates and in younger children, according to recent study findings published in Science.

“If someone has never been exposed to dengue, [Dengvaxia] seems to act like a silent infection,” Neil M. Ferguson, DPhil, director of the MRC Centre for Outbreak Analysis and Modeling at Imperial College London, said in a press release. “The initial exposure to the virus from the vaccine primes the immune system, so when they are infected again, the symptoms are more likely to be severe.”

Neil Ferguson, MD
Neil M. Ferguson

To expose the benefits and risks from Dengvaxia (CYD-TDV, Sanofi Pasteur), a recombinant chimeric live-attenuated dengue virus vaccine, Ferguson and colleagues developed mathematical models of the four dengue virus serotypes’ transmission and applied it to efficacy data available from two clinical trials. One trial, held in Southeast Asia, included an estimated 10,000 children aged 2 to 14 years; the other trial in Latin America included about 21,000 children aged 9 to 16 years.

Both trials reported CYD-TDV had an efficacy rate of about 60% against symptomatic dengue as well as increased protection against severe dengue and serotype variation efficacy. Ferguson and colleagues wrote, however, that both trials demonstrated a higher efficacy for children who were seropositive for dengue at vaccination, but low efficacy in patients who were seronegative at vaccination.

The researchers simulated the effect of vaccination at 80% coverage to fit their model’s prediction rates with those of the clinical trials. While the “poorest aspect of model fit is to the sevenfold greater incidence in hospitalization with dengue” seen among children aged 2 to 5 years who were vaccinated vs. controls during follow-up in Southeast Asia, the model predicted near precise measurements to the trials. Data analysis showed that positive and negative impact on occurrence of symptomatic dengue and hospitalized dengue were dependent on time lapse, prior exposure, age at exposure and location.

“Our model refines estimates of which places would see a decline in dengue incidence with large-scale vaccination programs, and which places should not implement programs at this point in time,” Ferguson said in the release. “These results present the first published, independent predictions of the potential impact of vaccination that take account of recent data showing that the vaccine can increase the risk of severe dengue disease in young children.” – by Kate Sherrer

Disclosure: The researchers report no relevant financial disclosures.