Dengue Fever: Vaccine

Dengue Fever: Vaccine

Continuing with our Back to College series we bring to your our article on Dengue Fever: Vaccine.

Dengue vaccine is a vaccine to prevent dengue fever in humans. The WHO recommends the vaccine as a possible option in areas of the world where the disease is common.

The development of vaccine for dengue fever began as early as 1929. However, it was been hindered by incomplete knowledge of the disease pathogenesis.

Moreover, it was later hindered by the need to simultaneously create a stable immunity against all four Dengue serotypes.

Several vaccine candidates are in development including live attenuated, inactivated, DNA and subunit vaccines. Live attenuated vaccine candidates are the furthest along in development

In 2016 a partially effective vaccine for dengue fever (Dengvaxia) became commercially available in 11 countries: Mexico, the Philippines, Indonesia, Brazil, El Salvador, Costa Rica, Paragua,  Guatamala, Peru, Thailand, and Singapore.

In Indonesia it costs about US$207 for the recommended three doses. WHO recommends that use be limited to areas where the disease is common because vaccination may actually increase the risk of dengue fever in people who have not been previously infected with the dengue virus. This can be a result of the phenonmenon of antibody-dependent enhancement.

Status of Vaccine Development

The first dengue vaccine, Dengvaxia (CYD-TDV) by Sanofi Pasteur, was first registered in Mexico in December, 2015. CYD-TDV is a live recombinant tetravalent dengue vaccine that has been evaluated as a 3-dose series on a 0/6/12 month schedule in Phase III clinical studies. It has been registered for use in individuals 9-45 years of age living in endemic areas.

Infection by one of the four dengue virus serotypes has been shown to confer lasting protection against homotypic re-infection, but only transient protection against a secondary heterotypic infection. Moreover, secondary heterotypic infection is associated with an increased risk of severe disease. This and other observations suggest an immunopathological component in dengue pathogenesis, which is referred to as immune enhancement of disease. Due to these dengue-specific complexities, vaccine development focuses on the generation of a tetravalent vaccine aimed at providing long-term protection against all virus serotypes. Additional challenges are posed by the lack of an adequate animal disease model and the resulting uncertainty around correlates of protection.

Ongoing phase III trials in Latin America and Asia involve over 31,000 children between the ages of 2 and 14 years. In the first reports from the trials, vaccine efficacy was 56.5% in the Asian study. Om the second report 64.7% in the Latin American study in patients who received at least one injection of the vaccine. Overall, Efficacy varied by serotype.

In both trials vaccine reduced by about 80% the number of severe dengue cases. An analysis of both the studies at the 3rd year of follow-up showed that the efficacy of the vaccine was 65.6% in preventing hospitalization in children older than 9 years of age, but considerably greater (81.9%) for children who were seropositive (indicating previous dengue infection) at baseline.

Vaccine Approval

Mexico, Philippines, and Brazil have approved the vaccine in December 2015. Moreover, El Salvador, Costa Rica, Paraguay, Guatemala, Peru, Indonesia, Thailand and Singapore have approved the vaccine in 2016. Tradenamed Dengvaxia, has been approved for use of those aged nine and older. The vaccine can prevent all four serotypes.

Prospect of Dengue Vaccine in India

In the past decade, India has shown an increasing trend in the number of reported dengue cases.

According to the National Vector Borne Disease Control Programme (NVBDCP) 18 out of 35 states are now endemic for dengue. Additionally, the spread of the disease to suburban and rural areas, the actual cases may be in millions.

Although there has been a decline in dengue-associated mortality, hospitalization rates due to severe dengue during outbreaks are on the rise.

Due to repeated dengue outbreaks the financial burden on the Healthcare Sector has increased. This emphasises the need for a cost-effective dengue vaccine as preventive strategy, in conjunction with vector control.

Moreover, a strong surveillance system needs to be in place before any vaccine trial takes place.  Resource limited rural and suburban settings are a challenge to implement such a system.

Usage: Government officials from India had shown an appropriately guarded approach towards the use of dengue vaccines. This was done in absence of adequate safety and efficacy data.

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