Disappointment over new Dengue vaccine?

By Dr Astrid Arellano, Infectious Diseases Physician

Dengue is a Flavivirus infection transmitted by the Aedes aegypti and Aedes albopictus species of mosquito – four serotypes (DEN-1, DEN-2, DEN-3 and DEN-4) circulate globally. Although most do not, a person who contracts Dengue can develop symptoms. Infected individuals become immune to that serotype but are susceptible to others and at higher risk of severe disease if they contract a different serotype.

Over 400 million people worldwide acquire Dengue with an estimated 500,000 developing severe Dengue-shock-syndrome that causes 25,000 deaths each year. Australia reports >2000 cases of Dengue every year with most being acquired overseas. Outbreaks occur in Queensland with 385 cases reported in 2016.

Overall, Dengue remains a risk for Australians who travel overseas and mosquito avoidance is the mainstay for the prevention (see Table).

Appraisal of the vaccine.

Dengvaxia® is a live attenuated recombinant tetravalent Dengue vaccine. It has been approved in 19 countries but only extensively used in the Philippines and Brazil. The vaccine is administered as 3 doses of 0.5mL, given every 6-months. This induces neutralising antibodies against all 4 serotypes but titres are highest in individuals previously infected with Dengue. Pooled vaccine efficacy in seropositive individuals is reported at 78.2%, whereas only 38% of seronegative people respond to the vaccine. The youngest age group aged 2-5 years reported only 33% vaccine efficacy.

There has been significant concern regarding vaccine safety with high numbers of seronegative individuals, especially young children, developing more severe disease when infected with Dengue post Dengvaxia® vaccination. This led to revised product labelling (December 2017) and the recommendation that Dengvaxia® be restricted to those >9 years who live in a Dengue-endemic area or those who have serologic evidence of prior Dengue infection.

Opinion

Why is it unlikely Dengvaxia® will take off in Australia (TGA registered in 2017 but currently not available for prescribing.)

  • Most Australians travelling to Dengue endemic areas are seronegative and the vaccine is contraindicated for them.
  • Vaccination schedule (3 injections over 12 months) is impractical for one-off Bali holiday makers.
  • Children below 5 years, at highest risk of severe Dengue disease, are not able to be vaccinated with Dengvaxia® due to poor efficacy in this age group and a higher risk of severe Dengue post vaccination.
  • There is no data on vaccination in immunocompromised individuals. As a live-attenuated vaccine, the usual contraindications apply.

Table: Dengue Fever Profile

Incubation period 3-14 days
Symptoms Fever, headache, retro-orbital pain, myalgia and arthralgia, rash
Laboratory confirmation Positive Dengue virus and NS1 antigen by RT-PCR within 1-3 days of onset

Positive IgM (ELISA)

Leucopaenia and thrombocytopaenia common

Management Supportive
Prevention Vector control, mosquito avoidance (long sleeved clothing/DEET mosquito repellent/mosquito nets and coils)

Fig.1 Maculopapular rash of Dengue

References:

Dengue vaccine: WHO position paper July 2016

Vaccines and Global Health: The Week in Review, 2 December 2017, Centre for Vaccine Ethics and Policy

WHO Updated Q&A related to information presented in the Sanofi Pasteur press release on dengue vaccine Dengvaxia® (30 Nov 2017)

Author competing interests: nil relevant. Questions? Contact the editor.

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