Patient Bulletin

The dengue vaccine

dr Michael Sandberg

The development of a safe and effective dengue vaccine has taken many years. We now offer the new dengue vaccine.

Dengue is a nasty mosquito-borne illness. I am writing this as so many of us go on holidays to infected areas and dengue is increasing nearly exponentially. We have seen our patients so very unwell with this illness, such that one never forgets it. Many are admitted to hospital. We are excited to be able to offer this new vaccine as it is a real medical advance.

For those who have had dengue before using the vaccine is straightforward and advised. However it is not yet licensed for those who have never had dengue. Although one can consider giving vaccines off-licence so long as all understand the pros and cons. This article shares some of the issues involved. The main object is not to get the severe form of haemorrhagic dengue which is almost always related to a second infection. There will however be some of us who would wish to take the opportunity to have the vaccine off-licence to prevent getting dengue for a first time, as it is really hellish compared to flu. For many people being off work for 4 weeks has serious implications.

DENGUE FEVER

If you acquire it a second time, there is a 1 in 6 chance of a serious haemorrhagic dengue with bleeding problems, ​clotting issues and fluid shifts needing intravenous resuscitation. The mortality of haemorrhagic dengue varies depending ​on the clinical setting. In high quality medical facilities, it may be as low as 0.5%. However in epidemic local settings it can ​be up to 10- 15%.

We now as per the WHO advise vaccination for people travelling to the areas below if they have previously had dengue.

Two vaccines are licensed:

• Qdenga by Takeda (which we favour)
  

• Dengvaxia by Sanofi Pasteur.
  

We recommend QDenga vaccine and have it in stock.

Dengue is caused by one of the four dengue viruses (DENV 1-4).

In India, Latin America and Southeast Asia, all 4 serotypes circulate with different ones predominating during various ​periods.

Symptoms:

• Severe headaches, bone pains, fever.
• Eye discomfort, fatigue and rash.
• Respiratory or gastrointestinal complaints
• Plasma leakage
• Intravascular volume depletion needing intravenous fluid replacement.

Individuals are at the greatest risk of severe dengue and haemorrhagic fever when they experience two ​sequential infections of different strains separated in time by more than 18 months. (Cross-type immunity wanes ​at 18 months to two years.)

This phenomenon is called “antibody dependent enhancement”.

Severe dengue may also occur in infants with circulating heterotopic antibodies passively acquired from the dengue ​immunity of their mother.

Following recovery from a second infection, a broadly protective immune response is induced and severe disease ​following a third or fourth infection is rare.

Currently there are no antivirals licensed for dengue. Prevention is the key.

DENGUE FEVER

Conditions where dengue severity is elevated:

• Renal and cardiovascular disease.
  
• Pregnancy is associated with high-risk pregnancy complications including mortality and stillbirths.
  

Dengue viruses are flaviviruses

Infection with a specific serotype induces sustained protection against the same serotype.

The catch - if you have not previously had dengue

QDenga vaccine – the manufacturing - company is sensitive to the fact that the immunity produced

against serotype 3 and type IV is potentially less good.

The QDENGA vaccine manufacturer Takeda is confident that it produces a vibrant response to ​dengue types 1 and 2. The weaker response to type 3 is slightly better than the response to type IV.

In February 2024 QDENGA vaccinated children with no previous infection. Those who were ​immunised had more hospital admissions compared to the group not being vaccinated. The ​infections were due to DENV-3 type. So it was a negative effect as with the other vaccine: Sanofi’s ​Dengvaxia.

Patients will therefore need to do a blood test to check if you have ever had it before unless you have ​previous laboratory confirmation before being vaccinated.

It is not licensed for children less than 9 years old.

Haemorrhagic fever

Treatment involves intravenous fluids, oxygen, sometimes positive pressure ventilation and ​management of bleeding and thrombotic elements.

Where treatment is of high quality, the risk of death should be less than 5% and potentially less than ​1%. However, in poorer countries the mortality of haemorrhagic fever could be 10 to15%.

The Qdenga tetravalent vaccine is a live attenuated vaccine with a DENV-2 strain providing the ​backbone vaccine through 3 other strains:TDV -1 TDV - 3 and TDV- 4.

The vaccine has a shelf life of 18 months and should be stored at 2 to 8 °C.

The vaccine schedule is two doses administered subcutaneously with an interval of 3 months ​between doses.

(If the second dose is delayed for any reason it is not necessary to restart the series.)

In the UK the licence is for those aged 6 to 65 years.

Side effects of the vaccine

Soreness at injection site, pruritus 0.7%, bruising 0.6%, pyrexia 0.2%.

Headaches and malaise can last for a few days.

Severe allergic reactions are rare.

Anaphylaxis to the vaccine is very rare.

CDC MAP DENGUE PREVELANCE

Vaccine immunity

Tetravalent seropositivity increases from 85.3% one month after the first dose to 99.5% one month after the ​second dose.

By month 51 there is over 76% immunity, whereas it was 80% in the preceding months.

Trial Results

Among seropositive subjects there were 5 cases of severe dengue on placebo compared with one case in the ​vaccine group.

Among seronegative subjects in the placebo group there were no cases of severe dengue compared to 2 ​cases to date of DNV 3 in the vaccine group

The vaccine is not licensed for:

1. Pregnant women who were excluded from the trial so we have no data.

2. Immunocompromised individuals.

There is no safety data on the vaccine in immunocompromised individuals including those with HIV ​infection, so the vaccine should be avoided in pregnant and lactating women and immunocompromised ​persons including those with HIV infection.

WHO advice

WHO advises that until the efficacy risk profile for DENV-3 AND DENV-4 in seronegative persons has been ​more thoroughly assessed it does not recommend

the use of the vaccine in low to moderate dengue transmission settings.

At the moment there is no data on the use of booster doses, while noting some waning. Studies on boosting ​doses are currently active.

Concomitant vaccines

The vaccine can be co-administered with tetanus and diphtheria and acellular pertussis vaccine.

It can be given with yellow fever and hepatitis A vaccines, and also it can be co-administered with other ​inactivated subunit, or mRNA vaccines except for live vaccines when more data is required.

Patients should be observed for at least 15 minutes following vaccination.

Contraindications

As it is a live attenuated vaccine it is contraindicated in those with acquired immune deficiency or receiving ​immunosuppressive therapies such as chemotherapy or high doses of steroids: 20 mg/day or greater. It is ​also contraindicated in HIV patients.

The greatest benefit of QDenga vaccination will be in the setting of a type II or type I destination.

Blood investigations for diagnosing dengue

At the Practice we are happy to discuss the dengue vaccine situation if you are travelling to an affected area. Even just ​suffering the illness without complications is really unpleasant for two to four weeks.

In a fortnight we will be able to do a blood test to confirm if you have had dengue before, and thus advise about ​vaccination.

If you have not had dengue before we would consider and discuss off-licence use sharing the figures. There are many ​who think it likely that in a year or two the vaccine will be licensed for those who have never had the infection, such is ​the unpleasantness and life disruption of a first illness.

Michael Sandberg.

Medical Director 90 Sloane Street