Why Is the Dengue Vaccine Needed? An Associate Professor Answers More Questions About the Vaccine

WORDS ASSOCIATE PROFESSOR DR VERNA LEE KAR MUN

FEATURED EXPERT
ASSOCIATE PROFESSOR DR VERNA LEE KAR MUN
Family Medicine Specialist
IMU Healthcare
WHY IS THE QDENGA VACCINE NECESSARY? WE ALREADY HAVE PREVENTIVE MEASURES SUCH AS FOGGING TO PREVENT THE AEDES MOSQUITO FROM BREEDING.

Fogging is effective in killing the Aedes mosquitoes. Its effect is immediate, extending to an average of 72 hours.

Fogging Works, but There Are Some Drawbacks

While fogging has been the main means to mitigate dengue infection in Malaysia, however, health offices are usually informed after the infection have been notified. As a result, fogging by itself does not reduce severe dengue infection that requires hospitalizations.

Furthermore, the resistance of the Aedes mosquitoes to insecticides is increasing. This decreases the effectiveness of fogging to control the population of these mosquitoes.

The Role of Dengue Vaccines

On the other hand, dengue vaccines have been proven to be effective in reducing the numbers of severe dengue infection requiring hospitalizations.

THERE WAS SOME CONTROVERSY WITH REGARDS TO THE SAFETY PROFILE OF THE PREVIOUS DENGUE VACCINE. SHOULD WE BE CONCERNED ABOUT THE QDENGA VACCINE?

Just like any new drug or new medical technology, there is very limited data from clinical practice in the early days. There would be many concerns.

Dengvaxia, the First Dengue Vaccine

The first dengue vaccine, Dengvaxia, was approved in April 2018.

It is safe in persons who have had dengue virus infection in the past (seropositive individuals), but it also increases the risk of severe dengue in those who experience their first natural dengue infection after receiving their vaccination (seronegative individuals).

Hence, pre-vaccination screening for past dengue infection is recommended before one receives the Dengvaxia vaccine. Only people with evidence of past dengue infection—indicated by the presence of dengue IgG antibody in their blood—would receive this vaccination.

About the Newest Vaccine, Qdenga

A second vaccine for dengue, Qdenga, received prequalification from the World Health Organization (WHO) on 10 May 2024.

Is it safe?

  • Overall, during the clinical trials, the vaccine was well tolerated. The most frequent reported vaccine-related adverse events were injection site itchiness, bruising, and fever.
  • An excess of hospitalized dengue virus serotype 3 (DENV3) infections was reported among baseline seronegative children, but it was not statistically significant.
  • There was also an excess of cases of severe dengue among seronegative vaccinees, all of which were caused by DENV3, but, again, the difference was not statistically significant.
  • An increase in the risk of dengue infection requiring hospitalization or severe dengue due to DENV3 in vaccinated seronegative subjects cannot be conclusively ruled out. We probably need to wait for more data.

How about allergy reactions?

During the clinical trial, no cases of severe allergy reaction or anaphylaxis were observed.

However, cases of anaphylaxis associated with this new vaccine occurred following the vaccine’s introduction to children between the age of 10 and 14 years in Brazil since February 2024, with 16 cases were reported (4.4/100,000 doses administered), including 3 cases of anaphylactic shock (0.8/100,000 doses administered).

The currently approved package insert for the vaccine describes precautionary measures to mitigate the risk of anaphylaxis. A full assessment of the national immunization programme is underway.

THE QDENGA VACCINE IS SAID TO BE ABLE TO IMMUNIZE AGAINST ALL FOUR SEROTYPES OF DENGUE VIRUS. WHY IS THIS A GOOD THING?

Dengue viruses belong to the genus Flavivirus.

The dengue virus. Click on the image for a larger, clearer version.

Flaviviruses are lipid-enveloped, single-stranded RNA viruses. The structural pre-membrane (prM) and envelope (E) proteins are embedded in the lipid envelope and are displayed on the surface of virions.

There are 4 dengue virus serotypes (DENV1, DENV2, DENV3, and DENV4); the serotypes share structural proteins (prM and E) but are genetically and serologically distinct.

Infection with 1 serotype induces sustained protection against the same serotype only. Although uncommon, an individual without a vaccine can be infected by each serotype for a total of 4 infections during their lifetime.

Serotypes and Infections

People who acquire a second dengue infection caused by a different serotype are at a higher risk for severe dengue once cross-protection induced by the first infection wanes.

Potential mechanisms for increased risk of severe dengue caused by a second infection include:

  • Cross-reactive antibodies binding to a different DENV serotype, which then enable uptake in inflammatory cells. This leads to higher and more prolonged virus count in the blood circulation (higher temperature and prolonged fever) that induces imbalanced pro-inflammatory and anti-inflammatory responses often referred to as antibody-dependent enhancement.
  • The action of the non-structural protein 1 (NS1) on the blood vessel wall or endothelium can trigger the release of active chemicals from immune cells.
  • Both the above will result in endothelial hyperpermeability and vascular leak (leading to hypovolemic shock and bleeding).

How the Vaccine Is Beneficial

Both dengue vaccines are tetravalent live-attenuated vaccines.

The new vaccine, Qdenga, induces a broad spectrum of immune responses which include:

  • Neutralizing antibodies with a 50% reduction against all 4 dengue virus serotypes.
  • Cross-reactive antibodies that block the activity of the NS1 protein.
  • Type-specific memory B cells to all four serotypes.

This means the vaccine can protect us from severe dengue infection by all the 4 serotypes. This is a good thing.

5 Popular Dengue Myths Debunked by a Family Medicine Specialist

WORDS LIM TECK CHOON

FEATURED EXPERT
ASSOCIATE PROFESSOR DR VERNA LEE KAR MUN
Family Medicine Specialist
International Medical University (IMU)
Myth 1
YOU ONLY CATCH DENGUE ONCE IN YOUR LIFETIME 

Unfortunately, no.

“There are 4 dengue serotypes,” says Associate Professor Dr Verna Lee Kar Mun.

Serotype is a word used to describe a strain of microorganism, which means that there are 4 different types of the dengue virus that can infect us.

This means that each of us can get infected up to 4 times, once with each serotype, and achieve total immunity to dengue only after being infected with all 4 serotypes!

“However, before you start thinking it’s a good idea to get infected four times, bear in mind that subsequent infections are likely to be more serious than the first,” warns Assoc Prof Dr Verna, “and each infection only increases your chances of getting severe dengue.”

Myth 2
YOU’RE GETTING BETTER WHEN YOUR FEVER GOES AWAY

Well, things are not so simple.

You see, according to Assoc Prof Dr Verna, there are 3 different stages of dengue fever.

  • Febrile phase: 1 to 2 days of high fever that begins suddenly. During this time, we’re likely to have experience aches, headache with pain behind the eyes, flushed faces, and sometimes blotchy skin or rashes.
  • Critical phase: the fever subsides, and we may feel that we are getting better. However, these 1 to 2 days are also a period when our blood capillaries may leak plasma, leading to a sudden drop in blood pressure and sending us into shock.
  • The next phase will depend on the outcome of the critical phase. We may get better after receiving proper medical treatment and proceed to the recovery phase, or we may get worse and experience severe dengue instead.

“Many viral illnesses such as dengue are self-limiting, which means they will naturally subside,” Assoc Prof Dr Verna shares. “In most cases, patients only need self-care at home, and the most important thing to remember is to take plenty of fluids to prevent the dehydration that comes with plasma leakage.”

“Anyone who gets dengue fever should aim to drink at least 3 litres of water daily for the first 3 days,” she adds.

Myth 3
DENGUE IS ONLY A SMALL CONCERN; AFTER ALL, YOU CAN GET BETTER FROM PRACTICING SELF CARE AT HOME

Not necessarily true.

“An estimated 1% of patients will experience severe dengue, also known as haemorrhagic dengue, which will require hospitalization,” says Assoc Prof Dr Verna.

She goes on to explain that one may begin to experience bleeding during the febrile phase, usually in the skin or gums. If the bleeding weren’t managed well, the dengue will worsen during the critical phase, forcing us to be admitted into the hospital.

“Those with a healthy immune system usually recover in 2 days, but if there is inflammation affecting the organs such as the heart, liver or brain, it can take up to a week, longer if there are other complications,” she goes on to say.

Myth 4
YOU SHOULD ONLY TEST FOR DENGUE AFTER 3 DAYS 

“It is true that the initial symptoms are vague, as a fever can be a sign of many different illnesses,” says Assoc Prof Dr Verna.

However, with dengue, the high fever usually comes suddenly.

“The S1 dengue rapid antigen test can detect dengue from the first day, so don’t delay seeking medical advice if you suddenly develop a high fever,” she advises.

Delay in getting tested may lead to severe consequences, as we will enter the critical phase 1 to 2 days after catching dengue—a time when our condition can suddenly take a turn for the worse!

Myth 5
ONCE YOUR NEIGHBOURHOOD HAS BEEN FOGGED, THERE IS NO NEED TO DO ANYTHING ELSE TO PREVENT DENGUE

Not true.

Assoc Prof Dr Verna reveals that while fogging helps to kill adult mosquitoes and getting rid of stagnant water in public drains and other places helps to prevent breeding sites, this method are only partially effective.

To illustrate, millions are spent on fogging efforts every year—an estimated RM777 million was spent on fogging efforts in the 2009 to 2010 period—but dengue remains prevalent to this day. There is even evidence that mosquitoes have grown resistant to the common insecticides used in fogging!

“On a personal level, all of us can do something at home to help prevent mosquito bites and breeding sites. We need to make a bigger effort to protect ourselves and our loved ones by making sure our home environment is clear of any breeding sites, covering up exposed skin and using mosquito repellents, especially during sunrise and sundown,” she advises.