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.

Expert Answers All the Important Questions You Have about the New Dengue Vaccine

WORDS LIM TECK CHOON

With the Qdenga® dengue vaccine officially launched by pharmaceutical company Takeda Malaysia in Malaysia on 11 June 2024, we manage to get some important answers from Dr Goh Choo Beng about dengue and this vaccine.

FEATURED EXPERT
DR GOH CHOO BENG
Head of Medical Affairs
Takeda India & Southeast Asia
What does it do?

Prevention of dengue caused by any of the 4 dengue serotypes.

The clinical trial of the vaccine found that it can:

  • Prevent 80.2% of symptomatic dengue cases at 12 months after receiving the vaccination.
  • Prevent 90.4% of hospitalizations at 18 months after vaccination.
Who can receive the vaccine?

Qdenga® can be administered to individuals 4 years old and above.

How many doses do I need?

Two doses. The second dose will be given three months after the first dose.

Where can I get it?

Currently it’s available at general practitioner or GP clinics as well as private hospitals.

How much is the vaccine?

The price will be set by the clinic or the hospital, so it’s best to consult them about the price.

How does this vaccine work?

Dr Goh explains that the Qdenga® vaccine has a backbone that is based on the live-attenuated DENV2 serotype of the dengue virus, with recombinant strains expressing surface proteins for DENV1, DENV3 and DENV4.

This way, the vaccine will protect an individual from all 4 dengue serotypes.

Is it safe for individuals that have not contracted dengue before?

Yes. People that have no history of dengue fever as well as people that have had dengue can safely receive the vaccine.

No blood tests are necessary before receiving the vaccine.

What are the side effects?

Short term side effects are common ones associated with vaccination, such as redness and soreness at site of injection. These side effects are mild and temporary.

At the time of writing, there is an ongoing clinical trial that is monitoring and closely following selected individuals that have received the vaccine since about 4.5 years ago. So far, the investigators have found that:

  • The protection afforded by the vaccine persists 4.5 years after receiving the vaccine.
  • There is no long-term serious side effect seen so far.

15 Facts & Tips That Moms & Dads Should Know When It Comes to Dengue & Their Kids

WORDS LIM TECK CHOON

FEATURED EXPERT
DR YONG JUNINA FADZIL
Consultant Paediatrician and Paediatric Cardiologist
Klinik Pakar Kanak-Kanak Junina
FOR PARENTS WITH BABIES BELOW 6 MONTHS OF AGE
  1. According to Dr Yong Junina, young babies with dengue may not show specific symptoms—they may not even exhibit fever.
  2. Furthermore, fever is also a symptom of many other childhood illnesses. Thus, even when a child has fever, it can be challenging for a doctor to identify the exact cause of the fever.
  3. Also, a child’s condition may worsen quickly if left untreated.
  4. Hence, Dr Yong Junina advises parents with a child of under 6 months of age to promptly seek medical attention when their child appears unwell.
FOR PARENTS OF SLIGHTLY OLDER CHILDREN
  1. “Older children may still experience difficulties in communicating their conditions to their parents,” Dr Yong Junina shares.
  2. Generally, unwell children tend to consume less fluids, and severe dengue can cause fluid leakage from blood vessels, resulting in reduced urine output. Dehydration, regardless of the cause, can be perilous, especially in young children.
  3. Hence, bring the child to see a doctor promptly when they show such signs of being unwell.
SOME POSSIBLE SIGNS THAT A CHILD MAY HAVE DENGUE
  • Lethargy.
  • Body ache.
  • Pain behind the eyes.
  • Headaches.
  • Parents can check whether their child’s hands and feet feel cold. They can also press on the child’s fingertips to observe how quickly the fingertips regain their normal colour.
HOW DENGUE AMONG YOUNG CHILDREN IS TREATED
  1. Dr Yong Junina tells us that young children are more likely to develop severe dengue and related complications, such as dengue shock syndrome.
  2. Dengue shock syndrome is the result of dengue-causing viruses triggering a chain of reactions that cause one’s blood vessels to leak. Eventually, the person experiences sudden drop in blood pressure, internal bleeding, and even organ failure. This is a serious medical emergency that can lead to death if not treated quickly!
  3. Dr Yong points out that children with severe dengue will need to be admitted into the hospital. There, they will undergo repeated blood tests and possibly be put on drip.
  4. “Throughout all this, parents would need to stay with them, affecting their work and ability to care for the rest of the family,” she says. “Among daily wage earners, the loss of income would be significant.”
PROTECTING YOUR CHILD FROM DENGUE
  1. “There is no preventive method that is 100% effective,” says Dr Yong Junina. Hence, it is important for parents to practice vigilance.
  2. Keep the house free of potential mosquito breeding grounds by ensuring there is no stagnant water.
    • Aedes mosquitoes, the ones responsible for infecting us with dengue, breed in clean water, so make sure pails are covered and use larvicide in any places that water may collect in.
    • Remember to check aquariums and containers of aquatic pets (such as terrapins), receptacles for catching residual water from plants and dishracks, and containers of water-based plants such as money plants and hydroponics.
  3. Keep windows closed at dawn and dusk, as these moments are when the Aedes mosquitoes are more active, and sleep with long-sleeved clothing.
  4. Use mosquito repellents. There is a wide range of products available, including chemical-free products infused with lemongrass.

Top Dengue-Related Highlights from the Dengue Prevention Advocacy Malaysia Launch

WORDS LIM TECK CHOON

ABOUT THE DENGUE PREVENTION ADVOCACY MALAYSIA (DPAM) GROUP
  • DPAM is an independent advocacy group co-jointly led by the Malaysian Paediatric Association (MPA), the Malaysian Society of Infection Control and Infectious Disease (MyICID), the Malaysian Society of Infectious Diseases and Chemotherapy (MSIDC), and the Malaysian Public Health Physicians Association (PPPKAM).
  • DPAM collaborates with the Malaysian Society of Parasitology and Tropical Medicine (MSPTM), the Malaysian Medical Association (MMA), Asia-Pacific Academic Consortium for Public Health Kuala Lumpur (APACPH-KL) and Rotary International District 3300.
  • DPAM is established to support the efforts of the Ministry of Health in strengthening dengue prevention, management, and control in Malaysia.
WHY DPAM IS NECESSARY: A POTENTIAL EMERGING DENGUE EMERGENCY
FEATURED EXPERT
DR HUSNINA IBRAHIM
Deputy Director of Disease Control Division (Communicable Diseases)
Ministry of Health Malaysia
  • Malaysia had its worst dengue outbreak in 2019, over 130,000 cases and 182 deaths.
  • The numbers declined during the MCO a few years ago. During this new normal, however, dengue numbers are once again on the rise.
  • From January to epidemiology week-22 this year, there has been a 158% rise in dengue cases and 183% increase in the deaths compared with the same period last year.

Dr Husnina Ibrahim, the Deputy Director of Disease Control Division (Communicable Diseases), said: “As Malaysia typically experiences a surge in dengue cases every 4 to 5 years, it was projected that an outbreak is due around this or next year, with an estimated number of cases potentially surpassing the historic 2019 outbreak.”

RECENT ADVANCES YIELD POSITIVE RESULTS IN THE PREVENTION & CONTROL OF DENGUE
Wolbachia-infected mosquitoes
  • The introduction of Wolbachia-infected mosquitoes has significantly reduced dengue cases in 16 out of 19 localities, by 33% to 100%.
  • Wolbachia is a type of bacteria that can infect many species of invertebrates—organism with no backbone—including mosquitoes such as Aedes aegypti, the mosquito that carries and spreads the dengue viruses.
  • Male Aedes aegypti infected with Wolbachia will mate with female mosquitoes, but the resulting eggs will not hatch.
  • This reduces the number of Aedes aegypti mosquitoes.
Implementation of comprehensive guidelines, proper training, and a critical review of dengue mortality

These efforts have reduced the case-fatality rate by 87.3% from 2000 to 2022.

SETTING TARGETS FOR FUTURE DENGUE PREVENTION & CONTROL EFFORTS
  • The Ministry of Health has in place the National Dengue Prevention and Control Strategic Plan 2022-2026, which aims to annually reduce the number of dengue cases by 5% while maintaining the proportion of deaths compared to the number of cases (case fatality rate or CFR) below 0.2%.
  • The Ministry aims to reduce the CFR to 0% by 2030—which is to say, there should be no deaths due to dengue by that year.
DPAM TO PLAY AN ACTIVE ROLE IN SUPPORTING THE EFFORTS OF THE MINISTRY OF HEALTH TO ACHIEVE THESE TARGETS
FEATURED EXPERT
PROFESSOR DATUK DR ZULKIFLI ISMAIL
Consultant Paediatrician and Paediatric Cardiologist
Chairman of the Dengue Prevention Advocacy Malaysia (DPAM)

Professor Datuk Dr. Zulkifli Ismail expresses his optimism that the Ministry of Health’s aforementioned targets are achievable with the active involvement of key stakeholders such as the government, civil society, academia, private sector, media, and the community.

DPAM aims to synergize efforts by various of these stakeholders in assisting the Ministry of Health to achieve its national and global dengue targets through the strengthening of dengue prevention, management, and control in Malaysia.

He said, “DPAM will focus its efforts on healthcare professional and public education and communication, local research, guideline recommendations, as well as policy recommendations.”

To foster and strengthen regional collaborations, DPAM will work closely with the Asian Dengue Voice & Action (ADVA), a regional advocacy group. Their first collaborative initiative is the hosting of the 7th Asia Dengue Summit in Malaysia next year.

DPAM also released a Resolution Paper that contained key strategies for all relevant stakeholders to create a “whole of society” approach.

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.