Wiser to hold off dengue vaccine, for now

KUALA LUMPUR: When the first dengue vaccine in the world Dengvaxia was cleared for release in Mexico in December 2015, the Malaysian Health Ministry hesitated to introduce it in the country.

Perhaps for good reason too.

To date, the vaccine has been licensed in Mexico, the Philippines, Brazil, El Savador and more recently, Costa Rica. This is amid concerns on the safety, efficacy and cost of the vaccine.

The Malaysian government has not bowed down to pressure from certain quarters to implement the vaccine and made it clear that it would wait until June to decide on whether to use Dengvaxia in the country.

When Bernama recently contacted the Director General of Health Datuk Dr Noor Hisham Abdullah on the matter, he said that the country has to wait further as WHO's guidelines and recommendations on Dengvaxia usage would only be released in July.

Dengvaxia was developed by the French drug maker Sanofi. Its Pasteur division had been researching the tropical disease for over 20 years, spending some €1.5 billion (about RM7 billion) on it as well as on manufacturing investments.

Dengvaxia in the Phillippines

The Philippines introduced the dengue vaccine in the country in April, making it the first Asian country to do so.

Its Department of Health launched a programme to vaccinate one million nine-year-olds amid safety concerns expressed by public health advocates.

More than 200,000 school students in Manila have been inoculated as of May and the department hopes to reach its target by the year-end.

Public health advocates had earlier urged the ministry to delay the roll-out of Dengvaxia due the vaccine possibly increasing the disease's severity.

According to Singaporean daily the Straits Times, Professor Dr Antonio Dans of Manila's UP's College of Medicine had warned that while the vaccine could reduce the number of dengue cases it could later increase the disease's severity.

This phenomenon is known as "antibody-dependent enhancement".

"The real dengue we are afraid of is severe dengue, not the mild ones. If a vaccine prevents mild disease but causes severe dengue, we shouldn't be using it at all," he had said in a statement.

Citing Sanofi's own studies, he said this could happen three years after the vaccine's introduction.

The Philippine's WHO representative Gundo Weller had backed the country's use of Dengvaxia although in its website WHO said it was still awaiting the submission of an application from Sanofi for the prequalification of the vaccine.

Local media network GMA reported this has raised the ire of some medical professionals in the country who felt that the immunisation programme should not have preceded the prequalification process.

Prequalification is a standard procedure by WHO to ensure that vaccines purchased by the UN and government procurement agencies are safe and effective.

"As health advocates, we appeal to the Health Ministry to wait until the study is completed and put in place safeguards to protect children from possible adverse effects on their health," the Philippine College of Physicians Foundation president Anthony Leachon was reported as saying.

The other countries that have approved of the vaccine have yet to launch public campaigns like in the Philippines.

Dengvaxia

On Dec 9, 2015 Sanofi Pasteur announced that the Mexican authorities have approved of Dengvaxia, thus making it the first vaccine licensed in the world for dengue prevention.

Its final clinical trial was conducted in 2014 on 20,875 children aged 9-16 years old across five countries in Latin America - Brazil, Columbia, Honduras, Mexico and Puerto Rico.

The Latin American trial results indicated a 50.3% efficacy against serotype 1 (DEN1), 42.3% against DEN2, 74% against DEN3 and 77.7% against DEN4.

In Southeast Asia, the clinical trials carried out on 10,275 healthy children aged 2-14 years old in Malaysia, Indonesia, the Philippines, Thailand and Vietnam showed the vaccine reduced dengue by 56.5% in the vaccinated group compared with the control placebo group, as observed during 25 months of
active surveillance.

The data also showed good serotype specific protection, with better protection shown against DEN3 and 4 (75%).

However, as with the Latin American trials, the vaccine showed less protection against DEN1 (50%)
and least to DEN2 (35%).

Despite that, it is found to be 88% effective against dengue haemorrhagic fever.

Part of the hesitation of the Malaysian government in introducing the vaccine is due to the poor efficacy rate of Dengvaxia on serotype 2, which is the most prevalent in Malaysia.

The Health Minister Datuk S. Subramaniam earlier this year said that scientific data showed that it could only give effective protection to 47% of dengue patients. It was also not suitable for children under nine
years old.

"As such it will take a longer time to study its effectiveness by the Technical and Scientific Committee on dengue vaccines before the vaccine can be used in the country," he had said.

Eminent virologist Prof Emeritus Dr Lam Sai Kit had expressed disappointment over the Health Ministry's decision but understood the concerns given.

"As the founding chairperson of the Asia Pacific Steering Committee for Dengue Vaccine to Vaccination Programme, we are monitoring this vaccine closely making sure it is efficacious, protective and above all, safe.

"This vaccine has undergone rigorous clinical trials, involving over 31,000 persons in 10 countries. I can't think of any vaccines that have been so vigorously tested. The results of the Asian and Latin American trials have been published in top scientific journals and have been studied closely," Lam had said to Bernama.

Newer vaccines on the way

WHO cited 390 million cases of dengue every year in more than 100 countries, mostly in the developing world. Of the figure, an estimated half a million people contract severe dengue.

The difficulty in developing a vaccine for dengue is mainly because the virus comes in four strains. If a person is infected with more than one type of dengue, there is a greater chance of the virus causing hospitalisation or death.

The US is currently working on another dengue vaccine called TV003, which is said to offer strong protection against all four strains of the dengue virus.

Leading the study is an associate professor at Johns Hopkins Bloomberg School of Public Health, Dr Anna P. Durbin, who has said the first Phase III efficacy trial of the vaccine has already taken place.

TV003, however, has at this stage shown similar issues as Dengvaxia in its efficacy in protecting against serotype 2 of the virus. Its researchers are now looking into ways it could be improved to specifically protect against the strain prevalent in Southeast Asia.

In Singapore, the government has decided that the vaccine is unsuitable for use in the country as the best protection it offered is against two of the less prevalent strains in the country.

The country is however participating in a Phase II trial for another dengue vaccine candidate, Takeda's Tetravalent Dengue Vaccine (TDV) by the Japan-based Takeda Pharmaceutical.

Takeda's Tetravalent Dengue Vaccine (TDV) is a tetravalent vaccine aimed at two different serotype 2 potencies. Besides Singapore, it is also undergoing phase II trials in Thailand, Colombia and Puerto Rico.

Cost

Although the decision on whether to use Dengvaxia is up to individual governments, the burden of costs needs to be taken into consideration.

The senior advisor in WHO's Initiative for Vaccine Research Joachim Hombach said that while the organisation could provide information resources, it could do little to offset the challenges that came with a vaccination programme.

"You need to buy the vaccine and it costs a lot money, and you are in the business for many years. It's essentially an open-ended commitment.

"You don't want to be in a situation where you introduce a vaccine and then two years later you say, sorry, we are running out of money and we have to stop this programme."

Malaysia needs to seriously weigh in on whether the benefits of the vaccination programme will outweigh the costs.

A study by Universiti Malaya Medical Centre in collaboration with Brandeis University in 2012 showed that the economic burden of dengue in Malaysia was some RM360 million per year.

In Asia alone the annual economic cost of dengue illness is about US$2 billion (RM8.53 billion) and this does not include the cost of vector control. — Bernama