The Case For Dengue Vaccines In Malaysia

A public health expert from MOH says a dengue vaccine is a dream come true for a communicable disease, but asks if a vaccine is effective enough to eliminate dengue, like elimination strategies for measles, malaria, or cervical cancer.

KUALA LUMPUR, Dec 14 – Public health experts in Malaysia, both in the Ministry of Health (MOH) and in academia, are weighing the possibility of introducing a dengue vaccine as a preventive measure against the mosquito-borne disease in the country.

Local scientists and regulators are still reviewing the feasibility of Takeda’s tetravalent dengue vaccine, following regulatory approvals made on the two vaccines in a number of countries in Europe, the Americas, and Asia. In Asia, Takeda’s dengue vaccine known as Qdenga (TAK-003) is approved in Indonesia and Thailand.

The European Union (EU) approved Takeda’s dengue vaccine in December 2022.

Over the last two decades, dengue infections have jumped eightfold to almost 400 million a year, according to one estimate by researchers at the University of Oxford

The World Health Organization (WHO) said about half the world’s population are at risk of infection with dengue viruses, with Asia carrying 70 per cent of the disease burden. Experts warn that climate change will likely accelerate the spread of mosquitoes that carry the virus.

Malaysia has so far implemented several vector control strategies to prevent transmission of dengue and control outbreaks, including expanding the use of Wolbachia-infected mosquitoes to biologically control the spread of dengue in persistent hotspots.

Despite extensive research and development for dengue fever treatments and vaccines, effective solutions for the disease have not been achieved. 

This is reflected in MOH’s National Strategic Plan For Dengue 2022-2026, which does not include or allude to the use of any dengue vaccines, said Dr Wan Ming Keong, a senior principal assistant director of vector-borne disease under MOH’s disease control division.

Dr Wan was speaking at a roundtable discussion on dengue vaccines organised by the Galen Centre for Health and Social Policy and supported by Takeda Malaysia on November 25 last year.

However, Dr Wan said he “sees the potential” if, at all, the ministry has a candidate vaccine.

“I believe a dengue vaccine is a dream come true [to address] any communicable disease, and especially, for us in public health. But what we are looking at, of course, is it has to be safe, which means not only are we looking at no adverse effects, we’re also looking at the androgenicity and possible viremia. 

“Efficacy, we’re looking at a very high efficacious vaccine. Why? Because it will play a part in our dengue direction – are we talking about elimination or are we talking about control? 

“At the moment, we have a number of measures in place for dengue control which means it’s just for checking dengue endemicity. We do not want it (dengue) to become an epidemic. We have our conventional chemical push biological approach. We have our structural modifications integrated vector management, things like that.

“All these, at best, we call them control tools. We can never go to elimination like, for example, with measles and malaria. So can this dengue vaccine change the paradigm? 

“Is their efficacy high enough that we can say this will be our elimination tool for dengue a what we have with let’s say, cervical cancer and the human papillomavirus (HPV) vaccine where given their high efficacy, they can go for elimination of cervical cancer?

“These are the questions we would like to ask – whether there is long-term immunity. And we know that the challenging part for dengue is it has four serotypes and because of that each infection can only [offer] protection for the same serotype, not for others,” Dr Wan said.

Apart from vaccine safety and efficacy, Dr Wan also spoke about other considerations on how a dengue vaccine can fit into existing strategies such as prevention levels, distribution of the vaccine, pre-vaccination testing requirements, and cost effectiveness.

“The question is not, are we ready?” Dr Wan said. “The question is, is the vaccine ready?”

Health director-general Dr Muhammad Radzi Abu Hassan reported last Tuesday that dengue fever cases in the country nearly doubled to 111,417 cases this year until the 48th epidemiological week (November 26 to December 2) from 58,239 cases in the same period in 2022, marking an increase of 53,178 cases (91.3 per cent).

Eighty-four deaths from dengue fever complications were reported this year up to the 48th epidemdiological week, a 115 per cent increase from 39 fatalities in the same period last year.

Financing A Dengue Vaccine 

Prof Dr Sharifa Ezat Wan Puteh, a public health specialist at Universiti Kebangsaan Malaysia (UKM), said there was also a need to consider financing models to make dengue vaccines available in Malaysia.

Dr Sharifa Ezat said papers published on Sanofi’s Dengvaxia lists the vaccine at US$99 (RM437) per dose, which she described as “quite high”. Another study published found an incremental cost-effectiveness ratio of US$122,000 per quality-adjusted life year (QALY) gained per vaccination, which Dr Sharifa Ezat said is “exuberant”.

QALY is a summary outcome measure used to quantify the effectiveness of a particular intervention. One QALY is equal to one year of life in perfect health. 

“We come from a so-called upper middle income country and because of the economic downturn, we’re looking at WHO’s standards, meaning we want a range of between 1 and 3 per cent of Malaysia’s GDP per capita. 

“In fact, there were also some proposals during Covid-19 to consider half of GDP because we are so poor, in that sense, you know, to obtain an outcome. Therefore, if possible, we want something that is very cheap. 

“Are we going to fully subsidise it? Are we going to combine with the private sector? Is there going to be a benefit package if this is going to be insured later on? Who is going to deliver this? Will it be the school health programme or nurses, which is the usual scenario in Malaysia. As we know, public health activities are poorly funded,” Dr Sharifa Ezat said.

Dr Sharifa Ezat further questioned if it was possible to have partnerships with the industry or other stakeholders to co-sponsor a dengue vaccine in Malaysia.

“We’ve looked at some of the patient-assisted programmes, things like leukaemia where they have partners with industry or developers of the vaccines and they can subsidise some of these oncology treatments, which can be very costly.

“The majority of patients in Ampang [Hospital], for example, [who are on] oncology treatment, they actually have subsidised care provided through this pet programme. I’m not sure whether for dengue we are able to, sort of, catch a partner,” Dr Sharifa Ezat said.

The CYD-TDV tetravalent vaccine by French pharmaceutical company Sanofi is the first dengue vaccine to be licensed. It was first licensed in Mexico in December 2015 for use in individuals aged 9 to 45 years living in endemic areas, and is now licensed in 20 countries.

In the United States, the Food and Drug Administration (FDA) in May 2019 approved CYD-TDV for the prevention of dengue disease caused by all dengue virus serotypes in people ages 9 through 16 who have laboratory-confirmed previous dengue infection and who live in endemic areas. Dengue is endemic in the U.S. territories of American Samoa, Guam, Puerto Rico and the U.S. Virgin Islands.

The Centers for Disease Control and Prevention (CDC), citing studies published in The New England Journal of Medicine, said among children 9-16 years old with previous dengue virus infection, CYD-TDV has an efficacy of about 80 per cent against the outcomes of symptomatic virologically confirmed dengue, hospitalisation for dengue, and severe dengue.

Japanese drugmaker Takeda’s TAK-003 vaccine is also being widely considered for prevention against dengue in various parts of the world, with Brazil, Argentina, Thailand, Indonesia and the EU approving the use of the dengue vaccine.

A study of TAK 003 showed 80 per cent efficacy at preventing symptomatic infection at 12 months and 90 per cent efficacy at preventing hospitalisations at 18 months. The two-shot series showed the ability to provide protection for 4.5 years.

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