KUALA LUMPUR: While no specific treatment is available for dengue fever, a solution could be in the works in the form of vaccines.
The New Sunday Times recently learnt that Tokyo-based pharmaceutical company Takeda is seeking approval in Malaysia for its newly developed Qdenga (TAK-003) dengue vaccine.
"Takeda is committed to creating good access to this vaccine for a lot of dengue-endemic countries, including Malaysia," said Takeda Pharmaceuticals (Asia Pacific) Pte Ltd vaccines medical lead Dr Andrew Green.
"We are in talks with the Health Ministry and various universities, including Universiti Malaya. So we are working, collaborating very closely, not just with the government sector," he said on the sidelines of the 20th International Congress on Tropical Medicine and Malaria in Bangkok, Thailand, recently.
The Japanese drugmaker continues to progress regulatory filings in other dengue-endemic countries in Asia and Latin America.
Currently, only Dengvaxia (CYD-TDV) from Sanofi Pasteur has been licensed in some countries for dengue vaccination. Malaysia did not approve its use. About five more vaccine candidates are in development. Two of them, the one by Takeda and another by the United States National Institutes of Health and the Butantan Institute in Brazil, are now in Phase 3 trials.
Qdenga (TAK-003) was recently approved by the European Union, making it the second jab approved by the bloc. The two-dose live attenuated vaccine is authorised for use in the EU in people aged 4 and older to prevent any of the four serotypes of dengue, regardless of prior exposure to the disease.
Qdenga is also approved in Indonesia for use in individuals aged 6 to 45.
The vaccine is based on the DENV-2 strain of the dengue virus that has been weakened, with DNA from the other three serotypes added in. According to data from a pivotal trial, the vaccine can induce immune responses against all four dengue types.
In 2019, Takeda published the results of a trial across eight countries, involving roughly 19,000 children aged between 4 and 16. One year after immunisation, the vaccine had an efficacy of 80 per cent against symptomatic dengue and 95 per cent against hospitalisation.
In June, Takeda said 4.5 years after immunisation, the efficacy dropped to 61 per cent for symptomatic infection and 84 per cent for hospitalisation.
However, epidemiologist and health informatician Professor Datuk Dr Awang Bulgiba Awang Mahmud of Universiti Malaya stressed that the Qdenga vaccine should be trialed before a decision was made on using it to vaccinate the population.
"We should also consider a proper cost-benefit analysis of vaccination as, generally, dengue rarely results in death or long-term disability."
He said Dengvaxia had some promise, but events surrounding the possibility of antibody-dependent enhancement (ADE) caused issues with its rollout in the Philippines.
"Whether ADE will occur with the Qdenga vaccine remains to be seen and Malaysia needs to be cautious of this possibility.
"Even though Indonesia intends to use Qdenga, the same concerns about ADE have been raised."
The simple definition of ADE is "raising antibodies that don't protect, but actually make a viral infection even worse".
Dengvaxia had a high-profile launch in the Philippines in 2016 and had been used in a wide-spread school vaccination programme. It was later linked to the deaths of children.
Public health expert Datuk Dr Zainal Ariffin Omar said an effective vaccine should be capable of preventing all dengue serotypes from infecting the body, effective for children as well as adults and had few harmful side effects.
"Dengvaxia only partially protects against dengue, mainly DENV-3 and DENV-4, and is effective only in those aged 9 to 45.
"Dengvaxia was offered to Malaysia, but it was rejected as it failed in the technical evaluation. Qdenga offers hope for dengue management in Malaysia. But it has to undergo rigorous tests and clinical evaluation in Malaysia."
Environmental health scientist Professor Dr Jamal Hisham Hashim said Qdenga could be considered for approval in Malaysia, but should not be made mandatory.
"Qdenga should be used judiciously if it is approved. It can be recommended for high-risk individuals, such as outdoor workers like farmers and construction workers, and especially for those who work at dawn or dusk, when Aedes mosquitoes are most active."
The EU recommends European travellers or expatriates travelling to countries where dengue is endemic, like Indonesia and Malaysia, to take Qdenga before returning to their countries so that the disease can't be brought back and spread there, especially when the mosquito vector, Aedes aegypti, is present.
Public health expert and epidemiologist Professor Datuk Dr Lokman Hakim Sulaiman said Takeda's Phase 3 data seemed to show no safety concerns with regard to it behaving like a primary infection.
"If our National Pharmaceutical Regulatory Agency approves the vaccine for use, then I do not see the necessity of repeating efficacy and safety trials."
He suggested conducting close post-market surveillance and a pilot programme in a small area.
He said even if a dengue vaccine was only 50 per cent effective, it would still significantly reduce risk of infection and transmission, contributing to better control.
"The cost of managing dengue runs into the billions in severe outbreak. One point for the Health Ministry to think about is what is the entry point for the vaccination if they decide to use it?
"The peak age group is between 20 and 30. It may be worth considering secondary school children, taking into account that HPV vaccination is already required for 13-year-olds.
"It is not cost effective to run
a mass dengue vaccination programme. It should be prioritised in high-risk urban areas."
According to studies, the economic impact of dengue is substantial, including lost work days (7.2 to 8.8 days) and lost school days (3.2 to 4.1 days).
It is estimated that the total
annual cost of dengue prevention and illness in Malaysia in 2009/2010 was RM777 million.