SINGAPORE: Is a future with zero dengue deaths possible in Singapore? That is a question that’s likely been asked a thousand times over.

Singapore continues to wage its war against dengue since the first outbreak recorded in 1960. More than 11,000 dengue cases have been reported in the first 37 weeks of 2024, exceeding the 9,949 cases logged for the whole of 2023. Thirteen people have died from local dengue infections between January and June this year, more than double the six deaths in 2023.

The World Health Organization, as part of its sustainable development goals, has set a target of zero dengue deaths by 2030.

Singapore’s efforts to combat dengue are highly laudable, going back five decades. If any country in the world can drive dengue deaths to zero, it’s Singapore. However, this requires careful strategic planning and collaboration on many fronts.

REPORTED DENGUE CASES MERELY TIP OF THE ICEBERG

The Aedes House Index, which measures the percentage of inspected premises tested positive for Aedes larvae or pupae, has dropped from about 50 per cent in the 1960s to less than 5 per cent in the late 1970s, and has remained remarkedly low since the 1980s.

Singapore has had an annual dengue case fatality rate not exceeding 0.2 per cent for the past few years.

Under Project Wolbachia, which was launched in Singapore in 2016, lab-grown non-biting male Aedes aegypti mosquitoes carrying the Wolbachia bacteria are released at selected locations. When they mate with the urban female Aedes aegypti mosquitoes, their resultant eggs do not hatch, thereby helping to suppress the Aedes aegypti mosquito population.

The project now covers about 480,000 households. Residents living in areas with at least one year of mosquito releases under Project Wolbachia are up to 77 per cent less likely to be infected with dengue, according to NEA’s data from 2019 to 2022.

Ongoing public education and community outreach efforts include colour-coded dengue alert banners, and emphasis on the collective public efforts against mosquito breeding and dengue transmission.

However, despite these efforts, Singapore continues to experience large outbreaks episodically.

In 2020, Singapore reached new heights with 35,210 dengue cases and 32 deaths. The cases again surpassed the 30,000-mark in 2022, recording a total of 32,154 cases with 19 deaths. Although 2023 was considered a “good year”, there were still 9,949 cases and six deaths.

These reported cases are just the tip of the iceberg. The majority of dengue infections are asymptomatic or subclinical. This means infected individuals have few or no symptoms and would not know that they have dengue.

Further, even for those who do go on to develop symptoms, the infectious virus is present in their blood before the onset of symptoms, further emphasising the importance of taking precautions against mosquito bites at all times.

The relative success of vector control in Singapore also means that most of our population get their first dengue infection much later in life compared to our grandparents who would have been infected as children. This low herd immunity status leaves us vulnerable and open to repeated cycles of outbreaks.

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To effectively control dengue outbreaks in Singapore, a concerted and multipronged approach is essential. One of the important components of this approach is continuous biomedical research, coupled with global collaboration among governments, academic institutions and pharmaceutical companies to co-develop novel drugs and preventive therapies to prevent and treat dengue.

Ensuring early detection and access to proper medical care for dengue has significantly lowered fatality rates. However, there are no drugs available commercially at present specifically designed to treat dengue. Garnering pharmaceutical companies’ interest in developing such drugs to treat and prevent acute infections, which are not as lucrative as chronic diseases drugs, can be difficult.

Furthermore, developing a safe and effective vaccine is challenging due to the immune complexity of the dengue virus. There are four different dengue serotypes and all four co-circulate locally. A person infected by one serotype gains immunity to that specific serotype, but this same immunity can sometimes worsen a second infection from another serotype.

A vaccine that offers protection against all four serotypes would be a game changer.

The availability of such a vaccine, one that is effective against the predominant circulating dengue serotypes, does not worsen subsequent infections and can be given to a wide age range including older adults, would be instrumental in reducing the healthcare burden of dengue in Singapore.

Currently, Singapore has only one licensed dengue vaccine, Dengvaxia. The vaccine is only recommended for those aged 12 to 45 years old with prior infection. As such, its use locally so far has been limited.

Sanofi, however, recently announced that they will discontinue production of Dengvaxia due to a lack of demand globally.

Another vaccine that was recently launched in several countries is Qdenga. It has been approved in countries including Indonesia, Thailand, Vietnam and conditional approval in Malaysia for use regardless of prior infection.

A study has shown that Qdenga was about 84 per cent effective in reducing hospitalisation and 61 per cent effective in preventing symptomatic dengue cases at four-and-a-half years after being administered.

However, for countries with low to moderate dengue transmission, including Singapore (Singapore is considered to have a low dengue transmission), the World Health Organization’s position paper in May 2024 currently does not recommend Qdenga’s inclusion into national vaccination programmes.

While Qdenga has high efficacy against serotype 2, the predominant serotype historically responsible for most outbreaks in Singapore, it does not appear to protect against serotype 3 and it is unclear if it protects against serotype 4.

In Singapore, the manufacturer has also withdrawn its application to register Qdenga here following a review by the Health Sciences Authority on initial submitted scientific data.

A third dengue vaccine, TV003, has recently completed clinical trials in Brazil with promising results. Longer-term follow-up data is pending.

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While the quest for a universal dengue vaccine continues, more can be done to effectively diagnose and treat dengue.

Novel diagnostic tools that do not rely on blood tests - perhaps using saliva or urine - would be useful. As would a user-friendly point-of-care test-kit, which would allow for earlier detection, even before the onset of symptoms.

This would allow infected persons to take extra precautions to avoid mosquito bites to break the transmission chain. It would also allow for early identification of dengue clusters and treatment.  

Currently, the management of dengue patients is largely supportive and directed at relieving symptoms. The majority of patients are managed in the outpatient setting, with patients educated to be on alert for the warning signs of severe dengue. To reinforce these efforts, the current national guidelines for dengue clinical management are being reviewed and updated.

While Singapore has built a strong foundation in its fight against dengue, the World Health Organization’s target of zero dengue deaths by 2030 will remain a lofty dream until every available tool in the arsenal can truly be harnessed.

Dr Chia Po Ying is Consultant, National Centre for Infectious Diseases. Dr Jolene Oon is Senior Consultant, Division of Infectious Diseases, Department of Medicinerby63, National University Hospital.

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