Waiting for universal dengue vaccine & drugs, South Asia battles ‘silent pandemic’

New Delhi/Bangkok: She was six when she got dengue. Three decades on, Pink’s battle with the formidable disease often neglected in public health priorities is a narrative that unfolds in detail in the recesses of her memory.

The 36-year-old’s vivid recall took her to Siriraj Hospital in Bangkok so she could get a vaccination against the debilitating mosquito-borne infection. There are no vaccines anywhere in the world that can target all the four variants of the virus and Pink is amongst the lucky few to be able to access a preventive - even if it only provides partial protection.

The available vaccines, covering only two serotypes, are largely inaccessible and unaffordable in most parts of South Asia, including India.

"I grappled with dengue at the age of six, and when the cases surged again in Bangkok this August, I decided to get vaccinated. The rationale is simple -- to shield from a disease that not only jeopardises your livelihood and well-being but can also be fatal," Pink told PTI in the bustling Siriraj hospital.

The challenges are many. Even when the vaccine is available, the procedure is labyrinthine.

“The hospital had to first confirm if I had a previous infection before administering the vaccine. For many of my friends who have never been infected, the shot cannot be given,” Pink said.

Beyond the prerequisites for receiving the vaccine, its steep cost and scarcity, experts shed light on the often overlooked problems associated with the tropical neglected disease that poses a threat to half of the world’s population but lacks a cure or full protection.

In India, where there is no vaccine available right now, challenges are accentuated further due to a large population that is at infection risk and a high number of under-reported cases, said experts.

A recent study by researchers at Bengaluru's Indian Institute of Science (IISc)revealed that the dengue virus has undergone “dramatic” evolution over the last few decades in the country, underscoring the urgent need to develop not just a vaccine but also drug treatments specific to the variant in the country.

“In terms of protection that can be induced with vaccines and drugs, this doesn’t exist in India at present,” said Swetha Raghavan, a postdoctoral fellow at the National Centre for Biological Sciences (NCBS) in Bengaluru.

Three experimental vaccines that target all four variants of the virus are currently in clinical trials across the world, said Rahul Roy, an IISc scientist.

“In India, we also expect to see clinical trials for all three vaccines,” he said.

Most people with dengue have mild or no symptoms and will get better in up to two weeks. Symptoms include high fever, severe headache, muscle and joint pains, swollen glands, and rash.

However, severe symptoms such as shooting abdominal pain, bleeding gums or nose, and blood in vomit or stool, often come after the fever has gone, and can be fatal. Current symptomatic treatment only alleviates symptoms without targeting the virus itself.

Panisadee Avirutnan, chief of the Dengue Hemorrhagic Fever Research Unit at Siriraj Hospital, terms dengue a silent pandemic.

“One of the main challenges in developing a preventive is that the virus has four serotypes or variants, making it difficult to create a vaccine that can target all four equally,” she told PTI.

According to her, despite the genetic similarity of dengue variants, the immune response to one serotype does not necessarily provide cross-protection. She also highlighted the presence of genetic variations within the serotypes, making it even more challenging to design a vaccine.

“The vaccine effort is also hampered by antibody-dependent enhancement (ADE), whereby cross-reactive antibodies against one serotype can enhance subsequent infection by a different variant,” Avirutnan said.

The first registered vaccine, developed by the French pharmaceutical company Sanofi, exhibited an overall efficacy rate of 60 per cent but suboptimal protection against serotype 2 and the potential to cause more severe disease in previously uninfected children.

Another registered vaccine from the Japanese pharmaceutical company Takeda shows promise with a 73 per cent overall efficacy rate against symptomatic dengue. However, it falls short in addressing serotypes 3 and 4, said Avirutnan.

A third vaccine, TV003, developed by the US National Institute of Allergy and Infectious Diseases (NAID), is currently undergoing testing in Brazil.

While the first two vaccines are available in Thailand, costing around 5,000 Baht (INR 11,500) for both doses, these options remain inaccessible in many other countries, including India.

This is especially concerning given that a significant portion of the population in India is at risk of contracting dengue, noted Kavita Singh from the non-profit Drugs for Neglected Disease Initiative (DNDi).

“ICMR is planning the third phase of clinical trial of the vaccine candidate being developed by NAID in India," Singh told PTI.

Thailand saw over 123,000 (1.2 lakh) reported cases and over 120 deaths till November last year, as per data gathering platform Statista.

In 2023, India officially recorded nearly 95,000 cases and 91 deaths by September 17. In 2022, the number was 2.33 lakh with 303 deaths.

Kulkanya Chokephaibulkit, head of the Division of Pediatric Infectious Diseases, Siriraj Hospital, said the absence of effective drugs for treatment is another hurdle. This challenge is further compounded by the lack of a reliable animal model for testing potential drugs.

“A good animal model could represent the full spectrum of dengue viral disease in humans,” Chokephaibulkit said.

“Natural infection can protect you from other serotypes for up to six months. When that immunity fades it does something in the body that can enhance infection severity from other serotypes,” Avirutnan added.

She said some patients mistakenly perceive dengue as a self-resolving ailment, akin to a common cold, opting to stay home during the initial stages, inadvertently reaching a critical period characterised by uncompensated shock.

Complicating matters is the fact that 80 per cent of individuals with dengue display no symptoms, becoming unwitting carriers of the virus.

“This silent transmission, as they move about, exposes more mosquitoes to the virus, perpetuating a cycle that poses a heightened risk to others,” Chokephaibulkit said.

Experts also stressed on the need for government funding.

“Currently, we use our lab funding. Now because dengue is a threat to the developed world we expect more interest from governments,” Avirutnan said.

Going forward, Chokephaibulkit emphasised the crucial role of sustained mosquito population control efforts, adding that global collaboration becomes imperative as climate change extends dengue's reach into new frontiers.

The experts advocate the widespread availability of rapid diagnostic tests for dengue, similar to self-tests used for COVID-19.

To address the treatment gap, the Dengue Alliance has been established with its key partners being the DNDi, the Translational Health Science and Technology Institute (THSTI) in Delhi, the Ministry of Health of Malaysia, the Siriraj Hospital Faculty of Medicine at Mahidol University in Thailand, and the Oswaldo Cruz Foundation and Federal University of Minas Gerais (UFMG) in Brazil.

As Pink sits in the waiting room of Siriraj Hospital, ready to receive her vaccination, she sees her decision to take the vaccine as a proactive step in contributing to the collective effort to combat dengue rather than being a passive survivor.