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Dengue, caused by the virus that is transmitted by the bite of the female Aedes aegypti mosquito and, to a lesser extent, the Aedes albopictus mosquito, is an acute disease characterized mainly by high fever, body pains and redness of the skin.
A small fraction of those that show symptoms You may experience worsening of the disease at the end of the first week. These cases, classified as dengue with warning signs and severe dengue by the World Health Organization, are the most worrying and cause significant morbidity and mortality in tropical and subtropical regions around the world.
In dengue with warning signs, in addition to the classic symptoms, small amounts of blood in the mucous membranes, bruising, abdominal pain, vomiting, dehydration, restlessness, dizziness, excessive tiredness and drowsiness may occur.
Severe dengue is the result of an increased systemic inflammatory reaction, which disrupts blood clotting and causes fluid loss. Consequences can include heavy bleeding and a sudden drop in blood pressure, which are responsible for the shock associated with dengue, the leading cause of death.
The number of people with severe disease is small compared to the total incidence of the disease. Of the three million confirmed cases of dengue in Brazil in 2023, only 0.1% presented the worst symptoms of the disease, according to the World Health Organization.
However, as The number of cases continues to increase in 2024., this small percentage has a large impact, putting even greater pressure on health services. Brazil recorded more than one million suspected cases and dozens of deaths from dengue in 2024 until early March 2024, according to the Ministry of Health, a fairly significant increase compared to the same period in 2023.
This situation is part of a significant global increase in the disease, which has already registered five million cases in 129 countries.
The main victims
Young children and older people may find it more difficult to cope with serious infections due to immunity problems. Another important factor related to severe dengue is that it is more common in the second and third infection. Since there are four viruses that cause dengue worldwide, DENV-1, DENV-2, DENV-3 and DENV-4, a given person can be infected four times.
The chance of developing the most severe symptoms in the first infection is low, but increases in the second and third, especially among people with other diseases. This appears to be because antibodies produced by the body against one type of dengue virus facilitate the entry of a second dengue virus, which is not completely neutralized.
It would seem that these enter cells more easily and multiply more quickly. This mechanism is known as “antibody-dependent enhancement.” With the increase in the number of cases, the phenomenon requires special attention.
To avoid this situation, it is preferable to have protection against the four types of dengue viruses. In times of cyclical outbreaks, we can no longer remain uncovered. Then it will depend on vaccination to help us achieve this goal.
Single-dose vaccine
A dengue vaccine must be able to achieve high efficacy against all four viruses, be safe and ultimately help contain the spread of the virus. That is, it must induce protection against at least three and preferably against all four dengue viruses at the same time, as if it were four vaccines in one.
Offering this possibility in less time, that is, in a single dose, could be a turning point in guaranteeing complete protection more quickly, potentially stopping outbreaks and protecting those who need it most.
The Butantan Institute has been working on the development of a vaccine against dengue since the late 1990s. We recently published primary results of phase 3 of the vaccine candidate in The New England Journal of Medicine.
With a single injection it provides good protection in a very elastic age range, from two to incomplete 60 years, according to published results. It also has the advantage of being able to apply to those who have already been infected or not by the dengue virus.
Protection was observed in all age groups, with 90% in adults aged 18 to 59 years, 77.8% in those aged seven to 17 years and 80.1% in children aged two to six years. The analysis of the immunogen’s effectiveness was carried out over two years with just under 17,000 volunteers in 16 research centers. The study is in its final phase and will be completed in June 2024.
The next step will be to finalize the file with all the study information to request registration with the National Health Surveillance Agency of Brazil, Anvisa, until the second half of 2024.
At a time when dengue is advancing worldwide due to climate change, the arrival of a new single-dose vaccine to prevent epidemics and deaths could be a key weapon in the fight against dengue.
Esper Georges Kallás He is Director of the Butantan Institute and Full Professor of the Department of Infectious and Parasitic Diseases of the Faculty of Medicine of USP.
This article was first published in The conversation.