“This tiredness was so bad that I couldn’t bear it, and it’s terrible when you have to take care of a child, isn’t it? My head hurt, my eyes hurt – I couldn’t keep them open for long,” recalls Ana Luísa Braga.
The 38-year-old, a social worker and mother of a three-year-old, from Belo Horizonte, the capital of Minas Gerais state in Brazil, fell ill with dengue fever in March.
She is one of millions feeling the effects of the virus this year as the world grapples with its biggest outbreak ever. Matters have reached their end highest number on record in 2023, with 6.5 million reported worldwide – and 2024 is likely to double that figure, with 12.4 million cases so far.
The mosquitoes that spread the virus take advantage of increased urbanization, and changes in climate and temperature. At the same time, high obesity rates and other chronic health conditions make people more vulnerable, scientists say.
Dengue is sometimes known as “breakbone fever” – a description that resonated with Braga. “I consider myself to have a high pain tolerance, but the pain was so intense.”
She required hospital treatment after deteriorating to the point of vomiting and unable to eat or drink. “Even after being hospitalized for five days, I only gradually started to get better. The fatigue in particular did not leave me for about 15 days,” she says.
The World Health Organization estimates that 4 billion people are at risk of dengue and related viruses, rising to 5 billion by 2050. The rapid spread over recent years is “a worrying trend”, said Dr Tedros Adhanom Ghebreyesus, director-general of the WHO.
On October 3, he had a global strategy “to fight rising dengue” and other diseases spread by the same mosquitoes, such as Zika and chikungunya. Actions in the plan, ranging from surveillance to mosquito control efforts, will require $55m (£42m) over the next year.
Deadly combination of factors
Most of this and last year’s dengue cases are in Latin America, with high numbers also reported in parts of Africa and Southeast Asia. But infections are popping up worldwide, including in continent of Europe.
The world is facing a combination of factors, including the climate crisis, increased migration and urbanisation, says Prof Sophie Yacoub, head of the dengue research group at Oxford University’s clinical research unit in Ho Chi Minh City, Vietnam.
The mosquito species that tends to carry dengue is Aedes aegyptiespecially in Southeast Asia. But a second type can also spread the virus: Aedes albopictus – the tiger mosquito. It can survive in a wider range of temperatures, and has established itself in new areas. It is well adapted to urban environments and can breed in a small amount of standing water.
“This is what causes local transmission Europefor example, and it also pushes up to China and the southern states of America,” says Yacoub.
Changes in climate not only help mosquitoes survive in new areas, but can cause extreme weather events such as flooding, which create new breeding grounds. Heat waves can speed up reproductive cycles.
Dr Najmul Haider, a lecturer in epidemiology at Keele University, published a paper in September in the journal IJID Regions, an official journal of the International Society for Infectious Diseases, which highlights rising case numbers. He wanted, he says, “to warn that this is an alarming number and that the number is increasing”.
This is also, he says, probably an underestimate: “Remember, most of the dengue cases are asymptomatic or very mild, they don’t go to the health care system, they don’t get diagnosed, so they go undetected.”
Haider warns that there could be a second infection riskier as the first. This is because dengue fever has four different versions, known as serotypes. Each reacts differently with antibodies in human blood.
People develop immunity to the serotype with which they are first infected. But during a subsequent infection, with a different serotype, the body can produce antibodies against the first serotype it encountered. These bind to virus particles, but fail to neutralize them. Instead, they end up creating an extreme immune response, which can end in organ failure.
Part of the reason for the increase in cases in Brazil is that all four serotypes are circulating simultaneously for the first time, officials say.
Haider said the historically lower death rate of dengue than malaria, a disease spread by a different type of mosquito, made it less of a priority – especially in countries with limited resources.
However, its death rate is beginning to change, says Yacoub. “A lot of people dismissed it as another viral disease – but actually we’re seeing a higher death rate now.
“There are similar risk factors to Covid-19 – so people with obesityor diabetes, or other comorbidities have a higher risk of severe dengue and higher mortality. And I think since dengue affects many countries that also have increasing obesity or diabetes, these two pandemics are kind of colliding.
In Vietnam, she says, “we’re seeing a lot of obesity now in our teenage kids, and they’re the ones coming in [for hospital treatment]”.
Clinical trials and vaccines
There is no treatment for dengue, with hospital care typically supporting the body as it fights the infection. A trial of a promising antiviral drug developed by Johnson & Johnson was discontinued earlier this month.
Yacoub’s group is conducting trials to find out if repurposed antiviral drugs already used for other infections can be effective against dengue, and others to see if therapies that focus on changing patients’ immune responses can help. She hopes for results within the next few years.
There are also efforts to set up a large global trial looking at multiple treatments at once, similar to the recovery trial that took place during Covid-19 established that cheap steroid dexamethasone can help patients. “It would just be an ongoing recruitment platform trial across 10 different countries, with thousands of patients being enrolled,” says Yacoub. “That kind of size trial is what we need to really generate that robust evidence.”
Two dengue vaccines have made it to the market, but one, Dengvaxia, is only useful in people who have been infected – otherwise it can increase the risk of serious infection. This limits its usefulness, especially for mass vaccination campaigns.
The second, Qdenga, is seen as more promising and is used in Brazil to bring cases under control in dengue hotspots. Daniel Soranz, Rio’s municipal health secretary, says: “In the 1940s, Brazil organized itself to vaccinate the entire population against yellow fever and eradicate it. So it is possible to do the same with dengue. I believe that in five or six years, once we have the vaccine on a large scale, we will be able to eradicate dengue in Brazil.”
The traditional middle route
For now, and in the absence of new medicines, many people in hot spots use traditional remedies such as papaya tea, often on the advice of medical professionals and despite a lack of scientific evidence to support their use.
Solange Fletcher-Herbert’s 16-year-old son Sjelan contracted dengue while on holiday in Tobago. She knew avoid aspirin and ibuprofen because they may increase the risk of bleeding complications. “We started giving him Pepto-Bismol to settle his stomach, paracetamol and just coconut water to keep his electrolytes up,” she says.
After he was ill for a few days, she sought help at a private hospital near her home in Diego Martin, Trinidad. “He couldn’t eat, he was really, really sick,” she says. “They had to put him on a drip.”
When he was discharged, the family was told to focus on raising his platelets. One good friend, a doctor, suggested that they try brewing a tea with young papaya leaves for Sjelan – a remedy also endorsed by the teenager’s grandmother.
“So we got it for him, cooked it and within two days he had to go back to have his platelets tested. Within two days of drinking it, his platelets were completely back and he was doing so much better,” says Fletcher-Herbert. “Just to see him turn around, I swear by those papaya leaves. And I know many people who have had the same experience say the same thing.”
Dr Michael Head of the University of Southampton says there is some evidence that compounds in papaya may have an impact on blood clotting, but little is known about what dose would be needed to be effective.
“Given dengue is a high burden and sometimes serious infection, treatment options would be useful,” he says. “Further research into potential antiviral drugs, whether based on papaya or anything else, is likely to be necessary for long-term global control of dengue fever.”