There is no mosquito-transmitted viral infection in the world that spreads faster than dengue, a serious public health problem in more than 100 countries.
According to the WHO, 40% of the world's population is at risk from infection with this tropical disease, which is increasingly capable of spreading in the territories where it was endemic but also in the new ones it is colonizing. While Central America, South America and Southeast Asia concentrate by far the highest viral load, in recent years dengue is spreading to new areas, such as Europe, a continent without tropical or subtropical climates until recently absolutely unknown to us. Temples of the Egyptians the mosquito that acts as the main transmitting vector.
Despite efforts to stop the ravages of this infection, experts predict that this insect responsible for its expansion will adapt increasingly better to various environments. “Global warming, changes in soil and rainfall patterns are allowing it to survive and thrive in environments and regions that were previously unfavorable,” says Luis del Carpio, a Veracruz doctor who is an expert in this disease and a member of the Mexican Society of Virology. .
With 4.1 million infections and 2,049 deaths in 2023, according to data from the Pan American Health Organization (PAHO), Latin America has never recorded higher rates than recent ones. This year, outbreaks are active in 15 countries, causing the most lethal crises in Argentina, Bolivia and Brazil, regions that reached a record number of registered cases. In Mexico, the epidemic spreads unchecked. “The latest data from the Ministry of Health reflected that those affected by this disease in the first weeks of 2024 already exceeded 5,000, up to five times more than in that same period last year, when they did not reach a thousand,” says de Carpio. , witness of how the clinical cases he deals with in his office present themselves in increasingly anomalous and worrying ways. In 2023, more than 200 people died from the bite of the cursed mosquito in Mexico, with the most affected states being Guerrero, Quintana Roo, Yucatán and Veracruz.
In the latter, accustomed to the scourge of infection, del Carpio had never observed the severity with which it is appearing, with disconcerting effects. “The symptoms used to focus on fever, headache, vomiting, muscle pain… But, since last year, the cases we treat in consultation are atypical, with worrying respiratory symptoms; patients who present dengue hepatitis or severe pneumonia. In fact, on many occasions they experience Covid-19 infections,” details the virologist. His research team is one of those responsible for discovering how DENV-3, one of the four circulating varieties of the pathogen, is the one that is gaining the most ground over the other serotypes in Mexico. “We were used to outbreaks caused by DENV-2 but it is DENV-3 that has been devastating Mexico since 2023, a change in the disease that takes us by surprise, with the appearance of more cases, of greater severity and atypical,” he declares.
“Currently the four serotypes of the virus circulate in Mexico, but before 2006 the serotypes that predominated were DENV2 and DENV3, introduced to the continent in 1982 and 1995, respectively,” explains José Manuel Reyes, from the Adolfo Ruiz Cortines National Medical Center. ”in the Port of Veracruz and also a member of the Mexican Society of Virology. Although this last variety has been associated with severe dengue since the late 1980s, its reintroduction in Brazil and its spread throughout the American continent has appeared in recent years in various forms. “Currently, it is the different genetic varieties of DENV3 that pose a great challenge for the Public Health of our country,” the researcher explains.
In addition to the four serotypes that make up the pathogen, each of them includes its own genotypes, that is, subvariations in the genome. And it is in this versatility of the infectious agent, which affects both its transmissibility and dangerousness to attack the human organism, where lies the great complexity of dealing with it. “In the case of DENV3, it is genotype 3 that is associated with these aggressive outbreaks that lead to severe symptoms in India, Africa and Latin America, suggesting a role for viral genetics in the severity of dengue. The most recent sequences of the GIII-American-I lineage of DENV-3 were reported for the first time in Mexico in 2021,” details Reyes, who has been researching the disease so difficult to eradicate for more than a decade.
So far, there are two main alternatives to deal with the infection. Colombia and Honduras, for example, have chosen to avoid being bitten by the disease through the wolbachia method: the release of aedes specimens modified with the wolbachia bacteria, incapable of transmitting dengue so that they reproduce with the local population and end up replacing it. . This method has already been tested in Mexico. “In Baja California Sur, for example, a similar control program was implemented in 2018 after a serious outbreak. But we don't know if it worked because there are no published results,” warns del Carpio.
The second scientific weapon that the authorities have are vaccines, a method that Brazil has pioneered, with more than 1,684,781 cases and hundreds of deaths so far this year, the worst data in the last four decades. To put an end to the dramatic situation, the government decided to vaccinate more than 3 million of its population with the Qdenga vaccine, becoming the first country to offer an immunizer against dengue in the universal public health system.
From the Japanese pharmaceutical company Takeda, this injection is the second to hit the market and presents many improvements than the pioneer, Dengvaxia, over which so many controversies hang over. Studies after its implementation in different countries warned of the increased risk of developing severe forms of dengue after the administration of this vaccine to people without prior contact with the virus. “Vaccinated people who had not had dengue fever would never suffer more severe effects of the disease with this vaccine,” says Reyes, recalling the various health scandals that this injection caused in some places in the world, such as in the Philippines, where after its administration, in the 2017, there was a high rate of hospitalization and death in children who had been injected with the drug.
Last year, the Federal Commission for the Protection against Sanitary Risks (Cofepris) of Mexico launched an emergency statement on the use of this immunological after having detected that this biological had been supplied to children under 9 years of age. A measure discouraged by expert organizations. Currently, Dengaxia, which does not even have an updated registry in Mexico, is only approved for the prevention of dengue in people between 9 and 45 years of age with previous dengue infection confirmed by a laboratory test. “Something so difficult to achieve in rural communities in Mexico, the places where infection is hardest hit,” says del Carpio.
“And, although the latest trials with Qdenga have shown its long-term efficacy in preventing symptomatic dengue caused by all four serotypes in previously exposed people, the data suggest a lack of efficacy against DENV-3 in those who have never been infected.” , adds Torres.
Recently, the preliminary results of a third vaccine in a phase 3 study developed by the Butantan Institute of Brazil were published. Butantan-DV consists of a single dose and appears to have promising benefits in people aged 2 to 59 years. “But the immunizer is still in the development phase. Despite the advances and availability of vaccines, there is still a need to have one that is truly safe and effective regardless of serological status, that is, regardless of whether someone has previously had the infection or not. That is why there is a lot of faith in studies with antivirals, especially to treat serious cases in Mexico. “Our country is leaning towards research with drugs with the potential to combat dengue,” says del Carpio.
Torres has been working in this field for more than a decade, explaining that “both to prevent and treat the disease, efforts are being made to position drugs already approved by the Federal Commission for the Protection against Sanitary Risks (COFEPRIS). Medications that we know are safe and are used for other diseases.” This is the case of metformin (MET), used for the treatment of type 2 diabetes, and which has already demonstrated an effect in blocking virus replication.
The study is still in the early stages. “At the moment it has only demonstrated its effect in mice, in which it reduces discomfort and lengthens life,” emphasizes Torres, part of the team involved in the search for antivirals. According to the researcher, “the most innovative of the possible treatments that are being investigated to combat dengue infection is the combination of some commonly used drugs,” such as the mixture of atorvastatin, for the prevention of cardiovascular diseases, with ivermectin. , an animal antiparasitic and to treat scabies in humans.
While laboratories are trying to develop increasingly effective solutions against the evil that plagues Latin America, both experts agree on the importance of directing efforts to the epidemiological surveillance of dengue without looking away from other associated infections. The Aedes mosquito not only transmits dengue, but also other arboviruses, such as Zika and chikungunya. “Which leads to incorrect diagnoses and subsequent diseases. Some patients may have multiple infections. And coinfections can also occur with other pathogens, such as SARS-CoV-2, enterovirus or influenza, causing exacerbated reactions,” points out Torres, part of the team that detected the first reports of patients infected at the same time with dengue and SARS-CoV. -2 reported in Mexico.
In addition to strengthening disease prevention and control systems, experts call for special attention to the crucial role that climate change is playing in both the explosion and expansion of outbreaks. “Dengue is gaining territory in the world, the responsible vectors show increasing competence, capacity and potential, and are surpassing their presence to heights never recorded and breaking paradigms. For this reason, we must not only be attentive to the alterations in clinical cases but also to the evolution of adaptation that these combative mosquitoes are making and their unpredictable behavior,” del Carpio concludes bluntly.
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