It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Amid record year for dengue infections, new study finds climate change responsible for 19% of today’s rising dengue burden
Second study reveals how one Brazilian city escaped a historic outbreak this year by deploying mosquitoes carrying the Wolbachia bacteria that interferes with dengue transmission
American Society of Tropical Medicine & Hygiene
NEW ORLEANS (November 16, 2024) — Climate change is having a massive global impact on dengue transmission, accounting for 19% of the current dengue burden, with a potential to spark an additional 40%-60% spike by 2050 — and by as much as 150%-200% in some areas — according to a new study presented today at the Annual Meeting of the American Society of Tropical Medicine and Hygiene (ASTMH).
The findings from researchers at Stanford and Harvard Universities offer the most definitive evidence to date that climate change is a big factor driving a global surge in the mosquito-borne disease. Countries in the Americas alone have recorded almost 12 million cases in 2024 compared to 4.6 million in 2023, and locally acquired infections have been reported in California and Florida. The study also carries warnings of even sharper increases to come.
“We looked at data on dengue incidence and climate variation across 21 countries in Asia and the Americas and found that there is a clear and direct relationship between rising temperatures and rising infections,” said Erin Mordecai, PhD, an infectious disease ecologist at Stanford’s Woods Institute for the Environment and the study’s senior author. “It’s evidence that climate change already has become a significant threat to human health and, for dengue in particular, our data suggests the impact could get much worse.”
While some dengue infections produce only mild symptoms, others cause excruciating joint pain (earning dengue the nickname “breakbone fever”), and severe cases can lead to bleeding complications and shock. There are no drugs to treat the disease and while there are two licensed dengue vaccines available, some dengue experts have pointed to challenges with both that could limit widespread adoption.
The study finds that amid dengue’s growing threat, moderating global warming by reducing emissions would also moderate climate impacts on dengue infections. The analysis shows that with sharp cuts in emissions, areas now on track to experience a 60% increase would instead see about a 40% rise in dengue infections between now and 2050. However, with global climate models predicting that temperatures will continue to increase even with large reductions in emissions, the researchers found that 17 of the 21 countries studied still would see climate-driven increases in dengue even under the most optimistic scenarios for carbon cuts.
Mordecai said the study was inspired by laboratory tests that found mosquitoes that carry dengue progressively churn out more and more virus as temperatures rise within a specific range. She said this temperature-induced bump starts at about 20 degrees Celsius (68 degrees Fahrenheit), then intensifies before peaking at about 28 or 29 C (about 82 F).
Her team then looked at 21 dengue endemic countries, including Brazil, Peru, Mexico, Colombia, Vietnam and Cambodia, which regularly collect data on infection rates. They also looked at other factors that can affect dengue infection rates — like rainfall patterns, seasonal changes, virus types, economic shocks and population density — in order to isolate whether there was a distinct temperature effect.
Mordecai said that dengue-endemic areas that are just now entering that 20 C to 29 C sweet-spot for virus transmission — parts of Peru, Mexico, Bolivia and Brazil — could face the biggest future risks, with infections over the next few decades rising 150% to 200%.
Meanwhile, the study found that areas already on the high end of the temperature range, like southern Vietnam, will experience little additional climate impacts and potentially a minor decrease. Overall, the analysis revealed that there are at least 257 million people now living in places where climate warming could cause dengue incidence to double in the next 25 years.
Mordecai said the study probably underestimates the climate-related dengue threat. That’s because researchers were unable to predict potential climate impacts on dengue-endemic areas that have not consistently tracked infections, which includes large parts of sub-Saharan Africa and South Asia. Also, Mordecai said they were unable to quantify future impacts for areas like the southern regions of the continental United States, where dengue is just starting to emerge as a local threat. “But as more and more of the U.S. moves into that optimal temperature range for dengue, the number of locally acquired infections will likely rise, though it’s too early to say how that will affect the global burden,” she said.
A Possible Solution: A Second Study Credits Common Bacteria with Protecting Brazilian City from Dengue Storm
With climate change acting as an accelerant fueling dengue’s surge, new findings presented at the ASTMH Annual Meeting provide some of the best evidence to date that releasing mosquitoes that carry a common bacteria called Wolbachia may offer a powerful tool to fend off intense outbreaks of the disease.
The study by researchers from the World Mosquito Program found that in 2024, as Brazil battled its largest dengue outbreak on record, there was only a small rise in Niterói, a city of half a million people close to Rio de Janeiro. The study credits the fact that five years ago, a partnership between the World Mosquito Program and Brazil’s Ministry of Health blanketed three-quarters of Niterói with mosquitoes infectedwith Wolbachia, a naturally occurring bacteria that has been shown to inhibit a mosquito’s ability to transmit dengue and other viruses. Deployments into the remaining areas were completed in May 2023.
“We already saw infections essentially flatline in Niterói after the Wolbachia deployment, and while there was a small increase in 2024, the caseload was still 90% lower than before the deployment — and nothing like what was happening in the rest of Brazil,” said Katie Anders, PhD, director of impact assessment at the World Mosquito Program, which has been leading a global effort to fight dengue with Wolbachia-infected mosquitoes. “The fact that Wolbachia has sustained itself in the mosquito population for years now and remained effective during a record year for dengue outbreaks shows that Wolbachia can provide long-term protection for communities against the increasingly frequent surges in dengue that we’re seeing globally.”
Anders said that since Wolbachia has been rolled out across Niterói, dengue incidence has dropped to an average of 84 cases per 100,000 people per year, compared to an average rate of 913 cases per 100,000 people per year in the 10 years pre-Wolbachia. The 1,736 dengue cases reported in Niterói from January to June 2024 represent a rate of 336 per 100,000 in 2024. That’s compared to a rate of 3,121 nationwide and 1,816 in Rio de Janeiro state during the same period. Overall, in 2024, Brazil has recorded 9.6 million dengue cases — more than twice as many as in 2023 — and 5,300 dengue-related deaths.
Other trials spearheaded by the World Mosquito Program, including large-scale releases in urban areas of Colombia and Indonesia, have reported significant reductions in dengue. They also have shown that Wolbachia is safe for humans, animals and the surrounding environment. But Anders said the protective effect documented in Niterói stands out for occurring amid such an intense wave of disease.
“In Brazil, we’re in the process of moving past Wolbachia as an experimental measure to its use as a cornerstone of dengue control,” said Luciano Moreira, PhD, the World Mosquito Program project lead in Brazil. “We’ve partnered with the Brazilian government to build a Wolbachia mosquito production facility that will enable deployment in multiple cities simultaneously — with the goal of protecting many millions of people.”
Anders noted that the production facility in Brazil is a significant step because one the biggest barriers to using Wolbachia on a large scale is that it requires releasing a large number of infected mosquitoes to spread the bacteria into the local mosquito population. She also said that governments and donors must be willing to invest with an understanding that Wolbachia is a preventative measure, not a tool for combating an ongoing outbreak — it requires a couple of years to implement and reach full effectiveness.
However, Wolbachia-infected mosquitoes transmit the bacteria to their offspring, which, according to Anders, means its protective effect could persist in a local population for many years. She said that evidence from the site of a 2011 release of Wolbachia-infectedmosquitoes in Northern Australia showed the bacteria was still present in 90% of the local mosquito population more than 10 years after releases finished.
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About the American Society of Tropical Medicine and Hygiene
The American Society of Tropical Medicine and Hygiene, founded in 1903, is the largest international scientific organization of experts dedicated to reducing the worldwide burden of tropical infectious diseases and improving global health. It accomplishes this through generating and sharing scientific evidence, informing health policies and practices, fostering career development, recognizing excellence, and advocating for investment in tropical medicine/global health research. For more information, visit astmh.org.
Thursday, February 02, 2023
Mapping Mexico’s dengue fever hotspots
Rutgers researcher co-creates tool to help identify outbreaks and prioritize virus control efforts
As many as one in five dengue fever deaths in the Americas occur in Mexico, and the rate of the disease’s severity has been increasing for decades, according to the World Health Organization. Now, a Rutgers researcher has generated data that could help curb the mosquito-borne illness in the country.
Ubydul Haque, an assistant professor of global health at the Rutgers Global Health Institute, has analyzed data from Mexico’s Ministry of Health to identify dengue fever hotspots. Working with epidemiologists at the University of North Texas and Universidad Autónoma de Nuevo León, the team calculated environmental and socioeconomic risk factors and mapped areas where severe outbreaks occur.
The findings are published in the journal Ecological Informatics.
“These maps can aid health officials in targeting fogging activities or enhancing surveillance,” Haque said. “By knowing where severe dengue fever frequently occurs, we can significantly reduce the number of cases.”
Dengue fever has been reported in 28 of 32 states in Mexico, and researchers have long known that socioeconomic status and weather affect dengue fever case counts in those states. But the factors contributing to disease severity hasn’t been studied.
Past work also has failed to account for geographic distribution of variants, or serotypes. There are four dengue virus serotypes – DENV-1, DENV-2, DENV-3 and DENV-4 – and transmissibility and lethality differ by each.
To fill these research gaps, Haque analyzed laboratory-confirmed dengue fever infections from 71,059 individuals in 2,469 Mexican municipalities collected between 2012 and 2020. Samples included serotype classification.
This data was overlaid with localized weather and socioeconomic statistics, such as literacy, access to health services, electricity and sanitation.
As expected, each degree Celsius increase in temperature was associated with lower rates of occurrence of the virus – mosquito eggs don’t hatch well in high heat – while increasing humidity was associated with an increase in the rate of each virus serotype.
Moreover, the researchers determined that lower socioeconomic status increases risk of dengue fever, and indicators such as access to education, information and infrastructure are better predictive factors of dengue fever distribution.
From this data, the researchers produced heatmaps highlighting dengue virus distribution and severity. Hotspots were generally observed in humid coastal regions at lower altitude. Throughout the country, the most prevalent serotype was DENV-2 and the least prevalent was DENV-4, Haque said.
While efforts are underway to develop DENV-specific vaccines, mosquito control programs such as fogging, and drone surveillance remain the most effective means of slowing the disease’s spread. Haque said data visualization can help health officials plan where to target their activities.
“From our data we know that DENV-2 is deadlier compared to other serotypes,” Haque said. “If regional health officials had limited resources for their control program, they could focus most of their resources in places where DENV-2 was prevalent.”
The WHO estimates dengue fever infects as many as 400 million people every year, killing thousands. With climate change predicted to increase dengue fever cases in Mexico over the coming decades, continuous surveillance of serotype patterns will be essential to preventing or slowing the rate of increase, Haque said.
The ecological determinants of severe dengue: A Bayesian inferential model
https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue Dengue and severe dengue - World Health Organization (WHO) Jan 10, 2022 ... Dengue is a mosquito-borne viral disease that has rapidly spread to all regions of WHO in recent years. Dengue virus is transmitted by female ...
https://en.wikipedia.org/wiki/Dengue_fever Dengue fever - Wikipedia Dengue fever virus (DENV) is an RNA virus ; The dengue virus genome ; Dengue virus is primarily transmitted by Aedes mosquitos, particularly A. aegypti. · These ... Dengue fever, a man-made disease
Apr 30th 1998 | JAKARTA
THE ECONOMIST
EXCERPT
SUPERSTITIOUS South-East Asians might suspect a supernatural curse. Reeling from economic turmoil, and bracing themselves for a return of the smog that forest fires last year belched over much of the region, they are also now battling the Aedes aegypti mosquito, and the disease it carries: dengue fever. In most of the tropical world, dengue is ever-present, and spreading. Last year saw the highest-ever recorded number of infected people in the Americas, with Brazil and Cuba especially badly hit. This year dengue has reached pandemic proportions in Indonesia and Thailand, and Malaysia, Cambodia and Vietnam are all experiencing serious outbreaks. Most sufferers are children. As with the smog, it is tempting, but unfair, to blame mother nature. The weather patterns brought by the El Niño effect have mucked about with the mosquito's life-cycle, just as they have delayed the rains to douse the burning trees. But dengue is a disease of urbanisation and human travel. In the words of Suchitra Nimmannitya, a Thai specialist on the disease, the infected Aedes aegypti is “a man-made mosquito”.
I faced a serious ethical dilemma while attending a couple of cases of dengue fever at a ward in the Kolkata Municipal Corporation (KMC) area during September 2013. Two patients had tested positive for dengue IgM antibody by MAC ELISA. Adjacent to their house was a vacant plot of around 1500 sq feet and this was heaped with domestic waste from the neighbouring houses. The waste comprised plastic cups, thermocol plates, plastic bags and boxes of biscuits, cakes, chips and other foodstuff, coconut shells, bicycle tyres and earthen pots. These served as a permanent breeding ground for Aedes mosquitoes, the vector for the dengue virus. The owner of the land lived elsewhere and the local people had been dumping their domestic waste here indiscriminately, without the owner’s permission. They had converted the area into an unauthorised garbage dump, despite the fact that the conservancy workers of the KMC visited the place for house collection of wastes every day.
Later, I came to know that two more NS1-reactive dengue cases had been reported from the same locality the following week. I informed the KMC health department about the matter, as dengue is a notifiable disease here. Health workers from the KMC visited the area and discovered several plastic cups, earthen pots, coconut shells and the like, which contained stagnant water. Larval and pupal stages of the Aedes species were found on the rooftops of most houses in the locality. Van-fogging of the area with adulticides was performed, as well as source reduction, followed by chemical (Temephos 50% EC) spraying in the moist areas and other possible breeding sites that could not be destroyed. Last year, there had been a dengue outbreak in the area and three deaths due to dengue shock syndrome were reported. The KMC authorities have been sending surveillance workers with information, education and communication (IEC) materials, such as handbills, to this area on a weekly basis for the past six months. They have even hired an auto-rickshaw and fitted it with a microphone to conduct IEC activities in the area twice a week. Their field workers and surveillance workers have been carrying out anti-larval activities, such as source destruction and chemical spraying, and conducting active surveillance for new cases of fever throughout the year. Further, IEC activities are being carried out through television, FM radio, newspapers, electricity bills, handbills, and so on.
Despite the above measures, people continue to dispose of waste indiscriminately, resulting in the accumulation of stagnant water. Therefore, it was evident that mere IEC and chemical spraying would not suffice; the civic authorities would need to take decisive action to improve the environment.
Despite the outbreak of dengue in the area the previous year, the residents failed to reduce the sources conducive to the breeding of mosquitoes in their own premises. Even after the enormous efforts of the KMC health department, they failed to realise how they themselves had promoted the breeding of Aedes mosquitoes. Should people have the liberty not to keep their premises clean when this can make others ill and even result in their deaths? Should the authorities, in the interest of beneficence and justice for the larger community, have the right to forcibly take action to clean up people’s premises? Should people have the right to convert others’ premises into an unauthorised dumping ground, endangering the life of others in the community? Should the authorities, in the interest of non-maleficence and justice for the owner, as well as beneficence for the community, have the right to take legal action against such transgressions? The dilemma remains unanswered.
About the Authors Subhasis Bhandari (subhasisbhandari@gmail.com) General Physician and Health Research Scholar Bhandari House, 151, Diamond Harbour Road, Behala, Kolkata 700034
Monday, September 08, 2025
Duke-NUS study reveals how dengue rewires the immune system, reshaping vaccine response
Research helps explain why vaccines work better for people with prior infection and why even an imperfect vaccine can be used safely to prevent dengue
SINGAPORE, 8 SEPTEMBER 2025—Just as a computer’s operating system can be rewritten after a major update, dengue infection can ‘re-programme’ the body’s immune system, leaving a long-lasting genetic imprint that influences how people respond to future infections—an effect not seen with vaccination.
These novel insights from a recent study shed light on the mechanics of dengue disease progression and vaccine action, filling an important knowledge gap on how even imperfect vaccines can be used safely. It also paves the way for the future development of safer and more effective dengue vaccines. The research was published in the journal Med, by scientists at Duke-NUS Medical School in collaboration with an international team of researchers.
Dengue is a mosquito-borne virus that affects millions of people in tropical and subtropical regions each year. The illness can range from a mild fever with rash to a severe, life-threatening disease involving bleeding and organ failure. As there are four different types of dengue viruses, everyone is theoretically vulnerable to being infected up to four different times in a lifetime.
Currently, dengue vaccines have limitations—they are more effective in preventing the disease in people who have been infected with dengue previously. In such individuals, vaccination protects against illness from all four types of dengue viruses. The conventional thinking is that vaccination activates memory immune cells generated from prior dengue virus infection, to boost protection against the remaining types of dengue viruses. Without such pre-existing immune cells, the quality of the immune response to vaccination is thought to be poorer.
On these grounds, vaccines that have been approved by the World Health Organization require more than one dose. Theoretically, the first dose should generate immune cells resembling those formed following a previous dengue infection. The second vaccine dose would then activate these cells to enhance protection against dengue. However, the immune response to the second dose is still lower than in those with prior infection with just one dose.
To understand how the immune response to vaccination is different from that of natural dengue virus infection, the researchers conducted a clinical trial involving 26 volunteers in the US from 2018 to 2020. Participants received two doses of a dengue vaccine[1], administered 90 days apart. The team then analysed and compared blood samples from those volunteers who had previously been infected with dengue with those who had not. To ensure wider representation, around 50 volunteers from Singapore with no recent dengue virus infection also contributed blood samples to be analysed from 2022 to 2023.
The team discovered that even before being vaccinated, those with prior dengue infection already showed distinct patterns of gene activity. Surprisingly, these gene activity patterns were not found in the memory cells that produce antibodies, but in specific types of immune cells that the dengue virus infects.
Dr Eugenia Ong, Principal Research Scientist from the Emerging Infectious Diseases Programme at Duke-NUS Medical School and first author of the study, explained:
“Our findings show that natural dengue infection can leave a lasting genetic imprint on the immune system. Instead of returning to normal, the immune system resets into a new baseline—one that may explain why second infections are often more severe.”
Because of this new baseline, the scientists found that in those who had been infected with dengue previously, the first dose of the vaccine triggered a stronger immune response than in those without a previous dengue infection. As vaccination, unlike natural infection, does not leave an imprint, the immune response in those without prior dengue virus infection remain lower than in those with prior dengue, even with two doses of the vaccine.
This long-term imprinting, also known as trained immunity, has been observed in other infections, like malaria, and after certain vaccines, such as BCG. This study adds dengue to that list and shows that both the type and intensity of infection matter.
Professor Ooi Eng Eong from the Emerging Infectious Diseases Programme at Duke-NUS Medical School and senior author of the study, explained:
“Think of it as training for a sport—the immune system only gets a real workout from the full game—the equivalent of a natural infection. A light warm-up from vaccination isn’t enough to reprogramme it. This reveals a threshold of immune response needed to leave an imprint on the immune system.”
A particular set of imprint that the researchers found involved genes that normally trigger immediate antiviral response to infection. These genes were less active in those with prior dengue infection. The dampened response means that upon vaccination (which uses a weakened viral strain), the resulting infection generates high levels of antibodies against the dengue virus. However, the dampened antiviral response may also explain why a second dengue infection with another dengue virus strain, often carries a higher risk of progressing to severe illness.
Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS Medical School, said:
“As dengue continues to affect millions across Asia, Latin America and other tropical regions, this study closes a critical gap in our understanding of how infection reshapes the immune system. These insights are vital not only for developing better vaccines but also for guiding global and national health policies. At Duke-NUS, our goal is to ensure that discoveries like these translate into real protection for the communities most at risk.”
The team hopes their work will encourage more research into the long-term effects of immune reprogramming and its impact on responses to other infections and vaccines. They also hope that this new evidence would shape advocacy and global health policies on dengue vaccines that have been approved or are close to being approved. The scientists feel it is unlikely that a perfect dengue vaccine would be developed in the next 10 years—current vaccines, although imperfect, can still be used safety to reduce the estimated 100 million cases of dengue globally each year.
Duke-NUS is Singapore’s flagship graduate entry medical school, established in 2005 with a strategic, government-led partnership between two world-class institutions: Duke University School of Medicine and the National University of Singapore (NUS). Through an innovative curriculum, students at Duke-NUS are nurtured to become multi-faceted ‘Clinicians Plus’ poised to steer the healthcare and biomedical ecosystem in Singapore and beyond. A leader in ground-breaking research and translational innovation, Duke-NUS has gained international renown through its five Signature Research Programmes and ten Centres. The enduring impact of its discoveries is amplified by its successful Academic Medicine partnership with Singapore Health Services (SingHealth), Singapore’s largest healthcare group. This strategic alliance has led to the creation of 15 Academic Clinical Programmes, which harness multi-disciplinary research and education to transform medicine and improve lives.
LA JOLLA, CA—Children who experience multiple cases of dengue virus develop an army of dengue-fighting T cells, according to a new study led by scientists at La Jolla Institute for Immunology (LJI).
The findings, published recently in JCI Insights, suggest that these T cells are key to dengue virus immunity. In fact, most children who experienced two or more dengue infections showed very minor symptoms—or no symptoms at all—when they caught the virus again.
"We saw a significant T cell response in children who had been infected more than once before," says study leader and LJI Assistant Professor Daniela Weiskopf, Ph.D.
Dengue virus infects up to 400 million people each year, and there are few vaccines and no approved therapies available for any of the four species, or "serotypes," of the virus. The researchers hope their findings can inform the development of a dengue virus vaccine that prompts a similarly strong T cell response.
This research comes as dengue-carrying mosquitos expand their territory into new regions, including Southern California. Health officials in California reported the state's first-ever case of locally acquired dengue virus in 2023. Since then, Los Angeles County has reported 12 additional cases of locally acquired dengue virus, and San Diego County has confirmed two locally acquired cases.
"Dengue virus is expanding into areas where the majority of people have never seen the virus," says Weiskopf, who is a member of LJI's Center for Vaccine Innovation. "That will change the game."
T cells help fight dengue
Weiskopf and her colleagues set out to understand how T cells might sway the severity of dengue virus infection. Are T cells helping or hurting young patients?
After all, the immune system has to strike a careful balance when fighting viruses. A weak T cell response makes it tough to fight infection. On the other hand, an overzealous T cell response can cause harmful inflammation and potentially fatal complications.
The researchers studied a group of 71 children in Managua, Nicaragua, a region where dengue virus is endemic. Since 2004, study co-author Eva Harris, Ph.D., Director of the Center for Global Public Health at UC Berkeley, has worked with Nicaraguan scientists to study dengue infections in this patient group.
These children, ages 2 to 17, come in for regular blood draws to test for antibodies against dengue virus. By detecting a rise in these antibodies, compared to the previous year, researchers can tell if a child has dealt with a past dengue virus infection. Importantly, researchers can also use the blood test to catch inapparent cases of dengue infection—where a child has been exposed to the virus but is showing no clinical symptoms.
The researchers found that the number of dengue-fighting T cells in these children builds up with each infection, and these T cells appeared to be helping the pediatric patients.
Children with a history of two or more dengue infections were much less likely to show clinical symptoms if they caught the virus again. Meanwhile, children only infected once were more likely to show clinical symptoms of disease during a later infection.
Next steps toward a life-saving vaccine
The new study may offer context for why a recent dengue virus vaccine, called Dengvaxia, appeared safe and effective in just a subset of patients at risk for dengue infection. The vaccine was only FDA-approved for children who were ages 9 to 16—and lived in a dengue-endemic area, assuming that they have experienced dengue infection by that age. Subsequent licensure in other countries required an antigen test to prove previous exposure.
The vaccine didn't work if a person hadn't been exposed to dengue virus before. Could it be that their T cells weren't ready to jump into action?
As the new study suggests, it may take multiple dengue virus exposures to gain immunity. Weiskopf says scientists will continue to investigate how to harness T cells to fight dengue virus.
"There's a lot more work to be done," says Weiskopf.
This study was supported by the National Institute of Allergy and Infectious Diseases/National Institutes of Health (grant P01 AI106695.) DOI: 10.1172/jci.insight.179771
Existing methods used to analyze the impact of climate variables on dengue fever showed that small changes in the data resulted in varying relationships between climatic factors and dengue incidence. In contrast, the recently developed GOBI method (Park et al., Nature Communications, 2023) consistently provides accurate results.
The research team led by KIM Jae Kyoung, Professor in the Department of Mathematical Sciences at KAIST and Chief Investigator of the Biomedical Mathematics Group at the Institute for Basic Science (IBS), has unveiled new insights into how weather influences the spread of dengue fever. Their study identifies temperature and rainfall as critical factors driving the global surge in dengue cases and offers actionable strategies for mitigating the disease's impact.
Dengue fever, a mosquito-borne disease, poses an increasingly alarming public health challenge. According to the World Health Organization, reported dengue cases surged from 4.1 million in 2023 to over 10.6 million in 2024 in North and South America alone. This number represents the highest global count ever reported. While climatic factors such as temperature and rainfall are known to drive this trend, their complex relationship with dengue dynamics remains poorly understood. Previous studies have struggled to reconcile conflicting findings - some suggest rainfall accelerates dengue transmission, while others indicate it suppresses it.
The IBS research team hypothesized that these inconsistencies stem from the limitations of traditional methods that focus on linear relationships or independent effects. To address this, the researchers utilized GOBI (General ODE-Based Inference), a novel causal inference framework that the IBS group developed in 2023. This method captures both nonlinear and combined effects of climatic factors, enabling a more nuanced analysis of the relationship between weather and dengue incidence.
The study focused on 16 regions of the Philippines, selected for their diverse climatic conditions, to examine how temperature and rainfall jointly affect dengue dynamics. There were distinct patterns of dengue regulation across the Philippines, driven by the combined effects of temperature and rainfall. Rising temperatures were consistently associated with higher dengue incidence across all regions. On the other hand, rainfall showed contrasting effects depending on the location of the region. In eastern areas, rainfall increased dengue incidence, while in western regions, rainfall suppressed it.
The most important factor turned out to be the variation in dry season length, which was identified as critical to explaining the contrasting effects of rainfall. In regions with low variation in dry season length, rainfall tended to flush out stagnant water, reducing mosquito breeding sites and suppressing dengue transmission. On the other hand, in regions with high variation in dry season length, sporadic rainfall created new breeding sites and weakened the flushing effect, driving an increase in mosquito populations and dengue cases.
The role of dry season length has largely been overlooked in previous research but proved to be a decisive factor in this study. This discovery offers a fresh perspective on the intricate relationship between rainfall and dengue dynamics.
To validate their findings, the researchers extended their analysis to Puerto Rico, a region with distinct climatic zones. Data from municipalities including San Juan, Adjuntas, and Ponce exhibited similar regulation patterns, underscoring the generalizability of the results.
“Our findings provide robust evidence for how climatic factors influence dengue transmission in diverse environments. This represents a significant step toward understanding how climate change may impact mosquito-borne diseases globally,” said first author Olive R. CAWIDING.
The study’s findings have immediate applications for optimizing dengue intervention strategies. For low-variation regions, natural flushing effects during the rainy season may allow for scaled-back intervention efforts, freeing resources for other priorities. Specifically, consistent and year-round intervention efforts are necessary in high-variation regions to counteract the breeding-friendly conditions created by sporadic rainfall.
Furthermore, the study highlights the importance of monitoring dry season length as a predictive factor for dengue outbreaks. By tailoring strategies to specific regional climate patterns, public health agencies can allocate resources more efficiently and effectively to combat the spread of dengue.
The study represents a significant turning point in understanding how climate change impacts not only dengue fever, but also other climate-driven diseases such as malaria, influenza, and the Zika virus.
CI KIM Jae Kyoung stated, “This research is crucial as it overcomes the limitations of traditional methods for detecting nonlinear relationships and clearly elucidates the complex interactions between climatic variables and infectious diseases through an advanced causal inference algorithm. This approach can also be applied to the analysis of various diseases linked to climate.”
While the study provides robust insights, the researchers acknowledge certain limitations, including the lack of mosquito population data and socioeconomic factors such as healthcare accessibility and human mobility. Future studies with access to more granular data, such as weekly dengue incidence and mosquito dynamics, could further refine these findings.
The study, titled “Disentangling climate’s dual role in dengue dynamics: a multi-region causal analysis study,” was published online in Science Advances, a sister journal of Science.
Figure 2. Analysis of five years of climate change and dengue fever incidence data from 16 regions in the Philippines reveals clear patterns in the relationships between climatic variables and dengue incidence
Temperature consistently acts as a key factor driving increased dengue fever incidence across all regions. In contrast, rainfall had location-dependent effects: it increased dengue incidence in the eastern regions and reduced incidence in the western regions.
In regions where the dry season length is consistent, rainfall tends to suppress dengue fever incidence, whereas in regions with inconsistent dry season duration, rainfall tends to promote dengue fever incidence.
(From left to right) Olive R. CAWIDING (IBS/KAIST, first author), CI KIM Jae Kyoung (IBS/KAIST, corresponding author).
The reemergence of dengue virus serotype 3 (DENV-3) in Brazil after 17 years could help worsen fresh outbreaks of the disease there since the population is not immunized against this serotype, and serotypes 1 and 2 (DENV-1 and DENV-2) continue to circulate.
The warning features in an article written by researchers at the São José do Rio Preto Medical School (FAMERP) in São Paulo state, and published in the Journal of Clinical Virology.
“The last significant DENV-3 epidemic in Brazil, and more specifically in São José do Rio Preto, occurred more than 15 years ago [in 2007]. DENV-1 and DENV-2 are continuously circulating in Brazil. If DENV-3 establishes itself again and the situation persists [with these serotypes co-circulating], severe forms of dengue epidemic could result. This is precisely the situation we’re experiencing right now in São José do Rio Preto,” Maurício Lacerda Nogueira, a professor at FAMERP and last author of the article, told Agência FAPESP.
For 20 years, Nogueira and colleagues have conducted a Thematic Project that is supported by FAPESP and includes genomic and epidemiological surveillance of dengue and other diseases caused by insect-born viruses (arboviruses) in São José do Rio Preto, where dengue has been endemic for several decades, with a succession of outbreaks caused by different serotypes.
“The annual average temperature in São José do Rio Preto is about 25 °C , and rainfall averages about 2,000 millimeters per year. This warm wet weather creates ideal conditions for the mosquitos that transmit arboviruses to breed and makes the city a suitable place for genomic and epidemiological monitoring of arboviruses, including dengue. We’ve been doing this for a long time, so we’re able to make reliable epidemiological inferences,” Lacerda said.
The researchers have documented a rise in cases of the disease caused by DENV-3 in the city since late 2023 via active surveillance of arboviruses in patients with dengue-like symptoms treated at Hospital de Base and UPAs (public clinics specializing in medium-complexity cases).
Thirty-one blood samples collected between November 2023 and November 2024 tested positive for DENV-3. The most common symptoms were muscle pain, headache, and fever.
“In 2023-24, we had a dengue epidemic in São José do Rio Preto, caused mainly by DENV-1 and -2. In mid-2024, DENV-1 almost disappeared, and DENV-2 became the main agent. The number of DENV-3 cases then began to rise, and it’s now the main agent in the city,” Lacerda said.
Studies conducted by other groups show that the last outbreak of dengue in Brazil, in 2021, was caused by DENV-1, and that sequential infection by DENV-3 is associated with increased severity during epidemics.
“However, we didn’t observe increased severity in the patients who participated in our study,” Lacerda said.
Need for active surveillance
The researchers also sequenced the genomes and analyzed the phylogenies of the viral isolates collected from the blood samples donated by patients with acute fever. The results of the analysis showed that the DENV-3 strain in question belonged to the same lineage as the one identified in Florida (USA) and the Caribbean, and differed from the strains of DENV-3 that circulated in Brazil in the 2000s.
These findings suggest that the outbreak of DENV-3 in Florida and the Caribbean in 2022-24 probably contributed to the introduction of the virus to Brazil and its spread throughout the country, according to the researchers.
“This demonstrates the extent to which molecular and genomic surveillance of circulating DENV strains is crucial to public health preparedness efforts and the response to the surge in cases of the disease,” Lacerda said.
Dengue transmission is widespread across tropical and subtropical regions worldwide. However, at-risk areas have expanded in past decades, owing mainly to climate change and an increased range of Aedes aegypti, the mosquito that transmits the virus, the article notes.
Brazil is the most affected country in the Americas and has long been hyperendemic for all dengue virus serotypes. In recent years, DENV-1 and -2 have been the most common serotypes in circulation. Although DENV-3 was detected during the period discussed in the article, the number of cases was very small. In fact, fewer than 100 cases were reported nationwide between 2010 and 2022. However, the number of cases reported increased in 2023, reaching 106, and jumped to 1,008 in 2024.
“We’ve been studying dengue in Brazil since 2010, and the epidemiological pattern is similar to that observed for SARS-CoV-2 during the COVID-19 pandemic. When a different serotype emerges, it escapes the population’s established immunity, and an epidemic occurs shortly afterward. We’re seeing this now with DENV-3,” Lacerda said.
About FAPESP
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the state of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration.
Scientists at Sanaria and Seattle Children’s Research Institute’s Center for Global Infectious Disease Research (CGIDR) have unveiled a groundbreaking malaria vaccine, Sanaria®PfSPZ-LARC2 Vaccine, designed to provide high-level protection with just one dose. This innovative approach leverages decades of research and cutting-edge genetic engineering to combat one of the world’s deadliest diseases.
Malaria continues to impose a devastating burden worldwide, with 263 million cases and nearly 600,000 deaths reported in 2023, most of those being in children under 5. The World Health Organization (WHO) has called for an ambitious goal of 90% protection against Plasmodium falciparum (Pf) infection. Despite significant investment and the introduction of vaccines such as RTS,S and R21, that goal has not been attained. Recent data suggest that PfSPZ-LARC2’s single-dose approach could redefine malaria prevention and elimination efforts globally and have put the WHO goal within sight.
The Science Behind the PfSPZ-LARC2 Vaccine
LARC (Late liver stage-Arresting and Replication-Competent) describes genetically weakened parasites that replicate in the liver, but halt progression before reaching the blood stage, ensuring the recipient of the vaccine remains safe, symptom-free from malaria, and protected from disease. Using advanced genetic engineering, researchers deleted two critical parasite genes, Mei2 and LINUP, from the Pf genome. These deletions ensure that the parasites replicate in the liver but cannot advance to the blood stage, rendering the vaccine incapable of causing disease or transmitting, while preserving protection.
This innovative dual-gene deletion approach builds on the team’s earlier research with PfSPZ-LARC1, in which only the Mei2 gene was deleted. By adding the LINUP deletion, the team further increased the vaccine’s safety, making LARC2 a promising candidate for widespread use. Preclinical studies have shown that LARC vaccines are significantly more potent and protective than existing options.
Promising Results and Future Trials
A pivotal study published in Nature Medicine in January 2025 showcased the remarkable potential of LARC vaccines. Researchers at Leiden University Medical Center tested a LARC1 parasite with the deletion of the Mei2 gene alone (called GA2 by the Leiden team) and demonstrated that this provided 90% protection against controlled human malaria infection (CHMI) after a single immunization via mosquito bite—an unprecedented result in malaria vaccine research.
The success of GA2 strongly validates the use of genetically weakened parasites to achieve high levels of immunity. While GA2 demonstrated exceptional efficacy with a single-gene deletion (Mei2), the PfSPZ-LARC2 Vaccine builds upon this foundation by incorporating dual deletions to ensure that PfSPZ-LARC2 preserves the protective efficacy observed in GA2 while meeting rigorous safety standards necessary for widespread use.
Although GA2 demonstrated exceptional efficacy, its administration method (via mosquito bites) cannot be used for a deployed vaccine. In contrast, the injectable PfSPZ-LARC2 Vaccine meets regulatory standards for clinical development and can be manufactured and distributed on a large scale.
Clinical trials of PfSPZ-LARC2 are scheduled for 2025 in the U.S., Germany, and Burkina Faso. These trials will evaluate the vaccine’s safety and efficacy in diverse populations and environments. Results from these trials are expected to provide critical insights into the vaccine’s global deployment potential within the next three years.
Expert Commentary
The breakthrough has garnered enthusiastic support from leading experts:
“We are excited about assessing PfSPZ-LARC2 Vaccine in Burkina Faso, as it is the only malaria vaccine in development that has the potential of achieving the WHO goal of at least 90% protection against Pf infection,” said Professor Sodiomon Sirima of GRAS (Groupe de Recherche Action en Santé) and principal investigator on the upcoming Burkina Faso trial.
“We have worked for two decades to develop a highly protective, cost-effective PfSPZ vaccine. PfSPZ vaccines have provided the highest levels of protection against controlled human malaria infection and the only malaria vaccines shown to protect against Pf infection for two years without boosting, including in pregnancy. PfSPZ-LARC2 Vaccine is our 3rd generation vaccine, and expected to be our flagship going forward,” said Dr. Stephen L. Hoffman, Sanaria’s CEO.
In a News & Views article in Nature Medicine, Dr. Stefan Kappe of CGIDR pointed out that immunization with GA2 gave unprecedented protection against malaria infection with a single shot, indicating that LARC vaccines are potentially transformational tools that could make malaria eradication with a vaccine a reality.
Addressing the Global Malaria Crisis
Despite over $4 billion in annual investments for malaria control measures, global case numbers and deaths have remained stagnant over the past decade. The WHO’s call for a vaccine that provides at least 90% protection underscores the urgent need for innovative solutions. The development of PfSPZ-LARC2 Vaccine to prevent infection, clinical disease, and transmission is timely as it comes at a time of increasing Pf drug resistance, enhancing spread of malaria due to climate change, and uncertainty of government commitments to global health, all which have the potential to lead to rapid increases in malaria cases and deaths.
PfSPZ-LARC2 Vaccine’s single-dose regimen, unparalleled protection rates, and potential for broad accessibility position it as a game-changer in global health efforts. By targeting the parasite at a critical stage of its life cycle, this vaccine could finally make malaria elimination a reality.
About Sanaria Inc.
Founded in 2003, Sanaria Inc. is dedicated to developing and commercializing whole-parasite malaria vaccines that provide high-level, long-lasting protection against Plasmodium falciparum, the primary cause of severe malaria worldwide. Sanaria’s research and development operations are headquartered in Rockville, Maryland. Learn more at sanaria.com.
Forward-Looking Statements
This news release contains certain forward-looking statements that involve known and unknown risks and uncertainties, which may cause actual results to differ materially from anticipated results or achievements expressed or implied by the statements made. Such statements include the availability of an effective vaccine, the expectations for eliminating malaria, and beliefs concerning the suitability of a successful vaccine. These forward-looking statements are further qualified by important factors that could cause actual results to differ materially from those in the forward-looking statements. These factors include, without limitation, the Company’s ability to raise sufficient funds, the regulatory approval process, clinical trials results, the Company’s patent portfolio, dependence on key personnel and other risks associated with vaccine development. For further information contact Alexander Hoffman, sanaria@sanaria.com, 301-770-3222.
