Virus World

A new vaccine for dengue received prequalification from the World Health Organization (WHO) on 10 May 2024. TAK-003 is the second dengue vaccine to be prequalified by WHO. Developed by Takeda, it is a live-attenuated vaccine containing weakened versions of the four serotypes of the virus that cause dengue. 

WHO recommends the use of TAK-003 in children aged 6–16 years in settings with high dengue burden and transmission intensity. The vaccine should be administered in a 2-dose schedule with a 3-month interval between doses.  “The prequalification of TAK-003 is an important step in the expansion of global access to dengue vaccines, as it is now eligible for procurement by UN agencies including UNICEF and PAHO,” said Dr Rogerio Gaspar, WHO Director for Regulation and Prequalification.  “With only two dengue vaccines to date prequalified, we look forward to more vaccine developers coming forward for assessment, so that we can ensure vaccines reach all communities who need it.” The WHO prequalification list also includes CYD-TDV vaccine against dengue developed by Sanofi Pasteur.  Dengue is a vector-borne disease transmitted by the bite of an infected mosquito. Severe dengue is a potentially lethal complication which can develop from dengue infections.  It is estimated that there are over 100-400 million cases of dengue worldwide each year and 3.8 billion people living in dengue endemic countries, most of which are in Asia, Africa, and the Americas. The largest number of dengue cases reported was in 2023 with the WHO Region of the Americas reporting 4.5 million cases and 2300 deaths. Dengue cases are likely to increase and expand geographically due to climate change and urbanization.

A study led by Brazilian researchers shows that people who have had the Zika virus run a higher risk of subsequently having severe dengue and being hospitalized. The finding is highly relevant to the development of a Zika vaccine.According to the scientific literature, a second infection by any of the four known dengue serotypes is known to be typically more severe than the first, but until now no correlation between this fact and the occurrence of other diseases had been investigated. The study is published in the journal PLOS Neglected Tropical Diseases. The mechanism that exacerbates dengue infection following a case of Zika differs from that of two consecutive infections by the dengue virus, the authors conclude. The viral load is higher in the second dengue episode, with high levels of inflammatory cytokines not seen in Zika. Detection of other markers suggested that the increase in severity may be due to activation of T cells, key parts of the immune system that help produce antibodies, in a pathogenic immune response that has been termed the "original antigenic sin." The process involves so-called T-cell memory, a response in which T cells produced during a previous infection stimulate the production of more T cells to combat a new infection. Because these new cells are not specific to the virus, they trigger an excessive release of inflammatory cytokines, which attack the organism's proteins and tissues, potentially leading to hemorrhage.

The researchers analyzed samples from 1,043 laboratory-confirmed dengue patients, identifying those with prior Zika and dengue infections. The cases occurred in 2019 in São José do Rio Preto, a large city in São Paulo state, Brazil, considered hyperendemic for dengue since more than 70% of the population has had the disease. Its climate and geography favor the circulation of arboviruses throughout the year. Dengue epidemics occurred there in 2010, 2013, 2015, 2016 and 2019, with a record number of cases involving serotype 2. "We concluded that a prior dengue infection was not a risk factor for severity, probably because the patients were already into their third or fourth infection. Prior Zika infection, however, was important and an aggravating factor in a second dengue episode. This led us to suggest novel mechanisms and renew our knowledge of the natural history of the disease," Cássia Fernanda Estofolete, an infectious disease specialist at the São José do Rio Preto Medical School (FAMERP) and first author of the article, told Agência FAPESP. "Our findings confirmed the results of a previous study involving children who had Zika in Nicaragua. Later, when they had dengue, the risk of severity increased. We showed the same thing [risk of severe dengue increased by prior Zika or dengue] for adults in Brazil. We also showed that ADE [antibody-dependent enhancement, in which—instead of providing protection—antibodies enhance viral entry into host cells and can exacerbate the disease] is non-classical," said corresponding author Maurício Lacerda Nogueira. "This raises questions about the type of Zika vaccine that should be used and the optimal timing: should it be administered with a dengue vaccine in order to avoid this problem of one following the other, for example? There are various possibilities, which need to be understood to ensure correct prescription. In Brazil, it's still more important to give the dengue vaccine first because of the number of cases," added Nogueira.

Published in PLOS Neglected Diseases:

https://doi.org/10.1371/journal.pntd.0011710

Climate change is shifting the ranges of many disease-carrying species like ticks and mosquitoes. Scientists warn that the U.S. is underprepared for a potentially devastating surge in infections. In the summer and fall of 2021, West Nile virus spread rapidly through Arizona’s Maricopa County and other areas of the state. The outbreak, with more than 1,700 cases reported and 127 deaths. was the largest in the United States since the mosquito-borne virus first emerged in this country in 1999. But with the nation facing a far larger public health crisis with the Covid-19 pandemic, it went almost unnoticed. Even before Covid-19 arrived, the public health response to diseases transmitted to humans by vectors like fleas, ticks and mosquitoes — including West Nile, Zika, dengue fever, Lyme disease, and others — was muted, perhaps because the number of reported cases has been relatively low, and the public largely unaware of the health risks such diseases pose. With climate change accelerating, however, shifting the ranges of many disease-carrying species and sharply increasing infections, scientists and others warn that the nation’s public officials, as well as hospitals and doctors, are underprepared for a potentially devastating surge in infections. Research on vector-borne diseases and disease surveillance, they note, are underfunded by federal and local governments, leaving the country vulnerable to outbreaks.

“Without sustained funding in local vector control and surveillance, it ends up stymieing that response of looking for the threats before they become really huge causes for concern for local public health,” said Chelsea Gridley-Smith, director of environmental health for the National Association of County and City Health Officials (NACCHO). In the United States, cases of 17 different vector-borne diseases have been reported to the Centers for Disease Control and Prevention, and nine pathogens new to the country have been identified since 2004, according to a 2020 report by the agency, which noted that the data for 2019 and 2020 might be incomplete due to underreporting during the Covid-19 pandemic. Reported cases of vector-borne diseases more than doubled from 2004-2019, to more than 800,000 cases. But those figures are almost certainly an undercount, CDC officials said in a presentation to Congress last year. Only 2% to 3% of West Nile cases and about 10% of Lyme disease cases are reported, said Lyle Petersen, the director of the CDC’s Division of Vector-Borne Diseases in Fort Collins, Colo. Overall, cases of vector-borne diseases are probably underreported by 10-fold to 80-fold, according to Benjamin Beard, the CDC division’s deputy director.

Petersen noted that addressing vector-borne disease involves formidable challenges, including a lack of vaccines for diseases found in the continental United States; the difficulty in diagnosing some diseases in their early stages; and the sheer number of emerging pathogens. Tick-borne diseases comprise the largest share of vector-borne diseases by far — over 80% of reported cases are caused by ticks. Longer summers, rising temperatures, and the expanding ranges of tick species such as Ixodes scapularis, the black-legged tick, and Amblyomma americanum, the lone star tick, are leading to an increased chance of human exposure to pathogens over a larger geographic area. The range of Ixodes scapularis, a tick that transmits Lyme and other diseases, expanded greatly over two decades, with the number of counties with established populations more than doubling from 1996 to 2015.

Similarly, milder year-round temperatures mean that some mosquitoes may overwinter or emerge earlier in the spring. In the case of West Nile, this affects not just the mosquitoes carrying the virus but the virus itself, which replicates faster in warm temperatures. “So the mosquitoes actually are more infectious to people when they bite them,” Beard said. Nelson Nicolasora, medical director for the infectious disease program at Banner University Medical Center in Phoenix, said that while the 2021 West Nile virus outbreak was “nothing like” the Covid-19 pandemic, the illness was “life-changing” for people who suffered debilitating neurological disease. West Nile usually causes mild, flu-like symptoms, but about 1 in 150 people who are infected will develop severe neuroinvasive disease. “It can be devastating,” Nicolasora said. Two of his patients died during the 2021 outbreak, he said, and others faced serious short-term and longer-term effects: Some required a ventilator to breathe, or rehabilitation to regain the ability to walk. Irene Ruberto, vector-borne and zoonotic disease program manager at the Arizona Department of Health Services, said that even though public health officials in the state were aware of the cyclical nature of West Nile virus infections from year to year, they had no idea the infection rate would be so high in 2021. It’s difficult to predict how many infections will occur in a given year, Ruberto said, because many factors are involved, including mosquito density, local environments, and the climate.

“We do know that birds play a role,” acting as an amplifying host for the virus, Ruberto said, which adds complexity to understanding virus transmission. While West Nile is transmitted to humans by mosquitoes, mosquitoes get the virus through biting an infected wild bird. And different species of birds vary in their ability to transmit the virus once they’re infected. Ruberto said the state health department in Arizona doesn’t on its own have the funding or the capacity to analyze the 2021 outbreak to understand the factors that drove it. Instead, she said, the department is working with the CDC and universities to study the 2021 data and develop a model to predict future outbreaks. However, Ruberto said she’s even more concerned about the emergence in her state of another vector-borne disease: dengue fever. In 2022, two locally transmitted cases of dengue were discovered in Arizona, the first appearance of the disease in the state in modern times. Though dengue — known colloquially as “breakbone fever” because of the severe joint pain and muscle spasms it can cause — is also transmitted by mosquitoes, it differs from West Nile in an important way: The virus can be spread from one infected person to another person through a mosquito bite...

Scientists sent mice on scented chases and swabbed the armpits of people infected with dengue to pinpoint an odor that attracts mosquitoes. Being bit by a mosquito carrying dengue or Zika virus can make you sick. The infection can also make you even more attractive for other mosquitoes, new research finds. It’s an itchy concern for anyone infected, but also poses a major risk to communities at large: Mosquitoes that aren’t already carrying the viruses could be more drawn to sick humans, become infected, and go on to infect more humans. The spread of dengue, in particular, is a threat, with about half the world’s population at risk and hundreds of millions of cases each year. Most cases are asymptomatic, but serious cases can lead to fever and vomiting, and in some instances, organ failure or death. The study, published Thursday in Cell, identifies a specific scent emitted from both Zika- and dengue-infected mice that makes them more attractive to mosquitos than those without the viruses. It also points to a potential route to neutralize the olfactory flag. “This is a highly, highly influential study,” said Nikolaos Vasilakis, a professor of pathology at the University of Texas Medical Branch in Galveston who was not involved with the research. “I’m pretty sure it’s going to foster or spin off several new lines of experimentation to get a better understanding of what’s happening in humans.” In the experiments, performed at Tsinghua University in Beijing, mosquitos in a cage could enter a chamber with virus-infected mice or one with healthy mice. The mosquitos had no preference among the mice when the experimental group was newly infected, but on days four and six of infection, around 70% of the mosquitos flew to the infected group.  “An essential scientific question is how mosquitoes effectively orient to viremic hosts with a high frequency,” lead author Gong Cheng wrote in an email. Body temperature, carbon dioxide levels, and scent are all known factors in attracting mosquitos to a host. The researchers isolated each factor in repeated experiments to systematically eliminate temperature and carbon dioxide and identify scent as the attractant.

To determine exactly what caused the change in scent, they analyzed hundreds of potential volatile compounds emitted from the sick mice and narrowed it down to one, called acetophenone. The amount of acetophenone on the infected mice was found to be 10 times higher than on the uninfected ones. “Regarding virus-induced changes in behavior, this study is like a unicorn because of how in-depth they were able to go on all these levels,” said Megan Wise de Valdez, an associate professor of biology at Texas A&M in San Antonio, who was also not involved. She said the study’s methodology was so rigorous she plans to teach it in the classroom. Still, when it comes to results, “a mouse is a mouse is a mouse is a mouse,” said Vasilakis — meaning the stronger insights come from looking at humans. So the researchers took it a step further.  They applied acetophenone to human hands and found it had a similar effect in attracting mosquitos. And after finding that dengue patients were putting out higher levels of acetophenone than healthy people, they collected odors from the armpits of both and applied the scent extracts to filter paper. The perfumed papers were stuck to a human volunteer’s hand in the trapping chambers. Those with the odors of dengue patients attracted more mosquitos. After pinpointing the cause of the increased attraction, the researchers tested a possible solution. They’d found that when viruses like Zika or dengue invade the body, they suppress a particular antimicrobial protein on the skin that controls acetophenone. Researchers were able to reactivate that protein and stop the overproduction of acetophenone by feeding the mice isotretinoin, a vitamin A derivative often used as acne medication. After that, mosquitos fed on the treated mice less than the untreated mice. “If that holds in longitudinal studies, then there is hope that this is going to be an extremely effective tool in the arsenal that we have against infectious diseases,” said Vasilakis. The researchers will focus their next studies on both the host — by testing potential treatments to suppress acetophenone in human dengue patients — and the vector, by searching for the genetic key in mosquitos that identifies and seeks the acetophenone, and attempting to remove it. In the global effort to fight the viruses, this research lays new groundwork. But it will likely take years to decades before we have a solution as simple as a pill for patients to ward off hungry mosquitos.

Research Published in Cell (June 30, 2022):

https://www.sciencedirect.com/science/article/abs/pii/S0092867422006419 

Singapore has just begun to get its second wave of coronavirus under control. Now, it's on track to face its worst-ever outbreak of another viral infection: dengue. More than 14,000 dengue cases have been reported in the city-state since the start of the year, according to the National Environment Agency (NEA). The total number for the whole year is expected to exceed the 22,170 cases reported in 2013 -- the largest dengue outbreak in Singapore's history, the agency said.

Dengue is a viral infection transmitted by the Aedes mosquito, the same insect responsible for spreading Zika, chikungunya and yellow fever. It is commonly found in hot, wet regions of the tropics and subtropics during the rainy months. Only about 25% of those infected show symptoms, which include high fever, severe headaches, muscle and joint pains. Extreme cases can bring bleeding, breathing difficulties, organ failure, and potentially death. In Singapore, 16 people have died of dengue this year -- twice the death toll of 2013. The warmer months from June to October are traditionally peak dengue season in the city state, due to accelerated development of the Aedes mosquito and the shorter incubation period of the Dengue virus. 

Recover from dengue once, and you’re not necessarily free and clear. The mosquito-borne disease marked by fever, rash, and debilitating pain results from any of four genetically distinct versions of the dengue virus. Previously infected people who get hit with a second of these “serotypes” can face more severe, even life-threatening symptoms. Now, by endowing a line of mosquitoes with an antibody against the virus, researchers have for the first time made insects that—at least in lab tests—appear unable to spread any form of the disease. In theory, these mosquitoes could be released into the wild to suppress the circulation of the virus. “This is right on the money,” says Alexander Franz, a biologist at the University of Missouri, Columbia, who studies insect-borne viruses. “This is what you need to do if you really want to have a strong effect on dengue prevalence.”

Conventional control strategies for dengue, such as removing stagnant water where mosquitoes breed, spraying insecticides, and protecting people with bed nets, have failed to defeat the virus, which infects up to 400 million people a year in regions near the tropics. So some researchers are trying to defeat dengue from inside the mosquito that has just drunk infected blood. The goal is to keep the virus from spreading to the insect’s saliva, where it can be injected into the next person bitten....

Mosquitoes don’t make antibodies to target pathogens like we do, but giving them the ability to make one of these immune proteins could help them fight off an infection that they would otherwise pass on to people. In previous studies, researchers endowed mosquitoes that carry the malaria parasite Plasmodium with an antibody that kept the pathogen out of their saliva.

The new study applies a similar principle to the dengue virus. Molecular biologist Omar Akbari of the University of California, San Diego, and colleagues reengineered the human antidengue antibody to simplify its structure, making its gene easier to insert into the mosquito genome. They injected the slimmed-down antibody gene into the embryos of Aedes aegypti mosquitoes, which spread dengue. Then, they bred the resulting insects to make offspring with two copies of the new gene, which is activated only when blood enters the gut. After the engineered mosquitoes drank blood infected with any one of the four dengue serotypes, they had no detectable dengue virus in their saliva, the researchers report today in PLOS Pathogens.

In the lab, these genetically engineered mosquitoes could mate and produce healthy offspring. They developed slightly slower than typical mosquitoes, and the females had slightly shorter life spans, but it’s hard to gauge from these initial tests how fit these mosquitoes will be compared with their wild counterparts, Akbari says.

Overall, the work is promising, Franz says. But future tests will need to demonstrate that the dengue virus doesn’t quickly mutate and evade the antibody’s grip, and that the inserted gene is stable—able to produce the antibody in the mosquito gut generation after generation. If it does, he says, “I think this probably a winner.”

Original report Published in PLOS Pathogens (January 16, 2020):

https://doi.org/10.1371/journal.ppat.1008103

An international team of scientists have reported an effective and environmentally sustainable way to block the transmission of mosquito-borne dengue virus, in trials carried out in Malaysia. The breakthrough has major implications for countries with hot climates such as island nations in the South Pacific to Saudi Arabia, Africa and South America, all of which experience dengue, Zika, yellow fever and chikungunya.

Using a strain of the bacteria Wolbachia, which inhibit mosquitoes from transmitting viruses to humans, researchers at the Universities of Melbourne and Glasgow and the Institute for Medical Research in Malaysia were able to successfully reduce cases of dengue at sites in Kuala Lumpur. Their data, published today in Current Biology, shows that mosquitoes carrying the wAlbB strain of Wolbachia, when released into the wild, had the effect of reducing the incidence of dengue cases by 40 per cent. Previously, scientists including Professor Ary Hoffmann from the University of Melbourne, have carried out successful mosquito releases using a different strain of the Wolbachia bacteria, but while this strain was able to invade wild populations in some conditions, it did not appear to be suitable for use in the very hot conditions experienced in equatorial countries such as Malaysia. 

Now, this international team of researchers from Melbourne, Glasgow and Malaysia has shown that the wAlbB strain of Wolbachia is stable and effective, even in daily peak temperatures of 36°Celsius and higher, as commonly experienced in areas of Malaysia where dengue is prevalent. Professor Hoffmann, from Melbourne University's Bio21 Institute, said the findings could make a difference to a number of countries who have dengue. "This study provides us with a new Wolbachia strain for field release and highlights disease impact within a complex urban setting where dengue incidence rates are high. The intervention succeeded despite ongoing pesticide applications and other challenges that can make it hard for the Wolbachia to become established. The approach holds promise not only in Malaysia but also in other countries."

Each year there are around 90 million symptomatic cases of dengue, with severe disease in around 1 per cent of cases, including life-threatening haemorrhage or shock syndrome. In Malaysia alone, over 100,000 dengue cases were reported in 2016, with an annual cost estimated at $US175 million. Researchers released batches of Aedes aegypti mosquitoes carrying the wAlbB strain of Wolbachia into the wild, in six different sites in greater Kuala Lumpur with high levels of dengue transmission. The Wolbachia carrying mosquitoes - both male and female - then went on to mate with the wild mosquito population, resulting in the spread and establishment of the virus-inhibiting bacteria. In some sites, Wolbachia-carrying mosquitoes were measured at over 90 per cent frequency more than a year after the mosquito releases ended....

Published in Current Biology (November 21, 2019):

https://doi.org/10.1016/j.cub.2019.11.007

Spanish health authorities have confirmed a case of a man spreading dengue through sex, a world first for a virus which until recently was thought to be transmitted only by mosquitos. The case concerns a 41-year-old man from Madrid who contracted dengue after having sex with his male partner who picked up the virus from a mosquito bite during a trip to Cuba, said Susana Jimenez of the Madrid region's public health department. His dengue infection was confirmed in September and it puzzled doctors because he had not travelled to a country where the disease, which causes severe flu-like symptoms such as high fever and body aches, is common, she added.

"His partner presented the same symptoms as him but lighter around ten days earlier, and he had previously visited Cuba and the Dominican Republic," she said. "An analysis of their sperm was carried out and it revealed that not only did they have dengue but that it was exactly the same virus which circulates in Cuba." A "likely' case of sexual transmission of dengue between a man and a woman was the subject of a recent scientific article in South Korea, she said.

In an e-mail sent to AFP, the Stockholm-based European Centre for Disease Prevention and Control (ECDC), which monitors health and disease in Europe, said this was "to our knowledge, the first sexual transmission of the dengue virus among men who have sex with men." 

Dengue is transmitted mainly by the Aedes Aegypti mosquito, which thrives in densely-populated tropical climates and breeds in stagnant pools of water. It kills 10,000 people a year and infects over 100 million. The disease is fatal only in extreme cases but the symptoms are extremely unpleasant, including a high fever, severe headaches and vomiting. It also exacts a heavy economic burden on countries as sufferers are unable to work, as well as overwhelming health services when there is a severe outbreak. It is most serious - and deadly - in children, especially young girls. Scientists do not know why. Dengue is most commonly caught by people traveling to hotter climates such as South East Asia, Africa, Australia, the Caribbean and South and Central America. 

Better knowledge of the face of the current dengue virus (DENV) epidemiology in Africa can help to implement efficient strategies to curb the burden of dengue fever. We conducted this systematic review and meta-analysis to determine the prevalence of DENV infection in Africa. We searched PubMed, EMBASE, African Journals Online, and Africa Index Medicus from January 1st, 2000 to June 10th, 2019 without any language restriction.

We used a random-effects model to pool studies. A total of 76 studies (80,977 participants; 24 countries) were included. No study had high risk of bias. Twenty-two (29%) had moderate and 54 (71%) had low risk of bias. In apparently healthy individuals, the pooled prevalence of DENV was 15.6% (95% confidence interval 9.9–22.2), 3.5% (0.8–7.8), and 0.0% (0.0–0.5) respectively for immunoglobulins (Ig) G, IgM, and for ribonucleic acid (RNA) in apparently healthy populations. In populations presenting with fever, the prevalence was 24.8% (13.8–37.8), 10.8% (3.8–20.6k) and 8.4% (3.7–14.4) for IgG, IgM, and for RNA respectively. There was heterogeneity in the distribution between different regions of Africa.

The prevalence of DENV infection is high in the African continent. Dengue fever therefore deserves more attention from healthcare workers, researchers, and health policy makers.

Study Published on Scientific Reports (Open Access):

https://doi.org/10.1038/s41598-019-50135-x

Researchers led by Duke-NUS Medical School have discovered that tryptase, an enzyme in human cells that acts like scissors to cut up nearby proteins, is responsible for blood vessel leakage in severe dengue hemorrhagic fever. The finding suggests a possible new treatment strategy using the tryptase inhibitor, nafamostat mesylate, for severe dengue disease—a potentially fatal condition for which no targeted treatment is currently available.

The dengue virus infects about 390 million people globally each year, causing substantial morbidity and mortality. While most patients experience dengue fever or a mild form of the disease, a small percentage develops dengue hemorrhagic fever (DHF), the more severe occurrence of dengue wherein blood 'leaks' from ruptured blood vessels. This can lead to dengue shock syndrome (DSS) – the final stage of DHF—where the circulatory system fails, sending the body into bleeding and shock, which is fatal without prompt treatment. 

How dengue patients go on to develop these severe conditions had not been clearly understood and, as a result, no targeted treatments have been developed to prevent hemorrhaging or reverse shock in infected patients. "We discovered that, in severe cases, a particular enzyme called tryptase cuts the proteins that act as seals between blood vessel cells, resulting in blood vessel leakage and shock during dengue infection," said Assistant Professor Ashley St. John, from Duke-NUS' Emerging Infectious Diseases Programme, corresponding author of the study.

Based on this finding, the team wanted to know if a drug specific to inhibiting tryptase could be used to treat the hemorrhaging. Nafamostat mesylate, a clinically-approved tryptase inhibitor with a good safety profile, was tested using preclinical models. They found that administration of this drug, which is already used for the treatment of certain bleeding complications in some countries, prevented vascular leakage in the dengue model. Even delayed treatment with the drug was significantly effective in reducing dengue vascular leakage in a preclinical model of severe disease. The team also observed tryptase levels were very high in the blood of severe dengue patients who experienced DHF/DSS, but low in patients who easily recovered, affirming the link between high levels of the enzyme and severe dengue disease.

The findings were first published on July 2, 2019 in the Journal of Clinical Investigation:

https://doi.org/10.1172/JCI128426

The FDA has granted investigational new drug status to PrimeVax’s combo therapy, which uses dengue virus and dendritic cells to fight cancer. The investigational new drug (IND) application is for patients with melanoma (skin cancer) who have failed prior immune checkpoint inhibitors. Hospital sites are being prepared to start dosing patients with the therapies. 

“Today, I am proud to report that we have successfully built [the] dengue virus into our clinical design, and have gained alignment with FDA on this novel therapeutic approach,” Tony Chen, PrimeVax’s CEO, said in a press release. PrimeVax is developing a multi-mechanism treatment strategy that takes advantage of the body’s  immune system to fight malignant cells. It combines immune cells called stimulatory dendritic cells with the dengue virus to trigger a broader and stronger immune response against resistant cancer cells. 

The company established an exclusive agreement with the U.S. Army to use a specific dengue virus strain (dengue virus-1 #45AZ5) to treat cancer in January 2019. This dengue strain has a zero mortality rate and is well-tolerated. By using the Army’s dengue virus, researchers aim to induce a systemic fever in a controlled manner. This will trigger a common immune response and create a pro-inflammatory status in patients, activating the therapeutic dendritic cells to specifically target the malignant cells. To evaluate the safety and effectiveness of this strategy, the company is launching three Phase 1 clinical trials in patients with advanced melanoma. The main goal is to identify the best treatment protocol and potential safety issues. Researchers will also evaluate the anti-cancer activity of the different approaches by determining response and survival rates.

A massive upsurge in dengue cases marked by multiple outbreaks is occurring worldwide and raising new questions about who is at elevated risk of severe forms of the mosquito-transmitted disease. Incidence of the infection has increased by orders of magnitude throughout the so-called dengue belt, which encompasses Central and South America, Sub-Saharan Africa, Southeast Asia and swaths of the South Pacific, home to densely populated islands. Dengue, without question, is the most widespread and rapidly increasing vector-borne disease in the world, according to the World Health Organization. In the Americas alone, more than 5.2 million cases have been documented and more than 1,000 deaths were reported within the first three months of 2024, the Pan American Health Organization reported in April, noting a marked surge over the same period in 2023. The story is similar in other dengue-affected areas of the world where lapses in vector control have conspired with global climate change to create an explosion of bloodthirsty mosquitoes, swarms of them moving into regions once considered dengue-free. Only female mosquitoes feed on blood, they're in constant need of the nutrients in it to nurture their eggs. Now, more than two decades of dengue surveillance in Thailand is answering a slew of questions at a time when the world needs guidance most. Findings from the research have revealed how various subgroups—what virologists call subtypes—of the dengue virus influence future risk of severe infection. It has been known for years that those who become infected in subsequent outbreaks, after a usually mild bout with a first-time infection, are at significant risk of severe disease in later dengue exposures. New research finally has analyzed more than 15,000 cases to discern why that is so.

Writing in Science Translational Medicine, a global team of scientists has explained how the four dengue viral subtypes—DENV-1, 2, 3, and 4—influence the risk of repeated severe infections. The findings provide a new framework for disease monitoring and lay the foundation for vaccination strategies as the new dengue immunizations emerge. The team also underscored how dengue, a pernicious tropical malady, can be understood within the context of other common viral diseases that circle the globe. "The ability of viruses, such as SARS-CoV- 2 and influenza, to continuously change their genetic structure in response to the selective pressure of population immunity complicates control efforts," said Dr. Lin Wang, lead author of the dengue study. "In the case of dengue virus, an arbovirus that infects more than 100 million people each year, the situation is even more complex," Wang continued. "Individuals with high dengue virus antibody titers are protected from infection and developing severe disease. "However, individuals with sub-neutralizing antibody titers have been shown to have the highest risk of severe disease, through multiple hypothesized mechanisms including antibody-dependent enhancement," emphasized Wang, a researcher in the genetics department at the University of Cambridge in England. A dengue infection can be tricky. Some patients who have weathered an infection but get infected in a subsequent outbreak can have more severe symptoms the second time around. Yet, most research on repeat dengue infections has regarded each of the serotypes as no different from the other, Wang and colleagues contend, noting that an assessment of each serotype's genetic differences was needed to provide a clearer picture of potential risks.

To develop that clearer picture, researchers studied each serotype in more than 15,000 patients' infections as a way to peel away much of the mystery surrounding why first-time dengue illnesses are traditionally milder than subsequent ones. Working with Wang were collaborators from two centers in Bangkok, Thailand; multiple research institutes in the United States and one in France. To determine how each of the viral serotypes affects the risk of severe disease, Wang and colleagues analyzed viral genetic data. The team also studied cases of patients hospitalized for dengue to determine which viral subtype caused their infections. Researchers gathered data from 21 years of dengue surveillance, ranging from 1994 to 2014, in a children's hospital in Bangkok, encompassing 15,281 individual cases. This allowed them to find repeat cases and each viral subtype in all infections. Based on the pediatric patients' hospital records, researchers discovered a link between hospitalization and the order in which patients became infected with different dengue-virus serotypes. They were also able to determine which combinations of viral subtypes pointed to mild or severe forms of dengue. For instance, people who became infected with serotypes that were very similar, such as DENV-3 and DENV-4, or very different serotypes as in the case of DENV-1 and DENV-4, tended to have a lower risk of severe disease during the second infection.  That said, patients who were infected with serotypes that were only moderately different had a higher risk of severe symptoms in subsequent infections. The highest risk group in this category involved patients who had an initial infection with DENV-2 followed by a subsequent infection triggered by DENV-1.

The new research adds clarity to a disease risk that may seem paradoxical to the lay public. For example, most people infected with dengue virus for the first time develop extremely mild signs of the disease or none at all. But for those who do get sick, soaring fever, headache, body aches, nausea and rash are the primary symptoms, and they intensify in severe manifestations of the infection. For more than a century a severe bout with dengue has been known as breakbone fever because of the intensity of the pain and accompanying muscle spasms. The virus is carried in the tropics and subtropics by Aedes aegypti and Aedes albopictus mosquitoes, which are endemic in the dengue belt. But while the belt, which runs through latitudes 35-degrees North and 35-degrees South, has traditionally been home to dengue-carrying mosquitoes, the arthropods have been extending their range northward as global climate change intensifies, scientists say. Wang, meanwhile, reports that the collaborative research has set the stage to better understand immune system function in subsequent, severe dengue infections. "These findings suggest that immune imprinting helps determine dengue disease risk and provides a pathway to monitor the changing risk profile of populations and to quantifying risk profiles of candidate vaccines," Wang concluded. "This will become increasingly important as dengue vaccines begin to get used."

Research published in Science Translational Medicine (April 24, 2024):

https://doi.org/10.1126/scitranslmed.adk3259 

Dengue disease is highly prevalent in tropical and subtropical regions worldwide. However, its pathogenesis is still incompletely understood, particularly in comparison to other endemic viruses. Antibody-dependent enhancement (ADE) is a well-known phenomenon for dengue viruses. Given the recent surge in dengue cases and potential cross-reactivity with SARS-CoV-2 antibodies, this study explores the impact of anti-SARS-CoV-2 antibodies on DENV-2 infection. The study assessed the cross-reactivity of SARS-CoV-2 antibodies with the DENV-2 Virus. Human convalescent plasma samples collected during different waves of COVID-19 and monoclonal and polyclonal antibodies raised against SARS-CoV-2 were examined for their potential to cause ADE of DENV-2 infection using cell-based assays.

The study found that anti-SARS-CoV-2 antibodies acquired from natural infection in humans or through experimental immunization in animals were cross-reactive with DENV-2 and had the potential to enhance DENV-2 infection in K562 and U937 cells. In-silico and in-vitro studies indicated a strong interaction between SARS-CoV-2 antibodies and DENV-2 E-protein, providing a molecular basis for these findings. This study is the first to demonstrate that anti-SARS-CoV-2 antibodies can cross-react with DENV-2 and can enhance its infection through ADE. These findings have implications for SARS-CoV-2 vaccine development and deployment strategies in regions where dengue is endemic.

Preprint available in bioRxiV (Oct. 10, 2023):

https://doi.org/10.1101/2023.10.09.557914 

Mosquito-borne viruses increasingly threaten human populations due to accelerating changes in climate, human and mosquito migration, and land use practices. Over the last three decades, the global distribution of dengue has rapidly expanded, causing detrimental health and economic problems in many areas of the world. To develop effective disease control measures and plan for future epidemics, there is an urgent need to map the current and future transmission potential of dengue across both endemic and emerging areas. Expanding and applying Index P, a previously developed mosquito-borne viral suitability measure, we map the global climate-driven transmission potential of dengue virus transmitted by Aedes aegypti mosquitoes from 1981 to 2019. This database of dengue transmission suitability maps and an R package for Index P estimations are offered to the public health community as resources towards the identification of past, current and future transmission hotspots. These resources and the studies they facilitate can contribute to the planning of disease control and prevention strategies, especially in areas where surveillance is unreliable or non-existent.

Preprint in medRxiv (Nov. 5, 2022):

https://doi.org/10.1101/2022.11.04.22281958 

Researchers have developed a potent inhibitor of the dengue virus, which causes roughly 100 million cases of symptomatic cases of dengue fever annually. There are no antiviral agents available to prevent or treat the approximately 96 million symptomatic cases of dengue fever, annually. But the need for new treatments is growing. The disease is caused by the mosquito-borne dengue virus, which is found in nearly all (sub)tropical regions, but especially in Latin America and Asia. The frequency of outbreaks continues to grow, and the virus is expected to impact billions more in the coming decades as the virus spreads to other regions due to climate change and other global trends. Now, a group from the KU Leuven Rega Institute and Centre for Drug Design and Discovery (CD3) have developed an ultrapotent inhibitor of the dengue virus. The antiviral molecule is exceptionally effective against all known dengue variants and could be used for therapeutic and prevention purposes. This work is published in Nature in the paper, “A pan-serotype dengue virus inhibitor targeting the NS3–NS4B interaction.” 

The highly potent dengue virus inhibitor (JNJ-A07) has a unique mechanism, explained Johan Neyts, PhD, professor of virology at the Rega Institute at KU Leuven. “Together with the research group of Ralf Bartenschlager, PhD, from Heidelberg University, we demonstrated that our inhibitor prevents the interaction between two viral proteins that are part of a kind of copier for the genetic material of the virus. If this interaction is blocked, the virus can no longer copy its genetic material. As a result, no new virus particles are produced.” The antiviral exerts nanomolar to picomolar activity against a panel of 21 clinical isolates that, the group reported, “represent the natural genetic diversity of known genotypes and serotypes.” The molecule, they said, reveals a previously undescribed mechanism of antiviral action by preventing the formation of the viral replication complex by blocking the interaction between two viral proteins (NS3 and NS4B), In addition, the antiviral has a high barrier to resistance.  Research in mice suggests that the inhibitor could also be used for prevention purposes. These findings are cause for optimism, as the existing dengue vaccine only offers partial protection.

“Even a low dose of the drug administered via the oral route proved to be very effective,” noted Suzanne Kaptein, PhD, biological group leader at the Rega Institute at KU Leuven. “What is more, the treatment is still effective when the infection is already at its peak. In these cases, the number of virus particles in the blood dropped drastically within 24 hours after the start of the treatment. This goes to show how extremely potent the antiviral drug is.” “Potent and safe dengue drugs that can be easily taken as tablets could offer anyone effective protection for a certain period of time,” explained Neyts. “Think of people living in areas with an ongoing dengue outbreak, for instance: they could take a dengue drug for a couple of days or weeks. The tablets could also protect travelers or NGO workers during their stay in high-risk regions.” The antiviral drug will be developed in an easy-to-administer formulation that can be optimized for the treatment and prevention of the disease in dengue-endemic tropical and subtropical regions. The development of the antiviral was a long haul, said Neyts. “We started this project in 2009. First, we examined many thousands of molecules in a compound library of the CD3 to find one or more molecules that inhibit the virus in lab-grown cells. In other words: we started looking for a needle in a haystack. As soon as we were able to identify such molecules, the medicinal chemists at CD3 could start to work with them. They created many versions of the molecules to boost their efficacy against the virus.” There are four types of dengue viruses, and the molecule needed to be equally effective against all four of them, added Patrick Chaltin, PhD, managing director, CD3. “It was no easy feat to reach that goal: the optimization process involved about 2,000 steps. Years of intensive collaboration have now resulted in an ultra-potent dengue inhibitor that we are proud to present.”

See also original findings published in Nature (Oct. 6, 2021):

https://doi.org/10.1038/s41586-021-03990-6 

A study of Nicaraguan children links prior Zika virus infection with aggravated dengue fever symptoms. The 2015–16 Zika virus epidemic that spread through Central and South America was followed last year by a surge in dengue virus cases. While this unfortunate series of diseases battered the region’s populace, it gave scientists, who had been following a cohort of several thousand children in the area, the opportunity to study how these two flaviviruses might jointly affect the immune system. That research has revealed that kids infected with dengue virus are more likely to suffer worse symptoms if they had previously been infected with Zika than if they hadn’t. The findings, reported in Science today (August 27), indicate that antibody-dependent enhancement—a phenomenon known for making a second infection with a virus worse than the first—is not limited to influencing infections by the same pathogen. This raises concerns that such cross-species effects may occur for other types of viruses—including coronaviruses—and may impact vaccine safety, scientists say.

“It’s a pretty amazing story. [It] addresses what I think is the most important question in the field that has emerged following the Zika virus outbreak, and that is, how do Zika virus and dengue virus influence each other?” says virologist Jean Lim of the Icahn School of Medicine at Mount Sinai who was not part of the research team. Dengue and Zika viruses are closely related members of the flavivirus genus and are both transmitted to humans via the bites of infected mosquitoes. Dengue virus infection can be asymptomatic or can cause symptoms such as fever, headache, muscle aches, and rash. In some cases the disease can be severe, causing hemorrhagic fever and even shock (a dangerous drop in blood pressure). Zika virus causes a mostly mild disease—characterized by fever, rash, and joint pain—that resolves within a week, but in adults it can occasionally cause Guillain-Barré syndrome, an autoimmune condition affecting the peripheral nerves, and in pregnant women, the virus can lead to brain defects in the developing fetus including microcephaly. 

There are four strains, or serotypes, of dengue virus and infection by one type has a curious effect on infection by another, explains epidemiologist Isabel Rodriguez-Barraquer of the University of California (UC), San Francisco, who also did not work on the project. While an infection with the same serotype twice will not cause disease the second time around, if a different serotype causes the second infection, the existing antibodies fail to neutralize the virus and actually assist its entry into host cells. “The antibodies that your body builds after that first infection make the second infection worse and that’s often referred to as antibody-dependent enhancement,” Rodriquez-Barraquer says. This phenomenon is also thought to explain the worsening of disease severity seen after dengue vaccination.  Because Zika is closely related to dengue, “when Zika came along there was a question [of whether] there was going to be some sort of immunological interaction,” says UC Berkeley’s Eva Harris. And her group was in a perfect position to provide an answer, she adds, thanks to a long-standing collaboration with scientists in Nicaragua who have been monitoring infections, measuring antibody titers, and collecting other data from a rolling cohort of children since 2004.

In an earlier study, Harris’s group had shown that dengue infections preceding the Zika outbreak that started in 2015 offered a slightly protective effect against Zika severity, at least in children. Then, in 2019, when a major epidemic of dengue infections blew through the region—the worst in Nicaragua’s history—the group looked at the reverse scenario: whether prior Zika infection influenced dengue severity.  A total of 302 children of a cohort of 3,434 were diagnosed with symptomatic dengue fever between 2019 and 2020, confirmed via PCR amplification of the virus’s genetic material. By analyzing the infection history of the cohort, the team then calculated that children who had had a prior Zika infection had a roughly 12 percent chance of developing symptomatic dengue, compared with an only a 3.5 percent chance for children that had had no prior flavivirus exposure. Children who had had one prior dengue infection had a roughly 9 percent chance of later symptomatic disease. Prior Zika or dengue infection also increased the risk that a child would experience the most severe symptoms of dengue—hemorrhagic fever and shock—compared with children who had not previously had flavivirus disease, the team showed...

Published in Science (August 28, 2020):

https://doi.org/10.1126/science.abb6143

A new study led by scientists at the Walter Reed Army Institute of Research has shown for the first time that a single dose of an experimental Zika vaccine in a dengue-experienced individual can boost pre-existing flavivirus immunity and elicit protective cross-neutralizing antibody responses against both Zika and dengue viruses. Findings were published today in Nature Medicine. Researchers analyzed the antibody responses of a dengue-experienced volunteer who participated in a Phase 1 clinical trial of the WRAIR-developed Zika purified inactivated virus vaccine. They identified a potent cross-reactive antibody called MZ4 that demonstrated a potent ability to neutralize the Zika virus as well as the dengue virus serotype-2 strain. In addition, MZ4 protected against Zika and dengue in a mouse model of infection. 

"Rapid-onset countermeasures are needed to protect military personnel, travelers and residents in areas where emerging infections such as Zika and dengue viruses are already widespread and expanding," said Dr. Kayvon Modjarrad, who leads the U.S. Army Zika vaccine program, directs the Emerging Infectious Diseases Branch at WRAIR and is one of the lead authors on the paper. "These results demonstrate the potential for MZ4 to be part of the prevention toolbox for these diseases." The individual's immune profile was compared to trial volunteers who had no previous exposure to dengue virus. While the volunteer with prior dengue exposure experienced a sharp increase in antibodies that neutralize Zika and dengue viruses, following just one dose of the ZPIV vaccine, the dengue-naïve trial participants required two vaccinations to reach a similar magnitude of Zika antibody responses. Additionally, no cross-reactive antibody response to dengue virus. 

"These new findings indicate that an effective Zika vaccine could both boost dengue virus immune responses and generate potent Zika neutralizing antibodies that might have unique potential as a prevention tool in regions where both dengue and Zika are prevalent," said Dr. Shelly Krebs, a B cell researcher at WRAIR and senior author of the paper....

Published in Nat. Medicine (February 3, 2020):

https://doi.org/10.1038/s41591-019-0746-2

By folding snippets of DNA into the shape of a five-pointed star using structural DNA nanotechnology, researchers have created a trap that captures Dengue virus as it floats in the bloodstream. Once sprung, the trap—which is non-toxic and is naturally cleared from the body—lights up. It's the most sensitive test for the mosquito-borne diseases yet devised. Published today in Nature Chemistry, this detection technique could be expanded to other viruses and adapted to kill the viruses it snares.

"This is more sensitive than any other way of detecting Dengue, beating the clinical test by more than 100 fold," said Xing Wang, the corresponding author of the study, an assistant professor of chemistry and member of the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselaer Polytechnic Institute at the time of the research. "The binding is tight and the specificity is high, enabling us to distinguish the presence of Dengue on the first day of infection." A trap could be effective against many different viruses because, in order to infect their host, all viruses must first latch onto a cell wall and disgorge their genetic instructions into the cell. In 2016 research conducted at CBIS, Rensselaer chemist Robert Linhardt and Rensselaer chemical engineer Jonathan Dordick constructed a synthetic polymer configured to match a sequence of sialic acid latch points on the influenza virus. In the lung, influenza must bind to sialic acid to invade lung cells. The synthetic trap worked as a decoy, catching influenza before it latched onto lung cells.

The treatment reduced influenza A mortality in mice from 100% to 25% over 14 days. However, Linhardt and Dordick, who are both co-authors on the new study, expected that the synthetic polymer they had used as framework for the trap might prove toxic to the body and was unlikely to be accepted as a therapeutic. Structural DNA nanotechnology—an established method of folding strands of DNA into designed, customized geometric shapes and objects—offered the research team a non-toxic, biodegradable alternative on which to construct a new trap, said Wang. The spherical surface of Dengue, like the closely related Zika virus, are studded with multiple latch points to catch a cell surface.

By superimposing various DNA nanostructural shapes onto images of the virus, the team settled on a five-pointed star—they call it a "DNA star"—as the best match between points on the DNA shape and latch points on the virus. Wang took the lead on producing the DNA star. He also attached specific aptamers—molecules the viral latches will bind to—precisely to the tips and vertices of the star so that they would align with the distribution of the latches on the virus. "You could overlay the star onto the virus and target a whole hemisphere of the sphere precisely," said Wang, now at the University of Illinois at Urbana-Champaign. "All the ligands that would target the antigens of this virus would overlay perfectly with a DNA star. If we were only able to make a connection in one place it would be a weak binder, but with ten aptamers connecting the virus to the star, we have a tight hold on the target." Once bound to the virus, the DNA star starts to fluoresce, making it easily visible in a blood test....

Published in Nature Chemistry (November 25, 2019):

https://doi.org/10.1038/s41557-019-0369-8

Mosquitoes zapped with radiation to make them sterile are set to be released into the wild in a bid to fight outbreaks of dengue fever.  The World Health Organization has announced that from next year it will start large-scale studies of what is known as the sterile insect technique. This involves irradiating male Aedes mosquitoes, the species responsible for the spread of diseases such as dengue, Zika and chikungunya. The scientists hope that the sterile males will be released in such large numbers that they will overwhelm the native male population and then go on to mate with females. But they will produce no offspring so the insect population will reduce over time, alongside the number of cases of the disease. The technique has been used for about 50 years in the management of agricultural pests, such as the Mediterranean fruit fly, and experts are confident that it poses no risk to either human health or the environment. 

WHO has been working with organisations including the International Atomic Energy Agency (IAEA) and the Food and Agriculture Organisation on preliminary studies in countries including Bangladesh, Cuba, Brazil and Mauritius. Dengue fever has become a major health threat with 110 countries around the world suffering outbreaks this year. WHO believes that as many as five million cases may be reported by the end of 2019 - up from an average of three million in previous years. Urbanisation and climate change are expected to see the mosquito responsible for transmitting the disease spread to new areas.  Raman Velayudhan, coordinator of WHO’s department of neglected tropical diseases, said there was a desperate need for new tools to control the Aedes mosquito which lives in urban areas, bites during the day and whose eggs are able to survive for long periods. 

“It’s a unique mosquito which has silently expanded and today is present in over 130 countries,” he told a press conference, where the trial was announced. Experts insist the technique is safe - the mosquitoes are not “radioactive” and there is no genetic mutation. WHO also stresses that the technique will not harm the wider eco-system. There are more than 3,500 different types of mosquito that serve as food for animals so removing one species will have little impact. The IAEA is looking at refining the technique for malaria-carrying mosquitoes, although Dr Velayudhan said there were already control tools for this mosquito, such as bed nets and indoor residual spraying. 

Takeda has laid out considerable time, effort and money on its dengue vaccine program despite Sanofi's trouble with its earlier entrant. Now, the Japanese drugmaker is touting phase 3 data showing the vaccine was 80% effective at preventing dengue.

In a study called Tides, investigators tested the Takeda vaccine, TAK-003, against placebo in more than 20,000 participants aged four to 16 in dengue-endemic countries in Latin America and Asia. Twice as many participants received the vaccine as those who received placebo. In those who received both doses, the vaccine was 80.2% effective, the team reported Wednesday. Investigators tracked 61 cases of dengue in the vaccine group versus 149 in the placebo group, according to results published in The New England Journal of Medicine. 

Importantly, efficacy varied among dengue serotypes. The vaccine was 73.7% effective against dengue serotype 1, 97.7% effective against serotype 2 and 62.6% effective against serotype 3. The investigators didn't track enough serotype 4 cases to reach an efficacy determination. The shot was 95.4% effective in preventing dengue that required hospitalization; there were five hospitalizations in the vaccine group versus 53 in the placebo group. The company has said it expects phase 3 studies to form the basis for regulatory submissions. Derek Wallace, Takeda’s dengue vaccine program chief, told FiercePharma the company is “encouraged by the data” as the results demonstrate the vaccine “has a potential to have a very big impact” on the dengue burden worldwide.

Takeda is particularly pleased about the vaccine’s performance in participants who hadn't had a prior dengue infection, Wallace said. In that group, the vaccine was 74.9% effective in preventing dengue. Pharma watchers may remember that Sanofi's dengue vaccine, the world's first, tripped up because of safety problems in those who hadn't had prior infections. The French drugmaker rolled out the shot in 2016, but in late 2017, the company said a new analysis had found it could cause more serious disease in those who’d been infected before. The disclosure triggered outrage in the Philippines, where officials had started a vaccination campaign. All told, the scandal knocked Sanofi’s vaccine off its launch trajectory and the company faced numerous questions about the vaccine's safety and its rollout in the Philippines. Dengvaxia originally had blockbuster expectations, but in 2018, its sales weren’t significant enough for Sanofi to disclose. Still, Takeda isn't backing down from the dengue vaccine challenge. The company just this week opened a €130 million plant in Germany to meet global demand for the shot once it launches. The drugmaker plans to employ up to 200 workers at the plant. 

Clinical Study published in New England Journal of Medicine (November 6, 2019):

https://doi.org/10.1056/NEJMoa1903869

Mosquitoes are more likely to acquire the dengue virus when they feed on blood with low levels of iron, researchers report. Supplementing people's diets with iron in places where both iron deficiency anemia and dengue fever are a problem could potentially limit transmission of the disease, but there are risks.

Dengue fever is a disease spread by mosquitoes in the tropics, primarily Central America and northern South America, the Caribbean, sub-Saharan Africa and southeast Asia. It has also been transmitted in the southeastern US. Dengue causes a fever, rash, and terrible aches, and can also lead to shock and death. It causes about 60 million cases a year, with 18% requiring hospitalization and about 13,600 deaths, and costs about $9 billion annually worldwide. 

Dengue is most commonly acquired in urban environments, and the expansion of cities in the tropics has been accompanied by an expansion in dengue infections. A vaccine exists, but it can actually make the disease worse if given to someone who has never been previously infected. Public health officials are actively looking for ways to reduce the prevalence of the disease. 

UConn Health immunologist Penghua Wang wanted to see if blood quality had an impact on the spread of dengue virus. Blood levels of various substances can vary tremendously from person to person, even among healthy people. Wang and colleagues at Tsinghua University and State Key Laboratory of Infectious Disease Prevention and Control in Beijing, King Mongkut's Institute of Technology Ladkrabang in Bangkok, and the 920 Hospital Joint Logistics Support Force in Kunming ran a series of experiments to explore the idea.  They collected fresh blood from healthy human volunteers, then added dengue virus to each sample. Then they fed the blood to mosquitoes, and checked how many mosquitoes were infected from each batch. They found it varied quite a lot. And the variation correlated very closely with the level of iron in the blood.

"The more iron in the blood, the fewer mosquitoes were infected," says Wang. The team found it held true in a mouse model, too: mosquitoes feeding on mice infected with dengue were much more likely to acquire the virus if the mice were anemic. The reason has to do with the mosquitoes' own immune systems. Cells in a mosquito's gut take up iron in the blood and use it to produce reactive oxygen. The reactive oxygen kills the dengue virus. 

"In areas where dengue is endemic, iron deficiency is more common. It doesn't necessarily explain it, the high prevalence of dengue...but it could be possible that iron supplementation could reduce dengue transmission to mosquitoes in those areas," Wang says. But there's a big caveat. Malaria tends to be common in the same areas as dengue. And plasmodium, the microorganism that causes malaria, thrives in an iron rich environment and might actually worsen if everyone is supplementing with iron. Public health authorities need to weigh the costs and benefits before embarking on any population-wide supplementation program....

Published on September 16, 2019 in Nature Microbiology:

https://doi.org/10.1038/s41564-019-0555-x

Of Honduras' 32 public hospitals, 26 are overflowing with patients due to what health authorities are calling the worst dengue fever epidemic in the past half century. The disease has struck 28,000 people this year, of which 54, mostly children, have died.

Officials have called a national emergency to fight the dengue-causing aedes aegypti mosquito and a fumigation program has been launched in homes and public buildings. The only effective measure to halt the epidemic "is to destroy the mosquito's breeding grounds and this is something that every one of us has to do in our homes, where we work and also in every public area," said Hernandez. It's a critical situation with the three-month long rainy season about to begin, meaning that breeding grounds will soon proliferate and the mosquito's numbers could soar.