Dengue News: UNSW and Stanford Study Shows That Dengue Virus Targets And Causes Disruptions In Immune System Leading To Disease Severity In Some

Dengue News: Dengue fever, a mosquito-borne viral illness, affects millions of people annually, primarily in tropical and subtropical regions of the world. While most dengue cases are mild, some individuals experience a severe form of the disease that can lead to organ failure and even death. Among those most vulnerable to severe dengue are children, and until recently, the reasons behind this discrepancy remained a mystery. However, a groundbreaking collaborative study conducted by researchers from the University of New South Wales (UNSW) in Sydney, Australia, and Stanford University in the United States has shed light on this issue. Their research reveals that the dengue virus can cause disruptions in the immune system of children, leading to a phenomenon known as "immune confusion."


 
These insights from the study covered in this Dengue News report could potentially pave the way for improved diagnostic methods and targeted therapeutics to manage severe dengue cases.
 
The study's significance lies in its potential to identify early warning signs of severe dengue and to understand the mechanisms underlying the immune system's response to the virus. Dengue fever is a significant public health concern, with approximately 400 million people infected annually. The disease primarily plagues regions in Africa, Asia, and South America during the wet season.
 
Although dengue virus is not endemic in Australia, the presence of the Aedes aegypti mosquito, the primary vector for the virus, in North Queensland has led to occasional outbreaks. The researchers emphasized the importance of this study, even for regions not typically associated with dengue, as climate change can expand the habitat range of these mosquitoes, potentially increasing the risk.
 
For many years, the lack of a licensed dengue vaccine and an absence of effective antiviral treatments have left healthcare professionals with limited tools to manage severe dengue cases. Sanofi's Dengvaxia, the sole licensed dengue vaccine, faced challenges related to safety and efficacy, resulting in limited uptake. Consequently, the need for a deeper understanding of the disease's underlying mechanisms has become increasingly pressing. This collaborative study sought to address this knowledge gap, focusing on children who are at a higher risk of developing severe dengue.
 
The research involved 19 Colombian children who presented with early-stage dengue virus infection, with approximately half of them progressing to severe disease. To establish a control group, the researchers included four healthy children who were undergoing routine checkups or elective procedures. Blood samples collected on the first day the dengue-infected children presented with symptoms were subjected to advanced analysis techniques, such as single cell RNA sequencing. This innovative approach enabled the researchers to examine individual immune cells and their behavior, aiming to identify early indicators of severe dengue.
 
The collaboration between experts in immunology, clinical medicine, and specialists in data analytics and computational science was crucial to the study's success. Dr Fabio Zanini, a co-senior author of the study, bridged the gap between physics and bioinformatics to apply his expertise in medical research. Dr Shirit Einav, another co-senior author from Stanford University, brought a clinical research perspective, specializing in infectious diseases.
 
The study's findings highlighted three significant changes in the immune cells of children who progressed to severe dengue.
 
-Firstly, antigen-presenting cells, responsible for presenting virus fragments as a warning of infection, displayed altered behavior.
 
-Secondly, B cells, which usually produce antibodies to combat infections, were heavily infected with the dengue virus, impairing their ability to generate these critical defense molecules.
 
-Lastly, natural killer cells and T cells, typically responsible for attacking virus-infected cells, appeared to be in a state of quiescence or exhaustion, failing to perform their virus-killing role effectively.
 
This "immune confusion" renders the immune system ineffective in protecting the child from the dengue virus, resulting in severe disease. These findings offer a glimpse into the complex interplay of immune responses and virus interactions in severe dengue cases. Understanding these early immune system disruptions is crucial, as it can inform the development of diagnostic tests that identify patients at risk of developing severe dengue.
 
Current diagnostic methods rely on clinical parameters that become evident only late in the disease course, leading to the hospitalization and monitoring of symptomatic patients. Developing more sensitive and specific tests could optimize healthcare resources and minimize waste.
 
Moreover, the knowledge gained from this study could also be harnessed for therapeutic purposes. Targeting the identified immune system disruptions with appropriate therapeutics may prevent the progression of dengue to its severe form.
 
For example, clinicians could prescribe drugs to reactivate natural killer cells and T cells, enabling them to mount an effective defense against the virus. The potential for therapeutic interventions brings hope to the field of dengue management, which has long been plagued by limited treatment options.
 
The study represents a remarkable example of interdisciplinary collaboration, where scientists from various backgrounds came together to address a significant global health issue. Dr Zanini emphasized the importance of teamwork in advancing scientific understanding and solving complex problems. The combination of expertise in physics, bioinformatics, clinical medicine, and infectious diseases allowed the research to emerge successfully, providing valuable insights into severe dengue's pathogenesis.
 
In conclusion, dengue fever remains a significant public health concern, particularly in tropical and subtropical regions. Severe dengue cases pose a serious threat, especially to children, and understanding the mechanisms underlying this severe progression is crucial.
 
The collaborative study by researchers from UNSW Sydney and Stanford University has revealed that the dengue virus can disrupt the immune system, leading to "immune confusion." This groundbreaking insight can be used to develop more effective diagnostic tests and potentially identify patients at risk of severe dengue early in the disease course. Additionally, the study's findings pave the way for the development of targeted therapeutics to prevent the progression of dengue to its severe form, offering new hope in the fight against this challenging disease. The importance of interdisciplinary collaboration in advancing scientific knowledge is exemplified in this study, which brings together experts from various fields to tackle a pressing global health issue.
 
The study findings were published in the peer reviewed journal: Nature Immunology.
https://www.nature.com/articles/s41590-023-01654-3
 
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