The implications of this discovery extend to public health, particularly in the development and deployment of dengue vaccine strategies.
Aedes aegypti mosquito. (Creative Commons)
Dengue, a global epidemic, contributes to over 100 million cases annually, presenting a spectrum from mild fever to severe complications like haemorrhage and shock, often leading to fatalities.
The prevailing understanding suggests that severe dengue instances primarily arise during secondary infections, attributed to antibody-dependent enhancement following a prior infection with a distinct dengue virus serotype. Despite India bearing the highest dengue burden globally, there remains limited knowledge regarding the severity of the disease and its connection to primary and secondary dengue infections.
Contrary to the commonly accepted notion that dengue poses greater severity during secondary infections, a recent collaborative study conducted by the International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi has unveiled a noteworthy occurrence of severe disease conditions in primary dengue infections.
The findings, featured in Nature Medicine, present an examination of severe dengue cases within a cohort of children in India. Surprisingly, the analysis reveals that over 50 percent of these cases can be attributed to primary infections rather than secondary ones.
The paper titled “Severe disease during both primary and secondary virus infections in pediatric populations” was authored by Dr Anmol Chandele, the Group Leader of the ICGEB-Emory Vaccine Program in collaboration with Emory School of Medicine, Atlanta, GA, USA, the All India Institute of Medical Sciences (AIIMS), New Delhi, and St John’s National Academy of Health Sciences, Bengaluru, India.
Over the last two decades, India has witnessed a substantial increase in dengue infections, establishing itself as one of the global hotspots for this disease. With four serotypes of the dengue virus, patients typically fall into two categories: those undergoing the infection for the first time, termed primary infections, and those experiencing a recurrence after a prior exposure, known as secondary infections.
Traditionally, the prevailing belief has centred around the notion that only secondary infections pose significant risks. Consequently, much of the research into vaccine development and treatment has concentrated on this group. However, this long-standing perception is now facing a challenge.
A recent comprehensive study conducted in India, employing a broad sampling approach, has unveiled a shift in perspective. The research indicates that it is not solely secondary infections that present severe risks; primary infections can also lead to critical outcomes, potentially endangering the lives of patients.
This revelation prompts a reevaluation of our understanding of dengue and the strategies implemented to combat this widespread disease.
“Dengue is a huge public health problem in India. Many patients develop severe disease that can also be sometimes fatal. However, much of the ongoing vaccine intervention research is based on the currently widely held global belief that primary dengue infections are not usually dangerous and that the severe dengue disease is mainly due to secondary dengue infections,” Dr Chandele said in a statement.
“Our study questions this currently widely held belief and shows that primary infections constitute a substantial fraction of severe disease cases and fatalities,” Dr Chandele added.
The researchers studied 619 children diagnosed with febrile dengue infections, confirmed by laboratory tests, across three hospitals in different regions of India. To distinguish between primary and secondary infections, they utilised IgM:IgG ratios determined through a dengue-specific enzyme-linked immunosorbent assay, adhering to World Health Organization guidelines.
Surprisingly, the findings revealed that primary dengue infections constituted more than half of the total clinical cases (344 out of 619), severe dengue cases (112 out of 202), and fatalities (5 out of 7).
Consistent with the classification based on binding antibody data, the study also highlighted significantly lower dengue neutralising antibody titers in primary infections compared to secondary infections. This provides valuable insights into the immune response dynamics and challenges the traditional understanding of the severity of dengue infections, particularly emphasising the substantial impact of primary infections on clinical outcomes.
The implications of this discovery extend significantly to public health, particularly in the development and deployment of secure and efficacious vaccine strategies for dengue control. These insights bear relevance not only within the Indian landscape but also globally, given the continued worldwide spread of dengue viruses.
Italy serves as a noteworthy illustration of dengue’s expanding reach, as underscored by a recent study. Dr Alessandro Marcello, the Head of the ICGEB Molecular Virology Laboratory situated in the Area Science Park in Trieste, Italy, played a collaborative role in this research. This underscores the urgency of a comprehensive and global approach in addressing the challenges posed by dengue’s proliferation.
“During 2023, in Italy we had the highest number of cases and autochthonous transmissions of dengue so far. Climate change, above all, but also the movement of people, are the biggest contributors to the circulation of dengue in new areas. The study by our Indian colleagues shows us the need to protect our population also from the first encounter with the virus,” Dr Marcello said in a statement.
The Chandele lab studies human immunology of infectious diseases, vaccine research and therapeutics. The ICGEB-Emory Vaccine Program is a unique partnership established to facilitate international collaborations in vaccine research for tackling diseases of public health importance in developing countries.
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