Dengue is currently regarded as the most common arthropod-borne viral disease in tropical and subtropical areas, with an estimated 50–100 million infections occurring each year. Dengue virus infection is the cause of the debilitating diseases dengue fever and dengue hemorrhagic fever.
Mast cells are widely recognized for their immune functions and as cellular regulators of vascular integrity in human skin. Mast cells are strongly activated by the DENV virus, particularly when MCs are sensitized with heterologous anti-DENV anti-bodies during secondary infection, which results in activation and degranulation of potent vasoactive mediators pre-stored in the granules. These mediators act directly on vascular endothelium, increase permeability and induce vascular leakage – the mast cell activation levels correlate with disease severity in human patients.
Currently, no targeted treatments exist to limit vascular leakage during DENV infection. Initial clinical trials with mast cell stabilizers and leukotriene antagonists have shown moderate clinical efficacy. Our mast cell targeted therapy with a rapid and dose-dependent inhibition of mast cell activity within 60 minutes could limit severe dengue disease significantly and constitute a major advance for the clinical management of dengue fever.
The global incidence of dengue has grown dramatically in recent decades and now about 50% of the world’s population is at risk. Around 500,000 people, mostly children, are hospitalized with severe dengue each year. Every 20 minutes a life is lost to dengue. Depending on the available medical care the death rate from severe dengue varies between 1% up to as high as 20%.
- Juliet Morrisona, Abhay P. S. Rathoreb, C., Chinmay K. Mantrib, Siti A. B. Amanb, Andrew Nishidad and Ashley L. St. John: Transcriptional profiling confirms the therapeutic effects of mast cell stabilization in a dengue disease model, Journal of Virology Aug 2017, 91 (18) e00617-17;
- Berlin Londono-Renteria, Julio C. Marinez-Angarita, Andrea Troupin, and Tonya M. Colpitts: Role of mast cells in dengue virus pathogenesis, DNA and cell biology 2017 36:6, 423-427
- Diamond MS, Pierson TC. Molecular insight into Dengue virus pathogenesis and its implications for disease control. Cell. 2015;162(3):488–492. doi:10.1016/j.cell.2015.07.005
- Dengue: Falling between the cracks, the malaria consortium, 24. November 2016
- Panisadee Avirutnan, Ponpan Matangkasombut: Infectious disease: Unmasking the role of mast cells in dengue, eLife 2013;2:e00767