A preliminary study on efficacy of rupatadine for the treatment of acute dengue infection

Abstract

Currently there are no specific treatments available for acute dengue infection. We considered that rupatadine, a platelet-activating factor receptor inhibitor, might modulate dengue-associated vascular leak. The effects of rupatadine were assessed in vitro, and in a dengue model, which showed that rupatadine significantly reduced endothelial permeability by dengue sera in vitro, and significantly inhibited the increased haematocrit in dengue-infected mice with dose-dependency. We conducted a randomised, placebo-controlled trial in 183 adult patients in Sri Lanka with acute dengue, which showed that rupatadine up to 40 mg daily appeared safe and well-tolerated with similar proportions of adverse events with rupatadine and placebo. Although the primary end-point of a significant reduction in fluid leakage (development of pleural effusions or ascites) was not met, post-hoc analyses revealed small but significant differences in several parameters on individual illness days - higher platelet counts and lower aspartate-aminotransferase levels on day 7 in the rupatadine group compared to the placebo group, and smaller effusions on day 8 in the subgroup of patients with pleural effusions. However, due to the small sample size and range of recruitment time, the potential beneficial effects of rupatadine require further evaluation in large studies focused on recruitment during the early febrile phase.

MCP-1 LEVELS AND ATYPICAL LYMPHOCYTES IN EARLY FEVER OF DENGUE VIRUS INFECTION WITH NON-STRUCTURAL PROTEIN 1 (NS-1) ANTIGEN TEST IN dr DARSONO HOSPITAL, PACITAN

“…20 PAF was previously found to be an important contributor to vascular leak and PAF receptor blockade was found to inhibit the effects of acute dengue sera on the expression of the tight junction protein ZO-1, and in the reduction of trans-endothelial resistance. 15 Endocytosed DENV like particles has been proven by ultrastructural analysis of platelets from patients with dengue. In vitro studies identified the mechanisms of DENV binding and internalization by platelets requiring DC-SIGN and heparan sulfate proteoglycans for viral attachment.…”

“…Other mediators that are known to cause vascular leak include bradykinins, complement proteins C3a and C5a, IL-33, fibrin products, prostaglandins E2, F2a, and D2. 15 Hemorrhagic manifestation in Dengue virus Infection patients are not common and within mild to severe. Skin hemorrhage, including petechiae and purpura, are the most common, along with gum bleeding, epistaxis, menorrhagia, and gastrointestinal bleeding.…”

“…MCP-1 levels in the plasma of DF and DHF patients were increased significantly. 15 Monocyte Chemoattractant Protein(MCP)-1/ CCL2 is chemokine which regulates the movement of monocytes/macrophages. 16 The production of MCP-1 and monokine induced by gamma interferon (MIG) from monocytes or macrophages could be induced by interferon (IFN)-γ upon DENV infection in order to recruit more leucocytes to the site of infection for viral clearance.…”

Management of dengue infection: improving morbidity

“…Therefore rupatadine might modulate dengue-associated vascular leak acting through PAF receptors. A randomised, placebocontrolled trial in 183 adult patients in Sri Lanka with acute dengue, showed that rupatadine up to 40 mg daily appeared to be safe and well-tolerated with minimum adverse events [42]. Higher platelet counts and lower transaminase levels on day 7 were seen in the rupatadine group compared to the placebo.…”

“…Higher platelet counts and lower transaminase levels on day 7 were seen in the rupatadine group compared to the placebo. Authors concluded that the potential beneficial effect of rupatadine requires further evaluation in large studies focused on recruitment during the early febrile phase [42].…”