Editorial commentary. Short-course oral corticosteroid therapy is not effective in early dengue infection.

Dengue is the most important mosquito-borne viral disease worldwide [1]. More than 3 billion people in >120 countries are at risk from dengue with 50–100 million infections each year, of which >2 million will have severe dengue infection, including dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Dengue is a disease with great morbidity, but fortunately only <25 000 die of the disease. Clinical manifestations vary from asymptomatic, to febrile illness, to severe dengue involving systemic plasma leakage with thrombocytopenia and coagulopathy [2]. Severe disease is usually seen at a time after viremia has reduced to low or undetectable levels, suggesting that it is an immunopathologically mediated disease [3]. Although it is clear that cells of the mononuclear phagocytic lineage are infected, our understanding of the cell and tissue tropism of dengue viruse (DENV) is limited. The disease is caused by 4 serologically and genetically related viruses, called DENV-1, DENV-2, DENV-3, and DENV-4, which are members of the flavivirus genus, whose prototype species is yellow fever virus [1, 4]. The 4 DENVs are often considered serotypes, like the 3 poliovirus serotypes; however, the 4 DENVs are distinct viral species and have the same relationships to each other as 4 members of the Japanese encephalitis complex of viruses ( Japanese encephalitis, Murray Valley encephalitis, St Louis encephalitis, and West Nile virus). Taking the above-mentioned together, it is not surprising that the development of vaccines or antiviral drugs against dengue has been and continues to be a complex issue. Currently, there are no licensed drugs or vaccines to treat or prevent dengue, although there are candidate vaccines in phase 2/3 clinical trials [5]. Even if a vaccine were available tomorrow, there would be still a need for antiviral drugs. Antiviral drug development has focused on 2 approaches: identifying candidate drugs that act specifically against virus-encoded proteins, and drug regimens that can provide supportive therapy and augment the patient’s response to the virus infection [6]. A number of candidate antiviral drugs are in advanced preclinical development and a few are in early clinical development, but none are in clinical efficacy studies. Thus, supportive therapy regimens are an area of keen interest. The study by Dong et al in this issue of Clinical Infectious Diseases, “A Randomized Placebo-Controlled Trial to Investigate the Effects of Short-Course Oral Corticosteroid Therapy in Early Dengue Infection in Vietnamese Patients,” investigates an important area of potential supportive therapy, namely, the use of oral corticosteroid therapy to combat clinical dengue disease. There have been a number of suggestions in the literature that corticosteroids may have a beneficial effect on patients following infection by viral and bacterial agents where the host immune response contributes to clinical disease. Clearly, dengue is a disease for which corticosteroids could be considered as an intervention, in particular a short course of oral steroid therapy to suppress the inflammatory response early in the disease course to reduce the potential of severe dengue disease, but this has not been studied systematically until now. Dong et al investigated the effects of short-term oral corticosteroid therapy given early in dengue infection with a randomized, placebo-controlled, blinded trial of clinical outcomes of serologically and virologically documented dengue disease in 225 children who were given either 2 days of low or high doses of oral Received 16 July 2012; accepted 24 July 2012; electronically published 3 August 2012. Correspondence: Alan D. T. Barrett, PhD, Department of Pathology, Sealy Center for Vaccine Development, Center for Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, and Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-0436 ([email protected]). Clinical Infectious Diseases 2012;55(9):1225–6 © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/cid/cis657