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Intraepidemic increases in dengue disease severity: applying lessons on surveillance & transmission

    Scott B Halstead

    Scott B Halstead is an independent consultant. In 2010–2013, he served as Senior Advisor at the Dengue Vaccine Initiative, International Vaccine Institute (Seoul, Korea). In 2002–2010, he was Director of Supportive R&D, Pediatric Dengue Vaccine Initiative, International Vaccine Institute (Seoul, Korea). After obtaining a MD, he completed hospital training in internal medicine, and in 1957–1968 he served in the US Army Medical Corps at the Department of Virus and Rickettsial Diseases, 406th Medical General Laboratory (Sagami Ono, Japan), the Department of Virus Diseases, Walter Reed Army Institute of Research (Washington DC, USA), the Virology Department, South East Asia Treaty Organization Medical Research Laboratory (Bangkok, Thailand) and the Yale Arbovirus Research Unit (CT, USA). In 1968–1983, he was Professor and Chair, Department of Tropical Medicine and Medical Microbiology, John Burns School of Medicine, University of Hawaii at Manoa (USA). In 1983–1995, at the Rockefeller Foundation (NY, USA), he served successively as Associate, Deputy and Acting Director of the Health Sciences Division. In 1995–1999, he was Scientific Director, Infectious Diseases Program, US Navy (MD, USA) and Senior Scientist, Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University (MD, USA). He is a world leader in research on dengue and other arthropod-borne viral infections. He has published over 400 scientific papers and book chapters on many areas of vaccine research and in international health development. In 1990, while with the Rockefeller Foundation, he co-founded the Children’s Vaccine Initiative. He graduated from Yale University (CT, USA) with a BA in 1951 and from Columbia University (NY, USA) with a MD in 1955.

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    Published Online:10 Feb 2014https://doi.org/10.2217/ebo.13.741
    Abstract:

    Summary Sudden increases in disease severity, manifested in Cuba by month-to-month changes in proportion of severe to mild disease and case–fatality rates were reported among secondary dengue virus type 2 (DENV2) infections in 1981 and 1997. A similar phenomenon was described for secondary DENV3 infections in 2001. Year-to-year increases in the proportion of severe DENV2 disease have been described in Nicaragua and Taiwan. Full-length sequencing of over 200 viruses recovered from before and after pathogenicity changes in Nicaragua identified a complex stable clade change, consisting of nine amino acid changes, one each in envelope, NS3, NS4B and capsid, two in NS1 and three in NS5, as well as four changes to the nontranslated region. Secondary DENV2 infections with this clade change resulted in severe disease in children who had previously experienced DENV3 infections. A clade change was also found in the 1997 Cuban outbreak and consisted of single amino acid changes in NS1 and NS5. The NS1 change, T164S, was dominant, occurring in February and persisted to the end of the outbreak in July. This clade change was also correlated with a progressive increase in the epidemic reproductive number (R0). In Taiwan, only a silent clade change was detected between viruses recovered before and during the period of increased severity. This phenomenon provides abundant research reagents in Cuba and Nicaragua including monotypic DENV1 or DENV3 human sera and the DENV2s recovered before and after the pathogenicity changes. These should be tested in primary human myeloid cells as a useful in vitro model to study intrinsic mechanisms of antibody-dependent dengue infection enhancement.

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