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1 April 2007

Volume 195, Number 7
The Journal of Infectious Diseases 2007;195:1007–1013
© 2007 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2007/19507-0014$15.00
DOI: 10.1086/511825
MAJOR ARTICLE

Natural History of Dengue Virus (DENV)–1 and DENV‐4 Infections: Reanalysis of Classic Studies

Hiroshi Nishiura1,2 and

Scott B. Halstead3,4

1Department of Medical Biometry, University of Tübingen, Tübingen, Germany; 2Research Center for Tropical Infectious Diseases, Nagasaki University Institute of Tropical Medicine, Nagasaki, Japan; 3Department of Preventive Medicine and Biometrics, Uniformed Services University of Health Sciences, Bethesda, Maryland; 4Pediatric Dengue Vaccine Initiative, International Vaccine Institute, Seoul, Korea

Background.The natural history of wild‐type dengue virus (DENV) infections of humans, including incubation and infectious periods, requires further study.

Methods.Two experimental studies in the Philippines of DENV‐4 (1924–1925) and DENV‐1 (1929–1930) were reexamined. The intrinsic incubation periods were fitted to log‐normal distribution using the maximum likelihood method, and the infectious and extrinsic incubation periods were assessed by proportions of successful transmissions causing clinically apparent dengue. Correlations between the intrinsic incubation period and other variables and univariate associations between clinical severity and serotype were also examined.

Results. incubation periods were and days for DENV‐4 and DENV‐1, respectively. Significant negative correlations were observed between the incubation period and duration of fever ( and −0.33). Even 1 and 2 days before the onset of fever, 80.0% (95% confidence interval [CI], 44.9%–100%) and 25.0% (CI, 0%–67.4%) of biting experiments caused clinically apparent dengue. DENV‐1 infections resulted in a significantly longer duration of fever than DENV‐4 infections ( ).

Conclusions.Incubation period was negatively correlated with disease severity, potentially reflecting a dose‐response mechanism. The historical data provided useful details concerning serotype differences in the natural history of primary DENV infections.

Received 1 September 2006; accepted 22 October 2006; electronically published 15 February 2007.

Reprints or correspondence: Dr. Hiroshi Nishiura, Dept. of Medical Biometry, University of Tübingen, Westbahnhofstr. 55, Tübingen, D‐72070, Germany ().

Cited by

Clive R. Seed, Philip Kiely, Catherine A. Hyland, Anthony J. Keller. (2009) The risk of dengue transmission by blood during a 2004 outbreak in Cairns, Australia. Transfusion 49:7, 1482-1487
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D. Teo, L. C. Ng, S. Lam. (2009) Is dengue a threat to the blood supply?. Transfusion Medicine 19:2, 66-77
Online publication date: 1-May-2009.
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Xia Jin. (2008) Cellular and molecular basis of antibody-dependent enhancement in human dengue pathogenesis. Future Virology 3:4, 343-361
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Hamish Mohammed, Jeffrey M. Linnen, Jorge L. Muoz-Jordn, Kay Tomashek, Gregory Foster, Amy S. Broulik, Lyle Petersen, Susan L. Stramer. (2008) Dengue virus in blood donations, Puerto Rico, 2005. Transfusion 48:7, 1348-1354
Online publication date: 1-Aug-2008.
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Scott B. Halstead. (2008) Dengue Virus–Mosquito Interactions. Annual Review of Entomology 53:1, 273-291
Online publication date: 1-Feb-2008.
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  • Potential conflicts of interest: none reported.

    Financial support: Banyu Life Science Foundation International (to H.N.).

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