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1 August 2007

Volume 196, Number 3
The Journal of Infectious Diseases 2007;196:416–424
© 2007 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2007/19603-0012$15.00
DOI: 10.1086/519170
MAJOR ARTICLE

Maternal Antibody and Viral Factors in the Pathogenesis of Dengue Virus in Infants

Cameron P. Simmons,1

Tran Nguyen Bich Chau,1

Tran Thi Thuy,3

Nguyen Minh Tuan,2

Dang Minh Hoang,1

Nguyen Thanh Thien,2

Le Bich Lien,2

Nguyen Thien Quy,1

Nguyen Trong Hieu,4

Tran Tinh Hien,5

Catriona McElnea,7

Paul Young,6

Steve Whitehead,8

Nguyen Thanh Hung,2 and

Jeremy Farrar1

1Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 2Department of Dengue Haemorrhagic Fever, Children’s Hospital No. 1, 3Department of Infectious Diseases, Children’s Hospital No. 2, 4Department of Neonatology, Hung Vuong Hospital, and 5Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; 6School of Molecular and Microbial Sciences, University of Queensland, St. Lucia, and 7Panbio Ltd., Sinnamon Park, Brisbane, Australia; 8Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland

The pathogenesis of dengue in infants is poorly understood. We postulated that dengue severity in infants would be positively associated with markers of viral burden and that maternally derived, neutralizing anti‐dengue antibody would have decayed before the age at which infants with dengue presented to the hospital. In 75 Vietnamese infants with primary dengue, we found significant heterogeneity in viremia and NS1 antigenemia at hospital presentation, and these factors were independent of disease grade or continuous measures of disease severity. Neutralizing antibody titers, predicted in each infant at the time of their illness, suggested that the majority of infants (65%) experienced dengue hemorrhagic fever when the maternally derived neutralizing antibody titer had declined to <1:20. Collectively, these data have important implications for dengue vaccine research because they suggest that viral burden may not solely explain severe dengue in infants and that neutralizing antibody is a reasonable but not absolute marker of protective immunity in infants.

Received 10 January 2007; accepted 22 February 2007; electronically published 19 June 2007.

Reprints or correspondence: Cameron Simmons, Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 190 Ben Ham Tu, Dist. 5, Ho Chi Minh City, Vietnam ().

Cited by

Tran Nguyen Bich Chau, Nguyen Than Ha Quyen, Tran Thi Thuy, Nguyen Minh Tuan, Dang Minh Hoang, Nguyen Thi Phuong Dung, Le Bich Lien, Nguyen Thien Quy, Nguyen Trong Hieu, Lu Thi Minh Hieu, Tran Tinh Hien, Nguyen Thanh Hung, Jeremy Farrar, and Cameron P. Simmons. (2008) Dengue in Vietnamese Infants—Results of Infection-Enhancement Assays Correlate with Age-Related Disease Epidemiology, and Cellular Immune Responses Correlate with Disease Severity. The Journal of Infectious Diseases 198:4, 516-524
Online publication date: 15-Aug-2008.
Abstract-Full Text-PDF Version (435 kB)
Jeffrey M. Linnen, Elizabeth Vinelli, Ester C. Sabino, Leslie H. Tobler, Catherine Hyland, Tzong-Hae Lee, Daniel P. Kolk, Amy S. Broulik, Cynthia S. Collins, Robert S. Lanciotti, Michael P. Busch. (2008) Dengue viremia in blood donors from Honduras, Brazil, and Australia. Transfusion 48:7, 1355-1362
Online publication date: 1-Aug-2008.
CrossRef
Xia Jin. (2008) Cellular and molecular basis of antibody-dependent enhancement in human dengue pathogenesis. Future Virology 3:4, 343-361
Online publication date: 1-Aug-2008.
CrossRef

  • Potential conflicts of interest: none reported.

    Financial support: Wellcome Trust; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. The NS1‐based assays were in part supported by the Australian Research Council.

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