A shorter time interval between first and second dengue infections is associated with protection from clinical Illness in a school-based cohort in Thailand

Kathryn B. Anderson; Robert V. Gibbons; Derek A.T. Cummings; Ananda Nisalak; Sharone Green; Daniel H. Libraty; Richard G. Jarman; Anon Srikiatkhachorn; Mammen P. Mammen; Buddhari Darunee; In Kyu Yoon; Timothy P. Endy

doi:10.1093/infdis/jit436

A shorter time interval between first and second dengue infections is associated with protection from clinical Illness in a school-based cohort in Thailand

Kathryn B. Anderson, Robert V. Gibbons, Derek A.T. Cummings, Ananda Nisalak, Sharone Green, Daniel H. Libraty, Richard G. Jarman, Anon Srikiatkhachorn, Mammen P. Mammen, Buddhari Darunee, In Kyu Yoon, Timothy P. Endy

Medicine - Administration

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Abstract

Background. Despite the strong association between secondary dengue virus (DENV) infections and dengue hemorrhagic fever (DHF), the majority of secondary infections are subclinical or mild. The determinants of clinical severity remain unclear, though studies indicate a titer-dependent and time-dependent role of cross-protective anti-DENV antibodies.Methods. Data from 2 sequential prospective cohort studies were analyzed for subclinical and symptomatic DENV infections in schoolchildren in Kamphaeng Phet, Thailand (1998-2002 and 2004-2007). Children experiencing ≥1 DENV infection were selected as the population for analysis (contributing 2169 person-years of follow-up).Results. In total, 1696 children had ≥1 DENV infection detected during their enrollment; 268 experienced 2 or more infections. A shorter time interval between infections was associated with subclinical infection in children seronegative for DENV at enrollment, for whom a second-detected DENV infection is more likely to reflect a true second infection (average of 2.6 years between infections for DHF, 1.9 for DF, and 1.6 for subclinical infections).Conclusions. These findings support a pathogenesis model where cross-reactive antibodies wane from higher-titer, protective levels to lower-titer, detrimental levels. This is one of the first studies of human subjects to suggest a window of cross-protection following DENV infection since Sabin's challenge studies in the 1940s.

Original language	English (US)
Pages (from-to)	360-368
Number of pages	9
Journal	Journal of Infectious Diseases
Volume	209
Issue number	3
DOIs	https://doi.org/10.1093/infdis/jit436
State	Published - 2014

Bibliographical note

Funding Information:
Acknowledgments. We thank Alan Rothman, John McGowan, Ruth Berkelman, and Dana Flanders for their careful review and helpful comments on the analysis and the article. We thank the staff at the Department of Virology, Armed Forces Research Institute of Medical Science (Bangkok, Thailand) for their careful diagnostic testing and data collection and entry. We acknowledge the support of the Office of the Provincial Public Health, Kamphaeng Phet province, and the clinical research nurses at AFRIMS and the support staff at the Kamphaeng Phet Field Station for all their efforts. This project and publication was made possible by Dissertation grant 1R36CK00104 from the Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH) grant P01 AI034533, the Military Infectious Diseases Research Program (MIDRP) and the United States Army Medical Research and Materiel Command, Ft Detrick, MD, USA. The opinions expressed in this manuscript do not necessarily represent the official views of the US NIH, the US Department of Defense, or the US Department of the Army.

Funding Information:
Financial support. The clinical trial was supported by the United States Army Medical Research and Materiel Command, Ft Detrick, MD, USA. The analysis was supported by Dissertation grant 1R36CK00104 from the CDC, NIH Grant P01 AI034533, and the Military Infectious Diseases Research Program (MIDRP). The opinions expressed in this manuscript do not necessarily represent the official views of the US Department of Defense, or the US Department of the Army.

Keywords

antibodies
dengue
epidemiology
immunity
pathogenesis
prospective cohort study

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Anderson, K. B., Gibbons, R. V., Cummings, D. A. T., Nisalak, A., Green, S., Libraty, D. H., Jarman, R. G., Srikiatkhachorn, A., Mammen, M. P., Darunee, B., Yoon, I. K., & Endy, T. P. (2014). A shorter time interval between first and second dengue infections is associated with protection from clinical Illness in a school-based cohort in Thailand. Journal of Infectious Diseases, 209(3), 360-368. https://doi.org/10.1093/infdis/jit436

Anderson, KB, Gibbons, RV, Cummings, DAT, Nisalak, A, Green, S, Libraty, DH, Jarman, RG, Srikiatkhachorn, A, Mammen, MP, Darunee, B, Yoon, IK & Endy, TP 2014, 'A shorter time interval between first and second dengue infections is associated with protection from clinical Illness in a school-based cohort in Thailand', Journal of Infectious Diseases, vol. 209, no. 3, pp. 360-368. https://doi.org/10.1093/infdis/jit436

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title = "A shorter time interval between first and second dengue infections is associated with protection from clinical Illness in a school-based cohort in Thailand",

abstract = "Background. Despite the strong association between secondary dengue virus (DENV) infections and dengue hemorrhagic fever (DHF), the majority of secondary infections are subclinical or mild. The determinants of clinical severity remain unclear, though studies indicate a titer-dependent and time-dependent role of cross-protective anti-DENV antibodies.Methods. Data from 2 sequential prospective cohort studies were analyzed for subclinical and symptomatic DENV infections in schoolchildren in Kamphaeng Phet, Thailand (1998-2002 and 2004-2007). Children experiencing ≥1 DENV infection were selected as the population for analysis (contributing 2169 person-years of follow-up).Results. In total, 1696 children had ≥1 DENV infection detected during their enrollment; 268 experienced 2 or more infections. A shorter time interval between infections was associated with subclinical infection in children seronegative for DENV at enrollment, for whom a second-detected DENV infection is more likely to reflect a true second infection (average of 2.6 years between infections for DHF, 1.9 for DF, and 1.6 for subclinical infections).Conclusions. These findings support a pathogenesis model where cross-reactive antibodies wane from higher-titer, protective levels to lower-titer, detrimental levels. This is one of the first studies of human subjects to suggest a window of cross-protection following DENV infection since Sabin's challenge studies in the 1940s.",

keywords = "antibodies, dengue, epidemiology, immunity, pathogenesis, prospective cohort study",

author = "Anderson, {Kathryn B.} and Gibbons, {Robert V.} and Cummings, {Derek A.T.} and Ananda Nisalak and Sharone Green and Libraty, {Daniel H.} and Jarman, {Richard G.} and Anon Srikiatkhachorn and Mammen, {Mammen P.} and Buddhari Darunee and Yoon, {In Kyu} and Endy, {Timothy P.}",

note = "Funding Information: Acknowledgments. We thank Alan Rothman, John McGowan, Ruth Berkelman, and Dana Flanders for their careful review and helpful comments on the analysis and the article. We thank the staff at the Department of Virology, Armed Forces Research Institute of Medical Science (Bangkok, Thailand) for their careful diagnostic testing and data collection and entry. We acknowledge the support of the Office of the Provincial Public Health, Kamphaeng Phet province, and the clinical research nurses at AFRIMS and the support staff at the Kamphaeng Phet Field Station for all their efforts. This project and publication was made possible by Dissertation grant 1R36CK00104 from the Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH) grant P01 AI034533, the Military Infectious Diseases Research Program (MIDRP) and the United States Army Medical Research and Materiel Command, Ft Detrick, MD, USA. The opinions expressed in this manuscript do not necessarily represent the official views of the US NIH, the US Department of Defense, or the US Department of the Army. Funding Information: Financial support. The clinical trial was supported by the United States Army Medical Research and Materiel Command, Ft Detrick, MD, USA. The analysis was supported by Dissertation grant 1R36CK00104 from the CDC, NIH Grant P01 AI034533, and the Military Infectious Diseases Research Program (MIDRP). The opinions expressed in this manuscript do not necessarily represent the official views of the US Department of Defense, or the US Department of the Army.",

year = "2014",

doi = "10.1093/infdis/jit436",

language = "English (US)",

volume = "209",

pages = "360--368",

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TY - JOUR

T1 - A shorter time interval between first and second dengue infections is associated with protection from clinical Illness in a school-based cohort in Thailand

AU - Anderson, Kathryn B.

AU - Gibbons, Robert V.

AU - Cummings, Derek A.T.

AU - Nisalak, Ananda

AU - Green, Sharone

AU - Libraty, Daniel H.

AU - Jarman, Richard G.

AU - Srikiatkhachorn, Anon

AU - Mammen, Mammen P.

AU - Darunee, Buddhari

AU - Yoon, In Kyu

AU - Endy, Timothy P.

N1 - Funding Information: Acknowledgments. We thank Alan Rothman, John McGowan, Ruth Berkelman, and Dana Flanders for their careful review and helpful comments on the analysis and the article. We thank the staff at the Department of Virology, Armed Forces Research Institute of Medical Science (Bangkok, Thailand) for their careful diagnostic testing and data collection and entry. We acknowledge the support of the Office of the Provincial Public Health, Kamphaeng Phet province, and the clinical research nurses at AFRIMS and the support staff at the Kamphaeng Phet Field Station for all their efforts. This project and publication was made possible by Dissertation grant 1R36CK00104 from the Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH) grant P01 AI034533, the Military Infectious Diseases Research Program (MIDRP) and the United States Army Medical Research and Materiel Command, Ft Detrick, MD, USA. The opinions expressed in this manuscript do not necessarily represent the official views of the US NIH, the US Department of Defense, or the US Department of the Army. Funding Information: Financial support. The clinical trial was supported by the United States Army Medical Research and Materiel Command, Ft Detrick, MD, USA. The analysis was supported by Dissertation grant 1R36CK00104 from the CDC, NIH Grant P01 AI034533, and the Military Infectious Diseases Research Program (MIDRP). The opinions expressed in this manuscript do not necessarily represent the official views of the US Department of Defense, or the US Department of the Army.

PY - 2014

Y1 - 2014

N2 - Background. Despite the strong association between secondary dengue virus (DENV) infections and dengue hemorrhagic fever (DHF), the majority of secondary infections are subclinical or mild. The determinants of clinical severity remain unclear, though studies indicate a titer-dependent and time-dependent role of cross-protective anti-DENV antibodies.Methods. Data from 2 sequential prospective cohort studies were analyzed for subclinical and symptomatic DENV infections in schoolchildren in Kamphaeng Phet, Thailand (1998-2002 and 2004-2007). Children experiencing ≥1 DENV infection were selected as the population for analysis (contributing 2169 person-years of follow-up).Results. In total, 1696 children had ≥1 DENV infection detected during their enrollment; 268 experienced 2 or more infections. A shorter time interval between infections was associated with subclinical infection in children seronegative for DENV at enrollment, for whom a second-detected DENV infection is more likely to reflect a true second infection (average of 2.6 years between infections for DHF, 1.9 for DF, and 1.6 for subclinical infections).Conclusions. These findings support a pathogenesis model where cross-reactive antibodies wane from higher-titer, protective levels to lower-titer, detrimental levels. This is one of the first studies of human subjects to suggest a window of cross-protection following DENV infection since Sabin's challenge studies in the 1940s.

AB - Background. Despite the strong association between secondary dengue virus (DENV) infections and dengue hemorrhagic fever (DHF), the majority of secondary infections are subclinical or mild. The determinants of clinical severity remain unclear, though studies indicate a titer-dependent and time-dependent role of cross-protective anti-DENV antibodies.Methods. Data from 2 sequential prospective cohort studies were analyzed for subclinical and symptomatic DENV infections in schoolchildren in Kamphaeng Phet, Thailand (1998-2002 and 2004-2007). Children experiencing ≥1 DENV infection were selected as the population for analysis (contributing 2169 person-years of follow-up).Results. In total, 1696 children had ≥1 DENV infection detected during their enrollment; 268 experienced 2 or more infections. A shorter time interval between infections was associated with subclinical infection in children seronegative for DENV at enrollment, for whom a second-detected DENV infection is more likely to reflect a true second infection (average of 2.6 years between infections for DHF, 1.9 for DF, and 1.6 for subclinical infections).Conclusions. These findings support a pathogenesis model where cross-reactive antibodies wane from higher-titer, protective levels to lower-titer, detrimental levels. This is one of the first studies of human subjects to suggest a window of cross-protection following DENV infection since Sabin's challenge studies in the 1940s.

KW - antibodies

KW - dengue

KW - epidemiology

KW - immunity

KW - pathogenesis

KW - prospective cohort study

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SN - 0022-1899

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JO - Journal of Infectious Diseases

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A shorter time interval between first and second dengue infections is associated with protection from clinical Illness in a school-based cohort in Thailand

Abstract

Bibliographical note

Keywords

UN SDGs

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