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Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 1999 Apr 29;354(1384):757–768. doi: 10.1098/rstb.1999.0428

Transmission dynamics and epidemiology of dengue: insights from age-stratified sero-prevalence surveys.

N M Ferguson 1, C A Donnelly 1, R M Anderson 1
PMCID: PMC1692557  PMID: 10365401

Abstract

The relationship between infection with the four major serotypes of dengue virus and the occurrence of different forms of disease is complex and not fully understood. Interpreting longitudinal records of the incidence of serious disease to gain insight into the transmission dynamics and epidemiology of the virus is therefore complicated. Since age reflects duration of exposure, age-stratified, strain-specific serological surveys carried out at one point in time, or over a short time interval, can potentially provide a rich source of information on longitudinal patterns. This paper describes the development and application (to data collected in Thailand) of statistically rigorous methods designed to estimate time-varying, strain-specific forces of infection, and thus basic reproduction numbers, from cross-sectional serological data. The analyses provide support for the hypothesis that antibody-dependent enhancement of transmission influences observed epidemiological pattern. Age-stratified serological data also reveal evidence of a propensity for the annual incidence of infection to oscillate over time with a frequency of several years. The latter observation is consistent with the predictions of simple mathematical models of the transmission dynamics of the virus. The estimates of the basic reproduction numbers obtained are similar in magnitude for each dengue serotype, being in the range of four to six. Such values are higher than those obtained from earlier analyses, and the implications of this for dengue control are discussed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ades A. E., Nokes D. J. Modeling age- and time-specific incidence from seroprevalence:toxoplasmosis. Am J Epidemiol. 1993 May 1;137(9):1022–1034. doi: 10.1093/oxfordjournals.aje.a116758. [DOI] [PubMed] [Google Scholar]
  2. Anderson R. M., May R. M. Age-related changes in the rate of disease transmission: implications for the design of vaccination programmes. J Hyg (Lond) 1985 Jun;94(3):365–436. doi: 10.1017/s002217240006160x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Briseño-García B., Gómez-Dantés H., Argott-Ramírez E., Montesano R., Vázquez-Martínez A. L., Ibáez-Bernal S., Madrigal-Ayala G., Ruíz-Matus C., Flisser A., Tapia-Conyer R. Potential risk for dengue hemorrhagic fever: the isolation of serotype dengue-3 in Mexico. Emerg Infect Dis. 1996 Apr-Jun;2(2):133–135. doi: 10.3201/eid0202.960210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dietz K., Schenzle D. Proportionate mixing models for age-dependent infection transmission. J Math Biol. 1985;22(1):117–120. doi: 10.1007/BF00276550. [DOI] [PubMed] [Google Scholar]
  5. Dove A. Dengue fever on the increase. Nat Med. 1998 May;4(5):543–543. doi: 10.1038/nm0598-543b. [DOI] [PubMed] [Google Scholar]
  6. Ferguson N., Anderson R., Gupta S. The effect of antibody-dependent enhancement on the transmission dynamics and persistence of multiple-strain pathogens. Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):790–794. doi: 10.1073/pnas.96.2.790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Grenfell B. T., Anderson R. M. The estimation of age-related rates of infection from case notifications and serological data. J Hyg (Lond) 1985 Oct;95(2):419–436. doi: 10.1017/s0022172400062859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gritsun T. S., Holmes E. C., Gould E. A. Analysis of flavivirus envelope proteins reveals variable domains that reflect their antigenicity and may determine their pathogenesis. Virus Res. 1995 Mar;35(3):307–321. doi: 10.1016/0168-1702(94)00090-y. [DOI] [PubMed] [Google Scholar]
  9. Gubler D. J. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev. 1998 Jul;11(3):480–496. doi: 10.1128/cmr.11.3.480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gupta S., Ferguson N., Anderson R. Chaos, persistence, and evolution of strain structure in antigenically diverse infectious agents. Science. 1998 May 8;280(5365):912–915. doi: 10.1126/science.280.5365.912. [DOI] [PubMed] [Google Scholar]
  11. Gupta S., Trenholme K., Anderson R. M., Day K. P. Antigenic diversity and the transmission dynamics of Plasmodium falciparum. Science. 1994 Feb 18;263(5149):961–963. doi: 10.1126/science.8310293. [DOI] [PubMed] [Google Scholar]
  12. Halstead S. B., Chow J. S., Marchette N. J. Immunological enhancement of dengue virus replication. Nat New Biol. 1973 May 2;243(122):24–26. [PubMed] [Google Scholar]
  13. Halstead S. B. Immune enhancement of viral infection. Prog Allergy. 1982;31:301–364. [PubMed] [Google Scholar]
  14. Halstead S. B. In vivo enhancement of dengue virus infection in rhesus monkeys by passively transferred antibody. J Infect Dis. 1979 Oct;140(4):527–533. doi: 10.1093/infdis/140.4.527. [DOI] [PubMed] [Google Scholar]
  15. Halstead S. B., O'Rourke E. J., Allison A. C. Dengue viruses and mononuclear phagocytes. II. Identity of blood and tissue leukocytes supporting in vitro infection. J Exp Med. 1977 Jul 1;146(1):218–229. doi: 10.1084/jem.146.1.218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Halstead S. B., O'Rourke E. J. Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody. J Exp Med. 1977 Jul 1;146(1):201–217. doi: 10.1084/jem.146.1.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Halstead S. B. Pathogenesis of dengue: challenges to molecular biology. Science. 1988 Jan 29;239(4839):476–481. doi: 10.1126/science.3277268. [DOI] [PubMed] [Google Scholar]
  18. Kliks S. C., Nimmanitya S., Nisalak A., Burke D. S. Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants. Am J Trop Med Hyg. 1988 Mar;38(2):411–419. doi: 10.4269/ajtmh.1988.38.411. [DOI] [PubMed] [Google Scholar]
  19. Kliks S. Antibody-enhanced infection of monocytes as the pathogenetic mechanism for severe dengue illness. AIDS Res Hum Retroviruses. 1990 Aug;6(8):993–998. doi: 10.1089/aid.1990.6.993. [DOI] [PubMed] [Google Scholar]
  20. Koopman J. S., Prevots D. R., Vaca Marin M. A., Gomez Dantes H., Zarate Aquino M. L., Longini I. M., Jr, Sepulveda Amor J. Determinants and predictors of dengue infection in Mexico. Am J Epidemiol. 1991 Jun 1;133(11):1168–1178. doi: 10.1093/oxfordjournals.aje.a115829. [DOI] [PubMed] [Google Scholar]
  21. Kuno G., Gubler D. J., Oliver A. Use of 'original antigenic sin' theory to determine the serotypes of previous dengue infections. Trans R Soc Trop Med Hyg. 1993 Jan-Feb;87(1):103–105. doi: 10.1016/0035-9203(93)90444-u. [DOI] [PubMed] [Google Scholar]
  22. Macdonald G. The dynamics of helminth infections, with special reference to schistosomes. Trans R Soc Trop Med Hyg. 1965 Sep;59(5):489–506. doi: 10.1016/0035-9203(65)90152-5. [DOI] [PubMed] [Google Scholar]
  23. Mady B. J., Erbe D. V., Kurane I., Fanger M. W., Ennis F. A. Antibody-dependent enhancement of dengue virus infection mediated by bispecific antibodies against cell surface molecules other than Fc gamma receptors. J Immunol. 1991 Nov 1;147(9):3139–3144. [PubMed] [Google Scholar]
  24. Newton E. A., Reiter P. A model of the transmission of dengue fever with an evaluation of the impact of ultra-low volume (ULV) insecticide applications on dengue epidemics. Am J Trop Med Hyg. 1992 Dec;47(6):709–720. doi: 10.4269/ajtmh.1992.47.709. [DOI] [PubMed] [Google Scholar]
  25. Okuno Y., Fukunaga T., Srisupaluck S., Kasemsarn P., Dharakul C., Sangkawibha N. Serological and virological studies on patients with dengue hemorrhagic fever (DHF) in Chanthaburi province, Thailand. I. Serological studies on paired sera from DHF patients by neutralization (N), hemagglutination inhibition (HI) and staining tests. Biken J. 1980 Sep;23(3):113–121. [PubMed] [Google Scholar]
  26. Peiris J. S., Gordon S., Unkeless J. C., Porterfield J. S. Monoclonal anti-Fc receptor IgG blocks antibody enhancement of viral replication in macrophages. Nature. 1981 Jan 15;289(5794):189–191. doi: 10.1038/289189a0. [DOI] [PubMed] [Google Scholar]
  27. Rigau-Pérez J. G., Clark G. G., Gubler D. J., Reiter P., Sanders E. J., Vorndam A. V. Dengue and dengue haemorrhagic fever. Lancet. 1998 Sep 19;352(9132):971–977. doi: 10.1016/s0140-6736(97)12483-7. [DOI] [PubMed] [Google Scholar]
  28. Robinson W. E., Jr, Montefiori D. C., Mitchell W. M. Antibody-dependent enhancement of human immunodeficiency virus type 1 infection. Lancet. 1988 Apr 9;1(8589):790–794. doi: 10.1016/s0140-6736(88)91657-1. [DOI] [PubMed] [Google Scholar]
  29. Sangkawibha N., Rojanasuphot S., Ahandrik S., Viriyapongse S., Jatanasen S., Salitul V., Phanthumachinda B., Halstead S. B. Risk factors in dengue shock syndrome: a prospective epidemiologic study in Rayong, Thailand. I. The 1980 outbreak. Am J Epidemiol. 1984 Nov;120(5):653–669. doi: 10.1093/oxfordjournals.aje.a113932. [DOI] [PubMed] [Google Scholar]
  30. Takeda A., Tuazon C. U., Ennis F. A. Antibody-enhanced infection by HIV-1 via Fc receptor-mediated entry. Science. 1988 Oct 28;242(4878):580–583. doi: 10.1126/science.2972065. [DOI] [PubMed] [Google Scholar]
  31. Thein S., Aung M. M., Shwe T. N., Aye M., Zaw A., Aye K., Aye K. M., Aaskov J. Risk factors in dengue shock syndrome. Am J Trop Med Hyg. 1997 May;56(5):566–572. doi: 10.4269/ajtmh.1997.56.566. [DOI] [PubMed] [Google Scholar]

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