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Host immunity and synchronized epidemics of syphilis across the United States

Nature volume 433, pages 417–421 (2005)Cite this article

Abstract

A central question in population ecology is the role of ‘exogenous’ environmental factors versus density-dependent ‘endogenous’ biological factors in driving changes in population numbers1. This question is also central to infectious disease epidemiology, where changes in disease incidence due to behavioural or environmental change must be distinguished from the nonlinear dynamics of the parasite population2. Repeated epidemics of primary and secondary syphilis infection in the United States over the past 50 yr have previously been attributed to social and behavioural changes3. Here, we show that these epidemics represent a rare example of unforced, endogenous oscillations in disease incidence, with an 8–11-yr period that is predicted by the natural dynamics of syphilis infection, to which there is partially protective immunity4. This conclusion is supported by the absence of oscillations in gonorrhoea cases, where a protective immune response is absent5,6. We further demonstrate increased synchrony of syphilis oscillations across cities over time, providing empirical evidence for an increasingly connected sexual network in the United States.

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Figure 1: Syphilis and gonorrhoea cases in the United States.
Figure 2: Oscillations in syphilis incidence due to immunity.
Figure 3: The metapopulation dynamics of syphilis.

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References

  1. Bjornstad, O. N. & Grenfell, B. T. Noisy clockwork: Time series analysis of population fluctuations in animals. Science 293, 638–643 (2001)

    Article  CAS  Google Scholar 

  2. Pascual, M., Rodo, X., Ellner, S. P., Colwell, R. & Bouma, M. J. Cholera dynamics and el Nino-Southern Oscillation. Science 289, 1766–1769 (2000)

    Article  ADS  CAS  Google Scholar 

  3. Nakashima, A. K., Rolfs, R. T., Flock, M. L., Kilmarx, P. & Greenspan, J. R. Epidemiology of syphilis in the United States, 1941–1993. Sex. Transm. Dis. 23, 16–23 (1996)

    Article  CAS  Google Scholar 

  4. Morgan, C. A., Lukehart, S. A. & Van Voorhis, W. C. Protection against syphilis correlates with specificity of antibodies to the variable regions of Treponema pallidum repeat protein K. Infect. Immun. 71, 5605–5612 (2003)

    Article  CAS  Google Scholar 

  5. Fox, K. K. et al. Longitudinal evaluation of serovar-specific immunity to Neisseria gonorrhoeae . Am. J. Epidemiol. 149, 353–358 (1999)

    Article  CAS  Google Scholar 

  6. Schmidt, K. A. et al. Experimental gonococcal urethritis and reinfection with homologous gonococci in male volunteers. Sex. Transm. Dis. 28, 555–564 (2001)

    Article  CAS  Google Scholar 

  7. Chatfield, C. The Analysis of Time Series: an Introduction 6th edn (Chapman & Hall/CRC, Boca Raton, 2003)

    MATH  Google Scholar 

  8. Grenfell, B. T., Bjornstad, O. N. & Kappey, J. Travelling waves and spatial hierarchies in measles epidemics. Nature 414, 716–723 (2001)

    Article  ADS  CAS  Google Scholar 

  9. Hethcote, H. W. & Yorke, J. A. Gonorrhea Transmission Dynamics and Control in Lecture Notes Biomath no. 56 (Springer, Berlin, 1984)

    Book  Google Scholar 

  10. Garnett, G. P., Aral, S. O., Hoyle, D. V., Cates, W. & Anderson, R. M. The natural history of syphilis: Implications for the transmission dynamics and control of infection. Sex. Transm. Dis. 24, 185–200 (1997)

    Article  CAS  Google Scholar 

  11. Garnett, G. P., Mertz, K. J., Finelli, L., Levine, W. C. & St Louis, M. E. The transmission dynamics of gonorrhoea: modelling the reported behaviour of infected patients from Newark, New Jersey. Phil. Trans. R. Soc. Lond. B 354, 787–797 (1999)

    Article  CAS  Google Scholar 

  12. Hook, E. W. et al. Delayed presentation to clinics for sexually transmitted diseases by symptomatic patients—A potential contributor to continuing STD morbidity. Sex. Transm. Dis. 24, 443–448 (1997)

    Article  Google Scholar 

  13. Greenberg, J. B. et al. Learning from clients: An opportunity for sexually transmitted disease programs. J. Public Health Manage Pract. 8, 59–68 (2002)

    Article  Google Scholar 

  14. Wasserheit, J. N. & Aral, S. O. The dynamic topology of sexually transmitted disease epidemics: implications for prevention strategies. J. Infect. Dis. 174(suppl. 2), S201–S213 (1996)

    Article  Google Scholar 

  15. Hamers, F. F. et al. Syphilis and Gonorrhea in Miami—Similar clustering, different trends. Am. J. Public Health 85, 1104–1108 (1995)

    Article  CAS  Google Scholar 

  16. Bailey, N. T. J. The Mathematical Theory of Infectious Diseases and its Applications 2nd edn (Griffin, London, 1975)

    MATH  Google Scholar 

  17. Lloyd, A. L. & May, R. M. Spatial heterogeneity in epidemic models. J. Theor. Biol. 179, 1–11 (1996)

    Article  CAS  Google Scholar 

  18. U.S. Department of Transportation Bureau of Transportation Statistics. National Transportation Statistics 2003 (U.S. Government Printing Office, Washington DC, 2003)

    Google Scholar 

  19. Cliff, A. D., Haggett, P. & Smallman-Raynor, M. in Deciphering Global Epidemics: Analytical Approaches to the Disease Records of World Cities, 1888–1912 (eds Baker, A. R. H., Dennis, R. & Holdsworth, D.) (Cambridge Univ. Press, Cambridge, 1998)

    Book  Google Scholar 

  20. Wallace, R., Huang, Y. S., Gould, P. & Wallace, D. The hierarchical diffusion of AIDS and violent crime among US metropolitan regions: Inner-city decay, stochastic resonance and reversal of the mortality transition. Soc. Sci. Med. 44, 935–947 (1997)

    Article  CAS  Google Scholar 

  21. Keeling, M. J. & Rohani, P. Estimating spatial coupling in epidemiological systems: a mechanistic approach. Ecol. Lett. 5, 20–29 (2002)

    Article  Google Scholar 

  22. Lloyd, A. L. & Jansen, V. A. A. Spatiotemporal dynamics of epidemics: synchrony in metapopulation models. Math. Biosci. 188, 1–16 (2004)

    Article  MathSciNet  Google Scholar 

  23. Aral, S. O. The social context of syphilis persistence in the southeastern United States. Sex. Transm. Dis. 23, 9–15 (1996)

    Article  CAS  Google Scholar 

  24. Kuperman, M. & Abramson, G. Small world effect in an epidemiological model. Phys. Rev. Lett. 86, 2909–2912 (2001)

    Article  ADS  CAS  Google Scholar 

  25. Chesson, H. W., Dee, T. S. & Aral, S. O. AIDS mortality may have contributed to the decline in syphilis rates in the United States in the 1990s. Sex. Transm. Dis. 30, 419–424 (2003)

    Article  Google Scholar 

  26. Kahn, R. H., Heffelfinger, J. D. & Berman, S. M. Syphilis outbreaks among men who have sex with men—A public health trend of concern. Sex. Transm. Dis. 29, 285–287 (2002)

    Article  Google Scholar 

  27. Wolitski, R. J., Valdiserri, R. O., Denning, P. H. & Levine, W. C. Are we headed for a resurgence of the HIV epidemic among men who have sex with men? Am. J. Public Health 91, 883–888 (2001)

    Article  CAS  Google Scholar 

  28. Bjørnstad, O. N., Ims, R. A. & Lambin, X. Spatial population dynamics: analyzing patterns and processes of population synchrony. Trends Ecol. Evol. 14, 427–432 (1999)

    Article  Google Scholar 

  29. Nåsell, I. Stochastic models of some endemic infections. Math. Biosci. 179, 1–19 (2002)

    Article  MathSciNet  Google Scholar 

  30. Gibson, C. Population of the 100 Largest Cities and Other Urban Places in the United States: 1790–1990 (Working Paper No. 27, Population Division, US Census Bureau, Washington DC, 1998)

    Google Scholar 

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Acknowledgements

The authors are grateful to M. Flock and S. Berman at the US Centers for Disease Control and Prevention for making available the disease case reports and for discussion on data quality. We also thank J. Truscott, J. Lewis, P. White, N. Ferguson, S. Riley and O. Bjørnstad for advice and help in analysis of periodic time-series data. N.C.G. and C.F. would like to thank the Royal Society, and G.P.G. and C.F. the Medical Research Council for funding.

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Authors and Affiliations

  1. Department of Infectious Disease Epidemiology, Imperial College London, Norfolk Place, W2 1PG, London, UK

    Nicholas C. Grassly, Christophe Fraser & Geoffrey P. Garnett

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  1. Nicholas C. Grassly
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  2. Christophe Fraser
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  3. Geoffrey P. Garnett
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Correspondence to Nicholas C. Grassly.

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Supplementary information

Supplementary Methods

Provides a more detailed description of the data, and the spectral and cross-correlation analyses used, together with additional details and results for the SIRS model. (DOC 90 kb)

Supplementary Table 1

Lists the possible transitions and associated rates for the SIRS model of infection. (DOC 29 kb)

Supplementary Figure 1

Comparison of the deterministic and stochastic SIRS model, demonstrating sustained oscillations in prevalence in the stochastic case, even when a significant fraction of individuals fail to develop protective immunity after infection. (PDF 49 kb)

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Grassly, N., Fraser, C. & Garnett, G. Host immunity and synchronized epidemics of syphilis across the United States. Nature 433, 417–421 (2005). https://doi.org/10.1038/nature03072

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