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Classic Dose‐Response and Time Postinoculation Models for Leptospira

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  • Toru Watanabe
  • Sondra S. Teske
  • Charles N. Haas

Abstract

Leptospirosis is a preeminent zoonotic disease concentrated in tropical areas, and prevalent in both industrialized and rural settings. Dose‐response models were generated from 22 data sets reported in 10 different studies. All of the selected studies used rodent subjects, primarily hamsters, with the predominant endpoint as mortality with the challenge strain administered intraperitoneally. Dose‐response models based on a single evaluation postinfection displayed median lethal dose (LD50) estimates that ranged between 1 and 107 leptospirae depending upon the strain's virulence and the period elapsed since the initial exposure inoculation. Twelve of the 22 data sets measured the number of affected subjects daily over an extended period, so dose‐response models with time‐dependent parameters were estimated. Pooling between data sets produced seven common dose‐response models and one time‐dependent model. These pooled common models had data sets with different test subject hosts, and between disparate leptospiral strains tested on identical hosts. Comparative modeling was done with parallel tests to test the effects of a single different variable of either strain or test host and quantify the difference by calculating a dose multiplication factor. Statistical pooling implies that the mechanistic processes of leptospirosis can be represented by the same dose‐response model for different experimental infection tests even though they may involve different host species, routes, and leptospiral strains, although the cause of this pathophysiological phenomenon has not yet been identified.

Suggested Citation

  • Toru Watanabe & Sondra S. Teske & Charles N. Haas, 2014. "Classic Dose‐Response and Time Postinoculation Models for Leptospira," Risk Analysis, John Wiley & Sons, vol. 34(3), pages 465-484, March.
  • Handle: RePEc:wly:riskan:v:34:y:2014:i:3:p:465-484
    DOI: 10.1111/risa.12122
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    References listed on IDEAS

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    1. Toru Watanabe & Timothy A. Bartrand & Tatsuo Omura & Charles N. Haas, 2012. "Dose‐Response Assessment for Influenza A Virus Based on Data Sets of Infection with its Live Attenuated Reassortants," Risk Analysis, John Wiley & Sons, vol. 32(3), pages 555-565, March.
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    Cited by:

    1. Margaret E. Coleman & Harry M. Marks & Timothy A. Bartrand & Darrell W. Donahue & Stephanie A. Hines & Jason E. Comer & Sarah C. Taft, 2017. "Modeling Rabbit Responses to Single and Multiple Aerosol Exposures of Bacillus anthracis Spores," Risk Analysis, John Wiley & Sons, vol. 37(5), pages 943-957, May.

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