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Estimate Prior Distribution for Environmental Half-Saturation Constant (kappa)

Source: R/est_kappa_prior.R
est_kappa_prior.Rd

This function compiles a meta-analysis of published Vibrio cholerae infectious dose (ID50) estimates and fits a lognormal prior distribution for the environmental dose-response half-saturation constant \(\kappa\) used in the MOSAIC environmental force-of-infection term: $$\lambda_W \propto D / (\kappa + D), \quad D = W / N$$ In the engine (rng mode, since v0.89.0) the dose \(D\) is the per-capita environmental load \(W/N\) – cells shed into the patch reservoir per resident – not a water concentration (sim_components.R, EnvToHuman step). \(\kappa\) is therefore a per-capita half-saturation dose. The prior below is anchored on volunteer ID50 data (CFU ingested); the conversion from cells per capita to an ingested dose is absorbed into the shedding rates \(\zeta_1, \zeta_2\), so the ID50 scale is a literature anchor for \(\kappa\), not a unit identity.

Usage

est_kappa_prior(PATHS)

Arguments

PATHS

A list of paths generated by get_paths(). Must include:

  • MODEL_INPUT: directory where parameter CSVs are saved.

  • DOCS_FIGURES: directory where the summary figure is saved.

Value

Invisibly returns a list with elements:

  • data: the source meta-analysis table.

  • fit: fitted lognormal parameters (meanlog, sdlog, median, mode, ci_lower, ci_upper).

  • param_df: long-format parameter data frame (as saved to disk).

Details

The function assembles a literature table of ID50 estimates spanning direct human-volunteer challenge studies (Hornick 1971, Cash 1974, Levine 1981/1988, Tacket 1999), QMRA Beta-Poisson fits (Haas, Rose & Gerba 1999), expert-review summaries (Nelson et al. 2009, Kaper et al. 1995), and values adopted by convention in the cholera modelling literature (Codeco 2001, Hartley et al. 2006). Each source is weighted by its relevance to the endemic / buffered exposure context most relevant to sub-Saharan African transmission settings. A lognormal is then fit by weighted maximum-likelihood on the log10 scale.

The MOSAIC dose-response follows Codeco (2001) and Hartley et al. (2006): the infection hazard is a saturating Michaelis-Menten function of environmental concentration with half-saturation \(\kappa\). Historical cholera models have fixed \(\kappa = 10^6\) cells, a value traceable to Sack (1971) and Hornick et al. (1971) under unbuffered water-only exposure in healthy adults. Modern re-analyses of buffered-exposure volunteer studies (NaHCO3 neutralisation, representative of typical endemic exposure through food or contaminated drinking water) consistently support a lower central estimate of \(\sim 10^5\) CFU, with substantial between-study heterogeneity.

Fitting: each source contributes a point estimate \(\log_{10} \kappa_i\) with weight \(w_i\) reflecting its evidentiary quality. The weighted mean and standard deviation on the log10 scale are converted directly to the lognormal meanlog and sdlog (meanlog = mu_log10 * ln 10, sdlog = sd_log10 * ln 10); no further refit is applied.

References

  • Hornick RB, et al. (1971). The Broad Street pump revisited: response of volunteers to ingested cholera vibrios. Bull N Y Acad Med 47(10):1181-91.

  • Cash RA, et al. (1974). Response of man to infection with Vibrio cholerae. I. Clinical, serologic, and bacteriologic responses to a known inoculum. J Infect Dis 129(1):45-52.

  • Levine MM, et al. (1981). Volunteer studies in development of vaccines against cholera and enterotoxigenic Escherichia coli: a review. In: Holme T, et al., eds. Acute Enteric Infections in Children.

  • Levine MM, et al. (1988). Safety, immunogenicity, and efficacy of recombinant live oral cholera vaccines, CVD 103 and CVD 103-HgR. Lancet 2(8609):467-70.

  • Tacket CO, et al. (1999). Initial clinical studies of CVD 112 V.cholerae O139 live oral vaccine. Infect Immun 67(12):6346-49.

  • Haas CN, Rose JB, Gerba CP (1999). Quantitative Microbial Risk Assessment. Wiley, New York.

  • Codeco CT (2001). Endemic and epidemic dynamics of cholera: the role of the aquatic reservoir. BMC Infect Dis 1:1.

  • Hartley DM, Morris JG, Smith DL (2006). Hyperinfectivity: a critical element in the ability of V. cholerae to cause epidemics? PLoS Med 3(1):e7.

  • Kaper JB, Morris JG, Levine MM (1995). Cholera. Clin Microbiol Rev 8(1):48-86.

  • Nelson EJ, Harris JB, Morris JG, Calderwood SB, Camilli A (2009). Cholera transmission: the host, pathogen and bacteriophage dynamic. Nat Rev Microbiol 7(10):693-702.

  • QMRA Wiki: Vibrio cholerae dose-response models. https://qmrawiki.org/experiments/vibrio-cholerae

Examples

if (FALSE) { # \dontrun{
PATHS <- get_paths()
est_kappa_prior(PATHS)
} # }