Difference between revisions of "Rhinovirus: Dose Response Models"

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Hendley, J.O., Edmondson Jr., W.P. and Gwaltney Jr., J.M. (1972) [http://www.jstor.org/stable/30108503 Relation between naturally acquired immunity and infectivity of two rhinoviruses involunteers]. ''Journal of Infectious Diseases'' '''125''', 243-248.
 
Hendley, J.O., Edmondson Jr., W.P. and Gwaltney Jr., J.M. (1972) [http://www.jstor.org/stable/30108503 Relation between naturally acquired immunity and infectivity of two rhinoviruses involunteers]. ''Journal of Infectious Diseases'' '''125''', 243-248.
  
[[Category:Dose Response Model]]
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[[Category:Dose Response Model]][[Category:Virus]]

Revision as of 17:43, 19 March 2012

Rhinovirus

Author: Yin Huang
If you want to download this chapter in pdf format, please click here
If you want to download the excel spreadsheet of tables, please click the captions of tables. If you want to download a specific figure, just click on the figure


General overview

Rhinoviruses belong to the Picornaviridae family, small icosahedral viruses made of a protein capsid that encases a single-stranded, positive-sense RNA molecule. About 100 different serotypes have been identified and characterized by their own specific antigens.

Rhinoviruses are responsible for 30 to 50% of adult colds and 10 to 25% of colds in children. Other cold-causing viruses are adenoviruses, coronaviruses, coxsackieviruses, echoviruses, orthomyxoviruses, paramyxoviruses, respiratory syncytial virus, and enteroviruses, each of which produces infections with slightly different patterns of symptoms and severity. Several of the above-mentioned viruses also account for other more severe illnesses (Bella and Rossmann 1999).




Summary Data

Hendley et al. (1972) inoculated young adult volunteers over the age of 21 with Rhinovirus type 39 (RV 39), strain SF 299, and rhinovirus type 14 (RV 14), strain SF 765, via intranasal exposure route. Shedding of the challenge virus and/or a fourfold or greater in- crease in titer of serum antibody to a homotypic rhinovirus were accepted as evidence of infection.

Table 6.1. Summary of the rhinovirus data and best fits
Experiment number Reference Host type/pathogen strain Route/number of doses Dose units Response Best-fit model Best-fit parameters ID50
1* Hendley et al., 1972 humans/ rhinovirus type 14, strain SF 765 oral/6 pfu infection Beta-Poisson α = 0.20

N50 = 9.22

9.22
2 Hendley et al., 1972 humans/ rhinovirus type 39, strain SF 299 oral/6 pfu infection - α = 0.22

N50 = 1.81

1.81

No acceptable fit for experiment 2.


Optimized Models and Fitting Analyses

Optimization Output for experiment 1

Table 6.2: human/type 14 strain SF 765model data
Dose Infected Non-infected Total
3.00E+02 10 2 12
1.50E+02 27 13 40
1.50E+01 6 4 10
5.00E+00 4 6 10
1.50E+00 4 6 10
5.00E-01 1 8 9
Hendley et al., 1972.


Table 6.3: Goodness of fit and model selection
Model Deviance Δ Degrees
of Freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 51.84 50.16 5 3.84
0
11.07
0
Beta Poisson 1.68 4 9.49
0.794
Beta Poisson is best fitting model
Table 6.4 Optimized parameters for the best fitting (beta Poisson), obtained from 10,000 bootstrap iterations
Parameter MLE Estimate Percentiles
0.50% 2.5% 5% 95% 97.5% 99.5%
α 0.20 -- -- -- -- -- --
N50 9.22 -- -- -- -- -- --
LD50 9.22 1.42 2.62 3.35 25.38 31.90 50.18


Figure 6.1 Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.
Figure 6.2 beta Poisson model plot, with confidence bounds around optimized model




Optimization Output for experiment 2

Table 6.5: human/type 39 strain SF 299 model data
Dose Infected Non-infected Total
5.00E+01 47 15 62
5.00E+00 5 11 16
1.50E+00 22 11 33
5.00E-01 8 16 24
1.50E-01 2 7 9
5.00E-02 0 11 11
Hendley et al., 1972.


Table 6.6: Goodness of fit and model selection
Model Deviance Δ Degrees
of Freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 129.77 117.41 5 3.84
0
11.07
0
Beta Poisson 12.36 4 9.49
0.149
Beta Poisson is best fitting model
Table 6.7 Optimized parameters for the best fitting (beta Poisson), obtained from 10,000 bootstrap iterations
Parameter MLE Estimate Percentiles
0.50% 2.5% 5% 95% 97.5% 99.5%
α 0.22 -- -- -- -- -- --
N50 1.81 -- -- -- -- -- --
LD50 1.81 0.69 0.87 0.98 3.76 4.52 Inf


Figure 6.3 Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.
Figure 6.4 beta Poisson model plot, with confidence bounds around optimized model



Summary

The responses caused by doses less than one observed in these two experiments should be due to the uncertainties of dose counting in the original study.




References

Bella, J. and Rossmann, M.G. (1999) Review: Rhinoviruses and their icam receptors. Journal of Structural Biology 128, 69–74.

Hendley, J.O., Edmondson Jr., W.P. and Gwaltney Jr., J.M. (1972) Relation between naturally acquired immunity and infectivity of two rhinoviruses involunteers. Journal of Infectious Diseases 125, 243-248.