Difference between revisions of "Adenovirus: Dose Response Models"

From QMRAwiki
Jump to: navigation, search
(Optimized Models and Fitting Analyses)
Line 187: Line 187:
  
 
Gray, G. C., J. D. Callahan, et al. (1999). "[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2640764/ Respiratory diseases among U.S. military personnel: countering emerging threats.]" Emerging Infectious Diseases '''5'''(3): 379-385.
 
Gray, G. C., J. D. Callahan, et al. (1999). "[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2640764/ Respiratory diseases among U.S. military personnel: countering emerging threats.]" Emerging Infectious Diseases '''5'''(3): 379-385.
 +
 +
 +
 +
[[Category:Dose Response Model]]

Revision as of 21:43, 11 November 2011

Adenovirus

Author: Sushil Tamrakar
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


Overview of Adenovirus

Adenoviruses are medium-sized (90-100 nm), nonenveloped (naked) icosohedral viruses containing double-stranded DNA. There are more than 52 immunologically distinct types that can cause infections in humans. Adenoviruses are unusually stable to chemical and physical agents and to adverse pH conditions, thus allowing for prolonged survival outside of the body(CDC 2010).

Adenoviruses most commonly cause respiratory illness and Respiratory infections, the most commoncause of acute infectious disease in U.S. adults (Gray, Callahan et al. 1999) however, depending on the infecting serotype, they may also cause various other illnesses, such as gastroenteritis, conjunctivitis, cystitis (bladder infection), and rash illness. Symptoms of respiratory illness caused by adenovirus infection range from the common cold syndrome to pneumonia, croup, and bronchitis (CDC 2010).

Acute respiratory disease (ARD), which was first recognized among military recruits during World War II, caused by adenovirus infections (Gray, Callahan et al. 1999; CDC 2010). Although epidemiologic characteristics of the adenoviruses vary by type, all are transmitted by direct contact, fecal-oral transmission, and occasionally waterborne transmission.

ARD is most often associated with adenovirus types 4 and 7, and more recently adenovirus 14, in the United States. Enteric adenoviruses 40 and 41 cause gastroenteritis, usually in children. For some adenovirus serotypes, the clinical spectrum of disease associated with infection varies depending on the site of infection; for example, infection with adenovirus 7 acquired by inhalation is associated with severe lower respiratory tract disease, whereas oral transmission of the virus typically causes no or mild disease(CDC 2010).




Summary of data

Couch, R. B., T. R. Cate, et al. (1966). "Effect of route of inoculation on experimental respiratory viral disease in volunteers and evidence for airborne transmission." Microbiol. Mol. Biol. Rev. 30(3): 517-529.- In this study, several healthy adult male volunteers were exposed to aerosols containing adenovirus type 4 (Couch, Cate et al. 1966).

Couch, R. B., V. Knight, et al. (1969). "The minimal infectious dose of adenovirus type 4; the case for natural transmission by viral aerosol.." Trans Am Clin Climatol Assoc. 80: 205-211.- In this study, human volunteers were inoculated intaranasally with adenovirus type 4 (Couch, Knight et al. 1969).

Table 1.1. Summary of data for Adenovirus
Experiment Number Reference Host Type/Pathogen Strain Route/# of Doses Dose Units Response Best Fit Model Optimized Parameter(s) ID50
1 Couch, Cate et al. 1966 Humans/type 4 Inhalation – 4 TICD50 Infection Exponential k = 0.61 1.14
2 Couch, Knight et al. 1969 Humans/type 4 Intranasal – 5 TICD50 Infection Exponential k = 0.015 45.87



Optimized Models and Fitting Analyses

Optimization Output for experiment 1

Table 1.2. Humans/ type 4 Strain model data
Dose Infected Not infected Total
1000 6 0 6
11 3 0 3
5 3 0 3
1 1 2 3
Couch, Cate et al. 1966


Table 1.3. Goodness of Fit and Model Selection
Model Deviance Δ Degrees
of Freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 0.49 7.00E-04 3 3.84
0.979
7.81
0.922
Beta Poisson 0.49 2 5.99
0.784
Exponential is best fitting model
Table 1.4 Optimized parameters for the best fitting (Exponential), obtained from 10,000 bootstrap iterations
Parameter MLE Estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
k 0.61 0.39 0.39 0.39 1.13 22.73 22.73
LD50 (TCID) 1.14 0.030 0.030 0.61 1.79 1.79 1.79


Figure 1.1 Parameter histogram for exponential model(uncertainty of the parameter)
Figure 1.2 Exponential model plot, with confidence bounds around optimized model



Optimized Models and Fitting Analyses

Optimization Output for experiment 2

Table 1.5. Humans/ type 4 Strain model data
Dose Infected Not infected Total
400 3 0 3
79 2 1 3
14 1 1 2
10 0 2 2
3 0 6 6
Couch, Knight et al. 1969


Table 1.6. Goodness of Fit and Model Selection
Model Deviance Δ Degrees
of Freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 2.14 1.2E-03 4 3.84
0.973
9.49
0.710
Beta Poisson 2.14 3 7.81
0.544
Exponential is best fitting model
Table 1.7 Optimized parameters for the best fitting (Exponential), obtained from 10,000 bootstrap iterations
Parameter MLE Estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
k 0.015 4.00E-03 5.89E-03 6.35E-03 4.56E-02 4.56E-02 4.56E-02
ID50 45.87 15.21 15.21 15.21 109.15 117.79 173.13


Figure 1.3 Parameter histogram for exponential model
Figure 1.4 Exponential model plot, with confidence bounds around optimized model



References

CDC (2010). Adenoviruses, CDC, Division of Viral Diseases.

Couch, R. B., T. R. Cate, et al. (1966). "Effect of route of inoculation on experimental respiratory viral disease in volunteers and evidence for airborne transmission." Microbiol. Mol. Biol. Rev. 30(3): 517-529.

Couch, R. B., V. Knight, et al. (1969). "The minimal infectious dose of adenovirus type 4; the case for natural transmission by viral aerosol." Trans Am Clin Climatol Assoc. 80: 205-211.

Gray, G. C., J. D. Callahan, et al. (1999). "Respiratory diseases among U.S. military personnel: countering emerging threats." Emerging Infectious Diseases 5(3): 379-385.