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General Overview

Adenoviruses are medium-sized (90-100 nm), nonenveloped (naked) icosohedral viruses containing double-stranded DNA. According to the CDC[1], there are more than 52 immunologically distinct types that can cause infections in humans and animals. Adenoviruses are unusually stable to chemical and physical agents and to adverse pH conditions, thus allowing for prolonged survival outside of the body.

According to Gray, Callahan et al.[2], denoviruses most commonly cause respiratory illness the most commoncause of acute infectious disease in U.S. adults. However, depending on the infecting serotype, they also cause various other illnesses, such as gastroenteritis, conjunctivitis, cystitis (bladder infection), and rash illness. The CDC[1] states that symptoms of respiratory illness caused by adenovirus infection range from the common cold syndrome to pneumonia, croup, and bronchitis.

Acute respiratory disease (ARD), which was first recognized among military recruits during World War II, caused by adenovirus infections, according to the CDC[1] and Gray, Callahan et al.[2]. Although epidemiologic characteristics of the adenoviruses vary by type, all are transmitted by direct contact, fecal-oral transmission, and waterborne transmission.

ARD is most often associated with adenovirus types 4 and 7, and more recently adenovirus 14, in the United States. The CDC[1] states that 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.

 

Summary of data

"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.[3]).

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.[4]).

ID # of Doses Agent Strain Dose Units Host type Μodel Optimized parameters Response type Reference
255 5 type 4 TCID50 human exponential k = 1.51E-02
LD50/ID50 = 4.59E+01
 		 infection

Schiff et al.[5]
31 4 type 4 TCID50 human exponential k = 6.07E-01
LD50/ID50 = 1.14E+00
 		 infection

 

Couch, Cate et al.[3]

Optimization Output for Exp. 255:

Experiment ID: 255

# of Doses: 5

Agent Strain: type 4

Dose Units: TCID50

Host type: human

Μodel: exponential

Optimized parameters:
k = 1.51E-02
LD50/ID50 = 4.59E+01
 

Humans/ type 4 Strain model data [1]
Dose Infected Non-infected Total
3 0 6 6
10 0 2 2
14 1 1 2
79 2 1 3
400 3 0 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 2.14 -0.00118 4 3.84 
1		 9.49 
0.71
Beta Poisson 2.14 3 7.81 
0.544
Exponential is preferred to beta-Poisson; cannot reject good fit for exponential.

 

Optimized k parameter for the exponential model, from 10000 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
k 1.51E-02 4.00E-03 5.88E-03 6.35E-03 4.56E-02 4.56E-02 4.56E-02
ID50/LD50/ETC* 4.59E+01 1.52E+01 1.52E+01 1.52E+01 1.09E+02 1.18E+02 1.73E+02
*Not a parameter of the exponential model; however, it facilitates comparison with other models.

 

Parameter histogram for exponential model (uncertainty of the parameter)

Exponential model plot, with confidence bounds around optimized model

Optimization Output for Exp. 31:

Best Fit

Experiment ID: 31

# of Doses: 4

Agent Strain: type 4

 Dose Units: TCID50

Host type: human

Μodel: exponential

Optimized parameters:
k = 6.07E-01
LD50/ID50 = 1.14E+00

Humans/ type 4 Strain model data [1]
Dose Infected Non-infected Total
1 1 2 3
5 3 0 3
11 3 0 3
1000 6 0 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 0.487 -0.000723 3 3.84 
1		 7.81 
0.922
Beta Poisson 0.488 2 5.99 
0.784
Exponential is preferred to beta-Poisson; cannot reject good fit for exponential.

 

Optimized k parameter for the exponential model, from 10000 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
k 6.07E-01 3.87E-01 3.87E-01 3.87E-01 1.13E+00 1.13E+00 1.13E+00
ID50/LD50/ETC* 1.14E+00 6.11E-01 6.11E-01 6.11E-01 1.79E+00 1.79E+00 1.79E+00
*Not a parameter of the exponential model; however, it facilitates comparison with other models.

 

Parameter histogram for exponential model (uncertainty of the parameter)

Exponential model plot, with confidence bounds around optimized model

References

  1. Citekey 1266 not found
  2. Citekey 1264 not found
  3. Couch, R. B., Cate T. R., Douglas R. G., Gerone P. J., & Knight V. (1966).  Effect of route of inoculation on experimental respiratory viral disease in volunteers and evidence for airborne transmission. Bacteriological Reviews. 30, 3.
  4. Citekey 1265 not found
  5. Schiff, G. M., Stefanović G. M., Young E. C., Sander D. S., Pennekamp J. K., & Ward R. L. (1984).  Studies of echovirus-12 in volunteers: determination of minimal infectious dose and the effect of previous infection on infectious dose. The Journal of infectious diseases. 150, 6.
ID # of Doses Agent Strain Dose Units Host type Μodel Optimized parameters Response type Reference
255 5 type 4 TCID50 human exponential
k = 1.51E-02
LD50/ID50 = 4.59E+01

infection Schiff, G M., et al. "Studies of echovirus-12 in volunteers: determination of minimal infectious dose and the effect of previous infection on infectious dose." The Journal of infectious diseases. 150 (1984): 6.
31 4 type 4 TCID50 human exponential
k = 6.07E-01
LD50/ID50 = 1.14E+00

infection Couch, R B., et al. "Effect of route of inoculation on experimental respiratory viral disease in volunteers and evidence for airborne transmission." Bacteriological Reviews. 30 (1966): 3.
Experiment ID:
255
# of Doses:
5
Agent Strain:
type 4
Dose Units:
TCID50
Host type:
human
Μodel:
exponential
Optimized parameters:
k = 1.51E-02
LD50/ID50 = 4.59E+01

Reference:
Humans/ type 4 Strain model data [1]
Dose Infected Non-infected Total
3 0 6 6
10 0 2 2
14 1 1 2
79 2 1 3
400 3 0 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 2.14 -0.00118 4 3.84 
1		 9.49 
0.71
Beta Poisson 2.14 3 7.81 
0.544
Exponential is preferred to beta-Poisson; cannot reject good fit for exponential.

 

Optimized k parameter for the exponential model, from 10000 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
k 1.51E-02 4.00E-03 5.88E-03 6.35E-03 4.56E-02 4.56E-02 4.56E-02
ID50/LD50/ETC* 4.59E+01 1.52E+01 1.52E+01 1.52E+01 1.09E+02 1.18E+02 1.73E+02
*Not a parameter of the exponential model; however, it facilitates comparison with other models.

 

Parameter histogram for exponential model (uncertainty of the parameter)

Exponential model plot, with confidence bounds around optimized model

References

  1. Citekey 1265 not found
Recommended
Experiment ID:
31
# of Doses:
4
Agent Strain:
type 4
Dose Units:
TCID50
Host type:
human
Μodel:
exponential
Optimized parameters:
k = 6.07E-01
LD50/ID50 = 1.14E+00

Reference:
Humans/ type 4 Strain model data [1]
Dose Infected Non-infected Total
1 1 2 3
5 3 0 3
11 3 0 3
1000 6 0 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 0.487 -0.000723 3 3.84 
1		 7.81 
0.922
Beta Poisson 0.488 2 5.99 
0.784
Exponential is preferred to beta-Poisson; cannot reject good fit for exponential.

 

Optimized k parameter for the exponential model, from 10000 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
k 6.07E-01 3.87E-01 3.87E-01 3.87E-01 1.13E+00 1.13E+00 1.13E+00
ID50/LD50/ETC* 1.14E+00 6.11E-01 6.11E-01 6.11E-01 1.79E+00 1.79E+00 1.79E+00
*Not a parameter of the exponential model; however, it facilitates comparison with other models.

 

Parameter histogram for exponential model (uncertainty of the parameter)

Exponential model plot, with confidence bounds around optimized model

References

  1. Couch, R. B., Cate T. R., Douglas R. G., Gerone P. J., & Knight V. (1966).  Effect of route of inoculation on experimental respiratory viral disease in volunteers and evidence for airborne transmission. Bacteriological Reviews. 30, 3.