General Overview

The bacterium Bukholderia pseudomallei (B. pseudomallei) is a gram negative bacterium and is present in numerous tropical regions such as Central and South America and Southeast Asia causes Melioidosis, typically infects horses, mules and donkeys but can also present a potentially life threatening disease in humans as well. Burkholderia mallei (B. mallei) is a close relative of B. pseudomallei both of which have been categorized as a B level bioterror agent by the CDC. No dose response models are currently available for B. mallei.

http://www.cdc.gov/melioidosis/

Liu et al. in 2002 examined infection through intranasal route to mimic infection through inhalation. C57BL/6 mice and BALB/c mice were inoculated intranasally to B. pseudomallei KHW strain and mortality was recorded as response (Liu, Koo et al. 2002). Miller et al.(1948) explored infection in guinea pigs via intraperitoneal route(Miller, Pannell et al. 1948). Similarly, Brett and Woods(1996) experimented infection in diabetic rats with B. pseuomallei 316c strain (Brett and Woods 1996.

Recommended Model

Since the data of C57BL/6 mice and diabetic rat could be pooled and intranasal exposure is closer to inhalation which is the likeliest exposure route for humans, the pooled data sets and resulting models is preferred.

 

ID # of Doses Agent Strain Dose Units Host type Μodel Optimized parameters Response type Reference
17 5 KHW CFU BALB/c mice exponential
k = 1.04E-02
LD50/ID50 = 6.63E+01

infection Liu, B., et al. "Model of Differential Susceptibility to Mucosal Burkholderia pseudomallei Infection." Infection and Immunity. 70 (2002): 2.
18 5 KHW CFU C57BL/6 mice exponential
k = 1.00E-04
LD50/ID50 = 6.92E+03

infection Liu, B., et al. "Model of Differential Susceptibility to Mucosal Burkholderia pseudomallei Infection." Infection and Immunity. 70 (2002): 2.
18,23 10 KHW,316c CFU C57BL/6 mice and diabetic rat beta-Poisson a = 3.28E-01

LD50/ID50 = 5.43E+03
N50 = 5.43E+03
death Brett, Paul J., and Donald E. Woods. "Structural and immunological characterization of Burkholderia pseudomallei O-polysaccharide-flagellin protein conjugates." Infection and immunity. 64 (1996): 2824-2828.
21 6 W294 CFU guinea pig beta-Poisson a = 2.67E-01

LD50/ID50 = 2.55E+02
N50 = 2.55E+02
death Miller, W. R., et al. "Studies on Certain Biological Characteristics of Malleomyces mallei and Malleomyces pseudomallei." Journal of Bacteriology. 55 (1948): 1.
21,23 11 W294, 316c CFU guinea pig and diabetic rat beta-Poisson a = 2.13E-01

LD50/ID50 = 4.77E+02
N50 = 4.77E+02
death Miller, W. R., et al. "Studies on Certain Biological Characteristics of Malleomyces mallei and Malleomyces pseudomallei." Journal of Bacteriology. 55 (1948): 1.
23 5 316c CFU diabetic rat beta-Poisson a = 2.65E-01

LD50/ID50 = 2.27E+03
N50 = 2.27E+03
death Brett, P. J., and D. E. Woods. "Pathogenesis of and immunity to melioidosis." Acta Tropica. 74 (2000): 2.
Experiment ID:
17
# of Doses:
5
Agent Strain:
KHW
Dose Units:
CFU
Host type:
BALB/c mice
Μodel:
exponential
Optimized parameters:
k = 1.04E-02
LD50/ID50 = 6.63E+01

Reference:
Experiment ID:
18
# of Doses:
5
Agent Strain:
KHW
Dose Units:
CFU
Host type:
C57BL/6 mice
Μodel:
exponential
Optimized parameters:
k = 1.00E-04
LD50/ID50 = 6.92E+03

Reference:
Best Fit
Experiment ID:
18,23
# of Doses:
10
Agent Strain:
KHW,316c
Dose Units:
CFU
Host type:
C57BL/6 mice and diabetic rat
Μodel:
beta-Poisson
Optimized parameters: a = 3.28E-01

LD50/ID50 = 5.43E+03
N50 = 5.43E+03
Reference:
Experiment ID:
21
# of Doses:
6
Agent Strain:
W294
Dose Units:
CFU
Host type:
guinea pig
Μodel:
beta-Poisson
Optimized parameters: a = 2.67E-01

LD50/ID50 = 2.55E+02
N50 = 2.55E+02
Reference:
Experiment ID:
21,23
# of Doses:
11
Agent Strain:
W294, 316c
Dose Units:
CFU
Host type:
guinea pig and diabetic rat
Μodel:
beta-Poisson
Optimized parameters: a = 2.13E-01

LD50/ID50 = 4.77E+02
N50 = 4.77E+02
Reference:
Experiment ID:
23
# of Doses:
5
Agent Strain:
316c
Dose Units:
CFU
Host type:
diabetic rat
Μodel:
beta-Poisson
Optimized parameters: a = 2.65E-01

LD50/ID50 = 2.27E+03
N50 = 2.27E+03
Reference: