U.S. patent application number 15/466814 was filed with the patent office on 2017-09-28 for methods and compositions for reducing antibiotic administration to farm animals.
The applicant listed for this patent is Advanced Animal Diagnotics, Inc.. Invention is credited to Deborah Asion, Norah Gerow Bate, Stefano Bresolin, David A. Calderwood, Jorge Carlos Correa, Joy Parr Drach, Tobias M. Heineck, Mitchell Hockett, Erik J. Jensen, Jasper N. Pollard, Rodolfo R. Rodriguez, John Richard Sink.
Application Number | 20170276663 15/466814 |
Document ID | / |
Family ID | 59897827 |
Filed Date | 2017-09-28 |
United States Patent
Application |
20170276663 |
Kind Code |
A1 |
Drach; Joy Parr ; et
al. |
September 28, 2017 |
METHODS AND COMPOSITIONS FOR REDUCING ANTIBIOTIC ADMINISTRATION TO
FARM ANIMALS
Abstract
The present invention provides a method of identifying an animal
for which antibiotic treatment, anti-infective treatment, probiotic
treatment, immunostimulant treatment, additional monitoring and/or
a separate or alternative management strategy is appropriate,
comprising: a) collecting a sample from said animal; b) performing
a leukocyte differential cell count on said sample; c) comparing
said leukocyte differential cell count of (b) with an index of
infection; and d) initiating antibiotic treatment, anti-infective
treatment, probiotic treatment, immunostimulant treatment,
additional monitoring and/or a separate or alternative management
strategy of said animal on the basis of said comparing step.
Inventors: |
Drach; Joy Parr; (Pontiac,
IL) ; Hockett; Mitchell; (Raleigh, NC) ;
Bresolin; Stefano; (Gamer, NC) ; Jensen; Erik J.;
(Hillsborough, NC) ; Heineck; Tobias M.; (Durham,
NC) ; Pollard; Jasper N.; (Durham, NC) ;
Asion; Deborah; (Durham, NC) ; Rodriguez; Rodolfo
R.; (Cary, NC) ; Calderwood; David A.; (Chapel
Hill, NC) ; Bate; Norah Gerow; (Raleigh, NC) ;
Sink; John Richard; (Raleigh, NC) ; Correa; Jorge
Carlos; (Raleigh, NC) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Advanced Animal Diagnotics, Inc. |
Morrisville |
NC |
US |
|
|
Family ID: |
59897827 |
Appl. No.: |
15/466814 |
Filed: |
March 22, 2017 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62311706 |
Mar 22, 2016 |
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
G01N 33/5091 20130101;
G01N 33/56972 20130101; G01N 2800/52 20130101; G01N 33/492
20130101; G01N 2800/50 20130101 |
International
Class: |
G01N 33/49 20060101
G01N033/49 |
Claims
1. A method of identifying an animal for which antibiotic
treatment, anti-infective treatment, probiotic treatment,
immunostimulant treatment, additional monitoring and/or a separate
or alternative management strategy is appropriate, comprising: a)
collecting a sample from said animal; b) performing a leukocyte
differential cell count on said sample; c) comparing said leukocyte
differential cell count of (b) with an index of infection; and d)
initiating antibiotic treatment, anti-infective treatment,
probiotic treatment, immunostimulant treatment, additional
monitoring and/or a separate or alternative management strategy of
said animal on the basis of said comparing step.
2. A method of determining need for and/or timing of antibiotic
treatment, anti-infective treatment, probiotic treatment,
immunostimulant treatment, additional monitoring and/or a separate
or alternative management strategy of an animal, comprising: a)
collecting a sample from said animal; b) performing a leukocyte
differential cell count on said sample; c) comparing said leukocyte
differential cell count of (b) with an index of infection; and d)
identifying the need for and/or timing of the antibiotic treatment,
anti-infective treatment, probiotic treatment, immunostimulant
treatment, additional monitoring and/or a separate or alternative
management strategy of said animal on the basis of said comparing
step.
3. The method of claim 1, wherein said index of infection is
selected from the group consisting of: a) a neutrophil value in a
range from X.sub.N.times.10.sup.3 cells/microliter to
Y.sub.N.times.10.sup.3 cells/microliter, wherein X.sub.N is 0, 0.1,
0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4,
1.5, 1.6, or 1.7.times.10.sup.3 neutrophils per microliter, and
Y.sub.N is 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0,
5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3,
6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6,
7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9,
9.0, 10.0, 10.1, 10.2, 10.3, 10.4, 10.5, 10.6, 10.7, 10.8, 10.9,
11.0, 11.1, 11.2, 11.3, 11.4, 11.5, 11.6, 11.7, 11.8, 11.9, or
12.0.times.10.sup.3 neutrophils per microliter; b) a lymphocyte
value in a range from X.sub.L.times.10.sup.3 cells/microliter to
Y.sub.L.times.10.sup.3 cells/microliter, wherein X.sub.L is 3.9,
4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2,
5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5,
6.6, 6.7, 6.8, 6.9, or 7.0.times.10.sup.3 lymphocytes per
microliter, and Y.sub.L is 10.0, 10.1, 10.2, 10.3, 10.4, 10.5,
10.6, 10.7, 10.8, 10.9, 11.0, 11.1, 11.2, 11.3, 11.4, 11.5, 11.6,
11.7 11.8, 11.9, 12.0, 12.1, 12.2, or 12.3.times.10.sup.3
lymphocytes per microliter; c) an eosinophil value in a range from
X.sub.E.times.10.sup.3 cells/microliter to Y.sub.E.times.10.sup.3
cells/microliter, wherein X.sub.E is 0.0.times.10.sup.3 eosinophils
per microliter and Y.sub.E is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7,
0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or
2.0.times.10.sup.3 eosinophils per microliter; and d) any
combination of (a), (b) and (c) above.
4. The method of claim 2, wherein said index of infection is
selected from the group consisting of: a) a neutrophil value in a
range from X.sub.N.times.10.sup.3 cells/microliter to
Y.sub.N.times.10.sup.3 cells/microliter, wherein X.sub.N is about
0.0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2,
1.3, 1.4, 1.5, 1.6, or 1.7.times.10.sup.3 neutrophils per
microliter, and Y.sub.N is about 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6,
4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9,
6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2,
7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5,
8.6, 8.7, 8.8, 8.9, 9.0, 10.0, 10.1, 10.2, 10.3, 10.4, 10.5, 10.6,
10.7, 10.8, 10.9, 11.0, 11.1, 11.2, 11.3, 11.4, 11.5, 11.6, 11.7,
11.8, 11.9, or 12.0.times.10.sup.3 neutrophils per microliter; b) a
lymphocyte value in a range from X.sub.L.times.10.sup.3
cells/microliter to Y.sub.L.times.10.sup.3 cells/microliter,
wherein X.sub.L is about 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6,
4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9,
6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, or
7.0.times.10.sup.3 lymphocytes per microliter, and Y.sub.L is about
10.0, 10.1, 10.2, 10.3, 10.4, 10.5, 10.6, 10.7, 10.8, 10.9, 11.0,
11.1, 11.2, 11.3, 11.4, 11.5, 11.6, 11.7, 11.8, 11.9, 12.0, 12.1,
12.2, or 12.3.times.10.sup.3 lymphocytes per microliter; c) an
eosinophil value in a range from X.sub.E.times.10.sup.3
cells/microliter to Y.sub.E.times.10.sup.3 cells/microliter,
wherein X.sub.E is 0.0.times.10.sup.3 eosinophils per microliter
and Y.sub.E is about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9,
1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or
2.0.times.10.sup.3 eosinophils per microliter; and d) any
combination of (a), (b) and (c) above.
5. The method of claim 3, wherein said comparing step comprises
comparing a neutrophil value in the leukocyte differential cell
count with the neutrophil value of (a), comparing a lymphocyte
value in the leukocyte differential cell count with the lymphocyte
value of (b), and/or comparing a eosinophil value in the leukocyte
differential cell count with the eosinophil value of (c), in any
combination, wherein a neutrophil value, a lymphocyte value and/or
an eosinophil value that is outside of the range of the respective
neutrophil value of (a), the lymphocyte value of (b) and/or the
eosinophil value of (c) identifies that antibiotic treatment,
anti-infective treatment, probiotic treatment, immunostimulant
treatment, additional monitoring and/or a separate or alternative
management strategy is appropriate for said animal.
6. The method of claim 4, wherein said comparing step comprises
comparing a neutrophil value in the leukocyte differential cell
count with the neutrophil value of (a), comparing a lymphocyte
value in the leukocyte differential cell count with the lymphocyte
value of (b), and/or comparing a eosinophil value in the leukocyte
differential cell count with the eosinophil value of (c), in any
combination, wherein a neutrophil value, a lymphocyte value and/or
an eosinophil value that is outside of the range of the respective
neutrophil value of (a), the lymphocyte value of (b) and/or the
eosinophil value of (c) identifies that the antibiotic treatment,
anti-infective treatment, probiotic treatment, immunostimulant
treatment, additional monitoring and/or a separate or alternative
management strategy is needed and/or should be continued or
initiated.
7. A method of reducing or discontinuing antibiotic treatment,
anti-infective treatment, probiotic treatment, immunostimulant
treatment, additional monitoring and/or a separate or alternative
management strategy of an animal that is receiving antibiotic
treatment, anti-infective treatment, probiotic treatment,
immunostimulant treatment, additional monitoring and/or a separate
or alternative management strategy, comprising: a) collecting a
sample from said animal; b) performing a leukocyte differential
cell count on said sample; c) comparing said leukocyte differential
cell count of (b) with an index of infection; and d) identifying
that reducing or discontinuing antibiotic treatment, anti-infective
treatment, probiotic treatment, immunostimulant treatment,
additional monitoring and/or a separate or alternative management
strategy of said animal is appropriate on the basis of said
comparing step.
8. The method of claim 7, wherein said index of infection is
selected from the group consisting of: a) a neutrophil value in a
range from X.sub.N.times.10.sup.3 cells/microliter to
Y.sub.N.times.10.sup.3 cells/microliter, wherein X.sub.N is about
0.0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2,
1.3, 1.4, 1.5, 1.6, or 1.7.times.10.sup.3 neutrophils per
microliter, and Y.sub.N is about 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6,
4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9,
6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2,
7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5,
8.6, 8.7, 8.8, 8.9, 9.0, 10.0, 10.1, 10.2, 10.3, 10.4, 10.5, 10.6,
10.7, 10.8, 10.9, 11.0, 11.1, 11.2, 11.3, 11.4, 11.5, 11.6, 11.7,
11.8, 11.9, or 12.0.times.10.sup.3 neutrophils per microliter; b) a
lymphocyte value in a range from X.sub.L.times.10.sup.3
cells/microliter to Y.sub.L.times.10.sup.3 cells/microliter,
wherein X.sub.L is about 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6,
4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9,
6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, or
7.0.times.10.sup.3 lymphocytes per microliter, and Y.sub.L is about
10.0, 10.1, 10.2, 10.3, 10.4, 10.5, 10.6, 10.7, 10.8, 10.9, 11.0,
11.1, 11.2, 11.3, 11.4, 11.5, 11.6, 11.7, 11.8, 11.9, 12.0, 12.1,
12.2, or 12.3.times.10.sup.3 lymphocytes per microliter; c) an
eosinophil value in a range from X.sub.E.times.10.sup.3
cells/microliter to Y.sub.E.times.10.sup.3 cells/microliter,
wherein X.sub.E is 0.0.times.10.sup.3 eosinophils per microliter
and Y.sub.E is about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9,
1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or
2.0.times.10.sup.3 eosinophils per microliter; and d) any
combination of (a), (b) and (c) above.
9. The method of claim 7, wherein said comparing step comprises
comparing a neutrophil value in the leukocyte differential cell
count with the neutrophil value of (a), comparing a lymphocyte
value in the leukocyte differential cell count with the lymphocyte
value of (b), and/or comparing a eosinophil value in the leukocyte
differential cell count with the eosinophil value of (c), in any
combination, wherein a neutrophil value, a lymphocyte value and/or
an eosinophil value that is within the range of the respective
neutrophil value of (a), the lymphocyte value of (b) and/or the
eosinophil value of (c) identifies that reduction or
discontinuation of the antibiotic treatment, anti-infective
treatment, probiotic treatment, immunostimulant treatment,
additional monitoring and/or a separate or alternative management
strategy is appropriate for said animal.
10. The method of claim 1, wherein said animal is in a group of
animals.
11. The method of claim 10, wherein a leukocyte differential cell
count is performed on a sample collected from each animal in said
group of animals and compared with an index of infection and said
each animal is assigned to either a normal subgroup or an abnormal
subgroup on the basis of said comparing step.
12. The method of claim 11, wherein animals of said normal subgroup
and animals of said abnormal subgroup are fed out together for a
period of weeks and/or months while only animals of said abnormal
subgroup are administered an antibiotic treatment, anti-infective
treatment, probiotic treatment, immunostimulant treatment,
additional monitoring and/or a separate or alternative management
strategy.
13. The method of claim 11, wherein animals of said normal subgroup
and animals of said abnormal subgroup are fed out together for a
period of weeks and/or months while animals of said normal subgroup
and animals of said abnormal subgroup are administered an
antibiotic treatment, anti-infective treatment, probiotic
treatment, immunostimulant treatment, additional monitoring and/or
a separate or alternative management strategy.
14. The method of claim 11, wherein animals of said abnormal
subgroup are segregated from animals of said normal subgroup.
15. The method of claim 1, wherein said collecting step comprises
dispensing said sample into a cartridge, and said performing step
is carried out with said sample in said cartridge.
16. The method of claim 15, wherein said cartridge is pre-warmed to
a pre-determined temperature, and said performing step is carried
out with a cartridge reader pre-warmed to substantially the same
pre-determined temperature.
17. The method of claim 1, wherein said collecting step includes
transferring said sample to an automated microscope cartridge.
18. The method of claim 1, wherein said animal is selected from the
group consisting of beef cattle, dairy cattle, sheep, pigs, goats,
and poultry.
19. A method of tracking illness and/or antibiotic treatment in a
group of animals, comprising: (a) selecting an individual animal
present in the group of animals; (b) collecting a sample from said
animal of (a); (c) performing a leukocyte differential count on
said sample; (d) comparing said leukocyte differential count of (c)
to an index of infection; (e) assigning said individual animal to
either a normal subgroup or an abnormal subgroup on the basis of
said comparing step; (f) generating an electronic record for said
animal comprising said animal's identity, said animal's leukocyte
differential count history, said animal's illness history, and said
animal's treatment and/or management strategy history; and (g)
repeating steps (a) through (f) until all animals in said group of
animals are assigned to either said normal subgroup or said
abnormal subgroup and said electronic records are stored in a
database.
20. The method of claim 19, wherein said collecting step comprises
dispensing said sample into a cartridge, and said performing step
is carried out with said sample in said cartridge.
21. The method of claim 20, wherein said cartridge is pre-warmed to
a pre-determined temperature, and said performing step is carried
out with a cartridge reader pre-warmed to substantially the same
pre-determined temperature.
22. The method of claim 19, wherein said collecting step includes
transferring said sample to an automated microscope cartridge.
23. The method of claim 19, wherein the steps are carried out
chute-side or pen-side in an average time of not more than about 5,
2 or 1 minutes.
24. The method of claim 19, further comprising the step of
administering an antibiotic treatment, anti-infective treatment,
probiotic treatment, immunostimulant treatment, additional
monitoring and/or a separate or alternative management strategy to
animals of said abnormal subgroup and not to animals of said normal
subgroup; (ii) hospitalizing animals of said abnormal subgroup and
not animals of said normal subgroup; and/or (iii) quarantining
animals of said abnormal subgroup from animals of said normal
subgroup.
25. The method of claim 19, further comprising the step of feeding
out animals of said normal subgroup and/or animals of said abnormal
subgroup; and/or (ii) periodically recording the weight of animals
of said normal subgroup and/or of animals of said abnormal
subgroup.
26. The method of claim 19, wherein animals of said normal subgroup
and animals of said abnormal subgroup are fed out together for a
period of weeks and/or months while only animals of said abnormal
subgroup are administered an antibiotic treatment, anti-infective
treatment, probiotic treatment, immunostimulant treatment,
additional monitoring and/or a separate or alternative management
strategy.
27. The method of claim 19, wherein animals of said normal subgroup
and animals of said abnormal subgroup are fed out together for a
period of weeks and/or months while animals of said normal subgroup
and animals of said abnormal subgroup are administered an
antibiotic treatment, anti-infective treatment, probiotic
treatment, immunostimulant treatment, additional monitoring and/or
a separate or alternative management strategy.
28. A method for transferring health information to one or more
parties, wherein health data are collected as described in claim
19, uploaded to a web database documenting animals' health status,
treatment status and/or subgroup, and made accessible to said one
or more parties.
29. The method of claim 19, wherein animals of said abnormal
subgroup are segregated from animals of said normal subgroup.
30. The method of claim 29, wherein animals of said abnormal
subgroup are not administered an antibiotic treatment,
anti-infective treatment, probiotic treatment, immunostimulant
treatment, additional monitoring and/or a separate or alternative
management strategy.
31. The method of claim 19, wherein said animals are selected from
the group consisting of beef cattle, dairy cows, sheep, pigs,
goats, and poultry.
32. The method of claim 19, wherein said index of infection is
selected from the group consisting of: a) a neutrophil value in a
range from X.sub.N.times.10.sup.3 cells/microliter to
Y.sub.N.times.10.sup.3 cells/microliter, wherein X.sub.N is about
0.0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2,
1.3, 1.4, 1.5, 1.6, or 1.7.times.10.sup.3 neutrophils per
microliter, and Y.sub.N is about 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6,
4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9,
6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2,
7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5,
8.6, 8.7, 8.8, 8.9, 9.0, 10.0, 10.1, 10.2, 10.3, 10.4, 10.5, 10.6,
10.7, 10.8, 10.9, 11.0, 11.1, 11.2, 11.3, 11.4, 11.5, 11.6, 11.7,
11.8, 11.9, or 12.0.times.10.sup.3 neutrophils per microliter; b) a
lymphocyte value in a range from X.sub.L.times.10.sup.3
cells/microliter to Y.sub.L.times.10.sup.3 cells/microliter,
wherein X.sub.L is about 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6,
4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9,
6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, or
7.0.times.10.sup.3 lymphocytes per microliter, and Y.sub.L is about
10.0, 10.1, 10.2, 10.3, 10.4, 10.5, 10.6, 10.7, 10.8, 10.9, 11.0,
11.1, 11.2, 11.3, 11.4, 11.5, 11.6, 11.7, 11.8, 11.9, 12.0, 12.1,
12.2, or 12.3.times.10.sup.3 lymphocytes per microliter; c) an
eosinophil value in a range from X.sub.E.times.10.sup.3
cells/microliter to Y.sub.E.times.10.sup.3 cells/microliter,
wherein X.sub.E is 0.0.times.10.sup.3 eosinophils per microliter
and Y.sub.E is about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9,
1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or
2.0.times.10.sup.3 eosinophils per microliter; and d) any
combination of (a), (b) and (c) above.
33. An apparatus, comprising: (a) a housing having at least a first
interior chamber; (b) an automated microscope in said first
interior chamber; (c) at least one first cartridge dispenser in
said first interior chamber; (d) at least one first cartridge
dispenser access door in said housing and operatively associated
with said first cartridge dispenser; (e) at least one first fresh
cartridge access port in said housing and operatively associated
with said first cartridge dispenser; (f) a filled cartridge insert
port in said housing and operatively associated with said automated
microscope; and (g) at least one heater operatively associated with
said housing configured to heat both said automated microscope and
said at least a first cartridge dispenser.
34. The apparatus of claim 33, further comprising: (h) a second
cartridge dispenser in said first interior chamber; (i) a second
cartridge dispenser access door in said housing and operatively
associated with said second cartridge dispenser; and (j) a second
individual cartridge access port in said housing and operatively
associated with said second cartridge dispenser.
35. The apparatus of claim 33, further comprising: a heater
controller operatively associated with said at least one heater;
and at least one temperature sensor in said housing operatively
associated with said heater controller.
36. A combination apparatus, comprising: (a) a first housing having
at least a first interior chamber; (b) an automated microscope in
said first interior chamber; (c) a second housing having at least a
second interior chamber; (d) at least one first cartridge dispenser
in said second interior chamber; (e) at least one first cartridge
dispenser access door in said second housing and operatively
associated with said first cartridge dispenser; (f) at least a
first fresh cartridge access port in said second housing and
operatively associated with said first cartridge dispenser; (g) a
filled cartridge insert port in said first housing and operatively
associated with said automated microscope; and (h) at least one
heater operatively associated with each of said first and second
housings configured to heat both said automated microscope and said
at least a first cartridge dispenser.
37. The combination apparatus of claim 36, further comprising: (i)
a second cartridge dispenser in said second interior chamber; (j) a
second cartridge dispenser access door in said second housing and
operatively associated with said second cartridge dispenser; and
(k) a second individual cartridge access port in said second
housing and operatively associated with said second cartridge
dispenser.
38. The combination apparatus of claim 36, further comprising: a
heater controller operatively associated with each of said at least
one heater; and at least one temperature sensor in each of said
housings and operatively associated with said heater
controller.
39. The method of claim 1, carried out with the apparatus of claim
33.
40. The method of claim 1, carried out with the combination
apparatus of claim 36.
Description
STATEMENT OF PRIORITY
[0001] This application claims the benefit, under 35 U.S.C.
.sctn.119(e), of U.S. Provisional Application Ser. No. 62/311,706,
filed Mar. 22, 2016, the entire contents of which are incorporated
by reference herein.
BACKGROUND OF THE INVENTION
[0002] In the production of farm animals such as beef cattle, swine
and poultry, mass treatment of groups of animals with antibiotics
to prevent disease outbreaks is common. There is, however, an
increasing desire to reduce the administration of such antibiotics,
particularly where the animals are raised as food for human
consumption.
[0003] Unfortunately, livestock producers have few tools to
identify which animals need treatment; it is difficult to
distinguish infected animals that benefit from antibiotic treatment
from those that are not infected. As animals are co-mingled, they
are more likely to become infected, but infected animals may be
difficult to distinguish from uninfected animals based on
temperature or antibody response, especially if the exposure was
recent. Animals, unlike humans, cannot provide a verbal response to
a question of whether or not they feel sick. Finally, farm animals
are often raised in large herds or flocks, and the amount of time
available to diagnose an individual, animal is often extremely
limited. Hence, in an effort to keep animals healthy and in an
effort to ensure animals who need treatment get treated, entire
herds or flocks are often administered an antibiotic, whether or
not it is required by all members of that herd or flock.
Alternatively, some pens or groups may receive no antibiotic even
though individuals in the group may be infected.
[0004] Accordingly, new techniques are needed to rapidly diagnose
those animals likely to have a current infection so they can be
managed differently from those that do not show the signature of
infection.
[0005] The present invention overcomes previous shortcomings in the
art by providing methods and compositions for reducing antibiotic
administration to farm animals.
SUMMARY OF THE INVENTION
[0006] In one aspect, the present invention provides a method of
identifying an animal for which antibiotic treatment,
anti-infective treatment, probiotic treatment, immunostimulant
treatment, additional monitoring and/or a separate or alternative
management strategy is appropriate, comprising: a) collecting a
sample from said animal; b) performing a leukocyte differential
cell count on said sample; c) comparing said leukocyte differential
cell count of (b) with an index of infection; and d) initiating
antibiotic treatment, anti-infective treatment, probiotic
treatment, immunostimulant treatment, additional monitoring and/or
a separate or alternative management strategy of said animal on the
basis of said comparing step.
[0007] In a further aspect, the present invention provides a method
of determining need for and/or timing of antibiotic treatment,
anti-infective treatment, probiotic treatment, immunostimulant
treatment, additional monitoring and/or a separate or alternative
management strategy of an animal, comprising: a) collecting a
sample from said animal; b) performing a leukocyte differential
cell count on said sample; c) comparing said leukocyte differential
cell count of (b) with an index of infection; and d) identifying
the need for and/or timing of the antibiotic treatment,
anti-infective treatment, probiotic treatment, immunostimulant
treatment, additional monitoring and/or a separate or alternative
management strategy of said animal on the basis of said comparing
step.
[0008] In an additional aspect, the present invention provides a
method of reducing or discontinuing antibiotic treatment,
anti-infective treatment, probiotic treatment, immunostimulant
treatment, additional monitoring and/or a separate or alternative
management strategy of an animal that is receiving antibiotic
treatment, anti-infective treatment, probiotic treatment,
immunostimulant treatment, additional monitoring and/or a separate
or alternative management strategy, comprising: a) collecting a
sample from said animal; b) performing a leukocyte differential
cell count on said sample; c) comparing said leukocyte differential
cell count of (b) with an index of infection; and d) identifying
that reducing or discontinuing antibiotic treatment, anti-infective
treatment, probiotic treatment, immunostimulant treatment,
additional monitoring and/or a separate or alternative management
strategy of said animal is appropriate on the basis of said
comparing step.
[0009] In another aspect, the present invention provides a method
of tracking illness and/or treatment (e.g., antibiotic treatment)
in a group of animals, comprising: (a) selecting an individual
animal present in the group of animals; (b) collecting a sample
from said animal of (a); (c) performing a leukocyte differential
count on said sample; (d) comparing said leukocyte differential
count of (c) to an index of infection; (e) assigning said
individual animal to either a normal subgroup or an abnormal
subgroup on the basis of said comparing step; (f) generating an
electronic record for said animal comprising said animal's
identity, said animal's leukocyte differential count history, said
animal's illness history, and said animal's treatment and/or
management strategy history; and (g) repeating steps (a) through
(f) until all animals in said group of animals are assigned to
either said normal subgroup or said abnormal subgroup and said
electronic records are stored in a database.
[0010] In yet further aspects, the present invention provides an
apparatus, comprising: (a) a housing having at least a first
interior chamber; (b) an automated microscope in said first
interior chamber; (c) at least one first cartridge dispenser in
said first interior chamber; (d) at least one first cartridge
dispenser access door in said housing and operatively associated
with said first cartridge dispenser; (e) at least one first fresh
cartridge access port in said housing and operatively associated
with said first cartridge dispenser; (f) a filled cartridge insert
port in said housing and operatively associated with said automated
microscope; and (g) at least one heater operatively associated with
said housing configured to heat both said automated microscope and
said at least a first cartridge dispenser.
[0011] The present invention also provides a combination apparatus,
comprising: (a) a first housing having at least a first interior
chamber; (b) an automated microscope in said first interior
chamber; (c) a second housing having at least a second interior
chamber; (d) at least one first cartridge dispenser in said second
interior chamber; (e) at least one first cartridge dispenser access
door in said second housing and operatively associated with said
first cartridge dispenser; (f) at least a first fresh cartridge
access port in said second housing and operatively associated with
said first cartridge dispenser; (g) a filled cartridge insert port
in said first housing and operatively associated with said
automated microscope; and (h) at least one heater operatively
associated with each of said first and second housings configured
to heat both said automated microscope and said at least a first
cartridge dispenser.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] FIG. 1 is a schematic overview of a method of the present
invention.
[0013] FIG. 2 is a flow diagram of the screening and sorting steps
of one embodiment of a method of the present invention.
[0014] FIG. 3A is an internal schematic diagram of one embodiment
of an apparatus useful for carrying out a method of the present
invention.
[0015] FIG. 3B is an external schematic diagram of the apparatus of
FIG. 3A.
[0016] FIG. 4A is an internal schematic diagram of a second
embodiment of an apparatus useful for carrying out a method of the
present invention.
[0017] FIG. 4B is an external schematic diagram of the apparatus of
FIG. 4A.
[0018] FIG. 5 is a perspective view of a cartridge dispenser useful
in an apparatus of FIGS. 3A, 3B, 4A, and 4B.
[0019] FIG. 6 is a schematic diagram of an imaging reader for
imaging a sample.
DETAILED DESCRIPTION OF THE INVENTION
[0020] The present invention is now described more fully
hereinafter with reference to the accompanying drawings, in which
embodiments of the invention are shown. This invention may,
however, be embodied in many different forms and should not be
construed as limited to the embodiments set forth herein; rather
these embodiments are provided so that this disclosure will be
thorough and complete and will fully convey the scope of the
invention to those skilled in the art.
[0021] Like numbers refer to like elements throughout. In the
figures, the thickness of certain lines, layers, components,
elements or features may be exaggerated for clarity. Where used,
broken lines illustrate optional features or operations unless
specified otherwise.
[0022] A subject "in need thereof" as used herein refers to a
subject that can benefit from the therapeutic and/or prophylactic
effects of the treatments and/or actions of the present invention.
Such a subject can be a subject diagnosed with a disease or
disorder of this invention, a subject suspected of having or
developing a disorder or disease of this invention, and/or a
subject determined to be at increased risk of having or developing
a disease or disorder of this invention.
[0023] By the term "treat," "treating," or "treatment of" (and
grammatical variations thereof) it is meant that the severity of
the subject's condition is reduced, at least partially improved or
ameliorated, and/or that some alleviation, mitigation or decrease
in at least one clinical symptom is achieved and/or there is a
delay in the progression of the disease or disorder.
[0024] The terms "prevent," "preventing," and "prevention of" (and
grammatical variations thereof) refer to reduction and/or delay of
the onset and/or progression of a disease, disorder and/or a
clinical symptom(s) in a subject and/or a reduction in the severity
of the onset and/or progression of the disease, disorder and/or
clinical symptom(s) relative to what would occur in the absence of
the methods of the invention. The prevention can be complete, e.g.,
the total absence of the disease, disorder and/or clinical
symptom(s). The prevention can also be partial, such that the
occurrence of the disease, disorder and/or clinical symptom(s) in
the subject and/or the severity of onset and/or the progression is
less than what would occur in the absence of a composition of the
present invention.
[0025] As used herein, the terms "therapeutically effective amount"
or "effective amount" refer to an amount of a composition or
formulation or treatment of this invention that elicits a
therapeutically useful response in a subject. Those skilled in the
art will appreciate that the therapeutic effects need not be
complete or curative, as long as some benefit is provided to the
subject.
[0026] As used in the description of the invention and the appended
claims, the singular forms "a," "an" and "the" are intended to
include the plural forms as well, unless the context clearly
indicates otherwise. For example, "a cell" can mean a single cell
or a multiplicity of cells.
[0027] Also as used herein, "and/or" refers to and encompasses any
and all possible combinations of one or more of the associated
listed items, as well as the lack of combinations when interpreted
in the alternative ("or").
[0028] As used herein, the transitional phrase "consisting
essentially of" (and grammatical variants) is to be interpreted as
encompassing the recited materials or steps "and those that do not
materially affect the basic and novel characteristic(s)" of the
claimed invention. See, In re Herz, 537 F.2d 549, 551-52, 190
U.S.P.Q. 461, 463 (CCPA 1976) (emphasis in the original); see also
MPEP .sctn.2111.03. Thus, the term "consisting essentially of" as
used herein should not be interpreted as equivalent to
"comprising."
[0029] It will be further understood that the terms "comprises"
and/or "comprising," when used in this specification, specify the
presence of stated features, integers, steps, operations, elements,
and/or components, but do not preclude the presence or addition of
one or more other features, integers, steps, operations, elements,
components, and/or groups thereof. As used herein the term "and/or"
includes any and all combinations of one or more of the associated
listed items.
[0030] The term "about," as used herein when referring to a
measurable value such as an amount or concentration (e.g., the
amount of the benzodiazepine in the pharmaceutical composition) and
the like, is meant to encompass variations of 20%, 10%, 5%, 1%,
0.5%, 0.4% 0.3%, 0.2% or 0.1% of the specified value.
[0031] Unless the context indicates otherwise, it is specifically
intended that the various features of the invention described
herein can be used in any combination. For example, features
described in relation to one embodiment may also be applicable to
and combinable with other embodiments and aspects of the
invention.
[0032] Moreover, the present invention also contemplates that in
some embodiments of the invention, any feature or combination of
features set forth herein can be excluded or omitted. To
illustrate, if the specification states that a complex comprises
components A, B and C, it is specifically intended that any of A, B
or C, or a combination thereof, can be omitted and disclaimed.
[0033] Unless otherwise defined, all terms (including technical and
scientific terms) used herein have the same meaning as commonly
understood by one of ordinary skill in the art to which this
invention belongs. It will be further understood that terms, such
as those defined in commonly used dictionaries, should be
interpreted as having a meaning that is consistent with their
meaning in the context of the present application and relevant art
and should not be interpreted in an idealized or overly formal
sense unless expressly so defined herein. The terminology used in
the description of the invention herein is for the purpose of
describing particular embodiments only and is not intended to be
limiting of the invention.
[0034] All publications, patent applications, patents and other
non-patent references mentioned herein are incorporated by
reference herein in their entirety.
[0035] It will be understood that when an element is referred to as
being "on," "attached" to, "connected" to, "coupled" with,
"contacting," etc., another element, it can be directly on,
attached to, connected to, coupled with and/or contacting the other
element or intervening elements can also be present. In contrast,
when an element is referred to as being, for example, "directly
on," "directly attached" to, "directly connected" to, "directly
coupled" with or "directly contacting" another element, there are
no intervening elements present. It will also be appreciated by
those of skill in the art that references to a structure or feature
that is disposed "adjacent" another feature can have portions that
overlap or underlie the adjacent feature.
[0036] Spatially relative terms, such as "under," "below," "lower,"
"over," "upper" and the like, may be used herein for ease of
description to describe an element's or feature's relationship to
another element(s) or feature(s) as illustrated in the figures. It
will be understood that the spatially relative terms are intended
to encompass different orientations of the device in use or
operation in addition to the orientation depicted in the figures.
For example, if the device in the figures is inverted, elements
described as "under" or "beneath" other elements or features would
then be oriented "over" the other elements or features. Thus the
exemplary term "under" can encompass both an orientation of over
and under. The device may otherwise be oriented (rotated 90 degrees
or at other orientations) and the spatially relative descriptors
used herein interpreted accordingly. Similarly, the terms
"upwardly," "downwardly," "vertical," "horizontal" and the like are
used herein for the purpose of explanation only, unless
specifically indicated otherwise.
[0037] It will be understood that, although the terms first,
second, etc., may be used herein to describe various elements,
components, regions, layers and/or sections, these elements,
components, regions, layers and/or sections should not be limited
by these terms. Rather, these terms are only used to distinguish
one element, component, region, layer and/or section, from another
element, component, region, layer and/or section. Thus, a first
element, component, region, layer or section discussed herein could
be termed a second element, component, region, layer or section
without departing from the teachings of the present invention. The
sequence of operations (or steps) is not limited to the order
presented in the claims or figures unless specifically indicated
otherwise.
[0038] Animals on which the embodiments of the present invention
may be implemented include, but are not limited to, beef cattle,
dairy cattle, sheep, pigs, goats, rabbits and poultry (e.g.,
chickens, turkeys, ducks, geese, quail, pheasant, partridge such as
Chukar Partridge, etc.).
[0039] Antibiotics or immunostimulants which may be administered to
animals in accordance with the present invention include, but are
not limited to the following antibiotic classes: aminocoumarins,
aminoglycosides, amphenicols, cephalosporins, diaminopyrimidines,
fluoroquinolones, glycolipids, ionophores, lincosamides,
macrolides, penicillins, pleuromutilins, polypeptides,
quinoxalines, streptogramins, sulfonamides, tetracyclines and
combinations thereof.
[0040] Administration of antibiotics may be carried out by any
suitable technique, including oral administration (e.g., by
including the antibiotic compound in the feed of the animal as a
feed additive), parenteral injection (e.g., intravenous injection,
subcutaneous injection, intraarterial injection, intramuscular
injection, etc.), etc.
[0041] A sample of this invention can include blood, milk,
colostrum, urine, nasal mucous, vaginal secretions, mucous
secretions, joint fluid, cerebrospinal fluid, fluid from aspirate,
fluid from drainage, fluid from lavage or washing, tissue or any
other biological sample from an animal that can contain
leukocytes.
[0042] In one embodiment, the present invention provides a method
of identifying an animal for which antibiotic treatment,
anti-infective treatment, probiotic treatment, immunostimulant
treatment, additional monitoring and/or a separate or alternative
management strategy is appropriate, comprising: a) collecting a
sample from said animal; b) performing a leukocyte differential
cell count on said sample; c) comparing said leukocyte differential
cell count of (b) with an index of infection; and d) initiating
antibiotic treatment, anti-infective treatment, probiotic
treatment, immunostimulant treatment, additional monitoring and/or
a separate or alternative management strategy of said animal on the
basis of said comparing step.
[0043] In the method described above, the comparing step can
comprise, consist essentially of, or consist of comparing a
neutrophil value in the leukocyte differential cell count with the
neutrophil value of (a), comparing a lymphocyte value in the
leukocyte differential cell count with the lymphocyte value of (b),
and/or comparing a eosinophil value in the leukocyte differential
cell count with the eosinophil value of (c), in any combination,
wherein a neutrophil value, a lymphocyte value and/or an eosinophil
value that is outside of the range of the respective neutrophil
value of (a), the lymphocyte value of (b) and/or the eosinophil
value of (c) identifies that antibiotic treatment, anti-infective
treatment, probiotic treatment, immunostimulant treatment,
additional monitoring and/or a separate or alternative management
strategy is appropriate for said animal.
[0044] In a further embodiment, the present invention provides a
method of determining need for and/or timing of antibiotic
treatment, anti-infective treatment, probiotic treatment,
immunostimulant treatment, additional monitoring and/or a separate
or alternative management strategy of an animal (e.g., an animal in
need thereof), comprising: a) collecting a sample from said animal;
b) performing a leukocyte differential cell count on said sample;
c) comparing said leukocyte differential cell count of (b) with an
index of infection; and d) identifying the need for and/or timing
of the antibiotic treatment, anti-infective treatment, probiotic
treatment, immunostimulant treatment, additional monitoring and/or
a separate or alternative management strategy of said animal on the
basis of said comparing step.
[0045] In the method described above, the comparing step can
comprise, consist essentially of or consist of comparing a
neutrophil value in the leukocyte differential cell count with the
neutrophil value of (a), comparing a lymphocyte value in the
leukocyte differential cell count with the lymphocyte value of (b),
and/or comparing a eosinophil value in the leukocyte differential
cell count with the eosinophil value of (c), in any combination,
wherein a neutrophil value, a lymphocyte value and/or an eosinophil
value that is outside of the range of the respective neutrophil
value of (a), the lymphocyte value of (b) and/or the eosinophil
value of (c) identifies that antibiotic treatment, anti-infective
treatment, probiotic treatment, immunostimulant treatment,
additional monitoring and/or a separate or alternative management
strategy is appropriate for said animal.
[0046] The present invention additionally provides a method of
reducing or discontinuing antibiotic treatment, anti-infective
treatment, probiotic treatment, immunostimulant treatment,
additional monitoring and/or a separate or alternative management
strategy of an animal that is receiving antibiotic treatment,
anti-infective treatment, probiotic treatment, immunostimulant
treatment, additional monitoring and/or a separate or alternative
management strategy, comprising: a) collecting a sample from said
animal; b) performing a leukocyte differential cell count on said
sample; c) comparing said leukocyte differential cell count of (b)
with an index of infection; and d) identifying or determining that
reducing or discontinuing antibiotic treatment, anti-infective
treatment, probiotic treatment, immunostimulant treatment,
additional monitoring and/or a separate or alternative management
strategy of said animal is appropriate on the basis of said
comparing step.
[0047] In the method described above, the comparing step comprises
comparing a neutrophil value in the leukocyte differential cell
count with the neutrophil value of (a), comparing a lymphocyte
value in the leukocyte differential cell count with the lymphocyte
value of (b), and/or comparing a eosinophil value in the leukocyte
differential cell count with the eosinophil value of (c), in any
combination, wherein a neutrophil value, a lymphocyte value and/or
an eosinophil value that is within the range of the respective
neutrophil value of (a), the lymphocyte value of (b) and/or the
eosinophil value of (c) identifies that reduction or
discontinuation of the antibiotic treatment, anti-infective
treatment, probiotic treatment, immunostimulant treatment,
additional monitoring and/or a separate or alternative management
strategy is appropriate for said animal.
[0048] In the methods of this invention, an index of infection can
be, but is not limited to, a) a neutrophil value in a range from
about X.sub.N.times.10.sup.3 cells/microliter to about
Y.sub.N.times.10.sup.3 cells/microliter, wherein X.sub.N is 0, 0.1,
0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4,
1.5, 1.6, or 1.7.times.10.sup.3 neutrophils per microliter, and
Y.sub.N is 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0,
5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3,
6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6,
7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9,
9.0, 10.0, 10.1, 10.2, 10.3, 10.4, 10.5, 10.6, 10.7, 10.8, 10.9,
11.0, 11.1, 11.2, 11.3, 11.4, 11.5, 11.6, 11.7, 11.8, 11.9, or
12.0.times.10.sup.3 neutrophils per microliter; b) a lymphocyte
value in a range from about X.sub.L.times.10.sup.3 cells/microliter
to about Y.sub.L.times.10.sup.3 cells/microliter, wherein X.sub.L
is 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1,
5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4,
6.5, 6.6, 6.7, 6.8, 6.9, or 7.0.times.10.sup.3 lymphocytes per
microliter, and Y.sub.L is 10.0, 10.1, 10.2, 10.3, 10.4, 10.5,
10.6, 10.7, 10.8, 10.9, 11.0, 11.1, 11.2, 11.3, 11.4, 11.5, 11.6,
11.7 11.8, 11.9, 12.0, 12.1, 12.2, or 12.3.times.10.sup.3
lymphocytes per microliter; c) an eosinophil value in a range from
about X.sub.E.times.10.sup.3 cells/microliter to about
Y.sub.E.times.10.sup.3 cells/microliter, wherein X.sub.E is
0.0.times.10.sup.3 eosinophils per microliter and Y.sub.E is 0.1,
0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4,
1.5, 1.6, 1.7, 1.8, 1.9, or 2.0.times.10.sup.3 eosinophils per
microliter; and d) any combination of (a), (b) and (c). It is
understood that the values recited herein include any fraction of
one tenth, one hundredth or one thousandth, etc., of said recited
values. For example, a range from 0.0 to 0.1 includes 0.01, 0.02,
0.03, 0.04, 0.05, 0.06, 0.07, 0.08 0.09; a range from 1.0 to 1.1
includes 1.01, 1.02, 1.03, 1.04, 1.05, 1.06, 0.07, 1.08, 1.09; and
a range from 1.1 to 1.2 includes 1.11, 1.12, 1.13, 1.14, 1.15,
1.16, 1.17, 1.18, 1.19, etc., as if each individual value was
explicitly set forth herein.
[0049] In some embodiments, (a), (b) and (c) may be calculated as a
percentage of total cells (e.g., total white blood cells).
[0050] In some embodiments, different indices may be used to
optimize different end points. There are scenarios where minimizing
hospital pulls (morbidity) is the most advantageous for the animal
management strategy. Alternatively, maximizing weight gain could be
the preferred animal management strategy. For example, to maximize
an animal's weight gain, thresholds of neutrophils between 1.3 and
5.8.times.10.sup.3 cells per microliter and of lymphocytes between
(f) and 11.3.times.10.sup.3 cells per microliter can be used.
Another example would be a logical index for reducing morbidity
such as: If eosinophils generally equal zero and neutrophils are in
a range of 0.8 and 4.0.times.10.sup.3 cells per microliter and
lymphocytes are in a range of 7.0 and 10.8.times.10.sup.3 cells per
microliter, or if eosinophils are greater than zero cells per
microliter and neutrophils are in a range from 1.66 and
5.4.times.10 3 cells per microliter and lymphocytes are in a range
from 4.1 and 10.2.times.10.sup.3 cells per microliter as measured
in a sample from an animal or a plurality of animals in a group,
then morbidity (e.g., the number of sick animals, can be
minimized.
[0051] In some embodiments of this invention, an index of infection
can be a monocyte value in a range from about
X.sub.M.times.10.sup.3 cells/microliter to about
Y.sub.M.times.10.sup.3 cells/microliter, wherein X.sub.M is
0.0.times.10.sup.3 monocytes per microliter and Y.sub.M is 0.1,
0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4,
1.5, 1.6, 1.7, 1.8, 1.9, or 2.0.times.10.sup.3 monocytes per
microliter.
[0052] In some embodiments of this invention, an index of infection
can be a basophil value in a range from about
X.sub.M.times.10.sup.3 cells/microliter to about
Y.sub.M.times.10.sup.3 cells/microliter, wherein X.sub.M is
0.0.times.10.sup.3 basophils per microliter and Y.sub.M is 0.1,
0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4,
1.5, 1.6, 1.7, 1.8, 1.9, or 2.0.times.10.sup.3 basophils per
microliter.
[0053] In some embodiments, an index for neutrophils, lymphocytes,
eosinophils, basophils and any other white blood cell type
described herein may be calculated as a percentage of total cells
(e.g., total white blood cells).
[0054] The indices for neutrophils, lymphocytes, eosinophils,
monocytes and basophils described herein can be used singly or in
any combination in the methods of this invention.
[0055] In the methods of this invention, an animal can be present
in a group of animals (e.g., in a herd or flock or population,
etc.). Each animal can be present singly, or in combination with
other animals in the group of animals, in an enclosure, a pen, a
corral, a coop, a dwelling, a barn, a field, a pasture, a
container, a chute, etc., as would be known in the art. In some
embodiments, one or more (including all) of the steps of the
methods of this invention can be carried out on site, e.g., at the
location where the animal or group of animals may be present,
including, for example, chute-side or pen-side. In some
embodiments, the methods of this invention can be carried out in an
average time of not more than about 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1
minutes. In particular embodiments, the steps are carried out
chute-side and/or pen-side in an average time of not more than
about 5, 2 or 1 minutes.
[0056] In some embodiments, the leukocyte differential cell count
can be performed on a sample collected from each animal in a group
of animals and compared with an index of infection and each animal
can then be assigned to either a normal subgroup or an abnormal
subgroup on the basis of said comparing step.
[0057] In some embodiments, animals of said normal subgroup and
animals of said abnormal subgroup can be fed out together for a
period of weeks and/or months while only animals of said abnormal
subgroup are administered an antibiotic treatment, anti-infective
treatment, probiotic treatment, immunostimulant treatment,
additional monitoring and/or a separate or alternative management
strategy.
[0058] In some embodiments, animals of said normal subgroup and
animals of said abnormal subgroup are fed out together for a period
of weeks and/or months while animals of said normal subgroup and
animals of said abnormal subgroup are administered an antibiotic
treatment, anti-infective treatment, probiotic treatment,
immunostimulant treatment, additional monitoring and/or a separate
or alternative management strategy.
[0059] In some embodiments, animals of said abnormal subgroup are
segregated from animals of said normal subgroup.
[0060] In additional embodiments, the present invention provides a
method of tracking illness and/or treatment in a group of animals,
comprising: (a) selecting an individual animal present in the group
of animals; (b) collecting a sample from said animal of (a); (c)
performing a leukocyte differential count on said sample; (d)
comparing said leukocyte differential count of (c) to an index of
infection; (e) assigning said individual animal to either a normal
subgroup or an abnormal subgroup on the basis of said comparing
step; (f) generating an electronic record for said animal
comprising said animal's identity, said animal's leukocyte
differential count history, said animal's illness history, and said
animal's treatment and/or management strategy history; and (g)
repeating steps (a) through (f) until all animals in said group of
animals are assigned to either said normal subgroup or said
abnormal subgroup and said electronic records are stored in a
database.
[0061] In some embodiments, the collecting step of the methods
described herein comprises dispensing said sample into a cartridge,
and said performing or generating step can be carried out with said
sample in said cartridge.
[0062] In some embodiments, the cartridge can be pre-warmed to a
pre-determined temperature, and said performing step or generating
step can be carried out with a cartridge reader pre-warmed to
substantially the same pre-determined temperature.
[0063] In some embodiments, wherein said collecting step includes
transferring said sample to an automated microscope cartridge.
[0064] In some embodiments, the methods of this invention can
comprise the step of administering an antibiotic treatment,
anti-infective treatment, probiotic treatment, immunostimulant
treatment, additional monitoring and/or a separate or alternative
management strategy to animals of said abnormal subgroup and not to
animals of said normal subgroup; (ii) hospitalizing animals of said
abnormal subgroup and not animals of said normal subgroup; and/or
(iii) quarantining animals of said abnormal subgroup from animals
of said normal subgroup.
[0065] In some embodiments, the methods of this invention can
further comprise the step of feeding out animals of said normal
subgroup and/or animals of said abnormal subgroup; and/or (ii)
periodically recording the weight of animals of said normal
subgroup and/or of animals of said abnormal subgroup.
[0066] In some embodiments, animals of said normal subgroup and
animals of said abnormal subgroup are fed out together for a period
of weeks and/or months while only animals of said abnormal subgroup
are administered an antibiotic treatment, anti-infective treatment,
probiotic treatment, immunostimulant treatment, additional
monitoring and/or a separate or alternative or different management
strategy.
[0067] Nonlimiting examples of a management strategy of this
invention include culling, antibiotic treatment, immunostimulant
treatment, individualized treatment, group treatment and/or
segregation. By alternative or different management strategy, in
some embodiments, it is meant that the management strategy can be
changed from a previous management strategy.
[0068] In some embodiments, animals of said normal subgroup and
animals of said abnormal subgroup are fed out together for a period
of weeks and/or months while animals of said normal subgroup and
animals of said abnormal subgroup are administered an antibiotic
treatment, anti-infective treatment, probiotic treatment,
immunostimulant treatment, additional monitoring and/or a separate
or alternative management strategy.
[0069] In some embodiments, animals of said abnormal subgroup are
segregated from animals of said normal subgroup.
[0070] In some embodiment, animals of said abnormal subgroup are
not administered an antibiotic treatment, anti-infective treatment,
probiotic treatment, immunostimulant treatment, additional
monitoring and/or a separate or alternative management
strategy.
[0071] The present invention additionally provides a method for
transferring health information to one or more parties, wherein
health data are collected as described herein, uploaded to a web
database documenting animals' health status, treatment status
and/or subgroup, and made accessible to said one or more
parties.
[0072] In additional embodiments of this invention, an apparatus is
provided, comprising: (a) a housing having at least a first
interior chamber; (b) an automated microscope in said first
interior chamber; (c) at least one first cartridge dispenser in
said first interior chamber; (d) at least one first cartridge
dispenser access door in said housing and operatively associated
with said first cartridge dispenser; (e) at least one first fresh
cartridge access port in said housing and operatively associated
with said first cartridge dispenser; (f) a filled cartridge insert
port in said housing and operatively associated with said automated
microscope; and (g) at least one heater operatively associated with
said housing configured to heat both said automated microscope and
said at least a first cartridge dispenser.
[0073] In some embodiments, the apparatus of this invention can
also comprise (h) a second cartridge dispenser in said first
interior chamber; (i) a second cartridge dispenser access door in
said housing and operatively associated with said second cartridge
dispenser; and (j) a second individual cartridge access port in
said housing and operatively associated with said second cartridge
dispenser.
[0074] In some embodiments, the apparatus of this invention can
further comprise a heater controller operatively associated with
said at least one heater; and at least one temperature sensor in
said housing operatively associated with said heater
controller.
[0075] In a further embodiment, the present invention provides a
combination apparatus, comprising: (a) a first housing having at
least a first interior chamber; (b) an automated microscope in said
first interior chamber; (c) a second housing having at least a
second interior chamber; (d) at least one first cartridge dispenser
in said second interior chamber; (e) at least one first cartridge
dispenser access door in said second housing and operatively
associated with said first cartridge dispenser; (f) at least a
first fresh cartridge access port in said second housing and
operatively associated with said first cartridge dispenser; (g) a
filled cartridge insert port in said first housing and operatively
associated with said automated microscope; and (h) at least one
heater operatively associated with each of said first and second
housings configured to heat both said automated microscope and said
at least a first cartridge dispenser.
[0076] In some embodiments, the combination apparatus of this
invention can further comprise (i) a second cartridge dispenser in
said second interior chamber; (j) a second cartridge dispenser
access door in said second housing and operatively associated with
said second cartridge dispenser; and (k) a second individual
cartridge access port in said second housing and operatively
associated with said second cartridge dispenser.
[0077] In an additional embodiment, the combination apparatus of
this invention can also further comprise a heater controller
operatively associated with each of said at least one heater; and
at least one temperature sensor in each of said housings and
operatively associated with said heater controller.
[0078] It will be understood that the methods of this invention can
be carried out with the apparatus of this invention and/or with the
combination apparatus of this invention. The present invention
provides, among other things, a rapid test that can conveniently be
run at key animal movement times or on a repeated basis to
determine likely risk of current infection (particularly odds of
being sent to the hospital) and effect on performance (weight gain)
so the producer can make management decisions (especially related
to penning and treatment) to maximize individual animal health and
economics. This predictive tool will help producers (for example,
cattle feeders) make more informed decisions about animal
management on arrival at the feedlot and or in the hospital,
allowing for documentation of precise antibiotic use, reduced
costs, improved animal welfare and better herd management
practices.
[0079] While aspects of the present invention are described
primarily with respect to beef cattle, the invention may also be
used in the management of other farm animal industries, such as
swine and poultry. For example, the movement of pigs to a nursery,
gilt developing unit, breeding herd, or finishing house represents
key animal movement times that are similar to that of cattle
arriving at the feedlot. The invention can also be useful when
animals are re-grouped and moved within the same facility, or at
any time the risk of exposure to infection is high. Any time
animals are exposed to new penmates or environment, the risk for
transmission of new pathogens that can result in infection is
increased. Another example of a key animal movement time in which
animals are exposed to new potential infection based on co-mingling
is the transfer of cattle from a cow-calf operation to
stocker-backgrounder operation.
[0080] Accordingly, an aspect of the invention is a method of
reducing or targeting antibiotic treatment of a group of farm
animals or identifying individual animals that would benefit from
antibiotic treatment, culling/harvesting early, additional testing
or separate management strategy, comprising the steps of: (a)
selecting an individual animal of the group (for example, while
passing the animals sequentially through a single-file transfer
chute); (b) collecting a sample from the individual animal (for
example, while the animal is in the single-file transfer chute);
(c) generating a leukocyte count, and or a differential cell count
(for example, a lymphocyte, eosinophil, basophil, monocyte,
neutrophil or band neutrophil count, such as by a white blood cell
differential including number and/or percent of each relevant cell
type in the sample, alone or in combination with ratios of blood
cell types, combination of cell types and ratios of combinations of
cell types, total leukocyte count, body temperature, and/or red
blood cell count, optionally in combination with the animals' sex,
breed, weight, age or body temperature) from the blood sample (for
example, while the animal is in the single-file transfer chute);
(d) comparing the cell count to an index of infection (for example,
while the animal is in the single-file transfer chute); (e)
transferring (for example, from the single-file transfer chute,
through a single gate or one of at least a pair of gates), based on
the index of infection, the individual animal to either a normal
subgroup or an abnormal subgroup (for example, by: (i) passing the
animal through one gate, or at least a pair of gates, to separate
pens; and/or (ii) administering animals assigned to the abnormal
subgroup an antibiotic, such as by parenteral injection, while the
animal is still in the single-file transfer chute; etc., typically
wherein both the normal subgroup and the abnormal subgroup are
contained in the same, or separate, confined animal feeding
operation (CAFO), such as a feedlot(s)); and (f) repeating steps
(a) through (e) until all animals from the group are assigned to
either the normal subgroup or the abnormal subgroup These groups
may or may not be physically separated.
[0081] Another aspect of the invention is a method of determining
need for or timing of antibiotic treatment, additional testing,
culling or alternative management of a group of farm animals or
other animals that are grouped and moved in pens (for example,
swine or pigs), comprising the steps of: (a) collecting a sample
from a portion (for example, two, three, four, or five or more, but
less than all) of individual animals of the pen or group (for
example, at random); (b) generating a leukocyte differential count
from the samples; (c) comparing the leukocyte differential counts
to an index of infection; and then (d) if a sufficient number of
animals are infected based on above, intervening with measures such
as feed ration changes or antibiotic use to protect the health of
the group.
[0082] A further aspect of the invention is a method of tracking
illness and/or antibiotic treatment in farm animals, especially at
times of animal movement or co-mingling, comprising the steps of:
(a) identifying an individual animal (for example, by
electronically reading a tag on or associated with the animal
(e.g., an active or passive RFID or bar-coded animal identification
tag), or by manually recording an alphanumeric indicator on or
associated with that animal (e.g., into the same automated
microscope/reader in which the differential and/or leukocyte count
is generated)); (b) collecting a sample from the animal (for
example, including transferring the sample to an automated
microscope/reader cartridge); (c) tying the sample to the animal
(for example, by electronically reading a tag on or associated with
the cartridge (e.g., an active or passive RFID or bar-coded
cartridge identification tag), or by manually recording an
alphanumeric indicator on or associated with that cartridge (e.g.,
into the same automated microscope/reader in which the differential
and/or leukocyte count is generated)); (d) generating a white blood
cell differential and/or leukocyte count (e.g. of all white blood
cell types) from the sample; (e) comparing the differential and/or
leukocyte count to an index of infection to assign the individual
animal to either a normal subgroup or an abnormal subgroup (e.g., a
group for which antibiotic administration, immunostimulant
administration, probiotic, feed additive, anti infective,
hospitalization, culling and/or quarantine is justified); (f)
generating an electronic record for the animal (e.g., stored on the
automated microscope and/or uploaded to a database on the world
wide web) containing the animal's identity, white blood cell
differential and/or leukocyte count, optionally but preferably such
that the record can be subsequently audited to demonstrate
treatment of only of animals in the abnormal subgroup and not
animals in the normal subgroup; (g) repeating steps (a) through (f)
until all animals from the group are tested and assigned to either
the normal subgroup or the abnormal subgroup and the electronic
records are stored in a common database. In some embodiments, the
method further includes entering antibiotic treatment data for each
animal in the electronic record corresponding to each animal in the
database; and (h) optionally, but in some embodiments preferably,
feeding out the animals of both the subgroups for at least 1, 2, 3
or 4 weeks, up to 6 weeks or more (e.g., for poultry), or at least
1, 2, 3, or 4 months, up to 10 months or more (e.g., for cattle),
while administering only the animals of the abnormal subgroup an
antibiotic.
[0083] In some embodiments of the foregoing, the method further
includes feeding out the animals (of both the subgroups) for at
least 1, 2, 3 or 4 weeks, up to 6 weeks or more (e.g., for poultry
or swine), or at least 1, 2, 3, or 4 months, up to 10 months or
more (e.g., for cattle or swine), while administering only the
animals of the abnormal subgroup an antibiotic. The normal
subgroups may also be treated if received follow on testing (i.e.,
as in a hospital test).
[0084] In some embodiments of the foregoing, the generating step is
carried out with an automated microscope.
[0085] In some embodiments of the foregoing, the collecting step is
carried out by venipuncture (for example, from the jugular vein or
tail vein) or lancing of a capillary bed (for example, in the ear
or snout of the animal).
[0086] In some embodiments of the foregoing, the collecting step
(b), the generating step (c), and the comparing step (d) are
together carried out chute-side or pen-side in an average time of
not more than 5, 4, 3, 2, or 1 minutes.
[0087] In some embodiments of the foregoing, the animals of the
abnormal subgroup are segregated from the animals of the normal
subgroup to minimize transmission of sickness, optionally with or
without administration of antibiotics or immunostimulants to
animals of the abnormal subgroup (that is, are quarantined or
hospitalized only).
[0088] In some embodiments of the foregoing, the animals of the
normal subgroup are enrolled in a natural or organic feeding or
maintenance program (for example, a certified organic or
antibiotic-free program).
[0089] In some embodiments of the foregoing, the collecting step
comprises dispensing the sample into a cartridge (e.g. an automated
microscope reader cartridge), and the generating step is carried
out with the sample in the cartridge (e.g., with the cartridge
inserted in an automated microscope).
[0090] In some embodiments of the foregoing, the cartridge is
pre-warmed to a pre-determined temperature (e.g., about 60, 65, 70,
75, 80, 85, 90, 95, 100, 105, 110 degrees Fahrenheit, etc.), and
the generating step is carried out with a cartridge reader
pre-warmed to the substantially the same pre-determined temperature
(e.g., within five or ten degrees thereof).
[0091] In the methods of this invention, an index of infection can
be, but is not limited to, a) a neutrophil value in a range from
about X.sub.N.times.10.sup.3 cells/microliter to about
Y.sub.N.times.10.sup.3 cells/microliter, wherein X.sub.N is 0, 0.1,
0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4,
1.5, 1.6, or 1.7.times.10.sup.3 neutrophils per microliter, and
Y.sub.N is 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0,
5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3,
6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6,
7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9,
9.0, 10.0, 10.1, 10.2, 10.3, 10.4, 10.5, 10.6, 10.7, 10.8, 10.9,
11.0, 11.1, 11.2, 11.3, 11.4, 11.5, 11.6, 11.7, 11.8, 11.9, or
12.0.times.10.sup.3 neutrophils per microliter; b) a lymphocyte
value in a range from about X.sub.L.times.10.sup.3 cells/microliter
to about Y.sub.L.times.10.sup.3 cells/microliter, wherein X.sub.L
is 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1,
5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4,
6.5, 6.6, 6.7, 6.8, 6.9, or 7.0.times.10.sup.3 lymphocytes per
microliter, and Y.sub.L is 10.0, 10.1, 10.2, 10.3, 10.4, 10.5,
10.6, 10.7, 10.8, 10.9, 11.0, 11.1, 11.2, 11.3, 11.4, 11.5, 11.6,
11.7 11.8, 11.9, 12.0, 12.1, 12.2, or 12.3.times.10.sup.3
lymphocytes per microliter; c) an eosinophil value in a range from
about X.sub.E.times.10.sup.3 cells/microliter to about
Y.sub.E.times.10.sup.3 cells/microliter, wherein X.sub.E is
0.0.times.10.sup.3 eosinophils per microliter and Y.sub.E is 0.1,
0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4,
1.5, 1.6, 1.7, 1.8, 1.9, or 2.0.times.10.sup.3 eosinophils per
microliter; and d) any combination of (a), (b) and (c).
[0092] Some embodiments of the foregoing further comprise the step
of: (i) administering an antibiotic or immunostimulant to the
animals of the abnormal subgroup and not the normal subgroup; (ii)
hospitalizing the animals of the abnormal subgroup and not the
normal subgroup; and/or (iii) quarantining the animals of the
abnormal subgroup from the animals of the normal subgroup; (iv)
culling the animals of the abnormal subgroup, which the selection
of any of the afore management decisions can be aided by the
leukogram profile.
[0093] Some embodiments of the foregoing further comprising the
step of: (i) feeding out the animals of the normal subgroup and/or
the abnormal subgroup; and/or (ii) periodically recording the
weight of animals of the normal subgroup and/or the abnormal
subgroup (e.g., and entering that weight into the corresponding
electronic record for each the animal).
[0094] The present invention further provides a method for
transferring health information to various animal owners wherein
health data is collected as described herein, uploaded to a web
database documenting animals' health status or subgroup, and data
is accessed by the next entity in chain of custody of the animal to
make treatment, grouping or management decisions.
[0095] The present invention further provides a method as described
herein for predicting animal performance, especially average daily
gain and/or hospitalization rate, based on chute-side/pen-side
white blood cell differential at times of animal
movement/co-mingling.
[0096] In some embodiments, the collecting step (b), the tying step
(c), the generating step (d) and the comparing step (e) are
together carried out chute-side or pen-side in an average time of
not more than 5, 2, or 1 minutes.
[0097] Also described herein is an apparatus useful in a system for
reducing antibiotic administration to a group of farm animals,
including: (a) a housing having at least a first interior chamber;
(b) an automated microscope in the first interior chamber; (c) at
least a first cartridge dispenser in the first interior chamber;
(d) at least a first cartridge dispenser access door in the housing
and operatively associated with the first cartridge dispenser
(e.g., for re-filling the cartridge dispenser with a plurality of
fresh cartridges, which then may be warmed); (e) at least a first
fresh cartridge access port in the housing (optionally in the
access door) and operatively associated with the first cartridge
dispenser; (f) a filled cartridge insert port in the housing and
operatively associated with the automated microscope; and (g) at
least one heater operatively associated with the housing configured
to heat (e.g., to substantially the same temperature) both the
automated microscope and the at least a first cartridge dispenser.
The apparatus may further include: (h) a second cartridge dispenser
in the first interior chamber; (i) a second cartridge dispenser
access door in the housing and operatively associated with the
second cartridge dispenser; and (j) a second individual cartridge
access port in the housing and operatively associated with the
second cartridge dispenser; (k) a separate detached heating chamber
that is substantially the same temperature as the housing, or other
suitable operating temperature. The apparatus may further include:
a heater controller operatively associated with the at least one
heater; and at least one temperature sensor in the housing
operatively associated with the heater controller.
[0098] Also described herein is a combination apparatus useful in a
system for reducing antibiotic administration to a group of farm
animals, including: (a) a first housing having at least a first
interior chamber; (b) an automated microscope in the first interior
chamber; (c) a second housing having at least a second interior
chamber; (d) at least a first cartridge dispenser in the second
interior chamber; (e) at least a first cartridge dispenser access
door in the second housing and operatively associated with the
first cartridge dispenser (e.g., for re-filling the cartridge
dispenser with a plurality of fresh cartridges, which then may be
warmed); (f) at least a first fresh cartridge access port in the
second housing (optionally in the access door) and operatively
associated with the first cartridge dispenser; (g) a filled
cartridge insert port in the first housing and operatively
associated with the automated microscope; and (h) at least one
heater operatively associated with each of the first and second
housings configured to heat (e.g., to substantially the same
temperature) both the automated microscope and the at least a first
cartridge dispenser. The apparatus may further include: (i) a
second cartridge dispenser in the second interior chamber; (j) a
second cartridge dispenser access door in the second housing and
operatively associated with the second cartridge dispenser; and (k)
a second individual cartridge access port in the second housing and
operatively associated with the second cartridge dispenser. The
apparatus may further include: a heater controller operatively
associated with each of the at least one heater; and at least one
temperature sensor in each of the housings and operatively
associated with the heater controller.
[0099] Animal agriculture is under increasing pressure to minimize
antibiotic use because of rising public health concerns over
antibiotic-resistant bacteria that can directly and indirectly
foster antibiotic resistance in humans. In 2013, the Centers for
Disease Control and Prevention (CDC) estimated that more than 2
million human illnesses and 23,000 human deaths are caused by
antibiotic resistance in the US annually. Estimates of economic
loss due to antibiotic resistance in the US vary but could be as
high as $20 billion in direct healthcare cost and $35 billion per
year including lost productivity (in 2008 dollars). A 2013 CDC
publication called for a "change in the way antibiotics are used"
as "perhaps the single most important action need to greatly slow
down the development and spread of antibiotic-resistant
infections." The present invention aims to create that change by
giving livestock producers a fast, accurate screening tool to
separate healthy animals from animals who would benefit from
antibiotic intervention.
[0100] FIG. 1 schematically illustrates one embodiment of the
invention, in which incoming beef cattle are sorted into a group
that has the abnormal immune signature of infection, and as such,
would either receive antibiotic treatment, additional testing, or
be segregated, marked or managed separately, alone or in
combination with any of the previous actions, and a group that has
a normal, healthy blood profile and does not receive antibiotic
treatment, segregation, or additional testing. Whenever treatment
is referred to, it is used interchangeably with segregation,
additional testing or managing separately. Screening and sorting is
illustrated more fully in FIG. 2. In the non-limiting example
embodiment, an animal is selected from the group, an automated
microscope reader cartridge is dispensed and in cold temperatures
would have first been pre-warmed (the details of which are
discussed further below), a sample collected from the animal
(before or after dispensing of the cartridge) is deposited into the
cartridge, the cartridge inserted into an automated microscope
reader which carries out a leukocyte differential cell count, and
generates an indication of whether or not that animal should
receive antibiotic treatment based on a previously determined index
of infection. The animal is then directed into the appropriate
(normal/abnormal) group, the cartridge removed from the reader, and
the process repeated with the next animal until all animals are
screened.
[0101] A sample can be collected by any suitable technique with any
suitable apparatus, such as a lance, hollow needle, syringe,
capillary action chamber, or combination thereof. A currently
preferred device for collecting blood or other samples from cattle
or cows is that described in PCT Publication No. WO 2017/019743,
the disclosure of which is incorporated herein by reference in its
entirety. From such initial collection device(s), the unclotted
blood (with or without anti-coagulants) can then be transferred to
the automated microscope cartridge.
[0102] Examples of automated microscope cartridges and automated
microscope readers that perform leukocyte differential cell counts,
and which may be adapted to carry out the present invention,
include those described in U.S. Pat. No. 6,350,613 to Wardlaw,
Levine, and Rodriguez, and in US Patent Application Publication No.
US 2014/0009596 to Bresolin, Calderwood et al., the disclosures of
which are incorporated by reference herein in their entirety. In
general, the microscope cartridge includes a bottom portion, an
optically transparent top portion (a "cover slip" or "window"), a
flat or wedge-shaped chamber therebetween, and a port in fluid
communication with that chamber for filling the chamber with a
sample. When inserted into the automated microscope, imaging of
cells in the sample can be carried out through the "window" or
"cover slip," and a leukocyte count and/or differential can be
generated automatically from those images.
[0103] Assignment of direction of the animal to a particular
subgroup can optionally be carried out with the aid of an automated
gate and chute system, such as described in U.S. Pat. No. 5,673,647
to Pratt and U.S. Pat. No. 8,418,660 to Hulls (which may be
operatively linked or associated with the apparatus determining
"normal" or "abnormal" status), before the animal departs from the
chute or location in which the screening procedure has been carried
out, or by any other suitable technique.
[0104] FIGS. 3-5 schematically illustrate a non-limiting example of
an automated microscope apparatus of the invention. The apparatus
generally includes (as is known in the art) an outer housing, and a
cartridge reader (for example, an XYZ stage for receiving the
cartridge, an automated microscope, and (optionally but in some
embodiments preferably) a controller for the XYZ stage and
automated microscope, and a computer and associated software for
performing the leukocyte differential count and generating an
indication of abnormal, which would indicate infection or stress,
or normal, indicating no infection (such may also be located in a
separate, local, device, or remotely or "on the cloud").
Additionally, the device includes at least one fresh cartridge
dispenser (preferably at least two, as illustrated, and optionally
three or more) located inside the housing, at least one heater,
preferably a heater controller, and preferably at least one
temperature sensor. The heater(s) and temperature sensor(s) are
positioned to maintain the contents of the housing, particularly
the fresh cartridges in the cartridge dispensers, and the cartridge
reader, at substantially the same temperature, to minimize thermal
shock during cartridge reading in cold temperatures, as discussed
below. The housing can be provided with an access door (e.g.
top-hinged, side hinged, etc.) for removal of an empty cartridge
dispenser and replacing it with a fresh cartridge dispenser filled
with fresh cartridges. Or the cartridge dispenser can be
permanently or semi-permanently fixed in the housing, and the
access door configured to simply allow re-filling of an empty
dispenser with fresh cartridges. An additional or separate access
door (slot, or opening) for removal of individual fresh cartridges
may be provided, optionally aided with a mechanical or
electromechanical ejector mechanism. The presence of two cartridge
dispensers allows fresh recently filled cartridges in one dispenser
to be brought up to temperature while previously warmed cartridges
are being dispensed from the other dispenser.
[0105] While the cartridge dispensers and cartridge reader are, in
the embodiment of FIGS. 3A-3B, kept in a common housing, in the
alternate embodiment of FIGS. 4A-4B the cartridge dispensers and
cartridge reader are contained in separate housings with the
components divided between two different housings, but with
temperature regulated in a coordinated manner to be substantially
the same in both (e.g., with a common controller, or with two
separate controllers that control the two units in a coordinated
manner).
[0106] An exemplary imaging reader 10 according to some embodiments
is illustrated in FIG. 6. The imaging reader 10 includes a camera
12, a sample 14, a controller 16, and a display 18. As illustrated,
the camera 12 is configured to image the sample 14, which may be
inserted into the imaging reader 10, for example, using a sample
cartridge. The camera 12 may include any optical components for
imaging the sample, including a light source, lenses, and the like.
The camera 12 may be any suitable imaging device, such as a CCD
device, and may detect and produce digital images and/or intensity
values of various signals. The imaging reader may be an automated
microscope apparatus.
[0107] Individual components of the imaging reader 10 described
herein may be as known in the art, or variations thereof that will
be apparent to those skilled in the art based on the instant
disclosure and prior automated microscopy apparatus such as
described in U.S. Pat. No. 4,998,284 to Bacus; U.S. Pat. No.
5,790,710 to Price; U.S. Pat. No. 6,381,058 to Ramm; U.S. Pat. No.
6,929,953 to Wardlaw; U.S. Pat. No. 6,927,903 to Stuckey; U.S. Pat.
No. 8,000,511 to Perz; U.S. Pat. No. 8,045,165 to Wardlaw; U.S.
Pat. No. 8,081,303 to Levine; US Patent Application Nos.
2001/0041347 to Sammak; or 2009/0233329 to Rodriguez. The imaging
reader 10 may be a QSCOUT.TM. reader commercially available from
Advanced Animal Diagnostics (Research Triangle Park, N.C.,
USA).
[0108] The controller 16 may include a computer processor and may
be configured to receive intensity values and/or images from the
camera 12 and to analyze the intensity values and/or images and to
display the results on the display 18.
[0109] The controller 16 may be further configured to carry out
various automated steps of the methods described herein.
[0110] A nonlimiting example of an apparatus of this invention is
the QSCOUT.RTM. reader, which uses a 365 nm excitation light to
induce fluorescence of European microspheres. The signal is passed
through a focal lens and then through a 610 nm emission filter and
then to a monochrome camera. Images are processed for signal
intensity from the camera to the onboard PC (computer). Results are
then displayed on the color touchscreen.
[0111] The present invention is explained in greater detail in the
following non-limiting Examples.
Examples
[0112] As one example, blood is collected from beef cattle chute
side from the jugular vein, ear vein, tail vein, etc using any
suitable blood collection and transfer device. From the collection
and transfer device, the blood is transferred into an automated
microscope cartridge. In a preferred embodiment, the cartridge has
one microfluidic chamber, is 15 u deep, with a 9 mm.times.18 mm
optically transparent cover slip, to allow for rapid fill at the
low temperatures typically encountered during cattle transfer in
the winter. There are other geometries that can accomplish this,
such as (i) a coverslip that is 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6,
6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9,
8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9.0, 9.1, 9.2,
9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 10.1, 10.2, 10.3, 10.4,
10.5, 10.6, 10.7, 10.8, 10.9, 11.0, 11.1, 11.2, 11.3, 11.4, 11.5,
11.6, 11.7, 11.8, 11.9, 12.0, 12.1, 12.2, 12.3, 12.4, 12.5, 12.6,
12.7, 12.8, 12.9, 13.0, 13.1, 13.2, 13.3, 13.4, 13.5, 13.6, 13.7,
13.8, 13.9, 14.0, 14.1, 14.2, 14.3, 14.4, 14.5, 14.6, 14.7, 14.8,
14.9, 15.0, 15.1, 15.2, 15.3, 15.4, 15.5, 15.6, 15.7, 15.8, 15.9,
16.0, 16.1, 16.2, 16.3, 16.4, 16.5, 16.6, 16.7, 16.8, 16.9, 17.0,
17.1, 17.2, 17.3, 17.4, 17.5, 17.6, 17.7, 17.8, 17.9, 18, 18.1 m in
one side and in any combination in the same plane such that the
other side can be 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9,
7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2,
8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5,
9.6, 9.7, 9.8, 9.9, 10.0, 10.1, 10.2, 10.3, 10.4, 10.5, 10.6, 10.7,
10.8, 10.9, 11.0, 11.1, 11.2, 11.3, 11.4, 11.5, 11.6, 11.7, 11.8,
11.9, 12.0, 12.1, 12.2, 12.3, 12.4, 12.5, 12.6, 12.7, 12.8, 12.9,
13.0, 13.1, 13.2, 13.3, 13.4, 13.5, 13.6, 13.7, 13.8, 13.9, 14.0,
14.1, 14.2, 14.3, 14.4, 14.5, 14.6, 14.7, 14.8, 14.9, 15.0, 15.1,
15.2, 15.3, 15.4, 15.5, 15.6, 15.7, 15.8, 15.9, 16.0, 16.1, 16.2,
16.3, 16.4, 16.5, 16.6, 16.7, 16.8, 16.9, 17.0, 17.1, 17.2, 17.3,
17.4, 17.5, 17.6, 17.7, 17.8, 17.9, 18, 18.1 mm; (ii) at a depth of
5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2,
6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5,
7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8,
8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 10.1,
10.2, 10.3, 10.4, 10.5, 10.6, 10.7, 10.8, 10.9, 11.0, 11.1, 11.2,
11.3, 11.4, 11.5, 11.6, 11.7, 11.8, 11.9, 12.0, 12.1, 12.2, 12.3,
12.4, 12.5, 12.6, 12.7, 12.8, 12.9, 13.0, 13.1, 13.2, 13.3, 13.4,
13.5, 13.6, 13.7, 13.8, 13.9, 14.0, 14.1, 14.2, 14.3, 14.4, 14.5,
14.6, 14.7, 14.8, 14.9, 15.0, 15.1, 15.2, 15.3, 15.4, 15.5, 15.6,
15.7, 15.8, 15.9, 16.0, 16.1, 16.2, 16.3, 16.4, 16.5, 16.6, 16.7,
16.8, 16.9, 17.0, 17.1, 17.2, 17.3, 17.4, 17.5, 17.6, 17.7, 17.8,
17.9, 18.0, 18.1, 18.2, 18.3, 18.4, 18.5, 18.6, 18.7, 18.8, 18.9,
19.0, 19.1, 19.2, 19.3, 19.4, 19.5, 19.6, 19.7, 19.8, 19.9 or 20.0
microns deep; (iii) may not have straight and orthogonal sides
(e.g. a molded contoured edge); (iv) may not be parallel and thus
may have an angle of 0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8,
0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1,
2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0 degrees (v) will have
either a predetermined known volume range of the sample area (i.e.,
its viewing area multiplied by its depth) or will have a measured
known volume used in the cells per volume calculations that can be
(a) entered manually into the instrument or (b) read by the
instrument via encoding technology such as barcoding or RFID.
[0113] A suitable automated microscope is an AAD QScout automated
microscope/leukocyte reader (available from Advanced Animal
Diagnostics, Inc., 633 Davis Drive, Suite 460, Morrisville, N.C.
27560 USA) modified as described above to contain a thermally
protected storage area for fresh cartridges, and to keep the
automated microscope itself at substantially the same temperature
as those fresh cartridges. In general, it is important in chemistry
and biological applications to keep the device and the cartridge at
a minimum of 70 degrees F., and preferably closer to 90 degrees F.
Since the unit is typically operated outside and exposed to very
cold temperatures on the feedlot, this thermal protection is
important to prevent thermal "shock" the white blood cells that may
occur in colder ambient temperatures and impede successful stain
penetration when the sample is added to the fresh slide.
[0114] Furthermore, keeping the fresh cartridges and instrument at
substantially the same temperature reduces the effect of
coefficient of thermal expansion mismatch (CTE mismatch). The
cartridge is typically made of multiple materials, and contains a
space or void into which fresh sample fills. Any CTE mismatch can
cause slight warping which can lead to cells drifting out of the
focal plane of the automated microscope. Maintaining uniform
temperatures reduces this effect, allowing for fewer focal points
and decreasing overall time to result. Otherwise, the operator
would have to continually refocus to maintain focal plane as the
slide expands and contracts.
[0115] The AAD QScout reader can produce the following results from
a sample (e.g., a blood sample): (1) total leukocyte count per
milliliter; (2) total lymphocyte count per milliliter; (3) total
neutrophil count per milliliter; (4) total eosinophil count per
milliliter; (5) total monocyte count per milliliter; (6) total
basophil count per milliliter: (7) percent neutrophil, percent
eosinophil, percent lymphocyte, percent monocyte, and percent
basophil; and (6) detection of immature, non-segmented neutrophils
including band neutrophils. In a non-limiting example, an "index of
infection" based on total neutrophils per milliliter and total
lymphocytes per milliliter is generated, as shown in FIG. 6.
Additionally, other variants may optionally be included, such as
ratios of the above blood cell types, combination of cell types and
ratios of combinations of cell types, total leukocyte count, body
temperature, and/or red blood cell count, optionally in combination
with the animals' sex, weight, age and body temperature.
[0116] The animals identified as being "abnormal" in FIG. 6 can
have a variety of pathogens and be at different points in the
disease cycle. The automated differential allows for detection of
"suspect viral" or suspect bacterial" allowing the producer to
quarantine animals for improved herd management. Animals may be
segregated into groups that are more likely to have a weight gain
response to treatment vs. groups that are more likely to not have a
weight gain response but are much less likely result in clinical
illness based on treatment as demonstrated by being sent to the
hospital pen.
[0117] Common practice in feed yards is the use of metaphylaxis,
medication of an entire group of incoming cattle. A preliminary
study moderate risk cattle suggests that approximately 85% of the
cattle are "normal" and do not need to be treated with antibiotics
upon arrival. On 10,000 head, this can equate to $100,000-$200,000
in antibiotic savings and reduce unnecessary use of antibiotics. In
addition, in our preliminary studies, there is no substantial
difference in average daily weight gain (ADG) between populations
of "normal" animals receiving antibiotics and "normal" animals not
receiving antibiotics. However, there is a difference between the
ADG of "abnormal" animals receiving antibiotics and "abnormal
animals" not receiving antibiotics: in our preliminary study, the
"abnormal" animals that were treated outperformed the "abnormal"
animals left untreated by approximately 0.35 pounds per day through
40 days on feed.
[0118] Workflow.
[0119] The end-to-end process of sampling and testing cattle may be
driven by bar code readers, RFID readers and/or simple numeric
keypads. The ear tag or other identification tag of the animal is
scanned into the QScout Reader (or the ID typed in with a keypad),
the blood sample is drawn and blood placed in the automated
microscope cartridge. The cartridge has its own bar code on the
bottom label that is scanned by an on board scanner when the
cartridge is retracted into the Reader. The QScout reader
automatically associates that cartridge sample and test result with
the animal ID scanned earlier. Test results are stored in a
database residing in the QScout for on board reporting, and also
pushed to a website database, where the producer can have access to
all of his animals tested and can looking at test results from one
unit, multiple units, multiple locations, etc.
[0120] The foregoing is illustrative of the present invention, and
is not to be construed as limiting thereof. The invention is
defined by the following claims, with equivalents of the claims to
be included therein.
* * * * *