Signatures and determinants for diagnosing infections in non-human subjects and methods of use thereof

Abstract

Antibiotics (Abx) are the world's most misused drugs. Antibiotics misuse occurs when the drug is administered in case of a non-bacterial infection (such as a viral infection) for which it is ineffective. Overall, it is estimated that 40-70% of the worldwide Abx courses are mis-prescribed. The financial and health consequences of Abx over-prescription include the direct cost of the drugs, as well as the indirect costs of their side effects, which are estimated at >$15 billion annually. Furthermore, over-prescription directly causes the emergence of Abx-resistant strains of bacteria, which are recognized as one of the major threats to public health today. This generates an immediate need for reliable diagnostics to assist physicians in correct Abx prescription, especially at the point-of-care (POC) where most Abx are prescribed. Accordingly, some aspects of the present invention provide methods using biomarkers for rapidly detecting the source of infection and administrating the appropriate treatment.

1 - 4 . (canceled) 
     
     
         5 . A method of treating a bacterial infection or a mixed bacterial/viral infection in a non-human subject comprising:
 a. measuring the polypeptide concentration of TNF-related apoptosis-inducing ligand (TRAIL) in a sample derived from the non-human subject; and   b. treating the bacterial infection or the mixed bacterial/viral infection of the non-human subject with an antibiotic if the polypeptide concentration of TRAIL determined in step (a) is lower than a pre-determined threshold value.   
     
     
         6 . A method of treating a viral infection in a non-human subject comprising:
 a. measuring the polypeptide concentration of TRAIL in a sample derived from the non-human subject; and   b. treating the viral infection of the subject with an anti-viral agent if the polypeptide concentration of TRAIL determined in step (a) is higher than a pre-determined threshold value.   
     
     
         7 - 9 . (canceled) 
     
     
         10 . The method of  claim 5 , further comprising measuring the polypeptide concentration of:
 i. CRP and SAA;   ii. CRP and IP10;   iii. CRP and PCT;   iv. CRP and IL1RA;   v. CRP and B2M;   vi. CRP and Mac-2BP;   vii. CRP, SAA and PCT;   viii. CRP, Mac-2BP and SAA;   ix. CRP, SAA and IP10;   x. CRP, SAA and IL1RA;   xi. CRP, SAA, PCT and IP10;   xii. CRP, SAA, PCT and IL1RA; or   xiii. CRP, SAA, IP10 and IL1RA.   
     
     
         11 - 16 . (canceled) 
     
     
         17 . The method of  claim 5 , further comprising measuring the polypeptide concentration of one or more polypeptide selected from the group consisting of SAA, IL6, IL8, PCT and TREM-1. 
     
     
         18 - 33 . (canceled) 
     
     
         34 . The method of  claim 5 , wherein the sample is whole blood or a fraction thereof. 
     
     
         35 . The method of  claim 34 , wherein said blood fraction sample comprises cells selected from the group consisting of lymphocytes, monocytes and granulocytes. 
     
     
         36 . The method of  claim 34 , wherein said blood fraction sample comprises serum or plasma. 
     
     
         37 . The method of  claim 5 , wherein the expression level of the polypeptide is determined electrophoretically, or immunochemically. 
     
     
         38 . The method of  claim 37 , wherein the immunochemical detection is by flow cytometry, radioimmunoassay, immunofluorescence assay or by an enzyme-linked immunosorbent assay. 
     
     
         39 . The method of  claim 5 , wherein the concentration of TRAIL is measured within about 24 hours after sample is obtained. 
     
     
         40 . The method of  claim 5 , wherein the concentration of TRAIL is measured in a sample that was stored at 12° C. or lower, wherein the said storage begins less than 24 hours after the sample is obtained. 
     
     
         41 . The method of  claim 5 , further comprising age normalization of the polypeptide concentration. 
     
     
         42 - 47 . (canceled) 
     
     
         48 . The method of  claim 6 , further comprising measuring the polypeptide concentration of:
 i. CRP and SAA;   ii. CRP and IP10;   iii. CRP and PCT;   iv. CRP and IL1RA;   v. CRP and B2M;   vi. CRP and Mac-2BP;   vii. CRP, SAA and PCT;   viii. CRP, Mac-2BP and SAA;   ix. CRP, SAA and IP10;   x. CRP, SAA and IL1RA;   xi. CRP, SAA, PCT and IP10;   xii. CRP, SAA, PCT and IL1RA; or   xiii. CRP, SAA, IP10 and IL1RA.   
     
     
         49 . The method of  claim 6 , further comprising measuring the polypeptide concentration of one or more polypeptide selected from the group consisting of SAA, IL6, IL8, PCT and TREM-1. 
     
     
         50 . A composition of matter for detection of TRAIL comprising a blood sample derived from a non-human subject having an infection which comprises an antibody which binds to said TRAIL.