Diagnostic method for bacterial meningitis

• US 9,759,720 B2
• Filed: 09/23/2011
• Issued: 09/12/2017
• Est. Priority Date: 09/24/2010
• Status: Active Grant

• Current Assignee: Hansa Biopharma AB
• Original Assignee: Hansa Medical AB
• Inventors: Bjrck, Lars, Christensson, Bertil, Herwald, Heiko, Linder, Adam, kesson, Per
• Primary Examiner(s): Cordero Garcia, Marcela M
• Assistant Examiner(s): Mader, Catherine
• Application Number:
  US13/825,528
• Publication Number:
  US 20140080754A1
• Time in Patent Office: 2,181 Days
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: G01N 2333/4721 Cationic antimicrobial peptides, e.g. defensins
• CPC Class Codes: G01N 33/56911 Bacteria
• CPC Class Codes: G01N 33/56944 Streptococcus
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

It has been demonstrated that the level of HBP increases in individuals that have bacterial meningitis. Accordingly, the level of HBP in an individual can be used to determine whether or not an individual has bacterial meningitis.

Claims

1. A method of distinguishing acute bacterial meningitis infection from viral meningitis, encephalitis, neuroborreliosis or absence of meningitis infection, the method comprising:

providing a cerebrospinal fluid sample obtained from an individual suspected of having meningitis;

contacting the sample with an antibody which binds specifically to Heparin Binding Protein (HBP;

Cationic Anti-microbial Protein 37;

Azurocidin);

quantitating the amount of antibody-HBP complex to measure the HBP level in the sample; and

detecting acute bacterial meningitis infection at 90% Sensitivity or greater and at 93% Specificity or greater based on the measured HBP level in the cerebrospinal fluid to distinguish in the individual an acute bacterial meningitis infection from viral meningitis, encephalitis, neuroborreliosis or absence of meningitis infection.

2. The method according to claim 1, wherein the individual is a mammal.

3. The method according to claim 2, wherein the mammal is a human.

4. The method according to claim 3, wherein the detecting acute bacterial meningitis infection is at 90% Sensitivity or greater and at about 100% Specificity based on the measured HBP level in the cerebrospinal fluid.

5. The method according to claim 3, wherein the detecting of acute bacterial meningitis infection at about 90% Sensitivity or greater and 93% Specificity or greater is determined by a Receiver Operating Characteristic (ROC).

6. The method according to claim 3, wherein the 90% Sensitivity or greater and about 100% Specificity for detecting acute bacterial meningitis infection is a threshold value of about 50 ng/mL HBP in the cerebrospinal fluid.

7. The method according to claim 3, wherein the cerebrospinal fluid sample is obtained by lumbar puncture.

8. The method according to claim 3, wherein the individual has received prophylactic antibiotic treatment but has not been confirmed as having bacterial meningitis infection.

9. The method according to claim 8, wherein the individual has received antibiotic treatment for less than 48 hrs.

10. The method according to claim 3, wherein quantitating the amount of antibody bound to HBP is by enzyme linked immunosorbent assay (ELISA).

11. The method according to claim 3, wherein quantitating the amount of antibody bound to HBP is by a dipstick assay, wherein the dipstick comprises an antibody which binds specifically to HBP.

12. The method according to claim 3, wherein the individual has recently undergone a neurosurgical operation.

13. The method according to claim 3 wherein the individual has a history of skull trauma and/or an anatomical abnormality affecting the cranial, cervical or lumbosacral regions.

14. The method according to claim 3, wherein the individual is immunocompromised;

the individual has a cochlear implant;

the individual has a cranial or neurosurgical implant, or any combination thereof.

15. The method according to claim 3, further comprising determining levels of one or more of:

white blood cell count, neutrophil count, glucose, and protein in the cerebrospinal fluid sample.