Compositions and methods for the detection of tuberculosis
AssigneeWashington University
InventorsJennifer Philips, Pallavi Chandra, Heloise Coullon
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Abstract
Methods for diagnosis of bacterial infections (e.g., tuberculosis) are disclosed. In particular, the disclosure relates to the use of a panel of biomarkers for aiding diagnosis, prognosis, and treatment of bacterial infections such as tuberculosis. The identified biomarkers can be used to detect active infection as well as bacterial burden, and for monitoring responses to treatment.
Claims20
A method of treating a subject in need thereof with tuberculosis, a non-tuberculous mycobacteria infection, a Rhodococcus infection, or a Nocardia infection, the method comprising:
- a) measuring levels of one or more of a cholesterol, an oxidated cholesterol derivative, an oxysterol, a 3β-hydroxycholestenoic acid, a 3-oxocholestenoic acid, and a 3-oxo-oxysterol, in a biological sample obtained from the subject;
- b) administering a treatment comprising an effective amount of a corticosteroid or at least one antibiotic selected from the group consisting of rifampicin, isoniazid, pyrazinamide, and ethambutol to the subject, wherein the subject has been determined to have an increased level of one or more of the oxidated cholesterol derivative, the 3-oxocholestenoic acid, and the 3-oxo-oxysterol in the biological sample relative to a respective reference value obtained from a healthy control based upon the measurement in step a).
A method of treating a subject in need thereof having a tuberculosis, a non-tuberculous mycobacteria infection, a Rhodococcus infection, or a Nocardia infection, the method comprising:
- a) quantifying, in a first biological sample obtained from the subject, levels of one or more of a cholesterol, an oxidated cholesterol derivative, an oxysterol, 3β-hydroxycholestenoic acid, a 3-oxocholestenoic acid, and a 3-oxo-oxysterol;
- b) administering a first dose of a corticosteroid or at least one antibiotic selected from the group consisting of rifampicin, isoniazid, pyrazinamide, and ethambutol to the subject, wherein the subject has been determined to have an increased level of one or more of oxidated cholesterol derivative, 3-oxocholestenoic acid, and the 3-oxo-oxysterol in the biological sample relative to respective reference value obtained from a healthy control based upon the measurement in step a);
- c) quantifying, in a second biological sample obtained from the subject after the treatment, one or more of the cholesterol, oxidated cholesterol derivative, oxysterol, 3β-hydroxycholestenoic acid, 3-oxocholestenoic acid, and 3-oxo-oxysterol and
- i) detecting no change or a decrease in the amount of the one or more of cholesterol, oxidated cholesterol derivative, 3-oxocholestenoic acid, or 3-oxo-oxysterol in the second sample, as compared to the first sample;
- or (ii) detecting an increase in one or more of cholesterol, oxidated cholesterol derivative, 3-oxocholestenoic acid, or 3-oxo-oxysterol increases in the second sample as compared to the first sample wherein the increase is less than an increase that occurs in a control group of subjects with the same infection but were not administered treatment;
- and
- d) administering a second dose of the corticosteroid or the at least one antibiotic to the subject, wherein the second dose administered is adjusted based up on the no change, decrease, or increase in the amount of the one or more of the cholesterol, oxidated cholesterol derivative, 3-oxocholestenoic acid, or 3-oxo-oxysterol in the second sample relative to respective reference value obtained from a healthy control.
Dependencies are inferred from the claim text.