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.
Claims33
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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) providing a biological sample from the subject;
- b) measuring levels of one or more of cholesterol, an oxidated cholesterol derivative, an oxysterol, a 3β-hydroxycholestenoic acid, 3-oxocholestenoic acid, and a 3-oxo-oxysterol, in the biological sample;
- c) diagnosing the subject with tuberculosis or a non-tuberculous mycobacteria infection, Rhodococcus infection or Nocardia infection by analyzing the levels of expression of one or more of cholesterol, an oxidated cholesterol derivative, an oxysterol, and a 3-oxo-oxysterol in comparison to respective reference values from a healthy control, wherein increased levels of the oxidated cholesterol derivative 3-oxocholestenoic acid, and/or the 3-oxo-oxysterol compared to the reference value indicate that the subject has tuberculosis, a non-tuberculous mycobacteria infection, a Rhodococcus infection, or a Nocardia infection;
- and
- d) administering 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 diagnosed according to step (c).
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A method of treating a subject in need thereof having tuberculosis or 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 cholesterol, an oxidated cholesterol derivative, an oxysterol, 3β-hydroxycholestenoic acid, 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;
- and
- c) quantifying, in a second biological sample obtained from the subject after the treatment, the one or more of cholesterol, oxidated cholesterol derivative, oxysterol, 3β-hydroxycholestenoic acid, 3-oxocholestenoic acid, and/or 3-oxo-oxysterol quantified in step (a) 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 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 wherein the increase is less than an increase that occurs in a control group of subjects with the same infection but not administered treatment;
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- d) administering a second dose of the corticosteroid or the at least one antibiotic to the subject, wherein the dose is adjusted based on the no change, decrease, or increase in the amount of the one or more of cholesterol, oxidated cholesterol derivative, 3-oxocholestenoic acid, or 3-oxo-oxysterol in the second sample detected step (c).
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Dependencies are inferred from the claim text.