Tuberculosis laboratory findings

Tuberculosis Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Tuberculosis from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Children
HIV Coinfection
Diagnosis
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
Chest X Ray
CT
MRI
Echocardiography or Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Special Conditions
Drug-resistant
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Tuberculosis laboratory findings On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Tuberculosis laboratory findings All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Tuberculosis laboratory findings
CDC on Tuberculosis laboratory findings
Tuberculosis laboratory findings in the news
Blogs on Tuberculosis laboratory findings
Directions to Hospitals Treating Tuberculosis
Risk calculators and risk factors for Tuberculosis laboratory findings

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

Laboratory Findings

Routine laboratory exams are usually in the normal ranges. In some patients the following abnormalities may be observed:

• Mild normocytic anemia may be present in almost half of patients.
• Increased erythrocyte sedimentation rate (ESR)
• Mild leukocytosis
• Hyponatremia
• Hypercalcemia
• Elevated alkaline phosphatase levels
• Mild elevation of liver enzymes
• Findings of adrenal insufficiency in case of adrenal involvement (low cortisol and aldosterone levels)

Acid-Fast Bacili

The presence of acid-fast-bacilli (AFB) on a sputum smear or other specimen often indicates TB disease. Acid-fast microscopy is easy and quick, but it does not confirm a diagnosis of TB because some acid-fast-bacilli are not M. tuberculosis. Therefore, a culture is done on all initial samples to confirm the diagnosis.

Sputum smears and cultures should be done for acid-fast bacilli if the patient is producing sputum. The preferred method for this is fluorescence microscopy (auramine-rhodamine staining), which is more sensitive than conventional Ziehl-Neelsen staining.

If no sputum is being produced, specimens can be obtained by inducing sputum, gastric washings, a laryngeal swab, bronchoscopy with bronchoalveolar lavage, or fine needle aspiration of a collection. A comparative study found that inducing three sputum samples is more sensitive than three gastric washings.

Other mycobacteria are also acid-fast. If the smear is positive, PCR or gene probe tests can distinguish M. tuberculosis from other mycobacteria. Even if sputum smear is negative, tuberculosis must be considered and is only excluded after negative cultures.

Culture

Culture: Distinctive clusters of colorless Mycobacterium tuberculosis

A positive culture for M. tuberculosis confirms the diagnosis of TB disease. Culture examinations should be completed on all specimens, regardless of AFB smear results. Laboratories should report positive results on smears and cultures within 24 hours by telephone or fax to the primary health care provider and to the state or local TB control program, as required by law.

Many types of cultures are available for M. tuberculosis, this include Löwenstein-Jensen (LJ), Kirchner, or Middlebrook media. . Culture of Mycobacteria usually takes 4 to 8 weeks to grow and can distinguish from several types of mycobacteria Other forms of culture are available, this include automated systems in which the mycobacteria grow at a faster rate. MB/BacT, BACTEC 9000, and the Mycobacterial Growth Indicator Tube (MGIT). The microscopic-observation drug-susceptibility (MODS) culture is considered a faster and more accurate method .

A sample of pleural exudate can be analyzed by cytopathology or at a cell count lab. Samples are usually lymphocyte predominant, and cytopathology is more accurate than cell count labs at detecting lymphs. If there is more fluid present, then an AFB lab is more appropriate. A pleural exudate lab test may find sterile pyuria (especially in HIV positive patients), but overall this finding is fairly uncommon. Most extra-pulmonary TB is pauci-bacillary, so the yield of tests is very low. A negative results does not exclude a tuberculosis infection.

Drug Resistance

For all patients, the initial M. tuberculosis isolate should be tested for drug resistance. It is crucial to identify drug resistance as early as possible to ensure effective treatment. Drug susceptibility patterns should be repeated for patients who do not respond adequately to treatment or who have positive culture results despite 3 months of therapy. Susceptibility results from laboratories should be promptly reported to the primary health care provider and the state or local TB control program.

Fluid Analysis

• Peritoneal Fluid: Leucocyte count: 150-4000 mm³, lymphocytic pleocytosis, protein > 3.0 g/dL, increased LDH.
• Cerebrospinal Fluid: High protein, low glucose, increased number of lymphocytes, increased LDH

Urinalysis

• For renal tuberculosis, the classic laboratory finding is sterile pyuria with microscopic hematuria.

Interferon-Gamma Release Assays (IGRAs)

Interferon-Gamma Release Assays (IGRAs) are whole-blood tests that can aid in diagnosing Mycobacterium tuberculosis infection. They do not help differentiate latent tuberculosis infection (LTBI) from tuberculosis disease. Two IGRAs that have been approved by the U.S. Food and Drug Administration (FDA) are commercially available in the U.S, The QuantiFERON®-TB Gold In-Tube test (QFT-GIT) and the T-SPOT®.TB test (T-Spot).

IGRAs measure a person’s immune reactivity to M. tuberculosis. White blood cells from most persons that have been infected with M. tuberculosis will release interferon-gamma (IFN-g) when mixed with antigens (substances that can produce an immune response) derived from M. tuberculosis.

To conduct the tests, fresh blood samples are mixed with antigens and controls. The antigens, testing methods, and interpretation criteria for IGRAs differ.

Differences in Currently Available IGRAs

	QuantiFERON	T-SPOT
Initial Process	Process whole blood within 16 hours	Process peripheral blood mononuclear cells (PBMCs) within 8 hours, or if T-Cell Xtend® is used, within 30 hours
M. tuberculosis Antigen	Single mixture of synthetic peptides representing ESAT-6, CFP-10 & TB7.7.	Separate mixtures of synthetic peptides representing ESAT-6 & CFP-10
Measurement	IFN-g concentration	Number of IFN-g producing cells (spots)
Possible Results	Positive, negative, indeterminate	Positive, negative, indeterminate, borderline
Table adapted from CDC

Advantages and Disadvantages of IGRAs

Advantages	Disadvantages
It requires a single patient visit to conduct the test. The results can be available within 24 hours. It does not boost responses measured by subsequent tests. A history of prior BCG (bacille Calmette-Guérin) vaccination does not cause a false-positive IGRA test result.	The blood samples must be processed within 8-30 hours after collection while white blood cells are still viable. Errors in collecting or transporting blood specimens or in running and interpreting the assay can decrease the accuracy of IGRAs. There is limited data on the use of IGRAs to predict who will progress to TB disease in the future. There is limited data on the use of IGRAs for: Children younger than 5 years of age Persons recently exposed to M. tuberculosis Immunocompromised persons Serial testing It may be expensive
Table adapted from CDC