Tuberculosis is diagnosed by finding Mycobacterium tuberculosis bacteria in a clinical specimen taken from the patient. While other investigations may strongly suggest tuberculosis as the diagnosis, they cannot confirm it.

A complete medical evaluation for tuberculosis (TB) must include a medical history, a physical examination, a chest X-ray and microbiological examination (of sputum or some other appropriate sample). It may also include a tuberculin skin test, other scans and X-rays, surgical biopsy.

Medical history The medical history includes obtaining the symptoms of pulmonary TB: productive, prolonged cough of three or more weeks, chest pain, and hemoptysis. Systemic symptoms include low grade remittent fever, chills, night sweats, appetite loss, weight loss, easy fatiguability, and production of sputum that starts out mucoid but changes to purulent.Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; & Mitchell, Richard N. (2007). Robbins Basic Pathology (8th ed.). Saunders Elsevier. pp. 516-522 Other parts of the medical history include prior TB exposure, infection or disease and medical conditions that increase risk for TB disease such as HIV infection. Depending on the sort of patient population surveyed, as few as 20%, or as many as 75% of pulmonary tuberculosis cases may be without symptoms.Burke and Parnell. Minimal Pulmonary Tuberculosis. 1948. 59:348 Canadian Medical Association Journal.

Tuberculosis should be suspected in adults when a pneumonia-like illness has persisted longer than three weeks, or when a respiratory illness in an otherwise healthy individual does not respond to regular antibiotics.

The diagnosis is particularly challenging in children because they more commonly have extrapulmonary disease and present with less mycobacteria (paucibacillary disease).

Physical examination A physical examination is done to assess the patient's general health. It cannot be used to confirm or rule out TB. However, certain findings are suggestive of TB. For example, blood in the sputum, significant weight loss and drenching night sweats may be due to TB.

Tuberculosis classification (Class 0 to 5) used in the US is based on the pathogenesis of the disease. The U.S. Citizenship and Immigration Services has an additional TB classification (Class A, B1, or B2) for immigrants and refugees developed by the Centers for Disease Control and Prevention (CDC). The (Class) B notification program is an important screening strategy to identify new arrivals who have a high risk for TB.

Microbiological studies

A definitive diagnosis of tuberculosis can only be made by culturing Mycobacterium tuberculosis organisms from a specimen taken from the patient (most often sputum, but may also include pus, CSF, biopsied tissue, etc.). A diagnosis made other than by culture may only be classified as "probable" or "presumed". For a diagnosis negating the possibility of tuberculosis infection, most protocols require that two separate cultures both test negative.

Sputum 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. In cases where there is no spontaneous sputum production, a sample can be induced, usually by inhalation of a nebulized saline or saline with bronchodilator solution. A comparative study found that inducing three sputum samples is more sensitive than three gastric washings.

Nucleic acid amplification tests (NAAT) Nucleic acid amplification tests (NAAT) for TB are a heterogeneous group of tests that use either the polymerase chain reaction (PCR) technique or transcription-mediated amplification (TMA) or other forms of nucleic acid amplification methods to detect mycobacterial nucleic acid. These tests vary in which nucleic acid sequence they detect and vary in their accuracy. In the 2000s, the two most common commercially available tests were the amplified mycobacterium tuberculosis direct test (MTD, Gen-Probe) and Amplicor (Roche Diagnostics). In 2007, a systematic review of NAAT by the NHS Health Technology Assessment Programme concluded that "NAAT test accuracy to be far superior when applied to respiratory samples as opposed to other specimens. Although the results were not statistically significant, the AMTD test appears to perform better than other currently available commercial tests." Xpert ® MTB/RIF and Xpert MTB/RIF Ultra has high specificity in diagnosing extrapulmonary tuberculosis and is accurate in detecting rifampicin resistance. However, clinicians should rely on clinical judgement to diagnose TB meningitis when culture results are negative.

A 2007 before-after observational study found that use of the MTD test reduced inappropriate tuberculosis therapy. The study found the accuracy of the MTD test as follows: Overall sensitivity 92%, specificity 99%. In Smear positive patients high sensitivity 99%, specificity 98%. In smear negative patients low sensitivity 62%, but high specificity 99%.

NAA techniques such as polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) are the basis of molecular diagnosis of TB. To detection of MTB in samples different molecular methods and assays have been defined. Real-time PCR (RT-PCR), microarrays, PURE-LAMP, NGS, and WGS are assays that applicable for all taxa and genes, but some assays have been designed for correct and specific detection of MTB such as Amplicor MTB, Cobas TaqMan MTB, E-MTD, FluoroType MTB, LPA (Genotype MTB/R), Anyplex MTB, Xpert MTB, and Genedrive MTB

In 2010 the Xpert MTB/RIF test, another NAAT for TB, became commercially available and, as the CDC said in 2015, it began "revolutionizing tuberculosis (TB) control by contributing to the rapid diagnosis of TB disease and drug resistance. The test simultaneously detects Mycobacterium tuberculosis complex (MTBC) and resistance to rifampin (RIF) in less than 2 hours. In comparison, standard cultures can take 2 to 6 weeks for MTBC to grow and conventional drug resistance tests can add 3 more weeks." The Xpert MTB/RIF Ultra improves upon the Xpert MTB/RIF test.

Culture Many types of microbiological culture are available. Traditionally, cultures have used the Löwenstein-Jensen (LJ), Kirchner, or Middlebrook media (7H9, 7H10, and 7H11). A culture of the AFB can distinguish the various forms of mycobacteria, although results from this may take four to eight weeks for a conclusive answer. New automated systems that are faster include the MB/BacT, BACTEC 9000, VersaTREK, and the Mycobacterial Growth Indicator Tube (MGIT). The Microscopic Observation Drug Susceptibility assay culture may be a faster and more accurate method.

Radiography

Chest X-ray and CT

In active pulmonary TB, infiltrates or consolidations and/or cavities are often seen in the upper lungs with or without mediastinal or hilar lymphadenopathy or pleural effusions (tuberculous pleurisy). However, lesions may appear anywhere in the lungs. In disseminated TB a pattern of many tiny nodules throughout the lung fields is common—the so-called miliary TB. In HIV and other immunosuppressed persons, any abnormality may indicate TB or the chest X-ray may even appear entirely normal.

Abnormalities on chest radiographs may be suggestive of, but are not necessarily diagnostic of, TB. However, chest radiographs may be used to rule out the possibility of pulmonary TB in a person who has a positive reaction to the tuberculin skin test and no symptoms of the disease.

Cavitation or consolidation of the apexes of the upper lobes of the lung or the tree-in-bud sign may be visible on an affected patient's chest X-ray. The tree-in-bud sign may appear on the chest CTs of some patients affected by tuberculosis, but it is not specific to tuberculosis.

FDG PET/CT FDG PET/CT can play several useful roles in patients with confirmed or suspected TB. These roles include detection of active TB lesions, assessment of disease activity, differentiation between active and latent disease, assessment of disease extent (staging), monitoring response to treatment, and identification of potential biopsy target.

Abreugraphy

A variant of the chest X-Ray, abreugraphy (from the name of its inventor, Dr. Manuel Dias de Abreu) was a small radiographic image, also called miniature mass radiography (MMR) or miniature chest radiograph. Though its resolution is limited (it doesn't allow the diagnosis of lung cancer, for example) it is sufficiently accurate for diagnosis of tuberculosis.

Much less expensive than traditional X-Ray, MMR was quickly adopted and extensively utilized in some countries, in the 1950s. For example, in Brazil and in Japan, tuberculosis prevention laws went into effect, obligating ca. 60% of the population to undergo MMR screening.

The procedure went out of favor, as the incidence of tuberculosis dramatically decreased, but is still used in certain situations, such as the screening of prisoners and immigration applicants.

Immunological tests

Tuberculin skin test

Two tests are available: the Mantoux and Heaf tests.

Mantoux skin test

The Mantoux skin test is used in the United States and is endorsed by the American Thoracic Society and Centers for Disease Control and Prevention (CDC).

If a person has had a history of a positive tuberculin skin test, another skin test is not needed.

Heaf test

The Heaf test was used in the United Kingdom until 2005, and is graded on a four-point scale. The Mantoux test is now used.

The equivalent Mantoux test positive levels done with 10 TU (0.1 ml 100 TU/ml, 1:1000) are 0–4 mm induration (Heaf 0 to 1) 5–14 mm induration (Heaf 2) Greater than 15 mm induration (Heaf 3 to 5)

CDC classification of tuberculin reaction An induration (palpable raised hardened area of skin) of more than 5–15 mm (depending upon the person's risk factors) to 10 Mantoux units is considered a positive result, indicating TB infection. 5 mm or more is positive in HIV-positive person Recent contacts of TB case Persons with nodular or fibrotic changes on CXR consistent with old healed TB Patients with organ transplants and other immunosuppressed patients 10 mm or more is positive in Recent arrivals (less than 5 years) from high-prevalent countries Injection drug users Residents and employees of high-risk congregate settings (e.g., prisons, nursing homes, hospitals, homeless shelters, etc.) Mycobacteriology lab personnel Persons with clinical conditions that place them at high risk (e.g., diabetes, prolonged corticosteroid therapy, leukemia, end-stage renal disease, chronic malabsorption syndromes, low body weight, etc.) Children less than 4 years of age, or children and adolescents exposed to adults in high-risk categories 15 mm or more is positive in Persons with no known risk factors for TB (Note: Targeted skin testing programs should only be conducted among high-risk groups)

A tuberculin test conversion is defined as an increase of 10 mm or more within a 2-year period, regardless of age.

Tuberculin skin test after BCG vaccine