Editing Tuberculosis (section)

== Diagnosis ==
{{Main|Diagnosis of tuberculosis}}[[File:TB in sputum.png|thumb|''M. tuberculosis'' ([[Ziehl-Neelsen stain|stained red]]) in [[sputum]]]]Diagnosis of tuberculosis is often difficult. Symptoms manifest slowly, and are generally [[Signs and symptoms|non-specific]], e.g. cough, fatigue, fever which could be caused by a number of other factors.<ref>{{Citation |last1=Tobin |first1=Ellis H. |title=Tuberculosis Overview |date=22 December 2024 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK441916/ |access-date=2025-03-27 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=28722945 |last2=Tristram |first2=Debbie}}</ref> The conclusive test for pulmonary TB is a [[Microbiological culture|bacterial culture]] taken from a sample of sputum, but this is slow to give a result, and does not detect latent TB. Extra-pulmonary TB infection can affect the kidneys, spine, brain, lymph nodes, or bones - a sample cannot easily be obtained for culture.<ref>{{Cite web |last=CDC |date=2025-01-30 |title=Clinical Overview of Tuberculosis Disease |url=https://www.cdc.gov/tb/hcp/clinical-overview/tuberculosis-disease.html |access-date=2025-03-29 |website=Tuberculosis (TB) |language=en-us}}</ref> Tests based on the [[immune response]] are sensitive but are likely to give [[False positives and false negatives|false negatives]] in those with [[Immunodeficiency|weak immune systems]] such as very young patients and those [[Coinfection|coinfected]] with HIV. Another issue affecting diagnosis in many parts of the world is that TB infection is most common in [[Least developed countries|resource-poor]] settings where sophisticated laboratories are rarely available.<ref>{{Cite journal |last1=Datta |first1=Sumona |last2=Evans |first2=Carlton A. |date=2020-09-01 |title=The uncertainty of tuberculosis diagnosis |journal=The Lancet Infectious Diseases |language=English |volume=20 |issue=9 |pages=1002–1004 |doi=10.1016/S1473-3099(20)30400-X |issn=1473-3099 |pmid=32437698|pmc=7234790 }}</ref><ref>{{Cite web |last1=Hewison |first1=Cathy |last2=Gomez |first2=Diana |last3=Deborggraeve |first3=Stijn |date=2022-10-24 |title=The deadly gap in diagnosing children with tuberculosis |url=https://msf-access.medium.com/the-deadly-gap-in-diagnosing-children-with-tuberculosis-2f0673117940 |access-date=2025-03-29 |website=MSF Access Campaign |language=en}}</ref>

A diagnosis of TB should be considered in those with signs of lung disease or [[constitutional symptoms]] lasting longer than two weeks.<ref name="Escalante-2009">{{cite journal |vauthors=Escalante P |date=June 2009 |title=In the clinic. Tuberculosis |journal=Annals of Internal Medicine |volume=150 |issue=11 |pages=ITC61-614; quiz ITV616 |doi=10.7326/0003-4819-150-11-200906020-01006 |pmid=19487708 |s2cid=639982}}</ref> Diagnosis of TB, whether latent or active, starts with medical history and physical examination. Subsequently a number of tests can be performed to refine the diagnosis:<ref>{{Cite web |last=CDC |date=2025-01-30 |title=Clinical and Laboratory Diagnosis for Tuberculosis |url=https://www.cdc.gov/tb/hcp/testing-diagnosis/clinical-and-laboratory-diagnosis.html |access-date=2025-03-29 |website=Centers for Disease Control and Prevention |language=en-us}}</ref>  A [[chest X-ray]] and multiple [[sputum culture]]s for [[acid-fast bacilli]] are typically part of the initial evaluation.<ref name="Escalante-2009" />

=== Mantoux test ===
[[File:Mantoux_tuberculin_skin_test.jpg|thumb|The Mantoux skin test consists of an injection of a small quantity of PPD [[tuberculin]] just below the skin on the forearm.]]
The [[Mantoux test|Mantoux tuberculin skin test]] is often used to screen people at high risk for TB such as health workers or close contacts of TB patients, who may not display symptoms of infection.<ref name="Escalante-2009" /> In the Mantoux test, a small quantity of tuberculin antigen is injected intradermally on the forearm.<ref>{{cite web |date=October 2011 |title=TB Elimination - Tuberculin Skin Testing |url=https://www.cdc.gov/tb/publications/factsheets/testing/skintesting.pdf |access-date=5 June 2017 |website=CDC.gov |publisher=CDC - National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention - Division of Tuberculosis Elimination}}</ref><ref>{{cite web |title=The Mantoux test: Administration, reading and interpretation |url=http://www.immunisation.nhs.uk/files/mantouxtest.pdf |archive-url=https://web.archive.org/web/20100215105953/http://www.immunisation.nhs.uk/files/mantouxtest.pdf |archive-date=15 February 2010 |access-date=5 June 2017 |website=NHS.uk}}</ref> The result of the test is read after 48 to 72 hours. A person who has been exposed to the bacteria would be expected to mount an immune response; the reaction is read by measuring the diameter of the raised area.<ref>{{Cite web |title=Mantoux Tuberculin Skin Test |url=https://www.cdc.gov/tb/education/mantoux/pdf/Mantoux_TB_Skin_Test.pdf |access-date=30 March 2025 |website=Centers for Disease Control and Prevention}}</ref> Vaccination with  Bacille Calmette-Guerin (BCG) may result in a false-positive result. Several factors may lead to false negatives; these include HIV infection, some viral illnesses, and overwhelming TB disease.<ref>{{Cite web |date=2014 |title=Table A3.1, Causes of false-negative and false-positive tuberculin skin tests |url=https://www.ncbi.nlm.nih.gov/books/NBK214439/table/annex3.t1/?report=objectonly |access-date=2025-03-30 |website=www.ncbi.nlm.nih.gov |language=en}}</ref><ref>{{Cite journal |last1=Nayak |first1=Surajit |last2=Acharjya |first2=Basanti |date=April 2012 |title=Mantoux test and its interpretation |journal=Indian Dermatology Online Journal |language=en-US |volume=3 |issue=1 |pages=2–6 |doi=10.4103/2229-5178.93479 |doi-access=free |issn=2229-5178 |pmc=3481914 |pmid=23130251}}</ref>

=== Interferon-Gamma Release Assay ===
The [[Interferon gamma release assay|Interferon-Gamma Release Assay]] (IGRA) is recommended in those who are positive to the Mantoux test.<ref>{{NICE|117|Tuberculosis|2011}}</ref> This test mixes a blood sample with antigenic material derived from the TB bacterium. If the patient has developed an immune response to a TB infection, white blood cells in the sample will release interferon-gamma (IFN-γ), which can be measured.<ref name="CDC_Testing_2024">{{Cite web |date=2024-09-12 |title=Clinical Testing Guidance for Tuberculosis: Interferon Gamma Release Assay |url=https://www.cdc.gov/tb/hcp/testing-diagnosis/interferon-gamma-release-assay.html |access-date=2025-03-30 |website=Centers for Disease Control and Prevention |language=en-us}}</ref> This test is more reliable than the Mantoux test, and does not give a false positive after BCG vaccination; <ref name="CDC_Testing_2024" /> however it may give a positive result in case of infection by the related bacteria ''M. szulgai'', ''M. marinum'', and ''M. kansasii''.<ref>{{cite book |url=https://books.google.com/books?id=rAT1bdnDakAC&pg=PA544 |title=Textbook of Pulmonary and Critical Care Medicine |publisher=Jaypee Brothers Medical Publishers |year=2011 |isbn=978-93-5025-073-0 |veditors=Jindal SK |location=New Delhi |page=544 |archive-url=https://web.archive.org/web/20150906185238/https://books.google.com/books?id=rAT1bdnDakAC&pg=PA544 |archive-date=6 September 2015 |url-status=live}}</ref>

=== Chest radiograph ===
In active pulmonary TB, infiltrates (opaque areas) or scarring are visible in the lungs on a chest X-ray. Infiltrates are suggestive but not necessarily diagnostic of TB. Other lung diseases can mimic the appearance of TB; and this test will not detect extrapulmonary infection or a recent infection.<ref>{{Cite web |last=Sherrell |first=Zia |date=2023-12-20 |title=Chest X-ray for tuberculosis (TB): What to expect, results, and more |url=https://www.medicalnewstoday.com/articles/tuberculosis-x-ray |access-date=2025-03-30 |website=www.medicalnewstoday.com |language=en}}</ref>

=== Microbiological studies ===
[[File:TB_Culture.jpg|thumb|A close-up of ''[[Mycobacterium tuberculosis]]'' in a culture medium]]
A definitive diagnosis of tuberculosis can be made by detecting ''[[Mycobacterium tuberculosis]]'' organisms in a specimen taken from the patient (most often [[sputum]], but may also be [[pus]], [[cerebrospinal fluid]], [[Biopsy|biopsied]] tissue, etc.).<ref>{{Citation |last1=Tobin |first1=Ellis H. |title=Tuberculosis Overview |date=22 December 2024 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK441916/ |access-date=2025-03-27 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=28722945 |last2=Tristram |first2=Debbie}}</ref> The specimen is examined by [[fluorescence microscopy]].<ref>{{cite journal |vauthors=Steingart KR, Henry M, Ng V, Hopewell PC, Ramsay A, Cunningham J, Urbanczik R, Perkins M, Aziz MA, Pai M |date=September 2006 |title=Fluorescence versus conventional sputum smear microscopy for tuberculosis: a systematic review |journal=The Lancet. Infectious Diseases |volume=6 |issue=9 |pages=570–81 |doi=10.1016/S1473-3099(06)70578-3 |pmid=16931408}}</ref> The bacterium is slow growing so a cell culture may take several weeks to yield a result.<ref>{{Cite web |title=Acid-Fast Bacillus (AFB) Tests |url=https://medlineplus.gov/lab-tests/acid-fast-bacillus-afb-tests/ |access-date=2025-03-31 |website=MedlinePlus |language=en}}</ref>

=== Other tests ===
[[Nucleic acid amplification test]]s (NAAT) and [[adenosine deaminase]] testing may allow rapid diagnosis of TB.<ref>{{cite journal |vauthors=Bento J, Silva AS, Rodrigues F, Duarte R |date=2011 |title=[Diagnostic tools in tuberculosis] |journal=Acta Médica Portuguesa |volume=24 |issue=1 |pages=145–54 |doi=10.20344/amp.333 |pmid=21672452 |s2cid=76156550 |doi-access=free}}</ref><ref name="CDC_Xpert_2024" /> In December 2010, the World Health Organization endorsed the Xpert MTB/RIF system (a NAAT) for diagnosis of tuberculosis in endemic countries.<ref>[https://web.archive.org/web/20101210115147/http://www.who.int/mediacentre/news/releases/2010/tb_test_20101208/en/index.html "WHO endorses new rapid tuberculosis test"] 8 December 2010. Retrieved on 12 June 2012</ref>

Blood tests to detect antibodies are not [[sensitivity and specificity|specific or sensitive]], so they are not recommended.<ref>{{cite journal |vauthors=Steingart KR, Flores LL, Dendukuri N, Schiller I, Laal S, Ramsay A, Hopewell PC, Pai M |date=August 2011 |title=Commercial serological tests for the diagnosis of active pulmonary and extrapulmonary tuberculosis: an updated systematic review and meta-analysis |journal=PLOS Medicine |volume=8 |issue=8 |page=e1001062 |doi=10.1371/journal.pmed.1001062 |pmc=3153457 |pmid=21857806 |doi-access=free |veditors=Evans C}}</ref>

[[Polymerase chain reaction|PCR]] testing for ''Mycobacterium tuberculosis'' is often required for the diagnosis of [[urogenital tuberculosis]] and may also be used to diagnose tuberculosis in other tissues. It is highly sensitive and specific with good turnaround time.<ref name="Figueiredo-2017" />