Tuberculosis resident survival guide: Difference between revisions
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{{SK}}[[TB]], [[PPD-tuberculin skin test|PPD]], [[mycobacterium tuberculosis]] | {{SK}}[[TB]], [[PPD-tuberculin skin test|PPD]], [[mycobacterium tuberculosis]] | ||
==Overview== | ==Overview== | ||
[[Tuberculosis]] (TB) is a common and very contagious [[infectious disease]] caused by [[Mycobacterium tuberculosis|Mycobacterium tuberculosis bacteria]] (MTB). MTB can affect every [[system]] of the [[human body]], but most commonly affects the [[Tuberculosis, pulmonary|respiratory system]] since this organism grow vigorously in high [[oxygen]] environments. It is calculated that more than a third of the world's [[population]] has been exposed to [[Mycobacterium tuberculosis|MTB]], being the vast majority of them [[asymptomatic]] and maintaining as [[Latent tuberculosis|latent]]. [[Symptoms]] of [[respiratory]] active tuberculosis includes [[hemoptysis]], [[shortness of breath]], [[fever]], [[chills]], [[night sweats]], and [[weight loss]]. Usually [[latent tuberculosis]] is treated with a regimen of 6-9 months of [[rifampin]] or [[isoniazid]], while active [[TB]] is managed with a phase of four antituberculous agents ([[rifampin]], [[isoniazid]], [[ethambutol]], [[pyrazinamide]]) for 2 months to later be continued only by [[isoniazid]] and [[rifampin]] 4 more months. | [[Tuberculosis]] (TB) is a common and very contagious [[infectious disease]] caused by [[Mycobacterium tuberculosis|Mycobacterium tuberculosis bacteria]] (MTB). MTB can affect every [[system]] of the [[human body]], but most commonly affects the [[Tuberculosis, pulmonary|respiratory system]] since this organism grow vigorously in high [[oxygen]] environments. It is calculated that more than a third of the world's [[population]] has been exposed to [[Mycobacterium tuberculosis|MTB]], being the vast majority of them [[asymptomatic]] and maintaining as [[Latent tuberculosis|latent]]. [[Symptoms]] of [[respiratory]] active tuberculosis includes [[hemoptysis]], [[shortness of breath]], [[fever]], [[chills]], [[night sweats]], and [[weight loss]]. Usually [[latent tuberculosis]] is treated with a regimen of 6-9 months of [[rifampin]] or [[isoniazid]], while active [[TB]] is managed with a phase of four antituberculous agents ([[rifampin]], [[isoniazid]], [[ethambutol]], [[pyrazinamide]]) for 2 months to later be continued only by [[isoniazid]] and [[rifampin]] 4 more months. | ||
==Diagnostic Criteria== | ==Diagnostic Criteria== | ||
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===Test for latent tuberculosis=== | ===Test for latent tuberculosis=== | ||
*[[Tuberculin test|Tuberculin skin test]]. Also known as [[Mantoux test]] or [[PPD-tuberculin skin test|PPD]] consists in the visualization of the [[skin]] reaction after the injection of [[Mycobacterium tuberculosis|M. tuberculosis]] [[antigens]] 24, 48, and 72 hours after. A positive result is interpreted as the following: | *[[Tuberculin test|Tuberculin skin test]]. Also known as [[Mantoux test]] or [[PPD-tuberculin skin test|PPD]] consists in the visualization of the [[skin]] reaction after the injection of [[Mycobacterium tuberculosis|M. tuberculosis]] [[antigens]] 24, 48, and 72 hours after. A positive result is interpreted as the following:<ref name="pmid23130251">{{cite journal |vauthors=Nayak S, Acharjya B |title=Mantoux test and its interpretation |journal=Indian Dermatol Online J |volume=3 |issue=1 |pages=2–6 |date=January 2012 |pmid=23130251 |pmc=3481914 |doi=10.4103/2229-5178.93479 |url=}}</ref><ref name="pmid30576322">{{cite journal |vauthors=Slogotskaya L, Bogorodskaya E, Ivanova D, Sevostyanova T |title=Comparative sensitivity of the test with tuberculosis recombinant allergen, containing ESAT6-CFP10 protein, and Mantoux test with 2 TU PPD-L in newly diagnosed tuberculosis children and adolescents in Moscow |journal=PLoS ONE |volume=13 |issue=12 |pages=e0208705 |date=2018 |pmid=30576322 |pmc=6303070 |doi=10.1371/journal.pone.0208705 |url=}}</ref><ref name="pmid32310497">{{cite journal |vauthors=Pahal P, Sharma S |title= |journal= |volume= |issue= |pages= |date= |pmid=32310497 |doi= |url=}}</ref><ref name="pmid25861338">{{cite journal |vauthors=Ryu YJ |title=Diagnosis of pulmonary tuberculosis: recent advances and diagnostic algorithms |journal=Tuberc Respir Dis (Seoul) |volume=78 |issue=2 |pages=64–71 |date=April 2015 |pmid=25861338 |pmc=4388902 |doi=10.4046/trd.2015.78.2.64 |url=}}</ref> | ||
**>5 mm: [[HIV]] infected patients, [[CXR]] that suggests [[TB]] [[infection]], individuals taking [[steroids]] | **>5 mm: [[HIV]] infected patients, [[CXR]] that suggests [[TB]] [[infection]], individuals taking [[steroids]] | ||
**>10 mm: [[Healthcare]] workers, [[nursing home]] dweller, [[parenteral]] [[drug]] users, patients with [[immunocompromised]] [[diseases]] | **>10 mm: [[Healthcare]] workers, [[nursing home]] dweller, [[parenteral]] [[drug]] users, patients with [[immunocompromised]] [[diseases]] | ||
**>15 mm: All individuals not cathegorized above | **>15 mm: All individuals not cathegorized above | ||
*[[QuantiFERON|QuantiFERON-TB]]. Detects [[cell-mediated immunity]] to [[tuberculin]] | *[[QuantiFERON|QuantiFERON-TB]]. Detects [[cell-mediated immunity]] to [[tuberculin]].<ref name="pmid31586819">{{cite journal |vauthors=Pourakbari B, Mamishi S, Benvari S, Mahmoudi S |title=Comparison of the QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In-Tube interferon-γ release assays: A systematic review and meta-analysis |journal=Adv Med Sci |volume=64 |issue=2 |pages=437–443 |date=September 2019 |pmid=31586819 |doi=10.1016/j.advms.2019.09.001 |url=}}</ref><ref name="pmid25861338" /> | ||
*[[QuantiFERON-TB Gold]]. Detects [[Interferon-gamma|IFN-g]] released by sensitized [[T cells]] by [[M. tuberculosis]] antigens ''[[in vitro]]'' | *[[QuantiFERON-TB Gold]]. Detects [[Interferon-gamma|IFN-g]] released by sensitized [[T cells]] by [[M. tuberculosis]] antigens ''[[in vitro]].<ref name="pmid31586819" /><ref name="pmid25861338" />'' | ||
*T SPOT-TB. Detects [[T cells]] stimulated by [[M. tuberculosis]] | *T SPOT-TB. Detects [[T cells]] stimulated by [[M. tuberculosis]].<ref name="pmid31414740">{{cite journal |vauthors=Zhu M, Zhu Z, Yang J, Hu K |title=Performance Evaluation of IGRA-ELISA and T-SPOT.TB for Diagnosing Tuberculosis Infection |journal=Clin. Lab. |volume=65 |issue=8 |pages= |date=August 2019 |pmid=31414740 |doi=10.7754/Clin.Lab.2019.181109 |url=}}</ref><ref name="pmid29318113">{{cite journal |vauthors=Zhu F, Ou Q, Zheng J |title=Application Values of T-SPOT.TB in Clinical Rapid Diagnosis of Tuberculosis |journal=Iran. J. Public Health |volume=47 |issue=1 |pages=18–23 |date=January 2018 |pmid=29318113 |pmc=5756596 |doi= |url=}}</ref><ref name="pmid25861338" /> | ||
*AMPLICOR assay. Uses [[Polymerase chain reaction|DNA polymerase chain reaction]] (PCR) to amplify [[nucleic acid]] targets. | *AMPLICOR assay. Uses [[Polymerase chain reaction|DNA polymerase chain reaction]] (PCR) to amplify [[nucleic acid]] targets.<ref name="pmid11052908">{{cite journal |vauthors=Bonington A, Strang JI, Klapper PE, Hood SV, Parish A, Swift PJ, Damba J, Stevens H, Sawyer L, Potgieter G, Bailey A, Wilkins EG |title=TB PCR in the early diagnosis of tuberculous meningitis: evaluation of the Roche semi-automated COBAS Amplicor MTB test with reference to the manual Amplicor MTB PCR test. |journal=Tuber. Lung Dis. |volume=80 |issue=4-5 |pages=191–6 |date=2000 |pmid=11052908 |doi=10.1054/tuld.2000.0246 |url=}}</ref><ref name="pmid25861338" /> | ||
===Tests for active tuberculosis disease=== | ===Tests for active tuberculosis disease=== | ||
*[[Microbiological]] detection: | *[[Microbiological]] detection: | ||
**[[AFB stain|Acid fast bacilli]] [[stain]]. This tests is relatively fast and cheap but presents with a high number of [[false positive]]<nowiki/>s, since may detect [[Mycobacterium bovis]] or NBT | **[[AFB stain|Acid fast bacilli]] [[stain]]. This tests is relatively fast and cheap but presents with a high number of [[false positive]]<nowiki/>s, since may detect [[Mycobacterium bovis]] or NBT.<ref name="pmid25130623">{{cite journal |vauthors=Ryan GJ, Shapiro HM, Lenaerts AJ |title=Improving acid-fast fluorescent staining for the detection of mycobacteria using a new nucleic acid staining approach |journal=Tuberculosis (Edinb) |volume=94 |issue=5 |pages=511–8 |date=September 2014 |pmid=25130623 |doi=10.1016/j.tube.2014.07.004 |url=}}</ref><ref name="pmid30725806">{{cite journal |vauthors=Bayot ML, Mirza TM, Sharma S |title= |journal= |volume= |issue= |pages= |date= |pmid=30725806 |doi= |url=}}</ref> | ||
**[[Mycobacterial]] culture. This test is cheap but takes weeks to have results. Culture may be done in 3 types of media: solid media (Lowenstein Jensen), agar-based media (Middlebrook 7H10 and 7H11), and liquid media (Middlebrook 7H12). | **[[Mycobacterial]] culture. This test is cheap but takes weeks to have results. Culture may be done in 3 types of media: solid media (Lowenstein Jensen), agar-based media (Middlebrook 7H10 and 7H11), and liquid media (Middlebrook 7H12).<ref name="pmid22978323">{{cite journal |vauthors=Demers AM, Verver S, Boulle A, Warren R, van Helden P, Behr MA, Coetzee D |title=High yield of culture-based diagnosis in a TB-endemic setting |journal=BMC Infect. Dis. |volume=12 |issue= |pages=218 |date=September 2012 |pmid=22978323 |pmc=3482573 |doi=10.1186/1471-2334-12-218 |url=}}</ref> | ||
**[[NAAT|Nucleic acid amplification assays]]. This test is rapid and specific to [[Mycobacterium tuberculosis|M. tuberculosi]]<nowiki/>s but costly and gives no [[Drug susceptibility testing|drug susceptibility]] | **[[NAAT|Nucleic acid amplification assays]]. This test is rapid and specific to [[Mycobacterium tuberculosis|M. tuberculosi]]<nowiki/>s but costly and gives no [[Drug susceptibility testing|drug susceptibility]].<ref name="pmid22137190">{{cite journal |vauthors=Hughes R, Wonderling D, Li B, Higgins B |title=The cost effectiveness of Nucleic Acid Amplification Techniques for the diagnosis of tuberculosis |journal=Respir Med |volume=106 |issue=2 |pages=300–7 |date=February 2012 |pmid=22137190 |doi=10.1016/j.rmed.2011.10.005 |url=}}</ref> | ||
*Response to [[therapy]]. Clinical response to antituberculous [[drugs]] may be an indicator of [[Tuberculosis|TB infection]], but [[lead time bias]] should assesed | *Response to [[therapy]]. Clinical response to antituberculous [[drugs]] may be an indicator of [[Tuberculosis|TB infection]], but [[lead time bias]] should assesed | ||
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==Causes== | ==Causes== | ||
*[[Tuberculosis]] infection is caused by [[mycobacterium tuberculosis]] which is [[Transmission|transmitted]] from person to person by [[inhalation]] of [[aerosols]] from an affected individual with active TB. | *[[Tuberculosis]] infection is caused by [[mycobacterium tuberculosis]] which is [[Transmission|transmitted]] from person to person by [[inhalation]] of [[aerosols]] from an affected individual with active TB.<ref name="pmid29452616">{{cite journal |vauthors=Ankrah AO, Glaudemans AWJM, Maes A, Van de Wiele C, Dierckx RAJO, Vorster M, Sathekge MM |title=Tuberculosis |journal=Semin Nucl Med |volume=48 |issue=2 |pages=108–130 |date=March 2018 |pmid=29452616 |doi=10.1053/j.semnuclmed.2017.10.005 |url=}}</ref> | ||
*[[Tuberculosis]] may be spread through [[cough]], [[sneezing]], singing, spitting, or even talking because these particles may remain suspended in the air for several hours. | *[[Tuberculosis]] may be spread through [[cough]], [[sneezing]], singing, spitting, or even talking because these particles may remain suspended in the air for several hours. | ||
* | |||
== | ==Diagnostic Approach== | ||
Shown below is an algorithm summarizing the diagnosis of Tuberculosis according the the Association of chest physicians guidelines | Shown below is an algorithm summarizing the diagnosis of Tuberculosis according the the Association of chest physicians guidelines: | ||
<br /> | |||
{{familytree/start |summary=PE diagnosis Algorithm.}} | {{familytree/start |summary=PE diagnosis Algorithm.}} | ||
{{familytree | | | | | | | | | A01 | | | A01= Presumptive [[TB]] }} | {{familytree | | | | | | | | | A01 | | | A01= Presumptive [[TB]] }} | ||
| Line 51: | Line 54: | ||
{{familytree | | | | | | | | | | |!| | }} | {{familytree | | | | | | | | | | |!| | }} | ||
{{familytree | | | | | | | | | | A01 | | A01= Indeterminate of 2nd sample, collect fresh sample of liquid culture/ [http://Line%20Probe%20Assay Line Probe Assay] }} | {{familytree | | | | | | | | | | A01 | | A01= Indeterminate of 2nd sample, collect fresh sample of liquid culture/ [http://Line%20Probe%20Assay Line Probe Assay] }} | ||
{{familytree/end}} | {{familytree/end}}<br /> | ||
==Treatment== | |||
{{familytree/start |summary=PE diagnosis Algorithm.}} | Shown below is an algorithm summarizing the [[treatment]] of [[Tuberculosis]] according the the Centers of Disease Control and Prevention guidelines (CDC):<ref name="urltb_therapeutic_tables [TUSOM | Pharmwiki]">{{cite web |url=http://tmedweb.tulane.edu/pharmwiki/doku.php/tb_therapeutic_tables |title=tb_therapeutic_tables [TUSOM | Pharmwiki] |format= |work= |accessdate=}}</ref> | ||
<br />{{familytree/start |summary=PE diagnosis Algorithm.}} | |||
{{familytree | | | | | | | | | A01 | | | A01= Presumptive [[TB]] }} | {{familytree | | | | | | | | | A01 | | | A01= Presumptive [[TB]] }} | ||
{{familytree | | | | | | | | | |!| | | | }} | {{familytree | | | | | | | | | |!| | | | }} | ||
| Line 74: | Line 78: | ||
==Do's== | ==Do's== | ||
* | *For long use of [[isoniazide]], such as the management of [[TB]] always use [[pyridoxine]] (vitamin B6) to prevent [[peripheral neuropathy]].<ref name="urltb_therapeutic_tables [TUSOM | Pharmwiki]" /> | ||
*Be aware of [[drug]] interactions between [[rifampin]] and [[antivirals]] in patients with [[HIV]]. | |||
==Don'ts== | ==Don'ts== | ||
Revision as of 05:47, 6 September 2020
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Moises Romo M.D.
Synonyms and keywords:TB, PPD, mycobacterium tuberculosis
Overview
Tuberculosis (TB) is a common and very contagious infectious disease caused by Mycobacterium tuberculosis bacteria (MTB). MTB can affect every system of the human body, but most commonly affects the respiratory system since this organism grow vigorously in high oxygen environments. It is calculated that more than a third of the world's population has been exposed to MTB, being the vast majority of them asymptomatic and maintaining as latent. Symptoms of respiratory active tuberculosis includes hemoptysis, shortness of breath, fever, chills, night sweats, and weight loss. Usually latent tuberculosis is treated with a regimen of 6-9 months of rifampin or isoniazid, while active TB is managed with a phase of four antituberculous agents (rifampin, isoniazid, ethambutol, pyrazinamide) for 2 months to later be continued only by isoniazid and rifampin 4 more months.
Diagnostic Criteria
Test for latent tuberculosis
- Tuberculin skin test. Also known as Mantoux test or PPD consists in the visualization of the skin reaction after the injection of M. tuberculosis antigens 24, 48, and 72 hours after. A positive result is interpreted as the following:[1][2][3][4]
- >5 mm: HIV infected patients, CXR that suggests TB infection, individuals taking steroids
- >10 mm: Healthcare workers, nursing home dweller, parenteral drug users, patients with immunocompromised diseases
- >15 mm: All individuals not cathegorized above
- QuantiFERON-TB. Detects cell-mediated immunity to tuberculin.[5][4]
- QuantiFERON-TB Gold. Detects IFN-g released by sensitized T cells by M. tuberculosis antigens in vitro.[5][4]
- T SPOT-TB. Detects T cells stimulated by M. tuberculosis.[6][7][4]
- AMPLICOR assay. Uses DNA polymerase chain reaction (PCR) to amplify nucleic acid targets.[8][4]
Tests for active tuberculosis disease
- Microbiological detection:
- Acid fast bacilli stain. This tests is relatively fast and cheap but presents with a high number of false positives, since may detect Mycobacterium bovis or NBT.[9][10]
- Mycobacterial culture. This test is cheap but takes weeks to have results. Culture may be done in 3 types of media: solid media (Lowenstein Jensen), agar-based media (Middlebrook 7H10 and 7H11), and liquid media (Middlebrook 7H12).[11]
- Nucleic acid amplification assays. This test is rapid and specific to M. tuberculosis but costly and gives no drug susceptibility.[12]
- Response to therapy. Clinical response to antituberculous drugs may be an indicator of TB infection, but lead time bias should assesed
Causes
- Tuberculosis infection is caused by mycobacterium tuberculosis which is transmitted from person to person by inhalation of aerosols from an affected individual with active TB.[13]
- Tuberculosis may be spread through cough, sneezing, singing, spitting, or even talking because these particles may remain suspended in the air for several hours.
Diagnostic Approach
Shown below is an algorithm summarizing the diagnosis of Tuberculosis according the the Association of chest physicians guidelines:
| Presumptive TB | |||||||||||||||||||||||||||||||||||||||||||||||||
| Sputum examination + Chest X-ray | |||||||||||||||||||||||||||||||||||||||||||||||||
| Sputum positive for TB, Chest X-ray suggestive of TB | Sputum positive for TB, Chest X-ray not suggestive of TB | Sputum negative for TB, Chest X-ray suggestive of TB | Sputum negative for TB, Chest X-ray not suggestive of TB | High clinical suspicion for TB | |||||||||||||||||||||||||||||||||||||||||||||
| Cartridge-Based Nucleic Acid Amplification Test | |||||||||||||||||||||||||||||||||||||||||||||||||
| Mycobacterium tuberculosis detected | Mycobacterium tuberculosis not detected or Cartridge-Based Nucleic Acid Amplification Test result not available | Considere alternate diagnosis | |||||||||||||||||||||||||||||||||||||||||||||||
| Rifampicin sensitive | Rifampicin indeterminate | Rifampicin resistant | Clinically diagnosed TB | Alternate diagnosis | |||||||||||||||||||||||||||||||||||||||||||||
| Microbiologically confirmed TB | Repeat Cartridge-Based Nucleic Acid Amplification Test on 2nd sample | Refer to management of Rifampicin resistance | |||||||||||||||||||||||||||||||||||||||||||||||
| Indeterminate of 2nd sample, collect fresh sample of liquid culture/ Line Probe Assay | |||||||||||||||||||||||||||||||||||||||||||||||||
Treatment
Shown below is an algorithm summarizing the treatment of Tuberculosis according the the Centers of Disease Control and Prevention guidelines (CDC):[14]
| Presumptive TB | |||||||||||||||||||||||||||||||||||||||
| Place patient on RIPE (rifampin, isoniazide, pyrazinamide, ethambutol) | |||||||||||||||||||||||||||||||||||||||
| Did the specimen sent for culture at the initial evaluation return positive? | |||||||||||||||||||||||||||||||||||||||
| Yes | No | ||||||||||||||||||||||||||||||||||||||
| Give isoniazide and rifampin for 4 months | |||||||||||||||||||||||||||||||||||||||
| Was there cavitation on initial chest X-ray? | No | Is the patient HIV positive? | No | ||||||||||||||||||||||||||||||||||||
| Yes | Yes | Give isoniazide and rifampin for 4 months | |||||||||||||||||||||||||||||||||||||
| Give isoniazide and rifampin for 7 months | |||||||||||||||||||||||||||||||||||||||
Do's
- For long use of isoniazide, such as the management of TB always use pyridoxine (vitamin B6) to prevent peripheral neuropathy.[14]
- Be aware of drug interactions between rifampin and antivirals in patients with HIV.
Don'ts
- The content in this section is in bullet points.
References
- ↑ Nayak S, Acharjya B (January 2012). "Mantoux test and its interpretation". Indian Dermatol Online J. 3 (1): 2–6. doi:10.4103/2229-5178.93479. PMC 3481914. PMID 23130251.
- ↑ Slogotskaya L, Bogorodskaya E, Ivanova D, Sevostyanova T (2018). "Comparative sensitivity of the test with tuberculosis recombinant allergen, containing ESAT6-CFP10 protein, and Mantoux test with 2 TU PPD-L in newly diagnosed tuberculosis children and adolescents in Moscow". PLoS ONE. 13 (12): e0208705. doi:10.1371/journal.pone.0208705. PMC 6303070. PMID 30576322.
- ↑ Pahal P, Sharma S. PMID 32310497 Check
|pmid=value (help). Missing or empty|title=(help) - ↑ 4.0 4.1 4.2 4.3 4.4 Ryu YJ (April 2015). "Diagnosis of pulmonary tuberculosis: recent advances and diagnostic algorithms". Tuberc Respir Dis (Seoul). 78 (2): 64–71. doi:10.4046/trd.2015.78.2.64. PMC 4388902. PMID 25861338.
- ↑ 5.0 5.1 Pourakbari B, Mamishi S, Benvari S, Mahmoudi S (September 2019). "Comparison of the QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In-Tube interferon-γ release assays: A systematic review and meta-analysis". Adv Med Sci. 64 (2): 437–443. doi:10.1016/j.advms.2019.09.001. PMID 31586819.
- ↑ Zhu M, Zhu Z, Yang J, Hu K (August 2019). "Performance Evaluation of IGRA-ELISA and T-SPOT.TB for Diagnosing Tuberculosis Infection". Clin. Lab. 65 (8). doi:10.7754/Clin.Lab.2019.181109. PMID 31414740.
- ↑ Zhu F, Ou Q, Zheng J (January 2018). "Application Values of T-SPOT.TB in Clinical Rapid Diagnosis of Tuberculosis". Iran. J. Public Health. 47 (1): 18–23. PMC 5756596. PMID 29318113.
- ↑ Bonington A, Strang JI, Klapper PE, Hood SV, Parish A, Swift PJ, Damba J, Stevens H, Sawyer L, Potgieter G, Bailey A, Wilkins EG (2000). "TB PCR in the early diagnosis of tuberculous meningitis: evaluation of the Roche semi-automated COBAS Amplicor MTB test with reference to the manual Amplicor MTB PCR test". Tuber. Lung Dis. 80 (4–5): 191–6. doi:10.1054/tuld.2000.0246. PMID 11052908.
- ↑ Ryan GJ, Shapiro HM, Lenaerts AJ (September 2014). "Improving acid-fast fluorescent staining for the detection of mycobacteria using a new nucleic acid staining approach". Tuberculosis (Edinb). 94 (5): 511–8. doi:10.1016/j.tube.2014.07.004. PMID 25130623.
- ↑ Bayot ML, Mirza TM, Sharma S. PMID 30725806. Missing or empty
|title=(help) - ↑ Demers AM, Verver S, Boulle A, Warren R, van Helden P, Behr MA, Coetzee D (September 2012). "High yield of culture-based diagnosis in a TB-endemic setting". BMC Infect. Dis. 12: 218. doi:10.1186/1471-2334-12-218. PMC 3482573. PMID 22978323.
- ↑ Hughes R, Wonderling D, Li B, Higgins B (February 2012). "The cost effectiveness of Nucleic Acid Amplification Techniques for the diagnosis of tuberculosis". Respir Med. 106 (2): 300–7. doi:10.1016/j.rmed.2011.10.005. PMID 22137190.
- ↑ Ankrah AO, Glaudemans A, Maes A, Van de Wiele C, Dierckx R, Vorster M, Sathekge MM (March 2018). "Tuberculosis". Semin Nucl Med. 48 (2): 108–130. doi:10.1053/j.semnuclmed.2017.10.005. PMID 29452616. Vancouver style error: initials (help)
- ↑ 14.0 14.1 "tb_therapeutic_tables [TUSOM | Pharmwiki]".