Tuberculosis - causes, symptoms, diagnosis, treatment, pathology — Transcript

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6. 0:19It’s estimated that about two billion people worldwide are infected with mycobacterium
7. 0:25tuberculosis, often just shortened to tuberculosis or simply ‘TB’.
8. 0:29Two billion is a ton of people, but even though they’re infected, that doesn’t mean all
9. 0:34those people have symptoms, the vast majority, about 90-95%, aren’t even aware they’re
10. 0:40infected.
11. 0:41And this is because usually the immune system can contain it such that it isn’t able to
12. 0:45multiply, and often remains latent, or dormant, as opposed to active, which usually causes
13. 0:50symptoms and can be spread to others.
14. 0:53If the host’s immune system becomes debilitated at some point down the road, like with AIDS
15. 0:57or some other illness, or as a person grows older, it can be allowed to reactivate, or
16. 1:02basically wake up and become very serious, especially if it spreads through the body.
17. 1:10Mycobacteria are an interesting bunch, they’re slender, rod-shaped, and need oxygen to survive,
18. 1:15in other words, they’re “strict aerobes”.
19. 1:17They’ve got an unusually waxy cell wall, which is mainly a result of the production
20. 1:22of mycolic acid.
21. 1:24Because of this waxy cell wall, they’re “acid-fast”, meaning that it can hold
22. 1:27on to a dye in spite of being exposed to alcohol, leaving it bright red colored when a Ziehl–Neelsen
23. 1:33stain is used.
24. 1:34The wall also makes them incredibly hardy, and allows them to resist weak disinfectants
25. 1:38and survive on dry surfaces for months at a time.
26. 1:43Now Mycobacterium tuberculosis is usually transmitted via inhalation, which is how they
27. 1:48gain entry into the lungs.
28. 1:50Now, we breathe in all sorts of virus and bacteria all the time, but we’ve got defenses
29. 1:55that take care of most of them.
30. 1:57For one, air that we breathe in is turbulent in the upper airways, and drives most bacteria
31. 2:01against mucus which is then cleared pretty quickly.
32. 2:04Ultimately, though, TB can avoid the mucus traps and make its way to the deep airways
33. 2:08and alveoli where we have macrophages which eat up foreign cells, digest, and destroy
34. 2:13them.
35. 2:14With TB, they recognize foreign proteins on their cell surface, and phagocytize them,
36. 2:19or essentially package them into a space called a phagosome.
37. 2:22With most cases, the macrophage then fuses the phagosome with a lysosome, which has hydrolytic
38. 2:27enzymes that can pretty much break down any biochemical molecule.
39. 2:30TB’s tricky, though, and once inside the macrophage, they produce a protein that inhibits
40. 2:35this fusion, which allows the mycobacterium to survive.
41. 2:38It doesn’t just survive, though, it proliferates, and creates a localized infection.
42. 2:44At this point somebody has developed primary tuberculosis, which means that they have signs
43. 2:49of infection soon after being exposed to TB.
44. 2:52Even though it sounds bad, most people at this stage are actually asymptomatic or maybe
45. 2:56have a mild flu-like illness.
46. 2:58About 3 weeks after initial infection, cell-mediated immunity kicks in, and immune cells surround
47. 3:04the site of TB infection, creating a granuloma, essentially an attempt to wall off the bacteria
48. 3:09and prevent it from spreading.
49. 3:12The tissue inside the middle dies as a result, a process referred to as caseous necrosis,
50. 3:17which means “cheese-like” necrosis, since the dead tissue is soft, white, and looks
51. 3:22a bit like cheese.
52. 3:23This area is known as a “Ghon focus”.
53. 3:26TB also gets to hilar lymph nodes, either carried over by immune cells through the lymph
54. 3:31or by direct extension of the Ghon focus infection and causes caseation there as well, and together,
55. 3:37this caseating tissue and associated lymph node make up the characteristic “Ghon complex”.
56. 3:42Ghon complexes are usually subpleural and occur in the lower lobes of the lungs.
57. 3:48The tissue that’s encapsulated by the granuloma undergoes fibrosis, and often calcification,
58. 3:54producing scar tissue that can be seen on x-ray, this calcified ghon complex is called
59. 3:58a “Ranke complex”.
60. 4:01In some cases, although a scar is leftover, the mycobacteria is killed off by the immune
61. 4:06system, and that’s the end of that.
62. 4:08In other cases, even though they were walled off, they remain viable, and are therefore
63. 4:13still alive, but they’re just dormant.
64. 4:17If and when a person’s immune system becomes compromised, like with AIDS or with aging,
65. 4:21the Ghon focus can become reactivated, and the infection can spread to either one or
66. 4:26both upper lobes of the lungs, it’s thought that this is because oxygenation is greatest
67. 4:30in these areas, and TB being an aerobe, prefers areas of greater oxygenation.
68. 4:35Since they were previously exposed, the immune system’s memory T cells quickly release
69. 4:40cytokines to try and control the new outbreak, which forms more areas of caseous necrosis,
70. 4:46this time, though, it tends to cavitate, or form cavities, which can allow the bacteria
71. 4:50to disseminate, or spread through airways and lymphatic channels to other parts of the
72. 4:54lungs, which can cause bronchopneumonia; but it can also spread via the vascular system
73. 4:59and infect almost every other tissues in the body, called systemic miliary TB.
74. 5:05When TB spreads to other tissues, it causes complications related to the organ affected.
75. 5:10Kidneys are commonly affected, resulting in sterile pyuria, or high levels of white blood
76. 5:14cells in the urine.
77. 5:15It might also spread to the meninges of the brain, causing meningitis, the lumbar vertebrae,
78. 5:21causing Pott disease, the adrenal glands causing addison’s disease, the liver causing hepatitis,
79. 5:28and the cervical lymph nodes causing lymphadenitis in the neck, also known as scrofula.
80. 5:36Testing for TB often starts with a purified protein derivative or PPD intradermal skin
81. 5:41test, sometimes known as a tuberculin skin test, Mantoux test, or simply TB test.
82. 5:47With this test, tuberculin is injected between layers of the dermis, tuberculin is a component
83. 5:52of the bacteria, and if a person has previously been exposed to TB, the immune system reacts
84. 5:57to the tuberculin and produces a small, localized reaction within 48 to 72 hours; if the reaction
85. 6:03creates a large enough area of induration (rather than just redness), it’s considered
86. 6:07to be a positive test.
87. 6:10Positive tuberculin tests simply mean the patient’s been exposed at some point to
88. 6:13TB—it doesn’t differentiate between active and latent disease.
89. 6:18As an alternative to tuberculin skin tests, there are also interferon gamma release assays
90. 6:23(or IGRAs) which look for evidence in the blood of previous exposure to TB proteins.
91. 6:29Since this one’s a blood test, you don’t need to show up again to have the test read
92. 6:32like you do with the PPD.
93. 6:34Also, the IGRA is more specific to TB rather than other types of mycobacterial infections
94. 6:40and is unlikely to be positive as a result of having BCG vaccine in the past, a vaccine
95. 6:45that protects against TB.
96. 6:46And this is a pretty useful feature of IGRAs, since BCG vaccine is given to many children
97. 6:52around the world to prevent disseminated TB.
98. 6:56After doing a screening test with PPD or IGRA, anyone with a positive result typically gets
99. 7:01a chest Xray to look for signs of active TB disease.
100. 7:04In patients with symptoms like as fevers, night sweats, weight loss, and coughing up
101. 7:08blood, or hemoptysis.
102. 7:09it’s important to collect samples from either the sputum, or via a bronchoalveolar lavage,
103. 7:15which is where a bronchoscope is inserted through the mouth or nose into the lungs,
104. 7:19fluid is squirted, and then the fluid is collected.
105. 7:22These samples can get sent to the lab for staining, culture, and PCR to look evidence
106. 7:27of mycobacterium tuberculosis.
107. 7:33Treatment of latent TB infection typically involves using a single drug for a prolonged
108. 7:37period of time—the most common approach is Isoniazid for 9 months.
109. 7:41Treatment of active TB disease is typically done with different combinations of anti-TB
110. 7:45antibiotics, like isoniazid, rifampin, ethambutol, and pyrazinamide,which results in patients
111. 7:52being non-infectious to others usually within a few weeks.
112. 7:56Until that point, though, patients can spread TB to others and it’s typically adults with
113. 8:00reactivated TB that are the most infectious.
114. 8:04As a result, patients are typically kept in negative pressure rooms and visitors are asked
115. 8:08to wear protective N-95 masks that can’t filter out oil aerosols (N for “not resistant
116. 8:13to oil”) but can filter out at least 95% of other aerosols (in this case TB).
117. 8:20Even after patients are no longer contagious, they’re typically kept on multiple medications
118. 8:24for many months to be sure the bacteria are destroyed usually with directly observed therapy
119. 8:28or DOT where somebody watches and confirms that you’re taking the medication.
120. 8:33Additionally, there’s an enormous worry about new drug-resistant strains of TB that
121. 8:39are causing infections in various parts of the world.
122. 8:42You may hear of MDR-TB or Multi-drug resistant TB or even XDR-TB which is Extremely drug
123. 8:49resistant TB which is incredibly hard to treat because they don’t die in the presence of
124. 8:53our usual antibiotics.
125. 8:56The bottom line is that to get an effective treatment, it’s super important to make
126. 8:59sure that the drugs being used will work against the specific strain of TB, that multiple medications
127. 9:04are used together to prevent drug resistance from developing, and that medications are
128. 9:08used for the entire course of therapy so that all of the mycobacterium tuberculosis is killed
129. 9:13off.
130. 9:14Recently, the US Food and Drug Administration has approved a breakthrough medication for
131. 9:19XDR-TB, called pretomanid.
132. 9:21According to recent studies, a combination of pretomanid, bedaquiline and linezolid has
133. 9:26been effective for almost 90% of XDR-TB cases.
134. 9:30As an added bonus, this combination therapy can be taken orally, and is also very well
135. 9:34tolerated compared with other XDR-TB drug regimens.
136. 9:39Alright, as a quick recap.
137. 9:42Tuberculosis, or TB, is an infection caused by Mycobacterium tuberculosis, that mainly
138. 9:47affects the lungs.
139. 9:493 weeks after the primary infection, the immune system tries to contain the infection by creating
140. 9:54a granuloma, and the tissue in the middle undergoes caseous necrosis, resulting in an
141. 9:58area called Ghon focus.
142. 10:00TB also extends to nearby hilar lymph nodes, causing caseous necrosis there as well.
143. 10:06Ghon focus plus the affected lymph node make up the characteristic Ghon complex.
144. 10:11If the immune system becomes compromised, like with AIDS, or older age, Ghon focus can
145. 10:16reactivate, and the infection may spread to one or both upper lobes of the lungs, where
146. 10:21it forms cavities.
147. 10:22From cavities, bacteria can disseminate to other parts of the lungs, causing bronchopneumonia,
148. 10:27but it can also spread through the vascular system and infect almost every tissue in the
149. 10:31body, which is called systemic miliary TB.
150. 10:34Testing for TB starts with a PPD intradermal skin test, or with an IGRA blood test, and
151. 10:40a chest X-ray can identify signs of active TB disease.
152. 10:44In patients with fevers, night sweats, weight loss, and hemoptysis, a sputum sample can
153. 10:48be stained, cultured and PCR can be done to look for Mycobacterium tuberculosis.
154. 10:54Treatment of active TB includes a combination of antibiotics, given for several months,
155. 10:59and special regimens are used for MDR-TB and XDR-TB.