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Mycobacterium Tuberculosis
BS 3rd semester presentation
By
SikandarAli
Submittedto: Sir Musawir khan
Department Of Microbiology
introduction
The mycobacteria are rod-shaped, aerobic bacteria .
Mycobacterium is a genus of Actinobacteria, given
its own family, the Mycobacteriaceae.
Over 190 species are recognized in this genus
This genus includes pathogens known to cause
serious diseases in mammals,
including tuberculosis (Mycobacterium tuberculosis)
and leprosy (Mycobacterium leprae) in humans.
They are Facultative intracellular pathogens usually
infecting mononuclear phagocytes (e.g.
macrophages).
MORPHOLOGY
SHAPE - long, slender, straight, curved rod.
 SIZE - 2-4 micrometers in length and 0.2-0.5 um
in width.
 Mycolic acid, waxes & lipids are present in cell
wall
 The high lipid content (approximately 60%) of
their cell wall makes mycobacteria acid-fast and
hydrophobic.
 Neither gram-positive nor gram-negative.
CULTURE:
 Mycobacteria are aerobes.
 substances are either solid substances on culture
plates, or bottles of liquid known as culture broths.
 Grow slowly: 14-15 hours
 Optimum temperature: 37degree C. Do not grow
below 25degree C.
 pH between 6.4 to 7.0
 Grow only in specially enriched media containing
egg, potatoes.
 Colonies appear in 2-6 weeks
ACID FAST BACILLI:
 Mycobateria are virtually the only bacteria that
are acid-fast because of the presence of mycolic
acid and their lipid-rich cell walls, which are
relatively impermeable to various basic dyes
unless the dyes are combined with phenol.
 Once stained, the cells resist decolourization
with acidified organic solvents and are therefore
called "acid-fast". Carbol Fuchsin Stain (Ziehl-
Neelsen).
Species
Growth on Bacteriologic
Media
Temperature (˚C)
Source or Mode of
Transmission
M. tuberculosis Slow (weeks) 37 Respiratory droplets
M. bovis Slow (weeks) 37 Milk from infected animals
M. leprae None 32 Prolonged close contact
Atypical mycobacteria (ex.
M. kansasii)
Slow (weeks) 37 Soil and water
M. marinum Slow (weeks) 32 Water
M. avium- intracellulare
complex
Slow (weeks) 37 Soil and water
M. fortuitum-chelonae
complex
Rapid (days) 37
Soil and water
Mycobacterium Tuberculosis
 It causes TUBERCULOSIS which is the most
common cause of death due to bacterial infection
worldwide.
 Tuberculosis (TB) is a potentially serious infectious
disease that mainly affects our lungs.
 Tuberculosis (TB) stays one of the major worldwide
wellbeing dangers prompting dismalness and
mortality.
 Mycobacterium Tuberculosis, is transmitted through
the air as it does not thrive on surfaces
 M. tuberculosis is resistant to dehydration and so
survives in dried expectorated sputum; this property
may be important in its transmission by aerosol.
Types
History
 On March 24, 1882, Dr. Robert Koch announced
the discovery of Mycobacterium tuberculosis, the
bacteria that causes tuberculosis (TB). at a time
when one of every seven deaths in Europe was
caused by TB
 Isolated the mammalian tubercle bacillus on Heat
Coagulated Bovine Serum and proved its causative
role in Tuberculosis.
 He received the Nobel Prize in physiology and
medicine in 1905 for this discovery.
Cases of Pakistan
323,255
355,502
358,886
275,279
0 50,000 100,000 150,000 200,000 250,000 300,000 350,000 400,000
2015
2016
2017
2018
case
(NTP) National TB control program
(WHO) the world health Organization
TRANSMISSION
 Tuberculosis (TB) bacteria get into the air when
a person with TB speaks, coughs or sings
 Tuberculosis is not easily transmitted. Family
members living together are at highest risk. Risk
of transmission is very small in casual contacts.
Only one third of exposed persons become
infected.
 TB is not transmitted through dishes, drinks,
food, clothes or surfaces.
Pathogenesis
 TB pathogenesis can be divided in four well-defined events
 1st
 Inhalation of the mycobacteria:is followed by its interaction with
resident macrophages through cellular receptors and its
internalization.
 Macrophage bactericidal mechanisms are then activated,
 The efficient killing of mycobacteria depends on pathogen and host
factors.
 2nd step
 Inflammatory cell recruitment: survived mycobacteria proliferate
within macrophages inducing the production of pro inflammatory
cytokines.
 The local inflammatory environment induces the recruitment of
several cell types including monocytes, neutrophils, and dendritic
cells to the site of infection.
Pathogenesis
 3rd
 High levels of TNF-α contribute to control Mycobacterium tb growth and granuloma formation.
 Control of mycobacteria proliferation: arrival of immune cells to the site of infection including T
cells, which become organized in characteristic structures called granulomas efficiently stop
mycobacteria proliferation and contain the mycobacteria within the granuloma walls preventing its
spread.
 Characteristic of this structure is the presence of foam cells resulting from the differentiation of
chronically activated macrophages.
 Mycobacteria containment eventually becomes stable (latent) infection.
 4th
 Post primary TB: mycobacteria persistence associated with a failure in the immunosurveillance
system increases the risk that latent disease becomes reactivated, inducing the damage of nearby
bronchi and conditioning the spreading of the Mycobacterium tb to other areas of the lung and the
transmission of the disease.
Signs and symptoms
 symptoms of active TB include:
• Coughing that lasts three or
more weeks.
• Coughing up blood.
• Chest pain, or pain with breathing
or coughing.
• Unintentional weight loss.
• Fatigue.
• Fever.
• Night sweats.
• Chills.
Risk Factors
 contact with a known TB case, e.g. family
member or friend
 migration from a country with a high incidence
of TB
 history of travel to an area with a high incidence
of TB
 smoking
 alcohol and/or drug abuse
 malnutrition
 homelessness
Preventions
 There are several other TB prevention
activities. This includes preventing people
with latent TB from developing active, and
infectious, TB disease.
 TB infection control which means
preventing the transmission of TB in such
settings as hospitals & prisons.
 The pasteurization of milk also helps to
prevent humans from getting bovine TB.
 It does little to interrupt the transmission of
TB among adults.
Diagnosis
 During the physical exam, your doctor will check your lymph
nodes for swelling and use a stethoscope to listen carefully to
the sounds your lungs make while you breathe.
 PPD tuberculin:
 just below the skin of your inside forearm. You should feel
only a slight needle prick.
 Within 48 to 72 hours, a health care professional will check
your arm for swelling at the injection site. A hard, raised red
bump means you're likely to have TB infection.
 Blood test
 Blood tests may be used to confirm or rule out latent or active
tuberculosis. These tests use sophisticated technology to
measure your immune system's reaction to TB bacteria.
Diagnosis
 Imaging tests
 If you've had a positive skin test, your doctor is likely to order a
chest X-ray or a CT scan. This may show white spots in your
lungs where your immune system has walled off TB bacteria, or
it may reveal changes in your lungs caused by active
tuberculosis.
 Sputum tests
 If your chest X-ray shows signs of tuberculosis, your doctor may
take samples of your sputum — the mucus that comes up when
you cough. The samples are tested for TB bacteria.
 Sputum samples can also be used to test for drug-resistant strains
of TB. This helps your doctor choose the medications that are
most likely to work
Treatment
For initial empiric treatment of TB, start patients on a 4-
drug regimen:
Isoniazid, (Myrin Fort)
Pifampin, (Myrin Fort)
pyrazinamide (Pyrazid)
streptomycin
2nd line
Kanamycin (KM); (kanacyn)
capreomycin, (Capreomycin)
Ciprofloxacin (CIP), (ciproxin)
Ethionamide, (Ethomid)
Terizidone, (Terizidone)
3rd line
 Third-line drugs (WHO group 5) include drugs that may be
useful, but have doubtful or unproven efficacy:
 Rifabutin (RIFABUTIN)
 Clarithromycin (CLR); (Klaricid)
 Linezolid (LZD); (ZOLREST)
 Thioacetazone (T); (isoniazid)
 Thioridazine; (Diagesic-P)
 Arginine; (Permen)
 Vitamin D; (Osnate-D)
 Bedaquiline; (Sirturo)
Thank you
s

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Mycobacterium tuberculosis by Sikander ali Sumalani

  • 1. Mycobacterium Tuberculosis BS 3rd semester presentation By SikandarAli Submittedto: Sir Musawir khan Department Of Microbiology
  • 2. introduction The mycobacteria are rod-shaped, aerobic bacteria . Mycobacterium is a genus of Actinobacteria, given its own family, the Mycobacteriaceae. Over 190 species are recognized in this genus This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis (Mycobacterium tuberculosis) and leprosy (Mycobacterium leprae) in humans. They are Facultative intracellular pathogens usually infecting mononuclear phagocytes (e.g. macrophages).
  • 3. MORPHOLOGY SHAPE - long, slender, straight, curved rod.  SIZE - 2-4 micrometers in length and 0.2-0.5 um in width.  Mycolic acid, waxes & lipids are present in cell wall  The high lipid content (approximately 60%) of their cell wall makes mycobacteria acid-fast and hydrophobic.  Neither gram-positive nor gram-negative.
  • 4. CULTURE:  Mycobacteria are aerobes.  substances are either solid substances on culture plates, or bottles of liquid known as culture broths.  Grow slowly: 14-15 hours  Optimum temperature: 37degree C. Do not grow below 25degree C.  pH between 6.4 to 7.0  Grow only in specially enriched media containing egg, potatoes.  Colonies appear in 2-6 weeks
  • 5. ACID FAST BACILLI:  Mycobateria are virtually the only bacteria that are acid-fast because of the presence of mycolic acid and their lipid-rich cell walls, which are relatively impermeable to various basic dyes unless the dyes are combined with phenol.  Once stained, the cells resist decolourization with acidified organic solvents and are therefore called "acid-fast". Carbol Fuchsin Stain (Ziehl- Neelsen).
  • 6. Species Growth on Bacteriologic Media Temperature (˚C) Source or Mode of Transmission M. tuberculosis Slow (weeks) 37 Respiratory droplets M. bovis Slow (weeks) 37 Milk from infected animals M. leprae None 32 Prolonged close contact Atypical mycobacteria (ex. M. kansasii) Slow (weeks) 37 Soil and water M. marinum Slow (weeks) 32 Water M. avium- intracellulare complex Slow (weeks) 37 Soil and water M. fortuitum-chelonae complex Rapid (days) 37 Soil and water
  • 7. Mycobacterium Tuberculosis  It causes TUBERCULOSIS which is the most common cause of death due to bacterial infection worldwide.  Tuberculosis (TB) is a potentially serious infectious disease that mainly affects our lungs.  Tuberculosis (TB) stays one of the major worldwide wellbeing dangers prompting dismalness and mortality.  Mycobacterium Tuberculosis, is transmitted through the air as it does not thrive on surfaces  M. tuberculosis is resistant to dehydration and so survives in dried expectorated sputum; this property may be important in its transmission by aerosol.
  • 9. History  On March 24, 1882, Dr. Robert Koch announced the discovery of Mycobacterium tuberculosis, the bacteria that causes tuberculosis (TB). at a time when one of every seven deaths in Europe was caused by TB  Isolated the mammalian tubercle bacillus on Heat Coagulated Bovine Serum and proved its causative role in Tuberculosis.  He received the Nobel Prize in physiology and medicine in 1905 for this discovery.
  • 10. Cases of Pakistan 323,255 355,502 358,886 275,279 0 50,000 100,000 150,000 200,000 250,000 300,000 350,000 400,000 2015 2016 2017 2018 case (NTP) National TB control program (WHO) the world health Organization
  • 11. TRANSMISSION  Tuberculosis (TB) bacteria get into the air when a person with TB speaks, coughs or sings  Tuberculosis is not easily transmitted. Family members living together are at highest risk. Risk of transmission is very small in casual contacts. Only one third of exposed persons become infected.  TB is not transmitted through dishes, drinks, food, clothes or surfaces.
  • 12. Pathogenesis  TB pathogenesis can be divided in four well-defined events  1st  Inhalation of the mycobacteria:is followed by its interaction with resident macrophages through cellular receptors and its internalization.  Macrophage bactericidal mechanisms are then activated,  The efficient killing of mycobacteria depends on pathogen and host factors.  2nd step  Inflammatory cell recruitment: survived mycobacteria proliferate within macrophages inducing the production of pro inflammatory cytokines.  The local inflammatory environment induces the recruitment of several cell types including monocytes, neutrophils, and dendritic cells to the site of infection.
  • 13. Pathogenesis  3rd  High levels of TNF-α contribute to control Mycobacterium tb growth and granuloma formation.  Control of mycobacteria proliferation: arrival of immune cells to the site of infection including T cells, which become organized in characteristic structures called granulomas efficiently stop mycobacteria proliferation and contain the mycobacteria within the granuloma walls preventing its spread.  Characteristic of this structure is the presence of foam cells resulting from the differentiation of chronically activated macrophages.  Mycobacteria containment eventually becomes stable (latent) infection.  4th  Post primary TB: mycobacteria persistence associated with a failure in the immunosurveillance system increases the risk that latent disease becomes reactivated, inducing the damage of nearby bronchi and conditioning the spreading of the Mycobacterium tb to other areas of the lung and the transmission of the disease.
  • 14. Signs and symptoms  symptoms of active TB include: • Coughing that lasts three or more weeks. • Coughing up blood. • Chest pain, or pain with breathing or coughing. • Unintentional weight loss. • Fatigue. • Fever. • Night sweats. • Chills.
  • 15. Risk Factors  contact with a known TB case, e.g. family member or friend  migration from a country with a high incidence of TB  history of travel to an area with a high incidence of TB  smoking  alcohol and/or drug abuse  malnutrition  homelessness
  • 16. Preventions  There are several other TB prevention activities. This includes preventing people with latent TB from developing active, and infectious, TB disease.  TB infection control which means preventing the transmission of TB in such settings as hospitals & prisons.  The pasteurization of milk also helps to prevent humans from getting bovine TB.  It does little to interrupt the transmission of TB among adults.
  • 17. Diagnosis  During the physical exam, your doctor will check your lymph nodes for swelling and use a stethoscope to listen carefully to the sounds your lungs make while you breathe.  PPD tuberculin:  just below the skin of your inside forearm. You should feel only a slight needle prick.  Within 48 to 72 hours, a health care professional will check your arm for swelling at the injection site. A hard, raised red bump means you're likely to have TB infection.  Blood test  Blood tests may be used to confirm or rule out latent or active tuberculosis. These tests use sophisticated technology to measure your immune system's reaction to TB bacteria.
  • 18. Diagnosis  Imaging tests  If you've had a positive skin test, your doctor is likely to order a chest X-ray or a CT scan. This may show white spots in your lungs where your immune system has walled off TB bacteria, or it may reveal changes in your lungs caused by active tuberculosis.  Sputum tests  If your chest X-ray shows signs of tuberculosis, your doctor may take samples of your sputum — the mucus that comes up when you cough. The samples are tested for TB bacteria.  Sputum samples can also be used to test for drug-resistant strains of TB. This helps your doctor choose the medications that are most likely to work
  • 19. Treatment For initial empiric treatment of TB, start patients on a 4- drug regimen: Isoniazid, (Myrin Fort) Pifampin, (Myrin Fort) pyrazinamide (Pyrazid) streptomycin 2nd line Kanamycin (KM); (kanacyn) capreomycin, (Capreomycin) Ciprofloxacin (CIP), (ciproxin) Ethionamide, (Ethomid) Terizidone, (Terizidone)
  • 20. 3rd line  Third-line drugs (WHO group 5) include drugs that may be useful, but have doubtful or unproven efficacy:  Rifabutin (RIFABUTIN)  Clarithromycin (CLR); (Klaricid)  Linezolid (LZD); (ZOLREST)  Thioacetazone (T); (isoniazid)  Thioridazine; (Diagesic-P)  Arginine; (Permen)  Vitamin D; (Osnate-D)  Bedaquiline; (Sirturo)

Editor's Notes

  1. 1) Mycobacteria is a gram-positive: (Aerobic) oxygen & (Anaerobic) without oxygen: 2) Actinobacteria Actino-bacteria (phylum) (Mycobacteriaceae) myco-beacteria-ceae 3) ### 4) Leprosy = the affect  skin, mucous membranes, and nerves, causing discoloration and lumps on the skin 5) Facultative= (fac·​ul·​ta·​tive) permission, mononuclear= cell having a round nucleus. These cells consist of lymphocytes (T cells, B cells, NK cells) 
  2. Morphology= a study of structure or form 1) Straight = سیدها هونا 3) Mycolic acid = any of vaiow long fatty acids found in the cell wells of mycolata taxon 4) hydrophobic molecules do not dissolve in water
  3. 6) Enriched = bather Meat extracts = keema
  4. dyes= color 2) phenol = acdic compound
  5. m.tuberculosis = human M.bovis = cattle (janwer) contaminated milk M.leprae = skin , eyes nose etc Atypical mycobacteria = don’t cause tuberculosis but they still harm people affect their immunity such AS AIDS. M.marinum = skin or soft tissue injuries (free living bactirea ) M.avium-m.intracellulare complex= respiratory illnes births & humans (especially in immunocompromised ) EX AIDS: M.fortuitum-chelonae complex= skin, osteomyelitis (inflammation of the bone) joint infaction Meningeal tuberculosis = membranes surrounding the brain & spinal cord
  6. 3) Wellbeing= اچھی طرح سے Prompting = فوری طور پر Dismalness= خرابی Mortality= شرح اموات 4) ماکوبوبیکٹیریم نری رن، ہوا کے ذریعے منتقل کیا جاتا ہے کیونکہ اس سطحوں پر نہیں چلتا ہے 5) expectorated (ex·​pec·​to·​rate) = کھینچنے یا ہاکی کرنے اور پھینکنے سے حلق یا پھیپھڑوں سے نکالنا Aerosol = پانی کے مہیں قطرے یا کِسی ٹھوس مادّے کے ذرات جو فِضا میں معلق 
  7. Latent TB Infection Many of those who are infected with TB do not develop overt disease. They have no symptoms and their chest x-ray may be normal. The only manifestation of this encounter may be reaction to the tuberculin skin test (TST) or interferon-gamma release assay (IGRA). However, there is an ongoing risk that the latent infection may escalate to active disease. Active tb Active TB is an illness in which the TB bacteria are rapidly multiplying and invading different organs of the body. The typical symptoms of active TB variably include cough, phlegm, chest pain, weakness, weight loss, fever, chills and sweating at night. A person with active pulmonary TB disease may spread TB to others by airborne transmission of infectious particles coughed into the air.
  8. 2015= 3 lak 23 hazar 2 so 55 2016= 3 lak 55 hazar 5 so 2 2017= 3 lak 58 hazar 8 so 86 2018= 2 lak 75 hazar 2 so 79 Point = In 2017, 87% of new TB cases occurred in the 30 high TB burden countries. Eight  countries accounted for two thirds of the new TB cases: India,China,Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh and South Africa.
  9. 1st 2) two main mechanisms, which are either bactericidal or bacteriostatic. Bactericidal antibiotics kill the bacteria and bacteriostatic antibiotics suppress the growth of bacteria 2nd Proliferate = increase rapidly in numbe
  10. 3rd 1) Tumor necrosis factor is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction
  11. 2) Prisons = jael
  12. 2)PPD= A purified protein derivative (PPD) test
  13. First line Isoniazid is an antibiotic and works by stopping the growth of bacteria: Side affect = nausea, vomiting, upset stomach, fever, or rash. 2) Rifampin= synthesis of host bacterial proteins/ mycolic Acid Side affect : gas, upset stomach, muscle weakness, pain in your arms or legs 3) Pyrazinamide kills or stops the growth of certain bacteria Side affect; abdominal pain, yellowing eyes or skin, or dark urine 4) Streptomycin= It works by killing the organisms that cause the infection Side affect = nausea,vomiting,stomach upset 2nd line Kanamycin; streptomycin-resistant tubercle bacilli. Except for its lower cost, kanamycin offers no advantage over amikacin in combination therapy and has substantial ototoxicity. Side affect= skin rash or itching, hives, allergic reaction, headache, fever, nausea, or vomiting. can harm the kidneys 2) Capreomycin=These antibiotics have the ability to kill a wide variety of bacteria Side affect = swelling, rapid weight gain, sound in your ears,, hearing loss 3) ciprofloxacin= by stopping the growth of bacteria. Side affect= fast or pounding heartbeats, swelling, tenderness, loss of movement in any of your joints 4) Ethionamide= only bacterial infections. It will not work for viral infections Side affect= nausea, vomiting, diarrhea, stomach pain 5) terizidone= Terizidone acts by preventing cell wall synthesis by inhibiting two necessary enzymes: Side affect= nausea, vomiting and skin allergies.
  14. 1) Rifabutin= rifamycin antibiotic. It works by stopping the growth of bacteria. Saide affect= muscle weakness or pain, eye pain or redness 2) Clarithromycin= It works by stopping the growth of bacteria. Saide affect= gastrointestinal (GI) effects, headache, longer time for blood to clot 3) linezolid=drug‐resistandrug‐resistan kill bacteria Side affect= fungal infections, low platelet count (thrombocytopenia), fever, chills 4) Thioacetazone =Thioacetazone is never used alone to treat TB, because by itself it is weak and ineffective against the bacteria. It is only used as a combination with first-line TB medications, such as isoniazid and rifampicin. It is used primarily to prevent the development of bacteria that are resistant to first-line drugs, and to treat patients infected with drug-resistant TB. Side affect= nausea and vomiting, dizziness, slurred speech 5) Thioridazine = combination with the standard regimen in a well validated murine TB Side affect =dry mouth,stuffy nose, 6) Arginine= L-arginine has the potential to improve outcomes in active tuberculosis. Side affects= abdominal pain, bloating, diarrhea, gout, blood abnormalities, allergies, airway inflammation 7) Vit D= TB during the pre-antibiotic era, trials in recent years have continued to assess its role in the treatment and prevention of TB Side affect = Kidney stones. urination. 8) Bedaquiline= Specifically it is used to treat multi-drug-resistant tuberculosis Side affect= nausea.joint pain.headache.coughing up blood.chest pain.weight loss.