Kingdom: Bacteria Phylum: Actinobacteria Order: Actinomycetales Suborder: Corynebacterineae Family: Mycobacteriaceae Genus: Mycobacterium Species: M.

tuberculosis

Mycobacterium tuberculosis

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 Weakly Gram-positive, Non motile, rod-shaped bacterium Acid fast bacilli Can grow at 37C At 68Co Catalase (-), At 37Co Catalase (+) Produce Niacin Obligate aerobe (Apex of lung) Facultative intracellular parasite

Slow generation time, 15-20 hours

Lowenstein-Jensen medium - egg based, small and buff colored colonies, takes 4-6 weeks. Middlebrook's medium which is an agar based medium

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Mycobacterium tuberculosis. Acid-fast stain. CDC. Mycobacterium tuberculosis on Lowenstein-Jensen medium. CDC.

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Cell Wall
Peptidoglycan made of complex lipids. Over 60% of the mycobacterial cell wall is lipid.
Mycolic acids
Inhibits action of cationic proteins, lysozyme, and oxygen radicals in Phagosome Inhibits compliment activity Hydrophobic - inhibits permeability

Cord factor:
Trehalose 6.6 dimycolate serpentine cording toxic to mammalian cells and inhibit PMN migration Increases TNF secretion

Wax-D:
LAM, sulfatides, Glycolipid

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Virulent factors for Pathogenesis

Adhesion:
Bind directly to mannose receptors on macrophages via glycolipid, LAM, indirectly via certain complement receptors or Fc receptors Pili

Intracellular Growth:

Cord factor - Antibodies and complement are ineffective, Inhibit phagosomelysosome fusion Glycolipids, sulfatides and LAM down regulate the oxidative cytotoxic mechanism The oxidative burst inhibited by production of catalase and superoxide dismutase enzymes. Iron is essential for growth
Antigen 85 complex Slow generation time High lipid concentration in cell wall Cord factor Lipoarabinominun (LAM)
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Immunity escape & Tubercle formation:

 The high concentration of lipids in the cell wall

Impermeability to stains and dyes Resistance to many antibiotics Resistance to killing by acidic and alkaline compounds Resistance to osmotic lysis via complement deposition

Resistance to lethal oxidations and survival inside of macrophages

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Epidemiology
Transmission by Respiratory droplet Approx. 10 million new cases every year. Low treatment compliance and thus multi-drug resistance is a big problem. Urban / HIV / poverty / AIDS

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Dr.Aravind

MTB Enters Lungs

Pathogenesis
Primary Lesion Heals, It Becomes Fibrous And Calcifies Ghons Complex Growing Tubercle Bronchi Damage And Dissemination To Other Parts Called Milliary Tuberculosis

Taken By Alveolar Inactivated Macrophages

Replicate And Bursts Inactivated Macrophages Attracts More Macrophages And T Cells

Tubercle Formation, Enzymes Pored By Activated Macrophages Leads Caseation Necrosis

T cells Release INF Activates Macrophages

Tubercles Liquefy And Burst And Spread, Results In Cavity Formation

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Tissue damage and symptoms By CMI

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Dr.Aravind

TB infection is not considered a case of TB disease.

Tuberculosis: Infection vs Disease

TB Infection MTB present Tuberculin skin test positive Chest X-ray normal Sputum smears and cultures negative No symptoms Not infectious Not defined as a case of TB

TB disease in lungs MTB present Tuberculin skin test positive Chest X-ray usually reveals lesion Sputum smears and cultures positive Symptoms such as cough, fever, weight loss Often infectious before treatment Defined as a case of TB
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Clinical Features
Primary TB Fever, malaise Xrays- black color patches on lungs, hilar lymph nodal enlargement, calcification GHONs Complex If disseminated- Milliary TB

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Reactivation TB More Than 50 Years Of Age Simon foci More Prone: Immune Compromised, Malnutrition, Alcoholics, Diabetics, Drug Abusers, Sudden Depression, Young Pregnant Females, AIDS Patients Symptoms- Dry Cough, Blood In sputum , Fever, Chills, Malaise, Fatigue, Night Sweating, Weight Loss Extra Pulmonary Infections- Pleura, Bones - Potts Disease, CNS Meningitis Xrays- Cavities In Lung Not Treated- Death Will Occur
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Diagnosis
Tuberculin or Mantoux test:
HIGH-RISK: > 5 mm is positive. For immunocompromised. LOW-RISK (health-care workers): > 10 mm is positive. NO-RISK: Healthy businessman having no situational exposure. > 15 mm is positive.

X ray L J media culture takes 4-6 weeks BACTEC system - TB growth can be detected in 9-16 days.
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 Fibrosis and cavity formation in right upper lobe Fibrosis and cavity formation left upper lobe.

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Dr.Aravind

Treatment:
Use multi-drug therapy

1st two months- Isoniazid & Rifampacin & Pyrazinamide

Next 4 months- Isoniazid & Rifampacin If drugs are resistant, have to add Streptomycin/ Ethambutol

Prevention
Use UV light in hospitals Use BCG vaccine In high risk (family), use Ethambutol for six months
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