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BY RANJEET RAMAN MYCOBACTERIA-MICRO {S1}. M. leprae – Leprosy A chronic infection caused by M. leprae that affects the cooler parts of the body, including.

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Presentation on theme: "BY RANJEET RAMAN MYCOBACTERIA-MICRO {S1}. M. leprae – Leprosy A chronic infection caused by M. leprae that affects the cooler parts of the body, including."— Presentation transcript:


2 M. leprae – Leprosy A chronic infection caused by M. leprae that affects the cooler parts of the body, including skin, ​ testes, anterior portion of eyes, fingers and toes. Peripheral nerves are heavily targeted.

3 Tuberculoid leprosy has a strong immune response with lots of activated macrophages (giant ​ cells, granulomas) and lymphocytes. Lepromatous leprosy has a weak immune response. Bacilli multiply within macrophages.

4 Transmission is usually through nasal discharge. This is the only mycobacterium that targets ​ nerves.

5 Non-tuberculosis Mycobacteria There are four groups as separated by their growing characteristics in the presence of light. ​ Generally acquired from environment, not other people. Found in soil, water, plants, etc. In HIV patients, frequently see the Mycobacterium avium/ intracellular complex (MAC).

6 M. tuberculosis – Tuberculosis Originally described by Robert Koch, it comes in epidemics that may ebb and flow over ​ centuries at a time. One third of the world population is infected.

7 The mycobacteria are Gram+ rods. Non-motile, non-sporulating. Obligate aerobes that grow ​ very slowly intracellularly or extracellularly. Their cell walls are full of lipid, which makes them acid fast with Ziehl-Neelson stain. ​ The lipids are very long mycolic acids. This is highly characteristic of tuberculosis bacilli. ​ Cultured on solid egg-based Lowenstein-Jensen media.

8 M. tuberculosis is not found free in nature. It goes between people as tiny airborne droplets and ​ deposit in terminal alveoli. Particulate respirators are required to prevent inhalation.

9 Primary Infections with Tuberculosis Simply because of the distribution of air flow, airborne droplets usually land in lower or middle ​ lung lobes (terminal alveoli). They elicit a PMN reaction that is then taken over by ​ macrophages. Although mycobacteria are engulfed by macrophages, they are viable and ​ multiply.

10 Macrophages may also enter lymphatics and carry bacilli to lymph nodes. The first lesion (in the lower lobe) is the ”Ghon focus.” When it spreads to the lymph nodes it is ​ the Ghon complex. Bacilli spread via blood to the lung apex because of high O2 tension ​ and lymphostasis. There they create the “Simon foci.”

11 The activated macrophages will fuse and form granulomas, which are good at killing ​ mycobacteria. The presence of granulomas and caseous necrosis is a strong sign of TB. As it heals, the lesions may disappear or may fibrose or calcify. Bacteria often persist for years ​ in these scarred nodules.

12 Miliary TB: occurs if a progressive primary tuberculosis expands the Ghon complex, erode into ​ bloodstream, and spread to distant organs. There will be tons of small equally sized ​ lesions in multiple organs.

13 Tuberculous bronchopneumonia: occurs if the complex erodes into the airway instead of the ​ blood. Bacilli spread via air throughout lung. There will be clustered nodules of very ​ different sizes. If the lesions erode into the pleura, patient will have “empyema.”

14 Post-Primary Tuberculosis May develop as a reaction from previously healed TB infection or a new infection. Remember ​ that bacilli remain viable for years in healed lesions, usually in the Simon foci. 2% of PPD positive patients with apical fibrotic lesions will develop disease again within 5 years.

15 Cavitation is the hallmark of post-primary TB. Occurs when caseous necrosis becomes ​ liquefactive and dissolves away. Cavitation usually in apices of the lungs. Alternatively, ​ the lesion can form an aspirgilloma – a ball of fungus in the cavity. This whole process ​ is called ”fibrocaseous cavitary tuberculosis.” If it cavitates into a vessel, there can be ​ major hemorrhage into the lung.

16 HIV and Tuberculosis HIV depletes CD4 helper-T cells but also macrophages. Patients with HIV show high rate of ​ extrapulmonary TB. Lung lesions are often non- apical and non-cavitary. Rather, they ​ form loose granulomas and do not show caseation. Directly Observed Therapy (DOT) ensures regimen compliance. Helps prevent resistance.

17 Drugs to Treat Mycobacterial Infections Mycobacterial cell walls are uniquely highly lipophilic (mycolic acids). This ​ makes them acid fast when stained with Ziehl-Neelson stain. Mycobacteria replicate ​ both intracellularly and extracellularly.

18 Primary resistance is frequent – mycobacteria often have genetic resistance to drugs even before ​ they are exposed. Really only a problem in active TB, not in someone who’s just PPD ​ positive. Therefore, a single drug (isoniazid) is adequate to treat just a positive PPD.

19 Secondary/acquired resistance occurs after regimen noncompliance. MDR = resistance to ​ isoniazid and Rifampin. Two months of four drugs, then four months of two drugs.

20 DRUGS TO TREAT TB Isoniazid (INH) The first version of this drug was toxic because it also acted as a potent MAOI. Isoniazid is bactericidal by inhibiting synthesis of mycolic acids and metabolic pathways. It accumulates inside mycobacteria, and can form oxygen free-radicals.

21 Resistance often occurs when TB deletes a gene called katG, which normally activates INH. ​ Also, point mutations in (inhA?), a mycolic acid synthesis enzyme, creates resistance.

22 INH is metabolized by acetylation. People who are “slow acetylators” will accumulate the drug, ​ causing a reversible hepatitis. Neurotoxicity also occurs, but is prevented by co- ​ administration with pyridoxine.

23 Rifampin Highly bactericidal drug that inhibits RNA polymerases. Good against mycobacteria, Gram+ and ​ some Gram- including Neisseria. Resistance occurs by mutations in RNA polymerases.

24 Rifampin induces P450 metabolism! Will enhance elimination of contraceptives, Coumarin, etc. ​ Other adverse effects include orange discoloration of urine/tears, and flu-like symptoms.

25 Pyrazinamide An analogue of nicotinamide. Especially good at killing active intracellular mycobacteria, but ​ not at dormant organisms. One side effect is hyperuricemia, so watch for gout.

26 Ethambutol Ethambutol is bacteriostatic. Inhibits RNA and mycolic acid synthesis. Major toxicity is optic ​ neuritis with color blindness and loss of peripheral vision. Streptomycin A mainstay of the four-drug acute treatment of TB.

27 Para- amino salicylic acid (PAS) Not used in the U.S. because the drug can induce lupus.

28 DRUGS TO TREAT LEPROSY Dapsone Inhibits folate synthesis. Broad spectrum coverage similar to the sulfonamides. Major toxicity is severe hemolytic uremic syndrome (HUS) in patients with G6PD deficiency. HUS is seen classically with Dapsone or Primaquine therapy. May also see erythema nodosum leprosum when initiating Dapsone therapy.

29 Clofazimine A dye derivative. Causes red/blue skin pigmentation. DRUGS TO TREAT OTHER MYCOBACTERIAL INFECTIONS Rifabutin This is actually just like Rifampin and is much more effective, but way more expensive. Used for prophylaxis of M. avium infections in AIDS patients. Like Rifampin, can cause orange discoloration of urine/sweat/tears, and immunologic uveitis. Also like Rifampin, it can induce p450, but weakly.

30 Macrolides and fluoroquinalones are effective against mycobacteria. Penicillin derivatives are ​ not effective because they don’t kill intracellular mycobacteria.

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