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8/2/2019 My Co Bacteria 1

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Mycobacteria

Dr. Sri Mulyaningsih

Important Human Pathogens

yco ac er um u ercu os s

Mycobacterium leprae (uncommon)


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Lipid Rich Cell Wall of MycobacteriumMycolic acids

CMN Group: Unusual cell wall lipids (mycolic acids,etc.)

(Purified Protein Derivative)

Mycobacterium tuberculosisM.tuberculosis complex includes several species:1. Mycobacterium tuberculosis2. Mycobacterium bovis unpasteurized milk; recent

rash of cases in US3. Mycobacterium bovis BCG

. canetti = rare causes of tuberculosis in Africa

5. Mycobacterium microti = pathogen for rodents


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Organism characteristics

1. Aerobic, non motile, non spore forming bacillus2. High cell wall content of high molecular weight

lipids mycolic acid3. SLOW GROWTH RATE

a. generation time of 20 hours vs E.coli eneration time o 20 minutes

b. 38 weeks before growth on solid media;c. implications for length of treatment for complete

sterilization compared with most bacterial pathogens

Pathogenesis of Tuberculosis Inhalation of small (15 m) droplet nuclei

con a n ng . u ercu os s expe e y coughing, sneezing, or talking of another individual with cavitary tuberculosis

Primary infection by M . tuberculosis of non immune alveolar macro ha es with unrestrained proliferation within the infected macrophages


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Lungs are the portal of entry except M. bovis in unpasteurized

dairy products from other countriesInhalation of droplet nuclei (bacillus 5 microns): from infectious

, PPD

a. cough: most efficient at 3000 infectious droplet nuclei per cough

b. talking: similar quantity over 5 minutesc. sneezing more efficient than coughing; singing intermediate

between talking and coughing.d. Bacillus remains alive and infectious in air for long period;

ventilation key in preventing transmission; isolation of patient and mandated number of air exchanges in hospital rooms

Pathogenesis of Tuberculosis Dissemination of infected macrophages

roug e ra n ng ymp a cs n o e circulation

Development within 38 weeks of a CD4+ T cell dependent cell mediated immune res onse with ranuloma formation and macrophage activation at sites of infection


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Pathogenesis of Tuberculosis Active infection usually transformed into

atent n ect on except ons: n ants, With decrement in Tcell dependent cell

mediated immunity (years later) infection reactivated with development of tuberculosis HIV infection diabetes mellitus renal

disease, cancer, advanced age)

Pathogenesis of Tuberculosis Reactivation of M . tuberculosis infection with

par a mmun y pro uces g ssue concentrations of mycobacterial antigens that provoke an intense mononuclear cell response (type 4 hyper sensitivity reaction)


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Pathogenesis of Tuberculosis Dense mononuclear cell infiltrates damage

t ssue ue to re ease o act ve oxygen ra ca s and lysosomal neutral proteases

Tissue damage occurs as caseation necrosis that progresses to liquefaction necrosis in the absence of tuberculosis dru treatment


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Clinical Features of Tuberculosis Apical cavitary lesions in upper lobes of lung

y ray m o t e c est Positive tuberculin skin test with PPD

(purified protein derivative)

Chest X Ray of Patient with Active Pulmonary Tuberculosis


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Tuberculosis and the Disadvantaged

Homeless persons Intravenous drug abusers Prison inmates (Russia and other previous

states of the Soviet Union) Recent immigrants to the United States (Asia,

a n mer ca

HIV1 infection/AIDS

Epidemiology World wide: WHO Maps: Estimated incidence vs. case

notifications1. M. tuberculosis infects one third worlds population

causes 8 million new cases active disease annually2. Causes 2 million deaths= 2nd only to HIV as cause of

death from infectious agent world wide among adults3. HIV/TB relationship has exacerbated problem with TB

ncreas ng n areas w t g nc ence spec a y sub Saharan Africa4. Absolute numbers of cases of TB highest in Asia


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Epidemiology

Downward trend in incidence even before advent of

Annual decrease in mortality and morbidity of 4%6% in developed countries

between 1900 and WW2: Better living conditions less conducive to airborne

spread.

Advent of

antibiotics

late

1940s

(Streptomycin)

and

INH

in 1952: Tuberculosis is curable

Diagnostic procedures: SPUTUM: staining, cultures and molecular

diagnostics

1. Acid fast stain :

ZiehlNeelsen stain=fixed smear covered with carbol fuchsin, heated, rinsed, decolorized with acid alcohol; Kinyoun stain is similar but

ea ng unnecessarySMEAR POSITIVITY MEANS AT LEAST 10,000

ORGANISMS/mL SPUTUM


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Diagnostic procedures

2. Culture :a. o me a= owenste n ensen egg aseb. Middlebrook 7H11 (agar based): can detect

colony morphology, mixed infections; can detect 10 100 organisms/mL; 38 weeks incubation to detect organisms

CULTURE NECESSARY TO DETERMINE DRUG SUSCEPTIBILITIES

Lowenstein Jensen Egg Base Medium Coagulated whole eggs Potato flour Glycerol Defined salts Malachite Green (0.025 g/100 mL)

(Petragnani 0.052 g/100 mL)(ATS 0.020 g/100 mL)


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Middlebrook Agar Base 7H10 Medium Defined salts am ns an o ac ors Oleic acid Albumin Catalase

Dextrose Malachite Green (0.0025g/100 mL)


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Diagnostic procedures3. Nucleic acid amplification

can detect M. tuberculosis com lex in resh s utum: developed world technologytoo costly for resource poor countries

4. DNA fingerprinting : Molecular epidemiologic tool: RFLP (Restriction fragment length polymorphism); also developed world technologyRestriction endonuclease produces DNA fragments; separate fragments by electrophoresis; probe to repetitive DNA sequence=Insertion sequence (IS)6110 numerous copies of IS6110 present in M.tuberculosischromosome at highly variable locations


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Treatment

1. Always use at least 2 drugs; usua y eg n w t or pen ng sens t v t es

2. Prolonged length necessary: 69 months if organism pan sensitive

3. Directly Observed Therapy for all patients. , , ,

educationb. Daily treatment for first 2 months;

TreatmentDrugs: ALL GIVEN ONCE DAILY TOGETHER: NEVER DIVIDE

DOSES1. Isoniazid=INH; bactericidal against dividing organisms2. Rifampin=RMP=bactericidal; Enables short course

treatmentdrug drug interactions: RMP is potent inducer of hepatic microsomal enzymes: cytochrome p450

3. Pyrazinamide=PZA; Enables shortening of regimen from 9

4. Ethambutol=EMB: Used in drug resistance and situations where INH or RMP cannot be used (INH hepatotoxicity; RMP drug drug interactions)


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Prevention: BCGMost widely used and most controversial vaccine in the

worldA. What is it?

M. bovis strain attenuated through serial passageB. Does it work?

1. Largest study: India= no protection from TB infection2. Other studies: England= protection from TB infection3. Prevalence of non tuberculous mycobacteria in given region may

4. Background prevalence of tuberculosis determines utility

C. Who

uses

it?Newborns vaccinated in all high prevalence areas of world

shown on first map

Mycobacterium leprae


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Mycobacterium leprae Infections

Mycobacterium leprae Infections (cont.)


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Tuberculoid vs. Lepromatous Leprosy Clinical Manifestations and Immunogenicity

Lepromatous vs. Tuberculoid Leprosy


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Lepromatous Leprosy (Early/Late Stages)

Lepromatous Leprosy Pre and Post Treatment

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