medical Microbiology lecture power point ppt mycobacteria

1. MycobacteriuMycobacteriumm

2. The only genus of Mycobacteriaceae under Actinomycetales.
Systematics
属放 菌目分枝杆菌科的菌属线

3. classificationclassification groupsgroups
M. tuberculosis complexM. tuberculosis complex
Non-tuberculous mycobacteria groupNon-tuberculous mycobacteria group II
Non-tuberculous mycobacteria group ⅡNon-tuberculous mycobacteria group Ⅱ
Non-tuberculoustuberculous mycobacteriaNon-tuberculoustuberculous mycobacteria
group Ⅲgroup Ⅲ
Rapidly growingRapidly growing Non-tuberculous mycobacteria group ⅣNon-tuberculous mycobacteria group Ⅳ
unknownunknown Mycobacterium leprae
Classification
According to the Classification program of International
Working Group on Mycobacterial Taxonomy[tæk's nəmi]ɑːSlowlygrowing

4. 1 ． Slender or slightly curved bacilli ， Branch-like
arrangement or gathered in small clumps.
2 ． G+
， but difficult to stain, enlongation the dyeing time or
Improve the dyeing temperature, they can be stained, and
once stained they cannot decolorized by acid-alcohol.
3 ． The cell wall contains large amount of lipid, which is highly
related to their staining characterisctics, resistance and
pathogenesis
4 ． Except capsule, no other special structure, no endotoxin and
exotoxin.
Common characters

5. Mycobacterium tuberculosisMycobacterium tuberculosis
(Tubercle ['tu bəkl]ː(Tubercle ['tu bəkl]ː Bacilli)Bacilli)

6. ☆ Koch discovered the tuberculosis
pathogen in 1882
☆ In 1886, tuberculosis pathogen was
named Mycobacterium tuberculosis by
Lenmann and Nenmann.

7. 1. an ancient infectous disease, and it is also an important
infectious diseases in developing countries nowadays.
2. 1/3 of the worldwide population are infected with the
tubercle bacillitubercle bacilli, and 70% of these infected persons are in
Asia.
In China before liberation, the mortality rate in TB
patients ranks first in the various cause of death
3. WHO reported that sixty-five million people are infected
with mycobacterium tuberculosis every year. The global TB
incidence rate has an average annual increase of 0.4%.
Prevalence of TB

9. ▲ AIDS, drug abuse, alcoholism, poverty.
▲ The flow of high-risk groups, the increase of immigrants
and refugees.
▲ Drug-resistant strains, especially the emergence and
prevalence of multi-resistant strains.
▲ Not standardized in Prophylaxis [ pr f 'læks s] andˌ ɑː ɪ ɪ
treatment.
▲ The administration of immunosuppressive agents.
Reasons for recovery of TB Incidence:

10. In April 1993, the World Health Organization promote
the "global TB state of emergency Declaration"
March, 24 of each year was determined as “World TB
Day” in 1995

11. Acid-fast bacilli
Morphology
■ pink in a contrasting
background.
■ slim and pleomorphic
rods.
■ non-motile
■ capsulate
■ arranged singly or in
small clumps in clinical
specimens, but it form
“serpentine ['s rpənti n]cords”ɜː ː
in
pure culture.

12. Cultural characters
Obligate, high nutritional requirement, grow slowly,
rough colony
Greedy: can only grow in medium containing serum, egg yolk,
potato flour, glycerol ['gl sə ro l]ɪ ˌ ʊ , asparagine
[ə'spærə d i n]ˌ ʒ ː 天门冬酰胺 and some inorganic salt
(lowenstein-jensen medium) (Malachite ['mæləka t]greenɪ is
added to inhibit the growth of gram positive bacteria)

13. Reasons for slow growth:
▲ Strong hydrophobic of the lipid-enriched cell wall, the
permeability of nutrients into the cell is inhibited.
▲ Deficiency of DNA-dependent RNA polymerase
▲ Lack of oxygen
Lazy: grow slowly. The double time is about 15 ～ 18 hours.
The dry, rough, buff-colored colonies usually appear
after 3-6 weeks of incubation.

14. Colonies of M.tuberculosis on
Lowenstein-Jensen medium
Ugly: dry, rough, small and buff colored colonies after 4 ～ 6
weeks of incubation.
Cauliflower

15. Eight Week Growth of
Mycobacterium tuberculosis on
Lowenstein-Jensen Agar

16. ●Resistant to
※ Dry: it can survive for long period in dried sputum.
※ Acid and alkali ['ælkəla ]ɪ : they can be used to eliminate
contaminating organisms and for the “concentration”of M.
tuberculosis in clinical specimens.
※ Basic dyestuff: they can be used as a selective substance in
Lowenstein-Jensen medium.
※ Routine used antibiotics, such as penicillin
Resistance

17. ● Sensitive to
※ Liposoluble disinfectant such as ethanol
※ Humid heat, so pasteurization can kill them.
※ Ultraviolet light, Bedclothes can be Disinfected by solarization
or ultraviolet radiation.
※ Antituberculotics such as streptomycin, isoniazid 异烟肼 ,
rifampicin [ra 'fæmpəs n], etc.ɪ ɪ

18. Variability
13y230g
special medium
Morphology variation
Virulence variation
Resistence variation drugs
Bacterial L-form( 29.9 ％ -45.5%)
Chronic patient(poor prognosis)
Routine examination (-)
Endogenous infection
Poisonous attenuated

19. PathogenesisPathogenesis
Lipid
mycolic acid phospholipid Wax D sulfatide
[s lfe 'ta d]ʌ ɪ ɪ
chemotaxis to
monocytes
granuloma
destroy
membrane of
mitochondria
hyperplasia of
monocytes
macrophages are
tranformed into
epithelioid cell
adjuvant
（ Type IV
hypersensitivi
ty ）
inhibit
phagocytes
Protein
PPD （ Type IV hypersensitivity ）

20. Lipid-Rich Cell Wall of Mycobacterium
Mycolic acids
CMN Group:
Unusual cell wall
lipids (mycolic
acids,etc.)
(Purified Protein Derivative)
[æræb n læk'tænɪ ɒɡə
阿拉伯半乳聚糖
[ma k 'le t]ɪ ə ɪ
霉菌酸酯

21. Diagram of a
Granuloma
NOTE: ultimately a
fibrin layer develops
around granuloma
(fibrosis), further
“walling off” the
lesion.
Typical progression
in pulmonary TB
involves
caseation[ ke si 'eˌ ɪ ː
ən]ɪʃ 酪化作用 ,
calcification and
cavity formation.

22. TransmissionTransmission
※※ ThroughThrough respiratory tract, alimentary [æl 'mentər ]ɪ ɪrespiratory tract, alimentary [æl 'mentər ]ɪ ɪ 消消
化的化的 tract, injured skin.tract, injured skin.
※※ TB in the lungs or throat can be infectious. This meansTB in the lungs or throat can be infectious. This means
that the bacteria can be spread to other people. TB inthat the bacteria can be spread to other people. TB in
other parts of the body, such as the kidney or spine, isother parts of the body, such as the kidney or spine, is
usually not infectious.usually not infectious.
※※ Spread by droplet nuclei (coughs, sneezes, speaks, or
sings).
PathogenesisPathogenesis

23. 10% of infected persons with normal immune
systems develop TB at some point in life
HIV is the strongest risk factor for development
of TB if infected
Certain medical conditions increase risk that
TB infection will progress to TB disease
Pathogenesis

24. Conditions That Increase the Risk of Progression to TB Disease
※ HIV infection
※ Substance abuse
※ Recent infection
※ Chest radiograph findings suggestive of previous TB
※ Diabetes mellitus
※ Silicosis
※ Prolonged corticosteriod therapy
※ Other immunosuppressive therapy

25. Conditions That Increase the Risk of Progression to TB Disease
※ Cancer of the head and neck
※ End-stage renal disease
※ Intestinal bypass or gastrectomy [gæs'trektəm ]ɪ 胃切
除术
※ Chronic malabsorption syndromes
※ Low body weight (10% or more below)

26. 1) Lung infection1) Lung infection
2) Out lung infection2) Out lung infection
primary infectionprimary infection
secondary infectionsecondary infection
Pathogenesis

27. Common Sites of TB Disease
•Lung （ the most common site ）
•Pleura
•Central nervous system
•Lymphatic system
•Genitourinary systems
•Bones and joints
•Disseminated or miliary['m l er ]ɪ ɪˌ ɪ 栗粒状的 TB
Mycobacterium tuberculosisMycobacterium tuberculosis can infect (disseminate) and
cause disease in many different body locations such as:

28. Symptoms of Pulmonary TB
※ Productive, prolonged cough (duration of >=3 weeks)
※ Chest pain
※ Hemoptysis [h 'm ptəs s]ɪ ɒ ɪ 咳血

29. Systemic Symptoms of TB
※ Fever
※ Chills
※ Night sweats
※ Appetite loss
※ Weight loss
※ Easy
※ fatigability[fæt gə'b lət ]ɪ ɪ ɪ

30. Primary TuberculosisPrimary Tuberculosis
TB alveolus [æl'vi l s]ːə ə
engulf
multiplication porta pulmonis
lymph nodes
destroy macrophages
inflammation
lymph
lymphangitis[l mf n'd a t s]ɪ ə ʒ ɪ ɪ
lymphadenitis[l m fæd 'na t s]ɪ ˌ ɪ ɪ ɪ
primary malignant syndrome
tubercle /caseous necrosis
recovery dissemination

31. Sencondary TuberculosisSencondary Tuberculosis
endogenous TB
Multiplication
low immunity
exogenous TB
Caseous necrosis
Open pulmonary tuberculosis

32. Macrophages containing
TB bacilli clump
together and begin to
form tubercles.
(granulomatous
response)
With time, the centers of
the tubercles become
necrotic and form
cheesy acellular masses
of caseous materials.
(caseous lesion)

33. Activation of macrophages -> cytokine secretion, IL-
1: fever;tNF: lipid metabolism, weight loss, tissue
necrosis;Oxygen radicals: tissue damages
Tissue necrosis -> inflammation -> mucous
secretion, destruction of blood vessels -> frequent
cough and bloody sputum

34. PULMONARY TUBERCULOSISPULMONARY TUBERCULOSIS
Large caseating tubercle Miliary tubercles
HUMAN LUNGHUMAN LUNG HUMAN LUNGHUMAN LUNG
TUBERCULOSISTUBERCULOSIS

35. immunity
1 ． Infection immunity.
2 ． Cellular immunity plays an important role in Anti-TB
immunity .
3 ． Specific antibody can only kill extracellular tubercle
bacillus, specific antibody has no killing effect on the
intracellular bacteria
4 ． Immunity and hypersensitivity is co-exit.

36. Previous infection with TB
or immunized Guinea pigs
Guinea pigs
24-48 hrs
10-14d
Local swelling, shadow ulceration
Local swelling, ulceration
Recovery
necrosis
Toxic TB
Dissemination
subcutaneous injection Koch's postulate
['p st le t]ɑː ʃə ɪ

37. Tuberculin Skin TestTuberculin Skin Test
Testing for TB Disease and Infection
※※ Tuberculin is a mixture known as purified protein derivativesTuberculin is a mixture known as purified protein derivatives
(PPD) from TB bacilli.(PPD) from TB bacilli.
※※ It is a test for delayed type hypersensitivity. Positive reaction,It is a test for delayed type hypersensitivity. Positive reaction,
reddening and thickening (> 5mm) at the site of injection afterreddening and thickening (> 5mm) at the site of injection after
2-3 days2-3 days, indicates cellular immunity to tubercle bacilli., indicates cellular immunity to tubercle bacilli.

38. Tuberculin skin test
Intradermal injection of PPD

39. Reading the Tuberculin Skin Test
•Read reaction 48-72 hours after injection
•Measure the induration only
•Record the reaction in millimeters
The lesion isThe lesion is
characterized bycharacterized by
erythema (redness) ,erythema (redness) ,
swelling and indurationswelling and induration
(raised and hard).(raised and hard).

40. ＜＜ 5 mm5 mm negativenegative
5-15 mm5-15 mm positivepositive
≥≥15 mm15 mm Strong positiveStrong positive
Interpretive standard of Tuberculin Skin Test

41. Classifying the Tuberculin Reaction
>=5 mm is classified as positive in
※ HIV-positive persons
※ Recent contacts of TB case
※ Persons with fibrotic changes on chest radiograph consistent
with old healed TB
※ Patients with organ transplants and other immunosuppressed
patients

42. Classifying the Tuberculin Reaction
>=10 mm is classified as positive in
※ Recent arrivals from high-prevalence countries
※ Injection drug users
※ Residents and employees of high-risk congregate settings
※ Mycobacteriology laboratory personnel
※ Persons with clinical conditions that place them at high risk
※ Children and adolescents exposed to adults in high-risk
categories

43. Factors that May Affect the Skin Test Reaction
Type of Reaction Possible Cause
False-positive Infected with Nontuberculous mycobacteria
BCG vaccination
Anergy
False-negative Recent TB infection
Very young age (< 6 months)
Live-virus vaccination
Overwhelming TB disease

44. ※ Do not rule out diagnosis based on negative skin test result
※ Consider anergy in persons with no reaction if
—HIV infected
—Overwhelming TB disease
—Severe or febrile illness
—Viral infections
—Live-virus vaccinations
—Immunosuppressive therapy.
※ Anergy skin testing no longer routinely recommended
Anergy

45. TreatmentTreatment
※※ multiple drugsmultiple drugs
※※ usually lasts from 6-9 months.usually lasts from 6-9 months.
△△ rifampin (RIF)rifampin (RIF)
△△ isoniazid (INH),isoniazid (INH),
△△ pyrazinamide (PZA,pyrazinamide (PZA, 吡嗪酰胺 ) [p rə'z nəma d]ɪ ɪ ɪ) [p rə'z nəma d]ɪ ɪ ɪ
△△ ethambutol (EMB,ethambutol (EMB, 乙胺丁醇 ) [eθ'æmbj t lʊ ɒ) [eθ'æmbj t lʊ ɒ
△△ streptomycin (SM)streptomycin (SM)

46. ※ Provide safest, most effective therapy in shortest time
※ Multiple drugs to which the organisms are susceptible
※ Never add single drug to failing regimen
※ Ensure adherence to therapy
Basic Principles of Treatment

47. Infectiousness
Patients should be considered infectious if they
▲ Are coughing
▲ Are undergoing cough-inducing or aerosol-generating
procedures
▲ Have sputum smears positive for acid-fast bacilli and they
▲ Are not receiving therapy, or
▲ Have just started therapy, or
▲ Have poor clinical response to therapy.

48. ※※ vaccine against M.TB. :vaccine against M.TB. :
BCGBCG ((Bacillus Calmette–Guérin ))
※※ BCG consists of a live attenuated strain derived fromBCG consists of a live attenuated strain derived from
Mycobacterium bovisMycobacterium bovis. This strain of. This strain of MycobacteriumMycobacterium
has remained avirulent for over 60 years.has remained avirulent for over 60 years.
PreventionPrevention

49. BCG is not adapt to anyone, contraindicated in persons with
impaired immune response from
BCG Contraindications
※ HIV infection
※ Congenital immunodeficiency
※ Leukemia
※ Lymphoma [l m'fo mə]ɪ ʊ
※ Generalized malignancy
※ Receiving high-dose steroid therapy
※ Receiving alkylating ['ælkə le t] agentsˌ ɪ
※ Receiving antimetabolites [æn't mtæbəla ts]ɪ ɪ
※ Receiving radiation therapy

50. Exercises
BCGBCG Tuberculin Skin TestTuberculin Skin Test
MycobacteriumMycobacterium
1.The biological characteristics and1.The biological characteristics and
pathogenicity of M. tuberculosis?pathogenicity of M. tuberculosis?
2.The immunity of M. tuberculosis?2.The immunity of M. tuberculosis?