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classificationclassification groupsgroups
M. tuberculosis complexM. tuberculosis complex
Non-tuberculous mycobacteria group Non-tuberculous mycobacteria group II
Non-tuberculous mycobacteria group ⅡNon-tuberculous mycobacteria group Ⅱ
Non-tuberculoustuberculous mycobacteria Non-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'sɑːnəmi]
Slow
ly grow
ing
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
Mycobacterium tuberculosis Mycobacterium tuberculosis
(Tubercle ['tuːbəkl] (Tubercle ['tuːbəkl] Bacilli)Bacilli)
☆ Koch discovered the tuberculosis
pathogen in 1882
☆ In 1886, tuberculosis pathogen was
named Mycobacterium tuberculosis by
Lenmann and Nenmann.
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
▲ 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 [ˌprɑːfɪ'læksɪs] and
treatment.
▲ The administration of immunosuppressive agents.
Reasons for recovery of TB Incidence:
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
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 ['sɜːrpəntiːn]cords” in
pure culture.
Cultural characters
Obligate, high nutritional requirement, grow slowly,
rough colony
Greedy: can only grow in medium containing serum, egg yolk,
potato flour, glycerol ['glɪsəˌroʊl] , asparagine
[ə'spærəˌdʒiːn] 天门冬酰胺 and some inorganic salt
(lowenstein-jensen medium) (Malachite ['mæləkaɪt]green is
added to inhibit the growth of gram positive bacteria)
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.
Colonies of M.tuberculosis on Lowenstein-Jensen medium
Ugly: dry, rough, small and buff colored colonies after 4 ~ 6
weeks of incubation.
Cauliflower
●Resistant to
※ Dry: it can survive for long period in dried sputum.
※ Acid and alkali ['ælkəlaɪ]: 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
● 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 [raɪ'fæmpəsɪn], etc.
Variability
13y230gspecial 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
PathogenesisPathogenesis
Lipid
mycolic acid phospholipid Wax D sulfatide [sʌlfeɪ'taɪd]
chemotaxis to monocytes granuloma destroy membrane of mitochondria
hyperplasia of monocytes
macrophages are tranformed into epithelioid cell
adjuvant (Type IV hypersensitivity )
inhibit phagocytes
Protein PPD ( Type IV hypersensitivity )
polysachride help entry ;Anti-Phagocytic effects
Lipid-Rich Cell Wall of MycobacteriumMycolic acids
CMN Group: Unusual cell wall lipids (mycolic acids,etc.)
(Purified Protein Derivative)
[æræbɪnɒɡəlæk'tæn]阿拉伯半乳聚糖
[maɪkə'leɪt]霉菌酸酯
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[ˌkeɪsiː'eɪʃən] 酪化作用 , calcification and cavity formation.
TransmissionTransmission
※ ※ Through Through respiratory tract, alimentary [ælɪ'mentərɪ] respiratory tract, alimentary [ælɪ'mentərɪ] 消消
化的化的 tract, injured skin.tract, injured skin.
※ ※ TB in the lungs or throat can be infectious. This means TB in the lungs or throat can be infectious. This means
that the bacteria can be spread to other people. TB in that the bacteria can be spread to other people. TB in
other parts of the body, such as the kidney or spine, is other 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
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
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
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'trektəmɪ] 胃切除术
※ Chronic malabsorption syndromes
※ Low body weight (10% or more below)
1) Lung infection1) Lung infection
2) Out lung infection2) Out lung infection
primary infectionprimary infection
secondary infectionsecondary infection
Pathogenesis
Common Sites of TB Disease
•Lung ( the most common site )•Pleura
•Central nervous system
•Lymphatic system
•Genitourinary systems
•Bones and joints
•Disseminated or miliary['mɪlɪˌerɪ] 栗粒状的 TB
Mycobacterium tuberculosisMycobacterium tuberculosis can infect (disseminate) and
cause disease in many different body locations such as:
Symptoms of Pulmonary TB
※ Productive, prolonged cough (duration of >=3 weeks)
※ Chest pain
※ Hemoptysis [hɪ'mɒptəsɪs] 咳血
Systemic Symptoms of TB
※ Fever
※ Chills
※ Night sweats
※ Appetite loss
※ Weight loss
※ Easy
※ fatigability[fætɪgə'bɪlətɪ]
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 ɪlymphadenitis[l m fæd 'na t s]ɪ ɪ ɪ ɪˌ
primary malignant syndrome
tubercle /caseous necrosis
recovery dissemination
Sencondary TuberculosisSencondary Tuberculosis
endogenous TB
Multiplication
low immunity
exogenous TB
Caseous necrosis
Open pulmonary tuberculosis
Macrophages containing TB bacilli clump together and begin to form tubercles. (granulomatousresponse)
With time, the centers of the tubercles become necrotic and form cheesy acellular masses of caseous materials. (caseous lesion)
Activation of macrophages -> cytokine secretion, IL-1: fever;tNF: lipid metabolism, weight loss, tissue necrosis;Oxygen radicals: tissue damagesTissue necrosis -> inflammation -> mucous secretion, destruction of blood vessels -> frequent cough and bloody sputum
PULMONARY TUBERCULOSISPULMONARY TUBERCULOSIS
Large caseating tubercle Miliary tubercles
HUMAN LUNGHUMAN LUNG HUMAN LUNGHUMAN LUNG
TUBERCULOSISTUBERCULOSIS
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.
Previous infection with TBor immunized Guinea pigs
Guinea pigs
24-48 hrs10-14d
Local swelling, shadow ulceration
Local swelling, ulceration
Recovery
necrosis
Toxic TB
Dissemination
subcutaneous injection
Koch's postulate ['pɑ st le t]ː ʃə ɪ
Tuberculin Skin TestTuberculin Skin Test Testing for TB Disease and Infection
※ ※ Tuberculin is a mixture known as purified protein derivatives Tuberculin 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 after reddening 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.
Reading the Tuberculin Skin Test
•Read reaction 48-72 hours after injection
•Measure the induration only
•Record the reaction in millimeters
The lesion is The lesion is
characterized by characterized by
erythema erythema
(redness) , (redness) ,
swelling and swelling and
induration (raised induration (raised
and hard).and hard).
<< 5 mm5 mm negativenegative
5-15 mm5-15 mm positivepositive
≥≥15 mm15 mm Strong positiveStrong positive
Interpretive standard of Tuberculin Skin Test
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
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
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
※ 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
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 ) [pɪrə'zɪnəmaɪd]) [pɪrə'zɪnəmaɪd]
△ △ ethambutol (EMB,ethambutol (EMB, 乙胺丁醇 ) [eθ'æmbjʊtɒl) [eθ'æmbjʊtɒl
△ △ streptomycin (SM)streptomycin (SM)
※ 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
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.
※ ※ vaccine against M.TB. :vaccine against M.TB. :
BCGBCG ( (Bacillus Calmette–Guérin ))
※ ※ BCG consists of a live attenuated strain derived from BCG 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
BCG is not adapt to anyone, contraindicated in persons with impaired immune response from
BCG Contraindications
※ HIV infection
※ Congenital immunodeficiency
※ Leukemia
※ Lymphoma [lɪm'foʊmə]
※ Generalized malignancy
※ Receiving high-dose steroid therapy
※ Receiving alkylating ['ælkəˌleɪt] agents
※ Receiving antimetabolites [æn'tɪmtæbəlaɪts]
※ Receiving radiation therapy