Introduction:Infects one third of world population..!responsible for 8to 12million cases of active tuberculosis each year,3 million deaths due to TB every yearUnder privileged population - Crowding, Poverty, malnutrition, single male..! economic burden.Since 1985 incidence is increasing in westAIDS, Diabetes, Immunosuppressed patients, Drug resistance.

*TB in the United StatesFrom 1953 to 1984, reported cases decreased by approximately 5.6% each yearFrom 1985 to 1992, reported cases increased by 20%25,313 cases reported in 1993Since 1993, cases are steadily declining

*Factors Contributing to the Increase in TB CasesHIV epidemicIncreased immigration from high-prevalence countriesTransmission of TB in congregate settings (e.g., correctional facilities, long term care)Deterioration of the public health care infrastructure

*Sites of TB DiseasePulmonary TB occurs in the lungs85% of all TB cases are pulmonary Extrapulmonary TB occurs in places other than the lungs, including the:LarynxLymph nodesBrain and spineKidneys Bones and jointsMiliary TB occurs when tubercle bacilli enter the bloodstream and are carried to all parts of the body

*Not Everyone Exposed Becomes Infected Probability of transmission depends on: Infectiousness Type of environment Length of exposure 10% of infected persons will develop TB disease

*Persons at Risk for Developing TB DiseasePersons at high risk for developing TB disease fall into 2 categoriesThose who have been recently infectedThose with clinical conditions that increase their risk of progressing from LTBI to TB disease

*Recent Infection as a Risk FactorPersons more likely to have been recently infected includeClose contacts to persons with infectious TBSkin test converters (within past 2 years)Recent immigrants from TB-endemic areas (within 5 years of arrival to the U.S.)Children 5 years with a positive TSTResidents and employees of high-risk congregate settings (e.g. correctional facilities, homeless shelters, healthcare facilities)

*Increased Risk for Progression to TB DiseasePersons more likely to progress from LTBI to TB disease includeHIV infected personsThose with history of prior, untreated TBUnderweight or malnourished personsInjection drug useThose receiving TNF- antagonists for treatment of rheumatoid arthritis or Crohns diseaseCertain medical conditions

*Latent TB Infection (LTBI) Occurs when person breathes in bacteria and it reaches the air sacs (alveoli) of lung Immune system keeps bacilli contained and under control

Person is not infectious and has no symptoms

*TB Disease Occurs when immune system cannot keep bacilli contained

Bacilli begin to multiply rapidly

Person develops TB symptoms

*LTBI vs. TB Disease

LTBITB DiseaseTubercle bacilli in the bodyTST or QFT-Gold result usually positiveChest x-ray usually normalChest x-ray usually abnormalSputum smears and cultures negativeSymptoms smears and cultures positiveNo symptomsSymptoms such as cough, fever, weight, lossNot infectiousOften infectious before treatmentNot a case of TBA case of TB

*Transmission and Pathogenesis of TBCaused by Mycobacterium tuberculosis (M. tuberculosis) Spread person to person through airborne particles that contain M. tuberculosis, called droplet nucleiTransmission occurs when an infectious person coughs, sneezes, laughs, or singsProlonged contact needed for transmission 10% of infected persons will develop TB disease at some point in their lives

Once organisms have made their way into the lunghost response can be completely effective and kill all bacilli no developing tuberculosisthe organisms begin to multiply and grow immediately after infection primary tuberculosisbacilli may become dormant and never cause disease at all latent infectionthe latent organisms can eventually begin to grow reactivation tuberculosis

Binding of M.tb to Monocytes and MacrophagesThrough complement receptors CR1, CR3, and CR4mannose receptors (MMRc) mediated through the mycobacterial surface glycoprotein lipoarabinomannan (LAM)CD 14SP-Ascavenger receptors ligand for

Fate of M.tuberculosis after PhagocytosisThey are subject to killing via a variety of mechanisms:Phagosome-lysosome fusionGeneration of reactive oxygen intermediatesGeneration of reactive nitrogen intermediates, particularly nitric oxideMycobacteria have ability to evade killing by macraphage

Phox : phagocyte NADPH oxydase O2NADPHNADPH+O2-O2 -+H2OH2O2 + OH*H2O2 MPOCl-HOCl- + OH*antibacterialphox

LPSIL-1TNFIFN-INOSDeaminasioxydativeL-argininNO+H2O2peroxynitritNO+Thiol groupsnitrosothiol

Other immune cells help macrophage in controlling growth of mycobacteria

Cytotoxic T-lymphocytes- can ingest macrophages that have engulfed mycobacteria - secrete small proteins such as TIA-1 apoptosis

Microbiology of TB:Mycobacteria fungus like.. Bacilli, Aerobic, non motile, no toxins, no spore. Mycolic acid wax in cell wall Carbol dye - Acid & alcohol fast (AFB)M. tuberculosis & M. bovis M. avium, M.intracellulare in AIDS - Atypical TB

Properties of Mycobacterium spp.Acid-fast rodsCells are hydrophobic (they grow inclumps or at the surface of media)Cells are more resistant than other vegetative cells to:AcidBaseChemicals (5% phenol)Drying

AFB - Ziehl-Nielson stain

Colony Morphology LJ Slant

PPD Tuberculin TestingSub cutaneousWeal formationItching no scratch.Read after 72 hours.Induration size. 5-10-15mm (non-ende)< 72 hour is not diag*+ve after 2-4 weeks.BCG gives + result.

PPD result after 72 hours.

*Groups to Target with the Tuberculin Skin TestPersons with or at risk for HIV infectionClose contacts of persons with infectious TBPersons with certain medical conditionsInjection drug usersForeign-born persons from areas where TB is commonMedically underserved, low-income populationsResidents of high-risk congregate settings Locally identified high-prevalence groups

*Administering the TSTUse Mantoux tuberculin skin test 0.1 mL of 5-TU of purified protein derivative (PPD) solution injected intradermallyUse a 27 gauge needleProduce a wheal that is 6-10mm in diameter

*Reading the TSTRead within 48-72 hoursMeasure induration, not erythemaPositive reactions can be measured accurately for up to 7 daysNegative reactions can be read accurately for only 72 hours

*TST Interpretation - 1 5 mm of induration is positive in:HIV-infected personsClose contacts to an infectious TB casePersons who have chest x-ray findings consistent with prior untreated TB Organ transplant recipientsPersons who are immunosuppressed (e.g., those taking the equivalent of >15 mg/d of prednisone for 1 month or those taking TNF- antagonists)

*TST Interpretation - 2 10 mm induration is positive in:Recent immigrants (within last 5 years) from a high-prevalence country Injection drug users Persons with other high-risk medical conditions Residents or employees of high-risk congregate settingsMycobacteriology laboratory personnelChildren < 4 years of age; infants, children, and adolescents exposed to adults at high risk

*TST Interpretation - 3 15 mm induration is positive in:Persons with no known risk factors for TB

*Evaluation for TB Medical history Physical examination Mantoux tuberculin skin test Chest x-ray Bacteriologic exam (smear and culture)

*Symptoms of TBProductive prolonged cough*Chest pain*Hemoptysis*Fever and chillsNight sweatsFatigueLoss of appetiteWeight loss*Commonly seen in cases of pulmonary TB

*Chest x-RayObtain chest x-ray for patients with positive TST results or with symptoms suggestive of TB

*Sputum CollectionSputum specimens are essential to confirm TBSpecimens should be from lung secretions, not salivaCollect 3 specimens on 3 different daysSpontaneous morning sputum more desirable than induced specimensCollect sputum before treatment is initiated

*Smear ExaminationStrongly consider TB in patients with smears containing acid-fast bacilli (AFB)

Use subsequent smear examinations to assess patients infectiousness and response to treatment

*CultureUsed to confirm diagnosis of TBCulture all specimens, even if smear is negativeInitial drug isolate should be used to determine drug susceptibility

Drugs Sensitivity Testing(DST)

Mengetahui tingkat kepekaan isolat kuman terhadap antibiotik

Banyak metode, sesuaikan dengan kuman isolat

Sumber referensi klinisi Acuan pemilihat obat Studi epidemiologi- MDR TB- XDR TB

Uji Resistensi kuman TBAda 2 pendekatan1. Uji fenotipik- pengujian fakta biologis kuman TB2. Uji genotipik- keberadaan gen gen penyandi sifat resisten kuman : rpoB , inhA, katG gyrA

Di Indonesia :1. Cara proporsi2. Cara konsentrasi absolut3. Cara rasio resisten4. Cara media cair5. Cara deteksi netabolit6. Cara mycobacteriophaga7. Deteksi gen penyandi sifat resisten

Uji resistensi cara proporsi-Angka proporsi resisten (pR) jml koloni pada medium + obatJml koloni pada medium tanpa obatx100 %Jika pR < 1% dinyatakan sensitifJika pR 1% dinyatakan resisten

Untuk menilai pR

- dipakai angka tertinggi jml koloni kuman pada media bebas obat.

- untuk medium yang mengandung obat pilih pengenceran yang menghasilkan jml koloni 20 200, jika tidak ada pilih pengenceran yang menghasilkan jml koloni 5 - 19

Yang perlu dipersiapkan1. Suspensi kuman a. Suspensi kuman konsentrasi 1mg / mlb. Suspensi kuman konsentrasi 0,5 1,0 standart Mc Farland. Buat seri pengenceran 10-3 dan 10-5 (estimasi jml koloni 104 dan 102 kuman per ml )

2. Medium LJ dengan OATIsoniazid (INH): 0,2 g/mlStreptomycin (S): 4 g/mlRifampicin: 40 g/mlEhambutol: 2 g/ml3. Medium LJ tanpa OAT

Perlakuan 1. Untuk setiap OAT diapkan 6 botol LJ (4 botol tanpa obat dan 2 botol dengan obat) 2. Dari 4 botol tanpa obat, 2 diinokulasi suspen- si kuman pengenceran 10-3 dan 2 ditanami pengenceran 10-5 3. Pembacaan hasil dikaukan pada hari ke 28 dan 42 (kontrol)

4. Skala pembacaan hasil

PembacaanPencatatan>500 koloni4+200-500 koloni3+100-200 koloni2+20-100 koloni1+1-19 koloniTulis jml koloniTidak pertumbuhan0

5. Pembacaan hasilSuspensi (1mg/ml 107/mlpengen-ceran(Estimasi kuman)S(1) pada 10-3, H(12) pada 10-5, R(8) pada 10-3 , E(20) pada 10-5

Media tanpa obatMedia dgn obat (mg/lt)S(4) H(0)R(4)E(2) 10-1 ( 106) 10-2 ( 105) 10-3 ( 104)3+ , 4+4+(>500)13+82+ 10-4 ( 103) 10-5 ( 102)35 ,4545012020pR

PerhitunganStreptomycin +(500)

Uji Rasio Resiten Menggunakan medium padat (LJ) Penentuan resisten dilakukan dengan memban- dingkan dengan kuman standart H37Rv Medium LJ dengan obat dengan berbagai konsentrasi Resistensi dinyatakan dengan : A . H37Rv. B% Jika nilai A > 4 dinyatakan resisten Jika nilai B > 1% dinyatakan resisten 5

Medium LJ dengan obat yang dipakai

Streptomycin : 1 , 10 dan 100 g/mlIsoniazid : 0,1 , 1 dan 10 g/mlRifampicin : 2,5 ; 5 ; 10 dan 20 g/mlEthambutol : 1 ; 10 dan 100 g/ml

Uji kepekaan M.tb terhadap streptomycinResisten A x H37Rv (B%)Resisten 100 x H37Rv (26%)

LJ dgnobat0 g/mlkontrl1 g/ml10 g/ml100g/ml

Sampelpenderita

H37 Rv300

200200

100150

080

0

Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*Appendix 12 - Fundamentals of TB Presentation*