Tuberculosi S: – Elisabeth Kasih –

TUBERCULOSI S – Elisabeth Kasih –

Case 1 • An. Aldo (2 thn) tinggal di perumahan yg padat. Tetangga Aldo diketahui sering batukbatuk dgn badan kurus & sering mampir utk menggoda Aldo. Suatu hari ditemukan pembengkakan di daerah leher kiri Aldo. Oleh keluarga, Aldo dibawa ke dokter anak & setelah dilakukan tes Mantoux ditemukan hasil (+). Jelaskan patofisiologi & metode diagnostik tes Mantoux serta penatalaksanaan utk An. Aldo!

Case 2 • Bpk. Mukidi (56 thn) adlh salah 1 pekerja pabrik di kawasan Surabaya Utara. Bpk. Mukidi adlh perokok aktif. Belakangan ini ia sering mengeluh batuk-batuk, keringat dingin pd waktu malam hari & penurunan BB kurang lebih 5 kg dlm 1 bln terakhir, pdhl Bpk. Mukidi tdk menjalani diet. Jelaskan patofisiologi penyakit apakah yg terjadi pd Bpk. Mukidi, apa saja pemeriksaan penunjang yg dilakukan utk menegakkan diagnosis tsb & penatalaksanaannya!

Case 3 • Stlh Bpk. Mukidi periksa ke dokter, ia mendapatkan terapi selama 6 bln. Namun ketika memperoleh obat, Bpk. Mukidi kerap mual & muntah sehingga tdk melanjutkan obat tsb tanpa sepengetahuan dokter. Batuknya tambah jauh lebih parah & BB-nya menurun drastis. 4 bln kemudian Bpk. Mukidi periksa lagi ke dokter & diberikan obat yg sama selama 6 bln, namun stlh 3 bln ternyata didapatkan BTA-nya masih (+), kemudian dirujuk ke RS Seger Waras & dilakukan pemeriksaan lbh lanjut di sana. Ternyata ditemukan bhw ia sdh resisten dg pengobatan isoniazid & rifampicin. Jelaskan patofisiologi penyakit apakah yg terjadi pd Bpk. Mukidi, apa saja pemeriksaan penunjang yg dilakukan utk menegakkan diagnosis tsb & penatalaksanaannya!

Case 4 • Ny. Roryta (60 thn) memiliki suami yang batuk cukup lama, kurang lebih 6 bln. Tiba-tiba suatu hari ditemukan benjolan di punggung Ny. Roryta yg semakin lama semakin membesar, sehingga badan Ny. Roryta menjadi terkesan bungkuk. Selain itu, Ny. Roryta juga mengalami penurunan BB, dlm 3 bln terakhir BB-nya sdh turun 4 kg. Jelaskan patofisiologi penyakit apakah yg terjadi pd Ny. Roryta, apa saja pemeriksaan penunjang yg dilakukan utk menegakkan diagnosis tsb & penatalaksanaannya!

Case 5 • Ibu Markonah (36 thn) mengalami batuk lama kurang lebih 5 bln terakhir disertai badan yg semakin kurus. Ternyata Ibu Markonah (+) hamil 3 bln. Ketika dilakukan pemeriksaan di puskesmas utk skrining kehamilannya, ditemukan bhw Ibu Markonah jg menderita TB paru (+). Bgmn penatalaksanaannya? Apa saja yg harus diperhatikan pd kasus ini?

Transmission & Pathogenesis • Caused by Mycobacterium tuberculosis • Airborne transmission

Transmission & Pathogenesis Effective immune response Infection limited to small area of lung Immune response insufficient

Terminology • Miliary TB  occurs when tubercle bacilli enter the bloodstream & are carried to all parts of the body • Latent TB  occurs when person breathes in bacteria & it reaches alveoli, but immune system keeps bacilli contained & under control  person is not infectious & has no symptom • Multidrug resistant TB  TB is resistant to ≥ 2 of the 1st line medication

Virulence • Probability of transmission depends on: • Infectiousness • Type of environment • Length of exposure

• 10% of infected person will eventually develop TB disease • 5% within 1-2 years • 5% at some point in their lives

Virulence Exposure to TB No infection (70-90%)

Infection (10-30%)

Latent TB (90%)

Active TB (10%)

Never develop Active disease

Die within 2 years

Untreated Survive

Treated Die

Cured

Risky Patients • Persons at high risk for developing TB disease divided into 2 categories: • Those who have been recently infected • Those with clinical conditions that increase their risk of progressing from LTBI to TB disease

Risk Factors • Close contact to persons with infectious TB • Skin test converter (within past 2 years) • Recent immigrants from TB-endemic areas (within 5 years of arrival) • Children ≤ 5 years with a (+) TST • Residents & employees of high-risk congregate settings (ex: homeless shelter, healthcare facilities)

Risk Factors for Progression TB • Persons more likely to progress from LTBI to TB disease include: • HIV infected • Those with history of prior, untreated TB • Underweight/ malnourished • Injection drug use • Those receiving TNF-α antagonist (for treatment RA/ Crohn’s disease) • Certain medical conditions

LTBI vs TB Disease LTBI

TB Disease

Tubercle bacilli in the body TST or QFT-Gold® result usually positive Chest x-ray usually Chest x-ray usually normal abnormal Sputum smears and cultures Symptoms smears and negative cultures positive Symptoms such as cough, No symptoms fever, weight, loss Often infectious before Not infectious treatment Not a case of TB A case of TB

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

Tuberculosis Test • Detect persons with LTBI who would benefit from treatment • De-emphasize testing of groups of people who are not at risk (mass screening) • Consider using a risk assessment tool • Testing should be done only if there is an intent to treat • Can help reduce the waste of resources & prevent unnecessary treatment

Groups Need to Test • Persons with/ at risk for HIV infection • Close contacts of persons with infectious TB • Persons with certain medical conditions • Injection drug users • Foreign-born persons from endemic area • Medically undeserved, low-income populations

Tuberculin Skin Test (TST) • Mantoux tuberculin skin test • 0.1 mL of purified protein derivative (PPD) solution injected intradermally • Produce a wheal that is 6-10 mm in diameter

TST Reading • Read within 48-72 hours • Measure induration, not erythema • (+) reactions  can be measured accurately for up to 7 days • (–) reactions  can be read accurately for only 72 hours

TST Interpretation ≥ 5 mm induration (+) in: • HIV-infected patients • Close contacts to an infectious TB case • Persons who have chest X-ray findings consistent with prior untreated TB • Organ transplant recipients • Persons who are immunosuppressed (ex: those taking the equivalent of > 15 mg/d of prednisone for 1 month or TNF-α antagonists)

TST Interpretation ≥ 10 mm induration (+) in: • Recent immigrants (within last 5 years) from high-prevalence area • Injection drug users • Persons with high-risk medical conditions • Residents/ employees of high-risk congregate settings • Mycobacteriology laboratory personnel • Children < 4 y.o.; infants, children & adolescents exposed to adults at high risk

TST Interpretation ≥ 15 mm induration (+) in: • Persons with no known risk factors for TB

Recording TST Results • Record results in millimeters of induration, not “negative” or “positive” • Only trained healthcare professionals should read & interpret TST results

False (+) TST Reactions • Non tuberculous mycobacteria • Reactions are usually ≤ 10mm of induration

• BCG vaccination • Reactivity in BCG vaccine recipients generally wanes over time • Positive TST results is likely due to TB infection if risk factors are present • BCG-vaccinated persons with positive TST result should be evaluated for treatment of LTBI • QFT is able to distinguish M. tuberculosis from other mycobacteria & BCG vaccine

False (–) TST Reactions • Anergy/ inability to react to TST because of weakened immune system • Recent TB infection (2-10 weeks after exposure) • Very young age (newborns) • Recent live-virus vaccination can temporarily suppress TST reactivity • Poor TST administration technique (too shallow or too deep, or wheal is too small)

Boosting • Some people with history of LTBI lose their ability to react to tuberculin (immune system “forgets” how to react to TB-like substance, i.e., PPD) • Initial TST may stimulate (boost) the ability to react to tuberculin • (+) reactions to subsequent tests may be misinterpreted as new infections rather than “boosted” reactions

Chest X-Ray • Obtain chest x-ray for patients with (+) TST results/ with symptoms suggestive of TB • Abnormal chest X-ray, by itself, cannot confirm the diagnosis of TB but can be used in conjunction with other diagnostic indicators

Sputum Collection • Sputum specimens are essential to confirm TB • Specimens should be from lung secretions (not saliva)

• Collect 3 specimens on 3 different days • Spontaneous morning sputum more desirable than induced specimens • Collect sputum before treatment is initiated

Culture • Used to confirm diagnosis of TB • Culture all specimens, even if smear is negative • Initial drug isolate should be used to determine drug susceptibility

Infectiousness • Patients should be considered infectious if they:

• are undergoing cough-inducing procedures • have sputum smears positive for acidfast bacilli (AFB) and: • are not receiving treatment • have just started treatment, or • have a poor clinical or bacterial response to Tx

• have cavitary disease

• Extrapulmonary TB Px are

not

Infectiousness • Patients are not considered infectious if they meet all these criteria: • Received adequate treatment for 2-3 weeks • Favorable clinical response to treatment • 3 consecutive (–) sputum smears results from sputum collected on different days

Decrease Transmission • Instruct patient to: • Cover mouth when coughing or sneezing • Wear mask as instructed • Open windows to assure proper ventilation • Do not go to work or school until instructed by physician • Avoid public places • Limit visitors • Maintain home or hospital isolation as

Symptoms • Productive prolonged cough* • Chest pain* • Hemoptysis* • Fever and chills • Night sweats • Fatigue • Loss of appetite • Weight loss *) Commonly seen in cases of pulmonary TB

Treatment of TB Isoniazid (INH) Rifampi n (RIF)

Strept omyci n

1st line drugs Ethambutol (EMB) Pyrazinamid e (PYR)

Treatment of Latent TB • Daily Isoniazid therapy (for 9 months) • Monitor patients for signs & symptoms of LFT & peripheral neuropathy

• Alternate regimen  Rifampin (for 4 months)

Treatment of TB Disease • Adjust regimen  when resistance appears/ patient has difficulty with any of the medications • Never add a single drug to a failing regimen!! • Promote adherence & ensure treatment completion

Treatment of MDR-TB • Resistance to INH, RIF, PZA & ethambutol should be treated with quinolones & at least 1 of 3 injectable drugs (amikacin, kanamycin, capreomycin) • Should be added with: • Amikacin • Kanamycin • Fluoroquinolones

Indication for 2nd Line Drugs • Resistance to the 1st line drugs • Failure of clinical response • Increase of risky effects • Patient was not tolerating the 1st line drugs

2nd Line Drugs Ethionamide

Capreomycin

Cycloserine

Paraaminosalicylic acid

Rifapentine

Amikacin

Fluoroquinolones

Monitoring • Closely monitoring LFT (every 2 week until the 8th)  esp for INH & PYR • Instruct patients to immediately report: • Rash • Nausea, loss of appetite, vomiting, abdominal pain • Persistently dark urine • Fatigue or weakness • Persistent numbness in hands or feet

Drug Resistance • Primary  infection with a strain of M. tuberculosis that is already resistant to one or more drugs • Acquired  infection with a strain of M. tuberculosis that becomes drug resistant due to inappropriate/ inadequate treatment

Barriers to Adherence • Stigma • Extensive duration of treatment • Adverse reactions to medications • Concerns of toxicity • Lack of knowledge about TB & its treatment

Improving Adherence • Adherence is the responsibility of the provider (not the patient) & can be ensured by: • Patient education • Directly observed therapy (DOT) • Case management • Incentives/ enablers

Directly Observed Therapy (DOT) • Health care worker watches patient swallow each dose of medication • The best way to ensure adherence • Should be used with all intermittent regimens • Reduces relapse of TB disease & drug resistance

Measures to Promote Adherence • Develop an individualized treatment plan for each patient • Provide culturally & linguistically appropriate care to patient • Educate patient about TB • Use incentives & enablers to address barriers • Facilitate access to health & social services

Completion of Therapy • Based on total number of doses administered (not duration of treatment) • Extend or re-start if there were frequent/ prolonged interruptions

Meeting the Challenge • Prevent TB by assessing risk factors • If risk is present  perform TST • If TST (+)  rule out active disease • If active disease is ruled out  initiate treatment for LTBI • If treatment is initiated  ensure completion

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