medical update webinar: management of tb in the elderly december 16, 2008 reynard j. mcdonald, m.d....

Medical Update Webinar:Management of TB in the Elderly

Medical Update Webinar:Management of TB in the Elderly

December 16, 2008

Reynard J. McDonald, M.D.

Professor of Medicine

Medical Director, Lattimore Clinic

Epidemiology - 1Epidemiology - 1

PathogenesisPathogenesis

• Primary TB infection is acquired by inhaling droplet nuclei containing viable M. tuberculosis

• These inhaled tubercle bacilli may evade destruction by host immune mechanisms and remain dormant as long as the host cell-mediated immunity remains intact

Pathogenesis - 2Pathogenesis - 2

• In the elderly, reactivation is often caused by diseases common to the geriatric (≥ 65y) age group (eg: diabetes mellitus, malignancies, chronic renal failure), poor nutrition, and the use of immunosuppressants, especially corticosteroids


• The host immune response that occurs as a result of infection with M. tuberculosis is not fully understood

• A major component of the immune system affected by aging is a decline in the ability of aging T- lymphocytes to produce specific cytokines

• Macrophage function appears to remain intact

• Some infected older persons, given enough time, will eventually eliminate the viable AFB and revert to a negative tuberculin reaction status

• These older persons have no lasting immunity and are thus susceptible to reinfection


• In the geriatric population, tuberculosis disease occurs most frequently due to endogenous reactivation of dormant pulmonary foci resulting from earlier infection with M. tuberculosis (recrudescent disease)

• Factors including malnutrition, homelessness, imprisonment, substance abuse, and immune dysfunction caused by disease, drugs or aging can reactivate dormant bacilli

Diagnosis: Clinical ManifestationsDiagnosis: Clinical Manifestations

• The clinical manifestations of tuberculosis differ depending on the site of involvement of the disease

• In >80% of cases of tuberculosis in the elderly, the lung is the site of involvement

• Symptoms are non-specific particularly in the elderly, indeed the patient may be asymptomatic, and a high index of suspicion is therefore required for early diagnosis and treatment

Diagnosis: Clinical Manifestations - 2Diagnosis: Clinical Manifestations - 2

• The most common symptom is cough

• The cough is usually nonproductive at its onset, but progressive, and may become productive of mucopurulent or blood-streaked sputum

• Other symptoms include fever, night sweats and weight loss

Diagnosis: Clinical Manifestations - 3 Diagnosis: Clinical Manifestations - 3

• The presence of acute or chronic illnesses existing concurrently with tuberculosis may obscure the diagnosis by altering the presentation

• Tuberculosis in an elderly person with chronic obstructive pulmonary disease (COPD) or lung cancer may be misdiagnosed, delaying therapy or may be completely missed, only to be found at autopsy

Diagnosis: Radiological Features Diagnosis: Radiological Features

• Primary TB can involve any lung segment but usually involves the middle or lower lobes as well as the mediastinal or hilar lymph nodes

• Infiltrates in the elderly may be interstitial, lobar, patchy or cavitary, and bilateral

Diagnosis: Radiological Features - 2 Diagnosis: Radiological Features - 2

• The usual sites of lung involvement for reactivated TB are the apical and posterior segments of the upper lobes and the superior segments of the lower lobes

• However, the lower lung fields and the anterior segment of the upper lobes may also be involved

Diagnosis: Primary TB in an Adult

Diagnosis: Post-Primary (Reactivation) TB (PA View)

Diagnosis: Post-Primary (Reactivation) TB (Lateral View)

Diagnosis: AFB Smear, Culture, and Nucleic Acid Amplification Test

Diagnosis: AFB Smear, Culture, and Nucleic Acid Amplification Test

• Elderly patients suspected of having pulmonary tuberculosis should have 10 cc of an early morning sputum specimen collected and submitted for smear and culture for acid-fast bacilli or PCR

Diagnosis: AFB Smear, Culture, and Nucleic Acid Amplification Test - 2


• 50 – 80% of patients with pulmonary tuberculosis will have sputum smears that are positive for AFB

• When smears are positive, the collection of three culture specimens on separate days is adequate



• Elderly patients are frequently unable to spontaneously produce sputum

• Under these circumstances, sputum induction by inhalation of a saline aerosol is successful in 30-60% of patients

• When lower-risk methods of collecting sputum are unsuccessful, fiber optic bronchoscopy (FOB) is a high-yield procedure that may be of benefit

Identifying Risk Factors Identifying Risk Factors

• Those who have been recently infected

• Those with clinical conditions that increase their risk of progressing from LTBI to TB disease

Persons at high risk for developing TB disease fall into 2 categories:

Identifying Risk Factors: Increased Risk for Progression to

TB Disease


TB Disease

• HIV-infected persons

• Those with a history of prior, untreated TB or fibrotic lesions on chest radiograph

Persons more likely to progress from LTBI to TB disease include:


TB Disease - 2


TB Disease - 2

• Underweight or malnourished persons

• Injection drug users

• Those receiving TNF-α antagonists for treatment of rheumatoid arthritis or Crohn’s disease


TB Disease - 3


TB Disease - 3

Persons with certain medical conditions such as:– Silicosis– Diabetes mellitus– Chronic renal failure or on hemodialysis– Solid organ transplantation (e.g., heart,

kidney)– Carcinoma of head or neck– Gastrectomy or jejunoilial bypass

Diagnosis: Testing for M. tuberculosis Infection

Diagnosis: Testing for M. tuberculosis Infection

Mantoux tuberculin skin test (TST)

Skin test that produces delayed-type hypersensitivity reaction in persons with M. tuberculosis infection

QuantiFERON® - Gold

Blood test that measures and compares amount of interferon-gamma (IFN-) released by blood cells in response to antigens

Diagnosis: Mantoux Tuberculin Skin TestDiagnosis: Mantoux Tuberculin Skin Test

• Preferred method of skin testing for M. tuberculosis infection

• TST is useful for:

– Determining how many people in a group are infected (e.g., contact investigation)

– Examining persons who have symptoms of TB

• Multiple puncture tests (e.g., Tine Test) are inaccurate and not recommended

Diagnosis: Administering the TSTDiagnosis: Administering the TST

• Inject 0.1 ml of 5 TU PPD tuberculin solution intradermally on volar surface of lower arm using a 27-gauge needle

• Produce a wheal 6 to 10 mm in diameter

Diagnosis: Reading the TSTDiagnosis: Reading the TST

• Measure reaction in 48 to 72 hours

• Measure induration, not erythema

• Record reaction in millimeters, not “negative” or “positive”

• Ensure trained health care professional measures and interprets the TST

Diagnosis: TST Interpretation Diagnosis: TST Interpretation

5-mm induration is interpreted as positive in:

• HIV-infected persons

• Close contacts to an infectious TB case

• Persons with chest radiographs consistent with prior untreated TB

Diagnosis: TST Interpretation - 2Diagnosis: TST Interpretation - 2


• Organ transplant recipients

• Other immunosuppressed patients (e.g., those taking the equivalent of >15 mg/d of prednisone for 1 month or those taking TNF-α antagonists)

Diagnosis: TST Interpretation - 3 Diagnosis: TST Interpretation - 3


• Recent immigrants

• Injection drug users

• Residents or employees of congregate settings

• Mycobacteriology laboratory personnel

• Persons with clinical conditions that place them at high risk

Diagnosis: TST Interpretation - 4Diagnosis: TST Interpretation - 4

• Persons with no known risk factors for TB*

*Although skin testing programs should be conducted only among high-risk groups, certain individuals may require TST for employment or school attendance. Diagnosis and treatment of LTBI should always be tied to risk assessment.


____________________________________________________

Diagnosis: TST BoostingDiagnosis: TST Boosting

• Some people with LTBI may have a negative skin test reaction when tested years after infection because of a waning response

• An initial skin test may stimulate (boost) the ability to react to tuberculin

• Positive reactions to subsequent tests may be misinterpreted as new infections rather than “boosted” reactions

Diagnosis: Two-Step TestingDiagnosis: Two-Step Testing

• A strategy to determine the difference between boosted reactions and reactions due to recent infection– If first TST is positive, consider the person

infected– If first TST is negative, give second TST 1–3

weeks later– If second TST is positive, consider the person

infected– If second TST is negative, consider the person

uninfected at baseline

Diagnosis: Two-Step Testing -2Diagnosis: Two-Step Testing -2

• Use two-step tests for initial baseline skin testing of adults who will be retested periodically (e.g., health care workers)

Diagnosis: QuantiFERON®-Gold Test Diagnosis: QuantiFERON®-Gold Test

• Whole-blood test used to detect M. tuberculosis infection

• Approved by the U.S. Food and Drug Administration (FDA)

• Entails mixing blood samples with antigens from M. tuberculosis, M. avium complex, and controls and incubating for 16 to 24 hours

Diagnosis: QuantiFERON®-Gold Test - 2 Diagnosis: QuantiFERON®-Gold Test - 2

• Cells that recognize the antigen release interferon-

• Amount of interferon released in response to tuberculin is compared to amount released in response to other antigens5

5MMWR January 31,2003; 52 (RR-02): 15-18 and CDC Fact Sheet Document # 250103, March 2003

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Prevention and Treatment:Isoniazid Regimens

Prevention and Treatment:Isoniazid Regimens

• 9-month regimen of isoniazid (INH) is the preferred regimen

• 6-month regimen is less effective but may be used if unable to complete 9 months

• May be given daily or intermittently (twice weekly)– Use directly observed therapy (DOT) for

intermittent regimen

Prevention and Treatment:Isoniazid Regimens - 2

Prevention and Treatment:Isoniazid Regimens - 2

• INH daily for 9 months (270 doses within 12 months)

• INH twice/week for 9 months (76 doses within 12 months)

• INH daily for 6 months (180 doses within 9 months)

• INH twice/week for 6 months (52 doses within 9 months)

Prevention and Treatment:Rifampin Regimens

Prevention and Treatment:Rifampin Regimens

• Rifampin (RIF) given daily for 4 months is an acceptable alternative when treatment with INH is not feasible (120 doses within 6 mos.)

• In situations where RIF cannot be used (e.g., HIV-infected persons receiving protease inhibitors), rifabutin may be substituted

Prevention and Treatment:Clinical Monitoring

Prevention and Treatment:Clinical Monitoring

• Rash

• Anorexia, nausea, vomiting, or abdominal pain in right upper quadrant

• Fatigue or weakness

• Dark urine

• Persistent numbness in hands or feet

Instruct patient to report signs or symptoms of adverse drug reactions

Prevention and Treatment:Clinical Monitoring - 2

Prevention and Treatment:Clinical Monitoring - 2

• Incidence of hepatitis in persons taking INH is lower than previously thought (0.1 to 0.15%)

• Hepatitis risk increases with age– Uncommon in persons < 20 years old– Nearly 2% in persons 50 to 64 years old

• Risk increased with underlying liver disease or heavy alcohol consumption

Prevention and Treatment:Laboratory Monitoring

Prevention and Treatment:Laboratory Monitoring

• Asymptomatic elevation of hepatic enzymes seen in 10%-20% of people taking INH

– Levels usually return to normal after completion of treatment

• Some experts recommend withholding INH if transaminase level exceeds 3 times the upper limit of normal if patient has symptoms of hepatotoxicity, and 5 times the upper limit of normal if patient is asymptomatic7

7MMWR June 9, 2000; 49(No. RR-6): 39

Prevention and Treatment: Treatment of Tuberculosis Prevention and Treatment: Treatment of Tuberculosis

Clinically Significant Drug-Drug Interactions Involving the Rifamycins

Clinically Significant Drug-Drug Interactions Involving the Rifamycins

Drug Class Drugs whose concentration are substantially decreased by rifamycins (references)

Clinically Significant Drug-Drug Interactions Involving the Rifamycins -

2

Clinically Significant Drug-Drug Interactions Involving the Rifamycins -

2Drug Class Drugs whose concentration are substantially

decreased by rifamycins (references)

QUESTIONS & DISCUSSION

Case ReportCase Report

March 25 – PA CXR March 25 – Lateral CXR

Case Report Case Report

March 29 – PA CXR


April 6 – PA CXR


April 13 – RAO CXR


April 21 – AP CXR


Autopsy – Rt. lung


Lung bx – Alveoli filled with proteinatious material


Lung bx - Granuloma


ZN Stain – AFB+

medical update webinar: management of tb in the elderly december 16, 2008 reynard j. mcdonald, m.d....

Documents

intact slide

bilateral slide

treatment slide

reinfection slide

autopsy slide

tuberculosis disease

weight loss slide

lattimore clinic slide