-15- TB

September-19-08 9:20 AM

NOTES: Dont need to know the different definitions fo tb, jus tknow different ways it can manifest itself. Isolateion until 3 days of negative sputum! No treatments oF TBs or Virals- Straightforward treatments required for bacterial pneumos!!! Physical findings Physical: * Fever - low grade, intermittent * Lymphadenopathy - cervical * Cachexia * Abnormal lung sounds * Pleural effusion * Ronchi, crepitations Diagnosis Two most important diagnostic tests are: - random sample sputum staining for acid-fast bacilli - chest radiography. Initiate treatment if either of these tests indicates active disease. Do not delay the diagnosis until the following day for patients at high risk for active disease. Sputum: * Ziehl-Neelsen staining of sputum * Attempt several sputum collections or induce sputum production by respiratory physiotherapy. * The absence of a positive smear result does not exclude active TB infection. Blood culture Helps establish the diagnosis of active TB Recommended in * All patients infected with HIV who are suspected of tuberculosis * Any patient with a high suspicion for active tuberculosis. All patients who are diagnosed with active TB and who are not known to be HIV positive should undergo HIV testing Chest radiography * May indicate active disease in the symptomatic patient even with negative sputum smear. * Active primary TB: ipsilateral hilar adenopathy, often accompanied by atelectasis. * Reactivation TB: pulmonary lesions are located in the posterior segment of the right upper lobe, apicoposterior segment of the left upper lobe, and apical segments of the lower lobes. Tuberculin test * Tuberculin skin testing using 5 units (0.1 mL) of purified protein derivative (PPD) injected intradermally * Positive criteria are population dependent, but any induration of 5 mm or more is now suspect. * Induration, not erythema, is measured 48-72 hours following injection. * False negative: infants, patients with immuno -suppressive conditions and overwhelming TB * False positive: BCG, Nontuberculus mycobacteria BCG Vaccine * Bacilli Calmette-Guerin * Only used in high rate countries to prevent childhood TB meningitis and Miliary TB * Can do TST- same cut offs: 5mm and 10mm * High Risk: HIV, TB contact, Txs, Immunocompressed, IV drug users, less then 5 yrs from endemic country Treatment * Isolate any patient with suspected TB infection in a private room (not cohorted, as in the past) with negative pressure. * Continue isolation until sputum smears return negative results 3 consecutive times. * Treatment markedly reduces infectivity - The first dose of medication reduces the bacillary load 10-fold. - Therapy for 2 weeks reduces the bacillary load by a 100-fold factor (CDC, 1997). * Initial 4-drug therapy is recommended in most areas. Intermittent treatment is as effective as daily treatment (~2% relapses) with the advantage of increased compliance * Six-month course, daily therapy Initial 2 months - INH 300 mg qd; Rifampin (RIF) 600 mg qd); Pyrazinamide (PZA) 2 g qd; and Ethambutol (ETB) 2 g qd Final 4 months - INH 300 mg qd and RIF 600 mg qd or, alternatively, INH 900 mg and RIF 600 mg twice weekly. Six-month course, directly observed intermittent therapy (Denver protocol) - The compliance rate is 91%. * Initial 2 weeks (all PO doses except for streptomycin, which is administered IM) - INH 300 mg qd, RIF 600 mg qd, PZA 2 g qd, and Streptomycin 1 g qd * Next 6 weeks - Same drugs twice weekly * Final 18 weeks - INH and RIF only, twice weekly Special cases * HIV positive - Extend the treatment protocol to a minimum of 9 months with at least 6 months culture-negative sputum. * Pregnant - A 9-month daily course of INH, RIF, and ETB is recommended in the doses above. Breastfeeding is permitted. PZA is contraindicated due to inadequate teratogenicity data. Streptomycin is discouraged unless other drugs are contraindicated (16% fetal ototoxicity). * Patients who have meningitis - Dexamethasone added to routine 4-drug therapy reduces complications. Multidrug-resistant tuberculosis * Administer all of the following - An injectable anti-TB aminoglycoside (eg, amikacin, capreomycin, kanamycin), - A fluoroquinolone (eg, ciprofloxacin, ofloxacin), - ETB, PZA, INH, RIF, and cycloserine, ethionamide, or amino salicylic acid. * Consider rifabutin substitution for RIF, as approximately 30% of RIF-resistant strains are rifabutin sensitive. * Do not use intermittent therapy. * Clusters of MDR TB with 7-drug resistance have been reported and have a high infectivity rate. Medical Legal Pitfalls, see slideshow

Lecture: * Chronic disease usually affecting lungs but may involve other organs as well * One of the oldest disease known * Caused by Mycobaterium tuberculosis * If untreated, disease may be fatal in more than half cases within 5 years * Frequency: In the US: - 4-6% of population carries a latent TB infection - 25,000-30,000 new cases of active TB annually. Since 1985 incidence of the disease has increased dramatically Internationally: - Latent TB infections are present in one third (1.7 billion individuals) of the worlds population - 20 million cases of active TB - 10 million new cases diagnosed each year. Mortality/Morbidity: - Main in morbidity and mortality due to infectious diseases - Responsible for more deaths worldwide than all other infectious diseases combined. - In the US, 2800 TB deaths are reported annually. Race: - No racial preferences - In US, minorities account for ~70% of diagnosed TB cases. - Socioeconomic factors. - Immigrants from Mexico, Africa, Southeast Asia, the Caribbean, and Latin America 4-5 x higher prevalence Age: Peak incidence: Non white 25-40 yrs; White 70 yrs. The best way to prevent the disease is to cure infectious cases at an early stage, since this also puts a stop to transmission. The BCG vaccination of infants helps to avoid the most serious forms of childhood tuberculosis. Infecting eight million new victims a year, tuberculosis also has a deadly link with AIDS. * People infected with both HIV and the tuberculosis bacillus have a 25-fold increased risk of developing potentially fatal disease. Pathophysiology * M tuberculosis primarily is spread as an airborne aerosol from infected to noninfected individuals * Transdermal and gastrointestinal (GI) transmission also have been reported. * Infected patients living in crowded or closed environments pose a particular risk for noninfected persons. * Initial TB infection may result in a latent or dormant infection in hosts with normally functioning immune systems. * Infected end organs typically have high regional oxygen tension (apices of the lungs, kidneys, bones, meninges, eye, and choroid). * The hallmark of extrapulmonary TB histopathology is the caseating granuloma consisting of giant cells with central caseating necrosis. Rarely, if ever, are any TB bacilli seen. * Acid fast bacilli: * Tuberculous infection occurs as a consequence of the inhalation of bacillus-laden droplets expelled from an infected host. * Development of an infection depends on prolonged exposure (on the order of weeks but may occur in days) to an individual with active pulmonary tuberculosis. * Once the organism is inhaled, it travels via the airways to the pulmonary parenchyma where it is deposited. Although the organism may be deposited in any lobe, a predilection for the lower lobes exists more for right lobe??. * * * * * Host immune reactions to its antigenic cell wall proteins main cause of tissue destruction . The organism is ingested by alveolar macrophages, which then attempt to phagocytize the bacilli. Sometimes the alveolar macrophages are unsuccessful in completely destroying the bacilli As a consequence, bacilli often remain viable within the macrophages in immunocompetent individuals. Subsequently, bacilli may travel via the pulmonary lymphatics, or they may enter the vascular system and seed distant sites such as the liver, spleen, or bone marrow.

Primary tuberculosis: * In most immunocompetent individuals, macrophages are successful in containing the bacilli, and the infection is self-limited and often subclinical - This contained infection is called primary tuberculosis. * Primary tuberculosis is seen in children in endemic regions. * With AIDS, adults may present with primary tuberculosis. * Skin test conversion and identification of a Ghon complex on chest radiography are the only means of identifying such cases. Progressive primary tuberculosis: * In some patients, pulmonary macrophages are unable to contain the bacilli and are overwhelmed, leading to a clinically apparent infection. * This is more common in immunocompromised, notably the population with HIV/AIDS. * Patients may present with pulmonary manifestations (often with miliary tuberculosis) or with manifestations of systemic or disseminated disease. Post-primary tuberculosis (reactivation): * Seen in patients in whom the initial infection was contained successfully by the pulmonary macrophages. * Bacilli remaining viable within the macrophages. * Infection results when the host's immune status (T cells) is compromised. * This form may appear in the elderly population Extrapulmonary tuberculosis * Lymph nodes cervical, supraclavicular * Pleura pleural effusion, empyema * Genitourinary tract * Bones and joints spine > hips > knees * Meninges * Peritoneum History Classic features associated with active TB are: * Productive cough * Hemoptysis blood streaked sputum * Fever evening rise * Night sweats * Anorexia * Weight loss Symptoms of extrapulmonary tuberculosis may be nonspecific. * Classic symptoms are often absent, particularly in patients who are immunocompromised or elderly. * Up to 20% of patients with active TB may be asymptomatic.

Notes By:

Block I Page 1