Pulmonary Tuberculosis PDF

Pulmonary tuberculosis ILOs At the end of this session, the student will be able to: ▪ Define TB and its etiology and classification. ▪ Identify different routes of spread of TB. ▪ Identify the management plan of TB. ▪ Describe the preventive measures to guard against TB...

Pulmonary tuberculosis ILOs At the end of this session, the student will be able to: ▪ Define TB and its etiology and classification. ▪ Identify different routes of spread of TB. ▪ Identify the management plan of TB. ▪ Describe the preventive measures to guard against TB infection. Definition and Classification Tuberculosis (TB) Is a chronic bacterial infection caused by mycobacterium tuberculosis (MTB)which is a highly host adapted intracellular bacterial pathogen of macrophages. Exposure to MTB bacilli lead to formation of a caseating granuloma with central area of caseation surrounded by epithelioid cells and langhans giant cells followed by an outer layer of lymphocytes and fibrous tissue. Figure 1: Tuberculous granuloma. Normal lung tissue is lost and replaced by a mass of fibrous tissue with granulomatous inflammation characterised by large numbers of macrophages and multinucleate giant cells (white arrow). The central area of this focus shows caseous degeneration (black arrow). The disease is caused by aerobic bacilli which when stained they resist decolorization by strong acids, so-called acid-fast bacilli (AFB) in the direct smear stained by the "Ziehl-Neelsen method” the AFB take red color against blue background. Page 1 of 12  Tuberculous infection is usually caused by “human mycobacterium tuberculosis" transmitted through droplets. However less than 1% of TB Infection is attributed to the bovine mycobacterium TB (Mycobacterium Bovis) where infection occurs through the alimentary canal from infected milk. After exposure to infection, only a minority of individuals (between 10-15%) will ever develop TB, depending on the host immune system. The development TB disease is interaction between the virulence of the bacteria and host immunity which results in primary TB and post-primary TB (Secondary TB). Primary TB (The Primary Complex) Comprises the reaction at the site of the initial infection (lung-tonsil-intestine), together with that which develops in the regional lymph nodes. Primary TB of the lung consists of a parenchymal component and a glandular component in the form of hilar lymphadenopathy with the lymphangitis of lymphatics connecting both lesions. This develops within 4-6 weeks of first infection and its progress is limited and there are few, if any, symptoms. Such parenchymal component is usually peripherally located at the lower part of the upper lobe or the upper part of the lower lobe. The lymph nodes of the primary TB subside, and the peripheral lung lesion becomes reduced to a small nodule, or they may calcify and become evident on the chest x-ray indefinitely (Ghon′s focus) denoting complete healing of primary TB. However, healing maybe incomplete and the AFB are still viable at the site of primary TB of the lung for a long period. Reactivation of this incompletely healed primary TB is one of the sources of post-primary TB. Post primary TB. Post-primary disease refers to exogenous (‘new’ infection) or endogenous (reactivation of a dormant primary lesion) infection in a person who has been sensitized by earlier exposure. It is most frequently pulmonary and characteristically occurs in the apex of an upper lobe, where the oxygen tension favors survival of the strictly aerobic organism. The onset is usually insidious, developing slowly over several weeks. Fate of primary TB:(figure 2) Healing (Ghon′s focus) Development of allergic (hypersensitivity) reactions Page 2 of 12  Allergic reaction may occur secondary to exposure to the foreign protein of the AFB (tuberculo-protein). Such allergic reaction maybe manifested in different forms such as development of tuberculin hyper-sensitivity (tuberculin test becomes positive), erythema nodosum, phlectinular conjunctivitis, pleural effusion and epituberculosis. Epituberculosis occurs from development of allergic reaction around the parenchymal as well as the glandular components of the primary TB. Such enlarged hilar lymph nodes especially in children, may compress a bronchus causing atelectasis and consolidation and may appear as a transient diffuse area of radiological hazy opacification. Spread Spread of primary TB of the lung lead to post-primary tuberculosis. Spread of primary TB of the lung may occur by several routes: Bronchial Spread leading to “Bronchogenic pulmonary TB”: this results in TB pneumonia, TB bronchopneumonia, nodular infiltration, cavities surrounded by small nodules, fibro cavitary TB or TB lesions maybe confined to the bronchial tree (endobronchial TB). Lymphatic spread (lymph-borne TB) This leads to mediastinal lymphadenopathy. Enlargement of lymph nodes around the middle lobe bronchus in children has a special importance. Extrinsic bronchial compression decreases the caliber of the middle lobe bronchus resulting in repeated bronchial infection i.e., obstructive pneumonitis and is called middle lobe syndrome. If the bronchial obstruction persists, the lobe becomes atelectatic then permanent damage in form of bronchiectasis occurs. It should be noted that the lymph drains ultimately in the blood stream. Accordingly, the fate of TB lymphatic spread can be ultimately similar to that caused by hematogenous TB. Hematogenous TB (blood steam spread) Blood-borne dissemination gives rise to miliary TB, which may present acutely but more frequently is characterised by 2–3 weeks of fever, night sweats, anorexia, weight loss and a dry cough. Hepatosplenomegaly may develop and the presence of a headache may indicate coexistent tuberculous meningitis. Auscultation of the chest is frequently normal but in more advanced disease widespread crackles are evident. Fundoscopy may show choroidal tubercles. The classical appearances on chest X-ray are of fine 1–2mm lesions (‘millet seed’) distributed throughout the lung fields, although occasionally the Page 3 of 12  appearances are coarser. Anemia and leucopenia reflect bone marrow involvement. Figure 2. Primary pulmonary tuberculosis. (1) Spread from the primary focusto hilar and mediastinal lymph glands to form the ‘primary complex’, which heals spontaneously in most cases. (2) Direct extension of the primary focus – progressive pulmonary tuberculosis. (3) Spread to the pleura – tuberculous pleurisy and pleural effusion. (4) Blood-borne spread: few bacilli – pulmonary, skeletal, renal, genitourinary infection, often months or years later; massive spread – miliary pulmonary tuberculosis and meningitis. Clinical picture Symptoms: TB may be accidently discovered during radiological examination despite absence of symptoms. Common chest symptoms are cough (dry or with expectoration) hemoptysis or chest pain. Exertional dyspnea can occur secondary to massive pleural effusion, tension pneumothorax, atelectasis or chronic miliary TB causing interstitial fibrosis. Page 4 of 12  TB can also present by night fever, sweating, anorexia, loss of weight, lassitude, easy fatigability, frequent colds, or even amenorrhea in females. Concurrent systemic involvement by TB may be another manifestation of extra pulmonary TB. Signs: Almost any combination of physical signs may be found e.g., consolidation, atelectasis, effusion, fibrosis, or pneumothorax. On the other hand, the signs may be slight e.g., apical crepitations. Attention should be paid for manifestations of extra pulmonary dissemination (organ TB) and for any TB complications e.g., amyloidosis (nephrotic syndrome), suprarenal affection, aspergilloma in a tuberculous cavity, TB empyema or pyo-pneumothorax from ruptured TB cavity, cor-pulmonale, malignancy (scar carcinoma), pericardial effusion, polyserositis, and respiratory insufficiency. Clubbing do not occur in pulmonary TB except if complicated by TB bronchiectasis, TB empyema or interstitial fibrosis. Lower limb oedema in TB may be related to hypoproteinemia in TB bronchiectasis or nephrotic syndrome in amyloid kidney or right heart failure from extensive TB. Differential diagnosis Because of the wide range of symptoms and sign of pulmonary TB, it can be included in the differential diagnosis of most respiratory diseases. MTB should be differentiated from infection by atypical mycobacteria which can cause manifestations similar to TB. Atypical mycobacterial species include, M. scrofulaceum, M. intracellulare and M. fortuitum. They can simulate tuberculous infections and occur more frequently in immunocompromised patients e.g., with HIV-infection (AIDS). Investigations The diagnosis is usually made in one of three ways: smear or culture of sputum (or other sample as pus, CSF, urine, biopsy tissue), or histology with the identification of caseating granulomas on biopsy. Bacteriological examination (is mandatory for TB diagnosis) Smear: Page 5 of 12  Using "direct microscopy" in the ZiehlNeelsen method, the films need < 5,000 AFB/ml to be positive. We use sulphuric acid and carbol fuchsin to identify the acid fast-alcohol fast bacilli which appear as "red bacilli”. Specimens used in smear examination includes 3 successive sample of sputum (expectorated sputum or induced sputum obtained by nebulized hypertonic saline) gastric lavage especially in children or bronchoalveolar lavage (BAL). Culture and drug sensitivity: Solid media (Löwenstein–Jensen, Middlebrook) takes 6 weeks or longer, although use of the mycobacterial growth indicator tube (MGIT) culture system (liquid media) can lead to positive cultures within days. Other rapid cultures are: Bactec-system which is a radiometric method using radioactive carbon (C14) in liquid media. Result of culture requires about 2 weeks. Nucleic acid amplification techniques include: Gene Xpert MTB /RIF assay: can simultaneously detect MTB and identify rifampicin resistance (which is strongly associated with MDR – TB) within 2hours and has been recommended by the WHO for use in regions with high rates of HIV/TB co-infection or MDR –TB. Polymerase chain reaction (PCR): This technique is capable of detecting one AFB/ml. It involves amplification of a single molecule of DNA of the tubercle bacilli within few hours to obtain millions of copies of the DNA of the TB bacilli. Chest X –Ray (CXR) (figure 3) Classically CXR shows upper lobe infiltrates with cavitation. May be associated with hilar or paratracheal lymphadenopathy. May show changes consistent with prior TB infection, with fibrous scar tissue and calcification. HIV – infected patients typically have less CXR changes and are less likely to have cavitary disease miliary pattern is more common in later stage of AIDS All patients with non – pulmonary TB should have a CXR to exclude or confirm pulmonary disease high resolution CT scan of chest (HRCT) can be also used for diagnosis of TB. Page 6 of 12 Upper fibro cavitary lesion Miliary TB Bilateral hilar lymphadenopathy Figure 3. Chest X-ray: major manifestations and differential diagnosis of pulmonary tuberculosis. Blood examination: Erythrocytes sedimentation rate is high. Complete blood picture: in acute miliary TB, there may be leukoamid reaction or thrombocytopenia secondary to be bone marrow infiltration by TB. Page 7 of 12  Serum electrolytes:(Na+ and K+) may show abnormalities (hyponatremia and hyperkalemia) in miliary TB secondary to suprarenal affection. In the latter condition cortisol level is low. Tuberculin test: This test study the "cell mediated immunity" which is influenced by the T- lymphocytes. (N.B: CD4 is the T-helper lymphocytes and CD8 is the T- suppressor lymphocytes). After 4-8 weeks from the initial infection a cell mediated i.e., delayed (type IV) hypersensitivity reaction to the (tuberculo- protein) is developed. It is demonstrated by intradermal injection of such protein. The injected material is the purified protein derivative (PPD) of the cultured tubercle bacilli (figure 4). The response to tuberculin test takes the form of a raised area of induration. Tuberculin skin test is read after 48-72 hour. An induration of 10 mm is considered as positive test. Positive test denotes TB infection either latent or active. False positive test occurs in BCG vaccinated person and infection with other non-MTB. Figure 4: Tuberculin test. A. inject of PPD in the forearm. B. reading of induration area after 48—72 hours. False negative tuberculin test i.e., negative test despite presence of tuberculous infection could be encountered in the following circumstances: Viral infections (measles). - Bacterial infections (typhoid). Fungal infection. - Renal failure. Lymphoma. - Sarcoidosis. Page 8 of 12  Use of corticosteroids - Immunocompromised person. Extremes of age - Overwhelming TB infection. Skin anergy Factors related to the tuberculin test can lead to false negative test e.g., chemical denaturation of the fresh tuberculin, improper storage, and injection subcutaneously instead of intradermally. Interferon gamma release assay (IGRA) IGRA two blood tests (T-spot. and quantiferon TB gold) are available and are based on the detection of IFN-Ύ released by T – cells in response to MTB – specific antigens. IGRA has high sensitivity, but low specificity i.e., a negative or low result rules out active or latent TB, but a positive result cannot differentiate between the two. Bronchoscopy may be needed to obtain bronchoalveolar lavage (BAL) in case of no sputum or lymph node sample if there is high clinical suspicion. Treatment Patient isolation during the 1st 2 weeks of treatment to decrease likhood of disease transimision. Utilisation of the mask in case of contact. The following table shows the different anti TB drugs with their usual side effects. 1st line anti TB drugs: Drug Usual side effects Monitoring ISONIAZID Peripheral neuritis –as INH interferes with SGOT/SGPT metabolism of vitamin B6 give it as (50 (INH) mg/day) – hepatitis – convulsions (Liver enzymes) RIFAMPICIN SGOT/SGPT Hepatotoxicity -jaundice (RMP) Serum bilirubin ETHAMBUTOL Retrobulbar (optic) neuritis (reversible Visual acuity red- with discontinuation of the drug)- not used green colour (EMB) in children discrimination Page 9 of 12 PYRAZINAIDE SGOT/SGPT Hepatotoxicity – gout (PZA) Blood uric acid Page 10 of 12  2ndline anti TB drugs: Drug Usual side effects Monitoring Hearing STREPTOMYCIN Ototoxicity, (decreed hearing, tinnitus). exam, audiogram, (SM) Nephrotoxicity urea & creatinine KANAMYCIN As streptomycin CYCLOSERINE Psychosis – personality changes – convulsions PAS GIT toxicity – hepatotoxicity -rash SGOT/SGPT ETHIONAMIDE Same as in PAS drug VANCOMYCIN Same as in streptomycin CAPREOMYCIN Same as in streptomycin but not for pediatric use INH = Isonicotinic acid hydrazide ** PAS = Para amino salicylic acid Treatment Strategy Multidrug regimens are indicated for all cases of active disease. Start treatment with 4 drugs (rifampin, isoniazid, pyrazinamide, ethambutol) for 2 months then continue with Rifampin and Isoniazid for another 4 months. In some cases, regime is extended for 9 months. Regimen should be adjusted according to drug sensitivity. DOT (directly observed therapy) is the one recommended by the WHO for treatment. Monitoring of the liver enzymes, blood count and visual disturbances are important during the course of treatment. Drug Resistance Patients who do not have a favorable bacteriologic response early during treatment present a difficult problem. Drug resistance may be primary due to infection by organism which is resistant to drugs. Page 11 of 12  Acquired drug resistance which occurs because of inadequate treatment or non- compliance by the patient. Drug resistance may be mono resistance to one drug or multi-drug resistance as in case of resistance to rifampin and isoniazid. These cases need special regimen of treatment for extended period of time with close follow up. In cases of MDR –TB, we do culture and sensitivity and give at least two drugs or more with documented sensitivity preferably under direct observation (DOT). Treatment of MDR – TB should be tailored according to the results of culture and sensitivity tests. At least three new drugs not given previously (one parenteral and two oral) to which TB bacilli are fully susceptible, are added to the regimen. In addition, drugs to which the organisms are partially susceptible or drugs. Latent TB infection is defined as a positive tuberculin test or IGRA, showing MTB infection but with a normal CXR and no symptoms. This represents the presence of a small total number of mycobacterial with good host immune system. It should be distinguished from active disease which is usually accompanied by symptoms and an abnormal CXR. Prevention (Vaccination) BCG has been given to more persons (between 3 and 5 billion) than any other vaccine. In Egypt it is part of the expanded program of immunization given to all children in the first 3 months of age. BCG does not protect against TB infection but decreases the incidence of most serious forms like military TB and TB meningitis. Page 12 of 12