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College of Medicine Al-Mustansiriyah University

Prof. Riyadh K Lafta

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tuberculosis infectious disease healthcare medicine

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This presentation details tuberculosis, covering its transmission, impact, diagnosis, and treatment strategies. It's a comprehensive overview of the disease aimed at a medical audience.

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Tuberculosis Prof. Riyadh K Lafta College of Medicine/Mustansiriyah University T.B is a bacterial, infectious disease caused by Mycobacterium Tuberculosis complex (Human, Bovis and Africana), these organisms are also known as tubercle bacilli (because they cause lesion called tubercle...

Tuberculosis Prof. Riyadh K Lafta College of Medicine/Mustansiriyah University T.B is a bacterial, infectious disease caused by Mycobacterium Tuberculosis complex (Human, Bovis and Africana), these organisms are also known as tubercle bacilli (because they cause lesion called tubercle) or acid fast bacilli (A.F.B) because it resist the acid decolorization during the staining process. T.B affects all races, all ages & all organs. Infection occurs almost exclusively through the respiratory system by inhalation of tubercle bacilli. The lung is the main organ affected. Each smear-positive PTB (pulmonary TB) will transmit infection to (10 – 15 persons) in year. Those who will be infected with TB will not necessarily get the disease, the immune system "walls off" the TB bacilli, which can remain dormant for years. About 5 -10 % of the infected individuals, have chance of developing TB disease during their lifetime. Nearly one third of the global population i.e. two billion people is infected with Mycobacterium tuberculosis and at risk of developing the disease. More than eight million people develop active Tuberculosis every year, and about two million die. Impact: More than 90% of global TB cases and deaths occur in the developing world, where 75% of cases are in the most economically productive age group (15-54 years). An adult with TB loses on average three to four months of work time, which results in the loss of 20- 30% of annual household income. The main reasons for the increasing burden of TB are: poverty, collapse of health infrastructure, weak national TB control programs and the impact of HIV. Iraq is considered to be a middle burden country with TB, and occupies rank 108 globally and 7 in eastern Mediterranean region among countries with TB burden size. According to WHO report, the estimated incidence of TB in Iraq is 45/100000 population (i.e. estimated total new TB cases is around 15000 per year), while the prevalence is 74/100000 and the mortality is 3/100000. ansmission of Infection? - Air Borne: When patients with PTB speak, particularly when they cough or sneeze, they produce an aerosol of droplets from the bronchial tree, each of which contains a number of bacilli, the number of infectious droplets projected into atmosphere by a patient is very high when coughing (3500) or sneezing (1 million). When they come into contact with air they rapidly dry and become very light particles, However, they still containing live bacilli, that remain suspended in the air. In enclosed space, the droplets can remain suspended for long time, and the bacilli remain alive for long time in the dark. The closer and more prolonged the contact with an infectious patient, the greater the risk of infection, as this linked to the density of the bacilli in the air the individual breaths and the amount of the air inhaled. - Ingestion: by contaminated un -pasteurized milk (M. bovis). - Rare routes of transmission: cutaneous, trans placental, & transsexual transmissions. Incubation period: Incubation period is 3-8 weeks in primary TB, and up to years in post primary TB Timetable of TB Time from infection Manifestation Primary complex, 3-8 weeks positive tuberculin skin test 3-6 months Meningeal, milliary, plural disease Up to 3 years GI, bone and joint, lymph node Around 8 years Renal tract inf. Post - primary disease due to From 3 years onwards reactivation or inf. Evolution of infection 1. Primary Tuberculosis: When a few virulent tubercle bacilli penetrate the pulmonary alveoli of a healthy person, they are phagocytosed by the alveolar macrophages, in which they multiply. Other macrophages and monocytes are attracted and participate in the process of defense against infection. The resulting (infectious focus) made up of inflammatory cells, is referred to as primary focus. The bacilli and the antigens that they liberate are drained by the macrophages through the lymphatic system to the nearest lymph nodes. Inside the lymph node, the T lymphocytes identify the M. tuberculosis antigens and are transformed in to specific T lymphocytes, leading to liberation of lymphokines and activation of macrophages that inhibit the growth of the phagocytosed bacilli. The inflammatory tissue formed in the primary focus is replaced by fibrous scar tissue in which the macrophages containing bacilli are isolated and die. This primary focus is the site of tuberculosis-specific caseating necrosis. This focus contains (1000-10000) bacilli which gradually lose their viability and multiply more and more slowly. Some bacilli can survive for months or years, these are known as (Latent bacilli) this is indicated by the development of a delayed-type hypersensitivity which can be demonstrated by tuberculin skin test and this process takes period about 6-8 weeks from the beginning of the infection. 2. Secondary focus: Post primary Before immunity is established, bacilli from the primary infectious focus or from the nearest lymph node are transported and disseminated throughout the body by lymph system and then via the blood stream. Secondary foci containing a limited number of bacilli are thus constituted, particularly in the lymph nodes, serous membranes, meningies, bones, liver, kidneys and lungs. As soon as an immune response is mounted, most of these foci spontaneously resolve. However, a number of bacilli may remain latent in the secondary foci for months or even years. Primary TB is mostly pulmonary and may be extra- pulmonary e.g. intestinal primary TB. In 80 – 90 % of infected individual's immunity will take the upper hand, ending in spontaneous healing, resolution fibrosis and calcification. In 10 – 20 % of infected individual virulence takes the upper hand and may result in active disease. This results in primary TB when initial infection causes the individual to develop clinical disease. In most instances, even where there are clinical signs present, immunity will get the role to play and the disease will regress spontaneously. Where it does not, progressive primary TB or disseminated TB may occur. When should tuberculosis be suspected? The onset of the disease is often insidious; symptoms often develop slowly, on several weeks. Chest symptoms are often nonspecific, cough is almost always present with sputum production. Possibly chest pain &/or dyspnea. Less commonly haemoptysis may occur. Systemic symptoms: fever in the evening (on average 38°C) heavy night sweat, loss of appetite, loss of weight & a general sense of malaise. Suspected TB patient is any patient have cough more than 3 weeks not responding to ordinary treatment. Case Definition: A case of T.B is defined as a patient on whom tuberculosis has been confirmed by bacteriology or diagnosed by a clinician. What determines case definition? 1. Site of T.B disease: T.B affects the lungs in more than 80% of cases & called pulmonary T.B. T.B affects various organs called extra pulmonary T.B. 2. Severity of T.B disease: Bacillary load, extent of the disease & anatomical site is considered in determining T.B disease severity. 3. Bacteriological result of sputum smear examination: a. Smear positive pulmonary tuberculosis (PTB) Either a patient with at least two sputum specimens positive for A.F.B by microscopy. Or patient with one sputum specimen positive for A.F.B & radiographic abnormalities consistent with active pulmonary T.B, decision by a physician to treat with a full curative course of anti T.B chemotherapy. -Or with at least one sputum specimen positive for A.F.B with culture positive for A.F.B - Under programmed conditions when microscopy lab services are available and diagnostic criteria are properly applied, Pulmonary T.B smear positive cases represent at least 65% of the total (PTB) cases in adults and 50% or more of all T.B cases. b. Smear negative (PTB): Either a patient fulfills all the following criteria. -Two sets (taken at least 2 weeks apart) of at least two sputum specimen negative for A.F.B. - Radiographic abnormalities consistent with active pulmonary TB & a lack of clinical response despite one week of broad spectrum antibiotics (except quinolones). - A decision by a physician to treat with full curative course of anti T.B chemotherapy. - Or a patient who fulfills the following criteria with three specimen of sputum smear negative for A.F.B, radiographic abnormalities consistent with active pulmonary TB, and a decision by physician to treat with full curative course of anti-TB chemotherapy. c. Extra – pulmonary TB: are patients with tuberculosis in organs other than the lungs (e.g. pleura, lymph nodes, abdomen, genitourinary tract, skin, joints and bones, meningies). Diagnosis should be based on one culture positive specimen or histological or strong clinical evidence consistent with active extra- pulmonary disease, followed by a decision by a clinician to treat with a full course of anti-TB chemotherapy. A patient in whom both pulmonary and extra-pulmonary tuberculosis has been diagnosed should classify as pulmonary case. 4. Case classification according to previous treatment.: On diagnosis, patients are classified for registration according to previous TB treatment: New case: Patient who has never had treatment for tuberculosis or who has taken anti T.B chemotherapy for less than 4 weeks. Relapse: patient who has been declared cured of sputum positive pulmonary T.B in the past by a physician after one full course of chemotherapy & now has become bacteriologically positive (at least one smear or culture) tuberculosis. Treatment failure: Patient who while on treatment remained or become again smear positive 5 months after commencing treatment. It is also a patient who was initially smear negative before starting treatment and become smear positive after second month of treatment. Treatment defaulter: patient who does not take drugs or interrupts treatment for two months or more & return to the health services with smear positive sputum consider as treatment failure or return with smear negative. He should continue his Rx. but from the start. Chronic cases: Patient who remained or became again smear positive after completing a fully supervised retreatment regimen. Diagnosis of pulmonary TB in adult: a. If after interview and clinical examination there is no evidence of another cardio pulmonary condition in a patient who presents with cough lasting for more than 3 weeks pulmonary tuberculosis should be suspected. Bacteriological examination of the sputum must be performed on 3 consecutive sputum for direct smear examination of A.F.B. Nodules: round shadow with clearly defined borders. Patchy shadow: irregular border infiltration. Cavities are the most characteristic sign of T.B. Some radiographic shadow show T.B sequel: Nodules that are fully or partially calcified. Satellite abnormalities. Fibrosis. Diagnosis of pulmonary Points to be remembered in the diagnosis of pulmonary T.B: 1.Over 80% of patients with smear positive pulmonary T.B have at least one or more respiratory symptoms for more than three weeks. 2.The most frequent respiratory symptom is the cough followed by expectoration. Over 90% of patients with smear positive pulmonary T.B develop cough while only 20% of them have haemoptysis. 3.The bacteriological examination of the sputum is the only way in which the diagnosis of pulmonary T.B can be confirmed. 4.X- Ray diagnosis of T.B is unreliable because other chest disease can look like T.B on x- ray. 5.The tuberculin test has a limited value in clinical work in adult but Over 90% with a cavitory pulmonary T.B or with extensive abnormal infiltration are smear positive, therefore a patient with cavitation on chest x ray & repeated specimen smear for A.F.B were negative, probably has a disease other than T.B. Disciplines in the management of TB 1. Physician should manage T.B cases without any deviation in combination of drugs, dosage, duration of treatment & type of regimen used. 1. Physician demands not only a detailed knowledge of the drugs available but also of the most appropriate regimen for the individual patient. 1. The available drugs must not be abused by inadequately trained doctors. 4. Anti T.B chemotherapy is by far the most important measures in the treatment of all forms of T.B and should be given to every patient with active disease while surgery plays a minor role. 5. It is wasteful to treat patients who do not need it and expose them to the risk of drug toxicity and to the domestic penalties as being labeled tuberculosis. 6. Hospitalization in itself has little or no effect on the outcome of treatment. A patient who takes the drugs regularly will do equally well whether treatment in or out of the hospital. However, regular & direct supervision of patients is of Para most important. 7. Inpatients treatment is indicated for severely ill, and for those with complications of T.B (e.g. haemoptysis, spontaneous pneumothorax) as for those with other serious co-existent disease requiring hospitalization. 8. Pregnant women with T.B should start or continue their treatment for T.B in the same way as other patients; however, Streptomycin should not be used because of the risk of toxicity to the inborn child. 9. The use of Rifampicin or Streptomycin for diseases other than mycobacterium diseases should be avoided or limited to very carefully considered indication. 10. Anti T.B drugs are relatively toxic & mild side effects are not uncommon, but in most cases no need for drug withdrawal. Minor side effects are relatively few cause discomfort, they often respond to symptomatic or simple treatment. Major side effects are those giving rise to serious health hazard & required discontinuation of the drug & referral to chest physician. 11. Major (essential) anti T.B drugs: There are 3 main properties of anti T.B; bactericidal ability, sterilizing ability and ability to prevent resistance. They posses these properties to different extent. Isoniazide (H) Rifampicin (R) streptomycin (S) Ethambutol (E) Pyrazinamid (Z) All are able to cure 100% of new cases with sensitive bacilli. Treatment of T.B is the main weapon against the fight of the disease, the bases of this treatment is chemotherapy. What is D.O.T.S? Direct Observation Treatment Short course (D.O.T.S). D.O.T.S is the new W.H.O. strategy, it is based on one priority, to ensure that all sputum smear positive pulmonary T.B complete a full course of chemotherapy with direct observation of swallowing the drug during the period of treatment or at least during the initial phase of treatment. The main advantage of D.O.T.S is that treatment is carried out entirely under program supervision. No concealed irregularity can occur as it can in self- administration regimen, the treatment observer ensures that medicines are taken at the correct interval & in the correct dosage & with that certainly come benefits both for the patient & the community. Perhaps the most immediately apparent are: The high cure rate associated with assured completion of treatment. Dramatic reduction in development of drug resistance. Adverse effects and treatment complications can be quickly identified & addressed. The basic rules for efficient T.B treatment is an initial intensive phase associating at least four major anti T.B drugs administrated daily during two months followed by continuation phase during the next four months with two major anti T.B drugs. D.O.T.S strategy required five conditions: The political will of the government. Existence of laboratories network to identify smear positive pulmonary T.B patients. A network of peripheral health centers. Regular supply of drugs and reagents. Organization of permanent surveillance system in order to supervise the tasks of program and to evaluate its epidemiological impact. To cure T.B patients. To prevent death. To prevent relapse. To decrease transmission to others. W.H.O recommended certain regimens for each patient category: Category I: Smear positive case or smear negative severely ill patient or seriously ill extra pulmonary T.B, e.g. T.B meningitis, Milliary T.B, T.B pericarditis & T.B peritonitis, new cases that are not treated previously as pulmonary TB or serious extra pulmonary T.B (meningitis). First line standard regimen (2HRZ E or (S) +4RH) Category II: Failure, after failure of a default, defaulter, relapses. First line treatment regimen (2HRZES + 1HRZE + 5HRE). Category III: Less severe sputum smear negative pulmonary TB and less severe type of extra pulmonary TB. First line standard regimen (2HRZ + 4RH). Category IV: Chronic or drug resistant TB cases. Second line regimen. Optimal management of new cases of T.B Initial daily intensive phase: is supervised by medical staff or (his family or others). Containing Rifampicin 450 mg if the patient weight < 50 Kg & 600 mg if his weight is more. Continuation phase: Preferable to be supervised on the day of receiving the drug, contain daily Rifampcin & INH for next 4 months. Possible alternative regimens for treatment category Alternative T.B. Rx. T.B. regimens reatment category T.B. Patient Initial Phase Continuation  New S + ve patient  PTB  New S – ve patient 2HRZ E or I  4HR or 6HE PTB with extensive parenchyma (S) involvement  New cases of severe extra PTB  Sputum S + ve 2HRZES  Relapse II  + 5HRE Treatment failure  Treatment after interruption 1HRZE  New S – ve PTB (other than in III category I) 2HRZE 4HR or 6HE  New less severe of extra PTB NOT APPLICABLE  Chronic cases (still sputum refer to WHO guidelines for( IV positive after supervised use of second line drugs in compliance, improper drug regimen, etc.).Primary Drugresistance resistance TB is prevented by giving 6the patient patients (DR) combination of drugs. Secondary (acquired) TB resistance is expected to be developed in: A large bacillary population such as patient with cavitations. Inadequate regimens (inappropriate drugs, insufficient dosage). Treatment of DR TB should be done by or in close consultation with an expert in the management of these cases & in hospital. A single new drug should never be added to a failing regimen. Treatment duration for DR TB patient may last 18- 24 months by using 4-6 drugs (capriomycin, cyclocerin, ethionamide, levofloxacine, and PAS). Management of contacts of smear positive cases Children age & adults: any person who coughs & who was in contact with smear positive index case (smear positive pulmonary TB patient) should have three sputum exam…. Children

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