pulmonary tb for 5th years students

Pulmonary tuberculosis

Pulmonary tuberculosis

By Dr alaa metwally Ass. Prof. of chest diseases

ObjectivesKnow what is TB, historical overviewDefine what bacteria can cause tuberculosis.Describe how someone can get TB .Describe how TB is diagnosed.Describe the treatment process for someone diagnosed with TB..

How long has TB been infecting humans?TB disease has been found in the mummies of ancient Egyptians and Indians

Global problem for thousands of years

Consumption, white plague, Captain of the men of death!

Cause of TB identified 24 March 1882 by Dr. Robert Koch

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The distribution of TB in mummies shows that it has been geographically widespread since early human history.

A potted history of TB ((Tubercle Bacillus1882 TB bacilli identified by Koch1907 TST - tuberculin skin test (von Pirquet) 1919 BCG Bacille Calmette & Guerin vaccine1943 Schatz & Waksman discover streptomycin1948 BMRC trial of streptomycin vs bed rest1952 Development of isoniazid1966 Development of rifampicin1978 Short course chemotherapy (DOTS)

5TB in the United StatesFrom 1953 to 1984, reported cases decreased by approximately 5.6% each yearFrom 1985 to 1992, reported cases increased by 20% (HIV resurgance)25,313 cases reported in 1993Since 1993, cases are steadily declining

Appendix 12 - Fundamentals of TB Presentation5

What is TB?TB is a disease caused by a bacteria (single-cell organism), the tubercle bacillus, TB.

More specifically, it is a type of mycobacteriamyco means waxy in latin and refers to TBs waxy cell wallThere are 70 different types of mycobacteriaKilled in the sun light Killed by temperature 60cAerobic, gm+ve, acid fast, alchohol fast

6Not all mycobacterias are harmful but MTB is the most harmful to humans

Five types of M.tuberculosis: human, bovine, murine, avian, and reptilian. Only human and bovine are important clinically.

Direct sunlight kills the bacilli in 5 minutes.Bacilli may survive in dark for 5 months.

In sputum, bacilli resist even 5% phenol for several hours, but 1% sodium hypochlorate liquefies the sputum and kills tuberculous bacilli rapidly.

Tuberculous bacilli are destroyed by heat of 60oC at 20 minutes and 70oC at 5 minutes.

M.tuberculosis and M.bovis

Size 0.3-0.6 micron x 2-4 micron Celll wall;A)Plasma membrane; Peptidoglicans Arabinogalactan Micolik aside B)Complex polymers

Antigens; 38 kd, 88kd, Antigen 5, Antigen A6, Lipoarabinomannan(LAM), Cord Factor

What is TB? The scientific name for the TB microbe is Tubercle bacillus or Mycobacterium tuberculosis M.tb

99TB has lots of names, and lots of ways to refer to itThe TB bacteria is named for both its appearance (myco) and the disease it causes (tuberculosis). Other names:baceria/bacterium; bacillus/bacilli; germ; critter; microbe; ect.

Transmission95% TB is an airborne disease, transmitted by particles, or droplet nuclei that are expelled when persons who have pulmonary or laryngeal TB sneeze, cough, speak or sing1.4% By drinking infected milk1.4% Inoculation of bacilli by skin and mucosal contusionsCongenital TB

11Airborne Transmission ofTB

Transmission occurs when an infectious person coughs, sneezes, laughs, or sings Spread person to person through airborne particles that contain M. tuberculosis, called droplet nuclei

Prolonged contact needed for transmission 10% of infected persons will develop TB disease at some point in their lives


12InfectiousnessPatients should be considered infectious if they: Are undergoing cough-inducing procedures Have sputum smears positive for acid-fast bacilli Are not receiving treatment Have just started treatment, or Have a poor clinical or bacterial response to treatment Have cavitary disease

Extra-pulmonary TB patients are not infectious


TB Infection and DiseaseThe lungs are the most common place for TB. This is known as pulmonary TB.TB of the voice box is the second most common and is usually called laryngeal TB.

Not all TB infections lead to TB disease

Latent TB infection ( LTBI) occurs when the immune system has contains TB and prevents disease. Active TB disease refers to the time when TB breaks out and causes disease.

TB Infection & DiseaseThere are 2 Categories of TB: Latent & ActiveTB infection of the lungs fall into 2 categories of disease: Latent TB or Active TB.

Latent TB means a person is infected by TB bacteria, but not diseased, cannot infect others, and is not coughing or appearing sick.

Latent TB means the bodys immune system has contained the infection.

TB - Infection & DiseaseCategories of TB - ActiveActive pulmonary and laryngeal TB means a person infected with the TB bacteria is sick and can infect others unless they are taking medicine prescribed by their physician to treat TB.

17LTBI vs TB DiseaseLTBITB DiseaseTubercle bacilli in the bodyTST or QFT-Gold result usually positiveChest x-ray usually normalChest x-ray usually abnormalSputum smears and cultures negativeSymptoms smears and cultures positiveNo symptomsSymptoms such as cough, fever, weight, lossNot infectiousOften infectious before treatmentNot a case of TBA case of TB


18Increased Risk for TB DiseasePersons more likely to progress from LTBI to TB disease include;

HIV infected personsThose with history of prior, untreated TBUnderweight or malnourished personsInjection drug useThose receiving TNF- antagonists for treatment of rheumatoid arthritis or Crohns diseaseCertain medical conditions


Common Sites of TB DiseaseLungsPleuraCentral nervous systemLymphatic systemGenitourinary systemsBones and jointsDisseminated (miliary TB)Pericardial disease

Source: CDC, 2001.

TB is most common in the lungs.Pericardial disease very common in this region and is one of the serious forms of TB2005 statistics from ETR in Botswana 88% of patients with TB disease had pulmonary TB

Source: Centers for Disease Control and Prevention. Self-Study Modules on Tuberculosis. 2001. Atlanta, GA. Mod 1, Fig 1.7. Accessed from: http://www2a.cdc.gov/phtn/tbmodules/modules1-5/m1/con6b.htm

What is happening after infection

(Pathology)

Primary pulmonary TBThe first meeting of the TB bacillus with immune system, is the Primary TBOther terms, childhood TB

Stage IDroplet nuclei containing between one to 10 bacilli and a diameter close to 10 m are expelled with the cough, suspended in the air and transported by air currents.

Some of these droplet nuclei, usually larger than 10 m, are inhaled and anchored in the upper respiratory tract

The mucus and the ciliary system of the respiratory tract avoid further progression of mycobacteria.

Dannenberg, Jr AM Immunol Today 1991

Stage II:Symbiotic stageSubsequently, alveolar macrophages phagocytose the inhaled bacilliThese first macrophages are unable to kill mycobacteria The bacilli continue their replication inside these cells Logarithmic multiplication of the mycobacteria takes place within the macrophage at the primary infection site.

Stage III: CMI and DTH 2-4 weeks, stage of tuberculin conversionTwo or three weeks after the initial M. tuberculosis infection, a cell-mediated immune response is fully established While CD4+ T helper cells activate the macrophages to kill the intracellular bacteria and finally cause epithelioid granuloma formation,CD8+ suppressor T cells lyse the infected macrophages, resulting in the formation of caseous granulomas with central necrosisThe only evidence of a real and effective infection is a positive TST

The hallmark of active TB infection is tubercle: The predominant cells are non- lymphoid mononuclear cells. Epithelioid cells. Langhan's giant cells. Central necrosis. The pathological hallmark of TB is the granuloma formation

Granuloma

The prepheral rim of lymphocytes and mononuclear cells. Epithelioid cells (large activated macrophages) Langhan's giant cells. Fused actviated macrophages with multiple nucleiCentral necrosis.

Stage IV:Liquefaction Rapid replication of Bacilli, stage of symptomsReactivation, liquefaction, cavitationBacilli begins to replicate Extra cellularly Airborde spread is possible; Transmission

The primary complex The combination of

Enlarged hilar L.node andPulmonary focous of caseastion andThe intervening lymph vesselIs called the primary complexWhen this pulmonary focus, and L N are calcifiedThe complex is called Rank Triad

How are these stages presented clinicallyProgression of the pulmonary parenchymal component leads to enlargement of the caseous area and may lead to pneumonia, atelectasis.

This is more likely to occur in young children than in adolescentsThe child usually appears ill with symptoms of fever, cough, malaise and weight loss

This form presents classic signs of pneumonia, including tachypnea, dullness to percussion, nasal flaring, grunting, egophony, decreased breath sounds, and crackles

Fate of the primary complex95% of the primary complex is resolved spontaneously

Only 5 % will progress to progressive primary TB Facors that may lead to progress of the primary infection include;Immunosuppression by drugs or diseasesMalnutritionHeavy load of bacilli, milliary TB

32TB Disease

Occurs when immune system cannot keep bacilli contained

Bacilli begin to multiply rapidly

Person develops TB symptoms


Features of primary TB (Childhood TB)

50 % of pediatric patients may remain asymptomatic with subtle abnormalities on the chest radiographPrimary TB in children has a low bacillary load and cavities are also rarely present.The disease more often progresses from an initial or primary infection. Children younger than five years old may develop disseminated TB in the form of miliary disease or Tuberculosis every where

Common Sites of TB DiseaseLungsPleuraCentral nervous systemLymphatic systemGenitourinary systemsBones and jointsDisseminated (miliary TB)Pericardial disease

Source: CDC, 2001.

TB is most common in the lungs.Pericardial disease very common in this region and is one of the serious forms of TB2005 statistics from ETR in Botswana 88% of patients with TB disease had pulmonary TB

Source: Centers for Disease Control and Prevention. Self-Study Modules on Tuberculosis. 2001. Atlanta, GA. Mod 1, Fig 1.7. Accessed from: http://www2a.cdc.gov/phtn/tbmodules/modules1-5/m1/con6b.htm

Symptoms vary according to the degree of airway irritation and obstructionFrequently a persistent cough that may mimic pertussis and Mild fever70 % of the primary foci are subpleural, 25% of cases have multiple parenchymal foci A common radiographic sequence is adenopathy followed by localized hyperinflation and then atelectasis of contiguous parenchymaAdenopathies are more striking than parenchymal focus Adenopathies heal with calsification

Primary pulmonary Tuberculosis

Pulmonary InfectionAffected regional lymph nodes attach to the bronchus

In some children, particularly infants, the lymph nodes continue to enlarge, resulting in lymphobronchial involvement, in which the affected bronchus may become partially or totally obstructed (epi-tuberculosis)

The area of caseation may discharge into a bronchus, resulting in the formation of a cavity with possible endotracheal spread

The most frequently affected lobes are the right upper, the right middle, and the left upper lobe

Primary TB in adult...The differences Primary infection in adolescent and adult occur between the age of 16-30 years, The pulmonary component overshadows the glandular component, Rigid structure and increase diameter of bronchi make its occlusion and stenosis less common, Local progression more common.Primary pleural effusion more common.Haematogenous spread is more common in those who developed pleural effusion.

Pleural InvolvementPleural involvement may result from direct spread of caseous material from a subpleural parenchymal or lymph node focus, or from hematogenous spread

The presence of caseous material in the pleural space may trigger a hypersensitivity reaction, with the accumulation of serous straw-colored fluid containing few tubercle bacilli

This exudate has a high protein count and lymphocyte predominance; the number of polymorphonuclear cells depends on the acuteness of onset

Although direct microscopy often is negative, culture yields may be as high as 70 percent

Pleural involvement85 % acute onset of fever, 52 % chest pain on deep inspiration28 % shortness of breath

Pleural effusion due to TB usually occurs in older children The pain accompanies the onset of the pleural effusion, but after that the pleural involvement is painless. Fever usually persists for 14-21 days.The signs of pleural effusion include tachypnea, respiratory distress, decreased breath sounds, dullness to percussion,and occasionally, features of mediastinalshift.

Post- primary TB, secondary TBAny forms other than primary pulmonary TB is termed ; post primary TB, secondary TB, reactivation TB, adulthood TB

Disease names related to different clinical forms of TB Name Clinical formPhthisis Original Greek name for TBLung Sickness TBConsumption TBLupus vulgaris TB of the skinMesenteric disease TB of the abdominal lymph nodesPotts disease TB of the spineScrofula TB of the neck lymph nodesKing's evil TB of the neck lymph nodesWhite Plague TB especially of the lungsWhite swelling TB of the bonesMiliary TB Disseminated TB

Who is a TB Suspect?

Any person who presents with symptoms or signs suggestive of TB, in particular cough of long duration (more than 2 weeks).Source: WHO, 2003

This WHO definition is also the Botswana definition for a TB SuspectProlonged cough alone is enough to make one a TB suspectCertainly people who present with TB will most likely have other symptoms, but the basic definition is very simple

Source: Treatment of Tuberculosis: Guidelines for National Programmes, Third Edition. Geneva (Switzerland), World Health Organization; 2003 [cited September 22, 2007]. Available from: http://whqlibdoc.who.int/hq/2003/WHO_CDS_TB_2003.313_eng.pdf.

Diagnosis of TB

By Dr alaa metwally Ass. Prof. of chest diseases

Even if a Skin Test is Negative

ChicllsFFeverTHINK TB!ChillsFatigueDifficultyin BreathingAnorexiaLossof AppetiteNight sweatsCoughingup Blood

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Diagnosis of TuberculosisPriority is in diagnosing and curing infectious casesALL persons with TB symptoms should also be tested for HIVRoutine HIV testingRapid HIV testing available in all public health facilities

Case Finding Highest priority to find and cure infectious cases: people with smear-positive PTBTwo ways of identifying TB cases:Passive case finding: illness diagnosed when patient presents for medical care at health facilityActive case finding: health workers actively search for patients with TB in the community

Emphasise that when a patient presents for care at a medical facility, the provider must ACTIVELY pursue the diagnosis of tuberculosis if a cough has been present for 2-3 weeksAsk participants to think of an example of active case finding. Possible answer: contact tracing

Case Finding Most common tools for case finding include:History takingPhysical examinationSputum examinationX-ray examinationTuberculin skin testing

Active Case FindingContact investigation most common method Other methods include special surveys based on:Geography Targeted testing of defined populations (e.g., schools, prisons)

Clinical PresentationTake a thorough history for each patientDetermine if signs and symptoms point to pulmonary or extrapulmonary TBAlso obtain medical and social historyDo a general physical examination with additional care to detect signs of tuberculosis

Medical HistoryHave you had close contact with someone with TB?Do you have a cough? How long, dry, productive, colour?Is blood present in your sputum?Do you have chest pain? When & where?Do you have shortness of breath? How long?Do you sweat profusely at night?Have you lost weight?When did you start losing weight?When did you lose your appetite?How long have you been feeling weak and tired?Do you smoke?Have you previously been tested for TB?Do you know your HIV status?Source: Chiang C-V et al., 2007.

Taking a good medical history is the first step to diagnosis when a patient presents with symptomsThere is a correlation between cigarette smoking and the risk of developing active TB. There is also an increased risk of TB relapse.Research indicates that smoking interferes with macrophage and ciliary function

Source: Chiang, C-V et.al., Associations between tobacco and tuberculosis, Int J Tuberc Lung Dis. 2007; 11(3):258-262.

53Symptoms of TBProductive prolonged cough*Chest pain*Hemoptysis*Fever and chillsNight sweatsFatigueLoss of appetiteWeight loss*Commonly seen in cases of pulmonary TB


54Chest x-RayObtain chest x-ray for patients with positive TST results or 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


Role of RadiographyChest X-Ray (CXR) can support a diagnosis of PTBNot used routinely for follow-upPTB can exist with normal CXRMust be interpreted with other informationHistory and examSputum smear resultsAlso useful in diagnosing other types of TB, especially in bones, joints, and spine

Refer to 5.3.4 in Botswana National Tuberculosis Programme ManualRadiography has more than 90% sensitivity but only 65-70% specificity for detecting PTB. A chest x-ray is an important tool in supporting the diagnosis of PTB in symptomatic individuals whose sputum smears are negative for AFB but it is not possible to diagnose PB using chest x-rays only. Therefore, always request sputum smear examination for all TB suspects. Radiography is also useful in diagnosing other types of TB, particularly disease of the bones, joints, and spineRadiographic appearances suggestive of active TB: Shadows in one or both upper zonesCavities in one or both upper zonesMiliary patternPersistent shadows after pneumonia treatmentPleural effusionIntrathoracic adenopathyPericardial effusionA combination of any of the above, especially in HIV-infected patientsAll district hospitals have x-rays and radiology technicians Ask the question: What is the role of x-ray in a smear positive patient that completed treatment?

Courtesy of: San Francisco City and County Dept. of Public Health, TB Division

This is a pretty typical adult type TB with cavitary disease in both upper lobes, relative sparing in lower lobes

Image courtesy of San Francisco City and County Dept. of Public Health, TB Division

62 m c cough

LUL cavities and bilateral endobronchial spreadDdx: TB, CA

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69 m with worsening COPD

LUL cavitary lung opacity; TB Ddx:CA, abscess

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Right lung from elderly homeless man showing cavitation and consolidation Cavitation, consolidation of RUL in a 25 y woman. Sputum smear was positive for AFB.

Diagnosis of Active TB

60DPThe picture on the left shows the right lung from an elderly homeless man who died of TB. Consolidation of granulomatis tissue and cavitation can be seen.The chest x-ray is from a 25 year old Somali woman. It shows what the pathologic specimen seen on the left may look like on x-ray. The right upper lobe of the right lung has numerous areas of cavitation and consolidation. The womans AFB sputum smear was positive.RIAReference 7

Value of radiology in TB : Early detection of TB.The extent of lesions.Response to treatment.Follow up.

Bacterilogical tests

63Sputum examination for AFB Sputum specimens are essential to confirm TBSpecimens should be from lung secretions, not salivaCollect 3 specimens on 3 different daysSpontaneous morning sputum more desirable than induced specimensCollect sputum before treatment is initiated


64Smear ExaminationDirect sputum smear examination is the most simple, cheap tool in Dx of TB.TB is considered in patients with smears containing acid-fast bacilli (AFB)

Use subsequent smear examinations to assess patients infectiousness and response to treatment


Sputum Ziehl Nielsen stainingZiehl Nielsen is a stain for TB Bacilli, First, smear is heated to dissolve lipids in the cell wall to allow dye to penetrate cell wall. after heating the primary stain,strong carbol fucsin is applied.Decolorization of the smear by strong alchohol 70%, or conc sulphuric acid.The counter stain, methelen blue is then applied.

Direct Microscopy is the most reliable and cost effective way to identify persons who are most likely to transmit TB to others

ITECH, 2006 University of Alabama at Birmingham, Department of Pathology

Two (2) or more positive sputum smears provide the most reliable diagnosis of pulmonary TB disease. It is inexpensive and widely available throughout Botswana, and it identifies the persons who are most infectious and so most important to treat from a public health perspectiveSource: left- ITECH, 2006Source: right- PEIR Digital Library [database on the Internet}. University of Alabama at Birmingham; Department of Pathology. Cited 2008 Feb 4. Image #2885. Available from: http://peir2.path.uab.edu/pdl/dbra.cgi?uid=default&view_search=1.

67Culture, sputum, fluidsUsed to confirm diagnosis of TBCulture all specimens, even if smear is negativeInitial drug isolate should be used to determine drug susceptibility


Culture of mycobacteria is a much more sensitive test than smear examination and has been estimated to detect 10-100 viable mycobacteria per ml of sample and in case of active disease they are found to be 80% sensitive and 99% specific.Culture-based Methods

Media used for cultivation may either be;

Solid media (6-8 weeks):Lowenstein Jensens (L-J) media,an egg-based medium

Middlebrook 7H10 and 7H11 are agar-based media.Liquid media (few days to 2 weeks):Middlebrooks 7H9. Bactic 460, based on assesment of radiolabelled CO2 consumptionbetter but expensive,

Immunological tests

Tuberculin Skin Test TSTTST is done by intradermal injection of 0.1 ml of PPD into the volar aspect of the forearm.Result is red 72 hours later.TSTPositive supports but does not make diagnosisNegative does not exclude TB as possible diagnosis

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Reading the Tuberculin Skin Test (TST)Measure reaction in 48 to 72 hoursMeasure induration, not erythema (redness)Record reaction in millimeters, not negative or positiveEnsure trained health care professional measures and interprets the TST (PPD)

73Main Point: quick basic review on reading TST. Induration vs. redness. Document in mm not just negative or positive.

#16

TST result > 5mm Contact with infectious cases Abnormal Chest X ray HIV infection and other immunocompromised>10 mm Certain medical risk factors: Hodgkin, diabetes Mellitus , renal diseases, malnutrionBirth or previous residence in high prevalence areasOccupation in health care field, exposure to patients with TBClose contact with a high risk adult Residence in long term care or correction facilities>15mm No risk factor

75False Positive TST ReactionsNontuberculous mycobacteriaReactions are usually 10mm of indurationBCG vaccinationReactivity in BCG vaccine recipients generally wanes over timePositive TST results is likely due to TB infection if risk factors are presentBCG-vaccinated persons with positive TST result should be evaluated for treatment of LTBIQFT is able to distinguish M.tb from other mycobacteria and BCG vaccine


76False Negative TST ReactionsAnergy, or inability to react to TST because of weakened immune systemRecent TB infection (2-10 weeks after exposure)Very young age (newborns)Recent live-virus vaccination can temporarily suppress TST reactivityPoor TST administration technique (too shallow or too deep, or wheal is too small)


77BoostingSome 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 tuberculinPositive reactions to subsequent tests may be misinterpreted as new infections rather than boosted reactions


78Two-Step Testing - 1A strategy for differentiating between boosted reactions and reactions caused by recent TB infectionUse two-step testing for initial (baseline) skin testing of adults who will be re-tested periodically2nd skin test given 1-3 weeks after baseline


79Two-Step Testing - 2If the 1st TST is positive, consider the person infectedIf the 1st TST is negative, administer 2nd TST in 1-3 weeksIf the 2nd TST is positive, consider the person infectedIf the 2nd TST is negative, consider the person uninfected at baseline


The QuantiFERON-TB test (QFT-TST).Was approved by the FDA in 2001 as an aid for detecting latent TB infection. QFT is a blood test that measures interferon-gamma released from sensitized lymphocytes in whole blood incubated overnight with purified protein derivative (PPD) from M. tuberculosis and control antigens. The TST and QFT do not measure the same components of the immunologic response and are not interchangeable. Due to lack of specificity of this test, it has not been used widely.

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The QuantiFERON-gold test (QFT-G).QuantiFERON gold (G) test; using more specific antigenic protiens which are mixtures of synthetic peptides simulating two proteins present in M. tuberculosis: early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10).

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ESAT-6 and CFP-10 are secreted by all M. tuberculosis and pathogenic M. bovis strains. Because these proteins are absent from all Bacille Calmette-Gurin (BCG) vaccine strains and from commonly encountered nontuberculous mycobacteria (NTM) except M. kansasii, M. szulgai, and M. marinum, QFT-G is expected to be more specific for M. tuberculosis than tests that use tuberculin purified protein derivative (PPD) as the antigen.

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On May, 2005, this new in vitro test, QuantiFERON-TB Gold, received final approval from the (FDA) as an aid in diagnosing Mycobacterium tuberculosis infection, including both latent tuberculosis infection (LTBI) and tuberculosis (TB) disease. This enzyme-linked immunosorbent assay test detects the release of interferon-gamma (IFN-g) in fresh heparinized whole blood from sensitized persons when it is incubated with mixtures of synthetic peptides simulating two proteins present in M. tuberculosis:

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QFT-G is not affected by prior BCG vaccination and is expected to be less influenced by previous infection with nontuberculous mycobacteria, while TSTs are variably affected by these factors.

However, there is still little data in children and immunosuppressed (HIV) individuals.

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QFT-G does not trigger boosting response because it does not expose persons to antigen. Injection of PPD for the TST can boost subsequent TST responses, primarily in persons who have been infected with NTM or vaccinated with BCG.

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After incubation, the concentration of IFN-g in the plasma is determined by ELISA by using the reagents included in the test kit. The amount of IFN-g released is determined by subtracting the amount in the nil from the amount in the ESAT-6, CFP-10, or mitogen-stimulated plasma. QFT-G test results can be calculated by using software provided by the manufacturer.

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Biochemichal tests

Biochemical testsNiacin accumulation testp- nitrobenzoic acidNitrate reduction testCatalase test Pyrazinamidase testthiophen-2-carboxylic acid hydrazideTuberculostearic acid Radioactive Bromide Partition TestA basic indolic compoundGlutaraldehyde test

Adenosine deaminase activityA non-specific product of activated host T-lymphocytes. Its normal serum level is 8-20 IU/LIs an enzyme involved in the metabolism of purines. Its presence is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues.The utility of ADA determination in body fluids (spinal, pleural, ascitic, pericardial)

The specificity is very high in fluids with a lymphocyte-to-neutrophil ratio higher than 0.75. The suggested laboratory cut-off of ADA activity is 40 U/L for pleural, peritoneal and pericardial fluids and 10 U/L for cerebrospinal fluid.

Biopsy

Granuloma formation

Treatment for Active TBWhen a person with active TB is diagnosed, they should be;

Isolated from other people until the medication begins to kill the bacteria- usually 2 weeks.Notification of the local health authorities.HIV screeningContact monitoringMedical treatment initiation

93Treatment of Latent TB InfectionDaily Isoniazid therapy for 9 months Monitor patients for signs and symptoms of hepatitis and peripheral neuropathy

Alternate regimen Rifampin for 4 months


Treatment for Active TBTB is curable, IF it is diagnosed early and appropriate treatment is started promptly.Active TB can be spread to other people if the person is not taking medication to kill the bacteria!

Treatment for Active TBThe CDC recommends that infections due to Mycobacterium tuberculosis be treated with several drugs in addition to INH: Rifampin, Ethambutol, Streptomycin, and Pyrazinamide.

TreatmentThe Aims of anti-TB Treatment

To cure the patient of TBTo prevent death from active TB or its late effectsTo prevent TB relapse or recurrent diseaseTo prevent the development of drug resistanceTo decrease TB transmission to others.

96Mortality rates are higher with HIVRapid progression of TBDelays in seeking careDelays in making the diagnosis of TB

Antituberculosis Drugs Currently UsedFirst-line DrugsIsoniazidRifampinRifapentineRifabutinEthambutolPyrazinamide

Second-line DrugsCycloserineEthionamideLevofloxacinMoxifloxacinGatifloxacinP-Aminosalicylic acidStreptomycinAmikacin/kanamycinCapreomycinLinezolid

DrugDaily dose mg/kg (max)Weekly 2 times a week mg/kg(max)Side effectIsoniazid510(300mg)2040(900mg) hepatitis , neuritishypersensitivityRifampin1020(600mg)1020(600mg)Orange coulor of urine, vomiting, hepatitis, influenza like syndrome, trhombocytopenia, Pyrazinamide2540 (2000mg)5070 (4000mg)Hepatotoxick hiperrisemi,artralgia,GS symptomsEthambutol15-25(2500mg)50(2500mg)Optic neuritis, GS symptoms after 7 years of age Streptomycin20-40 (1000mg)Ototoxidity , nefrotoxic Ethionamide1020(1000mg)-GS symptoms, hepatotoxic,, hypothroidy

TreatmentDivided into two phases:

Intensive phase (all 4 drugs) for 2-3 months depending on if the patient has been treated before.

Continuation phase (rifampicin and isoniazid) for 4-7 months, depending on whether you have been treated before. 7months continuation phase , for; cavitary lesions, twice weekly regimen, retreatment, relapse.

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100Treatment of TB DiseaseInclude four 1st-line drugs in initial regimenIsoniazid (INH)Rifampin (RIF)Pyrazinamide (PZA)Ethambutol (EMB)Adjust regimen when drug susceptibility results become available or if patient has difficulty with any of the medicationsNever add a single drug to a failing regimenPromote adherence and ensure treatment completion


Steroid; indicationsMeningitisPleural involvementPericarditisPeritonitisSevere Miliary TBAtelectasis or obstruction

2 mg/kg/day for 15 days. than in decreased doses, Stop 4-6 weeks after

102Improving AdherenceAdherence is the responsibility of the provider, not the patient and can be ensured by:Patient educationDirectly observed therapy (DOT)Case managementIncentives/enablers


103Directly Observed Therapy (DOT)Health care worker watches patient swallow each dose of medicationDOT is the best way to ensure adherenceShould be used with all intermittent regimensReduces relapse of TB disease and acquired drug resistance


Indication of surgery in TB Large cavity with high bacillary load not responding to medical tttMassive hemoptysisDestroyed lobe or lung causing V/Q mismatch.Extensive pleural fibrosis causing restriction of ventilation.Localized post TB bronchiactasis.Persistent broncho-pleural fistula.

105Clinical Monitoring Instruct patients taking TB medications to immediately report the following:RashNausea, loss of appetite, vomiting, abdominal painPersistently dark urineFatigue or weaknessPersistent numbness in hands or feet


Treatment outcomes Complete cure; persistent sputum veTreatment failure; persistent sputum +ve 5 months during ttt.Relapse; conversion to sputum ve on starting ttt, then recurrence to +ve after ttt completion.Death; during treatment or after ttt completion by TB complication.

Thank you

pulmonary tb for 5th years students

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