Presented By :Ala’a Al-Dlahmeh

Pulmonary

tuberculosis

Supervised By: Dr. Waleed Al-

Momani

Department of Allied Medical

Science

Al-Balqa' Applied University

Pulmonary

Tuberculosis

Definitions

Tuberculosis or TB (tubercles bacillus) is :

a contagious bacterial infection that attacks the lungs can also transmitted to other parts of the body.

A Global public health Emergency :

is the number one single infectious disease killer, taking nearly 3 million lives per year .

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Causes

Mycobacterium tuberculosis Mycobacterium africanum Mycobacterium microti Mycobacterium Bovisall cause tuberculosis (TB) and

are members of the tuberculosis species complex but the main cause is Mycobacterium tuberculosis . Ref(4)

Sings & Symptoms

Cough (that lasts 3 weeks or longer, and can bring up with blood) .

Chest pain .Fever .Fatigue .Loss of appetite . weight loss .Chills and night sweats . Ref(4)

TransmissionRespiratory route

M.Tuberculosis Inhalation of air dropletthat contain tubercle bacillus Intestinal route

M. bovis drinking or eating contaminated, unpasteurized (raw) milk or milk products.(uncommon)

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Respiratory Rout• Infection requires of inhalation

particles small enough to traverse the upper respiratory defenses and deposit deep in the lung (alveoli).

• Large droplets tend to lodge in the more proximal airways and typically do not result in infection.

• when a person who is sick with active disease coughs, sneezes, or laughs.

• To become infected with TB, a person usually needs to share air space with someone sick with TB disease.

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Risk factors

A healthy immune system can often successfully fight TB bacteria, but your body can't mount an effective defense if your resistance is low. diseases and medications can weaken your immune system, including :

• HIV/AIDS• Diabetes• Chemotherapy • Malnutrition• Advanced age• Immunosuppressive medications

• for people who live in or travel to countries that have high rates of tuberculosis such as (Sub-Saharan Africa, India, China, Mexico, Southeast Asia)

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10% chance that a

latent infection will progress to

TB disease.

50% death rate for these active TB casesif untreated.

90% of those infected with M. tuberculosis have asymptomatic, latent TB infection (LTBI)

Tb Infection

TB infection begins when the mycobacteria reach the pulmonary alveoli, where they invade and replicate within the endosomes of alveolar macrophages.

Stage 1

tubercle bacilli

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Lymphocytes and fibroblasts are among the cells that aggregate to form granulomas surrounding the infected macrophages To prevents dissemination of the mycobacteria & provides a local environment for interaction of cells of the immune system.

Stage2

granulomas

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Bacteria inside the granuloma can become dormant, resulting in a latent infection. Another feature of the granulomas of human tuberculosis is the development of abnormal cell death (necrosis) in the center of tubercles. To the naked eye this has the texture of soft white cheese and is termed caseous necrosis.

Stage 3

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The caseous centers of the tubercles liquefy, and the organism begins to rapidly multiply extracellularly. After time, the large antigen load causes the walls of nearby bronchi to become necrotic and rupture. This results in cavity formation. Ghon complex. Typically, the Ghon complex is readily visible upon chest X-ray. caseous necrosis.

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Milliary or extrapulmonary stage : is the hematogenous spread of MTB .“Milliary" is derived from the fact that metastasizing tubercles are about the same size “millet seed”.Two types of lesions caused by milliary TB:

I. Exudative lesions result from the accumulation of PMN's around MTB. Here the bacteria replicate with virtually no resistance. formation of a "soft tubercle".

II. Productive “granulomatous” lesions occur when the host becomes hypersensitive to tuberculoprotein. formation of a "hard tubercle".

Stage 4

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Reactivation Of Tuberculosis

Only persons with latent infection have high risk of Tuberculosis Reactivation.cased by tubercle bacilli that have survived in the primary lesion.Reactivation infection characterized by chronic tissue lesions, formation of tubercle caseation and fibrosis.The reactivation type almost always begins at the apex of the lung, where the oxygen tension (PO2) is highest.

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Tubercle bacilli Characteristics

Gram resistance (acid fast bacilli) Obligate aerobe & MesophileNon-spore-forming & Non-motile rodSlow generation time:15-18 hours Lipid rich cell wall contains:

Mycolic acids 50% of cell wall dry weight.Cord Factor responsible for the serpentine

cording, toxic to mammalian cells ,an inhibitor of PMN migration & resistance to detergents, antibacterial. Ref(1)

Diagnostic steps

History and clinical examination

Radiographic features

Bacteriologic evaluation

“The first rule of TB diagnosis: is to think of TB….”

The physician Include TB in his differential diagnosis when history & symptoms are consistent with TB diagnosis THEN he will recomendrd appropriate diagnostic tests to prove the infection.

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History and clinical examination

Chest X-rayTuberculosis creates cavities visible in x-rays like this one in the patient's right upper lobe. Abnormalities on chest radiographs may be suggestive of, but are never diagnostic of TB. However, chest radiographs may be used to rule out the possibility of pulmonary TB in a person who has a positive reaction to the tuberculin skin test and no symptoms of disease.

Chest X-ray

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Radiographic features

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Conventional diagnostic methods {smear, culture}

Immunologic diagnosis{tuberculin test , IN gamma assay}

New diagnostic methods {NNA, BACTEC, MGIT}

Bacteriologic evaluation

3

Fresh sputum ,gastric washing , urin, pleural fluid , cerebrospinal fluid , biopsy material , blood.

Specimens :

Decontamination & concentration of specimens : sputum Specimens (nonsteril) should be :• Liquefied with N-acetyl-L-cysteine• Decontaminated with NaOH• Neutralized with buffer• concentrated by centrifugation.Specimens processed in this way can be used for acid fast stains and for culture.

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Acid Fast Bacilli “AFB” Smear

Specimen examined for acid fast bacilli by staining:

Ziehl-neelson Acid Fast Staining

Auramine-rhodamine Staining

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I. Solid media1. Löwenstein-Jensen (egg and also contain high concentrations of malachite green to overcome contamination with other bacteria).2. Middlebrook 7H10 & 7H11 are ( containe defined vitamins, salts, catalase, glycerol, olic asid and albumin to neutrelize toxic effect of fatty acids).

Acid Fast Bacilli “AFB” culture

II. liquid media*1. BACTEC TB-4602. MGIT960 systems *(new diagnostic methods)

Acid fast bacilli (AFB) smear microscopy and culture are still the “gold standards” for the diagnosis of active TB but this conventional methods for culture required (6-8) weeks for isolation from media.

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Immunologic diagnosis

γ-Interferon release assays (GIRA)

Tuberculin Skin Test

γ-Interferon release assays (GIRA)

Test rely on the fact that T-lymphocytes will release γ-interferon when exposed to specific antigens. These tests are mostly developed for the field of tuberculosis diagnosis, but in theory, may be used in the diagnosis of other diseases which rely on cell-mediated immunity.

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Tuberculin kin Test

Purified Protein Derivative (PPD) : is a concentrated filter of broth in which tubercle bacilli have grown for 6 weeks(old).• A dose of 0.1 ml of 5-TU PPD injected.• measuring the size of induration 48-

72 hours.• positive if ≥ 10 mm induration size.• Standard method for screening &

measuring of a person’s cellular response.

1 2

Positive Reaction

person infected in the past or latent TB infection

After BCG vaccination, but this may last for only 3-7 years .

Persons are retested 2 weeks later; their PPD skin test “boosted” by the recent antigen injection. High risk of (endogenous infection)

Edema

erythema

necrosis

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Negative Reaction

persons who have NEVER been infected, they are not subject to that risk, though they may become infected from an external source (exogenous infection)

New Diagnostic MethodsMycobacteria Growth Indicator Tube

(MGIT).

BACTEC TB-460.

Nucleic Acid Amplification Method (NAA).

Mycobacteria Growth Indicator Tube (MGIT)

Is an automated system that exploits the fluorescence of an oxygen sensor to detect growth of mycobacteria in culture. The instrument scans the MGIT every 60 minutes for increased fluorescence. Analysis of the fluorescence is used to determine if the tube is Positive contains approximately 105 to 106 (CFU/mL). Negative tubes remain for a minimum of 42 days (up to 56 days)

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The BACTEC TB-460

Is an automated radiometric culture method used for the rapid growth of mycobacteria.

The methodology uses a liquid Middlebrook 7H12 medium that contains radiometric palmitic acid labeled with radioactive (14 C).

Production of 14 CO2 by the metabolizing organisms provides a growth index for the mycobacteria. Growth is generally detected within 9-16 days

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Nucleic Acid Amplification Method

polymerase chain reaction [PCR] allows the direct identification of M.tuberculosis in clinical specimens.

Contamination of samples by products of previous amplification and the presence of inhibitors in the sample may lead to false-positive or false-negative results

Treatment

Latent infectionA person with a positive skin test, a normal chest X-ray, no symptoms and is not contagious. treatment with an antibiotic may be recommended for this person to prevent the TB from turning into an active infection. The antibiotic used for this purpose is called isoniazid (INH). If taken for six to 12 months, it will prevent the TB from becoming active in the future.

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Treatment

Active infection Active TB is treated with a combination of isoniazid along with Rifampin, ethambutol and pyrazinamide are the drugs commonly used to treat active TB. Four drugs are often taken for the first two months of therapy to help kill any potentially resistant strains of bacteria. Then the number is usually reduced to two drugs for the remainder of the treatment based on drug-sensitivity testing. Ref(4)

Multi Drug Resistance Tuberculosis(MDR –TB)

between one in 10^6 and one in 10^8 tubercle bacilli are spontaneous mutants resistance to first-line antituberculosis drugs. When the drugs are used singly, the resistant tubercle bacilli emerge rapidly and multiply. Treatment of MDR-TB must be done on the basis of sensitivity testing. It is impossible to treat such patients without this information. patient should be started on SHREZ (Streptomycin+isonicotinyl Hydrazine +Rifampicin +Ethambutol+pyraZinamide)Ref(4)

Prevention & Control prompt and effective treatment of

patients with active tuberculosis and carefully follow-up of their contacts with tuberculin tests and x-rays .

Drug treatment of asymptomatic tuberculin-positive persons .

Immunization: BCG (bacillus calmette-guerin) used to induce a certain amount of resistance in those heavily exposed to infection

The eradication of tuberculosis in cattles and the pasteurization of milk have greatly reduced M.bovis infections.

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Prevent latent TB from becoming active

prevent TB by TB vaccine (BCG)Prevent inject illegal drugs.Do not spend long periods of time in

stuffy, enclosed rooms with anyone who has active TB until that person has been treated for at least 2 weeks.

Use protective measures, such as face masks, if you work in a facility that cares for people who have untreated TB.

Precaution Tips

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TB control in Jordan

Jordanian Anti TB Association is providing support to the national TB programme through financial aid to TB patients & health education. Jordan also made good progress in the TB Elimination Initiative by lowering the incidence rate of smear positive new cases to 6 per 100,000 populations.At 2010 there's 336 case of TB in Jordan

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DOTS

The WHO-recommended Directly Observed Treatment, Short Course (DOTS) strategy was launched formally as Revised National TB Control programme in India in 1997. Since then DOTS has been widely advocated and successfully applied. DOTS is the most effective strategy available for controlling TB.

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Ref(1) Tuberculosis, NICE Clinical Guideline (March 2011); Clinical diagnosis and management of tuberculosis, and measures for its prevention and control.

Ref(2) Landau, Elaine. Tuberculosis. New York: F. Watts, 1995http://www.healthofchildren.com/T/Tuberculosis.

Ref(3) The Stop TB Strategy: building on and enhancing DOTS to meet the TB-related Millennium Development GoalsWHO. Geneva, World Health Organization, 2006b (WHO/HTM/STB/2006.37).

Ref(4) G.Brooks , K.Carrroll , J.Butel , S.Melnicks (Medical Microbiology 24th Edition ) Jawetz , Melnicks Dahlberg's .

REFERENCES

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