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Tuberculosis is a chronic respiratory tract disease established by Mycobacterium tuberculosis complex infection and represented clinically as primary,

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Presentation on theme: "Tuberculosis is a chronic respiratory tract disease established by Mycobacterium tuberculosis complex infection and represented clinically as primary,"— Presentation transcript:

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2 Tuberculosis is a chronic respiratory tract disease established by Mycobacterium tuberculosis complex infection and represented clinically as primary, secondary disease, or latency. Mycobacterium tuberculosis complex: M. tuberculosis, M. bovis, and M. africanum.

3 WHO (2013)  9 million people developed TB in 2013, most of them are from South East Asia, India alone account for 24% of these cases.  1 million cases were HIV positive.  1.5 million died from the disease including 360 000 deaths among HIV-positive people.  25% to 33% of the world’s population live with silent latent M. tuberculosis infection.  Prevalence in Saudi Arabia in 2012 ≈ 4900 case and 1100 deaths.

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5 Mycobacterium tuberculosis was identified and described on 24 March 1882 by a German physician Robert Koch. Morphology: slightly curved to straight bacillus. Obligate aerobic, acid fast, non motile, non spore forming bacilli. Contains mycolic acid in their cell wall; resistant to dryness and phagocytosis. Slow grower: duplication time ~24 hours

6 Reservoir: Human. Transmission: T.B spread from person to person through the air by droplet nuclei (0.5-5µm in diameter) which can be produced by coughing, sneezing, or to a lesser extent speaking or singing. Droplet nuclei may remain suspended in the air for long time;(isolation rooms in hospitals). Droplet nuclei is ideal for bypassing the upper airways.

7 Pertussis, H. influenzae, influenza, Neisseria Meningitidis, Yersinia Pestis,...... Herpes Zoster, Measles, SARS, Tuberculosis

8 M. bovis  Reservoir: Cattle & related animals.  Transmission: o Eating or drinking contaminated, unpasteurized dairy products. o Direct contact and inhalation of aerosol droplets from infected animals. o From person to person through droplet nuclei  Infected cattle must be culled.  Symptoms of TB disease caused by M. bovis are similar to those of M. tuberculosis.

9 Risk factors for rapid spreading of Mycobacterium tuberculosis: Crowded living conditions. HIV infection. Excess alcohol consuming. Traveling to countries with high prevalence rate.

10 Pathogenesis: o Do not produce exotoxins or endotoxin. o Able to survive inside the macrophages (chronic granulomatous inflammation). o Tissue damage is induced by the host immune response. o Clinical presentations are divided to: Primary infection. Latent infection. Secondary infection

11 Primary infection:  Bacilli settle in the middle lung zones; where airflow is greatest.  Inhaled bacilli are engulfed by alveolar macrophage where they continue to multiply leading to rupture of macrophage, reals of bacilli and infection of other macrophage (active primary T.B).

12  Infected macrophages are carried by lymphatics to regional tracheobronchial lymph nodes: › Activation of lymphocytes (TH1: cell mediated immune response; granuloma formation) + Enlargement of lymph nodes (Ghon’s complex) › Lymphohematogenous spread: lymph nodes, vertebrae, kidneys, meninges and lung apices.

13 Outcome of Primary Infection: In 90% of cases, (children ˃ 5 years old, teens and adults): strong immunity: delayed type hypersensitivity: latent dormant tuberculosis with granuloma formation (little or no symptoms) In 10 % of cases (infants and children younger than 5 years old, elderly persons and HIV patients): weak immunity: little or no hypersensitivity immune reaction: progressive primary tuberculosis. lympho-hematogenous dissemination (meninges, bone, apices of lungs, kidneys……

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15 Secondary Tuberculosis (Endogenous Reactivation) Occurs within 2 years of initial infection but can occur any time there after due to impairment of cellular immunity. Major causes of cellular immunity depression: malnutrition, immunosuppressive drugs (corticosteroids), malignancy, HIV (the most important cause).

16 Most common site of reactivation is the lung apex; granulomatous lesions become necrotic (caseous necrosis), enlarge, liquefy, rupture and discharge their content into bronchi : Creation of well aerated cavity; microbial proliferation. Distribution within the lung (tuberculous pneumonia). Coughing of large numbers of bacteria. Coughing up bloody sputum.

17 10%90%

18 In cervical LN: scrofula Pott’s disease

19 A person with Latent TB Inf.A person with active TB Has no symptoms Has symptoms that may include: o Chronic cough lasts ˃ 3 weeks o weight loss o Fever & chills o sweating at night o coughing up blood or sputum o bad appetite o weakness & fatigue o pain in the chest Cannot spread infection to others May spread infection to others Usually positive skin test or blood test Usually positive skin test or blood test. Has a normal chest x-ray and a negative sputum smear May have an abnormal chest x-ray and positive sputum smear or culture Needs treatment to prevent TB disease Needs treatment to treat TB disease n

20 HIV infection inhibit cellular immunity. Patients with HIV infection can be infected by MTC (Mycobacterium tuberculosis complex), or MOTT (Mycobacterium other than tuberculosis). MOTT: M. avium, M. intracellulare, and M. kansasii. Tuberculosis is an AIDS defining condition. It is the leading cause of death among adults living with HIV/AIDS. The WHO recommends TB screening at HIV diagnosis and during follow up.

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22  Chest X-ray.  Clinical specimens: Sputum, transtracheal aspiration, bronchoalveolar lavage.  Mantoux skin test (Tuberculin).  Microscopy: by Ziehl –Neelsen (ZN) stain, or by fluorescent microscope.  Culture: Isolation & antibiotics sensitivity of mycobacterium species.  PCR: Highly sensitive. Detection of mycobacterial genetic material and to determine antibiotic susceptibility.

23 Chest X-ray Cavitation in the right lung and fibrosis in the left.

24 Tuberculin skin tests (Mantoux test): o Delayed type hypersensitivity (DTH). o Purified protein derivative (PPD) injected intradermally. o Results: Induration is measured after 48- 72 hours (DTH). Negative < 5 mm Intermediate reaction 5-9 mm. Positive reaction ˃ 9mm.

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26 M. Tuberculosis appear as thin pink rods in ZN stain

27 o Cultured for primary isolation & antibiotic susceptibility. o Strict aerobic grows slowly (2-4 weeks). o Optimum temperature growth is 37 C. o Egg enriched medium: Löwenstein–Jensen medium (L.J) or Middle-brook medium. o The growth is enhanced by adding pyruvate and glycerol to the media. o M. tuberculosis are niacin producers.

28 TB Culture Culture characteristics of tubercle bacilli on LJ medium (dry, rough, cream colored colonies)

29  Difference between M. tuberculosis and MOTT :(M. avium, M. intracellulare, and M. kansasii). M. tuberculosis is a non chromogenic bacteria. Does not grow on media contain p- nitrobenzoic acid.

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31 Treatment of T.B: Extensive time periods (6-9 months). Direct observation treatment (DOT). Combined multidrug treatment to reduce anti tuberculous resistance. First line anti-t.b drugs: Isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol. Phases of Treatment: -Initial phase: The four drugs for 2 months. -Continuation phase: INH and RIF for four or seven months.

32 Vaccination: Bacillus Calmette – Guérin (BCG) vaccine: Live attenuated low virulent M. bovis strain. Effective in protection of children from serious forms of disease such as meningitis. Not so effective to protect adults.

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