Tuberculosis

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1. Submitted To : Dr. Zeshan Nawaz Subject : Advanced Epidemiology Topic : Tuberculosis Presented by : Iqbal Danish Department of Microbiology 2 nd Semester

2. INTRODUCTION Tuberculosis ( TB ) is a potentially fatal contagious disease that can affect almost any part of the body but is mainly an infection of the lungs. “WHO” Tuberculosis also call “TB” Is An Infectious Bacterial Disease Caused By Mycobacterium tuberculosis , which result in granulomatous formation in lungs and is major health problem in developing countries.   Historically called " consumption " due to the weight loss. “Tubercle” meaning Round nodule/Swelling. “ Osis ” means Condition In1882: Robert Koch ,a German scientist announced the discovery of M. tuberculosis .

3. General characteristics Acid fast bacilli Obligate aerobe Intracellular Non spore forming Non motile Mesophile Slow generation time 15-20 hours Lipid rich cell wall contains mycolic acid (long chain fatty acids) 60% of cell dry weight. Because the cells are hydrophobic and tend to clump together, they are impermeable to the usual stains e.g. Gram staining.

4. Transmission M. tuberculosis is transmitted from person to person by respiratory aerosol. In air tiny droplets of 0.5-5 um in diameter persist when infected person cough, sneeze or laugh and remain for several hours. In developed countries, most tuberculosis is due to reactivation in elderly, malnourished men. In developing countries , M. bovis is found in cow's milk, which, unless pasteurized, can cause gastrointestinal tuberculosis in humans. Only 10 percent of those infected individuals may progress to a manifest disease.

5. Pathogenesis: Target is macrophages and reticuloendothelial cells. On entry in the phagosome it releases “exported repetitive protein "prevent fusing of phagosome with lysosome so degrading enzymes have no action on organism. Ghon's complex  is a lesion seen in the lung that is caused by tuberculosis. The lesions consist of a calcified  focus  of infection and an associated lymph node. Primary infection is reactivated in apices in well oxygenated areas of kidney, brain and bones mostly in immunocompromised patients. Lesions depends on presence of organism and host response. Exudate lesion Granulomatous lesion Formed at the initial stage of infection mainly in lungs Central, bacillus is surrounded by epithelial cell. Granulomas composed of transformed macrophages,epitheloid cells, lymphocytes . Causes acute inflammatory response bacteria proliferate in pulmonary alveolar macrophage and air spaces.

6. Spread of organism Tubercle dissolves in bronchus, empty in caseous contents, spread organism to other parts of lungs. In blood stream it disseminate if cell mediated immunity fails in early stage. Memory T cells release cytokines try to control outbreak of bacteria and form caseous necrosis.

7. Clinical manifestation: Asymptomatic Low grade fever Night sweating Cough Dyspnea Chest pain Lethargy Anorexia Weight loss Hemoptysis Pneumonia

8. CLASSICATION Pulmonary TB Primary Disease Secondary Disease Extrapulmonary TB Lymph node TB Pleural TB TB of upper airways Skeletal TB Genitourinary TB Miliary TB Pericardial TB Gastrointestinal TB Tuberculous Meningitis Less common forms

9. PRIMARY TB Bacilli are engulfed by Alveolar Macrophages Multiply and give raise to Sub pleural focus lower lobes& lower part of upper lobes are infected called as Ghon’s focus or Child hood TB. The Ghon focus together with hilary lymph node constitute the Primary complex, leads to fibrosis after 3- 8 weeks of infection. Lesions forming after infection are peripheral. Heals in 2 – 6 months, calcified forms ranke complex. Some bacteria remain alive and produce latent infections. Infection activated in immunosuppressed conditions e.g. HIV and AIDS Can lead to Meningitis, Miliary tuberculosis, other disseminated Tuberculosis

10. Secondary Tuberculosis The infection in individuals who has been previously infected or sensitized is called secondary or post primary or reinfection or chronic tuberculosis. Mainly occurs due to Reactivation of Latent infection. May also due to Exogenous reinfection . Differs from Primary Infection. Leads to; Cavitation's of Lungs, Enlargement of Lymph nodes, Expectoration of Bacteria laden sputum. Dissemination into Lungs and other extra pulmonary areas.

11. Extra Pulmonary TB 20% of patients of TB Patient 1) Lymph node TB ( tuberculuous lymphadenitis) Seen frequently in HIV infected patients. Painless swelling of lymph nodes most commonly at cervical and Supraclavical (Scrofula) 2) Pleural TB Involvement of pleura is common in Primary TB results from penetration of tubercle bacilli into pleural space. 3) TB of Upper airways Involvement of larynx, pharynx and epiglottis. Dysphagia , chronic productive cough

12. 4) Genitourinary TB 15% of all Extra pulmonary cases. Any part of the genitourinary tract get infected. Urinary frequency, Dysuria , Haematuria . 5) Skeletal TB Involvement of weight bearing parts like spine, hip, knee. Pain in hip joints n knees, swelling of knees, trauma. 6) Gastrointestinal TB Involvement of any part of GI Tract. Abdominal pain, diarrhea , weight loss 7) TB Meningitis & Tuberculoma 5% of All Extra pulmonary TB. Under 5 yrs.of age are more prone, blood-brain barrier is passed. Results from Hematogenous spread forming tubercules which burst and infect meningies

13. 8) TB Pericardiatis 1- 8% of All Extra pulmonary TB cases. Spreads mainly in mediastinal or hilar nodes or from lungs. 9) Miliary or disseminated TB Results from Hematogenous spread through retrograde transport of Tubercle Bacilli. Spread is due to entry of infection into pulmonary vein producing lesions in different extra pulmonary sites. 10) Less common Extra Pulmonary TB Uveitis , painfull Hypersensitivity Related to phlyctenular conjuctivis .

14. TB ANNUAL REPORT WHO 2018 Pakistan is 5 TH in ranking among countries with highest incidence. Total registered TB patients 3,68,897 in 2017.

15. RISK FACTORS (1)Poverty and poor housing (2) Contribution of HIV and TB is deadly in 2017 300,000 people with HIV died of TB. (3)Prisoners (4)Alcoholism and Drug abuse. (5)Kidney disease and diabetes. (6)Working in healthcare. (7) WHO stimates 8% of TB cases world wide can be linked to smoking. (8) Babies, children and elderly people. (9) Malnutrition

16. MDR-TB and XDR-TB MDR-TB MDR-TB is a form of TB infection caused by bacteria that are resistant with at least two of most powerful first line anti-TB medications/drugs ( isoniazid and rifampicin ) Second line anti-TB drugs make it treatable and curable however, second line is limited and require extensive chemotherapy ( upto 2 years) with medicines that are expensive and toxic. WHO approved use of short, standardized regimen for MDR-TB patients that included 9-12 month and less expensive than conventional 2 year medication.

17. XDR-TB XDR-TB is a form of TB infection caused by bacteria that are resistant to most effective drugs of second line of anti-TB drugs. 8.5% from MDR-TB had XDR-TB in year 2017. longer regimen with addition of one new drugs ( bedquiline and delamanid ) HIV and TB HIV weakens the immune system and increases the risk of Tuberculosis. HIV and TB disease risk increases when; HIV in endemic. Resources are limited. Latent TB could advance to TB (if HIV present). Treatment for HIV by “Antiretroviral Therapy (ART) decreases the chance of occurrence of TB from latent TB.

18. Diagnosis History and clinical examination Chest X-ray Tuberculosis creates cavities visible in x-rays like this one in the patient's right upper lobe. Abnormalities on chest Bacteriologic Evaluation Direct smear microscopy Microscopic examination of a specimen of three morning successive sputum. Stained by the Ziehl-Neelsen method or Auramine rhodamine stain ( flourescent microscopy).

19. Culture test Löwenstein -Jensen Middlebrook 7H10 & 7H11 Acid fast bacilli (AFB) smear microscopy and culture are still the “gold Standards” for the diagnosis of active TB. But conventional culture methods require (6-8) weeks for isolation.

20. Tuberculin Skin Test (TST) Mantoux tuberculin skin test Purified Protein Derivative (PPD): 0.1 ml is injected intradermally . Most people infected by M. tuberculosis are vaccinated by BCG. will react to TST and develop an induration at the site of injection. Diameter of this induration is measured after 48-72 hours. Induration of diameter 10mm or more is considered positive, 5mm or less is negative.

21. Interpretation for tst IN GAMMA ASSAY OR y - Interferon release assays (GIRA ) Test rely on the fact that T-Lymphocytes Will Release γ-interferon. When exposed to specific antigens. Gene expert

22. Anti-TB drugs

23. Challenges to Treating TB/HIV Latent TB/HIV: Rifampin - Isoniazid based regimens for 12 weeks--- once weekly 4 months----- daily Rifampin and ART 9 months----- daily Isoniazid, Rifampin and ART Active TB/HIV: Intensive phase: Isoniazid, Rifamycin, Pyrazinamide , Ethambutol----- first 2 months . Continuous phase: Isoniazid and Rifamycin----- 4 months according to CDC.