Lecture 9_Mycobacteria 2 PDF

Acid-fast bacteria: Mycobacteria Click to edit Master subtitle style Prepare by: Dr. Nasser Al-Qurainy Presented by: Dr. Fahad Alsaab  Objectives ▪ By the end of this session, the students should be able to: Describe the epidemiology, pathogenesis, immunity...

Acid-fast bacteria: Mycobacteria Click to edit Master subtitle style Prepare by: Dr. Nasser Al-Qurainy Presented by: Dr. Fahad Alsaab  Objectives ▪ By the end of this session, the students should be able to: Describe the epidemiology, pathogenesis, immunity, and clinical significance of Mycobacterium tuberculosis infections Describe the clinical, radiological, and laboratory diagnosis of active tuberculosis disease and latent tuberculosis infection Recognize the methods of treatment and prevention by the BCG vaccine Discuss the pathogenicity and clinical significance of leprosy 2 General features Mycolic acids ▪ Long slender rods (bacillus) that are non-motile. ▪ No spores, aerobic. ▪ Slow rate of replication: It divides every 16 to 20 hours, compared with other bacteria (E. coli divides every 20 min). ▪ Classified as Gram positive bacteria BUT does not stain well with the Gram stain (due to the Cell Wall high lipid content of its cell wall). ▪ Cell walls unique: Consist of 60% lipid, including long-chain and β-hydroxylated fatty acids know as mycolic acids Result in waxy cell surface, strongly hydrophobic, and acid-fast staining bacterium. What is Acid fast bacteria (AFB)? is a term that used to describe bacteria that resist Acid fast stain: carbol fuchsin (red) decolorization with acid-alcohol. Counterstain: methylene blue 3 MTB Complex & NTM o Mycobacterium tuberculosis (MTB) Complex: A group of Mycobacterium species that can cause Tuberculosis. Includes: M. bovis, M. africanum, M. canetti and M. microti o Non-Tuberculosis Mycobacteria (NTM): Mycobacteria species that do not cause TB, but cause pulmonary diseases resembling TB. Includes: M. avium and M. kansasii 4 Mycobacterium tuberculosis – Epidemiology ▪ Causes Tuberculosis (TB) Highly contagious air-borne disease that infects the lungs (pulmonary TB) ▪ Mycobacterial infections are intracellular, and generally result in the formation of slow-growing granulomatous lesions ▪ 1/3 of the world’s population is infected, with 30 million people with active disease ▪ ~1.5 million deaths per year ▪ TB infections are declining in the U.S. but in Africa and Asia they are increasing ▪ Several factors have contributed to the rise of TB infections ▪ HIV/AIDS epidemic ▪ Immigration ▪ Overcrowding ▪ Multi-drug resistant TB 5 M. tuberculosis – Transmission ▪ Transmission only occurs from people who have active TB and not latent TB. ▪ 1 person with TB can infect 10-15 individuals per year. ▪ Main route of transmission is through aerosols that are produced by coughing and/or sneezing. ▪ Symptoms: cough (with blood), chest pain, fever, night sweats, loss of weight and appetite. ▪ Risk: People in areas with high incidence of TB Close contacts of a TB patient HIV infected individuals Drug users People using immunosuppressant drugs 6 M. tuberculosis – Pathogenesis ▪ After being inhaled, TB infection starts when the bacteria reaches the alveoli, where they multiply in pulmonary epithelium or macrophages ▪ The virulence of M. tuberculosis is attributed to its capacity to survive and proliferate within macrophages by producing sulfolipids that prevent the fusion of phagocytic vesicles with lysosomes. ▪ In 2-4 weeks, many bacteria are destroyed, but some survive and spread by blood to extra pulmonary sites ▪ Bacteria multiply to form a tubercle ▪ After a few weeks, macrophages die, releasing bacteria & forming a center surrounded by Macrophages and Lymphocytes – disease may become dormant ▪ Some individuals, mature Tubercle is formed – fibroblast surround tubercle ▪ Eventually, tubercle ruptures, allowing bacteria to spread throughout the respiratory system and body 7 M. tuberculosis – Clinical Significance (i) ▪ Stages of M. tuberculosis infection: ▪ Primary tuberculosis: ▪ Occurs in a person who has never had contact with the organism. ▪ ~90% of infections become arrested / dormant (Latent infection) and most people are unaware. ▪ Only evidence can be a +ve tuberculin test. ▪ Chest X-ray may reveal the initial pulmonary tubercle. ▪ ~10% will develop clinical tuberculosis. ▪ Primary disease-initial phase: ▪ Initial lesions in a small bronchiole or alveolus. ▪ Bacteria grow well in phagocytes and are transported via lymphatic system to lymph nodes. ▪ Mild or asymptomatic with exudative lesions in which fluid and PMN’s accumulate around bacteria. 8 M. tuberculosis – Clinical Significance (ii) ▪ Stages of M. tuberculosis infection: ▪ Primary disease – tubercle formation: ▪ Productive lesion is formed with the formation of tubercles. ▪ Large area of macrophages, surrounded by epithelioid cells, surrounded by fibroblasts. ▪ Center of tubercle – necrosis (caseous center). ▪ Primary disease – course: ▪ Lesion may arrest (dormant). ▪ Lesion may break down and facilitate the spread of infection via lymph and the bloodstream spreading to the liver, spleen, kidneys, bone, meninges. ▪ Secondary disease – reactivation: ▪ Caused from a dormant tubercle. ▪ Destruction of lung tissue. ▪ Large lesions, organisms in sputum. 9 M. Tuberculosis – Clinical Significance (iii) Tuberculin Skin Test (Mantoux skin test ) Known as Mantoux skin test for Test can be used to document tuberculosis (PPD= purified protein if a person has had exposure derivative = called tuberculin). to M. tuberculosis but cannot tell you if a person has active Delayed hypersenstivity reaction to disease. protein antigens of M. tuberculosis. A person who has received the After injection of PPD under the skin BCG vaccine (TB vaccine), may (intradermally), a health professional also give a false positive. will measure the size of hardening (induration) after 48-72 hours. Results depend on size and individual history. 11 M. tuberculosis - Identification ▪ Identification: ✓ Sputum smear can be tested for acid-fast Bacilli. ✓ Chest X- ray. ✓ Blood [Interferon Gamma Release Assay (IGRA)] ✓ Flourescence Microscopy. ✓ Most definitive is to culture the organism ✓ Lowenstein Jensen medium (14-28 days). ✓ PCR – polymerase chain reaction. 12 M. tuberculosis - Treatment ▪ Treatment: ▪ Drug Resistance major challenge!! ▪ Requires a long course of treatment ▪ Multiple drugs used: ▪ M. tuberculosis hides inside macrophages ▪ Isoniazid ▪ Shielded from drugs inside tubercle ▪ Rifampin ▪ 12-18 months was previously used ▪ Ethambutol ▪ Now ~ 6 months ▪ Streptomycin ▪ **Low patient compliance** ▪ Pyrazinamide 13 BCG vaccine (TB vaccine) ✓ Produced from Bacillus Calmette-Guerin (is derived from an attenuated strain of Mycobacterium bovis). ✓ Vaccine is ~ 80% protective against serious forms of TB. ✓ Duration of immunity is about 10-15 years. ✓ In some countries, the vaccine given only to tuberculin-negative individuals at sustained high risk of infection, such as certain healthcare workers and those in areas with prevalent multi-drug- resistant TB. ✓ Certain conditions that affect the immune system (cancer, recent chemotherapy, late-stage AIDS) may cause a false-negative test result. 14 Leprosy (Hansen's Disease) ▪ Hansen’s disease (also known as leprosy) is an infection caused by slow-growing bacteria called Mycobacterium leprae. ▪ Causes damage to the skin and the peripheral nervous system. ▪ Starts with pale patches on the skin (often ignored). ▪ Disease develops slowly (6 months – 40 years). ▪ Human to human transmission. ▪ 10-12 million cases worldwide every year. 15 Mycobacterium leprae ▪ Is non-Tuberculosis Mycobacteria (NTM) discovered by Hansen 1873. ▪ Causes leprosy (Hansen's Disease) and ▪ Starts as painless skin lesions, ulcers. ▪ Can develop into large ulcerations, facial disfigurement. ▪ Identification ▪ Acid-fast stain from nasal mucosa or skin smear. ▪ Cannot be cultured (Armadillo’s used for obtaining M. leprae). ▪ Treatment ▪ Drugs: Dapsone, Rifampin, Clofazamine. ▪ If damage to the nerves, antibiotics alone will not restore function. ▪ Other forms of treatment will be needed, including physiotherapy. 16 Thank you 17