Respiratory Bacteria (M) PDF

OBJECTIVES : Describe the properties, pathogenesis and clinical significance of the following Mycobacterium tuberculosis as respiratory pathogens Mycobacterium tuberculosis Mycobacterium tuberculosis Mycobacterium tuberculosis was first identified by Robert Koch. They are more than 10...

OBJECTIVES : Describe the properties, pathogenesis and clinical significance of the following Mycobacterium tuberculosis as respiratory pathogens Mycobacterium tuberculosis Mycobacterium tuberculosis Mycobacterium tuberculosis was first identified by Robert Koch. They are more than 100 named species of mycobacteria. The name mycobacteria meaning fungus like bacteria is derived from mould like appearance of mycobacterium tuberculosis when grown in liquid media. They are also called acid fast because they resist decolourization by dilute mineral acids as the cell wall are rich in lipids ( mycolic acids, waxes and phosphatides). Morphology- OBLIGATE AEROBE Size- 3 micron in length and 0.3 microns Shape- Straight or slightly curved rod Arrangement - singly, pairs or small clumps Nonmotile, nonsporing and noncapsulated Staining reaction – Ziehl Neelsen staining Acid fastness, beaded forms commonly seen Fluorescent stain – Auramine Rhodamine stain PATHOGENESIS – Mode of infection :- Almost all infections with M. tuberculosis are due to inhalation of droplet nuclei—infectious particles from a person with pulmonary TB aerosolized by coughing, sneezing, or talking—which dry while airborne, remain suspended for long periods, and reach the terminal air passages. Direct inhalation of aerosolized bacilli contained in droplet nuclei of expectorated sputum. Coughing sneezing etc release 3000 droplet nuclei. Processing clinical specimens in the lab and other procedures can lead to infection. Ingestion : Infection also occurs infrequently through infected milk.( M. bovis is found in cow’s milk, which, unless pasteurized, can cause gastrointestinal tuberculosis  How is TB Transmitted? Person-to-person through the air by a person with TB disease of the lungs Source: CDC, 2000 ▪ Less frequently transmitted by: Ingestion of Mycobacterium found in unpasteurized milk products Laboratory accident.. Mycobacterium tuberculosis is an opportunistic organism Decrease in immunity make a person susceptible of tuberculosis E.g, AIDs , chronic steroid use. Children , old age people and pregnant women are more prone to have tuberculosis because of weak immune system. Tuberculosis is closely linked to both overcrowding and malnutrition, making it one of the principal Diseases of poverty.  Virulence Mechanism : Ability to survive within the macrophage. It inhibits a. Phagosome acidification , Mycobacterial urease helps prevent acidification of the phagosome, thus limiting the effectiveness of bactericidal enzymes. b. Phagosome- lysosomal fusion: The organism produces a protein called “exported repetitive protein” that prevents the phagosome from fusing with the lysosome, thereby allowing the organism to escape the degradative enzymes in the lysosome.  Cord formation (trehalose dimycolate) is correlated with virulence. A cord factor inhibits migration of leukocytes, cause chronic granulomas LAM (lipoarabinomannan) inhibits macrophage activation by interferon gamma. The organism also secretes abundant superoxide dismutase, catalase, and other antioxidants that detoxify reactive oxygen species generated by phagocyte. Phosphatidase play role in Caseous necrosis  IMMUNOLOGY TB is type of infections that require a cellular immune response for their control. An effective immune response against M. tuberculosis infection relies on CD4+ T cells and the cytokines interleukin (IL)-12, interferon-γ, and tumor necrosis factor (TNF). CD4+ Th1 cells, which secrete interferon-γ, are central to the protective immune response against M. tuberculosis CD4+ T-cell production of interferon-γ activates macrophages at the site of antigen.  Activated macrophages accumulate high concentrations of lytic enzymes and reactive metabolites that greatly increase their mycobactericidal competence, causing a decrease in the mycobacterial load Epithelioid cells, characteristic of the tuberculous granuloma, are highly stimulated macrophages. The Langhans giant cell consists of fused macrophages oriented around TB antigen with the multiple nuclei in a peripheral position However cellular immune responses are responsible also for tissue damage, formation of pulmonary cavities. MECHANISM : After initial inhalation, M. tuberculosis must bypass mechanical barriers, ciliated respiratory epithelial cells, and mucins in the upper airways to arrive in the alveolar spaces. In the alveoli, M. tuberculosis is phagocytized by the alveolar macrophage. The alveolar macrophage may successfully kill the mycobacteria through phagosome maturation, fusion with the lysosome. Alternatively the mycobacteria may release virulence factors that delay phagosome maturation. M. tuberculosis uses several strategies to survive within macrophage phagosomes while delaying or preventing effective immune response  If the initial infection is successful, unrestrained replication proceeds for weeks, both in the initial focus and in lymphohematogenous metastatic foci. The development of adaptive cellular immunity is delayed and takes approximately 4 to 8 weeks and ultimately supervenes  Pathogenesis of Tuberculosis ▪ After 3 weeks of infection, cell mediated immunity develops and ends up in formation of Epithelioid granulomas with T cells, macrophages & giant cells , central caseation and peripheral fibrosis called as Ghons focus. ▪ The classical location of Ghon focus is either in the upper part of the lower lobe or lower part of the upper lobe If the Ghon focus also involves infection of adjacent lymphatics and hilar lymph nodes, it is known as the Ghon's complex or Primary complex. If a Ghon's complex undergoes fibrosis and calcification it is called a Ranke complex.  Ghon focus.  Macrophages, epithelioid cells, T lymphocytes & fibroblasts aggregate to form granulomas, with lymphocytes surrounding the infected macrophages. When other macrophages attack the infected macrophage, they fuse together to form a giant multinucleated cell in the alveolar lumen. The granuloma may prevent dissemination of the Mycobacteria. Bacteria inside the granuloma can become dormant, resulting in latent infection.  Spread of the M.tb within the body A tubercle can erode into a bronchus, empty its caseous contents, and spread the organism to other parts of the lungs, to the gastrointestinal tract if swallowed, It can disseminate via the bloodstream to many internal organs. Dissemination can occur at an early stage if cell-mediated immunity fails to clear the initial infection or at a late stage if a person becomes immunocompromised.  Mycobacterium tuberculosis is an opportunistic organism Decrease in immunity make a person susceptible of tuberculosis E.g, HIV , chronic steroid use. Children , old age people and pregnant women are more prone to have tuberculosis because of weak immune system. Tuberculosis is closely linked to both overcrowding and malnutrition, making it one of the principal Diseases of poverty. After Mycobacterium tuberculosis is transmitted into body how it proceeds?. Primary tuberculosis. It is the form of disease that develops in a previously unexposed, and therefore unsensitized persons. Latent tuberculosis It means a patient is infected with M tb, but the patient does not have active tuberculosis because of immune system keeps the bacteria under control (Granuloma). The main risk is that approximately 10% of these patients will go on to develop active tuberculosis latter in life span particularly if they get immunocompromized..  Clinical significance of Tuberculosis Pulmonary TB : Pain in the chest, coughing up blood or sputum, fatigue, weight loss, anorexia, fever, sweating at night Extrapulmonary TB Central nervous system (in tuberculous meningitis), the lymphatic system (in scrofula of the neck), the genitourinary system (in urogenital tuberculosis), and the bones and joints (in Pott disease of the spine), etc. A potentially more serious, widespread form of TB is called "disseminated tuberculosis", it is also known as miliary tuberculosis  Scrofula Cervical lymphadenitis that presents as swollen, nontender lymph nodes, usually unilaterally.  The major pathogens are Mycobacterium tuberculosis, the cause of tuberculosis, and Mycobacterium leprae, the cause of leprosy. Atypical mycobacteria, such as Mycobacterium avium- intracellulare complex and Mycobacterium kansasii, can cause tuberculosis-like disease but are less frequent pathogens. Rapidly growing mycobacteria, such as Mycobacterium chelonae, occasionally cause human disease in immunocompromised patients. There are more than 170 Mycobacterium species,eg Mycobacterium bovis, Mycobacterium africanum, Mycobacterium kansasii etc  Burden of TB M. tuberculosis infects 1.7 billion people or approximately one- quarter of the world’s population and caused 10.4 million new cases of TB and approximately 1.7 million deaths in 2016. TB is the leading cause of death worldwide resulting from a single infectious agent, ranking above HIV since 2014. Immunocompromise due to HIV infection is a risk factor for TB, and 374,000 TB deaths are in HIV-infected individuals. Drug-resistant TB is emerging globally, with approximately 490,000 new MDR-TB cases in 2016. Two factors essential for the rapid spread of M. tuberculosis are crowded living conditions and a population with little native resistance. References : 1.Medical Microbiology & Immunology by Warren Levinson. 2.Text Book of Medical Microbiology by Jawitz. 3. Oxford handbook of infectious diseases.