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THE INFECTIOUS DISEASES Infectious disease – disease caused by an infectious agent such as a bacterium, virus, protozoan, or fungus that can be passed on to others. Infection is complex process of interaction between pathogen and human body Pathogen – an infectious agent that causes disease. Host – an organism infected by another organism. Virulence – the relative ability of an agent to cause rapid and severe disease in a host. Most infectious agents that cause disease are microscopic in size and thus, are called microbes or microorganisms. Different groups of agents that cause disease are: Prions Bacteria Viruses Protozoa (Protists) Fungi Helminths (Animals - Prions: Are apparently composed of abnormal forms of a host protein, termed prion protein (PrP) . The name derives from proteinaceous infectious particles. PrP is normally found in neurons. Diseases occur when the prion protein undergoes a conformational change that confers resistance to proteases. These agents cause transmissible spongiform encephalopathies, including: 1-kuru (associated with human cannibalism) 2-Creutzfeldt-Jakob disease (CJD; associated with corneal transplants). 3- bovine spongiform encephalopathy (BSE; better known as mad cow disease). 4- variant Creutzfeldt-Jakob disease (vCJD; likely transmitted to humans from BSE-infected cattle). 2-Viruses -Viruses are obligate intracellular parasites that depend on the host cell's metabolic machinery for their replication. -Viruses are classified by their nucleic acid genome (DNA or RNA but not both) . Rota virus from the (Reoviridae DS RNA) cause Childhood diarrhea. Parvovirus from the (Parvoviridae SS DNA) cause Erythema infectiosum, aplastic anemia Bacteriophages, Plasmids, Transposons These are mobile genetic elements that infect bacteria and can indirectly cause human diseases by encoding bacterial virulence factors (e.g., adhesins, toxins, or enzymes that confer antibiotic resistance). Exchange of these elements between bacteria often endows the recipient with a survival advantage ( antibiotic resistance). 3- Bacteria Bacterial cells are prokaryotes, meaning that they have a cell membrane but lack membrane-bound nuclei and other membraneenclosed organelles . Bacteria are classified by: 1- Gram staining (positive or negative). 2- Shape ( spherical ones are cocci and rod-shaped ones are bacilli). 3- Form of respiration (aerobic or anaerobic) 4- Chlamydiae, Rickettsiae, Mycoplasmas These microbes are grouped together because, like other bacteria, they divide by binary fission and are sensitive to antibiotics, but they lack certain structures e.g., Mycoplasma lack a cell wall. M. pneumoniae causes an atypical pneumonia Chlamydia cannot synthesize ATP. Chlamydia trachomatis cause female sterility (by scarring and narrowing of the fallopian tubes) and blindness (by chronic inflammation of the conjunctiva . Chlamydia and Rickettsiae are obligate intracellular organisms. Rickettsiae causes a hemorrhagic vasculitis by injuring endothelial cells, but may also cause a transient pneumonia or hepatitis (Q fever). Infectious agents cause disease - - Not all pathogens have the same probability to cause disease as a result of host variation in the general population ( age, nutritional status, co-morbid disease, immune status) . Location in the body is also important in whether a pathogens cause diseases. e.g., E. coli in colon are normal flora but when present in lung causes pneumonia and in urinary bladder cause cystitis. Infectious diseases are particularly important causes of death among: 1- the elderly people. 2-patients with acquired immunodeficiency syndrome (AIDS). 3- patients with chronic diseases. 4-patients who receive immunosuppressive drugs. How microorganisms transmitted? Direct/Indirect contact (person to person) Airborne carried in the air Oral route enters body through water, food dirty hands Insects and Pests picked up on insects and pests and transferred Classification of Infectious Disease By duration Acute – develops and runs its course quickly. Chronic – develops more slowly and is usually less severe, but may persist for a long, indefinite period of time. Latent – characterized by periods of no symptoms between outbreaks of illness. By location Local – confined to a specific area of the body. Systemic – a generalized illness that infects most of the body with pathogens distributed widely in tissues. By timing Primary – initial infection in a previously healthy person. Secondary – infection that occurs in a person weakened by a primary infection Host Barriers to Infection Skin The defense properties are : 1-The dense, keratinized outer layer of skin is a natural barrier to infection . 2-the low pH of the skin (about 5.5) . 3-the presence of fatty acids inhibit growth of microorganisms other than residents of the normal flora Break down properties in the skin barrier 1-Most M.O penetrate through breaks in the skin, including : superficial pricks (fungal infections). wounds (staphylococci). burns (Pseudomonas aeruginosa). 2-certain types of fungi (dermatophytes) can infect the stratum corneum, hair, and nails . 3-few M.O are able to traverse the unbroken skin,ex: Schistosoma larvae penetrate swimmers' skin by releasing collagenase, elastase, and other enzymes that dissolve the extracellular matrix. 4-Needle sticks can expose the recipient to potentially infected blood and may transmit HBV, HCV, or HIV. 5- Some pathogens penetrate the skin via an insect or animal bite ,ex: - mosquitoes (malaria, leishmaniasis) -lice break the skin and transmit arboviruses (causes of yellow fever and encephalitis) - Dog bite can lead to infections with rabies virus. Gastrointestinal Tract The defense properties are: 1-Acidic gastric secretions . 2-the viscous mucous layer covering the gut . 3-lytic pancreatic enzymes and bile detergents . 4-mucosal antimicrobial peptides called defensins . 5-normal flora . 6-secreted IgA antibodies Break down properties of gastrointistinal tract 1-Low gastric acidity . 2-Antibiotics that unbalance the normal bacterial flora(pseudomembranous colitis). 3- mechanical obstruction. 4-Most enveloped viruses are killed by the bile and digestive enzymes, but nonenveloped viruses may be resistant ( hepatitis A virus, rotaviruses, reoviruses). Respiratory Tract Defense properties: 1-Large microbes are trapped in the mucociliary that lines the nose and the upper respiratory tract. 2-Microorganisms are trapped in the mucus secreted by goblet cells and are then transported by ciliary action to the back of the throat, where they are swallowed and cleared. 3- Organisms smaller than 5 µm travel directly to the alveoli, where they are phagocytosed by alveolar macrophages or by neutrophils recruited to the lung by cytokines. Breakdown properties 1-Damage to the mucociliary defense results from repeated insults in smokers and patients with cystic fibrosis. 2-influenza viruses possess hemagglutinin proteins bind to sialic acid on the surface of epithelial cells lead to engulf the virus then entry and replication within the host cell. 3-influenza viruses possess Neuraminidase that lowers the viscosity of mucus and facilitates viral transit within the respiratory tract. 4-Certain respiratory bacterial pathogens can impair ciliary activity,ex: Haemophilus influenza and Bordetella pertussis elaborate toxins that paralyze mucosal cilia . Spread of microorganism Some microorganisms proliferate locally, at the site of infection, whereas others penetrate the epithelial barrier and spread to other sites via the lymphatic, blood, or nerves. 1- Locally proliferate in site of infection e.g.,(cholera can stay superficial and confined to the lumen of hollow viscera, papillomaviruses, dermatophytes pathogens can adhere to epithelial cells. 2- Many of pathogens (bacteria, fungi and helminthes) are invasive using their ability to motile and secrete lytic enzymes (staphylococci secrete hyaluronidase, which degrades the extracellular matrix between host cells). 4- Some pathogens may be transported free in blood e.g.,( bacteria and fungi, some protozoa (African trypanosomes), and all helminthes are transported free in the plasma. 5- M. tubercolosis foci can disseminate from lung by blood and lymph system and form secondary foci in other organ . They can be: A-single and large (a solitary abscess or tuberculoma) B- multiple and tiny ( miliary tuberculosis). (A) Pulmonary TB will create a hole in the lungs. (B) Miliary tuberculosis of the spleen 6- Some viruses and protozoa are infect leukocytes and able to carry by which ex. (herpesviruses, HIV, mycobacteria, Leishmania and Toxoplasma). 7- Certain viruses (Colorado tick fever virus) and parasites (Plasmodium) are carried by red blood cells. 8- Viruses also may propagate from cell to cell by fusion or transport within nerves (rabies virus). 9 - Chickenpox and measles viruses can arise at sites distant from those of pathogens entry, they enter through the airways but cause rashes for chickenpox and lesion for measles in the skin. 10- Poliovirus enters through the intestine but kills motor neurons. 11- Schistosoma mansoni penetrate the skin but localize in portal and mesenteric blood vessels. 12 - Rubella virus can transported by vertical transmission by placenta. 13- Infection also can occur during passage through the birth canal ( gonoccocal and chlamydial infections) Release of Microbes from the Body For transmission of disease to occur, exit of a microorganism from the host's body is as important as the original entry . Release route of microbes can occur by skin shedding, coughing, sneezing, urination or defecation, or through insect vectors. Some enteric pathogens are shed for long periods by asymptomatic carrier hosts (Salmonella typhi). Transmission from person to person can occur by respiratory (Influenza, TB ), fecal-oral (Hepatitis A virus) or sexual routes (HIV). Viruses infecting the salivary glands (EBV, CMV, mumps viruses) are transmitted principally by talking. M.O can transmitted from animals to humans by invertebrate vectors such as insects or directly from animals to humans (zoonotic infections) e.g., listeriosis Mechanisms of Host – mediated Immune injury Host immune response to microbes can be sometimes the cause of tissue injury. The best example for injurious effect mediated by the cell mediated immunity, is the immune response to mycobacteria. The granulomatous inflammatory reaction to TB is a delayed hypersensitivity response that sequesters the bacilli and prevents spread, but also can produce tissue damage and fibrosis. Other example :the liver damage following hepatitis B virus infection of hepatocytes is mainly due to the immune response to the infected liver cells and not to cytopathic effects of the virus. The humoral immune response to microbes also can have pathologic consequences. e.g., following infection with βhemolytic streptococci, antibodies produced to the streptococcal M protein can cross-react with cardiac proteins and become deposited in the heart, and lead to rheumatic fever. IMMUNE EVASION BY MICROBES (1) Remaining inaccessible to the host immune system. - Microbes that propagate in the lumen of the intestine (e.g., Clostridium difficile) or gallbladder ( Salmonella typhi) are concealed from many host immune defenses. -Some larger parasites ( the larvae - of tapeworms) form cysts in host tissues that are covered by a dense fibrous capsule and are thus inaccessible to host immune cells and antibodies. (2) resisting innate immune defenses (inactivating antibodies or complement), resist phagocytosis, growing within phagocytes after ingestion. Some M.O secrete proteases that degrade antibodies such as Neisseria, Haemophilus, and Streptococcus. Other M.O escape from killing by phagocytic cells and complement. e.g., the capsule of all the major bacteria that cause pneumonia or meningitis (pneumococcus, meningococcus and Haemophilus influenzae) makes them more virulent by shielding bacterial antigens and by preventing phagocytosis of the organisms by neutrophils. (3) varying or shedding antigens. Microbes can evade immune responses either by varying antigens or by shedding antigens. - Streptococcus pneumonia exhibit antigenic variation ,their are at least 80 different serotypes of these microbes, each with different capsular polysaccharides. -Cercariae of Schistosoma mansoni shed their antigens within minutes of penetrating the skin, preventing recognition by host antibodies. (4) suppressing the host adaptive immune response, ex: by inhibiting MHC expression and antigen presentation. some microbes use a strategy of reducing the ability of CD4 helper T cells and CD8 cytotoxic T cells to recognize infected cells. CMV, EBV inhibit production of MHC class I protein or alter their intracellular trafficking, impairing peptide to CD8 T cells and preventing killing of infected cells. Patterns of inflammatory responses to infection There are five major histologic patterns of tissue reaction in infections 1- Suppurative Inflammation. 2- Mononuclear and Granulomatous Inflammation. 3- Cytopathic-Cytoproliferative response. 4- Necrotizing response. 5- Chronic Inflammation and Scarring. Suppurative inflammation It is the reaction to acute tissue damage. Characterized by increased vascular permeability and leukocyte exudates, predominantly of neutrophils. Suppurative inflammation is a response to certain types of bacteria that are “pyogenic” (pus producing), e.g., S. aureus, S. pneumoniae, etc. The neutrophils are recruited to the site of infection by release of chemoattractants from the "pyogenic" organisms and from host cells. Collections of neutrophils may give rise to localized liquefactive necrosis, forming abscesses. The necrotic tissue and inflammatory cells constitute pus. The sizes of exudative lesions vary from tiny microabscesses formed in multiple organs during bacterial sepsis secondary to a colonized heart valve to diffuse involvement of entire lobes of the lung during pneumonia. Suppurative inflammation. polymorphonuclear exudate. Mononuclear and Granulomatous Inflammation Diffuse mononuclear interstitial infiltrates are a common feature of all chronic inflammatory processes, but when they develop acutely, they often are a response to viruses, intracellular bacteria or intracellular parasites, spirochetes and helminths provoke chronic inflammatory responses. Mononuclear cell predominates within the inflammatory lesion depends on the host immune response to the organism. For example, mostly plasma cells are seen in the primary and secondary lesions of syphilis, whereas lymphocytes predominate in HBV infection or viral infections of the brain. Granulomatous Inflammation is a distinctive form of mononuclear inflammation usually evoked by infectious agents that resist eradication (e.g., M. tuberculosis, Histoplasma capsulatum, schistosome eggs) and are capable of stimulating strong T cell-mediated immunity. Granulomatous inflammation is characterized by accumulation of activated macrophages called "epithelioid" cells, which may fuse to form giant cells. In some cases, there is a central area of caseous necrosis . Chronic inflammation Mononuclear inflammation The morphologic spectrum of tuberculosis. A characteristic tubercle at low magnification (A) and in detail (B) illustrates central caseation surrounded by epithelioid and multinucleated giant cells. This is the usual response seen in patients who have developed cell mediated immunity to the organism. Cytopathic- Cytoproliferative response It is usually produced by viruses. The lesions are characterized by cell necrosis or cellular proliferation, usually with sparse inflammatory cells. Some viruses replicate within cells and make viral aggregates that are visible as inclusion bodies (e.g., herpesviruses or adenovirus). Other viruses induce cells to fuse and form multinucleated cells called polykaryons (e.g., measles virus or herpesviruses). Focal cell damage in the skin may cause epithelial cells to become detached, forming blisters. Some viruses can cause epithelial cells to proliferate (e.g., venereal warts caused by human papillomavirus or the umbilicated papules of molluscum contagiosum caused by poxviruses). viruses can cause dysplastic changes and contribute to the development of malignant neoplasms (HBV, HCV, EBV, HIV, HPV). Necrotizing response Clostridium perfringens and other organisms that secrete powerful toxins can cause such rapid and severe necrosis that tissue damage is the dominant feature. Entamoeba histolytica causes colonic ulcers and liver abscesses characterized by Extensive tissue destruction with liquefactive necrosis. Chronic Inflammation and Scarring The final common pathway of many infections is chronic inflammation, which can lead to extensive scarring. For example, chronic HBV infection may cause cirrhosis of the liver, in which dense fibrous septae surround nodules of regenerating hepatocytes. Sometimes the exuberant scarring response is the major cause of dysfunction (ex: the fibrosis of the urinary bladder wall caused by schistosomal eggs or the constrictive fibrous pericarditis caused by tuberculosis). Schistosoma haematobium infection of the bladder with numerous calcified eggs and extensive scarring Diagnosis of infectious diseases Epidemiological dates Clinical features Symptoms and signs Laboratory findings Routine examination of blood, urine, feces Bio-chemical examinations Etiological examinations Direct exam Isolation of pathogen Molecular biological examinations Immunological examinations Endoscope examinations Image examinations Prevention of infectious disease Management of source of infection Cut off of route Personal hygiene, public hygiene, insecticide, disinfection Protect susceptible population Vaccines Active immunization Passive immunization