Bacterial Infection PDF

Bacterial Infection By the end of this lecture, students will be able to: 1. Differentiate between colonization , infection and disease. 2. Define carriers of infection and site of carriage 3. Distinguish between true pathogen and opportunistic pathogen 4. List types of infectio...

Bacterial Infection By the end of this lecture, students will be able to: 1. Differentiate between colonization , infection and disease. 2. Define carriers of infection and site of carriage 3. Distinguish between true pathogen and opportunistic pathogen 4. List types of infections 5. Illustrate stages of bacterial pathogenesis 6. Explain factors that govern disease production by bacteria 7. Explain virulence factors of bacteria 8. Compare between exotoxins and endotoxins  Host – parasite relationship can be viewed as a series of stages Contact Infection Disease Not all contacts lead to infection, and not all infection lead to disease depending on: Host Degree of resistance pathogenicity What is Colonization? The presence of new micro- organisms that are not members of normal flora, pathogenic or non- pathogenic, in large numbers, on a host without tissue damage or clinical disease. What is infection? Infection: is the process by which the parasite enters into relationship with the host. What is disease? Disease: is the destruction of host tissues by organisms due to invasion of tissues, toxins or other virulence factors It requires the following: 1. A source of infection: which may be man (case or carrier), animal or soil. 2. Mode of transmission: e.g., insects bite, fecal contamination of food, inhalation of droplets, sexual contact, blood transfusion or transplacental. 3. A portal of entry into the host e.g., gastrointestinal, genitourinary, respiratorytracts, skin and mucous membranes and through abrasions, insect bites or injections. 4. Multiplication of the parasite within the host: the parasite may multiply locally at the portal of entry or it may spread through the tissues, blood or lymphatics to reach a target organ. 5. Portal of exit from the host e.g.,in urine, stools, respiratory, genital discharges or from the blood by insects or injections Carriers *Definition : is an apparently healthy individuals carrying a pathogenic organism without showing clinical manifestations. *They can transmit disease during incubation period or permanent (chronic) as in hepatitis B. Short story * Mary Mallon , also known as Typhoid Mary, was an Irish- American cook. * She was the first person in the United States identified as an asymptomatic carrier of the pathogen associated with typhoid fever. * She was presumed to have infected 51 people, three of whom died, over the course of her career as a cook. * She was twice forcibly isolated by public health authorities and died after a total of nearly three decades in isolation.  Carriers * The site of carriage may be : intestinal, urinary, nasopharyngeal , nasal , skin, blood. * Carriers are more serious than cases as they: Not confined to bed. They don’t show manifestation of disease Communicate with public. Carry organism in inter-epidemic period.  Types of Pathogens The pathogens : microorganisms capable of causing disease. Two main types of pathogens : 1. True pathogens : capable of causing disease in healthy persons. 2. Opportunistic pathogen : rarely cause disease in immune- competent people but can cause serious infections in immune-compromised patients. (frequently members of the body's normal flora).  Types of infection According to the extent of spread: 1. Localized: at the portal of entry. 2. Systemic: spread to several sites and tissue fluids  Types of infection According to the progress of the infection: 1. Acute : arise quickly (e.g. tonsillitis) and progress rapidly. 2. Latent: the microbe can persist for years and cause minimal clinical disease with the ability to reactivate. 3. Chronic: the organisms continue to grow with or without producing symptoms (important source→public health hazard).  Types of infection According to the sequence of infection: 1-Primary infection:t he initial infection caused by the organism. 2-Secondary infection: occurs if the initial infection is complicated by other infection caused by a different organism.  Types of infection According to the distribution: 1-Endemic infection: which is constantly present at a low level in a specific population. 2-Epidemic infection: that occurs much more frequently than usual. 3-Pandemic infection that has a worldwide distribution. Chain of infection  Stages of infection The time from initial contacts with the infectious The Incubation agents to the appearance of the first symptoms. period The earliest symptoms of infection appear as a vague feeling of discomfort, generalized body ache The prodromal stage The specific signs and symptoms exhibited by the Period of patients according to the site of infection. invasion The period of recovery. Convalescent period  Sequence of Bacterial Pathogenesis 1. Transmission from an external source into the portal of entry. 2. Evasion of primary host defenses such as skin or stomach acid. 3. Adherence to mucous membranes, usually by bacterial pili. 4. Colonization by growth of the bacteria at the site of adherence. 5. Disease symptoms cased by toxin production or invasion accompanied by inflammation. 6. Host responses, both nonspecific and specific (immunity) during steps 3,4 and 5. 7. Progression or resolution of the disease. Factors governing disease production Microbial factors Host factors Important Definitions  Pathogenicity and Virulence Pathogenicity: the ability of the organism to cause a disease (qualitative) Infectious dose: the dose of an organism required to cause disease varies greatly among pathogenic bacteria. Virulence: the degree of pathogenicity (quantitative) Virulence factors: structures or products that help the microbe to overcome host defense mechanisms and produce disease.  1. Transmissibility The first step of the infectious process is the entry of the microorganism into the host. Once entry is achieved, the pathogen must overcome a diversity of host defenses before it can establish itself.  2. Adherence Some bacteria (for example, Escherichia coli) use their pili to adhere to the surface of host cells.  Adherence is mediated by: a-Pili: are specialized structures of the bacteria that facilitate the attachment of bacterial cells to the surface of the human cells e.g. Neisseria gonorrhea. b-Extracellular polysaccharides (Glycocalyx): some bacteria as Streptococcus mutans produce glycocalyx that help it to adhere to enamel surface or prostheses.  3- Biofilm Formation Biofilm is an aggregation of interactive bacteria attached to living or non- living surfaces or to each other and encase in an extracellular polysaccharide matrix. Dental plaque on solid enamel surfaces is classic example of biofilm. Bacteria in biofims maintain the population density by constantly secreting low levels of chemicals called quorum-sensing molecules which tend to repulse incoming bacteria or activate the bacteria to seek new place. Infection associated with biofilms are difficult to eradicate as the attached organisms in biofilms exhibit higher resistant to antimicrobial than their living planktonic form, for example chronic periodontal infections due to dental plaque.  This is due to: The extracellular polysaccharide matrix offered protection from the host immune mechanism. Poor penetration of antimicrobials into the deeper layers. Degradation of antimicrobials as they penetrate the biofilm. Difference in pH and redox potential gradients that is not suitable for the optimal activity of the drug. Gene expression and gene transfer leading to more virulent or resistant organisms.  4. Invasiveness Invasive bacteria can enter host cells or penetrate mucosal surfaces → spreading from initial site of infection. Bacterial enzymes e.g. Collagenase and Hyaluronidases facilitate invasiveness.  5. Toxins Toxins produced by bacteria are classified into exotoxins (extracellular toxins) and endotoxins (Lipopolysaccharides). Septic Shock The endotoxin: acts as a superantigen which stimulates the release of IL-1, TNF, bradykinin and other mediators. The biological effects of endotoxin include, fever, hypotension, activation of complement, increased vascular permeability, disseminated intravascular coagulation “DIC”, thrombosis, purpural rash and ischemia. Septicshock can cause death of the patient even though antibiotics have killed the bacteria in the blood.  Exotoxins Endotoxins Source Certain species of Outer cell membrane of most gram ⊕ and gram ⊝ gram ⊝ bacteria bacteria Secreted from cell Yes No Chemistry Polypeptide Lipid A component of LPS Location of genes Plasmid or Bacterial chromosome bacteriophage Adverse effects High Low Antigenicity Highly antigenic Weakly immunogenic Vaccines Toxoids used as No toxoids, no vaccines vaccines Heat stability Destroyed rapidly at Stable at 100°C for 1 hr 60°C Receptors Bind to specific No specific receptors receptors on cells Fever production Not produce fever Occasionally produce fever via release of interleukin-1 and other mediators  5. Enzymes A. Collagenase and Hyaluronidases degrades collagen and hyaluronic acid, respectively and promotes spread of infection in tissue. e.g. cellulitis by Strept pyogenes.  5. Enzymes B. Coagulase produced by Staphylococcus aureus coagulates plasma, forming fibrin walls around staphylococcal lesions, which may help protect them from phagocytosis or from destruction within phagocytic cells.  Coagulaseproduced by Staphylococci works in conjunction with blood factors to coagulate plasma, contributes to the formation of fibrin walls around staphylococcal lesions, which may help protect them from phagocytosis or from destruction within phagocytic cells.  5. Enzymes C. IgA1 Proteases that split and inactivate IgA1 the primary antibody found on mucosal surfaces D. Leukocidines destroy both neutrophils and macrophages. Factors that interfere with the host defense mechanisms (e.g. phagocytosis): a-The polysaccharide capsule: as in Streptococcus pneumonia and Neisseria meningitis, prevents the phagocytes from adherence to the bacteria. b-The cell wall proteins: such as M protein of the group A streptococci and Protein A of the Staphylococci, are also antiphagocytic  References Microbiology Department Book for Students Oxford Handbook of Medical Sciences, 2nd edition, Chapter 12 infection and immunity. First aid for the USMLE Step 1, 2019, Section II (Microbiology). 1-All of the following are characters of endotoxin EXCEPT: Heat stable Protein polysaccharide lipid complex Action is often enzymatic Produced by gram negative bacteria Poorly immunogenic 2-Exotoxin have all of the following characters EXCEPT: Enzymatic action Specific tissue affinity Active in minute dose Polysaccharide lipid in nature Strong immunogen 3-Mediate adherence to epithelial surfaces: Capsule Glycocalyx Cell wall Ordinary pili Sex pili 4- Invasiveness of bacteria could be facilitated by: Coagulase enzyme Collagenase enzyme Catalase enzyme Urease enzyme Exotoxin with enzymatic activity