infection and inflammation. adult health

infection

1. Infection and inflammation UNIVERSITY INSTITUTE OF NURSING

2. What is Infection An infection is the colonization of a host by Microbial species. Infecting Microbes seek to use the host's resources to reproduce, often resulting in disease. I nfections are usually considered to be caused by microscopic organisms like viruses, prions, bacteria, and viroids, though larger organisms like macro parasites and fungi can also infect.

3. Basis of Classification of Infections Infections are classified in multiple ways. They are classified by the causative agent as well as by the constellation of symptoms and medical signs that are produced. An infection that produces symptoms is an apparent infection. An infection that is active, but does not produce noticeable symptoms, may be called in apparent , silent , or subclinical . An infection that is inactive or dormant is called a latent infection

4. Understandi ng Infection and Disease Definitions The Normal Flora of Humans Generalized Stages of Infection Virulence Factors and Toxins

5. What Causes an Infectious Disease Infection is caused by microorganism The microorganism may be a bacteria, a virus, a parasite or a fungus Baci l l us an t hracis ba c t e ri a – Pu b l i c Hea l t h I ma g e L i br a ry D r . T . V .R a o MD 5

6. O v e r view Types of Microorganisms Principles of Infection Transmission Host resistance Virulence and pathogenicity Control of transmission and infection Development of Infection Onset and course Clinical signs and symptoms Diagnostic tests Antimicrobial Drugs Example of Infection: Influenza

7. Conditions required for infection to spread from one person to another 1. One person must be infected with a microorganism 2. The other person must be susceptible to infection with that microorganism 3. The microorganism must be able to leave the body of the infected person and enter the body of the susceptible person.

8. Types of infection Colonization – infection present on surface of body – Organism propagating at a rate sufficient to maintain its numbers without producing identifiable evidence of any reaction in host Inapparent or subclinical infection organism not only multiplying but also causes a measurable reaction that is however not clinically detectable Symptomatic infection Organism causes clinically detectable reaction

9. Time parameters of interaction Latency Period = the time between infection agent and onset of infectiousness Incubation Period = the time between infection and onset of symptoms Latency per iod may not be the sam e as the inc u D r . T b . V . R a a o M t D ion period 9

10. Definitions Disease and Infectious Disease Disease Any deviation from a condition of good health and well-being Infectious Disease A disease condition caused by the presence or growth of infectious microorganisms or parasites

11. D e finitio n s Pathogenicity and Virulence Pathogenicity The ability of a microbe to cause disease This term is often used to describe or compare species Virulence The degree of pathogenicity in a microorganism This term is often used to describe or compare strains within a species

12. D e finitio n s Acute infection vs. chronic infection Acute Infection An infection characterized by sudden onset, rapid progression, and often with severe symptoms Chronic Infection An infection characterized by delayed onset and slow progression

13. D e finitio n s Primary infection vs. secondary infection Primary Infection An infection that develops in an otherwise healthy individual Secondary Infection An infection that develops in an individual who is already infected with a different pathogen

14. D e finitio n s Localized infection vs. systemic infection Localized Infection An infection that is restricted to a specific location or region within the body of the host Systemic Infection An infection that has spread to several regions or areas in the body of the host

15. . Definitions Clinical infection vs. subclinical infection – Clinical Infection An infection with obvious observable or detectable symptoms – Subclinical Infection An infection with few or no obvious symptoms D r . T . V .R a o MD 15

16. D e finitio n s Opportunistic infection – An infection caused by microorganisms that are commonly found in the host’s environment This term is often used to refer to infections caused by organisms in the normal flo ra

17. Defining The suffix “-emia” A suffix meaning “presence of an infectious agent” Bacteremia = Presence of infectious bacteria Viremia = Presence of infectious virus Fungemia = Presence of infectious fungus Septicemia = Presence of an infectious agent in the bloodstream

18. Definitions The suffix “-itis” A suffix meaning “inflammation of” Examples: – P h a r y n git i s = I n flamm a tion o f the pha r y n x – Endocarditis = Inflammation of the heart chambers – Ga s t r oe nt er i tis = I n flamm a tion o f the gastrointestinal tract

19. Definitions Epidemiology The study of the transmission of disease Communicable Disease A disease that can be transmitted from one individual to another Contagious Disease A communicable disease that is easily spread from one individual to another Non communicable Disease A disease that is not transmitted from one individual to another

20. Definitions Endemic Disease A disease condition that is normally found in a certain percentage of a population Epidemic Disease A disease condition present in a greater than usual percentage of a specific population Pandemic Disease An epidemic affecting a large geographical area; often on a global scale

21. Definitions Reservoir of Infection The source of an infectious agent Carrier An individual who carries an infectious agent without manifesting symptoms, yet who can transmit the agent to another individual Fomites Any inanimate object capable of being an intermediate in the indirect transmission of an infectious agent

22. Definitions Animal Vectors An animal (nonhuman) that can transmit an infectious agent to humans Two types: mechanical and biological Biological animal vectors: The infectious agent must incubate in the animal host as part of the agent’s developmental cycle; eg, the transmission of malaria by infected mosquitoes Mechanical animal vectors: The infectious agent is physically transmitted by the animal vector, but the agent does not incubate or grow in the animal; eg, the transmission of bacteria sticking to the feet of flies

23. Definitions Direct Mechanisms of Disease Transmission Directly From Person to Person Examples: Direct Skin Contact Airborne (Aerosols) From Mother to fetus

24. Indirect Transmission Indirect Mechanisms of Disease Transmission – E x amp l es: Food & Waterborne Transmission Fomites Animal Vectors

25. The Normal Flora of Humans Types of Symbiosis Mutualism A symbiotic relationship in which both species benefit Commensalism A symbiotic relationship in which one species benefits, and the other species is neither helped nor harmed

26. The Normal Flora of Humans Types of Symbiosis (cont.) Parasitism A symbiotic relationship in which one species benefits, and the other species is harmed Generally, the species that benefits (the parasite) is much smaller than the species that is harmed (the host)

27. . The Normal Flora of Humans Normal flora is present in skin upper respiratory tract oral cavity intestine, especially large intestine vaginal tract Very little normal flora in eyes & stomach

28. The Normal Flora is absent Notably absent in most all internal organs Absent in: lower respiratory tract muscle tissue blood & tissue fluid cerebrospinal fluid peritoneum pericardium meninges

29. The Normal Flora of Humans Benefits of the normal flora Nutrient production/processing eg Vitamin K production by E. coli Competition with pathogenic microbes Normal development of the immune system Normal flora and opportunistic infections

30. Development of Infection: Onset and Course Incubation period Organism present; no clinical signs, symptoms Prodromal period Symptoms; don’t feel like yourself Acute period Fully developed infection

31. Development of Infection: Clinical Signs and Symptoms Local signs Inflammation Purulent exudate if bacterial infection; serous exudate if viral Tissue necrosis Lymphadenopathy Respiratory effects Systemic signs Fever, fatigue, headache, nausea

32. Generalized Stages of Infection Entry of Pathogen Portal of Entry Colonization Usually at the site of entry Incubation Period Asymptomatic period Between the initial contact with the microbe and the appearance of the first symptoms

33. Generalized Stages of Infection Prodromal Symptoms Initial Symptoms Invasive period Increasing Severity of Symptoms Fever Inflammation and Swelling Tissue Damage Infection May Spread to Other Sites Acme (Fastigium)

34. Modes of Transmission Direct contact Indirect contact Droplet t r ansmission Hands Vector-borne Nosocom ial

35. Modes of Transmission Direct tran s mi s si o n Indirect transmission Direct contact Airborne Droplet spread Vehicle borne Vector borne

36. Virulence and Pathogenicity Pathogenicity: capacity of microbes to cause disease Virulence: degree of pathogenicity of specific microbe Based on: Invasive qualities Toxic qualities Presence of pili or fimbriae for adhesion Ability to avoid host defenses (mutate) D r . T . V .R a o MD 38

37. Virulence Factors and Toxins State of the Host Immune System Number of Pathogenic Cells encountered by the Host – I n f ectiou s Dos e D r . T . V .R a o MD 39

38. Virulence Factors and Toxins Enzymatic Virulence Factors Examples: Coagulase ( Staphylococcus aureus ) Streptokinase ( Streptococcus pyogenes ) Hyaluronidase (Many pathogens) Collagenase (Many pathogens) Leukocidin (Many pathogens) Hemolysin (Many pathogens)

39. Virulence Factors and Toxins Adhesion Factors Examples: Protein A ( S t ap h y l o c o c cus aureus ) Protein M ( Stre p t o c o c cus pyogenes )

40. Virulence Factors and Toxins Exotoxins A type of bacterial toxin with the following properties: May be produced by either gram-positive or gram- negative bacteria Is secreted by the bacteria The action of the exotoxin does not necessarily require the presence of the bacteria in the host Most exotoxins are peptide or protein Most exotoxins are heat sensitive (exception: enterotoxin of Staphylococcus aureus )

41. Virulence Factors and Toxins Exotoxins (cont.) Classes of exotoxins: Neurotoxic, cytotoxic, or enterotoxic exotoxins Neurotoxins: Interfere with proper synaptic transmissions in neurons Cytotoxins: Inhibit specific cellular activities, such as protein synthesis Enterotoxins: Interfere with water reabsorption in the large intestine; irritate the lining of the gastrointestinal tract

42. Virulence Factors and Toxins Endotoxins A type of bacterial toxin having the following properties: Produced only by gram-negative bacteria Endotoxins are a component of the gram-negative cell wall The action of endotoxin requires the presence of the bacteria in the host. The endotoxin may be released from the cell wall as the cells die and disintegrate

43. Virulence Factors and Toxins Endotoxins (cont.) Endotoxin is composed of Lipid A: Part of the lipopolysaccharide layer Mode of action: Irritation/inflammation of epithelium, GI irritation, capillary/blood vessel inflammation, hemorrhaging

44. Development of Infection: Diagnostic Tests Cultures and stains bacteria Blood tests Bacteria Leukocytosis Virus Leukopenia Increase in neutrophils w/ acute; increase in lymphocytes and monocytes w/ chronic Radiologic exams

45. Steps to Minimize Risk of Infection Locate, remove reservoir host Block portal exit of microbes from reservoir Know mode(s) of transmission of specific infections Block portals of entry Cleaning Sterilization Disinfectants Antiseptics

46. Hospital acquired infections Infection which was neither present nor incubating at the time of admission Includes infection which only becomes apparent after discharge from hospital but which was acquired during hospitalisation (Rcn, 1995) Also called nosocomial infection

47. Modes of spread Two sources of infection : Endogenous or self-infection - organisms which are harmless in one site can be pathogenic when transferred to another site e.g., E. coli Exogenous or cross-infection - organisms transmitted from another source e.g., nurse, doctor, other patient, environment (Peto, 1998)

48. 1st principle of infection prévention at least 35-50% of all nosocomial infections are associated with patient care practices: Use and care of urinary catheters Use and care of vascular access lines Therapy and support of pulmonary functions Experience with surgical procedures Hand hygiene and standard precautions

49. Basic steps in Prevention of Infection There are possible treatment and prevention to stop the infection cycle. This is through adequate hygiene, sanitary environment maintenance and health education.

50. and have no effect on viral ones. Antimicrobial agents In Infection Anti-infective drugs such as antibiotics, antiviral, antifungal and ant tubercular drugs suppress infection. It can be administered by mouth, topically or intravenously depending on the infection extent and severity. Sometimes, if drug resistance is known, multiple drugs are used to stop drug resistance and increase drug effectiveness. Antibiotics only work for bacterial infection

51. Acute and Chronic Inflammation

52. Introd u c t i on Inflammation is a defensive host response to foreign invaders and necrotic tissue. Can be acute or chronic.

53. Acute inflammation

54. Acute inflammation Immediate and early response to tissue injury ( physical, chemical, microbiologic, etc. ) Acute inflammation has two major components : Vascular changes Cellular events

55. Vascular change

56. Vascular change The main vascular reactions of acute inflammation are increased blood flow followed by vasodilation and increased vascular permeability: warmth and redness Opens microvascular beds and protein-rich fluid moves into extravascular tissues Migration of leukocytes ( principally neutrophils)

57. Increased vascular permeability This will leads to the movement of protein-rich fluid and blood cells into the extravascular tissue. The resulting protein-rich accumulation is called an exudate. Increases interstitial osmotic pressure contributing to edema.

58. Vascular leakage several mechanisms may contribute to increased vascular permeablity: Endothelial cell contraction that leading to intracellular gaps of venules This occur after binding of histamines and bradykinins, and many other mediators and is usually short-lived (15 – 30 min.)

59. Vascular leakage Cytokine mediators (TNF, IL-1) induce endothelial cell junction retraction through cytoskeleton reorganization This reaction may take 4 – 6 hrs to develop ,and lasting for 24 hrs or more

60. Vascular leakage Endothelial injuries result in vascular leakage by causing direct endothelial cell necrosis, detachment making them leaky until they are repaired or may cause delayed damage as in thermal, certain bacterial toxins or Ultraviolet injury.

61. Vascular leakage Certain mediators such as vascular endothelial growth factor (VEGF) may cause increased transcytosis via intracellular vesicles which travel from the luminal to basement membrane surface of the endothelial cell All or any combination of these events may occur in response to a given stimulus

62. Leukocyte cellular events

63. Leukocyte cellular events ■ Leukocytes leave the vascular lumen to the extravascular space through the following sequence of events: ■ ■ Margination and rolling along the vessel wall Firm adhesion and transmigration between endothelial cells Chemotaxis and activation

64. Margination and Rolling ■ With increased vascular permeability, fluid leaves the vessel causing leukocytes to settle-out of the central flow column and “marginate” along the endothelial surface Endothelial cells and leukocytes have complementary surface adhesion molecules which briefly stick and release causing the leukocyte to roll along the endothelium until it eventually comes to a stop as mutual adhesion reaches a peak

65. Margination and Rolling Early rolling adhesion mediated by selectin family of adhesion molecules: E-selectin (on endothelium cell) P-selectin (present on platelets, endothelium) L-selectin (on the surface of most leukocytes)

66. A d h e s i o n ■ The rolling leukocytes are able to sense change on the endothelium that initiate the next step in the reaction of leukocytes, which is firm adhesion to endothelial surface Occur as leukocytes adhere to the endothelial surface and is mediated by the interaction of integrins on leukocytes binding to IG-family adhesion proteins on the endothelium. ■

67. Transmigration (diapedesis) Is the movement of leukocyte across the endothelial surface Occurs after firm adhesion and mediated by palatelete endothelial cell adhesion molecules-1 (PECAM –1) on both leukocyte and endothelium

68. Chemotaxis ■ Leukocytes follow chemical gradient to site of injury this process called (chemotaxis) Chemotactic factors for neutrophils, produced at the site of injury, include: ■ ■ ■ Bacterial products Components of complement system especially (C5a) Cytokines.

69. Phagocytosis Phagocytosis is the ingestion of particulate material by phagocytic cell neutrophils and monocytes-macrophages are the most important phagocytic cells

70. Phagocytosis consists of three steps: Recognition and attachment of the particle Engulfment (form phagocytic vacuole) Killing and degradation of the ingested materials.

71. Defe c t s o f leu k o cy t e func t ion Defects of leukocyte adhesion: Leukocyte adhesion deficiency type I : is associated with recurrent bacterial infections. Leukocyte adhesion deficiency type 2 : is associated with recurrent bacterial infections and result from mutations in the gene that required for the synthesis of sialyl-lewis X on neutrophils.

72. Defe c t s o f leu k o cy t e func t ion Defects of chemotaxis/phagocytosis: Microtubule assembly defect leads to impaired locomotion and lysosomal degranulation (Chediak-Higashi Syndrome)

73. Possible outcomes of acute inflammation

74. Possible outcomes of acute inflammation Complete resolution of tissue structure and function: ■ ■ When the injury is limited or short-lived. There has been no or little tissue damage When the injured tissue is capable of regeneration Scarring (fibrosis): ■ When inflammation occur in tissues that do not regenerate The injured tissue is filled with connective tissue

75. Outcomes (cont’d) Abscess formation occurs with some bacterial or fungal infections Progression to chronic inflammation.

76. Chronic inflammation

77. Chronic inflammation Is inflammation of prolonged duration (week to years) in which continuing inflammation, tissue injury, and healing, often by fibrosis, proceed simultaneously.

78. Chronic inflammation ■ ■ ■ Is characterized by a different set of reactions: Lymphocyte, macrophage, plasma cell (mononuclear cell) infiltration Tissue destruction by inflammatory cells Repair with fibrosis and angiogenesis (new vessel formation)

79. ■ Chronic inflammation may arise in the following setting : ■ ■ Persistent injury or infection (ulcer, TB) Prolonged toxic agent exposure (silica) Autoimmune disease states (RA, SLE)

80. Chronic inflammatory cells and mediators

81. Chronic inflammatory cells and mediators Macrophages The dominant cells. Scattered all over (Kupffer cells, sinus histiocytes, alveolar macrophages, etc. Derived from circulating blood monocytes and reach site of injury within 24 – 48 hrs and transform to macrophages.

82. Chronic inflammatory cells and mediators ■ ■ Two majors pathways of macrophage activation: Classical macrophage activation: induced byT cell-derived cytokines, endotoxins, and other products of inflammation Alternative macrophage activation: induced by cytokines produced by T lymphocytes and other cell including mast cell and eosinophils

83. Chronic inflammatory cells and mediators ■ ■ ■ Macrophages have several roles in host defense and inflammatory reaction: Ingest and eliminate microbes and dead tissue. Initiate the process of tissue repair. Secrete mediators of inflammation such as cytokines.

84. Chronic inflammatory cells and mediators Lymphocytes (T - B ) Antigen-activated (via macrophages and dendritic cells) Lymphocytes and macrophages interact in a bidirectional way and these interaction play an important role in propagating chronic inflammation lymphocyte release macrophage-activating cytokines (in turn, macrophages release lymphocyte-activating cytokines until inflammatory stimulus is removed)

85. Chronic inflammatory cells and mediators Eosinophils Found especially at sites of parasitic infections, and as part of immune reaction mediated by IgE Typically associated with allergies.

86. Granulomatous Inflammation

87. Granulomatous Inflammation Is a distinctive pattern of chronic inflammation characterized by aggregates of activated macrophages and scattered lymphocytes.

88. Granulomatous Inflammation can form under three setting : Persistance T-cell response to certain microbes (such as TB) In some immune mediated inflammatory diseases (Crohn disease) In sarcoidosis disease in response to relatively inert foreign bodies(suture or splinter)

89. Systemic effects

90. Systemic effects F e ve r ■ ■ The most prominent manifestation of acute-phase response. Fever is produced in response to pyrogens which stimulate prostoglandine synthesis. PGE stimulate the production of neurotransmitters to reset the temperature at a higher level.

91. Systemic effects (cont’d) Le u kocy t os is ■ Is a common feature of inflammatory reaction, espicially those induced by bacterial infection Elevated white blood cell count. Other manifestations include: ■ ■ Increased heart rate and blood pressure. Decreased sweating. Sepsis in severe bacterial infection.

92. THANKS