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Chapter 12 Mechanisms of Infectious Disease Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Terminology Involved in the Study of Infectious Disease • Host—any organism capable of supporting the nutritional and physical growth requirements of another organism • Infectious disease—the disease state brought about by the interaction with another organism • Colonization—the presence and multiplication of a living organism on or within the host • Microflora—bacteria inhabiting exposed surfaces of the body • Virulence—the disease-inducing potential Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Terminology Involved in the Study of Infectious Disease (cont.) • Pathogens—microorganisms so virulent that they are rarely found in the absence of disease • Saprophytes—free-living organisms obtaining their growth from dead or decaying organic material from the environment Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Terminology Involved in the Study of Infectious Disease (cont.) • Mutualism: an interaction in which the microorganism and the host both derive benefits from the interaction • Commensalism: an interaction in which colonizing bacteria acquire nutritional needs and shelter but the host body not affected • Parasitic relationship: only the infecting organism benefits from the relationship – If the host sustains injury or pathologic damage, the process is called an infectious disease. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Agents of Infectious Disease • Prions • Viruses • Bacteria • Rickettsiaceae • Chlamydiaceae • Fungi • Parasites Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Viruses • Smallest pathogens • Have no organized cellular structure • Consist of a protein coat surrounding a nucleic acid core of DNA or RNA • Are incapable of replication outside a living cell Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Microorganisms • Eukaryotes (Fungi) – Contain a membrane-bound nucleus • Prokaryotes (Bacteria) – The nucleus is not separated. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Classification of Bacteria • According to the microscopic appearance • According to staining of the cell – Gram-positive organisms: stained purple by a primary basic dye (usually crystal violet) – Gram-negative organisms: not stained by the crystal violet but are counterstained red by a second dye (safranin) Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Parasites • Types – Protozoa – Helminths – Arthropods • Method of Infecting – These members of the animal kingdom infect and cause diseases in other animals. – These animals then transmit disease to humans. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Rickettsiaceae, Anaplasmataceae, Chlamydiaceae, Coxiella • Organisms that combine the characteristics of viral and bacterial agents to produce disease in humans – Are obligate intracellular pathogens like the viruses – Produce a rigid peptidoglycan cell wall – Reproduce asexually by cellular division – Contain RNA and DNA similar to the bacteria Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question • Which of the following pathogens does not fit the typical description of an organism? − A. Viruses − B. Bacteria − C. Rickettsiaceae − D. Chlamydiaceae − E. Fungi − F. Parasites Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer • A. Viruses • Rationale: Viruses have no organized cellular structure. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Classification of Infectious Disease • Incidence • Portal of entry • Source • Symptoms • Disease course • Site of infection • Virulence factors Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Epidemiology (Terminology) • Epidemiology: the study of factors, events, and circumstances that influence the transmission of infectious diseases among humans • Incidence: the number of new cases of an infectious disease that occur within a defined population • Prevalence: the number of active cases at any given time Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Incidence of Disease • Endemic disease: found in a particular geographic region – The incidence and prevalence are expected and relatively stable. • Epidemic: Abrupt and unexpected increase in the incidence of disease over endemic rates • Pandemic: Spread of disease beyond continental boundaries Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Portals of Entry • Penetration • Direct contact • Ingestion • Inhalation Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Source of an Infectious Disease • Location – Nosocomial: develop in hospitalized patients – Community acquired: acquired outside of health care facilities • Host – An object or substance from which the infectious agent was acquired – May be endogenous or exogenous Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Symptomatology • Specific: reflects the site of infection (e.g., diarrhea, rash, convulsions, hemorrhage, pneumonia) • Nonspecific: can be shared by a number of diverse infectious diseases (e.g., symptoms such as fever, myalgia, headache) • Obvious: predictable patterns (e.g., chickenpox and measles) • Covert: may require laboratory testing to detect (e.g., hepatitis or increased white blood cell count) Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Disease Course in Infection • Incubation period • Prodromal stage • Acute stage • Convalescent stage • Resolution stage Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Factors Influencing the Site of an Infectious Disease • Type of pathogen • Portal of entry • Competence of the host’s immunologic defense system Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question • Is the following statement true or false? • The symptoms of an infection are always obvious and apparent. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer • False • Rationale: Symptoms may be covert or nonspecific in presentation. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Types of Antimicrobial Agents • Antibacterial agents • Antiviral agents • Antifungal agents • Antiparasitic agents Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Drug Resistance • Bacterial resistance mechanisms • Antiviral resistance mechanisms – Inactivate antibiotics – Nuceoloside analogs – Genetically alter antibiotic binding sites – Protease inhibitors – Bypass antibiotic activity – Changes in the bacterial cell wall • Need for combination or alternating therapy with multiple antiretroviral agents Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Intravenous Immunoglobulin and Cytokine Therapy • Supplementing or stimulating the host’s immune response so that the spread of a pathogen is limited or reversed • Pathogen-specific antibodies given to the patient as an infusion to facilitate neutralization, phagocytosis, and clearance of infectious agents above and beyond the capabilities of the diseased host Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Criteria for Diagnosis of an Infectious Disease • The recovery of a probable pathogen or evidence of its presence from the infected sites of a diseased host • Accurate documentation of clinical signs and symptoms (symptomatology) compatible with an infectious process Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Techniques for Laboratory Diagnosis of an Infectious Agent • Culture • Serology or detection of characteristic antigens • Genomic sequences or metabolites produced by the pathogen Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Categories of Virulence Factors • Toxins • Adhesion factors • Evasive factors • Invasive factors Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Nonpharmacological Intervention • Surgical interventions – Providing access to an infected site by antimicrobial agents (drainage of an abscess) – Cleaning of the site (debridement) – Removing infected organs or tissue (e.g., appendectomy). Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question • Is the following statement true or false? • Surgical therapy is used in tandem with antibiotic treatment in some cases of severe infection. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer • True Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Antibiotic Mechanisms • Interference with a specific step in bacterial cell wall synthesis • Inhibition of bacterial protein synthesis • Interruption of bacterial nucleic acid synthesis • Interference with normal bacterial metabolism Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Classification of Antibiotic Action • Bactericidal—if it causes irreversible and lethal damage to the bacterial pathogen • Bacteriostatic—if its inhibitory effects on bacterial growth are reversed when the agent is eliminated Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Classification and Target Site of Antibacterial Agents • Penicillins: cell wall • Cephalosporins: cell wall • Monobactams: cell wall • Aminoglycosides: ribosomes • Tetracyclines: ribosomes • Macrolides: ribosomes • Sulfonamides: folic acid synthesis • Glycopeptides: ribosomes • Quinolones: DNA synthesis Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Weapons of Bioterrorism • Category A Agents – Plague – Tularemia – Smallpox – Hemorrhagic fever viruses • Category B Agents – Agents of food-borne and water-borne diseases – Agents of zoonotic infections Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Weapons of Bioterrorism (cont.) • Category B Agents (cont.) – Viral encephalitides – Toxins from castor bean • Category C Agents – Mycobacterium tuberculosis – Nipah virus and hantavirus – Tick-borne and Yellow fever viruses – Cryptosporidium parvum Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins