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Chapter 9 Overview 9.1 Causes of Infectious Diseases Pathogens such as viruses, prions, bacteria, protozoans, helminths, and fungi can cause disease. True pathogens cause disease in a regularly healthy host; opportunistic pathogens require a weakened host or a disruption in the norma...

Chapter 9 Overview 9.1 Causes of Infectious Diseases Pathogens such as viruses, prions, bacteria, protozoans, helminths, and fungi can cause disease. True pathogens cause disease in a regularly healthy host; opportunistic pathogens require a weakened host or a disruption in the normal flora. Vocabulary related to infectious diseases: Sporadic cases of disease are scattered or isolated infections in a particular population, while endemic diseases are routinely found in a specified population or region. An epidemic is a widespread outbreak of disease in a particular region during a specified time frame; an epidemic that spreads to numerous countries is called a pandemic. Zoonotic diseases are transmitted from animals to humans. Infectious diseases can be communicable (spread from person to person) or noncommunicable (not spread from person to person). A contagious disease is a communicable disease that is easily spread in a population. Pathogens can cause latent infections (asymptomatic) or active infections in which the patient has signs and symptoms of disease.  Signs are objective indicators of disease that can be witnessed or verified. Symptoms are subjective and mainly sensed by the patient. Acute diseases have a rapid onset and rapid progression; chronic diseases are characterized by slower onset and progression. Koch’s postulates of disease help identify the causative agent of infectious diseases. Koch’s postulates are The same organism must be present in every case of the disease. The organism must be isolated from the diseased host and grown as a pure culture. The isolated organism should cause the disease in question when it is introduced (inoculated) into a susceptible host (a host that can develop the disease). The organism must then be re-isolated from the inoculated, diseased animal. 9.2 Infectious Disease Transmission and Stages To cause disease, an infectious agent must be transmitted to a susceptible host. A reservoir is the animate or inanimate habitat where the pathogen is naturally found. In contrast, a source disseminates the agent from the reservoir to new hosts. Transmission of an infectious disease can be through direct or indirect contact. Direct contact transmission: host is infected by direct physical contact with the source of the pathogen. Indirect contact transmission: the pathogen spreads from a source to a host without direct physical contact. There are three general types of indirect transmission: airborne, vehicle, and vector.  The five general stages of infectious disease are the incubation period, the prodromal phase, an acute phase, a period of decline, and a convalescent phase. 9.3 Epidemiology Essentials Epidemiology seeks to understand and prevent illness (infectious and noninfectious) in populations. The two general goals of epidemiology are to: (1) describe the nature, cause, and extent of new or existing diseases in populations and (2) intervene to protect and improve health in populations. The epidemiological triangle represents the what (etiological agent), who (host), and where (environment) of disease. In general, disease can be established whenever an environment in which the etiological agent can thrive overlaps with the susceptible host’s environment. Public education, quarantine, and vector control are ways to break the epidemiological triangle. Epidemiology is the foundation of public health. The CDC is a U.S. health agency that oversees national epidemiological endeavors such as disease surveillance. Public health agencies affect human health at a variety of levels—from health awareness campaigns to research. Epidemiology is a necessary partner with public health. 9.4 Epidemiological Measures and Studies  Measures of frequency and association are useful in epidemiology. Measures of frequency describe the occurrence of a disease in a population during a certain period of time; they reveal the degree of morbidity (existence of disease) in a population. Examples include prevalence and incidence rates. A prevalence rate describes the overall occurrence of a disease in a population in a given period of time. An incidence rate describes new occurrences of a disease in a population in a specified period of time. Measures of association reveal risks associated with a particular disease. The most common association measure is mortality rate. Epidemiological studies are descriptive or analytical. Descriptive studies describe the occurrence and distribution of disease so that hypotheses can be developed and then tested using analytical approaches; data is often collected through correlation studies, case reports, and cross-sectional studies. Analytical studies investigate the etiological agent of a disease, what specific factors lead to disease, and how the disease can be treated or prevented. Analytical epidemiology studies are either observational or experimental. 9.5 Epidemiology in Clinical Settings  Healthcare-acquired infections (HAIs) are infections that develop as a result of a healthcare intervention; they are a major concern in healthcare settings because they are dangerous and expensive. HAIs are transmitted by direct and indirect contact. Contaminated medical devices and healthcare workers’ hands are the most common sources. Bacteria are the most common cause of HAIs (although viruses, fungi, and parasites can also be culprits). Hand washing is the easiest and most significant way to reduce HAIs. Hospital epidemiology involves the surveillance, prevention, and control of HAIs and monitoring antibiotic-resistant strains. 9.6 Surveillance, Eradication, and Ethics in Epidemiology Surveillance programs are used to monitor, control, and prevent disease. The CDC develops surveillance recommendations and collects, then shares, surveillance data with healthcare providers and the general public; diseases that the CDC recommends monitoring are called notifiable diseases. Emerging diseases are linked to changes in the environment and changes in sociocultural practices. When a disease is declared eradicated, there are no longer any cases of the infectious disease anywhere in the world.  Ethics in epidemiology and public health includes research ethics, protecting the well-being of a population while respecting individual freedoms, guaranteeing fair distribution of public resources, and ensuring that public health priorities are based on evidence. Chapter 10 Overview 10.1 Basics of Host–Microbe Interactions The host–microbe interaction does not always lead to disease and often has roles in health. Mutualism is a type of symbiotic relationship in which both participants benefit. In comparison, commensalism is a relationship in which one organism benefits and the other is not affected. It was formerly thought that our normal microbiota had a commensal relationship with us, but based on the benefits discussed in this chapter, it is increasingly evident that we have a mutualistic relationship. Opportunistic pathogens often live among the normal microbiota, but do not cause disease unless an opportunity (weakened immunity or disruption in the normal microbiota) develops. Tropism is the specificity a pathogen has for infecting a defined host or host tissue; it can change as pathogens evolve. 10.2 Introduction to Virulence Virulence describes the degree or extent of disease that a pathogen causes. Pathogenicity is the ability of a microbe to cause disease. Key virulence factors  include toxins and tools that help pathogens adhere to host cells, invade tissues, acquire nutrients, and evade immune defenses. Host properties, host–microbe interactions, and environmental factors all influence virulence and pathogenicity. Not all pathogens are equally virulent. Pathogens balance maximally exploiting their host with promoting transmission. A pathogen’s R0 value describes disease spread in a fully susceptible population when no interventions have been applied; the Re value describes transmission in the midst of an epidemic where not all hosts are susceptible and/or interventions to combat transmission may have been applied. Infectious dose-50 ID50 describes how many cells or virions are needed to establish an infection in 50 percent of exposed susceptible hosts. The more infectious the pathogen is, the lower the ID50. Just because a pathogen is highly infectious doesn’t mean it is especially dangerous. Lethal dose-50 LD50 is the amount of toxin needed to kill 50 percent of affected hosts that are not treated. The lethality of an infectious agent is usually expressed as mortality rate rather than as LD50. Two main classes of bacterial toxins are endotoxins and exotoxins. Gram-negative bacteria make endotoxin. In high quantities, endotoxin causes endotoxic shock (sepsis). Exotoxins are made by Gram-positive and Gram-negative bacteria and are often classified into three main families based on their mode of action. 10.3 Five Steps to Infection  First, pathogens must enter a host. A portal of entry is any site that a pathogen uses to enter the host. It is usually determined by the mode of transmission. Second, pathogens must adhere to host tissues. Adhesins are virulence factors that help infectious agents stick to host cells. Biofilms facilitate pathogen adhesion and serve as a source of infection. Third, pathogens must invade host tissues and obtain nutrients. Invasins are virulence factors that break down host tissue to help with this. Host cell invasion by pathogens often causes cytopathic effects. Fourth, pathogens must avoid host defenses. They may hide from immune defenses using latency, living intracellularly, or applying antigenic variation, mimicry, or masking. Other pathogens undermine host immune defenses by interfering with phagocytosis and suppressing the immune response. Fifth, pathogens must transmit to new hosts. Portals of exit are often (though not always) the same as the portals of entry. A disease reservoir aids in transmission by making it possible for a pathogen to exist outside a host. 10.4 Safety and Health Care Four biosafety levels (BSLs) are assigned based on pathogenic features of the agent in question. BSL-1 agents present minimal risk to people, while BSL-4 agents have the highest risk. Managing biological risks is central to patient and healthcare worker safety.  Under standard precautions, blood, all bodily fluids, excretions and secretions (except sweat), mucosal membranes, nonintact skin, and fresh tissues are handled as though they are a source of bloodborne or other infectious agents irrespective of presumed or confirmed infection status. Transmission precautions are taken in addition to standard precautions to prevent direct contact, droplet, and airborne disease transmission and are also applied when a specific infectious agent is suspected or known to be present. COVID-19 transmission precautions are a blend of contact, droplet, and airborne transmission precautions. Chapter 11 Overview 11.1 Overview of the Immune System and Its Responses Immune responses recognize diverse pathogens, kill identified invaders, and discriminate between self and foreign. The immune system has two collaborative branches. Innate immunity is a nonspecific, immediate defense that doesn’t require specialized training. Adaptive immunity acts more slowly, but is trainable, has a memory component, and is highly specific. Normal microbiota have central roles in training and tempering immune responses. 11.2 Introduction to First-Line Defenses  First-line defenses prevent pathogen entry into the body; they include mechanical, chemical, and/or physical barriers. They are rarely fully separable from each other. Mechanical barriers (mucus, tears, flushing action of urine, etc.) limit pathogen entrance by rinsing, flushing, or trapping them. Chemical barriers (stomach acid, lysozyme, antimicrobial peptides, etc.) either directly attack invaders or establish an environment that limits pathogen ability to survive in a particular tissue. Physical barriers provide a physical blockade to entry; skin is the most important physical barrier. 11.3 Introduction to Second-Line Defenses and the Lymphatic System Second-line defenses are categorized as cellular or molecular. The lymphatic system collects, circulates, and filters body fluid to prevent edema and screens for foreign agents. Lymphatic capillaries collect lymph from tissue, convey it to nodes for filtering, and send lymph back into the blood supply (where it is called plasma) via veins. Primary lymphoid tissues (thymus and bone marrow) produce and mature leukocytes and other formed elements in blood. Secondary lymphoid tissues (lymph nodes, spleen, and mucosa-associated lymphoid tissue) bring leukocytes into contact with antigens to stimulate immune responses. Blood consists of plasma, leukocytes, and other formed elements. Granulocytes (basophils, eosinophils, neutrophils, and mast cells) are innate immunity  leukocytes. Innate-system agranulocytes include macrophages (immature version: monocytes), natural killer cells, and dendritic cells. Other agranulocytes, T cells and B cells, are adaptive actors. A differential white blood cell count determines if any leukocytes are over- or underrepresented in a patient’s blood. An increase in leukocytes is called leukocytosis. 11.4 Cellular Second-Line Defenses Phagocytosis is a special form of endocytosis. Phagocytes engulf nondissolved targets such as bacterial cells, viral particles, or general debris. Neutrophils, macrophages, and dendritic cells are key phagocytes. Neutrophils, which have multilobed nuclei and lightly stained cytoplasmic granules, are the most numerous leukocytes in circulation. These phagocytic first responders mostly combat bacteria. Eosinophils have double-lobed nuclei and large, red-orange staining cytoplasmic granules; they are moderately phagocytic cells with roles in asthma, allergy, and combating parasites. Basophils, rarest of the leukocytes, have double-lobed nuclei obscured by dark- purple staining cytoplasmic granules packed with histamine. They fight parasites and mediate allergies.  Mast cells reside in tissues and act as local lookouts. These moderately phagocytic cells attack bacteria, allergens, and parasites and activate adaptive immune responses. Monocytes have a large horseshoe-shaped nucleus; they mature into highly phagocytic macrophages as they migrate to tissues. Macrophages eliminate a wide range of invaders and activate adaptive immune responses. Dendritic cells are highly phagocytic, important activators of adaptive immunity and are found in tissues. Natural killer cells are innate immunity lymphocytes that protect against viruses, bacteria, parasites, and tumor cells. 11.5 Molecular Second-Line Defenses Leukocytes exert effects in part by releasing physiologically active cytokines into their local environment. Cytokines (which include chemokines, interleukins, interferons, and tumor necrosis factors) recruit other immune system cells to sites where they are needed, restrict pathogen growth, generate fever, and induce inflammation. Iron-binding proteins (ferritin, lactoferrin, hemoglobin, and transferrin) sequester iron to limit pathogen access to this essential nutrient.  Complement proteins are activated in a cascade fashion and promote opsonization, cytolysis using a membrane attack complex (MAC), and inflammation. Examples of pathways for activating complement proteins are the classical pathway (initiated by antibodies), the lectin pathway (initiated by binding sugars on a pathogen), and the alternative pathway (triggered by a direct association of complement proteins with a pathogen). 11.6 Inflammation and Fever Combined actions of cellular and molecular second-line defenses trigger inflammation and sometimes fever. Inflammation is a protective response initiated by tissue injury. Cardinal signs are redness, pain, local heat, and swelling. In extreme inflammation a fifth feature, loss of function, may occur. Inflammation recruits immune defenses to the injured tissue, limits spread of infectious agents, and delivers oxygen, nutrients, and chemical factors for tissue recovery. Inflammation occurs in three general phases: vascular changes, leukocyte recruitment, and resolution. Vascular changes of inflammation (vasodilation and increased vessel permeability) bring cellular and chemical defenses to the injury site. Histamines, kinins, and eicosanoids are central. Drugs that block pro-inflammatory mediators include  antihistamines, SAIDs, and NSAIDs. Vasodilation and increased vessel permeability both contribute to the cardinal signs of inflammation. The leukocyte recruitment phase of inflammation relies on chemoattractant molecules that stimulate leukocytes to exit the vasculature and migrate to injured tissue. Leukocytes undergo margination and diapedesis to exit vessels. As the initial threat passes, the resolution phase lessens inflammation so that host tissues do not experience unnecessary collateral damage. Wound healing starts during this phase. If resolution is not effective, chronic inflammation may develop. Fever (pyrexia) is abnormally high body temperature. Pyrogens such as endotoxin or other bacterial toxins trigger the brain’s hypothalamus to raise the body’s temperature. Low-grade fever is considered protective; fever approaching 40.5°C(105°F) that doesn’t decrease with treatment is a life-threatening medical emergency; a body temperature above 43°C(109.4°F) is fatal. Body temperature levels and patterns of temperature fluctuation help classify fevers.