Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Onchocerciasis wikipedia , lookup
Schistosoma mansoni wikipedia , lookup
Sexually transmitted infection wikipedia , lookup
Rocky Mountain spotted fever wikipedia , lookup
Chagas disease wikipedia , lookup
Hospital-acquired infection wikipedia , lookup
Eradication of infectious diseases wikipedia , lookup
Schistosomiasis wikipedia , lookup
Visceral leishmaniasis wikipedia , lookup
Coccidioidomycosis wikipedia , lookup
Pathology, Infection, and Disease Pathology: the study of disease Etiology: the study of the cause of a disease Pathogenesis: the development of disease Infection: colonization of the body by pathogens Disease: an abnormal state in which the body is not functioning normally © 2013 Pearson Education, Inc. Normal Microbiota and the Host Transient microbiota may be present for days, weeks, or months Normal microbiota permanently colonize the host Symbiosis is the relationship between normal microbiota and the host © 2013 Pearson Education, Inc. Figure 14.1 Representative normal microbiota for different regions of the body. Bacteria (orange spheres) on the surface of the nasal epithelium © 2013 Pearson Education, Inc. Bacteria (brown) on the lining of the stomach Bacteria (orange) in the small intestine Symbiosis In commensalism, one organism benefits, and the other is unaffected In mutualism, both organisms benefit In parasitism, one organism benefits at the expense of the other Some normal microbiota are opportunistic pathogens © 2013 Pearson Education, Inc. Table 14.1 Normal Microbiota on the Human Body Eyes (conjunctiva) Nose and throat (upper respiratory system) Mouth Skin Large intestine Urinary and reproductive systems (lower urethra in both sexes and vagina in females) © 2013 Pearson Education, Inc. Normal Microbiota and the Host Microbial antagonism is a competition between microbes Normal microbiota protect the host by Occupying niches that pathogens might occupy Producing acids Producing bacteriocins Probiotics: live microbes applied to or ingested into the body, intended to exert a beneficial effect © 2013 Pearson Education, Inc. Koch’s Postulates 1. The same pathogen must be present in every case of the disease. 2. The pathogen must be isolated from the diseased host and grown in pure culture. 3. The pathogen from the pure culture must cause the disease when it is inoculated into a healthy, susceptible laboratory animal. 4. The pathogen must be isolated from the inoculated animal and must be shown to be the original organism. © 2013 Pearson Education, Inc. Figure 14.3 Koch’s Postulates: Understanding Disease. 1 Microorganisms are isolated from a diseased or dead animal. 2a The microorganisms are grown in pure culture. 3 The microorganisms are injected into a healthy laboratory animal. Colony 2b The microorganisms are identified. 4 Disease is reproduced in a laboratory animal. 5a The microorganisms are isolated from this animal and grown in pure culture. 5b Microorganisms are identified. The microorganism from the diseased host caused the same disease in a laboratory host. © 2013 Pearson Education, Inc. Koch’s Postulates Koch’s postulates are used to prove the cause of an infectious disease Some pathogens can cause several disease conditions Some pathogens cause disease only in humans © 2013 Pearson Education, Inc. Classifying Infectious Diseases Symptom: a change in body function that is felt by a patient as a result of disease Sign: a change in a body that can be measured or observed as a result of disease Syndrome: a specific group of signs and symptoms that accompany a disease © 2013 Pearson Education, Inc. Classifying Infectious Diseases Communicable disease: a disease that is spread from one host to another Contagious disease: a disease that is easily spread from one host to another Noncommunicable disease: a disease that is not transmitted from one host to another © 2013 Pearson Education, Inc. Occurrence of a Disease Incidence: fraction of a population that contracts a disease during a specific time Prevalence: fraction of a population having a specific disease at a given time Sporadic disease: disease that occurs occasionally in a population © 2013 Pearson Education, Inc. Occurrence of a Disease Endemic disease: disease constantly present in a population Epidemic disease: disease acquired by many hosts in a given area in a short time Pandemic disease: worldwide epidemic Herd immunity: immunity in most of a population © 2013 Pearson Education, Inc. Figure 14.4 Reported AIDS cases in the United States. Number of cases 120,000 Second 250,000 cases First 250,000 cases Third 250,000 cases Fourth 250,000 Cases 100,000 80,000 Expansion of surveillance case definition 60,000 40,000 20,000 0 1979 1983 1987 1991 1995 Year © 2013 Pearson Education, Inc. 1999 2003 2007 Severity or Duration of a Disease Acute disease: symptoms develop rapidly Chronic disease: disease develops slowly Subacute disease: symptoms between acute and chronic Latent disease: disease with a period of no symptoms when the causative agent is inactive © 2013 Pearson Education, Inc. Extent of Host Involvement Local infection: pathogens are limited to a small area of the body Systemic infection: an infection throughout the body Focal infection: systemic infection that began as a local infection © 2013 Pearson Education, Inc. Extent of Host Involvement Sepsis: toxic inflammatory condition arising from the spread of microbes, especially bacteria or their toxins, from a focus of infection Bacteremia: bacteria in the blood Septicemia: growth of bacteria in the blood © 2013 Pearson Education, Inc. Extent of Host Involvement Toxemia: toxins in the blood Viremia: viruses in the blood Primary infection: acute infection that causes the initial illness Secondary infection: opportunistic infection after a primary (predisposing) infection Subclinical disease: no noticeable signs or symptoms (inapparent infection) © 2013 Pearson Education, Inc. Predisposing Factors Make the body more susceptible to disease Short urethra in females Inherited traits, such as the sickle cell gene Climate and weather Fatigue Age Lifestyle Chemotherapy © 2013 Pearson Education, Inc. Time © 2013 Pearson Education, Inc. Period of illness Period of decline Most severe signs and symptoms Signs and symptoms Period of convalescence Prodromal period (mild signs or symptoms) Incubation period (no signs or symptoms) Number of microbes Figure 14.5 The stages of a disease. Reservoirs of Infection Continual sources of infection Human: AIDS, gonorrhea Carriers may have inapparent infections or latent diseases Animal: rabies, Lyme disease Some zoonoses may be transmitted to humans Nonliving: botulism, tetanus Soil © 2013 Pearson Education, Inc. Transmission of Disease Contact Direct: requires close association between infected and susceptible host Indirect: spread by fomites Droplet: transmission via airborne droplets © 2013 Pearson Education, Inc. Figure 14.6ad Contact transmission. Direct contact transmission Droplet transmission © 2013 Pearson Education, Inc. Vehicle Transmission Transmission by an inanimate reservoir (food, water, air) © 2013 Pearson Education, Inc. Figure 14.7 Vehicle transmission. Water © 2013 Pearson Education, Inc. Food Air Vectors Arthropods, especially fleas, ticks, and mosquitoes Transmit disease by two general methods: Mechanical transmission: arthropod carries pathogen on feet Biological transmission: pathogen reproduces in vector © 2013 Pearson Education, Inc. Figure 14.8 Mechanical transmission. © 2013 Pearson Education, Inc. Figure 12.31 Mosquito. © 2013 Pearson Education, Inc. Nosocomial Infections Are acquired as a result of a hospital stay Affect 5–15% of all hospital patients © 2013 Pearson Education, Inc. Figure 14.6b Contact transmission. Preventing direct contact transmission through the use of gloves, masks, and face shields © 2013 Pearson Education, Inc. Figure 14.9 Nosocomial infections. Microorganisms in hospital environment Compromised host Nosocomial infection Chain of transmission © 2013 Pearson Education, Inc. © 2013 Pearson Education, Inc. Common Causes of Nosocomial Infections Coagulase-negative staphylococci S. aureus 15% Percentage Resistant to Antibiotics 89% 15% 80% Enterococcus 10% 4–71% 15–25% 3–32% 13% Not reported Percentage of Total Infections Gram-negative rods C. difficile © 2013 Pearson Education, Inc. MRSA USA100: 92% of health care strains USA300: 89% of community-acquired strains © 2013 Pearson Education, Inc. Emerging Infectious Diseases Diseases that are new, increasing in incidence, or showing a potential to increase in the near future © 2013 Pearson Education, Inc. Emerging Infectious Diseases Contributing factors Genetic recombination E. coli O157, avian influenza (H5N1) Evolution of new strains V. cholerae O139 Inappropriate use of antibiotics and pesticides Antibiotic-resistant strains Changes in weather patterns Hantavirus © 2013 Pearson Education, Inc. Emerging Infectious Diseases Modern transportation West Nile virus Ecological disaster, war, and expanding human settlement Coccidioidomycosis Animal control measures Lyme disease Public health failure Diphtheria © 2013 Pearson Education, Inc. Clinical Focus 13.1 Influenza: Crossing the Species Barrier Avian gene pool 1918 H1N1 Human H3N2 North American swine Triple reassortment H1N2 Eurasian swine H1N1 2009 H1N1 pandemic © 2013 Pearson Education, Inc. Epidemiology The study of where and when diseases occur Centers for Disease Control and Prevention (CDC) Collects and analyzes epidemiological information in the United States Publishes Morbidity and Mortality Weekly Report (MMWR) www.cdc.gov © 2013 Pearson Education, Inc. Epidemiology John Snow 1848–1849 Mapped the occurrence of cholera in London Ignaz Semmelweis 1846–1848 Showed that handwashing decreased the incidence of puerperal fever Florence Nightingale Showed that improved sanitation decreased the incidence of epidemic typhus © 2013 Pearson Education, Inc. 1858 Epidemiology Descriptive: collection and analysis of data Snow Analytical: comparison of a diseased group and a healthy group Nightingale Experimental: controlled experiments Semmelweis © 2013 Pearson Education, Inc. Epidemiology Case reporting: health care workers report specified disease to local, state, and national offices Nationally notifiable diseases: physicians are required to report occurrence © 2013 Pearson Education, Inc. The CDC Morbidity: incidence of a specific notifiable disease Mortality: deaths from notifiable diseases Morbidity rate: number of people affected in relation to the total population in a given time period Mortality rate: number of deaths from a disease in relation to the population in a given time © 2013 Pearson Education, Inc. Figure 14.10 a & b Epidemiological graphs. 40,000 Number of reported cases 35,000 30,000 25,000 20,000 15,000 10,000 5,000 0 1999 2000 2001 2002 2003 2004 2005 Apr May Jun Jul Month 2006 2007 2008 2009 2010 (a) Lyme disease cases, 1999–2010 600 Reported cases per 100,000 people 500 400 300 200 100 0 Jan Feb (b) Lyme disease by month, 2009 © 2013 Pearson Education, Inc. Mar Aug Sep Oct Nov Dec Figure 14.10c Epidemiological graphs. Reported cases per 100,000 people 120 100 80 60 40 20 0 1948 1958 1968 1978 Year Reported tuberculosis cases, 1948–2010 © 2013 Pearson Education, Inc. 1988 1998 2008 Mechanisms of Pathogenicity Pathogenicity: the ability to cause disease Virulence: the extent of pathogenicity © 2013 Pearson Education, Inc. Portals of Entry Mucous membranes Skin Parenteral route Preferred portal of entry © 2013 Pearson Education, Inc. Numbers of Invading Microbes ID50: infectious dose for 50% of the test population LD50: lethal dose (of a toxin) for 50% of the test population © 2013 Pearson Education, Inc. Bacillus anthracis Portal of Entry Skin ID50 10–50 endospores Inhalation 10,000–20,000 endospores Ingestion 250,000–1,000,000 endospores © 2013 Pearson Education, Inc. Toxins Portal of Entry Botulinum Shiga toxin Staphylococcal enterotoxin © 2013 Pearson Education, Inc. ID50 0.03 ng/kg 250 ng/kg 1350 ng/kg Adherence Adhesins/ligands bind to receptors on host cells Glycocalyx: Streptococcus mutans Fimbriae: Escherichia coli M protein: Streptococcus pyogenes Form biofilms © 2013 Pearson Education, Inc. Figure 15.1a Adherence. Adhesin (ligand) Pathogen Host cell surface Receptor Surface molecules on a pathogen, called adhesins or ligands, bind specifically to complementary surface receptors on cells of certain host tissues. © 2013 Pearson Education, Inc. Figure 15.1b-c Adherence. E. coli bacteria (yellow-green) on human urinary bladder cells © 2013 Pearson Education, Inc. Bacteria (purple) adhering to human skin Capsules Prevent phagocytosis Streptococcus pneumoniae Haemophilus influenzae Bacillus anthracis © 2013 Pearson Education, Inc. Cell Wall Components M protein resists phagocytosis Streptococcus pyogenes Opa protein inhibits T helper cells Neisseria gonorrhoeae Mycolic acid (waxy lipid) resists digestion Mycobacterium tuberculosis © 2013 Pearson Education, Inc. Enzymes Coagulase: coagulates fibrinogen Kinases: digest fibrin clots Hyaluronidase: hydrolyzes hyaluronic acid Collagenase: hydrolyzes collagen IgA proteases: destroy IgA antibodies © 2013 Pearson Education, Inc. Penetration into the Host Cell Cytoskeleton Invasins Salmonella alters host actin to enter a host cell Use actin to move from one cell to the next Listeria © 2013 Pearson Education, Inc. Figure 21.12 Cold sores, or fever blisters, caused by herpes simplex virus. © 2013 Pearson Education, Inc. Direct Damage Disrupt host cell function Produce waste products Toxins © 2013 Pearson Education, Inc. The Production of Toxins Toxin: substance that contributes to pathogenicity Toxigenicity: ability to produce a toxin Toxemia: presence of toxin in the host’s blood Toxoid: inactivated toxin used in a vaccine Antitoxin: antibodies against a specific toxin © 2013 Pearson Education, Inc. Figure 15.4 Mechanisms of Exotoxins and Endotoxins. exotoxins endotoxins Exotoxins are proteins produced inside pathogenic bacteria, most commonly grampositive bacteria, as part of their growth and metabolism. The exotoxins are then secreted into the surrounding medium during log phase. Endotoxins are the lipid portions of lipopolysaccharides (LPS) that are part of the outer membrane of the cell wall of gramnegative bacteria (lipid A; see Figure 4.13c). The endotoxins are liberated when the bacteria die and the cell wall breaks apart. Cell wall Exotoxin: toxic substances released outside the cell Clostridium botulinum, an example of a grampositive bacterium that produces exotoxins Salmonella typhimurium, an example of a gramnegative bacterium that produces endotoxins Endotoxins: toxins composed of lipids that are part of the cell membrane © 2013 Pearson Education, Inc. Exotoxins Specific for a structure or function in host cell © 2013 Pearson Education, Inc. Figure 15.5 The action of an A-B exotoxin. DNA Exotoxin mRNA A (active) A B (binding) B 1 Bacterium produces and releases exotoxin. 2 B (binding) component of exotoxin attaches to host cell receptor. 3 A-B exotoxin enters host cell by receptormediated endocytosis. 4 A-B exotoxin enclosed in pinched-off portion of plasma membrane during pinocytosis. 5 A-B components of exotoxin separate. The A component alters cell function by inhibiting protein synthesis. The B component is released from the host cell. Exotoxin polypeptides Bacterium A B Receptor Plasma membrane Nucleus Cytoplasm Host cell A B A B A B B A Protein © 2013 Pearson Education, Inc. Membrane-Disrupting Toxins Lyse host’s cells by Making protein channels in the plasma membrane – Leukocidins – Hemolysins – Streptolysins Disrupting phospholipid bilayer © 2013 Pearson Education, Inc. Superantigens Cause an intense immune response due to release of cytokines from host cells Symptoms: fever, nausea, vomiting, diarrhea, shock, and death © 2013 Pearson Education, Inc. Exotoxin Source Relation to microbe Chemistry Mostly gram-positive By-products of growing cell Protein Fever? No Neutralized by antitoxin? Yes LD50 © 2013 Pearson Education, Inc. Small Exotoxins and Lysogenic Conversion Exotoxin Corynebacterium diphtheriae A-B toxin Lysogeny + Streptococcus pyogenes Membrane-disrupting erythrogenic toxin + Clostridium botulinum A-B toxin; neurotoxin + C. tetani A-B toxin; neurotoxin Vibrio cholerae A-B toxin; enterotoxin + Staphylococcus aureus Superantigen + © 2013 Pearson Education, Inc. Endotoxins Source Relation to Microbe Chemistry Gram-negative Outer membrane Lipid A Fever? Yes Neutralized by Antitoxin? No LD50 © 2013 Pearson Education, Inc. Relatively large Figure 15.6 Endotoxins and the pyrogenic response. Macrophage Nucleus Endotoxin Endotoxin Hypothalamus of brain Prostaglandin Cytokines Fever Blood vessel Vacuole Pituitary gland Bacterium 1 A macrophage ingests a gram-negative bacterium. © 2013 Pearson Education, Inc. 2 The bacterium is degraded in a vacuole, releasing endotoxins that induce the macrophage to produce cytokines IL-1 and TNF-. 3 4 The cytokines are released into the bloodstream by the macrophages, through which they travel to the hypothalamus of the brain. The cytokines induce the hypothalamus to produce prostaglandins, which reset the body’s “thermostat” to a higher temperature, producing fever. Portals of Exit Respiratory tract Coughing and sneezing Gastrointestinal tract Feces and saliva Genitourinary tract Urine and vaginal secretions Skin Blood Arthropods that bite; needles or syringes © 2013 Pearson Education, Inc. Figure 15.9 Microbial Mechanisms of Pathogenicity. When the balance between host and microbe is tipped in favor of the microbe, an infection or disease results. Learning these mechanisms of microbial pathogenicity is fundamental to understanding how pathogens are able to overcome the host’s defenses. H1N1 flu virus portals of entry Mucous membranes • Respiratory tract • Gastrointestinal tract • Genitourinary tract • Conjunctiva Skin Parenteral route Number of invading microbes penetration or evasion of host defenses Capsules Cell wall components Enzymes Antigenic variation Invasins Intracellular growth Adherence Mycobacterium intracellulare Clostridium tetani Micrographs are not shown to scale. © 2013 Pearson Education, Inc. damage to host cells Siderophores Direct damage Toxins • Exotoxins • Endotoxins Lysogenic conversion Cytopathic effects portals of exit Generally the same as the portals of entry for a given microbe: • Mucous membranes • Skin • Parenteral route