Microbe-Human Interactions

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1 Chapter 13 Microbe-Human Interactions Infection, Disease, and Epidemiology Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

2 13.1 We Are Not Alone The human body exists in a state of dynamic equilibrium Many interactions between human body and microorganisms involve the development of biofilms Colonization of the body involves a constant give and take 2

3 Contact, Colonization, Infection, Disease Microbes that engage in mutual or commensal associations normal (resident) flora, indigenous flora, microbiota Infection a condition in which pathogenic microbes penetrate host defenses, enter tissues, and multiply Pathogen infectious agent Infectious disease an infection that causes damage or disruption to tissues and organs 3

4 Contact, Colonization, Infection, Disease Figure 13.1 Associations between microbes and humans 1 CONTACT* 2 Colonization with microbiota Microbes adhere to exposed body surfaces ** 3 INVASION Microbes cross lines of defense and enter sterile tissues Sinus 4 4 Meninges (of brain) Middle ear Carrier state develops Microbes are established in tissues but disease is not apparent *** 4 INFECTION Pathogenic microbes multiply in the tissues 3 Nasal mucosa 2 Pharynx Action of microbes Defenses hold pathogen in check Effects of microbes result in injury or disruption to tissues 1 Trachea Beneficial effects Adverse effects Immunity/repair of damage Morbidity/mortality occur Palate * Not all contacts lead to colonization or infection. ** Microbiota may invade, especially if defenses are compromised. *** Some pathogens may remain hidden in the body Alveolus Bronchiole 4 Bronchus 4

5 Resident Microbiota: The Human as a Habitat Most areas of the body in contact with the outside environment harbor resident microbes Internal organs, tissues, and fluids are microbe-free Transients microbes that occupy the body for only short periods Residents microbes that become established 5

6 The Human as a Habitat Bacterial flora benefit host by preventing overgrowth of harmful microbes microbial antagonism Endogenous infections occur when normal flora is introduced to a site that was previously sterile 6

7 Initial Colonization of the Newborn Uterus and contents are normally sterile and remain so until just before birth Breaking of fetal membrane exposes the infant; all subsequent handling and feeding continue to introduce what will be normal flora Figure 13.2 The origins of microbiota in newborns 7

8 Colonizers of the Human Skin Skin is the largest and most accessible organ Two cutaneous populations Transients: influenced by hygiene Residents: stable, predictable, less influenced by hygiene (a) Epidermis Dermis Subcutaneous tissue (b) Hair shaft Sweat pores Sebaceous (oil) gland Hair follicle Hair root Duct of sudoriferous (sweat) gland Figure 13.3 The landscape of the skin a. location of microbes, colored areas b. magnified view showing bacteria Janice Carr/CDC 8

9 Microbial Residents of the Gastrointestinal Tract GI tract is a long hollow tube, bounded by mucous membranes Tube is exposed to the environment Variations in flora distribution due to shifting conditions (ph, oxygen tension, anatomy) Oral cavity, large intestine, and rectum harbor appreciable flora Oral cavity Duodenum Large intestine Small intestine Pharynx Esophagus Stomach Figure 13.4 Distribution of microbes, colored areas Rectum Anal canal 9

10 Flora of the Mouth Most diverse and unique flora of the body Numerous adaptive niches Bacterial count of saliva (5 x 10 9 cells per milliliter) Most common are: Streptococcus species 10

11 Flora of the Large Intestine Has complex and profound interactions with host microbes per gram of feces Intestinal environment favors anaerobic bacteria Intestinal bacteria contribute to intestinal odor, called skatole, or when it escapes it is called flatulence 11

12 Inhabitants of the Respiratory Tract Figure 13.5 Colonized regions of the respiratory tract, colored areas Oral streptococci, first organisms to colonize Nasal entrance, nasal vestibule, anterior nasopharynx S. aureus Mucous membranes of nasopharynx Neisseria Tonsils and lower pharynx Haemophilus Nasal vestibule Nasal entrance Larynx Bronchus Bronchiol e Right lung Left lung Sinuses Nasal cavity Internal naris Soft palate Nasopharynx Epiglottis Trachea 12

13 Microbiota of the Genitourinary Tract Sites that harbor microflora Uterine tube Females: Vagina and outer opening of urethra Ovary Uterus Males: Anterior urethra Changes in physiology influence the composition of the normal flora Urinary bladder Urethra External reproductive organs Rectum Vagina Anus Vagina (estrogen, glycogen, ph) Urinary bladder Figure 13.6 Microbiota of the reproductive tract, in colored areas Penis Urethra Testis Anus 13 Rectum

14 Maintenance of the Normal Microbiota Normal flora is essential to the health of humans Flora create an environment that may prevent infections and can enhance host defenses Antibiotics, dietary changes, and disease may alter flora Probiotics introducing known microbes back into the body, they are beneficial and nonpathogenic 14

15 13.2 Major Factors in the Development of an Infection Figure 13.7 Flow diagram that reflects the events in entry, establishment, and exit of infectious agents Portal of entry Adhesion Invasion Multiplication Infection of target Disease Portal of exit Microbes evade barriers Microbes attach to host cells Microbes make pathway into cells Microbes grow and spread Microbes attack specific tissues Microbes damage tissues Microbes leave host 15

16 Major Factors in the Development of an Infection True pathogens capable of causing disease in healthy persons with normal immune defenses Influenza virus, plague bacillus, malarial protozoan Opportunistic pathogens cause disease when the host s defenses are compromised or when they grow in part of the body that is not natural to them Pseudomonas sp & Candida albicans Severity of the disease depends on the virulence of the pathogen; characteristic or structure that contributes to the ability of a microbe to cause disease is a virulence factor. 16

17 Biosafety Levels and Agents of Disease

18 Becoming Established: Phase One Portals of Entry Portals of entry characteristic route a microbe follows to enter the tissues of the body Exogenous agents originate from source outside the body Conjunctiva Respiratory tract Gastrointestinal tract Endogenous agents already exist on or in the body (normal flora) Skin Pregnancy and birth Urogenital tract Figure 13.8 Portals of entry 18

19 Portals of Entry Skin: nicks, abrasions, punctures, incisions Gastrointestinal tract: food, drink, and other ingested materials Respiratory tract: oral and nasal cavities Urogenital tract : sexual, displaced organisms Transplacental 19

20 Pathogens That Infect during Pregnancy STORCH - Syphilis, Toxoplasmosis, Other diseases (hepatitis B, AIDS and chlamydia), Rubella, Cytomegalovirus and Herpes simplex virus Figure 13.9 Transplacental infection of the fetus Maternal blood pools within intervillous space Bacterial cells Placenta Umbilical cord (a) Placenta (b) Umbilical cord Umbilical vein Umbilical arteries (fetal blood) Maternal blood vessel 20

21 Attaching to the Host: Phase Two Adhesion microbes gain a stable foothold at the portal of entry; dependent on binding between specific molecules on host and pathogen Fimbriae Bacteria Fimbrae Flagella Glycocalyx Cilia Suckers Hooks Barbs (a) Fimbriae Capsules (b) Capsules Host cell Host cell Bacterial cell Virus Spikes Figure Mechanisms of adhesion by pathogens (c) Spikes Host cell 21

22 Adhesion Properties of Microbes 22

23 Surviving Host Defenses Initial response of host defenses comes from phagocytes Antiphagocytic factors used to avoid phagocytosis Species of Staphylococcus and Streptococcus produce leukocidins, toxic to white blood cells Slime layer or capsule makes phagocytosis difficult Ability to survive intracellular phagocytosis Capsule Bacteria cannot be engulfed Phagocyte Blocked (c) Blocked phagocytic response Continued growth of microbes damages host tissue Figure Bacteria are able to escape phagocytosis 23

24 Invading the Host and Becoming Established: Phase Three Some pathogens produce a secretion system to insert specialized virulence proteins directly into the host cells Salmonella Microvilli Secretion system Pedestal Loss of microvilli Adhesion by fimbriae (d) Invasion factors Release of proteins Disruption of actin and ruffling Cell pulled into vacuole Salmonella multiplies internally Figure Events of Salmonella invasion into the intestine Systemic invasion Salmonella moves out of cell into deeper tissues 24

25 Causing Disease Virulence factors traits used to invade and establish themselves in the host, also determine the degree of tissue damage that occurs severity of disease Exoenzymes dissolve extracellular barriers and penetrate through or between cells Toxigenicity capacity to produce toxins at the site of multiplication Cell cement Epithelial cell Bacteria Bacteria Exotoxins Figure (a) Exoenzymes dissolve barriers to penetrate cells (b) Toxins diffuse to target cells, which are killed 25

26 Bacterial Toxins: A Potent Source of Cellular Damage 2 Types of Bacterial Toxins: Endotoxin: toxin that is not secreted but is released after the cell is damaged Composed of lipopolysaccharide (LPS), part of the outer membrane of gram-negative cell walls Exotoxin: toxin molecule secreted by a living bacterial cell into the infected tissue Strong specificity for a target cell Hemolysins A-B toxins (A-active, B-binding) 26

27 Bacterial Toxins: Exotoxins and Endotoxins Exotoxins Endotoxins Figure the effects of circulating exotoxins and endotoxins (a) Target organs are damaged; heart, muscles, blood cells, intestinal tract show dysfunctions. (b) General physiological effects fever, malaise, aches, shock 27

28 Intensity of symptoms Incubation period Prodromal stage Period of invasion Convalescent period 13.3 The Outcomes of Infection and Disease 4 distinct stages of clinical infections: Incubation period: time from initial contact with the infectious agent to the appearance of first symptoms; agent is multiplying but damage is insufficient to cause symptoms; several hours to several years Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Height of infection Initial exposure to microbe Time 28

29 Intensity of symptoms Incubation period Prodromal stage Period of invasion Convalescent period The Process of Infection and Disease Prodromal stage: vague feelings of discomfort; nonspecific complaints Period of invasion: multiplies at high levels, becomes well-established; more specific signs and symptoms Convalescent period: as person begins to respond to the infection, symptoms decline Figure Stages in infection and disease Height of infection Initial exposure to microbe Time 29

30 Patterns of Infection Localized infection microbes enter the body and remains confined to a specific tissue Systemic infection infection spreads to several sites and tissue fluids usually in the bloodstream Focal infection when infectious agent breaks loose from a local infection and is carried to other tissues Localized infection (boil) Systemic infection (influenza) Figure Infections with regard to location (c) Focal infection 30 (a) (b)

31 Patterns of Infection Mixed infection several microbes grow simultaneously at the infection site - polymicrobial Primary infection initial infection Secondary infection another infection by a different microbe Primary (urinary) infection Figure Infections with regard to location (e) Various microbes Secondary (vaginal) infection 31 (d) Mixed infection

32 Patterns of Infection Acute infection comes on rapidly, with severe but short-lived effects Chronic infections progress and persist over a long period of time 32

33 Signs and Symptoms: Warning Signals of Disease Earliest symptoms of disease as a result of the activation of the body defenses Fever, pain, soreness, swelling Signs of inflammation: Edema: accumulation of fluid Granulomas and abscesses: walled-off collections of inflammatory cells and microbes Lymphadenitis: swollen lymph nodes 33

34 Signs of Infection in the Blood Changes in the number of circulating white blood cells Leukocytosis: increase in white blood cells Leukopenia: decrease in white blood cells Septicemia: microorganisms are multiplying in the blood and present in large numbers Bacteremia: small numbers of bacteria present in blood not necessarily multiplying Viremia: small number of viruses present not necessarily multiplying 34

35 Infections That Go Unnoticed Asymptomatic (subclinical) infections although infected, the host doesn t show any signs of disease Inapparent infection, so person doesn t seek medical attention 35

36 The Portal of Exit: Vacating the Host Pathogens depart by a specific avenue; greatly influences the dissemination of infection Respiratory: mucus, sputum, nasal drainage, saliva Skin scales Fecal exit Urogenital tract Removal of blood Coughing, sneezing Skin cells (open lesion) Insect bite Removal of blood Figure Major portals of exit of infectious diseases Urine Feces 36

37 Persistence of Microbes and Pathologic Conditions Apparent recovery of host does not always mean the microbe has been removed Latency after the initial symptoms in certain chronic diseases, the microbe can periodically become active and produce a recurrent disease; person may or may not shed it during the latent stage, herpes Chronic carrier person with a latent infection who sheds the infectious agent, HIV Sequelae long-term or permanent damage to tissues or organs, Lyme disease can cause arthritis 37

38 13.4 Origins and Transmission Patterns of Infectious Microbes Reservoir primary habitat of pathogen in the natural world Human or animal carrier, soil, water, plants Source individual or object from which an infection is actually acquired 38

39 Living Reservoirs Carrier an individual who inconspicuously shelters a pathogen and spreads it to others; may or may not have experienced disease due to the microbe Asymptomatic carrier shows no symptoms Passive carrier contaminated healthcare provider picks up pathogens and transfers them to other patients Passive Figure carriers in transmission of infectious agents (c) Transfer of infectious agent through contact Infectious agent 39

40 Living Reservoirs Asymptomatic carrier shows no symptoms Incubation carriers: spread the infectious agent during the incubation period Convalescent carriers: recuperating without symptoms Chronic carrier: individual who shelters the infectious agent for a long period Figure carriers in transmission of infectious agents Asymptomatic Incubation Convalescent Chronic (a) Time (b) Stages of release during infection 40

41 Animals as Reservoirs and Sources A live animal (other than human) that transmits an infectious agent from one host to another is called a vector Majority of vectors are arthropods fleas, mosquitoes, flies, and ticks Some larger animals can also spread infection mammals, birds, lower vertebrates Biological vectors actively participate in a pathogen s life cycle Mechanical vector not necessary to the life cycle of an infectious agent and merely transports it without being infected 41

42 Animals as Reservoirs and Sources An infection indigenous to animals but naturally transmissible to humans is a zoonosis Humans don t transmit the disease to others At least 150 zoonoses exist worldwide; make up 70% of all new emerging diseases worldwide Impossible to eradicate the disease without eradicating the animal reservoir 42

43 Common Zoonotic Infections 43

44 The Acquisition and Transmission of Infectious Agents Communicable disease when an infected host can transmit the infectious agent to another host and establish infection in that host Highly communicable disease is contagious Non-communicable infectious disease does not arise through transmission from host to host Occurs primarily when a compromised person is invaded by his or her own normal microflora Contact with organism in natural, non-living reservoir 44

45 Patterns of Transmission Direct contact physical contact or fine aerosol droplets Indirect contact passes from infected host to intermediate conveyor and then to another host Vehicle: inanimate material, food, water, biological products, fomites Airborne: droplet nuclei, aerosols Figure a sneeze Marshall W. Jennison, Massachusetts Institute of Technology,

46 Figure How Communicable Infectious Diseases are Acquired Communicable Infectious Diseases Contact: Kissing, sex (Epstein-Barr virus, gonorrhea) Fomites (Staphylococcus aurreus) Droplets (colds, chickenpox Fecal-oral contamination can also lead to both of these types of transmission Direct Food, water, biological products (Salmonella, E. coli) Indirect (vehicles) Vertical (HIV syphilis) Droplet nuclei Biological Vector (West nile virus, malaria Aerosols Air (tuberculosis, influenza virus hantavirus) 46

47 Nosocomial Infections Diseases that are acquired or developed during a hospital stay From surgical procedures, equipment, personnel, and exposure to drugresistant microorganisms Enterococci Pseudomonas aeruginosa Staphylococcus aureus S. aureus Coagulase-negative staphylococci E. coli P. aeruginosa Coagulase-negative staphylococci Enterobacter spp. Other 12% Skin 8% Surgical wounds 17% Blood 6% Enterobacter spp. Coagulase-negative staphylococci Figure Candida spp. Urinary tract 39% Candida spp. Enterobacter spp. Enterococci E. coli P. aeruginosa 2 to 4 million cases/year in U.S. with approximately 90,000 deaths Enterococci E. coli P. aeruginosa S. aureus S. aureus P. aeruginosa Lower respiratory tract 18% Acinetobacter spp. Enterobacter spp. Klebsiella pneumoniae 47

48 Preventing Nosocomial Infections 48

49 Universal Blood and Body Fluid Precautions Stringent measures to prevent the spread of nosocomial infections from patient to patient, from patient to worker, and from worker to patient universal precautions Based on the assumption that all patient specimens could harbor infectious agents, so must be treated with the same degree of care 49

50 13.5 Epidemiology: The Study of Disease in Populations The study of the frequency and distribution of disease and health-related factors in human populations Surveillance collecting, analyzing, and reporting data on rates of occurrence, mortality, morbidity and transmission of infections Reportable, notifiable diseases must be reported to authorities Centers for Disease Control and Prevention (CDC) in Atlanta, GA principal government agency responsible for keeping track of infectious diseases nationwide 50

51 Frequency of Cases Prevalence total number of existing cases with respect to the entire population usually represented by a percentage of the population Incidence measures the number of new cases over a certain time period, as compared with the general healthy population Mortality rate the total number of deaths in a population due to a certain disease Morbidity rate number of people afflicted with a certain disease 51

52 8/15 Cases per 1,00,000 8/29 9/12 9/26 10/10 Epidemiological Data from the CDC 10/24 11/7 11/21 12/5 12/19 1 / 2 1/16 1/30 2/13 Incidence 2/27 3/13 3/27 4/10 4/24 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Infections with the outbreak strain of Salmonella Typhimurium, by date of illness onset (n=696 for whom information was reported as of April 20, 9pm EDT) Number of persons ,000 46,000 44,000 42,000 Illness that began during this time may not yet be reported Estimated numbers of adults and adolescents living With AIDS at the end of 2007 United States and dependent areas DC American Samoa Northern Marina Islands Guam 4 Estimated AIDS cases AK HI Puerto Rico U.S. Virgin Islands Data classed using quartiles Date of illness onset These numbers are point estimates, which result from adjustments for reported case counts. The reported case counts have been adjusted for reporting delays, but not for incomplete reporting. Data source: HIV/AIDS Surveillance Report, Vol. 19, table 14. Inset maps not to scale. *Some illness onset dates have been estimated from other reported information (a) (b) TB Case Rates by Age Group and Sex, United States, 2008 Reported TB Cases Race/Ethnicity* United States, <15 yrs yrs yrs yrs 65 yrs Male Female Native Hawaiian or Other Pacific Islander (<1%) Hispanic or Latino (29%) White (17%) American Indian or Alaska Native (1%) Asian (26%) Black or African-American (25%) *All races are non-hispanic. Persons reporting two or more races Accounted for less than 1% of all cases 52 (c)

53 Figure Patterns of Infectious Disease Occurrence Outbreaks Endemic disease that exhibits a relatively steady frequency over a long period of time in a particular geographic locale (a) Endemic Occurrence (Valley fever) Sporadic when occasional cases are reported at irregular intervals (b) Sporadic Occurrence (Measles) 53

54 Figure Patterns of Infectious Disease Occurrence Epidemic when prevalence of a disease is increasing beyond what is expected (c) Epidemic Occurrence (Syphilis) Pandemic epidemic across continents (d) Pandemic Occurrence (AIDS) 54

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