Touro PA Microbiology Lecture #6 PDF

Microbiology Lecture #6 2 Introduction • We contact numerous microorganisms daily • Breathe in, ingest with food and drink, pick up on skin • Most do not harm us • Some may colonize body surfaces; others shed with dead epithelial cells • Most swallowed microorganisms die in stomach or are elimina...

Microbiology Lecture #6 2 Introduction • We contact numerous microorganisms daily • Breathe in, ingest with food and drink, pick up on skin • Most do not harm us • Some may colonize body surfaces; others shed with dead epithelial cells • Most swallowed microorganisms die in stomach or are eliminated in feces • Relatively few are pathogens that cause damage to the human body • Distinct characteristics allow avoidance of some body defenses • Source: NIAID, NIH, Rocky Mountain Laboratories 3 Microbes, Health, and Disease • Most microbes are harmless; many are beneficial • Some can cause disease if there is an opportunity • Weaknesses or defects in immunity leave people vulnerable to invasion; these individuals are immunocompromised • Factors include malnutrition, cancer, AIDS, surgery, wounds, genetic defects, alcohol or drug abuse, and immunosuppressive therapy 4 The Anatomical Barriers as Ecosystems • Skin, mucous membranes are barriers, but also host complex ecosystem of microorganisms • Example of symbiosis or “living together” • Mutualism: both partners benefit • Example: in large intestine, some bacteria synthesize vitamin K and B vitamins, which host can absorb; bacteria are supplied with warmth, energy sources • Commensalism: one partner benefits, other is unharmed • Many microbes living on skin neither harmful nor helpful, but obtain food and necessities from host • Parasitism: one organism benefits at expense of other • All pathogens are parasites, but medical microbiologists often reserve for eukaryotic pathogens (for example, protozoa, helminths) 5 Composition of the Microbiome Colonization begins at birth; microbiome is different after vaginal birth than after caesarian birth Breastfeeding affects composition of microbiome Composition different among individuals and over time 6 Beneficial Roles of the Human Microbiome : Competitive Exclusion Significant contribution is protection against pathogens • Covering of binding sites prevents attachment • Consumption of available nutrients • Production of compounds toxic to other bacteria When microbiome is suppressed (for example, during antibiotic treatment), pathogens may colonize, cause disease • Some antibiotics inhibit Lactobacillus (in vagina of mature females, suppress growth of Candida albicans); results in vulvovaginal candidiasis • Oral antibiotics can inhibit intestinal microbiota, allow overgrowth of toxin-producing Clostridioides (Clostridium) difficile 7 Principles of Infectious Disease • Colonization refers to microbe establishing itself and multiplying; infection used for pathogen • Can be subclinical: no symptoms or mild symptoms • Infectious disease: prevents normal function • Symptoms are subjective effects experienced by patient (pain, nausea) • Signs are objective evidence (rash, pus formation, swelling) • Initial infection is primary infection • Damage can predispose individual to developing a secondary infection (respiratory illness impairing mucociliary escalator) 8 Pathogenicity Primary pathogen is microbe or virus that causes disease in otherwise healthy individual • Diseases such as plague, malaria, measles, influenza, diphtheria, tetanus, tuberculosis Opportunistic pathogen (opportunist) causes disease only when body’s immune defenses are compromised or when introduced into unusual location • Can be members of normal microbiota Virulence refers to degree of pathogenicity Virulence factors allow microorganism to cause disease 9 Characteristics of Infectious Disease Communicable or contagious diseases easily spread from one host to another Infectious dose: number of microbes necessary to establish infection • Shigellosis results from approximately 10 to 100 ingested Shigella • Salmonellosis results from as many as 106 ingested Salmonella enterica serotype Enteritidis • Difference partially reflects ability to survive stomach acid • ID50 is number of cells that infects 50% of population 10 Progression of Infectious Disease Incubation period: time between infection and onset • Varies considerably; depends on growth rate, host’s condition, infectious dose Illness: signs and symptoms of disease • May be preceded by prodromal phase (vague symptoms) Convalescence: recuperation, recovery from disease After recovery (or vaccination) memory cells usually protect from reinfection with the same microbe • Access the text alternative for slide images. 11 Progression of Infectious Disease • Many infectious agents can be spread during incubation and/or convalescent periods • Carriers may harbor and spread infectious agent for long periods of time in absence of signs or symptoms 12 Distribution of Pathogen Localized infection: microbe limited to small area (boil caused by Staphylococcus aureus) Systemic infection: agent spread throughout body (Lyme disease) Suffix -emia means “in the blood” • Bacteremia: bacteria circulating in blood • Not necessarily a disease state (can occur transiently following vigorous tooth brushing) • May lead to systemic inflammation called sepsis • Toxemia: toxins circulating in bloodstream • Viremia: viruses circulating in bloodstream 13 Disease Transmission • Portal of entry: body surface or orifice: entry route for pathogen • Respiratory pathogens generally cause disease only when inhaled (nose) • Intestinal pathogens generally cause disease only when ingested (mouth) • Fecal-oral transmission: fecal organisms transported to mouth and ingested 14 Portals of Exit • Body surface or orifice: exit route for pathogen • Intestinal tract: shed in feces (example, Vibrio cholerae) • Respiratory tract: exit in droplets of saliva, mucus (example, Mycobacterium tuberculosis) • Skin: shed on skin cells (example, Staphylococcus aureus) • Genital pathogens: semen, vaginal secretions (example, Neisseria gonorrhoeae) 15 Disease Transmission • Vertical transmission is pregnant woman to fetus or mother to infant during childbirth, breast feeding • Horizontal transmission is person to person via air, physical contact, ingestion of food or water, or vector • (talking): Fuse/Getty Images; (computer mouse): Ingram Publishing; (sneeze): ©Kent Wood/Science Source; (tick): ©Centers for Disease Control and Prevention; (foods): Mitch Hrdlicka/Photodisc/Getty Images 16 Disease Transmission 1 Direct transmission involves immediate transfer of infectious agent to portal of entry • Direct Contact: touch (handshake, sexual intercourse) • Easiest when infectious dose is low (Shigella) • Handwashing is important in preventing spread of infectious disease • Some pathogens cannot survive in environment, require intimate sexual contact (Treponema pallidum, Neisseria gonorrhoeae) • Droplet Transmission: can spread respiratory disease when pathogen-laden droplets are inhaled • Droplets generally fall to ground within a meter • Cover mouth when sneezing. 17 Disease Transmission 2 Indirect transmission occurs in several ways Airborne: respiratory diseases often transmitted by liquid droplets released while talking, etc. • Droplet nuclei remain suspended; inhaled, carry pathogens to lungs • One of the concerns with COVID-19 transmission, particularly indoors • Other airborne particles (dead skin cells, dust) • Crowds increase number of bacteria in air • Difficult to control • Ventilation systems, negative pressure, HEPA filters 18 Disease Transmission – Figure 19.6 Vehicle-borne: transmitted by objects, food, water • Fomites: inanimate objects • Clothing, keyboards, doorknobs, drinking glasses • Food and water: can become contaminated • Animal products (meat, eggs) from animal’s intestines • Cross-contamination: transfer between foods • Municipal water systems can distribute to large numbers • ©Glow Cuisine/ Getty Images 19 Disease Transmission 3 Vector-borne: a vector is a living organism that can carry a pathogen • Most often arthropods: mosquitoes, flies, fleas, lice, ticks • Mechanical vector carries microbe on its body from one location to another • Biological vector also participates in life cycle of pathogen • Plasmodium (malaria) multiplies to high numbers in mosquito • Vector control important in preventing diseases 20 Disease Transmission – Figure 19.7 • Vector: living organism that can carry a pathogen • Access the text alternative for slide images. 21 Invasion—Breaching the Anatomical Barriers • Penetrating the skin • Difficult barrier to penetrate; bacteria rely on injuries • Staphylococcus aureus enters via cut or wound; Yersinia pestis is injected by fleas • Penetrating mucous membranes • Entry point for most pathogens • Directed uptake by cells • Exploiting antigen-sampling processes 22 Establishing Infection • Adherence • Adhesins attach to host cell receptor • Often located at tips of pili called fimbriae • Can be component of capsules or various cell wall proteins • Binding highly specific; dictates type of cell to which bacterium can attach • Access the text alternative for slide images. 23 Directed Uptake by Cells Pathogen induces non-phagocytic cells to engulf them via endocytosis • Salmonella uses type III secretion system • Actin molecules in host cells rearrange, causing membrane ruffling • Ruffles enclose bacteria, bringing them into cell • ©Mark A. Jepson, University of Bristol 24 Secondary Lymphoid Organs Sites where lymphocytes gather to contact antigens • Lymph nodes, spleen, tonsils • Situated throughout body • Peyer’s patches allow sampling of intestinal contents via specialized M cells, dendritic cells • Part of mucosa-associated lymphoid tissue (MALT) • Mucosal immunity prevents microbial invasion via mucous membranes • Lymphoid tissues in gut are GUTassociated lymphoid tissue (GALT) • SALT, BALT, NALT… • Access the text alternative for slide images. 25 Exploiting Antigen-Sampling Processes • Mucosal-associated lymphoid tissue (MALT) samples material • Some pathogens use M cells to cross intestinal barrier • Shigella survives phagocytosis by macrophages; induces apoptosis; binds to base of mucosal epithelial cells and induces uptake • Some invade by alveolar macro-phages (Mycobacterium tuberculosis produces surface proteins, directs uptake, avoids macrophage activation) • Access the text alternative for slide images. 26 Establishing Infection • Colonization • After attachment, the microbe must multiply • Must deal with host defenses • Microbe may produce siderophores to bind iron • Competes with lactoferrin, transferrin of host • Microbe must avoid secretory IgA • Rapid pili turnover, antigenic variation, IgA proteases • Microbe must compete with normal microbiota; tolerate toxic products of other microbes 27 Mechanisms of Pathogenesis 1 • Several general patterns • Produce toxins that are then ingested • Colonization of mucous membranes, produce toxins • Invasion host tissues, avoid defenses • Invasion host tissues, produce toxins 28 Avoiding Destruction by Phagocytes Surviving within phagocytes allows pathogens to avoid antibodies, control some immune responses, and move throughout the body • Escape from phagosome: prior to lysis with lysosomes • Listeria monocytogenes produces molecule that forms pores in membrane; Shigella species lyse phagosome • Prevent phagosome-lysosome fusion: avoid destruction • Salmonella sense ingestion by macrophage, produce protein that blocks fusion process • Survive within phagolysosome: few can survive destructive environment • Coxiella burnetii (Q fever) can withstand; delays fusion, allows time to equip itself for growth 29 Avoiding Killing by Complement System Proteins Serum resistant bacteria • Neisseria gonorrhoeae hijacks mechanism that host uses to prevent their surfaces from activating complement • Organism binds complement regulatory proteins to avoid membrane attack complex (MAC) 30 Mechanisms of Pathogenesis 2 • Successful pathogen needs to overcome host defenses only long enough to multiply and exit • Pathogen that overwhelms the host may kill it and lose nutrients and opportunity for transmission Bacterial Infections of Upper Respiratory System • Pink eye, earache, and sinus infections • Common, often occur together, often from same agent • Signs and symptoms • Conjunctivitis (“pink eye”): tears, redness, swollen eyelids, sensitivity to bright light, pus • Otitis media: severe earache; inflammation behind the ear drum • Sinusitis: facial pain, pressure; headache, malaise, thick green nasal discharge may develop • Anita van den Broek/ Shutterstock 31 Pink Eye, Earache, and Sinus Infections 1 Causative Agents • Haemophilus influenzae (Gram-negative rod) and Streptococcus pneumoniae are common causes; others also cause • Conjunctivitis also caused by Staphylococcus aureus, enterobacteria, Neisseria gonorrhoeae, and Chlamydia trachomatis • Strains that infect conjunctiva have adhesins Pathogenesis of conjunctivitis • Organisms likely from airborne respiratory droplets or contaminated hands • Resist destruction by lysozyme 32 Pink Eye, Earache, and Sinus Infections Pathogenesis of otitis media, sinusitis • Usually preceded by infection of nasal cavity and pharynx that spreads through Eustachian tube • Damaged ciliated cells, results in inflammation and swelling, prevents movement of secretions • Fluid, pus collect behind eardrum, cause pressure • Eardrum may burst • Access the text alternative for slide images. 33 Pink Eye, Earache, and Sinus Infections 2 Epidemiology • Otitis media rare in first month of life, but common in early childhood; older children develop immunity so rare beyond age five • Nasal allergies, air pollution, smoking may play role • Sinusitis tends to affect adults and older children with more developed sinuses 34 Pink Eye, Earache, and Sinus Infections 3 Treatment and Prevention Antibiotics generally effective when properly used • Proper use decreases risk of complications (for example, meningitis) • Decongestants, antihistamines generally ineffective; can actually reduce immune response Bacterial conjunctivitis highly contagious • Preventive measures include handwashing, avoiding touching eyes Preventive measures for otitis media include plastic tubes through eardrums if chronic, or removal of adenoids to improve drainage 35 Bacterial Infections of Upper Respiratory System • Streptococcal Pharyngitis (“Strep Throat”) • Signs and Symptoms • Sore throat, difficulty swallowing, fever • Throat is red with patches of pus • Most patients recover after about a week; some have mild or no symptoms • Causative Agent is Streptococcus pyogenes • β-hemolysis of blood agar • Group A streptococcus (GAS) from Lancefield grouping • • ©Evans Roberts ©Evans Roberts 36 Streptococcal Pharyngitis • Pathogenesis of Streptococcus pyogenes • Proteins in the cell wall allow attachment to host cells • M protein acts as adhesin (200 antigenic types) • Antibodies that bind to it prevent infection • Antibodies to one strain do not stop others • Fibronectin-binding proteins adheres to fibrin of epithelial cells in throat • DNase, hyaluronidase, proteases degrade intracellular connections; streptokinase breaks blood clots • Access the text alternative for slide images. 37 Streptococcal Pharyngitis 1 • Pathogenesis of Streptococcus pyogenes • Avoidance of host immune system • Some have hyaluronic acid capsule thought to disguise bacteria from immune system • Streptolysins O and S make holes in membranes of erythrocytes and leukocytes; yields β-hemolysis, inhibits immune system 38 Streptococcal Pharyngitis 2 • Pathogenesis of Streptococcus pyogenes • Avoidance of host immune system • A few strains produce streptococcal pyrogenic exotoxins (SPEs) leading to high fever • May lead to scarlet fever, streptococcal toxic shock syndrome, “flesheating disease” 39 Streptococcal Pharyngitis 3 • Epidemiology of Streptococcus pyogenes • Naturally only infects humans • Spread by respiratory droplets or contaminated food • Nasal carriers more likely to spread than pharyngeal • Treatment and Prevention • Confirmation via diagnostic tests and throat culture • Treatment with penicillin prevents some post-streptococcal sequelae 40 Bacterial Infections of Upper Respiratory System 1 • Post-streptococcal sequelae (previous disease) • Complications • Thought to result from immune response • Acute rheumatic fever (ARF) can begin approximately 3 weeks after recovery • Fever, joint pains, chest pains, rash, nodules under skin • Carditis develops in 30 to 50% of patients, can lead to chronic rheumatic heart disease • Heart valve damage • Thought to involve autoimmune response 41 Post-Streptococcal Sequelae Acute post-streptococcal glomerulonephritis • Fever, fluid retention, high blood pressure; blood and protein in urine • S. pyogenes generally eliminated before symptoms appear • Damage to kidneys from inflammatory reaction to streptococcal antigens in kidney glomeruli • Antibodies bind, activate complement system • Only a few strains of S. pyogenes cause this • Access the text alternative for slide images. 42 Bacterial Infections of Upper Respiratory System 2 • Diphtheria is deadly toxin-mediated disease • Rare in U.S. because of immunization, found elsewhere • Epidemic (1990 to 1995) began in Russian Federation • Mild sore throat, slight fever, extreme fatigue • Swelling of neck, formation of pseudomembrane on tonsils and throat or in nasal cavity • Lymph nodes and neck tissue can swell; “bull-neck” • Heart and kidney failure and paralysis may occur later 43 Diphtheria Causative Agent: Corynebacterium diphtheriae • Club-shaped, often occur side by side in “palisades” • Release diphtheria toxin (powerful exotoxin) • Gene is carried by specific lysogenic bacteriophage • Isolated on selective medium containing potassium-tellurite (inhibits normal microbiota; C. diphtheriae forms dark colonies) • Dr. P.B. Smith/CDC 44 Diphtheria 1 Pathogenesis • Little invasive ability; disease by potent diphtheria exotoxin absorbed into bloodstream • Pseudomembrane made of cells killed by the exotoxin along with blood clots, fibrin, and leukocytes • May come loose and obstruct airways • A-B exotoxin: B subunit attaches to cell receptors; entire molecule taken up by endocytosis • Cells lacking receptor are unaffected • A subunit catalyzes reaction, inactivates elongation factor 2 (EF2) required for movement of ribosome on mRNA • Protein synthesis stops, cell dies 45 Diphtheria • Access the text alternative for slide images. 46 Diphtheria 2 Epidemiology: humans are primary reservoir • Spread by air; acquired via inhalation or from fomites Treatment and prevention • Injection of antiserum to toxin; delaying treatment to wait for culture results can be fatal • Antibiotics can clear C. diphtheriae, but toxins already absorbed are unaffected • Even with treatment, approximately 10% mortality • Immunization with toxoid very effective; inactivated toxoid included with childhood DTaP vaccination (diphtheria and tetanus toxoids with components of Bordetella pertussis) 47 Bacterial Infections of Lower Respiratory System 1 • Pneumococcal pneumonia • Account for approximately 1/3 of adult community-acquired pneumonia patients in the US • Signs and symptoms: cough, fever, chest pain, sputum production (incubation period 1 to 3 days) • Usually preceded by 1 to 2 days of runny nose, congestion that ends with sudden fever and shaking chills • Sputum becomes pinkish or rust-colored from blood • Severe chest pain aggravated by each breath or cough • Causes shallow rapid breathing • Patient develops cyanosis from poor oxygenation • Most patients improve after 3 to 5 days of antimicrobial treatment; full recovery can take weeks 48 Pneumococcal Pneumonia Causative Agent: Streptococcus pneumoniae • Gram-positive diplococcus known as pneumococcus • Thick polysaccharide capsule responsible for virulence • 90 different serotypes each with different capsular antigens • Certain serotypes more commonly invasive • Strains lacking capsule do not cause invasive disease • BSIP/Science Source 49 Pneumococcal Pneumonia Pathogenesis: • Capsule, pneumococcal surface protein (PspA) interfere with C3b of complement system, block phagocytosis • Pneumolysin damages ciliated epithelium • Inflammation in alveoli cause difficulty breathing; sputum coughed from lungs • Pneumococci may enter blood-stream, lead to sepsis of blood, endocarditis (heart valve infection), meningitis (infection of brain, spinal cord membranes) • In several days, antibodies allow phagocytosis and destruction of pneumococci, recovery • a: Hong xia/Shutterstock; b: skyhawk x/Shutterstock 50 Pneumococcal Pneumonia Epidemiology: Many healthy people carry encapsulated pneumococci in throat; mucociliary escalator effectively keeps from reaching lungs • Risk of infection increases when this defense is impaired • Increased risk in those over 50, or with heart or lung disease, diabetes or cancer Treatment and Prevention: penicillin cures if given early; resistant strains increasingly common • Conjugate vaccine (PCV13) against 13 strains available for children under 2, adults over 65 and those with certain health conditions • Vaccine (PPSV23) available for 23 most common pneumococcal strains 51 Bacterial Infections of Lower Respiratory System 2 • Klebsiella pneumonia • Enterobacteria such as Klebsiella species and other Gramnegative rods can cause pneumonia • Especially if host defenses are impaired • Cause most of the deaths from healthcare-associated infections • Signs and Symptoms: cough, chills, shortness of breath, fever, chest pain, cyanosis (incubation period 1 to 3 days) • Most symptoms similar to pneumococcal pneumonia • Distinguished by repeated chills, production of bloody jelly-like sputum different from blood-tinged sputum of pneumococcal pneumonia 52 Klebsiella Pneumonia Causative Agent: Klebsiella pneumoniae • Gram-negative rod with large capsule; produces big mucoid colonies • Normal microbiota of gastrointestinal tract; may be found in mouth and throat • Lisa Burgess/McGraw-Hill Education 53 Klebsiella Pneumonia 1 Pathogenesis • Contracted through secretions that are transmitted by contact, or from medical equipment (for example, ventilators) • Klebsiella colonize throat; reach lung via inhaled air, mucus • Adhesins aid colonization • Capsule is virulence factor: likely interferes with C3b • Siderophore “steals” iron, causing cellular stress that induces inflammation and spread of bacteria • Tissue death, lung abscesses may cause permanent damage to lung, perhaps leading to death • Often enters blood, septic shock 54 Klebsiella Pneumonia 2 Epidemiology: Klebsiella species widespread in nature • Commonly part of normal intestinal microbiota • Typically affects very old or very young, or those with compromised immune system (for example, alcoholics, patients in hospital or other institution) • Problem: • Strains circulating in hospitals, nursing homes often resistant to antimicrobials; increasingly multi-drug-resistant 55 Klebsiella Pneumonia 3 Treatment and Prevention: • Treated with antibiotics, but more strains are becoming antibiotic resistance • Surgery may be required to drain abscesses • No vaccine; follow infection control measures • Gloves, gowns, disinfection, handwashing, etc. • Wise use of antimicrobials to avoid resistance 56 Bacterial Infections of Lower Respiratory System 3 • Mycoplasma pneumonia • Leading pneumonia of children, young adults (college students, military recruits) • Generally mild; often called “walking pneumonia” or atypical pneumonia • Signs and Symptoms • Onset is gradual (incubation period 2 to 3 weeks) • Initial symptoms are sore throat, chills, fever, headache, muscle pain, fatigue • Dry cough after several days; mucoid sputum may be produced later • Some develop otitis media 57 Mycoplasma Pneumonia Causative Agent: Mycoplasma pneumoniae • Small bacterium lacking cell wall • Slow, aerobic growth • Colonies on agar look like fried eggs • ©Christine Citti 58 Mycoplasma Pneumonia 1 Pathogenesis • Only a few inhaled cells can start infection • Cells attach by specialized attachment organelle to the base of the cilia on the respiratory epithelium • Interfere with ciliary action, cause cells to slough off • Increases chance of secondary infection • Inflammatory response with accumulation of lymphocytes and macrophages thickens walls of bronchial tubes and alveoli 59 Mycoplasma Pneumonia 2 • Epidemiology: spread by aerosolized droplets shed before symptoms begin to many weeks afterward • Infections tend to be more common in summer and early fall • Accounts for approximately one fifth of bacterial pneumonias • Immunity following recovery not permanent; repeat infections have occurred within 5 years • Treatment and Prevention: M. pneumoniae lacks cell wall, so antibiotics that target cell wall are ineffective • Macrolides shorten illness if given early • No preventative measures except handwashing, avoiding crowding in schools, military facilities • No vaccines 60 Bacterial Infections of Lower Respiratory System • Pertussis (“whooping cough”) • Vaccination-preventable disease, but still endemic in many countries including U.S. • Causes up to half a million deaths annually globally • Source: CDC 61 Pertussis 1 Signs and Symptoms: incubation period of 7 to 10 and three stages • Catarrhal stage (inflammation of mucous membranes) • 1 to 2 weeks of signs resembling upper respiratory infection (runny nose, sneezing, low fever, mild cough) • Paroxysmal stage (repeated sudden attacks) • Frequent attacks of violent uncontrollable coughing lasting 1 to 6 weeks or longer • Dry but severe; small blood vessels in eyes rupture • Forceful inhalation of air: “whoop” sound • Vomiting, seizures, cyanosis may occur • Convalescent stage (recovery) • Not contagious; coughing decreases over several weeks 62 Pertussis 2 Causative Agent: Bordetella pertussis • Tiny encapsulated aerobic Gram-negative rod • Sensitive to sunlight, drying: quickly die outside of host Pathogenesis: cells are inhaled, attach to ciliated cells of respiratory epithelium • Colonizes the upper throat, trachea, bronchi, and bronchiole where they release toxins: • Pertussis toxin (PT) is A-B exotoxin: B attaches to receptors, A moves through cytoplasmic membrane Increases cAMP: yields increased mucus, decreased killing ability of phagocytes, release of lymphocytes into bloodstream, ineffectiveness of natural killer cells • Adenylate cyclase Toxin (ACT) lyses leukocytes; catalyzes ATP to cAMP • Tracheal cytotoxin (TCT) causes release of fever-inducing interleukin-1; toxic to ciliated epithelial cells 63 Pertussis Pathogenesis • Increased mucus production, decreased ciliary action results in severe cough • Some bronchioles completely obstructed, lead to small areas of collapsed lung • Spasms, partial mucus plugging let air enter but not escape • Chief cause of death is pneumonia due to B. pertussis or (more commonly) secondary bacterial infections • Access the text alternative for slide images. 64 Pertussis 3 Epidemiology: highly contagious • Spread via direct contact with respiratory secretions or inhaling airborne droplets • Patients most infectious during catarrhal stage • Classically disease of infants; most fatalities in those under 1 year of age • Milder in older children, adults; may be mistaken for another disease such as a common cold, transmission 65 Pertussis 4 Treatment and Prevention • Macrolides during catarrhal stage; ineffective in paroxysmal stage • Intensive supportive therapy sometimes needed in infants • Prevented with acellular pertussis vaccine (aP) given in combination with diphtheria and tetanus toxoids (DTaP) • Additional booster for adolescents (Tdap) • Also given to pregnant women to provide passive immunity to newborn • Tdap can be administered to adults every 10 years to continue protection against pertussis, tetanus and diphtheria. 66 Bacterial Infections of Lower Respiratory System • Tuberculosis (TB) • Once very common; incidence declined in industrialized nations as living standards improved • In 1985, incidence began to rise due to expanding AIDS epidemic, increasing prevalence of drug-resistant strains • CDC developed plan to increase efforts to identify and treat cases in high-risk groups • Incidence began to decrease by 1993 67 Tuberculosis 1 Signs and Symptoms • Initial infection by Mycobacterium tuberculosis is usually asymptomatic • Immune response controls, but unable to eliminate • Yields latent tuberculosis infection (LTBI); later may develop tuberculosis disease (TB disease), or active tuberculosis • Slight fever, weight loss, night sweating, persistent cough, often blood-streaked sputum, night sweating • Primarily infects lungs, but bacterial cells can travel through bloodstream to other tissues including kidneys, bones, joints, central nervous system 68 Tuberculosis 2 Causative Agent: Mycobacterium tuberculosis • Slender, acid-fast, rod-shaped bacterium • Strict aerobe with generation time over 16 hours • Unusual cell wall contains mycolic acids: cells resist drying, responsible for acid-fast staining • Easily killed by pasteurization • M. bovis, M. africanum and others, can also cause tuberculosis in humans or other animals • All are part of the Mycobacterium tuberculosis complex (MTBC) • Source: Dr. George P. Kubica/CDC 69 Tuberculosis 3 Pathogenesis: airborne cells inhaled into lungs • Alveolar macrophages quickly engulf; unable to destroy • Ingested bacteria manipulate macrophage to create environment in which they can multiply. • The bacteria then recruit more macrophages to the site, increasing the number of host cells to multiply in • Lymphocytes wall off infected area, granuloma forms • Called tubercles • In granuloma, effector helper T cells release cytokines • Activate macrophages to destroy mycobacteria but some hosts have been induced to become foamy macrophages; thought to help bacteria survive in these cells 70 Tuberculosis 4 Pathogenesis • Fibrous layer forms around macrophages, keeps lymphocytes outside of tubercle • Layer calcifies and can be seen on X-rays • Some mycobacteria survive; prevented from multiplying by low pH and low O2 • Remain as latent TB infection (LTBI) • In many cases infection resolves • Active TB results if inflammatory response cannot contain or destroy mycobacteria if immunity becomes impaired by stress, age, or disease 71 Tuberculosis 5 Pathogenesis • Macrophages in tubercle die; bacteria, enzymes, cytokines released, forming area of necrosis • Caseous necrosis; foamy macrophages (with lipids) thought to play important role • Tubercle ruptures, releases bacteria, dead material • Causes large lung defect called tuberculous cavity • Spreads bacteria in lungs • Lung cavity persists, enlarges for months or years, spreads bacteria; can be transmitted by coughing 72 Tuberculosis • a: kaling2100/Shutterstock; b: Jose Luis Calvo/Shutterstock • Access the text alternative for slide images. 73 Tuberculosis 6 Epidemiology: Approximately 13 million Americans have LTBI • Only approximately 5 to 10% will reactivate, progress to active TB • Transmission almost entirely via respiratory route • 10 or fewer inhaled mycobacterium can cause infection • Frequency of coughing, ventilation, crowding, immunodeficiency (especially AIDS) important • Identification of infection • Tuberculin skin test (TST; Mantoux test) • Blood tests (IGRAs) • Xpert MTB/RIF (detect Mycobacterium DNA) • CDC 74 Tuberculosis 7 Treatment and Prevention: multiple drugs over long time • Combination therapy needed; mycobacteria grow slowly, resist body defenses; mutants likely present given high numbers of cells involved in infection • Rifampin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol (EMB) given for 2 months; then INH, RIF for another 4 to 7 months • Resistant strains often evolve as symptoms disappear, and patient becomes careless in taking medications (non-compliance) • DOTS (directly observed therapy short-course) used 75 Tuberculosis 8 Treatment and Prevention • In U.S., skin or blood tests, lung X-rays used to identify cases; both TB disease and are LTBI treated • Prevention and control are global challenge • BCG vaccine used in many countries (live attenuated from M. bovis); prevents childhood TB, but ineffective against LTBI reactivation • BCG vaccine discouraged in U.S. as it causes positive tuberculin test • Interferes with disease prevention • Not safe in severely immunocompromised patients • New vaccines being developed 76 Bacterial Infections of Lower Respiratory System 4 • Legionnaires’ Disease (Legionella Pneumonia) • Not known until attendees of 1976 American Legion Convention in Philadelphia developed mysterious pneumonia • Fatal in many cases • Signs and Symptoms: headache, muscle aches, high fever, confusion, shaking chills (incubation 2 to 10 days) • Dry cough develops, produces sputum, sometimes blood • Shortness of breath • About 25% of cases have digestive tract symptoms (for example, diarrhea, abdominal pain, vomiting) • Recovery is slow; weakness, fatigue last for weeks 77 Legionnaires’ Disease 1 Causative Agent: Legionella species • L. pneumophila • Gram-negative rod • Facultative intracellular parasite; survives well in freshwater protozoans, including their cysts 78 Legionnaires’ Disease 2 Pathogenesis • Acquired by inhaling aerosolized water with organism • Promote uptake by alveolar macrophages • Bacteria survive by preventing phagosome-lysosome fusion; multiply within macrophages • Alveolar cell necrosis and inflammatory response lead to abscesses, pneumonia, pleurisy, and often bacteremia • Fatal respiratory failure in about 15% of hospitalized cases 79 Legionnaires’ Disease 3 Epidemiology • Widespread in warm natural waters containing protozoa, which house the bacteria • Also found in water systems • L. pneumophila protected from chlorine inside protozoa • Common in aquatic environments; also found in water from air conditioners, and in produce misters • Acquisition via aspiration of contaminated drinking water rare • No direct person-to-person spread 80 Legionnaires’ Disease 4 Treatment and Prevention: • Appropriate antibiotic (for example, macrolide or fluoroquinolone) • Some require O2 therapy • Prevention directed at equipment design to minimize aerosols, disinfection procedures 81 Bacterial Infections of Lower Respiratory System 5 • Inhalation anthrax • Primarily a disease of livestock; but Bacillus anthracis is also a Category A bioterrorism agent • Signs and Symptoms • Begins with flu-like symptoms in 1 week to 2 months • Followed by fever, shortness of breath, chest pain, possibly cyanosis • Anthrax meningitis occurs in about half the cases 82 Inhalation Anthrax Causative Agent: Bacillus anthracis • Endospore-forming, Gram-positive, rod-shaped bacterium • Vegetative cells have capsule composed of amino acid polymer • J. Todd Parker, PhD, and Luis Lowe, MS; MPH/CDC 83 Inhalation Anthrax 1 Pathogenesis • Endospores inhaled, taken up by macrophages, and carried to lymph nodes in chest where they germinate • Anthrax toxin composed of three proteins • Protective antigen (PA) • Edema factor (EF) • Lethal factor (LF) • PA combines with either EF or LF to make anthrax toxins: • Toxin-producing, encapsulated cells enter bloodstream, damage endothelial cells; this leads to vascular leakage and pulmonary edema • Untreated, case-fatality rate is near 95%; early treatment reduces fatalities to about 45% 84 Inhalation Anthrax 2 Epidemiology • Zoonosis can be transmitted to humans working with animals or animal products • Not transmitted from person to person Treatment and Prevention • Antimicrobials doxycycline or ciprofloxacin, along with monoclonal antibody that binds to protective antigen (PA), preventing it from attaching to host cells • Prophylactic antimicrobial treatment for those suspected of having been exposed; up to 60 days • Control by reducing infection in livestock • Acellular vaccine available for those at increased risk 85 Viral Infections of the Lower Respiratory System 1 • Influenza (“Flu”) • Antigenic changes responsible for serious annual epidemics; infects approximately 20% of humans annually • Four influenza virus types (A, B, C, and D) classified based on core proteins; only types A and B cause human disease • Signs and Symptoms: • Headache, muscle aches, fever, sore throat, fatigue; peaks in 6 to 12 hours; dry cough develops and worsens over a few days (incubation period approximately 2 days) • Acute symptoms last approximately 1 week; lingering cough, fatigue, weakness last additional days or weeks • Influenza viruses do not cause “stomach flu” 86 Inhalation Too 88 Bacterial Diseases of Blood and Lymphatic Systems 4 • Plague (black death) • Killed about 25% of Europe’s population between 1346 and 1350; crowded conditions, rat populations Signs and Symptoms - three general types with different signs and symptoms: • Bubonic plague - most common; occurs as a result of being bitten by an infected flea; symptoms develop 2 to 6 days after the bite • Characterized by high fever and significantly enlarged and tender lymph nodes called buboes in the region that receives lymph drainage from the area of the flea bite • Without treatment, the patient often develops septicemic plague 89 Plague 1 • Signs and Symptoms • Septicemic plague results when the organism spreads via the bloodstream, typically after a flea bite • Endotoxin released by the bacteria results in high fever, shock, and disseminated intravascular coagulation (DIC) which causes bleeding into the skin and the organs, leading to red or black patches • Clots may interrupt blood flow in small blood vessels of fingers and toes, leading to tissue death and gangrene in those areas • Pneumonic plague - when organisms in the bloodstream spread to the lungs or may result when a person inhales respiratory droplets from an infected individual or animal • Characterized by headache, fever, cough and pneumonia accompanied by shortness of breath, chest pain, and possibly bloody sputum 90 Yersinia pestis Gram Stain • Plague • Causative Agent: Yersinia pestis • Gram-negative rod • CDC/Courtesy of Larry Stauffer, Oregon State Public Health Laboratory 91 Fleas Following a Blood Meal Plague • Pathogenesis • Forms biofilms in digestive tract of infected fleas, blocks tract • Fleas starve, increasing likelihood of feeding • Causes bacteria to be regurgitated (vomited) into bite wound • a: ©Science Source; b: Daniel Cooper/Getty Images 92 Plague 2 Pathogenesis • Multiple virulence factors allow avoidance of host defenses • Taken up by macrophages in regional lymph nodes; resist killing effects of macrophages; multiply • Genes for other products that allow the organism to survive in the host are also activated • Acute inflammatory reaction develops in lymph nodes, enlargement and marked tenderness that characterize bubonic plague 93 Plague 3 Pathogenesis • Infected macrophages die, release bacteria ready to withstand host defenses • Capsule to avoid phagocytosis • Yersinia outer proteins (YOPs) delivered into host cells by type III secretion system; multiple effects • Lymph nodes may become necrotic; allows large numbers bacteria spread into bloodstream • Endotoxins cause septicemic plague; shock, DIC • Dark hemorrhages and dusky color of skin and mucous membranes from DIC probably inspired the common name “black death” • leading to pneumonic plague; respiratory droplets can transmit fully virulent pathogen 94 Plague 4 Epidemiology • Zoonotic disease endemic in rodent populations in many regions of the world • In U.S., mostly occurs in western states • Globally, the majority of cases are in developing countries mostly in Africa and Asia • Wild rodents such as prairie dogs and their fleas are the main reservoirs • Rats, rabbits, dogs, cats can also be hosts • Hundreds of species of fleas are able to transmit plague; remain infectious for a year or more 95 Plague 5 Treatment and Prevention • Antimicrobial medications, especially if given intravenously within 24 hours of onset of symptoms • Rehydration and ventilation may be required in some cases • Bubonic plague has between 50 to 80% case-fatality if untreated • Often because Y. pestis enters the blood stream (septicemic plague) • Pneumonic plague has almost 100% case-fatality if untreated • Rodent control measures (garbage disposal, rat-proofing buildings, rat extermination programs) important • Extermination must be combined with insecticide use to prevent escape of infected fleas from dead rats • People at risk of flea bites should use insecticide containing DEET and gloves if handling potentially infected dead animals • No current vaccine, but efforts underway to develop one • Doxycycline given as preventive to exposed individuals