Microbial Diseases of the Respiratory System

Microbial Diseases of the Respiratory System Structures of the Respiratory System Structures of the Lower Respiratory System Structures of the Upper Respiratory System, Sinuses, and Ears LE A R N I N G O U TC O M E S 22.1 Describe the structures of the upper respiratory system. 22.2 Describe the anatomical relationship between the phar- ynx and the middle ears and sinuses. The upper respiratory system collects air; filters dust, pollen, microorganisms, and other contaminants from the air; and delivers it to the lower respiratory organs. The upper respiratory system includes the following: ­ • The nose is the only external part of the respiratory system. • The nasal cavity, which is lined with hairs and a ciliated mucous membrane, receives air from the nose. The hairs filter large dust particles and organisms from the air, while the sticky mucus traps smaller particles and microbes. Ciliary action moves nasal mucus and its contents down into the throat. Sinuses, which are air-filled, hollow regions of bones in the skull, often share fluids—and infecting microorganisms—with the nasal cavity. • The pharynx, which is shared with the digestive system, is lined with a ciliated mucous membrane that propels mucus and contaminants into the digestive system. (Note that mucus is a noun, and the spelling mucous is an adjective.) A flap extending from the roof of the mouth called the uvula partially closes the opening between the nasal cavity and the pharynx during swallowing. ­ Ducts from the eyes carry contaminants (see Chapter 15, Figure 15.3) into the pharynx. Auditory (eustachian, yū-stā′shŭn) tubes from the ears to the pharynx (FIGURE 22.1b) allow equalization of air pressure against the inner surfaces of the eardrums. Groups of lymphoid tissue called tonsils or adenoids are located near the junction of the nasal cavity, pharynx, and auditory tubes. The tonsils contain cells and chemicals to combat microbes in this frequent portal of entry. The mucus of the upper respiratory system contains antimicrobial chemicals, including defensins, lactoferrin, and lysozyme. Defensins are antimicrobial peptides that act against Gram-positive and Gram-negative bacteria, fungi, and some viruses. Lactoferrin sequesters iron, making this important nutrient unavailable to microbial contaminants. Lysozyme breaks down peptidoglycan in the bacterial cell wall. M22_BAUM7206_05_SE_C22.indd 672 The lower respiratory system consists of a series of tubes—the larynx (voice box), trachea (windpipe), bronchi, bronchioles, and smaller respiratory tubes—that lead to hundreds of millions of microscopic air sacs called alveoli (al-vē′ō-lī) (FIGURE 22.1c, d), which make up the lungs. Protective membranes called pleurae (plūr′ē) surround the lungs. The major respiratory muscle is the diaphragm, located below the lungs. Because the structures of the lower respiratory system resemble an upside-down tree with branches that gradually decrease in diameter while increasing in number, anatomists refer to it as the respiratory tree. In this analogy, the trachea is the trunk, the bronchi and smaller tubes are the branches, and the alveoli represent leaves. When the diaphragm contracts, the lungs inflate, and air flows from the nose through the pharynx and into the respiratory tree. The larynx contains the vocal cords, which vibrate as air flows over them. A cartilaginous flap called the epiglottis folds over the opening of the larynx during swallowing to prevent food and liquids from entering the lower respiratory organs. Air flows from the larynx through the trachea, through the bronchi and bronchioles, and into the alveoli of the lungs. In the alveoli, oxygen enters the blood by passing through the thin walls of the alveoli and blood capillaries. Carbon dioxide diffuses from the capillaries into the alveoli to be exhaled. Relaxation of the diaphragm, accompanied by contraction of a different set of small muscles attached to ribs, allows the lungs to deflate, and air flows out. A ciliated mucous membrane lines the trachea, bronchi, and bronchioles. The cilia beat synchronously about 1000 times per minute to carry mucus and trapped contaminants up to the pharynx. Physiologists refer to this action as a ciliary escala­ tor. The mucus and its contents pass into the digestive system, where digestive juices destroy them. Further protection from pathogens is provided by alveolar macrophages, which enter the alveoli from blood capillaries and devour microorganisms. Secretory antibodies (IgA), which are present in tears, saliva, and respiratory mucus, also provide protection from many pathogens. Microbiome of the Respiratory System LE A R N I N G O UTC O M E 22.3 Describe the microbiome of the upper and lower respiratory tracts. ­ igure The respiratory system serves the vital function of exchanging gases between the atmosphere and the blood. Anatomists commonly divide its structures into two divisions—the upper respiratory system and the lower respiratory system (F 22.1a). We begin our examination of respiratory anatomy by considering the upper respiratory system and the organs associated with it. The lower respiratory system normally lacks microorganisms because the ciliary escalator, secretory antibodies, and phagocytic cells clear the organs of contaminants. In contrast, many types of microorganisms live in the upper respiratory system. The nose, which is cooler than the rest of the respiratory system, supports the growth of bacteria such as species of Hae­ mophilus (hē-mof′i-lus) and Veillonella (vī-lō-nĕl′ă). Gram-positive Staphylococcus aureus (staf′i-lō-kok′ŭs o′rē-ŭs) lives in the nasal 11/23/16 3:42 AM       R Structures of the espiratory System Nasal cavity Auditory tube opening Upper respiratory system Sinuses Pharynx Middle ear Uvula Auditory (eustachian) tube External ear canal Epiglottis Larynx Trachea Lower respiratory system Tympanic membrane (eardrum) Pleurae Bronchus Pharynx (b) Bronchiole Bronchiole Diaphragm (a) Right lung (sectioned) Left lung Alveoli (c) Alveolar macrophage Capillary Alveolar sac igure ▲F 22.1 Structures of the respiratory system. (a) Section through the body showing the major respiratory organs. (b) Enlargement of a portion of the head showing the connection between the middle ear and the pharynx. (c) Enlargement of a distal end of the respiratory tree. (d) An alveolus. (d) cavities of about one-third of healthy Americans without causing disease but can be an opportunistic pathogen. So-called diphtheroids (dif′thĕ-royds) also commonly colonize the nose and nasal cavity. These harmless Gram-positive bacteria resemble the bacterium that causes a respiratory disease called diphtheria (discussed shortly). Gram-negative cocci, diphtheroids, opportunistic Staphy­ lococcus spp., and alpha-hemolytic streptococci, including M22_BAUM7206_05_SE_C22.indd 673 Streptococcus pneumoniae (strep-tō-kok′ŭs nū-mō′nē-ī), colonize the upper regions of the pharynx. The latter opportunistic pathogen causes most cases of pneumonia. Organisms in the pharynx can infect the middle ears and sinuses. The normal microbiome of the upper respiratory system limits infection and disease by removing nutrients and releasing substances that inhibit the growth of pathogens. However, some members of the normal microbiome can cause 11/23/16 3:42 AM r 22    Microbial Diseases of the espiratory System ­R p te ha       C opportunistic diseases when other defensive mechanisms are faulty. The following sections examine some of the more serious microbial respiratory diseases, beginning with bacterial diseases of the upper respiratory system and associated organs. h M W y e ell T Why do patients with methicillin-resistant Staphylococcus aureus (MRSA) as part of their normal nasal microbiota pose a risk to other patients in a hospital? Bacterial Diseases of the Upper Respiratory System, Sinuses, and Ears Bacteria can infect the upper respiratory system to cause diseases such as sore throat. They can also spread into the sinuses and auditory tubes. We begin our study of upper respiratory infections by examining a variety of diseases caused by species of Streptococcus. Streptococcal Respiratory Diseases LE A R N I N G O U TC O M E S 22.4 Describe four respiratory diseases caused by Streptococcus. 22.5 Identify the structures, enzymes, and toxins of group A Streptococcus (S. pyogenes) that enable this bacterium to survive against the body’s defenses and cause disease. Physicians recognize a variety of diseases of the respiratory system and associated organs caused by species of Streptococ­ cus, depending on the site of infection, the strain of bacteria, and the immune responses of the patient. Signs and Symptoms “Strep throat,” or streptococcal pharyngitis (strep′tō-kok′ăl far-injī′tis), is an inflammation of the pharynx caused by streptococci. The back of the pharynx appears red, with swollen lymph nodes and purulent (pus-containing) abscesses covering the tonsils (see Disease at a Glance 22.1 on p. 676). Pain during swallowing, bad breath, fever, malaise,1 and headache accompany pharyngitis. If bacteria spread into the lower respiratory tract, they may cause inflammation of the larynx or bronchi, conditions known as laryngitis and bronchitis, respectively. Laryngitis manifests as hoarseness; bronchitis reduces airflow, encourages mucus accumulation in the lungs, and triggers coughing. The disease scarlet fever, also known as scarlatina, can accompany pharyngitis caused by a strain of Streptococcus carrying a lysogenic bacteriophage that codes for pyro­ genic 2 (fever-generating) toxins, which are also erythrogenic 3 1French, meaning “discomfort.” Greek pyr, meaning “fire,” and genein, meaning “to produce.” 3From Greek erythros, meaning “red,” and genein, meaning “to produce.” 2From M22_BAUM7206_05_SE_C22.indd 674 (reddening). Typically, after one to two days of pharyngitis, such streptococci release their toxins, triggering fever and a rash that begins on the chest and spreads across the body. The tongue usually becomes strawberry red. The rash disappears after about a week, and the skin sloughs off in a manner reminiscent of staphylococcal scalded skin syndrome. Untreated streptococcal pharyngitis sometimes leads to complications such as acute glomerulonephritis, a disease of the kidneys (considered in Chapter 24), and rheumatic fever, in which inflammation leads to damage of heart valves and muscle. Though the exact cause of such damage is unknown, it appears that this disease is an autoimmune response in which antibodies directed against streptococcal antigens cross-react with heart antigens. In many patients, surgeons must replace damaged heart valves when the patient reaches middle age. Heart failure and death can occur. Pathogen and Virulence Factors The bacterial genus Streptococcus is a diverse assemblage of Gram-positive, facultatively anaerobic cocci arranged in pairs or chains. Researchers differentiate streptococci using several different, overlapping schemes, including serological classification based on the reactions of antibodies to specific bacterial antigens, type of hemolysis, and physiological properties as revealed by biochemical tests. A serological classification scheme developed in 1938 by Rebecca Lancefield (1895–1981) divides streptococci into serotype groups based on the bacteria’s antigens (known as Lancefield antigens). Lancefield group A Streptococcus (synonymously known as S. pyogenes, pī-oj′en-ēz) is the major cause of bacterial pharyngitis and scarlet and rheumatic fevers. The bacterium shows beta-hemolysis after 24 hours on blood agar plates (see Figure 6.12). In contrast, harmless streptococci of the upper respiratory system are either nonhemolytic or alpha-hemolytic. Strains of group A streptococci have a number of structures, enzymes, and toxins that enable them to survive as pathogens in the body. These include the following: • M protein causes inhibition of complement component C3b, thereby interfering with opsonization and lysis (see Figure 15.9). • The hyaluronic acid capsule may “camouflage” the bacterium from phagocytes. • Streptokinases are enzymes that break down blood clots, presumably enabling group A streptococci to spread rapidly through damaged tissues. • C5a peptidase is an enzyme that breaks down complement protein C5a, which is a chemotactic factor. With this enzyme, S. pyogenes decreases the movement of leukocytes into the site of infection. • Pyrogenic toxins (also called erythrogenic toxins) stimulate leukocytes to release cytokines that in turn stimulate fever, rash, and shock. • Streptolysins lyse erythrocytes, leukocytes, and platelets. 11/23/16 3:42 AM Pathogenesis ­ Streptococci cause a variety of illnesses depending on the virulence factors present in the various strains. S. pyogenes frequently infects the pharynx, but the resulting disease is usually temporary, lasting only until adaptive immune responses against bacterial antigens (particularly M protein and streptolysins) clear the pathogen, usually within a week. Typically, strep throat and streptococcal bronchitis occur only when normal, competing microbiota are missing, when a large inoculum enables the bacterium to gain a rapid foothold before antibodies are formed against it, or when adaptive immunity is impaired. S. pyogenes can invade deeper tissues and organs through a break in a mucous membrane to cause necrotizing fas­ ciitis (examined in Chapter 19). TABLE 22.1 Manifestations of Some Respiratory Diseases ­ One strain of group C Streptococcus (also called S. equisimilis, ek-wi-si′mi-lis) is also a pathogenic beta-hemolytic bacterium that causes some cases of streptococcal pharyngitis. However, unlike group A strep throat, this kind of group C pharyngitis does not lead to scarlet or rheumatic fevers.       R Bacterial Diseases of the Upper espiratory System, Sinuses, and Ears Ailment Manifestations Common Cold (Viral) Sneezing, rhinorrhea, congestion, sore throat, headache, malaise, cough Influenza (Viral) Fever, rhinorrhea, headache, body aches, fatigue, dry cough, pharyngitis, congestion “Strep” Throat (Bacterial) Fever, red and sore throat, swollen lymph nodes in neck Viral Pneumonia Fever, chills, mucus-producing cough, headache, body aches, fatigue Bacterial Pneumonia Fever, chills, congestion, cough, chest pain, rapid breathing, and possible nausea and vomiting Bronchitis (Viral or Bacterial) Mucus-producing cough, wheezing Inhalational Anthrax (Bacterial) Fever, malaise, cough, chest discomfort, vomiting Coronavirus Respiratory Syndromes (SARS, MERS) High fever ( 7 38°C), cough, shortness of breath Epidemiology Diagnosis, Treatment, and Prevention Microbiologists estimate that fewer than 50% of patients diagnosed with strep throat actually have it; the rest have viral pharyngitis. Given that the manifestations of bacterial and viral pharyngitis are nearly identical, a sure diagnosis requires serological testing. Correct diagnosis is essential because bacterial pharyngitis is treatable with antibacterial drugs, whereas viral pharyngitis is not. Because alpha-hemolytic and nonhemolytic streptococci are normally in the pharynx, the presence of streptococci in a respiratory sample is of little diagnostic value. Physicians should use immunological tests to identify the presence of antigens of beta-hemolytic strains of Streptococcus. M22_BAUM7206_05_SE_C22.indd 675 Penicillins, such as oral or intramuscular penicillin G, penicillin V, or amoxicillin, are very effective against both S. pyogenes and S. equisimilis. Physicians prescribe oral erythromycin or another macrolide to treat penicillin-sensitive patients. Antibodies against M protein provide long-term protection against S. pyogenes; however, antibodies directed against the M protein of one strain provide no protection against other strains. For this reason, a person can have strep throat more than once. Disease at a Glance 22.1 on p. 676 summarizes the manifestations of streptococcal pharyngitis. TABLE 22.1 compares and contrasts strep throat and bronchitis with other respiratory diseases. Diphtheria LE A R N I N G O UTC O M E S 22.6 Discuss the transmission of Corynebacterium diphtheriae and the effect of diphtheria toxin. 22.7 Describe diphtheria. Physicians have brought the deadly childhood disease diphtheria (dif-thēr′ē-ă) under control in industrialized countries using effective immunization. The disease is still a major threat to children living in less-developed regions of the world. Signs and Symptoms Diphtheria manifests as sore throat, localized pain, fever, pharyngitis, and the oozing of a fluid in the throat composed of intracellular fluid, blood-clotting factors, leukocytes, bacteria, and the remains of dead pharyngeal and laryngeal cells. The fluid thickens into a thick pseudomembrane (F 22.2), igure People spread S. pyogenes via respiratory droplets. Most cases of streptococcal pharyngitis occur during the winter and spring among elementary and middle school children, probably because of crowded conditions such as those in classrooms and day care centers. One person can spread sufficient bacteria to cause disease by coughing or sneezing within a radius of about 1.5 meters (5 feet) of another person. Group A Streptococcus formerly claimed the lives of millions, but because it is sensitive to antimicrobial drugs, its significance as a deadly pathogen has declined. Nevertheless, the bacterium still sickens thousands of Americans annually. The incidence of rheumatic fever has also declined significantly, from 7491 cases in 1964 to 112 cases in 1994, the last year rheumatic fever was nationally reportable. Epidemiologists do not understand fully the reason for this decline, but the introduction of antimicrobial drugs, which limit the growth of the bacterium and thereby the severity of streptococcal pharyngitis, likely has played a role. It also appears that there has been a decline in the strains of Streptococcus that cause rheumatic fever. 11/23/16 3:42 AM ­R r 22    Microbial Diseases of the espiratory System Gl nce a t A a te p isease D ha       C 22.1 Streptococcal Pharyngitis (Strep Throat) 1 Streptococcus pyogenes in respiratory droplets from a nearby cough or sneeze enter the body. 2 Pharyngitis results; the back of the pharynx reddens, lymph nodes swell, and tonsils abscess. Fever, malaise, and headache are typical. 3 If bacteria spread to larynx, laryngitis may result. 4 Infection of the bronchi causes bronchitis. 5 Erythrogenic toxins trigger scarlet fever, a rash that spreads from the chest, a strawberry-red tongue, headache, chills, and muscle aches. 6 Rheumatic fever may develop, with pain in heart and joints. 2 1 Pus pockets on tonsils 3 4 5 6 6 The reddened appearance and pus pockets of a throat with pharyngitis headache, chills, and muscle aches. Rheumatic fever may also develop; symptoms include fever, joint pain (knees, ankles, elbows, and wrists), joint swelling, and possible cardiac problems (chest pain, shortness of breath). Incubation period Strep throat: 3–5 days; scarlet fever: 1–2 days following strep symptoms; rheumatic fever: up to 20 days. Susceptibility Children are generally the most susceptible. Rheumatic fever is more common in children ages 6–15. Treatment A throat culture to diagnose bacterial cause is important. Once streptococcal which gives the disease its name: diphthera is a Greek word meaning “leather.” A pseudomembrane can adhere so tightly to the tonsils, uvula, roof of the mouth, pharynx, and larynx that it cannot be dislodged without ripping the underlying tissue and causing bleeding. In severe cases, the pseudomembrane can completely block the respiratory passages, resulting in death by suffocation. ­ Corynebacterium diphtheriae (kŏ-rī′nē-bak-tēr′ē-ŭm dif-thi′rē-ī) is a species of pleomorphic, non-endospore-forming, Grampositive bacteria that is ubiquitous in animals and humans, colonizing the skin and the respiratory, gastrointestinal, M22_BAUM7206_05_SE_C22.indd 676 ­ Pathogen and Virulence Factors infection is confirmed, the standard treatment is oral or intramuscular penicillin G, penicillin V, or amoxicillin. Erythromycin may be given to patients sensitive to penicillin. Scarlet fever and rheumatic fever are treated similarly. Prevention Sick individuals are contagious for at least two days following antibiotic therapy and should be kept at home so as not to infect others. Sore throats in children should be taken seriously and treated so that rheumatic fever does not develop. urinary, and genital tracts. The bacterium divides via a type of binary fission called snapping division, in which daughter cells remain attached to form characteristic V-shapes and sideby-side palisade arrangements (F 22.3). Although other diphtheroids can be pathogenic, the agent of diphtheria is the most common pathogen of this genus. Virulent C. diphtheriae contains a lysogenic phage that codes for diphtheria toxin. The phage and its toxin gene are directly responsible for the signs and symptoms of diphtheria. Like many bacterial toxins, diphtheria toxin consists of two polypeptides. One polypeptide binds to human growth factor receptor on many types of human cells, triggering endocytosis of the toxin. Once inside a cell, proteolytic enzymes split the igure Cause Group A streptococci ( Streptococcus pyogenes). Virulence factors Capsule, M protein, streptokinase, deoxyribonucleases, C5a peptidase, hyaluronidase, pyrogenic toxins, erythrogenic toxin, and streptolysins. Portal of entry Upper respiratory tract. Signs and symptoms Sore, red throat; difficulty swallowing; sudden fever; malaise; and loss of appetite. Can develop into scarlet fever, characterized by a “sandpapery” rash that first appears on the neck and chest and spreads all over the body, red “strawberry” tongue, 11/23/16 3:42 AM       R Bacterial Diseases of the Upper espiratory System, Sinuses, and Ears Pathogenesis and Epidemiology Pseudomembrane C. diphtheriae is transmitted from person to person via respiratory droplets or skin contact. Infections with C. diphtheriae have different effects depending on a host’s immune status and the site of infection. Infections in immune individuals are asymptomatic, whereas infections in immunocompromised individuals result in a mild respiratory disease. Respiratory infections of nonimmune people are most severe, resulting in the sudden and rapid signs and symptoms of diphtheria. Diphtheria is a leading cause of childhood death among the unimmunized. Before immunization, hundreds of thousands of cases of diphtheria occurred in the United States each year. In contrast, health care workers reported only 21 cases total from 1992 to 2015. Diagnosis, Treatment, and Prevention 22.2 A pseudomembrane, characteristic of igure ▲F ­ diphtheria. toxin molecule, releasing the second toxin polypeptide into the cytosol. This polypeptide enzymatically destroys a eukaryotic elongation factor—a protein required for translation of polypeptides. Because the action of the toxin is enzymatic, a single molecule of toxin sequentially destroys every molecule of elongation factor in a cell, completely blocking all polypeptide synthesis and resulting in cell death. Diphtheria toxin is thus one of the more potent toxins known. Palisade ­ ­ V-shapes Initial diagnosis of diphtheria is based on the presence of a pseudomembrane. Laboratory examination of the membrane or of tissue collected from the site of infection does not always reveal bacterial cells because the effects are due largely to the action of diphtheria toxin and not the cells directly. Diagnosis is based on observation of the pseudomembrane and an immunodiffusion assay, called an Elek test, in which antibodies against the toxin react with the toxin in a sample of fluid from the patient. The most important aspect of treatment of diphtheria is the administration of antitoxin (immunoglobulins against the toxin) to neutralize diphtheria toxin before it binds to cells; once the toxin binds to a cell, it enters via endocytosis and kills the cell. The Centers for Disease Control and Prevention (CDC) has approved macrolides (e.g., erythromycin) for patients older than six months and intramuscular penicillin for younger patients to treat diphtheria. Either type of drug kills Corynebacterium, preventing the synthesis of more toxin. In severe cases, a blocked airway must be opened surgically or bypassed with a tracheostomy tube. Because humans are the only known host for C. diphtheriae, the most effective way to prevent diphtheria is immunization. Immunization involves the DTaP4 (diphtheria, tetanus, acellular pertussis) vaccine. This combines diphtheria and tetanus toxoids (deactivated toxins) with antigens of the pertussis (whooping cough) bacterium. It is administered at 2, 4, 6, and 15–18 months, and 4–6 years of age, followed by booster immunizations without pertussis antigens (Td5 vaccine) every 10 years and a single dose of Tdap once in adulthood. Rhinosinusitis and Otitis Media LE A R N I N G O UTC O M E 22.8 Describe the causes, manifestations, diagnosis, treatment LM and the possibilities for preventing rhinosinusitis and otitis media. 20 µm ▲F ­ igure 22.3 Characteristic arrangements of Gram-stained cells of Corynebacterium diphtheriae. What ­ process produces these cellular arrangements? Figure 22.3 V-shapes and palisade arrangements result from the type of binary fission called snapping division. M22_BAUM7206_05_SE_C22.indd 677 4Capital letters indicate full-strength vaccine. letters indicate a reduced amount of vaccine. 5Lowercase 11/23/16 3:42 AM r 22    Microbial Diseases of the espiratory System ­R Signs and Symptoms In the past, pain and pressure in the region of an inflamed sinus was called simply sinusitis, but sinusitis rarely occurs without also involving the nasal mucous membrane; so, the condition is now called rhinosinusitis. Malaise typically accompanies the headache and inflamed nasal passages. Otitis media is a common and painful disease of early childhood that manifests with severe pain in the ears, which may end abruptly when the eardrum ruptures, releasing the pressure. Pressure on the eardrums may interfere with hearing and delay speech development in young children. Rarely, fever and vomiting may be present. Pathogens and Virulence Factors A number of bacteria that are normally part of the respiratory microbiota cause otitis media. These include Streptococcus pneu­ moniae, an alpha-hemolytic streptococcus that lacks specific Lancefield antigens (about 35% of cases); Staphylococcus aureus (1–2% of cases); Haemophilus influenzae (20–30% of cases); and Moraxella catarrhalis (10–15% of cases). These bacteria also cause most cases of rhinosinusitis. Additionally, Streptococcus pyogenes infections of the pharynx can spread into the sinuses and ears. There is some evidence that damage to the mucous membranes of the upper respiratory system and auditory tubes resulting from viral infections, cigarette smoke, and other irritants allows normal microbiota to become opportunistic pathogens. to blame for the spread of resistance to antimicrobials among bacterial populations. An infection is more likely to be bacterial if acute rhinosinusitis lasts more than 10 days, is accompanied by high fever and pus-filled nasal discharge, or worsens after a brief period of improvement. Physicians often treat bacterial rhinosinusitis with amoxicillin-clavulanic acid, which acts synergistically—each agent enhancing the antibacterial effect of the other. Cough suppressants may decrease the discomfort of rhinosinusitis and allow for sleep, but serious side effects, including death, have resulted from use of over-the-counter cough remedies by children under age four. There are no known ways to prevent rhinosinusitis, though some physicians recommend flushing the nasal and sinus cavities with a saline solution to reduce the duration of symptoms. 22.4). Extreme care One irrigation device is a Neti pot (F must be taken to ensure that the solution is sterile; people have died from brain infections by amoebas in nonsterile Neti pots. Physicians treat otitis media with amoxicillin and may take drastic measures to treat and limit recurrent disease. These include lancing the eardrum of the infected ear to relieve pressure, installing plastic tubes through the eardrum to allow drainage of fluid and pus, and removing the tonsils to allow fluid to drain more freely through the auditory tubes. Epidemiologists calculate that immunizations against influenzaviruses and S. pneumoniae could reduce the number of cases of childhood otitis media by more than 1 million per year. igure Bacteria resident in the pharynx can infect the nose and sinuses or middle ears via their connections with the throat, causing rhinosinusitis or otitis media6 (earache). ­ p te ha       C We have examined some bacterial diseases of the upper respiratory system. Now we turn our attention to viral infections of these organs. Pathogenesis and Epidemiology h M W y e T ell Infective agents spread from the pharynx into the sinuses via their connections with the throat. Similarly, the middle ears are infected via the auditory tubes. Inflammation, triggered by an infection, is responsible for the signs and symptoms of these diseases. Rhinosinusitis is more common in adults than in children, presumably because an adult’s sinuses are developed more fully. In contrast, otitis media is more common in children, because a child’s auditory tubes are more horizontal and have smaller diameters; thus, they are invaded and blocked more easily. More than 85% of children develop otitis media, accounting for almost half of all visits to pediatricians, but as children’s heads grow and they develop specific immunity to the various bacteria, otitis media becomes less common. Why must diphtheria immunization be boosted every 10 years? Diagnosis, Treatment, and Prevention Physicians often presume that the signs and symptoms of rhinosinusitis or otitis media indicate bacterial infection, but studies indicate that bacteria cause fewer than 10% of cases of rhinosinusitis. It is important that physicians determine whether an infection is bacterial or viral, because overuse of antibacterial drugs, which have no effect on viruses, is partly ▲F igure 22.4 Neti pot. Flushing the nasal cavities with saline solution can reduce the duration of rhinosinusitis, but extreme care must be taken to prevent life-threatening infection. 6From Greek ous, meaning “ear,” and itis, meaning “inflammation.” M22_BAUM7206_05_SE_C22.indd 678 11/23/16 3:42 AM       R Viral Diseases of the Upper espiratory System Viral Diseases of the Upper Respiratory System Viral respiratory diseases, such as the common cold and influenza, are among the more common human diseases. In the following sections, we examine the primary viral disease of the upper respiratory system—the common cold. Common Cold LE A R N I N G O U TC O M E 22.9 Describe the manifestations and characteristics of ­ common colds. ▲F 22.5 Artist’s rendition of a rhinovirus. This particular one is serotype 14. What other types of viruses cause common colds? igure The common cold is named well—colds are among the most common of human diseases; an adult averages two colds each year. However, there is no single common cause of the common cold—numerous viruses cause colds. Pathogens and Virulence Factors - igure Over 200 different serotypes (strains) of various viruses cause colds. The most common cold viruses—over 115 serotypes—are small viruses with naked polyhedral capsids in the genus Enterovirus of the family Picornaviridae8 (F 22.5). Other cold viruses include numerous serotypes of coronaviruses, over 30 different adenoviruses, several reoviruses, and a few paramyxoviruses. Enteroviruses infecting the nose are commonly called rhi­ noviruses, though this term is no longer an official viral taxon. Rhinoviruses are among the smallest of viruses, about 25 nm in diameter; 500 million rhinoviruses could sit side by side on the head of an ordinary straight pin. Almost all rhinoviruses attach to a human protein named ICAM 1, which is found on the cytoplasmic membranes of cells lining the nasal cavities. The complementary binding sites on the viruses lie at the bottom of deep, narrow clefts only 1.3–3 nm wide on the viral capsids. Such deep, narrow sites are protected from human antibodies and antiviral drugs; thus, prevention of common colds still eludes us. All cold viruses reproduce most effectively at about 33°C, which is the temperature of the nasal cavity. Cold viruses cannot infect the lower respiratory system because of the system’s higher temperature. Acid in the stomach and warmth inhibit cold viruses in the gastrointestinal tract. 7From 8From Greek rhis, meaning “nose,” and rhoia, meaning “to flow” (i.e., a runny nose). Latin pico, meaning “small,” and RNA virus. M22_BAUM7206_05_SE_C22.indd 679 P Pathogenesis After attaching to cells of the nasal mucous membrane, cold viruses cause the cells to synthesize many more viruses, then kill the cells. The new viruses are released to infect still more cells. When cold symptoms are most severe, over 100,000 virions/ml of nasal mucus may be present. They remain infective for hours outside the body. Infected cells lose their ciliary action and slough off when they die. These events trigger the release of inflammatory chemicals and stimulate nerve cells, triggering mucus production, sneezing, and localized inflammation of nasal tissue. Inflammation blocks nasal cavities, resulting in congestion. ­ Everyone is familiar with the sneezing, rhinorrhea,7 congestion, sore throat, malaise, and cough of a cold. Fever does not occur during a cold unless there is secondary bacterial infection. Signs and symptoms usually last a week, though sometimes a mild cough persists for several weeks. Figure 22.5 Besides rhinoviruses (in the family icornaviridae), adenoviruses, coronaviruses, reoviruses, and paramyxoviruses cause colds. Signs and Symptoms Epidemiology Rhinoviruses are extremely infective—a single virus is sufficient to cause a cold in 50% of infected individuals. Symptomatic or not, an infected person can spread viruses in aerosols produced by coughing or sneezing, via fomites (fō′mi-tēz, nonliving carriers of pathogens, such as door knobs), or via hand-to-hand contact. Epidemiologists do not agree on the most common method for transmitting cold viruses, but it appears that self-inoculation by touching the mucous membranes of the eyes, where tears can wash the viruses into the nasal cavity, is common. Studies have shown that explosive sneezes rarely transmit colds. Although people of all ages are susceptible to rhinoviruses, they can acquire some immunity against serotypes that have infected them in the past. For this reason, children typically have six to eight colds per year, younger adults have two to four, and adults over age 60 have one or fewer. An isolated population may acquire a certain amount of herd immunity by sharing infections of specific strains of rhinoviruses; however, 11/23/16 3:42 AM r 22    Microbial Diseases of the espiratory System ­R The manifestations of a cold are usually diagnostic. Laboratory tests are required only if the actual cause of infection is to be identified. While many home remedies and over-the-counter medicines exist to treat the signs and symptoms of common colds, none prevents colds. Antihistamines, decongestants, and pain relievers relieve the symptoms but do not reduce the duration of the disease. Rest and fluids allow the body to mount a more effective immune response; still, a cold lasts about a week. Studies of two common “cures”—zinc in lozenge or syrup form or large amounts of vitamin C—have yielded conflicting results: The majority of studies indicate no benefit for most people, whereas a few studies suggest that colds are shorter but not less frequent in patients who take either zinc or vitamin C before cold symptoms begin. One drug, pleconaril, taken at the onset of symptoms, reduces the seriousness and duration of colds caused by rhinoviruses. Because there are hundreds of differing cold viruses, an effective vaccine against all colds is not practical; such a vaccine would have to protect against all viral serotypes. Nevertheless, a live, attenuated vaccine is available against adenoviruses, though the vaccine is used currently only for military recruits. Because some adenoviruses of animals are known to be oncogenic (cancer causing), there is concern that widespread use of adenovirus vaccine would increase the number of cancer cases. Recently, scientists have discovered an antigen common to rhinoviruses, opening the possibility for developing a vaccine against rhinoviral colds. Hand antisepsis is probably the most important preventive measure against colds, especially if you have touched the hands of an infected person. Disinfection of fomites is somewhat effective in limiting the spread of cold viruses. Table 22.1 on p. 675 compares and contrasts common colds with other respiratory diseases. h M W y e ell T Why is it inappropriate to treat a cold with penicillin, erythromycin, or ciprofloxacin? Bacterial Diseases of the Lower Respiratory System The lower respiratory organs are axenic;9 that is, they are normally devoid of microorganisms. When bacteria successfully surmount the defenses of the respiratory system or when 9From Greek a, meaning “no,” and xenos, meaning “foreigner.” M22_BAUM7206_05_SE_C22.indd 680 Bacterial Pneumonias LE A R N I N G O UTC O M E S 22.10 Define pneumonia, empyema, and pleurisy. 22.11 Describe pneumococcal, primary atypical (mycoplas- mal), and Klebsiella pneumonias. 22.12 List five other bacterial species that can cause pneumonia. 22.13 Explain why scientists in different eras have classified mycoplasmas as viruses, Gram-negative bacteria, and Gram-positive bacteria. 22.14 Describe the features of mycoplasmal pneumonia. The term pneumonia (nū-mō′nē-ă) describes an inflammation of the lungs in which the alveoli and bronchioles become filled with fluid. In some patients, this fluid is pus—a condition known as empyema10 (em-pī-ē′mă). When the pleurae become inflamed, a painful condition called pleurisy results. An estimated 2–5 million cases of pneumonia occur annually. Physicians describe pneumonias according to the affected region of the lungs, the organism causing the disease, or the location of acquisition. For example, lobar pneumonia involves entire lobes of the lungs, and mycoplasmal pneumonia is pneumonia caused by the bacterium Mycoplasma (mī′kō-plaz-mă). Healthcare associated pneumonia (HAP), that is, pneumonia acquired in any health care setting, is a common illness among the elderly and immunosuppressed patients. One significant variety of HAP is ventilator associated pneumonia (VAP). A ventilator is a machine that provides oxygen to patients through a tube inserted through the nose, mouth, or a hole in the larynx. Bacterial biofilms can form in and on the tubes, causing VAP. A number of bacteria, viruses, and fungi cause pneumonia; bacterial pneumonias are the more serious and in adults the more common. In the following sections, we examine some of the more common bacterial pneumonias, beginning with the most prevalent—pneumococcal pneumonia. Pneumococcal Pneumonia Pneumonia caused by Streptococcus—also called pneumococcal pneumonia—is the most common type of bacterial pneumonia, accounting for most cases of community acquired pneumonia (CAP). - Diagnosis, Treatment, and Prevention disease or stress weakens those defenses, life-threatening diseases can result. These include bacterial pneumonias, Legionnaires’ disease, pertussis (whooping cough), and tuberculosis. - new serotypes introduced into a population by outsiders or by mutations ensure that no population is free of all colds. Besides causing colds, adenoviruses can also cause pharyngitis. For some reason, epidemics of respiratory adenoviruses occur on military bases but rarely under the similar conditions found in college dormitories. - p te ha       C Signs and Symptoms Pneumococcal pneumonia is usually lobar, affecting one or more lobes of the lungs. Signs and symptoms include fever; chills; congestion; cough; chest pain, which results in short, rapid breathing; and possibly nausea and vomiting. Blood frequently enters the lungs, causing coughed-up sputum to be rust colored. Neutrophils are present in the patient’s sputum smear. 10From Greek en, meaning “in,” and pyon, meaning “pus.” 11/23/16 3:42 AM TEM 200 nm ▲F ­ igure 22.6 Streptococcus pneumoniae, the most common cause of bacterial pneumonia. The cells are commonly paired and covered with a polysaccharide capsule. abusers, diabetics, and AIDS patients—groups whose immune responses are not fully active. Diagnosis, Treatment, and Prevention Medical laboratory technologists can quickly identify diplococci in Gram stains of sputum smears (see Disease at a Glance 22.2 on p. 684). Because the bacteria are sensitive to most antimicrobial drugs, health care workers must collect samples for smearing before antibacterial therapy has begun. Historically, laboratories confirm the presence of pneumococci with anticapsular antibodies that cause pneumococcal capsules to swell—a so-called quellung11 reaction. Penicillin has long been the drug of choice against S. pneu­ moniae, though about a third of pneumococcal isolates are now penicillin resistant. Physicians can substitute vancomycin when resistance to penicillins has been documented. The CDC recommends a vaccine against pneumococcus administered at 2, 4, 6, and 12–15 months of age and for all adults over age 65. Primary Atypical (Mycoplasmal) Pneumonia Mycoplasmal pneumonia is the leading type of pneumonia in children and young adults. Signs and Symptoms Early symptoms of mycoplasmal pneumonia, including fever, malaise, headache, sore throat, and excessive sweating, are not typical of other types of pneumonia; thus mycoplasmal pneumonia is called primary atypical pneumonia. The body responds to infection with a persistent, unproductive cough in an attempt to clear the lungs of the pathogen and accumulated mucus. Primary atypical pneumonia may last for several weeks, but it is usually not severe enough to require hospitalization or to cause death. Because symptoms can be mild, the disease is also sometimes called walking pneumonia. ­ Pathogenesis and Epidemiology Pneumococci are inhaled occasionally from the pharynx into lungs damaged either by a previous viral disease, such as influenza or measles, or by other conditions, such as alcoholism, congestive heart failure, or diabetes mellitus. Phosphorylcholine triggers endocytosis by lung cells, the capsule protects the bacterium, and thereby pneumococci live in and eventually kill lung cells. From their intracellular “hiding place,” S. pneumoniae bacteria can pass into the blood and brain to cause bacteremia and meningitis. As the bacteria multiply in the alveoli, they damage the lining of the alveoli, allowing erythrocytes, leukocytes, and blood plasma to enter the lung. This fluid fills the alveoli, reducing the lung’s ability to transfer oxygen to the blood and causing the pneumonia. Leukocytes attack the bacteria, in the process secreting inflammatory and fever-producing chemicals, which add to the manifestations of the disease. The body acts to limit migration of bacteria throughout the lungs by binding the microbes with the active sites of secretory IgA. The rest of the antibody molecule then binds to mucus, enabling mucus-enveloped bacteria to be swept from the airways by the action of ciliated epithelium. Pneumococcus counteracts this defense by secreting secretory IgA protease, which destroys IgA. Pneumococcal pneumonia constitutes about 85% of all cases of bacterial pneumonia, including about 30% of healthcare-associated pneumonias. It occurs most frequently in fall and winter in children, the elderly, alcohol and drug       Capsule igure Pathogen and Virulence Factors Louis Pasteur discovered S. pneu­ moniae, and microbiologists have studied the bacterium extensively over the last 125 years, including sequencing the entire genomes of more than 10 strains; nevertheless, scientists still do not fully understand its pathogenicity. The bacterium rarely reaches the lungs because the ciliary escalator sweeps it up and away. The bacterium is a Gram-positive coccus that is a normal member of the microbiota of the mouths and pharynges of 75% of humans without causing harm. Commonly known as pneumococcus, S. pneumoniae forms short chains or, more frequently, pairs. Pathogenic pneumococci secrete an attachment molecule, which is a poorly defined protein that mediates binding of the bacterium to epithelial cells of the pharynx. Virulent serotypes also have polysaccharide capsules (F 22.6) that protect them from lysis by phagocytes. A capsule is required for virulence, as observed by Griffith during his experiments concerning bacterial transformation (see Figure 7.33). Unencapsulated variants are avirulent because alveolar macrophages clear them from the lungs. In addition, S. pneumoniae inserts into its cell wall a chemical called phos­ phorylcholine, which by binding to receptors on cells in the lungs stimulates endocytosis of the bacterium. Pneumococci also secrete a cytotoxin called pneumolysin, which binds to cholesterol in the cytoplasmic membranes of ciliated epithelial cells, producing transmembrane pores that result in the lysis of the cells. Pneumolysin also suppresses the digestion of phagocytized bacteria by interfering with the action of lysosomes inside phagocytes. R L Bacterial Diseases of the ower espiratory System M22_BAUM7206_05_SE_C22.indd 681 11German for “swelling.” 11/23/16 3:42 AM r 22    Microbial Diseases of the espiratory System ­R te p ha       C Epidemiology Nasal secretions spread M. pneumoniae among people in close contact, such as classmates, family members, and dormitory residents. The disease is uncommon in children under age 5 or in older adults, but it is the most common form of pneumonia seen in high school and college students. However, because primary atypical pneumonia is not a reportable disease and is difficult to diagnose, the actual incidence of infection is unknown. Primary atypical pneumonia occurs throughout the year. This lack of seasonality is in contrast to pneumococcal pneumonia, which is more commonly seen in the fall and winter. igure ▲F 2.5 µm 22.7 Pleomorphic forms of Mycoplasma. Why do these Gram-positive bacteria appear pink when Gram stained? Figure 22.7 Mycoplasmas lack cell walls; therefore, the decolorizing step of the Gram procedure removes crystal violet from the cells. igure Pathogen and Virulence Factors Mycoplasma pneumoniae is a strictly aerobic, encapsulated mycoplasma. Mycoplasmas lack cell walls, allowing them to have a variety of shapes—they are 22.7). Further, mycoplasmas have lipids pleomorphic (F in their cytoplasmic membranes called sterols, a feature lacking in other prokaryotes. Mycoplasmas are the smallest free-living microbes; that is, microbes that can grow and reproduce independently of other cells. Their diameters range from 0.1 mm to 0.8 mm Originally, scientists thought mycoplasmas were viruses because their small size and flexibility enable them to squeeze through the pores of filters that were then commonly used to remove bacteria from solutions; however, mycoplasmas contain both RNA and DNA, and they divide by binary fission—traits that viruses lack. Before analysis of mycoplasmal rRNA sequences revealed that they are similar to Gram-positive organisms, mycoplasmas were classified as Gram-negative bacteria. Modern taxonomists and the second edition of Bergey’s Manual of Systematic Bacteriology now categorize mycoplasmas as low G + C, Grampositive bacteria in the phylum Firmicutes. Despite being Gram-positive, they appear pink when Gram stained, because they lack cell walls. M. pneumoniae is one of the few mycoplasmas that causes human disease. This is due partly to its production of an adhesive protein that attaches specifically to receptors located at the bases of cilia of epithelial cells lining the respiratory tracts of humans and to its capsule, which provides protection from phagocytosis. Pathogenesis Attachment of M. pneumoniae to the base of cilia causes the cilia to stop beating, and colonization eventually kills the epithelial cells. This interrupts the normal removal of mucus from the respiratory tract by the ciliary escalator, allowing colonization by other bacteria and causing a buildup of mucus that irritates the respiratory tract. M22_BAUM7206_05_SE_C22.indd 682 Klebsiella Pneumonia Gram-negative bacteria are the leading cause of nosocomial infections, and pneumonias caused by Gram-negative bacteria are among the leading causes of nosocomial deaths. Klebsiella pneumonia is one type of Gram-negative bacterial pneumonia. Signs and Symptoms Besides the common signs and symptoms of bacterial pneumonia—coughing, fever, and chest pain—Klebsiella pneumonia often involves destruction of alveoli, resulting in the production of thick, bloody sputum. Further, Klebsiella pneumonia patients often have recurrent chills. Mortality rates are higher than with pneumococcal or mycoplasmal pneumonias. Pathogen and Virulence Factors Klebsiella pneumoniae (kleb-sē-el′ă nū-mō′nē-ī) is an opportunistic pathogen that infects the respiratory systems of humans and animals following inhalation. It is a nonmotile, Gram-negative rod that produces a prominent 22.8) , giving Klebsiella colonies a mucoid capsule (F appearance and protecting the bacterium from phagocytosis. Besides causing pneumonia, K. pneumoniae may also be involved in meningitis, wound infections, and urinary tract infections. igure SEM Diagnosis, Treatment, and Prevention Diagnosis of primary atypical pneumonia is difficult because mycoplasmas are small and difficult to detect in clinical specimens or tissue samples. Further, mycoplasmas grow slowly in culture, requiring two to six weeks before colonies are visible. Colonies of M. pneumo­ niae have a grainy appearance when the bacteria grow on solid surfaces, unlike the “fried-egg” appearance of colonies of other species of Mycoplasma. Complement fixation, hemagglutination, and immunofluorescent tests confirm a diagnosis, but such tests are nonspecific and are not by themselves diagnostic. Physicians treat primary atypical pneumonia with antimicrobials such as erythromycin or doxycycline. Prevention is difficult because patients are often infective for long periods without signs or symptoms, and they remain infective even while undergoing antimicrobial treatment. Nevertheless, frequent handwashing, avoidance of contaminated fomites, and reducing aerosol dispersion can limit the spread of the pathogen and reduce the number of cases of disease. No vaccine against M. pneumonia is available. Pathogenesis and Epidemiology K. pneumoniae kills alveolar cells and often invades the blood, resulting in bacteremia. When the bacterial cells die, they release endotoxin, which can trigger shock and disseminated intravascular coagulation, leading to death. 11/23/16 3:42 AM ­ igure 22.8 The prominent capsule of Klebsiella pneumoniae. How does the capsule function as a virulence factor? Figure 22.8 Capsules inhibit phagocytosis and intracellular digestion by phagocytic cells. Alcoholics and other patients with compromised immunity such as the elderly, people with AIDS, and very young children are at greater risk of pulmonary disease, including Klebsiella pneumonia, because of their poor ability to clear aspirated oral secretions from their respiratory tracts. ­ Diagnosis, Treatment, and Prevention Physicians diagnose Klebsi­ ella pneumonia from its signs and symptoms and by culturing Klebsiella from sputum specimens. There is no specific treatment for the disease other than supportive care, rest, and feverreducing drugs. Cephalosporins are used against Klebsiella. Because of tissue damage and the release of endotoxin, damage to the lungs is often permanent and can be fatal despite treatment. No vaccine is available, and prevention involves good aseptic technique by health care workers. Other Bacterial Pneumonias Other species of bacteria also cause pneumonia. Normal respiratory microbiota such as the pleomorphic Gram-negative Hae­ mophilus influenzae and Gram-positive Staphylococcus aureus cause pneumonia with manifestations and treatment similar to those for pneumococcal pneumonia. S. aureus produces pus in a chest cavity in about 3% of patients. Fever, chills, cough, difficulty breathing, and frothy bloody sputum characterize a form of pneumonia called pneumonic plague, which is produced by the bubonic plague bacillus, Yersinia pestis (yer-sin′ē-ă pes′tis). This bacterium can enter the lungs in respiratory droplets or via the blood (see Figure 21.6c) and can cause pneumonia in just a few hours. Rapid shock and death result if a pneumonic plague patient is not treated promptly, but mortality is reduced to about 5% with treatment with streptomycin or gentamicin. (Chapter 21 discusses plague in more detail.) Chlamydias, which are Gram-negative, obligate intracellular parasites, can also cause respiratory diseases. Chlamydias form extremely small (0.2- 0.4 mm diameter), resistant Another bacterial disease of the lower respiratory system is also a pneumonia, but physicians and clinicians have given it a specific name—legionellosis. Legionnaires’ Disease LE A R N I N G O UTC O M E 22.15 Describe the features of Legionnaires’ disease. In 1976, joyous celebration of the 200th anniversary of the Declaration of Independence was curtailed in Philadelphia when over 200 American Legion members attending a convention were stricken with severe pneumonia; 29 died. After extensive epidemiological research, a new disease was identified and dubbed Legionnaires’ disease, or legionellosis. A previously unknown pathogen, Legionella (lē-jŭ-nel′lă), causes this disease. Signs and Symptoms Legionnaires’ disease is characterized by common features of pneumonia—fever, chills, a dry nonproductive cough, and headache; pleurisy—inflammation of the pleurae—may also develop. Complications involving the gastrointestinal tract, central nervous system, liver, and kidneys are common. If Legionnaires’ disease is not treated promptly, pulmonary function rapidly decreases, resulting in the death of up to 50% of patients. Pathogen and Virulence Factors Cells of Legionella are aerobic, slender, pleomorphic, Gramnegative bacteria that are classified in the taxon Gammaproteobacteria. They are extremely fastidious in their nutrient requirements, and laboratory media for culture of Legionella ­ 25 µm ▲F M22_BAUM7206_05_SE_C22.indd 683       structures called elementary bodies that act as infectious agents. Here we examine pneumonia caused by two chlamydias in the genus Chlamydophila (formerly known as Chlamydia). Chlamydophila psittaci12 (kla-mē-dof′ĭ-lă sit′ă-sē) causes psittacosis (sit-a-kō′ sis; also called ornithosis13, or-ni-thō′sis or parrot fever). Psittacosis is a disease of birds that can be transmitted to humans, in whom it typically causes flulike symptoms, though in some patients severe pneumonia occurs. Doxycycline is the drug of choice for treating psittacosis. Chlamydophila pneumoniae, spread in respiratory droplets, causes pneumonia as well as bronchitis and rhinosinusitis. Most infections with this bacterium are mild, producing only malaise and a chronic cough, and do not require specific treatment, though azithromycin or doxycycline can be prescribed. The prevalence of chlamydial pneumonia is unknown because most cases are never diagnosed or reported. Disease at a Glance 22.2 on p. 684 summarizes the features of eight types of bacterial pneumonia. Table 22.1 on p. 675 compares and contrasts bacterial pneumonia with other respiratory diseases. Capsules LM R L Bacterial Diseases of the ower espiratory System 12From 13From Greek psittakos, meaning “parrot.” Greek ornith, meaning “bird.” 11/23/16 3:42 AM ­R Gl nce a A a te ha r 22    Microbial Diseases of the espiratory System t D p isease       C 22.2 Bacterial Pneumonias Causes Streptococcus pneumoniae (Gram-positive diplococcus also known as pneumococcus), Mycoplasma pneumoniae (Gram-positive, but pinkstaining, pleomorphic bacterium), Klebsiella pneumoniae (Gram-negative bacillus), Haemophilus influenzae (Gram-negative pleomorphic coccobacillus), Staphylococcus aureus (Gram-positive coccus), Yersinia pestis (Gram-negative rod), and Chlamydophila psittaci and C. pneumoniae (obligate intracellular pleomorphic bacteria). Virulence factors Vary among pathogens but include attachment molecules, capsules, inhibitors of phagocytosis, and lipid A. Pairs Portal of entry Inhalation, also via blood in case of Yersinia. igure ▲F 22.9 Legionella pneumophila growing on buffered charcoal yeast extract agar. This bacterium cannot be ­ Signs and symptoms Dry, unproductive cough, headache, fever, chills, and chest pain. Bloody mucoid sputum with Klebsiella; frothy bloody sputum with Yersinia. grown in culture without such special media. Streptococcus pneumoniae. LM 20 µm P Incubation period neumococcus: 1–3 days; M. pneumoniae: 1–4 weeks; K. pneumoniae: 1–3 days; H. influenzae: 2–4 days; S. aureus: variable, usually days; Y. pestis: a few hours to 2 days; Chlamydophila spp.: 1–4 weeks. P Susceptibility neumococcus: immunocompromised individuals; M. pneumoniae: high school and college students; K. pneumoniae: hospitalized individuals; H. influenzae: infants and young children; S. aureus: the very young and patients with respiratory diseases, such as cystic fibrosis patients; Y. pestis: people exposed to bubonic plague; C. pneumoniae: most common in school-aged children; C. psittaci: individuals in close contact with birds. P Treatment neumococcus: penicillin G, vancomycin; Mycoplasma: a macrolide or tetracycline; K. pneumoniae: cephalosporin; H. influenzae: amoxicillin, cephalosporin; S. aureus: nafcillin, oxacillin, cloxacillin, dicloxacillin, vancomycin; Y. pestis: streptomycin, gentamycin; Chlamydophila spp.: erythromycin, tetracycline. Prevention Use general precautions, such as washing hands frequently. Stop smoking, and, in the case of C. psittaci, avoid infected birds. Vaccines against S. pneumoniae and H. influenzae are available. igure must be enhanced with iron salts and the amino acid cysteine. F 22 .9 shows colonies growing on one special medium—buffered charcoal yeast extract agar. Nineteen species are known to cause disease in humans, but 85% of all infections in humans are caused by L. pneumophila14 (noo-mō′fi-lă). Pathogenesis L. pneumophila presented a problem for early investigators: the bacterium is nearly ubiquitous in moist environmental samples, yet it cannot grow on common laboratory media. In the original epidemic, for example, Legionella was cultured from 14From Greek pneuma, meaning “breath,” and philos, meaning “love.” M22_BAUM7206_05_SE_C22.indd 684 condensation in hotel air conditioning ducts, an environment that seems unsuitable for such a fastidious microorganism. Investigations revealed that Legionella invades freshwater protozoa, typically amoebae, and reproduces inside phagocytic vesicles; thus, the bacterium survives in the environment as an intracellular parasite. Protozoa release Legionella-filled vesicles, and humans acquire the disease by inhaling the vesicles. Within human cells, L. pneumophila lives much as it does in the environment—as an intracellular parasite of macrophages and other cells. The bacterium kills human cells, causing tissue destruction and triggering inflammation of the lungs. For unknown reasons, Legionella rarely spreads outside the lungs. Epidemiology Legionella tolerates heat and chlorination, so it can live in water pipes and other domestic water sources; in fact, legionellosis was not a common disease until modern devices provided a suitable means of transmitting the bacteria to humans: showers, vaporizers, spa whirlpools, hot tubs, air conditioning systems, and cooling towers produce aerosols containing Legionella. Epidemiologists have never documented person-to-person spread of legionellosis. The CDC estimates that about 18,000 people contract Legionnaires’ disease each year, but most cases are so mild and isolated that they are never diagnosed or reported. Smokers, the elderly, patients with chronic respiratory diseases, and the immunocompromised are at greatest risk for infection and disease. Most documented cases occur in summer to early fall. Diagnosis, Treatment, and Prevention Physicians diagnose Legionnaires’ disease with fluorescent antibody staining or serological testing that reveals the presence of Legionella or antibodies against the bacterium in clinical samples. Physicians prescribe intravenous doxycycline, tigecycline, azithromycin, or a quinolone for treating severe cases of 11/23/16 3:42 AM Legionnaires’ disease. Mild cases can be treated with the same antibiotic orally. Eliminating Legionella from water supplies is not feasible, because chlorination and heating are only moderately successful against the microorganism. However, the bacterium is not highly virulent, so merely reducing its number is typically a successful control measure. Tuberculosis LE A R N I N G O U TC O M E S 22.16 Identify two effects of cord factor of Mycobacterium tuberculosis. 22.17 Describe the transmission and pathogenesis of M. tuber­ culosis and its effects on the body. 22.18 Discuss the epidemiology, diagnosis, treatment, and prevention of tuberculosis. 22.19 Define and contrast multi-drug-resistant and exten- sively drug-resistant tuberculosis. Tuberculosis (TB) is the leading disease killer in the world, though its importance to people in industrialized countries has declined as a result of successful surveillance and the use of effective antimicrobial drugs. Nevertheless, epidemiologists warn us that complacency can allow this terrible killer to resurge, as it did during the late 1900s in the United States after health departments shifted funds from TB eradication programs to other areas. Tuberculosis is caused by Mycobacterium tuberculosis (mī′kōbak-tēr′ē-ŭm too-ber-kyū-lō′sis), which is a Gram-positive rod with cell walls containing an abundance of mycolic (mi-kol′ic) acid. This waxy lipid is composed of chains of 60–90 carbon atoms and is directly responsible for many unique characteristics of M. tuberculosis and other mycobacteria. Specifically, mycobacteria: • Grow slowly (in part because of the time required to synthesize numerous molecules of mycolic acid). The generation time varies from hours to several days. • Are protected from lysis once they are phagocytized. • Are capable of intracellular growth. • Are resistant to Gram staining, detergents, many common antimicrobial drugs, and drying out. Because mycobacteria stain only weakly with the Gram procedure (if at all), the acid-fast staining procedure was developed to stain them (see Figure 4.17). Virulent strains of M. tuberculosis produce cord factor, a cell wall component that produces strands of daughter cells that remain attached to one another in parallel alignments, inhibits migration of neutrophils, and is toxic to mammalian cells. Mutant mycobacteria that are unable to synthesize cord factor do not cause disease. In most patients, the immune system reaches a stalemate with the bacterium: the immune system is able to prevent further spread of the pathogen and stop the progression of the disease, but it is not able to rid the body of all mycobacteria. M22_BAUM7206_05_SE_C22.indd 685       R L Bacterial Diseases of the ower espiratory System M. tuberculosis may remain dormant for decades within macrophages and in the centers of tubercles. Multi-drug-resistant (MDR) strains of M. tuberculosis— strains resistant to at least isoniazid (INH) and rifampin—have arisen in several countries. Health care officials are even more concerned about the emergence of extensively drug-resistant (XDR) tuberculosis, which is defined as disease caused by M. tuberculosis that is resistant in vitro to at least INH, rifampin, and three or more other antitubercular drugs. In one South African hospital, 52 of 53 XDR-TB patients died. Physicians administer levofloxacin combined with three to five other antibacterial drugs to treat MDR-TB. Physicians are heartened that bedaquiline—the first new anti-TB drug in over 40 years—was approved by the United States Food and Drug Administration (FDA) in 2013. Bedaquiline specifically inhibits ATP synthesis in mycobacteria. Its use is restricted to multidrug therapy against MDR-TB or XDR-TB. MDR and XDR strains make it more difficult to rid the world of tuberculosis, so officials encourage strict adherence to antitubercular drug regimens. The World Health Organization (WHO) and the CDC recommend a strategy of drug delivery called Directly Observed Treatment, Shortcourse (DOTS), in which health care workers observe patients to ensure they take their medications on schedule. Effective treatment of cases of MDR and XDR tuberculosis is thereby quite expensive. Researchers are developing a subcutaneous implant that would gradually deliver drugs directly into the body over a period of months so that direct observation is not required. Renewed efforts to detect and stop infection and the implementation of DOTS have reduced the number of reported U.S. cases of TB. The CDC predicts that the current downward trend in case number indicates that a TB-free country is attainable in the near future. Disease in Depth: Tuberculosis on pp. 686–687 examines aspects of tuberculosis in more detail. Pertussis (Whooping Cough) LE A R N I N G O UTC O M E 22.20 Describe the characteristics of pertussis. What could be more agonizing to parents than observing their child being tortured by persistent, powerful coughing spells that leave the child exhausted, blue, and with ruptured blood vessels in the eyes? Pertussis, commonly called whooping cough, produces these manifestations. Signs and Symptoms The beginning signs and symptoms of pertussis resemble those of a common cold—rhinorrhea, slight cough, and mild fever—if they occur at all. After one to two weeks, the signature symptom of severe coughing occurs. Vomiting, diarrhea, and choking can accompany this stage. Oxygen exchange in the lungs may be so severely limited that cyanosis develops (the patient turns blue), and death results. 11/23/16 3:42 AM DISEASE IN DEPTH SIGNS AND SYMPTOMS TUBERCULOSIS Signs and symptoms of TB are not always apparent, often limited to a minor cough and mild fever. Breathing difficulty, fatigue, malaise, weight loss, chest pain, wheezing, and coughing up blood characterize the disease as it progresses. Mycobacterium tuberculosis M any people think that tuberculosis (TB) is a disease of the past, one that has little importance to people living in industrialized countries. In part, this attitude results from the success health care workers have had in reducing the number of cases. Nevertheless, epidemiologists warn that complacency can allow this terrible killer to reemerge. 2 Macrophages in alveoli phagocytize mycobacteria but are unable to digest them, in part because the bacterium inhibits fusion of lysosomes to endocytic vesicles. 3 Instead, bacteria replicate freely within macrophages, gradually killing the phagocytes. Bacteria released from dead macrophages are phagocytized by other macrophages, beginning the cycle anew. Alveolus PATHOGENESIS primary tuberculosis 1 Mycobacterium typically infects the respiratory tract via inhalation of respiratory droplets from infected individuals. Macrophage Alveolus Macrophage engulfing Mycobacterium. INVESTIGATE IT! What does the development of XDR-TB (extensively drug-resistant strains of Mycobacterium tuberculosis) portend for the future of the disease? Scan this code to visit the Centers for Disease Control and Prevention website to investigate XDR-TB. Then go to MasteringMicrobiology to record your research findings. M22_BAUM7206_05_SE_C22.indd 686 SEM 5 μm EPIDEMIOLOGY Every second, someone in the world is infected with tuberculosis and on average four people die every minute, mostly in Asia and Africa. TB is on the decline in the U.S., though the CDC estimates that TB may still infect more than 9 million Americans. One third of the world’s population is infected, and over 9 million new cases are seen each year. Left, estimated new TB cases in 2010 per 100,000 (WHO) No data <100 100–300 <300 11/23/16 3:42 AM       PATHOGEN AND VIRULENCE FACTORS SEM 5 μm Mycobacterium tuberculosis is a high G + C, aerobic, Gram-positive rod. Virulent strains produce cord factor, a cell wall component that produces strands of daughter cells that remain attached to one another in parallel alignments. Cord factor also inhibits migration of neutrophils and is toxic to mammalian cells. Multi-drugresistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains of Mycobacterium make it more difficult to rid the world of TB. 4 Infected macrophages present antigen to T lymphocytes, which produce lymphokines that attract and activate more macrophages and trigger inflammation. Tightly packed macrophages surround the site of infection, forming a tubercle over a two- to three-month period. 5 Other cells deposit collagen fibers, enclosing infected macrophages and lung cells within the tubercle. Infected cells in the center die, releasing M. tuberculosis and producing caseous necrosis—the death of tissue that takes on a cheese-like consistency due to protein and fat released from dying cells. A stalemate between the bacterium and the body’s defenses develops. LM Cell walls contain mycolic acid, a waxy lipid that is responsible for unique characteristics of this pathogen, including slow growth, protection from lysis when cells are phagocytized, intracellular growth, and resistance to Gram staining, detergents, many common antimicrobial drugs, and drying out. (Slow growth is due in part to the time required to synthesize molecules of 15 μm mycolic acid.) Secondary/reactivated tuberculosis results when M. tuberculosis breaks the stalemate, ruptures the tubercle, and reestablishes an active infection. Reactivation occurs in about 10% of patients; patients whose immune systems are weakened by disease, poor nutrition, drug or alcohol abuse, or by other factors. disseminated tuberculosis results when macrophages carry the pathogen via blood and lymph nodes to other sites, including bone marrow, spleen, kidneys, spinal cord, and brain. Tuberculosis lesions in spleen. Tubercle Caseous necrosis Ruptured tubercle Tubercle in lung tissue. LM 50 μm Lung lesions caused by TB. DIAGNOSIS TREATMENT AND PREVENTION A tuberculin skin test is used to screen patients for TB exposure. A positive reaction is an enlarged, reddened, and raised lesion at the inoculation site. Chest X-ray films can reveal the presence of tubercles in the lungs. Primary TB usually occurs in the lower and central areas of the lung; secondary TB commonly appears higher. 10 mm M22_BAUM7206_05_SE_C22.indd 687 Mycobacteria Treatment combines pyrazinamide with isoniazid, rifampin, and either ethambutol or streptomycin for two months and then continues with the latter three drugs for an additional four months. Four to five different drugs (such as aminoglycosides, fluoroquinolones, bedaquiline, or cycloserine) are administered simultaneously to treat MDR-TB or XDR-TB. In countries where TB is common, health care workers immunize patients with BCG vaccine, which is not recommended for the immunocompromised because it can cause disease. Workers must avoid inhaling respiratory droplets from TB patients. 11/23/16 3:42 AM r 22    Microbial Diseases of the espiratory System Pertussis (Whooping Cough) Epithelial cell • Pertussis toxin, a portion of which interferes with ciliated epithelial cells’ metabolism, resulting in increased mucus production. (Note that pertussis toxin is both an adhesin and a toxin.) • Adenylate cyclase toxin, which triggers increased mucus production and inhibits leukocyte movement, phagocytosis, and killing. • Dermonecrotic toxin, which causes localized constriction and hemorrhage of blood vessels, resulting in cell death and tissue destruction. • Tracheal cytotoxin, which at low concentrations inhibits the movement of cilia on respiratory cells. Epithelial cilia Bordetella SEM Pertussis is highly contagious, spreading through the air in respiratory droplets; fortunately, the bacterium is fragile—it doesn’t survive long outside the body. It is considered a pediatric disease, as life-threatening cases occur in children younger than five years old. More than 60 million people worldwide suffer from pertussis each year. In the United States, the number of reported cases dropped below 1250 in 1981, but pertussis has become a reemerging disease—there were almost 50,000 reported cases in 2012, which had fallen to about 20,000 cases in 2015. All these figures considerably underestimate the actual number of cases, because patients with chronic coughs are not routinely 15From 16From Greek katarheo, meaning “to flow down.” Greek paroxysmos, meaning “to irritate.” M22_BAUM7206_05_SE_C22.indd 688 Cause Bordetella pertussis (Gram-negative coccobacillus). Virulence factors Adhesins that attach to tracheal cells; survives within phagosome; pertussis toxin causes human cells to make more receptors for Bordetella. Portal of entry Inhalation. Signs and symptoms Catarrhal stage begins with signs and symptoms resembling the common cold that last one to two weeks. The following paroxysmal stage lasts two to four weeks and is characterized by persistent, violent coughing spells that consist of three or four coughs without a breath, followed by a high-pitched, wheezing inhalation, or “whoop.” The convalescent stage lasts several weeks as the cough subsides. Incubation period 6–20 days, with an average of 7–10 days. Susceptibility Unimmunized children. Treatment Supportive care; erythromycin has only little effect on the course of disease but helps eliminate B. pertussis in the respiratory tract and thus helps reduce spread of pertussis to others. P Prevention DTa vaccine. tested for infection with Bordetella and because the disease in older children and adults is typically less severe and can be misdiagnosed as a cold or influenza. Diagnosis, Treatment, and Prevention The symptoms of pertussis are usually diagnostic. Even though health care workers may isolate B. pertussis from respiratory specimens, the bacterium is extremely sensitive to drying out, so specimens must be inoculated at the patient’s bedside onto Bordet Gengou medium, which is specially designed to support the growth of this bacterium. Treatment for pertussis is primarily supportive. By the time the disease is recognized, the immune system has often already “won the battle.” Recovery depends on regeneration of the tracheal epithelium, not on the number of bacteria; therefore, - Epidemiology 10 µm Bordetella. The bacteria attach to and infect ciliated epithelial cells, such as those of the trachea, eventually causing the death of the cells. Pathogenesis Via its adhesins, inhaled B. pertussis binds to cilia in the trachea (see Disease at a Glance 22.3), interfering with their action and stopping the ciliary escalator. Filamentous hemagglutinin also binds to the cytoplasmic membranes of neutrophils, initiating endocytosis of the bacterium. B. pertussis survives within the phagocytes, evading the immune system. Pertussis toxin causes infected cells to produce more receptors for filamentous hemagglutinin, leading to further bacterial attachment and phagocytosis. Pertussis progresses through four phases: incubation, catarrhal15 (kă-tah′răl), paroxysmal16 (par-ok-siz′măl), and convalescent; see Disease at a Glance 22.3. The characteristic sign of whooping cough occurs during the two to four weeks of the paroxysmal phase: to clear mucus from the lungs, the patient coughs two or three times without inhalation, followed by the characteristic “whoop” of inhalation through a congested trachea. Each day a patient may experience 40–50 of these coughing spells, which often end with vomiting and exhaustion. Coughing may be so brutal that blood vessels in the eyes burst. 22.3 Gl nce a A t D isease Pathogen and Virulence Factors Bordetella pertussis (bōr-dē-tel′ă per-tus′is), a small, aerobic, non-motile, Gram-negative coccobacillus in the class Betaproteobacteria, is responsible for pertussis. Various adhesins and toxins mediate the disease. Two adhesins are filamentous hemag­ glutinin and pertussis toxin. Four toxins are: a ­R p te ha       C 11/23/16 3:42 AM       c Clini al Case tudy R L Bacterial Diseases of the ower espiratory System The Coughing Cousin antibacterial drugs have little effect on the course of the disease, though they may reduce the patient’s infectivity. Daily erythromycin for two weeks is recommended to possibly provide protection for susceptible people in close contact with pertussis patients. Given that B. pertussis has no reservoir and that an effective vaccine (the “P” of DTP vaccine) has been available since 1949, whooping cough could be eradicated worldwide. Despite this possibility, pertussis remains. This is due in part to the refusal of parents to immunize their children following publicity concerning adverse reactions to endotoxin from the outer membranes of cell walls of Bordetella used in the original attenuated vaccine (DTP). Developed nations now use six doses of DTaP vaccine, which contains an acellular pertussis (aP) component that lacks endotoxin. DTaP has fewer side effects than DTP vaccine but is not as effective in engendering an immune response over time. Inhalational Anthrax LE A R N I N G O U TC O M E 22.21 Describe inhalational anthrax. The government classifies the bacillus of anthrax as one of a handful of potential biological terror agents. In 2001, a terrorist spread the disease via the U.S. postal system by sending letters filled with endospores. Twenty-two people sickened, and five died. There are three forms of anthrax: cutaneous anthrax (discussed in Chapter 19) manifests on the skin; gastrointes­ tinal anthrax is a rare human disease of the digestive system; and inhalational anthrax—the most severe form of anthrax in humans—is a respiratory disease and is examined here. Signs and Symptoms The initial symptoms of inhalational anthrax resemble those of a common cold or flu—sore throat, mild fever, myalgia (muscle M22_BAUM7206_05_SE_C22.indd 689 five years old and six weeks old and also come to the same office for health care. Both cousins appear well, without any signs or symptoms, and a review of their charts reveals they are current for all scheduled vaccines. Marjorie’s last vaccine was at age 16. 1. 2. 3. 4. 5. 6. Why should pertussis be something to consider? What are the three clinical stages of pertussis? If this is pertussis, why doesn’t Marjorie have the classic “whoop”? What are the CDC recommendations for adults ages 19–64? Which family members are at the highest risk in this situation? What test can her provider perform to confirm the suspicion that Marjorie has pertussis? 7. Is treatment recommended at this time? 8. How is pertussis spread, and how could Marjorie prevent the spread of her infection to others? aches), mild cough, and malaise. After several days, the symptoms progress to include more severe coughing, nausea, vomiting, fainting, confusion, lethargy, shock, and death. Pathogen and Virulence Factors Bacillus anthracis, a Gram-positive, endospore-forming, aerobic, rod-shaped bacterium, causes anthrax. Resistant endospores allow the bacillus to survive in the environment indefinitely. In the body, B. anthracis forms a protective capsule of glutamic acid, which inhibits phagocytosis by alveolar macrophages. The bacterium also secretes anthrax toxin, which kills human cells and triggers edema (swelling due to fluid accumulation). Pathogenesis and Epidemiology An infective dose of B. anthracis endospores involves inhalation of at least 8000 to 50,000 endospores. In the lungs, the endospores germinate, and vegetative cells secrete anthrax toxin, which impairs respiratory function, initiates toxemia, and often results in death. Anthrax does not spread from person to person; rather, people must acquire B. anthracis from infected animals either by contact or via inhalation of endospores in dust or on animal hides or wool. Most patients with inhalational anthrax die, even with full supportive care and timely use of antimicrobial drugs. Diagnosis, Treatment, and Prevention Clinicians can readily identify the large, Gram-positive cells of Bacillus in the sputum of patients, but endospores are seen rarely. Unlike harmless environmental species of Bacillus, laboratory-cultured B. anthracis colonies are sticky and nonhemolytic when grown on blood agar. Serological, DNA, and biochemical testing confirms the presence of B. anthracis. ­ S Twenty-one-year-old Marjorie comes to the family practice office for evaluation of a dry cough that has not gotten better over the last seven days. Before she started coughing, she had a mild fever, runny nose, and sneezing for 10 days, but she was able to carry out her usual routine. She reports having “coughing spells” frequently during the day and recalls one episode in which she gagged and vomited. She has a mild coughing episode while in the office, and although it is paroxysmal, there is no “whoop” noted. Marjorie is a part-time college student attending evening classes and helps her aunt with her younger cousins during the day. Her cousins are 11/23/16 3:42 AM r 22    Microbial Diseases of the espiratory System ­R te p ha       C Penicillin is the preferred drug for use in cases of inhalational anthrax; however, damage to the lungs and anthrax toxemia can be so severe and rapid that treatment is often ineffectual. During the bioterrorism attack of 2001, physicians learned that early and aggressive treatment of inhalational anthrax with antimicrobial drugs accompanied by persistent drainage of fluid from around the lungs increased the survival rate from less than 1% to almost 50%. In 2016, the FDA approved obiltoxaximab—a drug composed of monoclonal antibodies directed against an antigen of B. anthracis—for treatment and to administer to prevent development of disease in patients who have been infected with B. anthracis endospores. An efficacious vaccine is available to select military personnel, researchers, people who work closely with animals, and health care professionals with anthrax patients. Table 22.1 on p. 675 compares and contrasts inhalational anthrax with some other respiratory diseases. h M W y e ell T Mycoplasma pneumoniae is resistant to penicillin, though Mycoplasma does not synthesize an enzyme to break down penicillin. Explain why Mycoplasma is resistant to penicillin. ­ Viral Diseases of the Lower Respiratory System cities, 10,000 people died each week for several months. Could it happen again? In this section we will learn about the characteristics of influenzaviruses that enable flu to produce such devastating epidemics, and we will examine some ways to protect ourselves. Two species of viruses, designated types A and B, cause influenza. Each flu virion is segmented, needing eight different -ssRNA molecules, and is surrounded by a pleomorphic envelope studded with prominent glycoprotein spikes composed of either hemagglutinin18 (hē-mă-glū′ti-nin; HA) or neuraminidase (nūr-ă-min′i-dās; NA). Because influenzaviruses rarely attack cells outside the lungs, so-called stomach flu is probably caused by other viruses or bacteria. The genomes of flu viruses are extremely variable, especially with respect to the genes that code for HA and NA. Mutations in the genes coding for these glycoprotein spikes are responsible for the production of new strains of influenzavirus, via processes known as antigenic drift and antigenic shift. Epidemiologists are particularly concerned about changes in type A influenzaviruses of birds that carry antigens similar to those of major pandemics in 1918–19, 1957–58, and 1968–69. One virus of concern is H5N1, which kills more than 60% of people who contract the virus from infected birds. Fortunately, this virus does not move from person to person; people get it only from birds. Another virus, H1N1, caused a slow, worldwide pandemic beginning in 2009 in Mexico. H1N1 killed an estimated 284,400 that year. Most of its victims were under 65 years of age, which is unusual for a flu virus. In 2013, scientists became concerned about a rapidly expanding pandemic caused by another deadly influenzavirus, H7N9, which affects mainly the elderly, killing over 50% of its victims. Further, H7N9 resists all FDA-approved drugs used to treat flu. Hundreds of millions of dollars are spent each year in the United States on antihistamines and pain relievers to alleviate flu symptoms. Aspirin and aspirinlike products should not be used to treat the symptoms of flu in children and teenagers because of increased risk of Reye’s syndrome, which is a potentially fatal condition that sometimes follows viral infections, especially in children who have taken aspirin. Emerging Disease Case Study: H5N1 Influenza follows one patient’s experience with a deadly bird flu. Disease in Depth: Influenza on pp. 692–693 examines the disease in more detail. Table 22.1 on p. 675 compares and contrasts influenza with some other respiratory diseases. We have considered important bacterial and viral diseases of the upper respiratory system and bacterial diseases of the lower respiratory organs. Now we turn our attention to viral diseases of the lower respiratory system, beginning with influenza. Influenza LE A R N I N G O U TC O M E S 22.22 Describe the general characteristics of influenza and its viruses. 22.23 Describe the roles of hemagglutinin and neuraminidase in the replication cycle of influenzaviruses and in the origin of new influenzaviruses via antigenic drift and antigenic shift. Imagine being the only male elementary schoolchild in a midsized Swedish town because all of your peers died six winters ago; or imagine returning to college after a break, only to learn that half of your fraternity brothers had died during the previous two months. These stories are not fictional; they happened to relatives of this author during the great flu pandemic in the winter of 1918–19. During that winter, half the world’s population was infected with a new, extremely virulent strain of influenzavirus, and approximately 40 million died during that single influenza17 (in-flū-en′ză, or flu) season. In some U.S. 17Influenza, which is Italian for “influence,” derives from the mistaken idea that the alignment of celestial objects caused or influenced the disease. M22_BAUM7206_05_SE_C22.indd 690 Coronavirus Respiratory Syndromes LE A R N I N G O UTC O M E 22.24 Describe coronavirus respiratory syndromes. In the spring of 2003, severe acute respiratory syndrome (SARS) literally changed the face of China as people donned word hemagglutinin refers to these spikes’ ability to attach to and clump (agglutinate) erythrocytes. 18The 11/23/16 3:42 AM (a)       R L Viral Diseases of the ower espiratory System (b) R Signs and Symptoms masks to prevent the spread of this coronavirus disease. Similarly, another coronavirus disease, Middle East respiratory syndrome (MERS), is changing the face of the Middle East and the Republic of Korea (South Korea) (F 22.10). C ase isease g r n D gi E me igure Coronavirus respiratory syndromes manifest with a high fever (greater than 38°C) accompanied by shortness of breath, difficulty in breathing, malaise, and body aches. About 10–20% S y tud R igure ▲F 22.10 Prevention of coronavirus respiratory syndromes. (a) Ballet students in Hong Kong in 2003 donned facemasks to slow the spread of SA S virus. (b) ME S has struck the Middle East and Korea. H5N1 Influenza M22_BAUM7206_05_SE_C22.indd 691 RN RN exchange major pieces of A, producing a new, quite different strain of virus—a process called antigenic shift. The virus attacking Wang Fang was such a newly emerged influenzavirus, a strain that contained A from influenzaviruses of humans, birds, and swine in a novel combination. The virus, commonly called swine flu virus, is officially A(H5 1). This new strain can have devastating and sometimes fatal effects on hosts because it has antigenic combinations that the adaptive immune system has never seen before, necessitating a prolonged defensive response before the body can conquer the infection. During this period, the well-known signs and symptoms of flu play out. Wang Fang was exhausted and weak for another two weeks, but she survived the flu, though many other patients were not so fortunate. N School is supposed to be a time of exploration, learning, and fun, but Wang Fang was too sick to enjoy it right now. Her 104°F fever had lasted two very unpleasant days, but at last it had gone. For another two days she ached all over and was dizzy; her head felt as if it could explode at any moment; and the nausea, frequent vomiting, and extreme tiredness were unrelenting. For over a week, her tired red eyes stared listlessly as she struggled to cope with a constantly running nose, severe sore throat, and a dry hacking cough. Would this onslaught never end? A newly emerging strain of influenza type A had a victim in its grasp. Flu viruses infect birds, pigs, horses, and humans. These viruses normally mutate, producing slightly different strains every year—a process called antigenic drift. About once a decade, however, different strains of influenzaviruses infect a single cell, and within it they 1. Why do people who are immunized sometimes still get the flu? 2. What do the letters A, H, and N stand for in the name A(H5N1)? 3. Why are epidemiologists particularly concerned about bird influenzaviruses? 11/23/16 3:42 AM DISEASE IN DEPTH SIGNS & SYMPTOMS Following infection, influenza has an incubation period of about one day. The signs and symptoms of influenza usually include sudden fever between 39°C and 41°C (102–106°F), pharyngitis, congestion, dry cough, malaise, headache, and myalgia (muscle pain). Fever distinguishes a flu from a common cold. Most people recover in one to two weeks. INFLUENZA Influenzaviruses T wo strains of orthomyxoviruses, designated types A and B, cause influenza. The flu is a common respiratory disease, second in prevalence only to common colds, yet it has characteristics that can produce devastating epidemics. Hemagglutinin –ssRNA molecules (8 total) in helical capsid Neuraminidase Envelope VIRULENCE FACTORS Each flu virion is segmented, having eight different –ssRNA molecules, and is surrounded by a pleomorphic envelope studded with prominent glycoprotein spikes composed of either hemagglutinin (HA) or neuraminidase (NA). Both HA and NA play roles in attachment: NA spikes provide the virus access to cell surfaces by hydrolyzing mucus in the lungs, whereas HA spikes bind to pulmonary epithelial cells and trigger endocytosis. Scientists name influenza A viruses for the subtypes of glycoproteins they have. For example, influenzavirus H5N1 has hemagglutinin subtype five and neuraminidase subtype one. TEM 50 nm INVESTIGATE IT! Scan this QR code to watch Dr. Bauman's Video Tutor explore influenza. Then go to MasteringMicrobiology to investigate further and record your research findings on the following question: How can a student distinguish the flu from a common cold? EPIDEMIOLOGY Occasional outbreaks of very severe influenza Number of cases Avian influenzaviruses 2 4 6 8 10 12 Time (years) M22_BAUM7206_05_SE_C22.indd 692 14 16 18 20 People who get the flu one year are immunologically protected the next year from similar strains resulting from antigenic drift; thus, the total number of cases is typically lower every other year. In contrast, antigenic shift results in major changes in antigens every ten years, so epidemics occur about once a decade. Epidemiologists are concerned that a deadly pandemic of influenza A virus could recur if genes for antigens similar to those of the 1918 flu virus should combine in a new virus by antigenic shift. A virus of concern is H5N1, which kills more than 60% of people who contract the virus from birds. Another virus, H7N9, is resistant to all anti-flu drugs approved by the U.S. Food and Drug Administration (FDA). 11/23/16 3:42 AM       PATHOGENESIS Scene from the 1918–19 flu pandemic. Influenzaviruses enter the body via the respiratory route. Epithelial cells lining the lungs endocytize the viruses; viral envelopes then fuse with the membranes of endocytic vesicles, releasing the viral genome into the cytoplasm. Flu viruses multiply using +ssRNA for both translation and as a template for transcription of new –ssRNA viral genomes. Death of lung epithelial cells reduces the lungs’ first line of defense; as a result, flu patients are more susceptible to bacterial infections, such as with Haemophilus influenzae, which was mistakenly named as the cause of flu. Flu viruses exiting lung cells. TEM ANTIGENIC DRIFT Mutations and recombinations in the genes coding for HA and NA spikes are responsible for the production of new strains of influenza A and B viruses via a process known as antigenic drift. 1 Influenzavirus A or B enters host cell.1 ssRNA from virus 500 nm ANTIGENIC SHIFT Antigenic shift by influenza A virus occurs about once a decade. Influenza B virus does not undergo antigenic shift. 1 Two different strains of influenza A viruses enter the same host cell. 2 Mutation occurs during replication within host cell’s nucleus. 3 New strain of influenzavirus, differing slightly from original virus, exits cell. Nucleus 3 A new influenzavirus A, which can be very different from the original two viruses, exits cell. 2 Genes and antigens from both viral types are combined in new virions. DIAGNOSIS, TREATMENT, & PREVENTION The signs and symptoms of flu during a community-wide outbreak are sufficient for an initial diagnosis of influenza. Lab tests such as immunofluorescence, ELISA, polymerase chain reaction, and rapid antigen testing can distinguish strains of the flu virus. Early and accurate diagnosis is important because antiviral therapy must begin within 48 hours of infection to be effective. The Centers for Disease Control and Prevention (CDC) recommends the use of either of two drugs to treat flu: oseltamivir pills or inhaled zanamivir mist inhibit both M22_BAUM7206_05_SE_C22.indd 693 type A and type B neuraminidase. The CDC discourages use of two older drugs, amantadine and rimantadine, because influenza A viruses have grown resistant to both. Prevention is by immunization with multivalent vaccines, which are at least 70% effective. Scientists track changes in the HA and NA antigens of emerging viruses and use them to create new flu vaccines for each fall's flu season. Good personal hygiene, such as the use of hand antisepsis, can reduce the spread of flu. 11/23/16 3:42 AM r 22    Microbial Diseases of the espiratory System ­R Coronaviruses enter the body via respiratory droplets and adhere to lung cells. The virus destroys these cells, triggering the respiratory symptoms, and then spreads via the bloodstream to the heart and kidneys. Epidemiologists accomplished a notable task in tracking the spread of SARS in only six months from Guangdong Province, China, to an apartment building in Hong Kong, and from there to more than two dozen nations in Asia, Europe, and the Americas. WHO reported that 8098 people became sick and 774 died from SARS (9.6% mortality). Through an aggressive international effort involving identifying and sequencing the SARS virus genome, isolating patients, and screening all travelers from countries with reported SARS cases, the disease was brought under control within a year. Since that SARS pandemic, physicians have reported only about a dozen cases of SARS in China, including several cases among workers in SARS laboratories. MERS has not been contained as quickly. Epidemiologists first became aware of MERS in the spring of 2013 in Saudi Arabia. By June, the disease had spread across the Middle East and into Africa, Europe, and Asia. The greatest numbers of cases outside the Middle East have been in South Korea. Camels are the main host for the MERS virus. Diagnosis, Treatment, and Prevention Physicians diagnose coronavirus respiratory syndromes based upon signs and symptoms, particularly in patients in endemic areas, and confirm it by isolating the virus or antibodies against the virus in the patient’s blood. These techniques are not rapid; therefore, scientists are developing polymerase chain reaction (PCR) tests that will allow rapid diagnosis, which will help avoid future epidemics of SARS and MERS. Physicians provide supportive care for patients. As of 2012, no antiviral drug has proven universally effective against these viruses, though artificial passive administration of antibodies against the virus reduce viral replication. Scientists have developed recombinant DNA vaccines against the SARS virus and are testing the vaccines for safety and effectiveness. Scientists 19From Latin corona, meaning “a crown.” M22_BAUM7206_05_SE_C22.indd 694 a 22.4 Coronavirus Respiratory Syndromes RN R Cause SA S- and ME Sassociated coronavirus (positive, single-stranded (+ssrnA) helical viruses). A Virulence factors Intracellular replication cycle evades immune surveillance. R Portal of entry espiratory droplets enter through mucous membranes via close personto-person contact. Signs and symptoms High fever, headache and body aches, malaise, dry cough developing into pneumonia. Incubation period Generally 2–7 days, up to 10 days in some cases. Susceptibility Studies suggest that some people are genetically more susceptible than others are. TEM 40 nm MERS virus, a coronavirus. Treatment Treatment is mostly supportive, although studies show that antibodies against SA S may be effective in reducing viral replication. R Pathogenesis and Epidemiology Gl nce Prevention imit travel to endemic areas, use handwashing precautions, quarantine infected persons and their contacts. L Pathogen and Virulence Factors Coronaviruses19 are enveloped, +ssRNA viruses with helical capsids whose envelopes form crownlike halos around the capsids, giving the viruses their name (see Disease at a Glance 22.4). Because diseases of coronaviruses are usually mild— coronaviruses are the second most common causes of common colds—fatalities in the SARS and MERS pandemics are particularly alarming. a A t D R of patients have diarrhea. After about a week, patients develop a dry cough and pneumonia. About 10% of SARS patients die, and MERS may have a fatality rate of about 55%. Researchers have expressed some doubt about the latter statistic because the overall infection rate with MERS virus is unknown. isease p te ha       C have developed a vaccine against MERS to be used to immunize young camels—a strategy that portends to be the easiest way to protect humans. Despite the speed with which researchers identified and characterized the SARS virus using modern genetic and immunological techniques, the pandemic was brought under control using centuries-old methods of isolation and quarantine of SARS patients and their contacts. The combination of historical and modern epidemiological practices rendered the SARS pandemic much less severe than many epidemiologists and health officials first feared. Disease at a Glance 22.4 summarizes the characteristics of coronavirus respiratory syndromes. Table 22.1 on p. 675 compares and contrasts manifestations of some common respiratory diseases. Respiratory Syncytial Virus (RSV) Infection LE A R N I N G O UTC O M E S 22.25 Describe the features of respiratory syncytial virus infection. 22.26 Compare the effects of RSV infection in infants and adults. 11/23/16 3:42 AM Respiratory syncytial virus (RSV) infection is the most common childhood respiratory disease in newborns and young children. Annual community-wide outbreaks lasting four to six months are common during late fall, winter, and early spring. Multinucleated syncytium Newly infected cell Nucleus RSV Signs and Symptoms Pathogen RSV (genus Pneumovirus, family Paramyxoviridae) is an enveloped, helical, -ssRNA virus. It is relatively unstable outside the body, surviving only about five hours in the environment or two hours on skin or used facial tissues. Soap and water as well as disinfectants deactivate RSV. Pathogenesis igure As its name indicates, the virus causes syncytia to form in the lungs. A syncytium is a giant, multinucleated cell formed from the fusion of virally infected cells to neighboring cells (F 22.11). Plugs of mucus, fibrin, and dead cells in the bronchioles make it difficult to breathe. The action of cytotoxic T cells and other specific immune responses to RSV infection further damages the lungs. Epidemiology RSV spreads easily during close contact with infected persons, such as through kissing, touching, and shaking hands, and via contact with recently contaminated fomites. Spread via respiratory droplets is less frequent. Immunocompromised older patients and babies, especially those who are premature, are immune impaired, are exposed to tobacco smoke, attend day care, or have older school-aged siblings, are most at risk. RSV is prevalent in the United States; epidemiological studies reveal that about 98% of children in day care centers are infected by age three. Up to 125,000 of these children require hospitalization each year, and 2000 die. Additionally, RSV kills about 14,000 elderly patients annually. Diagnosis, Treatment, and Prevention Prompt diagnosis is essential if infected infants are to get the care they need. The signs of respiratory distress provide some diagnostic clues, but verification of RSV infection is made by immunoassay. Specimens of respiratory fluid may be tested by immunofluorescence, ELISA, or complementary nucleic acid probes. M22_BAUM7206_05_SE_C22.indd 695 Fused infected host cells Uninfected cell Newly infected cell Infected host cell Multinucleated syncytium RSV 22.11 A syncytium forms when RSV triggers ▲F infected cells to fuse with uninfected cells. Virions moving igure About four to six days following infection, RSV triggers fever, rhinorrhea (runny nose), cyanosis (blue cast to skin), coughing, and sometimes wheezing in babies and immunocompromised patients. RSV is the leading cause of bronchiolitis (inflammation of the bronchioles) and pneumonia among children less than one year of age and the leading respiratory killer of infants worldwide. Infections of RSV in older children and adults with normal immune systems results in coldlike symptoms. Some children develop tracheobronchitis, known commonly as croup (krūp), which is inflammation of the trachea and bronchi, resulting in breathing difficulty accompanied by a barking cough.       R L Viral Diseases of the ower espiratory System through these large multinucleated cells can infect new cells, all the while evading the host’s immune system. Older children and most adults require no treatment because their disease is mild. For younger children, supportive treatment includes administration of oxygen, intravenous fluids, drugs to reduce fever, and antibiotics to reduce secondary bacterial infections. Immunoglobulins against RSV, derived from blood donations, have proven effective for treating severe cases. Ribavirin via inhalation in mist form is used to treat extreme cases in premature and immunocompromised infants. Control of RSV is limited to attempts to delay infection of susceptible infants through proper aseptic techniques, especially by health care workers and day care employees. Handwashing and the use of gowns, goggles, masks, and gloves are important measures to reduce healthcare-associated infections. Attempts at developing a vaccine with deactivated RSV have proven difficult because the vaccine enhances the severity of the cellular immune response and lung damage. Disease at a Glance 22.5 summarizes characteristics of respiratory syncytial virus infection. Hantavirus Pulmonary Syndrome (HPS) LE A R N I N G O UTC O M E 22.27 Describe Hantavirus pulmonary syndrome. True story: A young Native American scores an impressive 44 points for his tribal team during a basketball game one night. After the game, he is aware of muscle pains but attributes them to his athletic endeavors; five days later he is dead, a victim of Hantavirus pulmonary syndrome (HPS). 11/23/16 3:42 AM ­R 22.5 Gl nce a t a te r 22    Microbial Diseases of the espiratory System A isease D p ha       C 90–100 nm Respiratory Syncytial Viral Infection Three negative ssRNA molecules within capsids Membrane glycoproteins Lipid envelope Capsid Negative ssRNA 22.12 igure R RN R Virulence factors Attaches to and enters human cells; intracellular replication cycle evades immune system; virus causes infected cells to fuse with their neighbors, so virus spreads without entering blood. ▲F Hantavirus is an enveloped, segmented, -ssRNA bunyavirus. What does the term segmented mean in reference to a viral genome? Figure 22.12 A segmented genome has more than one nucleic acid molecule. Cause espiratory syncytial virus ( SV) (Pneumovirus, enveloped, negative, single-stranded A (-ssrnA) virus). Portal of entry Inhalation. Incubation period Four to six days. and cause HPS. A viral protein inhibits cellular responses to interferon. Susceptibility Babies and the immunocompromised are most at risk of serious infection. Pathogenesis R Treatment Supportive respiratory care; antibodies against SV and inhaled ribavirin may slow the disease. Prevention Delay infection of newborns by proper aseptic technique, particularly handwashing. Signs and Symptoms Early symptoms of HPS include fever, fatigue, and muscle aches, particularly in the large muscles of the thighs, hips, and back. Some patients experience headache, chills, and gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and abdominal pain. An elevated leukocyte count and a low or falling platelet count are indicative of HPS. Four to ten days after the initial manifestations, the patient begins coughing, goes into shock, and has difficulty breathing as the lungs rapidly fill with fluid. Fifty percent of diagnosed patients die, drowning in their own fluids, despite intensive medical care. Pathogen igure Hantavirus (han′tā-vī-rŭs) is a genus of enveloped, segmented, -ssRNA viruses in the family Bunyaviridae (F 22.12) that infect various species of mice, particularly deer mice (see Disease at a Glance 22.6), without causing disease. Two American strains of Hantavirus are transmitted via inhalation in dried mouse urine, feces, or saliva to infect the lungs of humans M22_BAUM7206_05_SE_C22.indd 696 Following inhalation, Hantavirus enters the blood via an unknown mechanism and travels throughout the body, infecting the cells that make up blood capillary walls, particularly in the lungs. The body responds with inflammation, which causes the capillaries to leak fluid into the surrounding tissue. Blood pressure drops precipitously, and about 50% of patients die from pneumonia and shock. Epidemiology Epidemiologists have reported several hundred cases in the United States since HPS was first recognized during an epidemic in the Four Corners20 area of the United States in May 1993. Cases have been reported from most of the states west of the Mississippi River. The number of infections increases when abundant rainfall stimulates plant growth, providing abundant food material for the host mouse species. As the mouse population increases dramatically, humans are more likely to contact mice and their excrement and saliva. Despite a large number of virions in the blood vessels of infected humans, few viruses pass out of the lungs; therefore, person-to-person spread does not occur. ­ Signs and symptoms Fever, rhinorrhea, coughing, cyanosis. Diagnosis, Treatment, and Prevention Physicians diagnose Hantavirus pulmonary syndrome based on typical manifestations of the disease—low platelet count, 20Four meet. Corners is the geographic area where Arizona, Colorado, Utah, and New Mexico 11/23/16 3:42 AM A Blue Baby A woman reports to the emergency room in January with her cyanotic (bluecolored) 10-month-old child. The mother reports that the infant has had a runny nose, fever, and slight cough for a day and has had increasing trouble breathing. The child does not have a history of bronchial disease and was not premature. The mother also states that the infant’s five-year-old brother is recovering from symptoms that resemble a cold. ­ Other Viral Respiratory Diseases LE A R N I N G O U TC O M E ­ 22.28 Describe human Metapneumovirus and parainfluenza virus infections. 1. 2. 3. 4. 5. Gl nce a t A isease D a ­ Other viruses cause common respiratory illnesses in children, elderly adults, and the immunocompromised. Among these are Cytomegalovirus (examined in more detail in Chapter 21) Metap­ neumovirus (MPV), and parainfluenzaviruses. 22.6 Hantavirus Pulmonary Syndrome RN Cause Hantavirus (enveloped, segmented, negative, single-stranded A (-ssrnA) virus). Virulence factors Intracellular replication helps avoid immune surveillance, proteins inhibit interferon responses. Portal of entry Inhalation of infected rodent excrement or saliva. The deer mouse, Peromyscus maniculatus. Signs and symptoms Sudden onset of fever, fatigue, muscle aches, headache, chills, abdominal pain; followed by coughing and severe difficulty in breathing. Incubation period 14–30 days. What is the presumptive diagnosis? How can the doctor confirm the diagnosis? Describe the possible treatment for the child. Were the parents irresponsible for not immunizing their child? Is it likely that the infant caught the disease from his older brother? If so, why did the older child not display signs of respiratory distress? Metapneumovirus and parainfluenzaviruses are enveloped, unsegmented, -ssRNA viruses in the family Paramyxoviridae. Scientists discovered MPV in 2001 using nucleic acid probes, which bound to genetic sequences that did not match the sequences of any known organism or virus. Since then, researchers have found that antibodies against the virus form in all children by age five, and they estimate that MPV is second only to rhinoviruses as a common cause of viral respiratory disease. As with most viral diseases, there is no treatment. Three strains of parainfluenzaviruses cause croup and viral pneumonia, particularly in young children. There is no specific antiviral treatment beyond support and careful monitoring to ensure that airways do not become completely closed, requiring insertion of a breathing tube. Most patients recover from parainfluenza infections within two days. Frequent handwashing reduces the spread of the virus. To this point, we have considered respiratory diseases caused by bacteria and viruses. Next, we turn our attention to respiratory diseases caused by fungi. P Susceptibility eople exposed to rodents in endemic areas.       c Clini al Case tudy S sudden onset of fever, and muscle aches in the major muscles of the legs and trunk—in patients who have contacted mice. Diagnosis is confirmed by detection of anti-hantavirus IgM, a rising titer of similar IgG, or demonstration of hantaviral RNA in clinical specimens using polymerase chain reaction. No pharmacological treatment exists for HPS. Supportive care may include pulmonary intubation, fever-reducing drugs, pain medication, and supplemental oxygen. No vaccine against Hantavirus exists. Rodent control is necessary to prevent infection. This includes keeping food in sealed containers, blocking openings into homes (deer mice can squeeze through a hole the size of a man’s shirt button), sleeping on a ground cover when camping, and removing mouse feces, urine, and nesting material from the home. Disease at a Glance 22.6 summarizes the features of Hantavirus pulmonary syndrome. R L Viral Diseases of the ower espiratory System Prevention Avoid rodent droppings, camp on ground sheet, carefully clean out potential rodent nesting sites at home, and keep home clean. M22_BAUM7206_05_SE_C22.indd 697 h M W y e T ell Treatment Supportive therapy for symptoms must occur under hospital supervision. Why do epidemiologists think that there will be a major flu pandemic in people caused by bird influenzaviruses? 11/23/16 3:42 AM r 22    Microbial Diseases of the espiratory System ­R LE A R N I N G O U TC O M E 22.29 Define systemic mycosis. igure The number of cases of mycoses (diseases caused by fungi) has increased over the last two decades, mostly because AIDS patients are susceptible to fungal infections. The following sections examine three systemic mycoses—fungal infections that spread throughout the body—seen in North America (F 22.13) and a type of fungal pneumonia common to AIDS patients. We begin with a systemic mycosis caused by Coccidioides. Coccidioidomycosis LE A R N I N G O U TC O M E 22.30 Describe coccidioidomycosis. Coccidioidomycosis (kok-sid′ē-oy′dō-mī-kō′sis), commonly known as valley fever, occurs primarily in the San Joaquin Valley of California. Signs and Symptoms The major manifestation of coccidioidomycosis is pulmonary, initially resembling pneumonia or tuberculosis, though about (b) Blastomycosis 60% of patients experience only mild, unremarkable respiratory symptoms that typically resolve on their own. Other patients develop more severe infections characterized by fever, cough, chest pain, difficulty breathing, coughing up or spitting blood, headache, night sweats, weight loss, and pneumonia; in some individuals, a diffuse rash may appear on the trunk. In less than 1% of cases, generally in patients who are severely immunocompromised, the fungus spreads from the lungs to various other sites. Invasion of the central nervous system may result in meningitis, headache, nausea, and emotional disturbance. The fungus can also spread to the bones, joints, and subcutaneous tissues; subcutaneous lesions are inflamed masses of granular material (F 22.14). igure Mycoses of the Lower Respiratory System Pathogen and Virulence Factors Coccidioides immitis (kok-sid-ē-oy′dēz im′mi-tis) is a dimorphic soil fungus in the division Ascomycota. In the warm and dry summer and fall months, particularly in drought cycles, C. immitis grows as a mycelium and produces sturdy chains of asexual spores called arthroconidia. Mature arthroconidia germinate into mycelia. The fungus assumes a pathogenic yeast form at human body temperature. Pathogenesis Coccidioides enters the body through inhalation of arthroconidia from the soil. Disease begins as a generalized pulmonary infection that then spreads to the rest of the body. Arthroconidia germinate in the alveoli into a form called a spherule (sfer′ool) (F 22.15). As each spherule matures, it enlarges and igure p te ha       C (c) Histoplasmosis (a) Coccidioidomycosis igure ▲F 22.13 The geographic distributions of three systemic fungal diseases endemic to North America. M22_BAUM7206_05_SE_C22.indd 698 11/23/16 3:42 AM       R L Mycoses of the ower espiratory System Any activity that disrupts the soil can disseminate arthroconidia into the air. Local epidemics have occurred among archeologists, model plane enthusiasts practicing their hobby in the desert, and drivers of off-road vehicles. Windstorms and earthquakes can disturb large tracts of contaminated soil, spreading arthroconidia for miles. In 1978, many cases of coccidioidomycosis occurred in Sacramento, California, 500 miles north of the endemic area, following a severe dust storm in southern California. Diagnosis, Treatment, and Prevention P igure 22.14 Coccidioidomycosis lesions in subcutane▲F ous tissue. ainless lesions result from the spread of Coccidioides immitis from the lungs. generates a large number of spores via multiple divisions, until it ruptures and releases the spores into the surrounding tissue. Each spore then forms a new spherule to continue the cycle of division and release. This type of spreading growth accounts for the seriousness of coccidioidomycosis. Epidemiology Coccidioides is found almost exclusively in the southwestern United States and northern Mexico (FIGURE 22.13a). Small endemic areas also exist in semiarid parts of Central and South America. About 3% of people living in endemic areas develop the disease each year. Spores Blastomycosis LE A R N I N G O UTC O M E 22.31 Describe blastomycosis. Another systemic fungal disease that begins as a respiratory infection is blastomycosis (blas′tō-mī-kō′sis), which is endemic across the southeastern United States north to Canada (FIGURE 22.13b). ­ Spherule Diagnosis of coccidioidomycosis is based on the identification of spherules in clinical specimens; diagnosis is confirmed by injecting antigen beneath the skin and observing an inflammatory response. Although infections in otherwise healthy patients generally resolve on their own, when the fungus spreads to the brain and spinal cord the disease is fatal without treatment. Intravenous amphotericin B is the drug of choice; unfortunately, it is one of the more toxic antifungal agents to humans. In AIDS patients, maintenance therapy with other antifungal drugs, such as itraconazole or fluconazole, is recommended to prevent relapse or reinfection. The wearing of protective masks in endemic areas can prevent exposure to arthroconidia, although it may be impractical for daily use for all but those whose occupations put them at clear risk of infection. Signs and Symptoms igure Blastomycosis begins with flulike signs and symptoms. The fungus may then spread to cause cutaneous blastomycosis (in 60–70% of cases), which manifests as generally painless lesions 22.16). In roughly 30% of on the face or upper body (F cases, purulent (pus-filled) lesions may develop and expand in the bones, prostate, testes, or other organs as the yeast multiplies, resulting in necrosis (death of tissues) and cavity formation. Pathogen LM 22.15 Spherules of Coccidioides immitis. ote the N igure ▲F 10 µm numerous spores within a spherule. M22_BAUM7206_05_SE_C22.indd 699 A dimorphic, pathogenic ascomycete—Blastomyces dermatiti­ dis (blas-tō-mī′sēz der-mă-tit′i-dis)—causes blastomycosis. The fungus normally grows in soil rich in organic material such as decaying vegetation and animal wastes, where cool, damp conditions favor growth and sporulation. The fungus assumes a yeast form in the higher temperature of the human body. 11/23/16 3:42 AM r 22    Microbial Diseases of the espiratory System ­R p te ha       C Histoplasmosis LE A R N I N G O UTC O M E 22.32 Describe histoplasmosis. Histoplasmosis (his′tō-plaz-mō′sis) is the most common fungal disease affecting humans. Signs and Symptoms In almost 95% of individuals, histoplasmosis is asymptomatic, subclinical, and resolves without damage. About 5% of patients develop clinical histoplasmosis, which is characterized by severe coughing with blood-tinged sputum or skin lesions. An AIDS patient with histoplasmosis often rapidly develops an enlarged spleen and liver, which can be fatal. Some patients’ bodies mount a type I hypersensitivity reaction against the fungus in the eyes, producing inflammation and redness. Pathogen ▲F igure 22.16 Cutaneous blastomycosis in an American woman. The lesions result from the dissemination of Blastomyces dermatitidis from the lungs to the skin. Pathogenesis and Epidemiology Inhalation of dust carrying fungal spores infects the lungs. In the lungs, spores germinate to form yeasts and multiply. Initial pulmonary lesions are asymptomatic in most individuals. In otherwise healthy people, pulmonary blastomycosis and minor skin lesions typically resolve, though the disease may become chronic and fatal. Respiratory failure and death occur at a high frequency among immunocompromised patients. Epidemiologists have reported blastomycoses in Latin America, Africa, Asia, and Europe. One to two cases occur annually per 100,000 population in endemic areas. As Emerging Disease Case Study: Pulmonary Blastomycosis relates, the incidence of human infection is increasing. Diagnosis, Treatment, and Prevention Diagnosis relies on identification of B. dermatitidis in culture or direct examination of various samples such as sputum, bronchial washings, biopsies, cerebrospinal fluid, or skin scrapings. Observation of dimorphism in laboratory cultures coupled with microscopic examination is diagnostic. Physicians treat blastomycosis with amphotericin B for 10 weeks, though longer treatment may be necessary. Oral itraconazole may be used as an alternative but must be administered for 6 to 12 months. Relapse is common in AIDS patients, and suppressive maintenance therapy with itraconazole is recommended. Scientists have developed a live recombinant DNA vaccine against Blastomyces that provides protection in mice. M22_BAUM7206_05_SE_C22.indd 700 Histoplasma capsulation (his-tō-plaz′mă kap-soo-lā′tŭm), the causative agent of histoplasmosis, is a dimorphic ascomycete that is found in moist soils containing high levels of nitrogen such as from the droppings of bats and birds, especially chickens, starlings, and blackbirds. The fungus becomes a pathogenic yeast at human body temperature (37°C). Besides changing morphology, Histoplasma at this temperature produces several proteins that prevent full activation of macrophages and abrogate host defenses such as production of free radicals and antimicrobial peptides. Pathogenesis and Epidemiology H. capsulatum is an intracellular parasite that, upon inhalation, first attacks alveolar macrophages in the lungs. Infected macrophages disperse the fungus beyond the lungs via the blood and lymph. Cell-mediated immunity eventually develops, clearing the organism from healthy patients. Based on skin tests administered in the 1940s looking for an immune response to Histoplasma antigens, epidemiologists concluded that histoplasmosis is prevalent in the eastern United States along the Ohio and Mississippi river valleys (FIGURE 22.13c). Endemic areas also exist in Africa and Central and South America. People inhale spores that have become airborne when soil containing the fungus is disturbed by wind or by human activities. Diagnosis, Treatment, and Prevention Diagnosis of histoplasmosis is based on the identification of budding yeast within macrophages or in stained samples of skin scrapings, sputum, cerebrospinal fluid, or various tissues; the diagnosis is confirmed by the observation of dimorphism in cultures grown from such samples. Cultured H. capsulatum produces distinctively spiny spores that are also diagnostic (see Disease at a Glance 22.7 on p. 702). Antibody tests are not useful indicators of disease because many people have been 11/23/16 3:42 AM       R y tud S ase C isease g r n D gi E me L Mycoses of the ower espiratory System Pulmonary Blastomycosis P P exposed without becoming ill. In endemic regions of the United States, close to 90% of the population have antibodies against H. capsulatum. Infections in immunocompetent individuals typically resolve without treatment. When symptoms do not resolve, physicians can prescribe amphotericin B for one to two weeks followed by itraconazole for one year. Maintenance therapy for AIDS patients is recommended. Disease at a Glance 22.7 on p. 702 summarizes the features of histoplasmosis. Pneumocystis Pneumonia LE A R N I N G O U TC O M E 22.33 Describe Pneumocystis pneumonia. Before the AIDS epidemic, Pneumocystis pneumonia was observed only in malnourished premature infants and weak elderly patients; now, the disease is almost diagnostic for AIDS. The disease is known by the abbreviation PCP, which originally M22_BAUM7206_05_SE_C22.indd 701 P R P P had appeared on his face, neck, and legs. More alarming: his testes were swollen and aching. This was getting serious. Blastomyces, an emergent, dimorphic fungus, was attacking hil. Inhaled spores from hyphae growing on wet leaves primarily in Wisconsin and Ontario had germinated in hil’s lungs. The yeast phase was multiplying and spreading throughout his body, producing skin lesions that lasted for months, finally resolving into raised, wartlike scars. esearchers don’t know why blastomycosis is becoming more prevalent. erhaps it has to do with better diagnosis and reporting; perhaps it has to do with a growing number of AIDS patients who are susceptible to infection; or perhaps it has to do with more people like hil adventuring into the wilderness. The good news is that with proper diagnosis, hil got the treatment he needed— amphotericin B for two weeks followed by itraconazole for a year. He graduated, and now he is a nurse who knows that flulike symptoms can sometimes indicate serious fungal infection. P P P N P hil was glad he had spent two weeks this summer fishing, hiking, and camping in western Ontario. Canada is beautiful, and he had needed time off from his two jobs and full schedule of nursing classes. ow he was back in college, and memories of Canada were helping him cope with the stress. However, hil didn’t feel well. He was probably coming down with the flu—fever and chills, shivering and coughing, muscle aches, tiredness, a general feeling of yuckiness, and no runny nose; yes, it must be the flu. Or was it? He knew from microbiology class that many diseases of bacteria, protozoa, and viruses have flulike symptoms. hil had forgotten fungi. hil used every over-the-counter remedy, to no avail. He tried the health clinic on campus, but the antibiotics he received made things worse, not better. He was losing weight, and pus-filled, raised sores 1. Blastomyces is dimorphic; what does this adjective mean? 2. Why does AIDS increase the incidence of blastomycosis? 3. Given that Blastomyces is a mold that grows on dead leaves, how does it cause disease in people? stood for “Pneumocystis carinii pneumonia” (incorporating the microbe’s former name) but now can be considered to stand for “ Pneumocystis pneumonia.” Signs and Symptoms Signs and symptoms of Pneumocystis pneumonia include increasing difficulty in breathing, mild anemia, hypoxia (low tissue oxygen), and fever. A nonproductive cough occurs in some cases. Rarely, extrapulmonary lesions develop in the lymph nodes, spleen, liver, and bone marrow. If left untreated, Pneumocystis pneumonia involves more and more lung tissue until death occurs. Pathogen Pneumocystis jirovecii (nū-mō-sis′tis jē-rō-vĕt′zē-ē), which is a normal member of the respiratory microbiome, is an obligate parasitic ascomycete formerly known as “P. carinii.” Originally it was considered a protozoan because of its morphology and development, but scientists have reclassified it as a fungus based on rRNA nucleotide sequences and biochemistry. 11/23/16 3:42 AM ­R Gl nce a A a te ha r 22    Microbial Diseases of the espiratory System t D p isease       C 22.7 Histoplasmosis 1 Spores of Histoplasma capsulatum are present 4 Infected macrophages carry spores through in moist, nitrogen-rich soils, especially at sites of bat and bird droppings. circulatory and lymphatic systems. 5 Patient may develop chronic pulmonary 2 Airborne spores are inhaled. histoplasmosis with symptoms similar to those of tuberculosis. 3 Spores attack alveolar macrophages. Symptoms in 95% of infections are mild: coughing, aches, and pains. 6 Patient may develop chronic cutaneous histoplasmosis, characterized by ulcers. 7 Immunocompromised patients may develop systemic histoplasmosis characterized by enlargement of spleen and liver; death may result. 8 Ocular histoplasmosis may develop. Inflamed, red eyes indicate type I hypersensitivity to the fungus. Budding 8 1 2 3 5 Histoplasma capsulatum spores LM LM 25 µm 5 µm 4 6 7 Liver Cause Histoplasma capsulatum (dimorphic ascomycete fungus). Virulence factors Ability to change to infective, yeast form at 37ºC; production of proteins that inhibit macrophages and other immune responses. Portal of entry Inhalation. Signs and symptoms Dry, unproductive cough, shortness of breath, chest pain, fever, chills, headache, and malaise. Incubation period Approximately 10 days. Susceptibility Anyone, but more common in children up to 15 years old and those exposed to the soil in endemic areas. Pathogenesis and Epidemiology P. jirovecii cannot survive on its own in the environment; therefore, transmission most likely occurs through inhalation of droplet nuclei containing the fungus. In normal people, infection is asymptomatic, and generally clearance of the fungus from the body is followed by lasting immunity. However, some individuals may remain infected for years; in such carriers, the organism remains in the alveoli and can be passed in sputum and presumably in respiratory droplets. Once the fungus enters the lungs of an immunocompromised patient, it multiplies rapidly, extensively colonizing the lungs. M22_BAUM7206_05_SE_C22.indd 702 Spleen Treatment Itraconazole, ketoconazole, or amphotericin B. Prevention Minimize exposure to soil, especially near chicken coops or bat caves, or wear a mask. P. jirovecii is distributed worldwide in humans. Based on serological confirmation of antibodies, 75% of healthy children have been exposed to the fungus by age five, but disease results only in immunocompromised patients. Pneumocystis pneumonia is one of the more common diseases seen in AIDS patients. Diagnosis, Treatment, and Prevention Diagnosis of Pneumocystis pneumonia relies on clinical and microscopic findings. Chest X-ray films usually reveal abnormal lung features. Stained specimens of fluid from the lungs or from biopsies can reveal distinctive morphological forms of the 11/23/16 3:42 AM       Chapter Summary fungus (FIGURE 22.17). The use of fluorescent antibody on samples taken from patients is more sensitive and provides a more specific diagnosis. Although classified as a fungus, Pneumocystis does not respond to antifungal drugs; instead, both primary treatment and maintenance therapy are with an oral or intravenous combination of trimethoprim and sulfamethoxazole known as TMPSMX. It is virtually impossible to prevent infection because P. jirovecii is ubiquitous in humans; however, the fungus produces disease only in immunocompromised individuals, so steps to ensure a healthy immune system, such as stopping smoking, good nutrition, and preventing HIV infection, can prevent Pneumocystis pneumonia in most people. h Outbreaks of blastomycosis have occurred in Latin America even though the organism itself is not normally found there. Why might a few cases of blastomycosis appear outside endemic areas? Another Day Care Cold? 100 µm ▲F 22.17 Cysts of Pneumocystis jirovecii in lung tissue. Such microscopic findings are diagnostic for Pneumocystis pneumonia. had whooping cough; none of the affected children had been vaccinated against pertussis. 1. Explain how B. per tussis causes damage to the trachea and how this damage leads to the characteristic cough associated with pertussis. 2. Hailey’s infection could have been prevented with the DTaP vaccine—Claire’s argument against vaccinating Hailey was that it was a personal choice that impacted only Hailey. As a future health care professional, do you agree with Claire’s argument? Why or why not? S ummar C hapter P Dr. Fischer completes a preliminary examination of Hailey—based on her symptoms, in particular her cough, she believes that Hailey has pertussis: whooping cough. Dr. Fischer collects a nasopharyngeal swab to send for laboratory confirmation. Dr. Fischer tells Claire that Hailey most likely became infected at day care. Because Hailey isn’t vaccinated against the bacterium that causes the disease, Bordetella pertussis, she was susceptible to infection. The lab analysis confirms Dr. Fischer’s diagnosis. Because Hailey’s pertussis was diagnosed relatively early, Dr. Fischer prescribes a course of erythromycin. After completing five days of the antibiotics, Hailey should be able to safely return to day care without spreading the infection. ertussis is a reportable disease; Dr. Fischer reports the case to her local health department. The other sick kids at the day care also LM igure e M W y ell T Cyst y Structures of the Respiratory System (pp. 672–674) 1. The upper respiratory system—consisting of the nose, nasal cavity, and pharynx—collects and filters air. 2. Cilia move mucus with trapped microorganisms to the pharynx to be swallowed. M22_BAUM7206_05_SE_C22.indd 703 3. Chemicals and cells of the tonsils fight microbial contaminants. 4. The lower respiratory system resembles an upside-down tree, composed of the larynx, trachea, bronchi, bronchioles, and alveoli of the lungs. They carry air through progressively smaller tubes to eventually allow exchange of gases with the blood capillaries of the lungs. 11/23/16 3:42 AM r 22    Microbial Diseases of the espiratory System ­R p te ha       C 5. Pathogens cause inflammation of the respiratory tubes, resulting in restricted airflow. 6. Microbes stuck in mucus are carried by a ciliary escalator up and out of the bronchioles, bronchi, and trachea. 7. Alveolar macrophages and secretory antibodies (IgA) provide protection from many pathogens. 8. Harmless diphtheroids and other microbiota are commonly found in the nose and nasal cavity. Some may become opportunistic pathogens. Bacterial Diseases of the Upper Respiratory System, Sinuses, and Ears (pp. 674–678) 2. The most common type of pneumonia is pneumococcal pneumonia, which is caused by Streptococcus pneumoniae (commonly known as pneumococcus). 3. Mycoplasmal pneumonia, caused by Mycoplasma pneumoniae, is also called primary atypical pneumonia or walking pneumonia. 4. Klebsiella pneumonia produces thick, bloody sputum and recurrent chills. 5. Pneumonic plague is a form of pneumonia caused by Yersinia pes­ tis, the bubonic plague bacterium. 6. Chlamydophila psittaci causes psittacosis (ornithosis, parrot fever) in birds, which is a disease that can manifest as severe pneumonia in humans. 1. Streptococcal pharyngitis—caused by streptococcal inflammation of the pharynx—is commonly known as “strep throat.” 7. Chlamydophila pneumoniae causes bronchitis, chlamydial pneumonia, and rhinosinusitis. 2. Pharyngitis can progress into scarlet fever (scarlatina) when Streptococcus releases toxins that trigger fever and a bright red skin rash. 8. Legionnaires’ disease, or legionellosis, is a pneumonia caused by Legionella, a genus of bacteria that are transmitted in aerosols. 4. Inflammation of the larynx, laryngitis, causes hoarseness, and inflammation of the bronchi—bronchitis—results in restricted airflow to the lungs. 5. Group A Streptococcus (S. pyogenes) is the major cause of bacterial pharyngitis, scarlet fever, and rheumatic fever. Its survival in the body is aided by M protein, a hyaluronic acid capsule, pyrogenic toxins, streptolysins, and enzymes that allow the pathogen to spread in a variety of ways. 6. S. pyogenes from one individual travels via respiratory droplets to other individuals. 7. Corynebacterium diphtheriae produces a toxin that causes diphtheria, a disease characterized by the formation of a thick pseudomembrane on the surfaces of the upper respiratory tract. 8. Rhinosinusitis (inflammation of the nasal passages and sinuses) and otitis media (earache) are usually caused by S. pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, which spreads from the pharynx to the sinuses or ears. Viral Diseases of the Upper Respiratory System (pp. 679–680) 9. The cell wall of Mycobacterium tuberculosis contains mycolic acid, which protects the pathogen when it infects the lungs, where it forms nodules called tubercles and the disease tuberculosis (TB). Multi-drug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium pose a significant challenge to health care workers. 10. Cord factor is another cell wall component of M. tuberculosis that inhibits migration of neutrophils and kills cells. 11. A skin test determines whether a person has been exposed to M. tuberculosis antigens. Chest X-ray films reveal tubercles in the lungs. Directly Observed Treatment, Shortcourse (DOTS) is a strategy to ensure treatment of TB patients. 12. Bordetella pertussis causes pertussis (whooping cough) by interfering with ciliated epithelial cells of the trachea via adhesins and toxins. 13. Pertussis progresses in four stages: incubation, catarrhal phase, paroxysmal phase, and convalescent phase. 14. Bacillus anihracis causes the most lethal form of anthrax— inhalational anthrax, which progresses from the manifestations of a common cold to lethargy and shock. ­ 3. Untreated streptococcal pharyngitis can spread to cause complications in the kidneys (acute glomerulonephritis) and rheumatic fever, which may result in heart damage. Viral Diseases of the Lower Respiratory System (pp. 690–697) 1. Of the over 200 different serotypes of viruses that cause colds, the most common are in the genus Rhinovirus (family Picornaviridae). Some coronaviruses, adenoviruses, reoviruses, and paramyxoviruses also cause colds. 1. So-called A and B strains of orthomyxoviruses are surrounded by lipid envelopes with glycoprotein spikes composed of hemagglutinin (HA) or neuraminidase (NA) that play roles in the attachment of the viruses to the cells of the lungs to cause influenza (flu). 2. Cold viruses are sensitive to warm temperatures and low pH, so they do not infect the lower respiratory tract. 2. The accumulation of HA and NA mutations in a geographic area results in an increase in cases of flu and is called antigenic drift. 3. Rhinoviruses are extremely infective and are transmitted via respiratory droplets, skin contact, and fomites. 3. Antigenic shift is a major antigenic change resulting from the reassortment of genomes from different influenzavirus A strains. Such shifts may result in pandemics. Bacterial Diseases of the Lower Respiratory System (pp. 680–690) 1. Pneumonia results from pulmonary inflammation and the accumulation of fluid in the alveoli and bronchioles of the lungs. Physicians give different names to pneumonias, which are derived from the affected region of the lungs or from the causative organism. M22_BAUM7206_05_SE_C22.indd 704 4. Coronavirus respiratory syndromes, which include severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), are emerging diseases that destroy lung cells and spread via the bloodstream to the heart and kidneys. 5. Respiratory syncytial virus (RSV) infection is a common childhood respiratory disease. RSV causes giant, multinucleated cells 11/23/16 3:42 AM (syncytia) to form in the lungs, leading to bronchiolitis or tracheobronchitis, commonly known as croup. 6. Hantavirus pulmonary syndrome (HPS) is a potentially fatal respiratory disease caused by Hantavirus, which is transmitted in dried mouse excreta. 7. Parainfluenzavirus strains 1, 2, and 3 are associated with croup and viral pneumonia. 8. Metapneumovirus (MPV) is the second most common cause of respiratory tract disease in children. Mycoses of the Lower Respiratory System (pp. 698–703) r 2. Coccidioides immitis causes coccidioidomycosis, also known as valley fever. The initial manifestation resembles pneumonia or tuberculosis. In immunocompromised patients, the manifestations include meningitis, headache, nausea, and emotional disturbance. 3. Blastomyces dermatitidis causes blastomycosis, a systemic fungal disease that begins as a flulike infection. The fungus may spread to cause lesions on the upper body and destroy tissues in bone, prostate, testes, and other organs. 4. Histoplasma capsulatum causes histoplasmosis—the most common fungal systemic disease affecting humans. About 5% of patients develop clinical histoplasmosis. 5. Pneumocystis jirovecii causes Pneumocystis pneumonia in malnourished, premature, debilitated elderly, and immunocompromised patients. Review fo n uestio Q s 1. Mycoses are diseases caused by fungi; spread throughout the body, they are called systemic mycoses.       R Questions for eview Answers to the Questions for Review (except Short Answer questions) begin on p. A-1. Multiple Choice                    1. The movement of mucus from lungs to pharynx is due to . a. epiglottal flow c. sneezing b. a ciliary escalator d. pharyngeal reflux                    6. The action of streptolysin results in . a. the breaking of the hyaluronic acid capsule around cells b. the inhibition of complement protein and decrease in the number of leukocytes at the site of infection c. breaks in the membranes of erythrocytes, leukocytes, and platelets d. the destruction of streptococcal bacteria M22_BAUM7206_05_SE_C22.indd 705                    Fill in the Blanks 1. The medical name for the inflammation of the throat known as “strep throat” is .                    2. A thick, leathery membrane in the throat is a sign of . 3. RSV is characterized by the formation of giant multinucleated cells in the lungs called .                                       5. Group A Streptococcus is camouflaged from phagocytes by . a. M protein b. a hyaluronic acid capsule c. pus resulting from the action of streptokinase d. streptolysin 10. Which of the following is associated with the fusion of neighboring cells? a. neuraminidase b. respiratory syncytial virus c. tuberculin d. agglutinin                                       4. The glycoprotein spikes on influenzaviruses are composed of . a. cord factor b. hemagglutinin or neuraminidase c. streptokinase and hyaluronic acid d. M protein 9. The phase of whooping cough in which the characteristic “whoop” is obvious is the . a. paroxysmal phase b. catarrhal phase c. convalescent phase d. incubation phase 4. A drug commonly used to treat systemic fungal diseases is . 5. A condition in adolescents associated with taking aspirin to treat viral infections is syndrome.                    . 8. Which term associated with tuberculosis refers to protein and fat with a cheese-like consistency in the lungs? a. tubercles c. tuberculous cavities b. tuberculin tests d. caseous necrosis                    3. The major cause of bacterial pharyngitis is a. group A Streptococcus b. group B Streptococcus c. Mycobacterium d. Bordetella                                       2. Compared to the upper respiratory system, the lower respiratory system . a. provides an environment conducive to the growth of microorganisms b. is normally devoid of microorganisms c. provides an ideal environment for diphtheroids d. is several degrees cooler 7. Which pathogenic fungus is found in the droppings of bats, chickens, and blackbirds? a. Histoplasma capsulatum b. Blastomyces dermatitidis c. Coccidioides immitis d. parainfluenzavirus 11/23/16 3:42 AM ­R r 22    Microbial Diseases of the espiratory System te p ha       C Modified True/False ­ Modify each false statement to make it true by changing the underlined word(s). 1.                 A normal cold produces fever in most cases. 2.                 The number of fungal infections has increased over the last 20 years because of damp climatic conditions. 4.                 The formation of a hard, red lesion at the site of a tuberculosis skin test is a conclusive indication of the presence of the tuberculosis bacterium. 5.                 Death by pneumonia would be similar to drowning. t z I ! e isuali V 3.                 Antigenic shift accounts for an increase in flu infections at a locality every two years. 1. Color each map to show the general areas where each disease is endemic. Blastomycosis Coccidioidomycosis Histoplasmosis 2. Identify the following bacteria discussed in this chapter. M22_BAUM7206_05_SE_C22.indd 706 (a) (b) (c) (d) 11/23/16 3:42 AM 5. Describe the action of diphtheria toxin. Short Answer 1. What is the function of adenoids? ­ 2. Explain why the lower respiratory system is called the “respiratory tree.” 3. The microorganisms that cause diphtheria and pneumonia are frequently found in the upper pharynx of healthy individuals. Why do relatively few individuals contract these two illnesses? 6. Give two reasons why there is no prevention for the common cold. 7. Give two reasons why cold viruses are more prolific in the winter. 8. On what basis are antigens selected for the flu vaccine in the United States each year? 9. Contrast the way infections of Chlamydophila psittaci spread from the way C. pneumoniae spreads. 10. What does a positive tuberculin skin test reveal? g ki lT n n hi itica 4. After listening to a lecture on diseases caused by Streptococcus spp., a student exclaimed, “Do you mean to say that Streptococcus can make a person kill his own heart?” To what was the student referring? Cr       R Questions for eview 1. Explain the following identification label from a laboratory vial of influenza virus: B/HlN3. 2. An elderly man is admitted to the hospital with severe pneumonia, from which he eventually dies. What bacterial species is the most likely cause of his demise? What antimicrobial drug is effective against this species? How could the man have been protected from infection? Is the hospital staff at significant risk of infection from the man? Which groups of patients would be at risk if the man had visited their rooms before he died? 3. Compare and contrast viral pneumonia with bacterial pneumonia in terms of cause, prevention, and potential seriousness. 4. Laboratory observation of Pneumocystis jirovecii led one researcher to conclude that it was a protozoan. Why has it been classified as a fungus? 7. In mid-November, a worried couple brought their 29-day-old newborn to their small-town doctor’s office. The weak infant had been coughing severely over the past five days, so much so that she was choking on her formula. During her examination, the infant became blue and breathless. The baby girl tested positive on a DNA amplification test for Bordetella pertussis. (Adapted from MMWR 54:71–72, 2005.) Why is this disease so dangerous for small infants? Why did this baby become ill given that this disease is preventable with vaccination? 8. As you have probably noticed, colds occur more frequently in the fall and winter. One explanation is that more people are crowded together in buildings when school starts and the weather cools. Design an experiment or epidemiological survey to test the hypothesis that crowded conditions explain the prevalence of colds in the fall and winter. 9. Why don’t physicians try to prevent the spread of TB by simply administering prophylactic antimicrobial drugs to everyone living in endemic areas? 10. Could a traveler with coccidioidomycosis establish an endemic region of the disease in northern Russia? 6. Compare and contrast antigenic drift and antigenic shift in influenza A virus. 11. Statistically, men are more likely than women to contract histoplasmosis. What might explain this fact? ­ 5. A patient is admitted to a hospital in Ohio with a respiratory fungal infection. He had returned the previous month from a trip to Arizona, where he bought some dusty old blankets and two pots from a roadside vendor. What diseases might he have? M22_BAUM7206_05_SE_C22.indd 707 11/23/16 3:42 AM ­R       Chapter 22    Microbial Diseases of the espiratory System c Con ept Mapping Using the following terms, complete the concept map that describes tuberculosis. Acid-fast stain of sputum Antibiotic resistance Blood-tinged sputum Chest X-ray Cough Culture on special media Disseminated tuberculosis Dormant infection Ethambutol Extensive lung damage For 6–12 months Inflamed tuberculin skin test Isoniazid (INH) MDR-TB Mycobacterium tuberculosis Primary infection Rifampin XDR-TB Tuberculosis begins with inhalation of diagnosed by 1 12 with a combination of 8 establishing is treated Treatment is hampered by 16 9 13 10 14 11 15 2 may heal if exemplified by Strong immune response resulting in may progress to 3 Tubercular disease may spread to may remain Dormant for life M22_BAUM7206_05_SE_C22.indd 708 may reactivate to cause characterized by 5 17 6 18 7 Other body locations resulting in 4 3/6/18 4:41 PM