Microbial Diseases of the Skin and Wounds

Microbial Diseasesof the Skin and Wounds Structure of the Skin infection and disease unless it has been burned, broken, cut, or in some other way wounded. An adult’s skin covers about 2 square meters, making it one of the larger organs of the body. Human skin varies in thickness from 0.05 mm on the lips to 4.0 mm thick on the soles of the feet and in calluses, which cover areas of greatest wear and tear. Skin is composed of two distinct layers—the deeper dermis1 is covered by a superficial (outer) epidermis2 (FIGURE 19.1). The dermis is a tough, leathery structure composed of loosely packed cells, connecting protein fibers, small muscles, sweat glands, sebaceous (oil) glands, blood vessels, nerve endings, and hair follicles, which produce hairs that grow up through the dermis and epidermis. The dermis provides strength LE A R N I N G O U TC O M E 19.1 Describe the distinctive features of the main two layers of skin and of the hypodermis. Skin is a marvelous, flexible, tough membrane that is also called the cutaneous membrane. Skin does much more than keep the internal organs together. Your skin prevents excessive water loss, helps regulate body temperature via the production of sweat and the dilation or constriction of blood vessels, helps form vitamin D, and is involved in sensory phenomena. The skin also has numerous physical and chemical properties that make it a significant barrier against microbial invaders. It limits Dendritic cell Stratum corneum Hair Microbiota in stratum corneum Stratum granulosum Nails Skin Sweat pores Stratum spinosum (a) Hair shaft Epidermis Stratum basale Melanocyte (c) Basal cell Dermis Hypodermis Nerve Sweat gland Microbiota in sweat gland Pressure receptor Microbiota in hair follicle Blood vessels Hair root Hair follicles (b) Oil gland ­ H ▲ FIGURE 19.1 The skin. (a) air and nails are accessory structures of the skin. (b) Skin is composed of the outer epidermis and the deeper dermis. In addition, a layer of fat cells called the hypodermis lies beneath the dermis. (c) Detail of the epidermis. 1Greek, 2From M19_BAUM7206_05_SE_C19.indd 552 meaning “skin.” Greek epi, meaning “on.” 11/30/16 9:00 PM       Microbiome of the Skin Wounds are trauma to any tissue of the body. Cuts, abrasions, scrapes, surgery, inoculations, bites, and other penetrating skin wounds, as well as burns, breach the significant mechanical barrier provided by intact epidermis and dermis, allowing microbes to infect the warm, moist, deeper tissues of the body. Dirty wounds provide platforms for the growth of microbes and development of biofilms. Within a wound, microbes can multiply, producing enzymes and toxins that enhance their growth to the detriment of the host. The body starts to heal a wound by forming a blood clot to temporarily close the breach; then, neighboring connective and epithelial cells multiply and grow into the clot to restore the skin’s integrity. In most cases, other body defenses, including phagocytosis, complement, and inflammation, eliminate a wound infection. However, some infections overwhelm the body’s defenses, resulting in severe, even fatal, diseases. TELL ME WHY Why is the surface of the skin inhospitable for most microbes? Microbiome of the Skin LE A R N I N G O UTC O M E S 19.2 Define microbiome, and describe the major groups found on the skin. 19.3 Describe the beneficial aspects of the microbiota. Some yeasts and bacteria tolerate (and indeed thrive in) the harsh conditions of the epidermis, in the cavities of the hair follicles, and in the interiors of the sweat ducts. These normally harmless residents of the body make up the human microbiome, also called the microbiota (as we saw in Chapter 14). Members of the microbiome compete with potential pathogens for nutrients and space and produce chemicals that interfere with the growth of other microbes, providing further defense against infection. Though vigorous scrubbing may reduce the number of microorganisms on the skin, it can never eliminate them completely—microbes living deep in the hair follicles and sweat ducts soon recolonize the skin’s surface. Organisms of the microbiome typically grow in small clusters, particularly in the armpits and between the legs, where conditions are moister. Their waste products produce body odor. Significant members of the microbiome include small lipophilic4 yeasts such as Malassezia (mal-ă-sē’zē-ă), which digest sebum. Such yeasts are rarely pathogenic, though they can cause disease in immunosuppressed patients. Aerobic, Grampositive bacteria in the genera Staphylococcus5 (staf’i-lō-kok’ŭs) and Micrococcus6 (mī’krō-kok’ ŭs ) also grow on the skin of all individuals. These bacteria can tolerate salt concentrations of 5–10%. The most common species is Staphylococcus epidermidis (ep-i-der-mid’is). Diphtheroids are another common type of Gram-positive bacteria living on the skin. These pleomorphic bacilli are named for the similarity of their appearance to the pathogen Corynebacterium7 diphtheriae (kŏ-rī’nē-bak-tēr’ē-ŭm dif-thi’rē-ī), though diphtheroids of the microbiome are generally nonpat hoge n ic. A c om mo n t r ouble s ome d ipht h er oid i s Propionibacterium acnes (prō-pē-on-i-bak-tēr’ē-ŭm ak’nēz), which, as its name suggests, can cause acne, though it also provides protection by competing with pathogenic microbes. Propionibacteria reside in hair follicles, where they ferment carbohydrates to form propionic acid, which lowers the pH of the skin, acting as a further defense against additional infection. ­ ­ and flexibility and, along with its blood vessels, supports the growth of the overlying epidermis. The bloodless epidermis consists of four to five layers, each composed of layers of tightly packed cells. Basal cells of the epidermis, which adjoin the dermis, divide continuously, pushing their offspring toward the surface. As the daughter cells are pushed away from the dermal blood supply, they flatten and die, but not before modifying themselves. They absorb melanin, a pigment that is secreted by other cells in the basal layer and that gives skin its color. The more melanin, the darker the skin. Epidermal cells also fill with a waterproofing protein called keratin. A hardened form of keratin forms nails and hairs, which are accessory structures to the skin. Between the dying cells, defensive cells called dendritic cells phagocytize microbes that penetrate into the deeper layers of the epidermis and deliver microbial antigens to defensive lymphocytes. The surface of the skin is a generally inhospitable environment covered with salt (left behind as sweat evaporates) and sebum3—an oily lipid secreted by oil (sebaceous) glands in the dermis. Chemicals in sweat and sebum are antimicrobial, preventing the growth of many microorganisms. Thus, the outermost layer of skin consists of flattened, dead, dry, keratinized cells covered with oil and salt—a significant barrier to microbial invasion. Further, the skin sloughs off microbes attached to the outermost skin flakes as epidermal cells are continually pushed up from the basal layer. The body replaces the outer layers of the epidermis about once a month. The hypodermis is a layer of fat cells and fibers lying beneath the dermis. The hypodermis is not technically part of the skin; it is subcutaneous. Stored fat provides cushioning, insulation, and a ready energy source. The fibers in the hypodermis anchor the skin to the underlying tissues. Despite the inhospitable nature and defensive structures and chemicals of the skin, pathogenic microbes can still produce diseases, particularly if they penetrate the epidermis through wounds, or when the immune system is suppressed. Bacteria, viruses, fungi, protozoa, and arthropods are involved in skin diseases. Diseases of other body systems may also manifest themselves in the skin. We now survey such diseases, beginning with diseases caused by bacteria. Greek lipos, meaning “grease,” and philos, meaning “love.” Greek staphle, meaning “small bunch of grapes,” and kokkos, meaning “a berry.” 6From Greek micros, meaning “small.” 7 From Greek coryne, meaning “club.” 4From 5From 3From Latin sebum, meaning “grease.” M19_BAUM7206_05_SE_C19.indd 553 11/30/16 9:00 PM t a       Ch p er 19    Microbial Diseases of the Skin and Wounds TELL ME WHY Why is the normal skin microbiome considered beneficial to a person? Bacterial Diseases of the Skin and Wounds Bacteria infecting the skin cause diseases that range from mild acne to life-threatening infections. Skin-infecting bacteria include Staphylococcus, Streptococcus, Propionibacterium, Bartonella, Pseudo­ monas, and Rickettsia. We begin by examining diseases caused by one of the more common bacterial pathogens, Staphylococcus. Folliculitis Staphylococcus. 19.5 Discuss the virulence factors of Staphylococcus that enable it to be pathogenic, contrasting the virulence of S. aureus with that of S. epidermidis. 19.6 Describe the diagnosis, treatment, and prevention of folliculitis. Signs and Symptoms Folliculitis (fŏ-lik-yū-lī’tis) is an infection of a hair follicle in which the base of the follicle becomes red, swollen, and pus filled. This condition is often called a pimple. When it occurs at the base of an eyelid, it is called a sty. A furuncle (fyu’rŭng-kl), or boil, is a large, painful, raised nodular extension of folliculitis resulting from spread of the infection into surrounding tissues. When several furuncles join together—more frequently in areas where the skin is thick, such as at the back of the neck— they form a carbuncle (kar’bŭng-kl). In severe cases, the body responds to folliculitis by triggering fever. Pathogen and Virulence Factors The most common cause of folliculitis and associated infections of the skin is Staphylococcus—a genus of facultatively anaerobic, Gram-positive bacteria whose spherical cells are typically clustered in grapelike arrangements (FIGURE 19.2). Staphylococcal cells are salt tolerant: they are capable of growing in media containing up to 10% NaCl, which explains how they tolerate the salty surface of human skin. Additionally, staphylococci are tolerant of drying out, solar radiation, and heat (up to 60°C for 30 min), allowing them to survive on environmental surfaces as well as skin. Two species of Staphylococcus are typically found on human skin as well as in the upper respiratory, gastrointestinal, urinary, and genital tracts. Staphylococcus epidermidis, as its name suggests, is a major member of the microbiome, accounting for up to 90% of bacteria on the skin. The more virulent Staphylococcus aureus8 8Latin, meaning “gold,” from the color the colonies sometimes assume when growing on agar. M19_BAUM7206_05_SE_C19.indd 554 4 μm ▲ FIGURE 19.2 Staphylococcus. What accounts for the grapelike arrangement of staphylococcal cells? (o’rē-ŭs), which often grows in nasal passages, produces a variety of disease conditions and symptoms. Staphylococci have at least three categories of virulence factors that allow them to produce disease: enzymes, structures that enable them to evade phagocytosis, and toxins. Enzymes Virulent strains of S. aureus produce a number of enzymes that contribute to their survival and pathogenicity: • Coagulase clots blood, which may hide the bacterium from phagocytes. • Hyaluronidase breaks down hyaluronic acid, a major component of the matrix between cells, thus enabling the bacterium to spread between cells throughout the body. • Staphylokinase dissolves blood clots, which also allows staphylococci to spread to new locations. • Lipases, which are present in S. epidermidis as well, digest lipids, including sebum, providing staphylococci with food on the surface of skin, in hair follicles, and in sebaceous glands. • β­Lactamase plays no role in inhibiting the natural defenses of the body, but it does convey resistance to many beta-lactam antimicrobial drugs such as penicillin and cephalosporin—drugs that β­lactamase inactivates. ­ 19.4 List and describe four types of folliculitis caused by SEM Figure 19.2 The arrangement of staphylococcal cells is due to cell division in random planes. LE A R N I N G O U TC O M E S Structural Defenses Against Phagocytosis Both S. aureus and S. epi­ dermidis evade the body’s defenses by synthesizing loosely organized polysaccharide slime layers (sometimes called capsules) that inhibit chemotaxis of and phagocytosis by leukocytes. The slime layer also facilitates attachment of staphylococcal biofilms to artificial surfaces such as catheters, shunts, artificial heart valves, and synthetic joints. Cells of S. aureus are uniformly coated with protein A, which binds to the stems of class G antibodies (IgG). Antibodies are 11/30/16 9:00 PM E E GING DIS AS CAS STUDY E M ER E       Bacterial Diseases of the Skin and Wounds Buruli Ulcer fat and muscle cells. Though his hand continued to swell, making it difficult to work normally, it remained pain free. After six weeks of this condition, pain began suddenly and excruciatingly. The swollen finger ruptured, and a foul-smelling fluid saturated his camera. It was time to see a doctor. The physician diagnosed Buruli ulcer, an emerging disease that affects more and more people each year as a result of human encroachment into the swamps where Mycobacterium ulcerans lives. After two surgeries to remove dead tissue and bacteria, several skin grafts, and two months of treatment with the antimicrobial drugs rifampicin and streptomycin, Jacques returned home to France with scars that forever remind him of his adventure with M. ulcerans. Virulence Factor Humans transmit both species of Staphylococcus via direct contact between individuals as well as via fomites9 (fōm’i-tēz), 9Latin, S. epidermidis Coagulase + - Staphylokinase + - + + Lipase P β-Lactamase resent in 90% of strains - Factors That Inhibit Phagocytosis + + rotein A on cell surface + - Cytolytic toxins + - Leukocidin + - pidermal cell differentiation inhibitor + - P olysaccharide slime layer Toxins Toxic shock syndrome toxin resent in some strains - resent in some strains - P xfoliative toxin P Pathogenesis S. aureus Enzymes E Toxins Pathogenic Staphylococcus aureus possesses several toxins that contribute to virulence. Cytolytic toxins disrupt the cytoplasmic membranes of a variety of cells. Leukocidin kills leukocytes, providing Staphylococcus with additional protection against phagocytosis, and epidermal cell differentiation inhibitor is a protein that induces large holes in the linings of blood vessels, allowing access for the bacterium to invade body tissues. Some strains of S. aureus also produce exfoliative toxin or toxic shock syndrome toxin—proteins that cause staphylococcal scalded skin syndrome (discussed shortly) and staphylococcal toxic shock syndrome (see Chapter 24), respectively. TABLE 19.1 compares and contrasts virulence factors possessed by S. aureus and S. epidermidis. TABLE 19.1 Comparison of Virulence Factors of Two Staphylococcal Species P opsonins—they enhance phagocytosis—precisely because phagocytic cells bind to antibody stems (recall Chapter 16); therefore, protein A, by blocking the stems, effectively inhibits opsonization. Protein A also inhibits the complement cascade, which is triggered by antibody molecules bound to antigen (see Figure 15.9). 1. What might be a reason why a Buruli ulcer is initially painless? 2. Why was it necessary to administer antibacterial drugs for two months rather than two weeks? 3. What environmental similarities exist in the endemic countries? E H H R R ­ R R Jacques liked living in the Democratic epublic of the Congo (D C)—opportunities abounded for exploration, adventure, and wildlife photo graphy, the countryside was beautiful, and he found the people generally friendly. It was on a photographic excursion in the east of the country that Jacques met a not-so-friendly resident of the D C: an emerging mycobacterial pathogen. The photographer thought little of the small insect bite he received while documenting wildlife in the swamps along the great Congo iver, but he should have been concerned; Mycobacterium ulcerans had found a new home in his hand. Jacques would pay a grievous price for his lack of care. e continued to ignore the infection when it produced a small, painless nodule. e even ignored it when his finger swelled to twice its normal size; it was painless, and he could still meet his busy schedule. But the bacterium was producing a potent toxin known as mycolactone that destroys cells below the skin, especially meaning “tinder,” as in fire-starting material; singular: fomes (fo’mēz). M19_BAUM7206_05_SE_C19.indd 555 11/30/16 9:01 PM t which are inanimate carriers of infective agents. Contaminated clothing, bedsheets, and medical instruments are examples. Staphylococcus on the surface of the skin grows into hair follicles and invades sebaceous glands. This triggers fever and inflammation, which are natural responses against infection, and causes the follicle to enlarge and fill with pus composed of leukocytes, dead cells, and bacteria. The infection may spread into the hypodermis to form a furuncle or into neighboring hair follicles to form a carbuncle. S. aureus (and infrequently S. epidermidis) may also spread into the blood—a condition called bacteremia—and be carried to the lining of the heart, lungs, and bones, causing endocarditis, pneumonia, and osteomy­ elitis, respectively. TABLE 19.2 lists some of the many diseases caused by S. aureus. Epidemiology Staphylococcus epidermidis thrives on almost every square millimeter of human skin. Because it lacks the virulence factors of S. aureus, it seldom causes disease, though it can be an opportunistic pathogen in immunocompromised patients or when introduced into the body via intravenous catheters or on prosthetic devices such as artificial heart valves. Staphylococcus aureus, in contrast, is not a permanent resident but does grow on the skin or mucous membranes of most people at some time in their lives, particularly in the nostrils. About a fifth of the population carries the bacterium with no symptoms for a year or more. The bacterium also intermittently colonizes moist skin folds such as in the armpits and around the groin, often being transferred from the face via the hands. Diagnosis, Treatment, and Prevention ­ Diagnosis of staphylococcal folliculitis involves the detection of Gram-positive bacteria in grapelike arrangements isolated from pus. If staphylococci isolated from an infection are able to clot blood, then they are coagulase-positive S. aureus. Coagulasenegative staphylococcus is usually S. epidermidis, which is a normal part of the microbiome of the skin—its presence in a clinical sample is not normally indicative of staphylococcal disease. Physicians treat staphylococcal skin infections with topical mupirocin. Clinical practice has shown that it is critical to clean and drain abscesses of pus for topical therapy to be effective. Dicloxacillin—a semisynthetic oral form of penicillin not inactivated by β­lactamase—is another drug of choice for staphylococcal infections. Unfortunately, drug-resistant Staphylococcus aureus has emerged as a major health problem. Strains resistant to many common antimicrobial drugs, including natural penicillin, methicillin, macrolides, aminoglycosides, and cephalosporin, are known. Vancomycin is used to treat such infections. Lately, physicians have become concerned about the increasing prevalence of vancomycin-resistant strains of S. aureus (VRSA). Methicillin-resistant S. aureus (MRSA) has become more common in hospitals, so it is imperative that health care workers take precautions against introducing such bacteria into patients. Since Staphylococcus is part of the normal microbiome of many people’s skin, staphylococcal infections cannot be eliminated completely. Fortunately, because a large inoculum is required to cause disease, proper cleansing of wounds and surgical openings, attention to aseptic use of catheters and indwelling needles, and the appropriate use of antiseptics prevents MRSA infections in most patients. People wit h staphylococcal lesions should refrai n from working with food, patients with open wounds, immunocompromised patients, and women in labor, and they should not work in nurseries or operating rooms. The most important measures for protecting against healthcareassociated infection are proper aseptic techniques, particularly correct hand antisepsis. Scientists are currently testing a vaccine to protect patients from S. aureus infections. Such immunization, if it proves safe and effective, may have a significant effect on nosocomial morbidity and mortality. It would be especially good news for health care providers and their patients who are battling resistant strains of Staphylococcus. Staphylococcal Scalded Skin Syndrome LE A R N I N G O UTC O M E 19.7 Describe staphylococcal scalded skin syndrome, including its diagnosis, treatment, and prevention. ­ a       Ch p er 19    Microbial Diseases of the Skin and Wounds Signs and Symptoms ­ TABLE 19.2 Some Diseases Caused by Staphylococcus aureus Where Discussed Skin disease: folliculitis, sty, furuncle, carbuncle p. 554 Staphylococcal scalded skin syndrome p. 556 Impetigo p. 557 Staphylococcal toxic shock syndrome Chapter 24 Bacteremia Chapter 21 P E Disease ndocarditis Chapter 21 neumonia Chapter 22 Food poisoning M19_BAUM7206_05_SE_C19.indd 556 Chapter 23 In staphylococcal scalded skin syndrome (SSSS), cells of the outer epidermis separate from one another and from the underlying tissue (FIGURE 19.3) . SSSS involves a reddening and wrinkling of the skin that typically begins near the mouth, spreads over the entire body, and is followed by large blisters that contain clear fluid lacking bacteria or white blood cells. Within two days, the affected outer epidermis peels off in sheets, as though the flesh had been dipped into boiling water. Pathogen and Virulence Factors Five percent of strains of Staphylococcus aureus secrete one or two distinct exfoliative toxins that cause SSSS. Each toxin causes the dissolution of epidermal desmosomes, which are intercellular bridge proteins that hold together cytoplasmic membranes 11/30/16 9:01 PM       Bacterial Diseases of the Skin and Wounds class, treatment involves intravenous drugs such as semisynthetic nafcillin or oxacillin that do not allow β­lactamase to bind. Little can be done to prevent SSSS because S. aureus is normally on skin, and susceptible patients lack sufficient immunity. We have considered disease caused by Staphylococcus acting alone. Next we turn our attention to diseases of Streptococcus acting alone or in conjunction with Staphylococcus. Impetigo (Pyoderma) and Erysipelas LE A R N I N G O UTC O M E S 19.8 Distinguish the signs, symptoms, and causes of impetigo from those of erysipelas. 19.9 Describe the diagnosis, treatment, and prevention of impetigo and erysipelas. Signs and Symptoms ▲ FIGURE 19.3 Staphylococcal scalded skin syndrome. E xfoliative toxin, produced by some strains of Staphylococcus aureus, causes reddened patches of the epidermis to slough off. Which patients are most susceptible to exfoliative strains of S. aureus? Figure 19.3 Infants, the elderly, and immunosuppressed patients are most susceptible to SSSS. of adjoining cells. Both toxins affect keratinized cells of the epidermis. Pathogenesis The blood carries exfoliative toxins from sites of infection throughout the body. Such circulation of toxins in the blood is called toxemia. The body restores the lost epidermis within 7 to 10 days after protective antibodies circulate in the blood. Though 100% of the skin surface may be afflicted, scarring does not occur because the toxin does not affect the dermis. Mortality is rare; death, if it occurs, is most often due to secondary infections of skinless areas by yeasts such as Candida albicans (kan’did-ă al’bi-kanz) or bacteria such as Pseudomonas aeruginosa (soo-dō– mō’nas ā-roo-ji-nō’să). Impetigo (im-pe-tī’gō)—also called pyoderma10—is a contagious disease characterized by small, flattened, red patches that appear primarily on the face and limbs (FIGURE 19.4), particularly of children whose immune systems are incompletely developed. The patches develop into oozing, pus-filled vesicles on a red base. Such vesicles eventually break and form a thick, honey-colored, sticky crust that is attached firmly to the skin and may cause intense itching. Numerous vesicles at various stages of development characterize impetigo because bacteria from a vesicle spread to adjacent sites on the skin. When such an infection of the skin spreads into surrounding lymph nodes and triggers pain and inflammation, the condition is called erysipelas11 (er-i-sip’ĕ-las) (FIGURE 19.5). Erysipelas manifests as reddening of the skin on the face, arms, or legs. The red area has a distinct margin, almost as if it were painted onto Epidemiology SSSS is primarily a disease of infants and children under age five, though it can also affect the elderly and immunosuppressed patients, such as those with AIDS; antibodies apparently protect people with well-developed immune systems. Transmission is by person-to-person spread of the bacterium onto skin surfaces, where it penetrates cuts and abrasions. Diagnosis, Treatment, and Prevention ­ M19_BAUM7206_05_SE_C19.indd 557 ▲ FIGURE 19.4 Impetigo. eddened patches of skin become pus-filled vesicles that eventually form a honey-colored, sticky crust. R Diagnosis is made on the basis of the distinctive sloughing of the skin. Fluid in the blisters of SSSS does not contain S. aureus, since the disease is mediated by toxins released from a site of infection that may be elsewhere in the body. Since many strains of Staphylococcal aureus produce β­lactamase, which deactivates many drugs in the penicillin 10From 11From Greek pyon, meaning “pus,” and derma, meaning “skin.” Greek erythros, meaning “red,” and pella, meaning “skin.” 11/30/16 9:01 PM t a       Ch p er 19    Microbial Diseases of the Skin and Wounds sores, or other wounds where the skin’s integrity is compromised. Children are often infected just below the nose, where frequent wiping away of mucus abrades the skin. Some strains of S. pyogenes may spread from a site of impetigo or erysipelas into the blood (bacteremia) and thence into the kidneys, where they cause a disease of the kidneys known as acute glomerulone­ phritis. (Chapter 24 considers this condition in more detail.) Epidemiology ▲ FIGURE 19.5 Erysipelas. What chemicals cause the reddening of the skin in erysipelas? Figure 19.5 Proteinaceous pyrogenic toxins released by Streptococcus pyogenes cause the red skin seen in erysipelas patients. the skin. Swollen local lymph nodes, pain, fever, chills, and leuko­ cytosis—an abnormally large number of leukocytes in the blood— are also seen. Without treatment, erysipelas may be fatal, with mortality ranging from 2% to 17%. The very young, very old, and immunocompromised are more likely to die. Pathogens and Virulence Factors S. aureus acting alone causes about 80% of impetigo cases, and about 20% of cases involve Streptococcus pyogenes (strep-tōkok’ŭs pī-oj’en-ēz) alone or in conjunction with S. aureus. S. pyo­ genes, which is synonymously called group A Streptococcus after a particular carbohydrate antigen found on the cell’s surface, is a Gram-positive coccus whose offspring remain attached in chains following cell division. Besides causing 20% of impetigo cases, Streptococcus pyogenes is also the cause of erysipelas. S. pyogenes has virulence factors that contribute to impetigo: ­ • M protein is a cytoplasmic membrane component that destabilizes complement and interferes with phagocytosis and lysis of the bacterium. • A hyaluronic acid capsule serves to “camouflage” the bacterium, hiding it from phagocytes since hyaluronic acid is a natural chemical in the body. • Pyrogenic12 toxins (formerly called erythrogenic13 toxins) are proteins that stimulate macrophages and helper T lymphocytes to release cytokines that in turn stimulate fever, a widespread rash, and shock. Pathogenesis The bacteria of impetigo and erysipelas occasionally colonize the skin and then invade through scratches, abrasions, cold 12From Greek pyr, meaning “fire,” and genein, meaning “to produce.” 13From Greek erythros, meaning “red,” and genein, meaning “to produce.” M19_BAUM7206_05_SE_C19.indd 558 Both Staphylococcus and Streptococcus spread among individuals by person-to-person contact or via contaminated fomites such as toys, clothing, bedding, towels, or hairbrushes, particularly in warm, moist, summer conditions. Children two to five years of age are more likely to develop impetigo, though the bacteria can infect older children as well. Epidemics of impetigo in nurseries are of particular concern to hospital workers. Erysipelas occurs most commonly in children and the elderly. Diagnosis, Treatment, and Prevention Vesicles of impetigo are diagnostic. Further, the pus found in the blisters is filled with bacteria and white blood cells, which distinguishes impetigo from scalded skin syndrome. The presence of grapelike clusters of Gram-positive cocci indicates staphylococcal impetigo, whereas the presence of chains characterizes streptococcal impetigo and erysipelas. Treatment of impetigo involves topical mupirocin and oral clindamycin or doxycycline. Gentle washing with soap and water twice a day gently removes the crusts and infectious bacteria of impetigo. Physicians treat erysipelas with penicillin. Good general hygiene and cleanliness help to prevent impetigo and erysipelas. Abrasions and other breaks in the skin of children should be thoroughly cleansed with soap and water, particularly if there has been contact with impetigo patients or contaminated fomites. Necrotizing Fasciitis LE A R N I N G O UTC O M E S 19.10 Describe the actions of six virulence factors of Strepto­ coccus pyogenes. 19.11 Describe the pathogenesis, epidemiology, diagnosis, and treatment of necrotizing fasciitis. 19.12 Explain why preventing necrotizing fasciitis is difficult. “Bacteria Are Eating My Face Off!” screams a tabloid cover; although such a report is sensationalized, the condition is possible. Bacteria can destroy soft body tissues—a condition called “flesh-eating bacteria” by some news media and medically known as necrotizing fasciitis14 (ne’kro-tī-zing fas-ē-ī’tis). Disease in Depth: Necrotizing Fasciitis on pp. 560–561 visually presents the features of this disease in some detail. Greek nekros, meaning “corpse”; Latin fascia for “band,” referring to the bands of tough connective tissue that lie in the skin and surround muscles; and Greek itis, meaning “inflammation.” 14From 11/30/16 9:01 PM       Bacterial Diseases of the Skin and Wounds Most patients with necrotizing fasciitis initially report a hot, intensely painful, sunburn-like rash at the site of infection. Subsequently, patients develop fever, tiredness, and muscle aches. As tissue is destroyed, blood pressure drops, and patients become mentally confused and ultimately comatose. Several bacteria can cause necrotizing fasciitis, but the most common cause is Streptococcus pyogenes, also known as group A Streptococcus. In addition to the virulence factors listed in association with impetigo, strains of S. pyogenes that cause necrotizing fasciitis have factors that allow the bacterium to invade body tissues, resist phagocytosis, and damage cells and tissues. These virulence factors are considered in more detail in the Disease in Depth feature. The usual route of transmission for group A Streptococcus is from person to person through breaks in the skin. Necrotizing fasciitis has developed following surgery, abortion, and seemingly harmless events such as an insect bite or a needlestick to draw blood. Diabetes, cancer, and chickenpox increase the risk for developing necrotizing fasciitis. Necrotizing fasciitis should be considered a surgical emergency, and physicians must remove dead tissue immediately, repeating the procedure daily until bacterial destruction of tissue is halted. Doctors prescribe intravenous broad-spectrum antimicrobial drugs to curb the severity of disease and inhibit any remaining bacteria. One study has shown that clindamycin and penicillin when used together had a cure rate of 83%, compared to a cure rate of only 41% for penicillin alone. Acne 1 Normal skin Oily sebum produced by glands reaches the hair follicle and is discharged onto the skin surface via the pore. Pore Bacteria Sebum Sebaceous gland Hair follicle 2 Whitehead Inflamed skin swells over the pore when bacteria infect the hair follicle, causing the accumulation of colonizing bacteria and sebum. 3 Blackhead Dead and dying bacteria and sebum form a blockage of the pore. Blocked pore LE A R N I N G O U TC O M E S 19.13 Describe the progression of acne. 19.14 Discuss chemical and physical treatments for acne. The blackheads and pimples of acne are a well-known phenomenon. Pathogen The most common causes of acne are propionibacteria, which are small, Gram-positive, rod-shaped diphtheroids commonly found growing on the skin. They are named for the propionic acid that is a by-product of their fermentation of carbohydrates. The species most commonly involved in infections of humans is Propionibacterium acnes, which causes acne in 85% of afflicted adolescents and young adults. Staphylococcus aureus may also cause acne. 4 Pustule formation Severe inflammation of the hair follicle causes pustule formation and rupture, producing cystic acne, which is often resolved by scar tissue formation. Pus Pathogenesis FIGURE 19.6 illustrates the development of acne. Propionibacte­ M19_BAUM7206_05_SE_C19.indd 559 ▲ FIGURE 19.6 The development of acne. Which bacterial patho- gen is a common cause of cystic acne? Figure 19.6 Propionibacterium acnes is a common cause of acne. rium typically grows on sebum within the sebaceous glands of the skin 1 . Excessive oil production triggered by the hormones of adolescence, particularly testosterone in males, stimulates the growth of the bacteria, which secrete chemicals that attract leukocytes and trigger inflammation. The leukocytes phagocytize the bacteria and release chemicals that stimulate local inflammation. The combination of dead bacteria and dead and 11/30/16 9:01 PM DISEASE IN DEPTH SIGNS AND SYMPTOMS NECROTIZING FASCIITIS Necrotizing fasciitis is usually characterized by redness, intense pain, and swelling at the site of infection. Initially, the pain does not seem proportionate to the appearance of the infected area. As the bacterium digests muscle fascia—the connective tissue surrounding muscles— and fat tissue, the overlying skin becomes distended and discolored. Patients develop fever, nausea, and malaise, and they may become mentally confused as their blood pressure drops severely. Group A Streptococcus S treptococcus pyogenes can cause necrotizing soft tissue infections, sensationalized in the news as “flesh-eating strep” and medically known as necrotizing fasciitis. 2 S. pyogenes secretes enyzmes that allow the bacterium to invade body tissues. Streptokinases dissolve blood clots. Hyaluronidase breaks down hyaluronic acid between cells. Deoxyribonucleases break down DNA released from damaged host cells. PATHOGENESIS 1 S. pyogenes is passed from person to person and enters the body through breaks in the skin. It spreads rapidly along muscle fascia. INVESTIGATE IT! It can be easy to forget that this disease affects real people. Scan this code to read the stories of several survivors of necrotizing fasciitis at http://www.nnff.org. What do they have in common? Then go to MasteringMicrobiology to record your research findings. M19_BAUM7206_05_SE_C19.indd 560 EPIDEMIOLOGY Though there has been much recent press coverage, necrotizing fasciitis is not a new disease; it is possible that Hippocrates described the disease, and doctors in China definitively reported cases in 1924. There are about 500,000 cases of necrotizing fasciitis worldwide each year. About 20% of necrotizing fasciitis patients die. Greek physician Hippocrates (460–370 B.C.) may have described necrotizing fasciitis as early as the 5th century B.C. in Of the Epidemics. “…And there were great fallings off (sloughing) of the flesh, sinews, and bones…” (Book II, section III, part 4). 11/30/16 9:01 PM       PATHOGEN AND VIRULENCE FACTORS Several bacteria can cause necrotizing fasciitis, including Staphylococcus aureus, Clostridium perfringens, and Bacterioides fragilis, but Streptococcus pyogenes (group A Streptococcus), shown Gram-stained at left, is the most common cause. LM M protein on the surface of streptococcal cells helps the bacterium attach to nose and throat cells, and after entry into the body, M protein allows S. pyogenes to survive phagocytosis. M proteins SEM 15 µm 3 Other virulence factors include M protein. Strains of S. pyogenes that cause the condition have enzymes, such as deoxyribonucleases, hyaluronidase, and streptokinases that allow the bacterium to invade body tissues. Streptococcal M protein allows the bacterium to attach to nasopharyngeal cells and to resist phagocytosis. The toxins streptolysin S and exotoxin A damage cells and tissue. 4 µm 4 S. pyogenes also secretes toxins that damage tissue. Streptolysin S can kill many types of human cells, including neutrophils and erythrocytes. Exotoxin A triggers an overactive immune response that further damages healthy tissue. 5 Enzymes and toxins secreted by S. pyogenes can destroy tissue at the rate of several centimeters an hour. DIAGNOSIS, TREATMENT, AND PREVENTION Diagnosis is difficult because early symptoms are general and flulike. Extreme pain that seems out of proportion to an injury should be treated as a possible case of necrotizing fasciitis or infection with S. pyogenes. Affected tissue must be removed completely to prevent the spread of bacteria. Intravenous broad-spectrum antimicrobial drugs help curb the severity of the disease. It is difficult to prevent necrotizing fasciitis because S. pyogenes is commonly found on humans. Patients with diabetes, cancer, or chickenpox are M19_BAUM7206_05_SE_C19.indd 561 at a greater risk for necrotizing fasciitis. Any opening in the skin, even a minor cut, is a potential site of invasion by the bacterium; therefore, such openings should be washed thoroughly. 11/30/16 9:01 PM t a       Ch p er 19    Microbial Diseases of the Skin and Wounds living leukocytes makes up the white pus associated with the pimples of acne 2 . A blackhead is formed when a plug of dead and dying bacteria blocks the pore 3 . In cystic acne, a particularly severe form of the disease, bacteria form inflamed pustules (cysts) 4 that rupture, triggering the formation of scar tissue. Acne typically develops on those areas of the skin where sebaceous glands are most numerous, including the face, scalp, neck, chest, back, upper arms, and shoulders. Epidemiology The bacteria of acne are normal members of the microbiome that grow aggressively because of the large amount of sebum produced as a result of adolescent hormones, particularly testosterone. Though acne typically begins at adolescence, onset later in life is common. Acne is not a reportable disease, so its exact prevalence is not known; however, it is estimated that at least 75% of the world’s adolescents develop acne at some time. Severe cystic acne is much more rare. Diagnosis, Treatment, and Prevention Diagnosis of acne is easy. It is visible on the skin—for many adolescents, often embarrassingly visible. In most cases, the immune system is able to control Propionibacterium, and no treatment is required. For more severe cases, dermatologists may prescribe antimicrobial drugs such as doxycycline, which is highly concentrated in secretions of the skin. They also prescribe topical benzoyl peroxide, which causes exfoliation of dead skin cells, kills Propionibacterium, reduces the amount of lipid on the skin’s surface, and has beneficial oxidizing effects. Long-term antimicrobial use can destroy susceptible normal bacteria , making the individual more vulnerable to opportunistic fungi and to bacteria that are resistant to antimicrobial drugs. Retinoic acid (Accutane), a derivative of vitamin A, inhibits the formation of sebum, reducing the amount available for bacterial metabolism. Because Accutane can cause intestinal bleeding and birth defects, it is prescribed only for severe cases of acne and never for women who are or may become pregnant. A nonchemical treatment for acne is the use of ultraviolet light (wavelength 315–400 nm). This light, known as UVA, can kill P. acnes without causing harm to the body. In one study, two 15-minute exposures a week for a period of four weeks produced a 60% reduction in acne in 80% of patients for up to eight months. There are many common misconceptions about acne. Scientists have not shown any connection between acne and diet, including chocolate and oily foods—foods do not affect sebum production. Though cleaning the surface of the skin does not remove acne-producing bacteria (they live deep in the sebaceous glands), frequent cleansing may dry the skin, which helps loosen plugs from hair follicles. Signs and Symptoms Cat scratch disease involves fever for a few days, prolonged malaise, and localized swelling at the site of infection and nearby lymph nodes for several months (FIGURE 19.7). Pathogen and Virulence Factors Bartonella henselae (bar-tō-nel’ă hen’sel-ī), a Gram-negative aerobic bacillus, causes cat scratch disease. Its primary virulence factor is endotoxin (lipid A) found in the outer membrane of Gram-negative bacteria. Further, Bartonella can grow and reproduce inside red blood cells and in cells lining blood vessel walls. Pathogenesis and Epidemiology Cat scratches or bites, particularly wounds by kittens, introduce the bacterium into the skin. Blood-sucking arthropods such as fleas may also transmit the bacterium from cats to people. In the skin, the bacterium grows intracellularly. Bartonella releases endotoxin when it dies, which can trigger fever, blood clotting, inflammation, and possibly shock (see Figure 21.7). Though carried by cats, Bartonella apparently causes disease only in people; it is not known to cause disease in animals. Cat scratch disease has emerged as a relatively common and occasionally serious infection of children, affecting an estimated 22,000 children annually in the United States. Diagnosis, Treatment, and Prevention A positive indirect fluorescent antibody test against Bartonella antigens confirms a diagnosis of cat scratch disease in individuals who exhibit the characteristic signs and symptoms following exposure to cats. Physicians prescribe antimicrobials—often azithromycin—to treat cat scratch disease. Prevention involves avoiding cat-inflicted wounds and adequate cleansing of bites or scratches that do occur. Cat Scratch Disease LE A R N I N G O U TC O M E 19.15 Describe the cause, diagnosis, treatment, and prevention of cat scratch disease. M19_BAUM7206_05_SE_C19.indd 562 ▲ FIGURE 19.7 Cat scratch disease. Localized swelling at the site of cat scratches or bites is characteristic. 11/30/16 9:01 PM       Bacterial Diseases of the Skin and Wounds Pseudomonas Infection respirators, and humidifiers. Some strains can even grow using small amounts of nutrients left in distilled water. P. aeruginosa has numerous virulence factors: LE A R N I N G O U TC O M E S • Fimbriae and adhesins attach to host cells and enable biofilm formation. • Its capsule, composed of a mucoid polysaccharide, plays a role in bacterial attachment and biofilm formation, and it shields the bacterium from phagocytosis. • Neuraminidase modifies host cell receptor molecules to make bacterial attachment to the cells more likely. • Elastase breaks down elastic fiber, degrades complement components, and cleaves immunoglobulins A and G (IgA and IgG). • Endotoxin (lipid A) can trigger fever, blood clotting, inflammation, or possibly shock. • Exotoxin A and exoenzyme S, which inhibit eukaryotic protein synthesis, lead to host cell death. • Pyocyanin, the blue-green pigment of Pseudomonas, triggers the formation of reactive forms of oxygen (superoxide radical and peroxide anion) that damage host cells. 19.16 Describe Pseudomonas aeruginosa as an opportunistic pathogen of burn victims. 19.17 Explain the action of nine virulence factors of Pseudomonas. 19.18 Explain why diagnosis, treatment, and prevention of Pseudomonas infections are problematic. The skin is a critical barrier to the entrance of many pathogens. This fact is particularly evident in patients whose skin has been burned away by a fire or exposure to steam. In such patients, opportunistic pathogens gain access to the moist, nutrient-rich environment of the fascia and deeper tissues. The most common microorganism seen in burn victims is Pseudomonas aeru­ ginosa (soo-dō-mō’nas ā-roo-ji-nō’să). This bacterium may also infect other parts of the body, particularly the lungs. (Cystic fibrosis patients are at particular risk.) Signs and Symptoms When Pseudomonas aeruginosa invades the bloodstream, it causes fever, chills, and shock. Massive infections are often readily diagnosed because the bacterium typically produces a blue-green pigment, pyocyanin, that colors such infections (FIGURE 19.8). Pathogen and Virulence Factors Pseudomonas aeruginosa is a Gram-negative, aerobic bacillus that metabolizes a wide range of organic carbon and nitrogen sources. It is almost everywhere in soil, in decaying organic matter, and in almost every moist environment, including swimming pools, hot tubs, sponges, washcloths, and contact lens solutions. In hospitals, it grows in sinks, moist foods, vases of cut flowers, sponges, toilets, floor mops, dialysis machines, Pseudomonas aeruginosa is somewhat of a medical puzzle: despite its many virulence factors and ability to live in almost every moist environment using a wide variety of carbon sources, it rarely causes disease. The reason it is only a rare opportunist and not a common and formidable pathogen is that P. aerugi­ nosa cannot penetrate the intact structures, cells, and chemical defenses of the skin. This is fortunate, because the ubiquity and inherent resistance of Pseudomonas to a wide range of antimicrobial agents would make a more virulent microbe an almost insurmountable challenge to health care professionals. Pathogenesis The surface of a burned area provides a warm, moist environment that is quickly colonized by this ubiquitous opportunist. A thick, scablike crust naturally forms over the surface of a severe burn. Pseudomonas growing beneath the crust can move into the blood. Once inside the body, it kills cells and destroys tissues, and endotoxin mediates fever, vasodilation, inflammation, shock, and other symptoms. Microbes on the burned area are not readily accessible to medical workers because the crust is generally impermeable to antimicrobial drugs, and blood vessels are absent. Health care workers must remove the crust in a medical procedure termed debridement so that antimicrobial drugs can be effective. Epidemiology growing under the bandages produce the green color on this burn victim. What chemical is responsible for the green color of this infection? P Figure 19.8 The greenish-blue color of seudomonas infections is due to pyocyanin. M19_BAUM7206_05_SE_C19.indd 563 ­ ▲ FIGURE 19.8 Pseudomonas aeruginosa infection. Bacteria Although a natural inhabitant of bodies of water and moist soil, P. aeruginosa is rarely part of the human microbiome. Nevertheless, because of its ubiquity and virulence factors, this opportunistic pathogen is involved in about 10% of healthcare-associated infections and colonizes most immunocompromised patients. Once it breaches the skin or mucous membranes, P. aeru­ ginosa can successfully colonize almost any organ and system. 11/30/16 9:01 PM Besides skin infections, it can be involved in bacteremia, endocarditis, and urinary, ear, eye, nervous system, gastrointestinal, muscular, and skeletal infections. Infections in cystic fibrosis patients and in burn victims are most common. Almost two-thirds of burn victims develop environmental or healthcare-associated Pseudomonas infections. Swimmers can develop otitis externa, also called swimmer’s ear, which is a painful Pseudomonas infection of the external ear canal. The microbe can also infect the hair follicles of people who sit in contaminated hot tubs. Cause Pseudomonas aeruginosa (Gram-negative, aerobic, rodshaped bacterium). Virulence factors Fimbriae, adhesins, capsule, neuraminidase, elastase, endotoxin (lipid A), exotoxin A, exoenzyme S, pyocyanin. Portal of entry Contact with wounded skin or deeper tissues following severe burns; inhalation; healthcareassociated infections occur from Pseudomonas biofilms on endotracheal tubes. Signs and symptoms Characteristic blue-green color where the bacterium is growing; fever, blood clotting, inflammation, Pseudomonas infection under a nail. possible shock; with lung infections: breathlessness, coughing, wheezing, rapid breathing, and weight loss.  E Incubation period ight hours to five days. Susceptibility Burn victims, cancer patients, immunocompromised patients; cystic fibrosis patients are particularly at risk for lung infection. Treatment Simultaneous use of both a semisynthetic penicillin and a sulfonamide. Prevention The ubiquity of Pseudomonas in wet environments makes it nearly impossible to prevent exposure, but the bacterium does not invade intact tissue. Cutaneous Anthrax LE A R N I N G O UTC O M E 19.22 Describe cutaneous anthrax, including its cause and its effect on the skin. Many bacterial diseases that primarily affect other body systems also affect the skin. Anthrax is such a disease. Anthrax has three distinct clinical manifestations— gastrointestinal, inhalation, and cutaneous. Gastrointestinal anthrax is rare in humans. Here we briefly consider cutaneous anthrax. (Chapter 22 discusses the severe form of anthrax, systemic inhalation anthrax, in detail.) Cutaneous anthrax begins when Bacillus anthracis (basil’us an-thrā’sis) endospores, often shed by an infected animal, enter a wound in the skin, producing a solid skin nodule. The bacterium’s capsule inhibits phagocytosis by white blood cells, and the bacterium synthesizes three toxins that kill cells in the affected area. The nodule spreads to form a painless, swollen, black, crusty ulcer called an eschar15 (es’kar) (Disease at a Glance 19.2). LE A R N I N G O U TC O M E S 19.19 Describe the cause, diagnosis, treatment, and prevention of spotted fever rickettsioses. 19.20 Explain why rickettsias cannot live outside another cell. 19.21 Describe the pathogenesis, signs, and symptoms of Rocky Mountain spotted fever. A number of arthropod-borne rickettsias cause rashes in humans, which are called spotted fever rickettsioses. Disease in Depth on pp. 566–567 explores the most severe of these rickettsioses, Rocky Mountain spotted fever, and Emerging Disease Case Study: A New Cause of Spots considers a newly recognized spotted fever rickettsiosis. M19_BAUM7206_05_SE_C19.indd 564 ­ ­ Spotted Fever Rickettsiosis 19.1 Pseudomonas Infection Diagnosis, Treatment, and Prevention Diagnosis of Pseudomonas infection is not always easy because its presence in a cult ure may represent contamination acquired during collection, transport, or inoculation. Certainly, pyocyanin discoloration of tissues is indicative of massive infection. Treatment of P. aeruginosa can be frustrating. The bacterium is notoriously resistant to a wide range of antibacterial agents, including antimicrobial drugs, soaps, antibacterial dyes, and quaternary ammonium disinfectants. In fact, Pseudomonas has been reported to live in solutions of some antibacterial drugs and disinfectants. Resistance is due to the ability of various strains of Pseudomonas to metabolize many drugs, to the presence of nonspecific proton/drug antiports that pump many drugs out of the bacterium, and to the ability of its biofilm to resist the penetration of antibacterial chemicals. Physicians attempt to treat infections with at least two antimicrobial drugs simultaneously. A combination of sulfadiazine and piperacillin has proven effective in a susceptibility test. Pseudomonas aeruginosa is ubiquitous, so it is nearly impossible to prevent exposure; however, the bacterium rarely causes diseases because it does not normally penetrate the skin and mucous membranes, nor does it ultimately evade the body’s other defenses. Only in wounded patients does this opportunist thrive. Disease at a Glance 19.1 summarizes the characteristics of Pseudomonas skin infection. E E DIS AS AT A GLANC E  t a       Ch p er 19    Microbial Diseases of the Skin and Wounds 15From Greek eschara, meaning a “scab caused by burning.” 11/30/16 9:01 PM E E GING DIS AS CAS STUDY E M ER E       Bacterial Diseases of the Skin and Wounds A New Cause of Spots E E DIS AS AT A GLANC E  R R H H 19.2 Cutaneous Anthrax Cause Bacillus anthracis (facultatively anaerobic, endosporeforming, rod-shaped bacterium). Eschar E Virulence factors ndospore, capsule, three anthrax toxins. Portal of entry Direct contact of endospores with wounded skin, infected animals, or contaminated animal products. (Two other forms of anthrax—gastrointestinal and inhalation—have routes of entry via the gastrointestinal tract and respiratory tract, respectively. For more on inhalational anthrax, see Chapter 22.) Signs and symptoms Localized itching followed by a raised lesion that eventually forms a painless, black eschar (see photo) within 7 to 10 days. Incubation period Immediate response, within one day. Susceptibility The most commonly infected individuals are animal handlers. Treatment Doxycycline or ciprofloxacin are the preferred antimicrobials. There is no treatment for the toxin. Prevention Vaccinate livestock. The vaccine, considered safe for humans but recommended only for high-risk personnel, requires six doses over an 18-month period and annual boosters. M19_BAUM7206_05_SE_C19.indd 565 R P R in Texas, and orders a laboratory test using anti–Rickettsia rickettsii antibodies. The test comes back negative; David is not infected with R. rickettsii. e does not have MSF. The doctor takes a skin sample from the infected area and prescribes 100 mg of doxycycline twice daily for two weeks. The rash resolves in a week, and further polymerase chain reaction ( C ) testing on bacteria found in the sample of skin reveals R. parkeri. In the United States, the Gulf Coast tick, Amblyomma maculatum, is the vector for this bacterium that was long thought to be harmless to humans. David is one of the first of several dozen patients to tangle with this pathogen that is emerging as a threat in the southeast United States and in Argentina. H Fifty-two-year-old David has a good life. After 30 years serving the country as an Army officer, he has retired to the Texas Gulf Coast—a region of large oaks, mild winter weather, and great outdoor spaces. It’s a great place to retire and enjoy hiking through the woods and meadows photographing wildlife. It would be nearly perfect if some of the wildlife didn’t bite. Ubiquitous ants, pesky mosquitoes, and bloodsucking ticks seem to always be on the prowl. It’s a tick that brings him to his doctor today. The thing had bit him on his left shoulder, resulting in a huge boil that swelled and drained pus, though the lesion doesn’t hurt at all. is primary care physician doesn’t appear to be too concerned and prescribes amoxicillin for the boil. Three days later, David is back but feeling much worse. e has suddenly developed fever, headache, muscle pains, fatigue, and an alarming rash over most of his body. The physician now suspects ocky Mountain spotted fever ( MSF), though it’s relatively rare 1. Why didn’t the antibody test show infection? 2. What is PCR testing? 3. In a Gram-stained sample of David’s skin, what color would the rickettsias be? Anthrax, which means “charcoal” in Greek, is named for the black color of eschars. Physicians successfully treat cutaneous anthrax with oral antimicrobial drugs such as doxycycline or ciprofloxacin for 7–14 days. Treated cutaneous anthrax is rarely fatal. Preventing naturally occurring anthrax in humans requires controlling the disease in animals. Farmers in areas where anthrax is endemic must vaccinate their stock and bury or burn the carcasses of dead animals. Anthrax vaccine has proven effective and safe for humans, but it requires six doses over 18 months plus annual boosters. The Centers for Disease Control and Prevention (CDC) recommends treatment with both ciprofloxacin and doxycycline and postinfection immunization. Gas Gangrene LE A R N I N G O UTC O M E 19.23 Describe the signs, symptoms, cause, diagnosis, treat- ment, and prevention of gas gangrene. When blood supply to a tissue is interrupted, for example by a wound, a condition known as ischemia (is-kē’mē-ă)16 develops. The tissue becomes anaerobic, and necrosis (death) sets in. If the wound is infected with endospores of anaerobic Clostridium, 16From Greek ischo, meaning “to keep back,” and haima, meaning “blood.” 11/30/16 9:01 PM DISEASE IN DEPTH SIGNS AND SYMPTOMS Ric About 1 week after infection, patients experience fever, headache, chills, muscle pain, nausea, and vomiting. In most cases (90%), a spotted, non-itchy rash develops on the trunk and appendages, including palms and soles, sites not involved in rashes caused by the chickenpox or measles viruses. In about 50% of patients, the rash develops into subcutaneous hemorrhages called petechiae. In severe cases, the respiratory, central nervous, gastrointestinal, and renal systems fail. With treatment, only about 0.5% of patients die. ROCKY MOUNTAIN SPOTTED FEVER Rickettsia R INSIDE BLOOD VESSEL ickettsia rickettsii causes Rocky Mountain spotted fever (RMSF), the most severe and most reported spotted fever rickettsiosis. Hard ticks in the genus Dermacentor transmit R. rickettsii among humans and rodents. R. rickettsii is typically dormant in the salivary glands of its tick vectors; only when the arachnids feed for several hours is the bacterium infective. PATHOGENESIS INSIDE BLOOD VESSEL R. rickettsii escaping into cytosol Endothelial cells lining small blood vessel Endosome Engorged Dermacentor 2 R. rickettsi triggers endocytosis by cells lining blood vessels (endothelium); then it lyses the endosome’s membrane, escaping into the cytosol. 3 Rickettsias divide every 8–12 hours in the host cell's cytosol. Daughter rickettsias escape from long cytoplasmic extensions of the host cell and infect other endothelial cells. 1 Infected tick introduces R. rickettsii in its saliva. This occurs only after the tick has fed for at least six hours. Active bacteria are released into the mammalian host’s circulatory system. INVESTIGATE IT! Scan this QR code to watch Dr.Bauman's Video Tutor explore Rocky Mountain Spotted Fever. Then go to MasteringMicrobiology to investigate further and record your research findings on the following question: How do rickettsias avoid phagocytosis by macrophages or neutrophils? M19_BAUM7206_05_SE_C19.indd 566 EPIDEMIOLOGY Though the earliest documented cases of Rocky Mountain spotted fever were in the Rocky Mountains, the disease is actually more prevalent in the Appalachian Mountains. Cases of Rocky Mountain spotted fever in the United States, 2002–2014. 1–400 401–800 801–1200 1201–1600 1601–2000 >2000 12/16/16 12:03 AM       PATHOGEN Rickettsias VECTOR Rickettsia rickettsii is a small (0.3–1 µm), nonmotile, aerobic, Gram-negative, intracellular bacterium that has a cell wall of peptidoglycan and an outer membrane of lipopolysaccharide surrounded by a slime layer. Rickettsias do not Gram stain well, so scientists use the Gimenez stain (shown here). Rickettsias require a vector for transmission between hosts. For R. rickettsii, this vector is a hard tick of the genus Dermacentor. Male ticks infect female ticks during mating. Female ticks transmit bacteria to eggs forming in their ovaries—a process called transovarian transmission. Dermacentor can survive without feeding for more than four years, making tick elimination in the wild problematic. Rickettsias cannot use glucose as a nutrient; instead, they oxidize amino acids and Krebs cycle intermediates, such as glutamic acid and succinic acid. For this reason, rickettsias are obliged to live inside other cells, where these nutrients are provided. LM 1 μm 4 R. rickettsii secretes no toxins, and disease is not the product of immune response. Apparently, damage to the endothelial cells leads to leakage of blood into the tissues, which results in low blood pressure and insufficient nutrient and oxygen delivery to the body’s organs. Blood leaks into tissue R. rickettsii escaping an endothelial cell TEM 1 μm Subcutaneous hemorrhages (petechiae) of RMSF patient TREATMENT AND PREVENTION DIAGNOSIS Negative Positive Latex agglutination test M19_BAUM7206_05_SE_C19.indd 567 Serological tests such as latex agglutination and fluorescent antibody stains are used to confirm an initial diagnosis based on sudden fever and headache following exposure to hard ticks, plus a rash on the soles or palms. Nucleic acid probes of specimens from rash lesions provide specific and accurate diagnosis. Early diagnosis is crucial because prompt treatment often makes the difference between recovery and death. Physicians treat RMSF by removing the tick and prescribing doxycycline for most adults or chloramphenicol for children and pregnant women. An effective vaccine is not available. Wearing tight-fitting clothing, using tick repellents, promptly removing ticks, and avoiding tick-infested areas, especially in spring and summer when ticks are most voracious, help prevent infection. 12/16/16 12:03 AM Signs and Symptoms Gas Gangrene Clostridium is an anaerobic, Gram-positive, endospore-forming bacillus that is ubiquitous in soil, water, sewage, and the gastrointestinal tracts of animals and humans. It also grows in the vaginas of 1–9% of healthy women. Several species of Clostridium cause gas gangrene. Pathogenicity is due in great part to the ability of endospores to survive harsh conditions and to the vegetative cells’ secretion of 11 toxins that lyse erythrocytes and leukocytes, increase vascular permeability, reduce blood pressure, and kill cells, resulting in irreversible damage. C. perfringens, the species most frequently isolated from patients, is a large, almost rectangular cell. Although it is nonmotile, its rapid growth and reproduction (cell divisions every 12 minutes) enable it to rapidly colonize wounds. Pathogenesis and Epidemiology Clostridium does not affect healthy tissues and is not invasive. A traumatic event, such as a surgical incision, puncture wound, gunshot wound, crushing trauma, abortion, or compound fracture, must introduce endospores into dead tissue. There, in the anaerobic environment of dead tissue, they germinate and grow on nutrients released by the dead cells. Despite therapeutic care, the mortality rate for gas gangrene exceeds 40%. Clostridial toxins kill neighboring cells, and the bacterium spreads into the dead tissue. Diagnosis, Treatment, and Prevention The appearance of gas gangrene is usually diagnostic by itself, though the detection of large Gram-positive bacilli is confirmatory. The condition is often a medical emergency, and a physician must intervene quickly and aggressively to stop the spread 17From Greek gangraina, meaning “an eating sore.” M19_BAUM7206_05_SE_C19.indd 568 Cause Clostridium species, particularly C. perfringens (anaerobic, Gram-positive, endospore-forming rod). E Virulence factors ndospore, 11 toxins, rapid growth, and cell division. Portal of entry Clostridium endospores are introduced into dead tissue via a traumatic event such as surgical incision, puncture, gunshot wound, crushing trauma, abortion, or broken bones punching through the skin. Blackened dead tissue and bubbling of bacterial gas wastes in gas gangrene. Signs and symptoms Increased pain and swelling around injury, fever, initially pale skin that turns dusky and then progresses to dark red or purple, foul-smelling drainage from tissues, crepitation (crackly sound due to gas under the skin), and tachycardia. Untreated gas gangrene causes shock, coma, and death. Incubation period Generally less than 24 hours and no more than three days. Susceptibility Individuals with deep, lacerating wounds, particularly “dirty” wounds. Treatment Gas gangrene is a medical emergency, and prompt identification and treatment are crucial. Dead tissue must be surgically removed, and antitoxin, penicillin, and clindamycin administered. Prevention roper cleaning of wounds. of necrosis by surgically removing dead tissue and administering antitoxin and large doses of intravenous penicillin and clindamycin. Oxygen applied under high pressure may also be effective. It is difficult to prevent infections of C. perfringens because the organism is common in soil. Given that gas gangrene occurs following introduction of endospores into tissues, proper cleaning of wounds can prevent many cases of the disease. Disease at a Glance 19.3 summarizes the features of gas gangrene. We have examined some common bacterial pathogens and opportunists that infect or affect the skin. Other bacterial diseases also manifest signs in the skin but have their major effect elsewhere. (Later chapters discuss these diseases. For example, scarlet fever, which manifests with bright red skin, has its most serious effects on other body systems, and is discussed in Chapter 22.) Now we turn our attention to viral pathogens of skin. ­ Pathogens and Virulence Factors 19.3 P ­ Clostridium produces toxins that kill surrounding tissues, providing the bacterium with more nutrients and increasing the size of the anaerobic environment necessary for Clostridium to grow. The rapidly growing bacteria then spread into the surrounding tissue, causing the death of muscle and connective tissues. The immediate result is intense pain at the initial site of infection (often in a foot), followed by gas gangrene, which involves blackening of the infected muscle and skin and the production of bubbles of hydrogen and carbon dioxide gases that may break out with a frothy brownish fluid (see Disease at a Glance 19.3). The bubbles can be felt under the skin by palpation. Shock, kidney failure, and death can follow, often within a week of infection. E DIS AS AT A GLANC E then gas gangrene17 (also called simply gangrene) develops in the dead tissue. E  t a       Ch p er 19    Microbial Diseases of the Skin and Wounds TELL ME WHY Why do most cases of Rocky Mountain spotted fever occur in May, June, and July? 11/30/16 9:02 PM       Viral Diseases of the Skin and Wounds Viral Diseases of the Skin and Wounds CLINICAL CASE STUDY Many viral diseases are systemic in nature and spread by respiratory and oral routes; nevertheless, they manifest signs and symptoms in the skin. These include diseases of poxviruses, herpes infections, warts, chickenpox, shingles, rubella, measles, erythema infectiosum, and roseola. We begin our survey of viral skin diseases by considering infections of poxviruses. Diseases of Poxviruses LE A R N I N G O U TC O M E S 19.24 Describe the progression of lesions in poxvirus infections. 19.25 Discuss the historical importance of poxviruses in immunization. 19.26 Discuss worldwide smallpox eradication. Human diseases caused by poxviruses include smallpox and three diseases of animals—orf (sheep and goat pox), cowpox, and monkeypox—which rarely affect humans. (Despite its name, chickenpox is not caused by a poxvirus.) Smallpox and cowpox have played important roles in the history of microbiology, immunization, epidemiology, and medicine. Recall from Chapter 1 that Edward Jenner first demonstrated immunization using the relatively mild cowpox virus to protect against smallpox. He was successful because the antigens of cowpox virus are chemically similar to those of smallpox virus, so that exposure to cowpox results in immunological memory and subsequent resistance to both cowpox and smallpox. Smallpox was also the first human disease to be eradicated globally in nature. In 1967, the World Health Organization (WHO) began an extensive campaign of identifying and isolating smallpox victims, as well as vaccinating their contacts, wit h t he goal of completely elimi nat i ng t he disease. The efforts of WHO were successful, and in 1980 natural smallpox was declared eradicated—one of the great accomplishments of 20th-century medicine. Nevertheless, some scientists and government officials are concerned that smallpox could be reintroduced accidentally or through bioterrorism; therefore, knowledge of smallpox is necessary for health care providers. Signs and Symptoms All poxviruses produce lesions that progress through a series of stages (FIGURE 19.9). The lesions begin as flat, reddened macules18 (mak’yūlz), which then become raised sores called papules19 (pap’yūlz). When the lesions fill with clear fluid, they are called vesicles, which then progress to pus-filled pustules20 (pŭs’chūlz), which are also known as pox, or pocks (see Disease at a Glance 19.4 on p. 571) (Note: These terms for the stages of poxvirus lesions are also used to describe the lesions of other skin infections.) Poxvirus pustules then dry to form crusts. Because these lesions penetrate the dermis, they may M19_BAUM7206_05_SE_C19.indd 569 A Painful Rash A mother brings her three-year-old daughter to her pediatric office, stating that the girl has had fever and chills for three days. The girl also has a large, intensely red patch with a distinct margin on her leg and a nearby swollen lymph node. When the health care provider touches the area, it is firm and warm, and the girl screams in pain. Based on these observations, the provider makes a presumptive diagnosis and begins treatment. 1. Is it necessary for the provider to confirm the diagnosis with a lab test? Why or why not? 2. What was the diagnosis? The treatment? 3. How is this different from impetigo? 4. What is the causative agent associated with the girl’s condition? 5. How might the girl have contracted the condition? 6. What component(s) of the causative agent stimulated the fever and the lesion? 7. Why is it important for the provider to begin immediate treatment? result in characteristic scars, particularly on the face. Additionally, the disease is characterized by fever—as high as 42°C (107°F)—malaise, delirium, and prostration. Infection of the eye may induce blindness. Pathogens and Virulence Factors Poxviruses are DNA viruses. They have adhesion molecules allowing them to attach to a host cell’s cytoplasmic membrane, where they trigger their own endocytosis. Unlike other DNA viruses, they carry genes for transcription enzymes, which allow them to replicate entirely in the cytoplasm of a cell. The viruses also code for proteins that interfere with the actions of interferon, complement, and inflammation. Human poxvirus (Orthopoxvirus), known commonly as variola virus, attaches only to human cells. Humans do not easily contract the poxviruses of cows (Vaccinia), sheep, goats, or monkeys, because these animal viruses do not attach readily to human cells. Transmission of these poxviruses to humans requires prolonged close contact with infected animals, as Edward Jenner observed for milkmaids who contracted cowpox. From Latin maculatus, meaning “spotted.” From Latin papula, meaning “pimple.” 20 From Latin pustule, meaning “blister.” 18 19 11/30/16 9:02 PM t a       Ch p er 19    Microbial Diseases of the Skin and Wounds 1 Macule Epidermis Dermis 2 Papule Pathogenesis Close contact is necessary for infection with smallpox viruses. This occurs primarily through inhalation of viruses in droplets or dried crusts. Crusts can remain infective for two years. Smallpox viruses replicate in the respiratory tract and then spread via the blood and lymph throughout the body, causing the characteristic lesions on the skin about 12 days following infection and killing up to 40% of patients. In contrast, other poxviruses spread by direct contact and do not move extensively throughout the body. Infections of humans with these viruses are usually relatively mild, resulting in pox and scars but little other damage. In the case of cowpox, the advent of milking machines has reduced the number of cases to near zero in the industrialized world. Epidemiology 3 Vesicle Fluid 1 cm 4 Pustule Pus 5 Crust 6 Scar Smallpox virus exists in two strains: variola major causes severe disease with a mortality rate of 20% to 40% or higher, depending upon the age and general health of the host, whereas variola minor has a mortality rate of less than 1%. During the Middle Ages, 80% of the European population contracted smallpox. Later, European colonists unwittingly introduced smallpox into susceptible Native Americans, resulting in the death of as many as 3.5 million people. Stocks of variola virus are still maintained in laboratories in the United States and in the Russian Federation as research tools for investigations concerning virulence, pathogenicity, protection against bioterrorism, vaccination, and recombinant DNA technology. Some government officials believe that illicit stocks of smallpox virus are being kept in so-called rogue nations such as Iran and North Korea. Now that smallpox vaccination has been generally discontinued, experts are concerned that the world’s population is once again susceptible to smallpox epidemics should the virus be accidentally released from storage or used as a biological weapon. For this reason, some scientists advocate the destruction of all smallpox virus stocks; other scientists insist that we must maintain the virus in secure laboratories so that it is available for the development of more effective vaccines and treatments should the virus ever be disseminated. An upsurge in the number of monkeypox cases in humans has been seen in the past decade, including an epidemic in the U.S. Midwest in 2003. This upsurge is probably the result of humans moving into monkey habitats in Africa, the importation of pet animals from that continent, and possibly changes in viral antigens. The elimination of smallpox and the cessation of smallpox vaccination may have led to increased human susceptibility to monkeypox because smallpox vaccination also protects against monkeypox. Some scientists recommend that smallpox vaccination be reinstated in areas where monkeypox is endemic. Diagnosis, Treatment, and Prevention ▲ FIGURE 19.9 The stages of lesions of poxviral skin R infections. ed macules may become hard papules, then fluid-filled vesicles that become pus-filled pustules (pox), which sometimes crust over and leave scars. M19_BAUM7206_05_SE_C19.indd 570 Physicians diagnose diseases of poxviruses by their distinctive pox. Immediate immunization of people exposed to smallpox virus prevents the disease from developing. No treatment exists once smallpox develops. 11/30/16 9:02 PM       Viral Diseases of the Skin and Wounds E E DIS AS AT A GLANC E  Smallpox vaccinations ended in 1972 in most locales in the United States, in part because the vaccine caused adverse effects such as inflammation of the heart and, rarely, death. Now, in an effort to ward off potential bioterrorism, military personnel and selected health care providers are immunized. Interestingly, researchers have determined that adverse reactions to the vaccine are currently lower than historical rates, possibly because of better overall health care. They have also determined that previously immunized individuals can be successfully revaccinated with a diluted vaccine containing only 10% of the cowpox viruses in a standard vaccine. Disease at a Glance 19.4 summarizes the features of smallpox. 19.4 Smallpox Cause Orthopoxvirus (variola virus) (enveloped, doublestranded DNA virus). Virulence factors Intracellular infection, codes for proteins that inhibit interferon, complement, and inflammation. Portal of entry Inhalation of viruses in droplets or dried crusts. E Signs and symptoms The prodromal period (two to four days) includes high fever, headaches and body aches, and malaise. A rash begins in the mouth and spreads to the face and downward all over the body. The rash becomes papules, then vesicles, and finally pustules. ventually the pustules dry to form crusts. Scarring may result. Signs and Symptoms The name herpes, which is derived from a Greek word meaning “to creep,” is descriptive of the slowly spreading skin lesions that are seen with herpesviruses. About a week after infection, the viruses produce painful, itchy skin lesions on the lips (called fever blisters or cold sores) (FIGURE 19.10) or genitalia (called genital herpes). Initial infections may also be accompanied by flulike signs and symptoms, including malaise, fever, and muscle pain. Severe infections in which the lesions extend into the oral cavity, called herpetic gingivostomatitis,21 are most often seen in young patients and in patients with lowered immune function due to disease, chemotherapy, or radiation treatment. An inflamed blister called a whitlow22 (hwit’lō) may occur on a finger if herpesvirus enters a cut or break in the skin of a finger. Athletes may develop herpes lesions in a condition called herpes gladiatorum almost anywhere on their skin as a result of contact with herpes lesions during sports. One of the more distressing aspects of herpes infections is the recurrence of lesions. About two-thirds of patients with herpesvirus will experience recurrences during their lives as a result of the activation of latent viruses. After a primary infection, herpesviruses often enter sensory nerve cells and are carried by cytoplasmic flow to the base of the nerve, where they remain latent in the trigeminal, sacral, or other ganglia,23 as illustrated in FIGURE 19.11. Latent viruses may reactivate later in life as a result of immune suppression caused by stress, fever, trauma, sunlight, menstruation, or disease, and they may travel down the nerve to produce recurrent lesions as often as every two weeks. Fortunately, recurrent lesions are rarely as severe as those of initial infections because of immunological memory. Incubation period Average 12 to 14 days but can range from 7 to 17 days. The person is not contagious at this stage. H Susceptibility Currently, there is no naturally occurring smallpox. owever, if a bioterrorism event or accidental release were to occur, it is theorized that most people would be susceptible since regular vaccination was discontinued decades ago. Treatment Immediate vaccination; there is no other approved antiviral treatment for smallpox. Treatment includes supportive therapy. R Prevention outine vaccination was discontinued in most of the United States in 1972. In response to recent world events, the U.S. government ordered new production of the smallpox vaccine and is currently prepared in the event of an outbreak. ▲ FIGURE 19.10 Oral herpes lesions. What is the most likely pathoFigure 19.10 Human herpesvirus 1 causes approximately 90% of oral herpes lesions. Herpes Infections gen involved in oral herpes? LE A R N I N G O U TC O M E S 19.27 Describe the diseases caused by human herpesvirus 1 and human herpesvirus 2. 19.28 List conditions that may reactivate latent herpesviruses. M19_BAUM7206_05_SE_C19.indd 571 Latin gingival, meaning “gum”; Greek stoma, meaning “mouth”; and Greek itis, meaning “inflammation.” 22From Scandinavian whick, meaning “nail,” and flaw, meaning “crack.” 21From 23A ganglion is a collection of enlarged portions of nerve cells that contains the cells’ nuclei. 11/30/16 9:02 PM t a       Ch p er 19    Microbial Diseases of the Skin and Wounds Pathogenesis Ophthalmic branch Trigeminal (V) nerve ganglion Site of viral latency Herpesviruses are most often spread between mucous membranes of the mouth or genitals. The viruses may remain inactive inside infected cells, often for years. Inactive viruses may reactivate as a result of aging, chemotherapy, immunosuppression, or physical and emotional stress, causing a recurrence of the manifestations of their diseases. Herpesvirus attach to host cells through the fusion of their envelope with the cells’ cytoplasmic membranes. After the viral genome is replicated and assembled in a cell’s nucleus, a herpesvirus acquires an envelope from the nuclear membrane and exits the cell via exocytosis or cell lysis. Active lesions are the usual source of infection, though asymptomatic carriers can shed HHV-2 genitally. After entering the body through cracks or cuts in mucous membranes, viruses reproduce in epithelial cells near the site of infection and produce inflammation and cell death, resulting in painful, localized lesions on the skin. By causing infected cells to fuse with uninfected neighboring cells, both HHV-1 and HHV-2 can form a structure called a syncytium, which is a multinucleate cytoplasmic mass, allowing the viruses to spread and in the process avoid the host’s humoral immune system. Ocular herpes Maxillary branch Mandibular branch Brachial ganglia Site of viral latency Fever blisters Sacral ganglia Site of viral latency Epidemiology Genital herpes Whitlow ▲ FIGURE 19.11 Sites of events in herpesvirus infections. Infections typically occur when viruses invade the mucous membranes of either the lips or the genitalia, or through broken skin of a finger. Viruses may remain latent for years in the trigeminal, brachial, or sacral ganglia before traveling down nerve cells to cause recurrent symptoms in the lips, genitalia, fingers, or eyes (for ocular herpes). What factors may trigger the reactivation of latent herpesviruses and the recurrence of symptoms? Figure 19.11 Stress, trauma, sunlight, menstruation, or diseases such as AIDS may cause recurrent symptoms as a result of immune suppression. Pathogens and Virulence Factors ­ ­­ ­ Two enveloped viral species of Simplexvirus cause herpes: human herpesvirus 1 (HHV­1) and human herpesvirus 2 (HHV­2). Historically, HHV-1 has also been known as “above-the-waist herpes” virus, whereas HHV-2 has been known as “below-the-waist herpes” virus, though either strain can occur in either location. HHV-2 is also usually the species involved in neonatal herpes. TABLE 19.3 compares infections caused by human herpesviruses. (Chapter 24 discusses genital herpes in more detail.) Human herpesviruses produce various proteins that act as virulence factors: glycoproteins in the viral envelope mediate viral adhesion and fusion, and other proteins inactivate complement and gamma class antibodies (IgG). Initial infections with herpesviruses are usually age specific. Primary HHV-1 infections typically occur via casual contact during childhood and produce no signs or symptoms; in fact, by age 2, about 80% of children worldwide, including nearly all children in developing nations, have been asymptomatically infected with HHV-1. Most HHV-2 infections, by contrast, are acquired between the ages of 15 and 29 as a result of sexual activity, including oral sex. Symptomatic patients shed viruses about 6 days a month, whereas asymptomatic patients shed the same number of viruses but only for half as many days. Whitlow is a hazard for children who suck their thumbs, for patients with genital herpes, and especially for health care workers in the fields of obstetrics, respiratory care, gynecology, and dentistry who come into contact with herpes lesions. Although herpes infections in adults are painful and unpleasant, they are not life threatening. This is not the case for herpes infections in newborns. A fetus can be infected in utero when the virus crosses the placental barrier, but it is more likely that a baby is infected at birth through contact with lesions in the mother’s reproductive tract. Also, mothers with oral lesions can infect their babies if they kiss them on the mouth. Neonatal herpes infections can be very severe, with a mortality rate of 30% if the infection is cutaneous or oral, and 80% mortality when the central nervous system is infected. M19_BAUM7206_05_SE_C19.indd 572 Diagnosis, Treatment, and Prevention Physicians diagnose herpes infections by the presence of their characteristic, recurring lesions, especially on the lips and in the genital region. Microscopic examination of infected tissue 11/30/16 9:02 PM       Viral Diseases of the Skin and Wounds TABLE 19.3 Comparative Epidemiology and Pathology of Human Herpesvirus Infections HHV-2 Usual Diseases 90% of cold sores/fever blisters; whitlow 85% of genital herpes cases Mode of Transmission Close contact Sexual intercourse Site of Latency Trigeminal and brachial ganglia Sacral ganglia Locations of Lesions Face, mouth, and, rarely, trunk Other Complications 15% of genital herpes cases; pharyngitis; gingivostomatitis, ocular/ophthalmic herpes; herpes gladiatorum; 30% of neonatal herpes cases E E DIS AS AT A GLANC E  reveals syncytia. Positive diagnosis is achieved by immunoassay that demonstrates the presence of viral antigen. Herpes infections are among the few viral diseases that can be controlled with nucleoside analogs such as acyclovir or penciclovir. Topical applications of the drug limit the duration of the lesions and reduce viral shedding, though the drug does not cure the diseases or free nerve cells of viral infections. Health care workers can reduce their exposure to infection by wearing latex or nitrile gloves. Since a whitlow is a potential source of infection, symptomatic personnel should not work with patients, especially newborns, until the whitlow has healed. Disease at a Glance 19.5 summarizes the features of herpes skin infections. 19.5 Cause Human herpesvirus 1 and human herpesvirus 2 (enveloped doublestranded DNA viruses). Virulence factors Glycoproteins that allow viral attachment and entry, intracellular infections, proteins that inactivate complement and IgG. Warts LE A R N I N G O UTC O M E S 19.29 Describe four kinds of warts associated with papilloma- virus infections. 19.30 Describe the pathogenesis, treatment, and prevention of warts. Warts (papillomas) (pap-i-lō’maz) are generally benign growths of the epithelium of the skin or mucous membranes. Signs and Symptoms Warts form on many body surfaces. Generally, warts are painless, though they may itch or hurt, particularly plantar warts. Pathogens and Virulence Factors More than 100 different strains of Papillomavirus cause warts. Various strains infect either cutaneous or mucosal tissues, causing infected epithelial cells to divide. This produces warts on the skin or mucous membranes, respectively. Some strains of papillomaviruses integrate into host cell chromosomes, potentially triggering the action of oncogenes, which cause cancers. Pathogenesis Whitlow. Portal of entry Usually mucous membranes of the mouth or genitals. Signs and symptoms A prodromal period of malaise, fever, and/ or muscle pain may precede the typical blisters of a herpes infection. The blisters break, leaving a tender ulcer that may take several weeks to heal. Incubation period 10 to 14 days. Susceptibility Sexually active people have a greater risk of exposure to the disease, as does a baby during delivery by an infected mother. Treatment Topical or oral administration of antivirals such as acyclovir or penciclovir can shorten outbreaks, but there is currently no cure. Prevention Sexual abstinence, mutual monogamy, use of condoms, use of latex gloves by health care workers, and cesarean sections in infected mothers. Besides causing infected epithelial cells to divide, papillomaviruses cause the cells to develop distinctive vacuoles surrounding their nuclei and to form dense cytoplasm. The incubation time from infection to the development of a wart is usually three to four months. Warts are often unsightly, but most are harmless. Nevertheless, papillomaviruses may precipitate various head, neck, anal, vaginal, penile, and oral cancers. (Chapter 24 examines genital warts in more detail.) Epidemiology Papillomaviruses infect the skin through cuts or abrasions. They are transmitted via direct contact, including childbirth, and, because they are stable outside the body, via fomites. In a 24From M19_BAUM7206_05_SE_C19.indd 573 xternal genitalia and, less commonly, thighs, buttocks, and anus 10% of oral herpes cases; 70% of neonatal herpes cases ­ Herpes E HHV-1 Latin planta, meaning “sole” (of the foot). 11/30/16 9:02 PM t Diagnosis, Treatment, and Prevention Diagnosis of warts is usually a simple matter of observation, though only DNA probes can determine the exact strain of Papillomavirus involved. Warts usually regress over time as the cell-mediated immune system recognizes and attacks virally infected cells. Cosmetic concerns and the pain associated with some warts may necessitate removing infected tissue via surgery, freezing, cauterization (burning), laser, or the use of caustic chemicals, as are found in over-the-counter medications. These techniques are not always entirely satisfactory because viruses may remain latent in neighboring tissue and produce new warts at a later time. Laser surgery has the added risk of causing viruses to become airborne—some physicians have developed warts in their noses after inhaling airborne viruses during laser treatment of patients! Some patients have successfully removed warts by covering them with duct tape. Covered warts usually disappear within two months. Most types of warts are difficult to prevent. However, genital warts may be prevented by abstinence, mutual monogamy, or vaccine (see Chapter 24). Disease in Depth: Papillomas visually examines warts in more detail. Chickenpox and Shingles LE A R N I N G O U TC O M E S 19.31 Compare and contrast the signs, symptoms, and ­ treatment of chickenpox and shingles. 19.32 Explain the relationship between shingles and chickenpox. Chickenpox is one of numerous childhood diseases that produce skin lesions. The causative virus may become dormant and then years later reactivate to cause shingles. Signs and Symptoms ­ Chickenpox, which is medically termed varicella, is a highly infectious disease. About two to three weeks after infection with chickenpox virus, the patient develops a slight fever and characteristic skin lesions on the back and trunk that then spread to the face, neck, and limbs. In severe cases, the rash may spread into the mouth, pharynx, and vagina. Chickenpox lesions begin as macules, progress in one to two days to papules, and finally become thin-walled, fluid-filled vesicles on red bases, which have been called “teardrops on rose petals.” These vesicles turn cloudy, dry up, and crust over in a few days. Successive crops of lesions appear over a three- to five-day M19_BAUM7206_05_SE_C19.indd 574 period, so that at any given time all stages can be seen. Usually chickenpox is not life threatening, though it can, rarely, be fatal to newborns. Chickenpox virus can become latent within sensory nerves and may remain dormant for years. Stress, aging, or immune suppression reactivates the viruses in 15–20% of individuals who have had chickenpox. Reactivated viruses travel down the nerve they inhabit and produce an extremely painful skin rash near the end of the nerve. This rash, known as shingles or herpes zoster, forms in the band of skin associated with the nerve or in the eye. Shingles lesions are accompanied by a burning sensation, numbness, itchiness, or intense pain. After the scabs of shingles fall off, most people have no further skin manifestations, though the pain associated with shingles may remain for months or years after the lesions have healed. Some patients report that the pain is so intense they cannot wear clothing over the affected area for months or years. ­ process called autoinoculation, patients can spread wart viruses from one location to another on their own bodies. Viruses that cause genital warts invade the skin and mucous membranes of the penis (particularly when it is uncircumcised), vagina, and anus during sexual intercourse. ­ a       Ch p er 19    Microbial Diseases of the Skin and Wounds Pathogen A herpesvirus called varicella-zoster virus (VZV) (genus Var­ icellovirus) causes both chickenpox and shingles. (Note that chickenpox virus is not a poxvirus but a herpesvirus and that its Latin name is spelled differently from its English name.) VZV is named for the medical names of the two diseases. Pathogenesis Infection with VZV begins in the mucous membrane of the respiratory tract and then spreads into the liver, spleen, and lymph nodes via the blood and lymph. After two weeks, a second wave of viruses spreads via the blood throughout the body and to the skin. In the dermis, infected cells develop the characteristic rash, which is associated with fever and malaise. Viruses are shed before and during the symptoms through respiratory droplets and the fluid in lesions; dry crusts are not infective. Usually the disease is mild, but it may rarely be fatal, especially if associated with secondary bacterial infections. The virus becomes latent in nerve ganglia and can reactivate in adults, usually after age 45. Reactivated virus travels down the nerve to manifest the lesions of shingles in the band of skin innervated by the infected nerve. Epidemiology Chickenpox is most often seen in children. Before immunization became routine, about 90% of children developed chickenpox acquired through the respiratory route or by the introduction of viruses from vesicles into skin breaks. Chickenpox in adults is typically more severe than the childhood illness, presumably because much of the tissue damage results from a patient’s immune response, and adults have a more developed immune system than children. Adult patients may require hospitalization, since chickenpox infection in adults can lead to fatal pneumonia. 11/30/16 9:02 PM DISEASE IN DEPTH There are more than 100 strains of human papillomaviruses (HPV, family Papillomaviridae), each having a single molecule of doublestranded DNA contained in a naked icosahedral capsid. Half of HPVs can permanently integrate into human chromosomes, where they can trigger genital cancer, especially when they infect a patient who is also infected with herpesvirus. PAPILLOMAS Human papillomavirus Papillomaviruses shed from a wart TEM 60 nm P apillomaviruses cause papillomas, usually benign growths of the epithelium of the skin or mucous membranes commonly known as warts. Papillomas are most often found on fingers or toes (seed warts); deep in soles of feet (plantar warts); on the trunk, face, elbows, or knees (flat warts); or on the external genitalia or anus (condylomata acuminata). Certain strains of papillomaviruses can trigger cancers, such as those of genitalia. PATHOGENESIS 1 Papillomavirus is transmitted via direct contact or from contaminated fomites. Condylomata acuminata 2 Virus multiplies within cells. 3 Virus invades adjacent cells. 4 Rapid growth of virusinfected cells creates wart. 5 Virus is shed when dead skin cells are sloughed off. Papillomaviruses shedding from wart INVESTIGATE IT! Scan this QR code to watch Dr. Bauman’s Video Tutor explore papillomas. Then go to MasteringMicrobiology to investigate further and record your research findings on the following question: How can DNA viruses trigger cancer by inserting into an infected cell’s chromosomes? M19_BAUM7206_05_SE_C19.indd 575 TEM 600 nm DIAGNOSIS, TREATMENT, & PREVENTION Diagnosis of warts is usually a simple matter of observation, though only DNA probes can elucidate the exact strain of Papillomavirus involved. Warts usually regress over time as a cell-mediated immune response recognizes and attacks virally infected cells. Cosmetic concerns or pain associated with some warts may necessitate removing infected tissue via surgery, freezing, cauterization (burning), laser, or the use of caustic chemicals. Despite treatment, viruses may remain latent in neighboring tissue and produce new warts at a later time. Prevention is difficult; however, genital warts may be prevented by abstinence, mutual monogamy, or a vaccine against the more common strains associated with genital cancers. 12/16/16 12:03 AM t A Child with Warts R R R R 1. Is it possible that udy’s warts will spread to other parts of his body? 2. Is it possible for someone else to “catch” udy’s warts by shaking his hand? 3. If udy’s warts disappear without treatment, are they likely to return to the same sites on his hand? 4. Are the warts on udy’s finger likely to become cancerous? 5. Following surgical removal of the warts, is there a chance that udy will develop warts again? ­ R R After consulting a physician, his mother decides to have the warts surgically removed. R R Ten-year-old udy has several large warts on the fingers of his hands. They do not hurt, but their unsightly appearance causes him to shy away from people. e is afraid to shake hands or to play with other children, out of fear that he may transfer the warts to them. Initially, his mother tells him not to worry about them, but udy cannot help feeling selfconscious. Furthermore, udy fears that the warts may somehow spread on his own body. H CLINICAL CASE STUDY a       Ch p er 19    Microbial Diseases of the Skin and Wounds Only 15–20% of adults who had chickenpox as children will develop shingles. Presumably this is because most infected individuals develop complete immunity during their bout with chickenpox. Unlike the multiple recurrences of herpes simplex lesions, shingles usually occurs once; only about 4% of patients ever develop a second case of shingles. The risk of contracting shingles increases with age. A person who has never had chickenpox can acquire the disease from a shingles patient. This observation proved the two diseases have a common cause. The opposite is not true—a person cannot acquire shingles from a chickenpox victim. Diagnosis, Treatment, and Prevention Physicians diagnose chickenpox by the characteristic appearance of the lesions. It is more difficult to distinguish shingles from other types of skin lesions, though the localization within a band of skin on one side of the body is characteristic. Antibody tests are available to verify the diagnosis of both VZV infections. Uncomplicated chickenpox is typically self-limiting and requires no treatment other than relief of the symptoms with acetaminophen and antihistamines, though the antiviral drug acyclovir may reduce the severity and duration of chickenpox. Aspirin should not be given to children or adolescents with symptoms of chickenpox because of the risk of contracting Reye’s syndrome—a condition in which the liver and brain cease to function. Reye’s syndrome is associated with aspirin usage during several viral diseases. Treatment of shingles involves management of the symptoms, bed rest, and oral acyclovir. Loose-fitting clothing and nonadherent dressings may help prevent irritation of the lesions. Acyclovir provides relief from the painful rash for some patients, but it is not a cure. M19_BAUM7206_05_SE_C19.indd 576 It is difficult to prevent exposure to VZV because viruses are shed from patients before obvious signs appear. The Centers for Disease Control and Prevention (CDC) recommends immunization against chickenpox with attenuated varicella-zoster virus for all children between 12 and 18 months of age and a second dose before starting school. Since the vaccine provides protection against chickenpox, successfully vaccinated patients will not develop shingles later in life. The CDC recommends a single dose of a different, more potent, attenuated vaccine for adults aged 60 or older who had chickenpox as children and two doses of this vaccine for everyone older than 19 who has not had chickenpox or successful vaccination in childhood. Disease at a Glance 19.6 summarizes the features of varicella-zoster virus infections. Rubella LE A R N I N G O UTC O M E S 19.33 Describe rubella, including its cause, signs, and symptoms. 19.34 Explain why and how rubella has been eradicated as an endemic disease in the Americas. Rubella25 (rū-bel’ă), another of the childhood diseases that produces skin lesions, was first distinguished as a separate disease from measles by German physicians. Rubella has been known in the United States as German measles or three­day measles. 25Latin, meaning “little red.” 11/30/16 9:02 PM E E DIS AS AT A GLANC E        Viral Diseases of the Skin and Wounds 19.6 Chickenpox and Shingles 1 Inhalation of varicella-zoster virus. 4 Second viremia spreads viruses to skin, 7 Some viruses become latent (dormant) in 5 Viruses shed through respiratory droplets and 8 Upon reactivation, viruses travel inside nerve 6 Immune system eliminates viruses from blood 9 Rash develops in the band of skin innervated causing extensive rash. 2 Infected cells replicate and release virus into the blood (viremia) and lymph. fluid from skin lesions. 3 Viruses infect liver, spleen, and lymph nodes throughout body. and most cells. 1 Child 5 nerve ganglia. cells down the nerve to infect skin cells. by the infected nerve. Adult 6 2 4 8 7 3 9 5 Characteristic chickenpox lesions. Varicellovirus causes these thin-walled, fluid-filled vesicles on red bases. Cause Varicellovirus (varicella-zoster virus, VZV) (enveloped, double-stranded DNA virus). Virulence factors Intracellular infection, ability to lie dormant within nerve cells for years. Portal of entry Respiratory tract. Signs and symptoms Fever, characteristic rash on back and trunk that spreads to face and extremities. In 15–20% of cases, the virus reactivates years later, causing a painful shingles rash on a band of skin innervated by an infected nerve. Incubation period Two to three weeks. Susceptibility Chickenpox is a highly contagious disease to those who are not vaccinated or have not had it before. Persons who have had chickenpox previously are generally immune. Treatment Treatment is supportive therapy and the antiviral drug acyclovir or its derivatives. Signs and Symptoms Rubella is a generally harmless disease in children, causing only slightly swollen lymph nodes and a mild rash of flat, pink to red spots (macules) (see Disease at a Glance 19.7 on p. 578) that lasts about three days. Infections in adults are more severe and may result in arthritis or encephalitis. Rubella was not seen as a particularly serious disease until 1941, when Dr. Norman Gregg (1892–1966), an Australian eye M19_BAUM7206_05_SE_C19.indd 577 Characteristic shingles rash. Symptoms may be treated with acetaminophen and/or antihistamines. Aspirin should never be given to children with viral infections. Prevention The CDC recommends an attenuated vaccine for children, a single dose of a more potent attenuated vaccine for adults 19–49 who had chickenpox as children, and two doses of the latter for adults without chickenpox immunity. doctor, recognized that rubella infections of pregnant women resulted in teratogenic 26 birth defects in their babies. These effects include cardiac abnormalities, deafness, blindness, mental retardation, microcephaly,27 and growth retardation. Death of the fetus is also common. It is now known that the 26From 27 From Greek teras, meaning “monster,” and genein, meaning “to produce.” Greek mikro, meaning “small,” and kephale, meaning “to head.” 11/30/16 9:02 PM t E E DIS AS AT A GLANC particles) in respiratory droplets for approximately two weeks before and two weeks after the rash. The most severe form of rubella is in a fetus under 20 weeks old. 19.7 E  a       Ch p er 19    Microbial Diseases of the Skin and Wounds Rubella Diagnosis, Treatment, and Prevention Cause Rubivirus (rubella virus) (enveloped, positive, single-stranded NA virus). R Rubella is usually diagnosed by observation, which is confirmed by serological testing for IgM against rubella. No treatment is available, but immunization has proven effective at reducing the incidence of rubella in industrialized countries (FIGURE 19.12). Such immunization is aimed at reducing the number of rubella cases that might serve to introduce rubella to pregnant women. Rubella vaccine (combined with vaccine against measles and mumps as MMR) is made from a live, weakened virus and therefore should never be given to pregnant women or immunocompromised patients. Disease at a Glance 19.7 summarizes the features of rubella. Virulence factors Attachment proteins, intracellular infection. R Portal of entry espiratory tract. Signs and symptoms Mild rash of pink to red macules and swollen lymph nodes in children. Causes severe congenital defects in unborn babies, including deafness, blindness, microcephaly, and mental and growth retardation. Incubation period 7 to 14 days. Susceptibility Unvaccinated individuals and unborn babies. Treatment There is no specific treatment for rubella other than supportive therapy. R Prevention Immunization with the combined MM (measles, mumps, and rubella) vaccine. regnant women should not be given the live, attenuated vaccine. P Measles (Rubeola) LE A R N I N G O UTC O M E S 19.35 Describe the cause, signs and symptoms, and preven- tion of measles (rubeola). 19.36 Explain how subacute sclerosing panencephalitis (SSPE) develops from defective measles virions. Measles virus is another childhood disease that produces rashes. Measles, also known in the United States as rubeola28 or red measles, is the most contagious and one of the more serious childhood diseases. It should not be confused with the generally milder childhood rubella (German measles). Attenuated vaccine licensed 70 The rash of rubella. The disease, also known as German measles or three-day measles, is characterized by flattened red spots (macules). virus can move across the placenta even when the mother is asymptomatic. Pathogen and Pathogenesis 50 10 5 40 ‘06 ‘07 ‘08 ‘09 ‘10 ‘11 ‘12 ‘13 ‘14 ‘15 30 20 10 0 1966 ­ Rubella virus (Rubivirus) is an enveloped, icosahedral, single-stranded RNA virus. Rubella virus infects cells of the upper respiratory tract and spreads from there to lymph nodes, into the blood, and then throughout the body via the blood. Rubella virus does not kill infected cells, but it does cause dividing cells to make errors during DNA replication. The severity of rubella in adults is attributed to cell death resulting from a cellmediated immune response against virally infected cells. 15 Cases Cases (thousands) 60 20 ‘72 ‘78 ‘84 ‘90 Year ‘96 ‘02 ‘08 ‘14 ▲ FIGURE 19.12 The efficacy of immunization against rubella. The use of a live, attenuated virus vaccine has practically eliminated rubella in the United States. Epidemiology Rubella virus spreads through respiratory secretions and infects humans only. Patients shed virions (complete virus M19_BAUM7206_05_SE_C19.indd 578 28Rubeola is the name given to German measles (rubella) in some other countries. 11/30/16 9:02 PM       Viral Diseases of the Skin and Wounds Grandfather’s Shingles The Davises were excited about their newborn twin boys and couldn’t wait to take them to see Mrs. Davis’s father. Grand father was excited to see his first grandsons as well and thought their visit might help take his mind off the pain of his shingles, which had suddenly appeared only days before. ­ ­ CLINICAL CASE STUDY 7 measles patients in 1 million and is becoming much more rare as a result of childhood immunizations. TABLE 19.4 on p. 580 compares and contrasts the more serious measles with the milder rubella (German measles). 1. What virus is responsible for Grandfather’s shingles? 2. What likely triggered his case of shingles? 3. Are the new parents at risk of catching shingles from Grandfather? 4. Are the newborns at risk of contracting shingles from their grandfather? If Mrs. Davis asked your advice about taking her twins to visit her father, what would you recommend? 5. Could the twins be vaccinated against shingles before the visit? Signs and Symptoms Manifestations of measles include fever, sore throat, headache, dry cough, and conjunctivitis (inflammation of the lining of the eyelid). After two days of illness, lesions called Koplik’s spots appear on the mucous membrane of the mouth (FIGURE 19.13). These lesions, which have been described as crystals of salt surrounded by a red halo, last one to two days and provide a definitive diagnosis of measles. Red, raised (maculopapular) lesions then appear on the head and spread over the body. These later lesions, which initially are similar to those of rubella, are extensive and often fuse to form red patches, which gradually turn brown as the disease progresses. Rare complications of measles include pneumonia, encephalitis, deafness, blindness, and the extremely serious subacute sclerosing panencephalitis (SSPE). SSPE is a slow, progressive disease of the central nervous system that involves personality changes, loss of memory, muscle spasms, blindness, and death. The disease begins one to ten years after the initial infection with measles virus and lasts a few years before killing the patient. A defective measles virus that cannot make a capsid causes SSPE. The defective virus replicates and moves from brain cell to brain cell via cell fusion, limiting the functioning of infected cells and resulting in the symptoms. SSPE afflicts fewer than M19_BAUM7206_05_SE_C19.indd 579 Pathogen and Virulence Factors Measles virus (Morbillivirus) is a single-stranded RNA virus with an enveloped helical capsid. Besides adhesion proteins, the envelope has a fusion protein that triggers fusion between an infected cell and its neighbors, allowing the virus to pass from cell to cell and avoid antibodies. Pathogenesis Measles virus infects cells of the respiratory tract before spreading via lymph and blood throughout the body to infect the conjunctiva, urinary tract, small blood vessels, lymphatics, central nervous system, and skin. Cytotoxic T cells kill infected cells, causing most of the symptoms. Most patients recover within two to three weeks, though 1–5% of infected children die. Secondary infections by bacteria such as Staphylococcus or Streptococcus can increase the seriousness of measles. Patients with compromised cellular immunity, such as AIDS patients, can have continued measles infection, resulting in death. Epidemiology Measles virus is highly contagious. More than 80% of unvaccinated patients exposed to the virus develop symptoms 8–14 days later. Humans are the only host of measles virus, and a numerous, dense population of susceptible individuals must be present for the virus to spread via respiratory droplets from coughing and sneezing. In an unvaccinated population, measles outbreaks typically occur in one- to three-year epidemic cycles as a critical number of susceptible individuals is reached. Koplik’s spots in a mouth ▲ FIGURE 19.13 Oral lesions of measles (Koplik’s spots). 11/30/16 9:02 PM t a       Ch p er 19    Microbial Diseases of the Skin and Wounds TABLE 19.4 A Comparison of Measles and Rubella Complications Skin Rash Koplik’s Spots Rubella (also known as German measles, rubeola, or three-day measles) Togaviridae: Rubivirus Child, fetus Birth defects Mild Absent Measles (also known as rubeola or red measles) Paramyxoviridae: Morbillivirus Child neumonia, encephalitis, subacute sclerosing panencephalitis Every country in the Americas, even the poorest, has halted the spread of measles virus by immunization since the virus cannot spread when there are not enough susceptible people. Unfortunately, the immunization rate in Europe and in parts of the United States has decreased, allowing measles to reemerge (FIGURE 19.14). Epidemiologists are concerned about the reemergence of measles in Europe—the number of cases has at least quadrupled since 2009. This is directly related to the fact that vaccination rates in Europe have dropped below 90–95% of the population—the rate needed to halt viral transmission. The rate in the United Kingdom dropped to almost 50% following a fraudulent report in 1998 that suggested the vaccine caused autism in children. Diagnosis, Treatment, and Prevention The signs of measles, particularly Koplik’s spots, are sufficient for diagnosis, but serological testing can confirm the presence of measles antigen in respiratory and blood specimens. Treatment involves supportive therapy and administration of xtensive P Primary Patient(s) E Causative Agent P Disease resent vitamin A, antibodies against measles virus, and the antiviral drug ribavirin. Scientists introduced an effective, live, attenuated vaccine for measles in 1963. Research has shown that measles elimination requires achieving and sustaining a two-dose immunization coverage of at least 95% of a population. Pediatricians administer the two doses of measles vaccine, in combination with vaccines against mumps and rubella (MMR vaccine), to children in the United States at about 12 months and 4 years of age. In this manner, physicians have nearly eliminated measles as an endemic disease in the United States. Measles remains a frequent cause of death in other countries with lower immunization rates. Disease at a Glance 19.8 summarizes the features of measles. Other Viral Rashes LE A R N I N G O UTC O M E 19.37 Describe pathogenesis of erythema infectiosum and roseola infection. Rashes characterize other rare childhood viral diseases. Here we consider erythema infectiosum and roseola. 600 Cases 500 Cases (thousands) 800 400 Erythema Infectiosum 300 Erythema infectiosum (er-i-thē’mă in-fek-shē-ō’sŭm) is a respiratory disease caused by a single-stranded DNA (ssDNA) virus called B19 virus in the genus Erythrovirus, family Parvoviridae. As the name implies, the disease manifests as an infectious reddening of the skin. The disease is also known as fifth disease because it was the fifth childhood rash on a list used by pediatricians in the early 1900s. (The others were often listed as scarlet fever, rubella, measles, and a mild scarlet fever–like illness called Duke’s disease.) The rash of erythema infectiosum begins on the cheeks and spreads to the arms, thighs, buttocks, and trunk. The facial rash appears as if the patient has been slapped, a characteristic that child protection workers could misinterpret (FIGURE 19.15). Sunlight aggravates the rash at all stages; earlier lesions fade as the disease progresses, though they can reappear when the patient is exposed to sunlight. Infected adults who missed the disease in childhood may suffer anemia, joint pain, and rarely 200 600 100 400 ‘06 ‘07 ‘08 ‘09 ‘10 ‘11 ‘12 ‘13 ‘14 ‘15 Attenuated vaccine licensed 200 0 1950 ‘56 ‘62 ‘68 ‘74 ‘80 ‘86 Year ‘92 ‘98 ‘04 ‘10 ‘16 ▲ FIGURE 19.14 Measles cases in the United States since 1950. The number of cases has declined dramatically since immunization began in 1963. Why does the measles vaccine pose risks for immunocompromised contacts of vaccinated children? Figure 19.14 Measles vaccine is an attenuated live vaccine; thus, it can replicate and cause disease in immunocompromised patients. M19_BAUM7206_05_SE_C19.indd 580 11/30/16 9:02 PM 19.8 E  E E DIS AS AT A GLANC       H Mycoses of the air, Nails, and Skin Measles R Cause Morbillivirus (rubeola virus) (enveloped, negative, single-stranded NA virus). Virulence factors Adhesion proteins, fusion proteins, intracellular infection. R Portal of entry espiratory tract. Signs and symptoms Fever, sore throat, headache, dry cough, conjunctivitis, Koplik’s spots, and maculopapular rash. Incubation period 8 to 12 days. Susceptibility Unvaccinated individuals. Treatment Supportive therapy, ribavirin, vitamin A, and antibodies against the virus. characteristic of this parvovirus-caused disease. R Prevention Immunization with the combined MM (measles, mumps, and rubella) vaccine. The vaccine contains live, attenuated measles virus. ▲ FIGURE 19.15 A case of erythema infectiosum (fifth disease). Distinct reddening of facial skin that resembles the result of a slap is Now that we have examined some bacterial and viral diseases of the skin, we turn our attention to fungal diseases of the skin, hair, and nails. Mycoses of the Hair, Nails, and Skin LE A R N I N G O UTC O M E S 19.38 Define mycosis. 19.39 Describe four general types of mycoses based on loca- tion in the body. miscarriage in addition to the rash. Treatment involves use of nonsteroidal anti-inflammatory drugs (NSAIDs). Roseola Roseola (rō-zē-ō’lă) is an endemic illness of children characterized by an abrupt fever, sore throat, enlarged lymph nodes, and a faint pink rash on the face, neck, trunk, and thighs. The name of the disease is derived from its characteristic rose-colored rash. A herpesvirus in the genus Roseolovirus, known simply as human herpesvirus 6 (HHV-6), causes roseola. Some researchers link HHV-6 with the development of multiple sclerosis in adults, and there is some evidence that HHV-6 infection makes individuals more susceptible to HIV infection and AIDS. No pharmaceutical treatment exists. TELL ME WHY Why has the number of cases of measles increased dramatically, especially in Europe? M19_BAUM7206_05_SE_C19.indd 581 Mycoses (fungal diseases) are traditionally classified according to the locations within the body that they affect. Physicians classify mycoses as superficial (on the surface), cutaneous (in the skin), subcutaneous (in the hypodermis and muscles), or systemic (affecting numerous systems). The fungi that cause mycoses are mainly opportunistic. Superficial and cutaneous mycoses of the hair, nails, and skin are generally not life threatening, though they may cause chronic or recurring diseases. (Mycoses affecting the blood and organs of the body may also secondarily affect the skin, but they are considered in later chapters when we discuss the other body systems.) We begin our survey by considering mycoses affecting the hair, nails, and skin. Superficial Mycoses LE A R N I N G O UTC O M E 19.40 Describe the clinical and diagnostic features of superfi- cial fungi, as exemplified by Malassezia infections. 11/30/16 9:02 PM t a       Ch p er 19    Microbial Diseases of the Skin and Wounds Superficial mycoses, which are the most common fungal infections, are confined to the hair, nails, and outer layers of the skin, all of which are composed of dead cells filled with keratin. Surface mycoses are acquired by direct contact with the hyphae or spores of opportunistic fungi. An example of a superficial mycosis is pityriasis. Signs and Symptoms Pityriasis versicolor (pit-i-rī’ă-sis vēr’si-cŏl-ŏr) is characterized by hypopigmented or hyperpigmented patches of scaly skin resulting from fungal interference with melanin production (FIGURE 19.16). This condition, which typically occurs on the trunk, shoulders, and arms, and rarely on the face and neck, is called versicolor in reference to the variable pigmentation seen in affected individuals. Pathogens and Virulence Factors Malassezia furfur (mal-ă-sē’zē-ă fur’fur), a dimorphic basidiomycete and a normal inhabitant of human skin around the world, causes pityriasis. It feeds on oil produced by the skin, causing infections that tend to be chronic. Pathogenesis and Epidemiology Superficial fungi produce keratinase, an enzyme that dissolves keratin. These fungi do not penetrate living tissues and do not trigger immune responses, which differentiates them from the cutaneous and subcutaneous pathogens (discussed shortly). Transmission of the fungi of pityriasis onto the surface of the skin is usually mediated via shared hairbrushes and combs, and several members of a family may be infected at the same time. Adolescents are more likely to be afflicted, possibly as a result of increased sebum production related to hormonal changes. In severely immunocompromised patients, superficial infections can spread to cover significant areas of skin or invade deeper tissues and become systemic. Diagnosis, Treatment, and Prevention The quickest way to diagnose M. furfur infections is to examine the patient under ultraviolet illumination with a wavelength of 365 nm; patches of skin infected with M. furfur fluoresce pale green. However, fluorescence under ultraviolet is not a definitive diagnosis, because some other fungi also fluoresce. Definitive diagnosis requires microscopic examination. Preparations of skin samples mixed with 10% KOH reveal both masses of budding yeast and short hyphal forms that are diagnostic for M. furfur. Superficial Malassezia infections are treated topically with solutions of ciclopirox or antifungal imidazoles, such as ketoconazole shampoos. Alternatively, topical applications of zinc pyrithione, selenium sulfide lotions, or propylene glycol solutions can be used. Oral therapy with ketoconazole may be required to treat extensive infections and infections that do not respond to topical treatments. Relapses are common, and prophylactic topical treatment may be necessary. The skin takes months to regain its normal pigmentation following successful treatment. Cutaneous Mycoses LE A R N I N G O UTC O M E S 19.41 Describe dermatophytoses in general. 19.42 Explain why cutaneous mycoses are not as common as superficial mycoses. Some fungi that grow on humans manifest clinically as cutaneous lesions called dermatophytoses (der’mă-tō-fī-tō’sēz). They are caused by dermatophytes, which are fungi that grow on skin, nails, and hair and invade the body, where they stimulate cell-mediated immune responses that damage deeper tissues. Such triggering of immune responses distinguishes dermatophytoses from superficial fungal infections. Signs and Symptoms In the past, dermatophytoses were often called ringworms or tineas (tin’ē-ăs)29 because dermatophytes produce circular, scaly patches that made observers think a worm lay just below the surface of the skin (FIGURE 19.17). Though these diseases are doubly misnamed—worms are not involved, and the term phyte implies plants, not fungi—these common terms remain in use. Most dermatophytoses are clinically distinctive and so common that they are readily recognized; for example, athlete’s foot is a dermatophytosis (FIGURE 19.18). Dermatophytoses can have a variety of other clinical manifestations, some of which are summarized in TABLE 19.5. ▲ FIGURE 19.16 Pityriasis versicolor. The variably pigmented skin patches are caused by Malassezia furfur. M19_BAUM7206_05_SE_C19.indd 582 29Latin, meaning “worms.” 11/30/16 9:02 PM       H Mycoses of the air, Nails, and Skin ▲ FIGURE 19.18 Athlete’s foot. Dermatophytosis of skin on the foot. All three genera cause skin and nail infections, and Trichophyton species also infect hair. ▲ FIGURE 19.17 Dermatophytosis (ringworm). This is a cutaneous fungal disease, in this case on the neck. What three genera cause most dermatophytoses? E Figure 19.17 Trichophyton, Microsporum, and pidermophyton are the more common causes of ringworms. Pathogens Three genera of ascomycetes are responsible for most dermatophytoses: • Microsporum (mī-kros’po-rŭm) species • Trichophyton (trik-ō-fī’ton) species • Epidermophyton floccosum (ep’i-der-mof’i-ton flŏk’ō-sŭm) Pathogenesis Dermatophytes use keratin as a nutrient source and thus colonize dead layers of skin, nails, and hair. They also trigger destruction of living cells by the immune system. The fungi involved in cutaneous and subcutaneous mycoses commonly grow on decaying matter in the soil. Infection requires introduction of fungal elements into the living, deeper layers of skin. Thus, exposure is common, but infection is rare. Most dermatophytoses remain localized to the dermis and hypodermis; infections rarely become systemic. Epidemiology Dermatophytes are among the few contagious fungi. Spores and bits of hyphae, along with dead skin cells and hair, are TABLE 19.5 Common Dermatophytoses Common Signs Source Tinea pedis (“athlete’s foot”) Trichophyton rubrum; T. mentagrophytes var. interdigitale; Epidermophyton floccosum ed, raised lesions on and around the toes and soles of the feet; webbing between the toes is heavily infected uman reservoirs in toe webbing; carpeting holding infected skin cells Tinea cruris (“jock itch”) T. rubrum; T. mentagrophytes var. interdigitale; E. floccosum Tinea unguium (onychomycosis) T. rubrum; T. mentagrophytes var. interdigitale Superficial white onychomycosis: patches or pits on the nail surface Usually spreads from the feet H R ed, raised lesions on and around the groin and buttocks H Agents R Disease umans Invasive onychomycosis: yellowing and thickening of the distal nail plate, often leading to loss of the nail ed, raised, ringlike lesions occurring on various skin surfaces (tinea corporis on the trunk, tinea capitis on the scalp, tinea barbae of the beard) Can spread from other body sites; can be acquired following contact with contaminated soil or animals Tinea capitis M. canis; M. gypseum; T. equinum; T. verrucosum; T. tonsurans; T. violaceum; T. schoenleinii ctothrix invasion: fungus develops arthroconidia on the outside of the hair shafts, destroying the cuticle umans; can be acquired following contact with contaminated soil or animals E E ndothrix invasion: fungus develops arthroconidia inside the hair shaft without destruction H T. rubrum; Microsporum gypseum; M. canis R Tinea corporis Favus: crusts form on the scalp, with associated hair loss M19_BAUM7206_05_SE_C19.indd 583 11/30/16 9:02 PM t constantly shed from infected individuals, making recurrent infections common. Dermatophytes infecting humans are classified according to their natural habitats as follows: • Anthropophilic dermatophytes are associated with humans only and are transmitted either by close human contact or through the sharing of contaminated fomites. • Zoophilic dermatophytes are associated with animals; the fungi are transmitted to humans either by close contact with pets or other animals or through contaminated animal products such as wool. • Geophilic dermatophytes are soil fungi that are transmitted to humans via direct exposure to soil or to dusty animals. Diagnosis, Treatment, and Prevention Clinical observation is generally sufficient to diagnose infections with dermatophytes. Potassium hydroxide (KOH) preparations of skin or nail scrapings or hair samples can reveal hyphae and/or conidia (asexual spores), which confirm the diagnosis. When desired, the determination of the specific identity of a dermatophyte requires microscopic examination of a laboratory culture, which may take weeks because these fungi grow slowly in the laboratory. Limited infections can be treated effectively with topical antifungal agents, but more widespread infections of the scalp or skin, as well as nail infections, must be treated with oral agents. Terbinafine, administered topically for one to four weeks, is effective in most cases. Chronic or stubborn cases are treated with griseofulvin until cured. pe-drō’sō-ē), F. compacta (kom-pak’ta), Phialophora verrucosa (fī-ă-lof’ŏ-ră ver-ū-kō’să), and Cladophialophora carrionii (klădŏf’ē-ă-lŏf-ŏ-rā kar-rē-ŏn’-ē). Initially, chromoblastomycosis uniformly appears as small, itchy but painless, scaly lesions on the skin resulting from fungal growth in subcutaneous tissues near the site of a wound. Over the course of several years, the lesions progressively worsen, becoming large, flat to thick, tough, and wartlike. They become tumorlike and extensive if not treated (FIGURE 19.19). Inflammation, development of fibrous tissue, and abscess formation occur in surrounding tissues. The fungus can spread throughout the body. Microscopic examination of stained skin scrapings reveals the key distinguishing feature of this fungal disease—golden brown bodies that are distinctive and distinguishable from budding yeast. Determining the exact species of fungus relies on laboratory culture, macroscopic examination of colonies on agar, and microscopic examination of spores. Chromoblastomycosis is difficult to treat, especially in advanced cases, and often the disease cannot be cured. The earlier treatment begins, the more likely it will be successful. For treatment, physicians must remove infected and surrounding tissues—extensive lesions may require amputation— and prescribe a prolonged course of thiabendazole and 5-fluorocytosine. Despite the worldwide occurrence of the fungi, the overall incidence of chromoblastomycosis is relatively low. People who work daily in the soil with bare feet are at risk due to accidental foot wounds. The simple act of wearing shoes greatly reduces the number of infections. ­ a       Ch p er 19    Microbial Diseases of the Skin and Wounds Phaeohyphomycosis Wound Mycoses Of the more than 30 genera of fungi that cause phaeohyphomycosis31 (fē’ō-hī’fō-mī-kō’sis), the more common are the ascomycetes Alternaria (al-ter-nā’rē-ă), Exophiala (ek-sō-fī’ă-lă), Wangiella LE A R N I N G O U TC O M E S 19.43 State the specific difference between chromoblastomy- cosis and phaeohyphomycosis. 19.44 Define mycetomas, and describe their appearance, cause, and treatment. 19.45 Describe how the lesions of lymphocutaneous sporo- trichosis correlate with its spread through the lymphatic system. Some fungi grow on deeper tissues in the body, including the hypodermis and bone, but they do not become systemic; that is, they do not spread throughout the body’s systems. Such fungi eventually grow up into the epidermis to produce lesions on the skin’s surface. Among these mycoses of wounds are chromo­ blastomycosis and phaeohyphomycosis, which are similar mycoses caused by melanin-producing, dark-pigmented fungi; mycetoma; and sporotrichosis. Here we consider these conditions in order. Chromoblastomycosis ­ Four species of ascomycete fungi cause chromoblastomyco sis 30 (krō’mō-blas’tō-mī-kō’sis): Fonsecaea pedrosoi (fon-sē-sē’ă 30From Greek chroma, meaning “color”; blastos, meaning “germ”; and mykes, meaning “fungus.” M19_BAUM7206_05_SE_C19.indd 584 ▲ FIGURE 19.19 A leg with extensive lesions of chromoblastomycosis. Fonsecaea pedrosoi caused this case. Greek phaios, meaning “dusky”; hyphe, meaning “web”; and mykes, meaning “fungus.” 31From 11/30/16 9:02 PM CLINICAL CASE STUDY       H Mycoses of the air, Nails, and Skin (sood’-al-es-kē’rē-ă), Exophiala (ek-sō-fī’ă-lă), and Acremonium (ak-rĕ-mō’nē-ŭm). These fungi are distributed worldwide, but infection is most prevalent in countries near the equator. Prick wounds and scrapes caused by twigs, thorns, or leaves introduce these fungi into humans. As with chromoblastomycosis and phaeohyphomycosis, people who work barefoot in soil are most at risk, and wearing protective shoes or clothing can greatly reduce infection. Infection begins near the site of a wound with the formation of small, hard, subsurface nodules that slowly worsen and spread as time passes. Local swelling occurs, and ulcerated lesions produce pus. Infected areas release an oily fluid containing fungal spores and hyphae. The fungi spread to more tissues, destroying bone and causing permanent deformity (FIGURE 19.20). A combination of the symptoms and microscopic demonstration of fungi in samples from the infected area is diagnostic for mycetomas. Laboratory culture of specimens produces macroscopic colonies that can be identified down to the level of species. Treatment involves surgical removal of the mycetoma that may, in severe cases, involve amputation of an entire limb. Surgery is followed by one to three years of antifungal therapy with ketoconazole. Though slowly growing, the fungi invade body tissues; thus, even combinations of surgery and antifungal agents do not always cure the disease. Is It Athlete’s Foot? H H H H A 30-year-old man comes into a community clinic complaining of persistent redness, itching, and peeling skin on the soles of his feet and between his toes. e states that he works out daily and plays on several sports teams. e concluded that he has athlete’s foot, but every over-the-counter antifungal agent he has tried has failed to cure his condition. e has finally come to the clinic because his toenails have begun to thicken, yellow, and detach from the nail bed. is condition is pictured. 1. Given the information here, can athlete’s foot be diagnosed definitively? If not, what laboratory tests could be performed to positively diagnose the condition and identify the infecting organism? 2. What treatment is likely? Would the recommended treatment be different if two fungal species, and not just one fungal species, were present? Sporotrichosis ­ (wang-gē-el’ă), and Cladophialophora. Phaeohyphomycosis is acquired when spores, which are prevalent in indoor environments, including hospitals, enter open surgical or traumatic wounds. Phaeohyphomycoses are more variable in presentation than are chromoblastomycoses. For example, paranasal sinus phaeohyphomycosis involves colonization of the nasal passages and sinuses; it occurs in allergy sufferers and AIDS patients. In cerebral phaeohyphomycosis, the fungus actively invades the brain. Fortunately, this is the most rare form of phaeohyphomycosis and occurs only in the severely immunocompromised. Some cases of phaeohyphomycosis can be treated with itraconazole, but the disease is permanently destructive to tissues. Microscopic examination of stained skin scrapings, biopsy material, or cerebrospinal fluid (CSF) reveals brownpigmented hyphae, which are diagnostic. Determining the species of fungus relies on laboratory culture, macroscopic examination of colonies on agar, and microscopic examination of spores. Sporothrix schenckii (spōr’ō-thriks shen’kē-ē) is a dimorphic ascomycete that causes sporotrichosis (spōr’ō-tri-kō’sis), or rose gardener’s disease, a subcutaneous infection usually limited to the arms and legs. S. schenckii resides in the soil and is most commonly introduced in wounds by thorn pricks or wood splinters. Avid gardeners, farmers, and artisans who work with natural plant materials have the highest incidence of sporotrichosis. Though distributed throughout the tropics Mycetomas Fungal mycetomas (mī-sē-tō’maz) are tumorlike infections of the skin, fascia (lining of muscles), and bones of the hands or feet caused by soil fungi of several genera in the division Ascomycota: Madurella (mad’ū-rel’ă), Pseudallescheria M19_BAUM7206_05_SE_C19.indd 585 ▲ FIGURE 19.20 A mycetoma of the ankle. The bone and other tissues were invaded and destroyed by a fungus (in this case, Madurella mycetomatis). 11/30/16 9:02 PM t a       Ch p er 19    Microbial Diseases of the Skin and Wounds and subtropics, most cases occur in Latin America, Mexico, and Africa. The disease is also common in warm, moist areas of the United States. Fixed sporotrichosis initially appears as painless, nodular lesions that form around the site of inoculation. With time, these lesions produce a pus-filled discharge, but they remain localized and do not spread. In lymphocutaneous sporotrichosis, however, the fungus enters the lymphatic system near the site of a primary lesion, giving rise to secondary lesions on the skin surface along the course of lymphatic vessels (FIGURE 19.21). The fungus remains restricted to subcutaneous tissues and does not enter the blood. Microscopic observation of pus or biopsy tissue stained with silver can reveal budding yeast forms in severe infections, but often the fungus is present at a low density, making direct examination of clinical samples a difficult method of diagnosis. The patient’s history and clinical signs, plus the observation of the dimorphic nature of S. schenckii in laboratory culture, are considered diagnostic for sporotrichosis. Cutaneous lesions can be treated successfully with topical applications of saturated potassium iodide for several months. Itraconazole and amphotericin B are also useful treatments. Prevention requires wearing gloves, long clothing, and shoes to prevent inoculation. TELL ME WHY Onychomycoses (on’i-kō-mī-kō’sēs) are nail infections that can be caused by several species of fungi. Why are these mycoses so difficult to treat? Why is it generally necessary to treat patients with antifungal agents for long periods of time? Leishmaniasis LE A R N I N G O UTC O M E 19.46 Describe leishmaniasis, including its cause, signs and symptoms, pathogenesis, epidemiology, diagnosis, and treatment. Leishmaniasis (lēsh’mă-nī’ă-sis) is a zoonosis—a disease of animals transmitted to humans. An intracellular parasitic protozoan causes this disease of the skin and oral mucous membrane. Signs and Symptoms The clinical manifestations of leishmaniasis depend on the species of pathogen, the geographical location of hosts and vectors, and the immune response of the infected host. Three clinical forms of leishmaniasis are commonly observed: • Cutaneous leishmaniasis involves large, painless skin ulcers that form around bite wounds made by the disease vector. Such lesions often become secondarily infected with bacteria. Scars remain when the lesions heal. • Mucocutaneous leishmaniasis results when skin lesions enlarge to encompass the mucous membranes of the mouth, nose, or soft palate. Damage is severe and permanently disfiguring (FIGURE 19.22). Neither of these forms of leishmaniasis is fatal. • Visceral leishmaniasis (also known as kala­azar) is typically fatal in 100% of untreated cases. In this disease, macrophages spread the parasite to the liver, spleen, bone marrow, and lymph nodes. Inflammation, fever, weight loss, and anemia increase in severity as the disease progresses. Visceral leishmaniasis is becoming increasingly problematic as an opportunistic infection among AIDS patients. Parasitic Infestations of the Skin Some parasitic protozoa and arthropods infest the skin and cause diseases. Here we examine an example of each, beginning with leishmaniasis. ▲ FIGURE 19.21 Lymphocutaneous sporotrichosis on the arm. The locations of these secondary, subcutaneous lesions correspond to the course of lymphatic vessels leading from sites of primary, surface lesions. How is sporotrichosis contracted? Figure 19.21 Sporotrichosis is contracted when this soilborne fungus is inoculated into the skin by thorn pricks and scratches. M19_BAUM7206_05_SE_C19.indd 586 ▲ FIGURE 19.22 Mucocutaneous leishmaniasis. The large skin lesions are permanently disfiguring. 11/30/16 9:02 PM       P arasitic Infestations of the Skin CLINICAL CASE STUDY Diagnosis in the Desert E In the 1970s, archeologists unearthed a vast cemetery in the Atacama Desert of Chile. Because the Atacama is the driest desert on arth, bodies over 800 years old were better preserved than might be expected. Some facial and brain tissues were mummified. The skulls of four women appeared as if the bone had been eaten, though it was obvious to the archeologists that the women had lived with the condition and died from other causes. It wasn’t until 2009 that scientists were able to solve the mystery of these skulls. Genetic analysis of tissue samples revealed that a flagellated protozoan had moved from facial lesions to the women’s skulls, slowly eating them away over a 20-year period. 1. What skin pathogen caused the disfigurement? 2. How did the women become infected? 3. If the women were infected today, what treatment would be given? Most cases of leishmaniasis heal without treatment (though scars may remain) and confer immunity upon the recovered patient. At one time, lesions were purposely encouraged on the buttocks of small children both to induce immunity and to prevent lesions from forming elsewhere and leaving more-visible scars. Treatment, which is required for more serious infections, involves administering amphotericin B or sodium stibogluconate, an antimicrobial drug that contains the heavy metal antimony. Prevention is essentially limited to reducing exposure by controlling reservoir host and sand fly populations. For example, rodent nesting sites and burrows can be destroyed around human habitations to reduce contact with potentially infected reservoir populations. In some areas, infected dogs are also destroyed to eliminate this reservoir. Insecticide used around homes reduces the number of sand flies, and personal use of insect repellents, protective clothing, and netting further limits exposure. A vaccine for leishmaniasis does not currently exist. Scabies LE A R N I N G O UTC O M E 19.47 Describe the cause, signs and symptoms, and treatment of scabies. A 17th-century Italian physician made one of the earlier connections between tiny organisms and human disease by showing that an arachnid causes a common skin disease, scabies. Pathogen and Virulence Factors Signs and Symptoms Leishmania (lēsh-man’ē-ă), the cause of leishmaniasis, is a flagellated protozoan commonly hosted by wild and domestic dogs and small rodents. Infected female sand flies of the genera Phle­ botomus (fle-bot’ō-mŭs) and Lutzomyia (lūts-ŏm’yē-a) transmit Leishmania from animals to humans through their bites. Of the 30 known species of Leishmania, 21 can infect humans. Scabies is characterized by intense itching, especially at night, and a rash localized to infested areas of the skin. The rash appears as pimple-like irritations or short, slightly raised burrows under the surface of the skin. Lesions are more commonly found in the webbing between fingers; in skin folds of the wrists, elbows, or knees; and around the genitalia, though any area of skin can be affected. Scratching often compounds the symptoms by introducing Staphylococcus or Streptococcus into the wounds, which triggers bacterial infections, including impetigo. Pathogenesis and Epidemiology Upon initial infection, the parasites infect macrophages, which become activated but not sufficiently to kill the intracellular Leishmania. Chemicals released by infected macrophages stimulate inflammatory responses that continue to be propagated by the infection of additional macrophages. Leishmaniasis is endemic in parts of the tropics and subtropics, including Central and South America, central and southern Asia, Africa, Europe, and the Middle East. Of the more than 12 million new cases of leishmaniasis worldwide each year, over 60,000 are fatal. Diagnosis, Treatment, and Prevention Microscopic identification of protozoa in samples from cutaneous lesions, the spleen, or bone marrow is diagnostic. Immunoassays using antibodies to detect antigen confirm the diagnosis and identify the strain. Genetic analysis using PCR is needed for definitive speciation. M19_BAUM7206_05_SE_C19.indd 587 Pathogen and Virulence Factors The mite Sarcoptes scabiei (sar-kop’tēz skā’bē-ī) causes scabies. This burrowing arachnid has a body about 300 mm long covered with ridges, spines, and hairs (FIGURE 19.23). As it burrows, the mite damages nerve endings (see Figure 19.1a), and its antigens trigger inflammation. Pathogenesis and Epidemiology Adult female mites live up to a month in human skin, where they burrow to lay their eggs, producing the itching blisters. Symptoms may take four to six weeks to develop as type IV (delayed) hypersensitivity plays a role in a patient’s reaction. Infested patients spread the mites from one part of their body to another and pass the parasites to others during 11/30/16 9:02 PM t a       Ch p er 19    Microbial Diseases of the Skin and Wounds under age 15 and people with weakened immune systems. Epidemics occur among people in crowded conditions such as hospitals, nursing homes, army barracks, day care centers, prisons, and refugee camps. Diagnosis, Treatment, and Prevention SEM 100 µm ▲ FIGURE 19.23 Scabies mites (Sarcoptes scabiei) burrowing in human skin. Dermatologists diagnose scabies by the characteristic burrows of the mites and by finding the microscopic mites, eggs, or fecal matter in skin scrapings. However, since there are typically fewer than 10 mites on the entire body of a patient, clinicians may miss them. Treatment involves the use of mite-killing lotions applied to the entire body below the neck for eight hours. Since such lotions are absorbed into the blood, frequent use or application on infants or pregnant or lactating women is ill advised. All clothing, bedding, and towels of a patient must be thoroughly washed in hot water and dried in a hot dryer to kill mites and their eggs. Itching may continue for two to three weeks after all mites have been killed. Immunity to scabies does not develop; the only preventive is good personal hygiene. Patients must avoid contact with infested individuals and their fomites. TELL ME WHY Why don’t physicians prescribe penicillin or erythromycin to treat leishmaniasis? E E GING DIS AS CAS STUDY E M ER E prolonged bodily contact or by sharing clothing, towels, or bedding, particularly in crowded conditions regardless of personal hygiene. Sexual transmission is common. Physicians estimate that 300 million individuals develop scabies each year throughout the world; most are children Monkeypox H H M19_BAUM7206_05_SE_C19.indd 588 ­ ­ ­ Jacob’s doctor had been unable to diagnose the disease, but an infectious disease specialist had finally confirmed monkeypox—a disease named for monkeys who can get the disease. In reality, monkeypox is a disease of rodents, including prairie dogs. Final investigation revealed that the pet wholesaler who had supplied Doggy to Jacob’s pet store in Illinois had also supplied African monkeys to stores in Texas. At least one of those monkeys had been infected with monkeypox virus—a virus closely related to smallpox virus. The monkey had infected Doggy, who had then infected Jacob. Jacob was sick for four weeks, but monkeypox is not as virulent as smallpox, so Jacob recovered with only some scars as a reminder that not all unusual pets are a blessing. ­ Jacob was excited about the pet he got for his birthday; he was the only boy at school who had a prairie dog! Common dogs were boring; his prairie dog could climb up the drapes, run through plastic tube mazes, and sit on Jacob’s shoulder to eat. “Doggy” was the best. In fact, everything would have been just about perfect if only Jacob weren’t sick in bed. Two weeks after his birthday, Jacob was exhausted and felt terrible. e had fever accompanied by headache and muscle aches, so his mother kept him home from school. Then the lymph nodes in his neck and armpits became swollen, and he developed frightening, large raised lesions all over his face and hands. e was really sick. For the next three weeks, the lesions became crusty and then fell off, only to be replaced by new lesions. Jacob felt awful and missed playing with Doggy, who had been confined to his cage while Jacob stayed in bed. 1. Why did Jacob’s lymph nodes swell during the course of a skin disease? 2. Why didn’t the doctor prescribe penicillin or tetracycline? 3. How can a virus of rodents possibly cause a disease of monkeys and humans? 11/30/16 9:03 PM       Chapter Summary A Case of Acne or Something More? H After examining Kate and hearing about her trip to Colorado, Dr. Moore tells Kate that she most likely got an infection from the hot tub at the resort. The doctor takes a specimen from Kate’s pimples to send for lab analysis. The pimples are the result of folliculitis; while Kate is currently feeling some discomfort, the condition should clear up on its own. Dr. Moore recommends the use of an over-the-counter anti-itch cream containing hydrocortisone to help relieve some of the discomfort. e also recommends that Kate contact the resort and inform them of her condition; other guests may also have been infected. When Kate contacts the resort, she finds out that four other guests have already reported similar symptoms after using the hot 589 tub. The resort manager informs Kate that the local health department tested the hot tub and found Pseudomonas aeruginosa. Dr. Moore calls Kate with the lab results—P. aeruginosa was cultured from her pimples. Kate continues to use the anti-itch cream, and within a week, her pimples are gone. 1. What are two virulence factors that P. aeruginosa uses to cause infection? Explain how each of these contributes to pathogenicity. 2. Describe the steps in the development of Kate’s folliculitis. Start with Kate’s soaking in the hot tub through the formation of her pimples. CHAPTER SUMMARY Structure of the Skin (pp. 552–553) 1. The skin is composed of a dermis and an epidermis. 2. The leathery dermis, which contains sweat glands, oil glands, and hair follicles, provides strength and resiliency and supports the overlying epidermis. The epidermis, which is continually replaced, is an oily, salty, waterproof barrier against pathogens. 3. A skin wound is trauma to the epidermis or dermis. Pathogens can enter the body through wounds. Microbiome of the Skin (pp. 553–554) 1. The skin surface, hair follicles, and sweat ducts are home to a variety of members of the microbiome, or normal microbiota. Examples include Staphylococcus and diphtheroids. Bacterial Diseases of the Skin and Wounds (pp. 554–569) 1. Folliculitis can occur at the base of a hair follicle (called a pimple) or at the base of an eyelid (called a sty). A boil, or furuncle, results when infection spreads to surrounding tissues. When several furuncles join, a carbuncle is formed. 2. Staphylococcus epidermidis and S. aureus are common on the skin. Virulence factors of the latter include enzymes, antiphagocytic capsule, protein A, and toxins. 3. Because resistant strains of Staphylococcus have become common, aseptic techniques are especially important in hospitals to protect patients. M19_BAUM7206_05_SE_C19.indd 589 4. Some strains of Staphylococcus aureus secrete exfoliative toxins that dissolve the proteins that hold cell membranes together. The result is staphylococcal scalded skin syndrome (SSSS), a condition in which the epidermis peels off in sheets. 5. Impetigo, also called pyoderma, is a contagious skin disease caused by Staphylococcus aureus or Streptococcus pyogenes (group A Streptococcus). Erysipelas results when impetigo infections spread to lymph nodes. Impetigo and erysipelas are more common in children and in the elderly. 6. Necrotizing fasciitis, commonly caused by group A Streptococcus (S. pyogenes), is a painful disease characterized by a red painful lesion, flulike symptoms, digestion of connective tissue around muscles, toxemia, and often death. 7. Acne pimples are commonly composed of dead Propionibacterium acnes or Staphylococcus aureus bacteria combined with living leukocytes. Dead bacteria that block pores form blackheads. Cysts can rupture and form scar tissue. 8. Bartonella henselae is carried by cats and causes cat scratch disease when introduced through a scratch or bite. 9. Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen producing pyocyanin, a blue-green pigment. The microbe kills cells, destroys tissues, and triggers shock in immunocompromised patients and burn victims, and it causes otitis externa (swimmer’s ear). 10. Ticks carry rickettsias, which cause spotted fever rickettsioses, most notably Rocky Mountain spotted fever (RMSF) caused by Rickettsia rickettsii. Rash, flulike symptoms, and, sometimes, 11/30/16 9:03 PM 590     Chapter 19    Microbial Diseases of the Skin and Wounds subcutaneous hemorrhages called petechiae characterize rickettsiosis. In severe cases, system failures, encephalitis, and death occur. Koplik’s spots in the mouth. Rare complications include subacute sclerosing panencephalitis (SSPE), a slow progressive disease of the central nervous system. 11. Cutaneous anthrax results when Bacillus anthracis infects a cut in the skin, producing a crusty, black ulcer called an eschar. 9. Viruses also cause erythema infectiosum (fifth disease) and roseola. 12. Ischemia in a tissue results from interrupted blood supply; without oxygen, necrosis (death) sets in. Gas gangrene (gangrene) develops in dead tissue infected with Clostridium endospores. Mycoses of the Hair, Nails, and Skin (pp. 581–586) Viral Diseases of the Skin and Wounds (pp. 569–581) 1. Poxvirus causes smallpox, orf, cowpox, and monkeypox. Lesions progress from flat macules to raised papules, vesicles, and pusfilled pustules (also called pox). 2. Smallpox virus (variola virus) exists in two strains: variola major and variola minor. Except for laboratory stocks, worldwide immunization has eradicated smallpox virus. 3. Human herpesvirus 1 and human herpesvirus 2 cause oral and genital herpes. Herpetic gingivostomatitis is a severe infection in the oral cavity. If herpesvirus enters a cut in the finger, a whitlow (blister) may occur. Herpes gladiatorum is the name of lesions acquired by athletes. 4. Inactive herpesviruses in nerve cells may reactivate to cause recurrence of symptoms. 5. Warts (papillomas) are growths of epithelium or mucous membranes. 6. Varicella-zoster virus (VZV) causes chickenpox (also known as varicella) in children and adults, and it causes a recurrent disease, shingles (also known as herpes zoster), in adults. 7. Rubella (also called German measles or three-day measles) is caused by Rubivirus. The disease is mild in children but more serious in adults and fetuses. 8. Measles virus causes rubeola (red measles), a serious, contagious childhood disease characterized by widespread rash and by 1. Mycoses are fungal diseases. Superficial mycoses are fungal infections that produce the enzyme keratinase, which dissolves keratin of the hair, nails, and skin. Pityriasis versicolor results from interference with melanin production in patches of skin. 2. Cutaneous mycoses are dermatophytoses (formerly called ringworms or tineas). Fungi growing on skin, nails, or hair stimulate immune responses in underlying tissues, causing dermatophytoses. 3. Ascomycete fungi that infect wounds cause chromoblastomycosis, which progressively manifests as lesions, warts, and tumors. 4. Phaeohyphomycosis is typically caused by invasion of ascomycete (fungal) spores in traumatic or surgical wounds. 5. Several genera of soil ascomycetes cause invasive, tumorlike skin infections called mycetomas. 6. Sporotrichosis is a cutaneous or subcutaneous disease caused by inoculation with Sporothrix, often by thorn pricks from roses. Parasitic Infestations of the Skin (pp. 586–589) 1. Leishmania is a parasitic protozoan transmitted to humans by sand flies. It causes leishmaniasis, a zoonosis (disease of animals transmitted to humans) that can be cutaneous, mucocutaneous, or visceral. 2. The mite Sarcoptes scabiei causes scabies, a disease of itchy blisters, often on the webbing between the fingers. Scratching can introduce bacteria into the wounds, leading to impetigo. QUESTIONS FOR REVIEW Answers to the Questions for Review (except Short Answer questions) begin on page A-1. Multiple Choice 1. The epidermis                 . a. has an intricate network of blood vessels b. consists of layers of loosely packed cells c. contains a waterproofing protein d. has a thin layer of fat cells 2. The oily lipid secreted by glands in the dermis is called                 . a. keratin c. sebum b. fat d. hyaluronic acid 5. Which of the following pairs of diseases may be associated with S. pyogenes? a. impetigo and acne b. erysipelas and necrotizing fasciitis c. anthrax and blackheads d. whitlow and papillomas 3. The most severe form of acne is                 . a. a blackhead c. a pimple b. cystic acne d. excessive oil production 6. An eschar is                 . a. painless b. black c. a crusty ulcer d. All of the above describe an eschar. 4. Which of the following is not associated with impetigo? a. pus-filled vesicles c. Streptococcus pyogenes b. erysipelas d. pyocyanin 7. The opportunistic pathogen often seen in burn victims is                 . a. Pseudomonas c. Staphylococcus b. Streptococcus d. Dermacentor M19_BAUM7206_05_SE_C19.indd 590 11/30/16 9:03 PM 12. Which of the following is a concern for tissue that does not receive its needed blood supply? a. ischemia c. gas gangrene b. necrosis d. all of the above 13. Which of the following bacteria can have these virulence factors: coagulase, hyaluronidase, lipase, protein A? a. Staphylococcus c. Bartonella b. Streptococcus d. Clostridium 14. Which of the following is the vector for leishmaniasis? a. cat c. sand fly b. ringworm d. tick                  . Match the disease on the left with the causative pathogen on the right. 1.             Cat scratch disease A. Propionibacterium 2.             Acne B. Malassezia 3.             Spotted fever C. Bartonella 4.             Erysipelas D. Dermatophytes 5.             Pityriasis versicolor E. Variola major 6.             “Ringworm” F. Rickettsia 7.             Smallpox G. Simplexvirus 8.             Herpes H. Varicella-zoster virus 9.             Warts I. Rubivirus J. Roseolovirus 11.             Rubella K. Papillomavirus 12.             Measles L. Leishmania M. Morbillivirus N. Streptococcus Fill in the Blanks M19_BAUM7206_05_SE_C19.indd 591                                                           1. As a group, the normal microbial residents of the body make up the . 2. Staphylococcal scalded skin syndrome is caused by toxins produced by Staphylococcus aureus.                                                                                              , 6. Rocky Mountain spotted fever is transmitted by ticks of the genus .                              (also known 9. Clostridium perfringens causes most cases of                              8.                              cause warts. .                              10. Most pimples result from infection by , not from eating chocolate, drinking soft drinks, or consuming oily foods. True/False 1.              Vigorous scrubbing of the skin can eliminate microorganisms. 2.               Untreated cat scratch disease is fatal. 3.               A change in diet, such as avoiding greasy food, is highly effective in the treatment of acne. 4.               A number of fungi grow on the epidermal layer of skin, but they rarely become systemic infections. Matching 10.             Shingles . 5. Four types of folliculitis caused by Staphylococcus are , , and . 7. A single-stranded DNA virus causes as fifth disease) in humans. 11. Which of the following types of warts are found on the soles of the feet? a. flat warts c. genital warts b. seed warts d. plantar warts 15. Subacute sclerosing panencephalitis is caused by a. type III hypersensitivity c. measles virus b. seed warts d. a mite .                              10. What was the first disease for which immunization was perfected? a. smallpox c. ringworm b. polio d. measles 4. “Flesh-eating” disease is formally called                              9. A patient has oral lesions that look like salt crystals surrounded by a red halo. What disease is indicated? a. rubella c. measles b. chickenpox d. erysipelas 3. Pyoderma is a contagious skin disease also called                              8. Which of the following ascomycetes causes a cutaneous mycosis? a. Malassezia c. Phialophora b. Sporothrix d. Microsporum                             R Questions for eview 5.               Koplik’s spots are the lesions of chickenpox. Short Answer 1. Discuss the pros and cons of using long-term antibiotics to treat acne. 2. Discuss the problems associated with infections in burn victims. 3. Considering that Pseudomonas aeruginosa and Staphylococcus epider­ midis are ubiquitous and that each possesses numerous virulence factors, why do they rarely cause disease? 4. What distinguishes the rashes of chickenpox or measles from the rash of Rocky Mountain spotted fever? 5. Maria has patches of black scaly skin on her arm. Her physician suspects that she has Malassezia furfur. What is the quickest way to confirm this suspicion? 6. Describe four enzymes produced by Staphylococcus, and tell how each contributes to the bacterium’s survival and pathogenicity. 7. In 1955, Staphylococcus infections were effectively treated with penicillin. Why is this not the drug of choice now? 8. Larry has had flulike symptoms for three days accompanied by extreme shooting pains. What pathogen might be suspected? 9. Why are the terms dermatophytosis and ringworm inaccurate choices for the names of the superficial fungal infections they are associated with? 10. Mrs. Rathbone called the pediatrician concerning her young daughter Rene, who has had a rosy facial rash and coldlike sniffles for two weeks. What is the most likely cause of Rene’s problem? 11/30/16 9:03 PM t a       Ch p er 19    Microbial Diseases of the Skin and Wounds VISUALIZE IT! 1. Label each lesion seen in poxvirus infections. Fluid 1 cm a. ______________________________ b. ______________________________ c. ______________________________ e. ______________________________ f. ______________________________ Pus d. ______________________________ 2. Label the lesions of human herpesvirus occurring at each location. 3. Name the skin disease shown in each photo. a. ______________________________ b. ______________________________ a. _______________________________ b. ______________________________ c. _______________________________ d. ______________________________ c. ______________________________ d. ______________________________ M19_BAUM7206_05_SE_C19.indd 592 11/30/16 9:03 PM       R Questions for eview H ­ 1. A few days after the death of a hospitalized child from a methicillin-resistant Staphylococcus aureus (MRSA) infection, another child, who had been admitted to the hospital with viral pneumonia, worsened and died. An autopsy revealed that the second child also died from complications of MRSA. By what route was the second child likely infected? What should hospital personnel do to limit the transfer of MRSA and other bacteria among patients? 2. Why is it more difficult to rid a community of a disease transmitted by arthropods (for example, RMSF) than a disease transmitted via contaminated drinking water? 3. Clinically, all fungi that cause subcutaneous mycoses produce lesions on the skin around the site of inoculation. What are some of the things you would look for when attempting to distinguish among them? 4. Given the various predisposing factors that make humans susceptible to opportunistic infections, how can health care providers curtail the rising incidence of such infections? 5. Given the regions of the world where Leishmania and HIV are endemic, would you expect the incidence of leishmaniasis to increase or decrease in the next decade? Explain your answer. ­ 6. Most DNA viruses replicate within the nucleus of a host cell, using host enzymes to replicate their DNA. In contrast, poxviruses replicate in the cytoplasm of host cells. What problem does this create for poxvirus replication? How does the virus overcome this problem? 7. Certain features of smallpox viruses allowed them to be eradicated in nature. Which other viruses discussed in this chapter might be suitable candidates for eradication, and what features of their biology make them suitable candidates? M19_BAUM7206_05_SE_C19.indd 593 8. A week after spending their vacation rafting down the Colorado River, all five members of the Chen family developed cold sores on their lips. Their doctor told them that the lesions were caused by a herpesvirus. Mr. and Mrs. Chen were stunned: Isn’t herpes a sexually transmitted disease? How could it have affected their young children? 9. Propionibacterium acnes is a member of the skin microbiome that benefits the body by lowering the skin’s pH—an antimicrobial effect. However, P. acnes is also the leading cause of acne. How can a bacterium be normal and beneficial but also be pathogenic? 10. In 2009, several websites suggested spuriously that measles vaccine causes autism. What effect did these claims have on the number of measles cases in subsequent years? 11. Sporothrix, the cause of sporotrichosis (rose-gardener’s disease), is dimorphic. What feature characterizes dimorphic fungi? 12. Why do impetigo and erysipelas occur more commonly in children than in young adults? 13. The United States and Russia have repeatedly agreed to destroy their stocks of the smallpox virus, but the deadline for destruction has been postponed numerous times. In the meantime, the entire genome of variola major has been sequenced. What reasons can governments cite for maintaining smallpox viruses? Should all laboratory stores of smallpox viruses be destroyed? Given that the genome of the virus has been sequenced, and that DNA can be reconstructed if the sequence of nucleotides is known, would elimination of all laboratory stocks really be the extinction of the smallpox virus? 14. You learned about the creation and use of dichotomous keys on p. 118–119. Make a dichotomous key to distinguish among all the fungal mycoses covered in this chapter. ­ R C ITICAL T INKING 11/30/16 9:03 PM M ING APP CONC EPT       Chapter 19    Microbial Diseases of the Skin and Wounds Using the following terms, fill in this concept map that describes human herpesvirus. Oral herpes Polyhedral capsid Recurrences Simplexvirus Herpetic whitlow Human herpesvirus 2 Latency Life-threatening Ocular herpes Acyclovir Envelope Fever blisters Genital herpes Gingivostomatitis 1 characterized by partially controlled by Primary infection composed of dsDNA 4 includes 2 13 3 14 10 Human herpesvirus 1 most often causes 5 7 also known as most often causes 8 9 11 Neonatal herpes is a Cold sores Finger infection may be 12 6 M19_BAUM7206_05_SE_C19.indd 594 3/6/18 4:47 PM