Microbial Diseases of the Urinary and Reproductive Systems

­       Microbial Diseases of the Urinary and Reproductive Systems    Structures of the Urinary and Reproductive Systems and cleanse blood flowing through the capillaries, removing wastes to produce urine, which flows into the thousands of collecting ducts and from there via the renal pelvis into the ureter. The urinary and reproductive systems in females are anatomically distinct. In males, the two systems share a portion of the “plumbing.” Structures of the Reproductive Systems Structures of the Urinary System LE A R N I N G O U TC O M E 24.1 Describe the function and structures of the urinary system. 24.2 Describe the anatomies of the male and female reproduc- tive systems. The female reproductive system consists of two ovaries, two uter­ ine tubes (Fallopian tubes), a uterus (womb), a mucous-membranelined vagina (birth canal), and the external genitalia, which include the clitoris, two sets of labia (Latin, meaning “lips”), and the opening of the vagina (FIGURE 24.1c). The ovaries produce haploid ova (eggs) before birth and typically release one ovum (egg) per month beginning at puberty. Cilia lining the uterine tubes sweep ova toward the uterus, which develops a blood-rich, thickened wall in anticipation of pregnancy. When a sperm cell fuses with an ovum—a process called fertilization—the resulting zygote develops into an embryo that implants itself into the uterine wall, forms a placenta, and develops into a fetus. The placenta is a structure that places fetal blood vessels in close proximity to the mother’s blood vessels, allowing the fetus to absorb nutrients and oxygen and eliminate wastes; the two bloodstreams never mix. A fully developed fetus passes through the cervix (neck of the uterus) into the birth canal (vagina) to be born. When an ovum remains unfertilized, it and the lining of the uterus degenerate and pass out the vagina during menstruation in a monthly cycle. Ovarian hormones control the cyclic release of ova and the development and sloughing of the uterine lining. Microorganisms can invade the female reproductive tract via the moist mucous membrane of the vagina, especially during sexual intercourse; however, the normal microbiome helps maintain a vaginal pH of about 4.5, inhibiting the growth of pathogens. Male reproductive anatomy consists of two testes (testicles) located in an external pouch called the scrotum, a system of ducts, accessory glands, and the penis (FIGURE 24.1d). Beginning at puberty, each testis produces millions of sperm cells that mature and are stored in an epididymis—a coiled tube about 7 m long located above and behind each testis. Sperm pass from the epididymis via a tube, the ductus deferens, which joins the urethra near its exit from the urinary bladder inside the prostate—one of the male accessory glands. The prostate and other accessory glands add fluids to the sperm, forming semen, which passes from the penis. A hood of skin, the foreskin, covers the end of a penis. Circumcision involves cutting this skin away. Urinary or sexually transmitted microbes can invade the urethra or skin of the penis, including the foreskin. ▶ FIGURE 24.1 Urinary and reproductive systems. (a) Structures of the urinary and reproductive systems. (b) Anatomy of a kidney. ach kidney contains about 1.25 million nephrons (filtration units), which are each composed of blood vessels, a glomerulus, and tubules. (c) Sectioned view of female genital and urinary tracts. (d) Sectioned view of male genitourinary tract. E Two kidneys, connected by ureters to the urinary bladder, and a urethra make up the urinary system in both females and males (FIGURE 24.1a). The kidneys remove wastes from the blood, excreting them in urine, which travels down the ureters to the urinary bladder. The bladder stores urine until there is an opportunity to eliminate it through the urethra. The urethra may be a portal for the entrance of microorganisms, especially in females because a female urethra is shorter (about 4 cm long, exiting near the opening of the vagina) than a male urethra (about 20 cm long, exiting at the tip of the penis). The urethra in males also functions as part of the reproductive system. Each bean-shaped kidney has a mass of about 150 g and is roughly 11 cm * 6 cm * 3 cm in size—approximately the mass and size of a double deck of playing cards. A frontal section through a kidney reveals three distinct regions (FIGURE 24.1b). A tough fibrous renal1 capsule covers the outer surface. Beneath the capsule are an outer light-colored renal cortex and an inner, darker renal medulla. Conical structures called renal pyramids make up most of the renal medulla. The apices of the pyramids point into a hollow, flattened, funnel-like pelvis, which collects urine and empties it into the ureter. The ureter exits from the concave, medial surface of the kidney. Blood vessels also enter and exit the kidney at this point. Each renal pyramid contains nephrons, 2 which are the actual functional units of the kidneys; they filter blood to form urine. A kidney has about 1.25 million nephrons, each composed of a ball of blood capillaries, called a glomerulus, and a tube with three distinct regions. A glomerular (Bowman’s) capsule surrounds the glomerulus. Near the glomerulus, the tube loops back and forth and is called the proximal convoluted tubule. The tube then descends into the medulla as a U-shaped nephron loop (loop of Henle,3 hen-lē′) and returns as the distal convoluted tubule to touch the glomerular capsule. The distal convoluted tubule empties urine into another tube called a collecting duct. The combined length of all the tubules in a single kidney is about 145 km (90 miles)! Blood flows into the glomeruli through afferent arterioles and out through efferent arterioles; other arterioles twist around the convoluted tubules and the loops of Henle. Nephrons filter LE A R N I N G O UTC O M E Latin ren, meaning “kidney.” Greek nephros, meaning “kidney.” 3Named for German anatomist Friedrich Henle. 1From 2From M24_BAUM7206_05_SE_C24.indd 748 11/23/16 3:43 AM Proximal convoluted tubule Cortex Medulla Glomerulus Glomerular (Bowman’s) capsule Glomerular (Bowman’s) capsule Capsular space       R Structures of the Urinary and eproductive Systems Efferent arteriole Renal artery Renal pyramid Proximal convoluted tubule Peritubular capillaries Pelvis Renal vein Glomerulus Renal capsule Ureter Nephron loop (loop of Henle) Distal convoluted tubule Collecting duct Nephron Afferent arteriole Distal convoluted tubule Glomerulus (b) Uterine (Fallopian) tube Ureter Ovary Cervix Uterus Kidney Urinary bladder Rectum Ureter Urethra Uterus Clitoris Vagina Urinary bladder Labium minus Anus Urethra Labium majus (c) Ureter opening Urinary bladder Kidney Ureter Ductus deferens Rectum Urinary bladder Seminal vesicle Prostate gland Urethra Testis Urethra Anus Penis Epididymis (a) Midsagittal plane Testis Foreskin (d) M24_BAUM7206_05_SE_C24.indd 749 11/23/16 3:43 AM R ­ t a Microbiome of the Urinary and Reproductive Systems Bacterial Urinary Tract Infections LE A R N I N G O UTC O M E S 24.4 List four bacteria that can infect the urinary tract and LE A R N I N G O U TC O M E cause disease. 24.3 Describe the microbiome of the urinary and reproductive 24.5 Describe the features of urethritis, cystitis, and systems. pyelonephritis. The urethra normally supports the growth of some microbiota, chiefly avirulent species of Lactobacillus (lak-tō-bă-sil′ŭs), Staph­ ylococcus (staf′i-lō-kok′us), and Streptococcus (strep-tō-kok′ŭs). Occasionally other bacteria such as species of Mycobacterium (mī′kō-bak-tēr′ē-ŭm), Bacteroides (bac-ter-oy′dēz), Fusobacterium (fū-sō-bak-tēr′ē-ŭm), and Peptostreptococcus (pep′tō-strep-tōkok′ŭs) colonize the distal (far) end of a urethra. In both males and females, the rest of the urinary organs and the urine in them are axenic (lacking in microbial contaminants) because of the normally acidic pH of urine and the flushing action of urination. Microbiota of a urethra do contaminate urine during urination; for this reason, normally voided urine contains some bacteria, whereas urine collected directly from a urinary bladder via a catheter is typically sterile. A vagina is home to a wide assortment of microorganisms that vary with the levels of hormones, particularly estrogen. When estrogen levels rise, such as occurs at puberty, cells lining a vagina produce glycogen, a polysaccharide that lactobacilli convert into lactic acid. Acidity inhibits the growth of many opportunistic pathogens. Thus, prepubescent girls, who have little circulating estrogen, are more susceptible to vaginal infections. Likewise, as estrogen levels fall and rise during the menstrual cycle, some women cycle between periods of infection and periods of health. The microbiomes of the urethra and vagina serve to protect the body by outcompeting pathogens—a situation called microbial antagonism or microbial competition. In both males and females, microorganisms infecting the urethra can rarely move into the bladder, up the ureters, and infect the kidneys. Opportunistic and sexually transmitted microbes also infect the reproductive systems. In the following sections, we examine diseases of the urinary and reproductive systems, beginning with bacterial diseases of the urinary system. Why are newborn girls less likely to contract vaginal infections than are three-year-olds? ­ M24_BAUM7206_05_SE_C24.indd 750 About 7 million cases of urinary tract infections (UTIs) are diagnosed annually in the United States, mostly in women. Bacteria may trigger inflammation and pain in any or all of the urinary tract, including the urethra, urinary bladder, or kidneys— conditions called urethritis, cystitis,4 and pyelonephritis,5 respectively. Urinary bacteria can also infect a male sexual accessory organ, the prostate—a condition called prostatitis. Disease in Depth: Bacterial Urinary Tract Infections (pp. 752–753) considers these infections in more detail. Leptospirosis LE A R N I N G O UTC O M E S 24.7 Define zoonosis. 24.8 Describe the features of leptospirosis, including its cause, manifestations, pathogenesis, epidemiology, diagnosis, treatment, and prevention. Not all infections of the urinary system originate from fecal contamination. Leptospirosis (lep′tō-spī-rō′sis) is a zoonosis (zō-ō-nō′sis)—a disease primarily seen in animals that spreads to humans. The causative agent enters the body through breaks in the skin or mucous membranes and spreads to the urinary system from the blood. Signs and Symptoms An abrupt fever, myalgia (muscle pain), muscle stiffness, and headache characterize leptospirosis. Half of patients develop nausea, vomiting, and diarrhea; one-third have a dry cough. Leptospirosis is rarely fatal, but when it is, mortality is due to kidney and liver failure, meningitis, or respiratory distress. Over 200 strains of a Gram-negative spirochete cause leptospirosis. Taxonomists currently hypothesize that all the strains belong to a single species—Leptospira interrogans (lep′tō-spī′ră in-ter′ră-ganz). The specific epithet interrogans alludes to the fact that the end of the spirochete is hooked in a manner reminiscent of a question mark (FIGURE 24.2). This thin (0.1 mm diameter) aerobic pathogen is highly motile by means of two axial filaments, each of which is anchored at one end. Clinicians ­ Bacterial Diseases of the Urinary System Millions of girls and women in the United States suffer bacterial urinary tract infections (UTIs) each year. This includes about 600,000 patients who annually acquire healthcareassociated UTIs. Urinary tract infections are rare in boys and men. Systemic diseases can also affect the urinary system. acquiring a urinary tract infection. Pathogen h e M W y ell T 24.6 Describe five ways women can decrease their chance of ­       Ch p er 24    Microbial Diseases of the Urinary and eproductive Systems 4From 5From Greek kystis, meaning “bladder,” and itis, meaning “inflammation.” Greek pyel, meaning “vat” (referring to the renal pelvis). 11/23/16 3:43 AM SEM 0.5 µm ▲ FIGURE 24.2 Leptospira interrogans. This spirochete, which causes leptospirosis, appears hooked like a question mark.       R Nonvenereal Diseases of the eproductive Systems Intravenous penicillin G treats severe infections; oral doxycycline, ampicillin, or amoxicillin are drugs of choice for less severe cases. The most effective way to limit the spread of Lep­ tospira is to refrain from wading in, swimming in, or consuming water contaminated with animal urine. Rodent control is also important, but eradication is impractical because the spirochete has many animal reservoirs. An effective vaccine is available for livestock and pets. Disease at a Glance 24.1 on p. 754 summarizes the features of leptospirosis. Streptococcal Acute Glomerulonephritis LE A R N I N G O UTC O M E Epidemiology Leptospirosis occurs throughout the world. Farmers, ranchers, veterinarians, butchers, and people whose recreation takes them to potentially contaminated water are most at risk. National reporting in the United States ceased in part because the disease is rare in the United States; a total of only 89 cases occurred in 1993 and 1994, the last years that the disease was nationally reportable. Diagnosis, Treatment, and Prevention Leptospira does not stain well with Gram stain; therefore, a specific antibody test revealing the presence of the spirochete in blood or urine specimens is the preferred method of diagnosis. M24_BAUM7206_05_SE_C24.indd 751 ­ ­ ­ For an undetermined reason, the body does not remove from circulation antibodies bound to the antigens of some strains of group A Streptococcus (see p. 000). Instead, antibodyantigen complexes accumulate in the glomeruli of the kidneys, triggering inflammation of the glomeruli and nephrons, a condition called glomerulonephritis (glō-mār′yū-lō-nefrī′tis). This obstructs blood flow through the kidneys and leads to hypertension (high blood pressure) and low urine output. The patient’s urine often contains blood and proteins. Young patients usually recover fully from glomerulonephritis, but progressive and irreversible kidney damage may occur in adults. We have examined bacterial diseases of the urinary system. In the following section, we examine diseases of the reproductive systems that are not regularly transmitted sexually, that is, non­ venereal6 diseases. T M W y h Humans develop leptospirosis 2–26 days following direct contact with the urine of infected animals or with the spirochetes in animal-urine-contaminated streams, lakes, or moist soil, all environments in which the organisms can remain viable for six weeks or more. Person-to-person spread has not been observed. Because Leptospira is thin and highly motile, it can penetrate intact mucous membranes or enter through invisible cuts and scrapes in the skin. It corkscrews its way through these tissues and then travels via the bloodstream throughout the body, including the central nervous system, damaging cells lining small blood vessels and triggering fever and the other signs and symptoms. Eventually, the bacteremia resolves, and the spirochetes live only in the kidneys. As the disease progresses, the spirochetes are excreted in urine. acute glomerulonephritis. e Pathogenesis 24.9 Describe the manifestations and cause of streptococcal ell ­ and researchers grow Leptospira on special media enriched with bovine serum albumin or rabbit serum. Virulent strains of Leptospira make adhesins that attach to human cells, are motile, are chemotaxic toward hemoglobin, and are evidently able to evade antibody-complement activity. The exact nature and actions of these virulence factors require further study. L. interrogans normally lives in many wild and domestic animals—in particular, rats, raccoons, foxes, dogs, horses, cattle, and pigs—in which it grows asymptomatically in the kidney tubules. The spirochete can also survive in streams, rivers, and lakes. Why does insertion of a urinary catheter increase the likelihood of cystitis (inflammation of the bladder)? Nonvenereal Diseases of the Reproductive Systems In previous sections, we considered two nonvenereal diseases of the urinary systems of males and females. Now, we consider three nonvenereal diseases of the female reproductive system. Staphylococcal Toxic Shock Syndrome LE A R N I N G O UTC O M E 24.10 Describe the features of staphylococcal toxic shock syndrome. 6Venereal comes from the name Venus, the Roman goddess of sexual love. 11/23/16 3:43 AM DISEASE IN DEPTH SIGNS AND SYMPTOMS BACTERIAL URINARY TRACT INFECTIONS Patients with mild urethritis, cystitis, or pyelonephritis may have only a slight fever or no symptoms, but most of these diseases involve frequent, urgent, and painful urination—a condition called dysuria. The urine may be cloudy and bloody and have a strong, foul odor. Mental confusion, which results when the bacteria spread from the urinary system to the blood (bacteremia), is often seen in the elderly. Escherichia coli and other bacteria M illions of people in the United States, mostly girls and women, suffer bacterial urinary tract infections (UTIs) each year. This includes about 600,000 patients who annually acquire healthcare-associated UTIs. Urinary tract infections are rare in boys and men. Bacteria may trigger inflammation and pain in any or all of the urinary tract, including the urethra, urinary bladder, or kidneys—conditions called urethritis, cystitis, and pyelonephritis. PATHOGENESIS E. coli dividing by binary fission. TEM 1 μm In the Urethra (Urethritis) 1 E. coli is introduced into the urethra, often in fecal contamination. INVESTIGATE IT! Scan this QR code to watch Dr. Bauman's Video Tutor explore bacterial urinary tract infections. Then go to MasteringMicrobiology to investigate further and record your research findings on the following question: Why are UTIs the most common of healthcare-associated infections? M24_BAUM7206_05_SE_C24.indd 752 4 E. coli swims up the urethra. 2 E. coli adheres to epithelial cells in the urethra with fimbriae. 3 E. coli colonizes epithelial cells and begin to multiply by binary fission. EPIDEMIOLOGY UTIs are more common in females than males because female urethras are shorter and closer to the anus. Diabetics, nursing home patients, elderly men who have trouble emptying their bladders because of prostate enlargement, patients with urinary catheters, women who use diaphragms for birth control, and people who do not drink adequate fluids are also at risk for UTIs. Physician office Hospital outpatient 8674 809 Hospital emergency departments Number of health care visits in thousands for urinary tract infections reported in the United States 1510 1000 3000 5000 7000 9000 11/23/16 3:44 AM       PATHOGEN SEM Enteric bacteria—Gram-negative bacteria that are part of the intestinal microbiota—are the most common cause of urinary tract infections. Escherichia coli causes about 70% of cases; other bacteria from the intestinal tract, such as Proteus and Klebsiella, cause about 10% of UTIs. Nonintestinal bacteria, such as Pseudomonas and Staphylococcus, occasionally cause UTIs. 3 μm VIRULENCE FACTORS TEM E. coli, Proteus, and Pseudomonas have flagella that can propel the bacteria up the urinary tract. Strains of E. coli that infect the bladder have attachment fimbriae that bind specifically to epithelial cells lining the urinary bladder. Using fimbriae, these strains of E. coli move into bladder cells by an unknown mechanism and form biofilm-like aggregations within bladder cells’ cytosol, thus avoiding some of the body’s defenses. 1 μm 6b Cells of E. coli are released into bloodstream (bacteremia). In the Bladder (Cystitis) 5 E. coli invade bladder cells and multiplies within the cytosol, escaping many of the body's defenses. In the Kidney (Pyelonephritis) 6a E. coli ascends the ureter to the kidney where it triggers inflammation. E. coli infection of bladder cells SEM 10 μm DIAGNOSIS TREATMENT AND PREVENTION Urinalysis of patients with the signs and symptoms of urinary tract infections reveals leukocytes, erythrocytes, and the causative bacterium, usually E. coli. LM M24_BAUM7206_05_SE_C24.indd 753 Mild UTIs resolve on their own without treatment, though antimicrobial drugs, such as cephalosporins, sulfonamides, and semisynthetic penicillins, can prevent the spread of infection to the kidneys and blood. Wiping from front to back after defecation to avoid dragging bacteria from the anus into the urethra is the most important step females can take to prevent UTIs. 4 μm 11/23/16 3:44 AM e anc Gl a t eA R ­ t a is D e as       Ch p er 24    Microbial Diseases of the Urinary and eproductive Systems 24.1 Leptospirosis 1 Leptospira in urine-contaminated water enters the body through mucous membranes or skin abrasion. 2 The spirochetes infect the blood (bacteremia). Signs and Symptoms Sudden-onset fever, chills, vomiting, diarrhea, extremely low blood pressure, mental confusion, and a severe red rash (see Disease at a Glance 24.2) characterize staphylococcal toxic shock syndrome. Untreated TSS is fatal to 50% of patients when their blood pressure falls so low that the brain, heart, and other vital organs have an inadequate supply of oxygen—a condition known as shock. 3 Leptospira infects liver, central nervous system, kidneys, and other organs. Pathogen and Virulence Factors 4 In most patients, the infection becomes localized in the kidneys, which can be severely or fatally damaged. 5 Patient sheds Leptospira in urine. 3 1 2 3 4 3 1 Staphylococcus is normally part of the skin and mucous membrane microbiome. Strains of S. aureus that cause staphylococcal toxic shock syndrome produce certain exotoxins—soluble toxins released from cells—called toxic shock syndrome toxins (TSSTs). These exotoxins bind simultaneously to major histocompatibility complex II molecules on antigen-presenting cells and T cell receptors on T cells; however, they bind to sites other than the normal antigen-binding sites of these immune system molecules. When a toxin molecule binds two defensive cells together in this fashion, it activates the T cell. As a result of the action of many such toxin molecules, many more T cells are activated than in a cellular immune response. These activated T cells release an overabundance of cytokines that trigger the manifestations of TSS. TSST-1 causes 75% of cases of staphylococcal toxic shock syndrome. Other TSSTs, which are also enterotoxins (exotoxins that cause gastrointestinal distress when ingested), cause 25% of cases. Pathogenesis and Epidemiology Cause Leptospira interrogans (aerobic spirochete). Virulence factors Adhesins, motility, chemotaxis toward hemoglobin, ability to evade actions of antibodies and complement. Portal of entry Contact with urine of infected animals or contaminated water or soil. Signs and symptoms Myalgia, headache, abdominal pain, nausea, vomiting, and fever. Incubation period Two days to four weeks. Susceptibility All humans are susceptible regardless of age or sex. Treatment Oral doxycycline, chloramphenicol, erythromycin, or intravenous ampicillin for more severe cases. Prevention Use rodent controls and avoid water contaminated with animal urine. A vaccine is available for pets and livestock. Physicians first described toxic shock syndrome (TSS) in the late 1920s, but in the 1980s the condition became epidemic in the United States among menstruating women who used super-absorbent tampons. Once epidemiologists determined that certain strains of Staphylococcus aureus cause the syndrome, it also became known as staphylococcal toxic shock syndrome. M24_BAUM7206_05_SE_C24.indd 754 ­ 5 When strains of Staphylococcus that produce toxic shock syndrome toxin grow in the vagina or in a wound, the toxin is absorbed into the blood, triggering TSS. In the investigation of the 1980 epidemic among menstruating women, researchers discovered that S. aureus grows exceedingly well on superabsorbent tampons, especially when a blood-soaked tampon remained in place for a prolonged period. TSS occurs in males and females, but most cases have been identified in menstruating females. The U.S. Food and Drug Administration (FDA) ordered certain types of super-absorbent tampons withdrawn from the market in 1980, directed a reduction in the absorbency of all tampons in 1982, and mandated packaging educational information concerning the risks of TSS in every box of tampons beginning in 1982. These government directives reduced the number of cases of TSS in the United States from almost 1200 cases in 1980 to 99 in 2015 (FIGURE 24.3). At-risk individuals include women who use tampons, vaginal sponges, or diaphragms; newly delivered mothers; surgery patients, especially after nasal surgery where packing is employed to reduce bleeding; and anyone with an infection of S. aureus. Diagnosis, Treatment, and Prevention Physicians typically diagnose TSS based upon its signs and symptoms, particularly in menstruating women. In some cases, cultures of blood samples grow colonies of S. aureus. 11/23/16 3:44 AM Gl anc eA a D e is 1200 t Superabsorbent tampons withdrawn as       R Nonvenereal Diseases of the eproductive Systems e 24.2 Toxic Shock Syndrome 1000 E Cause xotoxin-producing strains of Staphylococcus aureus (Gram-positive coccus). 800 Virulence factors xotoxins, enterotoxins. 600 E Food and Drug Administration requires tampon labeling Portal of entry Staphylococcus either grows in the vagina or enters the body through a wound, grows, and produces toxin that enters the bloodstream. 400 200 0 1980 1985 1990 1995 2000 Year 2005 2010 2015 ▲ FIGURE 24.3 The incidence of staphylococcal toxic shock syndrome in the United States, 1979–2015. TSS is a medical emergency; patients experiencing a sudden onset of fever or rash, particularly during menstruation or following surgery, should seek immediate treatment. Treatment involves removal of foreign material (tampon, sponge, diaphragm, nasal packing) and drainage of infected wounds. Supportive measures include intravenous fluid to support falling blood pressure and dialysis when the kidneys are affected. Physicians administer nafcillin, oxacillin, or vancomycin to reduce the number of bacterial cells. Alternatively, one of three newly approved drugs—oritavancin, dalbavancin, or tedizolid— may be prescribed. In any case, physicians also can prescribe anti-TSST immunoglobulin to counteract the bacterial toxin and corticosteroids to counteract the manifestations of shock. Women can reduce the risk of TSS by avoiding the use of tampons, vaginal sponges, and birth control diaphragms. Using less absorbent tampons and changing tampons frequently are also beneficial. Disease at a Glance 24.2 summarizes the features of staphylococcal toxic shock syndrome. Bacterial Vaginosis LE A R N I N G O U TC O M E 24.11 Describe the characteristics of bacterial vaginosis. Bacteria can infect the warm, moist vaginal lining, causing bacterial vaginosis. The condition does not involve inflammation; therefore, the disease is “vaginosis” rather than “vaginitis.” Signs and Symptoms A homogenous white vaginal discharge with a “fishy” odor characterizes bacterial vaginosis. Some itching and irritation of the vaginal opening may also occur. Up to 50% of women with bacterial vaginosis report no symptoms. M24_BAUM7206_05_SE_C24.indd 755 Red rash of staphylococcal toxic shock syndrome. Signs and symptoms Sudden onset of high fever, vomiting, rash, extremely low blood pressure, and sore throat. Incubation period Two to three days. Susceptibility Menstruating women who use highly absorbent tampons for extended periods, newly delivered mothers, and surgery patients are at higher risk. Treatment Supportive therapy is extremely important; administration of vancomycin and antistaphylococcal immunoglobulin. Prevention Avoid vaginal insertions such as highly absorbent tampons, vaginal sponges, or diaphragms, or use them intermittently and for shorter periods. Pathogens Bacterial vaginosis results when the normal lactobacilli of the vagina are replaced with a large number of facultatively or obligate anaerobic bacteria such as Gram-positive Gardnerella vaginalis (gărd′ner-el′ă va-ji-nă′lis) and Mycoplasma hominis (mī′kō-plaz-mă ho′mi-nis). Scientists do not understand the underlying causes of this change in the microbiome. Pathogenesis and Epidemiology Scientists do not know the exact cause or causes of bacterial vaginosis. However, a decline in the number of lactobacilli populating the vagina results in a pH in the vagina higher than the normal 4.5. This either promotes or allows the growth of the bacteria associated with bacterial vaginosis. Bacterial vaginosis is associated with having multiple sexual partners and vaginal douching. Diagnosis, Treatment, and Prevention Physicians diagnose bacterial vaginosis by its signs, including odor, discharge characteristics, and vaginal pH greater than 4.5. The presence of so-called clue cells, which are vaginal epithelial cells completely covered with bacteria, supports the diagnosis of bacterial vaginosis (FIGURE 24.4). The U.S. Centers for Disease Control and Prevention (CDC) recommends treatment with oral or vaginal metronidazole or clindamycin. Researchers are studying the possibility of 11/23/16 3:44 AM R ­ t a       Ch p er 24    Microbial Diseases of the Urinary and eproductive Systems preventive measures, but sexual abstinence and refraining from douching are beneficial. Bacteria are not the only nonvenereal pathogens of the reproductive system; fungi, particularly yeasts, can also infect reproductive organs. In the next section, we examine the most common fungal infection of reproductive tracts. Nucleus of clue cell Bacteria Vaginal Candidiasis LE A R N I N G O UTC O M E S 24.12 Describe Candida albicans. 24.13 Describe the features of vaginal candidiasis. 24.14 Explain why women taking antibacterial drugs are at Normal, non-clue cell LM risk for candidiasis. Candidiasis (kan-di-dī′ă-sis) describes any of a variety of opportunistic yeast infections and diseases caused by various species of the genus Candida (kan′did-ă), most commonly C. albicans. Candidiasis can involve any mucous membrane. Candida normally lives in the gastrointestinal tract and vagina in competition with lactobacilli and other bacteria. If the vaginal pH becomes more alkaline than usual or if antibiotics disrupt normal bacterial populations in the vagina, Candida can multiply rapidly, resulting in candidiasis. In immunocompromised individuals, especially AIDS patients, Candida can become systemic. Disease in Depth: Candidiasis on pp. 758–759 discusses other features of candidiasis. Beneficial Microbes: Pharmacists of the Future? examines a novel way to deliver antimicrobial drugs directly to the vagina to prevent infections by Candida and other pathogens. 5 µm ▲ FIGURE 24.4 Clue cell. Clue cells are vaginal epithelial cells covered with bacteria that suggest a diagnosis of bacterial vaginosis. Name one bacterial species that can be found on a clue cell. Figure 24.4 Gardnerella vaginalis is frequently the bacterium covering clue cells. e s ob lM r ic n Be e ficia reestablishing the normal vaginal microbiome and pH through the use of lactobacilli vaginal suppositories or through the consumption of live cultures of Lactobacillus. Since physicians and researchers do not fully understand the development of bacterial vaginosis, there are no absolute Pharmacists of the Future? M24_BAUM7206_05_SE_C24.indd 756 H H Other researchers have altered strains of Lactobacillus—a common probiotic—to express cyanovirin, which is a protein that successfully inhibits IV. The idea is to colonize the vaginas of women at risk for infection with IV with this altered but otherwise normal member of the vaginal microbiome. The modified bacterium would act as a potent first line of defense against infection. Benefits of using microbiota to deliver antimicrobial drugs are numerous. Such a drug would be relatively less expensive to manufacture—bacteria at the site would be the “factory”—and delivery of the drug would be automatic, not requiring a prescription to be filled, delivered, or administered more than once. Further, the concentration of drug at a site could be maintained without depending on a patient to keep a set schedule. erhaps your future pharmacist will be a microbe that has been tailored to deliver antimicrobial chemicals precisely to sites of infection. P ­ H The microbiome of your body—the trillions of microbes that live in and on you—plays essential roles in maintaining your health. As they grow and reproduce, microbes utilize nutrients that would otherwise go to pathogens; they excrete vitamins, aid in digestion, and change the p of their environment, all of which benefit you. Now, scientists are on the verge of enhancing the protective role of the microbiome by giving some of the microbes genes that code for chemicals that inhibit pathogens without being deleterious to the normal microbiome or to us. In one experiment, researchers inserted a gene for an antibody against a yeast, Candida, into the genome of a benign species of Streptococcus bacteria that is a member of the microbiome. Mice with candidiasis that received the recombinant Streptococcus recovered twice as fast as mice that received fluconazole—a standard antifungal medication. Since Streptococcus is normally in the vagina, it can reproduce there, maintaining a constant level of protective chemicals without requiring reinoculation and without harming the mice. 11/23/16 3:44 AM LE A R N I N G O U TC O M E S 24.15 Discuss the incidence of STDs worldwide and in the United States. 24.16 Explain why adolescents are at greater risk than adults from STDs and the consequences of STDs. 24.17 Discuss prevention of STIs. 24.18 Describe the characteristics of pelvic inflammatory disease. Sexual activity transmits microbes between partners. When the microbes are potential pathogens, such transmission is known as a sexually transmitted infection (STI). Diseases resulting from STIs are sexually transmitted diseases (STDs), which are also known as venereal diseases. A pandemic of STDs has developed over the last 50 years. The World Health Organization (WHO) estimates that 333 million new cases of STDs occur worldwide each year, though 50–90% of STDs worldwide, including half of the STDs in the United States, remain unreported or undiagnosed. Some epidemiologists estimate that sexually transmitted viruses infect one in five Americans, including one-fourth of teenaged girls. About half of all STDs affect people under age 25. Young people often experiment with sex, and many believe that an STD “can’t happen to me.” Such an attitude can lead to behaviors that expose them to serious health risks. Additionally, embarrassment over contracting an STD can impair normal psychological development concerning sexuality. In all patients, the presence of lesions from STDs is a known risk factor for the transmission of HIV and the development of AIDS. A female adolescent is especially at risk for STDs in that her cervical lining is especially prone to bacterial invasion. For example, a sexually active 15-year-old girl, particularly if she has more than one sexual partner, has a 12.5% chance of developing pelvic inflammatory disease (PID), which is a general term for inflammation and pain in the uterus, uterine tubes, or ovaries; at age 24, the probability has decreased to 1.25%. Further, STDs are more likely to be asymptomatic in younger women. As a result, these patients do not seek treatment and suffer horrendous long-term consequences, including development of birth defects in their babies, ectopic7 pregnancy (implantation of a fetus outside the womb), miscarriage, sterility, or the development of cervical cancer. Disease at a Glance 24.3 examines features of pelvic inflammatory disease. 7From Greek ektos, meaning “outside,” and topos, meaning “place.” M24_BAUM7206_05_SE_C24.indd 757 Gl a t as eA e 24.3 Pelvic Inflammatory Disease (PID) P Cause Chlamydia trachomatis (Gram-negative obligate intracellular bacterium); Neisseria gonorrhoeae (Gram-negative diplococcus bacterium); or Gardnerella vaginalis (Gram-positive coccobacillus bacterium) in rare instances. In 30–40% of cases, ID is caused by infection with multiple bacteria simultaneously. Virulence factors Chlamydia—small size, intracellular lifestyle; Neisseria— capsule, fimbriae, lipid A; Gardnerella—ability to inhibit movement of neutrophils, adhesins, formation of biofilm. Portal of entry Mucous membrane of vagina, sexual transmission, and then migration ascending into the uterus or uterine tubes. Signs and symptoms Inflammation, fever, abdominal pain. eft untreated, ID can lead to ectopic pregnancies and sterility. L Sexually Transmitted Infections (STIs) and Diseases (STDs) D e P Why does Candida albicans, which is a member of the normal microbiome, sometimes cause disease? is h M W y e ell T anc       Sexually Transmitted Infections (STIs) and Diseases (STDs) Incubation period Months to years after initial infection. X-ray showing uterus at center left and an inflamed uterine (Fallopian) tube of PID at center right. Susceptibility Women with untreated gonorrhea or chlamydial infections, especially those under age 20. Treatment Antimicrobial drugs such as ofloxacin, metronidazole, doxycycline, and/or ceftriaxone. Prevention Abstinence or mutual monogamy with an uninfected partner; early treatment of all STDs. Condoms provide some protection from Neisseria infection but may increase chance of chlamydial infections. With the exception of cases arising from rape, every STI and STD can be prevented by practicing sexual abstinence or completely faithful mutual monogamy. Latex and polyurethane condoms reduce the risk of contracting many STIs, but condoms don’t provide complete protection; even properly used condoms have an annual failure rate of 17–25%. Further, epidemiological studies show that condoms must be used properly and consistently—that is, 100% of the time during every sex act—or they provide little to no risk reduction for most STDs. Numerous studies have shown that circumcision reduces a man’s chance of getting several sexually transmitted diseases. These include genital warts, AIDS, syphilis, genital herpes, and gonorrhea. Circumcision also reduces transmission of many of these diseases to the men’s sexual partners. Here, we consider some sexually transmitted bacterial, viral, and protozoan diseases, beginning with bacterial STDs. (Diseases of the skin and digestive system, such as scabies infection, giardiasis, shigellosis, and hepatitis, can be transmitted sexually. These infections are considered in the chapters covering the skin and digestive system.) 11/23/16 3:44 AM DISEASE IN DEPTH SIGNS & SYMPTOMS Candidiasis typically manifests as white plaques on the affected tissue. Vaginal candidiasis, shown on the left, manifests as white mucoid colonies growing on the mucous membrane of the vagina and the skin covering the vaginal labia. The yeast produces severe vaginal itching and burning, which urination intensifies. Sexual intercourse can be very painful. The vaginal discharge is often curdlike and slight. CANDIDIASIS Pseudohyphae stage of Candida albicans Vaginal candidiasis C andidiasis is any opportunistic fungal infection caused by various species of the genus Candida—most commonly Candida albicans. Candida species can infect tissues in essentially every body system, producing a wide range of disease manifestation in humans. In all cases, the fungus is opportunistic. Systemic disease is seen almost universally in immunocompromised individuals. Meningeal Oropharyngeal (thrush) Ocular Oropharyngeal (thrush) Esophageal Cutaneous Pulmonary Endocardial, myocardial, pericardial Gastrointestinal Hepatic and splenic Esophageal Peritoneal Neonatal and congenital (in females) Cutaneous Onychomycosis (nail infection) Onychomycosis (nail infection) Urinary tract Vulvovaginal (in females) Hepatic candidiasis Candidemia (in blood) Osteoarticular INVESTIGATE IT! EPIDEMIOLOGY Different segments of the population experience candidiasis at different rates. For example, oral candidiasis affects 10% of the elderly and nearly all people with AIDS. The CDC estimates that 75% of women will experience candidiasis at least once and almost 50% will have two or more episodes. Predisposing factors include cancer, invasive hospital procedures, antibacterial treatments, diabetes, severe burns, intravenous drug abuse, and AIDS. Scan this QR code to watch Dr. Bauman's Video Tutor explore candidiasis. Then go to MasteringMicrobiology to investigate further and record your research findings on the following question: A magazine claims that antibiotics cause candidiasis. Why is this statement only partially true? M24_BAUM7206_05_SE_C24.indd 758 Cutaneous candidiasis in AIDS patient 12/16/16 12:09 AM       PATHOGEN Pseudohypha LM DIAGNOSIS Candida albicans, the most common species causing candidiasis, is an opportunistic ascomycete yeast. It forms long cellular extensions called pseudohyphae because they appear similar to the true hyphae of filamentous fungi. Candida spp. are common members of the microbiota of the skin and mucous membranes; for example, the digestive and reproductive tracts of 40–80% of all healthy individuals harbor the yeast. 10 μm Physicians diagnose candidiasis on the basis of signs and demonstration of clusters of budding yeasts and pseudohyphae, which are buds remaining attached to the parent cell and appearing filamentous, like hyphae. Pseudohypha LM 40 μm PATHOGENESIS (Vaginal Candidiasis) Normal pH Candida albicans (yeast form) Lactobacillus More alkaline pH or following long-term usage of antibiotic Candida albicans (pseudohyphae form) 1 Candida albicans normally lives in the vagina in competition with Lactobacillus and other bacteria. Candida is one of the few fungi that can be transmitted between individuals. From its site as a normal inhabitant of the female reproductive tract, for example, it can pass to babies during childbirth and, rarely, to males during sexual contact. 2 If the vaginal pH becomes more alkaline than usual or if normal bacterial populations are reduced by antibiotics, Candida can multiply, triggering inflammation and other manifestations of candidiasis. TREATMENT & PREVENTION In immunocompetent patients, extensive external fungal growth is generally due to excessive friction and body moisture in skin folds or to preexisting diseases. Resolution involves treating the underlying problems in addition to administering topical antifungal agents. Oral candidiasis in infants and children is treated with nystatin. Azole suppositories, creams, and/or oral administration of fluconazole are used for vaginal candidiasis. Avoid persistent moisture in genital area; for example, do not wear wet bathing suits for prolonged periods. M24_BAUM7206_05_SE_C24.indd 759 The same infections in AIDS patients are much more difficult to treat because most superficial or mucous membrane infections in these patients do not respond well to topical antifungal treatments. Orally administered fluconazole is used for primary and maintenance therapy for candidiasis in AIDS patients. Invasive candidiasis requires treatment with amphotericin B and often with 5-fluorocytosine. Prophylactic treatment in AIDS patients may include oral fluconazole. 12/16/16 12:09 AM R ­ t h M W y e ell T a       Ch p er 24    Microbial Diseases of the Urinary and eproductive Systems Why have STIs and STDs become pandemic over the past 50 years? Bacterial STDs Bacterial infections are among the more familiar STDs. Bacteria involved in STDs survive poorly on dry cool, inanimate objects such as toilet seats; therefore, transmission is via sexual intercourse only. We begin with an examination of gonorrhea. Gonorrhea LE A R N I N G O U TC O M E S 24.19 Describe the origin of the name gonorrhea. 24.20 Compare and contrast the manifestations of gonorrhea in men and women. 24.21 Discuss the difficulties researchers face in developing an effective vaccine against Neisseria gonorrhoeae. Physicians have known about the sexually transmitted disease gonorrhea (gon-ō-rē′a) for centuries, although the disease was often confused with syphilis until the 19th century. In the 2nd century a.d., the Roman physician Claudius Galen named gonorrhea for what he thought was its cause—an excess of semen (gonorrhea means “flow of seed” in Greek). The disease is sometimes called “clap” from the archaic French word clapoir, meaning brothel. Pathogenesis Gonococci adhere, via their fimbriae and capsules, to epithelial cells of the mucous membranes lining much of the genital, urinary, and digestive tracts of humans. As few as 100 pairs of cells can cause disease. The bacterium does not attach to cells lining the vagina; instead, the bacteria most commonly infect the cervix of the uterus. Via fimbriae, N. gonorrhoeae can attach to sperm cells as they swim past, which allows the bacterium to hitchhike to the uterine tubes and beyond, producing pelvic inflammatory disease. Chronic infections can lead to scarring of the tubes, resulting in pregnancies outside the uterus or sterility. Gonococcal infections of organs outside the reproductive tracts also occur. Because a woman’s urethral opening is close to her vaginal opening, gonococci can infect the urethra during sexual intercourse. Anal intercourse can lead to procti­ tis (inflammation of the rectum), and oral sexual intercourse allows infection of the pharynx or gums, resulting in pharyngitis and gingivitis, respectively. These conditions are most commonly seen in men who have sex with men. Phagocytized bacteria survive and multiply within neutrophils, traveling within these leukocytes throughout the body. In very rare cases, gonococci travel to the joints, meninges, or heart, causing arthritis, meningitis, and endocarditis, respectively. Babies delivered vaginally by infected mothers can be infected in their eyes, resulting in inflammation of the cornea, ophthalmia neonatorum (inflammation of the conjunctiva in newborns), or blindness. Epidemiology In men, gonorrhea is usually insufferably symptomatic—acute inflammation typically occurs two to five days after infection in the urethra of the penis, causing extremely painful urination and a purulent (pus-filled) discharge. Rarely, the bacterium invades the prostate or epididymis, where the formation of scar tissue can render the man infertile. In contrast, gonorrhea in women is often asymptomatic— 50–80% of infected women have no symptoms or obvious signs of infection for years. It is only when they try to become pregnant that damage to the uterine tubes becomes obvious. About 25% of women with gonorrhea suffer pelvic inflammatory disease (see Disease at a Glance 24.3 on p. 757). Gonorrhea occurs in humans only. The number of cases among civilians in the United States has been declining over the past three decades (FIGURE 24.5a). Most civilian cases occur in adolescents, particularly among those in several southeastern states who have multiple sexual partners (FIGURE 24.5b). Infection is four times more common among blacks than nonblacks and slightly more common among males than females. An individual’s risk of infection increases with increasing frequency of sexual encounters. Women have a 50% chance of becoming infected during a single sexual encounter with an infected man, whereas men have only a 20% chance of infection during a single encounter with an infected woman. Infection of elementary-school-aged children with N. gonorrhoeae is strong evidence of sexual abuse by an adult. Pathogen and Virulence Factors Diagnosis, Treatment, and Prevention Neisseria gonorrhoeae (nī-se′rē-ă go-nor-rē′ī), also known as the gonococcus, causes gonorrhea. This Gram-negative bacterium usually forms pairs of cells that have fimbriae (see Disease at a Glance 24.4), polysaccharide capsules, and a major cell wall antigen called lipooligosaccharide (lip′ō-ol′ĭ-gō-sak′a-rīd, LOS), composed of lipid A (endotoxin) and sugar molecules. Cells that lack these three structural features are avirulent. The cocci also protect themselves from the immune system by secreting a protease enzyme that breaks down secretory IgA in mucus. The presence of Gram-negative diplococci in pus from an inflamed penis is sufficient for a diagnosis of symptomatic gonorrhea in men. For diagnosis of asymptomatic cases of gonorrhea in men and women, commercially available genetic probes provide direct, accurate, rapid detection of N. gonorrhoeae in clinical specimens. The treatment of gonorrhea is now complicated by the worldwide spread of gonococcal strains that are resistant to penicillin, tetracycline, erythromycin, aminoglycosides, and fluoroquinolones. Currently, the CDC recommends dual Signs and Symptoms M24_BAUM7206_05_SE_C24.indd 760 11/23/16 3:44 AM 400 Gonorrhea t as eA Gl anc D e a 500 is Incidence (per 100,000 population)       Bacterial STDs e 24.4 Cause Neisseria gonorrhoeae (Gram-negative diplococcus). 300 Virulence factors Capsule, fimbriae, lipooligosaccharide (lipid A, sugar), highly variable surface antigens among strains. Portal of entry Mucous membranes of genitalia; sexual transmission. 200 Signs and symptoms Men generally experience painful urination and pusfilled discharge. Women are generally asymptomatic. 100 Incubation period Two to five days. ‘40 ‘45 ‘50 ‘55 ‘60 ‘65 ‘70 ‘75 ‘80 ‘85 ‘90 ‘95 ‘00 ‘05 ‘10 ‘15 Year Susceptibility Sexually active individuals. Treatment Simultaneous ceftriaxone and azithromycin. Prevention ffective: Sexual abstinence, mutual monogamy. Somewhat effective: roper, consistent use of condoms. P E (a) Capsule Diplococci DC <19 19–100 >100 Diplococci of Neisseria gonorrhoeae. LM 10 µm (b) ▲ FIGURE 24.5 The incidence of civilian gonorrhea in the United States. (a) Incidence 1940–2015. (b) The geographic distribution of cases reported in 2013 by county per 100,000 population. What organism causes gonnorhea? Figure 24.5 Gonorrhea is cause by Neisseria gonorrhoeae. therapy with both ceftriaxone and azithromycin to treat gonorrhea and cefoxitin plus doxycycline to treat PID. There is no long-term specific immunity against N. gonor­ rhoeae, and thus people can contract gonorrhea multiple times. This lack of immunity is explained in part by the highly variable surface antigens in this bacterium—immunity against one strain often provides no protection against other strains. The existence of many different strains has prevented the development of an effective vaccine. Routine administration of antimicrobial agents to newborns’ eyes successf ully prevents ophthalmic disease. Otherwise, chemical prophylaxis is ineffective in preventing disease. In fact, the use of antimicrobials to prevent genital disease may select for hardier resistant strains, worsening the situation. Preventive strategies, in order of effectiveness, are M24_BAUM7206_05_SE_C24.indd 761 sexual abstinence, monogamy with a faithful partner, and the 100% consistent and proper use of condoms. Efforts to stem the spread of gonorrhea focus on education to change sexual behavior, aggressive detection, and the screening of all sexual contacts of carriers. Disease at a Glance 24.4 summarizes the features of gonorrhea. Syphilis LE A R N I N G O UTC O M E S 24.22 Describe the four phases of untreated syphilis and the treatment for each. 24.23 Describe the cause, epidemiology, and prevention of syphilis. Europeans first recognized syphilis in 1495, leading some epidemiologists to hypothesize that Spanish explorers brought syphilis to Europe. Another hypothesis is that the causative 11/23/16 3:44 AM R ­ t a       Ch p er 24    Microbial Diseases of the Urinary and eproductive Systems bacterium evolved from a less pathogenic strain endemic to North Africa and that its spread throughout Europe was coincidental to Europeans’ explorations of the New World. In any case, this sexually transmitted disease continues to afflict millions worldwide. Signs and Symptoms There are four phases of syphilis: • Primary: A small, painless, reddened, hard lesion called a chancre (shang′ker) forms at the site of infection 10–21 days following exposure (FIGURE 24.6a). Although chancres typically form on the external genitalia, about 20% form in the mouth, around the anus, or on the fingers, lips, or nipples. Chancres are often unobserved, especially in women, in whom these lesions frequently form on the cervix. Chancres last three to six weeks. • Secondary: As the disease progresses, the patient suffers sore throat, headache, mild fever, malaise, myalgia, lymphadenopathy (diseased lymph nodes), and a widespread rash (FIGURE 24.6b) that can include the palms and the soles of the feet. Although this rash does not itch or hurt, it can persist for months. • Latent: This phase has no symptoms and may last a decade or longer. • Tertiary: Years later, some untreated patients experience dementia, blindness, paralysis, heart failure, or syphilitic gummas (gŭm′az), which are rubbery, swollen lesions that can occur in bones, in nervous tissue, or on the skin (FIGURE 24.6c). Gummas rarely develop in patients in countries where antimicrobial drugs are available. (a) ­ (b) Pathogen and Virulence Factors ­ Treponema pallidum (trep-ō-nē′mă pal′li-dŭm) causes syphilis. The helical cells of this spirochete are so narrow (0.1 mm) that they are difficult to see by regular light microscopy in Gramstained specimens. Therefore, scientists use either phasecontrast microscopy, dark-field microscopy, or special stains to increase contrast (see Disease at a Glance 24.5 on p. 764). The bacterium lives naturally only in humans, and because heat, disinfectants, soaps, drying, the concentration of oxygen in the air, and pH changes destroy it, Treponema cannot survive in the environment. In fact, scientists have not successfully cultured T. pallidum in cell-free media, though they have coaxed it to multiply in rabbits, monkeys, and rabbit epithelial cell cultures. In these laboratory conditions, it multiplies slowly (binary fission occurs once every 30 hours) and only for a few generations. Scientists have had difficulty identifying virulence factors of T. pallidum. They have used recombinant DNA techniques to insert genes from Treponema into Escherichia coli (esh-ĕr-ik′ē-ă kō′lī) and have then isolated the genes’ proteins. Some of these proteins apparently enable Treponema to adhere to human cells. Virulent strains also produce hyaluronidase, which may enable Treponema to infiltrate intercellular spaces. The bacterium has a glycocalyx, which may protect it from phagocytosis by leukocytes. ▲ FIGURE 24.6 The lesions of syphilis. (a) A chancre, a hardened and painless lesion of primary syphilis that forms at the site of infection, here the shaft of a penis. (b) Widespread rash characteristic of secondary syphilis. (c) A gumma of tertiary syphilis. This painful rubbery lesion often occurs on the skin or bones. Why are gummas rare in industrialized countries? Figure 24.6 Antimicrobial drugs, available in industrialized countries, effectively treat syphilis, halting the progression of the disease. M24_BAUM7206_05_SE_C24.indd 762 (c) Pathogenesis Because of its fastidiousness and sensitivity, T. pallidum must grow in humans and is transmitted almost solely via sexual contact, usually during the early stage of infection, when the spirochetes are most numerous. The risk of infection from a single unprotected sexual contact with an infected partner is 11/23/16 3:44 AM       Bacterial STDs c Clini al Case tudy A Painful Problem H S A 20-year-old man reports to his physician that he has experienced painful urination, as though he were urinating molten metal. e has also noticed a puslike discharge from his penis. A stained smear of the discharge is shown in the photo. LM 20 µm The man reports having been sexually active with two or three women in the previous six months. Because his partners reported being “absolutely sure” that they carried no sexually transmitted diseases, he had not used a condom. 1. What disease does this patient most likely have? What are the medical and common names for this disease? 2. How did the patient acquire the disease? 3. What could explain the lack of any history of sexually transmitted disease in his sexual partners? 4. What is the likely treatment? 5. Is the patient immune to future infections with this bacterium? Treponema, but rather with severe complications resulting from inflammation and a hyperimmune response against the pathogen. Gummas (painful, rubbery lesions, often on skin or bones), destruction of cardiovascular or central nervous system tissue, personality changes, insanity, and blindness are manifestations of tertiary syphilis. Congenital syphilis results when Treponema crosses the placenta from an infected mother to her fetus. Transmission to the fetus from a mother experiencing primary or secondary syphilis often results in the death of the fetus. If transmission occurs while the mother is in the latent phase of the disease, the fetus often suffers mental retardation and malformation of many organs. After birth, newborns with latent infections usually exhibit a widespread rash like that of secondary syphilis at some time during their first two years of life. Epidemiology Syphilis occurs worldwide; WHO estimates that syphilis afflicts more than 12 million new victims each year. The discovery and development of antimicrobial drugs has greatly reduced the number of cases in the United States (FIGURE 24.7a), though the disease remains endemic among sex workers, men who have sex with men, and users of illegal drugs. It occurs throughout the United States. The goal of the CDC to achieve an incidence of fewer than 0.2 cases of syphilis per 100,000 population in every county in the United States by 2010 was not met (FIGURE 24.7b). Diagnosis, Treatment, and Prevention 10–30%. T. pallidum can also be spread from mother to fetus and rarely through blood transfusion. It cannot be spread by fomites such as toilet seats, eating utensils, or clothing. Untreated syphilis can have four phases: primary, secondary, latent, and tertiary syphilis. In primary syphilis, a chancre forms at the site of infection. The center of the chancre fills with serum that is extremely infectious because of the presence of millions of spirochetes. Chancres remain for three to six weeks and then disappear without scarring. In about a third of cases, the disappearance of the chancre is the end of the disease. However, in most infections Treponema has invaded the bloodstream and spreads throughout the body to cause the symptoms and signs of secondary syphilis, including rash. Like the primary chancre, rash lesions are filled with spirochetes and are extremely contagious. People, including health care workers, are infected when fluid from the lesions enters breaks in the skin, though such nonsexual transmission of syphilis is rare. After several weeks or months, the rash gradually disappears, and the patient enters a stage called latent syphilis. This is a clinically inactive phase of the disease. The majority of cases do not advance beyond this point, especially in developed countries where antimicrobial drugs are in use. Latency may last 10 or more years, after which about a third of the originally infected patients proceed to tertiary syphilis. This phase is not associated with the direct effects of M24_BAUM7206_05_SE_C24.indd 763 The diagnosis of primary, secondary, and congenital syphilis is relatively easy and rapid using specific antibody tests against antigens of Treponema pallidum. One such test is MHA­TP (microhemagglutination assay against T. pallidum), which uses red blood cells that have been artificially coated with Trepo­ nema antigens. Antibodies in the serum of infected patients will agglutinate (clump) the red blood cells—a positive test for exposure to T. pallidum. Spirochetes can be observed (see Disease at a Glance 24.5) in fresh discharge from lesions, but only when microscopic observations of clinical samples are made immediately—Treponema rarely survives transport to a laboratory. Nonpathogenic spirochetes, which are a normal part of the oral microbiome, can yield false positive results, so clinical specimens from the mouth cannot be tested for syphilis. Tertiary syphilis is extremely difficult to diagnose because it mimics many other diseases, because few (if any) spirochetes are present, and because the signs and symptoms may occur years apart and seem unrelated to one another. Penicillin G is the drug of choice for treating primary, secondary, latent, and congenital syphilis. It does not work for tertiary syphilis, because this phase is a hyperimmune response, not an active infection. There is no proven alternative for patients who are allergic to penicillin. A vaccine against syphilis is not available, so abstinence, faithful mutual monogamy, or consistent and proper condom usage are the primary ways to avoid contracting syphilis. All sexual partners of syphilis patients must be treated with prophylactic penicillin G to prevent the spread of syphilis. 11/23/16 3:44 AM Cases (per 100,000) 60 anc is Virulence factors Glycocalyx, adhesins, hyaluronidase. 3 2 Portal of entry Mucous membranes of genitalia; sexual or congenital transmission. Signs and symptoms rimary syphilis: hard, nonpainful genital chancre that disappears after three to six weeks. LM 3 µm Secondary syphilis: sore throat, headache, mild Treponema pallidum, the cause of syphilis. fever, malaise, myalgia, A special silver stain makes the thin and rash that lasts several spirochetes visible. weeks or months. atent syphilis: generally asymptomatic; lasts for decades. Tertiary syphilis: dementia, blindness, paralysis, and gumma lesions. P 30 20 10 0 24.5 Cause Treponema pallidum (spirochete). 4 ‘03 ‘04 ‘05 ‘06 ‘07 ‘08 ‘09 ‘10 ‘11 ‘12 ‘13 ‘14 ‘15 40 e Syphilis 5 1 50 Gl ‘45 ‘50 ‘55 ‘60 ‘65 ‘70 ‘75 ‘80 ‘85 ‘90 ‘95 ‘00 ‘05 ‘10 ‘15 Year L Reported cases per 100,000 population 70 eA t D e 6 as 7 a R ­ t a       Ch p er 24    Microbial Diseases of the Urinary and eproductive Systems (a) Incubation period 10–90 days (average 21 days) for the primary form of the disease. Susceptibility Sexually active individuals and fetuses whose mothers are infected. P Treatment enicillin. Prevention Sexual abstinence, mutual monogamy, or use of condoms. (b) The most common sexually transmitted bacterium is Chlamydia trachomatis (kla-mid′ē-ă tra-kō′ma-tis), which causes several sexually transmitted and congenital diseases, including lympho­ granuloma venereum and trachoma. 0 >0–2.4 2.5–5.4 >5.4 Signs and Symptoms ▲ FIGURE 24.7 The incidence of syphilis in the United R States. (a) Nationwide incidence of syphilis, 1941–2015. (b) eported incidence of syphilis by county per 100,000 population, 2014. Disease at a Glance 24.5 summarizes the characteristics of syphilis. Chlamydial Infections LE A R N I N G O U TC O M E S 24.24 Describe lymphogranuloma venereum, including its manifestations, cause, pathogenesis, epidemiology, treatment, and prevention. 24.25 Explain how sexually inactive children may become infected with Chlamydia trachomatis and get trachoma. 24.26 Describe how pelvic inflammatory disease can result from Chlamydia infection. M24_BAUM7206_05_SE_C24.indd 764 About 85% of chlamydial genital tract infections in women are asymptomatic; in contrast, more than 75% of infected men show signs and symptoms similar to those of gonorrhea—urethritis, painful urination, and pus discharge from the penis. Chlamydial infection can also cause epididymitis (inflammation of the epididymis) or orchitis8 (inflammation of a testis) in males and pelvic inflammatory disease (PID) in females. Each of these three diseases can lead to sterility. (Disease at a Glance 24.3 on p. 757 examines PID caused by Chlamydia and other bacteria). When babies are infected at birth, an eye disease called trachoma develops. Trachoma is the leading cause of nontraumatic blindness in humans worldwide. A severe form of chlamydial STD in males and females is ly mphog ra nu loma venereu m 9 (lim′fō-g ra n-ū-lō′mă ve-ne′rē-um), which is characterized by a transient genital lesion at the site of infection on the penis, urethra, scrotum, vagina, cervix, or external female genitalia. This is followed by Greek orchis, meaning “testis,” and itis, meaning “inflammation.” Latin lympha, meaning “clear water”; Latin granulum, meaning “a small grain”; Greek oma, meaning “tumor” (swelling); and Latin Venus, the goddess of sexual love. 8From 9From 11/23/16 3:44 AM       Bacterial STDs development of a bubo (FIGURE 24.8)—a painfully inflamed lymph node—in the groin, fever, chills, anorexia, and muscle pain. Buboes may enlarge to the point that they rupture, producing draining sores. Pathogens and Virulence Factors Bacteria of the genus Chlamydia are nonmotile and grow and multiply only within vesicles inside host cells. Scientists once considered chlamydias to be viruses because of their small size and intracellular lifestyle. However, chlamydias are cellular and possess DNA, RNA, and functional 70S ribosomes. Two membranes, similar to those of a typical Gram-negative bacterium, surround each chlamydial cell, but there is no peptidoglycan between the membranes—chlamydias do not have cell walls. Because of their unusual features and unique rRNA nucleotide sequences, taxonomists now classify chlamydias in their own phylum: Chlamydiae. Chlamydia trachomatis has a very limited host range. With one exceptional strain, which may eventually be classified as a separate species, all strains of C. trachomatis are pathogens of humans, infecting the conjunctivas of the eyes, lungs, urinary tract, or genital tract. More than 10 strains of C. trachomatis cause STDs in humans; three of these—so-called LGV strains—trigger lymphogranuloma venereum. Other strains cause trachoma. Chlamydia has a unique developmental cycle involving two cellular morphologies, both of which can occur within the phagosome of a host cell (FIGURE 24.9a): tiny (0.290.4 mm), infectious cocci called elementary bodies (EBs) and larger (0.691.5 mm), pleomorphic, replicating, noninfectious reticulate bodies (RBs), which are also called initial bodies. Elementary bodies are the infective forms. They are relatively dormant, are resistant to environmental extremes, and can survive outside cells. RBs survive only inside cells and are reproductive rather than infective. In the life cycle of Chlamydia (FIGURE 24.9b), once an EB attaches to a host cell 1 , it enters by triggering endocytosis 2 . Once inside a vesicle, the EB converts into an RB 3 , which then divides rapidly to form many RBs 4 . About 21 hours after infection, RBs within the vesicle, which is now called an inclusion body, begin converting back to EBs 5 , and about 19 hours after that, the EBs are released from the host cell via exocytosis 6 , becoming available to infect new cells and completing the life cycle. Pathogenesis C. trachomatis enters the body through scrapes or cuts and infects cells of the conjunctiva or cells lining the mucous membranes of the trachea, bronchi, urethra, uterus, uterine tubes, anus, or rectum. Typically, the lesion at a site of infection is overlooked because it is small, is painless, and heals rapidly. Headache, muscle pain, and fever may occur during this stage of the disease. Proctitis10 may occur in men or women because of lymphatic spread of Chlamydia from the genitalia or urethra to the rectum. About 15% of the cases of proctitis in homosexual men result from the spread of C. trachomatis via anal intercourse. LGV strains of Chlamydia infect the lymph nodes in the groin, producing buboes. In a few patients, lymphogranuloma venereum proceeds to a third stage characterized by genital sores, constriction of the urethra, and severe genital swelling. Arthritis may also occur during this third stage, particularly in young white males for an unknown reason. The clinical manifestations of chlamydial infection, including pelvic inflammatory disease, result from the destruction of infected cells at the site of infection and from the inflammatory response this destruction stimulates. Chlamydia is the most common cause of infectious infertility in women worldwide. Reinfection in the same site by the same or a similar strain triggers a vigorous hypersensitive immune response that can result in blindness, sterility, or sexual dysfunction. Chlamydial infection in adolescence increases the risk of developing cervical cancer later in life. Trachoma strains of C. trachomatis multiply in cells of the conjunctiva, killing them and triggering a copious, purulent (pus-filled) discharge that causes the conjunctiva to become scarred. Such scarring in turn causes the patient’s eyelids to turn inward, such that the eyelashes scratch, irritate, and scar the cornea, which triggers an invasion of blood vessels into this normally clear surface of the eye. A scarred cornea becomes filled with blood vessels and is no longer transparent. The eventual result is blindness. Epidemiology ▲ FIGURE 24.8 An advanced case of lymphogranuloma venereum in a man. Which microorganism causes lymphogranuloma venereum? Figure 24.8 Chlamydia trachomatis causes lymphogranuloma venereum. M24_BAUM7206_05_SE_C24.indd 765 Infection with C. trachomatis is the most common of the reportable sexually transmitted diseases in the United States—over 1,425,303 cases in 2015—but epidemiologists estimate that another 3–4 million asymptomatic cases go unreported annually in the United States. Worldwide, an estimated 106 million 10From Greek proktos, meaning “rectum,” and itis, meaning “inflammation.” 11/23/16 3:44 AM Inclusion body ◀ FIGURE 24.9 The developmental forms and life cycle of Chlamydia. (a) lementary bodies and reticulate (initial) bodies within a E Reticulate body (RB) Elementary body (EB) R ­ t a       Ch p er 24    Microbial Diseases of the Urinary and eproductive Systems host cell’s vesicle. (b) The life cycle of Chlamydia. Times in parentheses refer to hours since infection. TEM (a) 1 µm 1 Elementary body (EB) attaches to receptor on host cell (0 hour). Diagnosis, Treatment, and Prevention 3 EB converts into reticulate body (RB) within vesicle (10 hours). Inclusion body (b) M24_BAUM7206_05_SE_C24.indd 766 4 RB divides rapidly, resulting in multiple RBs. The vesicle is now called an inclusion body. T M W y h EB inside endocytic vesicle. e Vesicle Historically, diagnosis of chlamydial infection involved demonstration of the bacterium inside cells from specimens obtained from the urethra or vagina by inserting, rotating, and then removing a sterile swab. Alternatively, clinicians amplified the number of bacterial cells by inoculating the specimen into a culture of susceptible human cells. They could then demonstrate the presence of Chlamydia in the cell culture by means of specific fluorescent antibodies or nucleic acid probes. Today, demonstration of chlamydial DNA in a specimen following PCR amplification of DNA is diagnostic for chlamydial infection. Physicians prescribe doxycycline or erythromycin to eliminate genital infections in adults. PID is treated with cefoxitin plus doxycycline. Trachoma strains of C. trachomatis infecting the eyes of newborns are initially treated with erythromycin cream and then with oral erythromycin for 14 days. Surgical correction of eyelid deformities may prevent the scratching, scarring, and blindness that typically result from eye infections. As with all STIs and STDs, abstinence or faithful mutual monogamy are the only preventives, though scientists are developing a vaccine. Blindness can be prevented only by prompt treatment with antibacterial agents and prevention of reinfection. Unfortunately, chlamydial infections are often asymptomatic and frequently occur among populations that have limited access to medical care. ell 2 EB triggers its own endocytosis by host cell. 6 EBs are released from host cell (40 hours). 5 Most RBs convert back into EBs (21 hours). cases of Chlamydia infection occur annually. Sexually transmitted chlamydial infections are most prevalent among women under the age of 20 because they are physiologically more susceptible to infection. LGV strains of Chlamydia are found primarily in the tropics. Researchers further estimate that over 500 million people worldwide, particularly children, contract eye infections with C. trachomatis. The bacterium infects children as they pass through the birth canal. The pathogen may also be transmitted from eye to eye via droplets, hands, contaminated fomites, or flies. Chlamydial eye infections are endemic in crowded, poor communities where people have poor personal hygiene, inadequate sanitation, and inferior medical care, particularly in the Middle East, North Africa, and India. Why is erythromycin substituted for tetracycline in treatment of chlamydial infections in children? Why are penicillins and cephalosporins useless against Chlamydia? Viral STDs Viruses are the most common causes of sexually transmitted diseases, including AIDS, herpes, and genital warts. The following sections examine herpes and genital warts. (Chapter 18 11/23/16 3:44 AM       Viral STDs c Clini al Case tudy ­ reparing for delivery, an obstetrician notices genital sores and severe swelling of the labia on a pregnant 24-year-old female. Upon questioning the woman, the doctor discovers that she previously had swollen and painful lymph nodes near her groin but did not seek treatment because she assumed it was related to the pregnancy. P S A Sick Mother-to-Be 1. What is the disease and causative agent? 2. What risk is there, if any, to the unborn child? 3. How should the doctor treat the woman? The newborn? 4. Left untreated, what symptoms, if any, would the newborn experience? 5. Left untreated, how might the disease progress in the woman? examines AIDS as a syndrome resulting from the collapse of the immune system.) Genital Herpes LE A R N I N G O U TC O M E S 24.27 Discuss the features of genital herpes, including mani- festations, treatment, and prevention. 24.28 List conditions that may reactivate latent genital herpes. The name herpes, which is derived from a Greek word meaning “to creep,” is descriptive of the slowly spreading skin lesions that are characteristic of herpesvirus infections. (Chapter 23 examines oral herpes; here we consider genital herpes.) Signs and Symptoms Genital herpes manifests as numerous small blisters on the genitals, around the rectum, or on adjacent areas of skin. The blisters, which are filled with clear, straw-colored fluid, eventually break and become painful ulcers. Patients often experience fever, malaise (feeling of general discomfort or uneasiness), myalgia, and decreased appetite. Pathogen and Virulence Factors Two enveloped, polyhedral, double-stranded DNA viruses called human herpesviruses (HHV, genus Simplexvirus) cause genital herpes. (These viruses were known previously as herpes simplex viruses, abbreviated HSV.) About 85% of cases M24_BAUM7206_05_SE_C24.indd 767 involve HHV­2, which has been called “below-the-waist herpesvirus.” HHV­1 (“oral herpesvirus” or “cold sore virus”) causes the remaining cases of genital herpes, usually following oral-genital sexual intercourse. HHV-2 can also cause oral lesions. (Chapter 23 discusses oral herpes in more detail.) Herpesviruses can become latent in nerve cells, hiding the viruses from immune surveillance. Pathogenesis The membrane of a herpesvirus attaches to and fuses with a host cell’s membrane, depositing the viral capsid and genome in the cytosol. The viral genome enters the cell’s nucleus, where new viruses are synthesized and assembled. Virions acquire envelopes from the nuclear membrane and exit the cell via exocytosis or cell lysis. There is an incubation period of about five days between infection and manifestations of disease. The fluid-filled blisters form as herpesvirus kills epithelial cells at a site of infection. When the blisters rupture, they release millions of herpesviruses and turn into painful ulcers. Infected people shed herpesviruses in mucous secretions even in the absence of lesions. In fact, asymptomatic patients may spread genital herpesviruses more frequently than patients with ulcers. Nerve cell nuclei are grouped in structures called gan­ glia (FIGURE 24.10). Some viruses remain latent as circular DNA within ganglia, becoming active and triggering recurrent lesions intermittently for years at sites innervated by the infected nerve. The patient may experience pain, tingling, burning, itching, or skin sensitivity at sites where new blisters will form. These may be far removed from the infected nucleus, such as the eye (FIGURE 24.11a). Scientists do not fully understand what causes viral latency or triggers recurrence, but the latter may be induced by emotional or physical stress, such as fever, trauma, sunlight, menstruation, mechanical irritation, fatigue, or the immunosuppression of AIDS. Herpesviruses spread by other than sexual means: Babies exposed to the initial genital herpes lesions as they pass through the birth canal can be infected. Herpesviruses can permanently disable or kill these young patients. Recurrent lesions, however, are not as harmful to newborns, presumably because maternal antibodies provide protection. Patients shedding herpesviruses from bursting blisters can infect their own or another person’s esophagus, eyes, or skin. A herpes blister on a finger is called whitlow (FIGURE 24.11b). Health care workers should always take precautions to protect themselves from ocular herpes and whitlow. Epidemiology Epidemiologists estimate that over 90% of the world’s population is infected with one or both human herpesviruses 1 and 2, and about 417 million are infected with HHV-2 and are at risk for genital herpes. In the United States, HHV-2 infects about 16%. Twice these numbers of people have antibodies against the viruses, indicating that they have been exposed. Genital herpes quadruples the risk of HIV infection, presumably because herpes lesions provide a path for HIV to enter the body. 11/23/16 3:44 AM Trigeminal (V) nerve ganglion (sites of viral latency) R ­ t a       Ch p er 24    Microbial Diseases of the Urinary and eproductive Systems Ocular herpes Ophthalmic branch Trigeminal nerve Maxillary branch Brachial nerve ganglia (sites of viral latency) Mandibular branch Fever blisters Sacral nerve ganglia (sites of viral latency) Circumcised males are at a lower risk for herpes infections, as are their female sexual partners. Herpes lesions in women are usually on the external genitalia, so use of a condom during sexual intercourse provides little protection to their partners. People with active lesions should not have sex until the crusts have disappeared. Even in the absence of lesions, condoms should be used for every sexual encounter because asymptomatic individuals still shed viruses on their skin. Valacyclovir—a nucleotide analog that interferes with viral replication more than cellular replication—reduces the risk of viral spread. Pregnant women with herpes infections, even if asymptomatic, should inform their doctors. To protect the baby, delivery should be by cesarean section (C-section) if genital lesions are present at the time of birth. Genital Warts LE A R N I N G O UTC O M E S 24.29 Describe the characteristics and prevention of genital warts. 24.30 Describe the connection between genital warts and cer- vical cancer. Pathogen, Signs, and Symptoms Genital herpes Whitlow ▲ FIGURE 24.10 Sites of events in genital herpesvirus infections. Infections occur when herpesviruses invade the lips, the genitalia, or broken skin. 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. What factors may trigger the reactivation of latent herpesviruses and the recurrence of symptoms? Figure 24.10 Emotional stress, fever, trauma, sunlight, menstruation, mechanical irritation, fatigue, or AIDS may trigger recurrent symptoms. Diagnosis, Treatment, and Prevention The characteristic lesions are indicative of genital herpes. Detection of herpesvirus DNA by PCR in fluid from a blister confirms the diagnosis. As with many viral diseases, there is no cure for genital herpes, though treatment can relieve and lessen the manifestations. Daily oral dose of acyclovir or other antiviral agents over a 6- to 12-month period can be effective in preventing recurrent genital herpes lesions and in reducing the spread of herpes infections to sexual partners. Some obstetricians prescribe acyclovir during the final weeks of pregnancy for women with a history of genital herpes. (Chapter 10 considers the actions of antiviral drugs.) Sexual abstinence and faithful monogamy between uninfected partners are the only sure ways of preventing genital infections. M24_BAUM7206_05_SE_C24.indd 768 Papillomas, or warts, are generally harmless growths of the epithelium of the skin on the face, trunk, hands, feet, elbows, knees, or genitalia caused by human papillomaviruses (HPVs). Genital warts appear on the genitalia, on surrounding skin, or in the anus and rectum when HPVs invade the skin or mucous membranes of the penis (particularly when it is uncircumcised), vagina, or anus during sexual intercourse. Papillomas range in size from almost undetectable small bumps to giant, cauliflower like growths called condylomata acuminata11 (kon-di-lō′mah-tă ă-kyū-mi-nah′tă) (see Disease in Depth: Papillomas on p. 770). Pathogenesis and Epidemiology The incubation time from infection to the development of a wart is usually three to four months. Although all warts can be painful and are often unsightly, genital warts are more distressing because they cause nearly all cervical cancers as well as some vaginal, oral, penile, and anal cancers. Genital warts are the most common sexually transmitted disease in the United States, mostly in young adults. Sexually active adolescents, uncircumcised men, and the sexual partners of these individuals are at greatest risk. Research suggests that if all men were circumcised, the worldwide incidence of cervical cancer would be reduced at least 43%. Diagnosis, Treatment, and Prevention Diagnosing warts is a simple matter of observation. Over-thecounter medications are often effective in removing warts from skin, but physicians recommend that such removal medications never be used on genital warts, in part because irritating 11From Greek kondyloma, meaning “knob,” and Latin acuminatus, meaning “pointed.” 11/23/16 3:44 AM       P rotozoan STDs (a) (b) ▲ FIGURE 24.11 Herpes lesions of the eyes and skin. (a) Ophthalmic, or ocular, herpes results from reactivation of latent viruses in the trigeminal ganglion. (b) A whitlow on a health care provider’s finger, resulting from the entry of herpesvirus through a break in the skin of the finger. How can health care providers protect themselves from a whitlow? Figure 24.11 Health care workers should always wear gloves when handling patients who have lesions. is not the usual way these protozoa are infective. This section examines Trichomonas, a protozoan that normally infects reproductive systems. Trichomoniasis LE A R N I N G O UTC O M E 24.31 Describe the features of trichomoniasis, including signs, symptoms, cause, pathogenesis, treatment, and prevention. Trichomonads are flagellated protozoan parasites of animals and humans. Only one species is pathogenic, Trichomonas vag­ inalis (trik-ō-mō′nas va-jin-al′is), which causes an STD called trichomoniasis (trik′ō-mō-nī′a-sis) or trich (trik). Signs and Symptoms ­ Trichomoniasis is usually symptomatic in women and asymptomatic in men. Infected women typically have a foul-smelling, yellowish green vaginal discharge and vaginal irritation. They may also have lesions in the genitalia, abdominal pain, painful urination, and pain during sexual intercourse. In a few infected men, T. vaginalis causes inflammation of the urethra or prostate—urethritis and prostatitis, respectively—which causes painful urination. These symptoms in men might be confused with those of gonorrhea. ­ chemicals may increase the transmission of other sexually transmitted diseases. Physicians can remove genital warts with surgery, freezing, burning, laser, or the use of caustic chemicals, though with any of these methods, viruses may remain in surrounding tissue, and warts may return. Effective treatment of genital cancers depends on early diagnosis resulting from thorough visual inspection of the genitalia in both sexes, and in women by a Papanicolaou (pa′pa-nē′ko-low) smear (Pap smear) to screen for cervical cancer. Treatment involves radiation or chemical therapy directed against reproducing tumor cells. Advanced cases of genital cancer necessitate removal of the entire diseased organ. Genital warts can be prevented by abstinence or mutual monogamy with an uninfected partner. Condoms may reduce the risk of infection with HPV but do not eliminate it. Using recombinant DNA techniques, scientists have created a vaccine that successfully prevents infection by the four most common strains of sexually transmitted papillomaviruses, including the strains associated with most cervical cancers. The CDC recommends three doses of HPV vaccine for all adolescents and adults younger than 50 years of age. Disease in Depth: Papillomas on p. 575 examines papillomas, including genital warts. h M W y e ell T ­ Why are DNA viruses, such as herpesviruses and papilloma viruses, more likely to cause recurrent diseases and cancers than are RNA viruses? Protozoan STDs ­ Sexual activit y can transmit several protozoa, including the transfer of intestinal parasites such as Giardia and Cryptosporidium during oral-anal intercourse; however, this M24_BAUM7206_05_SE_C24.indd 769 Pathogen and Virulence Factors Trichomonas is a leaf-shaped, parabasalid protozoan, averaging 13 mm in length and about half as wide. It has five anterior flagella and an undulating membrane (see Disease at a Glance 24.6). The protozoan lives solely in humans, inhabiting vaginas, urethras, and prostate glands. Trichomonas reproduces at pH 5 to pH 6. Normal lactobacilli keep the pH of the vagina at 4.0 to 4.5; thus, the vaginal microbiome helps keep Trichomonas in check. 11/23/16 3:44 AM R Thrush. Based on the man’s symptoms, what diagnosis can be made? What laboratory tests could confirm a diagnosis in this case? How did the man most likely acquire the infection? What changes to the man’s immune system allowed the opportunistic infections of Candida (thrush) and neumocystis (pneumonia) to arise? 5. What precautions should be taken with the patient’s blood? P 1. 2. 3. 4. Pathogenesis and Epidemiology Gl anc a eA t is D e as T. vaginalis does not produce cysts and cannot survive long in the relatively high oxygen concentration and dry atmosphere outside the body; therefore, infection is nearly always via sexual intercourse. However, epidemiologists have documented a few cases of Trichomonas transferring to patients on fomites such as damp washcloths. Presence of Trichomonas in newborns indicates that the flagellate can infect babies during their passage through the birth canal. e Diagnosis, Treatment, and Prevention Diagnosis usually relies on identifying motile Trichomonas in secretions from the vagina, urethra, or prostate. The protozoan is found in only about two-thirds of specimens from people who have it, so fluorescent antibody staining of smears or culturing the parasite provides confirmation of a diagnosis. Treatment is with a single 2-gram dose of metronidazole or tinidazole taken orally. A physician must treat the male partner at the same time, or the woman can be reinfected. No long-term immunity develops against T. vaginalis. Prevention depends on refraining from sexual intercourse with infected persons. Babies can be protected by treating their mothers with metronidazole before they give birth. Disease at a Glance 24.6 summarizes the features of trichomoniasis. T M W y h S A 25-year-old homosexual man was admitted to the hospital with oral candidiasis (thrush), diarrhea, unexplained weight loss, herpes lesions, and pneumonia. Cultures of pulmonary fluid revealed the presence of Pneumocystis jirovecii. The man admitted to frequently paying for sex. e A Very Sick Man For over 60 years, researchers have puzzled over the exact method of T. vaginalis pathogenicity. Virulence factors include the ability to adhere to human cells, enzymes that break down proteins, the ability to hemolyze blood, and production of a cell-detaching protein, which disrupts tissue integrity. Trichomoniasis is not a reportable disease in the United States. The World Health Organization estimates that about 143 million new cases occurred worldwide in 2012. The disease is the most common curable STD in women. People with multiple sex partners or other venereal diseases have the highest risk of contracting trichomoniasis. The disease increases patients’ susceptibility to infection by HIV and may increase the likelihood that they will pass HIV to their sexual partners. ell ­ c Clini al Case tudy t a       Ch p er 24    Microbial Diseases of the Urinary and eproductive Systems Why might a course of antibacterial drugs trigger a case of trichomoniasis in a female patient? 24.6 Trichomoniasis P Cause Trichomonas vaginalis, a single-celled, flagellated protozoan in the taxon arabasala. Prevention Abstinence, faithful monogamy of both partners, consistent and accurate condom usage. Virulence factors Adhesins, proteolytic enzymes, hemolysis, cell-detaching factor. Portal of entry Mucous membrane of genital tracts. Signs and symptoms In females: malodorous, yellow-green vaginal discharge, vaginal irritation, possibly spot bleeding, dysuria; in males: usually asymptomatic, though the disease may cause urethritis and prostatitis. Incubation period 4–28 days. Susceptibility Sexually active individuals, more commonly heterosexual than homosexual; uncircumcised males may be more at risk than are circumcised males; in pregnant women, trichomoniasis can result in low birth weight and premature birth of baby. Treatment Metronidazole or tinidazole. M24_BAUM7206_05_SE_C24.indd 770 LM 5 µm 11/23/16 3:44 AM       Chapter Summary P P 2. How are the life cycle of C. trachomatis and the host immune response responsible for Tina’s symptoms? y 1. Male and female urinary systems each consist of two kidneys composed of millions of nephrons that filter blood to form urine; two ureters that carry urine to a urinary bladder for temporary storage; and a urethra, which carries urine out of the body. The urethra may be a portal for the entrance of microorganisms. 2. The adult female reproductive system consists of two ovaries, which produce haploid ova, one of which is released monthly. Ova are swept through a uterine tube toward the blood-rich uterus, which is prepared for pregnancy. 3. If a sperm cell (haploid) fertilizes the ovum (also haploid), the resulting diploid zygote develops into an embryo that implants in the uterine wall and further develops into a fetus who passes through the cervix and the birth canal to be born approximately nine months from fertilization. 4. When an ovum is unfertilized, it and the lining of the uterus pass out of the vagina during menstruation. 5. The vaginal opening can be a portal for microorganisms, especially during sexual intercourse. 6. The adult male reproductive system consists of two sets of these structures: a testis (located in an external sac, the scrotum), an epididymis, and a ductus deferens. Sperm formed by a testis are stored in an epididymis and pass through a ductus deferens, into the single prostate, where the left and right ducts join the urethra, which passes through the prostate (where fluid is added to the sperm to form semen) and penis. Sexually transmitted microbes can enter the body through the urethra or skin of the penis. 7. The urinary tract, with the exception of the urethra, is typically axenic. A vagina supports a wide assortment of microorganisms. Members of the microbiomes of the urethra and of the vagina protect the body by microbial antagonism, also called microbial competition. Bacterial Diseases of the Urinary System (pp. 750–751) 1. Bacteria may trigger inflammation in the urethra (urethritis), urinary bladder (cystitis), prostate (prostatitis), or kidneys (pyelonephritis). These are all types of urinary tract infections (UTIs). 2. Mild urethritis, cystitis, or prostatitis cause problems with urination and produce fever. Pyelonephritis causes pain, higher fever, vomiting, and fatigue; if untreated, it can be fatal. 3. Enteric (fecal) bacteria most often cause UTIs. 4. The spirochete Leptospira interrogans, which is in the urine of infected animals, causes leptospirosis, a zoonotic disease (disease of animals acquired by humans), which results in bacteremia and infected kidneys. 5. When some strains of group A Streptococcus infect adults, antibody-antigen complexes accumulate in the glomeruli of the kidneys to trigger glomerulonephritis, inflammation of the glo meruli and nephrons. Streptococcal acute glomerulonephritis is a progressive and irreversible kidney disease in adults. ­ ummar S Structures of the Urinary and Reproductive Systems (pp. 748–750) M24_BAUM7206_05_SE_C24.indd 771 1. Why are chlamydias characterized as obligate intracellular pathogens? P e r C hapt P P P P P Dr. erry starts by updating Tina’s medical history, including her sexual activity. Tina reports that Marcus has been her only sexual partner for the last 15 months. Dr. erry also asks Tina whether they are using birth control in addition to her oral contraceptives; Tina indicates that since they were committed to a monogamous relationship, they stopped using condoms. Dr. erry performs a pelvic exam and takes a sample of fluid from Tina’s cervix. Dr. erry also notices a mucopurulent (containing pus and mucus) discharge from Tina’s cervix. The lab analysis of Tina’s cervical fluid indicates infection with Chlamydia trachomatis. The presence of C. trachomatis in addition to Tina’s other symptoms indicates that Tina has pelvic inflammatory disease ( ID). Dr. etty informs Tina that she must tell Marcus immediately so that he can be tested. If Tina has been sexually active only with Marcus, then Marcus acquired the infection from another partner; all of his partners must also be notified. Dr. etty starts Tina on a course of cefoxitin and doxycycline to treat the ID; however, only time will tell whether Tina suffers from any of the longterm complications from ID, such as infertility. P The Happiest of Times? 11/23/16 3:44 AM R ­ t a       Ch p er 24    Microbial Diseases of the Urinary and eproductive Systems Nonvenereal Diseases of the Reproductive Systems (pp. 751–757) ­ 1. Certain strains of Staphylococcus aureus cause staphylococcal toxic shock syndrome (TSS), a potentially fatal condition observed historically in menstruating females who use super-absorbent tampons. Toxins produced by S. aureus in the vagina or in a wound stimulate T cells to release excessive cytokines, which triggers TSS. 2. Facultative or obligate anaerobic bacteria infecting the vaginal lining may cause bacterial vaginosis, a noninflammatory condition associated with odiferous vaginal discharge. Risk factors include having multiple sexual partners and vaginal douching. Douching reduces the normal population of lactobacilli in the vagina, elevating the pH and allowing pathogenic bacteria to grow. 4. When Treponema spreads via the bloodstream, secondary syphilis results. It is characterized by malaise and a long-lasting, contagious skin rash. 5. Latent syphilis is a clinically inactive phase, which may last decades. 6. Tertiary syphilis is associated with severe complications resulting from inflammation and a hyperimmune response. Untreated patients can experience dementia, blindness, paralysis, heart failure, and syphilitic gummas (swollen lesions on skin or other organs). 7. Congenital syphilis is a disease of a fetus following transmission in the womb of an infected mother. The results may be death, mental retardation, rash, or the malformation of organs. 3. Following changes in vaginal pH or in the normal microbiome, opportunistic Candida albicans (yeast) causes vaginal candidiasis characterized by curdlike vaginal discharge, itching, and burning. 8. Chlamydia trachomatis is the most common sexually transmitted bacterium; infections are often asymptomatic in women and produce symptoms similar to gonorrhea in men. 4. Candida forms diagnostic cellular extensions called pseudohyphae 9. Chlamydial infection can also cause inflammation of an epididymis (epididymitis), inflammation of a testis (orchitis), eye disease in babies at birth (trachoma), and lymphogranuloma venereum, which is a genital lesion followed by the development of an inflamed lymph node (a bubo). Sexually Transmitted Infections (STIs) and Diseases (STDs) (pp. 757–760) 1. Sexually transmitted infections (STIs) involve microbes shared by sexual partners. When they cause disease, such disease is a sexually transmitted disease (STD). STDs are at epidemic proportions. 2. Pelvic inflammatory disease (PID) is a general term for inflammation and pain in the uterus, uterine tubes, or ovaries. Untreated PID can lead to ectopic pregnancies and sterility. Bacterial STDs (pp. 760–767) 1. Gonorrhea is caused by Neisseria gonorrhoeae, which adheres to the epithelial cells of mucous membranes, especially in the genital, urinary, and digestive tracts. It can cause painful urination and pus-filled discharge from the penis in men, uterine tube damage or pelvic inflammatory disease in women, and eye damage in newborns infected during birth. Many women are asymptomatic. When the bacterium travels inside leukocytes throughout the body, other organs are affected. 2. The spirochete Treponema pallidum causes syphilis, an STD with four phases. 1. Human herpesviruses HHV-2 (“below-the-waist” virus) and HHV-1 (the “cold-sore” virus) cause genital herpes, which is characterized by genital blisters full of virions. Some viruses remain latent in nerve ganglia and cause recurrent manifestations. 2. Herpesviruses also spread by nonsexual means, such as during birth or via contact with herpes blisters on the skin—a condition called whitlow. 3. Papillomavirus causes papillomas, or warts, which range in size from barely detectable to a cauliflower-like growth on the genitals called condylomata acuminata. Some human papillomaviruses cause cancers. Protozoan STDs (pp. 769–770) 1. Intestinal protozoa may be transferred by certain sexual practices. 2. The protozoan Trichomonas vaginalis causes trichomoniasis. 3. Trichomoniasis is symptomatic in women (an odiferous, yellowish green vaginal discharge and vaginal irritation) but usually asymptomatic in men. w vi R F r e e o u Q e stions 3. During primary syphilis, a small, hard, extremely infectious chancre (lesion) fills with spirochetes at the site of infection and remains for several weeks. Viral STDs (pp. 766–769) Answers to the Questions for Review (except Short Answer questions) begin on p. A-1. 1. The functional unit of a kidney is the a. pelvis b. nephron c. glomerulus d. renal pyramid M24_BAUM7206_05_SE_C24.indd 772                    Multiple Choice . 2. Which of the following sequences most accurately describes the passage of sperm through the reproductive tract? a. testis, epididymis, ductus deferens, urethra, penis b. testis, ductus deferens, epididymis, prostate, urethra c. scrotum, ductus deferens, epididymis, urethra, prepuce d. vas deferens, epididymis, prostate, urethra, penis 11/23/16 3:44 AM 5. Which stage of syphilis is characterized by chancres filled with contagious spirochetes? a. primary c. latent b. secondary d. tertiary .                    1.            Dysuria A. Inflammation of a kidney 2.            Bacteremia B. Inflammation of the prostate 3.            Zoonosis C. 4.            Ophthalmia neonatorum Inflammation of the urinary bladder D. Inflammation of a testis 5.            Proctitis E. Inflammation of the rectum 6.            Pyelonephritis F. Frequent, urgent, and painful urination G. Muscle pain 7.            Orchitis 8.            Gummas H. Inflammation of the conjunctiva in newborns 9.            Myalgia 10.            Cystitis I. Disease spread from animals to humans J. Rubbery, painfully swollen lesions in bones, nervous tissue, or on the skin K. Large cauliflower-like growths on the genitalia L. General term for an STD 11.            Whitlow 12.            Prostatitis 13.            Condylomata acuminata  6. Treatment of chlamydial infections involves a. erythromycin cream b. tetracycline c. surgical correction of eyelid deformities d. all of the above Match the term with its description. ­ 4. Select the true statement about gummas. a. Gummas are small, painless, reddened, hard lesions. b. Gummas are diseased lymph nodes, which may persist for months. c. Gummas typically form during the primary phase of syphilis. d. Gummas are rubbery, painfully swollen lesions. Matching                     3. Bacterial infection of the vagina that does not involve inflammation is called . a. bacterial virulence b. bacterial vaginitis c. bacterial vaginosis d. bacterial bulbosis 7. In which stage of syphilis is penicillin ineffective? a. primary syphilis b. secondary syphilis c. tertiary syphilis d. Penicillin is ineffective for all of the above.       R Questions for eview 14.            PID 15.            Venereal disease M. Infection of skin by herpesviruses 8. Which of the following is the most common of these sexually transmitted diseases in the United States? a. syphilis b. gonorrhea c. chlamydial infection d. AIDS                    9. A foul-smelling, yellowish green vaginal discharge characterizes . a. gonorrhea b. trichomoniasis c. chlamydial infection d. syphilis 10. Which of the following statements concerning properly used condoms is false? a. Condoms reduce the spread of genital warts. b. Condoms reduce the incidence of gonorrhea. c. Condoms may increase the likelihood of chlamydial infection. d. Condoms are effective in reducing the transmission of syphilis. N. Bacterial invasion of the bloodstream O. Inflammation of uterus, uterine tubes, and ovaries Match the organism with the disease it causes. 1.            Leptospira A. Cold sores 2.            Papillomavirus B. Toxic shock syndrome 3.            Chlamydia C. Genital warts 4.            Treponema D. Syphilis 5.            Neisseria E. Leptospirosis 6.            Staphylococcus F. Lymphogranuloma venereum 7.            Candida G. Genital herpes 8.            HHV-1 H. Gonorrhea 9.            HHV-2 I. Yeast infection                    3. When the normal lactobacilli of the vagina are replaced by Gard­ nerella vaginalis or Mycoplasma hominis, the resulting infection is called . M24_BAUM7206_05_SE_C24.indd 773                                       5. Trachoma, the leading cause of nontraumatic blindness in humans worldwide, is caused by the sexually transmitted bacterium . 6. The most common curable protozoan STD in women is                                       2. The majority (70%) of urinary tract infections are caused by the intestinal bacterium . 4. Three structural virulence factors of a virulent strain of Neisseria gonorrhoeae are , , and .                    of the penis.                    1. Circumcision involves cutting away the                    Fill in the Blanks . 11/23/16 3:44 AM R ­ t a       Ch p er 24    Microbial Diseases of the Urinary and eproductive Systems Modified True/False Change the underlined word or phrase in all false statements to make the statement true. 9. At a small farm, the children regularly played in a pond that was frequented by livestock. The children were unusually ill one year and complained of stomachaches, vomiting, headaches, and fever. What might be the cause? 1.                       Toxic shock syndrome is a sexually transmitted disease. 10. Why is there no effective vaccine against gonorrhea? 2.                       Nearly all AIDS patients develop candidiasis in their reproductive or digestive tracts. 12. Describe and sketch the developmental cycle of Chlamydia. 3.                       Gonorrhea is frequently transmitted via toilet seats. 4.                       The symptoms of gonorrhea in women are more obvious and painful than in men. 5.                       There is no cure for genital herpes. 6.                       The bacterium that causes syphilis is transmitted via contact with toilet seats, soiled clothing, or other fomites. 7.                       Evidence suggests that male circumcision reduces the risk of cervical cancer in female sexual partners. 11. Why is tertiary syphilis difficult to diagnose? 13. Contrast vaginosis with vaginitis. VISUALIZE IT! 1. Label the following stages and structures of the chlamydia life cycle: elementary body, endocytosis, vesicle, host cell, inclusion body, reticulate body. Indicate how many hours typically transpire at each lettered step. A (0 hour) (a) _______________ (f) _______________ ­ 8.                       Over-the-counter wart removal medications are recommended for genital warts. 9.                       There is a vaccine for some strains of cancer-causing papillomavirus. 10.                       A person infected with herpesvirus but lacking blisters frequently spreads genital herpes in mucous secretions. D ( _________ ) 11.                       Although usually sexually transmitted, trichomoniasis can be transferred via damp fomites. (b) _______________ Short Answer 1. The normal microbiome of the female reproductive tract helps maintain a vaginal pH of about 4.5. Why is this important? 2. If the urinary organs and the urine in them are usually axenic, why does normally voided urine contain bacteria? (c) _______________ C ( _________ ) 3. What structure found in Neisseria gonorrhoeae allows the bacterium to attach to sperm cells and travel up the uterine tubes to produce pelvic inflammatory disease? 4. The Smith family gets cold sores regularly. Suggest an explanation for why this problem occurs. B ( _________ ) 5. Why have scientists had problems identifying virulence factors of Treponema pallidum? 6. Why do physicians place antimicrobial agents in babies’ eyes at birth? 7. It has been observed that prepubescent girls are more susceptible to vaginal infections than adult women. Explain this observation, mentioning glycogen, lactic acid, pH, and estrogen in your discussion. 8. Although vaginal douching is a cleansing procedure, it can actually promote infection. Explain. M24_BAUM7206_05_SE_C24.indd 774 (e) ____________ (d) _______________ 11/23/16 3:44 AM       R Questions for eview (a) (b) (c) (d) k ing l Th in Cr itica 2. Name the following pathogens of the urinary/reproductive systems. 1. 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? Explain. 2. Some scientists think that syphilis is a New World disease brought to Europe by returning Spanish explorers; others think that syphilis traveled the opposite way. Design an experiment to test the two hypotheses. 5. After a patient complains that his eyes are extremely sensitive to light and feel gritty, his doctor informs him that he has ocular herpes. What causes ocular herpes? Which human herpesvirus, type 1 or type 2, is more likely to cause ocular herpes? Why? 6. Fifteen-year-old Dolores was embarrassed to talk with her mother about the pain she felt in her “private parts,” but she was worried she might have gotten a disease, despite Nick’s assurance that she was his “first.” Her mother insisted that Dolores see a doctor, who discovered cervical lesions caused by a virus associated with cancer. What sexually transmitted virus is involved? How does the physician treat the lesions? How could Dolores have protected herself? 3. Although laser surgery can successfully remove genital warts, some physicians are reluctant to choose this procedure. Explain the possible reason for this attitude, and suggest solutions. 7. Why does treatment of strep throat with an antibacterial drug increase the chance for vaginal candidiasis? 4. Discuss how the use of antimicrobials to prevent genital disease may have negative effects. 8. How could Koch’s postulates be applied to prove that HPV causes cervical cancer? M24_BAUM7206_05_SE_C24.indd 775 11/23/16 3:44 AM R ­       Chapter 24    Microbial Diseases of the Urinary and eproductive Systems c Con ept Mapping Using the following terms, complete this concept map that describes syphilis. Body-wide rash Cardiovascular syphilis Chancre Dark-field microscopy Spirochete Tertiary syphilis Treponema pallidum Penicillin Primary syphilis Secondary syphilis Serological tests Infect fetus in pregnant woman Latent stage Neurosyphilis Never progress Syphilis caused by 1 begins with 4 characterized by 5 characterized by 7 diagnosed by 14 treated with 15 may progress to 6 may progress to 8 10 Last for years may 9 causing Congenital syphilis may progress to 11 characterized by is impossible to culture in 2 12 3 Cell-free media M24_BAUM7206_05_SE_C24.indd 776 viewed with Gummas 13 3/6/18 4:38 PM