# Urogenital System Infections

## Bacterial Infections of the Urinary System

### Learning Objectives

By the end of this section, you will be able to:
1. Identify the most common bacterial pathogens that can cause urinary tract infections
2. Compare the major characteristics of specific bacterial diseases affecting the urinary tract
Urinary tract infections (UTIs) include infections of the urethra, bladder, and kidneys, and are common causes of urethritis, cystitis, pyelonephritis, and glomerulonephritis. Bacteria are the most common causes of UTIs, especially in the urethra and bladder.

### Cystitis

Cystitis is most often caused by a bacterial infection of the bladder, but it can also occur as a reaction to certain treatments or irritants such as radiation treatment, hygiene sprays, or spermicides. Common symptoms of cystitis include dysuria (urination accompanied by burning, discomfort, or pain), pyuria (pus in the urine), hematuria (blood in the urine), and bladder pain.
In women, bladder infections are more common because the urethra is short and located in close proximity to the anus, which can result in infections of the urinary tract by fecal bacteria. Bladder infections are also more common in the elderly because the bladder may not empty fully, causing urine to pool; the elderly may also have weaker immune systems that make them more vulnerable to infection. Conditions such as prostatitis in men or kidney stones in both men and women can impact proper drainage of urine and increase risk of bladder infections. Catheterization can also increase the risk of bladder infection (see Case in Point: Cystitis in the Elderly).
Gram-negative bacteria such as  (most commonly), , , and  cause most bladder infections. Gram-positive pathogens associated with cystitis include the coagulase-negative , , and . Routine manual urinalysis using a urine dipstick or test strip can be used for rapid screening of infection. These test strips () are either held in a urine stream or dipped in a sample of urine to test for the presence of nitrites, leukocyte esterase, protein, or blood that can indicate an active bacterial infection. The presence of nitrite may indicate the presence of E. coli or K. pneumonia; these bacteria produce nitrate reductase, which converts nitrate to nitrite. The leukocyte esterase (LE) test detects the presence of neutrophils as an indication of active infection.
Low specificity, sensitivity, or both, associated with these rapid screening tests require that care be taken in interpretation of results and in their use in diagnosis of urinary tract infections. Therefore, positive LE or nitrite results are followed by a urine culture to confirm a bladder infection. Urine culture is generally accomplished using blood agar and MacConkey agar, and it is important to culture a clean catch of urine to minimize contamination with normal microbiota of the penis and vagina. A clean catch of urine is accomplished by first washing the labia and urethral opening of female patients or the penis of male patients. The patient then releases a small amount of urine into the toilet bowl before stopping the flow of urine. Finally, the patient resumes urination, this time filling the container used to collect the specimen.
Bacterial cystitis is commonly treated with fluoroquinolones, nitrofurantoin, cephalosporins, or a combination of trimethoprim and sulfamethoxazole. Pain medications may provide relief for patients with dysuria. Treatment is more difficult in elderly patients, who experience a higher rate of complications such as sepsis and kidney infections.

### Kidney Infections (Pyelonephritis and Glomerulonephritis)

Pyelonephritis, an inflammation of the kidney, can be caused by bacteria that have spread from other parts of the urinary tract (such as the bladder). In addition, pyelonephritis can develop from bacteria that travel through the bloodstream to the kidney. When the infection spreads from the lower urinary tract, the causative agents are typically fecal bacteria such as E. coli. Common signs and symptoms include back pain (due to the location of the kidneys), fever, and nausea or vomiting. Gross hematuria (visible blood in the urine) occurs in 30–40% of women but is rare in men.Tibor Fulop. “Acute Pyelonephritis”  The infection can become serious, potentially leading to bacteremia and systemic effects that can become life-threatening. Scarring of the kidney can occur and persist after the infection has cleared, which may lead to dysfunction.
Diagnosis of pyelonephritis is made using microscopic examination of urine, culture of urine, testing for leukocyte esterase and nitrite levels, and examination of the urine for blood or protein. It is also important to use blood cultures to evaluate the spread of the pathogen into the bloodstream. Imaging of the kidneys may be performed in high-risk patients with diabetes or immunosuppression, the elderly, patients with previous renal damage, or to rule out an obstruction in the kidney. Pyelonephritis can be treated with either oral or intravenous antibiotics, including penicillins, cephalosporins, vancomycin, fluoroquinolones, carbapenems, and aminoglycosides.
Glomerulonephritis occurs when the glomeruli of the nephrons are damaged from inflammation. Whereas pyelonephritis is usually acute, glomerulonephritis may be acute or chronic. The most well-characterized mechanism of glomerulonephritis is the post-streptococcal sequelae associated with  throat and skin infections. Although S. pyogenes does not directly infect the glomeruli of the kidney, immune complexes that form in blood between S. pyogenes antigens and antibodies lodge in the capillary endothelial cell junctions of the glomeruli and trigger a damaging inflammatory response. Glomerulonephritis can also occur in patients with bacterial endocarditis (infection and inflammation of heart tissue); however, it is currently unknown whether glomerulonephritis associated with endocarditis is also immune-mediated.

### Leptospirosis

 are generally harmless spirochetes that are commonly found in the soil. However, some pathogenic species can cause an infection called leptospirosis in the kidneys and other organs (). Leptospirosis can produce fever, headache, chills, vomiting, diarrhea, and rash with severe muscular pain. If the disease continues to progress, infection of the kidney, meninges, or liver may occur and may lead to organ failure or meningitis. When the kidney and liver become seriously infected, it is called Weil’s disease. Pulmonary hemorrhagic syndrome can also develop in the lungs, and jaundice may occur.
Leptospira spp. are found widely in animals such as dogs, horses, cattle, pigs, and rodents, and are excreted in their urine. Humans generally become infected by coming in contact with contaminated soil or water, often while swimming or during flooding; infection can also occur through contact with body fluids containing the bacteria. The bacteria may enter the body through mucous membranes, skin injuries, or by ingestion. The mechanism of pathogenicity is not well understood.
Leptospirosis is extremely rare in the United States, although it is endemic in Hawaii; 50% of all cases in the United States come from Hawaii.Centers for Disease Control and Prevention. “Leptospirosis.” 2015. http://www.cdc.gov/leptospirosis/health_care_workers. It is more common in tropical than in temperate climates, and individuals who work with animals or animal products are most at risk. The bacteria can also be cultivated in specialized media, with growth observed in broth in a few days to four weeks; however, diagnosis of leptospirosis is generally made using faster methods, such as detection of antibodies to Leptospira spp. in patient samples using serologic testing. Polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), slide agglutination, and indirect immunofluorescence tests may all be used for diagnosis. Treatment for leptospirosis involves broad-spectrum antibiotics such as penicillin and doxycycline. For more serious cases of leptospirosis, antibiotics may be given intravenously.

### Nongonococcal Urethritis (NGU)

There are two main categories of bacterial urethritis: gonorrheal and nongonococcal. Gonorrheal urethritis is caused by Neisseria gonorrhoeae and is associated with gonorrhea, a common STI. This cause of urethritis will be discussed in Bacterial Infections of the Reproductive System. The term nongonococcal urethritis (NGU) refers to inflammation of the urethra that is unrelated to N. gonorrhoeae. In women, NGU is often asymptomatic. In men, NGU is typically a mild disease, but can lead to purulent discharge and dysuria. Because the symptoms are often mild or nonexistent, most infected individuals do not know that they are infected, yet they are carriers of the disease. Asymptomatic patients also have no reason to seek treatment, and although not common, untreated NGU can spread to the reproductive organs, causing pelvic inflammatory disease and salpingitis in women and epididymitis and prostatitis in men. Important bacterial pathogens that cause nongonococcal urethritis include , , , and .
C. trachomatis is a difficult-to-stain, gram-negative bacterium with an ovoid shape. An intracellular pathogen, C. trachomatis causes the most frequently reported STI in the United States, chlamydia. Although most persons infected with C. trachomatis are asymptomatic, some patients can present with NGU. C. trachomatis can also cause non-urogenital infections such as the ocular disease trachoma (see Bacterial Infections of the Skin and Eyes). The life cycle of C. trachomatis is illustrated in .
C. trachomatis has multiple possible virulence factors that are currently being studied to evaluate their roles in causing disease. These include polymorphic outer-membrane autotransporter proteins, stress response proteins, and type III secretion effectors. The type III secretion effectors have been identified in gram-negative pathogens, including C. trachomatis. This virulence factor is an assembly of more than 20 proteins that form what is called an injectisome for the transfer of other effector proteins that target the infected host cells. The outer-membrane autotransporter proteins are also an effective mechanism of delivering virulence factors involved in colonization, disease progression, and immune system evasion.
Other species associated with NGU include Mycoplasma genitalium, Ureaplasma urealyticum, and Mycoplasma hominis. These bacteria are commonly found in the normal microbiota of healthy individuals, who may acquire them during birth or through sexual contact, but they can sometimes cause infections leading to urethritis (in males and females) or vaginitis and cervicitis (in females).
M. genitalium is a more common cause of urethritis in most settings than N. gonorrhoeae, although it is less common than C. trachomatis. It is responsible for approximately 30% of recurrent or persistent infections, 20–25% of nonchlamydial NGU cases, and 15%–20% of NGU cases. M. genitalium attaches to epithelial cells and has substantial antigenic variation that helps it evade host immune responses. It has lipid-associated membrane proteins that are involved in causing inflammation.
Several possible virulence factors have been implicated in the pathogenesis of U. urealyticum (). These include the ureaplasma proteins phospholipase A, phospholipase C, multiple banded antigen (MBA), urease, and immunoglobulin α protease. The phospholipases are virulence factors that damage the cytoplasmic membrane of target cells. The immunoglobulin α protease is an important defense against antibodies. It can generate hydrogen peroxide, which may adversely affect host cell membranes through the production of reactive oxygen species.
Treatments differ for gonorrheal and nongonococcal urethritis. However, N. gonorrhoeae and C. trachomatis are often simultaneously present, which is an important consideration for treatment. NGU is most commonly treated using tetracyclines (such as doxycycline) and azithromycin; erythromycin is an alternative option. Tetracyclines and fluoroquinolones are most commonly used to treat U. urealyticum, but resistance to tetracyclines is becoming an increasing problem.Ken B Waites. “Ureaplasma Infection Medication.”  While tetracyclines have been the treatment of choice for M. hominis, increasing resistance means that other options must be used. Clindamycin and fluoroquinolones are alternatives. M. genitalium is generally susceptible to doxycycline, azithromycin, and moxifloxacin. Like other mycoplasma, M. genitalium does not have a cell wall and therefore β-lactams (including penicillins and cephalosporins) are not effective treatments.

### Key Concepts and Summary

1. Bacterial cystitis is commonly caused by fecal bacteria such as E. coli.
2. Pyelonephritis is a serious kidney infection that is often caused by bacteria that travel from infections elsewhere in the urinary tract and may cause systemic complications.
3. Leptospirosis is a bacterial infection of the kidney that can be transmitted by exposure to infected animal urine, especially in contaminated water. It is more common in tropical than in temperate climates.
4. Nongonococcal urethritis (NGU) is commonly caused by C. trachomatis, M. genitalium, Ureaplasma urealyticum, and M. hominis.
5. Diagnosis and treatment for bacterial urinary tract infections varies. Urinalysis (e.g., for leukocyte esterase levels, nitrite levels, microscopic evaluation, and culture of urine) is an important component in most cases. Broad-spectrum antibiotics are typically used.

### Multiple Choice

### Fill in the Blank

### Short Answer

### Critical Thinking


# Urogenital System Infections

## Bacterial Infections of the Reproductive System

### Learning Objectives

By the end of this section, you will be able to:
1. Identify the most common bacterial pathogens that can cause infections of the reproductive system
2. Compare the major characteristics of specific bacterial diseases affecting the reproductive system
In addition to infections of the urinary tract, bacteria commonly infect the reproductive tract. As with the urinary tract, parts of the reproductive system closest to the external environment are the most likely sites of infection. Often, the same microbes are capable of causing urinary tract and reproductive tract infections.

### Bacterial Vaginitis and Vaginosis

Inflammation of the vagina is called vaginitis, often caused by a bacterial infection. It is also possible to have an imbalance in the normal vaginal microbiota without inflammation called bacterial vaginosis (BV). Vaginosis may be asymptomatic or may cause mild symptoms such as a thin, white-to-yellow, homogeneous vaginal discharge, burning, odor, and itching. The major causative agent is , a gram-variable to gram-negative pleomorphic bacterium. Other causative agents include anaerobic species such as members of the genera  and . Additionally, ureaplasma and mycoplasma may be involved. The disease is usually self-limiting, although antibiotic treatment is recommended if symptoms develop.
G. vaginalis appears to be more virulent than other vaginal bacterial species potentially associated with BV. Like  spp., G. vaginalis is part of the normal vaginal microbiota, but when the population of Lactobacillus spp. decreases and the vaginal pH increases, G. vaginalis flourishes, causing vaginosis by attaching to vaginal epithelial cells and forming a thick protective biofilm. G. vaginalis also produces a cytotoxin called vaginolysin that lyses vaginal epithelial cells and red blood cells.
Since G. vaginalis can also be isolated from healthy women, the “gold standard” for the diagnosis of BV is direct examination of vaginal secretions and not the culture of G. vaginalis. Diagnosis of bacterial vaginosis from vaginal secretions can be accurately made in three ways. The first is to use a DNA probe. The second method is to assay for sialidase activity (sialidase is an enzyme produced by G. vaginalis and other bacteria associated with vaginosis, including Bacteroides spp.,  spp., and  spp.). The third method is to assess gram-stained vaginal smears for microscopic morphology and relative numbers and types of bacteria, squamous epithelial cells, and leukocytes. By examining slides prepared from vaginal swabs, it is possible to distinguish lactobacilli (long, gram-positive rods) from other gram-negative species responsible for BV. A shift in predominance from gram-positive bacilli to gram-negative coccobacilli can indicate BV. Additionally, the slide may contain so-called clue cells, which are epithelial cells that appear to have a granular or stippled appearance due to bacterial cells attached to their surface (). Presumptive diagnosis of bacterial vaginosis can involve an assessment of clinical symptoms and evaluation of vaginal fluids using Amsel’s diagnostic criteria which include 3 out of 4 of the following characteristics:
1. white to yellow discharge;
2. a fishy odor, most noticeable when 10% KOH is added;
3. pH greater than 4.5;
4. the presence of clue cells.
Treatment is often unnecessary because the infection often clears on its own. However, in some cases, antibiotics such as topical or oral clindamycin or metronidazole may be prescribed. Alternative treatments include oral tinidazole or clindamycin ovules (vaginal suppositories).

### Gonorrhea

Also known as the clap, gonorrhea is a common sexually transmitted disease of the reproductive system that is especially prevalent in individuals between the ages of 15 and 24. It is caused by , often called gonococcus or GC, which have fimbriae that allow the cells to attach to epithelial cells. It also has a type of lipopolysaccharide endotoxin called lipooligosaccharide as part of the outer membrane structure that enhances its pathogenicity. In addition to causing urethritis, N. gonorrhoeae can infect other body tissues such as the skin, meninges, pharynx, and conjunctiva.
Many infected individuals (both men and women) are asymptomatic carriers of gonorrhea. When symptoms do occur, they manifest differently in males and females. Males may develop pain and burning during urination and discharge from the penis that may be yellow, green, or white (). Less commonly, the testicles may become swollen or tender. Over time, these symptoms can increase and spread. In some cases, chronic infection develops. The disease can also develop in the rectum, causing symptoms such as discharge, soreness, bleeding, itching, and pain (especially in association with bowel movements).
Women may develop pelvic pain, discharge from the vagina, intermenstrual bleeding (i.e., bleeding not associated with normal menstruation), and pain or irritation associated with urination. As with men, the infection can become chronic. In women, however, chronic infection can cause increases in menstrual flow. Rectal infection can also occur, with the symptoms previously described for men. Infections that spread to the endometrium and fallopian tubes can cause pelvic inflammatory disease (PID), characterized by pain in the lower abdominal region, dysuria, vaginal discharge, and fever. PID can also lead to infertility through scarring and blockage of the fallopian tubes (salpingitis); it may also increase the risk of a life-threatening ectopic pregnancy, which occurs when a fertilized egg begins developing somewhere other than the uterus (e.g., in the fallopian tube or ovary).
When a gonorrhea infection disseminates throughout the body, serious complications can develop. The infection may spread through the blood (bacteremia) and affect organs throughout the body, including the heart (gonorrheal endocarditis), joints (gonorrheal arthritis), and meninges encasing the brain (meningitis).
Urethritis caused by N. gonorrhoeae can be difficult to treat due to antibiotic resistance (see Micro Connections). Some strains have developed resistance to the fluoroquinolones, so cephalosporins are often a first choice for treatment. Because co-infection with C. trachomatis is common, the CDC recommends treating with a combination regimen of ceftriaxone and azithromycin. Treatment of sexual partners is also recommended to avoid reinfection and spread of infection to others.Centers for Disease Control and Prevention. “2015 Sexually Transmitted Diseases Treatment Guidelines: Gonococcal Infections,” 2015. http://www.cdc.gov/std/tg2015/gonorrhea.htm.

### Chlamydia

 is the causative agent of the STI chlamydia (). While many Chlamydia infections are asymptomatic, chlamydia is a major cause of nongonococcal urethritis (NGU) and may also cause epididymitis and orchitis in men. In women, chlamydia infections can cause urethritis, salpingitis, and PID. In addition, chlamydial infections may be associated with an increased risk of cervical cancer.
Because chlamydia is widespread, often asymptomatic, and has the potential to cause substantial complications, routine screening is recommended for sexually active women who are under age 25, at high risk (i.e., not in a monogamous relationship), or beginning prenatal care.
Certain serovars of C. trachomatis can cause an infection of the lymphatic system in the groin known as lymphogranuloma venereum. This condition is commonly found in tropical regions and can also co-occur in conjunction with human immunodeficiency virus (HIV) infection. After the microbes invade the lymphatic system, buboes (large lymph nodes, see ) form and can burst, releasing pus through the skin. The male genitals can become greatly enlarged and in women the rectum may become narrow.
Urogenital infections caused by C. trachomatis can be treated using azithromycin or doxycycline (the recommended regimen from the CDC). Erythromycin, levofloxacin, and ofloxacin are alternatives.

### Syphilis

Syphilis is spread through direct physical (generally sexual) contact, and is caused by the gram-negative spirochete . T. pallidum has a relatively simple genome and lacks lipopolysaccharide endotoxin characteristic of gram-negative bacteria. However, it does contain lipoproteins that trigger an immune response in the host, causing tissue damage that may enhance the pathogen’s ability to disseminate while evading the host immune system.
After entering the body, T. pallidum moves rapidly into the bloodstream and other tissues. If not treated effectively, syphilis progresses through three distinct stages: primary, secondary, and tertiary. Primary syphilis appears as a single lesion on the cervix, penis, or anus within 10 to 90 days of transmission. Such lesions contain many T. pallidum cells and are highly infectious. The lesion, called a hard chancre, is initially hard and painless, but it soon develops into an ulcerated sore (). Localized lymph node swelling may occur as well. In some cases, these symptoms may be relatively mild, and the lesion may heal on its own within two to six weeks. Because the lesions are painless and often occur in hidden locations (e.g., the cervix or anus), infected individuals sometimes do not notice them.
The secondary stage generally develops once the primary chancre has healed or begun to heal. Secondary syphilis is characterized by a rash that affects the skin and mucous membranes of the mouth, vagina, or anus. The rash often begins on the palms or the soles of the feet and spreads to the trunk and the limbs (). The rash may take many forms, such as macular or papular. On mucous membranes, it may manifest as mucus patches or white, wartlike lesions called condylomata lata. The rash may be accompanied by malaise, fever, and swelling of lymph nodes. Individuals are highly contagious in the secondary stage, which lasts two to six weeks and is recurrent in about 25% of cases.
After the secondary phase, syphilis can enter a latent phase, in which there are no symptoms but microbial levels remain high. Blood tests can still detect the disease during latency. The latent phase can persist for years.
Tertiary syphilis, which may occur 10 to 20 years after infection, produces the most severe symptoms and can be fatal. Granulomatous lesions called gummas may develop in a variety of locations, including mucous membranes, bones, and internal organs (). Gummas can be large and destructive, potentially causing massive tissue damage. The most deadly lesions are those of the cardiovascular system (cardiovascular syphilis) and the central nervous system (neurosyphilis). Cardiovascular syphilis can result in a fatal aortic aneurysm (rupture of the aorta) or coronary stenosis (a blockage of the coronary artery). Damage to the central nervous system can cause dementia, personality changes, seizures, general paralysis, speech impairment, loss of vision and hearing, and loss of bowel and bladder control.
The recommended methods for diagnosing early syphilis are darkfield or brightfield (silver stain) microscopy of tissue or exudate from lesions to detect T. pallidum (). If these methods are not available, two types of serologic tests (treponemal and nontreponemal) can be used for a presumptive diagnosis once the spirochete has spread in the body. Nontreponemal serologic tests include the Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin (RPR) tests. These are similar screening tests that detect nonspecific antibodies (those for lipid antigens produced during infection) rather than those produced against the spirochete. Treponemal serologic tests measure antibodies directed against T. pallidum antigens using particle agglutination (T. pallidum passive particle agglutination or TP-PA), immunofluorescence (the fluorescent T. pallidum antibody absorption or FTA-ABS), various enzyme reactions (enzyme immunoassays or EIAs) and chemiluminescence immunoassays (CIA). Confirmatory testing, rather than screening, must be done using treponemal rather than nontreponemal tests because only the former tests for antibodies to spirochete antigens. Both treponemal and nontreponemal tests should be used (as opposed to just one) since both tests have limitations than can result in false positives or false negatives.
Neurosyphilis cannot be diagnosed using a single test. With or without clinical signs, it is generally necessary to assess a variety of factors, including reactive serologic test results, cerebrospinal fluid cell count abnormalities, cerebrospinal fluid protein abnormalities, or reactive VDRL-CSF (the VDRL test of cerebrospinal fluid). The VDRL-CSF is highly specific, but not sufficiently sensitive for conclusive diagnosis.
The recommended treatment for syphilis is parenteral penicillin G (especially long-acting benzathine penicillin, although the exact choice depends on the stage of disease). Other options include tetracycline and doxycycline.

### Congenital Syphilis

Congenital syphilis is passed by mother to fetus when untreated primary or secondary syphilis is present. In many cases, infection may lead to miscarriage or stillbirth. Children born with congenital syphilis show symptoms of secondary syphilis and may develop mucus patches that deform the nose. In infants, gummas can cause significant tissue damage to organs and teeth. Many other complications may develop, such as osteochondritis, anemia, blindness, bone deformations, neurosyphilis, and cardiovascular lesions. Because congenital syphilis poses such a risk to the fetus, expectant mothers are screened for syphilis infection during the first trimester of pregnancy as part of the TORCH panel of prenatal tests.

### Chancroid

The sexually transmitted infection chancroid is caused by the gram-negative rod . It is characterized by soft chancres () on the genitals or other areas associated with sexual contact, such as the mouth and anus. Unlike the hard chancres associated with syphilis, soft chancres develop into painful, open sores that may bleed or produce fluid that is highly contagious. In addition to causing chancres, the bacteria can invade the lymph nodes, potentially leading to pus discharge through the skin from lymph nodes in the groin. Like other genital lesions, soft chancres are of particular concern because they compromise the protective barriers of the skin or mucous membranes, making individuals more susceptible to HIV and other sexually transmitted diseases.
Several virulence factors have been associated with H. ducreyi, including lipooligosaccharides, protective outer membrane proteins, antiphagocytic proteins, secretory proteins, and collagen-specific adhesin NcaA. The collagen-specific adhesion NcaA plays an important role in initial cellular attachment and colonization. Outer membrane proteins DsrA and DltA have been shown to provide protection from serum-mediated killing by antibodies and complement.
H. ducreyi is difficult to culture; thus, diagnosis is generally based on clinical observation of genital ulcers and tests that rule out other diseases with similar ulcers, such as syphilis and genital herpes. PCR tests for H. ducreyi have been developed in some laboratories, but as of 2015 none had been cleared by the US Food and Drug Administration (FDA).Centers for Disease Control and Prevention. “2015 Sexually Transmitted Diseases Treatment Guidelines: Chancroid,” 2015. http://www.cdc.gov/std/tg2015/chancroid.htm. Recommended treatments for chancroid include antibiotics such as azithromycin, ciprofloxacin, erythromycin and ceftriaxone. Resistance to ciprofloxacin and erythromycin has been reported.Ibid.

### Key Concepts and Summary

1. Bacterial vaginosis is caused by an imbalance in the vaginal microbiota, with a decrease in lactobacilli and an increase in vaginal pH. G. vaginalis is the most common cause of bacterial vaginosis, which is associated with vaginal discharge, odor, burning, and itching.
2. Gonorrhea is caused by N. gonorrhoeae, which can cause infection of the reproductive and urinary tracts and is associated with symptoms of urethritis. If left untreated, it can progress to epididymitis, salpingitis, and pelvic inflammatory disease and enter the bloodstream to infect other sites in the body.
3. Chlamydia is the most commonly reported STI and is caused by C. trachomatis. Most infections are asymptomatic, and infections that are not treated can spread to involve the epididymis of men and cause salpingitis and pelvic inflammatory disease in women.
4. Syphilis is caused by T. pallidum and has three stages, primary, secondary, and tertiary. Primary syphilis is associated with a painless hard chancre lesion on genitalia. Secondary syphilis is associated with skin and mucous membrane lesions. Tertiary syphilis is the most serious and life-threatening, and can involve serious nervous system damage.
5. Chancroid is an infection of the reproductive tract caused by H. ducreyi that results in the development of characteristic soft chancres.

### Multiple Choice

### Fill in the Blank

### Short Answer

### Critical Thinking


# Urogenital System Infections

## Viral Infections of the Reproductive System

### Learning Objectives

By the end of this section, you will be able to:
1. Identify the most common viruses that cause infections of the reproductive system
2. Compare the major characteristics of specific viral diseases affecting the reproductive system
Several viruses can cause serious problems for the human reproductive system. Most of these viral infections are incurable, increasing the risk of persistent sexual transmission. In addition, such viral infections are very common in the United States. For example, human papillomavirus (HPV) is the most common STI in the country, with an estimated prevalence of 79.1 million infections in 2008; herpes simplex virus 2 (HSV-2) is the next most prevalent STI at 24.1 million infections.Catherine Lindsey Satterwhite, Elizabeth Torrone, Elissa Meites, Eileen F. Dunne, Reena Mahajan, M. Cheryl Bañez Ocfemia, John Su, Fujie Xu, and Hillard Weinstock. “Sexually Transmitted Infections Among US Women and Men: Prevalence and Incidence Estimates, 2008.”  In this section, we will examine these and other major viral infections of the reproductive system.

### Genital Herpes

Genital herpes is a common condition caused by the herpes simplex virus (), an enveloped, double-stranded DNA virus that is classified into two distinct types. Herpes simplex virus has several virulence factors, including infected cell protein (ICP) 34.5, which helps in replication and inhibits the maturation of dendritic cells as a mechanism of avoiding elimination by the immune system. In addition, surface glycoproteins on the viral envelope promote the coating of herpes simplex virus with antibodies and complement factors, allowing the virus to appear as “self” and prevent immune system activation and elimination.
There are two herpes simplex virus types. While herpes simplex virus type 1 (HSV-1) is generally associated with oral lesions like cold sores or fever blisters (see Viral Infections of the Skin and Eyes), herpes simplex virus type 2 (HSV-2) is usually associated with genital herpes. However, both viruses can infect either location as well as other parts of the body. Oral-genital contact can spread either virus from the mouth to the genital region or vice versa.
Many infected individuals do not develop symptoms, and thus do not realize that they carry the virus. However, in some infected individuals, fever, chills, malaise, swollen lymph nodes, and pain precede the development of fluid-filled vesicles that may be irritating and uncomfortable. When these vesicles burst, they release infectious fluid and allow transmission of HSV. In addition, open herpes lesions can increase the risk of spreading or acquiring HIV.
In men, the herpes lesions typically develop on the penis and may be accompanied by a watery discharge. In women, the vesicles develop most commonly on the vulva, but may also develop on the vagina or cervix (). The symptoms are typically mild, although the lesions may be irritating or accompanied by urinary discomfort. Use of condoms may not always be an effective means of preventing transmission of genital herpes since the lesions can occur on areas other than the genitals.
Herpes simplex viruses can cause recurrent infections because the virus can become latent and then be reactivated. This occurs more commonly with HSV-2 than with HSV-1.Centers for Disease Control and Prevention. “2015 Sexually Transmitted Disease Treatment Guidelines: Genital Herpes,” 2015. http://www.cdc.gov/std/tg2015/herpes.htm. The virus moves down peripheral nerves, typically sensory neurons, to ganglia in the spine (either the trigeminal ganglion or the lumbar-sacral ganglia) and becomes latent. Reactivation can later occur, causing the formation of new vesicles. HSV-2 most effectively reactivates from the lumbar-sacral ganglia. Not everyone infected with HSV-2 experiences reactivations, which are typically associated with stressful conditions, and the frequency of reactivation varies throughout life and among individuals. Between outbreaks or when there are no obvious vesicles, the virus can still be transmitted.
Virologic and serologic techniques are used for diagnosis. The virus may be cultured from lesions. The immunostaining methods that are used to detect virus from cultures generally require less expertise than methods based on cytopathic effect (CPE), as well as being a less expensive option. However, PCR or other DNA amplification methods may be preferred because they provide the most rapid results without waiting for culture amplification. PCR is also best for detecting systemic infections. Serologic techniques are also useful in some circumstances, such as when symptoms persist but PCR testing is negative.
While there is no cure or vaccine for HSV-2 infections, antiviral medications are available that manage the infection by keeping the virus in its dormant or latent phase, reducing signs and symptoms. If the medication is discontinued, then the condition returns to its original severity. The recommended medications, which may be taken at the start of an outbreak or daily as a method of prophylaxis, are acyclovir, famciclovir, and valacyclovir.

### Neonatal Herpes

Herpes infections in newborns, referred to as neonatal herpes, are generally transmitted from the mother to the neonate during childbirth, when the child is exposed to pathogens in the birth canal. Infections can occur regardless of whether lesions are present in the birth canal. In most cases, the infection of the newborn is limited to skin, mucous membranes, and eyes, and outcomes are good. However, sometimes the virus becomes disseminated and spreads to the central nervous system, resulting in motor function deficits or death.
In some cases, infections can occur before birth when the virus crosses the placenta. This can cause serious complications in fetal development and may result in spontaneous abortion or severe disabilities if the fetus survives. The condition is most serious when the mother is infected with HSV for the first time during pregnancy. Thus, expectant mothers are screened for HSV infection during the first trimester of pregnancy as part of the TORCH panel of prenatal tests (see How Pathogens Cause Disease). Systemic acyclovir treatment is recommended to treat newborns with neonatal herpes.

### Human Papillomas

Warts of all types are caused by a variety of strains of human papillomavirus (HPV) (see Viral Infections of the Skin and Eyes). Condylomata acuminata, more commonly called genital warts or venereal warts (), are an extremely prevalent STI caused by certain strains of HPV. Condylomata are irregular, soft, pink growths that are found on external genitalia or the anus.
HPV is a small, non-enveloped virus with a circular double-stranded DNA genome. Researchers have identified over 200 different strains (called types) of HPV, with approximately 40 causing STIs. While some types of HPV cause genital warts, HPV infection is often asymptomatic and self-limiting. However, genital HPV infection often co-occurs with other STIs like syphilis or gonorrhea. Additionally, some forms of HPV (not the same ones associated with genital warts) are associated with cervical cancers. At least 14 oncogenic (cancer-causing) HPV types are known to have a causal association with cervical cancers. Examples of oncogenic HPV are types 16 and 18, which are associated with 70% of cervical cancers.Lauren Thaxton and Alan G. Waxman. “Cervical Cancer Prevention: Immunization and Screening 2015.”  Oncogenic HPV types can also cause oropharyngeal cancer, anal cancer, vaginal cancer, vulvar cancer, and penile cancer. Most of these cancers are caused by HPV type 16. HPV virulence factors include proteins (E6 and E7) that are capable of inactivating tumor suppressor proteins, leading to uncontrolled cell division and the development of cancer.
HPV cannot be cultured, so molecular tests are the primary method used to detect HPV. While routine HPV screening is not recommended for men, it is included in guidelines for women. An initial screening for HPV at age 30, conducted at the same time as a Pap test, is recommended. If the tests are negative, then further HPV testing is recommended every five years. More frequent testing may be needed in some cases. The protocols used to collect, transport, and store samples vary based on both the type of HPV testing and the purpose of the testing. This should be determined in individual cases in consultation with the laboratory that will perform the testing.
Because HPV testing is often conducted concurrently with Pap testing, the most common approach uses a single sample collection within one vial for both. This approach uses liquid-based cytology (LBC). The samples are then used for Pap smear cytology as well as HPV testing and genotyping. HPV can be recognized in Pap smears by the presence of cells called koilocytes (called koilocytosis or koilocytotic atypia). Koilocytes have a hyperchromatic atypical nucleus that stains darkly and a high ratio of nuclear material to cytoplasm. There is a distinct clear appearance around the nucleus called a perinuclear halo ().
Most HPV infections resolve spontaneously; however, various therapies are used to treat and remove warts. Topical medications such as imiquimod (which stimulates the production of interferon), podofilox, or sinecatechins, may be effective. Warts can also be removed using cryotherapy or surgery, but these approaches are less effective for genital warts than for other types of warts. Electrocauterization and carbon dioxide laser therapy are also used for wart removal.
Regular Pap testing can detect abnormal cells that might progress to cervical cancer, followed by biopsy and appropriate treatment. Vaccines for some of the high risk HPV types are now available. Gardasil vaccine includes types 6, 11, 16 and 18 (types 6 and 11 are associated with 90% of genital wart infections and types 16 and 18 are associated with 70% of cervical cancers). Gardasil 9 vaccinates against the previous four types and an additional five high-risk types (31, 33, 45, 52, and 58). Cervarix vaccine includes just HPV types 16 and 18. Vaccination is the most effective way to prevent infection with oncogenic HPV, but it is important to note that not all oncogenic HPV types are covered by the available vaccines. It is recommended for both boys and girls prior to sexual activity (usually between the ages of nine and fifteen).

### Key Concepts and Summary

1. Genital herpes is usually caused by HSV-2 (although HSV-1 can also be responsible) and may cause the development of infectious, potentially recurrent vesicles
2. Neonatal herpes can occur in babies born to infected mothers and can cause symptoms that range from relatively mild (more common) to severe.
3. Human papillomaviruses are the most common sexually transmitted viruses and include strains that cause genital warts as well as strains that cause cervical cancer.

### Multiple Choice

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### Short Answer

### Critical Thinking


# Urogenital System Infections

## Fungal Infections of the Reproductive System

### Learning Objectives

By the end of this section, you will be able to:
1. Summarize the important characteristics of vaginal candidiasis
Only one major fungal pathogen affects the urogenital system.  is a genus of fungi capable of existing in a yeast form or as a multicellular fungus. Candida spp. are commonly found in the normal, healthy microbiota of the skin, gastrointestinal tract, respiratory system, and female urogenital tract (). They can be pathogenic due to their ability to adhere to and invade host cells, form biofilms, secrete hydrolases (e.g., proteases, phospholipases, and lipases) that assist in their spread through tissues, and change their phenotypes to protect themselves from the immune system. However, they typically only cause disease in the female reproductive tract under conditions that compromise the host’s defenses. While there are at least 20 Candida species of clinical importance, C. albicans is the species most commonly responsible for fungal vaginitis.
As discussed earlier, lactobacilli in the vagina inhibit the growth of other organisms, including bacteria and Candida, but disruptions can allow Candida to increase in numbers. Typical disruptions include antibiotic therapy, illness (especially diabetes), pregnancy, and the presence of transient microbes. Immunosuppression can also play a role, and the severe immunosuppression associated with HIV infection often allows Candida to thrive. This can cause genital or vaginal candidiasis, a condition characterized by vaginitis and commonly known as a yeast infection. When a yeast infection develops, inflammation occurs along with symptoms of pruritus (itching), a thick white or yellow discharge, and odor.
Other forms of candidiasis include cutaneous candidiasis (see Mycoses of the Skin) and oral thrush (see Microbial Diseases of the Mouth and Oral Cavity). Although Candida spp. are found in the normal microbiota, Candida spp. may also be transmitted between individuals. Sexual contact is a common mode of transmission, although candidiasis is not considered an STI.
Diagnosis of vaginal candidiasis can be made using microscopic evaluation of vaginal secretions to determine whether there is an excess of Candida. Culturing approaches are less useful because Candida is part of the normal microbiota and will regularly appear. It is also easy to contaminate samples with Candida because it is so common, so care must be taken to handle clinical material appropriately. Samples can be refrigerated if there is a delay in handling. Candida is a dimorphic fungus, so it does not only exist in a yeast form; cultivation can be used to identify chlamydospores and pseudohyphae, which develop from germ tubes (). The presence of the germ tube can be used in a diagnostic test in which cultured yeast cells are combined with rabbit serum and observed after a few hours for the presence of germ tubes. Molecular tests are also available if needed. The Affirm VPII Microbial Identification Test, for instance, tests simultaneously for the vaginal microbes C. albicans, G. vaginalis (see Bacterial Infections of the Urinary System), and Trichomonas vaginalis (see Protozoan Infections of the Urogenital System).
Topical antifungal medications for vaginal candidiasis include butoconazole, miconazole, clotrimazole, tioconazole, and nystatin. Oral treatment with fluconazole can be used. There are often no clear precipitating factors for infection, so prevention is difficult.

### Key Concepts and Summary

1. Candida spp. are typically present in the normal microbiota in the body, including the skin, respiratory tract, gastrointestinal tract, and female urogenital system.
2. Disruptions in the normal vaginal microbiota can lead to an overgrowth of Candida, causing vaginal candidiasis.
3. Vaginal candidiasis can be treated with topical or oral fungicides. Prevention is difficult.

### Multiple Choice

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# Urogenital System Infections

## Protozoan Infections of the Urogenital System

### Learning Objectives

By the end of this section, you will be able to:
1. Identify the most common protozoan pathogen that causes infections of the reproductive system
2. Summarize the important characteristics of trichomoniasis
Only one major protozoan species causes infections in the urogenital system. Trichomoniasis, or “trich,” is the most common nonviral STI and is caused by a flagellated protozoan . T. vaginalis has an undulating membrane and, generally, an amoeboid shape when attached to cells in the vagina. In culture, it has an oval shape.
T. vaginalis is commonly found in the normal microbiota of the vagina. As with other vaginal pathogens, it can cause vaginitis when there is disruption to the normal microbiota. It is found only as a trophozoite and does not form cysts. T. vaginalis can adhere to cells using adhesins such as lipoglycans; it also has other cell-surface virulence factors, including tetraspanins that are involved in cell adhesion, motility, and tissue invasion. In addition, T. vaginalis is capable of phagocytosing other microbes of the normal microbiota, contributing to the development of an imbalance that is favorable to infection.
Both men and women can develop trichomoniasis. Men are generally asymptomatic, and although women are more likely to develop symptoms, they are often asymptomatic as well. When symptoms do occur, they are characteristic of urethritis. Men experience itching, irritation, discharge from the penis, and burning after urination or ejaculation. Women experience dysuria; itching, burning, redness, and soreness of the genitalia; and vaginal discharge. The infection may also spread to the cervix. Infection increases the risk of transmitting or acquiring HIV and is associated with pregnancy complications such as preterm birth.
Microscopic evaluation of wet mounts is an inexpensive and convenient method of diagnosis, but the sensitivity of this method is low (). Nucleic acid amplification testing (NAAT) is preferred due to its high sensitivity. Using wet mounts and then NAAT for those who initially test negative is one option to improve sensitivity. Samples may be obtained for NAAT using urine, vaginal, or endocervical specimens for women and with urine and urethral swabs for men. It is also possible to use other methods such as the OSOM  (an immunochromatographic test that detects antigen) and a DNA probe test for multiple species associated with vaginitis (the Affirm VPII Microbial Identification Test discussed in section 23.5).Association of Public Health Laboratories. “Advances in Laboratory Detection of  T. vaginalis is sometimes detected on a Pap test, but this is not considered diagnostic due to high rates of false positives and negatives. The recommended treatment for trichomoniasis is oral metronidazole or tinidazole. Sexual partners should be treated as well.

### Key Concepts and Summary

1. Trichomoniasis is a common STI caused by Trichomonas vaginalis.
2. T. vaginalis is common at low levels in the normal microbiota.
3. Trichomoniasis is often asymptomatic. When symptoms develop, trichomoniasis causes urinary discomfort, irritation, itching, burning, discharge from the penis (in men), and vaginal discharge (in women).
4. Trichomoniasis is treated with the antiflagellate drugs tinidazole and metronidazole.

### Multiple Choice

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### Short Answer


# Digestive System Infections

## Introduction

Gastrointestinal (GI) diseases are so common that, unfortunately, most people have had first-hand experience with the unpleasant symptoms, such as diarrhea, vomiting, and abdominal discomfort. The causes of gastrointestinal illness can vary widely, but such diseases can be grouped into two categories: those caused by infection (the growth of a pathogen in the GI tract) or intoxication (the presence of a microbial toxin in the GI tract).
Foodborne pathogens like  O157:H7 are among the most common sources of gastrointestinal disease. Contaminated food and water have always posed a health risk for humans, but in today’s global economy, outbreaks can occur on a much larger scale. E. coli O157:H7 is a potentially deadly strain of E. coli with a history of contaminating meat and produce that are not properly processed. The source of an E. coli O157:H7 outbreak can be difficult to trace, especially if the contaminated food is processed in a foreign country. Once the source is identified, authorities may issue recalls of the contaminated food products, but by then there are typically numerous cases of food poisoning, some of them fatal.


# Digestive System Infections

## Anatomy and Normal Microbiota of the Digestive System

### Learning Objectives

By the end of this section, you will be able to:
1. Describe the major anatomical features of the human digestive system
2. Describe the normal microbiota of various regions in the human digestive system
3. Explain how microorganisms overcome the defenses of the digestive tract to cause infection or intoxication
4. Describe general signs and symptoms associated with infections of the digestive system
The human digestive system, or the gastrointestinal (GI) tract, begins with the mouth and ends with the anus. The parts of the mouth include the teeth, the gums, the tongue, the oral vestibule (the space between the gums, lips, and teeth), and the oral cavity proper (the space behind the teeth and gums). Other parts of the GI tract are the pharynx, esophagus, stomach, small intestine, large intestine, rectum, and anus (). Accessory digestive organs include the salivary glands, liver, gallbladder, spleen, and pancreas.
The digestive system contains normal microbiota, including archaea, bacteria, fungi, protists, and even viruses. Because this microbiota is important for normal functioning of the digestive system, alterations to the microbiota by antibiotics or diet can be harmful. Additionally, the introduction of pathogens to the GI tract can cause infections and diseases. In this section, we will review the microbiota found in a healthy digestive tract and the general signs and symptoms associated with oral and GI infections.

### Anatomy and Normal Microbiota of the Oral Cavity

Food enters the digestive tract through the mouth, where mechanical digestion (by chewing) and chemical digestion (by enzymes in saliva) begin. Within the mouth are the tongue, teeth, and salivary glands, including the parotid, sublingual, and submandibular glands (). The salivary glands produce saliva, which lubricates food and contains digestive enzymes.
The structure of a tooth () begins with the visible outer surface, called the crown, which has to be extremely hard to withstand the force of biting and chewing. The crown is covered with enamel, which is the hardest material in the body. Underneath the crown, a layer of relatively hard dentin extends into the root of the tooth around the innermost pulp cavity, which includes the pulp chamber at the top of the tooth and pulp canal, or root canal, located in the root. The pulp that fills the pulp cavity is rich in blood vessels, lymphatic vessels, connective tissue, and nerves. The root of the tooth and some of the crown are covered with cementum, which works with the periodontal ligament to anchor the tooth in place in the jaw bone. The soft tissues surrounding the teeth and bones are called gums, or gingiva. The gingival space or gingival crevice is located between the gums and teeth.
Microbes such as bacteria and archaea are abundant in the mouth and coat all of the surfaces of the oral cavity. However, different structures, such as the teeth or cheeks, host unique communities of both aerobic and anaerobic microbes. Some factors appear to work against making the mouth hospitable to certain microbes. For example, chewing allows microbes to mix better with saliva so they can be swallowed or spit out more easily. Saliva also contains enzymes, including lysozyme, which can damage microbial cells. Recall that lysozyme is part of the first line of defense in the innate immune system and cleaves the β-(1,4) glycosidic linkages between N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) in bacterial peptidoglycan (see Chemical Defenses). Additionally, fluids containing immunoglobulins and phagocytic cells are produced in the gingival spaces. Despite all of these chemical and mechanical activities, the mouth supports a large microbial community.

### Anatomy and Normal Microbiota of the GI Tract

As food leaves the oral cavity, it travels through the pharynx, or the back of the throat, and moves into the esophagus, which carries the food from the pharynx to the stomach without adding any additional digestive enzymes. The stomach produces mucus to protect its lining, as well as digestive enzymes and acid to break down food. Partially digested food then leaves the stomach through the pyloric sphincter, reaching the first part of the small intestine called the duodenum. Pancreatic juice, which includes enzymes and bicarbonate ions, is released into the small intestine to neutralize the acidic material from the stomach and to assist in digestion. Bile, produced by the liver but stored in the gallbladder, is also released into the small intestine to emulsify fats so that they can travel in the watery environment of the small intestine. Digestion continues in the small intestine, where the majority of nutrients contained in the food are absorbed. Simple columnar epithelial cells called enterocytes line the lumen surface of the small intestinal folds called villi. Each enterocyte has smaller microvilli (cytoplasmic membrane extensions) on the cellular apical surface that increase the surface area to allow more absorption of nutrients to occur ().
Digested food leaves the small intestine and moves into the large intestine, or colon, where there is a more diverse microbiota. Near this junction, there is a small pouch in the large intestine called the cecum, which attaches to the appendix. Further digestion occurs throughout the colon and water is reabsorbed, then waste is excreted through the rectum, the last section of the colon, and out of the body through the anus ().
The environment of most of the GI tract is harsh, which serves two purposes: digestion and immunity. The stomach is an extremely acidic environment (pH 1.5–3.5) due to the gastric juices that break down food and kill many ingested microbes; this helps prevent infection from pathogens. The environment in the small intestine is less harsh and is able to support microbial communities. Microorganisms present in the small intestine can include lactobacilli, diptherioids and the fungus . On the other hand, the large intestine (colon) contains a diverse and abundant microbiota that is important for normal function. These microbes include  (especially the genera  and ) and  (especially members of the genus ). Methanogenic archaea and some fungi are also present, among many other species of bacteria. These microbes all aid in digestion and contribute to the production of feces, the waste excreted from the digestive tract, and flatus, the gas produced from microbial fermentation of undigested food. They can also produce valuable nutrients. For example, lactic acid bacteria such as bifidobacteria can synthesize vitamins, such as vitamin B12, folate, and riboflavin, that humans cannot synthesize themselves. E. coli found in the intestine can also break down food and help the body produce vitamin K, which is important for blood coagulation.
The GI tract has several other methods of reducing the risk of infection by pathogens. Small aggregates of underlying lymphoid tissue in the ileum, called Peyer’s patches (), detect pathogens in the intestines via microfold (M) cells, which transfer antigens from the lumen of the intestine to the lymphocytes on Peyer’s patches to induce an immune response. The Peyer’s patches then secrete IgA and other pathogen-specific antibodies into the intestinal lumen to help keep intestinal microbes at safe levels. Goblet cells, which are modified simple columnar epithelial cells, also line the GI tract (). Goblet cells secrete a gel-forming mucin, which is the major component of mucus. The production of a protective layer of mucus helps reduce the risk of pathogens reaching deeper tissues.
The constant movement of materials through the gastrointestinal tract also helps to move transient pathogens out of the body. In fact, feces are composed of approximately 25% microbes, 25% sloughed epithelial cells, 25% mucus, and 25% digested or undigested food. Finally, the normal microbiota provides an additional barrier to infection via a variety of mechanisms. For example, these organisms outcompete potential pathogens for space and nutrients within the intestine. This is known as competitive exclusion. Members of the microbiota may also secrete protein toxins known as bacteriocins that are able to bind to specific receptors on the surface of susceptible bacteria.

### General Signs and Symptoms of Oral and GI Disease

Despite numerous defense mechanisms that protect against infection, all parts of the digestive tract can become sites of infection or intoxication. The term food poisoning is sometimes used as a catch-all for GI infections and intoxications, but not all forms of GI disease originate with foodborne pathogens or toxins.
In the mouth, fermentation by anaerobic microbes produces acids that damage the teeth and gums. This can lead to tooth decay, cavities, and periodontal disease, a condition characterized by chronic inflammation and erosion of the gums. Additionally, some pathogens can cause infections of the mucosa, glands, and other structures in the mouth, resulting in inflammation, sores, cankers, and other lesions. An open sore in the mouth or GI tract is typically called an ulcer.
Infections and intoxications of the lower GI tract often produce symptoms such as nausea, vomiting, diarrhea, aches, and fever. In some cases, vomiting and diarrhea may cause severe dehydration and other complications that can become serious or fatal. Various clinical terms are used to describe gastrointestinal symptoms. For example, gastritis is an inflammation of the stomach lining that results in swelling and enteritis refers to inflammation of the intestinal mucosa. When the inflammation involves both the stomach lining and the intestinal lining, the condition is called gastroenteritis. Inflammation of the liver is called hepatitis. Inflammation of the colon, called colitis, commonly occurs in cases of food intoxication. Because an inflamed colon does not reabsorb water as effectively as it normally does, stools become watery, causing diarrhea. Damage to the epithelial cells of the colon can also cause bleeding and excess mucus to appear in watery stools, a condition called dysentery.

### Key Concepts and Summary

1. The digestive tract, consisting of the oral cavity, pharynx, esophagus, stomach, small intestine, and large intestine, has a normal microbiota that is important for health.
2. The constant movement of materials through the gastrointestinal canal, the protective layer of mucus, the normal microbiota, and the harsh chemical environment in the stomach and small intestine help to prevent colonization by pathogens.
3. Infections or microbial toxins in the oral cavity can cause tooth decay, periodontal disease, and various types of ulcers.
4. Infections and intoxications of the gastrointestinal tract can cause general symptoms such as nausea, vomiting, diarrhea, and fever. Localized inflammation of the GI tract can result in gastritis, enteritis, gastroenteritis, hepatitis, or colitis, and damage to epithelial cells of the colon can lead to dysentery.
5. Foodborne illness refers to infections or intoxications that originate with pathogens or toxins ingested in contaminated food or water.

### Multiple Choice

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### Short Answer


# Digestive System Infections

## Microbial Diseases of the Mouth and Oral Cavity

### Learning Objectives

By the end of this section, you will be able to:
1. Explain the role of microbial activity in diseases of the mouth and oral cavity
2. Compare the major characteristics of specific oral diseases and infections
Despite the presence of saliva and the mechanical forces of chewing and eating, some microbes thrive in the mouth. These microbes can cause damage to the teeth and can cause infections that have the potential to spread beyond the mouth and sometimes throughout the body.

### Dental Caries

Cavities of the teeth, known clinically as dental caries, are microbial lesions that cause damage to the teeth. Over time, the lesion can grow through the outer enamel layer to infect the underlying dentin or even the innermost pulp. If dental caries are not treated, the infection can become an abscess that spreads to the deeper tissues of the teeth, near the roots, or to the bloodstream.
Tooth decay results from the metabolic activity of microbes that live on the teeth. A layer of proteins and carbohydrates forms when clean teeth come into contact with saliva. Microbes are attracted to this food source and form a biofilm called plaque. The most important cariogenic species in these biofilms is . When sucrose, a disaccharide sugar from food, is broken down by bacteria in the mouth, glucose and fructose are produced. The glucose is used to make dextran, which is part of the extracellular matrix of the biofilm. Fructose is fermented, producing organic acids such as lactic acid. These acids dissolve the minerals of the tooth, including enamel, even though it is the hardest material in the body. The acids work even more quickly on exposed dentin (). Over time, the plaque biofilm can become thick and eventually calcify. When a heavy plaque deposit becomes hardened in this way, it is called tartar or dental calculus (). These substantial plaque biofilms can include a variety of bacterial species, including  and  species.
Some tooth decay is visible from the outside, but it is not always possible to see all decay or the extent of the decay. X-ray imaging is used to produce radiographs that can be studied to look for deeper decay and damage to the root or bone (). If not detected, the decay can reach the pulp or even spread to the bloodstream. Painful abscesses can develop.
To prevent tooth decay, prophylactic treatment and good hygiene are important. Regular tooth brushing and flossing physically removes microbes and combats microbial growth and biofilm formation. Toothpaste contains fluoride, which becomes incorporated into the hydroxyapatite of tooth enamel, protecting it against acidity caused by fermentation of mouth microbiota. Fluoride is also bacteriostatic, thus slowing enamel degradation. Antiseptic mouthwashes commonly contain plant-derived phenolics like thymol and eucalyptol and/or heavy metals like zinc chloride (see Using Chemicals to Control Microorganisms). Phenolics tend to be stable and persistent on surfaces, and they act through denaturing proteins and disrupting membranes.
Regular dental cleanings allow for the detection of decay at early stages and the removal of tartar. They may also help to draw attention to other concerns, such as damage to the enamel from acidic drinks. Reducing sugar consumption may help prevent damage that results from the microbial fermentation of sugars. Additionally, sugarless candies or gum with sugar alcohols (such as xylitol) can reduce the production of acids because these are fermented to nonacidic compounds (although excess consumption may lead to gastrointestinal distress). Fluoride treatment or ingesting fluoridated water strengthens the minerals in teeth and reduces the incidence of dental caries.
If caries develop, prompt treatment prevents worsening. Smaller areas of decay can be drilled to remove affected tissue and then filled. If the pulp is affected, then a root canal may be needed to completely remove the infected tissues to avoid continued spread of the infection, which could lead to painful abscesses.

### Periodontal Disease

In addition to damage to the teeth themselves, the surrounding structures can be affected by microbes. Periodontal disease is the result of infections that lead to inflammation and tissue damage in the structures surrounding the teeth. The progression from mild to severe periodontal disease is generally reversible and preventable with good oral hygiene.
Inflammation of the gums that can lead to irritation and bleeding is called gingivitis. When plaque accumulates on the teeth, bacteria colonize the gingival space. As this space becomes increasingly blocked, the environment becomes anaerobic. This allows a wide variety of microbes to colonize, including , , and . The bacterial products, which include lipopolysaccharide (LPS), proteases, lipoteichoic acids, and others, cause inflammation and gum damage (). It is possible that methanogenic archaeans (including Methanobrevibacter oralis and other  species) also contribute to disease progression as some species have been identified in patients with periodontal disease, but this has proven difficult to study.Hans-Peter Horz and Georg Conrads. “Methanogenic Hiroshi Maeda, Kimito Hirai, Junji Mineshiba, Tadashi Yamamoto, Susumu Kokeguchi, and Shogo Takashiba. “Medical Microbiological Approach to Archaea in Oral Infectious Diseases.” Paul W. Lepp, Mary M. Brinig, Cleber C. Ouverney, Katherine Palm, Gary C. Armitage, and David A. Relman. “Methanogenic  Gingivitis is diagnosed by visual inspection, including measuring pockets in the gums, and X-rays, and is usually treated using good dental hygiene and professional dental cleaning, with antibiotics reserved for severe cases.
Over time, chronic gingivitis can develop into the more serious condition of periodontitis (). When this happens, the gums recede and expose parts of the tooth below the crown. This newly exposed area is relatively unprotected, so bacteria can grow on it and spread underneath the enamel of the crown and cause cavities. Bacteria in the gingival space can also erode the cementum, which helps to hold the teeth in place. If not treated, erosion of cementum can lead to the movement or loss of teeth. The bones of the jaw can even erode if the infection spreads. This condition can be associated with bleeding and halitosis (bad breath). Cleaning and appropriate dental hygiene may be sufficient to treat periodontitis. However, in cases of severe periodontitis, an antibiotic may be given. Antibiotics may be given in pill form or applied directly to the gum (local treatment). Antibiotics given can include tetracycline, doxycycline, macrolides or β-lactams. Because periodontitis can be caused by a mix of microbes, a combination of antibiotics may be given.

### Trench Mouth

When certain bacteria, such as Prevotella intermedia, Fusobacterium species, and Treponema vicentii, are involved and periodontal disease progresses, acute necrotizing ulcerative gingivitis or trench mouth, also called Vincent's disease, can develop. This is severe periodontitis characterized by erosion of the gums, ulcers, substantial pain with chewing, and halitosis () that can be diagnosed by visual examination and X-rays. In countries with good medical and dental care, it is most common in individuals with weakened immune systems, such as patients with AIDS. In addition to cleaning and pain medication, patients may be prescribed antibiotics such as amoxicillin, amoxicillin clavulanate, clindamycin, or doxycycline.

### Oral Infections

As noted earlier, normal oral microbiota can cause dental and periodontal infections. However, there are number of other infections that can manifest in the oral cavity when other microbes are present.

### Herpetic Gingivostomatitis

As described in Viral Infections of the Skin and Eyes, infections by herpes simplex virus type 1 (HSV-1) frequently manifest as oral herpes, also called acute herpes labialis and characterized by cold sores on the lips, mouth, or gums. HSV-1 can also cause acute herpetic gingivostomatitis, a condition that results in ulcers of the mucous membranes inside the mouth (). Herpetic gingivostomatitis is normally self-limiting except in immunocompromised patients. Like oral herpes, the infection is generally diagnosed through clinical examination, but cultures or biopsies may be obtained if other signs or symptoms suggest the possibility of a different causative agent. If treatment is needed, mouthwashes or antiviral medications such as acyclovir, famciclovir, or valacyclovir may be used.

### Oral Thrush

The yeast  is part of the normal human microbiota, but overgrowths, especially of Candida albicans, can lead to infections in several parts of the body. When Candida infection develops in the oral cavity, it is called oral thrush. Oral thrush is most common in infants because they do not yet have well developed immune systems and have not acquired the robust normal microbiota that keeps Candida in check in adults. Oral thrush is also common in immunodeficient patients and is a common infection in patients with AIDS.
Oral thrush is characterized by the appearance of white patches and pseudomembranes in the mouth () and can be associated with bleeding. The infection may be treated topically with nystatin or clotrimazole oral suspensions, although systemic treatment is sometimes needed. In serious cases, systemic azoles such as fluconazole or itraconazole (for strains resistant to fluconazole), may be used. Amphotericin B can also be used if the infection is severe or if the Candida species is azole-resistant.

### Mumps

The viral disease mumps is an infection of the parotid glands, the largest of the three pairs of salivary glands (). The causative agent is mumps virus (MuV), a paramyxovirus with an envelope that has hemagglutinin and neuraminidase spikes. A fusion protein located on the surface of the envelope helps to fuse the viral envelope to the host cell plasma membrane.
Mumps virus is transmitted through respiratory droplets or through contact with contaminated saliva, making it quite contagious so that it can lead easily to epidemics. It causes fever, muscle pain, headache, pain with chewing, loss of appetite, fatigue, and weakness. There is swelling of the salivary glands and associated pain (). The virus can enter the bloodstream (viremia), allowing it to spread to the organs and the central nervous system. The infection ranges from subclinical cases to cases with serious complications, such as encephalitis, meningitis, and deafness. Inflammation of the pancreas, testes, ovaries, and breasts may also occur and cause permanent damage to those organs; despite these complications, a mumps infection rarely cause sterility.
Mumps can be recognized based on clinical signs and symptoms, and a diagnosis can be confirmed with laboratory testing. The virus can be identified using culture or molecular techniques such as RT-PCR. Serologic tests are also available, especially enzyme immunoassays that detect antibodies. There is no specific treatment for mumps, so supportive therapies are used. The most effective way to avoid infection is through vaccination. Although mumps used to be a common childhood disease, it is now rare in the United States due to vaccination with the measles, mumps, and rubella (MMR) vaccine.

### Key Concepts and Summary

1. Dental caries, tartar, and gingivitis are caused by overgrowth of oral bacteria, usually Streptococcus and Actinomyces species, as a result of insufficient dental hygiene.
2. Gingivitis can worsen, allowing Porphyromonas, Streptococcus, and Actinomyces species to spread and cause periodontitis. When Prevotella intermedia, Fusobacterium species, and Treponema vicentii are involved, it can lead to acute necrotizing ulcerative gingivitis.
3. The herpes simplex virus type 1 can cause lesions of the mouth and throat called herpetic gingivostomatitis.
4. Other infections of the mouth include oral thrush, a fungal infection caused by overgrowth of Candida yeast, and mumps, a viral infection of the salivary glands caused by the mumps virus, a paramyxovirus.

### Multiple Choice

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### Short Answer