Sexually transmitted infections/diseases (STIs/STDs) affect the same organs as the organs and structures covered in Chapter 16 (Infections of the Reproductive System). While affecting the same anatomical structures, the primary difference between infections of the reproductive system and sexually transmitted infections is the method of transmission. Sexual intercourse or any other sexual activity can lead to STIs, and eventually to STDs. Although the terms sexually transmitted infection and sexually transmitted disease are often used interchangeably, there is a distinction between the two. The term infection refers to just that, the presence of pathogenic organisms in a host, and symptoms of infection may be completely absent. The term disease refers to the appearance of symptoms and damaging effects as a result of an infection (see Chapter 9, Infection and Disease).

For the purpose of simplicity, STIs and STDs are referred to as STIs throughout this chapter. The organs that are affected by STIs in females are the ovaries, fallopian tubes, uterus, vagina, and external genitalia. In males the affected organs include the testes, prostate gland, urethra, and penis. Although reproductive organs are the primary targets, STIs may affect other organ systems and cause systemic problems. One of the likely reasons that sexual activity can lead to a high probability of STI transmission is the fact that most areas of the reproductive system are lined with mucous membranes, which are more susceptible to the penetration of pathogens than the skin (see Chapter 20, The Immune System). STIs can be caused by a variety of organisms including bacteria, fungi, viruses, and protozoa.

LIFE APPLICATION

Prevalence and Incidence of STIs and STDs

In statistical data, the term “prevalence” generally refers to the estimated population of people managing STIs or STDs at any given time. The term “incidence,” on the other hand, refers to the number of new cases of STIs or STDs diagnosed annually. STIs are among the most common causes of infectious diseases in the United States, and they affect men and women of all backgrounds and economic levels. According to the Centers for Disease Control and Prevention (CDC), the incidence of STIs is rising, partly because in the last few decades young people have become sexually active earlier, and marry later. Furthermore, the divorce rate has been increasing, resulting in people who are sexually active having multiple sex partners during their lifetime, thus having an increased risk of acquiring STIs. CDC statistics indicate the following for the United States:

• Prevalence: About 65 million people in the United States are living with an incurable STI (1 in 4, or 25%).

• Incidence: About 15.3 million new cases occur annually (1 in 17, or about 6%)

Bacterial Infections

Bacterial STIs include chlamydia, gonorrhea, syphilis, chancroid, and others. Most of these infections are treatable with antibiotics. However, with any of the bacterial STIs, when not diagnosed and treated early, significant problems including infertility may occur. Some strains of the bacteria causing STIs have also become resistant to certain antibiotics.

Gonorrhea

Gonorrhea is the most reported STI in the United States.* The infection is caused by the bacterium Neisseria gonorrhoeae, a gram-negative diplococcus, and humans are the only known natural host. Once thought to be rather fragile and fastidious, not surviving for long periods of time outside of the host, research has recently discovered strains that are capable of surviving in dried pus on a bed sheet for 6 weeks. The organism can be transmitted through vaginal, anal, and oral sexual activity. The typical incubation time for the infection is between 2 and 7 days. Gonorrhea can be transmitted by individuals who are asymptomatic. Up to 40% of males and between 60% and 80% of females may be infected without any symptoms, but they can act as carriers for up to 5 to 15 years. A small number of organisms, in some cases only about 1000, is required to cause an infection. The symptoms of gonorrhea vary between males and females (Box 17.1). Besides infections of the genitals, oral and anal sexual activity can also lead to gonorrheal infections in the pharynx and the rectum, leading to general systemic bacteremia. Symptoms of systemic gonorrheal infections include the following:

• Fever

• Endocarditis

• Skin lesions (Figure 17.1) that can move to the joints, causing arthritis

FIGURE 17.1 Skin lesions as a result of disseminated gonorrhea.
The lesions start as erythematous papules and often develop into necrotic, grayish central lesions surrounded by an erythematous base. (From Morse S, Ballard RC, Holmes KK, et al: *Atlas of sexually transmitted diseases and AIDS,* ed 3, St. Louis, 2003, Mosby.)

Gonorrhea increases the risks of other infections, including HIV and chlamydia. Men with prolonged infections may also develop an inflammation of the testicles called epididymitis, a condition often leading to infertility. Prolonged infections in women can result in pelvic inflammatory disease (see Chapter 16, Infections of the Reproductive System), which may include the uterus and fallopian tubes. Scar tissue in the fallopian tubes can prevent fertilization, and damage to the uterine wall can stop implantation of a fertilized ovum (zygote). Pelvic inflammatory disease also increases the risk of ectopic pregnancy.

During delivery gonorrhea can be passed from the infected mother to the baby as it moves through the birth canal (see Chapter 23, Human Age and Microorganisms). Infection of the newborn often leads to infection of the joints, blood infection (bacteremia), and/or blindness.

Diagnosis of gonorrhea is accomplished by identifying the organism by microscopic examination of discharge samples or in laboratory cultures of swabs from infected tissue. Treatment of gonorrhea originally involved sulfonamides and/or penicillin, but the organism has developed resistance to these antibiotics. Antibiotics currently used include ciprofloxacin, cefixime, ofloxacin, and levofloxacin.

Although treatment with antibiotics has a high success rate in eliminating the infection, any damage done to the organs during the infection is permanent.

At the present time there is no vaccine for gonorrhea but research is underway. Preventive measures to avoid contracting an infection include the following:

• Limiting the number of sex partners

• Informing partners about an infection

• Reporting signs or symptoms to a doctor

• Using condoms during sexual activity

• Abstaining from sexual activity

Syphilis

Syphilis has been in the human population for many years and is documented in many historical writings. Because it causes symptoms that can be associated with numerous other diseases, syphilis is sometimes referred to as the “great imitator.” It is caused by Treponema pallidum, a gram-negative spirochete. Humans are the organism’s only natural reservoir and transmission occurs through direct contact with sores of an infected person. Although the bacterium can be passed on through body fluids such as saliva, the primary means of transmission is through any sexual activity—vaginal, anal, or oral. A pregnant woman can also pass the infection on to her child during pregnancy. This infection is known as congenital syphilis (see Chapter 23, Human Age and Microorganisms).

Syphilis takes place in three stages, with an incubation time between 10 and 90 days after the initial infection. The initial symptoms may be mild and are sometimes difficult to diagnose because they resemble symptoms of other diseases such as gonorrhea. Many infected persons in the early stages do not realize that they are infected. If treated early, syphilis can be cured without any resulting serious or long-term health problems. Untreated, syphilis manifests itself in three stages: primary, secondary, and tertiary syphilis (Table 17.1).

TABLE 17.1

Stages of Syphilis

Stage	Time Frame	Symptoms
Primary	Ten to 90 d after initial infection	Small, red skin sores
Secondary	Two to 10 wk after primary stage	Red-brown rash on palms of hands and soles of feet; fever, swollen lymph nodes, sore throat, muscle and joint pain, loss of patches of hair, malaise, rash on skin and mucous membranes of mouth, throat, and cervix
Latent	After secondary stage	None
Tertiary	Many years from onset of the latent phase	Gummas—rubbery masses of tissue in various organs; memory loss, ataxia, paralysis, insanity, and finally death

• Primary syphilis represents itself as small, red sores (chancres) that appear on the body at the site of infection within 10 to 90 days after initial contact. These sores will eventually disappear, leaving a scar on the skin. if untreated, the symptoms will move to the secondary stage.

• Secondary syphilis occurs within 2 to 10 weeks of the primary stage (Figure 17.2). During this stage the organism enters the bloodstream and travels to other organ systems, causing a wide variety of symptoms including the following:

FIGURE 17.2 Rash of secondary syphilis. (From Habif TP: *Clinical dermatology: a color guide to diagnosis and therapy,* St. Louis, 1996, Mosby.)

• A red-brown rash on the palms of the hands and soles of the feet

• Fever

• Swollen lymph nodes

• Sore throat

• Muscle and joint pain

Without treatment at this point the disease will move into the tertiary stage:

• Tertiary syphilis is the final stage of the disease, characterized by gummas (lesions) that begin to affect vital organs including the eyes, liver, heart, kidneys, and the brain. This stage results in conditions such as:

• Loss of muscle control

• Vision problems followed by blindness

Patients with syphilis in the later stages are also at increased risk for HIV infection.

Pregnant women run the risk of passing the infection on to their unborn child and they have an increased risk for miscarriage, premature delivery, and stillbirth (see Chapter 23, Human Age and Microorganisms). Diagnosis of syphilis can be done by a number of different methods. Observing a sample from a lesion for the organism itself, using a dark-field microscope, is typically one of the first methods used for early detection. Along with microscopic examination, a number of blood-screening tests are available to confirm an infection. These include the following:

• Venereal disease research laboratory (VRDL) test

• Fluorescent treponemal antibody absorption (FTA-ABS) test

• Rapid plasma reagin (RPR) test

• Treponema pallidum hemagglutination assay (TPHA)

Because of the possibility that a single test may result in a false positive or negative reading during the different stages of the disease or under different circumstances, at least two blood tests are done to determine and confirm an infection. For example, the tests based on detection of antibodies are not useful in diagnosing the infection in a person who has had the disease previously, as the antibodies remain in the body for years.

Treatment for syphilis in the primary and secondary stages is fairly simple and can often be achieved with a single intramuscular dose of penicillin. In a more advanced stage of the infection hospitalization and a daily antibiotic regimen may be required. Tetracycline and erythromycin have proven to be effective for persons allergic to penicillin. At the present time there is no vaccine available; however, research is ongoing. Preventive measures to avoid contracting syphilis include the following:

• Avoiding contact with lesions and body fluids

• Use of condoms during intercourse

• Syphilis testing and treatment early in pregnancy

Chlamydia

Although usually referred to simply as chlamydia, the organism Chlamydia trachomatis, a gram-negative coccus and an intracellular obligate parasite, is responsible for a number of different infections of the reproductive system. These include nongonococcal urethritis (NGU), pelvic inflammatory disease (PID), and lymphogranuloma venereum (LGV). Chlamydial infections are now the most prevalent STIs in the United States (Box 17.2). Female carriers of the infection are often asymptomatic, thus increasing the transmission of chlamydial infections. Transmission occurs through exchange of semen or vaginal fluid during vaginal, oral, or anal sexual activity. Pregnant women can also pass the infection on to their child during labor and delivery. The incubation period is between 1 and 3 weeks before symptoms appear. The symptoms of a chlamydial infection tend to be very mild or virtually nonexistent. According to research data, up to 75% to 80% of infected women and up to 50% of infected men show no symptoms at all.

Left untreated, chlamydial infections can cause serious health problems in both men and women. In males the infection can lead to epididymitis, possibly resulting in sterility and other complications. Furthermore, in males an NGU chlamydial infection may manifest itself as urethritis (see Urinary Tract Infections in Chapter 15, Infections of the Urinary System) and in women as vulvovaginitis or cervicitis (inflammation of the cervix). Women are more likely to experience serious problems associated with a chlamydial infection in the form of PID (see Chapter 16, Infections of the Reproductive System). LGV chlamydial infections are 20 times more common in men than in women. The lesions characteristic of this type of infection usually heal on their own; however, 1 week to 2 months after the lesions heal the organism invades the lymph nodes, causing large, painful buboes. If the buboes are not drained, inflammation can create obstructions in the lymph vessels, causing massive enlargement of the external genitalia in both males and females.

Chlamydial infection can also be detrimental during a pregnancy, as it increases the possibility of a premature birth or ectopic pregnancy. In addition, the infection can be passed to the child during delivery, causing eye infections and pneumonia.

Diagnosis is typically accomplished by special staining and microscopic examination of pus from lymph nodes or discharge/lesion samples. Staining with iodine reveals the bacteria, as they appear as inclusions in the sample. Serological tests are obtainable but they frequently give false-positive results. At present there is no vaccine available for chlamydial infections; however, research is ongoing. Current treatment for all types of chlamydial infections consists of a course of antibiotics including tetracycline, azithromycin, and erythromycin. Preventive measures to avoid contracting a chlamydial infection include the following:

• Use of a condom during sexual activity

• Limiting the number of sex partners

• Annual STD testing

• Seeking immediate treatment if symptoms appear

• If infection is confirmed, notification of all sex partners

MEDICAL HIGHLIGHTS

Automated Testing System for STIs

In recent years, nucleic acid amplification tests for infectious diseases have come into use in many clinical microbiology laboratories. A number of these tests have been commercialized and approved by the U.S. Food and Drug Administration (FDA) for the testing of infectious organisms in clinical samples. In December 2003 the FDA approved an automated testing system for the diagnosis of chlamydia and gonorrhea. This automatic nucleic acid amplification system, called TIGRIS DTS produced by Gen-Probe (San Diego, CA), can rapidly diagnose chlamydia and gonorrhea.

Mycoplasmal and Ureaplasmal Nongonococcal Urethritis (NGU)

NGUs can also be caused by Mycoplasma hominis and Ureaplasma urealyticum. Both organisms are gram-negative pleomorphic bacteria that lack cell walls and are frequently found among the normal urogenital microflora, especially in women. Transmission occurs primarily through vaginal sexual activity. Although usually associated with NGU, M. hominis occasionally will cause PID in women and urethritis in men. Outward symptoms are generally not evident, but the effects can be serious, especially in pregnant women. M. hominis can colonize the placenta, causing spontaneous abortion, premature births, low birth rates, and ectopic pregnancies.

U. urealyticum is one of the smallest bacteria known to be a human pathogen. Infections caused by this pathogen account for more than half of all infections that eventually result in infertility of couples. Moreover, U. urealyticum is a major cause of fetal and neonatal death, premature births, miscarriages, and low birth weight.

Diagnosis is done by culturing the organism from the placenta, or in urethral and vaginal discharge. Serological tests such as complement fixation, enzyme immunoassays, and cold agglutinin tests are helpful in identifying these pathogens. Microscopy is not particularly useful because cell walls are absent and staining is thereby greatly reduced.

Treatment for these infections is typically tetracycline; however, erythromycin, spectinomycin, and clindamycin have also proven to be effective. Because of the lack of a cell wall, penicillin is not effective against these microbes (see Chapter 22, Antimicrobial Drugs). Preventive measures against these NGU infections include simply abstinence from sexual activity or use of a condom.

MEDICAL HIGHLIGHTS

Sexually Transmitted Toxic Shock Syndrome (TSS)

As discussed in Chapter 16, Staphylococcus aureus is a gram-positive coccus that produces a potent bacterial toxin capable of causing severe systemic problems. Research shows that certain strains of methicillin-resistant S. aureus can be transmitted through sexual activity and cause both local and systemic problems (toxic shock syndrome, TSS). According to the Centers for Disease Control and Prevention (CDC), the most common symptoms of staphylococcal TSS include the following:

• Fever higher than 38.9° C (102° F)

• Increased blood flow to mouth, eyes, and vagina, making them appear red

• Decreased urine output and sediment in urine

• Decreased liver function

• Bruising due to low blood platelet count

• Disorientation and confusion

Antibiotics other than methicillin may be prescribed for the treatment, depending on the specific strain of the bacterium. The antibiotic of choice for the treatment of TSS is usually vancomycin.

Chancroid

Chancroid infection is relatively rare in the United States but its incidence worldwide may be greater than that of either gonorrhea or syphilis. The soft chancres (Figure 17.3) of this infection distinguish it from the hard lesions that are characteristic of syphilis. The causative agent is Haemophilus ducreyi, a short gram-negative bacillus. Humans are the host for this organism, and the method of transmission is vaginal sex. Incubation time between initial infection and the appearance of symptoms is about 3 to 7 days. This infection affects both men and women, with a much higher incidence of infection noted among men. The primary symptom is the appearance of soft, painful lesions or chancres. These chancres bleed easily and usually appear on the genitals or in the genital area 3 to 5 days after exposure. On occasion an infection will be present without the lesions, but a burning sensation after urination occurs. Chancres can also appear in the mouth or on the lips, but regardless of their location, they are highly infective. Simply touching a chancre with bare skin can result in transmission of the infection. In about 30% of cases the infection will move to the groin area, where it will form enlarged masses of lymphatic tissue, called buboes. Each bubo will then enlarge greatly and can break through the skin, discharging pus. Untreated lesions can persist for months, but the infection will often resolve without treatment.

Diagnosis involves identifying the presence of the organism in scrapings from a lesion or from fluids from a bubo, by microscopy and subsequent biochemical testing and growth on selective media (specialized gonococcal agar, or GC agar). Treatment includes the use of tetracycline, erythromycin, sulfanilamide, and trimethoprim-sulfamethoxazole. Treatment will heal the lesions but deep tissue scarring may remain. As with most other sexually transmitted infections, preventive measures include abstinence from sexual activity, use of condoms, and protection from contact with lesions (primarily for caregivers). There is no vaccine presently available for this infection.

Donovanosis (Granuloma Inguinale)

Donovanosis is relatively uncommon in the United States, with most cases occurring among homosexual men. The infection is caused by Klebsiella granulomatis (the genus was previously called Calymmatobacterium), a gram-negative, encapsulated bacillus. The precise epidemiology of this infection is not fully established, but it does appear that many cases are sexually transmitted, whereas others are not. Whatever the method of transmission, the infection rate is relatively low and even with regular sexual contact the infection may not spread. If the disease occurs, the symptoms include the appearance of irregular, painless ulcers on or near the genitals within 9 to 50 days of the initial infection.

The infection can be spread by touching the ulcers, and subsequently contaminating other parts of the body. The ulcers may heal without treatment, but they do cause loss of skin pigment in the area of the lesion. Furthermore, if untreated, the infection can spread and result in extensive tissue damage.

Diagnosis is performed by staining of scrapings from the lesions and microscopic examination. The infection is confirmed by the presence of encapsulated bacteria inside macrophages. The bacteria themselves resemble the shape of closed safety pins and are called Donovan bodies. Antibiotic treatment may include the use of ampicillin, tetracycline, erythromycin, and gentamicin.

HEALTHCARE APPLICATION
Common Bacterial STIs

Infection	Organism	Symptoms	Treatment
Gonorrhea	Neisseria gonorrhoeae	Vary between females and males*	Ciprofloxacin, cefixime, ofloxacin, levofloxacin
Syphilis	Treponema pallidum	Differ with stages^†	Benzathine penicillin; azithromycin, doxycycline, tetracycline
Chlamydia	Chlamydia trachomatis	Depend on disease	Tetracycline, azithromycin, erythromycin
NGU	Ureaplasma urealyticum	May cause infertility; fetal and neonatal death; premature births, miscarriages, low birth weight	Tetracycline; erythromycin, spectinomycin, clindamycin
Chancroid	Haemophilus ducreyi	Soft chancres on genitals or genital areas	Tetracycline, erythromycin, sulfanilamide, trimethoprim-sulfamethoxazole
Donovanosis	Klebsiella granulomatis	Irregular, painless ulcers on or near genitals	Ampicillin, tetracycline, erythromycin, gentamicin

NGU, Nongonococcal urethritis.

^*See Table 17.1.

^†See Table 17.2.

Viral Infections

STIs caused by viruses are about as common today as those caused by bacteria. However, unlike bacterial STIs, viral STIs are at the present time incurable. The antiviral drugs available can be used to manage the disease but not to cure the disease.

HIV and AIDS

The human immunodeficiency virus (HIV) is the causative agent of acquired immune deficiency syndrome (AIDS), a secondary immune deficiency (see Chapter 20, The Immune System). AIDS is not a disease but a syndrome because it has complex signs and symptoms, and a variety of diseases are associated with a common cause. AIDS results in many opportunistic infections due to a severely compromised immune system.

MEDICAL HIGHLIGHTS

Selected Opportunistic Infections: AIDS

The infections listed in this highlight are only a few that are often associated with HIV infections and AIDS due to the compromised immune system. This list only provides samples and links for more information on each of the infections.

Bacterial infections

• Mycobacterium avium complex (comprising M. avium and M. intracellulare): The disease in not a reportable disease, but it has been reported that the incidence is decreasing among HIV-infected patients as a result of new treatment modalities. The symptoms of the disease in HIV patients include night sweats, weight loss, abdominal pain, fatigue, diarrhea, and anemia.

• http://www.cdc.gov/ncidod/dbmd/diseaseinfo/mycobacteriumavium_t.htm

• Salmonellosis (if recurrent): The frequency of salmonellosis (see Chapter 12) in patients with AIDS is estimated to be 20 times higher than in the general population.

• http://www.cdc.gov/nczved/dfbmd/disease_listing/salmonellosis_gi.html

• Syphilis: There is an estimated two- to fivefold increase in the risk of acquiring AIDS if exposed to that infection when syphilis is present.

• http://www.cdc.gov/std/syphilis/STDFact-Syphilis.htm

• Tuberculosis (see Chapter 11): Worldwide TB is one of the leading causes of death among HIV-infected persons.

• http://www.cdc.gov/tb/pubs/TB_HIVcoinfection/default.htm

Viral infections

• Cytomegalovirus: Infection with CMV is a major cause of disease and death among immunocompromised patients, including HIV-infected patients. In people with HIV, CMV can cause retinitis, which can cause blindness.

• http://www.cdc.gov/cmv/

• Hepatitis: HIV-positive persons also infected with hepatitis B virus are at increased risk for developing chronic HBV infection and can have serious medical complications, including an increased risk for liver-related morbidity and mortality. About one quarter of HIV-infected persons in the United States are also infected with hepatitis C, causing chronic liver disease and more rapid liver damage in HIV-infected people.

• http://www.cdc.gov/ncidod/diseases/hepatitis/index.htm

• Herpes: People infected with both HIV and the herpesvirus often have longer lasting, more frequent, and more severe outbreaks of herpes symptoms. Furthermore, it may cause HIV to multiply at a faster rate, causing AIDS.

• http://www.cdc.gov/std/herpes/STDFact-herpes.htm

Fungal infections

• Aspergillosis: Aspergillosis in patients with AIDS most commonly affects the lungs. Other sites, less commonly affected, include the blood, sinuses, skin, ear, brain, and heart.

• http://www.cdc.gov/nczved/dfbmd/disease_listing/aspergillosis_gi.html

• Candidiasis: 90% of patients with HIV/AIDS will develop candidiasis.

• http://www.cdc.gov/nczved/dfbmd/disease_listing/candidiasis_gi.html

• Coccidioidomycosis: Coccidioidomycosis during HIV infections has many different manifestations including diffuse, reticulonodular pneumonia; focal primary pneumonia; and disease disseminated beyond the thoracic cavity. Treatments currently available include polyene antifungal amphotericin B and triazole antifungals.

• http://health.utah.gov/epi/fact_sheets/cocci.html

• Histoplasmosis: Histoplasmosis in patients with AIDS almost always is manifested by symptoms of progressive disseminated disease. Advancement in antiviral therapy for AIDS has shown a decrease in the incidence of histoplasmosis among people with AIDS.

• http://www.cdc.gov/nczved/dfbmd/disease_listing/histoplasmosis_gi.html

HIV infection in humans is now a pandemic, that is, an infection that occurs worldwide. There are at least two types of the virus, HIV-1 and HIV-2, that are responsible for causing AIDS (discussed in Chapter 20). The HIV virus basically destroys the immune system, thus leaving the body open to various infections that ultimately prove fatal. The virus targets cells of the immune system including helper T cells, macrophages, dendritic cells, and Langerhans cells. As these components of the immune system battle the virus in the early stages of infection the virus survives but may be kept in check, and the result can be almost a draw between the body and the virus. However, over time the body’s ability to replace the cells of the immune system will be diminished and unable to keep up with the rapidly replicating, and usually mutating virus. Without the helper T cells and macrophages the B cells will not be stimulated to form plasma cells, which are responsible for producing the antibodies to fight the infection (see Chapter 20). A count of the helper T cells is a good indicator in predicting the progression of the infection and the onset of AIDS-related symptoms. The progression of HIV infections depends primarily on two factors: the actual amount of virus a person was exposed to, and how often repeated exposure occurred. According to the Centers for Disease Control and Prevention (CDC, Atlanta, GA) the stages of HIV infections are classified into four groups or stages (Table 17.2).

TABLE 17.2

Stages of HIV Infections and AIDS

Stage	Time Frame	Symptoms
1	1–12 mo	HIV antibodies appear; flulike symptoms
2	1–8 yr	Mild anemia, low white blood cell count, some decrease in T cell count, seborrheic dermatitis, shingles, hairy leukoplakia
3	9–15 yr	Moderate anemia, low albumin, low cholesterol, decrease in helper T cell count, severe dermatitis, thrush, weight loss, diarrhea, recurring fever, tuberculosis, various bacterial infections, recurrent shingles
4	Months to years	Death—usually 2 yr after diagnosis in men, 12–18 mo in women. Causes of death vary, but usually involve opportunistic infections, lymphoma, and wasting syndrome

Most patients with full-blown AIDS will also develop a malignancy called Kaposi’s sarcoma, in which blood vessels grow in a tangled mass filled with blood and rupture easily. The masses appear as pink or purple splotches on the skin but can also spread to organs of the digestive tract, the lungs, liver, spleen, and the lymph system.

Transmission of the HIV virus has been an area of contention among medical researchers. Most agree that casual contact will not result in transmission of the virus, that instead it requires more intimate contact with the body fluids of an infected person or is transmitted from mother to fetus. The fluids typically involved in transmission of the virus include blood, semen, and vaginal secretions. The portal of entry is usually a break in the skin or mucous membranes that come in contact with the infected fluid. Therefore any contact that involves the exchange of bodily fluids may allow the virus to be transmitted from person to person. These types of contact include the following:

• Sexual contact—all forms of sexual activity: Heterosexual and homosexual intercourse whether vaginal, anal, or oral

• Sharing contaminated needles between intravenous drug users

• Receiving any contaminated blood products

• Transfer from infected mother to infant either during the pregnancy, during delivery, or through breastfeeding

Diagnosis of HIV infections can include the following methods:

• Enzyme-linked immunosorbent assay (ELISA): This is typically the first step in HIV testing, which detects the presence of HIV antibodies in a sample of blood. If positive, the second step will be a confirmation test. If negative, testing stops here. This is the U.S. Food and Drug Administration (FDA)-approved method for detecting HIV infections.

• Western blot is used to confirm the positive ELISA results. This test involves detection of specific proteins present in the blood of an HIV-positive patient. Combined with the ELISA, a positive result with the Western blot is 99.9% accurate. This test is FDA approved for detecting an HIV infection.

• HIV polymerase chain reaction (HIV PCR) is used to detect the presence of specific DNA and RNA sequences that indicate the presence of HIV as the viral DNA/RNA circulate in the blood after infection has occurred. This test is FDA approved for detecting an HIV infection.

• OraSure is a home-type test using secretions from between the cheek and the gums to detect the presence of HIV antibodies; this is in contrast to the blood used in the three previous tests. The principle is essentially the same as with the ELISA, but involves a different sample type. This test is not currently approved by the FDA for a definitive diagnosis of HIV infection.

• Urinanalysis is also used to detect an HIV infection but tends to be inaccurate in the present form. This test is not FDA approved for detecting an HIV infection.

The ELISA, Western blot, and PCR methods are discussed in detail in Chapter 25 (Biotechnology). There are a number of testing methods and protocols being developed to improve the speed and accuracy of the tests.

At the present time there is no treatment that can cure an HIV infection. However, the FDA has approved more than 30 different drugs that have shown some success in inhibiting or slowing the infection’s progress. These drugs fall into seven categories:

1. Integrase inhibitors

2. Entry inhibitors

3. Nonnucleoside reverse transcriptase inhibitors (NNRTIs)

4. Nucleotide analogs

5. Protease inhibitors

6. Nucleoside reverse transcriptase inhibitors (NRTIs)

7. Combination medications

In addition to treating the HIV infection, a patient in advanced stages of the disease may require other drugs including antibiotics to treat opportunistic infections. These opportunistic infections include (but are not limited to) cytomegalovirus, encephalitis (Toxoplasma gondii), yeast infections (Candida albicans), and respiratory diseases.

Research in pursuit of a vaccine to prevent HIV infection is ongoing but no vaccine is currently available. Although vaccine research continues, many experts in the study of HIV have stated that because of the high mutation rate of the virus and the nature of the viral action itself, the development of a vaccine may be decades away.

Hepatitis B, C, and D

Hepatitis is an infection of the liver, capable of causing significant destruction of liver cells (see Chapter 9 [Infection and Disease] and Chapter 12 [Infections of the Gastrointestinal System]). Hepatitis B, C, and D viruses can be transmitted during sexual activity and are therefore considered STIs although they do not specifically target or affect organs of the reproductive system.

• Hepatitis B (HBV) transmission occurs when blood from an infected person enters the body of another. It can be transmitted through sexual activities with an infected person, by sharing needles, and from infected mother during birth or by breastfeeding. Transmission has also been documented through artificial insemination with contaminated semen. Furthermore, transmission can occur through needlesticks or exposure to sharps. The incubation time is between 45 and 180 days, with an average of about 90 days. The virus itself replicates in liver cells, lymph tissue, and hematopoietic tissue. The virus may stay in the blood for years and be passed on by the carrier at any time. The symptoms of a HBV infection are not immediately obvious but once they do appear they include the following:

• Yellowing of the skin

Hepatitis B infections can be prevented by vaccination, which is required for most healthcare providers or other persons who may be exposed to blood products. Three injections are given over a period of 6 months. This immunization has been shown to be effective in more than 90% of healthy individuals.

• Hepatitis C (HCV) in most cases is transmitted by blood-to-blood contact but may be sexually transmitted, especially among individuals already infected with another STI. Signs and symptoms of the infection are similar to those of hepatitis B infections. Hepatitis C can be either acute, that is, a short-term illness occurring within the first 6 months after exposure to the virus, or chronic. Seventy to eighty percent of acute infections will develop into a chronic infection, a serious disease that can result in long-term health problems, or even death. HCV RNA can be detected in the blood within 1 to 3 weeks of exposure, and antibodies to HCV can be detected in more than 97% of persons by 6 months after exposure. At present there is no vaccine available for hepatitis C and the CDC recommendations for prevention and control of HCV infections include screening and testing of blood donors, viral inactivation of plasma-derived products, risk reduction counseling, screening of persons at risk for HCV infection, and routine practice of infection control in healthcare settings.

• Hepatitis D (HDV) is caused by the hepatitis D virus, a defective virus that needs the hepatitis B virus to exist and therefore is found in the blood of persons infected with the HBV virus. HDV may worsen hepatitis B infection or existing hepatitis B liver disease. Symptoms of the infection are similar to those of HBV infections but may also include the following:

• Nausea and vomiting

• Fatigue

• Joint pain

• Dark (tea-colored) urine

Tests for the infection include liver enzymes, which are higher than normal; anti-delta agent antibody, which will be positive for HDV; and liver biopsy. Because hepatitis D occurs only in persons with hepatitis B infections, vaccination against HBV is recommended for people who are at high risk for HBV infections. Prompt recognition and treatment of HBV infection can help prevent HDV. Patients with a long-term HDV infection may be treated with interferon-α or a liver transplant.

Genital Herpes

Genital herpes, a highly contagious and common STI in the United States, is caused by the herpes simplex virus HSV-2 or HSV-1. Although most genital herpes is caused by HSV-2, it can also be caused by HSV-1, the organism that most commonly causes “fever blisters” of the mouth and lips (see Chapter 10, Infections of the Integumentary System, Soft Tissue, and Muscle). Genital herpes infections typically result in one or more blisters on or around the genitals or rectum. After the blisters break they leave tender sores that take 2 to 4 weeks to heal. Other outbreaks may occur weeks or months thereafter, with the number of outbreaks generally decreasing over the years. The signs and symptoms of the infection vary greatly and some individuals infected with HSV-2 may not be aware of their infection. Even without clear signs and symptoms of the infection HSV can be detected by the use of blood tests, because of the presence of antibodies.

There is no cure for herpes, but antiviral medications are available to shorten and even prevent an outbreak during the time the medication is taken. Persons with herpes lesions should abstain from sexual activity with an uninfected person. Although daily suppressive therapy for symptomatic herpes may reduce transmission, it needs to be noted that an infected person without lesion can still transmit the organism.

Neonatal herpes (see Chapter 23, Human Age and Microorganisms) is a condition of concern for women of childbearing age because the virus can cross the placenta and infect the fetus. Serious damage to the fetus may occur, including mental retardation and defective hearing and vision. Spontaneous abortions have also been reported. If the infection is acquired during the late stages of pregnancy a cesarean delivery is usually performed to protect the child.