Published in the Bulletin of Experimental Treatments for AIDS Autumn 2000 issue, by the San Francisco AIDS Foundation.

Autumn 2000 Table of Contents

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Sexually Transmitted Diseases and HIV Related Risks

Liz Highleyman

Some STDs, such as syphilis and genital herpes, can be characterized by genital ulcers or sores. Others, such as gonorrhea and chlamydia, can cause inflammation of the urethra (urethritis) or cervix (cervicitis) and genital discharge. However, many people with STDs, especially women, do not have any noticeable symptoms. In fact, M.L. Lamb of the U.S. Centers for Disease Control and Prevention (CDC) presented study results at the XIII International AIDS Conference in Durban, South Africa, this past July showing that the majority of STD cases were asymptomatic, or "silent"; rates of asymptomatic STDs (including gonorrhea, syphilis, chlamydia, and trichomoniasis) were nearly 50% in men and well over 50% in women. People can transmit STDs even if they have no symptoms.

Any condition characterized by genital sores and inflammation--whether sexually transmitted or not--can promote HIV transmission, both by making a person with an STD more likely to contract HIV, and by increasing the chances that a person coinfected with HIV and an STD will transmit HIV to a sexual partner.

Any sexually active person who experiences pain or burning during urination, genital discharge, sores or a rash in the genital or anal areas, or pain during sexual intercourse should see their health-care provider or visit an STD clinic. Because many people with HIV do not have symptoms, annual screening is recommended for sexually active people.

How Common Are STDs?

STDs are among the most common infectious diseases around the world. The U.S. has the highest STD rates in the industrialized world. The CDC estimates that there are over 15 million new cases of STDs in the U.S. annually (incidence); when the numbers of existing cases of chronic, incurable STDs are factored in, the numbers are much higher (prevalence). Globally, the World Health Organization (WHO) estimated in 1995 that 333 million new cases of curable (i.e., bacterial) STDs occur annually.

In the U.S., the incidence of STDs is highest in teenagers and young adults; people under age 25 account for about two-thirds of new sexually transmitted infections. STD rates are higher in the southeast region of the U.S. and in certain racial/ethnic groups (for example, the syphilis rate among African-Americans is 50 times higher than that among whites). Rates are also high among some populations of young men who have sex with men. STDs are associated with socioeconomic factors such as poverty and lack of regular health care, and with behavioral factors such as number of sex partners. The incidence of some STDs--such as chlamydia and herpes--has risen in the U.S. over the past decade, likely due in part to improved surveillance and detection methods. However, other STDs--such as syphilis--have become less common.

STD Prevention and Treatment

The same safer sex precautions recommended to prevent HIV transmission--the use of latex condoms and other barriers--reduce the risk of transmission of some STDs. However, because STDs can be spread through contact with lesions on the skin, which may occur on areas that are not covered by condoms or barriers, these methods are not completely effective. It is good practice to check sexual partners for sores, discharge, or other symptoms, but because people with no visible symptoms may still transmit STDs, this precaution is not foolproof. Because the risk factors for the various STDs are similar, a person who contracts one STD should be checked for others as well. The CDC recommends that people who are sexually active and not in a mutually monogamous relationship receive regular STD screenings, since early detection and treatment can prevent many of the serious adverse consequences associated with STDs.

Bacterial STDs (e.g., chancroid, chlamydia, gonorrhea, and syphilis) can be treated with antibiotics and are completely curable if detected and treated early. Once treatment begins, a person should take the full course of medication prescribed, even if symptoms disappear. Sexual partners should be treated at the same time to avoid passing an infection back and forth. Viral STDs (e.g., genital herpes, and human papillomavirus) are not curable (although they can be treated), and remain in the body for life. Several of the drugs used to treat STDs should not be used by pregnant women; any woman who is experiencing STD symptoms and may be pregnant should discuss treatment with an experienced health-care provider. See the treatment information below for specific STDs.

Bacterial STDs

Chancroid

Chancroid, caused by the Hemophilus ducreyi bacterium, is an ulcerative STD that causes soft lesions that are usually located on the genitals. The disease is endemic in some areas of the U.S. Chancroid lesions usually begin as elevated bumps that fill with pus and develop into open sores; usually there is only one ulcer, but in some cases there may be more. Men are more likely to have painful lesions than women; chancroid in women is often asymptomatic. The soft, tender chancroid lesions can be distinguished from syphilis chancres, which are typically firm and painless. Symptoms usually appear 3–10 days after exposure to the bacterium. About one-half of people with chancroid also have painful, swollen lymph nodes in the groin, usually on one side; the enlarged glands may fuse into a large mass called a bubo. Some people also experience genital discharge, painful urination or defecation, and pain during intercourse. Diagnosis is done by isolating H. ducreyi from a lesion and ruling out other STDs with similar symptoms such as syphilis and genital herpes.

Chancroid is treated with an antibiotic such as azithromycin, ceftriaxone, ciprofloxacin, or erythromycin. Buboes may need to be surgically drained.

Chlamydia

Chlamydia is caused by the Chlamydia trachomatis bacterium. It is one of the most common STDs in the U.S., with an estimated 3–4 million new cases annually; as many as one in 20 women of childbearing age may be infected. Chlamydia is the most common cause of nongonococcal urethritis (NGU). Its symptoms are similar to those of gonorrhea, and can include pain or burning during urination (especially in the morning); inflammation of the urethra, cervix, or rectum; pain and itching of the penis, vagina, or anus; and a whitish discharge from the penis or vagina. Symptoms typically begin two to three weeks after exposure to the bacterium. However, chlamydia is asymptomatic in as many as two-thirds of cases, especially in women, and regular screening is therefore recommended for sexually active women. One strain of chlamydia, prevalent in tropical climates but rare in the U.S., causes an STD called lymphogranuloma venereum (LGV) that is characterized by swollen lymph nodes in the groin.

Chlamydia is diagnosed by a culture test of genital fluid, a DNA amplification assay, or a recently approved urine test. It can be treated with antibiotics including azithromycin (Zithromax), ceftriaxone (Rocephin), doxycycline (Vibramycin), ofloxacin (Floxin), or erythromycin (Ilosone); penicillin is not effective. Because gonorrhea and chlamydia commonly occur together, combination antibiotic treatment is often given to combat both infections. If chlamydia is left untreated, it can cause pelvic inflammatory disease (PID) in women and epididymitis in men (see below). Chlamydia can be transmitted to newborns during birth, causing conjunctivitis (eye infection) or pneumonia.

Gonorrhea

Gonorrhea is caused by the Neisseria gonorrhoeae bacterium, which multiplies in warm, moist areas of the body. According to the CDC, U.S. gonorrhea rates increased by 9% in 1998 to 132.9 cases per 100,000 people, after declining for 12 years. Gonorrhea may be transmitted by vaginal, anal, or oral sex, and may affect the urethra, vagina, cervix, rectum, pharynx (throat), or eyes. Symptoms, which typically appear 2–14 days after exposure, include pain or burning during urination or defecation; a yellowish or greenish (pus-like) penile, vaginal, cervical, or rectal discharge; swelling and tenderness of the vulva; sore throat; and a false urge to urinate or defecate. An estimated 10% of men and up to 80% of women have no symptoms.

Gonorrhea is diagnosed using a Gram stain, in which a sample of genital fluid is dyed and examined under a microscope, or a DNA test; a urine test for gonorrhea is also available. In the 1980s, Neisseria gonorrhoeae developed resistance to penicillin and tetracycline (Sumycin, Achromycin), and the disease is now usually treated with oral antibiotics such as ceftriax-one, cefixime (Suprax), ciprofloxacin (Cipro), ofloxacin, azithromycin, or by injection. However, the incidence of fluoroquinolone and macrolide antibiotic resistant gonorrhea is rising; in September the CDC announced the first reported cases of azithromycin-resistant Neisseria gonorrhoeae in the U.S. Untreated gonorrhea can lead to PID or epididymitis, as well as damage to the joints. In pregnant women, gonorrhea is associated with premature labor, miscarriage, and stillbirth, and it may be transmitted to an infant during birth.

Granuloma Inguinale

Granuloma inguinale, also known as donovanosis, is caused by the Calymmatobacterium granulomatis bacterium. The disease is rare in the U.S. but endemic in some tropical areas of the world. Granuloma inguinale is characterized by painless, red, "beefy" lesions not accompanied by swollen groin lymph nodes. The disease is diagnosed by the identification of so-called Donovan bodies in a biopsy sample. Granuloma inguinale is treated with a course of antibiotics such as TMP-SMX (Bactrim, Septra), doxycycline, ciprofloxacin, or erythromycin. Pregnant and lactating women should be treated with erythromycin. In some cases, relapse can occur 6–18 months after effective initial therapy.

Syphilis

Syphilis, caused by the Treponema pallidum bacterium, has been called "the great imitator" because its symptoms vary widely and can mimic those of many other diseases. Syphilis is becoming rarer in the U.S.; in 1998, rates were the lowest ever seen since tracking began in 1941, at an average of 2.6 cases per 100,000 people (although the rate varies considerably by region and ethnic group). In 1999, the CDC launched a campaign to eradicate the disease in this country within five years.

Syphilis has a complex pathogenesis (course of development) characterized by primary, secondary, latent, and tertiary stages. Primary syphilis typically begins with a single sore or ulceration called a "chancre" on the penis or vulva, which appears 10–90 days after exposure to the bacterium; the chancre may also develop on the cervix, lips, or tongue, inside the vagina or anus, or on other parts of the body. The firm, usually painless lesion typically resolves without treatment after 1–6 weeks. Some people with primary syphilis have no symptoms. Secondary syphilis is characterized by flu-like symptoms including fatigue, sore throat, headache, joint aches, loss of appetite, and swollen glands; some people also experience patchy hair loss. People with this stage of disease may also develop a rash, which may range from round, brownish blotches (described as looking like pennies) to a red or pustular appearance; the rash may appear anywhere on the body, and usually affects the palms of the hands and soles of the feet. Secondary symptoms may last for a few weeks to a few months, and may come and go over the course of 1–2 years.

If syphilis remains untreated, symptoms disappear and the person can no longer transmit the disease sexually, but the bacteria remain latent (inactive) for years or even decades. Symptomatic late-stage or tertiary syphilis involves damage to the eyes, heart, bones, joints, and nervous system, and may be fatal. Some people develop soft tissue tumors called gummas. Syphilis that affects the brain is known as neurosyphilis, and may be characterized by headaches, seizures, personality changes, or dementia. A pregnant woman can transmit syphilis to her child, leading to stillbirth or to serious physical and mental disabilities in the newborn, a condition known as congenital syphilis.

Syphilis is diagnosed using the rapid plasma reagin (RPR) or Venereal Disease Research Laboratories (VDRL) blood tests, and confirmed with fluorescent treponemal antibody absorption (FTA-ABS) or Treponema pallidum hemagglutination antibody (TPHA) tests; darkfield microscope examination (which looks at an object illuminated from the side against a dark background) may also be used. Early-stage syphilis can be treated with a single injection of benzathine penicillin; more advanced stages may require longer courses of treatment. Ceftriaxone, doxycycline, tetracycline, or erythromycin may be used if a person is allergic to penicillin, although in some cases penicillin desensitization is recommended. Although syphilis antibodies remain in the body for life, a person can be reinfected with syphilis.

Viral STDs

Genital Herpes

Genital herpes is caused by the herpes simplex virus (HSV). Although HSV type 2 is classically associated with genital lesions and HSV type 1 is associated with oral lesions ("cold sores"), either type can affect either area of the body. HSV-2 is very common, with an estimated 45–60 million people infected in the U.S. and 1 million new infections annually; as many as 20% of U.S. adults may be infected with HSV type 2. Herpes is characterized by blisters on the genitals, inside the vagina or rectum, or around the mouth.

Sores typically develop 2–20 days after exposure to the virus, but may develop years later. The blisters often break open, forming painful ulcers. Some people also experience fever and swollen glands. The sores usually dry up, scab over, and heal without scarring after 2–7 weeks. Some people infected with HSV never develop recognizable symptoms. Studies have shown that HSV is present in genital fluids of people with genital herpes, even when they do not have active herpes lesions. Even after genital herpes lesions heal, the virus is not eradicated; instead it takes up residence in nerve endings and may be reactivated periodically.

Recurrent outbreaks are associated with several factors including emotional stress, illness, exposure to ultraviolet light, menstruation, and a weakened immune system. Recurrences may be preceded by prodromal (precursor) symptoms including itching and tingling in the area in which the outbreak will occur, pain in the groin or buttocks, and sometimes malaise. Transmission may occur during an active outbreak, but some people can transmit the virus when they have no symptoms, a phenomenon known as asymptomatic shedding, which may be due to the presence of HSV in genital fluids.

Recurrent outbreaks are typically milder than the initial episode, and outbreak frequency often decreases over time. Herpes can be transmitted from a mother to her newborn--especially if she is experiencing her first episode--leading to premature delivery, miscarriage, eye and nerve damage, mental retardation, and possibly death.

HSV infection is diagnosed with a blood test to detect antibodies. Although there is no cure for herpes, nucleoside analog antiviral drugs--acyclovir (Zovirax), valacyclovir (Valtrex), famciclovir (Famvir), and topical penciclovir (Denavir)--can suppress the virus and reduce the frequency, length, and severity of outbreaks, as well as the risk of transmitting herpes. Immediate treatment of infants born with herpes decreases the chance that they will develop serious illness. At the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) this past September, Spotswood Spruance, PharmD, and colleagues reported on a study of a new vaccine for genital herpes. The Simplirix vaccine, made by SmithKline Beecham, reduced the incidence of HSV type 2 infection by about 75% in HSV-negative women whose partners already were infected with herpes. However, the vaccine had "absolutely no effect" on HSV type 2 incidence in "high-risk" men, according to Spruance.

Human Papillomavirus and Genital Warts

Human papillomavirus (HPV) is a family of over 60 strains of virus that are associated with warts. Various so-called "low-risk" strains are associated with common warts or genital warts (also called condyloma accuminata). "High-risk" strains are associated with cervical, anal, or penile dysplasia (abnormal precancerous cell growth) and cancer. Many people are coinfected with both high-risk and low-risk strains. HPV is one of the most common STDs. It is estimated that 5.5 million new HPV infections occur in the U.S. annually, with a cumulative total of 30–40 million cases. The virus is spread by direct skin-to-skin contact with an infected person, and may occur even if the person is asymptomatic.

Genital warts usually appear a few weeks to several months after exposure. They typically begin as tiny bumps--which are usually not painful or itchy--on the penis, scrotum, vulva, or anus; inside the vagina or rectum; or on the cervix. The warts often occur in clusters and, if untreated, many grow into large fleshy masses; growth is more rapid in pregnant woman and in people with compromised immune systems. However, many people with HPV infection have no visible symptoms.

The presence of HPV can be detected by a blood test. Warts can be detected by visual inspection; application of vinegar may help make small warts more visible. There is no cure for HPV, and the virus remains in the body for life. However, there are a number of treatments for warts and dysplasia. Warts may be removed by freezing with liquid nitrogen (cryosurgery), burning (electrocauterization), or conventional surgery. Topical remedies include podofilox (Condylox), podophyllin (Podofin), trichloroacetic acid, 5-fluorouracil, and imiquimod (Aldara); podofilox, podophyllin, and 5-fluorouracil should not be used in pregnant women. Because many people report that podophyllin treatment is painful, more rapid methods of removing warts are preferred. If warts do not respond to these treatments, a doctor may inject interferon-alpha directly into the wart.

Dysplasia, which can progress to cancer, is quite treatable in early stages. The progressive stages of dysplasia are known by various names including cervical or anal intracellular neoplasia (CIN and AIN, respectively) and squamous intraepithelial lesions (SIL). Pap smears, which involve looking at a sample of cells under a microscope, are used to detect the condition as it develops. Regular cervical Pap smears have significantly reduced the death rate from cervical cancer, and some experts now recommend anal Pap smears for certain populations, including people who engage in receptive anal intercourse. An instrument called a colposcope also may be used to view cervical or anal cell changes. Early-stage dysplasia may be treated by freezing, burning, or cutting away the top layers of tissue, in the hope that normal cells will grow in its place. A promising HPV vaccine is currently under development by Merck Laboratories. (For more information on CIN, see BETA, June 1996; for more information on HPV and AIN, see BETA, September 1997.)

Parasitic STDs

Pubic Lice

Pubic lice, often referred to as "crabs," are caused by tiny insects called Phthirus pubis or Pediculosis pubis. The insects can spread through close skin-to-skin contact, but also via shared towels, clothing, or bedding.

Pubic lice typically live in the pubic hair, but may also take up residence in underarm hair, facial hair, eyebrows, or eyelashes. The primary symptom is itching, which usually begins within five days after exposure; the itching is due to an allergic reaction to the insect bites. Diagnosis is made by detecting the grayish or rust-colored parasites or their white eggs. Pubic lice are treated with over-the-counter topical preparations such as 1% permethrin (Nix) or prescription-strength 5% permethrin (Elimite). The prescription drug lindane (Kwell, Isotox) may also be used, but its use is becoming less common due to widespread resistance.

Other options are the new prescription medication methialine (Ovide) and a single 200 mg/kg dose of oral ivermectin (Stromectol). In addition, clothes and bedding should be washed in hot water and disinfected, and lice eggs can be combed out of the hair with a special, fine-toothed comb. Sometimes a second round of treatment is indicated 7–10 days later if a new set of eggs hatches. Sex partners should be evaluated and, if necessary, treated. Hydrocortisone or other over-the-counter anti-itch creams may be used to relieve symptoms during treatment.

Scabies

Scabies is caused by a mite, Sarcoptes scabiei, that burrows under the skin. The mites are easily transmitted through skin-to-skin contact or by sharing towels, bedding, and clothing. Although scabies can occur on any part of the body, it prefers moist folds, and most often attacks the genital area or the webbing between the fingers and toes. The female mites lay eggs under the skin, usually within ten days of exposure.

The primary symptom, which develops within about a month after exposure, is intense itching due to an allergic reaction to the insects’ bites; the itching is often worse at night. Some people develop an eczema-like rash. Diagnosis is made by detecting the mites, via a microscopic examination of skin scrapings, or their burrows. The burrows often appear as zigzag lines on the skin, and may be made more visible by applying ink. Treatments include lindane or 5% permethrin cream, which is applied over the entire body from the neck down and left on for 8–10 days; a repeat application may be necessary. Lindane is a highly toxic medication; pregnant or lactating women and children under the age of two should not use lindane. Ivermectin may also be used to treat scabies. Clothes, towels, and bedding should be washed in hot water.

Trichomoniasis

Trichomoniasis is caused by a protozoan parasite called Trichomonas vaginalis. There are an estimated five million new cases of trichomoniasis annually in the U.S. The parasite causes inflammation of the vagina and urethra. Symptoms of trichomoniasis usually appear 3–28 days after exposure to the parasite.

The primary symptom in women is a foamy, yellow-green vaginal discharge with a strong "fishy" odor; women may also experience genital irritation or itching, and swelling and redness of the vulva. Although most men with trichomoniasis are asymptomatic, some may experience irritation inside the urethra or under the foreskin, or mild penile discharge. Both women and men may feel a frequent urge to urinate and experience pain or burning during urination. Trichomoniasis in pregnant women can cause premature rupture of placental membranes, leading to pre-term labor; newborns can contract the infection during delivery.

Diagnosis is done with a laboratory test of a sample of discharged fluid; the parasite is harder to detect in men. The disease may be treated with a single oral dose of the antiparasitic drug metronidazole (Flagyl). Once they are cured, people may contract trichomoniasis again.

STDs Transmitted by Other Means

Bacterial Vaginosis

Bacterial vaginosis (BV), previously known as nonspecific vaginitis, is the most common cause of vaginal inflammation in women of childbearing age. BV occurs when the dominant bacterial flora of the vagina--primarily Lactobacillus--is disturbed, allowing the overgrowth of other bacteria such as Gardnerella vaginalis, Bacteroides, Mobiluncus, Mycoplasma hominis, and Ureaplasma urealyticum.

BV is not necessarily transmitted sexually; it is associated with sex with a new partner, douching, use of an intrauterine device for contraception, and changes in vaginal pH. Symptoms of BV include a watery or foamy, grayish or whitish vaginal discharge; abnormal "fishy" odor; pain or itching of the vulva; and burning during urination. Many women with BV are asymptomatic. Pregnant women with BV have higher rates of miscarriages and premature or underweight infants. In some cases, the bacteria that cause BV can make their way to the upper reproductive organs, leading to PID. Diagnosis of BV is done by examining a sample of discharged fluid under a microscope to look for "clue cells." BV may be treated with topical or oral therapies such as metronidazole or clindamycin (Cleocin). BV may recur after initial treatment.

Candidiasis

Candidiasis, commonly known as a "yeast infection," is an overgrowth of the Candida albicans fungus, or occasionally other Candida species. Candida albicans occurs normally in the vagina. Candidiasis may affect the entire body and is usually not transmitted sexually, but Candida overgrowth of the vulva and vagina may be spread through sexual activity. Symptoms of vulvovaginal candidiasis include a thick, white, lumpy discharge with a yeasty odor. Women may also experience pain, itching, redness, and swelling of the vulva, as well as pain during urination or sexual intercourse. Women with compromised immune systems may have longer-lasting and more frequent episodes. Candida may also cause an infection of the glans of the penis (balanitis) in men, although this is uncommon.

Candidiasis is diagnosed using a KOH preparation. Many women harbor Candida in the vagina with no symptoms. Unlike BV, candidiasis usually occurs with a normal vaginal pH. Candidiasis is treated with topical or intravaginal antifungal preparations such as clotrimazole (Mycelex, GyneLotrimin), miconazole (Monistat), terconazole (Terazole), or nystatin (Mycostatin); oral fluconazole (Diflucan), itra-conazole (Sporanox), or ketoconazole (Nizoral) may also be used, especially in treatment-resistant or recurrent cases. Candidiasis is common in pregnant women, who should receive only topical, not systemic, treatment. (For more information on candidiasis, see BETA, September 1995, page 28, and June 1995, p. 10.)

Cytomegalovirus

Cytomegalovirus (CMV), a member of the herpesvirus family, is best known as an opportunistic infection (OI) that affects people with compromised immune systems, for example due to HIV or immunosupressive drugs used with organ transplants. CMV infection is very common in the general population in the U.S., and a majority of adults harbors the virus. It is present in semen, vaginal fluid, saliva, and urine, and is easily transmitted sexually. CMV is also commonly transmitted from a pregnant woman to her child before birth or through breast-feeding. CMV usually does not cause symptoms in people with healthy immune systems, but some people experience a flu-like or mononucleosis-like illness characterized by fever, fatigue, weakness, and swollen glands.

In contrast, immuno-compromised people may develop serious illnesses such as retinitis (an inflammation of the retina of the eye, potentially leading to blindness), colitis (inflammation of the large intestine), polyneuritis (nerve inflammation), or pneumonia. CMV is diagnosed by a blood test or a culture test of body fluids. There is no cure for the disease, and people are thought to carry the virus for life. Disease progression in immuno-compromised persons can be reduced with intravenous antiviral medications such as ganciclovir (Cytovene), foscarnet (Foscavir), or cidofovir (Vistide). HIV-related CMV retinitis may be treated with eye injections or implants. Oral valganciclovir is also effective for HIV-related CMV retinitis. (For more information on CMV, see BETA, December 1994, p. 6.)

Hepatitis

Although not primarily appreciated as STDs, some hepatitis viruses can be transmitted through sexual activity. Hepatitis in general refers to an inflammation of the liver. Hepatitis A, caused by the hepatitis A virus (HAV), is spread through the fecal-oral route. It is most often contracted through contaminated food or water, but may also be transmitted through oral-anal sex (rimming) or activities that spread fecal matter to the mouth via the hands, penis, or sex toys. Hepatitis B and C, caused by the hepatitis B virus (HBV) and hepatitis C virus (HCV), respectively, are most often transmitted through blood (e.g., a needlestick injury, sharing of drug injection equipment), but may be transmitted sexually. Both viruses have been detected in the semen and vaginal fluids of infected persons. Sexual transmission is more common with HBV; the CDC estimates that there are about 77,000 sexually transmitted cases of HBV in the U.S. annually.

According to CDC estimates, up to 20% of HCV infections may be attributable to sexual contact, but most studies show a much lower rate. An analysis of several different studies revealed an average sexual transmission rate of 1.5% among long-term, monogamous heterosexual partners and up to 10% among long-term, monogamous gay male couples.

Symptoms of hepatitis include nausea, vomiting, fatigue, fever, abdominal pain, and loss of appetite; some people develop jaundice (yellowing of the skin and whites of the eyes). Many people infected with hepatitis B or C have no symptoms. Pregnant women can transmit hepatitis B or C to their infants. Hepatitis is diagnosed using a blood test. Hepatitis A usually resolves without treatment and does not become chronic; a person who has had HAV cannot become infected again. Both HBV and HCV may become chronic, potentially leading to liver scarring (cirrhosis), liver cancer, and liver failure. Chronic carriers of HBV or HCV, whether symptomatic and asymptomatic, can transmit the virus.

HBV and HCV are not easily treated, although there are several FDA-approved drugs. The most common treatments for HBV are interferon-alpha and 3TC (Epivir), and the standard treatment for HCV is interferon-alpha plus ribavirin (Rebetron). HAV and HBV can both be prevented with a vaccine, and vaccination is recommended for sexually active people. (For more information on hepatitis in general, see BETA, January 1998; for more information on HCV, see BETA, Year-End 1999.)

Intestinal Parasites and Bacteria

Several intestinal parasites and bacteria can be spread through sexual activity, especially oral-anal sex or other activities that spread fecal matter to the mouth via the hands, penis, or sex toys. However, worldwide these organisms are most commonly contracted through contaminated food or water. Parasitic organisms in this category include Entamoeba histolytica, Giardia lamblia, and species of Cryptosporidium, Microspor-idium, and Isospora. Bacteria that may be transmitted sexually include Salmonella, Shigella, and Escherichia coli. These microbes usually cause gastrointestinal illness (gastroenteritis) characterized by diarrhea, nausea, vomiting, abdominal cramps, fever, and blood in the stools; symptoms typically begin within 36 hours after exposure. Diagnosis is made by examining a fecal sample for specific organisms. Specific parasitic infections are treated with different medications; metronidazole is used for some of the most common organisms. Bacterial infections may be treated with drugs such as ciprofloxacin.

Molluscum Contagiosum

Molluscum contagiosum is a skin infection caused by a virus of the same name. It is transmissible by skin-to-skin contact and by sharing towels, clothing, or razors. The primary symptom is small flesh-colored, gray, or pinkish lesions with a central depression. Lesions may appear anywhere on the body, but are most often seen on the face, torso, thighs, buttocks, groin, or genitals; they may be tender or itchy. They usually appear 2–12 weeks after exposure to the virus and can last two weeks to several years if not removed. Outbreaks may be more extensive and last longer in people with compromised immune systems. Molluscum is diagnosed by the characteristic "umbilicated" appearance of the lesions, or by a microscopic examination of a sample scraped from a lesion. Lesions may be removed surgically or by freezing with liquid nitrogen, and may be treated topically with agents such as podophyllin, cantharidin (Cantharone), phenol, silver nitrate, trichloracetic acid, or iodine.

Sequellae of STDs

Pelvic Inflammatory Disease and Epididymitis

Pelvic inflammatory disease (PID) and epididymitis are not STDs, but rather long-term, serious complications of infection with various sexually transmitted organisms. PID is an infection of the upper female reproductive tract including the uterus, ovaries, and fallopian tubes. It is most often caused by Chlamydia trachomatis or Neisseria gonorrhoeae, but is also associated with Bacteriodes species. Bacteria may more easily enter the uterus and fallopian tubes during menstruation; douching may also help bacteria gain access to the internal reproductive organs, and therefore is not recommended. There are an estimated 1 million new cases of PID annually in the U.S.

PID may be asymptomatic at early stages, or may be characterized by symptoms such as vaginal discharge, prolonged menstrual periods, bleeding between periods, abdominal or lower back pain, fever or chills, nausea, painful sexual intercourse, and tenderness during a pelvic examination. The infection may damage the reproductive organs, potentially leading to life-threatening ectopic or tubal pregnany (in which a fertilized egg develops in a fallopian tube rather than the uterus) or infertility.

PID can be diagnosed by a pelvic examination or laparoscopy, in which a small, lighted instrument is inserted into an incision in the abdomen to view the internal organs. PID is treated with antibiotics to control the causative organism(s). Treatment is more successful the earlier it is begun; often the responsible agent cannot be easily identified, so a combination antibiotic regimen is used. In some cases, surgery may be required to remove scar tissue, abcesses, or heavily damaged organs. An estimated one-third of women who have had PID will develop the condition again, and the risk of infertility is increased with each subsequent episode.

Epididymitis is an infection of the epididymis, the tubes that store and carry sperm. As with PID, the causative organism is most often gonorrhea or chlamydia. Symptoms include pain in the testes, scrotum, or abdomen. Untreated infection can progress to infection of the entire testicle (orchitis). Epididymitis, like PID, is treated with antibiotic regimens. In severe cases, surgical removal of the testicle(s) may be necessary.

STDs and HIV

STDs are associated in several ways with HIV. Because STDs and HIV are spread by similar types of sexual activity, people who engage in behaviors that transmit HIV are also more likely to contract STDs, and vice versa. Persons who contract an STD may also have put themselves at risk for HIV and should be tested. Likewise, a person who contracts HIV should be tested for other STDs.

Epidemiological evidence shows that populations and geographical regions in the U.S. with the highest STD rates also tend to have the highest rates of HIV. According to the CDC, "The geographic distribution of heterosexual HIV transmission closely parallels that of other STDs." In the past decade, high HIV incidence rates have shifted toward women infected through heterosexual activity, young adults, African-Americans, and people living in the southeastern U.S., all populations with disproportionately high rates of STDs. At the Durban AIDS conference, J. Hanson and colleagues presented a study of HIV/STD incidence using a mathematical model based on medical records of 10,879 people attending a New Orleans STD clinic. The results suggested that the presence of an ulcerative or non-ulcerative STD increased the risk of contracting HIV among a predominantly heterosexual population; a recent gonorrhea diagnosis was associated with a greater than two-fold increase in HIV seroconversion in men.

High STD rates are also associated with high HIV rates in some populations of men who have sex with men (MSM), and may act as a predictor of an impending rise in HIV incidence. At the 7th Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco this past winter, L. Torian and colleagues presented study results showing that among MSM in New York City, the presence of syphilis or gonorrhea was a predictor of HIV infection. Because of this close association between HIV and STDs, according to the CDC, "STD surveillance can provide important indications of where HIV infection may spread, and where efforts to promote safer sexual behaviors should be targeted."

Also at the Durban conference, H. Chesson and colleagues from the CDC used a mathematical model to estimate that 5,052 new cases of HIV are attributable to STDs, including chlamydia (3,249 cases), syphilis (1,002 cases), gonorrhea (430 cases), and herpes (371 cases). At the 40th ICAAC held this year in Toronto, N.M. Ferguson and colleagues from Oxford University presented results derived from a mathematical model that suggested that STDs have a greater effect on HIV infectiousness (how likely people are to transmit HIV) than on HIV susceptibility (how likely they are to contract the virus).

Epidemiological Synergy

At the XI International Conference on AIDS held in Vancouver, Canada, in July 1996, Judith Wasserheit, MD, MPH, of the CDC presented a literature review of STDs and HIV transmission. An analysis of multiple studies on four continents showed that persons with both ulcerative and nonulcerative STDs have a 2–5 times greater risk of becoming infected with HIV. The presence of an STD increases both susceptibility to and infectiousness of HIV, a phenomenon Wasserheit referred to as "epidemiological synergy" when she first reported on this connection in 1992. This so-called "STD cofactor effect" for HIV transmission has been demonstrated for syphilis, chancroid, genital herpes, gonorrhea, chlamydia, and trichomoniasis; recent evidence suggests that bacterial vaginosis is also implicated in increased HIV transmission.

Having an STD can make it easier to become infected with HIV due to various biological mechanisms. First, a person who has an STD that causes genital ulcers--namely syphilis, chancroid, or genital herpes, sometimes referred to collectively as genital ulcer disease (GUD)--is more likely to contract HIV from an infected person because the open sores can serve as a portal for HIV to enter the body.

Second, STDs may increase the risk of contracting HIV by affecting the integrity of cells. At the 12th World AIDS Conference, held in Geneva, Switzerland, in June 1998, researchers from the CDC presented evidence that in people with certain STDs, epithelial cells lining the genital and urinary tracts do not function properly, resulting in gaps between the cells that make it easier for HIV to enter. Third, the presence of an STD increases the concentration of dendritic or Langerhans cells and CD4 T-cells (types of white blood cells) in the genital area and genital fluids, since these cells migrate to the site of an infection. Increased numbers of white blood cells present additional targets for HIV infection. This mechanism applies to nonulcerative STDs--such as chlamydia, gonorrhea, and trichomoniasis--as well as ulcerative STDs.

The presence of an STD also makes it more likely that a coinfected person will transmit HIV. First, the virus can be transmitted through open genital lesions, which may come into contact with a partner’s vaginal, anal, or oral mucous membranes during sexual activity. HIV is routinely detected in the fluid exuded from most types of genital ulcers in men and women with HIV; and these ulcers also may bleed. D. Cameron and colleagues reported in a 1989 issue of the Lancet that HIV positive women with STD-associated genital ulcers were more likely to transmit HIV to their male partners than HIV positive women without such ulcers. Second, HIV positive people with inflammatory STDs such as chlamydia or gonorrhea are more likely both to shed HIV in their semen and cervicovaginal fluids, and to have greater amounts of HIV in these fluids, compared to HIV positive people without STDs. In the June 28, 1997 issue of the Lancet, Myron Cohen, MD, and colleagues reported that, on average, semen HIV viral load was eight times higher in HIV positive Malawian men with urethritis compared to men without the condition, despite similar blood viral loads. After STD treatment, the men’s semen HIV viral loads returned to levels comparable to those of men without STDs. M. Laga presented evidence at the 6th CROI, held in Chicago in 1999, that HIV viral loads were also higher in the cervicovaginal fluids of women with an STD. At this year’s CROI, P.F. Barroso, MD, and colleagues from Johns Hopkins University demonstrated that some men whose semen HIV viral load decreased to undetectable levels with antiretroviral therapy experienced an increase in semen viral load after they acquired an STD. Barroso also reported at the 39th ICAAC in 1999 that men with genital warts had a significantly higher HIV viral load in their semen than those without genital warts.

How HIV Impacts Specific STDs

In addition to the epidemiological synergy between STD and HIV transmission, immune damage related to HIV can influence the progression of STDs. Several studies have shown that various STD symptoms may be more severe, last longer, and be harder to treat in people coinfected with HIV. In fact, some sexually transmitted organisms, such as CMV and Candida, may not cause illness at all in persons with intact immune systems, but can cause serious symptoms in persons with HIV/AIDS.

Herpes lesions may be more severe and longer-lasting, and outbreaks may occur more frequently in people with HIV/AIDS. Some people coinfected with HIV and HSV require suppressive oral antiviral therapy to keep outbreaks in check. Herpes is one of the ulcer-producing STDs that can facilitate HIV transmission, since HIV may be shed through the open lesions.

Persons coinfected with HIV and HPV are more likely than HIV negative persons to develop multiple genital warts and warts that endure longer, as well as giant condyloma that can grow rapidly to a large size, potentially obstructing the vagina, anus, or throat and necessitating surgical removal. These more severe warts are less likely to develop in HIV positive people on successful antiretroviral regimens. Even more worrisome, several studies have shown that women with HIV are more likely to develop cervical and anal dysplasia, and sexually active MSM with HIV are more likely to develop anal dysplasia. Most experts recommend more frequent cervical and anal Pap smears for women with HIV, followed by colposcopy if abnormal cells are present; some recommend annual screenings, while others suggest testing every six months.

A recent study published by Joel Palefsky, MD, and colleagues from the University of California at San Francisco (UCSF) and the Harvard School of Public Health predicted that regular anal Pap smears could reduce anal cancer in gay men with HIV. According to Dr. Palefsky, "The hope is that a simple, early screening procedure for HPV-induced anal cancer would lead to a . . . drop in disease and death" similar to that seen in women who receive regular cervical Pap smears. The research appeared in the June 1, 2000 issue of the American Journal of Medicine. Recent studies suggest that HPV-related dysplasia may progress more slowly in HIV positive people treated with effective anti-retroviral regimens.

Writing in the August 1998 issue of HIV Newsline, Jeanne Marrazzo, MD, and Christina Marra, MD, noted that coinfection with HIV could complicate the diagnosis and treatment of syphilis. In some cases, syphilis has been known to progress from primary to tertiary stages in just a few years in people with HIV, compared to decades in HIV negative persons. It is unclear whether HIV infection makes it more likely that a person coinfected with Treponema pallidum will develop neurosyphilis, since studies have yielded conflicting results.

Likewise, experts are divided about whether cerebrospinal fluid examination for neurosyphilis should be routinely done in HIV positive persons with early-stage syphilis. Treatment is also controversial, with one multicenter trial suggesting that treatment for primary and tertiary syphilis was less likely to be successful in people with HIV. The CDC’s 1998 STD treatment guidelines recommend, however, that HIV positive and HIV negative persons with early syphilis should receive the same treatment (single-dose benzathine penicillin); some experts prefer a more aggressive approach (e.g., three weekly injections of benzathine penicillin) for persons with HIV.

Bacterial vaginosis is common in women with HIV. Robert Goldenberg, MD, of the University of Alabama at Birmingham conducted a study showing that coinfected pregnant women were more likely to transmit HIV to their infants, in part due to the increased likelihood of premature rupture of placental membranes and inflammation of the chorionic and amniotic membranes. A study conducted by M. Cohen, MD, presented at the Durban AIDS conference showed that women with HIV were almost twice as likely as women without HIV (78% vs. 39%) to have plasma cell endometritis, an inflammation of the endometrium (lining of the uterus) that is associated with PID.

Many other STDs can be more severe in people with HIV/AIDS. Scabies--usually a fairly benign, if annoying, condition--can develop into Norwegian scabies, characterized by crusted, highly contagious and scaly skin lesions. HIV positive women are more likely than HIV negative women to have vulvovaginal candidiasis; in fact, it is often one of the first manifestations of HIV disease in women. Vaginal candidiasis in women with HIV may be severe and recurrent, and may require systemic suppressive antifungal treatment. Molluscum contagiosum outbreaks can be more widespread in people with HIV/AIDS; some people have reported that molluscum lesions resolve with successful antiretroviral treatment for HIV. Various parasitic infections such as Cryptosporidium, Microsporidium, and Isospora are especially harmful in people with suppressed immune systems, to the extent that they are considered OIs.

In addition, because some anti-HIV medications can cause symptoms that mirror those of intestinal parasites (e.g., diarrhea, abdominal cramps), parasitic infections may go unnoticed and untreated.

Some evidence also suggests that STDs may also affect HIV disease progression. J.N. Nkengasong reported at the Durban AIDS conference that among female sex workers with HIV in Abidjan, Côte d’Ivoire, coinfection with gonorrhea was associated with significantly higher HIV plasma viral loads, while coinfection with chlamydia, syphilis, and trichomoniasis were not. CD4 cell counts were also lower in women with STDs (an average of 488 cells/mm3) compared to women without STDs (an average of 640 cells/mm3).

Do STD Programs Influence HIV Rates?

Because of the associations between HIV and STDs, many experts believe that integrated programs to prevent and manage the diseases together are likely to be more effective than programs that treat HIV and STDs as distinct problems.

STD control measures have been in place for decades. When AIDS was first recognized in the U.S. in the early 1980s, many new prevention programs were put in place, followed in the late 1980s and 1990s by service organizations to provide supportive care and treatment, which were not linked to the public health infrastructure dealing with STDs. There were several reasons for this, including the gay community’s mobilization to create services for community members afflicted by HIV/AIDS. In addition, people with HIV/AIDS and their advocates were reluctant to accept traditional public health measures, such as contact tracing of sexual partners and names-based reporting, that are widely used to control other STDs. Over the past decade, however, studies have provided evidence that integrated STD and HIV control may be more effective, both globally and in the U.S.

Epidemiological research suggests that community-wide interventions to detect and treat STDs may reduce the incidence of HIV in a population. However, results are conflicting, and the magnitude of this effect is unknown. Notably, the two most well-known studies of STD interventions to prevent HIV transmission in Africa offered opposite results.

The first study took place in the rural Mwanza district of Tanzania. This randomized, controlled trial involved 12,000 adults in 12 matched villages. A comprehensive STD control program was instituted in six of the communities, which included improved STD clinic services, training of health-care providers in STD detection and treatment, ensuring availability of effective antibiotic drugs for curable STDs, and an ongoing STD education and outreach effort. The control villages continued their existing HIV prevention and treatment programs. After two years, the communities with the new STD control programs had a 42% lower incidence of heterosexually transmitted HIV than the control villages. The lower incidence was not related to changes in sexual behavior or condom use in the two sets of villages. Interestingly, the villages with the intervention had only slightly lower STD rates. The STD program cost just over $200 U.S. per HIV infection averted. Results of the Mwanza study were published in the August 26, 1995 issue of the Lancet and presented by Heiner Grosskurth and colleagues at the 1996 AIDS conference.

The second study, known as the Rakai STD Control for AIDS Prevention Study, was conducted in the Rakai district of Uganda. In this study, begun in 1994, researchers randomly assigned 56 villages to either an STD intervention or a control arm. The 6,602 HIV negative adults in the experimental arm received antibiotic treatment at home for a variety of STDs every ten months regardless of whether or not they exhibited STD symptoms. Treatment consisted of single oral doses of azithromycin, ciprofloxacin, and metro-nidazole, plus penicillin injections for those with blood tests that indicated syphilis. The 6,124 adults in the control arm did not receive such treatment. Both HIV and STDs were common in both groups, with STD rates ranging from 50% for bacterial vaginosis to 2% for gonorrhea. The Rakai trial did not include an ongoing program of STD education, diagnosis, or treatment. After the second two-month period, there was no difference in HIV incidence rates in the treatment and control arms; the rate of new HIV infections increased slightly for both groups. However, rates of curable STDs were reduced significantly, and maternal and infant health improved in the treatment arm. Results of the Rakai study were presented by Maria Wawer, MD, and colleagues at the 1998 AIDS Conference and published in the December 12, 1999 issue of the Lancet.

A comparison of the results of the two studies suggests that intensive, continuous, and ongoing STD prevention and control programs--which could help control STD treatment failures, recurrences, and reinfections--are likely more effective in reducing HIV than intermittent STD treatment. Also, the Tanzanian communities were at an early stage of the HIV epidemic, with an HIV prevalence rate of about 4%, while the Uganda communities were at a later stage, with an HIV prevalence rate of about 16%, suggesting that STD treatment may have a greater effect in reducing HIV transmission when HIV is less widespread. According to Wawer, "It may be that if you’re exposed to a lot of HIV, and the risk is high enough and frequent enough, sooner or later you’re going to get it, whether you have an STD or not." Also, persons in the Mwanza study were treated when they had STD symptoms, unlike those in the Rakai trial; treatment of symptomatic persons is likely to have a greater influence in reducing HIV transmission. A comparative presentation of the Mwanza and Rakai trials was published in the June 3, 2000 issue of the Lancet.

It is uncertain whether STD detection and treatment programs will have the same success in the U.S. as they had in Tanzania. The impact may be less because U.S. populations have an overall lower prevalence of STDs and less heterosexual transmission of HIV, and because existing STD control programs are more extensive and accessible than they are in resource-poor countries. However, William Kassler, MD, and colleagues from the CDC reviewed several local and national surveys conducted between 1990 and 1997. At the 1998 AIDS conference they reported that STD rates and HIV incidence in some U.S. populations, especially among young women, approach those found in Africa. The researchers concluded that "while the potential impact of [an STD control program] in the U.S. cannot be precisely quantified until implemented, the rates of STDs among certain groups at high risk for HIV suggest that the impact could be significant," and recommended controlled studies to assess the impact of STD interventions on HIV transmission.

Richard Rothenberg, MD, and colleagues from Emory University estimated that identifying and treating persons coinfected with both HIV and another STD could reduce the risk of HIV transmission to an uninfected sexual partner by 27%; their findings were reported in the August 2000 issue of Sexually Transmitted Diseases. The researchers examined 1–2 years’ worth of data on over 4,000 HIV positive persons treated at eight STD clinics in the U.S. during the early and mid-1990s. STD/HIV coinfection rates ranged from 13.9% in Miami to 67.6% in Chicago. The researchers calculated that the risk of HIV transmission from a coinfected person was three times higher than the risk of HIV transmission from an HIV positive person who did not also have another STD. The estimated potential reduction in HIV transmission that could be achieved with STD treatment ranged from 10% at the Los Angeles site to 38% at the Colorado Springs site. The researchers further estimated that if each coinfected person had only one unprotected sexual contact with an HIV negative person, 28 new HIV infections would likely occur from persons with untreated STDs, versus 16 new infections from people whose STDs were treated. According to Rothenberg, "effective treatment of . . . STDs [in coinfected persons] and interventions targeted to their social milieu should be implemented."

STD-HIV Recommendations

Because detecting and treating STDs can be such an effective tool in preventing HIV transmission, the CDC’s Advisory Committee on HIV and STD Prevention (ACHSP) suggests that strong linkages should be developed between STD and HIV programs, especially those that target high-risk groups such as heterosexually active young women. The Center for AIDS Prevention Studies (CAPS) at UCSF suggests that in addition to combining STD and HIV control programs, family planning programs should be integrated as well, since measures such as condom use can effectively address all three issues, and because young people are more likely to know someone who has had an STD or an unintended pregnancy than they are to know someone with HIV.

Because people with STDs are so often asymptomatic, the ACHSP recommends that expanded outreach and screening should be done to reach people who are not likely to make use of STD clinic services. Screening for chlamydia, gonorrhea, and syphilis, in particular, should be offered to all sexually active adolescents and young adults. Presumptive treatment, which is started before lab test results confirm a diagnosis, is appropriate for some populations, both because of the likelihood of transmitting an STD while waiting for test results and the unlikelihood of returning to a facility to receive results and treatment. STD detection and treatment services should be available at low or no cost, and should be provided at convenient locations and times, including evenings and weekends. Such services should be made available at hospital walk-in clinics and emergency rooms, community and migrant-worker health centers, family planning clinics, school-based clinics and other clinics for adolescents, correctional facility clinics, primary care physicians’ offices, and managed care institutions, as well as dedicated STD clinics.

In addition, STD screening and treatment should be a routine part of the care of persons with HIV. A recommended annual STD screening should include urine tests for chlamydia and gonorrhea, an RPR test for syphilis, a stool test for intestinal parasites, a test for hepatitis virus antibodies, and a vaginal and/or anal Pap smear. Sexually active people should be offered the HBV vaccine.

According to the ACHSP, "Early detection and treatment of curable STDs should become a major, explicit component of comprehensive HIV prevention programs at the national, state, and local levels . . . In areas where STDs that facilitate HIV transmission are prevalent, screening and treatment programs should be expanded."

Resources

CDC National STD Hotline: 800-227-8922
www.cdc.gov/nchstp/dstd/dstdp.html

American Social Health Association (ASHA)
www.ashastd.org
ASHA Herpes Hotline: 919-361-8488

NIAID Sexually Transmitted Diseases Fact Sheets
www.niaid.nih.gov/publications/stds.htm

Liz Highleyman is a freelance medical writer.

Selected Sources

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