DISEASE-SPECIFIC DIAGNOSIS, TREATMENT, AND PREVENTION

Most STIs are a threat to both the health of the patient and the health of the community, and treatment is always recommended. STIs present with a variety of syndromes, but their treatment depends on the specific agent causing the problems.

The following are the current recommended treatments for chlamydia, gonorrhea, syphilis, and HPV, the STIs recognized by the National Strategic Plan as reaching epidemic proportions. The drugs and administration regimens offered here are examples of current recommendations based on CDC guidelines, but actual treatments must be tailored to the specific patient.

(For a link to the most current CDC treatment recommendations, see “Resources” at the end of this course.)

Chlamydial Infections

Of the reportable diseases, chlamydial infections were the most common STDs/STIs in the United States in 2019. Chlamydial infections were more prevalent among young women, with 3,728.1 cases per 100,000, an increase of 10% from 2015. The rates among males increased 32.1% from 2015 to 2019, possibly a result of increased availability of urine testing and extragenital screening and increased transmission in males. Both genders show a decrease in the occurrence of chlamydia as age increases. However, many cases go undiagnosed because most people with chlamydia are asymptomatic and do not seek testing. Chlamydia can be prevented by using male latex condoms, abstinence, and monogamy (Workowski et al., 2021; CDC, 2021e).

CLINICAL MANIFESTATIONS

Chlamydial infections produce genital or lower urinary tract infections. After a person acquires a chlamydial infection, there is an incubation period of several weeks before the organism produces symptoms. But chlamydial infections are frequently asymptomatic; only 10% of men and 5%–30% of women with laboratory-confirmed chlamydial infection develop symptoms, potentially causing reinfection of sexual partners (CDC, 2021e).

In men, symptomatic chlamydial infections show up as urethritis or epididymitis, with pain and swelling around a testicle. Chlamydial urethritis produces a mucoid, mucopurulent, or purulent discharge; inflammation; pain on urination; and urethral itching.

In women, symptomatic chlamydial infections show up most often as cervicitis. Chlamydial cervicitis produces a mucopurulent or purulent discharge in the endocervical canal; pain on urination or during intercourse; and vaginal bleeding after intercourse or between periods. Alternately, chlamydial cervicitis sometimes gives no other findings than a friable cervix on speculum examination.

Untreated, chlamydial cervicitis can spread and cause PID, which can then lead to infertility or ectopic pregnancies; and women may eventually develop lower abdominal pain, lower back pain, nausea and vomiting, fever, painful sex, and breakthrough bleeding during the menstrual cycle. During vaginal births, pregnant women can pass chlamydial infections to their newborns. The resulting infection can cause pneumonia and conjunctivitis in the infant (CDC, 2021e).

SCREENING AND DIAGNOSIS OF CHLAMYDIA

The CDC recommends annual chlamydia screening for all sexually active females younger than 25 and for women 25 years and older with risk factors such as a new sex partner or multiple partners. Pregnant women should be screened during their first prenatal care visit (CDC, 2021f). For women, screening for asymptomatic cases is important because routine screening has been shown to reduce the number of cases of PID.

To make widespread screening practical, urine specimens and self-obtained vaginal swabs can be used because they provide effective samples for chlamydia screening tests, although examinations by a licensed provider are optimal. Urine samples are the test of choice for diagnosing chlamydia in men.

Diagnostic tests include urine sample, nucleic acid amplification, culture, and serology. Nucleic acid amplification tests (NAATs) are the most sensitive and can be performed on vaginal or urine specimens (CDC, 2021e).

Women diagnosed with chlamydial infection should be retested approximately three months after treatment (CDC, 2021e). Cultures can be used to diagnose rectal and pharyngeal chlamydia. Chlamydia cultures are also often combined with Pap smears.

TREATMENT OF CHLAMYDIAL INFECTIONS

Oral antibiotics are the standard treatment for chlamydial infections, which can be easily cured (CDC, 2021e). Patients with chlamydial infections should not have sexual intercourse until a week after the beginning of their treatment regimen. Although guidelines exist for the treatment of chlamydia, the healthcare provider must individualize the treatment regimen to meet the specific needs of each individual.

Gonorrhea

Gonorrhea is an infection of the mucous membranes caused by the diplococcus N. gonorrhoeae. It can be transmitted through sexual contact with the penis, vagina, mouth, or anus. It is about one third as common as chlamydial infections, although the two infections frequently coexist in an infected person. Untreated, gonorrhea also increases a person’s risk of acquiring or transmitting HIV. In 2019, approximately 616,392 new cases of gonorrhea were reported in the United States, and it is the second most common notifiable condition. Adolescents and young adults ages 15–24 years are at the highest risk for infection (CDC, 2021h, 2021s).

CLINICAL MANIFESTATIONS

In men, N. gonorrhoeae causes gonorrheal urethritis, producing symptoms such as pain or discomfort on urination and a purulent urethral discharge (CDC, 2021h). Untreated gonorrheal urethritis can develop into epididymitis (Workowski et al., 2021).

In women, N. gonorrhoeae that have invaded the urethral opening produce gonorrheal urethritis, and N. gonorrhoeae that have invaded the vagina produce gonorrheal cervicitis. Most women with urethral or cervical gonorrhea have mild or no symptoms and may infect sexual partners unwittingly (CDC, 2021t). When symptoms do occur, they can include purulent and sometimes odorous vaginal discharge, vaginal bleeding after intercourse, and pain or discomfort on urination. Gonorrhea can also infect the Bartholin’s glands. Untreated gonorrheal cervicitis sometimes ascends into the uterus and leads to PID, which typically presents with lower abdominal pain. On speculum examination, gonorrheal cervicitis appears as a swollen, friable cervix with a mucopurulent exudate.

Untreated, patients with a gonorrheal infection develop gonorrheal bacteremia with fever and, occasionally, septic arthritis. Gonorrheal bacteremia is also known as disseminated gonococcal infection (DGI). DGI is usually characterized by arthritis, tenosynovitis, and dermatitis and can be life threatening (CDC, 2021h). The untreated disease can also cause scarring of the Fallopian tubes, leading to infertility or tubal pregnancies.

It is also common for patients with gonorrhea to have trichomoniasis. In both males and females, oral sex can lead to gonococcal pharyngitis and anal sex to gonococcal proctitis. In the newborn, it manifests as a conjunctivitis that can cause blindness.

SCREENING AND DIAGNOSIS OF GONORRHEA

Gonorrhea infections are difficult to distinguish clinically, and lab tests are needed to make a definitive diagnosis.

It is recommended that two subpopulations have regular gonorrheal screenings and be counseled about the importance of using condoms:

• Sexually active women younger than 25 years of age
• Sexually active women age 25 and older who have a new sex partner, multiple partners, a partner who has other partners, or a sex partner who is a sex worker or who has an STI
• All pregnant women younger than 25 years of age
• Pregnant women 25 years of age and older who have a new sex partner, multiple partners, a partner who has other partners, or a sex partner who is a sex worker or who has an STI (CDC, 2021i)
• Men who have sex with men, who should receive screening for rectal, urethral, and pharyngeal gonorrhea
  (CDC, 2021i; CDC, 2021u)

People younger than 25 years, including sexually active adolescents, are at risk for gonorrhea infection, but there are no recommendations for screening due to insufficient evidence of its effectiveness in that age group.

Light microscopic examination of a sample of urethral discharge can diagnose gonorrhea in men. In male gonorrheal urethritis, stained microscope slides will show Gram-negative diplococci. For women, a more sensitive and specific test is needed, and NAATs of urine or of a swab of the affected area are the preferred test techniques (CDC, 2021h). Urine samples can be used to test for urethritis in all genders.

Vaginal swab specimens are used to test for cervicitis. Gonorrheal cervicitis produces sufficient discharge that swabs need not be taken by speculum examination. Instead, they can be collected blindly by the patient.

For oral or anal gonorrhea, pharyngeal or rectal swabs are taken and sent to the lab for culturing.

TREATMENT OF GONORRHEA

As with many STIs, the highest rates of successful treatments come when antimicrobial medicines can be taken in single doses administered at the time of diagnosis. Antimicrobial resistance is a growing problem in the treatment of gonorrhea, making eradication of the infection challenging in some individuals (CDC, 2021h). Although guidelines exist for the treatment of gonorrhea, the healthcare provider must individualize the treatment regimen to meet the specific needs of each individual.

Patients with gonorrhea often have other STDs/STIs and are therefore tested for HIV, chlamydia, trichomoniasis, and syphilis. They are also offered hepatitis B vaccination if they have not already been vaccinated.

Patients with uncomplicated urogenital or rectal gonorrhea who receive standard treatment recommendations do not require retesting for infection. Patients with pharyngeal infection are retested in 7–14 days using NAAT or cultures. However, if NAAT testing is positive, a culture should be obtained for antimicrobial susceptibility before receiving retreatment (CDC, 2021j).

Although treatment for gonorrhea is usually successful, patients with gonorrhea may become reinfected. Therefore, as for people with chlamydial infections, patients treated for gonorrhea are advised to return in three months for rescreening.

Syphilis

Syphilis is caused by the bacterium T. pallidum. In the United States, 133,945 new cases of syphilis were reported in 2020, with men who have sex with men accounting for 43% of all primary and secondary symphilis cases. Case rates are also increasing among heterosexual men and women in recent years (CDC, 2021k, 2021s).

Syphilis is transmitted by sexual contact. Pregnant women with syphilis can also transmit the disease to their newborn baby at the time of birth. The infant can then develop congenital syphilis, which when untreated can delay development, cause seizures, or even be fatal. Congenital syphilis is now referred to as a mother-to-child transmission and is projected to be eliminated from countries with limited resources by rapid method testing and a single injection of penicillin given antepartum (Fan et al., 2019).

CLINICAL MANIFESTATIONS

A syphilis infection begins locally and slowly spreads systemically. Over time, untreated syphilis will go through stages with different signs and symptoms. It can be fatal if untreated because of potential damage to the brain, heart, or nervous system. A person may come to a clinician initially with primary syphilis (i.e., a local genital infection) or a few months later with secondary syphilis (i.e., a systemic infection). The stages of syphilis infection are as follows:

• Primary syphilis. The hallmark of primary syphilis, a local infection, is the appearance of an ulcer called a chancre. Typically, there is only one chancre, located at the site of infection on the penis, vulva, cervix, perianal region, or oral mucosa. The chancre appears a few weeks after T. pallidum bacteria have invaded the skin. The incubation period is approximately 3 weeks. A syphilis chancre typically has firm, raised edges and a smooth internal base and is painless. Local lymph nodes may be enlarged. If untreated, chancres heal spontaneously in 3–6 weeks, leaving faint scars. Even if the chancre has disappeared, the infected person is very contagious during this phase of the disease (CDC, 2021k).
• Secondary syphilis. When primary syphilis is not treated, the chancre disappears for a few weeks and then reappears as secondary syphilis. Secondary syphilis is a systemic infection with flu-like symptoms (low-grade fever, headache, malaise, generalized lymphadenopathy) and a widespread, symmetrical, non-itchy maculopapular rash, first on the trunk and arms and later the palms and soles. The genital area may also have wart-like papules. During secondary syphilis, a person can develop syphilitic hepatitis or syphilitic glomerulonephritis.
• Latent syphilis. When secondary syphilis is untreated, the symptoms usually fade and the disease becomes quiescent, sometimes for years. This asymptomatic interim stage is called latent syphilis.
• Tertiary (late-stage) syphilis. Although rare, untreated syphilis may reemerge and cause symptomatic damage to a variety of organs. This can occur 10–30 years after the initial infection (CDC, 2021k). This is the final form of the disease, and it produces granulomatous or necrotic lesions that can involve the skin, eyes, central nervous system, heart, aorta, or bones. Today, tertiary syphilis is rare except in patients with a concurrent HIV infection.

SCREENING AND DIAGNOSIS OF SYPHILIS

Routine screening for syphilis is recommended for:

• Patients with any newly diagnosed STD/STI
• Patients at high risk for STDs/STIs
• All pregnant women

The laboratory tests to screen for syphilis include Venereal Disease Research Laboratory (VDRL), rapid plasma reagin (RPR), fluorescent treponemal antibody absorbed (FTA-ABS), and T. pallidum particle agglutination (TPPA). Diagnoses are more likely to be made using blood tests (CDC, 2017l).

The RPR and VDRL are called nontreponemal serologic tests because they are not specific for syphilis. False-positive nontreponemal serologic tests occur in patients with autoimmune disorders such as systemic lupus erythematosus and in a few other special populations. It usually takes at least a week after a patient acquires syphilis for these antibody tests to become positive.

People who have syphilis are more likely to have acquired other STIs. Therefore, patients with syphilis should also be tested for HIV, hepatitis B and C, chlamydia, and gonorrhea.

TREATMENT OF SYPHILIS

Intramuscular benzathine penicillin G is the treatment of choice for syphilis. In the first days after syphilis treatments, some people get a Jarisch-Herxheimer reaction (i.e., fever, myalgia, tachycardia, headaches, and hypotension), informally called Herx, which should not be mistaken for an allergic reaction. Reacting patients are treated with bed rest and nonsteroidal anti-inflammatory agents. Although guidelines exist for the treatment of syphilis, the healthcare provider must individualize the treatment regimen to meet the specific needs of each individual.

After treatment, patients should be retested at 6, 12, and 24 months for the presence of nontreponemal antibodies. Within a year, the patient’s nontreponemal antibody titers should have decreased at least fourfold. On the other hand, tests for treponemal antibodies will remain positive even after adequate therapy.

For pregnant women with syphilis treated at 24 weeks or earlier, titers should be tested after 8 weeks of treatment and again at delivery. Pregnant women who are treated after 24 weeks of gestation should have titers tested again at delivery (Workowski et al., 2021).

Genital HPV Infections

HPV infection, caused by small DNA viruses, is the most common STI in the United States. HPV is so common and contagious that almost all sexually active adults will have had at least one genital HPV infection during their lives if they are not vaccinated, and it is estimated that 1 in 100 of every sexually active person has genital warts caused by HPV at any given time. About 14 million people become newly infected each year (CDC, 2020c). About half of the new cases occur in people ages of 15–24. Women are more susceptible to acquiring genital HPV infections than are men. As with other STIs, HPV infections are most common in people with more than one sexual partner (CDC, 2021m; Workowski et al., 2021).

Hundreds of HPV types have been characterized, and approximately 40 of these can infect humans. Benign HPV lesions such as genital warts are caused by low-risk types of HPVs (e.g., HPV types 6 and 11). Rarer, malignant HPV lesions such as cervical cancer and cancers of the anus, penis, vagina, or vulva can be caused or facilitated by high-risk types of HPV (e.g., HPV types 16 and 18).

HPV infections can be sexually transmitted even when an infected person has no visible symptoms, and a condom is used. The common types of genital HPV infections can cause anogenital warts, called condyloma acuminata. HPV types 16 and 18 appear to cause the majority of cervical, vulvar, or penile cancer. HPV infections often disappear spontaneously or may need to be excised (CDC, 2021m; Workowski et al., 2021).

CLINICAL MANIFESTATIONS

Many HPV infections are asymptomatic, but some types of HPV infections cause common skin warts and plantar warts, while other types of HPV infections may cause genital warts and cancer of the vulva, vagina, penis, anus, or back of throat (Mayo Clinic, 2021b; CDC, 2021m).

Genital warts can also develop beyond the genitals. Perianal genital warts can be acquired by skin-to-skin contact, but intra-anal genital warts are transmitted through anal intercourse. Very rarely, newborns can be infected by HPV during the birth process (Syrjänen et al., 2021).

Most HPV infections are short-lived and spontaneously disappear in less than a year without causing clinical problems. However, HPV can cause cancer of the cervix as well as the vulva, vagina, penis, anus, and oropharynx. It can take years to decades for cancer to develop after contracting HPV (CDC, 2021m).

The aberrant cell growth caused by high-risk HPVs leads to squamous cell dysplasias (e.g., cervical dysplasia) and eventually to neoplasms, such as cervical intraepithelial neoplasias, squamous cell cancers, anal squamous cell cancers, or adenocarcinomas. HPV dysplasias in the cervix can usually be detected by Pap tests (NCI, 2021).

Genital warts vary widely in size. They can be as tiny as a pinhead or as large as a small cauliflower (1 cm to 2 cm in diameter), and they can occur singly or in clusters. The small warts tend to be on stalks. Genital warts are typically found on moist surfaces such as the labia, vagina, cervix, urethra, bladder, perianal skin, or anus. In women, the walls of the vagina and the surface of the cervix can also have genital warts (which are often flat patches). When external warts are present, women should have a speculum exam to search for internal warts.

In all genders, genital warts can grow along the internal walls of the urethra or bladder. Large or extensive warts around the urethral meatus indicate that the internal urinary tract should also be examined for warts.

SCREENING AND DIAGNOSIS OF GENITAL HPV INFECTIONS

A variety of organizations suggest that all women ages 21–29 years should have a cytology (Pap) test to screen for cervical cancer every three years. For women ages 30–65 years, a cytology test should be performed every three years, an HPV test every five years, or a cytology and an HPV test (co-testing) every five years. Cervical screening recommendations are the same for women who have received the HPV vaccine (CDC, 2021n).

HPV cannot be cultured. On the other hand, DNA from HPV viruses can be tested to determine whether the virus is one of the high-risk types. DNA testing and type classing are used to make judgments about dysplasias with unclear cytologic test results, and DNA tests are also a common adjunct to Pap testing of women older than 30 years of age. Tissue testing after biopsy provides a definitive diagnosis, as do PCR assays (Harding et al., 2020).

Genital warts, like cutaneous warts, can usually be diagnosed by their appearance, symptoms, and history. Genital warts caused by low-risk HPVs are soft, raised, skin-colored, and nontender. Most genital warts are asymptomatic, although sometimes they cause itching or burning (CDC, 2021m).

TREATMENT OF GENITAL HPV INFECTIONS

HPV infection itself cannot be treated, but lesions caused by the virus are treated by removal, which reduces infectivity but does not remove the presence of the virus.

About 25% of all genital warts will disappear on their own; nonetheless, most clinicians and patients elect to remove the warts. After treatment, the virus is still in the surrounding epithelium, and approximately one third of patients will have a recurrence of the warts. In addition, HPV infections are commonly reacquired from the patient’s sexual partner(s).

For squamous cell dysplasias, treatment is usually excision. Dysplasias are referred to a specialist for medical management.