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SCREENING, DIAGNOSIS, AND TREATMENT OF SEXUALLY TRANSMITTED DISEASES IN PRIMARY CARE SETTINGS (14HC03)

Bonnie Richards, DO, BSN, Patricia Mason, BS, PHA and Sindy M. Paul, MD, MPH, FACPM

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HUMAN PAPILLOMA VIRUS

Genital warts
Acknowledgement: From http://pearlypenilepapules.com/

Over 100 strains of HPV exist, of which 40 are capable of infecting the genital area. High-risk HPV types 16 and 18 are the cause of cervical cancer, anogenital cancer, penile, vulva, vaginal, as well as oropharyngeal cancers. Persistent high-risk HPV infection is a very strong risk factor for the development of precancerous or cancerous lesions. Low risk HPV infections, usually HPV 6 and 11, can cause genital warts and infection of the respiratory tract.2

Epidemiology

The CDC estimates that approximately 20 million Americans are infected with HPV, and 6 million new infections occur each year.9 Fifty percent of sexually active persons will acquire the infection at some point in their lifetime.9

Symptoms

HPV infection without any symptoms is common and usually has a self-limited course.2 Patients may present with genital warts, which are usually asymptomatic but may be pruritic or painful depending on their size and location. Typically warts appear around the vaginal introitus in women, on the penile shaft in circumcised males, or under the foreskin on uncircumcised males.2 However, genital warts can appear at multiple sites in the anogenital area. Again, cervical infection is usually asymptomatic.

Diagnosis

HPV: HPV tests are available for women aged >30 years undergoing cervical cancer screening. These tests should not be used formen, for women <20 years of age, or as a general test for STDs. These HPV tests detect viral nucleic acid (i.e., DNA or RNA) or capsid protein. Four tests have been approved by the FDA for use in the United States: the HC II High-Risk HPV test (Qiagen),HC II Low-Risk HPV test (Qiagen), Cervista HPV 16/18 test, and Cervista HPV High-Risk test (Hologics).

Genital warts: Diagnosis of genital warts is usually made clinically, but can also be confirmed with biopsy. The use of HPV DNA testing for genital wart diagnosis is not recommended, because test results would not alter clinical management of the condition.

The application of 3–5% acetic acid has been used by some providers to detect HPV-infected genital mucosa. However, acetic acid application is not a specific test for HPV infection. Therefore, the routine use of this procedure for screening to detect mucosal changes attributed to HPV infection is not recommended.

Although the Pap test should not be considered a screening test for STDs, diagnosis of cervical HPV infection is often made via an abnormal Pap test. HPV test are recommended for the triage of women aged ≥21 years who have abnormal Pap test results (ASC-US). 2

Screening

According to the USPSTF, there is insufficient evidence to test for HPV as a primary screen for cervical cancer and it is therefore not a recommendation in non-pregnant or pregnant women.5

Treatment

Treatment can be directed at genital warts or pathologic pre-cancerous lesions. In the absence of lesions, no specific treatment is recommended as infection will likely clear on its own, although they could remain unchanged, or increase in size or number. The main reason for treating genital warts is the amelioration of symptoms (including relieving cosmetic concerns). Available therapies for genital warts likely reduce, but probably do not eradicate, HPV infectivity. No evidence indicates that the presence of genital warts or their treatment is associated with the development of cervical cancer. Treatment can be applied by the provider or the patient.2

Recommended patient applied (to the affected area) treatment for external genital warts:

  • Podofilox 0.5% solution or
  • Imiquimod 5% cream or
  • Sinecatechins 15% ointment

Recommended provider applied treatment for external genital warts:

  • Cryotherapy with liquid nitrogen or cryoprobe in repeated applications every 1 to 2 weeks or
  • Podophyllin resin 10–25% in compound tincture of benzoin or
  • Trichloracetic 80–90% or
  • Surgical removal

Alternative treatment options include intralesional interferon, photodynamic therapy, and topical cidofovir. These treatments may be associated with increased side effects.2

Treatment of Partners

According to the CDC, HPV testing is not necessary in sexual partners of patients with genital warts. Patients should refrain from sexual activity until the warts are gone or removed. However, it should be noted that genital warts can be transmitted even when they are not visible.2

Prevention

HPV is a unique STD in that vaccines exist to prevent acquisition of the disease. The two HPV vaccines available in the United States are Cervarix® (against HPV 16 and 18) and Gardasil® (against HPV 6, 11, 16, and 18). Both of these vaccines provide protection against the HPV types that cause 70% of all cervical cancers.2 The HPV vaccine is recommended for girls 13 to 26 and can be administered to individuals as young as 9 years old. The Gardasil® vaccine can also be used in boys ages 9 to 26 to prevent genital warts. Both vaccines are given at 0, 1–2, and at 6 months. Women who have received the HPV vaccine should continue with cervical cancer screening, as 30% of cervical cancers are caused by HPV other than 16 or 18.2

Special Populations

In pregnant patients, treatment with Imiquimod, Sinecatechins, Podophyllin, and Podofilox should be avoided. Removal of warts can be considered, however resolution may be incomplete until after pregnancy, therefore it may be beneficial to wait until after pregnancy to treat.2 Pregnant women should be counseled about the small risk of development of respiratory Papillomatosis in their children. Cesarean section is only recommended if the pelvic outlet is obstructed due to vaginal warts. It is not clear whether a c-section can prevent neonatal HPV infection, therefore, it is not recommended for prevention of HPV transmission to the newborn.2

HIV patients are more likely to develop genital warts and to have lesions that are resistant to treatment. Treatment options are the same as for HIV-negative patients. Squamous cell carcinomas may occur more frequently in the HIV-positive patient; therefore, the clinician should have a low threshold for biopsy of any lesions.2

Follow Up

Convey the following key counseling messages to all clients diagnosed with HPV infection:

  • Genital HPV infection is very common. Most sexually active adults will get HPV at some point in their lives, though most will never know it because HPV infection usually has no signs or symptoms.

  • In most cases, HPV infection clears spontaneously, without causing any health problems. Nevertheless, some infections do progress to genital warts, precancers, and cancers.

  • Within an ongoing sexual relationship, both partners are usually infected at the time, even though signs of infection might not be apparent.

  • A diagnosis of HPV in one sex partner is not indicative of sexual infidelity in the other partner.

  • Treatments are available for the conditions caused by HPV (e.g., genital warts), but not for the virus itself.

  • HPV does not affect a woman’s fertility or ability to carry a pregnancy to term.

  • Correct and consistent male condom use might lower the chances of giving or getting genital HPV, but such use is not fully protective, because HPV can infect areas that are not covered by a condom.

  • Sexually active persons can lower their chances of getting HPV by limiting their number of partners. However, HPV is common and often goes unrecognized; persons with only one lifetime sex partner can have the infection. For this reason, the only definitive method to avoid giving and getting HPV infection and genital warts is to abstain from sexual activity.

  • Tests for HPV are now available to help providers screen for cervical cancer in certain women. These tests are not useful for screening adolescent females for cervical cancer, nor are they useful for screening for other HPV-related cancers or genital warts in men or women.

  • Vaccination protects against two types of HPV responsible for a majority of cervical cancer.

SYPHILIS

Primary syphilis, penile chancre Acknowledgement: Dr. John Toney, Southeast STD/HIV Prevention Training Center

Primary syphilis, penile chancre underside glans Acknowledgement: Public Health Agency of Canada

Secondary syphilis, palmar rash Acknowledgement: Dr. John Toney, Southeast STD/HIV Prevention Training Center

Syphilis is caused by the spirochete Treponema pallidum and is capable of infecting almost any organ in the body. Syphilis has been referred to as “the great imitator,” as many signs and symptoms are indistinguishable from other diseases.10

Epidemiology

According to the CDC, reported cases of primary and secondary syphilis continue to rise overall and in fact have increased nationally 39%since 2006.1 New Jersey has seen an increase of 41% over the same timeframe.4 On a positive note, as of November 2010, for the first time in five years, the number of cases among women in the U.S. did not increase.1 The largest increase in cases of syphilis has been among men who have sex with men (MSM), which accounted for nearly two-thirds of syphilis cases in 2009.1

Symptoms

Syphilis is unique in that it can have very different clinical presentations depending on the stage of disease.2 In the initial, primary phase, the patient may present with painless ulceration at the site of infection called a chancre.2 The chancre may last 3–6 weeks and will heal without treatment. If untreated, however, progression to secondary syphilis will occur.10

The secondary phase of the disease involves dissemination of the treponeme and manifests with a diffuse non-pruriticmacular rash typically on the palms and soles, lymphadenopathy, fever, neurological infection (cranial nerve abnormalities, meningitis, change in mental status, loss of vibratory sense, as well as auditory or ophthalmic abnormalities).2 Again, signs and symptoms of secondary syphilis will resolve without treatment. If untreated, the disease will progress to tertiary or latent syphilis.10

Tertiary, late stage, syphilis is characterized by gummatous lesions that can affect the heart, eyes, and neurological system. Patients may present with paresthesias, paralysis, visual changes, dementia, among other symptoms.10 Patients with latent disease (i.e., those lacking clinical manifestations) can develop late stage disease as many as 10 to 20 years after initial infection.10

Diagnosis

Early primary syphilis can be diagnosed by using darkfield microscopy of tissue or lesion exudate. Some laboratories may also offer PCR tests to detect T. pallidum. Serological testing for the disease can be divided into two general categories: non treponemal tests (VDRL,RPR) and treponemal tests (FTA-ABS, TP-PA, EIA). As each test has limitations, and the possibility of false positives, more than one type of serological test (non treponemal and treponemal) is needed for diagnosis.2

If neurosyphilis is suspected, CSF can be tested using VDRL. If CSF-VDRL is positive and there is no significant contamination with blood, it is considered diagnostic of neurosyphilis.2

Screening

Screening is recommended in the following high-risk groups:5

  • All pregnant women at the first prenatal visit
  • Commercial sex workers
  • Correctional facility inmates
  • Persons diagnosed with another STD
  • MSM who engage in high-risk behaviors

Treatment

According to CDC, parenteral Penicillin G is the preferred drug for all stages of syphilis. The type of preparation used (either benzathine, aqueous procaine, or aqueous crystalline), the dosage and the length of treatment all depend on the stage of disease at diagnosis.2

Recommended treatment for primary or secondary syphilis in non-pregnant adults:

  • Benzathine penicillin G 2.4million units IM as a single dose

Pregnant women with syphilis in any stage who report penicillin allergy as well as those with a penicillin allergy and questionable follow-up should be desensitized and treated with penicillin.2

Alternative (but less effective) treatments for primary or secondary syphilis in penicillin allergic patients:

  • Doxycycline 100mg po BID x 14 days or
  • Tetracycline 500mg po QID x 14 days or
  • Azithromycin 2 gm po as a single dose (Resistance has been documented; this should be used only when unable to use penicillin or doxycycline and should not be used in MSM)

Treatment for tertiary syphilis is as follows:

  • Benzathine penicillin G 2.4million units IM weekly x 3 weeks.
  • Patients unable to take penicillin should be treated in conjunction with an infectious disease specialist.

Treatment of early latent syphilis (syphilis acquired within the past year) is the same as treatment of primary or secondary disease. Treatment for late latent syphilis (syphilis acquired more than a year ago or of unknown duration) is as follows (if clinical evidence of neurologic involvement is observed, rule out neurosyphilis by cerebrospinal fluid (CSF) examination before treating for latent syphilis):

  • Benazathine penicillin G 2.4million units IM weekly x 3 weeks

Recommended treatment of neurosyphilis:

  • Aqueous crystalline penicillin G 3–4million units IV every 4 hours x 10–14 days.

Alternative (but more painful) treatment for neurosyphilis:

  • Procaine penicillin 2.4million units IM daily x 10–14 days plus probenecid 500mg po QID x 10–14 days.

Treatment of Partners

Transmission is thought to occur only when syphilitic lesions are present. Although such lesions are rare after the first year of infection, sexual exposure to a partner at any stage of the disease should prompt an evaluation and treatment according to the following: 2

  • Persons exposed within 90 days preceding diagnosis of primary, secondary, or early latent syphilis in a sex partner should be treated presumptively.

  • Persons exposed greater than 90 days before diagnosis of primary, secondary, or early latent syphilis should be treated presumptively if serological test results are not available immediately and opportunity for follow up is uncertain.

  • Long term sex partners of patients with latent syphilis should be evaluated clinically and serologically and treated based on findings.2 Non-treponemal serologic tests should be repeated at 6, 12, and 24 months. If infection has failed to clear, and neurosyphilis is not present, the patient should be treated for latent disease.2

Special populations

Alternatives to penicillin do not exist for pregnant patients, as parenteral penicillin G is the only medication with documented efficacy in pregnancy.2 Any pregnant women requiring treatment for syphilis who is allergic to penicillin should be desensitized and treated with penicillin appropriate for their stage of disease.

HIV-infected patients should be treated using the same recommendations as HIV-negative patients. Conduct follow-up serology at 3, 6, 9, 12, and 24 months to monitor for treatment failure. If persistent infection is suspected, treat for latent syphilis.2

Follow Up

Test-of-cure and Re-testing: Conduct clinical and serologic evaluation 6 months and 12 months after treatment; more frequent evaluation might be prudent if follow-up is uncertain. See definition of treatment failure in the CDC Sexually Transmitted Disease Treatment Guidelines, 2010. In the event of treatment failure or re-infection, evaluate for HIV, conduct CSF examination (to test for unrecognized CNS infection) and re-treat with weekly injections of benzathine penicillin G 2.4million units IM for 3 weeks (unless neurosyphilis is present, treat as recommended in the CDC Sexually Transmitted Disease Treatment Guidelines, 2010).2


TRICHOMONAS

Trichomoniasis is caused by the protozoan parasite Trichomonas vaginalis, which can lead to vaginitis in women and nongonococcal urethritis in men.2 Women can acquire the infection from infected men or women. However, men will more commonly acquire the infection from infected women.11

Epidemiology

Trichomonas is not a reportable disease, however it is considered to be the most common curable STD in young sexually active women. An estimated 7.4 million new cases occur annually in women and men.11 The high prevalence of disease in clinical and non-clinical settings should warrant a strong suspicion in those at-risk.12

Symptoms

The majority of infected men do not develop symptoms, however some may present with nongonococcal urethritis. Women may have minimal or no symptoms, but when symptomatic, they complain of foul smelling yellow-green vaginal discharge and vulva irritation.2

Diagnosis

In females, microscopic examination of vaginal discharge has a sensitivity of 60 to 70% for identifying the organism, but requires immediate evaluation of a wet preparation slide. A culture may be done in women with a negative microscopic exam and high suspicion of disease. The FDA has also approved point-of-care testing for trichomonas in women including the OSOM Trichomonas Rapid Test and Affirm VP III. Each of these tests can be performed on vaginal secretions and have a sensitivity of greater than 83%.2

In men, wet preparation and microscopic exam is not a sensitive test and point-of-care tests are not approved for use. Cultures of urethral swab, urine, or semen may be done, however NAAT testing of these specimens is a more sensitive method for diagnosis.2

Screening

The USPSTF does not address screening for trichomonas in their recommendations, however CDC recommends screening for T.vaginalis in women with new or multiple partners, a history of STDs, those who trade sex for drugs or money, and/or those who use injection drugs.2

Treatment

CDC-recommended treatment:

  • Metronidazole 2 gm po as a single dose or
  • Tinidazole 2 gm po as a single dose

Alternative treatment:

  • Metronidazole 500mg po BID x 7 days Metronidazole gel is much less efficacious than oral treatment, therefore use of topical treatment is not recommended.2

Treatment of Partners

Sexual partners should be treated and patients should abstain from sexual intercourse until both they and their partner have completed therapy and are asymptomatic.2

Special populations

Vaginal trichomonas in pregnancy is associated with premature rupture of membranes, preterm delivery, and low birth weight. Treatment with metronidazole has not been shown to decrease perinatal morbidity; however the CDC recommends that all pregnant women be considered for treatment regardless of stage of pregnancy. Treatment may relieve symptoms of vaginal discharge and may prevent infection of the newborn as well as preventing further sexual transmission. Pregnant women can be treated with 2 gm of Metronidazole at any stage, however tinidazole should be avoided.2

T.vaginalis infection in HIV-positive females may enhance the transmission of HIV by increasing shedding of the virus. In sexually active HIV-positive females, annual screening is recommended to prevent complications and possibly decrease HIV transmission.2

Follow Up

Re-testing: Because of the high risk of reinfection, consider rescreening sexually active women for T. vaginalis at 3 months following initial infection. No data support rescreening in men diagnosed with T. vaginalis. While most recurrent T. vaginalis infections are thought to result from having sex with an untreated partner (i.e., reinfection), some recurrent cases can be attributed to diminished susceptibility tometronidazole.

In the event of treatment failure (and reinfection is excluded), consider treating with metronidazole 500 mg orally twice daily for 7 days. For patients failing this regimen, consider treating with tinidazole or metronidazole at 2 g orally for 5 days.

 

 
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