Sexually transmitted diseases

Sarah Hall, DO, OSUMC, OSU Health Care Center, 2345 SW Blvd., Tulsa, OK 74012.

E-mail address: sarah.e.martin@okstate.edu.

KEYWORDS:

Sexually transmitted diseases;

Blood-borne diseases; Ulcerative lesions; Screening partners; Preventive measures

Sexually transmitted diseases (STDs) comprise a diverse group that includes blood-borne diseases, sexually transmitted infections (STIs), and ulcerative lesions. This area of medicine has been the cornerstone for many abstinence and safe-sex programs, research into new vaccinations, screening of partners, and infection prevention. Even with these great strides, we still see more and more individuals infected. Recently the Centers for Disease Control and Prevention changed their guidelines for screening in pregnant females regarding hepatitis B and recommendations for prophylaxis of neonates born from hepatitis B virus (HBV)–infected mothers. There is updated information on human papil- lomavirus (HPV) vaccination for young boys and research on the new HIV vaccination that is projected to curb those who are being infected with HPV and HIV. In addition to growing trends, current treatment, and prevention on sexually transmitted infections, there are now reports of cephalosporin resistance to gonorrhea. Unfamiliarity with ulcerative lesions is common and their presentation is revisited here and expanded for better understanding. Family medicine needs to focus attention both on how to better educate the patient population when screening those who are unknowingly infected, and how to prevent further spread.

With the ever-increasing trends and statistics, it is perti- nent for all primary care physicians in metropolitan or rural areas to revisit this area of medicine.

1877-573X/$ -see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.osfp.2011.06.003

‌Blood-borne diseases

Blood-borne diseases including hepatitis B virus (HBV), hepatitis C virus (HCV), HIV, and syphilis are still preva- lent in the United States.

‌Hepatitis

‌Background

‌Clinical manifestations

The onset of symptoms for both types of viral hepatitis can range from abrupt to insidious; symptoms include nau- sea, vomiting, diarrhea, constipation, fatigue, anorexia, my- algias, arthralgias, weakness, upper respiratory symptoms, low-grade fever, mild abdominal pain, and weight loss. Jaundice usually sets in after five to 10 days subsequent to other symptoms. Stool will start appearing acholic during this phase. Acute illness with HBV subsides after two to

‌Diagnosis

All pregnant females should be tested for HIV in the first trimester A 13

Second HIV test should be considered in third trimester for pregnant Females, or for those in high-prevalence areas

HIV should be confirmed with repeat HIV enzyme-linked immunoorbent assay and Western blot test to document seroconversion within four to six weeks

Education and counseling prevention should be provided to HIV patients to reduce the risk of transmission

Screening for other STDs (e.g., chlamydia, gonorrhea, syphilis), HBV, HCV, and tuberculosis in patients with acute HIV infection

C 13

C 12

C 12

C 12

Penicillin is effective in the prevention of congenital syphilis A 10

Tinidazole (Tindamax, Mission Pharmacal, San Antonio, TX) is an appropriate treatment B 6

option for metronidazole (Flagyl, Pfizer, Groton, CT)-resistant trichomoniasis

Treatment of trichomoniasis has not been shown to decrease the incidence of preterm birth A 10

Quinolones should not be used in the treatment of N. gonorrhoeae infection C 6

The use of expedited partner treatment decreases the risk of reinfection for patients B 6

treated for N. gonorrhoeae or C. trachomatis infection

Recommendation for treatment is “C” because the outcome is a surrogate marker (sustained virologic response) rather than mortality.

A = consistent, good-quality patient-orientated evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease- orientated evidence, usual practice, expert opinion, or case series.

For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.xml.

can be found in the CDC’s Morbidity and Mortality Weekly Report on immunization strategies to stop the eliminate the spread of HBV.30

‌Treatment

tients stop drinking alcohol and avoid using hepatotoxic drugs if they have known chronic HCV. The rate of hepatocellular carcinoma is increased 20-fold in patients with HCV and cirrhosis. There was a meta-analysis where ultrasound was used to follow the progression to hepatocellular carcinoma in patients with chronic HCV and cirrhosis; sensitivity and specificity were found to be approximately 94%.9

HCV transmission can be prevented through use of con- doms and education of partners regarding the potential transmission through body fluids. Partners and close con- tacts are advised to not share toothbrushes or razors.

‌HIV

‌Background/clinical manifestations

Primary HIV infection or acute retroviral syndrome, also known as acute human immunodeficiency virus infection, occurs just after initial HIV infection before seroconversion. Symptoms of HIV are very difficult to differentiate because they may mimic other viruses, such as influenza. Acute infection may present with fever, rash, malaise, sore throat, fatigue, myalgias/arthralgias, headache, anorexia, pharyngi-

‌Figure 1 HBV antigens and antibodies in the blood.

tis, lymphadenopathy, mucocutaneous ulcerations, diarrhea, or a combination of these symptoms. The initial symptoms manifest one to four weeks after transmission, and symp- toms may last for two to four weeks. Physical examination is nondiagnostic but may show hepatosplenomegaly.

‌Diagnosis

‌Screening

Any patient with acute HIV infection should be screened for tuberculosis and other STIs, including chlamydia, gon- orrhea, syphilis, and HBV/HCV.

‌Treatment/Vaccines

CD4+ T cells to be established early in the acute infection, thus not allowing HIV to be easily eradicated like other viruses. Research has been underway for a vaccine against

HIV.14

‌Prevention

‌Syphilis

‌Background/Clinical manifestations

Treponema pallidum is the spirochete that causes syph- ilis and after onset of infection has an incubation period of 10 to 90 days. Contact with infectious lesions or body fluids hastens spread of the disease. Other modes of infection include through vertical transmission and blood transfusion. Primary disease is denoted by a single, painless, indurated ulcer at the site of inoculation appearing about three weeks after contact and lasting for four to six weeks.2 The location of the ulcer can be found on the glans, corona, or perianal area on men and on the labial or anal area in women. Bilateral, nontender inguinal, or regional lymphadenopathy

‌Table 2 Blood-borne therapies

Disease Treatment Notes

HBV Supportive including bed rest and intravenous fluid therapy with 10% glucose

HCV Gold standard for treatment of chronic HCV is pegylated interferon (i.e., alfa-2a, alfa-2b) and ribavirin (Rebetol)*; length of tx based on genotype of HCV and virologic response to therapy

HIV acute infection is often supportive. For initial therapy two NRTIs along with either NNRTI (e.g., efavirenz) or a PI/r (e.g. lopinavir) are recommended

None

Before beginning therapy a CBC, CMP, UA, TSH, urine Beta HCG, viral load, genotype, HIV, and PT/PTT/INR need to be done as therapy has been associated leukopenia, thrombocytopenia, and autoimmune thyroiditis; Rebatol is renally cleared and therefore a baseline serum BUN/Cr should be done prior to treatment especially in those with renal insufficiency; Thirty percent of patients will experience depression, emotional labiality, or anger with HCV therapy, but rarely is it associated with suicidal ideation or hallucinations

Questions regarding HIV therapy is available on the AIDS info website at http://www.aidsinfo.nih.gov/guidelines/default.aspx

Guidelines are updated frequently

CBC = complete blood count; CMP = complete metabolic profile; UA = urine analysis; TSH = thyroid-stimulating hormone; HCG = human chorionic gonadotropin; PT = prothrombin time; PTT = partial thromboplastin time; INR = International Normalized Ratio; BUN = blood urea nitrogen; Cr = creatinine; NRTI = nucleoside reverse transcriptase inhibitors; NNRTI = nonnucleoside reverse transcriptase inhibitors; PI/r = ritonavir-boosted protease inhibitor.

Information taken from references 9, 10, and 16.

*Patients with chronic HCV and anemia, renal insufficiency, active alcohol use/or substance abuse, autoimmune hepatitis, decompensated cirrhosis, pregnancy, severe cardiopulmonary disease, uncontrolled major depression, or untreated hyperthyroidism are not suitable candidates for treatment.

also is often seen. Ulcers and adenopathy are predominantly painless and heal without treatment, therefore remaining unnoticed.17 This is defined as latent syphilis. The first year of the latent phase is called early latent syphilis. The time after the first year is referred to as late latent syphilis or latent syphilis of unknown length.2

‌Table 3 Patient-applied therapies

Medication Application Notes

Podofilox 0.5% solution/or gel Applied twice daily for 3 days, then off for 4 days; No more than 0.5 mL of solution used per optional repeat of treatment cycle 4 times* week and wart area not >10 cm2

Imiquimod 5% cream Applied three times per week at bedtime for 16 Area washed well 6-10 hours after

weeks; do not apply to the vaginal area† application

*Demonstration of podofilox solution in the office may be helpful.

†This cream should not be applied to the vaginal area because it has been associated with chronic ulceration. Pregnant females are strongly recommended to not use podofilox (Condylox, Watson Pharmaceuticals, Inc., Parsippany, NJ), imiquimod (Aldara, Meda Pharmaceuticals, Somerset, NJ), and podophyllin creams.

Information taken from references 2, 10, and 17.

weeks. This rash is associated with endarteritis and can become necrotic and pustular.2

Table 4 Physician-applied therapies

Medications

Cryotherapy with liquid nitrogen

Electrosurgery Laser Therapy

Applications

Used for multiple treatments from a single-use disposable applicator.

Lesions are 10-20 cm depending on the product and are followed-up in 1-2 weeks to repeat therapy

—

—

Advantages/disadvantages Notes

Unlike liquid nitrogen, the Long shelf life; some warts may probe temperature is not low need 2 or more applications enough to cause deep tissue

injury

—

—

Podophyllin resin 20%-1%

Used once and washed thoroughly 1-4 hours after treatment; may repeat treatment on a weekly basis as needed

Cotton tip applicator at 1-2– week intervals

—

Trichloroacetic acid (TCA)

—

Carbon dioxide laser alternative for surgical excision

In benzoin mixture; no open lesions or wounds caused by toxicity; amount <0.5 mL of podophyllin or an area of <10 cm2 of warts per session

Excess solution should be dabbed off with talcum powder or baking soda

Bichloroacateic acid (BCA) 10%-90%

Cotton tip applicator at 1-2– week intervals

Not used for large or keratinized warts; patients will complain of burning sensation that resolves in 2-5 minutes

Not used for large or keratinized warts; patients will complain of burning sensation that resolves in 2-5 minutes

Large area or large warts can be addressed at one time

Excess solution should be dabbed off with talcum powder or baking soda

Surgical excision

—

Electrocautery or sharply removed with tangential incision; bleeding controlled with electrocautery or silver nitrate sticks; lesions in or around the urethral meatus may suggest urethral or bladder condyloma, warranting cystourethroscopy; lesions on urethra or bladder should be cystoscopically excised

5-fluorouracil cream causes ulceration and acquired adenosis and is therefore no longer recommended. Topical application of Bacille Calmette-Guerin has shown to be promising; however, larger studies are needed to evaluate the safety and efficacy.

Information taken from references 2 and 17.

ble dorsalis, and gummas of skin and skeleton are some of the sequalae associated with tertiary syphilis.2

‌Diagnosis

To follow disease activity, RPR and VDRL should be per- formed in the same laboratory.

‌Screening

‌Treatment

Table 5 HSV treatment

Medication

Acyclovir

Initial

400 mg 3 times daily or 200 mg

5 times daily for 7-10 daily

Suppressive

400 mg twice daily

Episodic

200-800 mg every 6-12 hours for 5 days

Famciclovir

1 g twice daily for 7-10 days

250 mg every 8-12 hours for 125 mg twice daily for 5 days

7-10 days

500 mg or 1 g daily

Valacyclovir

500 mg 1g every 12-24 hours for 3-5 days

Information taken from references 2, 6, 17, and 23.

(IV) of 2.4 million U should be repeated weekly for a total of three doses. Doxycycline/tetracycline are extended for four weeks for patients with tertiary, latent, or late latent syphilis. Patients with neurosyphilis are treated with aque- ous crystalline penicillin G 3 to 4 million U IV every four hours for 10 to 14 days, or penicillin G procaine 2.4 million U i.m. daily plus probenecid 500 mg orally four times daily, each given for 10 to 14 days. Patients with sulfa allergy cannot be given probenecid. Nontreponemal antibody titers at six and 12 months should be followed. A repeat cerebro- spinal fluid examination should be done at three to six months after therapy and every six months afterward until normal results are obtained.2

‌Sexually transmitted infections

‌Trichomoniasis

‌Background/clinical manifestations

The incubation period for Trichomonas vaginalis is any- where from four to 28 days. This flagellated protozoan can live in the vagina, urethra, Bartholin glands, Skene’s glands, and prostate. It cannot inhabit the rectum or mouth. In males, this organism may go unnoticed; however, some men have urethral discharge, dysuria, and urinary urgency. For women with T. vaginalis infection, symptoms include sud- den onset of frothy white or green foul-smelling vaginal discharge, pruritus, erythema, dyspareunia, suprapubic dis- comfort, and urinary urgency.2,10 When infection becomes chronic, erythematous lesions are sometimes noted on the exocervix.17 T. vaginalis has been linked to increased risk of HIV transmission and adverse birth outcomes such as premature labor in pregnant females and low birth weight.2,10,17 On physical examination, frothy dis- charge and the characteristic “strawberry vulva” and/or “strawberry cervix” may be seen.

‌Diagnosis/Screening

‌Treatment

‌Chlamydia

‌Background/Clinical manifestations

‌Diagnosis/Screening

‌Treatment

‌Gonorrhea

‌Background/Clinical manifestations

‌Diagnosis/Screening

‌Treatment

‌Human papillomavirus (HPV)

‌Background/Clinical manifestations

Condylomata acuminata, or genital warts, are caused by HPV and are spread only through skin-to-skin contact. There are more than 100 subtypes, with as many as 30 that are transmitted through the genital-to-genital contact. Risk factors for this include having multiple sexual partners, early age onset of sexual intercourse, and having a sexual partner with HPV. The common types for genital warts are types 6 and 11, which are visible on physical examination. They can appear anywhere on the external genitalia. They can also be found on the cervix, vagina, urethra, anus, and mucous membranes (e.g., conjunctiva, mouth, and nasal passages). They appear as flesh-colored, flat, verrucous, or papillary lesions. People will typically be infected with more than one type. Of the known types that cause cancer (e.g., 16, 18, 31, 33, 35, 39, 45, and 51), types 6 and 11 are

‌Diagnosis

‌Screening

Currently the CDC recommends patients with genital warts be informed that HPV and recurrence is common in sexually active individuals and the incubation period can be long and erratic. Therefore, the length of infection and methods of prevention are not definitively known.2

‌Treatment

‌Prevention

In addition, patients should be told that regular and consistent use of condoms will decrease the chance of exposure to this infection.

‌Vaccines

Currently there are two virus-like vaccines that protect against HPV. The quadrivalent Gardasil (Merck & Co., Whitehouse Station, NJ) protects against HPV types 6, 11,

The CDC’s Advisory Committee on Immunization Prac- tices currently recommends routine vaccination of females aged nine to 26 with three doses of Gardasil at 0, 2, and 6 months for the quadrivalent version before sexual activity or known exposure to HPV. Recently, the ACIP allowed phy- sicians to vaccinate males aged nine to 26 years with Gar- dasil to prevent genital warts.18

‌Ulcerative lesions

There are several STIs characterized by the presence of genital ulcers, most commonly herpes simplex virus (HSV), chancroid, lymphogranuloma venereum, and granuloma in- guinale. Other differential diagnoses to be considered with ulcerative lesions that are non-sexually–transmitted include Behçet’s syndrome, drug reaction, erythema multiforme, Crohn’s disease, lichen planus, amebiasis, trauma, and car- cinoma. High-risk considerations for ulcerative diseases are: homosexuality, sex workers, young patients, pregnant females, women who have had a hysterectomy, and sexual contact with those who are affected.

‌Herpes simplex virus (HSV)

‌Background/Clinical manifestations

HSV is one of the most common viral STIs, with 50 million people currently infected. HSV is incurable. Genital

‌Diagnosis

‌Treatment

‌Prevention

Patients need to refrain from sexual activity while having breakouts or symptoms and need to be counseled that even when they are not having symptoms, it is still possible to transmit infection. Currently, development is underway of a vaccine based on mucosal immunity.17

‌Chancroid

‌Background/Clinical manifestations

‌Diagnosis

‌Treatment

Treatment of choice is azithromycin 1 g or ceftriaxone

they had intercourse either two weeks before or during the eruption of the ulcer. Patients often need relief from painful lymph nodes, and needle aspiration or incision and drainage of the nodes is permitted.

‌Lymphogranuloma venereum

‌Background/Clinical manifestations

‌Diagnosis

NAAT for C. trachomatis swab specimens with specific molecular typing and culture is commonly implemented; however, they are not specific for L. venereum caused by C. trachomatis.6 If a patient has symptoms, then specific typ- ing is required and contact with the state health department is needed.6 Complement fixation or indirect-fluorescence antibody titers can confirm the diagnosis; >64 units is diagnostic of infection with complement fixation.2 Direct immunofluorescence is a test licensed for detection of C. trachomatis from rectal swabs from symptomatic patients; however, this is a technically difficult test and has low sensitivity.25

‌Treatment

‌Granuloma inguinale

‌Background/Clinical manifestations

‌Diagnosis/Screening

‌Treatment

There are different treatments that can be used to treat disease. Doxycycline 100 mg twice daily, azithromycin 1 g once weekly, ciprofloxin 750 mg twice daily, or erythromy- cin 500 mg four times daily are recommended regimens that should be given for three weeks or until lesions have healed.27

‌Screening partners/behavioral counseling for prevention

of only questioning those who are considered more high risk.13

Therefore, physicians across the globe should make it their personal goal to screen, educate, and prevent these STDs, rather than brushing the matter off until the next appointment. STDs may be preventable with time, patience, and compassion toward every patient regardless of gender, race, or sexual preference. Providing information regarding STDs in office waiting areas, restrooms, patients’ rooms, pharmacies, local health departments, and homeless shelters will not only help prevent but will, more importantly, edu- cate patients on how to be smart and stand up for them- selves. In addition, providing information to patients breaks the barriers to screening and treatment.16

‌References

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4. ‌Centers for Disease Control and Prevention: Surveillance for acute viral hepatitis—United States, 2007. Surveillance Summaries, May 22. MMWR Morb Mortality Wkly Rep 58(No. SS-3), 2009

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26. ‌Richen J: Donovanosis (granuloma inguinale). Sexually Transmitted Infections 82:iv21-iv22, 2006

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