TRIPASS XR تري باس

 164 Lesions are most contagious during the

ulcerative phase. The median duration of viral shedding as defined from onset to the

last positive culture is about 12 days.

142 The mean time from the onset of vesicles to

the appearance of the crust stage (~10.5 days) correlates well with the duration of

viral shedding. However, there is considerable overlap between the duration of viral

shedding and the duration of crusting. Women require a longer healing time than men,

19.5 and 16.5 days, respectively.

142 The mean duration of viral shedding from the

cervix is 11.4 days. Therefore, patients should be advised to refrain from sexual

activity until the lesions have completely healed; however, subclinical viral shedding

may also transmit HSV-2.

A genital herpes infection may be acquired from an individual who has never had

symptomatic genital lesions. States of asymptomatic or subclinical viral shedding

occur in the majority of women with recurrent genital herpes as a result of

reactivation of latent infection. These recurrent infections can have a primary disease

presentation, causing the patient to blame the most proximate sexual partner when in

actuality the exposure could have occurred in the distant past.

165 Serologic and

virologic typing can be used to determine whether this is a true primary infection.

Using sensitive detection techniques, such as PCR, women with recurrent HSV

infections shed virus up to 28% of the time, but the relationship between a PCRpositive HSV test and true communicability has yet to be determined.

166

In addition,

asymptomatic spread can occur from multiple anatomic genital sites and in a bilateral

fashion, even with previous outbreaks of unilateral lesions.

167

Seropositive HSV patients also should be counseled to practice safer sex, using

male or female condoms, at all times, not just during symptomatic episodes.

168

Diagnostic Tests

CASE 72-14, QUESTION 4: Viral culture was negative for B.J., but HSV-2 point-of-care (POC) serology

was positive for both B.J. and his sexual partner. How should these laboratory tests to be interpreted?

The accuracy with which herpes genitalis can be diagnosed without the aid of

laboratory tests generally is difficult to achieve, especially if the infection is not

symptomatic. Thus, because of the potentially severe psychologic and physiologic

ramifications of such a diagnosis, either virologic and/or serologic confirmation of

the diagnosis may be obtained.

The laboratory diagnosis of HSV-1 or HSV-2 infection depends on isolation of

virus using viral culture, while HSV DNA detection by PCR is more expensive than

viral culture and not as widely available or HSV antigen detection using EIA or

DFA. Both PCR and EIA can differentiate HSV-1 from HSV-2. Currently, HSV DNA

PCR is the most sensitive method for detecting mucocutaneous herpes simplex

infection rather than simple viral culture in those with genital ulcers and is the

preferred method for CSF samples.

142 Tests that measure serologic response,

antibody production, are valuable in documenting primary infection, but they are not

very useful in recurrent infections or to determine when the initial infection occurred.

It is possible to differentiate between antibodies to HSV-1 and HSV-2 by means of

type-specific serologic assay. POC devices using HSV-2—specific antibody testing

kits offer ease, reduced time, differentiation between HSV-1 and HSV-2, and high

sensitivities and specificities.

12

,

169

,

170

Viral culture is more likely to yield false-negative results than other testing

methods.

12 A better antigen detection test could have been used, such as an EIA or

DFA. The lack of a positive viral culture does not rule out the diagnosis of a primary

infection in B.J., especially because the antibody test was positive. The fact that

B.J.’s partner’s antibody test was positive without a history of symptomatic disease

suggests a distant infection with asymptomatic shedding.

Treatment

CASE 72-14, QUESTION 5: How should B.J.’s lesions be managed? Because the likelihood of recurrence

of genital herpes is high, what treatment and prevention measures are recommended currently?

A diagnosis of genital herpes is concerning because there is no cure for the

condition. Therapies ranging from antiviral agents and photoinactivation to

investigational vaccines have been tried. Currently, only acyclovir (ACV),

famciclovir (FCV), and valacyclovir (VCV) are useful in the treatment and

prevention of genital herpes.

The ideal anti-HSV agent should (a) prevent infection, (b) shorten the clinical

course, (c) prevent the development of latency, (d) prevent recurrence in patients

with established latency, (e) decrease transmission of disease, and (f) eradicate

established latent infection.

142 To date, no agent has been successful in achieving all

of these goals.

All three agents, ACV, FCV, and VCV, are effective for the short-term treatment of

some HSV infections. ACV, a nucleoside analog, is a substrate for HSV-specific

thymidine kinase. Through a series of phosphorylation steps, ACV is transformed to

ACV-triphosphate, a competitive inhibitor of viral DNA polymerase. ACV has

potent in vitro activity against both HSV-1 and HSV-2 and is far less active against

varicella-zoster and CMV.

171 FCV, a prodrug of penciclovir, has increased oral

bioavailability compared with acyclovir. Once converted in the intestine and liver to

the active form, penciclovir, it is quickly phosphorylated in HSV in a similar manner

as ACV. VCV is the L-valyl ester prodrug of ACV. The oral bioavailability of VCV

is also significantly better than ACV, producing plasma levels of ACV comparable to

those attained with IV administered ACV, often eliminating the need for parenteral

therapy.

172 All three antiviral drugs are equally effective for genital herpes infections.

Intravenous ACV (5 mg/kg/dose every 8 hours) significantly reduced the duration

of viral shedding in primary genital herpes, decreasing the duration of signs and

symptoms of disease by a mean of 5 days, and the time to healing of lesions by a

mean of 6 to 12 days compared with placebo-treated patients.

12

,

173 Similar findings

have been shown in the immunocompromised patient population.

174

IV and oral ACV

or VCV also prevent HSV reactivation in seropositive immunocompromised patients

who are undergoing bone marrow transplantation.

175 For patients with HIV, ACV 400

mg PO 3 times daily, FCV 500 mg twice daily, or VCV 500 mg twice daily for 5 to

10 days have been used for recurrent episodes.

2 Currently, IV therapy is

recommended only for patients with severe genital or disseminated infections who

cannot take oral medication.

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p. 1530

Table 72-8

Antiviral Chemotherapy of Genital HSV-2 Infections

Acyclovir Valacyclovir Famciclovir Duration Comments

First clinical

episode

400 mg PO TID

or

200 mg PO 5 per

day

1 g PO BID 250 mg PO TID 7–10 days May extend

treatment duration if

healing is incomplete

Episodic

recurrent

infection

400 mg PO TID

or

800 mg PO BID

or

800 mg PO TID

× 2 days

1 g QD or

500 mg PO BID

× 3 days

125 mg PO BID

or 1,000 mg PO

BID × 1 day

or 500 mg PO ×

1, then 250 mg

BID × 2 days

5 days Most effective if

initiated within the

first 24 hours of

onset of lesions or

during the prodrome

Daily suppressive

therapy

400 mg PO BID

a 500 mg PO QD

b

or

1 g PO QD

250 mg PO BID Daily Reduces the

frequency of genital

herpes recurrences

by ≥75% among

patients who have

frequent recurrences

(i.e., ≥6 recurrences

per year); use should

be reevaluated at 1

year

Severe

disseminated

5–10 mg/kg IV

q8h

Not indicated Not indicated Variable Hospitalize and treat

until clinical

resolution of

symptoms

Follow-up IV

therapy with PO

ACV to complete 10

days

HIV-infected:

episodic

400 mg PO TID

or 200 mg 5 per

day

1 g PO BID

c 500 mg PO BID 5–10 days Treat until clinical

resolution of lesions

HIV-infected:

suppressive

400–800 mg PO

BID or TID

500 mg PO BID

d 500 mg PO BID

Note: Regimen recommendations derived from 2002 CDC Recommendations.

13

aSafety and efficacy up to 6 years have been documented with the use of acyclovir.

bValacyclovir 500 mg QD seems less effective in patients with >10 episodes per year. Thus, 1 g QD should be

used in these patients.

cDosages up to 8 g/day have been used, but an association with a syndrome resembling either hemolytic uremic

syndrome or thrombotic thrombocytopenic purpura was observed.

dEffective in decreasing both the rate of recurrences and the rate of subclinical shedding among HIV-infected

patients.

Topical therapy with ACV ointment (5% in polyethylene glycol) has minimal

effect on the duration of viral shedding, symptoms, and lesion healing in first-episode

primary genital herpes, and it has no effect on the recurrence rate

175 and is not

recommended for primary genital herpes. Penciclovir 1% cream applied every 2

hours while awake is effective for treatment of herpes simplex labialis,

176 but

insufficient data exist to recommend its use for genital herpes infections.

Oral antivirals speed the healing and resolution of symptoms of first and recurrent

episodes of genital HSV-2 infections.

177 Treatment of primary infection after the first

week of infection does change the natural history of recurrent outbreaks; thus, patients

should be educated about risk of sexual transmission and prompt recognition of signs

and symptoms and the early use of antivirals.

178 The frequency of recurrence

decreases with time in most patients. Recurrent episodes of genital HSV-2 infection

can be treated with any of the three available oral antivirals (Table 72-8). Rather

than having to go into clinic, patients with recurrent infection should have a supply of

their antiviral drug with them to allow early initiation of therapy, which may abort or

reduce symptoms by 1 to 2 days.

179

,

180

Daily suppressive therapy with ACV, FCV, or VCV reduces the frequency of

recurrent episodes up to 70% to 80% among patients with frequent (five to eight

episodes per year) genital herpes.

2

,

181 Recurrent outbreaks diminish with time; thus,

after each year of continuous suppressive therapy, an effort should be made to

discuss discontinuing therapy with the patient. The use of suppressive therapy does

not completely eliminate viral transmission. However, a randomized, controlled

clinical trial of serodiscordant HSV-2—positive couples demonstrated a statistically

significant decrease in the rate of transmission to uninfected partners when infected

partners took 500 mg/day of VCV.

154 This 8-month study was restricted to

heterosexual partners with fewer than 10 recurrences per year. The CDC

recommends various dosing regimens for VCV, but the 500-mg once-daily dose

appears to be less effective than the 1-g once-daily dose in patients with frequent

recurrent episodes (i.e., >10 episodes per year).

2 However, one meta-analysis

showed a consistent prophylactic benefit if VCV was dosed at 250 mg twice daily or

500 mg once daily.

182

Immunocompromised patients may require higher doses or

more frequent intervals for suppression.

183 Most cases of ACV-resistant HSV occurs

in the immunocompromised host; however, the resistance is less than 5%.

184 All

ACV-resistant strains are also resistant to VCV, and most are resistant to FCV as

well. Foscarnet 40 to 80 mg/kg IV every 8 hours or cidofovir 5 mg/kg once weekly

until clinical resolution may be used for severe ACV-resistant genital HSV

infections.

2 Cidofovir 1% gel (not commercially available in the United States but

has been compounded by pharmacists) applied once daily for 5 days may be an

alternative to IV foscarnet, but more studies are needed.

2

,

185

B.J. is not yet a candidate for daily suppressive ACV therapy. A summary of the

indications for ACV, FCV, and VCV is outlined in Table 72-8.

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ADVERSE EFFECTS

CASE 72-14, QUESTION 6: What adverse effects associated with ACV, FCV, or VCV should be

anticipated?

Overall, all forms of ACV, including VCV and FCV, are associated with relatively

few adverse reactions largely because of the drugs’ affinity for viral thymidine

kinase over cellular kinase.

Hematuria and an increase in blood urea nitrogen and serum creatinine may occur,

primarily in patients with underlying renal disease or those receiving concomitant

nephrotoxic agents. However, this complication is almost entirely associated with the

IV route. In addition, severe local reactions are possible with IV administration. In

patients with HIV/AIDS, VCV at a dosage of 8 g/day was associated with a

hemolytic uremic syndrome or thrombotic thrombocytopenic purpura-like syndrome.

However, this complication has not been observed with normal therapeutic doses. As

described previously, when given intravenously in high doses or with significant

dehydration, ACV crystallizes in the renal collecting tubules of animals, leading to

renal insufficiency.

186 ACV should not be rapidly infused or administered at

concentrations greater than 10 mg/mL. Dose adjustment is necessary for all three

antiviral agents in patients with decreased renal function.

Although neurotoxicity is a rare side effect, case reports of coma and delirium

have been reported in patients with renal failure.

187

,

188

Intravenous ACV occasionally has been associated with cutaneous irritation and

phlebitis, reversible leukopenia,

189 and transient elevations of liver transaminases.

Oral ACV and VCV are relatively safe and do not produce any serious side effects at

normal doses. Patients receiving oral ACV, VCV, or FCV may complain of nausea,

dizziness, diarrhea, and headaches.

Patient Education and Counseling

CASE 72-14, QUESTION 7: What are the roles for education and counseling in patients with genital herpes?

Are other forms of local or symptomatic care useful?

Most genital herpes infections are benign, and lesions heal spontaneously unless

the patient is immunocompromised or the lesions have become infected secondarily.

The patient should be instructed to keep the involved areas clean and dry. To prevent

autoinoculation, the patient should be told not to touch the lesions and to wash his

hands immediately afterward if he comes in contact with the lesion. Local anesthetics

provide relief from the pain of genital lesions, but they should be avoided if possible

because they counteract efforts to keep the lesions dry. Local corticosteroid therapy

is contraindicated because it may predispose the patient to secondary infections.

Patient counseling should include the source contact and any future partner. Health

care practitioners should attempt to relieve patients’ feelings of guilt and anxiety;

discussion of long-term consequences should take place after the acute symptoms of

the infection have resolved.

For individuals with frequent recurrences, efforts should be made to identify and

avoid stimulatory factors such as sunlight, trauma, or emotional stress. The

limitations of therapy and the decreased severity and frequency of recurrences with

time should be explained to the patient. The periods of infectivity and the need to

avoid sexual activity even when lesions are not present should be emphasized,

indicating the need for continuous barrier protection. Women with herpes genitalis

should be scheduled for routine Pap smears and should be instructed to discuss their

HSV with their physicians if they become pregnant.

Currently, there is no completely effective way to prevent the transmission of

HSV-2 infection. Barrier forms of contraception, in particular condoms, may reduce

the transmission of HSV, but this may be limited only to male-to-female transmission

owing to the large area that herpes lesions may occupy on the woman.

159 However,

greater use of condoms by men can increase protection and is recommended to

prevent HSV infections.

160 Nonoxynol-9, a spermicide that has in vitro anti-HSV

activity, is ineffective in the prevention of established genital HSV infection and may

actually increase the risk of transmission of HSV by causing genital ulceration.

190

Complications

CASE 72-15

QUESTION 1: M.F. is a 23-year-old, sexually active female student with a history of frequent and severe

recurrences of genital herpes since her initial infection 3 years ago. M.F. has tried numerous therapies, including

suppressive and episodic antivirals. None of these therapies has provided M.F. with any relief of her symptoms,

nor have they decreased the frequency of her recurrences. M.F. has read much in the lay press about herpes

and is concerned about the possible complications of the disease, especially cervical cancer. What are the

potential complications of herpes genitalis?

Previous research suggested that HSV-2 might be an oncogenic agent responsible

for carcinoma of the cervix. However, a large longitudinal nested case-control study

using nearly 20 years of seroepidemiologic and epidemiologic data combined with a

meta-analysis concluded that it is very unlikely that HSV-2 is associated with the

development of invasive cervical carcinoma.

191 Severe complications of herpes

genitalis include central nervous system disease, such as meningitis and encephalitis,

and disseminated disease.

142

PREGNANCY

CASE 72-16

QUESTION 1: A.P., a 26-year-old woman in her 32nd week of gestation, was hospitalized with complaints of

painful genital lesions, headache, fever, increased vaginal discharge, and dysuria of 1 week’s duration. Multiple

ulcerative lesions consistent with genital herpes were present on the cervix, vulva, labia minora, and thighs.

How should A.P. be treated?

Herpes genitalis seropositivity in pregnant women occurs more frequently than in

nonpregnant women, with 20% to 30% of all pregnant women having serologic

evidence of HSV-2 infection.

192 When HSV is acquired by the mother near the time of

delivery, transmission to the neonate can be 30% to 50% but less than 1% in those

who acquired it early in pregnancy or had recurrent infection.

2 Unfortunately, a large

proportion of those infections occurring during pregnancy are limited to the cervix

and are totally asymptomatic, often eluding diagnosis.

Pregnant patients with a history of recurrent genital herpes should be examined

carefully when they present in labor for evidence of active disease. The safety of

systemic ACV and VCV in pregnant women has not been established in controlled

trials, but the CDC cites the lack of documented fetal harm to assert that ACV can be

used safely in all stages of pregnancy.

2 Thus, it is reasonable to recommend ACV to

treat HSV in this patient. Some small studies suggest ACV administered for several

weeks before delivery may decrease recurrent outbreaks and lessen the need for

herpes-related cesarean section,

193 whereas a larger randomized clinical trial did not

show a benefit in reducing the

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p. 1532

need for a cesarean delivery with primary infection.

194

In general, it does seem that

patients with symptomatic genital herpes benefit from cesarean section.

195 The

manufacturer of Zovirax (ACV) maintains an extensive database of fetal

complications related to ACV use. To date, no link between ACV and birth defects

has been established.

196 The decision to treat HSV with ACV during pregnancy

should depend on the clinical severity of infection. Fetal exposure data to FCV or

VCV are limited. If the mother has an active herpes genitalis infection at the time of

delivery (either active genital lesions or HSV-2 cervicitis), the baby should be

delivered by cesarean section within 4 hours after the membranes have ruptured to

prevent exposure of the neonate to the virus.

142 However, if no genital lesions are

present at the time of labor, vaginal delivery may be recommended.

12 There is

evidence that up to 70% of neonatal herpes cases occur in asymptomatic women, and

the use of ACV or VCV after 36 weeks gestation may decrease clinical disease and

viral shedding to the fetus.

197

Neonatal herpes is a devastating systemic infection of the newborn, associated

with high morbidity and mortality, especially when infected with HSV-2 versus

HSV-1.

198 HSV is usually transmitted to the newborn during passage through an

infected birth canal, approximately 300 times greater than when HSV is not

present.

195 The risk of transmission to the newborn is greatest in mothers who acquire

an initial infection late in the third trimester and lower in mothers with recurrent

infection or those who acquire herpes in the first trimester (25%–50% vs. <1% for

preexisting infection).

198

GENITAL WARTS

CASE 72-17

QUESTION 1: S.L., a 19-year-old woman, presents to the women’s health clinic for her annual pelvic

examination. One week later, her Pap smear is read as showing koilocytosis. A colposcopy is subsequently

performed, revealing changes consistent with cervical flat warts. What is the cause of S.L.’s infection? How

should she be managed?

Human papiloma virus (HPV) is the cause of genital warts, or condylomata

acuminata. Types 6 and 11 account for more than 90% of genital warts.

199 Other types

of HPV, including 16 and 18, account for as much as 70% of cervical cancer

worldwide.

200

,

201 They are associated with Pap smear changes, including koilocytosis

and cervical dysplasia. In the United States, the seroprevalence of HPV 6, 11, 16,

and 18 is 32.5% for women and 12.2% among men aged 14 to 59 years.

202

Cervical intraepithelial neoplasia (CIN) is a common cervical cancer grading

system using histologic changes to classify specimens in three categories: CIN-1, -2,

and -3. The higher the number, the greater the chance of progressing to invasive

cervical cancer. Most new cases of HPV infection spontaneously regress but with

progressive histologic changes, the chance of spontaneously regressing diminishes

(CIN1, 60%; CIN2, 30%; CIN3, 10%).

203 Types of HPV are also classified as high

risk, or those likely to cause cancer, and low risk, those less likely to cause cancer.

HPV types 16, 18, 31, 33, 45, 52, and 58 are considered high risk and types 6 and 11

are low risk, the latter mostly resulting in genital warts. In women, visible warts

occur on the labia, introitus, and vagina. Subclinical lesions also commonly occur on

these sites and on the cervix, as in S.L.’s case. They are visible only by colposcopy

after applying acetic acid. Men can sexually transmit HPV infections to women as

well as exhibit genital warts, and anal and penile cancer associated with oncogenic

HPV types, especially type 16.

204 The goal of HPV therapy is the removal of

symptomatic warts. Several therapeutic options are available and include patientadministered treatments to visible warts, such as podofilox 0.5% solution or gel,

imiquimod 3.75% and 5% cream and sinecatechins 15% ointment; provideradministered products include topical treatments (podophyllin 10%–25%,

trichloroacetic acid 80%–90%, and cryotherapy), surgery (laser or scalpel), and

intralesional interferon.

12

In a recent meta-analysis, locally applied interferon

showed a 44% lesion clearance compared with 27.4% for systemic interferon.

205

None of these treatments can eradicate HPV infection or alter the natural history of

HPV. It is important to individualize therapy, considering location and number of

warts, patient preference, cost, and convenience.

Podophyllin, compounded as a 10% to 25% solution in tincture of benzoin, is

applied by the health care provider to visible warts. After application, it is washed

off 3 to 4 hours later and then reapplied once or twice a week until the warts have

disappeared. Podofilox 0.5% solution or gel, the active component of podophyllin

resin, may be applied by the patient with a cotton swab, or podofilox gel with a

finger, to visible genital warts twice a day for 3 days, followed by 4 days of no

therapy. A total of four cycles, 0.5 mL/day, or application of an area larger than 10

cm2 should not be exceeded. Podofilox solution is not suitable for use with perianal

warts; the gel is more practical for this region. Podophyllin is potentially neurotoxic

if absorbed in large amounts. Podofilox has the advantage over podophyllin resin in

that it has a longer shelf life, does not need to be washed off, and has less systemic

toxicity.

206 Therefore, it should be applied in limited doses and should also be

avoided in pregnancy. The rate of wart recurrence after podophyllin therapy is

extremely high, probably 50%. With the high cost of clinic care and the high

recurrence rate, home treatment of HPV with podofilox solution may be more cost

effective and equally efficacious.

207

Imiquimod induces cytokines and activates the cell-mediated immune system. In

initial trials, complete clearance of warts took place in 37% to 50% of

immunocompetent patients, but up to 20% experienced recurrence.

208 The 5% cream

is optimally applied by finger at bedtime 3 times per week and the 3.5% cream once

daily for up to 16 weeks.

209

,

210

It is usually left on for 6 to 10 hours before it is

washed off with soap and water. Imiquimod may take as long as 8 weeks before

warts are cleared. Mild-to-moderate local irritation occurs in more than half of the

patients who use it, especially when used daily instead of 3 times weekly as directed.

The cream may weaken condoms and diaphragms.

Sinecatechins are green-tea extracts that contain active catechins with purported

immunostimulatory, antiprofliferative, and antitumor properties. In the United States,

a 15% topical ointment is available. There are limited data on this product, but

literature suggests it may be more effective than imiquimod or podofilox by clearing

up to 55% of external genital warts.

211

It is applied by finger directly to the wart 3

times a day up to 16 weeks with the most common side effects being local erythema,

pruritus, burning, and pain.

12

Cryotherapy by application of liquid nitrogen can be more effective than

podophyllin, but it requires special equipment and highly trained personnel. Pain and

skin blistering after treatment is common. Cryotherapy is associated with minimal

systemic toxicity and is useful against oral, anal, urethral, and vaginal warts.

Trichloroacetic acid (80%–90%) is used topically in the treatment of some genital

warts, but its efficacy is uncertain. To date interferons are not recommended because

of expense and toxicity. Cases refractory to topical drug therapy should be

considered for surgical treatment.

Prevention

In 2006, the first vaccine to prevent HPV types 6, 11, 16, and 18 was approved in the

United States. This quadrivalent vaccine was

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p. 1533

tested in women from 15 to 26 years of age and demonstrated 98% to 100%

protection against HPV types contained in the vaccine.

212

,

213

In males, the

quadrivalent vaccine efficacy was 62.1% to 89.4% against genital warts, depending

upon previous HPV exposure, leading to its approval for men and boys 9 to 26 years

old.

214 Using bridging data, it is estimated that 99% to 100% of 9- to 15-year olds

will seroconvert. In 2014, a 9-valent HPV vaccine was approved to replace the

quadrivalent vaccine. The extra 5 types (31, 33, 45, 52, and 58) add 15% more

cervical cancer coverage protection to the 66% covered by types 16 and 18 in the

quadrivalent.

215 This three-dose series can be given as early as 9 years of age, but it

is CDC recommended at 11 to 12 years as part of a routine adolescent health care

visit and ideally before commencement of sexual activity. Because there are more

than 30 types of HPV associated with anogenital disease, a previous HPV infection is

not a contraindication to vaccination. It is also important to note that receipt of the

HPV vaccine does not change the recommendation for Pap smears. Lastly, it should

not be considered a therapeutic vaccine as it has no impact on active HPV infection.

VACCINES

Prevention and control of STDs have largely revolved around education and

antimicrobials. Immunization, however, holds the promise of protecting large

numbers of people before they are at risk for STDs as well as targeting those who

already have the infection. Hepatitis B is an example of an STD with a highly

effective vaccine that is now mandatory for school-aged children. The nine-valent

HPV vaccine is gaining momentum and a bivalent (HPV 16 and 18) is also approved

by the FDA, but the latter is not indicated for prevention of genital warts. Herpes

simplex vaccines have been extensively studied, but no candidate vaccine has been

submitted for approval.

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT11e. Below are the key references and websites for this

chapter, with the corresponding reference number in this chapter found in parentheses

after the reference.

Key References

CDC. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(3):1–138.

http://www.cdc.gov/std/tg2015/tg-2015-print.pdf. (2)

CDC. Sexually Transmitted Disease Surveillance 2007 Supplement, Gonococcal Isolate Surveillance Project

(GISP) Annual Report 2007. Atlanta, GA: U.S. Department of Health and Human Services, Centers for

Disease Control and Prevention, March 2009; 2009. (23).

Key Websites

Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2014. Atlanta: U.S.

Department of Health and Human Services; 2015; http://www.cdc.gov/std/stats. Accessed May 2, 2015.

US Department of Health and Human Services. Healthy People 2020 topics and objectives: sexually transmitted

diseases. 2011; http://www.healthypeople.gov/2020/topics-objectives/topic/sexually-transmitteddiseases/objectives. Accessed: May 2, 2015.

COMPLETE REFERENCES CHAPTER 72 SEXUALLY

TRANSMITTED DISEASES

Institute of Medicine: Committee on Prevention and Control of Sexually Transmitted Diseases. Washington, D.C.:

National Academy Press; 1997.

Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep.

2015;64(Rr-03):1–137.

CDC. Sexually Transmitted Disease Surveillance, 2009. Atlanta, GA: U.S. Department of Health and Human

Services; 2010. http://www.cdc.gov/std/stats09/surv2009-complete.pdf. Accessed June 15, 2017.

CDC. Sexually Transmitted Disease Surveillance 2013. Atlanta, GA: U.S. Department of Health and Human

Services; 2014. http://www.cdc.gov/std/stats13/surv2013-print.pdf. Accessed June 15, 2017.

U.S. Department of Health and Human Services. Healthy People 2020 topics and objectives:sexually transmitted

diseases; 2011. https://www.healthypeople.gov/2020/topics-objectives/topic/sexually-transmitteddiseases/objectives. Accessed June 15, 2017.

Nelson HD et al. Screening for Gonorrhea and Chlamydia: Systematic Review to Update the U.S. Preventive

Services Task Force Recommendations. Rockville, MD: U.S. Department of Health and Human Services;

2 0 1 4 . http://www.uspreventiveservicestaskforce.org/Home/GetFile/1/1729/gonochlames115/pdf.

Accessed June 15, 2017.

Holmes KK et al. An estimate of the risk of men acquiring gonorrhea by sexual contact with infected females. Am

J Epidemiol. 1970;91:170.

Hook EW, Hansfield H. Gonococcal infections in the adult. In: Holmes KK, ed. Sexually Transmitted Diseases

(electronic version). New York, NY: McGraw-Hill Health Professions Division; 2008.

Turner CF et al. Untreated gonococcal and chlamydial infection in a probability sample of adults. [Comment].

JAMA. 2002;287:726.

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