976 (e.g.

(e.g., spinal cord–injured persons) to prevent both infectious and in chronic interstitial nephritis; the primary etiologic factors in this
anatomic complications. condition are analgesic abuse, obstruction, reflux, and toxin expo-
sure. In the presence of underlying renal abnormalities (particularly
CANDIDURIA obstructing stones), infection as a secondary factor can accelerate renal
The appearance of Candida in the urine is an increasingly com- parenchymal damage. In spinal cord–injured patients, use of a long-
mon complication of indwelling catheterization, particularly for term indwelling bladder catheter is a well-documented risk factor for
patients in the intensive care unit, those taking broad-spectrum bladder cancer. Chronic bacteriuria resulting in chronic inflammation
antimicrobial drugs, and those with underlying diabetes mellitus. is one possible explanation for this observation.
In many studies, >50% of urinary Candida isolates have been found
to be non-albicans species. The clinical presentation varies from a ■■FURTHER READING
laboratory finding without symptoms to pyelonephritis and even Bent S et al: Does this woman have acute uncomplicated urinary tract
sepsis. Removal of the urethral catheter results in resolution of can- infection? JAMA 287:2701, 2002.
diduria in more than one-third of asymptomatic cases. Treatment of Grigoryan L et al: Urinary tract infections in young adults. JAMA
asymptomatic patients does not appear to decrease the frequency 312:1677, 2014.
of recurrence of candiduria. Therapy is recommended for patients Gupta K et al: International clinical practice guidelines for the treat-
who have symptomatic cystitis or pyelonephritis and for those who ment of acute uncomplicated cystitis and pyelonephritis in women:
are at high risk for disseminated disease. High-risk patients include A 2010 update by the Infectious Diseases Society of America and
those with neutropenia, those who are undergoing urologic manip- the European Society for Microbiology and Infectious Diseases. Clin
ulation, those who are clinically unstable, and low-birth-weight Infect Dis 52:e103, 2011.
infants. Fluconazole (200–400 mg/d for 7–14 days) reaches high Hooton TM et al: Diagnosis, prevention, and treatment of catheter-
levels in urine and is the first-line regimen for Candida infections associated urinary tract infection in adults: 2009 international clinical
of the urinary tract. Although instances of successful eradication practice guidelines from the Infectious Diseases Society of America.
of candiduria by some of the newer azoles and echinocandins have Clin Infect Dis 50:625, 2010.
been reported, these agents are characterized by only low-level uri- Hooton TM et al: Voided midstream urine culture and acute cystitis in
nary excretion and thus are not recommended. For Candida isolates premenopausal women. N Engl J Med 369; 1883, 2013.
with high levels of resistance to fluconazole, oral flucytosine and/ Nicolle LE et al: Infectious Diseases Society of America guidelines for
or parenteral amphotericin B are options. Bladder irrigation with the diagnosis and treatment of asymptomatic bacteriuria in adults.
amphotericin B generally is not recommended. Clin Infect Dis 40:643, 2005.
PART 5

■■PREVENTION OF RECURRENT UTI IN WOMEN

Recurrence of uncomplicated cystitis in reproductive-age women is
common, and a preventive strategy is indicated if recurrent UTIs are
interfering with a patient’s lifestyle. The threshold of two or more
131 Sexually Transmitted
Infections: Overview
Infectious Diseases

symptomatic episodes per year is not absolute; decisions about inter-

ventions should take the patient’s preferences into account. and Clinical Approach
Three prophylactic strategies are available: continuous, postcoital,
Jeanne M. Marrazzo, King K. Holmes
and patient-initiated therapy. Continuous prophylaxis and postcoital
prophylaxis usually entail low doses of TMP-SMX, a fluoroquinolone,
or nitrofurantoin. These regimens are all highly effective during the
period of active antibiotic intake. Typically, a prophylactic regimen CLASSIFICATION AND EPIDEMIOLOGY
is prescribed for 6 months and then discontinued, at which point the Worldwide, most adults acquire at least one sexually transmitted
rate of recurrent UTI often returns to baseline. If bothersome infections infection (STI), and many remain at risk for complications. Each day,
recur, the prophylactic program can be reinstituted for a longer period. for example, more than 1 million STIs are acquired worldwide, placing
Selection of resistant strains in the fecal flora has been documented in many affected persons at risk for adverse reproductive health outcomes
studies of women taking prophylactic antibiotics for 12 months. and neoplasia. Certain STIs, such as syphilis, gonorrhea, HIV infection,
Patient-initiated therapy involves supplying the patient with materi- hepatitis B, and chancroid, often occur in highly interconnected sexual
als for urine culture and with a course of antibiotics for self-medication networks characterized by high rates of partner change or multiple
at the first symptoms of infection. The urine culture is refrigerated and concurrent partners. Such networks, for example, often include per-
delivered to the physician’s office for confirmation of the diagnosis. sons who engage in transactional sex, men who have sex with men
When an established and reliable patient–provider relationship exists, (MSM), and persons involved in the use of illicit drugs, particularly
the urine culture can be omitted as long as the symptomatic episodes methamphetamine. Other STIs are distributed more evenly throughout
respond completely to short-course therapy and are not followed by populations. For example, chlamydial infections, genital human papil-
relapse. lomavirus (HPV) infections, and genital herpes can spread efficiently
Non-antimicrobial prevention is increasingly being studied. Lacto- even in relatively low-risk populations. Finally, modern technologies
bacillus probiotics are one appealing approach to UTI prevention, but based on detection of nucleic acid have accelerated elucidation of the
there is a paucity of data to support this strategy. Similarly, studies of role of sexual transmission in the spread of some viruses, including
cranberry products for UTI prevention have produced mixed results. Ebola virus and Zika virus, and have provided new evidence of appar-
Varied dosing and product composition between studies remains an ent sexual transmission of several bacteria, including group C Neisseria
issue for providing clinical guidance. meningitidis and anaerobes associated with bacterial vaginosis (BV).
In general, the product of three factors determines the initial rate of
■■PROGNOSIS spread of any STI within a population: rate of sexual exposure of sus-
Cystitis is a risk factor for recurrent cystitis and pyelonephritis. ASB ceptible to infectious people, efficiency of transmission per exposure,
is common among elderly and catheterized patients but does not in and duration of infectivity of those infected. Accordingly, efforts to
itself increase the risk of death. The relationships among recurrent UTI, prevent and control STIs aim to decrease the rate of sexual exposure
chronic pyelonephritis, and renal insufficiency have been widely stud- of susceptible to infected persons (e.g., through education and efforts
ied. In the absence of anatomic abnormalities such as reflux, recurrent to change sexual behavior norms and through control efforts aimed
infection in children and adults does not lead to chronic pyelonephritis at reducing the proportion of the population infected); to decrease
or to renal failure. Moreover, infection does not play a primary role the duration of infectivity (through early diagnosis and curative or

Harrisons_20e_Part5_p0859-p1648.indd 976 6/1/18 12:03 PM

 suppressive treatment); and to decrease the efficiency of transmission Organization estimated that 357 million new cases of four curable 977
(through promotion of condom use and safer sexual practices, use of STIs—gonorrhea, chlamydial infection, syphilis, and trichomoniasis—
effective vaccines, and male medical circumcision). occurred annually in recent years. Up to 50% of women of reproductive
In all societies, STIs rank among the most common of all infec- age in developing countries have BV (arguably acquired sexually). All
tious diseases, with at least 40 microorganisms now classified of these curable STIs have been associated with increased risk of HIV
as predominantly sexually transmitted or as frequently sexu- transmission or acquisition.
ally transmissible (Table 131-1). In developing countries, with In the United States, the prevalence of antibody to HSV-2 began to
three-quarters of the world’s population and 90% of the world’s STIs, fall in the late 1990s, especially among adolescents and young adults;
factors such as population growth (especially in adolescent and young- the decline was presumably due to delayed sexual debut, increased
adult age groups), rural-to-urban migration, wars, limited or no provision condom use, and lower rates of multiple (four or more) sex partners—
of reproductive health services for women, and poverty create excep- all well documented by the U.S. Youth Risk Behavior Surveillance
tional vulnerability to disease resulting from unprotected sex. During the System. The estimated annual incidence of HBV infection has also
1990s in China, Russia, the other states of the former Soviet Union, and declined dramatically since the mid-1980s; this decrease is probably
South Africa, internal social structures changed rapidly as borders attributable to now-widespread administration of hepatitis B vaccine
opened to the West, unleashing enormous new epidemics of HIV infec- in infancy. Genital HPV remains the most common sexually transmit-
tion and other STIs. Despite advances in the provision of highly effec- ted pathogen in the United States, infecting 60% of a cohort of initially
tive antiretroviral therapy worldwide, HIV remains the leading cause HPV-negative, sexually active Washington state college women within
of death in some developing countries, and HPV and hepatitis B virus 5 years in a study conducted from 1990 to 2000—i.e., during the pre–
(HBV) remain important causes of cervical and hepatocellular carci- HPV immunization era. The scale-up of HPV vaccine coverage among
noma, respectively—two of the most common (and preventable) malig- young women has already shown promise in reducing the incidence of
nancies in the developing world. Sexually transmitted herpes simplex infection with the HPV types included in the vaccines and of conditions
virus (HSV) infection causes most genital ulcer disease throughout the associated with these viruses.
world, and an increasing proportion of cases of genital herpes occur In industrialized countries, fear of HIV infection in the mid-1980s
in developing countries with generalized HIV epidemics, where the and through the mid-2000s, coupled with widespread behavioral
positive-feedback loop between HSV and HIV transmission remains interventions and better-organized systems of care for the curable
intractable. Despite this consistent link, randomized trials evaluating STIs, initially helped curb the transmission of several STDs. However,
the efficacy of antiviral therapy in suppressing HSV in both HIV- with well-tolerated and highly effective antiretroviral therapy now
uninfected and HIV-infected persons have demonstrated no protective available, HIV has become for many a chronic disease associated with

CHAPTER 131 Sexually Transmitted Infections: Overview and Clinical Approach

effect against acquisition or transmission of HIV. The World Health a normal life span and high quality of life. Rates of gonorrhea and
syphilis remain higher in the United States than in any other Western
industrialized country.
TABLE 131-1 Sexually Transmitted and Sexually Transmissible
Microorganisms In the United States, the Centers for Disease Control and Prevention
(CDC) has compiled reported rates of STIs since 1941. The incidence
BACTERIA VIRUSES OTHERa
of reported gonorrhea peaked at 468 cases per 100,000 population in
Transmitted in Adults Predominantly by Sexual Intercourse the mid-1970s and fell to a low of 98 cases per 100,000 in 2012. With
Neisseria gonorrhoeae HIV (types 1 and 2) Trichomonas vaginalis increased testing and more sensitive tests, the incidence of reported
Chlamydia trachomatis Human T-cell Pthirus pubis Chlamydia trachomatis infection has been increasing steadily since
Treponema pallidum lymphotropic virus reporting began in 1984, reaching an all-time peak of 457.6 cases per
type 1 100,000 in 2011. The incidence of primary and secondary syphilis per
Haemophilus ducreyi
Herpes simplex virus 100,000 peaked at 71 cases in 1946, fell rapidly to 3.9 cases in 1956,
Klebsiella
type 2 ranged from ~10 to 15 cases through 1987 (with markedly increased
(Calymmatobacterium)
granulomatis Human papillomavirus rates among MSM and African Americans), and then fell to a nadir
(multiple genital of 2.1 cases in 2000–2001 (with rates falling most rapidly among
Ureaplasma urealyticum
genotypes)
Mycoplasma genitalium heterosexual African Americans). However, since 1996, with the intro-
Hepatitis B virusb
duction of highly active antiretroviral therapy, gonorrhea, syphilis,
Molluscum contagiosum and chlamydial infection have had a remarkable resurgence among
virus
MSM in North America and Europe, where outbreaks of a rare type
Sexual Transmission Repeatedly Described but Not Well Defined or of chlamydial infection (lymphogranuloma venereum [LGV]) that
Not the Predominant Mode
had virtually disappeared during the AIDS era have occurred. In
Mycoplasma hominis Cytomegalovirus Candida albicans 2014, ~75% of primary and secondary syphilis cases reported to the
Gardnerella vaginalis and Human T-cell Sarcoptes scabiei CDC were in MSM. Moreover, the uptake of daily oral emtricitabine/
other vaginal bacteria lymphotropic virus tenofovir as oral pre-exposure prophylaxis for HIV-1 acquisition has
Group B Streptococcus type 2
increased among MSM since its initial approval for this purpose in 2012
Mobiluncus spp. Hepatitis C virus and has been associated with reports of reduced condom-use frequency
Helicobacter cinaedi (?) Hepatitis D virus and concomitantly increased STI acquisition. These developments have
Helicobacter fennelliae Herpes simplex virus resulted in a soaring incidence of STIs, with increasing co-infection with
type 1 HIV and other sexually transmitted pathogens (particularly Treponema
Anaerobes associated
with bacterial vaginosis Zika virus pallidum, the cause of syphilis; and Neisseria gonorrhoeae, the cause of
Leptotrichia/Sneathia Ebola virus gonorrhea), primarily among MSM.
Group C Neisseria (?) Epstein-Barr virus
meningitidis Human herpesvirus MANAGEMENT OF COMMON SEXUALLY
type 8 TRANSMITTED DISEASE (STD) SYNDROMES
Transmitted by Sexual Contact Involving Oral–Fecal Exposure; of Although other chapters discuss management of specific STIs, most
Declining Importance in Men Who Have Sex with Men patients are managed (at least initially) on the basis of presenting
Shigella spp. Hepatitis A virus Giardia lamblia symptoms and signs and associated risk factors, even in industrialized
Campylobacter spp. Entamoeba histolytica countries. Table 131-2 lists some of the most common clinical STD syn-
dromes and their microbial etiologies. Strategies for their management
a
Includes protozoa, ectoparasites, and fungi. bAmong U.S. patients for whom a
risk factor can be ascertained, most hepatitis B virus infections are transmitted are outlined below. Chapters 196 and 197 address the management of
sexually. infections with human retroviruses.

Harrisons_20e_Part5_p0859-p1648.indd 977 6/1/18 12:03 PM

 978 TABLE 131-2 Major Sexually Transmitted Disease Syndromes and Consideration of routine demographic data (e.g., gender, age, area of
Sexually Transmitted Microbial Etiologies residence) is a simple first step in this risk assessment. For example,
SEXUALLY TRANSMITTED MICROBIAL national guidelines strongly recommend routine screening of sexually
SYNDROME ETIOLOGIES active females ≤25 years of age for C. trachomatis infection. Table 131-3
AIDS HIV types 1 and 2 provides a set of 11 STD/HIV risk-assessment questions that clinicians
Urethritis: males Neisseria gonorrhoeae, Chlamydia can pose verbally or that health care systems can adapt (with yes/no
trachomatis, Mycoplasma genitalium, responses) into a routine self-administered questionnaire. The initial
Ureaplasma urealyticum (subspecies framing statement gives permission to discuss topics that may be diffi-
urealyticum), Trichomonas vaginalis, HSV, cult for the patient to disclose.
some anaerobic bacteria, Leptotrichia/ Risk assessment is followed by clinical assessment (elicitation of
Sneathia
information on specific current symptoms and signs of STDs). Con-
Epididymitis C. trachomatis, N. gonorrhoeae, and (in firmatory diagnostic tests (for persons with symptoms or signs) or
older men or men who have sex with men)
coliform bacteria
screening tests (for those without symptoms or signs) may involve
microscopic examination, culture, nucleic acid amplification tests
Lower genital tract infections:
females (NAATs), or serology. Initial syndrome-based treatment should cover
the most likely causes. For certain syndromes, results of rapid tests can
Cystitis/urethritis C. trachomatis, N. gonorrhoeae, HSV
narrow the spectrum of this initial therapy (e.g., pH of vaginal fluid
Mucopurulent cervicitis C. trachomatis, N. gonorrhoeae,
M. genitalium
for women with vaginal discharge, Gram’s stain of urethral discharge
for men with urethral discharge, rapid plasma reagin test for genital
Vulvitis Candida albicans, HSV
ulcer to assess the probability of syphilis). After the institution of
Bartholinitis C. albicans, T. vaginalis
treatment, STD management proceeds to the “4 Cs” of prevention and
Vulvovaginitis C. albicans, T. vaginalis control: contact tracing (see “Prevention and Control of STIs,” below),
BV BV-associated bacteria (see text)
Acute pelvic inflammatory N. gonorrhoeae, C. trachomatis,
disease BV-associated bacteria, M. genitalium,
group B streptococci TABLE 131-3 Eleven-Question STD/HIV Risk Assessment
Infertility N. gonorrhoeae, C. trachomatis, Framing Statement
BV-associated bacteria
In order to provide the best care for you today and to understand your risk for
Ulcerative lesions of the genitalia HSV-1, HSV-2, Treponema pallidum,
certain infections, it is necessary for us to talk about your sexual behavior.
Haemophilus ducreyi, C. trachomatis
PART 5

(LGV strains), Klebsiella Screening Questions

(Calymmatobacterium) granulomatis (1) Do you have any reason to think you might have a sexually transmitted
Complications of pregnancy/ Several pathogens implicated infection? If so, what reason?
puerperium (2) For all adolescents <18 years old: Have you begun having any kind of
Intestinal infections
Infectious Diseases

sex yet?
Proctitis C. trachomatis, N. gonorrhoeae, HSV, STD History
T. pallidum
(3) Have you ever had any sexually transmitted infections or any genital
 Proctocolitis or enterocolitis Campylobacter spp., Shigella spp., infections? If so, which ones?
Entamoeba histolytica, Helicobacter spp.,
other enteric pathogens Sexual Preference
Enteritis Giardia lamblia (4) Have you had sex with men, women, or both?
Acute arthritis with urogenital N. gonorrhoeae (e.g., DGI), C. trachomatis Injection Drug Use
infection or viremia (e.g., reactive arthritis), HBV (5) Have you ever injected yourself (“shot up”) with drugs? (If yes, have you
Genital and anal warts HPV (30 genital types) ever shared needles or injection equipment?)
Mononucleosis syndrome CMV, HIV, EBV (6) Have you ever had sex with a gay or bisexual man or with anyone who
Hepatitis Hepatitis viruses, T. pallidum, CMV, EBV had ever injected drugs?
Neoplasias Characteristics of Partner(s)
 Squamous cell dysplasias and HPV (especially types 16, 18, 31, 45) (7) Has your sex partner had any sexually transmitted infections? If so,
cancers of the cervix, anus, which ones?
vulva, vagina, or penis (8) Has your sex partner had other sex partners during the time you’ve been
 Kaposi’s sarcoma, body-cavity HHV-8 together?
lymphomas STD Symptoms Checklist
T cell leukemia HTLV-1 (9) Have you recently developed any of these symptoms?
Hepatocellular carcinoma HBV
For Men For Women
Tropical spastic paraparesis HTLV-1
(a) Discharge of pus (drip) from the (a) Abnormal vaginal discharge
Scabies Sarcoptes scabiei penis (increased amount, abnormal
Pubic lice Pthirus pubis (b) Genital sores (ulcers) or rash odor, abnormal yellow color)
Abbreviations: BV, bacterial vaginosis; CMV, cytomegalovirus; DGI, disseminated (b) Genital sores (ulcers), rash, or
gonococcal infection; EBV, Epstein-Barr virus; HBV, hepatitis B virus; HHV-8, itching
human herpesvirus type 8; HPV, human papillomavirus; HSV, herpes simplex virus;
Sexual Practices, Past 2 Months (for patients answering yes to any of
HTLV, human T-cell lymphotropic virus; LGV, lymphogranuloma venereum.
the above questions, to guide examination and testing)
(10) Now I’d like to ask what parts of your body may have been sexually
STD care and management begin with risk assessment and proceed exposed to an STD (e.g., your penis, mouth, vagina, anus).
to clinical assessment, diagnostic testing or screening, treatment, and Query about Interest in STD Screening Tests (for patients answering
prevention. Risk assessment guides detection and interpretation of no to all of the above questions)
symptoms that could denote an STD; decisions on screening or pro- (11) Would you like to be tested for HIV or any other STDs today? (If yes,
phylactic/preventive treatment; risk reduction counseling and inter- clinician can explore which STD and why.)
vention (e.g., hepatitis B vaccination); treatment of partners of patients Source: Adapted from JR Curtis, KK Holmes, in KK Holmes et al (eds): Sexually
with known infections; and behavioral risk reduction by the patient. Transmitted Diseases, 4th ed. New York, McGraw-Hill, 2008.

Harrisons_20e_Part5_p0859-p1648.indd 978 6/1/18 12:03 PM

 ensuring compliance with therapy, and counseling on risk reduction, 979
increasing proportion of men with symptoms and/or signs
including condom promotion and provision as well as motivational of urethritis are simultaneously assessed for infection with
interviewing for risk reduction. N. gonorrhoeae and C. trachomatis by NAATs of first-catch urine.
Consistent with current guidelines, all adults should be screened for The urine specimen tested should consist of the first 10–15 mL of
infection with HIV-1 at least once, and more frequently if they are at the stream, and, if possible, patients should not have voided for
elevated risk for acquisition of this infection. the prior 2 h. Culture or NAAT for N. gonorrhoeae may yield posi-
■■URETHRITIS IN MEN tive results even when Gram’s staining is negative; certain strains
Urethritis in men produces urethral discharge, dysuria, or both, usu- of N. gonorrhoeae can result in negative urethral Gram’s stains in
ally without frequency of urination. Causes include N. gonorrhoeae, up to 30% of cases of urethral infection. Results of tests for gono-
C. trachomatis, Mycoplasma genitalium, Ureaplasma urealyticum, Trichomonas coccal and chlamydial infection predict the patient’s prognosis
vaginalis, HSV, and (rarely) adenovirus. (with greater risk for recurrent NGU if neither chlamydiae nor
Until recently, C. trachomatis caused ~30–40% of cases of nongono- gonococci are found than if either is detected) and can guide both
coccal urethritis (NGU), particularly in heterosexual men; however, the the counseling given to the patient and the management of the
proportion of cases due to this organism has probably declined in some patient’s sexual partner(s).
populations served by effective chlamydial control programs, and older 4. Treat urethritis promptly while test results are pending.
men with urethritis appear less likely to have chlamydial infection.
HSV and T. vaginalis each cause a small proportion of NGU cases in the
United States. Recently, multiple studies have consistently implicated TREATMENT
M. genitalium as a probable cause of many Chlamydia-negative cases.
Fewer studies than in the past have implicated Ureaplasma; the ureaplas- Urethritis in Men
mas have been differentiated into U. urealyticum and Ureaplasma parvum,
Table 131-4 summarizes the steps in management of urethral dis-
and a few studies suggest that U. urealyticum—but not U. parvum—is
charge and/or dysuria in sexually active men.
associated with NGU. Coliform bacteria can cause urethritis in men
In practice, if Gram’s stain does not reveal gonococci, urethritis is
who practice insertive anal intercourse. More recently, anaerobic bac-
treated with a regimen effective for NGU, such as azithromycin or
teria that are characteristically involved in BV, especially Leptotrichia/
doxycycline. Both are effective. Although azithromycin has been more
Sneathia species, have occasionally been associated with urethritis in
effective than doxycycline for M. genitalium infection, the efficacy
heterosexual men. Recommendations for the initial diagnosis of ure-
of azithromycin for treatment of M. genitalium is rapidly declining.

CHAPTER 131 Sexually Transmitted Infections: Overview and Clinical Approach

thritis in men currently include specific tests only for N. gonorrhoeae and
Alternatives include moxifloxacin and pristinamycin, a stretogramin
C. trachomatis; they do not yet include testing for M. genitalium, although
antibiotic available in some countries. If gonococci are demonstrated
a NAAT is now commercially available for the latter.
by Gram’s stain or if no diagnostic tests are performed to exclude
gonorrhea definitively, treatment should include parenteral cepha-
APPROACH TO THE PATIENT losporin therapy for gonorrhea (Chap. 151) plus oral azithromycin,
primarily for additive activity against N. gonorrhoeae given concerns
Urethritis in Men about evolving cephalosporin resistance. Azithromycin is effective for
The following summarizes the approach to the male patient with treating C. trachomatis infection, which can cause urethral co-infection
suspected urethritis: in men with gonococcal urethritis. Sexual partners should also be
tested for gonorrhea and chlamydial infection. Regardless of whether
1. Establish the presence of urethritis. If proximal-to-distal “milking”
of the urethra does not express a purulent or mucopurulent
discharge, even after the patient has not voided for several hours TABLE 131-4 Management of Urethral Discharge in Men
(or preferably overnight), a Gram’s-stained smear of an anterior USUAL CAUSES USUAL INITIAL EVALUATION
urethral specimen obtained by passage of a small urethrogenital Chlamydia trachomatis Demonstration of urethral discharge or
swab 2–3 cm into the urethra usually reveals ≥2 neutrophils Neisseria gonorrhoeae pyuria
per 1000× field when urethritis is present; in gonococcal infec- Mycoplasma genitalium Exclusion of local or systemic
tion, such a smear usually reveals gram-negative intracellular complications
Ureaplasma urealyticum
diplococci as well. Alternatively, the centrifuged sediment of Urethral Gram’s stain to confirm
Trichomonas vaginalis
the first 20–30 mL of voided urine—ideally collected as the first urethritis, detect gram-negative diplococci
Herpes simplex virus
morning specimen—can be examined for inflammatory cells, Test for N. gonorrhoeae, C. trachomatis
either by microscopy showing ≥10 leukocytes per high-power Initial Treatment for Patient and Partners
field or by the leukocyte esterase test. Patients with symptoms Treat gonorrhea (unless excluded):
who lack objective evidence of urethritis generally do not benefit
Ceftriaxone (250 mg IMa) plus azithromycin (1 g PO)
from repeated courses of antibiotics, and other etiologies of such
symptoms may be considered. Management of Recurrence
2. Evaluate for complications or alternative diagnoses. A brief his- Confirm objective evidence of urethritis. If patient was reexposed to untreated
tory and examination can exclude epididymitis and systemic or new partner, repeat treatment of patient and partner.
complications, such as disseminated gonococcal infection (DGI) If patient was not reexposed, consider infection with T. vaginalisb or antibiotic-
and reactive arthritis. Although digital examination of the pros- resistant M. genitaliumc or Ureaplasma, and consider treatment with
metronidazole, azithromycin, or both.
tate gland seldom contributes to the evaluation of sexually active
young men with urethritis, men with dysuria who lack evidence a
Neither oral cephalosporins nor fluoroquinolones are recommended for treatment
of gonorrhea in the United States because of the emergence of increasing
of urethritis as well as sexually inactive men with urethritis fluoroquinolone resistance in N. gonorrhoeae, especially (but not only) among
should undergo prostate palpation, urinalysis, and urine culture men who have sex with men, and the decreasing susceptibility of a still-small
to exclude bacterial prostatitis and cystitis. proportion of gonococci to ceftriaxone (Fig. 131-1). Updates on the emergence of
antimicrobial resistance in N. gonorrhoeae can be obtained from the Centers for
3. Evaluate for gonococcal and chlamydial infection. An absence of Disease Control and Prevention at http://www.cdc.gov/std. bIn men, the diagnosis
typical gram-negative diplococci on Gram’s-stained smear of T. vaginalis infection requires culture, DNA testing, or nucleic acid amplification
of urethral exudate containing inflammatory cells warrants a testing (where available) of early-morning first-voided urine sediment or of a
preliminary diagnosis of NGU, as this test is 98% sensitive for urethral swab specimen obtained before voiding. cM. genitalium is often resistant
to doxycycline and azithromycin but is usually susceptible to the fluoroquinolone
the diagnosis of gonococcal urethral infection. However, an moxifloxacin. Moxifloxacin can be considered for treatment of refractory
nongonococcal, nonchlamydial urethritis.

Harrisons_20e_Part5_p0859-p1648.indd 979 6/1/18 12:03 PM

 980 they are tested for these infections, however, they should receive usually caused by urinary pathogens. These older men usually have
the same regimen given to the male index case. Patients with con- no urethritis but do have bacteriuria. Similarly, epididymitis in MSM
firmed persistence or recurrence of urethritis after treatment should who have practiced insertive rectal intercourse is often caused by
be re-treated with the initial regimen if they did not comply with the Enterobacteriaceae.
original treatment or were reexposed to an untreated partner. Most
persistent urethritis is due to M. genitalium, and prompt diagnostic
testing and/or treatment for M. genitalium is recommended.
TREATMENT
National and international guidelines do exist for treatment of Epididymitis
gonococcal urethritis, typically with ceftriaxone plus azithromycin.
However, consensus is still lacking on treatment of urethritis that Ceftriaxone (250 mg as a single dose IM) followed by doxycycline
persists after treatment and cure of gonorrhea. Ideally, the approach (100 mg by mouth twice daily for 10 days) constitutes effective
would involve testing for potential causes of the persistent urethritis treatment for epididymitis caused by N. gonorrhoeae or C. trachomatis.
(e.g., M. genitalium) and antimicrobial susceptibility testing in set- Neither oral cephalosporins nor fluoroquinolones are recommended
tings and populations where antimicrobial resistance is emerging. for treatment of gonorrhea in the United States because of resistance
Currently, assays are available that can detect M. genitalium, and in N. gonorrhoeae, especially (but not only) among MSM (Fig. 131-1).
some experts believe it is time to integrate such testing into STD When infection with Enterobacteriaceae is suspected, oral levofloxa-
care. If M. genitalium is detected, the persistent urethritis can be cin (500 mg once daily for 10 days) or ofloxacin (300 mg twice daily
treated with azithromycin or moxifloxacin in light of local patterns for 10 days) is effective for syndrome-based initial treatment of
of antimicrobial susceptibility. epididymitis; however, because this regimen is not effective against
In heterosexual men with a high likelihood of exposure to tricho- gonococcal or chlamydial infection, it should be combined with
moniasis, an intraurethral swab specimen and a first-voided urine effective therapy for possible gonococcal or chlamydial infection
sample should be tested for T. vaginalis (often by culture, although of the epididymis unless bacteriuria with Enterobacteriaceae is
NAATs are more sensitive and are approved for the diagnosis of tri- confirmed.
chomoniasis in women), and presumptive treatment with metroni-
dazole or tinidazole (2 g by mouth in a single dose) should be given.
For MSM, trichomoniasis is unlikely, and consideration of a course ■■URETHRITIS AND THE URETHRAL SYNDROME IN
of moxifloxacin is warranted. Because MSM also have the highest WOMEN
prevalence rates of antimicrobial-resistant N. gonorrhoeae, this possi- C. trachomatis, N. gonorrhoeae, and occasionally HSV cause symptom-
bility, even if apparently ruled out at the initial presentation, should atic urethritis—known as the urethral syndrome in women—that is
PART 5

be kept in mind. characterized by “internal” dysuria (usually without urinary urgency

or frequency), pyuria, and an absence of Escherichia coli and other uro-
pathogens at counts of ≥102/mL in urine. In contrast, the dysuria asso-
■■EPIDIDYMITIS ciated with vulvar herpes or vulvovaginal candidiasis (and perhaps
Acute epididymitis, almost always unilateral, produces pain, swelling, with trichomoniasis) is often described as “external,” being caused
Infectious Diseases

and tenderness of the epididymis, with or without symptoms or signs by painful contact of urine with the inflamed or ulcerated labia or
of urethritis. This condition must be differentiated from testicular tor- introitus. Acute onset, association with urinary urgency or frequency,
sion, tumor, and trauma. Torsion, a surgical emergency, usually occurs hematuria, or suprapubic bladder tenderness suggests bacterial cysti-
in the second or third decade of life and produces a sudden onset of tis. Among women with symptoms of acute bacterial cystitis, costover-
pain, elevation of the testicle within the scrotal sac, rotation of the epi- tebral pain and tenderness or fever suggest acute pyelonephritis. The
didymis from a posterior to an anterior position, and absence of blood management of bacterial urinary tract infection (UTI) is discussed in
flow on Doppler ultrasound. Persistence of symptoms after a course of Chap. 130.
therapy for epididymitis suggests the possibility of testicular tumor or Signs of vulvovaginitis, coupled with symptoms of external dys-
of a chronic granulomatous disease, such as tuberculosis. In sexually uria, suggest vulvar infection (e.g., with HSV or Candida albicans).
active men under age 35, acute epididymitis is caused most frequently Among dysuric women without signs of vulvovaginitis, bacterial UTI
by C. trachomatis and less commonly by N. gonorrhoeae and is usually must be differentiated from the urethral syndrome by assessment of
associated with overt or subclinical urethritis. Acute epididymitis risk, evaluation of the pattern of symptoms and signs, and specific
occurring in older men or following urinary tract instrumentation is microbiologic testing. An STI etiology of the urethral syndrome is

Percentage
1.5
Elevated cefixime MICs
Elevated ceftriaxone MICs
1.2

0.9

0.6

0.3

0.0
2006 2007* 2008* 2009 2010 2011 2012 2013 2014 2015
Year
*Isolates not tested for cefixime susceptibility in 2007 and 2008.
FIGURE 131-1 Proportion of Neisseria gonorrhoeae isolates with elevated minimal inhibitory concentrations (MICs) of ceftriaxone (≥0.125 μg/mL) and cefixime
(≥0.25 μg/mL), United States, 2006–2015. (From the Centers for Disease Control and Prevention: Gonococcal Isolate Surveillance Project [GISP], 2016.)

Harrisons_20e_Part5_p0859-p1648.indd 980 6/1/18 12:03 PM

 suggested by young age, more than one current sexual partner, a new used to characterize the vaginal bacteria using the Nugent score but 981
partner within the past month, a partner with urethritis, or coexisting is used primarily for research purposes and requires familiarity with
mucopurulent cervicitis (see below). The finding of a single urinary the morphotypes and scale involved.
pathogen, such as E. coli or Staphylococcus saprophyticus, at a concentration
of ≥102/mL in a properly collected specimen of midstream urine from a
dysuric woman with pyuria indicates probable bacterial UTI, whereas
TREATMENT
pyuria with <102 conventional uropathogens per milliliter of urine (“ster- Vaginal Discharge
ile” pyuria) suggests acute urethral syndrome due to C. trachomatis
or N. gonorrhoeae. Gonorrhea and chlamydial infection should be Patterns of treatment for abnormal vaginal discharge vary widely.
sought by specific tests (e.g., NAATs of vaginal secretions collected In developing countries, where clinics or pharmacies often dispense
with a swab). Among dysuric women with sterile pyuria caused by treatment based on symptoms alone without examination or test-
infection with N. gonorrhoeae or C. trachomatis, appropriate treatment ing, oral treatment with metronidazole—particularly with a 7-day
alleviates dysuria. The role of M. genitalium in the urethral syndrome regimen—provides reasonable coverage against both trichomoniasis
in women remains undefined. and BV, the usual causes of symptoms of vaginal discharge. Metroni-
dazole treatment of sex partners prevents reinfection of women with
T. vaginalis, although it does not help prevent the recurrence of BV.
■■VULVOVAGINAL INFECTIONS Guidelines for syndromic management promulgated by the World
Abnormal Vaginal Discharge If directly questioned about vagi- Health Organization suggest consideration of treatment for cervical
nal discharge during routine health checkups, many women acknowl- infection and for trichomoniasis, BV, and vulvovaginal candidiasis
edge having nonspecific symptoms of vaginal discharge that do not in women with symptoms of abnormal vaginal discharge. However,
correlate with objective signs of inflammation or with actual infection. it is important to note that the majority of chlamydial and gonococ-
However, unsolicited reporting of abnormal vaginal discharge often cal cervical infections produce no symptoms.
denotes BV or trichomoniasis. Specifically, an abnormally increased In industrialized countries, clinicians treating symptoms and
amount or an abnormal odor of the discharge is associated with one signs of abnormal vaginal discharge should, at a minimum, differen-
or both of these conditions. Cervical infection with N. gonorrhoeae or tiate between BV and trichomoniasis, because optimal management
C. trachomatis does not often cause an increased amount or abnormal of patients and partners differs for these two conditions.
odor of discharge; however, when these pathogens cause cervicitis,
they—like T. vaginalis—often result in an increased number of neu- Vaginal Trichomoniasis (See also Chap. 224) Symptomatic

CHAPTER 131 Sexually Transmitted Infections: Overview and Clinical Approach

trophils in vaginal fluid, which thus takes on a yellow color. Vulvar trichomoniasis characteristically produces a profuse, yellow, purulent,
conditions such as genital herpes or vulvovaginal candidiasis can homogeneous vaginal discharge and vulvar irritation, sometimes with
cause vulvar pruritus, burning, irritation, or lesions as well as external visible inflammation of the vaginal and vulvar epithelium and pete-
dysuria (as urine passes over the inflamed vulva or areas of epithelial chial lesions on the cervix (the so-called strawberry cervix, best visual-
disruption) or vulvar dyspareunia. ized by colposcopy). The pH of vaginal fluid—normally <4.7—usually
Certain vulvovaginal infections may have serious sequelae. Tricho- rises to ≥5. Microscopic examination of vaginal discharge mixed with
moniasis, BV, and vulvovaginal candidiasis have all been associated saline reveals motile trichomonads in most culture-positive cases.
with increased risk of acquisition of HIV infection; BV promotes HIV However, saline microscopy probably detects only one-half of all cases,
transmission from HIV-infected women to their male sex partners. and, especially in the absence of symptoms or signs, culture or NAAT
Vaginal trichomoniasis and BV early in pregnancy independently is usually required for detection of the organism. NAAT for T. vaginalis
predict premature onset of labor. BV can also lead to anaerobic bacte- is more sensitive than culture. Treatment of asymptomatic as well as
rial infection of the endometrium and salpinges. Vaginitis may be an symptomatic cases reduces rates of transmission and prevents later
early and prominent feature of toxic shock syndrome, and recurrent or development of symptoms.
chronic vulvovaginal candidiasis develops with increased frequency
among women who have systemic illnesses, such as diabetes mellitus
or HIV-related immunosuppression (although only a very small pro- TREATMENT
portion of women with recurrent vulvovaginal candidiasis in industri- Vaginal Trichomoniasis
alized countries actually have a serious predisposing illness).
Thus vulvovaginal symptoms or signs warrant careful evaluation, Only nitroimidazoles (e.g., metronidazole and tinidazole) consis-
including speculum and pelvic examination, diagnostic testing, and tently cure trichomoniasis. A single 2-g oral dose of metronidazole
appropriate therapy specific for the infection identified. Unfortunately, is effective and less expensive than the alternatives. Tinidazole has
clinicians do not always perform the tests required to establish the cause a longer half-life than metronidazole, causes fewer gastrointesti-
of such symptoms. Further, self-diagnosis of a specific type of infection— nal symptoms, and may be useful in treating trichomoniasis that
including vulvovaginal candidiasis—is often incorrect. The diagnosis fails to respond to metronidazole. Treatment of sexual partners—
and treatment of the three most common types of vaginal infection are facilitated by dispensing metronidazole to the female patient to give
summarized in Table 131-5. to her partner(s), with a warning about avoiding the concurrent
Inspection of the vulva and perineum may reveal tender genital use of alcohol—significantly reduces both the risk of reinfection
ulcerations or fissures (typically due to HSV infection or vulvovaginal and the reservoir of infection; treating partners is the standard of
candidiasis) or discharge visible at the introitus before insertion of a care. Intravaginal treatment with 0.75% metronidazole gel is not
speculum (suggestive of BV or trichomoniasis). Speculum examina- reliable for vaginal trichomoniasis. Thus, systemic use of metroni-
tion permits the clinician to discern whether the discharge appears dazole is still recommended throughout pregnancy for treatment
abnormal and whether it emanates from the cervical os (mucoid of trichomoniasis. In a large randomized trial, metronidazole treat-
and, if abnormal, yellow) or from the vagina (not mucoid, since the ment of trichomoniasis during pregnancy was associated with an
vaginal epithelium does not produce mucus). Symptoms or signs of increased frequency of perinatal morbidity. However, most studies,
abnormal vaginal discharge should prompt testing of vaginal fluid including randomized controlled trials, have shown no adverse
for pH, for a fishy odor when mixed with 10% KOH, and for certain effects of metronidazole use during pregnancy on preterm birth or
microscopic features when mixed with saline (motile trichomonads birth defects.
and/or “clue cells”) and with 10% KOH (pseudohyphae or hyphae
indicative of vulvovaginal candidiasis). Additional objective labo- Bacterial Vaginosis BV is a syndrome characterized by symp-
ratory tests, described below, are useful for establishing the cause of toms of vaginal malodor and increased white-gray discharge, which
abnormal vaginal discharge. Gram’s staining of vaginal fluid can be appears homogeneous, is low in viscosity, and uniformly covers the

Harrisons_20e_Part5_p0859-p1648.indd 981 6/1/18 12:03 PM

 982 TABLE 131-5 Diagnostic Features and Management of Vaginal Infection
NORMAL VAGINAL
FEATURE EXAMINATION VULVOVAGINAL CANDIDIASIS TRICHOMONAL VAGINITIS BACTERIAL VAGINOSIS
Etiology Uninfected; lactobacilli Candida albicans Trichomonas vaginalis Associated with Gardnerella
predominant vaginalis, various anaerobic and/
or noncultured bacteria, and
mycoplasmas
Typical symptoms None Vulvar itching and/or irritation Profuse discharge; Malodorous, slightly increased
vulvar itching discharge
Discharge
Amount Variable; usually scant Scant Often profuse Moderate
Colora Clear or translucent White White or yellow White or gray
Consistency Nonhomogeneous, Clumped; adherent plaques Homogeneous Homogeneous, low viscosity;
flocculent uniformly coats vaginal walls
Inflammation of vulvar None Erythema of vaginal epithelium, Erythema of vaginal and vulvar None
or vaginal epithelium introitus; vulvar dermatitis, epithelium; colpitis macularis
fissures common
pH of vaginal fluidb Usually ≤4.5 Usually ≤4.5 Usually ≥5 Usually >4.5
Amine (“fishy”) odor None None May be present Present
with 10% KOH
Microscopyc Normal epithelial cells; Leukocytes, epithelial cells; Leukocytes; motile Clue cells; few leukocytes;
lactobacilli predominant mycelia or pseudomycelia in up trichomonads seen in 80–90% no lactobacilli or only a few
to 80% of C. albicans culture– of symptomatic patients, outnumbered by profuse mixed
positive persons with typical less often in the absence of microbiota, nearly always including
symptoms symptoms G. vaginalis plus anaerobic species
on Gram’s stain (Nugent’s score ≥7)
Other laboratory Isolation of Candida spp. Isolation of T. vaginalis or
findings positive NAATd
Usual treatment None Azole cream, tablet, or Metronidazole or tinidazole, 2 g Metronidazole, 500 mg PO bid for
suppository—e.g., miconazole orally (single dose) 7 days
PART 5

(100-mg vaginal suppository) Metronidazole, 500 mg PO bid Metronidazole gel, 0.75%, one
or clotrimazole (100-mg vaginal for 7 days applicator (5 g) intravaginally once
tablet) once daily for 7 days daily for 5 days
Fluconazole, 150 mg orally Clindamycin, 2% cream, one full
(single dose) applicator vaginally each night for
Infectious Diseases

7 days
Usual management of None None; topical treatment if Examination for sexually None
sexual partner candidal dermatitis of penis is transmitted infection; treatment
detected with metronidazole, 2 g PO
(single dose)
a
Color of discharge is best determined by examination against the white background of a swab. bA pH determination is not useful if blood is present or if the test
is performed on endocervical secretions. cTo detect fungal elements, vaginal fluid is digested with 10% KOH prior to microscopic examination; to examine for other
features, fluid is mixed (1:1) with physiologic saline. Gram’s stain is also excellent for detecting yeasts (less predictive of vulvovaginitis) and pseudomycelia or mycelia
(strongly predictive of vulvovaginitis) and for distinguishing normal flora from the mixed flora seen in bacterial vaginosis, but it is less sensitive than the saline
preparation for detection of T. vaginalis. dNAAT, nucleic acid amplification test (where available).

vaginal mucosa. BV has been associated with an increased risk of

acquiring several other genital infections, including those caused by
HIV, C. trachomatis, and N. gonorrhoeae. Other possible risk factors
include recent unprotected vaginal intercourse, having a female sex
partner, and vaginal douching. Although bacteria associated with
BV have been detected under the foreskin of uncircumcised men and
have been associated with urethritis, metronidazole treatment of male
partners has not reduced the rate of recurrence of BV among affected
women.
Among women with BV, culture of vaginal fluid has shown mark-
edly increased prevalences and concentrations of Gardnerella vaginalis,
Mycoplasma hominis, and several anaerobic bacteria (e.g., Mobiluncus,
Prevotella [formerly Bacteroides], and some Peptostreptococcus species)
as well as an absence of hydrogen peroxide–producing Lactobacillus
species that constitute most of the normal vaginal microbiota and
help protect against cervical and vaginal infections. Broad-range poly-
merase chain reaction (PCR) amplification of 16S rDNA in vaginal
fluid, with subsequent identification of specific bacterial species by BV6: BVAB-1 (green) + BVAB-2 (red) + DAPI (blue)
various methods, has documented even greater bacterial diversity,
including several unique species not previously identified in culture FIGURE 131-2 Broad-range polymerase chain reaction amplification of 16S
rDNA in vaginal fluid from a woman with bacterial vaginosis (BV) shows a field of
(Fig. 131-2) and Atopobium vaginae, an organism that is strongly asso- bacteria hybridizing with probes for BV-associated bacterium 1 (BVAB-1, visible as
ciated with BV and is resistant to metronidazole. Other genera newly a thin, curved green rod) and for BVAB-2 (red). The inset shows that BVAB-1 has a
implicated in BV include Megasphaera, Leptotrichia, Eggerthella, and morphology similar to that of Mobiluncus (curved rod). (Reprinted with permission
Dialister. from DN Fredricks et al: N Engl J Med 353:1899, 2005.)

Harrisons_20e_Part5_p0859-p1648.indd 982 6/1/18 12:03 PM

 either confirmed or refuted, and a randomized multicenter trial in 983
the United States found no benefit of repeated intravaginal inocula-
tion of a vaginal peroxide-producing Lactobacillus species following
treatment of BV with metronidazole. A meta-analysis of 18 studies
concluded that BV during pregnancy substantially increased the
risk of preterm delivery and of spontaneous abortion. However, in
most studies, topical intravaginal treatment of BV with clindamycin
during pregnancy has not reduced adverse pregnancy outcomes.
Numerous trials of oral metronidazole treatment during pregnancy
have given inconsistent results, and recent reviews have concluded
that antenatal treatment of women with BV—including those with
previous preterm delivery—did not reduce the risk of preterm
delivery. The U.S. Preventive Services Task Force thus recommends
against routine screening of pregnant women for BV.

Vulvovaginal Pruritus, Burning, or Irritation Vulvovaginal

candidiasis produces vulvar pruritus, burning, or irritation, generally
without symptoms of increased vaginal discharge or malodor. Genital
FIGURE 131-3 Wet mount of vaginal fluid showing typical clue cells from herpes can produce similar symptoms, with lesions sometimes difficult
a woman with bacterial vaginosis. Note the obscured epithelial cell margins to distinguish from the fissures and inflammation caused by candidia-
and the granular appearance attributable to many adherent bacteria (×400).
(Photograph provided by Lorna K. Rabe, reprinted with permission from S Hillier sis. Signs of vulvovaginal candidiasis include vulvar erythema, edema,
et al, in KK Holmes et al [eds]: Sexually Transmitted Diseases, 4th ed. New York, fissures, and tenderness. With candidiasis, a white scanty vaginal dis-
McGraw-Hill, 2008.) charge sometimes takes the form of white thrush-like plaques or cottage
cheese-like curds adhering loosely to the vaginal epithelium. C. albicans
accounts for nearly all cases of symptomatic vulvovaginal candidiasis,
BV is conventionally diagnosed clinically with the Amsel criteria, which probably arise from endogenous strains of C. albicans that have
which include any three of the following four clinical abnormalities: (1) colonized the vagina or the intestinal tract. Complicated vulvovaginal

CHAPTER 131 Sexually Transmitted Infections: Overview and Clinical Approach

objective signs of increased white homogeneous vaginal discharge; (2) candidiasis includes cases that recur four or more times per year; are
a vaginal discharge pH of >4.5; (3) liberation of a distinct fishy odor unusually severe; are caused by non-albicans Candida species; or occur
(attributable to volatile amines such as trimethylamine) immediately in women with uncontrolled diabetes, debilitation, immunosuppres-
after vaginal secretions are mixed with a 10% solution of KOH; and sion, or pregnancy.
(4) microscopic demonstration of “clue cells” (vaginal epithelial cells In addition to compatible clinical symptoms, the diagnosis of vul-
coated with coccobacillary organisms, which have a granular appear- vovaginal candidiasis involves the demonstration of pseudohyphae or
ance and indistinct borders; Fig. 131-3) on a wet mount prepared by hyphae by microscopic examination of vaginal fluid mixed with saline
mixing vaginal secretions with normal saline in a ratio of ~1:1. or 10% KOH or subjected to Gram’s staining. Microscopic examination
is less sensitive than culture but correlates better with symptoms.
Culture is typically reserved for cases that do not respond to standard
TREATMENT first-line antimycotic agents and is undertaken to rule out imidazole or
Bacterial Vaginosis azole resistance (often associated with Candida glabrata) or before the
initiation of suppressive antifungal therapy for recurrent disease.
The standard dosage of oral metronidazole for the treatment of BV
is 500 mg twice daily for 7 days. The single 2-g oral dose of metro-
nidazole recommended for trichomoniasis produces significantly TREATMENT
lower short-term cure rates and should not be used. Intravaginal
treatment with 2% clindamycin cream (one full applicator [5 g con-
Vulvovaginal Pruritus, Burning, or Irritation
taining 100 mg of clindamycin phosphate] each night for 7 nights) Symptoms and signs of vulvovaginal candidiasis warrant treatment,
or with 0.75% metronidazole gel (one full applicator [5 g containing usually intravaginal administration of any of several imidazole anti-
37.5 mg of metronidazole] twice daily for 5 days) is also approved biotics (e.g., miconazole or clotrimazole) for 3–7 days or of a single
for use in the United States and does not elicit systemic adverse dose of oral fluconazole (Table 131-5). Over-the-counter marketing of
reactions; the response to both of these treatments is similar to the such preparations has reduced the cost of care and made treatment
response to oral metronidazole. Other alternatives include oral more convenient for many women with recurrent yeast vulvovagini-
clindamycin (300 mg twice daily for 7 days), clindamycin ovules tis. However, most women who purchase these preparations do not
(100 g intravaginally once at bedtime for 3 days), and oral tinidazole have vulvovaginal candidiasis, whereas many have other vaginal
(1 g daily for 5 days or 2 g daily for 3 days). Unfortunately, recur- infections that require different treatment. Therefore, only women
rence over the long term (i.e., several months later) is distressingly with classic symptoms of vulvar pruritus and a history of previous
common after either oral or intravaginal treatment. A randomized episodes of yeast vulvovaginitis documented by an experienced
trial comparing intravaginal gel containing 37.5 mg of metroni- clinician should self-treat. Short-course topical intravaginal azole
dazole with a suppository containing 500 mg of metronidazole plus drugs are effective for the treatment of uncomplicated vulvovaginal
nystatin (the latter not marketed in the United States) showed sig- candidiasis (e.g., clotrimazole, two 100-mg vaginal tablets daily for
nificantly higher rates of recurrence with the 37.5-mg regimen; this 3 days; or miconazole, a 1200-mg vaginal suppository as a single
result suggests that higher metronidazole dosages may be important dose). Single-dose oral treatment with fluconazole (150 mg) is also
in topical intravaginal therapy. Recurrences can be significantly effective and is preferred by many patients. Management of compli-
lessened with the twice-weekly use of suppressive intravaginal cated cases (see above) and those that do not respond to the usual
metronidazole gel. intravaginal or single-dose oral therapy often involves prolonged
Efforts to replenish numbers of vaginal lactobacilli that produce or periodic oral therapy; this situation is discussed extensively in
hydrogen peroxide and probably sustain vaginal health have been the 2015 CDC STD treatment guidelines (http://www.cdc.gov/std/
unsuccessful. While one randomized trial of orally ingested lactoba- treatment). Treatment of sexual partners is not routinely indicated.
cilli found reduced rates of recurrent BV, this result has not yet been

Harrisons_20e_Part5_p0859-p1648.indd 983 6/1/18 12:03 PM

 984 Other Causes of Vaginal Discharge or Vaginitis In the distinction among the causative pathogens. Unlike the endocervicitis
ulcerative vaginitis associated with staphylococcal toxic shock syn- produced by gonococcal or chlamydial infection, cervicitis caused by
drome, Staphylococcus aureus should be promptly identified in vaginal HSV produces ulcerative lesions on the stratified squamous epithelium
fluid by Gram’s stain and by culture. In desquamative inflammatory of the ectocervix as well as on the columnar epithelium. Yellow cervical
vaginitis, smears of vaginal fluid reveal neutrophils, massive vaginal mucus on a white swab removed from the endocervix indicates the
epithelial-cell exfoliation with increased numbers of parabasal cells, presence of polymorphonuclear leukocytes (PMNs). Gram’s staining
and gram-positive cocci; this syndrome may respond to treatment with may confirm their presence, although it adds relatively little to the
2% clindamycin cream, often given in combination with topical steroid diagnostic value of assessment for cervical signs. The presence of ≥20
preparations for several weeks. Additional causes of vaginitis and vul- PMNs per 1000× microscopic field within strands of cervical mucus
vovaginal symptoms include retained foreign bodies (e.g., tampons), not contaminated by vaginal squamous epithelial cells or vaginal bac-
cervical caps, vaginal spermicides, vaginal antiseptic preparations or teria indicates endocervicitis. Detection of intracellular gram-negative
douches, vaginal epithelial atrophy (in postmenopausal women or diplococci in carefully collected endocervical mucus is quite specific
during prolonged breast-feeding in the postpartum period), allergic but ≤50% sensitive for gonorrhea. Therefore, NAATs for N. gonorrhoeae
reactions to latex condoms, vaginal aphthae associated with HIV infec- and C. trachomatis are always indicated in the evaluation of MPC, as
tion or Behçet’s syndrome, and vestibulitis. is a careful evaluation of vaginal discharge for the causes of vaginitis
discussed above.
■■MUCOPURULENT CERVICITIS
Mucopurulent cervicitis (MPC) refers to inflammation of the columnar
epithelium and subepithelium of the endocervix and of any contiguous TREATMENT
columnar epithelium that lies exposed in an ectopic position on the Mucopurulent Cervicitis
ectocervix. MPC in women represents the “silent partner” of urethritis
in men, being equally common and often caused by the same agents Although the above criteria for MPC are neither highly specific nor
(N. gonorrhoeae, C. trachomatis, M. genitalium); however, MPC is more dif- highly predictive of gonococcal or chlamydial infection in some
ficult than urethritis to recognize, given the nonspecific nature of symp- settings, the 2015 CDC STD guidelines call for consideration of
toms (e.g., abnormal vaginal discharge) and the need for visualization empirical treatment for MPC, pending test results, in most cases.
by pelvic examination. As the most common manifestation of these Presumptive treatment with antibiotics active against C. trachomatis
serious bacterial infections in women, MPC can be a harbinger or sign should be provided for women at increased risk for this common STI
of upper genital tract infection, also known as pelvic inflammatory disease (risk factors: age <25 years, new or multiple sex partners, and unpro-
(PID; see below). In pregnant women, MPC can lead to obstetric com- tected sex), especially if follow-up cannot be ensured. Concurrent
plications. In the pre-NAAT era, more than one-third of cervicovaginal therapy for gonorrhea is indicated if the prevalence of this infection
PART 5

specimens tested for C. trachomatis, N. gonorrhoeae, M. genitalium, HSV, is substantial in the relevant patient population (e.g., young adults,
and T. vaginalis revealed no identifiable etiology for MPC (Fig. 131-4). a clinic with documented high prevalence). In this situation, ther-
More recent studies employing NAATs for these pathogens have still apy should include a single-dose regimen effective for gonorrhea
failed to identify a microbiologic etiology in nearly one-half of women plus treatment for chlamydial infection, as outlined in Table 131-4
Infectious Diseases

with MPC. Individual bacteria associated with BV may also elicit an for the treatment of urethritis. In settings where gonorrhea is much
inflammatory reaction at the cervix; thus, BV may be a cause of MPC. less common than chlamydial infection, initial therapy for chlamy-
The diagnosis of MPC rests on the detection of cardinal signs at the dial infection alone suffices, pending test results for gonorrhea.
cervix, including yellow mucopurulent discharge from the cervical os, The etiology and potential benefit of treatment for endocervicitis
endocervical bleeding upon gentle swabbing, and edematous cervical not associated with gonorrhea or chlamydial infection have not
ectopy (see below); the latter two findings are somewhat more common been established. Although the antimicrobial susceptibility of M.
with MPC due to chlamydial infection, but signs alone do not allow a genitalium is not yet well defined, the organism frequently persists
after doxycycline therapy, and it currently seems reasonable to use
azithromycin to treat possible M. genitalium infection in such cases.
MG/GC
With resistance of M. genitalium to azithromycin now recognized,
2% MG/GC/CT
MG/CT moxifloxacin may be a reasonable alternative. The sexual partner(s)
1% of a woman with MPC should be examined and given a regimen
2%
similar to that chosen for the woman unless results of tests for gon-
orrhea or chlamydial infection in either partner warrant different
HSV
5% therapy or no therapy.

GC/CT
7% ■■CERVICAL ECTOPY
Cervical ectopy, often mislabeled “cervical erosion,” is easily confused
No organism with infectious endocervicitis. Ectopy represents the presence of the
MG 35% one-cell-thick columnar epithelium extending from the endocervix
8%
out onto the visible ectocervix. In ectopy, the cervical os may contain
clear or slightly cloudy mucus but usually not yellow mucopus. Col-
TV poscopy shows intact epithelium. Normally found during adolescence
10% and early adulthood, ectopy gradually recedes through the second
and third decades of life, as squamous metaplasia replaces the ectopic
columnar epithelium. Oral contraceptive use favors the persistence or
GC CT reappearance of ectopy, while smoking apparently accelerates squa-
13% 17%
mous metaplasia. Cauterization of ectopy is not warranted. Ectopy
may render the cervix more susceptible to infection with N. gonorrhoeae,
C. trachomatis, or HIV.

FIGURE 131-4 Organisms detected among female sexually transmitted disease

■■PELVIC INFLAMMATORY DISEASE
clinic patients with mucopurulent cervicitis (n = 167). CT, Chlamydia trachomatis; The term pelvic inflammatory disease usually refers to infection that
GC, gonococcus; MG, Mycoplasma genitalium; TV, Trichomonas vaginalis; HSV, ascends from the cervix or vagina to involve the endometrium and/
herpes simplex virus. (Courtesy of Dr. Lisa Manhart; with permission.) or fallopian tubes. Infection can extend beyond the reproductive

Harrisons_20e_Part5_p0859-p1648.indd 984 6/1/18 12:03 PM

 tract to cause pelvic peritonitis, generalized peritonitis, perihepatitis, pelvic pain caused by salpingitis, with nausea, vomiting, and increased 985
perisplenitis, or pelvic abscess. Rarely, infection not related to specific abdominal tenderness if peritonitis develops.
sexually transmitted pathogens extends secondarily to the pelvic organs The abdominal pain in nontuberculous salpingitis is usually
(1) from adjacent foci of inflammation (e.g., appendicitis, regional ileitis, described as dull or aching. In some cases, pain is lacking or atypical,
or diverticulitis) or BV, (2) as a result of hematogenous dissemination but active inflammatory changes are found in the course of an unre-
(e.g., of tuberculosis or staphylococcal bacteremia), or (3) as a compli- lated evaluation or procedure, such as a laparoscopic evaluation for
cation of certain tropical diseases (e.g., schistosomiasis). Intrauterine infertility. Abnormal uterine bleeding precedes or coincides with the
infection can be primary (spontaneously occurring and usually sexually onset of pain in ~40% of women with PID, symptoms of urethritis
transmitted) or secondary to invasive intrauterine surgical procedures (dysuria) occur in 20%, and symptoms of proctitis (anorectal pain,
(e.g., dilation and curettage, termination of pregnancy, insertion of an tenesmus, and rectal discharge or bleeding) are occasionally seen in
intrauterine device [IUD], or hysterosalpingography) or to parturition. women with gonococcal or chlamydial infection.
Speculum examination shows evidence of MPC (yellow endocer-
Etiology The agents most often implicated in acute PID include the
vical discharge, easily induced endocervical bleeding) in the major-
primary causes of endocervicitis (N. gonorrhoeae, C. trachomatis, and M.
ity of women with gonococcal or chlamydial PID. Cervical motion
genitalium) and anaerobes associated with BV. In general, PID is most
tenderness is produced by stretching of the adnexal attachments on
often caused by N. gonorrhoeae in settings where there is a high inci-
the side toward which the cervix is pushed. Bimanual examination
dence of gonorrhea. M. genitalium has also been significantly associated
reveals uterine fundal tenderness due to endometritis and abnormal
with histopathologic diagnoses of endometritis and with salpingitis.
adnexal tenderness due to salpingitis that is usually, but not necessar-
Anaerobic and facultative organisms (especially Prevotella spe-
ily, bilateral. Adnexal swelling is palpable in about one-half of women
cies, peptostreptococci, E. coli, Haemophilus influenzae, and group
with acute salpingitis, but evaluation of the adnexae in a patient with
B streptococci) as well as genital mycoplasmas have been isolated
marked tenderness is not reliable. The initial temperature is >38°C
from the peritoneal fluid or fallopian tubes in a varying proportion
in only about one-third of patients with acute salpingitis. Laboratory
(typically one-fourth to one-third) of women with PID studied in
findings include elevation of the erythrocyte sedimentation rate (ESR)
the United States. The difficulty of determining the exact microbial
in 75% of patients with acute salpingitis and elevation of the peripheral
etiology of an individual case of PID—short of using invasive pro-
white blood cell count in up to 60%.
cedures for specimen collection—has implications for the approach
Unlike nontuberculous salpingitis, genital tuberculosis often occurs
to empirical antimicrobial treatment of this infection.
in older women, many of whom are postmenopausal. Presenting
Epidemiology In the United States, the estimated annual number symptoms include abnormal vaginal bleeding, pain (including

CHAPTER 131 Sexually Transmitted Infections: Overview and Clinical Approach

of initial visits to physicians’ offices for PID by women 15–44 years dysmenorrhea), and infertility. About one-quarter of these women
of age fell from an average of 400,000 during the 1980s to 250,000 in have had adnexal masses. Endometrial biopsy shows tuberculous
1999 and then to 51,000 in 2014. Hospitalizations for acute PID in the granulomas and provides optimal specimens for culture.
United States also declined steadily throughout the 1980s and early PERIHEPATITIS AND PERIAPPENDICITIS Pleuritic upper-abdominal pain
1990s but have remained fairly constant at 70,000–100,000 per year and tenderness, usually localized to the right upper quadrant (RUQ),
since 1995. Important risk factors for acute PID include the presence of develop in 3–10% of women with acute PID. Symptoms of perihepatitis
endocervical infection or BV, a history of salpingitis or of recent vagi- arise during or after the onset of symptoms of PID and may overshadow
nal douching, and recent insertion of an IUD. Certain other iatrogenic lower-abdominal symptoms, thereby leading to a mistaken diagnosis of
factors, such as dilation and curettage or cesarean section, can increase cholecystitis. In perhaps 5% of cases of acute salpingitis, early laparos-
the risk of PID, especially among women with endocervical gonococcal copy reveals perihepatic inflammation ranging from edema and ery-
or chlamydial infection or BV. Symptoms of N. gonorrhoeae–associated thema of the liver capsule to exudate with fibrinous adhesions between
and C. trachomatis–associated PID often begin during or soon after the the visceral and parietal peritoneum. When treatment is delayed and
menstrual period; this timing suggests that menstruation is a risk fac- laparoscopy is performed late, dense “violin-string” adhesions can be
tor for ascending infection from the cervix and vagina. Experimental seen over the liver; chronic exertional or positional RUQ pain ensues
inoculation of the fallopian tubes of nonhuman primates has shown when traction is placed on the adhesions. Although perihepatitis, also
that repeated exposure to C. trachomatis leads to the greatest degree of known as the Fitz-Hugh–Curtis syndrome, was for many years specifi-
tissue inflammation and damage; thus, immunopathology probably cally attributed to gonococcal salpingitis, most cases are now attributed
contributes to the pathogenesis of chlamydial salpingitis. Women using to chlamydial salpingitis. In patients with chlamydial salpingitis, serum
oral contraceptives appear to be at decreased risk of symptomatic PID, titers of microimmunofluorescent antibody to C. trachomatis are typi-
and tubal sterilization reduces the risk of salpingitis by preventing cally much higher when perihepatitis is present than when it is absent.
intraluminal spread of infection into the tubes. Physical findings include RUQ tenderness and usually include
Clinical Manifestations • ENDOMETRITIS: A CLINICAL PATHOLOGIC adnexal tenderness and cervicitis, even in patients whose symptoms
SYNDROME A study of women with clinically suspected PID who were do not suggest salpingitis. Results of liver function tests and RUQ
undergoing both endometrial biopsy and laparoscopy showed that ultrasonography are nearly always normal. The presence of MPC and
those with endometritis alone differed from those who also had sal- pelvic tenderness in a young woman with subacute pleuritic RUQ pain
pingitis in significantly less often having lower-quadrant, adnexal, or and normal ultrasonography of the gallbladder points to a diagnosis
cervical motion or abdominal rebound tenderness; fever; or elevated of perihepatitis.
C-reactive protein levels. In addition, women with endometritis alone Periappendicitis (appendiceal serositis without involvement of
differed from those with neither endometritis nor salpingitis in more the intestinal mucosa) has been found in ~5% of patients undergoing
often having gonorrhea, chlamydial infection, and risk factors such appendectomy for suspected appendicitis and can occur as a complica-
as douching or IUD use. Thus, women with endometritis alone were tion of gonococcal or chlamydial salpingitis.
intermediate between those with neither endometritis nor salpingitis Among women with salpingitis, HIV infection is associated with
and those with salpingitis with respect to risk factors, clinical manifes- increased severity of salpingitis and with tuboovarian abscess requir-
tations, cervical infection prevalence, and elevated C-reactive protein ing hospitalization and surgical drainage. Nonetheless, among women
level. Women with endometritis alone are at lower risk of subsequent with HIV infection and salpingitis, the clinical response to conventional
tubal occlusion and resulting infertility than are those with salpingitis. antimicrobial therapy (coupled with drainage of tuboovarian abscess,
when found) has usually been satisfactory.
SALPINGITIS Symptoms of nontuberculous salpingitis classically
evolve from a yellow or malodorous vaginal discharge caused by MPC Diagnosis Treatment appropriate for PID must not be withheld
and/or BV to midline abdominal pain and abnormal vaginal bleeding from patients who have an equivocal diagnosis; it is better to err
caused by endometritis and then to bilateral lower abdominal and on the side of overdiagnosis and overtreatment. On the other hand,

Harrisons_20e_Part5_p0859-p1648.indd 985 6/1/18 12:03 PM

 986 it is essential to differentiate between salpingitis and other pelvic TABLE 131-6 Combination Antimicrobial Regimens Recommended
pathology, particularly surgical emergencies such as appendicitis and for Outpatient Treatment or for Parenteral Treatment of Pelvic
ectopic pregnancy. Inflammatory Disease
Nothing short of laparoscopy definitively identifies salpingitis, OUTPATIENT REGIMENSa PARENTERAL REGIMENS
but routine laparoscopy to confirm suspected salpingitis is generally Ceftriaxone (250 mg IM once) Initiate parenteral therapy with either
impractical. Most patients with acute PID have lower abdominal plus of the following regimens; continue
pain of <3 weeks’ duration, pelvic tenderness on bimanual pelvic Doxycycline (100 mg PO bid for
parenteral therapy until 48 h after
examination, and evidence of lower genital tract infection (e.g., MPC). clinical improvement; then change to
14 days)
outpatient therapy, as described in
Approximately 60% of such patients have salpingitis at laparoscopy, plusb the text
and perhaps 10–20% have endometritis alone. Among the patients Metronidazole (500 mg PO bid for Regimen A
with these findings, a rectal temperature >38°C, a palpable adnexal 14 days)
Cefotetan (2 g IV q12h) or cefoxitin
mass, and elevation of the ESR to >15 mm/h also raise the proba-
(2 g IV q6h)
bility of salpingitis, which has been found at laparoscopy in 68% of
plus
patients with one of these additional findings, 90% of patients with
Doxycycline (100 mg IV or PO q12h)
two, and 96% of patients with three. However, only 17% of all patients
with laparoscopy-confirmed salpingitis have had all three additional Regimen B
findings. Clindamycin (900 mg IV q8h)
In a woman with pelvic pain and tenderness, increased numbers plus
of PMNs (30 per 1000× microscopic field in strands of cervical mucus) Gentamicin (loading dose of 2 mg/kg
or leukocytes outnumbering epithelial cells in vaginal fluid (in the IV or IM, then maintenance dose of
1.5 mg/kg q8h)
absence of trichomonal vaginitis, which also produces PMNs in vaginal
discharge) increase the predictive value of a clinical diagnosis of acute a
See text for discussion of options in the patient who is intolerant of
PID, as do onset with menses, history of recent abnormal menstrual cephalosporins. bThe addition of metronidazole is recommended by some experts,
particularly if bacterial vaginosis is present.
bleeding, presence of an IUD, history of salpingitis, and sexual expo-
Source: Adapted from Centers for Disease Control and Prevention: MMWR
sure to a male with urethritis. Appendicitis or another disorder of the Recomm Rep 59(RR-12):1, 2010.
gut is favored by the early onset of anorexia, nausea, or vomiting; the
onset of pain later than day 14 of the menstrual cycle; or unilateral
pain limited to the right or left lower quadrant. Whenever the diag-
nosis of PID is being considered, serum assays for human β-chorionic activity, such as ceftriaxone (to cover possible gonococcal infection)
PART 5

gonadotropin should be performed; these tests are usually positive followed by doxycycline (to cover possible chlamydial infection).
with ectopic pregnancy. Ultrasonography and MRI can be useful for Metronidazole can be added to enhance activity against anaerobes;
the identification of tuboovarian or pelvic abscess. MRI of the tubes this addition should be strongly considered if BV is documented.
can also show increased tubal diameter, intratubal fluid, or tubal wall Although few methodologically sound clinical trials (especially
thickening in cases of salpingitis. with prolonged follow-up) have been conducted, one meta-analysis
Infectious Diseases

The primary value of laparoscopy in women with lower abdominal suggested a benefit of providing good coverage against anaerobes.
pain is for the exclusion of other surgical problems that cannot be The CDC STD treatment guidelines recommend initiation of
resolved with non-invasive imaging. Some of the most common or empirical treatment for PID in sexually active young women and
serious problems that may be confused with salpingitis (e.g., acute other women at risk for PID if they are experiencing pelvic or lower
appendicitis, ectopic pregnancy, corpus luteum bleeding, ovarian abdominal pain, if no other cause for the pain can be identified, and
tumor) are unilateral. Unilateral pain or pelvic mass, although not if pelvic examination reveals one or more of the following criteria
incompatible with PID, is a strong indication for laparoscopy unless the for PID: cervical motion tenderness, uterine tenderness, or adnexal
clinical picture warrants laparotomy instead. Atypical clinical findings tenderness. Women with suspected PID can be treated as either
such as the absence of lower genital tract infection, a missed menstrual outpatients or inpatients. In the multicenter Pelvic Inflammatory
period, a positive pregnancy test, or failure to respond to appropriate Disease Evaluation and Clinical Health (PEACH) trial, 831 women
therapy are other common indications for laparoscopy. Endometrial with mild to moderately severe symptoms and signs of PID were
biopsy is relatively sensitive and specific for the diagnosis of endome- randomized to receive either inpatient treatment with IV cefoxitin
tritis, which correlates well with the presence of salpingitis. and doxycycline or outpatient treatment with a single IM dose of
cefoxitin plus oral doxycycline. Short-term clinical and microbio-
Vaginal or endocervical swab specimens should be obtained for
logic outcomes and long-term outcomes were equivalent in the two
NAATs for N. gonorrhoeae and C. trachomatis. At a minimum, vaginal
groups. Nonetheless, hospitalization should be considered when
fluid should be evaluated for the presence of PMNs, and endocervical
(1) the diagnosis is uncertain and surgical emergencies such as
secretions ideally should be assessed by Gram’s staining for PMNs and
appendicitis and ectopic pregnancy cannot be excluded, (2) the
gram-negative diplococci, which indicate gonococcal infection. The
patient is pregnant, (3) pelvic abscess is suspected, (4) severe illness
clinical diagnosis of PID made by expert gynecologists is confirmed
or nausea and vomiting preclude outpatient management, (5) the
by laparoscopy or endometrial biopsy in ~90% of women who also
patient has HIV infection, (6) the patient is assessed as unable to
have cultures positive for N. gonorrhoeae or C. trachomatis. Even among
follow or tolerate an outpatient regimen, or (7) the patient has failed
women with no symptoms suggestive of acute PID who were attending
to respond to outpatient therapy. Some experts also prefer to hos-
an STD clinic or a gynecology clinic in Pittsburgh, endometritis was
pitalize adolescents with PID for initial therapy, although younger
significantly associated with endocervical gonorrhea or chlamydial
women do as well as older women on outpatient therapy.
infection or with BV, being detected in 26%, 27%, and 15% of women
Currently, no agents other than parenteral cephalosporins pro-
with these conditions, respectively.
vide reliable coverage for gonococcal infection. Thus, adequate oral
treatment of women with serious intolerance to cephalosporins
is a challenge. If penicillins are an option, amoxicillin/clavulanic
TREATMENT acid combined with doxycycline has elicited a short-term clin-
Pelvic Inflammatory Disease ical response in one trial. Clinical trials performed outside the
United States support the effectiveness of oral moxifloxacin. In
Recommended combination regimens for ambulatory or parenteral this case, it is imperative to perform a sensitive diagnostic test for
management of PID are presented in Table 131-6. Women managed gonorrhea (ideally, a culture to test for antimicrobial susceptibility)
as outpatients should receive a combined regimen with broad before initiation of therapy. For women whose PID involves

Harrisons_20e_Part5_p0859-p1648.indd 986 6/1/18 12:03 PM

 quinolone-resistant N. gonorrhoeae, treatment is uncertain but could 987
include parenteral gentamicin or oral azithromycin, although the
latter agent has not been studied for this purpose.
For hospitalized patients, the following two parenteral regimens
(Table 131-6) have given nearly identical results in a multicenter
randomized trial:
1. Doxycycline plus either cefotetan or cefoxitin: Administration
of these drugs should be continued by the IV route for at least
48 h after the patient’s condition improves and then followed
with oral doxycycline (100 mg twice daily) to complete 14 days
of therapy.
2. Clindamycin plus gentamicin in patients with normal renal
function: Once-daily administration of gentamicin (with com-
bination of the total daily dose into a single daily dose) has not
been evaluated in PID but has been efficacious in other serious
infections and could be substituted. Treatment with these
drugs should be continued for at least 48 h after the patient’s
condition improves and then followed with oral doxycycline
(100 mg twice daily) or clindamycin (450 mg four times daily)
to complete 14 days of therapy. In cases with tuboovarian
abscess, clindamycin rather than doxycycline for continued
therapy provides better coverage for anaerobic infection.
FOLLOW-UP FIGURE 131-5 Chancroid: multiple, painful, punched-out ulcers with undermined
Hospitalized patients should show substantial clinical improvement borders on the labia occurring after autoinoculation.
within 3–5 days. Women treated as outpatients should be clinically
reevaluated within 72 h. A follow-up telephone survey of women
seen in an emergency department and given a prescription for 10 genital chlamydial infection. Despite this recommendation, screening

CHAPTER 131 Sexually Transmitted Infections: Overview and Clinical Approach

days of oral doxycycline for PID found that 28% never filled the coverage in many primary care settings remains low.
prescription and 41% stopped taking the medication early (after
an average of 4.1 days), often because of persistent symptoms, lack
■■ULCERATIVE GENITAL OR PERIANAL LESIONS
Genital ulceration reflects a set of important STIs, most of which
of symptoms, or side effects. Women not responding favorably to
sharply increase the risk of sexual acquisition and shedding of HIV. In
ambulatory therapy should be hospitalized for parenteral therapy
a 1996 study of genital ulcers in 10 of the U.S. cities with the highest
and further diagnostic evaluations, including a consideration of
rates of primary syphilis, PCR testing of ulcer specimens demonstrated
laparoscopy. Male sex partners should be evaluated and treated
HSV in 62% of patients, T. pallidum in 13%, and Haemophilus ducreyi
empirically for gonorrhea and chlamydial infection. After comple-
(the cause of chancroid) in 12–20%. Today, genital herpes represents an
tion of treatment, tests for persistent or recurrent infection with N.
even higher proportion of genital ulcers in the United States and other
gonorrhoeae or C. trachomatis should be performed if symptoms per-
industrialized countries.
sist or recur or if the patient has not complied with therapy or has
In Asia and Africa, chancroid (Fig. 131-5) was once considered
been reexposed to an untreated sex partner.
the most common type of genital ulcer, followed in frequency
SURGERY by primary syphilis and then genital herpes (Fig. 131-6). With
Surgery is necessary for the treatment of salpingitis only in the face increased efforts to control chancroid and syphilis and widespread use
of life-threatening infection (such as rupture or threatened rupture of broad-spectrum antibiotics to treat STI-related syndromes, together
of a tuboovarian abscess) or for drainage of an abscess. Conservative with more frequent recurrences or persistence of genital herpes attrib-
surgical procedures are usually sufficient. Pelvic abscesses can often utable to HIV infection, PCR testing of genital ulcers now clearly
be drained by posterior colpotomy, and peritoneal lavage can be
used for generalized peritonitis.

Prognosis Late sequelae include infertility due to bilateral tubal

occlusion, ectopic pregnancy due to tubal scarring without occlusion,
chronic pelvic pain, and recurrent salpingitis. The overall post-salpingitis
risk of infertility due to tubal occlusion in a large study in Sweden was
11% after one episode of salpingitis, 23% after two episodes, and 54%
after three or more episodes. A University of Washington study found
a sevenfold increase in the risk of ectopic pregnancy and an eightfold
increase in the rate of hysterectomy after PID.

Prevention A randomized controlled trial designed to determine

whether selective screening for chlamydial infection reduces the risk of
subsequent PID showed that women randomized to undergo screening
had a 56% lower rate of PID over the following year than did women
receiving the usual care without screening. This report helped prompt
U.S. national guidelines for risk-based chlamydial screening of young
women to reduce the incidence of PID and the prevalence of post-PID
sequelae, while also reducing sexual transmission of C. trachomatis. FIGURE 131-6 Genital herpes. A relatively mild, superficial ulcer is typically seen
The CDC and the U.S. Preventive Services Task Force recommend in episodic outbreaks. (Courtesy of Michael Remington, University of Washington
that sexually active women ≤25 years of age be screened annually for Virology Research Clinic.)

Harrisons_20e_Part5_p0859-p1648.indd 987 6/1/18 12:03 PM

 988 Diagnosis Although most genital ulcerations cannot be diagnosed
confidently on clinical grounds alone, clinical findings (Table 131-7)
and epidemiologic considerations can usually guide initial manage-
ment (Table 131-8) pending results of specific tests. Clinicians should
order a rapid serologic test for syphilis in all cases of genital ulcer. To
evaluate lesions except those highly characteristic of infection with
HSV (i.e., those with herpetic vesicles), dark-field microscopy, direct
immunofluorescence, and a NAAT for T. pallidum can be useful but
are rarely available. It is important to note that 30% of syphilitic
chancres—the primary ulcer of syphilis—are associated with an ini-
tially nonreactive syphilis serology. All patients presenting with genital
ulceration should be counseled and tested for HIV infection.
Typical vesicles or pustules or a cluster of painful ulcers preceded
by vesiculopustular lesions suggest genital herpes. These typical
clinical manifestations make detection of the virus optional; however,
many patients want confirmation of the diagnosis, and differentiation
of HSV-1 from HSV-2 has prognostic implications, because the latter
causes more frequent genital recurrences and is more infectious to
vulnerable sex partners.
FIGURE 131-7 Lymphogranuloma venereum (LGV): striking tender Painless, nontender, indurated ulcers with firm, nontender inguinal
lymphadenopathy occurring at the femoral and inguinal lymph nodes, separated by adenopathy suggest primary syphilis. If results of dark-field examina-
a groove made by Poupart’s ligament. This “sign-of-the-groove” is not considered tion and a rapid serologic test for syphilis are initially negative, or if
specific for LGV; for example, lymphomas may present with this sign.
these tests are not available, presumptive therapy should be provided
on the basis of the individual’s risk. With historically high rates of
implicates genital herpes as by far the most common cause of genital syphilis among MSM in the United States, therapy for this infection
ulceration in most developing countries. LGV due to C. trachomatis should not be withheld pending watchful waiting and/or subsequent
(Fig. 131-7) and donovanosis (granuloma inguinale, due to Klebsiella detection of seroconversion. Repeated serologic testing for syphilis
granulomatis; see Fig. 168-1) continue to cause genital ulceration in 1 or 2 weeks after treatment of seronegative primary syphilis usually
some developing countries. LGV virtually disappeared in industrial- demonstrates seroconversion.
PART 5

ized countries during the first 20 years of the HIV pandemic, but out- “Atypical” or clinically trivial ulcers may be more common manifes-
breaks are again occurring in Europe (including the United Kingdom), tations of genital herpes than classic vesiculopustular lesions. Specific
in North America, and in Australia. In these outbreaks, LGV typically tests for HSV in such lesions are therefore indicated (Chap. 187). Com-
presents as proctitis, with or without anal lesions, in men who report mercially available type-specific serologic tests for serum antibody to
unprotected receptive anal intercourse, very often in association with HSV-2 may give negative results, especially when patients present early
Infectious Diseases

HIV and/or hepatitis C virus infection; the latter may be an acute infec- with the initial episode of genital herpes or when HSV-1 is the cause of
tion acquired through the same exposure. Other causes of genital ulcers genital herpes (as is often the case today). Furthermore, a positive
include (1) candidiasis and traumatized genital warts—both readily test for antibody to HSV-2 does not prove that the current lesions
recognized; (2) lesions due to genital involvement by more widespread are herpetic, because nearly one-fifth of the general population of
dermatoses; (3) cutaneous manifestations of systemic diseases such as the United States (and no doubt a higher proportion of those at risk
genital mucosal ulceration in Stevens-Johnson syndrome or Behçet’s for other STIs) becomes seropositive for HSV-2 during early adulthood.
disease; (4) superinfections of lesions that may originally have been Although even “type-specific” tests for HSV-2 that are commercially
sexually acquired (for example, methicillin-resistant S. aureus compli- available in the United States are not 100% specific, a positive HSV-2
cating a genital ulcer due to HSV-2); and (5) localized drug reactions, serology does enable the clinician to tell the patient that he or she has
such as the ulcers occasionally seen with topical paromomycin cream probably had genital herpes, should learn to recognize symptoms,
or boric acid preparations. and should avoid sex during recurrences. In addition, because genital

TABLE 131-7 Clinical Features of Genital Ulcers

LYMPHOGRANULOMA
FEATURE SYPHILIS HERPES CHANCROID VENEREUM DONOVANOSIS
Incubation period 9–90 days 2–7 days 1–14 days 3 days–6 weeks 1–4 weeks
(up to 6 months)
Early primary lesions Papule Vesicle Pustule Papule, pustule, or Papule
vesicle
No. of lesions Usually one Multiple Usually multiple, may Usually one; often Variable
coalesce not detected, despite
lymphadenopathy
Diameter 5–15 mm 1–2 mm Variable 2–10 mm Variable
Edges Sharply demarcated, Erythematous Undermined, ragged, Elevated, round, or oval Elevated, irregular
elevated, round, or oval irregular
Depth Superficial or deep Superficial Excavated Superficial or deep Elevated
Base Smooth, nonpurulent, Serous, erythematous, Purulent, bleeds easily Variable, nonvascular Red and velvety, bleeds
relatively nonvascular nonvascular readily
Induration Firm None Soft Occasionally firm Firm
Pain Uncommon Frequently tender Usually very tender Variable Uncommon
Lymphadenopathy Firm, nontender, bilateral Firm, tender, often Tender, may suppurate, Tender, may suppurate, None; pseudobuboes
bilateral with initial loculated, usually loculated, usually
episode unilateral unilateral
Source: From RM Ballard, in KK Holmes et al (eds): Sexually Transmitted Diseases, 4th ed. New York, McGraw-Hill, 2008.

Harrisons_20e_Part5_p0859-p1648.indd 988 6/1/18 12:03 PM

 TABLE 131-8 Initial Management of Genital or Perianal Ulcer HIV infection) should generally receive initial treatment for syphi- 989
lis. Empirical therapy for chancroid should be considered if there
Causative Pathogens
has been an exposure in an area of the world where chancroid
HSV occurs or if regional lymph node suppuration is evident. Finally,
Treponema pallidum (primary syphilis) empirical antimicrobial therapy may be indicated if ulcers persist
Haemophilus ducreyi (chancroid) and the diagnosis remains unclear after a week of observation
Usual Initial Laboratory Evaluation despite attempts to diagnose herpes, syphilis, and chancroid.
Dark-field examination (if available), direct FA, or PCR for T. pallidum
RPR, VDRL, or EIA serologic test for syphilisa ■■PROCTITIS, PROCTOCOLITIS, ENTEROCOLITIS,
Culture, direct FA, ELISA, or PCR for HSV AND ENTERITIS
HSV-2-specific serology (consider) Sexually acquired proctitis, with inflammation limited to the rectal
In chancroid-endemic area: PCR or culture for H. ducreyi mucosa (the distal 10–12 cm), results from direct rectal inoculation of
Initial Treatment typical STD pathogens. In contrast, inflammation extending from the
Herpes confirmed or suspected (history or sign of vesicles): rectum to the colon (proctocolitis), involving both the small and the large
bowel (enterocolitis), or involving the small bowel alone (enteritis) can
Treat for genital herpes with acyclovir, valacyclovir, or famciclovir.
result from ingestion of typical intestinal pathogens through oral–anal
Syphilis confirmed (dark-field, FA, or PCR showing T. pallidum, or RPR reactive):
exposure during sexual contact. Anorectal pain and mucopurulent,
Benzathine penicillin (2.4 million units IM once to patient, to recent [e.g.,
bloody rectal discharge suggest proctitis or protocolitis. Proctitis
within 3 months] seronegative partner[s], and to all seropositive partners)b
commonly produces tenesmus (causing frequent attempts to defecate,
Chancroid confirmed or suspected (diagnostic test positive, or HSV and
syphilis excluded, and persistent lesion):
but not true diarrhea) and constipation, whereas proctocolitis and
enterocolitis more often cause true diarrhea. In all three conditions,
Ciprofloxacin (500 mg PO as single dose) or
anoscopy usually shows mucosal exudate and easily induced mucosal
Ceftriaxone (250 mg IM as single dose) or
bleeding (i.e., a positive “wipe test”), sometimes with petechiae or
Azithromycin (1 g PO as single dose)
mucosal ulcers. Exudate should be sampled for Gram’s staining and
a
If results are negative but primary syphilis is suspected, treat presumptively other microbiologic studies. Sigmoidoscopy or colonoscopy shows
when indicated by epidemiologic and sexual risk assessment; repeat in 1 week. inflammation limited to the rectum in proctitis or disease extending at
b
The same treatment regimen is also effective in HIV-infected persons with early
syphilis. least up into the sigmoid colon in proctocolitis.
The AIDS era brought an extraordinary shift in the clinical and eti-

CHAPTER 131 Sexually Transmitted Infections: Overview and Clinical Approach

Abbreviations: EIA, enzyme immunoassay; ELISA, enzyme-linked immunosorbent
assay; FA, fluorescent antibody; HSV, herpes simplex virus; PCR, polymerase ologic spectrum of intestinal infections among MSM. The number of
chain reaction; RPR, rapid plasma reagin; VDRL, Venereal Disease Research cases of the acute intestinal STIs described above fell as high-risk sexual
Laboratory.
behaviors became less common in this group. At the same time, the
number of AIDS-related opportunistic intestinal infections increased
shedding and sexual transmission of HSV-2 often occur in the absence
rapidly, many associated with chronic or recurrent symptoms. The
of symptoms and signs of recurrent herpetic lesions, persons who have
incidence of these opportunistic infections has since fallen with
a history of genital herpes or who are seropositive for HSV-2 should
increasingly widespread coverage of HIV-infected persons with effec-
consider the use of condoms or suppressive antiviral therapy, both of
tive antiretroviral therapy. Two species initially isolated in association
which can reduce the risk of HSV-2 transmission to a sexual partner.
with intestinal symptoms in MSM—now known as Helicobacter cinaedi
Demonstration of H. ducreyi by culture (or by PCR, where avail-
and Helicobacter fennelliae—have both been isolated from the blood of
able) is most useful when ulcers are painful and purulent, especially
HIV-infected men and other immunosuppressed persons, often in asso-
if inguinal lymphadenopathy with fluctuance or overlying erythema
is noted; if chancroid is prevalent in the community; or if the patient ciation with a syndrome of multifocal dermatitis and arthritis.
has recently had a sexual exposure elsewhere in a chancroid-endemic Acquisition of HSV, N. gonorrhoeae, or C. trachomatis (including LGV
area (e.g., a developing country). Enlarged, fluctuant lymph nodes strains of C. trachomatis) during receptive anorectal intercourse causes
should be aspirated for culture or PCR to detect H. ducreyi as well most cases of infectious proctitis in women and MSM. Primary and sec-
as for Gram’s staining and culture to rule out the presence of other ondary syphilis can also produce anal or anorectal lesions, with or with-
pyogenic bacteria. out symptoms. Gonococcal or chlamydial proctitis typically involves
When genital ulcers persist beyond the natural history of initial epi- the most distal rectal mucosa and the anal crypts and is clinically mild,
sodes of herpes (2–3 weeks) or of chancroid or syphilis (up to 6 weeks) without systemic manifestations. In contrast, primary proctitis due to
and do not resolve with syndrome-based antimicrobial therapy, then—in HSV and proctocolitis due to the strains of C. trachomatis that cause LGV
addition to the usual tests for herpes, syphilis, and chancroid—biopsy is usually produce severe anorectal pain and often cause fever. Perianal
indicated to exclude donovanosis as well as carcinoma and other nonve- ulcers and inguinal lymphadenopathy, most commonly due to HSV, can
nereal dermatoses. also occur with LGV or syphilis. Sacral nerve root radiculopathies, usu-
ally presenting as urinary retention, laxity of the anal sphincter, or consti-
pation, may complicate primary herpetic proctitis. In LGV, rectal biopsy
TREATMENT typically shows crypt abscesses, granulomas, and giant cells—findings
Ulcerative Genital or Perianal Lesions resembling those in Crohn’s disease; such findings should always
prompt rectal culture and serology for LGV, which is a curable infec-
Immediate syndrome-based treatment for acute genital ulcer (after tion. Syphilis can also produce rectal granulomas, usually in association
collection of all necessary diagnostic specimens at the first visit) is with infiltration by plasma cells or other mononuclear cells. Syphilis,
often appropriate before all test results become available because LGV, and HSV infection involving the rectum can produce perirectal
patients with typical initial or recurrent episodes of genital or adenopathy that is sometimes mistaken for malignancy; syphilis, LGV,
anorectal herpes can benefit from prompt oral antiviral therapy HSV infection, and chancroid involving the anus can produce inguinal
(Chap. 187); because early treatment of sexually transmitted causes adenopathy because anal lymphatics drain to inguinal lymph nodes.
of genital ulcers decreases further transmission; and because some Diarrhea and abdominal bloating or cramping pain without ano-
patients do not return for test results and treatment. A thorough rectal symptoms and with normal findings on anoscopy and sigmoi-
assessment of the patient’s sexual-risk profile and medical history doscopy occur with inflammation of the small intestine (enteritis) or
is critical in determining the course of initial management. The with proximal colitis. In MSM without HIV infection, enteritis is often
patient who has risk factors consistent with exposure to syphilis attributable to Giardia lamblia. Sexually acquired proctocolitis is most
(e.g., a male patient who reports sex with other men or who has often due to Campylobacter or Shigella species.

Harrisons_20e_Part5_p0859-p1648.indd 989 6/1/18 12:03 PM

 990
TREATMENT Number whose behaviors and ecologic settings result in exposure to STDs
Proctitis, Proctocolitis, Enterocolitis, and Enteritis Number who acquire STDs
Number who develop symptoms of STDs
Acute proctitis in persons who have practiced receptive anorec-
tal intercourse is usually sexually acquired. Such patients should Number who perceive the symptoms of STDs
undergo anoscopy to detect rectal ulcers or vesicles and petechiae Number who promptly seek
after swabbing of the rectal mucosa; to examine rectal exudates medical care when symptomatic
for PMNs and gram-negative diplococci; and to obtain rectal swab
Number seeking care
specimens for testing for rectal gonorrhea, chlamydial infection, who have ready access to care
herpes, and syphilis. Pending test results, patients with proctitis
Number perceived by
should receive empirical syndromic treatment—e.g., with ceftriax- clinicians as possibly having STDs
one (a single IM dose of 250 mg for gonorrhea) plus doxycycline
(100 mg by mouth twice daily for 7 days for possible chlamydial Number perceived as
infection) plus treatment for herpes or syphilis if indicated. If LGV possibly having STDs who
proctitis is proven or suspected, the recommended treatment is can be tested for STDs
doxycycline (100 mg by mouth twice daily for 21 days); alternatively, Number with objective evidence
of STDs who get proper
1 g of azithromycin once a week for 3 weeks is likely to be effective treatment for STDs
Number who comply
but is little studied. with treatment
Number whose partners are treated
and who are not reinfected

PREVENTION AND CONTROL OF STIs FIGURE 131-8 Critical control points for preventive and clinical interventions
Prevention and control of STIs require the following: against sexually transmitted diseases (STDs). (Adapted from HT Waller and MA
Piot: Bull World Health Organ 41:75, 1969 and 43:1, 1970; and from “Resource
1. Reduction of the average rate of sexual exposure to STIs through allocation model for public health planning—a case study of tuberculosis control,”
alteration of sexual risk behaviors and behavioral norms among Bull World Health Organ 48[Suppl], 1973.)
both susceptible and infected persons in all population groups. The
necessary changes include reduction in the total number of sexual
Force recommends screening sexually active female patients ≤25 years
partners and the number of concurrent sexual partners. The U.S.
of age for C. trachomatis whenever they present for health care (at least
Preventive Services Task Force recommends intensive behavioral
PART 5

once a year); older women should be tested if they have more than one
counseling for all sexually active adolescents and adults who are
sexual partner, have begun a new sexual relationship since the previ-
at increased risk for STIs (grade B recommendation). Motivational
ous test, or have another STI diagnosed. In women 25–29 years of age,
interviewing is one approach that has elicited behavioral changes,
chlamydial infection is uncommon but still may reach a prevalence of
including safer sex practices and more consistent contraception, that
3–5% in some settings; information provided by women in this age
Infectious Diseases

contribute to these goals.

group on a sex partner’s concurrency (whether a male partner has
2. Reduction of the efficiency of transmission through the promotion of
had another sex partner during the time they have been together) is
safer sexual practices, the use of condoms during casual or commer-
helpful in identifying women at increased risk. In some regions of the
cial sex, vaccination against HBV and HPV infection, male circumci-
United States, widespread selective screening and treatment of young
sion (which reduces risk of acquisition of HIV infection, chancroid,
women for cervical C. trachomatis infection have been associated with a
and perhaps other STIs), and a growing number of other approaches
50–60% drop in prevalence. Such screening and treatment also protect
(e.g., early detection and treatment of other STIs to reduce the effi-
the individual woman from PID. Sensitive urine-based genetic ampli-
ciency of sexual transmission of HIV). Longitudinal studies have
fication tests permit expansion of screening to men, teenage boys, and
shown that consistent condom use is associated with significant
girls in settings where examination is not planned or is impractical
protection of both males and females against all STIs that have been
(e.g., during pre-participation sports examinations or during initial
examined, including HIV, HPV, and HSV infections as well as gon-
medical evaluation of adolescent girls). Vaginal swabs—collected
orrhea and chlamydial infection. The only exceptions are probably
either by the health care provider at a pelvic examination or by the
sexually transmitted Pthirus pubis and Sarcoptes scabiei infestations.
woman herself—are highly sensitive and specific for the diagnosis of
3. Shortening of the duration of infectivity of STIs through early detec-
chlamydial and gonococcal infection; they are now the preferred type
tion and curative or suppressive treatment of patients and their
of specimen for screening and diagnosis of these infections.
sexual partners. The availability of curative therapy for hepatitis C
Although gonorrhea is now substantially less common than
virus infection and suppressive therapy for HBV infection exempli-
chlamydial infection in industrialized countries, screening tests for
fies new opportunities for shortening infectivity in major STIs.
N. gonorrhoeae are still appropriate for women and teenage girls attend-
Financial and time constraints imposed by many clinical practices, ing STD clinics and for sexually active teens and young women from
along with the reluctance of some clinicians to ask questions about areas of high gonorrhea prevalence. Multiplex NAATs that combine
stigmatized sexual behaviors, often curtail screening and prevention screening for N. gonorrhoeae and C. trachomatis—and, more recently,
services. As outlined in Fig. 131-8, the success of clinicians’ efforts to for T. vaginalis—in a single low-cost assay now facilitate the preven-
detect and treat STIs depends in part on societal efforts to teach young tion and control of these infections for populations at high risk.
people how to recognize symptoms of STIs; to motivate individuals All patients who have newly detected STIs or are at high risk for
with symptoms to seek care promptly; to educate persons who are STIs according to routine risk assessment as well as all pregnant
at risk but have no symptoms about what tests they should undergo women should be encouraged to undergo serologic testing for syphilis
routinely; and to make high-quality, appropriate care accessible, afford- and HIV infection, with appropriate HIV counseling before and after
able, and acceptable, especially to the young indigent patients most testing. Randomized trials have shown that risk-reduction counseling
likely to acquire an STI. of patients with STIs significantly lowers subsequent risk of acquir-
ing an STI; such counseling should now be considered a standard
STI RISK ASSESSMENT component of STI management. Preimmunization serologic testing
Because many infected individuals develop no symptoms or fail to for antibody to HBV is indicated for unvaccinated persons who are
recognize and report symptoms, clinicians should routinely perform known to be at high risk, such as MSM and people who use injection
an STI risk assessment for teenagers and young adults as a guide to drugs. In most young persons, however, it is more cost-effective to
selective screening. As stated earlier, the U.S. Preventive Services Task vaccinate against HBV without serologic screening. It is important

Harrisons_20e_Part5_p0859-p1648.indd 990 6/1/18 12:03 PM

 to recognize that, while immunization against HBV has contributed by physicians was infrequent. A randomized trial compared patients’ 991
to marked reductions in the incidence of infection with this virus, the delivery of therapy to partners exposed to gonorrhea or chlamydial
majority of new cases that do occur are acquired through sex. In 2006, infection with conventional notification and advice to partners to seek
the CDC’s Advisory Committee on Immunization Practices (ACIP) rec- evaluation for STD; patients’ delivery of partners’ therapy, also known
ommended the following: (1) Universal hepatitis B vaccination should as expedited partner therapy (EPT), significantly reduced combined rates
be implemented for all unvaccinated adults in settings in which a high of reinfection of the index patient with N. gonorrhoeae or C. trachomatis.
proportion of adults have risk factors for HBV infection (e.g., STD State-by-state variations in regulations governing this approach have
clinics, HIV testing and treatment facilities, drug-abuse treatment and not been well defined, but the 2015 CDC STD treatment guidelines
prevention settings, health care settings targeting services to injection describe its potential use. EPT, which is now commonly used by many
drug users or MSM, and correctional facilities). (2) In other primary practicing physicians, is currently permissible in 39 states and poten-
care and specialty medical settings that provide care to adults at risk for tially allowable in another 8. (Updated information on the legal status
HBV infection, health care providers should inform all patients about of EPT is available at http://www.cdc.gov/std/ept.)
the health benefits of vaccination, the risk factors for HBV infection, In summary, clinicians and public health agencies share respon-
and the persons for whom vaccination is recommended; they should sibility for the prevention and control of STIs. In the current health
vaccinate adults who report risk factors for HBV infection as well as care environment, the role of primary care clinicians has become
any adult who requests protection from HBV infection. To promote increasingly important in STI prevention as well as in diagnosis and
vaccination in all settings, health care providers should implement treatment, and the resurgence of bacterial STIs like syphilis and LGV
standing orders to identify adults recommended for hepatitis B among MSM—particularly those co-infected with HIV—emphasizes
vaccination, should administer hepatitis B vaccine as part of routine the need for risk assessment and routine screening.
clinical services, should not require acknowledgment of an HBV
infection risk factor for adult vaccination, and should use available ■■FURTHER READING
reimbursement mechanisms to remove financial barriers to hepatitis Clement ME et al: Treatment of syphilis: A systematic review. JAMA
B vaccination. 312:1905, 2014.
In 2007, the ACIP made its first recommendation for routine immu- Gottlieb SL et al: The global roadmap for advancing development of
nization of 9- to 26-year-old girls and women with the quadrivalent vaccines against sexually transmitted infections: Update and next
HPV vaccine (against HPV types 6, 11, 16, and 18). In 2011, the ACIP steps. Vaccine 34:2939, 2016.
recommended routine administration of quadrivalent HPV vaccine to Johnston C, Corey L: Current concepts for genital herpes simplex
boys at 11 or 12 years of age and to males 13–21 years of age who have virus infection: Diagnostics and pathogenesis of genital tract shed-

CHAPTER 132 Encephalitis

not yet been vaccinated or who have not completed the three-dose vac- ding. Clin Microbiol Rev 29:149, 2016.
cine series; HBV vaccination of men 22–26 years of age has also been Kirkcaldy RD et al: Neisseria gonorrhoeae antimicrobial resistance
recommended. Since that time, a nonavalent HPV vaccine has become among men who have sex with men and men who have sex exclu-
available and has largely replaced the earlier vaccines. The optimal age sively with women: The Gonococcal Isolate Surveillance Project,
for recommended vaccination is 11–12 years because of the very high 2005–2010. Ann Intern Med 158:321, 2013.
risk of HPV infection after sexual debut. Mlisana K et al: Symptomatic vaginal discharge is a poor predictor
Partner notification is the process of identifying and informing part- of sexually transmitted infections and genital tract inflammation in
ners of infected patients about possible exposure to an STI and of exam- high-risk women in South Africa. J Infect Dis 206:6, 2012.
ining, testing, vaccinating, and treating partners as appropriate. In a Newman L et al: Global estimates of the prevalence and incidence of
series of 22 reports concerning partner notification during the 1990s, four curable sexually transmitted infections in 2012 based on system-
index patients with gonorrhea or chlamydial infection named a mean atic review and global reporting. PLoS One 10:e0143304, 2015.
of 0.75–1.6 partners, of whom one-fourth to one-third were infected; Price MJ et al: Risk of pelvic inflammatory disease following Chlamydia
those with syphilis named 1.8–6.3 partners, with one-third to one-half trachomatis infection: Analysis of prospective studies with a multistate
infected; and those with HIV infection named 0.76–5.31 partners, with model. Am J Epidemiol 178:484, 2013.
up to one-fourth infected. Persons who transmit infection or who have Wandeler G et al: Hepatitis C virus infections in the Swiss HIV Cohort
recently been infected and are still in the incubation period usually Study: A rapidly evolving epidemic. Clin Infect Dis 55:1408, 2012.
have no symptoms or only mild symptoms and seek medical attention Workowski KA, Bolan GA: Sexually transmitted disease treatment
only when notified of their exposure. Therefore, the clinician must guidelines, 2015. MMWR Recomm Rep 64(RR-03):1, 2015.
encourage patients to participate in partner notification, must ensure Zakher B et al: Screening for gonorrhea and Chlamydia: A systematic
that exposed persons are notified and treated, and must guarantee review for the US Preventive Services Task Force. Ann Intern Med
confidentiality to all involved. In the United States, local health depart- 161:884, 2014.
ments often offer assistance in partner notification, treatment, and/or
counseling. It seems both feasible and most useful to notify those part-
ners exposed within the patient’s likely period of infectiousness, which

132 Encephalitis
is often considered the preceding 1 month for gonorrhea, 1–2 months for
chlamydial infection, and up to 3 months for early syphilis.
Persons with a new-onset STI always have a source contact who gave
them the infection; in addition, they may have a secondary (spread or Karen L. Roos, Kenneth L. Tyler
exposed) contact with whom they had sex after becoming infected. The
identification and treatment of these two types of contacts have differ-
ent objectives. Treatment of the source contact (often a casual contact) ■■DEFINITION
benefits the community by preventing further transmission and ben- Encephalitis is defined as an inflammation of the brain caused either
efits the source contact; treatment of the recently exposed secondary by infection, usually with a virus, or from a primary autoimmune pro-
contact (typically a spouse or another steady sexual partner) prevents cess. This chapter will focus on infectious causes of encephalitis; non-
the development of serious complications (such as PID) in the partner, infectious etiologies are considered elsewhere (Chaps. 90, 436, and 437).
reinfection of the index patient, and further spread of infection. A sur- In contrast to meningitis (Chaps. 133 and 134), in which the infectious
vey of a random sample of U.S. physicians found that most instructed process and associated inflammatory response are limited largely to the
patients to abstain from sex during treatment, to use condoms, and meninges, in encephalitis the brain parenchyma is also involved. Many
to inform their sex partners after being diagnosed with gonorrhea, patients with encephalitis also have evidence of associated meningitis
chlamydial infection, or syphilis; physicians sometimes gave the (meningoencephalitis) and, in some cases, involvement of the spinal
patients drugs for their partners. However, follow-up of the partners cord or nerve roots (encephalomyelitis, encephalomyeloradiculitis).

Harrisons_20e_Part5_p0859-p1648.indd 991 6/1/18 12:03 PM