Download Sexually Transmitted Diseases Other than Human

INVITED ARTICLE
AGING AND INFECTIOUS DISEASES
Kevin P. High, Section Editor
Sexually Transmitted Diseases
Other than Human Immunodeficiency
Virus Infection in Older Adults
Helene M. Calvet
Long Beach Department of Health and Human Services, Long Beach, and the California STD/HIV Prevention Training Center, Berkeley, California
Sexually active older adults may engage in activities that put them at risk for sexually transmitted diseases (STDs). A brief
review of the main STDs among older adults, including the epidemiology, clinical presentations, and diagnosis of and treatment
recommendations for such STDs, is presented.
Sexually transmitted diseases (STDs) constitute the most common reportable communicable diseases in the United States,
with 1700,000 cases of Chlamydia trachomatis (CT) infection
and 1350,000 cases of Neisseria gonorrhoeae infection reported
in 2000 [1]. The majority of these cases, however, occur among
adolescents and young adults, and older adults often are not
considered to be at risk for STDs. Studies show that many older
adults are sexually active, and many heath care practitioners
may not realize that older adults may engage in higher-risk
sexual activities. A survey of 1300 men and women ⭓60 years
of age, performed by the National Council on the Aging (Washington, DC) in 1998, found that 48% of the respondents were
sexually active [2]. Rates of sexual activity were higher among
individuals in their 60’s (of whom 71% of men and 51% of
women were sexually active), and they decreased among individuals in their 70’s (of whom 57% of men and 30% of
women were sexually active) and those in their 80’s (of whom
25% of men and 20% of women were sexually active).
Some older adults may have the desire to engage in sexual
activity, but they experience barriers, such as psychosocial factors (e.g., depression, performance anxiety, or loss of a partner
because of divorce, death, or disability) or medical conditions
Received 26 September 2002; accepted 26 November 2002; electronically published 17
February 2003.
This article was selected for inclusion in Clinical Infectious Diseases by Dr. Thomas T.
Yoshikawa during his time as Aging and Infectious Diseases Section Editor.
Reprints or correspondence: Dr. Helene M. Calvet, Long Beach Dept. of Health and Human
Services, 2525 Grand Ave., Long Beach, CA 90815 ([email protected]).
Clinical Infectious Diseases 2003; 36:609–14
2003 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2003/3605-0011$15.00
leading to erectile dysfunction or dyspareunia. The advent of
oral medications for the treatment of erectile dysfunction, such
as sildenafil citrate (Viagra; Pfizer [3]), is helping some individuals overcome that barrier, with Viagra having been prescribed for 110 million patients since its approval by the US
Food and Drug Administration (Rockville, MD).
Although a number of studies have investigated the sexual
behavior of older adults, patterns of condom use are not well
defined in this group; however, because the risk for STDs is
often linked to younger age or risk of pregnancy, older men
and women may be less likely to use condoms. In a survey of
12000 Americans ⭓50 years of age who were living in large
metropolitan areas, Stall and Catania [4] found that among
individuals reporting ⭓1 risk factor for HIV infection (e.g.,
multiple sexual partners, a sexual partner with a high risk for
HIV infection, receipt of a transfusion during 1978–1984, or
injection drug use), 73% were sexually active, and 83% of those
who were sexually active never used condoms. In a survey of
patients at a community-based family practice clinic, Murphree
and DeHaven [5] found that among unmarried women, condom use was significantly related to age !31 years, and that
patients 145 years of age seldom received counseling about
condoms. Although the rates of incidence of the reported STDs
(chlamydia infection, gonorrhea, and syphilis) among older
adults are low and have remained relatively stable during the
past 5 years, the fact that many older adults are sexually active
and may not use condoms when indicated can put them at
risk for STDs. The present article reviews the epidemiology of
STDs in older adults and the common clinical presentations
of STDs. Treatment for the diseases, as recommended by the
AGING AND INFECTIOUS DISEASES • CID 2003:36 (1 March) • 609
Table 1. Recommended and alternative regimens for the treatment of sexually transmitted diseases, according to the Centers for
Disease Control and Prevention (Atlanta, GA).
Sexually transmitted disease
Recommended regimen(s)
Alternative regimen(s)
Uncomplicated Chlamydia infection
Azithromycin, 1 g po, or Dox, 100 mg po b.i.d
for 7 days
Erythromycin base, 500 mg po q.i.d. for 7 days;
or erythromycin ethylsuccinate, 800 mg po
q.i.d. for 7 days; or Oflx, 300 mg po b.i.d. for
7 days; or Lvfx, 500 mg po q.d. for 7 days
Uncomplicated gonorrheaa,b infection
Cefixime, 400 mg po; or Ctri, 125 mg im; or
d
cd
ciprofloxacin, 500 mg po; or Oflx, , 400
c,d
mg po; or Lvfx, , 250 mg po
Spectinomycin, 2 g im
First clinical episode of herpes
Acy, either 400 mg po t.i.d. for 7–10 days or
200 mg po 5 times per day for 7–10 days;
or Fam, 250 mg po t.i.d. for 7–10 days; or
Val, 1 g po b.i.d. for 7–10 days
None
Episodic therapy for recurrent
episodes
Acy, either 400 mg po t.i.d. for 5 days, 200
mg po 5 times per day for 5 days, or 800
mg po b.i.d. for 5 days; or Fam, 125 mg po
b.i.d. for 5 days; or Val, either 500 mg po
b.i.d. for 3–5 days or 1 g po q.d. for 5 days
None
Suppressive therapy
Acy, 400 mg po b.i.d.; or Fam, 250 mg po
b.i.d.; or Val, either 500 mg po q.d. or
1 g po q.d.
None
Primary, secondary, and early
latent
Benzathine penicillin G, 2.4 million U im
⫻ 1 dose
Dox,e 100 mg po b.i.d. for 2 weeks; or Tet,e
500 mg po q.i.d. for 2 weeks; or Ctri,e 1 g
im/iv q.d. for 8–10 days, or azithromycin,e
2 g po
Late latent and unknown duration
Benzathine penicillin G, 7.2 million U, administered as 3 doses of 2.4 million U im, at
1-week intervals
Dox, 100 mg p.o. b.i.d. for 4 weeks; or Tet,
500 mg p.o.
q.i.d. for 4 weeks
Aqueous crystalline penicillin G, 18–24 million
U/day, administered as 3–4 million U iv q4h
for 10–14 days
Procaine penicillin G, 2.4 million U im q.d. for
10–14 days, plus probenecid, 500 mg po
q.i.d. for 10–14 days
Mtz, 2 g po
Mtz, 500 mg po b.i.d. for 7 days
c
c
Herpes simplex virus
Syphilis
Neurosyphilis
f
Trichomoniasisg
NOTE.
e
e
Acy, acyclovir; Ctri, ceftriaxone; Dox, doxycycline; Fam, famciclovir; Lvfx, levofloxacin; Mtz, metronidazole; Oflx, ofloxacin; Tet, tetracycline; Val, valacyclovir.
a
Cotreatment for Chlamydia infection is indicated unless Chlamydia infection is ruled out by use of sensitive technology.
b
If gonorrhea is documented and if it persists or recurs, test-of-cure culture is recommended to ensure that the patient does not have an untreated drugresistant gonorrhea infection.
c
Not recommended for pharyngeal gonococcal infection.
d
Because of fluoroquinolone-resistant strains in Hawaii and the Pacific Rim, fluoroquinolones should not be the first-line treatment if the patient was exposed
in these areas; use of fluoroquinolones for infections acquired in California is also inadvisable.
e
Consider for treatment of patients with allergy to penicillin; however, because the efficacy of regimens that do not contain penicillin has not been established,
and because compliance with some of these regimens may be difficult, close follow-up is essential. If compliance or follow-up cannot be ensured, then the
patient should be desensitized and treated with benzathine penicillin G.
f
Some specialists recommend use of benzathine penicillin G, 2.4 million U im weekly for 1–3 weeks after completion of initial treatment.
g
Documented infection for which treatment failed should be evaluated for metronidazole-resistant Trichomonas vaginalis. Contact the Centers for Disease
Control and Prevention (Atlanta, GA) at 404-639–8371 for more information.
Centers for Disease Control and Prevention (Atlanta, GA) is
summarized in table 1 [6].
CT INFECTION
CT infection is predominantly a disease of adolescent girls and
young women; its incidence appears to be highest among female
adolescents and young women 15–19 years of age (2447 cases
per 100,000 such individuals) [1]. The incidence of CT infection
in women decreases substantially after 30 years of age, likely
610 • CID 2003:36 (1 March) • AGING AND INFECTIOUS DISEASES
because the target cell for CT (i.e., the columnar epithelial cell,
which is present on the ectocervix of young women [cervical
ectopy]) is replaced by squamous epithelium through the process of squamous metaplasia that occurs with age. Among older
adults (those ⭓55 years of age), the reported incidence of CT
infection is !5 cases per 100,000 adults, but rates vary among
the different ethnic and racial groups.
CT can cause a variety of infections, including cervicitis,
urethritis, proctitis, follicular conjunctivitis, epididymitis, and
pelvic inflammatory disease (PID). In younger populations,
however, the majority of infections are asymptomatic. No data
are available on the proportion of cases of asymptomatic disease
in the older population. Many diagnostic tests for CT are commercially available and have been reviewed elsewhere [7], but
the most sensitive tests for CT infection of the genitals are the
nucleic acid amplification tests (NAATs), including PCR analysis, ligase chain reaction (LCR), transcription-mediated amplification, and strand-displacement amplification. PCR and
LCR have sensitivities of 90%–95%, with specificities of approximately 98%–100% [7]. All of the aforementioned tests are
approved for use with urine specimens, which obviates the need
for invasive tests. However, in populations in which the prevalence of CT infection is very low, such as older adults, the
positive predictive value of these tests can be low; therefore,
positive test results should be interpreted with caution, and
consideration should be given to use of a second testing modality for confirmation of the results.
Routine screening is not indicated for older adults, but diagnostic testing should be done for patients who present with
cervicitis, urethritis, or epididymitis and, especially, for patients
who report engaging in high-risk sexual practices. Recommended and alternative medications for the treatment of uncomplicated CT infection of the genitals are listed in table 1;
treatment of complicated infections is reviewed elsewhere [6].
Although drug resistance has been documented on occasion
[8], such resistance is thought to be extremely rare.
N. GONORRHOEAE INFECTION
Like chlamydia infection, disease due to the gonococcus (GC)
is predominantly seen among adolescents, with the highest incidence rates seen among 15–19-year-old female adolescents
and young women (716 cases per 100,000 such individuals)
[1]. Incidence rates decrease with age, with !10 infections occurring per 100,000 individuals ⭓55 years of age; as with CT
infection, rates of incidence of GC infection vary depending
on the sex and the ethnic and racial groups of individuals.
The clinical presentations of GC are similar to those of CT,
with cervicitis, urethritis, proctitis, PID, and epididymitis being
the most commonly encountered syndromes; however, GC can
also colonize mucosal surfaces asymptomatically. Unlike CT,
GC can disseminate hematogenously from any mucosal site,
causing disseminated gonococcal infection (DGI). DGI usually
presents with arthralgias, tenosynovitis, or arthritis and rash.
The rash, which is present in 2 of 3 patients, consists of a few
(!30) pustular or necrotic lesions on the distal extremities.
Highly sensitive tests for the diagnosis of GC infection include
culture, Gram staining of urethral discharge, DNA hybridization probe, or any of the same NAATs that are available for
diagnosis of CT infection. Because of its high specificity, culture
may be advantageous for older populations in which the prev-
alence of GC infection is low, and it also offers the opportunity
for sensitivity testing if needed. Routine screening is not recommended for older adults. Although currently recommended
therapies for GC infection include the use of fluoroquinolones
(FQs), resistance to FQs has been a problem in Hawaii, the
Pacific Rim, and parts of Asia for several years, so cephalosporins are the only recommended therapy for infections acquired in these areas [6]. Moderate levels of resistance to FQs
recently have been detected in California, so use of FQs in
California is not recommended [9].
SYPHILIS
The rate of incidence of early (recently acquired) syphilis is low
among older adults in the United States. Average incidence rates
of syphilis among adults ⭓55 years of age were stable during
1998–2000, with ⭐1 case occurring among 100,000 individuals
[1]. Late latent syphilis and, on occasion, neurosyphilis and
tertiary forms of syphilis probably are more commonly encountered in this age group. An overview of the different stages
of syphilis has been published elsewhere [10]. Tertiary syphilis,
although uncommon, can present with cardiovascular findings
(aortitis and aortic aneurysm) or gummas, and it usually occurs
5–25 years after infection [11]. Neurosyphilis can occur at any
stage of syphilis and can cause a variety of neurological syndromes. Syphilitic meningitis usually occurs early, within
months of infection. Strokes due to meningovascular syphilis
usually occur 5–12 years after infection, but they may occur
earlier. Later neurological manifestations, which occur decades
after infection and which usually present in older adults, may
include dementia (general paresis), tabes dorsalis, VIIIth nerve
deafness, or optic atrophy.
Many older adults may be tested for syphilis as part of a
workup for strokes, dementia, or other neurological disorders,
but the sensitivity of the nontreponemal tests (the Venereal
Disease Research Laboratory [VDRL] test and the rapid plasma
reagin [RPR] test) for later stages of syphilis may be low; up
to 25% of patients with late neurosyphilis have a negative serum
VDRL test result [10]. One study estimated that the rate of
false-negative results of the serum VDRL test in older populations may be substantial [12], so consideration could be given
to using a treponemal test (e.g., the fluorescent treponemal
antibody–absorbed test [FTA-ABS] or the particle agglutination
test for antibodies to Treponema pallidum (Serodia TP-PA; Fujirebio) if a clinical syndrome suggestive of active late syphilis
is present and if the initial result of the nontreponemal test is
negative. However, routine use of treponemal tests for older
adults with strokes or dementia is not routinely recommended
because the yield of such tests is low.
CSF analysis, including WBC count, protein level determination, and a CSF VDRL test, is more definitive in the diagnosis
AGING AND INFECTIOUS DISEASES • CID 2003:36 (1 March) • 611
of neurosyphilis. Findings of pleocytosis (WBC count, ⭓5 cells/
mL) or an elevated protein level are suggestive of neurosyphilis,
and a positive result of a CSF VDRL test is diagnostic (unless
the CSF is grossly bloody). The CSF VDRL test, however, is
relatively insensitive, and the finding of an isolated elevated
protein level in an older individual may be difficult to interpret,
because the CSF protein level normally increases with age. Because of problems with the FTA-ABS test’s specificity, it is not
recommended that the test be performed on CSF samples; however, because the test has a high sensitivity, a negative CSF FTAABS test result might be helpful in ruling out neurosyphilis in
unclear cases [10], such as those for which the CSF VDRL test
result is negative but for which suspicion of neurosyphilis remains because of clinical findings or other CSF abnormalities.
Penicillin remains the drug of choice for the treatment of syphilis, and, although a number of alternative therapies are possible
(see table 1), data regarding regimens that do not contain penicillin are limited, and close follow-up is indicated if a regimen
that does not contain penicillin is used.
HERPES SIMPLEX VIRUS (HSV)
Genital HSV infection is not a reportable disease in the United
States, but data from the National Health and Nutrition Examination Survey (NHANES), which used type-specific serologic testing for detection of HSV type 1 (HSV-1) and HSV
type 2 (HSV-2), estimated that ∼20% of the adult population
in the United States is infected with HSV-2. HSV-2 infection
usually is sexually acquired, with seroprevalence starting to increase at the onset of sexual activity and then increasing with
age. According to the findings of NHANES III, the strongest
predictors of positive HSV-2 serologic status were female sex,
black race or Mexican-American ethnic background, older age,
fewer years of formal education, income below the poverty
level, greater number of sexual partners during a lifetime, and
⭓1 instance of cocaine use [13]. The seroprevalence of HSV2 in adults ⭓50 of age averages ∼25% but is higher among
blacks (seroprevalence, 160%) and Mexican Americans (seroprevalence, ∼40%) [13].
A minority of patients who are seropositive for HSV-2 note
the typical vesicular outbreaks, but those without classic symptoms may experience atypical symptoms or may be asymptomatically shedding the virus. In general, clinical symptoms and
shedding decrease with time, and the prevalence and frequency
of symptoms and shedding in older adults, most of whom have
been infected for years, are unknown. Although sensitivity varies depending on the age and stage (primary vs. recurrent) of
the lesion, viral culture is useful for the diagnosis of lesions
with classic presentations. For patients with atypical or nonulcerative presentations, HSV-2 type-specific serologic testing
has been commercially available for several years. Type-specific
612 • CID 2003:36 (1 March) • AGING AND INFECTIOUS DISEASES
serologic tests should be considered for patients presenting with
bothersome recurrent genital symptoms (e.g., itching, burning,
irritation, etc.) without a defined cause. Routine testing of
asymptomatic older adults is discouraged because the seroprevalence of HSV-2 is known to be high, because therapy
would not be indicated unless the patients was symptomatic,
and because the psychological impact of such a diagnosis can
be significant.
HUMAN PAPILLOMAVIRUS (HPV)
HPV infection is considered to be the most common STD, with
10%–20% of younger (age, 15–49 years) sexually active individuals showing molecular evidence of infection, and with up
to 60% showing evidence of prior infection [14]. HPV infection
is not a reportable disease, but studies suggest that the prevalence of infection is highest among young sexually active
women and that it decreases with age. Most infections are
subclinical and self-limited, with a minority of patients developing anogenital warts and with ∼10% developing chronic infection, which can predispose the patient to anogenital cancer.
The incidence or prevalence of genital warts in older adults is
not known, but clinical experience suggests that most cases
occur in younger adults. Genital warts may be treated a variety
of ways, depending on the location and extent of the disease;
the choices of treatment modalities have been reviewed elsewhere [15].
For elderly individuals, a greater concern than genital warts
is HPV-related dysplasia or carcinoma. Approximately 25% of
new cases of invasive cervical cancer occur among women ⭓65
years of age, and, of women in this age group, only 52% have
had a Papanicolaou (Pap) smear performed within 3 years
before detection of disease [16]. HPV DNA has been detected
in association with up to 93% of cervical cancers, and the most
frequently detected HPV types associated with these cancers
are types 16 and 18. A comparative study of cervical cancer in
older women (those 62–85 years of age) and younger women
(those 28–61 years of age) found that the 2 patient groups were
similar with respect to the HPV types detected in association
with the cancers, the prevalence of HLA dr1501, and the occurrence of p53 mutations, which suggests that the pathogenesis
of cervical cancer in older women is similar to that in younger
women [17].
The frequency with which Pap smears should be performed
in older women is controversial, with many favoring screening
that occurs less frequently than on an annual basis for women
who have had normal results of recent Pap smears, and there
is no consensus on the age at which screening should be discontinued [18]. A new Bethesda System for reporting cervical
cytological results [19] and new guidelines for the management
of cervical cytological abnormalities [20] outline the approach
to abnormalities detected during the screening of older women.
Colposcopy with directed biopsy is indicated for most squamous abnormalities, except for atypical squamous cells of undetermined significance (ASC-US), for which testing for the
high-risk types of HPV-DNA is the preferred method to triage
younger women for either immediate colposcopy or moreconservative Pap smear follow-up. For older, postmenopausal
women with ASC-US who have clinical or cytological evidence
of vaginal atrophy, a reasonable option for follow-up is to prescribe a course of intravaginally administered estrogen (if it is
not contraindicated) and to perform a second Pap smear 1
week after completion of the treatment course [20]. If the results of the second Pap smear are negative for intraepithelial
lesion or malignancy, then close follow-up with another Pap
smear in 4–6 months is indicated. Another finding of ASC-US
or a more severe lesion at either follow-up should be evaluated
with colposcopy. A finding of atypical glandular cells in older
women is ominous, with a recent retrospective study showing
that 17% of women 150 years of age who had atypical glandular
cells of undetermined significance had some form of cancer
[21]. Uterine cancer was more common than cervical cancer;
therefore, in women 135 years of age, the recommended
workup of atypical glandular cells includes colposcopy with
endocervical sampling and endometrial biopsy.
of yeast vaginitis and BV among such women [22]. The epidemiology of trichomoniasis in older women is not well known,
but trichomoniasis can be asymptomatic, and long-term carriage of the disease in women has been described. Of note, in
the study by Spinillo et al. [22], trichomoniasis was significantly
more common among postmenopausal women compared with
women of reproductive age, although this study population was
likely affected by referral bias. Data from Denmark, however,
suggest that trichomoniasis affects a population older than that
affected by GC and CT, with the average age of women reported
to have trichomoniasis being 39 years, compared with 24 years
and 22 years for women with GC and CT, respectively [24].
Evaluation for complaints of vaginitis should include a speculum examination of the cervix and vaginal vault, with examination of vaginal secretions on saline wet mount and KOH
preparation and by assessment of vaginal pH. These examinations should yield sufficient information to allow for diagnosis of candidiasis, trichomoniasis, or BV, if present. The sensitivity of wet mount for the detection of Trichomonas
organisms is estimated to be ∼70%, so a more sensitive test
would be culture, which is now commercially available (InPouchTV; Biomed Diagnostics). Trichomoniasis should be suspected when a women has an abnormal discharge, an elevated
vaginal pH level, and evidence of inflammation (increased
number of WBCs) without evidence of cervicitis or candidiasis.
VAGINITIS
Acknowledgments
Vaginal discharge is a common complaint of women of childbearing age. Of the 3 main causes of vaginitis in younger
women—bacterial vaginosis (BV), candidiasis, and trichomoniasis—only trichomoniasis is clearly sexually transmitted. In
older, postmenopausal women, vaginitis is less likely to have 1
of these 3 etiologies, and it is more likely to be the result of
the atrophic effects of estrogen deficiency. Spinillo et al. [22]
compared postmenopausal women with control subjects of reproductive age who were seen at a vaginitis clinic, and they
found that only 38% of the postmenopausal women had BV,
trichomoniasis, or candidiasis diagnosed, compared with 53%
of the control subjects. The lack of estrogen in older women
leads to a thinning of the vaginal epithelium and a reduction
in epithelial glycogen content, which leads to alteration in the
vaginal pH and microflora. The vaginal microflora of women
of childbearing age is predominantly facultative lactobacilli,
whereas that of postmenopausal women not receiving estrogen
therapy shows not only a lower prevalence of lactobacilli but,
also, a 10–100-fold lower concentration of these organisms
when present [23]. However, in postmenopausal women, yeasts
and the organisms associated with BV (e.g., Prevotella bivia,
Gardnerella vaginalis, and Mycoplasma hominis) were isolated
less frequently in postmenopausal women than in women of
childbearing age, which possibly explains the lower incidence
We thank Thomas Yoshikawa, Gail Bolan, and Jeanne Marazzo for their review of the manuscript.
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