Bacterial Sexually Transmitted Diseases, Chlamydial Infection, Color Atlas & Synopsis of Sexually Transmitted Diseases, Third Edition, Atlas of Chlamydial Infection
Chlamydial Infection
Chlamydia trachomatis is a small bacterium that invades eukaryotic cells and requires cell culture for isolation. Chlamydial infection is the most prevalent bacterial sexually transmitted disease (STD) in industrialized countries and perhaps worldwide; along with genital herpes and human papillomavirus (HPV) infection, it is one of the three most common STDs in the United States. Some serological variants (serovars) of C. trachomatis cause blinding trachoma, a continuing public health problem in some developing countries. Three serovars, designated L1, L2, and L3, cause lymphogranuloma venereum (LGV), one of the five classic venereal diseases (with gonorrhea, syphilis, chancroid, and granuloma inguinale).
The LGV and trachoma serovars are uncommon in most populations in industrialized countries, but rectal infections with the L2 serovar have recently been resurgent among men who have sex with men
(MSM). Chlamydophila (formerly Chlamydia) pneumoniae is a related respiratory pathogen that has been linked with coronary artery disease and atherosclerosis; it is not sexually transmitted.
In adults, the dominant manifestations of infection with the non–LGV serovars of C. trachomatis are nongonococcal urethritis, cervicitis, proctitis, and conjunctivitis, all of which commonly are mild and often asymptomatic. This clinical spectrum is similar to that of gonorrhea, but with less florid inflammatory symptoms and signs, a longer incubation period, and more frequent subclinical infection.
Paradoxically, the outwardly mild nature of chlamydial infection may enhance the frequency of complications compared with gonorrhea, because treatment is often delayed and significant scarring (e.g., fallopian tube obstruction) can result from subclinical infection. The organism can be found in the upper genital tracts of most women with cervical infection, regardless of whether there are clinical manifestations of endometritis or salpingitis. Many women with tubal infertility or ectopic pregnancy following chlamydial infection have no past history of pelvic inflammatory disease (PID) or unexplained abdominal pain, indicating that subclinical salpingitis can result in tubal scarring. Repeat infection withC. trachomatis is associated with an elevated risk of complications, probably due to a vigorous anamnestic inflammatory response.
The development and widespread availability of nucleic acid amplification tests (NAATs) have markedly enhanced diagnosis. The prevalence of C. trachomatis in women declined modestly in several jurisdictions in the United States and western Europe following widespread introduction of systematic efforts to control chlamydial infections in the 1990s, based primarily on screening of sexually active women. However, most such geographic areas subsequently experienced substantial resurgences in prevalence in sexually active women, and probably in incidence, that could be attributed only in part to increased screening and use of improved diagnostic tests. It has been hypothesized that widespread screening and early treatment has had the paradoxical effect of enhancing the individual and perhaps population-level susceptibility to C. trachomatis, owing to reduced durable immunity that once resulted from more prolonged infections. The optimal approaches to preventing morbidity due to chlamydial infections, in particular the balance between further expansion of female screening, extending screening to sexually active men, and improved partner treatment, became the subject of debate in the late 2000s. Some experts have begun to question the utility of routine screening as a control strategy, but this stance is controversial, and the incidence of PID appears to be declining in the United States and the United Kingdom, plausibly the result of chlamydia prevention efforts based on screening. Routine screening of sexually active women and less extensive screening of males will continue in the foreseeable future.
EPIDEMIOLOGY
Incidence and Prevalence
• In the United States, 1.24 million cases reported in 2009; true estimated annual incidence 3–4 million
• Reported infections in the United States approximate 400 per 100,000 annually overall, 500–600 per 100,000 women, and 3,000 per 100,000 in females age 15–19 (equivalent to 3% of teen girls infected annually)
• True incidence rates are at least double these figures, due to underdiagnosis and underreporting
• Among women aged ≤25 years, prevalence averages ~5% in primary care practices and reproductive health clinics, 10–30% in STD clinics, and 5–10% in secondary school-based clinics, community centers, and social service sites
• Prevalence of urethral infection typically 5–10% in sexually active males aged 15–30 years; higher in MSM, including rectal infections
• LGV rare in the United States (reported cases <100/year in the 1990s) and western Europe; more common in some developing countries; recent increase in MSM
Transmission
• Exclusively by sexual contact or perinatally, except for transmission of trachoma serovars among children
• Pharyngeal infection and transmission by oral sex are rare, in contrast to gonorrhea
• LGV in MSM is transmitted by direct anal exposure, e.g., by hands or sex toys
Age
• Strong association with young age, probably due to both biological factors (e.g., physiologic cervical ectopy) and sexual behavior
• Peak incidence and prevalence age 15–19 years in females, 20–24 years in males
Sex
• More reported cases in women than men, because women are screened more frequently and many men are treated without diagnostic confirmation
• True M:F incidence ratio about 1:1
Sexual Orientation
• Common in MSM, but often undiagnosed due to high frequency of undetected rectal infection
• LGV occasionally causes severe proctitis in MSM
• Also common in some WSW without male partners, probably via shared vaginal secretions
Other Risk Factors
• In the United States, strong association with low socioeconomic and education levels and with African American or Hispanic race/ethnicity (as for most STDs)
HISTORY
Incubation Period
• Usually 1–3 weeks in those who develop symptoms; range 1 week to several months
• Many infections remain subclinical
Symptoms
• Males: Urethral discharge, often scant, and dysuria, usually mild, sometimes described as urethral
itching or tingling
• Females: Vaginal discharge, dysuria, intermenstrual or postcoital vaginal bleeding, low abdominal pain; or other symptoms of urethritis, cervicitis, salpingitis, epididymitis, or conjunctivitis
Epidemiologic and Exposure History
• Presence of STD risk factors and markers enhances risk, but infection is common in their absence
• Many infections persist for months and sometimes >1 year; recent sexual history often is a poor predictor of infection
PHYSICAL EXAMINATION
• Urethral, cervical, or anal discharge, usually mucoid or mucopurulent
• Edematous cervical ectopy in women
• Other signs of urethritis, cervicitis, salpingitis, proctitis, epididymitis, and other manifestations.
• Examination is often normal
LABORATORY DIAGNOSIS
Identification of the Organism
• Test of choice is NAAT, including transcription-mediated amplification (TMA), e.g. Aptima, strand
displacement assay (SDA), e.g. ProbeTec, or polymerase chain reaction (PCR), e.g. Amplicor
• NAAT sensitivity 90–95% for cervical, vaginal, or urethral swab, and urine specificity ≥99%, with rare false-positive results∗
• TMA and SDA are reliable for rectal infection and recommended for testing MSM
• Some combination NAATs are designed to detect both N. gonorrhoeae and C. trachomatis in single
specimens
• Culture detects 70–80% of cervical and urethral infections; substantial variability among laboratories
• Nonamplified DNA probe tests (e.g. Pace II) and assays to identify C. trachomatis antigens detect <80% of infections; approved only for urethral or cervical specimens; not recommended for routine use
• Currently available rapid (point of care) tests are insensitive and not recommended for routine use
• Pharyngeal infection is uncommon and no tests currently are approved or recommended for pharyngeal testing
Serology
• Microimmunofluorescence or complement fixation antibody tests useful in diagnosis of LGV (titer
≥1:128); sometimes used in evaluation of female infertility, but positive result does not necessarily indicate current infection
• Not recommended in other clinical settings
TREATMENT
Uncomplicated Infection
REGIMENS OF CHOICE
• Doxycycline 100 mg PO bid for 7 days
• Azithromycin 1.0 g PO, single dose
ALTERNATE REGIMENS
• Levofloxacin 500 mg PO once daily for 7 days
• Ofloxacin 300 mg PO bid for 7 days
• Erythromycin base 500 mg PO qid for 7 days (reduced efficacy)
Pregnant Women
• Azithromycin 1.0 g PO, single dose
• Amoxicillin 500 mg PO qid for 7–10 days
Lymphogranuloma Venereum
• Doxycycline 100 mg PO bid for 21 days
• Erythromycin base 500 mg PO qid for 21 days
• Azithromycin 1.0 g PO once weekly for 3 weeks (limited clinical experience)
Follow-up of Uncomplicated Infection
• Persistent or recurrent infection occurs within 3–6 months in 10–15% of treated patients
• Retest all patients 3–6 months after treatment (rescreening)
• Short-term test of cure (3–4 weeks):
° When therapeutic compliance is uncertain
° Pregnant women
° Following erythromycin or other nonstandard treatment
° Do not retest with NAAT <3 weeks after treatment, due to possible persistence of chlamydial DNA
despite successful eradication
MANAGEMENT OF SEX PARTNERS
• All sex partners in preceding month, as well as all likely source partners, should be tested for C. trachomatis and treated (without awaiting test results)
• Expedited partner treatment (EPT) (e.g., patient-delivered partner treatment) is indicated when partner compliance with direct health care is uncertain
° EPT is recommended by some experts as management of choice for all partners
° When practical, partners managed with EPT still should be examined, tested, and counseled
PREVENTION
Counseling
• Emphasize importance of preventing future infections, due to enhanced risk of complications, especially in women
• Encourage monogamy, condoms, selection of sex partners at low risk, and avoidance of concurrency (overlapping partnerships)
• Describe higher risk of HIV infection in persons with bacterial STD
Screening
• Screening sexually active young women is central to prevention
• Routinely test all sexually active women ≤20 years old
• Routinely test women 21–30 years old if ≥1 sex partner, new partner, or partner with symptoms of
urethritis
• Sexually active teen boys and young men (≤30 years old) should be routinely screened when practical
• Urine or self-collected swab testing by NAAT permits screening when genital examination impractical
• Routine rectal screening of MSM who participate in receptive anal intercourse
• Screen all pregnant women
Rescreening
• Routinely retest all patients 3–6 months after treatment, and/or whenever the patient returns for routine health care
• 10–20% of infected persons have recurrent or persistent infection at 3–6 months due to reinfection,
delayed treatment failure, or poor therapeutic compliance
Reporting
• Report cases as required by local regulation
3–1. Nongonococcal urethritis due to Chlamydia trachomatis. a. Mucopurulent urethral discharge. Gram-stained urethral smear showing PMNs without ICGND.
CASE 1:
Patient Profile Age 19, single heterosexual college sophomore
History Began new sexual relationship 6 weeks earlier; prior partnership ended 2 months ago; 3 weeks’ intermittent urethral discharge without dysuria; referred by his new partner after she had positive screening test for C. trachomatis
Examination Mucopurulent discharge expressed by urethral compression
Differential Diagnosis Nongonococcal urethritis (NGU); probably chlamydial based on exposure history; gonococcal, trichomonal, and herpetic urethritis possible but unlikely
Laboratory Urethral Gram stain showed 10–15 polymorphonuclear neutrophils (PMNs) per 1000 ×
field, without ICGND; NAATs for C. trachomatis (positive) and N. gonorrhoeae (negative); VDRL and HIV antibody test (both negative)
Diagnosis Chlamydial NGU
Treatment Azithromycin 1.0 g PO, single dose, directly observed
Sex Partner Management Offered expedited partner treatment (EPT) with azithromycin and cefixime for former girlfriend, but patient declined (“I don’t see her anymore”); advised to abstain from sex with current partner until 1 week and symptoms resolved
Follow-up Advised to return in 3 months for rescreening by urine NAAT, and counseled to convey
same advice to partner
Comment Mild symptoms resulted in delayed care (3 weeks) until partner’s chlamydial infection was diagnosed.
3–2. Mucopurulent cervicitis due to Chlamydia trachomatis.
CASE 2
Patient Profile Age 17, high school junior
History Asymptomatic; presented to a public reproductive health clinic for refill of her oral contraceptive prescription; sexually active for 6 weeks with a single male partner, a local college student; a prior relationship, with a high school classmate, ended 2 months earlier
Examination Mucopurulent exudate emanating from cervical os; small area of edematous cervical
ectopy; swab-induced endocervical bleeding
Differential Diagnosis Mucopurulent cervicitis; consider C. trachomatis, N. gonorrhoeae, Mycoplasma genitalium
Laboratory Cervical Gram-stained smear showed many PMNs, without ICGND; vaginal fluid pH 4.0 with negative KOH amine odor test; no yeast, clue cells, or trichomonads seen on KOH and saline wet mounts; cervical NAATs for C. trachomatis (positive) and N. gonorrhoeae (negative); serologic tests for syphilis and HIV (negative)
Diagnosis Mucopurulent cervicitis due to C. trachomatis
Treatment Azithromycin 1.0 g PO, single dose, directly observed
Follow-up Advised to return 3 months for rescreening by NAAT on self-collected vaginal swab
Sex Partner Management Offered and accepted EPT with azithromycin for current partner, who was away at university; referred former partner to clinic, tested positive for C. trachomatis and treated.
3–3. Chlamydial conjunctivitis (compare
with gonococcal conjunctivitis,
CASE 3
Patient Profile Age 22, female flight attendant
History Mild itching of eyes for 2–3 weeks; boyfriend was treated a month earlier for “urinary tract
infection”; they continued unprotected vaginal and oral sex following his treatment; no other sex partners in the past year
Examination Conjunctiva showed hypertrophied, “cobblestone” appearance, slight erythema; genital
examination normal, including cervix
Differential Diagnosis Conjunctivitis due to C. trachomatis, N. gonorrhoeae, Haemophilus influenzae, other pyogenic bacteria, viruses, or allergy; rule out cervical C. trachomatis infection
Laboratory Gram-stained conjunctival smear showed few mononuclear cells, rare PMNs, and no bacteria; C. trachomatis indentified by NAAT from conjunctival and cervical swabs; bacterial culture of conjunctiva negative for pathogens
Diagnosis Chlamydial conjunctivitis and asymptomatic cervical chlamydial infection
Treatment Doxycycline 100 mg PO bid for 7 days
Follow-up Advised to return after 3 months for rescreening with NAAT
Sex Partner Management Advised to refer her partner for reevaluation of probable NGU, suspected
to have been misdiagnosed as urinary tract infection (UTI); patient was skeptical partner would attend and was provided EPT with azithromycin 1.0 g
Comment Compare with gonococcal conjunctivitis, Fig. 4–3; probably acquired either through
autoinoculation from genital infection or by orogenital exposure; normal cervix and absence of genital symptoms are typical of chlamydial infection.
3–4. Lymphogranuloma venereum. Note separation of right lymph nodes by the
inguinal ligament (“groove sign”). The left inguinal node had ruptured spontaneously.
CASE 4
Patient Profile Age 27, unmarried man who immigrated from Ethiopia 3 weeks earlier; multiple female commercial sex partners
History Painful swellings in groin for 3 weeks; draining pus from left side for 1 week
Examination Inguinal lymphadenopathy bilaterally, with firm, moderately tender nodes, 1.5–3 cm in
diameter; left inguinal node had central softening and an overlying eschar; right nodes were divided by the inguinal ligament (“groove sign”); no urethral discharge, genital lesions, or skin rash
Differential Diagnosis LGV, pyogenic infection, cat-scratch disease; liquefaction and drainage make
syphilis and herpes unlikely; rule out tuberculous lymphadenitis, lymphoma, and HIV-related opportunistic diseases
Laboratory Urethral NAATs for N. gonorrhoeae and C. trachomatis (both negative); syphilis and HIV serology (both negative); aspirate of left inguinal node yielded scant pus, without organisms on Gram stain; few Staphylococcus epidermidis isolated, negative NAAT for C. trachomatis; chlamydia/LGV complement fixation test titer 1:1,024
Diagnosis Lymphogranuloma venereum
Treatment Doxycycline 100 mg orally bid for 3 weeks
Follow-up Repeated needle aspiration of left inguinal node (3 times over 8 days); repeat syphilis and
HIV serology after 3 months (negative)
Sex Partner Management Patient denied identifiable sex partners
Comment Absence of detectable cutaneous primary lesion or urethritis is typical of LGV; division of
involved lymph nodes by the inguinal ligament (“groove sign”) is classic but seen in a minority of cases; repeated needle aspiration of fluctuant nodes may help prevent spontaneous rupture and secondary infection; currently the most common clinical presentation of LGV in industrialized countries is proctitis in MSM
3–5. Probable lymphogranuloma venereum.
a. Fluctuant femoral lymphadenopathy with
intense overlying cutaneous erythema and
nonspecific exfoliation at presentation. b.
Improvement after 10 days treatment with
doxycycline 100 mg orally bid. Femoral
involvement is atypical in LGV and C.
trachomatis was not isolated by culture from
lymph node aspirate or urethra; NAAT was
not available. However, the LGV complement
fixation titer was reactive at a titer of
1:512. Papular genital warts also are present
on penile shaft
REFERENCES
H. Hunter Handsfield, MD, Color Atlas & Synopsis of Sexually Transmitted Diseases, Third Edition.
COMMENTS