SECTION 2 Syndromes by Body System:

Sexually Transmitted Diseases

66 
Chlamydia trachomatis Infection
STEPHEN J. JORDAN  |  WILLIAM M. GEISLER

KEY CONCEPTS CDC, which was the highest number of cases ever reported.3 Since
1987, the number and rate of reported chlamydia cases has increased
• Chlamydia and lymphogranuloma venereum (LGV) are sexually annually (Figure 66-1). Many chlamydia cases go undiagnosed, and it
transmitted infections caused by Chlamydia trachomatis, an is estimated that 2.8 million new chlamydia infections occur annually
obligate intracellular bacterium. in the USA.4 The estimated prevalence rate among sexually active
• Most chlamydia infections are asymptomatic. Symptoms of females aged 14–19 years is 6.8%, based on national surveys conducted
genital chlamydia include discharge and dysuria and are non- from 1999 to 2008.5 Rates among women are approximately double
specific, often overlapping with symptoms caused by other that of men, which has remained stable since the early 1990s.3 Preva-
sexually transmitted infections. lence rates vary significantly by age and race/ethnicity, with peak rates
• Upper genital tract complications from chlamydia include occurring in men and women aged 15–29 years and in non-Hispanic
pelvic inflammatory disease, tubal factor infertility, and ectopic African-Americans.3 Higher chlamydia prevalence rates, often exceed-
pregnancy in women and epididymitis in men. ing 10%, are also seen in select venues, such as sexually transmitted
disease (STD) clinics, emergency rooms and correctional facilities.
• All sexually active women aged <25 years should be screened Geographically, the South East USA has the highest reported chla-
for chlamydia annually.
mydia rates.3
• All persons who test positive for chlamydia should be treated, Young age is a strong risk factor for chlamydia, with rates highest
even if they are asymptomatic, to prevent complications and in those <25 years of age. Chlamydia rates decline in persons older
transmission of the infection. than 29, but may still be higher in those with other risk factors, includ-
• Recommended treatment for uncomplicated chlamydia is ing unprotected sex with a new partner or multiple partners and
either azithromycin 1 g single dose or doxycycline 100 mg having a sex partner who has a concurrent sex partner.6 Within the
twice daily for 7 days. USA, African-American men and women have the highest rates of
chlamydia, with an eight- and six-fold higher rate compared to Cau-
• All partners of chlamydia-infected patients should be treated. casian men and women, respectively.3 Hispanics and American Indian/
• As no vaccine exists, chlamydia control efforts rely on sex Alaskan natives also are disproportionately affected. Some potential
education, screening for asymptomatic infection, treating biologic risk factors have been identified. Bacterial vaginosis (BV) has
infected patients and their partners, and retesting for chla- been associated with incident chlamydia,7 and it has been postulated
mydia approximately 3 months after treatment. that indole produced by organisms causing BV favor C. trachomatis
survival.8 Select immunologic correlates have been associated with
recurrent chlamydia and chlamydia complications, especially human
leukocyte antigen (HLA) polymorphisms. It is likely that other immu-
Introduction nogenetic factors exist that influence susceptibility and protective
Chlamydia trachomatis is an obligate intracellular bacterium that immunity to chlamydia, but have yet to be elucidated.
infects human mucosal epithelial cells of the oropharynx, genital tract,
anorectal area and conjunctiva. C. trachomatis can be classified through Pathogenesis and Pathology
molecular and serologic typing techniques into two biovars in humans: LIFE CYCLE
(1) trachoma, which causes the ocular infection ‘trachoma’ and the
non-ulcerative infection of the oropharynx, genital tract, and anorectal C. trachomatis has a unique biphasic life cycle, existing either as an
area ‘chlamydia’, and (2) lymphogranuloma venereum (LGV), which infectious, but metabolically inert form termed the elementary body
causes a distinct ulcerative infection of the genital tract and anorectal (EB) or as a metabolically active form termed the reticulate body (RB).
area ‘LGV’. Within the biovars, serologic testing has differentiated the Upon transmission of EBs into the host, they can bind to columnar
organisms into 15 different major serovars and several minor variants: epithelial cells and enter the cell through phagocytosis, pinocytosis, or
Serotypes A–C for trachoma, D–K for chlamydia and L1–L3 for LGV.1 endocytosis and exist in the intracellular environment within a special-
This chapter will focus on the sexually transmitted infection (STI) ized vacuole called an inclusion body. EBs then differentiate into RBs
chlamydia in adolescents and adults. LGV is discussed in Chapter 64. and undergo approximately 8–12 cycles of binary cell division before
Trachoma is discussed in Chapter 16. differentiating back into EBs.9 Approximately 48 hours post-infection,
anywhere from 100 to 1000 new EBs are released from the lysed epi-
thelial cell to infect adjacent cells and perpetuate the cycle (Figure
Epidemiology 66-2). This self-propagation can lead to chronic infection, which is
Chlamydia is the most prevalent bacterial STI in the USA and world- asymptomatic in the majority of infected individuals yet associated
wide. The World Health Organization estimates the global burden of inflammation can result in significant morbidity.
chlamydia at over 100 million new cases annually.2 In 2014 they
released an updated report on global STI surveillance (http://www Pathogenesis and Immunity
.who.int/reproductivehealth/publications/rtis/stis-surveillance-2013/ It has been estimated that up to 16% of untreated C. trachomatis infec-
en/) and they are developing a new five year program on HIV/STI due tion may spread to the upper genital tract (uterus, fallopian tubes,
to be released in 2016. Chlamydia is a reportable infection to the ovaries, and/or the peritoneum), collectively called pelvic inflamma-
Centers for Disease Control and Prevention (CDC), which releases tory disease (PID),10 and the associated inflammation caused by the
annual epidemiologic surveillance data on chlamydia. In 2012, there persisting infection can lead to scarring/fibrosis; this can lead to further
were over 1.4 million chlamydia infections in the USA reported to the complications, including infertility, chronic pelvic pain and risk for
597
598 SECTION 2  Syndromes by Body System: Sexually Transmitted Diseases

Chlamydia rates by sex in the United States (1992–2012)

Rate (per 100 000 750 Men

population)
Women
600 Total

450

300

150

1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012
Year

Figure 66-1  Chlamydia – rates by sex, United States, 1992–2012. (Reproduced from Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveil-
lance 2012. US Department of Health and Human Services, 2013.)

chlamydia. As a result, different animal models have been used to

Chlamydia trachomatis life cycle characterize the immune response against chlamydia. Models demon-
strate that a host can clear chlamydia without treatment and develop
protective immune response, yet protection appears short-lived. In
mice, the most extensively studied model, CD4+ T-cells
producing interferon-gamma are essential for chlamydia clearance,
while CD8+ T-cells and antibody are not essential but likely are
1 contributory.13
In humans, limited studies suggest immunity does develop. Sur-
veillance studies demonstrate chlamydia is rare in older persons.
Studies of persons with prior chlamydia or a high likelihood (e.g.,
2 6 commercial sex workers) show they have a reduced risk of re-
infection.14,15 Studies that have evaluated for chlamydia resolution in
the relatively short interval between initial chlamydia screening and
returning within weeks for treatment of a positive chlamydia test have
7 demonstrated that chlamydia spontaneously resolves without treat-
ment, presumably by immune-mediated clearance, in up to 11–44%
3 of persons;16 one such study performed repeat chlamydia testing 6
months after treatment and found that women who spontaneously
4 resolved chlamydia prior to treatment had a fourfold lower rate of
chlamydia re-infection.17 The immune mechanisms that mediate pro-
5 tective immunity to chlamydia in humans have yet to be elucidated,
but limited evidence suggests T-cells producing interferon-gamma
likely contribute to protective immunity,18 similar to the response
characterized in animal models. Even though there is no effective
chlamydia vaccine available, there remains interest in vaccine develop-
Figure 66-2  Chlamydia trachomatis life cycle. (1) Elementary bodies (EBs) attach ment; potential vaccine candidates targerts include the C. trachomatis
to and are taken up by epithelial cells. (2) EBs differentiate into reticulate bodies
(RBs). (3) RBs divide by binary fission. (4) RBs differentiate back into EBs. (5) EBs major outer membrane protein (MOMP), which comprises over 60%
are released to infect other cells. (6) Alternate course under stressful conditions of the EB surface, as well as other select membrane proteins (e.g.,
(i.e. interferon-gamma exposure), leading to large, metabolically inactive persis- polymorphic membrane proteins).
tent forms. (7) With removal of stress, persistent forms return to replication and
infectious state. (Reprinted from Mandell, Douglas, and Bennett’s Principles and
Practices of Infectious Diseases. Copyright © 2010 Elsevier Inc.) Clinical Features
C. trachomatis infection causes a diverse spectrum of clinical disease
ectopic pregnancy. The specific pathways responsible for causing (Table 66-1), which can overlap with clinical syndromes of other STIs
pathologic responses have yet to be fully characterized, however poten- (e.g., gonorrhea, trichomoniasis, bacterial vaginosis). The incubation
tial mechanisms include: (1) infected epithelial cells releasing period for chlamydia is estimated to be from 1 to 3 weeks.
proteases, clotting factors and tissue growth factors that recruit inflam-
matory cells,11 and (2) autoimmune mechanisms, such as the presence GENITAL INFECTION IN FEMALES
of antibodies against C. trachomatis heat shock protein 60 (Hsp60), In the female lower genital tract, C. trachomatis primarily infects
which shares significant homology to human Hsp60.12 columnar epithelial cells of the endocervix. Up to 70% or more of
The natural history of chlamydia in humans remains poorly under- women with endocervical chlamydia are asymptomatic.19 Symptoms
stood, in part due to the ethical concerns in studying untreated when present are nonspecific and include vaginal discharge, itching,
 Chapter 66  Chlamydia trachomatis Infection 599

TABLE
66-1  Clinical Syndromes Caused by Chlamydia
Women Men Neonates*

Urethritis Urethritis Conjunctivitis

Cervicitis Epididymitis Pharyngitis
Pelvic inflammatory Proctitis or proctocolitis Respiratory
disease Conjunctivitis* infection
Proctitis or proctocolitis Pharyngitis
Conjunctivitis* Prostatitis
Bartholinitis Reactive arthritis
Pharyngitis
Reactive arthritis

*Not discussed in this chapter.

Figure 66-4  Cloudy urethral discharge in chlamydia urethritis. (Image courtesy

of the Freedom™ Network.)

increase the risk for ectopic pregnancy. Rarely, obstruction of the fal-
lopian tube may cause fluid to accumulate, forming a hydrosalpinx. In
pregnant women, chlamydia has been associated with pre-term deliv-
ery and premature rupture of membranes.21 Chlamydia can be trans-
mitted to neonates upon passage through the birth canal, which can
lead to conjunctivitis and/or pneumonia.

GENITAL INFECTION IN MALES

In the male genital tract, C. trachomatis causes urethritis and rarely
epididymitis, although up to 90% of men with urethral chlamydia are
believed to be asymptomatic.19 The most common symptom of lower
genital tract infection in men is dysuria, and other symptoms may
include increased urinary frequency, meatal itching/discomfort, and/
Figure 66-3  Mucopurulent endocervical discharge in cervicitis, which can be
caused by chlamydia. (Image courtesy of the Seattle STD/HIV Prevention Training
or a clear, cloudy, or purulent urethral discharge. The majority of men
Center.) with chlamydia will have a normal genital examination, but meatal
erythema and/or swelling may be noted with or without urethral dis-
charge (Figure 66-4). The urethra may need to be stripped to express
pain on intercourse (dyspareunia) and intermenstrual bleeding. On discharge at the meatus. Nongonococcal urethritis is caused by chla-
examination, up to 90% of women with asymptomatic endocervical mydia in 15–40% of cases, with lower rates occurring in older males.6
chlamydia will have a normal-appearing cervix.20 Asymptomatic or As in women, males with signs of urethral infection are often misdi-
symptomatic women with chlamydia may have cervical findings of agnosed as having a urinary tract infection (UTI), an uncommon
friability (bleeding easily induced with endocervical swab insertion) occurrence in men with normal urologic anatomy. Urethritis in sexu-
and/or discharge that can be cloudy or purulent (Figure 66-3). C. ally active young men should be presumed to be sexually transmitted,
trachomatis infection of the lower genital tract may also involve the with appropriate testing and treatment.
urethra or Bartholin’s glands, the former occurring in the majority of C. trachomatis can ascend to the epididymis and cause epididymitis,
women with endocervical chlamydia. Some women with chlamydia which typically presents as unilateral scrotal/testicular pain that may
urethritis present with an acute urethral syndrome, characterized by be associated with scrotal erythema, tenderness and/or swelling of the
dysuria (painful urination), urinary frequency and/or pyuria, which testicle/epididymis, and/or low-grade fever. On examination of the
sometimes is misdiagnosed as a urinary tract infection and treated scrotal contents, testicular swelling may be present (Figure 66-5), as
with antibiotics ineffective against chlamydia (e.g., trimethoprim– well as erythema, warmth and/or swelling of the overlying scrotum.
sulfamethoxazole or ciprofloxacin). Infection of the Bartholin’s glands Swelling and/or tenderness of the epididymis is usually present. Epi-
may cause ductal erythema and swelling, often with a purulent exudate. didymitis may be complicated by chronic testicular pain and/or infer-
C. trachomatis infection may ascend to the upper genital tract tility and rarely testicular abscess. Chlamydia prostatitis has been
causing PID, which can be asymptomatic or cause nonspecific symp- reported, but is exceedingly rare.
toms, including mild to severe pelvic and/or abdominal pain, dyspa-
reunia, intermenstrual bleeding, nausea, vomiting and/or fever. PID is RECTAL AND OROPHARYNGEAL CHLAMYDIA
usually diagnosed clinically based on bimanual examination findings In both men and women, C. trachomatis can infect the mucosal
of cervical motion tenderness, fundal tenderness and/or adnexal ten- surfaces of the rectum and oropharynx. Rectal chlamydia may
derness. Chronic salpingitis may lead to tubal-factor infertility and occur in women who do not engage in anal sex, presumably through
600 SECTION 2  Syndromes by Body System: Sexually Transmitted Diseases

TABLE CDC-Recommended Treatment for

66-2  Uncomplicated Chlamydia
Men/Nonpregnant Women Pregnant Women
Preferred: Preferred:
Azithromycin 1 g po x 1 dose Azithromycin 1 g po x 1 dose

or

Doxycycline 100 mg po twice daily

x 7 days

Alternative: Alternative:
Erythromycin 500 mg po four times Amoxicillin 500 mg po three times
daily x 7 days daily x 7 days

or or

Levofloxacin 500 mg po daily x Erythromycin 500 mg po four

7 days times daily x 7 days

or

Ofloxacin 300 mg po twice daily x

7 days

po, per os.

Figure 66-5  Unilateral testicular swelling in chlamydia epididymitis. (Image cour-
Reproduced from Centers for Disease Control and Prevention: Sexually
tesy of the Freedom™ Network.)
Transmitted Diseases Treatment Guidelines, 2015. MMWR Morb Mortal Wkly
Rep 2015; 64:1-138.

cross-contamination with vaginal secretions.22 Most anorectal infec- limited availability and sensitivity of the assay was only fair (60–80%).
tions are asymptomatic, but may result in anal pain, pruritus, bleeding, Earlier non-culture tests based on detection of non-amplified C. tra-
diarrhea and/or an anorectal discharge. On anorectal examination, chomatis antigen or nucleic acids were less technically demanding than
anorectal erythema, discharge and/or occasional ulceration may be culture, which allowed more widespread screening, however most had
noted. Chlamydia proctitis may be mistaken for inflammatory bowel lower test sensitivities. Highly sensitive nucleic acid amplification tests
disease. (NAATs) became available in the mid- to late 1990s and are now the
Little is known about the clinical significance of oropharyngeal recommended test for C. trachomatis detection. Compared with
chlamydia, and routine chlamydia screening of the oropharynx is not culture testing on urethral and cervical swabs, the current NAATs have
recommended. Most oropharyngeal infections are asymptomatic, with equally high specificity (>99%) but a much higher sensitivity (up to
sore throat being the most common symptom reported.23 On exami- 95% or higher) for these specimens.27 Also, NAAT can be performed
nation, pharyngeal erythema may be rarely noted. Because findings on a wider range of specimens (including urine and vaginal swabs),
from recent research studies suggest oropharyngeal chlamydia can be making it possible to test for chlamydia when genital examination is
sexually transmitted to genital sites,24,25 it is recommended that oro- not feasible. The CDC-recommended sample for chlamydia screening6
pharyngeal chlamydia be treated if detected. is first-catch urine in men, and a vaginal swab, either provider- or
self-collected, in women. NAAT is also the recommended assay for
REACTIVE ARTHRITIS anorectal and oropharyngeal chlamydia testing, but because the assay
Reactive arthritis is a rare complication of genital chlamydia. It is is not yet approved by the US Food and Drug Administration for use
characterized by an aseptic rheumatoid factor-negative asymmetric on these specimens, laboratories conducting such testing have estab-
polyarthritis that may be accompanied by conjunctivitis, a rash of the lished performance specifications when evaluating rectal or oropha-
extremities (keratoderma blennorrhagica), and/or painless oral ulcers. ryngeal swab specimens for C. trachomatis to meet CLIA (Clinical
Men may have a rash on the penile head (balanitis circinata). More Laboratory Improvement Amendments) regulatory requirements
rare clinical findings include uveitis and cardiac and/or neurologic prior to reporting results to clinical providers.
disease. The syndrome may develop as soon as 1–3 weeks after infec-
tion.26 There is a male predominance (>2 : 1) and the majority of cases
are associated with the HLA-B27 genotype.26 Management
Effective management of chlamydia involves a multifaceted approach.
Diagnosis In addition to promptly providing recommended antibiotic therapy,
Diagnosis of C. trachomatis infection in asymptomatic persons – the counseling and education aimed at preventing re-infection should be
majority of those with chlamydia – relies on performing a screening given and all sexual partners should be treated. In men and women
test to detect C. trachomatis. CDC recommends annual chlamydia with a chlamydia-associated syndrome, empiric treatment should be
screening in sexually active women aged <25 years and older women provided promptly, before results of diagnostic testing.
with risk factors (e.g., those who have a new sex partner or multiple
sex partners, and those reporting their sex partner may have a concur- ANTIBIOTIC THERAPY
rent sex partner); chlamydia screening in men is recommended for Uncomplicated Chlamydia
those in high chlamydia prevalence venues (e.g., STD clinics, correc- The CDC-recommended preferred and alternative antibiotic regimens
tional facilities).6 Because the symptoms and examination findings of for uncomplicated urogenital, anorectal and oropharyngeal chlamydia
C. trachomatis infection can overlap with those caused by other STIs, are listed in Table 66-2.6 A previous meta-analysis of 12 randomized
confirmation of chlamydia in individuals with symptoms or signs also controlled trials (RCTs) demonstrated that azithromycin and doxycy-
relies on detection of the organism. cline regimens were both highly efficacious for urogenital chlamydia,
Until the mid-1980s, culture was considered the gold standard for with cure rates of 97% and 98%, respectively.28 For anorectal chla-
C. trachomatis diagnosis, but it required technical expertise, had mydia, recent observational studies suggest that azithromycin may
 Chapter 66  Chlamydia trachomatis Infection 601

be associated with a lower cure rate, although there are no RCTs

for rectal chlamydia yet to confirm this.29 In patients who are at TABLE CDC-Recommended Treatment for Chlamydia
66-3  Complications
high risk for treatment nonadherence, the azithromycin regimen is
usually preferred as complete treatment can be given promptly as
directly observed therapy. Oropharyngeal chlamydia is treated with OUTPATIENT TREATMENT OF PELVIC INFLAMMATORY DISEASE
the same treatment regimens as genital and anorectal chlamydia as Doxycycline 100 mg po twice daily x 14 days
there are insufficient data to otherwise guide treatment. No changes plus either
in the treatment regimens are recommended for HIV-infected
patients. (1) Ceftriaxone 250 mg im x 1 dose
Gastrointestinal symptoms, including diarrhea, nausea and dys- or
pepsia, are common with all of the CDC-recommended chlamydia
(2) Cefoxitin 2 g im x 1 dose with probenecid 1 g po x 1 dose
treatment regimens. Azithromycin and doxycycline regimens should
be taken with food to minimize gastrointestinal side effects. Levofloxa- or
cin and ofloxacin may cause QT prolongation and should be avoided (3) Other parenteral third-generation cephalosporin (e.g. ceftizoxime or
in patients with this condition or at risk. Doxycycline can cause a cefotaxime)
photosensitivity reaction to sun and its use should either be avoided
in patients with frequent sun exposure or appropriate precautions with/without
taken. Metronidazole 500 mg po twice daily x 14 days
A pregnancy test should precede chlamydia treatment in women in
INPATIENT TREATMENT OF PELVIC INFLAMMATORY DISEASE
whom pregnancy is a possible concern as doxycycline and quinolones
should be avoided in pregnant patients. The CDC-recommended Regimen A
treatment regimens for chlamydia in pregnant women are listed in Doxycycline 100 mg po/iv every 12 hours
Table 66-2.6 Because there is concern that amoxicillin may induce C. plus either
trachomatis persistence, which has been demonstrated to occur in vitro
and in animals,30,31 and because treatment nonadherence with eryth- (1) Cefotetan 2 g iv every 12 hours
romycin regimens is high to due gastrointestinal side effects, the or
azithromycin regimen is the preferred treatment.
(2) Cefoxitin 2 g iv every 6 hours
Chlamydia Complications Regimen B
PID and epididymitis, both diagnosed based on clinical findings, are Clindamycin 900 mg iv every 8 hours
usually empirically treated before chlamydia is confirmed by testing.
For PID, a decision must be made on whether outpatient treatment is plus
appropriate or if hospitalization for parenteral antibiotics is warranted. Gentamicin loading dose iv/im (2 mg/kg body weight), followed by
In addition to provider judgment, the CDC recommends inpatient maintenance dose (1.5 mg/kg) every 8 hours
admission if women with PID are pregnant, cannot tolerate oral out-
OUTPATIENT TREATMENT OF EPIDIDYMITIS*
patient therapy, have failed outpatient treatment, have a severe illness,
have complicating factors (e.g., tubo-ovarian abscess), or if a surgical Doxycycline 100 mg po twice daily x 10 days
emergency (e.g., appendicitis) cannot be ruled out.6 Epididymitis plus
rarely requires inpatient admission, with the exception of outpatient
treatment failure or a complication (e.g., testicular abscess). Ceftriaxone 250 mg im x 1 dose
The CDC-recommended outpatient treatment regimens for PID
im, intramuscular; iv, intravascular; po, per os.
and epididymitis are shown in Table 66-3.6 Patients should be *Inpatient treatment of epididymitis is rarely required: consult with specialist.
instructed to return if clinical improvement (e.g., defervescence, Reproduced from Centers for Disease Control and Prevention: Sexually
decrease in pain) does not occur within 72 hours, in which case inpa- Transmitted Diseases Treatment Guidelines, 2015. MMWR Morb Mortal Wkly
tient admission would be appropriate for outpatient treatment failure. Rep 2015; 64:1-138.
Inpatient treatment regimens for PID are shown in Table 66-3.6
Parenteral antibiotic regimens can be converted to oral regimens after
24 hours of clinical improvement. Oral therapy with doxycycline tice of providing treatment to a patient’s partner without the partner
100 mg twice daily or clindamycin 450 mg four times daily should be having to be seen by a clinician, thereby expediting treatment. This
continued for 14 days of total therapy (based on whichever antibiotic usually entails a clinician giving the patient a packet for them to give
was used in the initial parenteral regimen). Azithromycin is not cur- to their partner (or each of their partners) that contains azithromycin
rently part of the recommended treatment regimens for PID or pills (totaling 1 g of azithromycin) and possibly medication instruc-
epididymitis due to the limited azithromycin efficacy data for these tions, condoms and/or an information sheet/pamphlet on chlamydia.
complications. EPT is widely accepted by most patients and their partners and evi-
dence suggests it may decrease the rate of chlamydia re-infections.32
MANAGEMENT OF SEX PARTNERS However, legal, financial and regulatory hurdles have delayed wide-
Patients should be instructed to refer their sex partners for evaluation, spread adoption in the USA. Currently in the USA, EPT may be per-
testing and treatment if they have had sexual contact within the past mitted in up to 35 states and appears to be either prohibited or only
60 days. The most recent sexual contact should receive testing and potentially allowable in 15 states and the District of Columbia (see
treatment, even if the time since the last sexual contact was >60 days http://www.cdc.gov/std/ept for updated information).
prior to symptoms or diagnosis. Partners of patients with chlamydia Repeat chlamydia detection within months of treatment is rarely
should receive CDC-recommended treatment for uncomplicated due to treatment failure, rather it usually results from repeat infection
chlamydia. from exposure to an untreated partner or a new partner with chla-
The two primary approaches to partner treatment are partner mydia. Patients should abstain from sexual intercourse until both they
referral and expedited partner therapy (EPT). Partner referral involves and their partners have been treated. Abstinence should be continued
the clinician recommending to the patient that he or she informs their for a full 7 days after single-dose therapy or until the full multidose
partner(s) that they may have been exposed to chlamydia and should regimen has been completed. Prompt partner treatment is essential in
go to a clinician for chlamydia testing and treatment. EPT is the prac- reducing risk for re-infection.
602 SECTION 2  Syndromes by Body System: Sexually Transmitted Diseases

PATIENT FOLLOW-UP does not prevent chlamydia. Unfortunately, although it is highly effec-
A test-of-cure is not recommended for chlamydia-infected men and tive and recommended for primary prevention of STIs, obtaining a
nonpregnant women unless symptoms persist or treatment adherence sexual history and asking about high-risk behaviors is not routinely
is in question. However, repeat chlamydia testing at approximately 3 done by many primary care providers. A survey of family physicians
months after treatment is recommended for all men and women diag- showed that only 18% routinely obtained a sexual history from patients
nosed with chlamydia as re-infection has been reported in up to and fewer than 20% routinely obtained information regarding high-
10–20% within months after treatment.33,34 If retesting at 3 months is risk activities.36 Since the highest proportion of chlamydia infections
not possible, clinicians should retest whenever persons return for care reported to the CDC are from private physicians/health maintenance
in the 1–12 months following treatment.6 organization (HMO) providers,3 primary care providers have a major
In pregnant women, a chlamydia test-of-cure is recommended at role in primary prevention of chlamydia. The mainstay of chlamydia
approximately 3–4 weeks after treatment as persistent chlamydia may prevention, however, involves secondary prevention: identification,
increase risk for maternal and fetal complications.6,35 Repeat chlamydia treatment and prevention of chlamydia re-infection in the index
testing earlier than 3 weeks increases the possibility of a false-positive patient and their sexual partner(s). This is done through CDC-
result due to the highly sensitive NAAT detecting residual nucleic acids recommended chlamydia screening and testing recommendations,
of nonviable C. trachomatis organisms that have not completely cleared timely treatment of patients and their partners, sex education regard-
from the urogenital tract. ing abstinence until treatment is complete and then the benefit of
barrier precautions for chlamydia prevention, and repeat chlamydia
Prevention testing at approximately 3 months after treatment. Globally, and in
particular in low- and middle-income countries, the challenges and
As no effective chlamydia vaccine is available at this time, prevention the response to them are somewhat different, WHO has very recently
efforts target reducing risk factors for chlamydia acquisition through published their new Global Strategy for Women’s, Children’s and Ado-
both primary and secondary prevention. Primary prevention involves lescent’s health 2016–2030, which provide prevention of STI, such as
STI education and screening for high-risk sexual behavior and coun- chlamydia.
seling on the use of barrier protection methods (e.g., condoms) to
prevent chlamydia. It should be stressed that hormonal-based contra- References available online at expertconsult.com.
ception (e.g., oral contraceptives, depot medroxyprogesterone acetate)

KEY REFERENCES
Blas M.M., Canchihuaman F.A., Alva I.E., et al.: Pregnancy Gaydos C.A., Cartwright C.P., Colaninno P., et al.: Perfor- randomized clinical trials. Sex Transm Dis 2002; 29:
outcomes in women infected with Chlamydia trachoma- mance of the Abbott RealTime CT/NG for detection of 497-502.
tis: a population-based cohort study in Washington State. Chlamydia trachomatis and Neisseria gonorrhoeae. J Clin Rank R.G., Whittum Hudson J.A.: Protective immunity to
Sex Transm Infect 2007; 83:314-318. Microbiol 2010; 48(9):3236-3243. chlamydial genital infection: evidence from animal
Centers for Disease Control and Prevention: Sexually Trans- Geisler W.M.: Duration of untreated, uncomplicated Chla- studies. J Infect Dis 2010; 201:168-177.
mitted Disease Surveillance 2012. Washington, DC: US mydia trachomatis genital infection and factors associated Shiely F., Hayes K., Thomas K.K., et al.: Expedited partner
Department of Health and Human Services; 2013. with chlamydia resolution: a review of human studies. therapy: a robust intervention. Sex Transm Dis 2010;
Centers for Disease Control and Prevention: Sexually J Infect Dis 2010; 201:104-113. 37:602-607.
transmitted diseases treatment guidelines, 2015. MMWR Hosenfeld C.B., Workowski K.A., Berman S., et al.: Repeat
Morb Mortal Wkly Rep 2015; 64:1-138. Available: www infection with chlamydia and gonorrhea among females:
.cdc.gov/std/tg2015/tg-2015-print.pdf. a systematic review of the literature. Sex Transm Dis 2009;
Farley T.A., Cohen D.A., Elkins W.: Asymptomatic sexually 36:478-489.
transmitted diseases: the case for screening. Prev Med Lau C.-Y., Qureshi A.K.: Azithromycin versus doxycycline
2003; 36:502-509. for genital chlamydial infections: a meta-analysis of
 Chapter 66  Chlamydia trachomatis Infection 602.e1

REFERENCES
1. Yuan Y., Zhang Y.X., Watkins N.G., et al.: Nucleotide 13. Rank R.G., Whittum Hudson J.A.: Protective immunity who have sex with men. Clin Infect Dis 2009; 49:1793-
and deduced amino acid sequences for the four variable to chlamydial genital infection: evidence from animal 1797.
domains of the major outer membrane proteins of the studies. J Infect Dis 2010; 201:168-177. 25. Marcus J.L., Kohn R.P., Barry P.M., et al.: Chlamydia
15 Chlamydia trachomatis serovars. Infect Immun 1989; 14. Katz B.P., Batteiger B.E., Jones R.B.: Effect of prior trachomatis and Neisseria gonorrhoeae transmission
57:1040-1049. sexually transmitted disease on the isolation of Chla- from the female oropharynx to the male urethra. Sex
2. World Health Organization (WHO): Global incidence mydia trachomatis. Sex Transm Dis 1987; 14:160- Transm Dis 2011; 38:372-373.
and prevalence of selected curable sexually transmitted 164. 26. Barth W.F., Segal K.: Reactive arthritis (Reiter’s syn-
infections – 2008. Geneva: WHO; 2012. 15. Brunham R.C., Kimani J., Bwayo J., et al.: The epide- drome). Am Fam Physician 1999; 60:499-503, 507.
3. Centers for Disease Control and Prevention: Sexually miology of Chlamydia trachomatis within a sexually 27. Gaydos C.A., Cartwright C.P., Colaninno P., et al.: Per-
Transmitted Disease Surveillance 2012. Washington, transmitted diseases core group. J Infect Dis 1996; formance of the Abbott RealTime CT/NG for detection
DC: US Department of Health and Human Services; 173:950-956. of Chlamydia trachomatis and Neisseria gonorrhoeae.
2013. 16. Geisler W.M.: Duration of untreated, uncomplicated J Clin Microbiol 2010; 48(9):3236-3243.
4. National Center for HIV/AIDS, Viral Hepatitis, STD, Chlamydia trachomatis genital infection and factors 28. Lau C.-Y., Qureshi A.K.: Azithromycin versus doxycy-
and TB Prevention (US): Incidence, prevalence, and cost associated with chlamydia resolution: a review of cline for genital chlamydial infections: a meta-analysis
of sexually transmitted infections in the United States. human studies. J Infect Dis 2010; 201:104-113. of randomized clinical trials. Sex Transm Dis 2002;
Atlanta, GA: CDC; 2013. 17. Geisler W.M., Lensing S.Y., Press C.G., et al.: Spontane- 29:497-502.
5. Centers for Disease Control and Prevention: CDC ous resolution of genital Chlamydia trachomatis infec- 29. Jordan S.J., Geisler W.M.: Azithromycin for rectal chla-
Grand Rounds: Chlamydia prevention: challenges and tion in women and protection from reinfection. J Infect mydia: is it time to leave azithromycin on the shelf? …
strategies for reducing disease burden and sequelae. Dis 2013; 207:1850-1856. Not yet. Sex Transm Dis 2014; 41:86-88.
MMWR Morb Mortal Wkly Rep 2011; 60:370-373. 18. Cohen C.R., Koochesfahani K.M., Meier A.S., et al.: 30. Mpiga P., Ravaoarinoro M.: Chlamydia trachomatis
6. Centers for Disease Control and Prevention: Sexually Immunoepidemiologic profile of Chlamydia trachoma- persistence: an update. Microbiol Res 2006; 161:9-19.
transmitted diseases treatment guidelines, 2015. tis infection: importance of heat-shock protein 60 and 31. Phillips Campbell R., Kintner J., Schoborg R.V.: Induc-
MMWR Morb Mortal Wkly Rep 2015; 64:1-138. Avail- interferon-γ. J Infect Dis 2005; 192:591-599. tion of the Chlamydia muridarum stress/persistence
able: www.cdc.gov/std/tg2015/tg-2015-print.pdf. 19. Farley T.A., Cohen D.A., Elkins W.: Asymptomatic response increases azithromycin treatment failure in a
7. Brotman R.M., Klebanoff M.A., Nansel T.R., et al.: Bac- sexually transmitted diseases: the case for screening. murine model of infection. Antimicrob Agents Che-
terial vaginosis assessed by gram stain and diminished Prev Med 2003; 36:502-509. mother 2014; 58:1782-1784.
colonization resistance to incident gonococcal, chla- 20. Geisler W.M., Chow J.M., Schachter J., et al.: Pelvic 32. Shiely F., Hayes K., Thomas K.K., et al.: Expedited
mydial, and trichomonal genital infection. J Infect Dis examination findings and Chlamydia trachomatis infec- partner therapy: a robust intervention. Sex Transm Dis
2010; 202:1907-1915. tion in asymptomatic young women screened with a 2010; 37:602-607.
8. Caldwell H.D., Wood H., Crane D., et al.: Polymor- nucleic acid amplification test. Sex Transm Dis 2007; 33. Hosenfeld C.B., Workowski K.A., Berman S., et al.:
phisms in Chlamydia trachomatis tryptophan synthase 34:335-338. Repeat infection with chlamydia and gonorrhea among
genes differentiate between genital and ocular isolates. 21. Blas M.M., Canchihuaman F.A., Alva I.E., et al.: Preg- females: a systematic review of the literature. Sex
J Clin Invest 2003; 111:1757-1769. nancy outcomes in women infected with Chlamydia Transm Dis 2009; 36:478-489.
9. Moulder J.W.: Interaction of chlamydiae and host cells trachomatis: a population-based cohort study in Wash- 34. Dunne E.F., Chapin J.B., Rietmeijer C.A., et al.: Rate
in vitro. Microbiol Rev 1991; 55:143-190. ington State. Sex Transm Infect 2007; 83:314-318. and predictors of repeat Chlamydia trachomatis infec-
10. Price M.J., Ades A.E., De Angelis D., et al.: Risk of pelvic 22. Barry P.M., Kent C.K., Philip S.S., et al.: Results of a tion among men. Sex Transm Dis 2008; 35:S40-S44.
inflammatory disease following Chlamydia trachomatis program to test women for rectal chlamydia and gonor- 35. Liu B., Roberts C.L., Clarke M., et al.: Chlamydia and
infection: analysis of prospective studies with a multi- rhea. Obstet Gynecol 2010; 115:753-759. gonorrhoea infections and the risk of adverse obstetric
state model. Am J Epidemiol 2013; 178:484-492. 23. Dudareva-Vizule S., Haar K., Sailer A., et al.: Prevalence outcomes: a retrospective cohort study. Sex Transm
11. Darville T., Hiltke T.J.: Pathogenesis of genital tract of pharyngeal and rectal Chlamydia trachomatis and Infect 2013; 89:672-678.
disease due to Chlamydia trachomatis. J Infect Dis 2010; Neisseria gonorrhoeae infections among men who have 36. McCance K.L., Moser R., Smith K.R.: A survey of phy-
201:114-125. sex with men in Germany. Sex Transm Infect 2014; sicians’ knowledge and application of AIDS prevention
12. Cappello F., Conway de Macario E., Di Felice V., et al.: 90:46-51. capabilities. Am J Prev Med 1991; 7:141-145.
Chlamydia trachomatis infection and anti-Hsp60 24. Bernstein K.T., Stephens S.C., Barry P.M., et al.: Chla-
immunity: the two sides of the coin. PLoS Pathog 2009; mydia trachomatis and Neisseria gonorrhoeae transmis-
5:e1000552. sion from the oropharynx to the urethra among men