1442 PART 5 Infectious Diseases

schools, and summer camps. Infections tend to be endemic, with sporadic epidemics every 4–7 years.

Most significantly, M. pneumoniae is a major cause of communityacquired respiratory illness in both children and adults and is often

grouped with Chlamydia pneumoniae and Legionella species as one of

the most important bacterial causes of “atypical” community-acquired

pneumonia. For community-acquired pneumonia in adults, M. pneumoniae is the most frequently detected “atypical” organism. Analysis of

13 studies of community-acquired pneumonia published between 1996

to 2001 (which included 6207 ambulatory and hospitalized adults)

showed that the overall prevalence of M. pneumoniae was 22.7%; by

comparison, the prevalence of C. pneumoniae was 11.7%, and that of

Legionella species was 4.6%. The summation of 26 more recent investigations of “atypical” organisms in community-acquired pneumonia in

adults published between 2002 to 2015 found the overall prevalence of

M. pneumoniae was 7.2%; by comparison, the prevalence of C. pneumoniae was 4.3%, and that of Legionella species was 2.8%. M. pneumoniae

pneumonia is also referred to as Eaton agent pneumonia (the organism

having first been isolated in the early 1940s by Monroe Eaton), primary

atypical pneumonia, and “walking” pneumonia.

■ CLINICAL MANIFESTATIONS

Upper Respiratory Tract Infections and Pneumonia Acute

M. pneumoniae infections generally manifest as pharyngitis, tracheobronchitis, reactive airway disease/wheezing, or a nonspecific upper

respiratory syndrome. Little evidence supports the commonly held

belief that this organism is an important cause of otitis media, with or

without bullous myringitis. Pneumonia develops in 3–13% of infected

individuals; its onset is usually gradual, occurring over several days,

but may be more abrupt. Although Mycoplasma pneumonia may begin

with a sore throat, the most common presenting symptom is cough.

The cough is typically nonproductive, but some patients produce sputum. Headache, malaise, chills, and fever are noted in the majority of

patients.

On physical examination, wheezes or rales are detected in ~80% of

patients with M. pneumoniae pneumonia. In many patients, however,

pneumonia can be diagnosed only by chest radiography. The most

common radiographic pattern is that of peribronchial pneumonia with

thickened bronchial markings, streaks of interstitial infiltration, and

areas of subsegmental atelectasis. Segmental or lobar consolidation is

not uncommon. While clinically evident pleural effusions are infrequent, lateral decubitus views reveal that up to 20% of patients have

pleural effusions.

Overall, the clinical presentation of pneumonia in an individual

patient is not useful for differentiating M. pneumoniae pneumonia

from other types of community-acquired pneumonia. The possibility

of M. pneumoniae infection deserves particular consideration when

community-acquired pneumonia fails to respond to treatment with a

penicillin or a cephalosporin—antibiotics that are ineffective against

mycoplasmas. Symptoms usually resolve within 2–3 weeks after the

onset of illness. Although M. pneumoniae pneumonia is generally

self-limited, appropriate antimicrobial therapy significantly shortens

the duration of clinical illness. Infection uncommonly results in critical

illness and only rarely in death. In some patients, long-term recurrent

wheezing or reactive airway disease may follow the resolution of acute

pneumonia. The significance of chronic infection, especially as it

relates to asthma, is an area of active investigation.

Extrapulmonary Manifestations An array of extrapulmonary

manifestations may develop during M. pneumoniae infection. The

most significant are neurologic, dermatologic, cardiac, rheumatologic,

and hematologic in nature. Extrapulmonary manifestations can be a

result of disseminated infection, especially in patients with humoral

immunodeficiencies (e.g., septic arthritis); postinfectious autoimmune phenomena (e.g., Guillain-Barré syndrome); or possibly ADPribosylating toxin. Overall, these manifestations are uncommon, given

the frequency of M. pneumoniae infection. Notably, many patients

with extrapulmonary M. pneumoniae disease do not have respiratory

disease.

TABLE 188-1 Diagnostic Tests for Respiratory Mycoplasma

pneumoniae Infectiona

TEST SENSITIVITY, % SPECIFICITY, %

Respiratory culture ≤60 100

Respiratory PCR 65–90 90–100

Serologic studiesb 55–100 55–100

a

A combination of PCR and serology is suggested for routine diagnosis. If macrolide

resistance is suspected, resistance testing by culture and/or PCR is available.

b

Acute- and convalescent-phase serum samples are recommended.

Abbreviation: PCR, polymerase chain reaction.

Skin eruptions described with M. pneumoniae infection include

erythematous (macular or maculopapular), vesicular, bullous, petechial, and urticarial rashes. In some reports, 17% of patients with

M. pneumoniae pneumonia have had an exanthem. Erythema multiforme major (Stevens-Johnson syndrome) is the most clinically

significant skin eruption associated with M. pneumoniae infection; it

appears to occur more commonly with M. pneumoniae than with other

infectious agents.

A wide spectrum of neurologic manifestations has been reported

with M. pneumoniae infection. The most common are meningoencephalitis, encephalitis, Guillain-Barré syndrome, and aseptic meningitis. M. pneumoniae has been implicated as a likely etiologic agent in

5–7% of cases of encephalitis. Other neurologic manifestations may

include cranial neuropathy, acute psychosis, cerebellar ataxia, acute

demyelinating encephalomyelitis, cerebrovascular thromboembolic

events, and transverse myelitis.

Hematologic manifestations of M. pneumoniae infection include

hemolytic anemia, aplastic anemia, cold agglutinins, disseminated

intravascular coagulation, and hypercoagulopathy. When anemia does

occur, it generally develops in the second or third week of illness.

In addition, hepatitis, glomerulonephritis, pancreatitis, myocarditis,

pericarditis, rhabdomyolysis, and arthritis (septic and reactive) have been

convincingly ascribed to M. pneumoniae infection. Septic arthritis has

been described most commonly in hypogammaglobulinemic patients.

■ DIAGNOSIS

Clinical findings, nonmicrobiologic laboratory tests, and chest radiography are not useful for differentiating M. pneumoniae pneumonia

from other types of community-acquired pneumonia. In addition,

since M. pneumoniae lacks a cell wall, it is not visible on Gram’s stain.

Although of historical interest, the measurement of cold agglutinin

titers is no longer recommended for the diagnosis of M. pneumoniae

infection because the findings are nonspecific and assays specific for

M. pneumoniae are now available.

Acute M. pneumoniae infection can be diagnosed by polymerase

chain reaction (PCR) detection of the organism in respiratory tract

secretions or by isolation of the organism in culture (Table 188-1).

Oropharyngeal, nasopharyngeal, and pulmonary specimens are all

acceptable for diagnosing M. pneumoniae pneumonia. Other bodily

fluids, such as cerebrospinal fluid, are acceptable for extrapulmonary

infection. M. pneumoniae culture (which requires special media) is not

recommended for routine diagnosis because the organism may take

weeks to grow and is often difficult to isolate from clinical specimens.

In contrast, PCR allows rapid, specific diagnosis earlier in the course

of clinical illness.

The diagnosis can also be established by serologic tests for IgM and IgG

antibodies to M. pneumoniae in paired (acute- and convalescent-phase)

serum samples; enzyme-linked immunoassay is the recommended

serologic method. An acute-phase sample alone is not adequate for

diagnosis, as antibodies to M. pneumoniae may not develop until

2 weeks into the illness; therefore, it is important to test paired samples.

In addition, IgM antibody to M. pneumoniae can persist for up to 1 year

after acute infection. Thus its presence may indicate recent rather than

acute infection.

The combination of PCR of respiratory tract secretions and serologic testing constitutes the most sensitive and rapid approach to the

diagnosis of M. pneumoniae infection.

1443CHAPTER 188 Infections Due to Mycoplasmas

TABLE 188-2 Antimicrobial Agents of Choice for Mycoplasma

Infectionsa

ORGANISM(S) DRUGS

Mycoplasma pneumoniae Azithromycin, clarithromycin, erythromycin,

doxycycline, levofloxacin, moxifloxacin,

gemifloxacin (not ciprofloxacin or ofloxacin)

Ureaplasma urealyticum,

Ureaplasma parvum

Azithromycin, clarithromycin, erythromycin,

doxycycline

Mycoplasma hominis Doxycycline, clindamycin

Mycoplasma genitalium Azithromycin, moxifloxacin

a

Antimicrobial resistance has been reported in mycoplasmas, as described

in the text.

TREATMENT

Mycoplasma pneumoniae Infections

Although in the majority of untreated cases symptoms resolve

within 2–3 weeks without significant associated morbidity, M.

pneumoniae pneumonia can be a serious illness that responds to

appropriate antimicrobial therapy (Table 188-2). Randomized,

double-blind, placebo-controlled trials in adults have demonstrated

that antimicrobial treatment significantly decreases the duration

of fever, cough, malaise, hospitalization, and radiologic abnormalities in M. pneumoniae pneumonia. Treatment options for acute

M. pneumoniae infection include macrolides (e.g., oral azithromycin,

500 mg on day 1, then 250 mg/d on days 2–5), tetracyclines (e.g.,

oral doxycycline, 100 mg twice daily for 7–14 days), and respiratory

fluoroquinolones. However, ciprofloxacin and ofloxacin are not

recommended because of their high minimal inhibitory concentrations against M. pneumoniae isolates and their poor performance

in experimental studies. A 7- to 14-day course of quinolone therapy appears adequate. Even though appropriate antibiotic therapy

significantly reduces the duration of respiratory illness, it does not

appear to shorten the duration of detection of M. pneumoniae by culture or PCR; therefore, a test of cure or eradication is not suggested.

In Japan and China, very high levels (up to ≥90%) of M. pneumoniae resistance to macrolides have been reported. In Europe

and to a lesser degree in the United States, macrolide-resistant M.

pneumoniae is emerging. In the United States, national surveillance

from 2018 found that 10.2% of isolates demonstrated macrolide

resistance. Furthermore, national surveillance from 2015–2018

found macrolide resistance of 15.2–21.7% in the eastern United

States and 1.9–2.8% in the western United States. Clinical studies

have demonstrated that, when treated with macrolides, patients

with community-acquired pneumonia due to macrolide-resistant

M. pneumoniae experience a significantly longer duration of symptoms than do patients infected with macrolide-sensitive organisms;

thus macrolide resistance in M. pneumoniae does appear to have

clinical significance. If macrolide resistance is prominent in a particular geographic locale or is suspected, then a nonmacrolide antibiotic

should be considered for treatment; in addition, in these instances, a

respiratory sample may be sent to a mycoplasma reference laboratory

for the detection of macrolide resistance by culture or PCR.

While the 2019 Infectious Diseases Society of America and

American Thoracic Society guidelines do not recommend routinely

using corticosteroids in community-acquired pneumonia, some

clinical literature suggests that the addition of glucocorticoids to

an antibiotic regimen may be of value for the treatment of severe

or refractory M. pneumoniae pneumonia. A 2019 meta-analysis

of 24 randomized controlled trials in children found that use of

corticosteroids in macrolide-refractory M. pneumoniae pneumonia

significantly reduced hospital days and duration of fever. Clinical

literature in adults also shows benefit, but these data are limited and

more observational in nature.

The roles of antimicrobial drugs, glucocorticoids, and IV immunoglobulin in the treatment of neurologic disease due to M. pneumoniae remain unknown.

UROGENITAL MYCOPLASMAS

■ EPIDEMIOLOGY

M. hominis, M. genitalium, U. urealyticum, and U. parvum can cause

urogenital tract disease. The significance of isolation of these organisms in a variety of other syndromes is unknown and in some cases is

being investigated. M. fermentans has not been shown convincingly to

cause human disease.

While urogenital mycoplasmas may be transmitted to a fetus during

passage through a colonized birth canal, sexual contact is the major

mode of transmission, and the risk of colonization increases dramatically with increasing numbers of sexual partners. In asymptomatic

women, these mycoplasmas may be found throughout the lower urogenital tract. The vagina yields the largest number of organisms; next

most densely colonized are the periurethral area and the cervix. Ureaplasmas are isolated less often from urine than from the cervix, but

M. hominis is found with approximately the same frequency at these

two sites. Ureaplasmas are isolated from the vagina of 40–80% of sexually active, asymptomatic women and M. hominis from 21–70%. The

two microorganisms are found concurrently in 31–60% of women. In

men, colonization with each organism is less prevalent. Mycoplasmas

have been isolated from urine, semen, and the distal urethra of asymptomatic men.

■ CLINICAL MANIFESTATIONS

Urethritis, Pyelonephritis, and Urinary Calculi In many

episodes of Chlamydia-negative nongonococcal urethritis, ureaplasmas

may be the causative agent. These organisms may also cause chronic

voiding symptoms in women. The common presence of ureaplasmas in

the urethra of asymptomatic men may suggest either that only certain

serovars are pathogenic or that predisposing factors, such as lack of

immunity, must exist in persons who develop symptomatic infection.

Alternatively, disease may develop only upon initial exposure to ureaplasmas. Ureaplasmas have been implicated in epididymitis. M. genitalium also appears to cause urethritis. M. genitalium and ureaplasmas

do not have a known role in prostatitis. M. hominis does not appear to

play a primary etiologic role in urethritis, epididymitis, or prostatitis.

Evidence suggests that M. hominis causes up to 5% of cases of acute

pyelonephritis. Ureaplasmas have not been associated with this disease.

Ureaplasmas play a limited role in the production of urinary calculi.

The frequency with which ureaplasmas reach the kidney, the predisposing factors that allow them to do so, and the relative frequency of

urinary tract calculi induced by this organism (compared with other

organisms) are not known.

Pelvic Inflammatory Disease M. hominis can cause pelvic

inflammatory disease. In most episodes, M. hominis occurs as part of

a polymicrobial infection, but the organism may play an independent

role in a limited number of cases. Data also support an association of

M. genitalium with pelvic inflammatory disease. Ureaplasmas are not

thought to cause pelvic inflammatory disease.

Postpartum and Postabortal Infection Studies implicate

M. hominis as the primary pathogen in ~5–10% of women who have

postpartum or postabortal fever; ureaplasmas have been implicated to

a lesser degree. These infections are generally self-limited; however, if

symptoms persist, specific antimicrobial therapy should be given. Ureaplasmas also appear to play a role in occasional postcesarean wound

infections.

Nonurogenital Infection In rare instances, M. hominis causes

nonurogenital infections, such as brain abscess, wound infection,

poststernotomy mediastinitis, endocarditis, and neonatal meningitis.

These infections are most common among immunocompromised

and hypogammaglobulinemic patients. Ureaplasmas and M. hominis

can cause septic arthritis in immunodeficient patients. Ureaplasmas

probably cause neonatal pneumonitis; their possible causal role in

the development of bronchopulmonary dysplasia—the chronic lung

disease of premature infants—has been extensively investigated, with

1444 PART 5 Infectious Diseases

most studies indicating at least a significant association. It is unclear

whether ureaplasmas and M. hominis cause infertility, spontaneous

abortion, premature labor, low birth weight, or chorioamnionitis.

■ DIAGNOSIS

Culture and PCR are both appropriate methods for the isolation of

urogenital mycoplasmas. Culture of these organisms, however, requires

special techniques and media that generally are available only at larger

medical centers and reference laboratories. Serologic testing is not

recommended for the clinical diagnosis of urogenital Mycoplasma

infections.

TREATMENT

Urogenital Mycoplasma Infections

Because colonization with urogenital mycoplasmas is common,

it appears at present that their isolation from the urogenital tract

in the absence of disease generally does not warrant treatment.

Macrolides and doxycycline are considered the antimicrobial agents

of choice for Ureaplasma infections (Table 188-2). Ureaplasma

resistance to macrolides, doxycycline, quinolones, and chloramphenicol has been reported. M. hominis is resistant to macrolides.

Doxycycline is generally the drug of choice for M. hominis infections, although resistance has been reported. Clindamycin is generally active against M. hominis. Quinolones are active in vitro against

M. hominis. For M. genitalium, the initial treatment of choice

appears to be azithromycin; moxifloxacin has been successfully

used to treat M. genitalium resistant to azithromycin.

■ FURTHER READING

Getman D et al: Mycoplasma genitalium prevalence, coinfection, and

macrolide antibiotic resistance frequency in a multicenter clinical

study cohort in the United States. J Clin Microbiol 54:2278, 2016.

Waites KB et al: Mycoplasma pneumoniae from the respiratory tract

and beyond. Clin Microbiol Rev 30:747, 2017.

Waites KB et al: Macrolide-resistant Mycoplasma pneumoniae in the

United States as determined from a national surveillance program.

J Clin Microbiol 57:e00968, 2019.

Workowski KA, Bolan GA: Sexually transmitted diseases treatment

guidelines, 2015. MMWR Recomm Rep 64:1, 2015.

Chlamydiae are obligate intracellular bacteria that cause a wide variety

of diseases in humans and animals.

ETIOLOGIC AGENTS

The chlamydiae were originally classified as four species in the genus

Chlamydia: C. trachomatis, C. pneumoniae, C. psittaci, and C. pecorum

(the last species being found in ruminants). The C. psittaci group has

been separated into three species: C. psittaci, C. felis, and C. abortus.

The mouse pneumonitis strain (MoPn) is now classified as C. muridarum, and the guinea pig inclusion conjunctivitis strain (GPIC) is now

designated C. caviae.

C. trachomatis is divided into two biovars: trachoma and LGV

(lymphogranuloma venereum). The trachoma biovar causes two

major types of disease in humans: ocular trachoma, the leading infectious cause of preventable blindness in the developing world; and

urogenital infections, which are sexually or neonatally transmitted.

The 18 serovars of C. trachomatis fall into three groups: the trachoma

189 Chlamydial Infections

Charlotte A. Gaydos, Thomas C. Quinn

FIGURE 189-1 Chlamydial intracellular inclusions filled with smaller dense

elementary bodies and larger reticulate bodies. (Reprinted with permission from WE

Stamm: Chlamydial infections, in Harrison’s Principles of Internal Medicine, 17th ed,

AS Fauci et al [eds]. New York, McGraw-Hill, 2008, p 1070.)

serovars A, B, Ba, and C; the oculogenital serovars D–K; and the LGV

serovars L1

–L3

. Serovars can be distinguished by serologic typing with

monoclonal antibodies or by molecular gene typing. However, serovar

identification usually is not important clinically, since the antibiotic

susceptibility pattern is the same for all three groups. The one exception applies when LGV is suspected on clinical grounds; in this situation, serovar determination is important because a longer treatment

duration is required for LGV strains.

BIOLOGY, GROWTH CYCLE,

AND PATHOGENESIS

■ BIOLOGY

During their intracellular growth, chlamydiae produce characteristic

intracytoplasmic inclusions that can be visualized by direct fluorescent antibody or Giemsa staining of infected clinical material, such as

conjunctival scrapings or cervical or urethral epithelial cells. Chlamydiae are nonmotile, gram-negative, obligate intracellular bacteria that

replicate within the cytoplasm of host cells, forming the characteristic

membrane-bound inclusions that are the basis for some diagnostic

tests. Originally considered to be large viruses, chlamydiae differ from

viruses in possessing RNA and DNA as well as a cell wall that is quite

similar in structure to the cell wall of typical gram-negative bacteria.

However, chlamydiae lack peptidoglycan; their structural integrity

depends on disulfide binding of outer-membrane proteins.

■ GROWTH CYCLE

Among the defining characteristics of chlamydiae is a unique growth

cycle that involves alternation between two highly specialized morphologic forms (Figs. 189-1 and 189-2): the elementary body, which is the

infectious form and is specifically adapted for extracellular survival,

and the metabolically active and replicating reticulate body, which is

not infectious, is adapted for an intracellular environment, and does

1445CHAPTER 189 Chlamydial Infections

1. Uptake of

 chlamydial EBs

2. Initial inclusions

3. Fusion of inclusions;

 appearance of RBs

4. Multiplication of RBs;

 enlargement of inclusion

7. Persistence associated

 with IFN-γ exposure;

 large aberrant RBs

5. Conversion of

 RBs to EBs

6. Release

 of EBs

8. Return to normal

 cycle with IFN-γ

 removal

Cell membrane

Cell cytoplasm

Cell nucleus

FIGURE 189-2 Chlamydial life cycle. EBs, elementary bodies; IFN-γ, interferon γ;

RBs, reticulate bodies. (Reproduced with permission from WE Stamm: Chlamydial

infections, in AS Fauci et al [eds]: Harrison’s Principles of Internal Medicine,

17th ed. New York, McGraw-Hill, 2008.)

not survive well outside the host cell. The biphasic growth cycle begins

with attachment of the elementary body (diameter, 0.25–0.35 μm) at

specific sites on the surface of the host cell. The elementary body enters

the cell through a process similar to receptor-mediated endocytosis

and resides in an inclusion, where the entire growth cycle is completed.

The chlamydiae prevent phagosome–lysosome fusion. The inclusion

membrane is modified by insertion of chlamydial antigens. Once the

elementary body has entered the cell, it reorganizes into a reticulate

body, which is larger (0.5–1 μm) and contains more RNA. After ~8 h,

the reticulate body starts to divide by binary fission. The intracytoplasmic, membrane-bound inclusion body containing the reticulate bodies

increases in size as the reticulate bodies multiply. Approximately 18–24 h

after infection of the cell, these reticulate bodies begin to become

elementary bodies by a reorganization or condensation process that is

poorly understood. After rupture of the inclusion body, the elementary

bodies are released to initiate another cycle of infection.

Chlamydiae are susceptible to many broad-spectrum antibiotics and

possess a number of enzymes, but they have a very restricted metabolic

capacity. None of these metabolic reactions result in the production of

energy. Chlamydiae have thus been considered to be energy parasites

that use the ATP produced by the host cell for their own metabolic

functions. Many aspects of chlamydial molecular biology are not well

understood, but the sequencing of several chlamydial genomes and

new proteomics research have provided researchers with many relevant

tools for elucidating the biology of the life cycle.

■ PATHOGENESIS

Genital infections are primarily caused by C. trachomatis serovars D–K,

with serovars D, E, and F involved most frequently. Molecular typing of

the major outer-membrane protein gene (omp1) from which serovar differences arise has been used to demonstrate that polymorphisms can occur

in isolates from patients who are exposed frequently to multiple infections, while less variation is observed in isolates from less sexually active

populations. Polymorphisms in the major outer-membrane protein may

provide antigenic variation, and the different forms allow persistence in the

community because immunity to one is not protective against the others.

The trachoma biovar is essentially a parasite of squamocolumnar

epithelial cells; the LGV biovar is more invasive and involves lymphoid

cells. As is typical of chlamydiae, C. trachomatis strains are capable of

causing chronic, clinically inapparent, asymptomatic infections. Because

the duration of the chlamydial growth cycle is ~48–72 h, the incubation period of sexually transmitted chlamydial infections is relatively

long—generally 1–3 weeks. C. trachomatis causes cell death as a result

of its replicative cycle and can induce cell damage whenever it persists.

However, few toxic effects are demonstrated, and cell death because of

chlamydial replication is not sufficient to account for disease manifestations, the majority of which are due to immunopathologic mechanisms

or nonspecific host responses to the organism or its by-products.

In recent years, the entire genomes of various chlamydial species

have been sequenced, the field of proteomics has become established, host innate immunity has been more precisely delineated,

and innovative host cell–chlamydial interaction studies have been

conducted. As a result, many insights have been gained into how

chlamydiae adapt and replicate in their intracellular environment and

produce disease. These insights into pathogenesis include information

on the regulation of gene expression, protein localization, the type III

secretion system, the roles of CD4+ and CD8+ T lymphocytes in the

host response, and T lymphocyte trafficking.

The chlamydial heat-shock protein, which shares antigenic epitopes

with similar proteins of other bacteria and with human heat-shock

protein, may sensitize the host, and repeated infections may cause host

cell damage. Persistent or recurrent chlamydial infections are associated with fibrosis, scarring, and complications following simple squamocolumnar epithelial infections. A common endpoint of these late

consequences is scarring of mucous membranes. Genital complications

can lead to pelvic inflammatory disease (PID) and its late consequences

of infertility, ectopic pregnancy, and chronic pelvic pain, while ocular

infections may lead to blinding trachoma. High levels of antibody

to human heat-shock protein have been associated with tubal factor

infertility and ectopic pregnancy. Without adequate therapy, chlamydial infections may persist for several years, although symptoms—if

present—usually abate.

Pathogenic mechanisms of C. pneumoniae have yet to be completely

elucidated. The same is true for C. psittaci, except that this agent infects

cells very efficiently and causes disease that may reflect direct cytopathic

effects.

C. TRACHOMATIS INFECTIONS

■ GENITAL INFECTIONS (SEE ALSO CHAP. 136)

Spectrum Although chlamydiae cause a number of human diseases, localized lower genital tract infections caused by C. trachomatis

and the sequelae of such infections are the most important in terms

of medical and economic impact. Oculogenital infections due to

C. trachomatis serovars D–K are transmitted during sexual contact or

from mother to baby during childbirth and are associated with many

syndromes, including cervicitis, salpingitis, acute urethral syndrome,

endometritis, ectopic pregnancy, infertility, and PID in female patients;

urethritis, proctitis, and epididymitis in male patients; and conjunctivitis and pneumonia in infants. Women bear the greatest burden of

morbidity because of the serious sequelae of these infections. Untreated

infections lead to PID, and multiple episodes of PID can lead to tubal

factor infertility and chronic pelvic pain. Studies estimate that up to

80–90% of women and >50% of men with C. trachomatis genital infections lack symptoms; other patients have very mild symptoms. Thus,

a large reservoir of infected persons continues to transmit infection to

sexual partners.

As their designations reflect, the LGV serovars (L1

, L2

, and L3

) cause

LGV, an invasive sexually transmitted disease (STD) characterized by

acute lymphadenitis with bubo formation and/or acute hemorrhagic

proctitis (see “LGV,” below).

Epidemiology • GLOBAL EPIDEMIOLOGY C. trachomatis genital

infections are global in distribution. The World Health Organization

(WHO) estimates that in 2016, 124.3 million new cases of chlamydia

occurred among adults and adolescents aged 15–49 years worldwide,

with a global incidence rate for chlamydia in 2016 to be 34 cases per

1446 PART 5 Infectious Diseases

1000 women (95% uncertainty interval [UI], 25–45) and 33 per 1000 men

(95% UI, 21–48) This figure makes chlamydial infection the most

prevalent bacterial sexually transmitted infection in the world. The

associated morbidity is substantial, and the economic cost is high.

U.S. EPIDEMIOLOGY In the United States, these infections are the

most commonly reported of all infectious diseases. In 2018, 1,758,668

cases were reported to the U.S. Centers for Disease Control and Prevention (CDC); however, the CDC estimates that 2–3 million new

cases occur per year, with substantial underreporting due to lack of

screening in some populations. Rates of infection have increased every

year; higher rates among women than among men reflect the focus on

expansion of screening programs for women during the past 25 years.

Use of increasingly sensitive diagnostic nucleic acid amplification tests,

an increased emphasis on case reporting, and improvements in the

information systems used have elevated the number of cases reported

every year. The CDC and other professional organizations recommend

annual screening of all sexually active women <25 years of age as well

as rescreening of previously infected individuals at 3 months. The 2018

case count corresponds to 539.9 cases per 100,000 population. Women

have the highest infection rates (692.7 cases per 100,000) compared

to the rate among men (380.6 cases per 100,000). Interestingly, with

the increased availability of urine testing and extragenital testing,

men—including gay, bisexual, and other men who have sex with men

(MSM)—are increasingly being tested for chlamydial infection. From

2017 to 2018, rates of chlamydial infection in men increased by 5.7%,

whereas rates in women rose by only 1.3% for age 15–19 years and 0.8%

for age 20–24 years during this period. Chlamydial infection rates vary

among different racial and ethnic minority populations.

The aforementioned statistics are based on case reporting. Studies

based on screening surveys estimate that the U.S. prevalence of C. trachomatis cervical infection is 5% among asymptomatic female college

students and prenatal patients, >10% for women seen in family planning clinics, and >20% for women seen in STD clinics. The prevalence

of genital C. trachomatis infections varies substantially by geographic

locale, with the highest rates in the southeastern United States. The

prevalence of C. trachomatis in the cervix of pregnant women is 5–10

times higher than that of Neisseria gonorrhoeae. The prevalence of

genital infection with either agent is highest among women who are

between the ages of 20 and 24. Recurrent infections are common

in these risk groups and are often acquired from untreated sexual

partners. The use of oral contraception and the presence of cervical

ectopy also confer an increased risk. The proportion of infections that

are asymptomatic appears to be higher for C. trachomatis than for

N. gonorrhoeae, and symptomatic C. trachomatis infections are clinically

less severe. Mild or asymptomatic C. trachomatis infections of the fallopian tubes nonetheless cause ongoing tubal damage and infertility.

The costs of C. trachomatis infections and their complications to the

U.S. health care system have recently been estimated to be >$516.7 million

annually.

Clinical Manifestations • NONGONOCOCCAL AND POSTGONOCOCCAL URETHRITIS C. trachomatis is the most common cause of nongonococcal urethritis (NGU) and postgonococcal urethritis (PGU).

The designation PGU refers to NGU developing in men 2–3 weeks

after treatment of gonococcal urethritis with single doses of agents

such as penicillin or cephalosporins, which lack antimicrobial activity

against chlamydiae. Current treatment regimens for gonorrhea have

evolved and now include combination therapy with ceftriaxone and

azithromycin; this current regimen is effective against concomitant

chlamydial infection. Thus, both the incidence of PGU and the causative role of C. trachomatis in this syndrome have declined.

In the United States, most of the estimated 2 million cases of acute

urethritis are NGU, and C. trachomatis is implicated in 30–50% of these

cases. The cause of most of the remaining cases of NGU is uncertain,

but recent evidence suggests that Mycoplasma genitalium, Trichomonas

vaginalis, and herpes simplex virus (HSV) cause some cases. The rate

of involvement of C. trachomatis in urethral infection ranges from

3–7% among asymptomatic men to 15–20% among symptomatic men

attending STD clinics. One recent multisite study of men in Baltimore,

Seattle, Denver, and San Francisco reported an overall chlamydial

prevalence of 7% in urine samples assessed by nucleic acid amplification tests (NAATs)—molecular tests that amplify the nucleic acids

in clinical specimens. As in women, infection in men is age related,

with young age as the greatest risk factor for chlamydial urethritis.

The prevalence among men is highest at 20–24 years of age. In STD

clinics, urethritis is usually less prevalent among MSM than among

heterosexual men.

NGU is diagnosed by documentation of a leukocyte urethral exudate and by exclusion of gonorrhea by Gram’s staining or culture. C.

trachomatis urethritis is generally less severe than gonococcal urethritis, although in any individual patient, these two forms of urethritis

cannot reliably be differentiated solely on clinical grounds. Symptoms

include urethral discharge (often whitish and mucoid rather than

frankly purulent), dysuria, and urethral itching. Physical examination

may reveal meatal erythema and tenderness as well as a urethral exudate that is often demonstrable only by stripping of the urethra.

At least one-third of male patients with C. trachomatis urethral infection have no evident signs or symptoms of urethritis. The availability

of NAATs for first-void urine specimens has facilitated broader-based

testing for asymptomatic infection in male patients. As a result,

asymptomatic chlamydial urethritis has been demonstrated in 5–10%

of sexually active male adolescents screened at school-based clinics or

community centers. Such patients generally have pyuria (≥15 leukocytes per 400× microscopic field in the sediment of first-void urine), a

positive leukocyte esterase test, or an increased number of leukocytes

on a Gram-stained smear prepared from a urogenital swab inserted

1–2 cm into the anterior urethra. When specific diagnostic tests for

chlamydiae are not available, the examination of an endourethral specimen for increased leukocytes is useful in differentiating between true

urethritis and functional symptoms in symptomatic patients or in making a presumptive diagnosis of C. trachomatis infection in high-risk

but asymptomatic men (e.g., male patients in STD clinics, sex partners

of women with nongonococcal salpingitis or mucopurulent cervicitis,

fathers of children with inclusion conjunctivitis). Alternatively, urethritis can be assayed noninvasively by examination of a first-void urine

sample for pyuria, either by microscopy or by the leukocyte esterase

test. Urine (or a urethral swab) can also be tested directly for chlamydiae by DNA amplification methods (NAATs), as described below

(see “Detection Methods”).

EPIDIDYMITIS Chlamydial urethritis may be followed by acute epididymitis, but this condition is rare, generally occurring in sexually

active patients <35 years of age; in older men, epididymitis is usually

associated with gram-negative bacterial infection and/or instrumentation procedures. An estimated 50–70% of cases of acute epididymitis

are caused by C. trachomatis. The condition usually presents as unilateral scrotal pain with tenderness, swelling, and fever in a young man,

often occurring in association with chlamydial urethritis. The illness

may be mild enough to treat with oral antibiotics on an outpatient basis

or severe enough to require hospitalization and parenteral therapy.

Testicular torsion should be excluded promptly by radionuclide scan,

Doppler flow study, or surgical exploration in a teenager or young adult

who presents with acute unilateral testicular pain without urethritis.

The possibility of testicular tumor or chronic infection (e.g., tuberculosis) should be excluded when a patient with unilateral intrascrotal pain

and swelling does not respond to appropriate antimicrobial therapy.

REACTIVE ARTHRITIS Reactive arthritis consists of conjunctivitis,

urethritis (or, in female patients, cervicitis), arthritis, and characteristic

mucocutaneous lesions. It may develop in 1–2% of cases of NGU and

is thought to be the most common type of peripheral inflammatory

arthritis in young men. C. trachomatis has been recovered from the

urethra of 16–44% of patients with reactive arthritis and 69% of men

who have signs of urogenital inflammation at the time of examination.

Antibodies to C. trachomatis have also been detected in 46–67% of

patients with reactive arthritis, and Chlamydia-specific cell-mediated

immunity has been documented in 72%. In addition, C. trachomatis

has been isolated from synovial biopsy samples from 15 of 29 patients

in a number of small series and from a smaller proportion of synovial

1447CHAPTER 189 Chlamydial Infections

fluid specimens. Chlamydial nucleic acids have been identified in synovial membranes and chlamydial elementary bodies in joint fluid. The

pathogenesis of reactive arthritis is unclear, but this condition probably represents an abnormal host response to a number of infectious

agents, including those associated with bacterial gastroenteritis (e.g.,

Salmonella, Shigella, Yersinia, or Campylobacter), or to infection with

C. trachomatis or N. gonorrhoeae. Since >80% of affected patients have

the HLA-B27 phenotype and since other mucosal infections produce

an identical syndrome, chlamydial infection is thought to initiate an

aberrant hyperreactive immune response that produces inflammation

of the involved target organs in these genetically predisposed individuals. Evidence of exaggerated cell-mediated and humoral immune

responses to chlamydial antigens in reactive arthritis supports this

hypothesis. The finding of chlamydial elementary bodies and DNA in

joint fluid and synovial tissue from patients with reactive arthritis suggests that chlamydiae may actually spread from genital to joint tissues

in these patients—perhaps in macrophages.

NGU is the initial manifestation of reactive arthritis in 80% of

patients, typically occurring within 14 days after sexual exposure. The

urethritis may be mild and may even go unnoticed by the patient.

Similarly, gonococcal urethritis may precede reactive arthritis, but

co-infection with an agent of NGU is difficult to rule out. The urethral

discharge may be purulent or mucopurulent, and patients may or may

not report dysuria. Accompanying prostatitis, usually asymptomatic,

has been described. Arthritis usually begins ~4 weeks after the onset

of urethritis but may develop sooner or, in a small percentage of

cases, may actually precede urethritis. The knees are most frequently

involved; next most commonly affected are the ankles and small joints

of the feet. Sacroiliitis, either symmetrical or asymmetrical, is documented in two-thirds of patients. Mild bilateral conjunctivitis, iritis,

keratitis, or uveitis is sometimes present but lasts for only a few days.

Finally, dermatologic manifestations occur in up to 50% of patients.

The initial lesions—usually papules with a central yellow spot—most

often involve the soles and palms and, in ~25% of patients, eventually epithelialize and thicken to produce keratoderma blenorrhagicum. Circinate balanitis is usually painless and occurs in fewer than

half of patients. The initial episode of reactive arthritis usually lasts

2–6 months.

PROCTITIS Primary anal or rectal infections with C. trachomatis have

been described in women and MSM who practice anal intercourse. In

these infections, rectal involvement is initially characterized by severe

anorectal pain, a bloody mucopurulent discharge, and tenesmus.

Oculogenital serovars D–K and LGV serovars L1

, L2

, and L3

 have been

found to cause proctitis. The LGV serovars are far more invasive and

cause much more severely symptomatic disease, including severe ulcerative proctocolitis that can be clinically confused with HSV proctitis.

Histologically, LGV proctitis may resemble Crohn’s disease in that

giant cell formation and granulomas are detected. In the United States

and Europe, cases of LGV proctitis occur almost exclusively in MSM,

many of whom have HIV infection.

The less invasive non-LGV serovars of C. trachomatis cause mild

proctitis. Many infected individuals are asymptomatic, and in these

cases, infection is diagnosed only by routine culture or NAAT of

rectal swabs. The number of fecal leukocytes is usually abnormal

in both asymptomatic and symptomatic cases. Sigmoidoscopy may

yield normal findings or may reveal mild inflammatory changes or

small erosions or follicles in the lower 10 cm of the rectum. Histologic

examination of rectal biopsies generally shows anal crypts and prominent follicles as well as neutrophilic infiltration of the lamina propria.

Chlamydial proctitis is best diagnosed by isolation of C. trachomatis

from the rectum and documentation of a response to appropriate therapy. NAATs are reportedly more sensitive than culture for diagnosis

and are also specific.

MUCOPURULENT CERVICITIS Although most women with chlamydial infections of the cervix have no symptoms, almost half generally have local signs of infection on examination. Cervicitis is

usually characterized by the presence of a mucopurulent discharge, with

>20 neutrophils per microscopic field visible in strands of cervical

mucus in a thinly smeared, Gram-stained preparation of endocervical

exudate. Hypertrophic ectopy of the cervix may also be evident as an

edematous area near the cervical os that is congested and bleeds easily

on minor trauma (e.g., when a specimen is collected with a swab). A

Papanicolaou smear shows increased numbers of neutrophils as well

as a characteristic pattern of mononuclear inflammatory cells, including plasma cells, transformed lymphocytes, and histiocytes. Cervical

biopsy shows a predominantly mononuclear cell infiltrate of the subepithelial stroma. Clinical experience and collaborative studies indicate

that a cutoff of >30 polymorphonuclear leukocytes (PMNs)/1000×

field in a Gram-stained smear of cervical mucus correlates best with

chlamydial or gonococcal cervicitis.

Clinical recognition of chlamydial cervicitis depends on a high

index of suspicion and careful cervical examination. No genital symptoms are specifically correlated with chlamydial cervical infection. The

differential diagnosis of a mucopurulent discharge from the endocervical canal in a young, sexually active woman includes gonococcal

endocervicitis, salpingitis, endometritis, and intrauterine contraceptive

device–induced inflammation. Diagnosis of cervicitis is based on the

presence of PMNs on a cervical swab as noted above; the presence of

chlamydiae is confirmed by either culture or NAAT.

PELVIC INFLAMMATORY DISEASE Inflammation of sections of the

fallopian tube is often referred to as salpingitis or PID. The proportion

of acute salpingitis cases caused by C. trachomatis varies geographically

and with the population studied. It has been estimated that C. trachomatis causes up to 50% of PID cases in the United States. PID occurs via

ascending intraluminal spread of C. trachomatis or N. gonorrhoeae from

the lower genital tract. Mucopurulent cervicitis is often followed by

endometritis, endosalpingitis, and finally pelvic peritonitis. Evidence

of mucopurulent cervicitis is often found in women with laparoscopically verified salpingitis. Similarly, endometritis, demonstrated by an

endometrial biopsy showing plasma cell infiltration of the endometrial

epithelium, is documented in most women with laparoscopy-verified

chlamydial (or gonococcal) salpingitis. Chlamydial endometritis can

also occur in the absence of clinical evidence of salpingitis. Histologic

evidence of endometritis has been correlated with a syndrome consisting

of vaginal bleeding, lower abdominal pain, and uterine tenderness in the

absence of adnexal tenderness. Chlamydial salpingitis produces milder

symptoms than gonococcal salpingitis and may be associated with less

marked adnexal tenderness. Thus, mild adnexal or uterine tenderness in

a sexually active woman with cervicitis suggests chlamydial PID.

Chronic untreated endometrial and tubal inflammation can result in

tubal scarring, impaired tubal function, tubal occlusion, and infertility

even among women who report no prior treatment for chlamydial

infection. C. trachomatis has been particularly implicated in “subclinical” PID on the basis of a lack of history of PID among Chlamydiaseropositive women with tubal damage and detection of chlamydial

DNA or antigen among asymptomatic women with tubal infertility.

These data suggest that the best method to prevent PID and its sequelae

is surveillance and control of lower genital tract infections along with

diagnosis and treatment of sex partners and prevention of reinfections.

Promotion of early symptom recognition and health care presentation

may reduce the frequency and severity of sequelae of PID.

PERIHEPATITIS Fitz-Hugh–Curtis syndrome was originally described

as a complication of gonococcal PID. However, studies over the past

several decades have suggested that chlamydial infection is more commonly associated with perihepatitis than is N. gonorrhoeae. Perihepatitis should be suspected in young, sexually active women who develop

right-upper-quadrant pain, fever, or nausea. Evidence of salpingitis

may or may not be found on examination. Frequently, perihepatitis

is strongly associated with extensive tubal scarring, adhesions, and

inflammation observed at laparoscopy, and high titers of antibody to

the 57-kDa chlamydial heat-shock protein have been documented.

Culture and/or serologic evidence of C. trachomatis is found in threefourths of women with this syndrome.

URETHRAL SYNDROME IN WOMEN In the absence of infection with

uropathogens such as coliforms or Staphylococcus saprophyticus,

C. trachomatis is the pathogen most commonly isolated from college

1448 PART 5 Infectious Diseases

women with dysuria, frequency, and pyuria. Screening studies can

recover C. trachomatis at both the cervix and the urethra; in up to 25%

of infected women, the organism is isolated only from the urethra.

The urethral syndrome in women consists of dysuria and frequency

in conjunction with chlamydial urethritis, pyuria, and no bacteriuria

or urinary pathogens. Although symptoms of the urethral syndrome

may develop in some women with chlamydial infection, the majority

of women attending STD clinics for urethral chlamydial infection do

not have dysuria or frequency. Even in women with chlamydial urethritis causing the acute urethral syndrome, signs of urethritis such as

urethral discharge, meatal redness, and swelling are uncommon. However, mucopurulent cervicitis in a woman presenting with dysuria

and frequency strongly suggests C. trachomatis urethritis. Other correlates of chlamydial urethral syndrome include a duration of dysuria

of >7–10 days, lack of hematuria, and lack of suprapubic tenderness.

Abnormal urethral Gram’s stains showing >10 PMNs/1000× field in

women with dysuria but without coliform bacteriuria support the

diagnosis of chlamydial urethritis. Other possible diagnoses include

gonococcal or trichomonal infection of the urethra.

INFECTION IN PREGNANCY AND THE NEONATAL PERIOD Infections

during pregnancy can be transmitted to infants during delivery.

Approximately 20–30% of infants exposed to C. trachomatis in the

birth canal develop conjunctivitis, and 10–15% subsequently develop

pneumonia. Consequently, all newborn infants receive ocular prophylaxis at birth to prevent ophthalmia neonatorum. Without treatment,

conjunctivitis usually develops at 5–19 days of life and often results in

a profuse mucopurulent discharge. Roughly half of infected infants

develop clinical evidence of inclusion conjunctivitis. However, it is

impossible to differentiate chlamydial conjunctivitis from other forms

of neonatal conjunctivitis (e.g., that due to N. gonorrhoeae, Haemophilus influenzae, Streptococcus pneumoniae, or HSV) on clinical

grounds; thus, laboratory diagnosis is required. Inclusions within epithelial cells are often detected in Giemsa-stained conjunctival smears,

but these smears are considerably less sensitive than cultures or NAATs

for chlamydiae. Gram-stained smears may show gonococci or occasional small gram-negative coccobacilli in Haemophilus conjunctivitis,

but smears should be accompanied by cultures or NAATs for these

agents.

C. trachomatis has also been isolated frequently and persistently

from the nasopharynx, rectum, and vagina of infected infants—occasionally for >1 year in the absence of treatment. In some cases, otitis

media results from perinatally acquired chlamydial infection. Pneumonia may develop in infants from 2 weeks to 4 months of age. C. trachomatis is estimated to cause 20–30% of pneumonia cases in infants

<6 months of age. Epidemiologic studies have linked chlamydial pulmonary infection in infants with increased occurrence of subacute lung

disease (bronchitis, asthma, wheezing) in later childhood.

LYMPHOGRANULOMA VENEREUM C. trachomatis serovars L1

, L2

, and

L3

 cause LGV, an invasive systemic STD. The peak incidence of LGV

corresponds with the age of greatest sexual activity: the second and

third decades of life. The worldwide incidence of LGV is falling, but

the disease is still endemic and a major cause of morbidity in parts of

Asia, Africa, South America, and the Caribbean. LGV is rare in industrialized countries; for more than a decade, the reported incidence in

the United States has been only 0.1 case per 100,000 population. In the

Bahamas, an apparent outbreak of LGV was described in association

with a concurrent increase in heterosexual infection with HIV. Reports

of outbreaks with the newly identified variant L2b in Europe, Australia,

and the United States indicate that LGV is becoming more prevalent

among MSM. These cases have usually presented as hemorrhagic

proctocolitis in HIV-positive men. More widespread use of NAATs for

identification of rectal infections may have enhanced case recognition.

LGV begins as a small painless papule that tends to ulcerate at the

site of inoculation, often escaping attention. This primary lesion heals

in a few days without scarring and is usually recognized as LGV only in

retrospect. LGV strains of C. trachomatis have occasionally been recovered from genital ulcers and from the urethra of men and the endocervix of women who present with inguinal adenopathy; these areas

may be the primary sites of infection in some cases. Proctitis is more

common among people who practice receptive anal intercourse, and an

elevated white blood cell count in anorectal smears may predict LGV

in these patients. Ulcer formation may facilitate transmission of HIV

infection and other sexually transmitted and blood-borne diseases.

As NAATs for C. trachomatis are being used more often, increasing numbers of cases of LGV proctitis are being recognized in MSM,

including HIV-infected MSM. Such patients present with anorectal

pain and mucopurulent, bloody rectal discharge. Sigmoidoscopy

reveals ulcerative proctitis or proctocolitis, with purulent exudate

and mucosal bleeding. Histopathologic findings in the rectal mucosa

include granulomas with giant cells, crypt abscesses, and extensive

inflammation. These clinical, sigmoidoscopic, and histopathologic

findings may closely resemble those of Crohn’s disease of the rectum.

The most common presenting picture in heterosexual men and

women is the inguinal syndrome, which is characterized by painful

inguinal lymphadenopathy beginning 2–6 weeks after presumed

exposure; in rare instances, the onset comes after a few months. The

inguinal adenopathy is unilateral in two-thirds of cases, and palpable

enlargement of the iliac and femoral nodes is often evident on the same

side as the enlarged inguinal nodes. The nodes are initially discrete, but

progressive periadenitis results in a matted mass of nodes that becomes

fluctuant and suppurative. The overlying skin becomes fixed, inflamed,

and thin, and multiple draining fistulas finally develop. Extensive

enlargement of chains of inguinal nodes above and below the inguinal

ligament (“the sign of the groove”) is not specific and, although not

uncommon, is documented in only a minority of cases. Spontaneous

healing usually takes place after several months; inguinal scars or

granulomatous masses of various sizes persist for life. Massive pelvic

lymphadenopathy may lead to exploratory laparotomy.

Constitutional symptoms are common during the stage of regional

lymphadenopathy and, in cases of proctitis, may include fever, chills,

headache, meningismus, anorexia, myalgias, and arthralgias. Other

systemic complications are infrequent but include arthritis with sterile

effusion, aseptic meningitis, meningoencephalitis, conjunctivitis, hepatitis, and erythema nodosum (Fig. A1-39). Complications of untreated

anorectal infection include perirectal abscess; anal fistulas; and rectovaginal, rectovesical, and ischiorectal fistulas. Secondary bacterial

infection probably contributes to these complications. Rectal stricture is

a late complication of anorectal infection and usually develops 2–6 cm

from the anal orifice—i.e., at a site within reach on digital rectal examination. A small percentage of cases of LGV in men present as chronic

progressive infiltrative, ulcerative, or fistular lesions of the penis,

urethra, or scrotum. Associated lymphatic obstruction may produce

elephantiasis. When urethral stricture occurs, it usually involves the

posterior urethra and causes incontinence or difficulty with urination.

Diagnosis • DETECTION METHODS Historically, chlamydiae were

cultivated in the yolk sac of embryonated eggs. The organisms can be

grown more easily in tissue culture, but cell culture—once considered

the diagnostic gold standard—has been replaced by nonculture assays

(Table 189-1). In general, culture for chlamydiae in clinical specimens

is now performed only in specialized laboratories. The first nonculture

assays, such as direct fluorescent antibody staining of clinical material

and enzyme immunoassay (EIA), have been replaced by NAATs, which

are currently recommended by the CDC as the diagnostic assays of

choice. At present, six NAAT assays cleared by the U.S. Food and Drug

Administration (FDA) are commercially available, some of which are

available as high-throughput robotic platforms. Point-of-care rapid

diagnostic assays are becoming available; they are of increasing interest

since patients can potentially be treated before leaving the clinic, thus

preventing forward transmission while patients wait for results from

tests with longer turnaround times.

CHOICE OF SPECIMEN Cervical and urethral swabs have traditionally been used for the diagnosis of STDs in female and male patients,

respectively. However, given the greatly increased sensitivity and

specificity of NAATs, less invasive samples (e.g., urine for both sexes

and vaginal swabs for women) can be used. For screening of asymptomatic women, the CDC now recommends that self-collected or