Chlamydia

Question 1

What kind of organism is C. trachomatis?

Answer 1

C. trachomatis is a small gram-negative bacterium that is an obligate intracellular parasite.

Question 2

Describe the life cycle of C. trachomatis.

Answer 2

●The small elementary bodies attach and penetrate into cells, changing into the metabolically active form, called the reticulate body, within six to eight hours. These forms create large inclusions within cells.
●The reticulate bodies then reorganize into small elementary bodies, and within two to three days the cell ruptures, releasing newly formed elementary bodies. Release of the elementary bodies initiates the replicative process, since this is the form that can infect new epithelial cells. The long growth cycle explains why treatment with agents with long half-lives or a prolonged course of antibiotics is necessary to eradicate infection.

Question 3

How is C. trachomatis transmitted?

Answer 3

In most countries, C. trachomatis infections among adults and adolescents are virtually all sexually transmitted.

Question 4

What is the incidence of Chlamydia infection in the US?

Answer 4

C. trachomatis is the most commonly reported bacterial infection in the US. In 2015, 1,526,658 chlamydial infections were reported to the Centers for Disease Control and Prevention and Prevention (CDC), reflecting an incidence rate of 478.8 cases per 100,000 people.

Question 5

What is the prevalence of Chlamydia infection in the US?

Answer 5

In one prospective study of 14,322 individuals between the ages of 18 and 26 years, the prevalence of chlamydia was 4.2 percent and, overall, was higher among women than men.

Question 6

What is the problem with standard epidemiological reports of Chlmaydia infections?

Answer 6

Extragenital sites are not typically specified in surveillance studies of C. trachomatis in heterosexual populations, but may serve as reservoirs for ongoing transmission. As an example, in a study of 4402 women attending a Baltimore STI clinic, the prevalence of rectally detected C. trachomatis was 3.7 percent; 13.8 percent of all chlamydial infections in women would have been missed with testing only at urogenital sites.

Question 7

Provide brief comment on coinfection with Chlamydia and other pathogens.

Answer 7

Co-infections with C. trachomatis and other urogenital sexually transmitted pathogens have frequently been reported among high-risk men and women. In some high-risk populations, up to 50% of people with Chlamydia were coinfected with another pathogen. These findings highlight the importance of evaluation for other sexually transmitted infections, particularly N. gonorrhoeae in patients with known C. trachomatis infection.

Question 8

What are the risk factors for C. trachomatis infection?

Answer 8

●Young age — Individuals less than 25 years, especially less than 20 years, tend to have the highest prevalence of chlamydia.
●Report of a new sex partner or more than one sex partner in the prior three months — These are not specific for C. trachomatis, but denote a risk for common sexually transmitted infections.
●History of previous C. trachomatis infection.
●Inconsistent use of condoms.

History of a different sexually transmitted infection (STI), including HIV, is also associated with a higher risk of chlamydia.

There is a high prevalence of both genital and extragenital chlamydia among men who have sex with men.

Question 9

What is the risk of repeat infection?

Answer 9

Several prospective studies have documented high rates of repeat infection in the months after an initial chlamydial infection.

In a study of 272 men aged 15 to 35 years, diagnosed with chlamydia, and subsequently followed for four months in three urban sites in the US (Baltimore, Denver, and San Francisco), repeat infection occurred in 13 percent (an estimated incidence of 45 infections per 100 person-years). Among 897 female adolescents diagnosed with an initial C. trachomatis infection at school-based health centers, 236 (26 percent) had one or more subsequent positive tests over the next year.

Question 10

Comment on the difference in risk in the following populations;

• MSM
• WSW

Answer 10

• MSM:
  Notably, there is a high incidence and prevalence of STIs, including C. trachomatis, among MSM. As an example, in 2015, the median site-specific prevalence of urogenital C. trachomatis among MSM tested at select STI clinics in the US was 16 percent (range by site: 12 to 18 percent). Although this may represent a sampling of a higher risk population, it may also underestimate the total burden of disease since extragenital C. trachomatis infections among MSM are common, asymptomatic, and not frequently sought using recommended diagnostic tests.

Similarly, in another study of MSM screened for chlamydia at urethral, rectal, and pharyngeal sites, rectal infections accounted for 53 percent of chlamydial infections and 86 percent of them were asymptomatic.

• WSW:
  In a study of women aged 15 to 24 years attending family planning clinics in the US Pacific Northwest during 1997 through 2005, the rate of C. trachomatis infection was unexpectedly higher among those who reported same sex behavior compared with those who reported exclusively heterosexual behavior (7.1 versus 5.3 percent).

Question 11

Is screening for Chlamydia infection necessary? Explain.

Answer 11

Because only the minority of chlamydial infections present as syndromes, including cervicitis, urethritis, proctitis, or pelvic inflammatory disease (PID), screening of asymptomatic persons plays a critical role in detecting the majority of infections.

Question 12

Comment on selective screening for Chlamydia in women.

Answer 12

Most experts agree that selective screening of appropriate women has been associated with widespread declines in reproductive tract sequelae; whether it has affected declines in prevalent infection remains debatable. In the US, the Centers for Disease Control and Prevention (CDC) and the US Preventive Services Task Force recommend that sexually active women ≤25 years of age be screened for genital chlamydial infection annually.

Pregnant women should also undergo screening to prevent maternal and neonatal complications. Screening of women older than 25 years is based on behavioral risk criteria. Because women who have sex with women remain at risk for chlamydial infection, sexual orientation should not affect the decision to screen if other risk factors are present.

There are no recommendations to routinely screen for rectal chlamydia infections in women, which are typically asymptomatic, as the adverse consequences of undetected, untreated infection at this site are not known.

Question 13

Comment on selective screening for Chlamydia in men.

Answer 13

The major rationale for screening among men is to reduce infection or reinfection of existing partners and transmission to new partners. Given the high rates of chlamydia detection among men who have sex with men (MSM), these men should undergo routine screening of sexually exposed sites (urethra and rectum). Routine screening of HIV-uninfected men who have sex with only women is not recommended unless they are seen in settings with known high prevalence, such as sexually transmitted infection (STIs) clinics or some correctional setting.

Question 14

Provide universal (non-gender-based) indications for selective screening for Chlamydia infection.

Answer 14

Other indications for screening include the presence or history of other STIs. HIV-infected individuals should be screened for chlamydia at baseline and at least annually thereafter if sexually active (with more frequent screening if high-risk sexual behavior is reported). Additionally, individuals diagnosed with chlamydia, gonorrhea, or, in women, trichomonas, are at relatively higher risk of infection with chlamydia in the subsequent several months. Thus, screening for chlamydia several months after a diagnosis of chlamydia, gonorrhea, or trichomoniasis detects substantial numbers of new infections and is recommended as a population-level prevention method.

Question 15

Outline the clinical syndromes caused by C. trachomatis infection in women.

Answer 15

The majority of women with C. trachomatis infection are asymptomatic.

Genital infection — In women, the cervix is the most commonly infected anatomic site, and a proportion of women may also have infection of the urethra. Untreated, cervical infection can ascend to cause pelvic inflammatory disease and its sequelae of infertility and chronic pain. Pregnant women with genital chlamydial infection are also at high risk for complications.

Cervicitis.

Dysuria-pyuria syndrome due to urethritis (+/- 25%).

PID.

Perihepatitis - Fitzhugh-Curtis syndrome; more commonly seen in actual PID, where it occurs in 5-15% of cases.

Complications of pregnancy - Beyond the risk of future ectopic pregnancy following chlamydia-associated PID, chlamydial genital infection during pregnancy can increase the risk for premature rupture of the membranes and preterm delivery; miscarriage and perinatal death were not associated with chlamydial infection.

Proctitis — While women can experience rectal infection with chlamydia, the responsible strains are the typical genital serovars (D through K), and they are typically asymptomatic and do not have long-term sequelae.

Question 16

Outline the clinical syndromes caused by C. trachomatis infection in men.

Answer 16

Urethritis — C. trachomatis is the most common cause of nongonococcal urethritis in men. The proportion of cases that are asymptomatic vary by population and range from 40 to 96 percent.

Epididymitis — C. trachomatis is one of the most frequent pathogens in epididymitis among sexually active men <35 years of age, along with N. gonorrhoeae. Asymptomatic urethritis frequently accompanies sexually transmitted epididymitis. In these cases, Gram stain of urethral secretions and urine microscopy can demonstrate polymorphonuclear leukocytes.

Prostatitis — C. trachomatis may be an etiology in some cases of chronic prostatitis, although this attribution remains highly speculative.

Proctitis — Chlamydial proctitis, defined as inflammation of the distal rectal mucosa, occurs primarily in men who have sex with men (MSM) who engage in receptive anal intercourse. In this group, infection is not uncommon and can be caused by D-K and L serovars. The non-LGV serovars that cause genital infection (serovars D through K) can also cause infection of the rectum, particularly in MSM, but in contrast to LGV, these infections are usually asymptomatic.

Reactive arthritis/reactive arthritis triad (RAT) — Approximately 1 percent of men with urethritis develop reactive arthritis, and approximately one-third of these patients have the complete reactive arthritis triad (RAT) formerly referred to as Reiter syndrome (arthritis, uveitis, and urethritis). C. trachomatis appears to be the most common inciting pathogen.

Question 17

Outline the clinical syndromes caused by C. trachomatis infection common to men and women.

Answer 17

Conjunctivitis — The C. trachomatis serovars that cause genital disease (D through K) can infect the epithelial cells of the conjunctiva. This typically occurs through direct inoculation with infected genital secretions. Sexually acquired chlamydial conjunctivitis typically presents as a non-purulent erythematous injection of the epithelial surface (inclusion conjunctivitis), which may take on a cobbled appearance.

Pharyngitis — C. trachomatis is not thought to be an important cause of pharyngitis. However, C. trachomatis has been detected in the pharynx using nucleic acid amplified testing, and some investigators postulate that this site serves as a reservoir of infection.

Genital lymphogranuloma venereum.

Question 18

Provide an overview of the diagnosis of C. trachomatis infection. Include the diagnosis of rectal and conjunctival chlamydia.

Answer 18

The diagnostic test of choice for chlamydial infection of the genitourinary tract is nucleic acid amplification testing (NAAT) of vaginal swabs for women or first-catch urine for men, although NAAT can also be performed on endocervical and urethral swab specimens. If NAAT methods are unavailable, antigen detection and genetic probe methods can be applied to endocervical or urethral swabs to diagnose chlamydia. In resource-limited settings, rapid tests for chlamydia may be used for diagnosis, if available. When no specific diagnostic tests are available, the presumptive diagnosis of chlamydia is made when symptoms and signs of the clinical syndromes associated with chlamydia are present in young or sexually active patients.

Rectal chlamydial infection in persons who engage in receptive anal intercourse can be diagnosed by testing a rectal swab specimen.

NAAT can be performed on conjunctival swabs to diagnose chlamydial conjunctivitis.

Question 19

Briefly elaborate on how to obtain a urine specimen for chlamydia testing in men.

Answer 19

First-catch urine submitted for NAAT should be collected from the initial stream (approximately the first 10 mL) without pre-cleansing of the genital areas. Ideally, the patient should not have voided in the two hours prior to specimen collection. The performance of these is not affected by the presence of purulent material or blood.

Question 20

Comment on the advantages of rapid tests for Chlamydia over NAAT.

Answer 20

Although NAAT has replaced culture as the new “gold standard”, same-day results have traditionally not been available. Furthermore, NAAT may be too expensive for use in resource-limited settings. The XPert CT/NG assay is a NAAT that can provide testing results for chlamydia (and gonorrhea) within 90 minutes. In the United States, this test is approved for use on endocervical or vaginal swabs, and urine.

Question 21

In which groups of patients is diagnostic testing indicated? In which groups is it not?

Answer 21

Symptomatic and at-risk asymptomatic patients — Any sexually active individual with signs and symptoms consistent with the clinical syndromes associated with chlamydia should undergo diagnostic testing for C. trachomatis.

Any patients with documented gonococcal infection should also undergo testing for chlamydia — It is important to note that N. gonorrhoeae not only causes similar clinical syndromes as C. trachomatis but also coexists in a significant proportion of patients with chlamydial infection. Thus, any testing for C. trachomatis should also prompt testing for N. gonorrhoeae.

Patients with persistent symptoms — Persistent symptoms related to chlamydial infection are usually due to recurrent infections. Clinicians should inquire about possible reinfection, including whether sex partners were treated. Nucleic acid amplification testing (NAAT) remains the test of choice to evaluate for reinfection in the setting of persistent symptoms regardless of interval since the prior treatment.

Recurrence of symptoms — Recurrence of symptoms after initial resolution should lead to a repeat evaluation for chlamydia and other sexually transmitted diseases that cause urethritis or cervicitis, including gonorrhea, bacterial vaginosis, and other pathogens. Nucleic acid amplification testing (NAAT) remains the test of choice to evaluate for reinfection in the setting of symptom recurrence regardless of interval since the prior treatment. A repeat diagnosis of chlamydia in a previously treated patient usually indicates reinfection, as noted above.

Patients with recent exposure — In patients who present within one to two weeks of a potential or known exposure to chlamydia (eg, sexual assault), diagnostic testing should not be used to inform the decision to treat. Such patients should be treated empirically.

Question 22

Which conditions should be considered in the differential diagnosis of urogenital chlamydia?

Answer 22

Other sexually transmitted pathogens, including N. gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium, can cause infections similar to C. trachomatis.

Question 23

Which conditions should be considered in the differential diagnosis of chlamydial proctitis?

Answer 23

The differential diagnosis of infectious proctitis in men who have sex with men (MSM) also includes N. gonorrhoeae, herpes simplex virus, and Treponema pallidum infections (/some combination of the above).

Question 24

What are the goals of treatment of Chlamydia?

Answer 24

●Prevent complicated infections related to chlamydia and their sequelae (eg, pelvic inflammatory disease, infertility, chronic pelvic pain, ectopic pregnancy, epididymitis).
●Decrease the risk of transmission to others; this includes sexual partners and infants at delivery, the latter group at risk of acquiring ocular or pulmonary chlamydial infection from an infected mother.
●Attain resolution of symptoms; between 83 and 86 percent of symptomatic patients with cervicitis or urethritis improve clinically within two weeks of starting treatment with doxycycline or azithromycin.

Question 25

What is the approach to treatment of Chlamydial infections?

Answer 25

●Active antimicrobial therapy;
●Directed or empiric therapy for concomitant gonococcal infection, if appropriate;
●Testing for other sexually transmitted infections, as infection with one increases the risk of coinfections;
●Discussion of the need for HIV testing, if HIV status is not known;
●Counseling on abstinence for one week following treatment;
●Counseling to return for persistent or recurrent symptoms;
●Retesting to evaluate for recurrent infection;
●Treatment of sexual partners.

Question 26

Which antimicrobials are used in the treatment of uncomplicated Chlamydial infection? Which one is better?

Answer 26

We typically suggest azithromycin (1 gram single-dose therapy) with observed therapy. Doxycycline (100 mg twice daily for seven days) can also be used in nonpregnant patients with counseling on the need for adherence for optimal outcome.

Doxycycline has been shown to be marginally more effective for genital chlamydia when directly observed therapy can be provided for the full course of treatment, but this is rarely possible.

Question 27

Discuss the relationship between the life cycle of C. trachomatis and antimicrobial selection.

Answer 27

The infectious form of the organism, the extracellular elementary body, is metabolically inert and resistant to killing. Thus, antibiotics must target the sequestered intracellular and intravacuolar phases of the life cycle of this pathogen. For this reason, antibiotics with good intracellular penetration must be used.

In addition, antibiotic concentrations must be present throughout the entire 36- to 48-hour life cycle of the organism. Thus, either a prolonged course of therapy or selection of an antibiotic with a long half-life is required to ensure adequate levels of the antibiotic agent.

Antibiotic resistance appears to be exceedingly rare. The intracellular nature of the pathogen eliminates the opportunity for rapid evolution of cell surface components that could contribute to drug resistance. Furthermore, the elementary body is relatively inert, which limits opportunities for replication and the generation of antibiotic-resistant mutations.

Question 28

Which antimicrobials may be used when azithro/doxy are contra-indicated or otherwise not tolerated? Write short notes on each.

Answer 28

Quinolones — The quinolones ofloxacin and levofloxacin are both highly effective against C. trachomatis but require a full week of therapy and are considerably more costly than either doxycycline or azithromycin. Furthermore, these drugs cannot be used in pregnancy or lactation and should not be administered to adolescents younger than 18 years of age due to concerns regarding bone abnormalities. Other quinolones, including ciprofloxacin, are either less effective or have not been tested against C. trachomatis.

For these reasons, ofloxacin and levofloxacin are recognized as alternative therapies in the fluoroquinolone class by the CDC; dose is as follows:
●Ofloxacin 300 mg orally twice daily for seven days
●Levofloxacin 500 mg orally once daily for seven days
We rarely use quinolones to treat C. trachomatis, but they are alternative options for the nonpregnant patient who cannot tolerate one of the first-line therapies.

Erythromycins and penicillins — These alternative regimens are notably inferior in their ability to affect microbial cure, with cure rates in the range of 85 to 89 percent. Their primary use is in pregnant women who cannot tolerate azithromycin. When these agents are used, test of cure should be performed to ensure microbiologic eradication.

Question 29

Comment on the management of gonococcal coinfection in C. trachomatis infection.

Answer 29

While it is important to confirm if Neisseria gonorrhoeae may coexist in patients with a diagnosis of chlamydial infection, presumptive therapy for gonorrhea is not routinely indicated for all patients.

A single injection of ceftriaxone (250 mg) cures the majority of uncomplicated gonococcal urogenital, anorectal, and pharyngeal infections. Ceftriaxone can also be used during pregnancy.

Question 30

What are the indications for empiric therapy?

Answer 30

Empiric therapy for chlamydial infection should be offered to persons who present with symptoms suggestive of infection (cervicitis, pelvic inflammatory disease, urethritis) if follow-up cannot be ensured and if relatively insensitive diagnostic testing is being used (eg, culture rather than nucleic acid amplification testing).

Patients with a recent known or possible sexual exposure to chlamydia should also be offered empiric therapy.

In addition, empiric therapy for chlamydia should be given to patients with documented gonococcal infection, unless nucleic acid amplification testing is negative.

Question 31

How is chlamydial proctitis treated?

Answer 31

Empiric therapy for both chlamydia and gonorrhea is indicated for the treatment of patients with acute proctitis. An empiric regimen of doxycycline (100 mg twice daily) plus a single intramuscular dose of ceftriaxone (250 mg) is active against both. The duration of doxycycline therapy depends on the severity of symptoms. Patients with severe proctitis may have lymphogranuloma venereum infection (LGV), which requires a full three-week course of doxycycline. For patients with mild proctitis, seven days of therapy is likely adequate; however, some clinicians reasonably opt to treat these patients with the three-week course recommended for presumed LGV.

We favor doxycycline over azithromycin as the anti-chlamydial agent for acute proctitis therapy in accordance with existing evidence, although clinical data to support this are of relatively low quality. In a meta-analysis of observational studies on treatment of predominantly asymptomatic rectal chlamydia, most of which used polymerase chain reaction (PCR) to assess microbial cure, efficacy rates for doxycycline and azithromycin were 99.6 and 82.9 percent, respectively

Question 32

How is chlamydial epididymitis treated?

Answer 32

N. gonorrhoeae or C. trachomatis are the most frequent laboratory-identified pathogens causing epididymitis among sexually active men <35 years of age.

The Centers for Disease Control and Prevention (CDC) guidelines recommend the combination of ceftriaxone (250 mg intramuscular as a single dose) plus doxycycline (100 mg orally twice daily) for 10 days for the treatment of sexually transmitted acute epididymitis. There are no data on the use of azithromycin for chlamydia in patients with epididymitis.

Ofloxacin (300 mg orally twice daily for 10 days) or levofloxacin (500 mg daily for 10 days) are given instead of doxycycline (with ceftriaxone) to patients with epididymitis who practice insertive anal sex (because of the possible involvement with enteric organisms) and can also be used for patients who are allergic to tetracyclines. Outpatient treatment is usually sufficient except for patients who appear toxic with a high fever or in those in whom severe pain necessitates the exclusion of another diagnosis such as testicular torsion or infarction.

Question 33

How is chlamydial PID treated?

Answer 33

When cervical infection is untreated, C. trachomatis ascends to the upper genital tract at least 20 percent of the time, which may manifest as either silent infection (“subclinical” pelvic inflammatory disease [PID], or silent endometritis) or overt PID. Therefore, women with cervicitis should undergo a physical examination to exclude signs of upper tract disease (eg, cervical motion, uterine, or adnexal tenderness). Apart from direct involvement of the pelvic organs, PID can also include peritonitis and inflammation of the liver capsule (Fitzhugh-Curtis syndrome). Treatment for PID should provide broad coverage for the wide array of implicated pathogens, including antibiotics active against C. trachomatis, most commonly doxycycline.

Question 34

How is oropharyngeal chlamydia treated?

Answer 34

The clinical significance of oropharyngeal chlamydia is uncertain. Some studies have suggested the feasibility of transmission from oropharyngeal to genital sites. Although the optimal treatment regimen for oropharyngeal chlamydia has not been well-studied, azithromycin or doxycycline is recommended, rather than ofloxacin or levofloxacin, if C. trachomatis is detected from an oropharyngeal sample.

Question 35

How is chlamydia in pregnant patients treated?

Answer 35

Treatment of chlamydia during pregnancy prevents transmission of C. trachomatis to infants during passage through the birth canal. The recommended regimens for treatment of the pregnant female is azithromycin (1 gram orally given as a single dose).
Women who cannot tolerate either of these regimens should be treated with amoxicillin or one of four erythromycin regimens, as follows.

●Amoxicillin (500 mg orally three times daily for seven days)
●Erythromycin base 500 mg orally four times daily for 7 days
●Erythromycin base 250 mg orally four times daily for 14 days
●Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days
●Erythromycin ethylsuccinate 400 mg orally four times daily for 14 days

Women who present in labor with an untreated prior positive chlamydial screening test should be treated immediately with one of the above regimens. However, this may not substantially decrease the risk of transmission of chlamydia to the newborn.

Question 36

Which anti-chlamydial agents are contra-indicated in pregnancy and lactation?

Answer 36

Doxycycline, levofloxacin, ofloxacin, and erythromycin estolate are contraindicated in pregnancy and lactation.

Question 37

How should pregnant patients treated for chlamydia be followed up?

Answer 37

Follow-up of pregnant women treated for documented C. trachomatis infection includes both test of cure and repeat testing for reinfection.

Cure rates of chlamydia in women who are pregnant are generally lower than in nonpregnant females, particularly with the alternative agent amoxicillin. For this reason, a test of cure is recommended for all pregnant women and should be performed no earlier than three weeks after treatment is completed.

As with all patients with documented C. trachomatis infection, pregnant women should undergo repeat testing to evaluate for reinfection three months following treatment.

Question 38

How does treatment of chlamydia in HIV patients differ from treatment in HIV negative patients?

Answer 38

The treatment of HIV-infected patients with chlamydial infections is the same as in HIV-seronegative patients.

Question 39

In terms of chlamydia management, what 4 things should patients be counselled about?

Answer 39

Medication adherence;
Sexual activity;
HIV counseling and testing;
Pregnancy testing.

Question 40

Which numerical fact adds weight to the obvious exhortation to patients to be compliant with their meds?

Answer 40

The importance of medication adherence was illustrated by a study in which imperfect adherence to a week-long course of oral doxycycline, defined as missing one or more daily doses, conferred a ninefold risk of microbiologic failure among men with urethritis due to C. trachomatis.

Question 41

How should patients be counselled around sexual activity post-chlamydia therapy?

Answer 41

Patients should be counseled to avoid sexual activity until seven days after initiating treatment; they may subsequently resume having sex provided that their symptoms have resolved and their sex partners have been treated. Persistence of symptoms may indicate infection with an additional pathogen (eg, Trichomonas vaginalis), reinfection, or incomplete adherence to the therapeutic regimen.

Question 42

Outline the approach to post-treatment follow up of chlamydia patients.

Answer 42

There are two different strategies for testing for chlamydia after treatment, including “test of cure,” which is performed no earlier than three weeks after treatment is completed, or “retesting,” which is performed approximately three months after treatment of infection, or if this is not possible, at the first visit thereafter within 12 months of treatment.

A test of cure should be obtained in pregnant women, patients with persistent symptoms, and patients who were treated with suboptimal antibiotic regimens, whereas retesting should be performed routinely on all patients with documented chlamydial infection.

Question 43

Which patients should not undergo test of cure and why?

Answer 43

Since cure rates of lower genital tract infection are generally high (>95 percent) in compliant, nonpregnant patients who are treated with azithromycin, doxycycline, levofloxacin, or ofloxacin, a test of cure is not indicated for these patients.

Question 44

Why should a test of cure not be performed within 3wks of treatment?

Answer 44

Test of cure should be performed no earlier than three weeks after treatment is completed. This is especially important when nucleic acid amplification tests (NAAT) are used, as they may be positive in the presence of dead organisms.

Question 45

How should patients with persistent symptoms be approached?

Answer 45

For patients with persistent or recurrent symptoms, clinicians should evaluate for possible reinfection, including inquiry about whether sex partners were treated, and for other sexually transmitted infections. The medical history should also assess whether the patient is using vaginal douches or other chemical irritants; such products can provoke a local inflammatory response with subsequent vaginal symptoms that can be confused with infection. Males with chronic prostatitis may also have evidence of chronic urethral inflammation, which may be confused with NGU.

Question 46

Which aetiological agents should be considered in those with persistent symptoms?

Answer 46

Other etiologic agents to consider include Mycoplasma genitalium, Ureaplasma, and genital herpes.

Question 47

Which aetiological agents should be considered in those with recurrent symptoms?

Answer 47

Recurrence of symptoms after initial resolution should lead to a repeat evaluation for chlamydia and other sexually transmitted infections that cause urethritis or cervicitis, including gonorrhea, bacterial vaginosis, and other pathogens.

Question 48

How should a repeat chlamydial infection be managed?

Answer 48

If C. trachomatis is again detected on repeat testing for persistent or recurrent symptoms or on routine repeat testing, we treat with azithromycin, as recommended for initial therapy, as long as there is no contraindication to doing so.

Persistence or recurrence of symptoms should not be attributed to C. trachomatis drug resistance; drug resistance to azithromycin or doxycycline has not been demonstrated to date.

Question 49

Write short notes on the management of sex partners of patients diagnosed with chlamydia.

Answer 49

Issues of reinfection — Sex partners are typically asymptomatic and, unless treated, will reinfect the index patient or spread infection to other partners. In fact, rates of reinfection among index cases of women with C. trachomatis range from 15 to 30 percent, and are typically associated with resumption of sex with previously established partners (not new partners).

Partner assessment and treatment — Ideally, sex partners of persons with chlamydial infection should be examined, tested for C. trachomatis and N. gonorrhoeae, treated, and counseled on prevention. This should occur for all individuals who had sexual contact with the patient within the 60 days prior to infection.

Expedited partner therapy — A strategy termed “expedited partner therapy” (EPT) has been proposed as an alternative way to increase the proportion of sex partners receiving treatment and to decrease rates of reinfection in the index patient. With EPT, treatment (without examination) is facilitated by giving an antibiotic or a prescription to the index patient or by calling in a prescription directly for the partner. EPT for chlamydia can be accomplished with single-dose oral therapy (azithromycin).

The limitations of this approach include lost opportunities for screening and counseling and a risk of adverse events related to antibiotic administration. In the United States, however, the Centers for Disease Control and Prevention consensus is that EPT offers a valuable means to control sexually transmitted infections and is an option for partner management, although ongoing evaluation of this approach is needed. Clinicians in the United States should routinely employ EPT for the partners of persons with chlamydial infection, to the extent permitted by regional laws and regulations where they are practicing, when follow-up is in question.