Genital chlamydial infections. 

Essentials of Diagnosis genital chlamydial infections.

 Clinical diagnosis is difficult because most genital chlamydial infections are asymptomatic and even when symptoms or signs are present, they are nonsp

The natural history of chlamydial infection is not yet fully understood, but Geisler and others have recently found that approximately 20% of individuals with genital chlamydial infection detected by screening have spontaneous resolution of their infection prior to returning for therapy, suggesting the host immune response, at least under some circumstances, eradicated the organism from the lower genital tract. In the majority of individuals, if not treated, infection tends to persist for weeks to months, and perhaps over a year in a small proportion of individuals. Stamm WE. Chlamydia trachomatis—the persistent pathogen: Thomas Parran Award Lecture. Sex Transm Dis 2001;28: 684–689. (Reviews chlamydial epidemiology, pathogenesis, and approaches to prevention over the past 25 years.) [PMID: 11625221]

Clinical Findings Symptoms, physical examination findings, and immediate laboratory findings (eg, results of urethral or endocervical Gram stains) in lower genital tract chlamydial infection are nonspecific and do not reliably distinguish chlamydia from other infections causing the same genital tract syndromes. Diagnostic assays to detect C trachomatis are essential to confirm the diagnosis of chlamydia. Imaging studies are not usually needed in uncomplicated genital chlamydial infection and will not be discussed further. Clinical findings in upper genital tract chlamydial infection (see Chapter 8) and anorectal infection (see Chapter 9) in men and women are discussed elsewhere in this book. Conjunctivitis caused by C trachomatis, usually resulting from autoinoculation from the genital tract, is rare. C trachomatis has been detected in the pharynx by culture and NAAT, yet it remains unclear whether clinically evident pharyngitis occurs and whether the organism is transmissible from the pharynx. The discussion that follows focuses on clinical findings in chlamydial infection of the lower genital tract.      chlamydial diagnostic infection procedure rickettsial viral,      Chlamydial Symptoms and Signs   Men Over 50% of men with urethral chlamydial infection are asymptomatic. Symptoms of chlamydial infection may include painful urination, urinary frequency, meatal itching or discomfort, and urethral discharge. If the patient has not voided recently, a urethral discharge may be apparent on examination and typically is clear or cloudy, often with mucus strands; accompanying the discharge may be meatal erythema or swelling, or both. However, it is important to recognize that asymptomatic urethral chlamydial infection without discharge occurs commonly. If no spontaneous discharge is noted, the urethra should be stripped ("milked") from the base of the penis to the urethral meatus and examined again. Unlike the LGV chlamydial strains, the non-LGV strains do not cause genital ulcers or significant lymph node swelling.   Women At least 75% of women with endocervical chlamydial infection are asymptomatic, and even when symptoms are present, they are nonspecific and often overlap with symptoms found in other vaginal or endocervical infections. Symptoms may include new or increased vaginal discharge, intermenstrual bleeding, lower abdominal pain, or pain during intercourse. Up to 50% or more of women with endocervical chlamydial infection have concomitant urethral infection and may present with painful urination or urinary frequency, or both. Many women also have asymptomatic rectal infection. Symptoms and signs of proctitis are rare with such non-LGV chlamydial strains. Even in the absence of symptoms, older studies using chlamydia culture have demonstrated up to one third of chlamydia-infected women have signs of infection on pelvic examination (Geisler and colleagues, utilizing NAATs, found fewer than 10% of asymptomatic women had signs of infection.) Mucopurulent endocervical discharge, easily induced endocervical bleeding ("friability"), and edematous ectopy are the signs most suggestive of chlamydial infection, yet all are nonspecific and may be seen in other sexually transmitted endocervical infections. Abnormal vaginal discharge (originating from the endocervix) may also be present. Although cervical ectopy may predispose to chlamydial infection (through increased exposure to susceptible columnar epithelial cells), ectopy without edema or congestion may be present in up to 60–80% of sexually active female adolescents and young adults, especially those using oral contraceptives, and is not indicative of chlamydial infection. Concomitant chlamydial infection of the Bartholin ducts may occur, manifesting as ductal erythema and swelling, often with purulent ductal exudate.   Laboratory Findings In chlamydial urethral infection, a Gram-stained smear made from an endourethral swab specimen often indicates the presence of urethritis (5 polymorphonuclear leukocytes [PMNs] per high-power field). However, Geisler and colleagues found that almost 20% of patients with chlamydial urethritis detected by NAAT had fewer than 5 or no PMNs visualized on a Gram-stained endourethral smear, suggesting that chlamydial infections may often mount a minimal inflammatory response or it may attenuate over time. Although an endourethral Gram stain can establish with a high degree of certainty whether gonorrhea is present in symptomatic urethritis, it does not exclude chlamydial infection, because C trachomatis cannot be visualized on a Gram stain. If microscopy is not available, then urinalysis can be performed on a first-voided urine specimen (ie, the first 10–15 mL of urine voided), and in younger men, the finding of a positive leukocyte esterase test or microscopic pyuria (>10 white blood cells in spun urine sediment per high-power field) is consistent with urethritis due C trachomatis or another sexually transmitted pathogen. A positive leukocyte esterase test or pyuria in older men might represent a urinary tract infection or sexually transmitted urethritis, and diagnostic testing should address both. In chlamydial endocervical infection, a Gram-stained smear of an endocervical swab specimen in a nonmenstruating woman often indicates the presence of cervicitis (30 white blood cells per high-power field). However, analogous to urethritis, in some patients with endocervical chlamydial infections, fewer than 30 white blood cells per high-power field are visualized, and some studies have suggested that a cutoff of more than 10 white blood cells per high-power field correlates better with cervicitis. Geisler and other researchers have also investigated the relationship of vaginal leukocyte counts (based on viewing a vaginal specimen wet mount at 400 x power) to endocervical chlamydial infection. In a recent study by Geisler and colleagues (performed in women with bacterial vaginosis), the presence of >5 white blood cells in at least one high power field predicted chlamydial infection, yet did not exclude the presence of other organisms.   Diagnostic Tests Because symptoms, examination findings, and microscopy do not reliably distinguish chlamydial infection from other organisms causing the same syndromes, patients suspected of having genital chlamydial infection should have specific diagnostic testing for C trachomatis. Confirmation of chlamydial infection is important for purposes of patient treatment, patient education, sex partner treatment, and for communicable disease reporting (to monitor the prevalence of chlamydia). Many different diagnostic assays are available for detection of C trachomatis (see Table 13–3). These vary in terms of test sensitivity, cost, and patient convenience. Table 13–3. Diagnostic Assays for Detection of Chlamydia trachomatis. Assay Sensitivitya (%)   Nucleic acid amplification tests (NAATs)b   80–95   Polymerase chain reaction     Strand displacement amplification     Transcription-mediated amplification   Direct fluorescent antibody 70–85 Tissue culture 70–85 Nucleic acid hybridization (DNA probe) 60–80 Enzyme immunoassay 50–75 aEstimated range of sensitivity, which may differ by gender, specimen type, or clinical presentation of infection. bIn contrast to most assays for chlamydia detection, which are performed only on genital swab specimens, NAATs can also be performed on urine or vaginal swabs (provider- or patient-collected). Screening Recommendations Populations with the greatest risk for genital chlamydial infection, yet who have unrecognized chlamydial infection, should also undergo chlamydial screening. The CDC and the US Preventive Services Task Force each currently recommends annual chlamydial screening for all sexually active women 25 years of age and younger, as well as for older at-risk women (eg, with new or multiple sex partners). The importance of annual chlamydial screening for young women is further emphasized by the inclusion of such screening as an element of the Health Plan Employer Data and Information Set (HEDIS) measures widely used to compare the quality of health care provision. The benefits of chlamydial screening have been demonstrated in parts of the United States where screening and treatment programs for women have reduced both the prevalence of infection and PID rates. Although no guidelines have been provided for chlamydial screening in men, consideration should be given for screening men 25 years of age and younger or those at higher risk if resources permit, especially in clinical populations with a high prevalence of disease.   Nonculture Tests Chlamydia culture has been the reference standard against which all other tests have been compared. However, nonculture tests are now far more commonly used because they are less technically demanding and may be less expensive and or more sensitive than chlamydia culture. The earliest nonculture screening tests for C trachomatis were based on detection of chlamydial antigen, rather than growth of the organism, and included enzyme immunoassays and direct fluorescent antibody tests. Nucleic acid hybridization tests (ie, DNA probes) then became available. These nonculture tests were less expensive and less technically demanding than culture; however, they also had lower test sensitivities and therefore failed to detect infections more often than culture, with the exception of direct fluorescent antibody testing, the sensitivity of which was similar to culture. Serologic assays for chlamydia have also been available yet are not widely used in the diagnosis of urogenital chlamydial infection because they do not distinguish past from current C trachomatis infection; cross-reacting antibody can occur with infections caused by other chlamydial species (eg, C pneumoniae); they may be negative in early or acute chlamydial infection, especially in men presenting with symptomatic nongonococcal urethritis (NGU); and titers are often low with superficial mucosal infections. NAATs became available for routine clinical use in the mid 1990s and are the preferred and recommended means for detecting C trachomatis infection. These tests offer two distinct advantages over culture or earlier nonculture-based chlamydia tests: (1) higher test sensitivity (approximately 15–20% higher than former tests), resulting from the amplification of nucleic acids, thereby improving the likelihood of detecting the organism (especially when the bacterial burden is low); and (2) greater patient convenience or satisfaction by using noninvasively collected specimens, including urine, tampons, or self-collected vaginal swabs. Hence, NAATs can facilitate chlamydia screening outside of conventional clinical settings. One disadvantage of NAATs is their higher cost. However, the higher test sensitivity may still allow NAATs to be more cost-effective than other chlamydia tests as their use may decrease the prevalence of genital chlamydia or PID.   Additional Tests for Coinfection Most individuals undergoing testing for chlamydia should also receive testing for gonorrhea, because coinfection with both organisms is common and their recommended treatments differ. Gaydos CA. Nucleic acid amplification tests for gonorrhea and chlamydia: Practice and applications. Infect Dis Clin North Am 2005;19:367–386. (Reviews the NAATs currently available for diagnosing chlamydia and their application to clinical care.) [PMID: 15963877] Geisler WM, Yu S, Hook EW III. Chlamydial and gonococcal infection in men without polymorphonuclear leukocytes on Gram stain: Implications for diagnostic approach and management. Sex Transm Dis 2005;32:630–634. (Gram stain evidence of urethral inflammation was absent in 12% of chlamydial and 5% of gonococcal infections, and symptoms and discharge may be absent in chlamydial infection detected by NAAT. Thus, without testing, many infections would go untreated, furthering the possibility of complications or partner transmission.) [PMID: 16205305] Geisler WM, Yu S, Venglarek M, Schwebke JR. Vaginal leucocyte counts in women with bacterial vaginosis: Relation to vaginal and cervical infections. Sex Transm Infect 2004;80:401–405. (An elevated vaginal leucocyte count in women with bacterial vaginosis was a strong predictor of vaginal or cervical infections. Vaginal leucocyte quantification may provide an alternative approach to assessing the need for empiric therapy for chlamydia and gonorrhoea, particularly in resource-limited high STD risk settings that provide syndromic management.) [PMID: 15459411]

Differential Diagnosis Men The differential diagnosis of genital chlamydial infection in men includes infection with Neisseria gonorrhoeae as well as other organisms causing NGU (see Chapter 3), primarily Trichomonas vaginalis, herpes simplex virus, genital Mycoplasma species (M genitalium), and possibly genital Ureaplasma species. All of these organisms can manifest as urethritis, with clinical findings similar to those in chlamydial infection. Although men presenting with symptomatic gonorrhea may have a more purulent urethral discharge and usually have gonococcal-like organisms on the urethral Gram stain, approximately 5% of men with symptomatic gonococcal urethritis have no evidence on Gram stain of gonococcal-like organisms, which emphasizes the importance of testing for gonorrhea even in individuals diagnosed with NGU. Genital herpes is a recognized cause of recurrent NGU, although the epidemiology, clinical findings, and treatment outcomes in NGU resulting from herpes infection have not been well characterized. T vaginalis is a protozoa causing NGU, which can be prevalent in high-risk populations (in an STD clinic in Birmingham, Alabama, the prevalence of trichomoniasis in men with NGU is approximately 15–20%). Trichomoniasis is not routinely tested for in men with NGU, in part due to limited sensitivity of currently available assays when used in men. However, this etiology should always be considered in men with recurrent or persistent NGU and appropriate empiric therapy included in this clinical setting. Genital Mycoplasma species, especially M genitalium, are now recognized as legitimate etiologic agents of NGU. However, commercial testing is not routinely available for this organism; research studies have employed culture and polymerase chain reaction techniques. Fortunately, the antimicrobial agents recommended for treatment of chlamydia also have the best activity against Mycoplasma urethritis, although tetracycline- or macrolide-resistant isolates of Mycoplasma have been reported. Ureaplasma species have been postulated as an etiology of NGU, but current evidence does not strongly support such an association. Analogous to genital Mycoplasma species, commercial testing is not routinely employed to test for genital Ureaplasma species, and the treatment employs the same antimicrobials used to treat chlamydia.   Women The differential diagnosis of genital chlamydial infection in women includes N gonorrhoeae as well as other organisms causing mucopurulent cervicitis (see Chapter 10); these include herpes simplex virus, bacterial species associated with bacterial vaginosis (eg, Gardnerella vaginalis), genital Mycoplasma species (M genitalium), and possibly genital Ureaplasma species. Approximately half of all cases of mucopurulent cervicitis are caused by chlamydia or gonorrhea, the two infections for which routine testing is performed in patients with cervicitis and for which empiric therapy is given. Bacterial vaginosis is a common disorder of the genital tract in women characterized by an alteration of the normal acidic, lactobacilli-predominant vaginal ecosystem to a vaginal environment dominated by organisms such as G vaginalis, Mobiluncus species, and anaerobes, with an accompanying increase in vaginal pH (see Chapter 11). Bacterial vaginosis has been associated with mucopurulent cervicitis, and some experts recommend treating bacterial vaginosis in women with cervicitis, especially if chlamydia and gonorrhea test results are negative. Genital herpes is a recognized cause of recurrent mucopurulent cervicitis, although the epidemiology, clinical findings, and treatment outcomes in cervicitis resulting from herpes infection have not been well characterized. Genital Mycoplasma species (M genitalium) and possibly genital Ureaplasma species may cause mucopurulent cervicitis, but as with urethritis, they are not routinely tested for and would already be empirically treated by the same treatment regimens used for chlamydia.

Complications   Upper Genital Tract Infection A major complication of lower genital tract chlamydial infection is spread of chlamydial infection to the upper genital tract. In men, this can cause acute epididymitis (see Chapter 6), which can lead to other complications, including testicular abscess (and possibly infarction), chronic testicular pain, chronic epididymitis, and infertility. In women, infection of the upper genital tract causes PID (see Chapter 8), which can lead to other complications, including ovarian abscess (and possibly infarction), infertility, chronic pelvic pain, and ectopic pregnancy. These complications are discussed in detail in the previously noted chapters.   Reiter Syndrome Concurrent or preceding genital chlamydial infection has been associated with Reiter syndrome, an aseptic inflammatory polyarthritis, the classic clinical manifestations of which include a trigger infection (STD: urethritis or cervicitis; non-STD: enteritis), associated with conjunctivitis, rheumatoid factor–negative asymmetric polyarthritis, and mucocutaneous lesions. Cardiac and neurologic manifestations can also occur but are rare. Reiter syndrome occurs more commonly in men and those with the HLA-B27 haplotype, the latter also having a more severe clinical course. It is believed that either whole chlamydial organisms or chlamydial nucleic acids or antigens disseminate beyond the genital tract to the synovium of joints and other structures in these patients. To date, viable C trachomatis organisms (other than non-LGV strains) have not been isolated outside the genital tract in these patients. Reiter syndrome associated with chlamydial infection is treated with antibiotics and anti-inflammatory agents (eg, indomethacin, nonsteroidal anti-inflammatory agents, etc).   Other Complications Chlamydial proctitis (see Chapter 9) can be complicated by strictures and fistulas; however, this is primarily limited to infections cause by LGV chlamydial strains and is further discussed in the previously noted chapter. C trachomatis has also been associated with culture-negative endocarditis, yet this reported association has been based primarily on diagnosis of chlamydia by serologic testing, which lacks specificity. Culture-negative endocarditis attributed to C trachomatis is a poorly characterized entity, and currently it remains unclear whether C trachomatis causes endocarditis.

Treatment for Genital chlamydial infections. Antimicrobial Therapy Antimicrobial agents represent the cornerstone of therapy for chlamydial infections. The antimicrobial agents with the greatest in vitro activity against C trachomatis and which are clinically most efficacious for uncomplicated chlamydial infection include the tetracyclines, macrolides, azalides (ie, azithromycin), and select fluoroquinolones. All of these agents achieve sufficient intracellular concentrations to treat this obligate intracellular pathogen. The current CDC recommendations for treatment of uncomplicated genital chlamydial infection are summarized in Table 13–4. Table 13–4. Antimicrobial Therapy for Uncomplicated Genital Chlamydial Infection.   Recommended Regimen Alternative Regimen Nonpregnant patients Azithromycin, 1 g PO in a single dose or Doxycycline, 100 mg PO twice daily for 7 d Ofloxacin, 300 mg PO twice daily for 7 d or Levofloxacin, 500 mg PO once daily for 7 d or Erythromycin base, 500 mg PO 4 times daily for 7 d or Erythromycin ethylsuccinate, 800 mg PO 4 times daily for 7 d Pregnant patients Azithromycin, 1 g PO in a single dosea or Amoxicillin, 500 mg PO 3 times daily for 7 d Erythromycin ethylsuccinate, 800 mg PO 4 times daily for 7 d or Erythromycin ethylsuccinate, 400 mg PO 4 times daily for 14 d or Erythromycin base, 250 mg PO 4 times daily for 14 d or Erythromycin base, 500 mg PO 4 times daily for 7 d aRecent literature supports the efficacy and safety of this regimen, and anecdotal experience suggests it is used far more widely than either erythromycin or amoxicillin for chlamydia-infected pregnant women. Based on Centers for Disease Control and Prevention; Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep 2006;55(RR-11):1–94.   Recommended Regimens The recommended antibiotic regimens for uncomplicated genital chlamydial infection in nonpregnant individuals are azithromycin, 1 g orally given as a single dose, or doxycycline, 100 mg twice daily orally for 7 days. Despite the convenience and the improved compliance of the single-dose azithromycin regimen, no significant differences have been demonstrated in the clinical efficacy or frequency of adverse reactions for azithromycin versus doxycycline. The major considerations in choosing azithromycin versus doxycycline in nonpregnant patients are cost, convenience, and drug allergies. Azithromycin is more convenient because of single-dose administration, which can be directly observed, but it costs more. Doxycycline is less expensive, yet less convenient because 14 capsules are taken over 7 days and complete treatment is not directly observed in most settings.   Alternative Regimens Ofloxacin, 400 mg orally twice daily for 7 days, or levofloxacin, 500 mg orally daily for 7 days, are recommended by the CDC for nonpregnant persons with chlamydial infection as alternatives to the azithromycin or doxycycline regimens previously described. Given the high cost of fluoroquinolones (compared with azithromycin or doxycycline), their longer duration of therapy (compared with azithromycin), and their contraindication in pregnancy (compared with azithromycin), for most patients these agents provide no significant advantage over the recommended doxycycline or azithromycin regimens. One of the previously listed fluoroquinolones may be considered for uncomplicated genital chlamydial infection when a patient is already being treated with this agent for a different clinical syndrome (eg, urinary tract infection), if a patient has an allergy to tetracyclines and azalides or macrolides, or if the patient presents with PID, in which ofloxacin or levofloxacin regimens (for 14 days) are recommended in the CDC's current STD treatment guidelines (see Chapter 8). Table 13–4 also lists erythromycin regimens that are considered as alternative therapy. Although erythromycin is inexpensive, the high rate of gastrointestinal side effects (especially diarrhea) limits compliance with the full treatment course and, as a result, may lead to lower clinical cure rates with these regimens. Thus, we do not recommend their use. Other macrolides, such as clarithromycin, do not offer advantages over azithromycin for treatment of genital chlamydial infection. Antimicrobial Considerations in Special Populations   Pregnant Women Doxycycline, ofloxacin, and levofloxacin are contraindicated in pregnant women. The 2006 CDC treatment guidelines recommend either amoxicillin, 500 mg orally three times daily for 7 days, or azithromycin, 1g single dose orally, in this patient population (see Table 13–4). Erythromycin, previously a first-line agent in the 2002 CDC treatment guidelines, is now listed as a alternative agent in the 2006 guidelines (see Table 13-4). Azithromycin was moved to a first-line agent in the 2006 guidelines because: 1) recent clinical trials of azithromycin versus comparator regimens (erythromycin or amoxicillin) in chlamydia-infected pregnant women have demonstrated azithromycin to be safe and just as or more efficacious as the comparator regimens, 2) anecdotal experience and discussion with experts suggested azithromycin was far more widely used than erythromycin or amoxicillin in these patients, and 3) erythromycin is poorly tolerated in pregnant women, which leads to greater noncompliance and lower efficacy. All three antibiotics are pregnancy category B drugs.   Adolescents Although there is some evidence for development of bone and joint disease in juvenile animals treated with fluoroquinolones, there is sufficient clinical experience in human adolescents (especially those >45 kg) to support use of the alternatively recommended fluoroquinolone regimens for chlamydia if doxycycline or azithromycin cannot be used. HIV-Infected Individuals There are no data to suggest that the efficacy of recommended antimicrobial regimens for chlamydia are altered in HIV-infected individuals, and the CDC recommends the same regimens in these patients. Other Management Considerations   Sexual Activity To prevent transmission to uninfected individuals, it is recommended that chlamydia-infected patients be instructed to abstain from sexual activity until completion of a recommended treatment regimen (ie, 7 days after receiving single-dose azithromycin or after finishing a 7-day course of doxycycline). For those persons unlikely to abstain during this period, strict compliance with condom use should be reinforced to prevent further transmission. Patients should also use these prevention measures until their sex partners have completed therapy.   Management of Sex Partners Treatment of sex partners of chlamydia-infected patients is important, both to prevent reinfection of the patient and to prevent further transmission to other susceptible individuals. Traditionally, chlamydia-infected patients have been instructed by providers to notify their partners that they have been exposed to chlamydia and should themselves be seen by a provider for testing and treatment. However, high rates of chlamydia reinfection suggest such partner notification practices often do not lead to treatment of the sex partner. Recent studies have explored the feasibility and efficacy (in preventing recurrence of chlamydia) of patients or providers delivering medication or a prescription directly to the sex partner (ie, expedited partner therapy [EPT]). Although further studies are needed, it appears that EPT is feasible and may decrease rates of chlamydia recurrence. There are, however, some concerns with EPT. One concern is the risk for an allergic reaction to the EPT in the sex partner, but serious drug reactions to doxycycline or azithromycin are very rare. There is some concern about the legality of EPT, as this issue is not clearly addressed in most states. However, anecdotal evidence and discussion with other experts suggests EPT is already a widespread clinical practice. An additional concern centers on the delivery of medication by male patients to female sex partners who have subclinical PID; providing EPT to these partners might deter them from seeking evaluation by a health care provider, thus leading to treatment for PID that may be insufficient. However, many of these female partners might not have sought provider evaluation anyway, and EPT may provide some benefit. Finally, another potential concern with EPT is reduced opportunities to screen partners for other STDs, including HIV infection, and to provide risk reduction education. Clinicians who use EPT are encouraged to provide educational materials for the partners and encourage them to seek evaluation, which will allow examination for clinical evidence of complications and testing for other STDs.   Follow-Up and "Test of Cure" Nonpregnant patients with uncomplicated genital chlamydial infection do not need repeat clinical or diagnostic evaluation after completion of therapy unless symptoms or signs of infection persist or recur. However, test of cure following treatment of uncomplicated genital chlamydial infections—usually more than 3 weeks after treatment—is recommended for pregnant women, a population in which treatment failures could lead to both maternal and neonatal complications.   Approach to Treatment Failure Chlamydia-infected patients with symptoms or signs of infection that persist or recur within a short time period (<4 weeks) after treatment are often labeled as "treatment failures." The first step in managing such patients is to repeat the clinical and diagnostic evaluation. This is done to confirm the presence of C trachomatis and to rule out other STDs. It is recommended that patients with clinical findings suggestive of chlamydial infection (urethritis, cervicitis, etc) receive empiric treatment with one of the CDC-recommended treatment regimens. Most cases of "treatment failure" are a result of reinfection of the patient by an untreated partner. Therefore, the next step is to ensure that sex partners receive treatment and both the patient and partner abstain until treatment is complete. No studies have definitely proved that treatment failure in the absence of reexposure to an infected partner occurs following recommended chlamydia treatment regimens, but there is indirect evidence suggesting it may. There is also no strong evidence to support that treatment failure is due to resistant C trachomatis isolates. Antibiotic resistance can be induced in vitro in C trachomatis, but wild-type resistance does not appear to be common in clinical isolates or to result in sustained transmission. "Repeat Testing" to Identify Chlamydia Recurrence Recurrence of chlamydial infection is common in women, occurring in 10–20% within 6 months of a prior chlamydial infection. The rate of recurrence in men is unclear, but our clinical experience suggests it is common. Recurrence of chlamydial infection can lead to upper genital tract complications in men and women, and may serve as a reservoir for repeated chlamydial infections. The current CDC treatment guidelines advise that all women with chlamydial infections be retested for chlamydial infection in about 3 months after treatment to rule out reinfection, and we believe that strong consideration should also be given to rescreening high-risk men following chlamydial infection if resources permit. Clinicians should have a system in place to recall patients treated for chlamydial infection for retesting in about 3 months. Some researchers are evaluating the feasibility of having patients repeat chlamydial testing by home self-collection and then mail in specimens (urine in men and vaginal swabs or urine in women). Centers for DiseccControl and Prevention; Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep 2006;55(RR-11):1–94. (These widely accepted guidelines, developed in consultation with professionals knowledgeable in the field of STDs, provides recommendations for management of chlamydial infections). [PMID: 16888612] Geisler WM. Approaches to the management of uncomplicated genital Chlamydia trachomatis infections. Exp Rev Anti Infect Ther 2004;2:771–785. (Reviews current and future approaches to management of chlamydia). [PMID: 15482239] Golden MR. Expedited partner therapy for sexually transmitted diseases. Clin Infect Dis 2005;41:630–633. (Informative editorial that includes a summary of the randomized, controlled trials of EPT for chlamydial infection.) [PMID: 16080085] Suchland RJ, Geisler WM, Stamm WE. Methodologies and cell lines used for antimicrobial susceptibility testing of Chlamydia spp. Antimicrob Agents Chemother 2003;47:636–642. (This article provides a basis for standardizing the methodologic approach and interpretation of antimicrobial testing of Chlamydia, and is one of the few studies to date assessing correlation of clinical outcomes in chlamydial infections with results of susceptibility testing)., and is one of the few studies to date assessing correlation of clinical outcomes in chlamydial infections with results of susceptibility testing).  [PMID: 12543671]

When to Refer to a Specialist Patients who present with recurrent C trachomatis infections and who deny reexposure to an untreated sex partner may benefit from referral to a specialist. Chlamydia genotyping is a tool we and other researchers have utilized to determine with a reasonable certainty whether the chlamydia strains in such patients with recurrent chlamydia are the same or a different genotype (the latter likely representing new infection). In those presenting with recurrent infection with the same chlamydial genotype, antimicrobial susceptibility testing may also be considered. However, such testing currently lacks a standardized methodology and is performed by us and only a few other researchers. Finally, referral to a urologist or gynecologist may also be of benefit in evaluating whether an upper genital tract infection (in men, prostatitis or epididymitis; in women, PID) may be present and serving as a nidus for reinfecting the lower genital tract.

Prognosis Initiation of appropriate antimicrobial therapy leads to improvement and eventual resolution of symptoms and signs of uncomplicated genital chlamydial infection within the first few days of therapy and to clinical and microbiologic cure after the completion of therapy in most patients. The key to prevention of recurrent chlamydial infection is ensuring patient compliance with treatment, achieving treatment of sex partners, providing STD education, and reenforcing the use of barrier precautions. With the availability of highly sensitive diagnostic tests for chlamydia (ie, NAATs), continued efforts toward sex partner treatment, rescreening chlamydia-infected women in a few months, and routine yearly chlamydia screening in women, we anticipate further decline in the prevalence of chlamydial infection and its associated complications in the United States.

Practice Points  Up to 50% or more of women with endocervical chlamydial infection have concomitant urethral infection and may present with painful urination or urinary frequency, or both.  NAATs are the preferred and recommended means for detecting C trachomatis infection.  Clinicians should have a system in place to recall patients treated for chlamydial infection for retesting in about 3 months.

ecific.

 Diagnosis relies on tests that detect the causative organism, Chlamydia trachomatis.

 Nucleic acid amplification tests (NAATs) have the greatest sensitivity and can be performed on noninvasively collected specimens (eg, urine or self-collected vaginal swabs).

General Considerations for genital chlamydial infections

Chlamydia trachomatis is responsible for a wide spectrum of clinical disease, particularly in the genital tract (see Table 13–1). Despite the availability of effective antimicrobial therapy and improved preventive efforts, genital chlamydial infections remain a worldwide public health concern, and the World Health Organization estimates that 90 million new cases occur worldwide each year. Genital chlamydial infection remains the most commonly reported bacterial sexually transmitted disease (STD) in the United States, producing an estimated four million new infections each year, according to the Centers for Disease Control and Prevention (CDC).

From the time genital chlamydial infections first became a reportable disease in the United States in 1986, a greater number of cases have been reported in women versus men, a finding that has been attributed to emphasis on chlamydial screening in women. Chlamydia causes significant morbidity, especially in women, who can develop upper genital tract infection (pelvic inflammatory disease [PID]), which can lead to chronic pelvic pain, tubal abscesses, ectopic pregnancy, and infertility; chlamydia is the leading preventable cause of infertility worldwide. Genital chlamydia can also increase the risk of acquisition and transmission of HIV.

Among the many risk factors for genital chlamydial infection (see Table 13–2), age is the strongest risk factor, with CDC surveillance studies demonstrating the highest chlamydial prevalence occurring in men and women younger than 25 years of age. A history of prior chlamydial infection is another strong predictor for current chlamydial infection. The majority of chlamydial infections in men and women are asymptomatic; therefore, the diagnosis of infection relies on identification of the organism through diagnostic testing. The availability of highly sensitive nucleic acid amplification tests (NAATs) should help to facilitate both improved rates of diagnosis and more widespread chlamydial screening, because such tests can be performed on noninvasively collected specimens (eg, urine and self-collected vaginal swabs). However, many barriers to screening exist, including lack of patient access to health care providers and lack of routine chlamydial testing in many medical settings.

Current management of genital chlamydial infection relies on effective antimicrobial therapy for infected patients and their sex partners, and routine rescreening 3 months after treatment. Although antimicrobial resistance in chlamydial infections has not been a major concern to date, evidence is building that suggests this may be a future problem. Recurrence of chlamydial infection in women is common, and the CDC recommends retesting at approximately 3 months following therapy. Development of an effective chlamydial vaccine is one of the priorities for the prevention and control of chlamydia, but efforts to date have been hindered by an incomplete understanding of the human host immune response to C trachomatis.

Pathogenesis

Chlamydiae are obligate intracellular bacteria that are energy parasites of infected host cells. In the genital tract, C trachomatis primarily infects columnar and transitional epithelial cells but not squamous epithelial cells, explaining in part why chlamydial infection in the female genital tract occurs in the endocervix and upper genital tract, but not the vagina. C trachomatis can be classified through molecular typing into strains causing ocular infections (trachoma), strains causing lymphogranuloma venereum (LGV) infection, and strains causing the characteristic lower genital tract and other mucosal infections outlined in Table 13–1.

All chlamydiae undergo a unique intracellular developmental cycle (see Figure 13–1) that is completed in 48–72 hours when infected cells release newly replicated chlamydial organisms; as a result, the incubation time in genital chlamydial infection ranges from 7 to 21 days (compared with as few as 24–48 hours in gonococcal infection). Diagnostic assays, especially those other than NAATs, that are performed within the first few days after exposure to chlamydia may yield a false-negative result due to low organism burden at that point.