1. Aetna considers Chlamydia trachomatis (C. trachomatis) screening a medically necessary preventive service according to the recommendations of the National Institute for Health and Clinical Excellence, United States Preventive Services Task Force (USPSTF) and the Centers for Disease Control and Prevention (CDC).  Chlamydia screening is recommended for the following groups:

   1. All pregnant women aged 24 years and younger;
   2. All sexually active women aged 24 years and younger; and 
   3. Other women with any of the following risk factors for C. trachomatis infection:
       
      
      1. Having had C. trachomatis or other sexually transmitted diseases in the past; or
      2. New or multiple sexual partners; or
      3. Not using condoms consistently or correctly; or
      4. Prior to undergoing uterine instrumentation for assessment and treatment of infertility.

      Aetna considers C. trachomatis screening experimental and investigational for asymptomatic men, and for women who do not meet the above criteria, because of insufficient evidence in the peer-reviewed literature.

2. Aetna considers C. trachomatis diagnostic testing medically necessary for members with signs or symptoms of C. trachomatis infection.

3. Aetna considers home testing for C. trachomatis experimental and investigational because of insufficient evidence in the peer-reviewed literature.

In its updated recommendations on Chlamydia trachomatis screening, the USPSTF strongly recommended that clinicians routinely screen all sexually active women aged 24 years and younger, and other asymptomatic women at increased risk for infection, for chlamydial infection (USPSTF, 2007).  Other risk factors for chlamydial infection include a history of chlamydial or other sexually transmitted infection, new or multiple sexual partners, inconsistent condom use, and exchanging sex for money or drugs. The USPSTF also recommended that clinicians routinely screen all asymptomatic pregnant women aged 24 years and younger for chlamydial infection.  The USPSTF made no recommendation for or against routinely screening asymptomatic low-risk women in the general population for chlamydial infection.  The USPSTF found at least fair evidence that screening low-risk women could detect some additional cases of Chlamydia trachomatis, but concluded that the potential benefits of screening low-risk women may be small and may not justify the possible harms.

The USPSTF made no recommendation for or against routine screening of asymptomatic, low-risk pregnant women aged 25 years and older for chlamydial infection.  The USPSTF found fair evidence that the benefits of screening low-risk pregnant women are small and may not justify the possible harms.

The USPSTF concluded that the evidence is insufficient to recommend for or against routinely screening asymptomatic men for chlamydial infection.  The USPSTF found no direct evidence to determine whether screening asymptomatic men for chlamydial infection is effective for reducing the incidence of new infections in women.

Chlamydia screening among young women under the age of 26 is a measure that has been adopted by the National Committee for Quality Assurance (NCQA) for inclusion in the Health Plan Employer Data and Information Set (HEDIS). C. trachomatis infection is the most common sexually transmitted disease (STD) in the United States affecting an estimated 4 million people.  Prevalence is highest in sexually active females under the age of 25 years.

Most C. trachomatis infections cause no symptoms.  Left untreated, C. trachomatis infection can lead to complications such as pelvic inflammatory disease in the female, which has emerged as a major cause of tubal factor infertility and ectopic pregnancy in women of childbearing age.  Chlamydia infection can be passed to the newborn during delivery through the birth canal with a manifestation of neonatal eye infection or pneumonia.  These sequelae are unfortunate because C. trachomatis infection is effectively treated with antibiotics.

Diagnosis is based on the detection of the microorganism itself, its antigens, or genetic material collected from the lower genital tract, or in some instances, a urine sample.  The sensitivity of tissue culture ranges from 65 to 80 %.  More available non-culture tests, such as the direct fluorescent antibody (DFA) and the enzyme immunoassay (EIA), which detect chlamydial antigens in clinical specimens have specificities from 96 to 99 %.  However, these tests with high specificity yield a large number of false- positives in a population with a low disease prevalence.  DNA amplified hybridization tests are both highly specific and sensitive and are proving to be the best tests in large scale screening.  Additionally, the LCR and the PCR can be performed on urine specimens.  New DNA amplified hybridization techniques such as transcription mediated amplification (TMA), Q-B replicase amplified hybridization, and nucleic acid sequence-based amplification (NASBA) are currently being investigated and appear to be very promising.

Rietmeijer et al (2008) assessed the recent U.S. literature on chlamydia positivity in chlamydia screening programs among asymptomatic men in non-sexually transmitted disease clinic settings.  These investigators reviewed published articles between 1995 and June 2007, using PubMed as the primary search tool.  Articles were abstracted and positivity rates summarized by type of venue, race/ethnicity, age group, and U.S. region.  The overall median positivity rate was 5.1 %.  The highest rates were observed among men tested in juvenile (7.9 %) and adult (6.8 %) detention facilities, among blacks (6.7 %), the 15 to 19 years old (6.1 %) and 20 to 24 years old (6.5 %) age groups, and among men screened in the southern United States (6.4 %).  Chlamydia rates among men are high in certain venues, particularly correctional settings, but also depend on the demographical composition of the target population and location.  The authors concluded that programs considering male chlamydia screening programs should conduct pilot programs to assess chlamydia positivity as well as feasibility and cost in target venues.

Gift and colleagues (2008) reviewed the literature on the cost-effectiveness of screening men for chlamydia.  The reviewed studies examined both proactive and opportunistic screening and included screening of risk groups and of the general population.  Some older studies included enzyme immunoassays; more recent studies featured nucleic acid amplification assays.  Six studies used dynamic transmission models; 14 studies analyzed male and female chlamydia screening interventions.  Several contained sufficient data to examine the cost-effectiveness of male screening compared with female screening.  Male screening was preferred to expanded female screening in 1 study.  In other studies, combined male and female screening programs were cost-saving.  The authors concluded thay studies comparing chlamydia screening in men with chlamydia screening in women may be the most useful for guidance to programs.  The studies which compared the 2 generally have found that screening men from the general population is not preferred to screening women from the general population, although 1 study found that screening of men from risk groups can be cost-effective compared with screening women from the general population. 

Michel and colleagues (2009) assessed the performance of a Conformitée Européenne (CE)-marked home test for chlamydia trachomatis (CT) that is available over the Internet.  A total of 231 eligible women attending the Social Hygiene Clinic (SHC) or Obstetrics-Gynecology (OB-GYN) Clinic in Iloilo City, Philippines were recruited to an evaluation of the HandiLab-C chlamydia home test (HandiLab-C).  One vaginal swab was tested with HandiLab-C on-site and the second in Cambridge, United Kingdom with 2 nucleic acid amplification tests (NAAT), the Roche Amplicor and Abbott m2000.  The organism load of NAAT-positive swabs was quantified.  Concordance between the NAATs was high (kappa agreement: 0.984).  Using the Abbott assay as the gold standard, the sensitivity and specificity of the Roche assay were 97.4 % and 100 %, respectively.  The prevalence of CT by Abbott was 8.0 % (8/100) in the OB-GYN Clinic and 23.7 % (31/131) at SHC.  The sensitivity of HandiLab-C was 12.5 % (1/8) and 19.4 % (6/31) in OB-GYN and SHC, respectively; with specificities of 93.5 % (86/92) and 88 % (88/100), respectively.  Overall positive and negative predictive values of HandiLab-C were 28 % and 84.5 % respectively.  No correlation between HandiLab-C performance and organism load (range of 1.3 x 10(2) to 1.4 x 10(7) bacteria/swab) was observed.  The authors concluded that the performance of HandiLab-C is very poor, with the test yielding more false-positive (18/193) than true-positive (7/38) results.  It remains accessible via the Internet under various brand names and has retained its CE mark.  This situation raises serious concerns about the regulation of diagnostic products available via the Internet and the standards of certain Notified Bodies that issue the CE mark.

Hadgu and Sternberg (2009) stated that Commercial NAATs have become one of the most frequently used tests for detecting CT.  However, published studies have raised important concerns regarding the NAAT evaluation process in general and their reproducibility and clinical specificity in particular.  This is because for many infectious diseases including chlamydia, a true gold standard simply does not exist and, as a result, estimation of test performance parameters in the absence of a gold standard is a difficult and challenging task.

Moncada et al (2009) stated that self-collected glans and rectal swab specimens from men who have sex with men (MSM) may be appropriate, convenient specimens for testing.  These researchers evaluated the use of self-collected swabs for the detection of CT and neisseria gonorrhoeae by a transcription-mediated amplification test (AC2; Aptima Combo 2; Gen-Probe Inc.) and a strand displacement amplification test (SDA; ProbeTec; Becton Dickinson Co.) in MSM seen at the city STD clinic in San Francisco, CA.  For the glans swab specimen, subjects enrolled early in the study rolled a Dacron swab across the meatus 3 times (method 1).  A slightly more invasive procedure was performed later in the study: the subjects inserted the swab 1/4 inch into the urethra, rotated the swab, and then withdrew the swab (method 2).  MSM self-collected a rectal swab specimen and also provided first-catch urine (FCU).  Additional rectal swab samples were then obtained by the clinician.  For the detection of CT and N. gonorrhoeae, all swabs were evaluated by AC2 and SDA, FCU was tested by AC2, and the clinician-collected rectal swabs were cultured.  A rectal true-positive (TP) result was defined as a culture-positive result for CT or N. gonorrhoeae, 2 or more positive NAAT results, or a single NAAT-positive result confirmed by an alternate amplification method (the Aptima CT or N. gonorrhoeae test).  A glans TP result was defined as a positive result for FCU, positive results for both glans specimens (one tested by AC2 and one tested by SDA), or a positive result for a single glans specimen confirmed by an alternate amplification method.  The prevalence rates of CT and N. gonorrhoeae by testing of FCU were 6.8 % (60/882 specimens) and 12.2 % (108/882 specimens), respectively.  Mixed results were obtained with the glans swab: N. gonorrhoeae detection by AC2 and SDA (method 1) had the best performance (sensitivities, greater than 92 %) with samples from a population with a higher prevalence of infection, but their performance for the detection of CT was poor and varied by collection method (sensitivities, 56 % to 68 %).  The prevalence rates of CT and N. gonorrhoeae in the rectum were 7.3 % (66/907 specimens) and 9.4 % (83/882 specimens), respectively.  The sensitivities of the tests with self-collected and clinician-collected rectal swab specimens were comparable (for CT, 41 % and 44 %, respectively, by SDA and 82 % and 71 %, respectively, by AC2; for N. gonorrhoeae, 77 % and 68 %, respectively, by SDA and 84 % and 78 %, respectively, by AC2).  AC2 and SDA were far superior to culture for the detection of CT and N. gonorrhoeae in the rectum, with both tests detecting at least twice as many infections.  While these investigators found self-collected rectal swabs from MSM to be valid specimens for testing, the sensitivities of the tests with glans swab specimens were disappointing except for those from patients with symptomatic N. gonorrhoeae infections.  The authors stated that self-collected glans swab specimens may not be appropriate for the detection of CT or for the detection of N. gonorrhoeae in low-risk or asymptomatic patients by AC2 and SDA, and they would not recommend their use; further studies are needed.

Cameron et al (2009) examined if postal testing kits (PTKs) or patient-delivered partner therapy (PDPT) for partners of women with CT reduce re-infection rates in women, compared with partner notification by patient referral.  A total of 330 testing positive for chlamydia, at clinics for genito-urinary medicine, family planning and termination of pregnancy in Edinburgh, were randomized to 1 of 3 partner interventions: (i) patient referral, (ii) PTK (partners post urine for testing), or (iii) PDPT (1 g azithromycin for partners).  Women submitted urine for chlamydia testing every 3 months.  The primary outcome was re-infection assessed as time to first positive result by the Cox proportional hazard regression.  The proportion of partners tested or treated with each intervention was determined.  Out of 330 women, 215 (65 %) were re-tested over 12 months.  There were 32 of 215 women (15 %) who re-tested positive (7, 15 and 10 women from the patient referral, PTK and PDPT groups, respectively).  There was no significant difference in re-infection between PDPT versus patient referral (hazard ratio [HR] 1.32, 95 % confidence interval [CI]: 0.50 to 3.56), PTK versus patient referral (HR 2.35, 95 % CI: 0.94 to 5.88) or PDPT versus PTK (HR 0.55, 95 % CI: 0.24 to 1.24).  There was no significant difference in the proportion of partners confirmed tested/treated between the patient referral (34 %) and PTK (41 %, p = 0.32) or PDPT (42 %, p = 0.28) groups.  The authors concluded that PTK and PDPT do not reduce re-infection rates in women with chlamydia compared with patient referral.  However, PDPT may offer other advantages such as simplicity and cost compared with patient referral.

Mania-Pramanik et al (2012) noted that in India, the impact of current C. trachomatis in reproductive health remains a neglected area of investigation.  These investigators examined if current chlamydia infection is associated with any clinical complication that needs the attention of clinical investigators.  In this cross-sectional study, these researchers enrolled 896 women attending the Gynecology Out Patient for the detection of C. trachomatis infection.  Polymerase chain reaction (PCR) was used to diagnose current C. trachomatis infection and ELISA for past infections.  Bacterial vaginosis, candida and trichomonas were screened.  The results of symptomatic and asymptomatic groups were compared.  The data was analyzed using Epi Info version 6 and "Z" test.  A probability value of p ≤ 0.05 was considered as significant.  Statistical analysis revealed significant association between current C. trachomatis infection with infertility when comparing infected fertile (18.6 % versus 9.4 %, odds ratio: 2.19, p< 0.0005) and uninfected infertile women (45.6 % versus 27.3%, odds ratio: 2.24, p < 0.0001).  Average infection rate was 12.1 %, highest in women with infertility (18.6 %) or with ectopic pregnancy (25 %).  Significant proportions of infected women with infertility (p < 0.01) or with recent pregnancy (p < 0.001) were asymptomatic.  Follow-up of infected women who became negative after treatment [28 women from infertility group and 9 women with recurrent spontaneous abortion (RSA)] revealed live-birth in 8 (21.6 %) women within 1 year, 4 with infertility and 4 with RSA.  The authors concluded that the findings of this study suggested association between current C. trachomatis infection and infertility.  Absence of signs and symptoms associated with this infection highlights its diagnosis in women with a history of infertility and RSA for their better management, as revealed by live-births with 1 year of follow-up.

Naderi et al (2012) stated that damage of the fallopian tube after sexually transmitted diseases like C. trachomatis, is an important risk factor for ectopic pregnancy (EP).  These researchers evaluated the prevalence of C. trachomatis infection in patients with EP in the southeastern part of Iran.  Polymerase chain reaction on fallopian tube tissue was applied to detect Chlamydia DNA in 42 patients with EP (EP group) and 87 patients without EP (control group) who underwent tubal ligation.  The same protocol was performed with urine samples taken from the husbands in both groups.  Out of all studied females, 5 patients in the EP group were PCR-positive for C. trachomatis and none of the control group subjects was PCR-positive for C. trachomatis infection (p < 0.05).  Among the husbands, the PCR result was positive in the urine of 19 males (9 in the EP group and 10 in the control group).  All PCR-positive women had husbands with PCR-positive urine samples.  No significant difference was found between chlamydia infection in the EP and the control groups regarding age, duration of marriage, contraceptive method and history of infertility surgery and pelvic pain.  There was no significant difference between prevalence of EP in women based on the PCR outcome in the husbands.  The chlamydia infection in men did not show any relation to the number of marriages.  The authors concluded that based on these findings, it can be concluded that chlamydia infection is an important risk factor of the fallopian tube damage and EP.  Thus, screening programs and treatment of chlamydia infection are recommended in young women and high-risk women and men.

Kamel et al (2013) stated that C. trachomatis infection is a worldwide-distributed sexually transmitted infection that may lead to infertility.  These researchers reported the prevalence of C. trachomatis infection among infertile women in Saudi Arabia.  A community-based study was carried out at the obstetrics and gynecology clinic at Jazan General Hospital, Saudi Arabia.  The study group included 640 Saudi infertile women aged between 18 and 40 years and who attended the gynecology clinic for infertility examination throughout 1 year of study (from July 1, 2011 to June 30, 2012).  The randomized control group included 100 Saudi fertile women who attended the obstetrics clinic for routine antenatal care.  All recruited women were screened for chlamydia infection by enzyme-linked immunosorbent assay (ELISA) for detection of serum-specific antibodies and then re-tested by the McCoy cell culture technique.  The prevalence of C. trachomatis infection among infertile women was high, at 15.0 %.  The rate of chlamydia infection detected by ELISA was 9.84 %, and it was 12.03 % by the culture method (p = 0.2443).  The authors concluded that high prevalence of C. trachomatis infection among Saudi infertile women demands a national screening program for early detection among infertile couples.

The National Institute for Health and Clinical Excellence’s guideline on “Fertility: Assessment and treatment for people with fertility problems” (NICE, 2013) recommended that “Before undergoing uterine instrumentation women should be offered screening for Chlamydia trachomatis using an appropriately sensitive technique”.

Appendix

The following tests are considered medically necessary for screening or diagnosis of C. trachomatis infection:

1. Cell culture
2. Enzyme immunoassay (EIA)
3. Direct fluorescent antibody (DFA)
4. DNA hybridization (DNA probe)
5. DNA amplified hybridization (nucleic acid amplification) which includes any of the following: