Performance of Treponemal Tests for the Diagnosis of Syphilis.

BACKGROUND: Treponemal immunoassays are increasingly used for syphilis screening with the reverse sequence algorithm. There are few data describing performance of treponemal immunoassays compared to traditional treponemal tests in patients with and without syphilis. METHODS: We calculated sensitivity and specificity of 7 treponemal assays: (1) ADVIA Centaur (chemiluminescence immunoassay [CIA]); (2) Bioplex 2200 (microbead immunoassay); (3) fluorescent treponemal antibody absorption test (FTA-ABS); (4) INNO-LIA (line immunoassay); (5) LIAISON CIA; (6) Treponema pallidum particle agglutination assay (TPPA); and (7) Trep-Sure (enzyme immunoassay [EIA]), using a reference standard combining clinical diagnosis and serology results. Sera were collected between May 2012-January 2013. Cases were characterized as: (1) current clinical diagnosis of syphilis: primary, secondary, early latent, late latent; (2) prior treated syphilis only; (3) no evidence of current syphilis, no prior history of syphilis, and at least 4 of 7 treponemal tests negative. RESULTS: Among 959 participants, 262 had current syphilis, 294 had prior syphilis, and 403 did not have syphilis. FTA-ABS was less sensitive for primary syphilis (78.2%) than the immunoassays or TPPA (94.5%-96.4%) (all P ≤ .01). All immunoassays were 100% sensitive for secondary syphilis, 95.2%-100% sensitive for early latent disease, and 86.8%-98.5% sensitive in late latent disease. TPPA had 100% specificity. CONCLUSIONS: Treponemal immunoassays demonstrated excellent sensitivity for secondary, early latent, and seropositive primary syphilis. Sensitivity of FTA-ABS in primary syphilis was poor. Given its high specificity and superior sensitivity, TPPA is preferred to adjudicate discordant results with the reverse sequence algorithm over the FTA-ABS.

Gaps in Chlamydia Treatment Within California Family Planning Clinics: Are Patients Filling Prescriptions?

BACKGROUND: Compared with receiving medication dispensed in a health center, patients receiving prescriptions must take additional steps for treatment. Few clinics have protocols for ensuring prescriptions are filled. This study evaluated prescription fill rates for chlamydia treatment based on claims data in California Title X clinics and examined fill rates by patient demographics and clinic type. METHODS: We collected treatment information during Title X site audits for a convenience sample of patients with a positive chlamydia test between January 2008 and March 2013. We categorized patients as receiving treatment on-site versus via prescription and matched prescriptions to pharmacy billing claims within 90 days of test date. We examined treatment rates by patient age, gender, and race/ethnicity, and by clinic type, and assessed the median time to treatment. RESULTS: Among 790 patients diagnosed with chlamydia across 79 clinics, 65% (n = 513) were treated on-site and 33% (n = 260) via prescription; 17 (2%) did not have treatment information. Sixty-seven percent of prescriptions had confirmed receipt of treatment. Prescription fill rates were lower for patients age 18 years and younger (47% vs. 71%, P < 0.01) and for patients attending federally qualified health centers compared with stand-alone family planning clinics (63% vs. 88%, P < 0.01). Median time to treatment was similar for patients treated on-site (5 days) or via prescription (4 days). CONCLUSIONS: Delays in chlamydia treatment increase risk of complications and ongoing transmission. Providing medications on-site can improve treatment rates, especially among younger patients. These insights can inform clinic treatment protocols and efforts to improve quality of chlamydia care.

Correlation of Treponemal Immunoassay Signal Strength Values with Reactivity of Confirmatory Treponemal Testing.

Automated treponemal immunoassays are used for syphilis screening with the reverse-sequence algorithm; discordant results (e.g., enzyme immunoassay [EIA] reactive and reactive plasma reagin [RPR] nonreactive) are resolved with a second treponemal test. We conducted a study to determine automated immunoassay signal strength values consistently correlating with reactive confirmatory treponemal testing. We conducted a cross-sectional analysis of four automated immunoassays (BioPlex 2200 microbead immunoassay [MBIA], Liaison chemiluminescence immunoassay [CIA], Advia-Centaur CIA, and Trep-Sure EIA) and three manual assays (Treponema pallidum particle agglutination [TP-PA], fluorescent treponemal antibody absorption [FTA-ABS] test, and Inno-LIA line immunoassay). We compared signal strength values of automated immunoassays and positive and negative agreement. Among 1,995 specimens, 908 (45.5%) were true positives (≥4/7 tests reactive) and 1,087 (54.5%) were true negatives (≥4/7 tests nonreactive). Positive agreement ranged from 86.1% (83.7 to 88.2%) for FTA-ABS to 99.7% (99.0 to 99.9%) for Advia-Centaur CIA; negative agreement ranged from 86.3% (84.1 to 88.2%) for Trep-Sure EIA to 100% for TP-PA (99.6 to 100%). Increasing signal strength values correlated with increasing reactivity of confirmatory testing (P < 0.0001 for all automated immunoassays by Cochran-Armitage test for trend). All automated immunoassays had signal strength cutoffs corresponding to ≥4/7 reactive treponemal tests. BioPlex MBIA and Liaison CIA had signal strength cutoffs correlating with ≥99% and 100% TP-PA reactivity, respectively. The Advia-Centaur CIA and Trep-Sure EIA had signal strength cutoffs correlating with at least 95% TP-PA reactivity. All automated immunoassays had signal strength cutoffs correlating with at least 95% FTA-ABS reactivity. Assuming that a 95% level of confirmation is adequate, these signal strength values can be used in lieu of confirmatory testing with TP-PA and FTA-ABS.

Characteristics Associated With Delivery of an Infant With Congenital Syphilis and Missed Opportunities for Prevention-California, 2012 to 2014.

BACKGROUND: Congenital syphilis (CS), the transmission of Treponema pallidum from mother to fetus during pregnancy, can cause adverse birth outcomes. In 2012 to 2014, the CS rate in California increased more than 200% from 6.6 to 20.3 cases per 100,000 live births. Our objectives were to identify characteristics associated with delivering an infant with CS and missed opportunities for prevention among syphilis-infected pregnant women in California. METHODS: We linked California Department of Public Health syphilis surveillance records from women aged 15 to 45 years-diagnosed from March 13, 2012, to December 31, 2014-to birth records. We compared characteristics among mothers who delivered an infant with CS (CS mothers) with mothers who delivered an infant without CS (non-CS mothers) by using χ or Fisher exact tests. To visualize gaps in prevention among syphilis-infected pregnant women, we constructed a CS prevention cascade, a figure that shows steps to prevent CS. RESULTS: During the selected period, 2498 women were diagnosed as having syphilis, and 427 (17%) linked to birth records; 164 (38%) were defined as CS mothers and 263 (62%) as non-CS mothers. Mothers with CS were more likely than non-CS mothers to have their first prenatal care visit in the third trimester. High proportions of mothers in both groups reported high-risk sexual behaviors, methamphetamine use, or incarceration (13%-29%). The CS prevention cascade showed decrements of 5% to 11% in prenatal care receipt, testing, and treatment steps; only 62% of potential CS births were prevented. CONCLUSIONS: Multifaceted efforts are needed to address gaps in the CS prevention cascade and reduce CS cases in California.

Trends in Chlamydia Screening, Test Positivity, and Treatment Among Females in California Juvenile Detention Facilities, 2003-2014.

BACKGROUND: Juvenile detention facilities house adolescents at high risk for sexually transmitted diseases. Collaboration between health departments and juvenile detention authorities can provide routine, cost-efficient chlamydia screening and treatment to females with limited access to care. We describe trends in screening, positivity, treatment, and associated costs in a well-established juvenile detention chlamydia screening program. METHODS: In the California Chlamydia Screening Project, juvenile detention facilities in 12 counties collected quarterly aggregate data on female census and line-listed chlamydia test results and treatment data from fiscal year (FY) 2003-2004 to FY 2013-2014. Trends in the proportion of females screened, positivity, and treatment by age, race/ethnicity, and facility volume were evaluated by Cochran-Armitage test. The median cost of the program per chlamydia positive identified was compared by facility in FY 2013-2014. RESULTS: Data from 59,518 test records among juvenile females indicated high screening rates (75.1%-79.4%). Chlamydia positivity, although consistently high, decreased from 14.8% in 2003-2004 to 11.5% in 2013-2014 (P < 0.001). Documented treatment decreased (88.8% in 2005-2006 to 79.0% in 2013-2014, P < 0.001); of those treated, treatment within 7 days increased (80.1% in 2005-2006 to 88.8% in 2013-2014, P < 0.001). The median cost per chlamydia positive identified was $708 (interquartile range, $669-$894) and was lowest for facilities with high chlamydia positivity. CONCLUSIONS: The California Chlamydia Screening Project demonstrated consistently high rates of chlamydia screening and positivity among adolescent females while keeping costs low for high-volume facilities. Further improvement in timely treatment rates remains a challenge for extending the impact of screening in this high-risk population.

Bacterial Sexually Transmitted Disease Screening Outside the Clinic--Implications for the Modern Sexually Transmitted Disease Program.

BACKGROUND: The development of noninvasive nucleic acid amplification tests for chlamydia and gonorrhea has facilitated innovation in moving sexually transmitted disease (STD) screening to nonclinical settings. However, limited data are available to inform local STD programs on evidence-based approaches to STD screening in nonclinical settings in the United States. METHODS: We conducted a systematic review of the literature published since 2000 related to chlamydia, gonorrhea, and syphilis screening in US correctional settings, bathhouses and sex venues, self-collected at-home testing, and other nonclinical sites. RESULTS: Sixty-four articles met eligibility criteria and were reviewed. Although data on testing volume and positivity were available, there were scarce data on the proportion of new positives treated and the programmatic costs for the various screening programs. Screening in correctional settings identified a sizable amount of asymptomatic infections. The value and sustainability of screening in the other nonclinical settings examined was not clear from the published literature. CONCLUSIONS: Local and state health departments should explore the development of sustainable jail and juvenile detention screening programs for STDs. Furthermore, local programs should pilot outreach and home-based STD screening programs to determine if they are identifying asymptomatic persons who would not have otherwise been found. Local programs are encouraged to present and publish their findings related to non-clinic-based screening to enhance the limited body of literature; data on the proportion of new infections treated and the local program costs are needed.

Discordant Syphilis Immunoassays in Pregnancy: Perinatal Outcomes and Implications for Clinical Management.

BACKGROUND: The reverse sequence algorithm is often used for prenatal syphilis screening by high-volume laboratories, beginning with a treponemal test such as the chemiluminescence immunoassay (CIA), followed by testing of CIA-positive (CIA(+)) specimens with the rapid plasma reagin test (RPR). The clinical significance of discordant serology (CIA(+)/RPR(-)) for maternal and neonatal outcomes is unknown. METHODS: From August 2007 to August 2010, all pregnant women at Kaiser Permanente Northern California with discordant treponemal serology underwent reflexive testing with Treponema pallidum particle agglutination assay (TP-PA) and were categorized as "TP-PA confirmed" (CIA(+)/RPR(-)/TP-PA(+)) or "isolated CIA positive" (CIA(+)/RPR(-)/TP-PA(-)). Demographic variables and clinical data were abstracted from the medical record and compared by TP-PA status. RESULTS: Of 194 pregnant women, 156 (80%) were CIA(+)/RPR(-)/TP-PA(-) and 38 (20%) were CIA(+)/RPR(-)/TP-PA(+). Among the 77 (49%) CIA(+)/RPR(-)/TP-PA(-) women who were retested, 53% became CIA(-). CIA(+)/RPR(-)/TP-PA(+) (n = 38) women were more likely to be older, have a prior history of sexually transmitted infections, and receive treatment for syphilis during pregnancy than women who were CIA(+)/RPR(-)/TP-PA(-) (all P < .005). Most pregnancies (189/194 [97.5%]) resulted in a live birth; there was no difference in birth outcomes according to TP-PA status and no stillbirths attributable to syphilis. CONCLUSIONS: Most pregnant women with discordant serology were CIA(+)/RPR(-)/TP-PA(-); more than half who were retested became CIA(-). CIA(+)/RPR(-)/TP-PA(-) serology in pregnancy is likely to be falsely positive. Reflexive testing of discordant specimens with TP-PA is important to stratify risk given the likelihood of false-positive results in this population.

Measuring the uptake and impact of Chlamydia screening programs--easier said than done.

The passage of the landmark United States (U.S.) Patient Protection and Affordable Care Act (ACA) of 2010 has placed a new emphasis on prevention services, including increased access, coverage, and improved quality of care. In this legislation, chlamydia screening qualifies along with other preventive services (The Patient Protection and Affordable Care Act, P.H. 111-148, March 2010, §2,713) as an essential health service benefit by virtue of having an "A" rating ("strongly recommended") from the U.S. Preventive Services Task Force. However, along with this important commitment of public health resources comes accountability by demonstrating outcomes and results. It should not come as a surprise that in the current era of unprecedented government budget reductions, there is a compelling need for evidence-based prioritization and impact assessment. Funding agencies increasingly need health program data to show the impact of investment in preventive services, and chlamydia screening is no exception. However, measuring the population-level impact of chlamydia screening expansion in the U.S. since the 1980s has been problematic; conflicting data on screening uptake, chlamydia burden, and adverse reproductive outcomes, including pelvic inflammatory disease (PID) and tubal factor infertility, have all been challenging to interpret, despite compelling epidemiologic evidence supporting intervention.

Evidence of human papillomavirus vaccine effectiveness in reducing genital warts: an analysis of California public family planning administrative claims data, 2007-2010.

Because of the rapid development of genital warts (GW) after infection, monitoring GW trends may provide early evidence of population-level human papillomavirus (HPV) vaccine effectiveness. Trends in GW diagnoses were assessed using public family planning administrative data. Between 2007 and 2010, among females younger than 21 years, these diagnoses decreased 35% from 0.94% to 0.61% (P(trend) < .001). Decreases were also observed among males younger than 21 years (19%); and among females and males ages 21-25 (10% and 11%, respectively). The diagnoses stabilized or increased among older age groups. HPV vaccine may be preventing GW among young people.

Screening for syphilis with the treponemal immunoassay: analysis of discordant serology results and implications for clinical management.

BACKGROUND: Screening for syphilis with treponemal chemiluminescence immunoassays (CIA) identifies patients with discordant serology who are not identified with traditional screening methods (eg, CIA-positive, rapid plasma regain (RPR)-negative). We sought to describe the clinical characteristics and management of patients with discordant syphilis serology. METHODS: From August 2007-October 2007, patients with CIA-positive, RPR-negative serology were tested with the Treponema pallidum particle agglutination assay (TP-PA) at Kaiser Permanente Northern California. Clinical and demographic characteristics, prior syphilis history and CIA index values were compared for CIA-positive, RPR-negative patients according to TP-PA status. RESULTS: Of 21,623 assays, 439 (2%) were CIA-positive and 255/439 (58%) were RPR-negative; subsequently, 184 (72%) were TP-PA-positive and 71 (28%) were TP-PA--negative. TP-PA--positive patients were more likely to be male, HIV-positive, homosexual, previously treated for syphilis (57% versus 9%), with higher median CIA index values (9.8 versus 1.6) (all P < .0001). After repeat testing, 7/31 (23%) CIA-positive, RPR-negative, TP-PA--negative patients seroreverted to CIA-negative. CONCLUSIONS: TP-PA results in conjunction with clinical/behavioral assessment helped guide the management of patients with CIA-positive, RPR-negative serology. TP-PA-positive patients were both highly likely to have prior syphilis and major epidemiologic risk factors for syphilis. CIA-positive, RPR-negative, TP-PA-negative serology may represent a false-positive CIA in low-prevalence populations.

High postnatal exposures to polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) via breast milk in California: does BDE-209 transfer to breast milk?

Breast milk samples collected during 2003-2005 from 82 first-time mothers in 24 communities located throughout California contained levels of polybrominated diphenyl ethers (∑(tri-hexa (8))PBDEs; median = 53.3 ng/g lw, range = 9.60-1291) and polychlorinated biphenyls (∑(12)PCBs; median = 73.4 ng/g lw, range = 22.2-433) that are among the highest in the world. PBDE levels varied 100-fold. BDE-47 was the dominant PBDE congener, with levels exceeding the U.S.EPA Reference Dose (RfD) for neurodevelopmental toxicity (100 ng/kg/day) in most (60%) breast milk samples. In some samples, BDE-209 (2/82) and/or BDE-153 (5/82) were the dominant congeners, suggesting that BDE-209 can transfer to breast milk and/or break down in the mother and transfer to the nursing infant as the lower-brominated PBDEs associated with adverse effects. PBDE levels in California breast milk are approaching those of PCBs, and the trend PBDEs > PCBs may continue as PBDEs migrate from products to the indoor and outdoor environments.

A closer look at age: deconstructing aggregate gonorrhea and chlamydia rates, California, 1998-2007.

BACKGROUND: Risk of gonorrheal (GC) and chlamydial (CT) infection is highly associated with age. Case rates typically are reported in 5-year categories. Highest rates are seen consistently in the 15- to 19-year and 20- to 24-year age groups for both genders. It is not clear how aggregate, age-specific rates mask finer differences in risk by single age across and within racial/ethnic groups. METHODS: California case-based surveillance data for 1998 through 2007 were used to calculate GC and CT rates by single age at diagnosis. The distribution of single gender and age-specific rates was compared with 5-year age-specific rates. Descriptive statistics for age by race/ethnicity were calculated, and trends over time were assessed. RESULTS: Female, single-age-specific GC and CT rates for 2007 increased strikingly during adolescence and then declined quickly. Male, single-age-specific GC rates declined more gradually than did CT rates. The rate for the aggregate 15- to 19-year-old age group fit the single-age rates poorly, particularly for females, who in 2007 had a peak rate at age 19 for GC (497 per 100,000) and for CT (3640 per 100,000), though the highest aggregate rate was for ages 20 to 24. Blacks had the youngest mean age for both GC and CT. Mean ages increased significantly from 1998 through 2007 for female GC and CT cases, as well as for male CT cases. CONCLUSIONS: Age and race/ethnicity data should be examined in finer detail than the 5-year aggregate data, in order to target sexually transmitted disease prevention and control interventions more effectively.

Sex and age correlates of Chlamydia prevalence in adolescents and adults entering correctional facilities, 2005: implications for screening policy.

OBJECTIVES: To evaluate sex and age correlates of chlamydia prevalence in incarcerated populations. METHODS: Cross-sectional analysis of chlamydia prevalence by demographic characteristics from incarcerated females and males entering selected juvenile and adult correctional facilities (jails) in the United States in 2005. RESULTS: A total of 97,681 and 52,485 incarcerated persons aged >/=12 years were screened for chlamydia in 141 juvenile and 22 adult correctional facilities, respectively. Overall, chlamydia prevalence was high in females (14.3% and 7.5%) in both juvenile and adult facilities when compared with that in males (6.0% and 4.6%). The chlamydia prevalence was higher in incarcerated females than in incarcerated males for persons 40 years; in males it was 8.8% in 18- to 20-year olds compared with 1.4% in those >40 years. CONCLUSIONS: The consistently high chlamydia prevalence among females in juvenile facilities and females (

Assessment of the Association of Chlamydia trachomatis Infection and Adverse Perinatal Outcomes with the Use of Population-Based Chlamydia Case Report Registries and Birth Records.

OBJECTIVE: We assessed the relationship between Chlamydia trachomatis (CT) infections identified during pregnancy and adverse perinatal birth outcomes (including premature rupture of membranes, preterm delivery, and low birthweight) by matching CT reports and birth records. METHODS: We merged California birth records from 1997, 1998, and 1999 with California CT reports from the same years to determine the proportion of birth records matched to a female CT report, using maternal last name, first name, date of birth, and county of residence. We used logistic regression to assess the crude and adjusted association between a CT report less than 10 months before the birth record date and premature rupture of membranes, preterm delivery, and low birthweight. These results were adjusted for age, race/ethnicity, level of education, and prenatal care. RESULTS: Of 675,786 birth records and 101,296 female CT reports, 14,039 women had a CT case report and a birth record; 10,917 birth records (1.6%) were matched to a CT report during pregnancy, and 10,940 (10.8%) of CT reports were matched to a birth record date 10 months after date of diagnosis/report. For premature rupture of membranes, the adjusted odds ratio (AOR) was 1.2, 95% confidence interval (CI) 1.0, 1.3; for low birthweight, the AOR was 1.2, 95% CI 1.1, 1.3. The reduction in birthweight associated with prenatal CT infection was 31.7 grams. CONCLUSIONS: The increased risk of adverse perinatal outcomes associated with prenatal CT infection supports current prenatal CT screening guidelines. Matching of surveillance and vital statistics data sources was an efficient method to assess this association.

Rectal Chlamydia trachomatis and Neisseria gonorrhoeae Infections Among Women Reporting Anal Intercourse.

OBJECTIVE: To examine the prevalence and treatment of rectal Chlamydia trachomatis and Neisseria gonorrhoeae infections among women reporting receptive anal intercourse in a network of sexually transmitted disease or sexual health clinics and estimate the proportion of missed infections if women were tested at the genital site only. METHODS: We conducted a cross-sectional analysis of C trachomatis and N gonorrhoeae test results from female patients reporting receptive anal intercourse in the preceding 3 months during visits to 24 sexually transmitted disease clinics from 2015 to 2016. Primary outcomes of interest were 1) anatomic site-specific C trachomatis and N gonorrhoeae testing and positivity among women attending selected U.S. sexually transmitted disease clinics who reported receptive anal intercourse and 2) the proportion of rectal infections that would have remained undetected if only genital sites were tested. RESULTS: Overall, 7.4% (3,743/50,785) of women reported receptive anal intercourse during the 2 years. Of the 2,818 women tested at both the genital and rectal sites for C trachomatis, 292 women were positive (61 genital only, 60 rectal only, and 171 at both sites). Of the 2,829 women tested at both the genital and rectal sites for N gonorrhoeae, 128 women were positive (31 genital only, 23 rectal only, and 74 at both sites). Among women tested at both anatomic sites, the proportion of missed C trachomatis infections would have been 20.5% and for N gonorrhoeae infections, 18.0%. CONCLUSION: Genital testing alone misses approximately one fifth of C trachomatis and N gonorrhoeae infections in women reporting receptive anal intercourse in our study population. Missed rectal infections may result in ongoing transmission to other sexual partners and reinfection.

Contraceptive Method Use and Chlamydia Positivity Among California Family Planning Clients: The Case for New Multipurpose Prevention Technologies.

BACKGROUND: Adolescent girls and young women experience high rates of sexually transmitted infection (STI) with currently available contraceptive methods, yet few studies examine the burden of chlamydial infection by contraceptive method used. MATERIALS AND METHODS: In this cross-sectional analysis, we linked July 2012-June 2013 claims from a publicly-funded family planning program in California to chlamydia laboratory test results. Female clients were classified by the most effective contraceptive method reported by providers during the year: tier 1 (high-efficacy permanent or long-acting reversible methods), tier 2 (shorter-acting hormonal methods), or tier 3 (barrier methods, emergency contraception, or natural family planning). In addition, we identified clients who received condoms from providers. We used log-binomial models to estimate adjusted prevalence ratios comparing chlamydia positivity by contraceptive method(s). RESULTS: Of 74,636 female clients of ages 15-29 years with chlamydia test results, 5.1% had at least one positive test during the year. Chlamydia positivity was highest among tier 2 users (5.3%) compared with 4.5% and 4.9% among tiers 1 and 3 users, respectively (p < 0.001). Positivity was higher among clients who received condoms from providers than those who did not (6.3% vs. 4.3%, p < 0.001). In adjusted analyses, there were no significant differences in positivity by contraceptive tier. However, clients who received condoms had 1.32 (95% confidence interval: 1.24-1.40) times the positivity of those who did not. CONCLUSIONS: We found high chlamydia positivity among young female family planning clients regardless of contraceptive method. The development and provision of additional Multipurpose Prevention Technologies that confer protection against both pregnancy and STIs may help to address unmet need for STI prevention.