CDC Laboratory Recommendations for Syphilis Testing, United States, 2024.

This report provides new CDC recommendations for tests that can support a diagnosis of syphilis, including serologic testing and methods for the identification of the causative agent Treponema pallidum. These comprehensive recommendations are the first published by CDC on laboratory testing for syphilis, which has traditionally been based on serologic algorithms to detect a humoral immune response to T. pallidum. These tests can be divided into nontreponemal and treponemal tests depending on whether they detect antibodies that are broadly reactive to lipoidal antigens shared by both host and T. pallidum or antibodies specific to T. pallidum, respectively. Both types of tests must be used in conjunction to help distinguish between an untreated infection or a past infection that has been successfully treated. Newer serologic tests allow for laboratory automation but must be used in an algorithm, which also can involve older manual serologic tests. Direct detection of T. pallidum continues to evolve from microscopic examination of material from lesions for visualization of T. pallidum to molecular detection of the organism. Limited point-of-care tests for syphilis are available in the United States; increased availability of point-of-care tests that are sensitive and specific could facilitate expansion of screening programs and reduce the time from test result to treatment. These recommendations are intended for use by clinical laboratory directors, laboratory staff, clinicians, and disease control personnel who must choose among the multiple available testing methods, establish standard operating procedures for collecting and processing specimens, interpret test results for laboratory reporting, and counsel and treat patients. Future revisions to these recommendations will be based on new research or technologic advancements for syphilis clinical laboratory science.

Incidence and Prevalence of Trichomonas vaginalis Infection Among Persons Aged 15 to 59 Years: United States, 2018.

BACKGROUND: Trichomonas vaginalis (TV) is a sexually transmitted parasite associated with multiple adverse outcomes in women. Estimating TV incidence is challenging because of its largely asymptomatic presentation. METHODS: Per-capita prevalence was estimated using the National Health and Nutrition Examination Survey, 2013 to 2018. Incidence was estimated using ordinary differential equations assuming static incidence at steady state and fit using Bayesian techniques. Model inputs included estimates of proportion of asymptomatic cases, natural clearance, and time to symptomatic treatment seeking. Posterior distributions were drawn, and uncertainty was reported, from 25th (Q1) to 75th (Q3) percentiles. Aggregated measures were estimated by combining component distributions. RESULTS: Among 15- to 59-year-olds in 2018, the number of prevalent TV infections was 2.6 (Q1, 2.4; Q3, 2.7) million overall, 470,000 (Q1, 414,000; Q3, 530,000) among men, and 2.1 (Q1, 2.0; Q3, 2.2) million among women; the numbers of incident infections were 6.9 (Q1, 6.2; Q3, 7.6) million, 3.3 (Q1, 2.8; Q3, 3.8) million, and 3.5 (Q1, 3.1; Q3, 4.0) million among all persons, men, and women, respectively. Persons aged 15 to 24 years comprised 15.6% and 16.3% of all prevalent and incident infections, respectively; prevalence and incidence in both sexes increased with age. Incidences in both sexes were highly dependent on estimates of natural clearance, which were based on few data. CONCLUSIONS: Prevalence and incidence of TV are substantial in the United States, particularly among those 25 years or older. Although estimated prevalence is higher in women, estimated incidence is similar in men and women. Data on key parameters of TV infection are limited; future research should focus on clarifying the natural history of TV.

Expanding U.S. Laboratory Capacity for Neisseria gonorrhoeae Antimicrobial Susceptibility Testing and Whole-Genome Sequencing through the CDC's Antibiotic Resistance Laboratory Network.

U.S. gonorrhea rates are rising, and antibiotic-resistant Neisseria gonorrhoeae (AR-Ng) is an urgent public health threat. Since implementation of nucleic acid amplification tests for N. gonorrhoeae identification, the capacity for culturing N. gonorrhoeae in the United States has declined, along with the ability to perform culture-based antimicrobial susceptibility testing (AST). Yet AST is critical for detecting and monitoring AR-Ng. In 2016, the CDC established the Antibiotic Resistance Laboratory Network (AR Lab Network) to shore up the national capacity for detecting several resistance threats including N. gonorrhoeae AR-Ng testing, a subactivity of the CDC's AR Lab Network, is performed in a tiered network of approximately 35 local laboratories, four regional laboratories (state public health laboratories in Maryland, Tennessee, Texas, and Washington), and the CDC's national reference laboratory. Local laboratories receive specimens from approximately 60 clinics associated with the Gonococcal Isolate Surveillance Project (GISP), enhanced GISP (eGISP), and the program Strengthening the U.S. Response to Resistant Gonorrhea (SURRG). They isolate and ship up to 20,000 isolates to regional laboratories for culture-based agar dilution AST with seven antibiotics and for whole-genome sequencing of up to 5,000 isolates. The CDC further examines concerning isolates and monitors genetic AR markers. During 2017 and 2018, the network tested 8,214 and 8,628 N. gonorrhoeae isolates, respectively, and the CDC received 531 and 646 concerning isolates and 605 and 3,159 sequences, respectively. In summary, the AR Lab Network supported the laboratory capacity for N. gonorrhoeae AST and associated genetic marker detection, expanding preexisting notification and analysis systems for resistance detection. Continued, robust AST and genomic capacity can help inform national public health monitoring and intervention.

Azithromycin Susceptibility Among Neisseria gonorrhoeae Isolates and Seasonal Macrolide Use.

Rising azithromycin nonsusceptibility among Neisseria gonorrhoeae isolates threatens current treatment recommendations, but the cause of this rise is not well understood. We performed an ecological study of seasonal patterns in macrolide use and azithromycin resistance in N. gonorrhoeae, finding that population-wide macrolide use is associated with increased azithromycin nonsusceptibility. These results, indicative of bystander selection, have implications for antibiotic prescribing guidelines.

Extragenital Chlamydia and Gonorrhea Among Community Venue-Attending Men Who Have Sex with Men - Five Cities, United States, 2017.

Sexually transmitted diseases (STDs) disproportionately affect gay, bisexual, and other men who have sex with men (MSM) in the United States (1). Because chlamydia and gonorrhea at extragenital (rectal and pharyngeal) anatomic sites are often asymptomatic, these anatomic sites serve as a reservoir of infection, which might contribute to gonococcal antimicrobial resistance (2) and increased risk for human immunodeficiency virus (HIV) transmission and acquisition (3). To ascertain prevalence of extragenital STDs, MSM attending community venues were recruited in five U.S. cities to provide self-collected swabs for chlamydia and gonorrhea screening as part of National HIV Behavioral Surveillance (NHBS). Overall, 2,075 MSM provided specimens with valid results, and 13.3% of participants were infected with at least one of the two pathogens in at least one of these two extragenital anatomic sites. Approximately one third of participating MSM had not been screened for STDs in the previous 12 months. MSM attending community venues had a high prevalence of asymptomatic extragenital STDs. The findings underscore the importance of sexually active MSM following current recommendations for STD screening at all exposed anatomic sites at least annually (4).

Performance of Chlamydia trachomatis OmcB Enzyme-Linked Immunosorbent Assay in Serodiagnosis of Chlamydia trachomatis Infection in Women.

Chlamydia trachomatis serological assays with improved sensitivity over commercially available assays are needed to evaluate the burden of C. trachomatis infection and the effectiveness of prevention efforts. We evaluated the performance of a C. trachomatis outer membrane complex protein B (OmcB) enzyme-linked immunosorbent assay (ELISA) in the detection of anti-C. trachomatis antibody responses in C. trachomatis-infected women. OmcB ELISA was less sensitive than our C. trachomatis elementary body (EB) ELISA, but it was highly specific. The magnitude of the antibody response was higher in African-Americans and those with prior C. trachomatis infection. Unlike EB ELISA, the IgG1 response to C. trachomatis OmcB was short-lived and was not maintained by repeat C. trachomatis infection.

Susceptibility of Neisseria gonorrhoeae to Gentamicin-Gonococcal Isolate Surveillance Project, 2015-2016.

The gentamicin minimum inhibitory concentrations (MICs) of Neisseria gonorrhoeae isolates were determined. Seventy-three percent of isolates demonstrated an MIC range of 8 to 16 µg/mL, and 27% demonstrated an MIC of 4 µg/mL or less. Significant associations between gentamicin MIC and resistance or reduced susceptibility to other antimicrobials were found.

Preparing for the Chlamydia and Gonorrhea Self-Test.

New technology may soon allow individuals to test themselves for chlamydia and gonorrhea. These new self-tests might help increase screening, but they will also bring new issues for treatment, prevention, and surveillance. Providers will need to decide how to respond to patients who present after a positive screening test and how to approach partner testing and treatment. Research will be needed to identify approaches to increase screening using these tests. Laboratory-based surveillance will not capture infections if testing does not involve a laboratory, so new surveillance techniques will be needed. Self-tests are new tools that will soon be available. We should be prepared to use them.

Improving STD service delivery: Would American patients and providers use self-tests for gonorrhea and chlamydia?

Chlamydia trachomatis (CT) and Neisseria gonorrhea (GC) are the most frequently reported notifiable diseases in the United States and costs for diagnosis and treatment of these two infections are approximately $700 million per year. A proposed new method for screening for these two infections is self-tests; similar to at-home pregnancy and HIV tests which do not include sending collected specimens to a laboratory for diagnosis. However, no such self-tests for sexually transmitted diseases (STD) have been approved by the Food and Drug Administration (FDA). To determine the acceptability of such a test, we used three surveys, conducted in 2017, including the American Men's Internet Survey, the SummerStyles survey, and the DocStyles survey to ask potential users about their interest in this type of test and how they might use it. Among our sampled population of men who have sex with men, 79.5% said they would prefer to take this type of test at home and 73.9% said they would be willing to pay at least $20 for the test. Among young adults (18-29 years), 54.1% indicated that they would like to take this test at home and 64.5% were willing to pay more than $10 for such a test. Among sampled physicians, 85.1% were "likely" or "very likely" to use an FDA-approved STD self-test in their office to screen for CT or GC. Self-tests for STDs are on our horizon and we need to be prepared to integrate these tests into our healthcare systems.

Immunoglobulin-Based Investigation of Spontaneous Resolution of Chlamydia trachomatis Infection.

Chlamydia trachomatis elementary body enzyme-linked immunosorbent assay (ELISA) was used to investigate serum anti-CT immunoglobulin G1 (IgG1; long-lived response) and immunoglobulin G3 (IgG3; short-lived response indicating more recent infection) from treatment (enrollment) and 6-month follow-up visits in 77 women previously classified as having spontaneous resolution of chlamydia. Of these women, 71.4% were IgG1+IgG3+, consistent with more recent chlamydia resolution. 15.6% were IgG3- at both visits, suggesting absence of recent chlamydia. Using elementary body ELISA, we demonstrated approximately 1 in 6 women classified as having spontaneous resolution of chlamydia might have been exposed to C. trachomatis but not infected. Further, we classified their possible infection stage.

Cluster of Neisseria gonorrhoeae Isolates With High-level Azithromycin Resistance and Decreased Ceftriaxone Susceptibility, Hawaii, 2016.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) currently recommends dual therapy with ceftriaxone and azithromycin for gonorrhea to ensure effective treatment and slow emergence of antimicrobial resistance. Since 2013, the prevalence of reduced azithromycin susceptibility increased in the United States; however, these strains were highly susceptible to cephalosporins. We identified a cluster of Neisseria gonorrhoeae isolates with high-level azithromycin resistance, several of which also demonstrated decreased ceftriaxone susceptibility. METHODS: Eight N. gonorrhoeae isolates collected from 7 patients on Oahu, Hawaii, seen 21 April 2016 through 10 May 2016 underwent routine Etest antimicrobial susceptibility testing by the Hawaii Department of Health. All demonstrated elevated azithromycin minimum inhibitory concentrations (MICs) >256 µg/mL and elevated ceftriaxone MICs (≥0.125 µg/mL). Isolates were sent to the University of Washington and CDC for confirmatory agar dilution testing; sequence data were sent to CDC for analysis. All patients were interviewed and treated, and when possible, partners were interviewed, tested, and treated. RESULTS: All isolates had azithromycin MICs >16 µg/mL and 5 had ceftriaxone MICs = 0.125 µg/mL by agar dilution. All isolates were ß-lactamase positive and were resistant to penicillin, tetracycline, and ciprofloxacin. Genomic analysis revealed genetic relatedness. No patients reported recent travel or antibiotic use, and no male patients reported male sex partners. All patients were successfully treated. CONCLUSIONS: This cluster of genetically related gonococcal isolates with decreased ceftriaxone susceptibility and high-level azithromycin resistance may bring the threat of treatment failure in the United States with the current recommended dual therapy one step closer.

Antimicrobial Drug Prescription and Neisseria gonorrhoeae Susceptibility, United States, 2005-2013.

We investigated whether outpatient antimicrobial drug prescribing is associated with Neisseria gonorrhoeae antimicrobial drug susceptibility in the United States. Using susceptibility data from the Gonococcal Isolate Surveillance Project during 2005-2013 and QuintilesIMS data on outpatient cephalosporin, macrolide, and fluoroquinolone prescribing, we constructed multivariable linear mixed models for each antimicrobial agent with 1-year lagged annual prescribing per 1,000 persons as the exposure and geometric mean MIC as the outcome of interest. Multivariable models did not demonstrate associations between antimicrobial drug prescribing and N. gonorrhoeae susceptibility for any of the studied antimicrobial drugs during 2005-2013. Elucidation of epidemiologic factors contributing to resistance, including further investigation of the potential role of antimicrobial drug use, is needed.

Azithromycin Resistance and Decreased Ceftriaxone Susceptibility in Neisseria gonorrhoeae, Hawaii, USA.

During 2016, eight Neisseria gonorrhoeae isolates from 7 patients in Hawaii were resistant to azithromycin; 5 had decreased in vitro susceptibility to ceftriaxone. Genomic analysis demonstrated a distinct phylogenetic clade when compared with local contemporary strains. Continued evolution and widespread transmission of these strains might challenge the effectiveness of current therapeutic options.

Population-attributable fraction of tubal factor infertility associated with chlamydia.

BACKGROUND: Chlamydia trachomatis infection is highly prevalent among young women in the United States. Prevention of long-term sequelae of infection, including tubal factor infertility, is a primary goal of chlamydia screening and treatment activities. However, the population-attributable fraction of tubal factor infertility associated with chlamydia is unclear, and optimal measures for assessing tubal factor infertility and prior chlamydia in epidemiological studies have not been established. Black women have increased rates of chlamydia and tubal factor infertility compared with White women but have been underrepresented in prior studies of the association of chlamydia and tubal factor infertility. OBJECTIVES: The objectives of the study were to estimate the population-attributable fraction of tubal factor infertility associated with Chlamydia trachomatis infection by race (Black, non-Black) and assess how different definitions of Chlamydia trachomatis seropositivity and tubal factor infertility affect population-attributable fraction estimates. STUDY DESIGN: We conducted a case-control study, enrolling infertile women attending infertility practices in Birmingham, AL, and Pittsburgh, PA, during October 2012 through June 2015. Tubal factor infertility case status was primarily defined by unilateral or bilateral fallopian tube occlusion (cases) or bilateral fallopian tube patency (controls) on hysterosalpingogram. Alternate tubal factor infertility definitions incorporated history suggestive of tubal damage or were based on laparoscopic evidence of tubal damage. We aimed to enroll all eligible women, with an expected ratio of 1 and 3 controls per case for Black and non-Black women, respectively. We assessed Chlamydia trachomatis seropositivity with a commercial assay and a more sensitive research assay; our primary measure of seropositivity was defined as positivity on either assay. We estimated Chlamydia trachomatis seropositivity and calculated Chlamydia trachomatis-tubal factor infertility odds ratios and population-attributable fraction, stratified by race. RESULTS: We enrolled 107 Black women (47 cases, 60 controls) and 620 non-Black women (140 cases, 480 controls). Chlamydia trachomatis seropositivity by either assay was 81% (95% confidence interval, 73-89%) among Black and 31% (95% confidence interval, 28-35%) among non-Black participants (P < .001). Using the primary Chlamydia trachomatis seropositivity and tubal factor infertility definitions, no significant association was detected between chlamydia and tubal factor infertility among Blacks (odds ratio, 1.22, 95% confidence interval, 0.45-3.28) or non-Blacks (odds ratio, 1.41, 95% confidence interval, 0.95-2.09), and the estimated population-attributable fraction was 15% (95% confidence interval, -97% to 68%) among Blacks and 11% (95% confidence interval, -3% to 23%) among non-Blacks. Use of alternate serological measures and tubal factor infertility definitions had an impact on the magnitude of the chlamydia-tubal factor infertility association and resulted in a significant association among non-Blacks. CONCLUSION: Low population-attributable fraction estimates suggest factors in addition to chlamydia contribute to tubal factor infertility in the study population. However, high background Chlamydia trachomatis seropositivity among controls, most striking among Black participants, could have obscured an association with tubal factor infertility and resulted in a population-attributable fraction that underestimates the true etiological role of chlamydia. Choice of chlamydia and tubal factor infertility definitions also has an impact on the odds ratio and population-attributable fraction estimates.

In vitro assessment of dual drug combinations to inhibit growth of Neisseria gonorrhoeae.

The development of resistance to first-line antimicrobial therapies has led to recommendations for combination therapies for the treatment of gonorrhea infection. Recent studies have shown the success of combination therapies in treating patients, but few have reported on the in vitro activities of these drug combinations. An in vitro assessment of azithromycin in combination with gentamicin demonstrated inhibition of growth and suggests that clinical trials may be warranted to assess the utility of this combination in treating gonorrhea infections.

Analysis of Neisseria gonorrhoeae azithromycin susceptibility in the United States by the Gonococcal Isolate Surveillance Project, 2005 to 2013.

Azithromycin, administered with ceftriaxone, is recommended by the CDC for the treatment of gonorrhea. Many experts have expressed concern about the ease with which Neisseria gonorrhoeae can acquire macrolide resistance. We sought to describe gonococcal azithromycin susceptibility in the United States and to determine whether azithromycin susceptibility has changed over time. We analyzed data from 2005 to 2013 from the Gonococcal Isolate Surveillance Project, a CDC-supported sentinel surveillance network that monitors gonococcal antimicrobial susceptibility. A total of 44,144 N. gonorrhoeae isolates were tested for azithromycin susceptibility by agar dilution methods. The overall azithromycin MIC50 was 0.25 µg/ml, and the MIC90 was 0.5 µg/ml. There were no overall temporal trends in geometric means. Isolates from men who had sex with men had significantly higher geometric mean MICs than isolates from men who had sex exclusively with women. The overall prevalence of reduced azithromycin susceptibility (MIC, ≥2 µg/ml) was 0.4% and varied by year from 0.3% (2006 and 2009) to 0.6% (2013). We did not find a clear temporal trend in gonococcal azithromycin MICs in the United States, and the prevalence of reduced azithromycin susceptibility remains low. These findings support the continued use of azithromycin in a combination therapy regimen for gonorrhea.

Comparison of Antimicrobial Susceptibility of Urogenital Neisseria gonorrhoeae Isolates Obtained From Women and Men.

BACKGROUND: The US system for gonococcal antimicrobial susceptibility surveillance monitors trends exclusively among men with urethral infection, the population from whom the yield of gonococcal culture is highest. Little is known about the susceptibility of female urogenital isolates, and it is unclear whether gonococcal susceptibility among men who report sex exclusively with women (MSW) is representative of susceptibility among women. METHODS: Using isolates collected during a recent treatment trial in 5 US cities, we performed a secondary analysis to compare antimicrobial susceptibilities of Neisseria gonorrhoeae urogenital isolates obtained from women, MSW, and men who have sex with men (MSM). Pretreatment isolates were collected from trial participants; minimum inhibitory concentrations (MICs) were determined by agar dilution. Geometric mean MICs were adjusted for geographic location using general linear models. RESULTS: Susceptibility data for urogenital isolates from 56 women, 252 MSW, and 170 MSM were studied. The adjusted geometric mean ceftriaxone MIC was similar among women (0.0067 µg/mL; 95% confidence interval [CI], 0.0049-0.0092 µg/mL) and MSW (0.0060 µg/mL; 95% CI, 0.0053-0.0066 µg/mL). In contrast, the adjusted geometric mean ceftriaxone MIC was higher among MSM (0.0098 µg/mL; 95% CI, 0.0082-0.0119 µg/mL) than among MSW. This same pattern was observed for other antimicrobials, including cefixime and azithromycin CONCLUSIONS: Ceftriaxone, cefixime, and azithromycin MICs were higher among MSM than among MSW, but were similar among women and MSW. These findings suggest that gonococcal antimicrobial susceptibility surveillance based on urethral isolates from MSW may adequately represent susceptibility of urogenital N. gonorrhoeae in women.

The efficacy and safety of gentamicin plus azithromycin and gemifloxacin plus azithromycin as treatment of uncomplicated gonorrhea.

BACKGROUND: Ceftriaxone is the foundation of currently recommended gonorrhea treatment. There is an urgent need for backup treatment options for patients with cephalosporin allergy or infections due to suspected cephalosporin-resistant Neisseria gonorrhoeae. We evaluated the efficacy and tolerability of 2 combinations of existing noncephalosporin antimicrobials for treatment of patients with urogenital gonorrhea. METHODS: We conducted a randomized, multisite, open-label, noncomparative trial in 5 outpatient sexually transmitted disease clinic sites in Alabama, California, Maryland, and Pennsylvania. Patients aged 15-60 years diagnosed with uncomplicated urogenital gonorrhea were randomly assigned to either gentamicin 240 mg intramuscularly plus azithromycin 2 g orally, or gemifloxacin 320 mg orally plus azithromycin 2 g orally. The primary outcome was microbiological cure of urogenital infections (negative follow-up culture) at 10-17 days after treatment among 401 participants in the per protocol population. RESULTS: Microbiological cure was achieved by 100% (lower 1-sided exact 95% confidence interval [CI] bound, 98.5%) of 202 evaluable participants receiving gentamicin/azithromycin, and 99.5% (lower 1-sided exact 95% CI bound, 97.6%) of 199 evaluable participants receiving gemifloxacin/azithromycin. Gentamicin/azithromycin cured 10 of 10 pharyngeal infections and 1 of 1 rectal infection; gemifloxacin/azithromycin cured 15 of 15 pharyngeal and 5 of 5 rectal infections. Gastrointestinal adverse events were common in both arms. CONCLUSIONS: Gentamicin/azithromycin and gemifloxacin/azithromycin were highly effective for treatment of urogenital gonorrhea. Gastrointestinal adverse events may limit routine use. These non-cephalosporin-based regimens may be useful alternative options for patients who cannot be treated with cephalosporin antimicrobials. Additional treatment options for gonorrhea are needed. Clinical Trials Registration. NCT00926796.

Trends in antimicrobial resistance in Neisseria gonorrhoeae in the USA: the Gonococcal Isolate Surveillance Project (GISP), January 2006-June 2012.

BACKGROUND: Neisseria gonorrhoeae has progressively developed resistance to sulfonamides, penicillin, tetracycline and fluoroquinolones, and gonococcal susceptibility to cephalosporins has been declining worldwide. METHODS: We described trends in gonococcal antimicrobial susceptibility in the USA from January 2006 through June 2012. Susceptibility data for cefixime, ceftriaxone, azithromycin, penicillin, tetracycline and ciprofloxacin were obtained from the Gonococcal Isolate Surveillance Project (GISP), a sentinel surveillance system that monitors antimicrobial susceptibility in urethral gonococcal isolates collected from symptomatic men at 25-30 sexually transmitted disease clinics throughout the USA. RESULTS: The percentage of isolates with elevated cefixime minimum inhibitory concentrations (MICs) (≥ 0.25 µg/mL) increased from 0.1% in 2006 to 1.4% in 2010-2011 and was 1.1% in the first 6 months of 2012. The percentage with elevated ceftriaxone MICs (≥ 0.125 µg/mL) increased from 0.1% in 2006 to 0.3%-0.4% during 2009 through the first 6 months of 2012. There were no temporal trends in the prevalence of elevated azithromycin MICs (≥ 2 µg/mL) (0.2%-0.5%). The prevalence of resistance remained high for penicillin (11.2%-13.2%), tetracycline (16.7%-22.8%) and ciprofloxacin (9.6%-14.8%). CONCLUSIONS: The proportion of gonococcal isolates with elevated cephalosporin MICs increased from 2006 to 2010, but plateaued during 2011 and the first 6 months of 2012. Resistance to previously recommended antimicrobials has persisted. As the number of antimicrobials available for gonorrhoea treatment dwindles, surveillance systems such as GISP will be critical to detect emerging resistance trends and guide treatment decisions.

Prevalence of Neisseria gonorrhoeae among persons 14 to 39 years of age, United States, 1999 to 2008.

BACKGROUND: Prevalence estimates from population-based surveys do not suffer from the same biases as case-report and clinic positivity data and may be better to monitor sexually transmitted disease morbidity over time. METHODS: We estimated the prevalence of Neisseria gonorrhoeae in a nationally representative sample of persons aged 14 to 39 years participating in the National Health and Nutrition Examination Survey. RESULTS: From 1999 to 2008, the overall prevalence of gonorrhea was 0.27% (95% confidence interval, 0.13%-0.47%). In the 2005 to 2006 and 2007 to 2008 cycles, prevalence approached 0% and was based on too few positive sample persons to obtain reliable estimates. In 2004, most infections were found in 1 survey location. DISCUSSION: Given the low prevalence and geographic clustering of disease, gonorrhea estimates from national probability surveys are often imprecise and unstable. In 2008, gonorrhea testing in National Health and Nutrition Examination Survey was discontinued. Continued surveillance of gonorrhea should include case reporting and prevalence estimates from local surveys and sentinel surveillance systems.