John R. Papp

Gonorrhea and chlamydia in the United States among persons 14 to 39 years of age, 1999 to 2002

Context Accurate information about the prevalence of sexually transmitted diseases is essential to the development of screening programs that effectively reduce disease burden. Contribution These data from the 19992002 National Health and Nutrition Examination Survey estimate the prevalence of gonorrhea and chlamydia among the U.S. population age 14 to 39 years to be 0.24% and 2.2%, respectively. Chlamydia prevalence was highest among younger women and persons with a history of gonorrhea or chlamydia infection. Cautions Although these are the most recently available data, they are more than 5 years old and did not permit estimation of prevalence by geographic region. Implication These data support current screening and treatment recommendations for chlamydia. The Editors Genital infections with Chlamydia trachomatis and Neisseria gonorrhoeae are important causes of cervicitis and urethritis, as well as pelvic inflammatory disease, ectopic pregnancy, chronic pelvic pain, and infertility, among women (1). In addition, nonulcerative sexually transmitted diseases (STDs), including chlamydia and gonorrhea, induce anogenital inflammation and can facilitate HIV infection (2). Chesson and colleagues (3) estimated total direct medical costs of

Epidemiology of Human Papillomavirus Infection and Abnormal Cytologic Test Results in an Urban Adolescent Population

248 million for chlamydia and

Nucleic Acid Amplification Tests for Diagnosis of Neisseria gonorrhoeae and Chlamydia trachomatis Rectal Infections

77 million for gonorrhea in 2000 among persons age 15 to 24 years. Chlamydia trachomatis infection is the most commonly reported nationally notifiable disease in the United States, with more than 900000 cases reported to state and local health departments in 2005. The second most commonly reported disease is N. gonorrhoeae, with more than 330000 cases reported in 2005 (4). Reported cases represent a partial index of disease burden from chlamydial and gonorrheal infection because many cases are asymptomatic and are not detected. On the basis of reported cases, persons 14 to 39 years of age account for more than 95% of chlamydial cases and more than 90% of gonorrheal cases in the United States (4). To our knowledge, the following report is the most comprehensive description of national disease burden from chlamydia and gonorrhea with results of C. trachomatis and N. gonorrhoeae testing from a representative sample of the civilian noninstitutionalized U.S. population age 14 to 39 years in the National Health and Nutrition Examination Survey (NHANES), 19992002. Methods Survey Design The NHANES is a series of cross-sectional surveys designed to provide national statistics on the health and nutritional status of the general household population through household interviews, standardized physical examinations, and the collection of biological samples in special mobile examination centers. In 1999, NHANES became a continuous survey, with data released every 2 years. The sampling plan of the survey is a stratified, multistage, probability cluster design that selects a sample representative of the U.S. civilian noninstitutionalized population. Data presented in this paper are from the 19992002 survey years. (Additional years of data on gonorrhea and chlamydia were collected in the NHANES survey for the 20032004 cycle, but testing was performed by using a different laboratory test, the Becton Dickinson ProbeTec [Becton Dickinson, Franklin Lakes, New Jersey], owing to the discontinuation of the Abbott LCx [Abbott Laboratories, Abbott Park, Illinois]. Disclosure risks with the NHANES 20032004 gonorrhea data led the National Center for Health Statistics, Centers for Disease Control and Prevention [CDC], to withhold the release of the gonorrhea data for public use. The chlamydia data did not demonstrate any disclosure risks, but because a different laboratory test was used, we felt it prudent to publish data through 2002 only. Once the 20052006 data are available for gonorrhea and chlamydia, the 20032004 data can be better assessed and a data update through 2006 can be published [20052006 data are anticipated to be released in mid- to late 2008 if no quality control issues arise].) Our sample includes 6632 participants, age 14 to 39 years, who were sampled from randomly selected U.S. locations. Adolescents (age 14 to 17 years), African Americans, and Mexican Americans were oversampled to improve precision of estimates for these subgroups. Race or ethnic group was categorized on the basis of the participants self-reported information as non-Hispanic white, non-Hispanic black, or Mexican American. Participants who did not fit into 1 of these categories were classified as other and were analyzed with the total sample but not in race or ethnic subgroups. All participants provided written informed consent. For minors (age <18 years), parents gave written consent, accompanied by the minors assent. An institutional review board at CDC reviewed and approved the study protocol. Sexual behavior data were collected in the mobile examination center during a private, audio, computer-assisted, self-interview. Sex was defined as vaginal, oral, or anal intercourse. In our analyses, we defined sexually experienced as reporting ever having had sex. Questions about history of gonorrhea and chlamydia diagnoses were asked only of sexually experienced persons 18 to 39 years of age. All NHANES participants who were tested for C. trachomatis and N. gonorrhoeae were given an opportunity to obtain their test results by telephone by using a confidential identification number. Reminder letters were sent to adults, and telephone calls were made to minors to encourage participants to call to learn about their test results. Laboratory Testing Urine specimens collected from participants were processed in the mobile examination center and shipped to CDC for C. trachomatis and N. gonorrhoeae testing by using a ligase chain reaction assay (LCx, Abbott Laboratories), according to the manufacturers instructions. Although it is not recommended for routine clinical practice, specimens positive for C. trachomatis or N. gonorrhoeae were retested from the original urine specimen by using the same assay for detection for the purposes of this survey. No retests yielded discrepant results. Specimens with negative results were not retested. After completion of data collection, Abbott Laboratories issued a recall for certain lots of N. gonorrhoeae LCx assay kits in 2002 (5). No affected lots were used in our survey. Abbott Laboratories discontinued marketing of both the N. gonorrhoeae and C. trachomatis LCx assay kits in 2003. In a letter to its customers, dated 10 January 2003, the manufacturer stated that discontinuation of the product was due to manufacturing issues. Statistical Analysis We performed statistical analyses by using SAS for Windows software, version 9.1 (SAS Institute, Cary, North Carolina), and SAS-callable SUDAAN (RTI, Research Triangle Park, North Carolina). Analyses performed with SUDAAN accounted for the complex survey design by incorporating the survey weights and using a Taylor series linearization to calculate variance estimates (6). Data were weighted to account for the unequal probability of selection and nonresponse to the interview and examination. We estimated the number of infections in the population by multiplying the 2000 U.S. Census figures for the noninstitutionalized civilian U.S. population (7) age 14 to 39 years by the weighted prevalence estimate. We calculated 95% CIs for the prevalence estimates by using a log transformation. We performed significance tests for the association between chlamydia and gonorrhea and other variables by using a chi-square statistic. The chi-square statistic was based on a test for no interaction in a log-linear model that was fit to the log of the estimated cell proportions (LLCHISQ test statistic in SUDAAN). We used logistic regression to test for the presence of a linear trend across the categories of an independent variable. We considered P values of 0.05 or less to be statistically significant. No adjustments were made for multiple comparisons. We computed the relative standard errors for each weighted estimate. The relative standard error summarizes how large the sampling variability is relative to the size of the point estimatethe higher the relative standard error, the less reliable the estimate. Relative standard errors greater than 30% are considered to be unstable and should be interpreted with caution. We performed logistic regression to identify the variables that were associated with C. trachomatis infection (logistic regression was not performed with N. gonorrhoeae infection as the outcome because of the small number of infected respondents). Survey variables associated with infection in the medical literature were considered for entry into our model. We included interview and mobile examination center data in the model only if the question had been asked of all persons age 14 to 39 years in the survey (for example, questions of history of gonorrhea or chlamydia diagnosis were not included). We included sex, age, and number of lifetime sexual partners in the model regardless of statistical significance on the basis of well-established epidemiologic evidence that these are important factors associated with chlamydia. This was followed by adding variables in order of statistical significance by using a step-up approach to the baseline model. The criteria for the variable to remain in the model were based on a P value of 0.05 or less (by Satterwaithe adjusted F test). Once all variables added into the baseline model were statistically significant and no further variables met the entry criteria, we reassessed all variables excluded from the model for data-based confounding. We entered each excluded variable individually into the model and retained it if any variable estimate changed by more than 30%. Once a model with all relevant main effects was selected, we evaluated all pairwise interactions. Pairwise interactions between sex and each variable in the model allowed us to explore whether any of the main effects differed betw

Chlamydia trachomatis trends in the United States among persons 14 to 39 years of age, 1999-2008.

We determined the prevalence of and the risk factors for human papillomavirus (HPV) infection and abnormal cytologic test results in 312 adolescent girls (mean age, 16.1 years). Subjects had a median of 2 years of sexual activity and 4 lifetime sex partners. Cervical HPV was detected by use of L1-consensus polymerase chain reaction in 64% of subjects; half of those with HPV had >1 type, and 77% had >/=1 high-risk type. Independent risk factors for HPV were lifetime number of sex partners, age of partner, and douching. Cytologic abnormalities were common (20.9% of subjects had atypical squamous cells of uncertain significance, and 17.0% had high- or low-grade squamous intraepithelial lesions) and were significantly associated with detection of HPV (P=.0001); however, most (51.6%) subjects with HPV had normal cytologic test results.

Evaluation of Antimicrobial Resistance and Treatment Failures for Chlamydia trachomatis: A Meeting Report

ABSTRACT It is uncertain which methods for the diagnosis of rectal gonococcal and chlamydial infection are optimal. This study evaluated the performance of culture and nucleic acid amplification tests (NAATs) for rectal chlamydial and gonococcal diagnosis. From July 2003 until February 2007, 441 rectal test sets were collected from individuals attending a sexually transmitted disease clinic and three HIV clinics who gave a history of anal intercourse or were women at high risk for Neisseria gonorrhoeae or Chlamydia trachomatis infections. Rectal swab specimens were tested using culture and commercial NAATs employing transcription-mediated amplification (TMA), strand displacement amplification (SDA), and PCR amplification. Test performance was evaluated using a rotating standard by which patients were classified as infected if either two or three comparator tests were positive. Test sensitivities for the detection of N. gonorrhoeae ranged from 66.7% to 71.9% for culture to 100% for TMA. Specificities were 99.7% to 100% for culture and greater than 95.5% for all three NAATs. Test sensitivities for C. trachomatis ranged from 36.1% to 45.7% for culture and among NAATS from 91.4% to 95.8% for PCR to 100% for TMA. Specificities of the NAATs ranged from 95.6% to 98.5% (two-of-three standard) and from 88.8% to 91.8% (three-of-three standard). Over 60% and 80% of gonococcal and chlamydial infections, respectively, among men who have sex with men and over 20% of chlamydial infections in women would have been missed if the rectal site had not been tested. Currently available NAATs are more sensitive for the detection of chlamydial and gonococcal infection at the rectal site than is culture.

Nucleic Acid Amplification Tests for Diagnosis of Neisseria gonorrhoeae Oropharyngeal Infections

Background: We report the first population-based assessment of national trends in chlamydia prevalence in the United States. Methods: We investigated trends in chlamydia prevalence in representative samples of the US population aged 14 to 39 years using data from five 2-year survey cycles of the National Health and Nutrition Examination Survey from 1999 to 2008. Prevalence estimates and 95% confidence intervals (CI) are reported stratified by age, gender, and race/ethnicity. Percent change in prevalence over this time period was estimated from regression models. Results: In the 2007–2008 cycle, chlamydia prevalence among participants aged 14 to 39 years was 1.6% (95% CI: 1.1%–2.4%). Prevalence was higher among females (2.2%, 95% CI: 1.4%–3.4%) than males (1.1%, 95% CI: 0.7%–1.7%). Prevalence among non-Hispanic black persons was 6.7% (95% CI: 4.6%–9.9%) and was 2.5% (95% CI: 1.6%–3.8%) among adolescents aged 14 to 19 years. Over the five 2-year cycles, there was an estimated 40% reduction (95% CI: 8%–61%) in prevalence among participants aged 14 to 39 years. Decreases in prevalence were notable in men (53% reduction, 95% CI: 19%–72%), adolescents aged 14 to 19 years (48% reduction, 95% CI: 11%–70%), and adolescent non-Hispanic black persons (45%, reduction, 95% CI: 4%–70%). There was no change in prevalence among females aged 14 to 25 years, the population targeted for routine annual screening. Conclusions: On the basis of population estimates of chlamydia prevalence, the overall chlamydia burden in the United States decreased from 1999 to 2008. However, there remains a need to reduce prevalence in populations most at risk and to reduce racial disparities.

Ongoing sexually transmitted disease acquisition and risk-taking behavior among US HIV-infected patients in primary care: implications for prevention interventions.

Each year, Chlamydia trachomatis causes ~3 million new infections and results in more than 1 billion dollars in medical costs in the United States. Repeat or persistent infection occurs in 10%-15% of women who are treated for C. trachomatis infection. However, the role played by antimicrobial resistance in C. trachomatis treatment failures or persistent infection is unclear. With researchers in the field, we reviewed current knowledge and available approaches for evaluating antimicrobial resistance and potential clinical treatment failures for C. trachomatis. We identified key research questions that require further investigation. To date, there have been no reports of clinical C. trachomatis isolates displaying in vitro homotypic resistance to antimicrobials, but in vitro heterotypic resistance in C. trachomatis has been described. Correlation between the results of existing in vitro antimicrobial susceptibility tests and clinical outcome after treatment for C. trachomatis infection is unknown. Animal models may provide insight into chlamydial persistence, since homotypic resistance against tetracycline has been described for Chlamydia suis in pigs. Evaluating C. trachomatis clinical treatment failures, interpreting laboratory findings, and correlating the 2 clearly remain extremely challenging undertakings.

Neisseria gonorrhoeae Antimicrobial Resistance Among Men Who Have Sex With Men and Men Who Have Sex Exclusively With Women: The Gonococcal Isolate Surveillance Project, 2005–2010

ABSTRACT The optimal methods for the diagnosis of pharyngeal Neisseria gonorrhoeae infection are uncertain. The objective of this study was to define the performance of culture and nucleic acid amplification tests (NAATs) for the diagnosis of pharyngeal N. gonorrhoeae. In this cross-sectional study, males and females >15 years old who acknowledged performing fellatio or cunnilingus (in the previous 2 months) were recruited from three clinics (two human immunodeficiency virus clinics and one sexually transmitted diseases clinic) located in Birmingham, AL. The test performance of culture for N. gonorrhoeae, the Gen-Probe Aptima Combo 2 transcription-mediated amplification assay (TMA), the BD ProbeTec ET amplified DNA strand displacement assay (SDA), and the Roche Cobas Amplicor PCR was defined by using a rotating “gold standard” of any positive results by two or three of the three tests that excluded the test being evaluated. A total of 961 evaluable test sets were collected. On the basis of a rotating gold standard of positive results by two of three comparator tests, the sensitivity and the specificity were as follows: culture for N. gonorrhoeae, 50.0% and 99.4%, respectively; PCR, 80.3% and 73.0%, respectively; TMA, 83.6% and 98.6%, respectively; and SDA, 93.2% and 96.3%, respectively. On the basis of a rotating gold standard of positive results by three of three comparator tests, the sensitivity and specificity were as follows: culture for N. gonorrhoeae, 65.4% and 99.0%, respectively; PCR, 91.9% and 71.8%, respectively; TMA, 100% and 96.2%, respectively; and SDA, 97.1% and 94.2%, respectively. In conclusion, currently available NAATs are more sensitive than culture for the detection of pharyngeal gonorrhea in at-risk patients. PCR is substantially less specific than culture, TMA, or SDA and should not be used for the detection of pharyngeal gonorrhea.

Neisseria gonorrhoeae Antimicrobial Susceptibility Surveillance - The Gonococcal Isolate Surveillance Project, 27 Sites, United States, 2014.

Background: To better understand the factors associated with HIV- and sexually transmitted disease (STD)-transmitting behavior among HIV-infected persons, we estimated STD prevalence and incidence and associated risk factors among a diverse sample of HIV-infected patients in primary care. Methods: We analyzed data from 557 participants in the SUN Study, a prospective observational cohort of HIV-infected adults in primary care in 4 US cities. At enrollment and 6 months thereafter, participants completed an audio computer-assisted self-interview about their sexual behavior, and were screened for genitourinary, rectal, and pharyngeal Neisseria gonorrhoeae and Chlamydia trachomatis infections by nucleic acid amplification testing, and for serologic evidence of syphilis. Women provided cervicovaginal samples and men provided urine to screen for Trichomonas vaginalis by polymerase chain reaction. Results: Thirteen percent of participants had a prevalent STD at enrollment and 7% an incident STD 6 months later. The most commonly diagnosed infections were rectal chlamydia, oropharyngeal gonorrhea, and chlamydial urethritis among the men and trichomoniasis among the women. Other than trichomoniasis, 94% of incident STDs were identified in men who have sex with men. Polysubstance abuse other than marijuana, and having ≥4 sex partners in the 6 months before testing were associated with diagnosis of an incident STD. Conclusions: STDs were commonly diagnosed among contemporary HIV-infected patients receiving routine outpatient care, particularly among sexually active men who have sex with men who used recreational drugs. These findings underscore the need for frequent STD screening, prevention counseling, and substance abuse treatment for HIV-infected persons in care.

The Efficacy and Safety of Gentamicin Plus Azithromycin and Gemifloxacin Plus Azithromycin as Treatment of Uncomplicated Gonorrhea

BACKGROUND Gonorrhea treatment has been complicated by antimicrobial resistance in Neisseria gonorrhoeae. Gonococcal fluoroquinolone resistance emerged more rapidly among men who have sex with men (MSM) than men who have sex exclusively with women (MSW). OBJECTIVE To determine whether N. gonorrhoeae urethral isolates from MSM were more likely than isolates from MSW to exhibit resistance to or elevated minimum inhibitory concentrations (MICs) of antimicrobials used to treat gonorrhea. DESIGN 6 years of surveillance data from the Gonococcal Isolate Surveillance Project. SETTING Publicly funded sexually transmitted disease clinics in 30 U.S. cities. PATIENTS Men with a total of 34 600 episodes of symptomatic urethral gonorrhea. MEASUREMENTS Percentage of isolates exhibiting resistance or elevated MICs and adjusted odds ratios for resistance or elevated MICs among isolates from MSM compared with isolates from MSW. RESULTS In all U.S. regions except the West, isolates from MSM were significantly more likely to exhibit elevated MICs of ceftriaxone and azithromycin than isolates from MSW (P < 0.050). Isolates from MSM had a high prevalence of resistance to ciprofloxacin, penicillin, and tetracycline and were significantly more likely to exhibit antimicrobial resistance than isolates from MSW (P < 0.001). LIMITATIONS Sentinel surveillance may not be representative of all patients with gonorrhea. HIV status, travel history, and antimicrobial use data were missing for some patients. CONCLUSION Men who have sex with men are vulnerable to the emerging threat of antimicrobial-resistant N. gonorrhoeae. Because antimicrobial susceptibility testing is not routinely done in clinical practice, clinicians should monitor for treatment failures among MSM diagnosed with gonorrhea. Strengthened prevention strategies for MSM and new antimicrobial treatment options are needed.