Stuart M. Berman

Sexually Transmitted Diseases Among American Youth: Incidence and Prevalence Estimates, 2000

CONTEXT In the United States, young people aged 15-24 represent 25% of the sexually experienced population. However, the incidence and prevalence of sexually transmitted diseases (STDs) among this age-group are unknown. METHODS Data from a variety of sources were used to estimate the incidence and prevalence of STDs among 15-24-year-olds in the United States in 2000. The quality and reliability of the estimates were categorized as good, fair or poor, depending on the quality of the data source. RESULTS Approximately 18.9 million new cases of STD occurred in 2000, of which 9.1 million (48%) were among persons aged 15-24. Three STDs (human papillomavirus, trichomoniasis and chlamydia) accounted for 88% of all new cases of STD among 15-24-year-olds. CONCLUSIONS These estimates emphasize the toll that STDs have on American youth. More representative data are needed to help monitor efforts at lowering the burden of these infections.

Prevalence of Sexually Transmitted Infections Among Female Adolescents Aged 14 to 19 in the United States

OBJECTIVE: Most young women initiate sexual activity during adolescence; risk for sexually transmitted infections (STIs) accompanies this initiation. In this study we estimated the prevalence of the most common STIs among a representative sample of female adolescents in the United States. METHODS: Data were analyzed from 838 females who were aged 14 to 19 and participating in the nationally representative National Health and Nutrition Examination Survey 2003–2004. After interview and examination, survey participants provided biological specimens for laboratory testing. The main outcome was weighted prevalence of at least 1 of 5 STIs: Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, herpes simplex virus type 2, and human papillomavirus (HPV) (any of 23 high-risk types or type 6 or 11). RESULTS: Prevalence of any of the 5 STIs was 24.1% among all and 37.7% among sexually experienced female adolescents. HPV (23 high-risk types or type 6 or 11) was the most common STI among all female adolescents (prevalence: 18.3%), followed by C trachomatis infection (prevalence: 3.9%). Prevalence of any of the STIs was 25.6% among those whose age was the same or 1 year greater than their age at sexual initiation and 19.7% among those who reported only 1 lifetime sex partner. CONCLUSIONS: The prevalence of STIs among female adolescents is substantial, and STIs begin to be acquired soon after sexual initiation and with few sex partners. These findings support early and comprehensive sex education, routine HPV vaccination at the age of 11 to 12 years, and C trachomatis screening of sexually active female adolescents.

The Prevalence of Trichomonas vaginalis Infection among Reproductive-Age Women in the United States, 2001–2004

BACKGROUND Trichomonas vaginalis infection is a common sexually transmitted protozoal infection and is associated with several adverse health outcomes, such as preterm birth, delivery of a low-birth weight infant, and facilitation of sexual transmission of human immunodeficiency virus. The annual incidence in the United States has been estimated to be 3-5 million cases. However, there are no data on the prevalence of trichomoniasis among all reproductive-age women. We estimated the prevalence of T. vaginalis infection from a nationally representative sample of women in the United States. METHODS Women aged 14-49 years who participated in the National Health and Examination Survey cycles for 2001-2004 provided self-collected vaginal swab specimens. The vaginal fluids extracted from these swabs were evaluated for the presence of T. vaginalis using polymerase chain reaction. RESULTS Overall, 3754 (81%) of 4646 women provided swab specimens. The prevalence of T. vaginalis infection was 3.1% (95% confidence interval [CI], 2.3%-4.3%); for non-Hispanic white women, it was 1.3% (95% CI, 0.7%-2.3%); for Mexican American women, it was 1.8% (95% CI, 0.9%-3.7%); and for non-Hispanic black women, it was 13.3% (95% CI, 10.0%-17.7%). Factors that remained associated with increased likelihood of T. vaginalis infection in multivariable analyses included non-Hispanic black race/ethnicity, being born in the United States, a greater number of lifetime sex partners, increasing age, lower educational level, poverty, and douching. CONCLUSIONS The prevalence of T. vaginalis infection among women in the United States was 3.1%. A significant racial disparity exists; the prevalence among non-Hispanic black women was 10.3 times higher than that among non-Hispanic white and Mexican American women. Optimal prevention and control strategies for T. vaginalis infection should be explored as a means of closing the racial disparity gaps and decreasing adverse health outcomes due to T. vaginalis infection.

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

CDC Sexually Transmitted Diseases Treatment Guidelines

248 million for chlamydia and

Patient-delivered partner treatment with azithromycin to prevent repeated Chlamydia trachomatis infection among women: A randomized, controlled trial

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

Repeat infection with chlamydia and gonorrhea among females: a systematic review of the literature.

Sexually transmitted diseases (STDs) constitute an epidemic of tremendous magnitude, with an estimated 15 million persons acquiring a new STD each year [1]. Effective clinical management of STDs represents a strategic element in prevention of HIV infection and in efforts to improve reproductive and sexual health. Clinicians who evaluate persons with STDs or those at risk for STDs should be aware of the current national guidelines for STD treatment. The 2002 Centers for Disease Control (CDC) guidelines for the treatment of STDs provide clinical guidance in the appropriate assessment and management of STDs [2]. The scope and content of these guidelines continues to evolve, reflecting changes not only in clinical experience and epidemiology but also in changes in the health care environment and the circumstances under which clinical services are delivered. The 2002 guidelines for the treatment of sexually transmitted diseases were developed in consultation with publicand private-sector professionals knowledgeable in the management of STDs, using an evidence-based approach. A systematic literature review was performed that focused on peer-reviewed journal articles and published abstracts that have become available since publication of the 1998 guidelines. On the basis of this review process, background papers were developed, and the available evidence was evaluated during a meeting of consultants in September 2000. A draft report was then circulated to professional associations, STD treatment experts, and other agencies,

Emerging Antimicrobial Resistance in Neisseria gonorrhoeae: Urgent Need to Strengthen Prevention Strategies

Background Repeated infection with Chlamydia trachomatis increases the risk for serious sequelae: pelvic inflammatory disease, ectopic pregnancy, infertility, and chronic pelvic pain. A substantial proportion of women treated for C trachomatis infection are reinfected by an untreated male sex partner in the first several months after treatment. Effective strategies to ensure partner treatment are needed. Goal The goal of the study was to determine whether repeated infections with C trachomatis can be reduced by giving women doses of azithromycin to deliver to male sex partners. Study Design A multicenter randomized controlled trial was conducted among 1787 women aged 14 to 34 years with uncomplicated C trachomatis genital infection diagnosed at family planning, adolescent, sexually transmitted disease, and primary care clinics or emergency or other hospital departments in five US cities. Women treated for infection were randomized to one of two groups: patient-delivered partner treatment (in which they were given a dose of azithromycin to deliver to each sex partner) or self-referral (in which they were asked to refer their sex partners for treatment). The main outcome measure was C trachomatis DNA detected by urine ligase chain reaction (LCR) or polymerase chain reaction (PCR) by 4 months after treatment. Results The characteristics of study participants enrolled in each arm were similar except for a small difference in the age distribution. Risk of reinfection was 20% lower among women in the patient-delivered partner treatment arm (87/728; 12%) than among those in the self-referral arm (106/726; 15%); however, this difference was not statistically significant (odds ratio, 0.80; 95% confidence interval, 0.62–1.05;P = 0.102). Women in the patient-delivered partner treatment arm reported high compliance with the intervention (82%). Conclusion Patient-delivered partner treatment for prevention of repeated C trachomatis infection among women is comparable to self-referral and may be an appropriate option for some patients.

High Risk of Brain Metastases in Surgically Staged IIIA Non–Small-Cell Lung Cancer Patients Treated With Surgery, Chemotherapy, and Radiation

Determining the magnitude of chlamydia and gonorrhea reinfection is critical to inform evidence-based clinical practice guidelines related to retesting after treatment. PubMed was used to identify peer-reviewed English language studies published in the past 30 years that estimated reinfection rates among females treated for chlamydia or gonorrhea. Included in this analysis were original studies conducted in the United States and other industrialized countries that reported data on chlamydia or gonorrhea reinfection in females. Studies were stratified into 3 tiers based on study design. Reinfection rates were examined in relation to the organism, study design, length of follow-up, and population characteristics. Of the 47 studies included, 16 were active cohort (Tier 1), 15 passive cohort (Tier 2), and 16 disease registry (Tier 3) studies. The overall median proportion of females reinfected with chlamydia was 13.9% (n = 38 studies). Modeled chlamydia reinfection within 12 months demonstrated peak rates of 19% to 20% at 8 to 10 months. The overall median proportion of females reinfected with gonorrhea was 11.7% (n = 17 studies). Younger age was associated with higher rates of both chlamydia and gonorrhea reinfection. High rates of reinfection with chlamydia and gonorrhea among females, along with practical considerations, warrant retesting 3 to 6 months after treatment of the initial infection. Further research should investigate effective interventions to reduce reinfection and to increase retesting.

Trends in primary and secondary syphilis among men who have sex with men in the United States.

Neisseria gonorrhoeae infection can cause cervicitis, urethritis, proctitis, pelvic inflammatory disease with long-term sequelae (infertility, ectopic pregnancy, chronic pelvic pain), adverse outcomes of pregnancy, and increased susceptibility to and transmission of HIV infection (1, 2). Neisseria gonorrhoeae infection is the second most common notifiable disease in the United States, with 358366 cases reported in 2006 (3). However, reported cases probably represent an underestimate of the actual disease burden because of underdiagnosis and underreporting; it is estimated that there were approximately 718000 incident gonorrhea cases in 2000 (4). After national implementation of gonorrhea control activities in the 1970s, the incidence of gonorrhea in the United States declined markedly, with a 74% reduction in rates from 1975 to 1997. Although rates have remained relatively stable over the past decade, in 2006 the national gonorrhea case rate (120.9 cases per 100000 population) increased for the second consecutive year, particularly in the western United States (3, 5). Rates of gonorrhea remain high in the South and among African Americans, adolescents, young adults, and men who have sex with men. Recent reports have also documented high rates of gonorrhea among HIV-infected men who have sex with men (3). Because of increased infection rates, high burden of disease, and the reproductive and economic implications of gonorrhea infection, prevention and control of gonorrhea is an important public health concern (6, 7). As current therapeutic options become more limited, we describe the emergent challenges to maintaining antimicrobial effectiveness and a comprehensive approach to gonorrhea control. Historical Perspective on Antimicrobial Resistance An essential element in gonorrhea control is the availability and provision of appropriate, effective antimicrobial therapy. Effective treatment not only eradicates infection in the affected individual and prevents the development of complications, it also has an important public health benefit of shortening the duration of infection, thus decreasing transmission and eliminating reservoirs of infection. However, over the past 60 years N. gonorrhoeae has developed resistance to multiple classes of antimicrobials (Appendix Figure). Sulfanilamides were used for gonococcal treatment after their introduction in 1936, but their efficacy was short-lived because of the rapid emergence of resistance by 1945 (8). Penicillin became the recommended antimicrobial regimen for the next 40 years. The progressive decline in susceptibilityinitially associated with chromosomally mediated resistance (exhibited by a stepwise increase in resistance) and later by the acquisition and spread of plasmids containing genes for penicillinase productionrequired serial increases in the recommended dose of intramuscular procaine penicillin (with probenecid) from 50000 units in 1945 to 4.8 million units by the early 1970s (9). In 1985, because of emerging penicillin resistance, ceftriaxone became a recommended regimen for the treatment of uncomplicated gonococcal infections (10). At the same time, tetracycline resistance (both plasmid and chromosomally mediated) was spreading to the extent that tetracycline was no longer a viable treatment option. By 1989, resistance to penicillin was sufficiently widespread that penicillin was no longer effective. Ceftriaxone then became the recommended regimen for gonorrhea therapy, with ciprofloxacin as an alternative treatment option (11). By 1993, on the basis of data regarding high efficacy, safety, and convenience as single-dose therapies, oral fluoroquinolones (ciprofloxacin, ofloxacin) were recommended as oral regimens for gonorrhea treatment, as was the oral third-generation cephalosporin cefixime (12). Appendix Figure. Historical perspective on antimicrobial resistance in the United States. QRNG = quinolone-resistant Neisseria gonorrhoeae; MSM = men who have sex with men. In 1986, concerns about emerging gonococcal antimicrobial resistance lead to the development of the Gonococcal Isolate Surveillance Project (GISP), a national sentinel surveillance system that monitors antimicrobial susceptibility in the United States. Each year, approximately 6000 urethral gonococcal isolates from men attending 25 to 30 sexually transmitted disease (STD) clinics throughout the country are collected and analyzed to provide national data that help guide treatment recommendations. The GISP findings of notable importance include the continued high prevalence of penicillin and tetracycline resistance, which has remained greater than 15%; the increasing prevalence of isolates with decreased susceptibility to macrolides; the appearance of a limited number of multidrug-resistant isolates with decreased susceptibility to cefixime (3); and most important, the dramatic spread of quinolone-resistant N. gonorrhoeae. Based in part on data from GISP, the emergence of quinolone-resistant N. gonorrhoeae was first identified in Hawaii in 1991, at about same time that it was recognized as a problem in Asia (13). Thereafter, sporadic occurrences of quinolone-resistant N. gonorrhoeae were noted in the United States throughout the 1990s. By 2000, quinolone-resistant N. gonorrhoeae was increasingly observed in persons who became infected in Asia, the Pacific Islands (including Hawaii), or California. As a result, fluoroquinolones were no longer recommended for treating gonorrhea acquired in those locales (14, 15). Over the next several years, GISP identified increased rates of quinolone-resistant N. gonorrhoeae among men who have sex with men. This finding prompted an advisory in 2004 that fluoroquinolones were no longer recommended for treating gonorrhea in men who have sex with men, regardless of locale (16). Most recently, data from GISP indicate that quinolone-resistant N. gonorrhoeae is widely dispersed in the United States and that in 2006 the infection accounted for 39% of gonococcal isolates in men who have sex with men and 7% in heterosexual men. On the basis of these cumulative data, the Centers for Disease Control and Prevention (CDC) announced that fluoroquinolones are no longer recommended for treating gonococcal infections and associated conditions, such as pelvic inflammatory disease or epididymitis, in any population in the United States (17). The antimicrobial resistance data from GISP have provided a rational basis for recommended gonococcal treatment regimens. However, data from this sentinel surveillance system have limitations. The GISP data may not be representative of the total population with gonorrhea in the United States, because the current national surveillance system oversamples West Coast locations (where new resistant strains have been first detected), evaluates only male urethral isolates obtained from STD clinics, and samples only a minority of reported gonococcal infections. Dramatic differences in quinolone-resistant N. gonorrhoeae prevalence by geographic location and sexual orientation illustrate the challenge of achieving accurate representation (18). The rapid spread throughout the United States of quinolone-resistant N. gonorrhoeae in heterosexual men, as well as among men who have sex with men, makes defining remaining pockets of continued susceptibility of N. gonorrhoeae problematic. These limitations highlight the difficulty of defining an appropriate sentinel population and a frequency of sampling with sufficient representation to assure susceptibility in a particular locale. Thus, there is a need to monitor antimicrobial resistance at the local level, which would provide a more in-depth understanding of resistance trends and contribute to decisions that affect treatment recommendations in various locations (19, 20). Evolution of Criteria for Gonorrhea Treatment Recommendations The epidemiology of antimicrobial resistance guides decisions about gonococcal treatment recommendations. As discussed, data from GISP are critical when evaluated along with other relevant data, such as those provided by the Gonococcal Antimicrobial Surveillance Program of the Western Pacific Regional Office of the World Health Organization (WHO) in Southeast Asia and the Pacific region. The CDC and the WHO have recommended a change in the treatment regimen when the prevalence of antimicrobial resistance exceeds 5% for a specific antibiotic, while taking into account the prevalence of gonorrhea in the community, the cost of diagnostic and treatment regimens, and the availability of antimicrobial susceptibility data (2123). An accepted definition of gonococcal treatment efficacy requires a cure rate of over 95% with a lower bound of the 95% CI of at least 90% (24). At the time this criterion was proposed, many antimicrobial regimens met this standard, but in an attempt to reduce the risk for therapeutic failure and development of antimicrobial resistance, more stringent criteria were proposed by Moran and colleagues (25). Their criteria specified that efficacy exceed 95% in summed clinical trials, but required that the lower bound of the 95% CI also be at least 95%. In addition to efficacy data, decisions regarding treatment recommendations involve consideration of other factors. These include administration of at least twice the minimum dose to ensure therapeutic reserve, documentation that susceptibility is not lower among organisms recovered after treatment, and evidence that the serum or plasma concentration with the recommended dose is at least 4 times the minimum inhibitory concentration required to inhibit 90% of strains (MIC90) for 10 hours after the concentration peak (25). These stringent clinical efficacy criteria (95% efficacy with 95% CI) were used to determine the gonorrhea treatment regimens recommended in the CDC STD Treatment Guidelines since 1993. However, it was recently suggested that these criteria be modified, given the propensity of N. gonorrhoeae to develo