Seroprevalence of Herpes Simplex Virus Types 1 and 2 Among Pregnant Women and Sexually Active, Nonpregnant Women in the United States.

Background: Neonatal herpes is a rare, devastating consequence of herpes simplex virus type 1 (HSV-1) or 2 (HSV-2) infection during pregnancy. The risk of neonatal infection is higher among pregnant women seronegative for HSV-1 or HSV-2 who acquire their first HSV infection near delivery. Methods: We estimated HSV-1 and HSV-2 seroprevalence among pregnant women aged 20-39 years in 1999-2014, assessed HSV seroprevalence changes between 1999-2006 and 2007-2014, and compared HSV seroprevalence between pregnant women and sexually active, nonpregnant women aged 20-39 years in 2007-2014 using National Health and Nutrition Examination Survey data. Results: Among pregnant women in 1999-2014, HSV-1 seroprevalence was 59.3%, HSV-2 seroprevalence was 21.1%, and HSV seronegativity was 30.6%. Between 1999-2006 and 2007-2014, HSV-1 and HSV-2 seroprevalence among pregnant women remained stable. However, among pregnant women with ≤3 sex partners (approximately 40% of all pregnant women), seronegativity for both HSV-1 and HSV-2 increased from 35.6% to 51.4% (P < .05). In 2007-2014, nonpregnant women who were (1) unmarried, (2) living below poverty level, or (3) had ≥4 sex partners were more likely than pregnant women to be seronegative for both HSV-1 and HSV-2 (P < .05). Conclusions: HSV-1 and HSV-2 seroprevalence among US pregnant women remained stable between 1999 and 2014. However, pregnant women with fewer sex partners were increasingly seronegative for both HSV-1 and HSV-2, indicating an increasing proportion of pregnant women who are vulnerable to primary HSV acquisition in pregnancy, which confers an increased risk of transmitting HSV to their neonates.

Monitoring for Human Papillomavirus Vaccine Impact Among Gay, Bisexual, and Other Men Who Have Sex With Men-United States, 2012-2014.

BACKGROUND: Gay, bisexual, and other men who have sex with men (MSM) are at high risk for human papillomavirus (HPV) infection; vaccination is recommended for US males, including MSM through age 26 years. We assessed evidence of HPV among vaccine-eligible MSM and transgender women to monitor vaccine impact. METHODS: During 2012-2014, MSM aged 18-26 years at select clinics completed a computer-assisted self-interview regarding sexual behavior, human immunodeficiency virus (HIV) status, and vaccinations. Self-collected anal swab and oral rinse specimens were tested for HPV DNA (37 types) by L1 consensus polymerase chain reaction; serum was tested for HPV antibodies (4 types) by a multiplexed virus-like particle-based immunoglobulin G direct enzyme-linked immunosorbent assay. RESULTS: Among 922 vaccine-eligible participants, the mean age was 23 years, and the mean number of lifetime sex partners was 37. Among 834 without HIV infection, any anal HPV was detected in 69.4% and any oral HPV in 8.4%, yet only 8.5% had evidence of exposure to all quadrivalent vaccine types. In multivariate analysis, HPV prevalence varied significantly (P < .05) by HIV status, sexual orientation, and lifetime number of sex partners, but not by race/ethnicity. DISCUSSIONS: Most young MSM lacked evidence of current or past infection with all vaccine-type HPV types, suggesting that they could benefit from vaccination. The impact of vaccination among MSM may be assessed by monitoring HPV prevalence, including in self-collected specimens.

Comparison of antimicrobial susceptibilities of pharyngeal, rectal, and urethral Neisseria gonorrhoeae isolates among men who have sex with men.

U.S. surveillance for Neisseria gonorrhoeae antimicrobial susceptibilities is based exclusively on male urethral isolates. These data inform gonorrhea treatment guidelines, including recommendations for the treatment of extragenital infections, but data on the susceptibilities of extragenital isolates are limited. We compared the antimicrobial susceptibilities of pharyngeal, rectal, and urethral gonococcal isolates collected from men who have sex with men (MSM), at five sentinel sites throughout the United States. MICs were determined by the agar dilution method. Generalized linear models were used to compare (i) the proportions of isolates with elevated MICs and (ii) geometric mean MICs according to anatomic site, adjusted for city. In December 2011 to September 2013, totals of 205 pharyngeal, 261 rectal, and 976 urethral isolates were obtained. The proportions of isolates with elevated ceftriaxone MICs (≥ 0.125 µg/ml) did not differ according to anatomic site (0.5% of pharyngeal isolates, 1.5% of rectal isolates, and 1.7% of urethral isolates, with a city-adjusted odds ratio [aOR] of 0.4 [95% confidence interval {CI}, 0.0 to 3.9] for pharyngeal versus urethral isolates and an aOR of 0.9 [95% CI, 0.2 to 4.2] for rectal versus urethral isolates). The city-adjusted geometric mean ceftriaxone MICs of pharyngeal (0.0153 µg/ml) and rectal (0.0157 µg/ml) isolates did not differ from that of urethral isolates (0.0150 µg/ml) (ratios of geometric mean MICs of 1.02 [95% CI, 0.90 to 1.17] and 1.05 [95% CI, 0.93 to 1.19], respectively). Similar results were observed for other antimicrobials, including cefixime and azithromycin. These findings suggest that, at the population level, gonococcal antimicrobial susceptibility surveillance based on urethral isolates from MSM adequately reflects the susceptibilities of N. gonorrhoeae strains circulating among MSM.

Would young women attending sexually transmitted disease clinics benefit from human papillomavirus vaccination? An assessment of human papillomavirus DNA and seropositivity from human papillomavirus sentinel surveillance, 2003-2005.

BACKGROUND: There are limited data on the proportion who have been exposed to vaccine-type human papillomavirus (HPV) among women attending sexually transmitted disease (STD) clinics; this information could inform the potential benefits of HPV vaccination for women attending this venue. METHODS: Human papillomavirus surveillance was conducted in STD clinics in Baltimore, MD; Boston, MA; Denver, CO; Los Angeles, CA; and Seattle, WA, among women receiving cervical cancer screening from January 2003 to December 2005. The women had specimens collected for cervical cytology HPV testing by L1 consensus polymerase chain reaction testing and serologic assessment for HPV 6, 11, 16, and 18 using the competitive Luminex immunoassay. Results from 880 women with adequate specimens were included. Women were HPV naïve if they were both HPV DNA negative and seronegative for a specific HPV type. RESULTS: One hundred seventy women (19.3%) had HPV 16, 18, 6, or 11 DNA, and 418 (47.5%) were HPV 16, 18, 6, or 11 seropositive. Four hundred ten (46.6%) women were naïve to all 4 types, 570 (64.8%) were naïve to both HPV 16 and 18, and 545 (61.9%) were naïve to both HPV 6 and 11. Almost all (99.3%) women were naïve to at least 1 vaccine HPV type. CONCLUSIONS: Almost half of young women age eligible for HPV vaccine and attending STD clinics were naïve to all 4 HPV types, and more than half were naïve to both HPV 16 and 18. This assessment suggests that most young women attending this venue might benefit from HPV vaccination.

Trends in seroprevalence of herpes simplex virus type 2 among non-Hispanic blacks and non-Hispanic whites aged 14 to 49 years--United States, 1988 to 2010.

OBJECTIVES: Genital herpes simplex virus type 2 (HSV-2) is one of the most prevalent sexually transmitted infections in the United States. We sought to assess differences in HSV-2 seroprevalence among non-Hispanic blacks and non-Hispanic whites and describe trends over time from 1988 to 2010. METHODS: Data from National Health and Nutrition Examination Surveys (NHANES) were used to determine national HSV-2 seroprevalence estimates from National Health and Nutrition Examination Surveys 1988 to 1994, 1999 to 2002, 2003 to 2006, and 2007 to 2010. Persons aged 14 to 49 years were included in the analyses. Race/Ethnicity was defined by self-report as non-Hispanic white or non-Hispanic black. Purified glycoprotein specific for HSV-2 was used to detect type-specific antibodies using an immunodot assay. The same assay was used in all surveys. History of diagnosed genital herpes was self-reported. RESULTS: Overall, HSV-2 seroprevalence decreased in the United States between 1988 to 1994 and 2007 to 2010, from 21.2% to 15.5%. Among non-Hispanic white females, HSV-2 seroprevalence decreased from 19.5% (1988-1994) to 15.3% (2007-2010; P < 0.001); HSV-2 seroprevalence remained stable among non-Hispanic black females, 52.5% (1988-1994) to 49.9% (2007-2010; P = 0.1). The female black/white prevalence ratio was 2.7 (95% confidence interval [CI], 2.4-3.0) in 1988 to 1994 increasing to 3.3 (95% CI, 2.9-3.7) in 2007 to 2010 (P = 0.01). Among males, the black/white prevalence ratio was 2.4 (95% CI, 1.9-2.9) in 1988 to 1994 increasing to 4.4 (95% CI, 3.3-5.8) in 2007 to 2010 (P = 0.001). The overall percentage of HSV-2-seropositive survey participants who reported never being told by a doctor or health care professional that they had genital herpes did not change significantly between 1988 to 1994 and 2007 to 2010 and remained high (90.7% and 87.4%, respectively). CONCLUSIONS: Although HSV-2 seroprevalence decreased overall, the decrease was most marked among non-Hispanic whites, and racial disparities significantly increased over time. These persistent disparities demonstrate the need for innovative prevention strategies among this at-risk population.

A comparison of the analytical level of agreement of nine treponemal assays for syphilis and possible implications for screening algorithms.

OBJECTIVE: The serological diagnosis of syphilis requires the detection of two distinct antibodies, the non-treponemal and trepomenal. Center for Disease Control and Prevention (CDC) recommends screening first with a non-treponemal test such as (Rapid Plasma Reagin/Venereal Disease Research Laboratory), and then confirming those results with one of the several treponemal tests (Fluorescent Treponemal Antibody-Absorption (FTA-ABS), Enzyme Immunoassay, chemiluminescence, treponema pallidum particle agglutination (TP-PA) or Point of Care). Owing to the high volume of samples processed by some laboratories using automated systems, the screening with treponemal assays and confirming with non-treponemal tests is becoming the established norm. The purpose of this study was to evaluate eight treponemal assays using TP-PA as the predicate assay. METHODS: 290 stored serum samples were tested qualitatively according to the manufacturer's directions. RESULTS: Concordance with specimens tested as reactive or non-reactive using TP-PA was: FTA-ABS 94.5-100%, Trep-Sure 100-98.9%, BioELISA 100-98.9%, INNO-LIA 99.1-99.4%, BIOLINE 100-98.9%, CAPTIA IgG 100-97.2%, Trep-ID 100-100% and LIAISON 100-99.4%. In order to properly evaluate the performance of these assays, the analytical sensitivity was determined by endpoint titration of serial dilutions of the reactive serum samples in normal sera. The median endpoint titre varied from 1:4 for FTA-ABS to 1:512 for Trep-Sure. CONCLUSIONS: The performance of the treponemal serological assays was comparable while using medium and high-titre sera. However, the varying performance on specimen dilutions suggests that there may be differences in sensitivity with low-titre sera that are more prevalent in primary and late syphilis cases.

Prevalence of circumcision among men and boys aged 14 to 59 years in the United States, National Health and Nutrition Examination Surveys 2005-2010.

BACKGROUND: In 2009, an estimated 3590 new heterosexually acquired HIV infections occurred in males in the United States. Three randomized controlled trials demonstrated that male circumcision decreased a man's risk for HIV acquisition through heterosexual sex. We describe circumcision prevalence in US males and determine circumcision prevalence among males potentially at increased risk for heterosexually acquired HIV infection. METHODS: We estimated circumcision prevalence among men and boys aged 14 to 59 years using data from the National Health and Nutrition Examination Surveys 2005-2010. We defined men and boys with 2 or more female partners in the last year as potentially at increased risk for heterosexually acquired HIV infection. RESULTS: Estimated circumcision prevalence was 80.5%. Prevalence varied significantly by year of birth, race/ethnicity, health insurance type, and family income. Circumcision prevalence among men and boys reporting 2 or more female partners in the last year was 80.4%, which corresponded to an estimated 3.5 million uncircumcised men and boys potentially at increased risk for heterosexually acquired HIV infection. Of these men and boys, 48.3% lacked health insurance. CONCLUSIONS: Circumcision prevalence in the United States differs by demographic group, and half of uncircumcised men and boys potentially at increased risk for heterosexually acquired HIV are uninsured. These data could inform recommendations and cost analyses concerning circumcision in the United States.

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.

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.

A prospective study of the psychosocial impact of a positive Chlamydia trachomatis laboratory test.

BACKGROUND: Few data exist on potential harms of chlamydia screening. We assessed the psychosocial impact of receiving a positive Chlamydia trachomatis test result. METHODS: We prospectively studied women ≥16 years of age undergoing chlamydia testing in 2 Midwestern family planning clinics. We surveyed women at baseline and about 1 month after receiving test results, using 9 validated psychosocial scales/subscales and chlamydia-specific questions. Changes in scale scores were calculated for each woman. Mean percent changes in scores for chlamydia-positive and -negative women were compared using a t test. RESULTS: We enrolled 1807 women (response rate, 84%). Of the 1688 women with test results, 149 (8.8%) tested positive. At follow-up, chlamydia-positive women (n = 71) had a 75% increase in anxiety about sexual aspects of their life on the Multidimensional Sexual Self-Concept Questionnaire (P < 0.001), significantly greater than the 26% increase among 280 randomly selected chlamydia-negative women (P = 0.02). There were no differences for the other 8 scales/subscales, including general measures of anxiety, depression, and self-esteem. Chlamydia-positive women were more likely than chlamydia-negative women to be "concerned about chlamydia" (80% vs. 40%, P < 0.001) and to report breaking up with a main partner (33% vs. 11%, P < 0.001) at follow-up. Women testing positive reported a range of chlamydia-specific concerns. CONCLUSIONS: Chlamydia-positive women had significant increases in anxiety about sex and concern about chlamydia, but did not have marked changes in more general measures of psychosocial well-being about 1 month after diagnosis. Chlamydia diagnoses were associated with some disruption of relationships with main partners. Chlamydia-specific concerns may guide counseling messages to minimize psychosocial impact.

Primary and secondary syphilis among black and Hispanic men who have sex with men: case report data from 27 States.

BACKGROUND: Until 2005, national-level data on the sex of sex partners that describe how primary and secondary syphilis affects men who have sex with men (MSM) of different races or ethnicities were not reported. OBJECTIVE: To present data from 27 states comparing trends in primary and secondary syphilis among MSM of different races or ethnicities. DESIGN: Review of case report data and regression analysis. SETTING: Federal database of case reports in the National Electronic Telecommunications System for Surveillance. PARTICIPANTS: Men reported to be MSM. MEASUREMENTS: Cases of primary and secondary syphilis per 100 000 males of matching race or ethnicity ("rates"), determined by using population data from the National Center for Health Statistics as the denominator to compare age and racial and ethnic differences. RESULTS: For each year during 2005 to 2008, 27 states from all U.S. census regions reported data on the sex of sex partners for 70% or more of male cases of primary and secondary syphilis. Regression analysis revealed significantly different trends in rates of primary and secondary syphilis: Absolute increases in rates among black MSM and Hispanic MSM were, respectively, 8.0 times and 2.4 times the absolute increase in rate among white MSM. By region, rates among MSM increased 30% in the Midwest, 48% in the South, 73% in the Northeast, and 77% in the West. By age group, the largest absolute increase in rates occurred among MSM aged 20 to 29 years. LIMITATION: Results from 27 states may not be generalizable to the United States as a whole. CONCLUSION: Rates of primary and secondary syphilis disproportionately increased among black and Hispanic MSM (compared with white MSM) and among young MSM. Care providers should offer counseling about safer sexual practices and screening for syphilis and other sexually transmitted infections when caring for MSM. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Parent attitudes about school requirements for human papillomavirus vaccine in high-risk communities of Los Angeles, California.

BACKGROUND: Human papillomavirus (HPV) immunization requirements for school entry could increase HPV vaccine uptake but are controversial. This study assessed parents' attitudes about HPV immunization requirements. METHODS: During October 2007 to June 2008, we conducted telephone surveys with 484 parents of girls attending middle/high schools serving communities in Los Angeles County with elevated cervical cancer rates. RESULTS: Parents were mostly Hispanic (81%) or African American (15%); 71% responded in Spanish. Many parents did not know if HPV vaccine works well (42%) or is unsafe (41%). Overall, 59% of parents agreed that laws requiring HPV vaccination for school attendance "are a good idea." In multivariable analysis, African Americans and Hispanics responding in English were less likely than Hispanics responding in Spanish to agree (aOR 0.1, 95% CI: 0.1-0.3; aOR 0.4, 95% CI: 0.2-0.8, respectively). Parents were less likely to agree with these laws if they did not believe the vaccine works well (aOR 0.2, 95% CI: 0.1-0.5) but more likely to agree if they believed the vaccine is not "too new for laws like these" (aOR 4.5, 95% CI: 2.6-8.0). Agreement with laws increased to 92% when including agreement that "these laws are okay only if parents can opt out." CONCLUSIONS: In this at-risk community, more than half of the parents agreed with HPV immunization requirements generally, and the vast majority agreed when including opt-out provisions. IMPACT: Support for HPV vaccine requirements may depend on race/ethnicity and inclusion of opt-out provisions. Information about vaccine efficacy and safety may increase support and reduce uncertainty about HPV vaccine in high-risk populations.

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

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.

Decreasing age disparities in syphilis and gonorrhea incidence rates in the United States, 1981--2005.

BACKGROUND: Compared to older age groups, teenagers and young adults in the United States are at high risk of acquiring sexually transmitted diseases (STDs). Although the disparity in STD rates across age groups is well documented, changes in the degree of disparity in STD rates across age groups over time have not been examined in detail. METHODS: We examined age-, sex-, and race-specific incidence rates of syphilis and gonorrhea in the United States (excluding New York owing to incomplete age- and race-specific data) from 1981 to 2005. STD rates in younger age groups (ages 15-29 years) were compared to STD rates in older age groups (ages 40-54 years) for each year over the 25-year period. We used regression analyses to examine the trend in the age rate ratio (STD rate in the younger age group divided by STD rate in the older age group) over time, adjusting for autocorrelation. RESULTS: The age disparity in syphilis and gonorrhea declined from 1981 to 2005. The estimated annual decline in the age rate ratio was 5.3% for syphilis and 2.0% for gonorrhea for all races overall (P <0.01). Overall, the age disparity in STD rates was more pronounced for females than males. CONCLUSIONS: Future research is needed to clarify the main determinants of the relative decline in STD rates in younger persons and to inform programmatic responses to the changing age disparity in STD rates.

Antimicrobial resistance for Neisseria gonorrhoeae in the United States, 1988 to 2003: the spread of fluoroquinolone resistance.

BACKGROUND: Over the past 60 years, Neisseria gonorrhoeae has acquired clinically significant resistance to sulfonamides, tetracyclines, penicillins, and ciprofloxacin. OBJECTIVE: To determine U.S. trends in the prevalence of antimicrobial resistance of N. gonorrhoeae from 1988 to 2003. DESIGN: 16-year, multisite, sentinel surveillance for gonococcal isolate susceptibility through the Gonococcal Isolate Surveillance Project (GISP). SETTING: Sexually transmitted disease clinics in 37 cities. PATIENTS: Male patients with a total of 82,064 episodes of urethral gonorrhea. MEASUREMENTS: Primary outcome measures included percentage of gonococcal isolates resistant to antimicrobials used to treat gonorrhea, percentage of patients treated with specific antimicrobials for gonorrhea, and trends of these measures over time. RESULTS: The median age of patients was 26 years, and 74.1% of patients were African American. The proportion of men treated with penicillins for gonorrhea declined from 39.5% in 1988 to 0% in 1994, while the proportion of those receiving fluoroquinolone treatment increased from 0% in 1988 to 42.0% in 2003. Penicillin resistance peaked at 19.6% in 1991, then declined to 6.5% in 2003. Tetracycline resistance peaked at 25.8% in 1997 and declined to 14.4% in 2003. The first fluoroquinolone-resistant isolate was found in 1991. Nationally, 0.4% of isolates were fluoroquinolone-resistant in 1999 and were identified in 39% of GISP cities. By 2003, 4.1% of isolates were fluoroquinolone-resistant and were identified in 70% of GISP cities. Isolates with decreased susceptibility to ceftriaxone, cefixime, azithromycin, and spectinomycin remained rare. In 2001, 3 multidrug-resistant isolates with decreased susceptibility to cefixime were identified. LIMITATION: Sentinel surveillance may not fully reflect trends for all patients with gonorrhea in the United States. CONCLUSIONS: Prevalence of penicillin resistance has declined in the years since gonorrhea treatment with penicillin was discontinued. Fluoroquinolone-resistant N. gonorrhoeae infections continue to increase at a time when fluoroquinolone use has increased. Ongoing nationwide and local antimicrobial susceptibility monitoring is crucial to ensure appropriate treatment of gonorrhea.

The general transition metal (Tro) and Zn2+ (Znu) transporters in Treponema pallidum: analysis of metal specificities and expression profiles.

Acquisition of transition metals is central to the struggle between a bacterial pathogen and its mammalian host. Previous studies demonstrated that Treponema pallidum encodes a cluster-9 (C9) ABC transporter (troABCD) whose solute-binding protein component (TroA) ligands Zn(2+) and Mn(2+) with essentially equal affinities. Bioinformatic analysis revealed that T. pallidum encodes an additional C9 transporter (tp0034-36) orthologous to Zn(2+)-uptake (Znu) systems in other bacteria; the binding protein component, ZnuA, contains a His-rich tract characteristic of C9 Zn(2+)-binding proteins. Metal analysis and metal-reconstitution studies demonstrated that ZnuA is a Zn(2+)-binding protein; parallel studies confirmed that TroA binds Zn(2+), Mn(2+) and Fe. Circular dichroism showed that ZnuA, but not TroA, undergoes conformational changes in the presence of Zn(2+). Using isothermal titration calorimetry (ITC), we demonstrated that TroA binds Zn(2+) and Mn(2+) with affinities approximately 100-fold greater than those previously reported. ITC analysis revealed that ZnuA contains multiple Zn(2+)-binding sites, two of which are high-affinity and presumed to be located within the binding pocket and His-rich loop. Quantitative reverse transcription polymerase chain reaction of tro and znu transcripts combined with immunoblot analysis of TroA and ZnuA confirmed that both transporters are simultaneously expressed in T. pallidum and that TroA is expressed at much greater levels than ZnuA. Collectively, our findings indicate that T. pallidum procures transition metals via the concerted utilization of its general metal (Tro) and Zn(2+) (Znu) transporters. Sequestration of periplasmic Zn(2+) by ZnuA may free up TroA binding capacity for the importation of Fe and Mn(2+).

Social capital and rates of gonorrhea and syphilis in the United States: spatial regression analyses of state-level associations.

We conducted spatial regression analysis to account for spatial clustering of sexually transmitted diseases (STDs) and to examine the state-level association between social capital (using Putnam's public use data set) and rates of gonorrhea and syphilis. We conducted the analysis for the 48 contiguous states of the United States for 1990, 1995, and 2000 and controlled for the effects of regional variation in STD rates, and for state variation in poverty, income inequality, racial composition, and percentage aged 15-34 years. We compared the results of the spatial regression analysis with those of ordinary least squares (OLS) regression. Controlling for all population-level variables, the percentage of variation explained by the OLS regression and by the spatial regression were similar (mid-90s for gonorrhea and low-70s for syphilis), the standardized parameter estimates were similar, and the spatial lag parameter was not statistically significant. Social capital was not associated with STD rates when state variation in racial composition was included in the regression analysis. In this analysis, states with a higher proportion of residents who were African-American had higher STD rates. When we did not control for racial composition, regression analysis showed that states with higher social capital had lower STD rates. We conjecture that sexual networks and sexual mixing drive the association between social capital and STD rates and highlight important measurement and research questions that need elucidation to understand fully the relationship between social capital and STDs.

Trends in pelvic inflammatory disease hospital discharges and ambulatory visits, United States, 1985-2001.

OBJECTIVE: The objective of this study was to describe the estimated trends in incidence of pelvic inflammatory disease (PID) among reproductive-aged women in hospital and ambulatory settings. STUDY: Analyses of PID estimates were performed. Three nationally representative surveys conducted by the National Center for Health Statistics (NCHS): National Hospital Discharge Survey (NHDS), National Hospital Ambulatory Medical Care Survey (NHAMCS), and National Ambulatory Medical Care Survey (NAMCS), were used to obtain the estimates of PID (defined by International Classification of Diseases, 9th Revision codes). National Disease and Therapeutic Index (NDTI) estimates were reviewed for comparison. RESULTS: Rates of hospitalized PID declined 68% overall from 1985 through 2001 (P <0.0001). Ambulatory data support a decrease in PID from 1985 to 2001. From 1995 to 2001, approximately 769,859 cases of acute and unspecified PID were diagnosed annually, 91% in ambulatory settings. CONCLUSIONS: PID has decreased in hospital and ambulatory settings. The expanded national surveys in outpatient and emergency departments provide more complete estimates for PID. Optimal management of PID should target ambulatory settings, where the majority of cases are diagnosed and treated.

A case-control study of syphilis among men who have sex with men in New York City: association With HIV infection.

OBJECTIVE: The objective of this study was to determine factors associated with syphilis among men who report sex with other men in New York City. DESIGN, SETTING AND STUDY SUBJECTS: We conducted a case-control study among 88 men who reported sex with men in the previous year, 18 to 55 years old and diagnosed with primary or secondary syphilis during 2001; and 176 control subjects frequently matched by age and type of health provider. RESULTS: HIV prevalence among syphilis cases was 48% compared with 15% among control subjects (P <0.001). Variables associated with syphilis in a multivariate model were HIV infection (odds ratio [OR], 7.3; 95% confidence interval [CI], 3.5-15.4), income >$30,000 per year (OR, 2.7; CI, 1.4-5.2), and barebacking (OR, 2.6; CI, 1.4-4.8). The median time since HIV diagnosis for HIV-positive was 6 years for cases and 7 years for control subjects (P = 0.70). Among HIV-infected participants, syphilis cases were more likely than control subjects to report being on antiretroviral therapy (69% vs. 44%, P = 0.05) and to report having undetectable viral load (58% vs. 24%, P = 0.02). CONCLUSION: HIV infection was strongly associated with syphilis in this study. High-risk behavior reported by both cases and control subjects indicates the potential for increased HIV transmission.