Sexually Transmitted Diseases

Published by Lippincott, Williams & Wilkins
Print ISSN: 0148-5717
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An estimated 4 million new cases of chlamydial infection occur each year. This experiment assessed the effects of a vaginally applied gel formulation of 0.25% chlorhexidine gluconate on chlamydial infection and on the vaginal ecosystem. Twelve monkeys were treated with a single application of 0.25% chlorhexidine gluconate. These animals were assessed for changes in vaginal flora before and at 30 minutes, 1 day, and 2 days postapplication by microbiologic analysis. Cervical and vaginal tissues were assessed by colposcopy at each time point. Five monkeys received a single application of 0.25% chlorhexidine gluconate gel followed (30 minutes) by a cervical inoculation with Chlamydia trachomatis. Four monkeys were inoculated with Chlamydia only. Cervicovaginal tissues were assessed via modified colposcopy, vaginal swabs were collected for assessment of vaginal flora, and cervical swabs were collected for detection of Chlamydia (culture/ligase chain reaction) at baseline and days 1, 2, and 7 postinoculation. Changes in vaginal flora were minimal in all monkeys. Application of 0.25% chlorhexidine gluconate did not affect adversely vaginal colonization by lactobacilli. All chlamydial infection control monkeys were infected, whereas none of the five monkeys pretreated with chlorhexidine gluconate were positive for C. trachomatis by culture or ligase chain reaction. Colposcopic observations remained largely unchanged in all groups. A 0.25% chlorhexidine gluconate gel was protective against chlamydial infection in all animals tested, had no adverse effect on the vaginal flora, and had minimal effect on cervicovaginal tissues after a single application.
 
Penile condylomata were eradicated from 26 (70%) of 37 and from 15 (63%) of 24 uncircumsized men with penile warts who performed one course of self-treatment with 0.5% podophyllotoxin in ethanol, which was applied twice daily for four and five days, respectively. In comparison with previous data on the efficacy for use of the same regimen for only three days, no major advantages were observed; instead, the frequency of local adverse effects was increased. However, because warts growing in a plaque-like fashion reacted favorably to the therapy, such lesions may be treated for four to five days if they are recalcitrant to the three-day regimen. The efficacy of application of 0.5% podophyllotoxin in ethanol only once daily was significantly lower than that resulting from application twice daily.
 
In a double-blind, placebo-controlled study, self-treatment with a 0.5% podophyllotoxin cream was evaluated among 60 women afflicted solely with outer vulvoanal warts; 12 women received treatment with placebo cream and 48 women with active substance, administered twice daily in 3-day cycles once weekly for up to 3 weeks. Patients who were not completely cured after three cycles were classified as treatment failures. Four patients treated with podophyllotoxin cream were excluded: two were considered drop-outs, another patient was concurrently afflicted with intraanal warts, and a fourth patient refused further therapy with the cream due to the severity of local side effects occurring from the first course of therapy. Of the remaining 44 patients treated with active substance, the primary cure rates were 43%, 66%, and 91% after 1, 2, and 3 treatment cycles, respectively. Within a 3-month follow-up period, 6 (14%) patients who were originally considered cured exhibited some degree of either "recurrence" or "reoccurrence". Thus, a complete and permanent cure from podophyllotoxin cream occurred in 38 out of 44 patients (77%). Placebo lacked therapeutic influence. A slight-to-moderate tenderness, pain, burning, or all of the above in the treated areas was noted by more than 60% of the women who were treated with the podophyllotoxin cream.
 
Penile condylomata were eradicated from 22 (54%) of 41 men whose lesions were painted twice (with a 72-hr interval) by the investigator with 8% podophyllotoxin in ethanol and from 83 (48%) of 173 men who self-administered either 0.5 to 1.0% topical preparations twice or thrice daily for three subsequent days. All regimens had identical efficacy; a higher frequency of mild local irritation in the self-medicating group may be outweighed by a relatively lower risk for hazardous systemic absorption. The rate of cure was higher when tumors afflicted the preputial cavity than the urinary meatus or penile skin and was lower when there were more than five warts, lesions grew in a plaque-like pattern, or duration of warts exceeded six months. Sixty-six men were sensitized with 2,4-dinitrochlorobenzene; the degree of response to subsequent challenge did not correlate to number or growth pattern of lesions or to cure rate.
 
Forty heterosexual male patients with therapy resistant penile warts of long duration (mean 12.9 months) were treated with carbon dioxide laser, immediately followed by topical application of 0.5% idoxuridine cream twice daily for 14 days. In case of incomplete or no response to the initial treatment, the treatment procedure was repeated once. All patients had previously been repeatedly treated with podophyllotoxin 0.5% solution and/or carbon dioxide laser surgery. After two weeks of treatment, 32 patients (80%) were completely healed. The remaining eight patients were retreated and four weeks after the start of the study 35 patients (87.5%) showed complete response. Three months after the study had been initiated 34 patients (85%) were still completely healed. No adverse reactions were observed. It was concluded that laser surgery followed by topical application of 0.5% idoxuridine cream for two to four weeks seems to be highly effective in the treatment of longstanding, therapy-resistant genital warts in men. Because of the uncontrolled nature of the present study and the relatively small number of patients treated, it would be important to carry out controlled studies in larger study populations and to carry out a follow-up examination of at least six months after treatment.
 
High-performance liquid chromatography was used for quantitative determination of podophyllotoxin in serum subsequent to repeated applications of a 0.5% ethanolic preparation on condylomata acuminata. The drug was not detectable in the serum of ten men treated with < or = 50 microliters. In serum of seven patients receiving 100-1,500 microliters on extraordinarily large en-plaque lesions, peak levels of 1-17 ng/ml were measured within 1-2 hr. The drug did not accumulate in serum. Dispersion of 100 microliters gave rise to peak levels of < or = 5.0 ng/ml and to subsequent levels of < or = 3.0 ng/ml for 4 hr. Larger doses gave rise to traceable amounts in serum for < or = 12 hr. Investigations with 52 patients indicated that volumes of > 100 microliters are rarely required for topical treatment of condylomata. It is concluded that application of volumes of < or = 250 microliters twice daily for three days would satisfy the most stringent safety precautions and avoid any danger of systemic toxicity. Potential hazards associated with use of the nonstandardized 20% podophyllin preparations are emphasized.
 
Bacterial vaginosis is the most common cause of vaginal symptoms in women and has potential complications. Efforts to improve treatment of this disease process are warranted. The goal of this study was to compare the safety and efficacy of once-daily intravaginal administration of 0.75% metronidazole gel for 5 days to the established twice-daily regimen in the treatment of bacterial vaginosis. Nonpregnant women with bacterial vaginosis diagnosed by accepted clinical criteria at 14 geographically diverse general gynecology clinics were enrolled in this prospective, randomized, investigator-blind, parallel study. They were treated with either once-daily or twice-daily 0.75% metronidazole gel 5 g intravaginally for 5 days and were reevaluated at 7 to 12 days and 28 to 35 days after completing treatment. Efficacy was determined by clinical criteria. Adverse drug reactions were monitored. Of the 514 evaluable women enrolled, bacterial vaginosis was cured at the first return visit among evaluable patients in 153 of 199 (77%) of those who received the once-daily and in 157 of 196 (80%) of those who received the twice-daily administration. Bacterial vaginosis was cured among evaluable patients at the final visit in 104 of 180 (58%) of those who received once-daily and 109 of 178 (61%) of those who received the twice-daily regimen. Intent-to-treat analysis showed cure at 1 month in 118 of 207 (57%) of those treated once daily and 129 of 209 (62%) of those treated twice daily. Side effects were mild, and none caused treatment discontinuation. Once-daily dosing of 0.75% metronidazole gel 5 g for 5 days yields efficacy, safety, and tolerance equivalent to the currently used twice-daily dosing in the treatment of bacterial vaginosis, adding another competitive choice to the available therapeutic options for this condition.
 
The objectives of this cross-sectional study were to determine correlates of syphilis seroprevalence among HIV-infected and -uninfected antenatal attendees in an African multisite clinical trial, and to improve strategies for maternal syphilis prevention. A total of 2,270 (86%) women were HIV-infected and 366 (14%) were HIV-uninfected. One hundred seventy-five (6.6%) were syphilis-seropositive (7.3% among HIV-infected and 2.6% HIV-uninfected women). Statistically significant correlates included geographic site (odds ratio [OR] = 4.5, Blantyre; OR = 3.2, Lilongwe; OR = 9.0, Lusaka vs. Dar es Salaam referent); HIV infection (OR = 3.3); age 20 to 24 years (OR = 2.5); being divorced, widowed, or separated (OR = 2.9); genital ulcer treatment in the last year (OR = 2.9); history of stillbirth (OR = 2.8, one stillbirth; OR = 4.3, 2-5 stillbirths); and history of preterm delivery (OR = 2.7, one preterm delivery). Many women without identified risk factors were syphilis-seropositive. Younger HIV-infected women were at highest risk. Universal integrated antenatal HIV and syphilis screening and treatment is essential in sub-Saharan African settings.
 
Several fastidious bacteria have been associated with bacterial vaginosis (BV), but their role in lactobacilli recolonization failure is unknown. We studied the effect of 7 BV-associated bacterial species and 2 Lactobacillus species on vaginal colonization with Lactobacillus crispatus CTV-05 (LACTIN-V). Twenty-four women with BV were given a 5-day course of metronidazole vaginal gel and then randomized 3:1 to receive either LACTIN-V or placebo applied vaginally once daily for 5 initial consecutive days, followed by a weekly application over 2 weeks. Vaginal swabs for L. crispatus CTV-05 culture and 9 bacterium-specific 16S rRNA gene quantitative polymerase chain reaction assays were analyzed on several study visits for the 18 women receiving LACTIN-V. Vaginal colonization with CTV-05 was achieved in 61% of the participants receiving LACTIN-V at either day 10 or day 28 visit and 44% at day 28. Participants not colonized with CTV-05 had generally higher median concentrations of BV-associated bacteria compared to those who colonized. Between enrollment and day 28, the median concentration of Gardnerella vaginalis minimally reduced from 10 to 10 16S rRNA gene copies per swab in women who colonized with CTV-05 but increased from 10 to 10 in those who failed to colonize (P = 0.19). Similarly, the median concentration of Atopobium spp. reduced from 10 16S rRNA gene copies per swab to below limit of detection in women who colonized with CTV-05, but increased from 10 to 10 in those who failed to colonize (P = 0.04). The presence of endogenous L. crispatus at enrollment was found to be significantly associated with a reduced odds of colonization with CTV-05 on day 28 (P = 0.003), and vaginal intercourse during the study significantly impaired successful CTV-05 colonization (P = 0.018). Vaginal concentration of certain BV-associated bacteria, vaginal intercourse during treatment, and the presence of endogenous L. crispatus at enrollment predict colonization with probiotic lactobacilli.
 
Bacterial vaginosis (BV) is a common vaginal infection caused by a lack of endogenous lactobacilli and overgrowth of pathogens that frequently recurs following antibiotic treatment. A phase 2a study assessed colonization efficiency, safety, tolerability, and acceptability of Lactobacillus crispatus CTV-05 (LACTIN-V) administered by a vaginal applicator. Twenty-four women with BV were randomized in a 3:1 ratio of active product to placebo. Participants used LACTIN-V at 2 × 10 colony-forming units (cfu)/dose or placebo for 5 initial consecutive days, followed by a weekly application over 2 weeks. They returned for follow-up on Days 10 and 28. Sixty-one percent of the 18 women randomized to the LACTIN-V group were colonized with L. crispatus CTV-05 at Day 10 or Day 28. Among LACTIN-V users with complete adherence to the study regimen, 78% were colonized at Day 10 or Day 28. Of the 120 adverse events (AEs) that occurred, 108 (90%) and 12 (10%) were of mild and moderate severity, respectively. AEs were evenly distributed between the LACTIN-V and placebo group. Of the total AEs, 93 (78%) were genitourinary in origin. The most common genitourinary AEs included vaginal discharge (46%), abdominal pain (46%), dysuria (21%), pollakiuria (21%), vaginal odor (21%), and genital pruritus (17%). No grade 3 or 4 AEs or serious AEs occurred and no deep epithelial disruption was seen during colposcopic evaluation. The product was well tolerated and accepted. LACTIN-V colonized well, and was safe and acceptable in women treated for BV.
 
Bacterial vaginosis is a very common vaginal infection. The lack of endogenous lactobacilli and overgrowth of pathogens facilitate numerous gynecological complications. A phase I dose-ranging safety trial tested the safety, tolerability, and acceptability of Lactobacillus crispatus CTV-05 (LACTIN-V) administered by vaginal applicator. Twelve healthy volunteers were enrolled in 3 blocks of 4 (5 x 10, 1 x 10, and 2 x 10 cfu/dose). Each block was randomized in a 3:1 ratio of active product to placebo. Participants used study product for 5 consecutive days, returned for follow-up on days 7 and 14, and had phone interviews on days 2 and 35. All 12 participants took 5 doses and completed study follow-up.Overall, 45 adverse events (AEs) occurred, of which 31 (69%) were genitourinary (GU) AEs. GU AEs appeared evenly distributed between the 3 treatment blocks and between LACTIN-V and placebo arms. The most common GU AEs were vaginal discharge in 5 subjects (42%), abdominal pain in 4 subjects (33%), metrorrhagia in 4 subjects (33%), vulvovaginitis in 4 subjects (33%), vaginal candidiasis in 3 subjects (25%), and vaginal odor in 3 subjects (25%). Forty-one (91%) AEs were mild (grade 1) in severity. All 4 moderate AEs (grade 2) were unrelated to product use. No grade 3 or 4 AEs or serious adverse events (SAE) occurred. Laboratory parameters and colposcopy findings were within normal limits or clinically insignificant. The product was well-tolerated and accepted. All 3 dose levels of LACTIN-V appeared to be safe and acceptable in healthy volunteers.
 
To determine risk factors for sexually transmitted infections (STIs) among women in Durban and Hlabisa (South Africa), Moshi (Tanzania), and Lusaka (Zambia). Between 2003 and 2004, 958 women at risk of STIs were enrolled in a 1-year prospective study. They were interviewed at each monthly visit, and samples for STI testing were collected during quarterly and other visits when clinically indicated. The incidence of infections as measured in person-years at risk (PYAR) was as follows: overall trichomoniasis, 31.9/100 PYAR; chlamydial infection in South Africa, 19.5/100 PYAR; chlamydial infection in Tanzania and Zambia, 4.9/100 PYAR; gonorrhea in South Africa, 16.5/100 PYAR; gonorrhea in Tanzania and Zambia, 5.3/100 PYAR; overall syphilis, 7.5/100 PYAR; and overall HIV, 3.8/100 PYAR. The incidence of most STIs was highest among the South African sites, where chlamydial infection and gonorrhea were detected by using a more sensitive assay. Independent risk factors included age, hormonal contraceptive methods, and measures of sexual behavior, including number of sex partners and occurrence of anal sex in the past 3 months. Women with incident HIV infection were at increased risk of chlamydial infection [odds ratio (OR) = 5.5, 95% confidence interval (CI): 2.0-15.2]and gonorrhea (OR = 5.7, 95% CI: 1.9-17.0) in South African sites. Despite ongoing counseling during the study, high-risk sexual behaviors were common, and consistent condom use remained low. The incidence of STIs, including HIV, was high among women in this study. These findings highlight the urgent need for effective HIV/STI prevention programs in this population.
 
Isolates of Neisseria gonorrhoeae requiring arginine, hypoxanthine, and uracil (AHU) appeared in Denmark in 1946, were preponderant in Seattle during the 1970s, were associated with disseminated gonococcal infections (DGI), and were primarily of the IA-1,2 serovar. To investigate the disappearance of the AHU/IA-1,2 phenotype and to examine by pulsed-field gel electrophoresis (PFGE) the genomic homogeneity of this unique phenotype isolated from Seattle-King County during the past decade. This retrospective study used data extracted from previous publications for the period 1971 through 1984, and from existing records at the Neisseria Reference Laboratory, University of Washington for the period 1985 through 1996. Samples (n = 68) of AHU/IA-1,2 isolates from 1984 to 1985 and 1988 to 1993 were analyzed using endonucleases NheI and XbaI. For comparison, 10 AHU/IB isolates were included in the study. AHU isolates, predominantly IA-1,2 strains accounted for 52% of the gonococcal isolates for the period 1971 through 1974, 40% for 1974 through 1976, 16% for 1984, and then declined from 7% in 1986 to 0% for each of the last 3 years, 1994 through 1996. Isolates with < or = 1 band difference after digestion with either NheI or XbaI were considered to belong to a single closely related pattern. Pulsed-field gel electrophoresis (PFGE) type designation was made from the combination of NheI and XbaI patterns. These criteria yielded 5 NheI and 8 XbaI PFGE patterns, and 11 PFGE types based on the combination of NheI and XbaI pattern. The most frequently occurring NheI and XbaI patterns accounted for 74% and 57% of isolates, respectively. One type persisted throughout the decade and accounted for 54% of the 68 isolates. Analysis of the 10 AHU/IB isolates yielded 7 NheI and 8 XbaI patterns that gave 9 types that were distinct from the types found in the AHU/IA-1,2 strains. The AHU/IA-1,2 phenotype first documented 50 years ago in Denmark still shows a high degree of genomic homogeneity during the past decade in Seattle. The implementation of screening, decreased rates of sexual exposure in the acquired immune deficiency syndrome era, or other factors may explain its apparent elimination in Seattle-King County.
 
A 1.0% gel formulation of C31G, a surfactant, has been shown to have in vitro antiviral and antibacterial activity. The goal of this study was to evaluate the safety and efficacy of vaginal and rectal applications of 1.0% Savvy (C31G) in the nonhuman primate model. The safety of repeated 1.0% C31G application was evaluated by microflora, pH, vaginal biopsy, colposcopy, and rectal lavage. Efficacy in preventing chlamydial infection was documented by culture, nucleic acid amplification tests, and serology. Repeated applications of Savvy (1.0% C31G) were not associated with significant changes in pH, microflora, or inflammatory infiltrates on tissues. No significant differences in epithelial desquamation were noted after rectal product use compared with placebo. Four of 6 animals were protected from chlamydial infection after pretreatment with Savvy. C31G was shown to be safe to both vaginal and rectal mucosal tissues and to the microflora with repeated daily use. Savvy has an acceptable safety profile after repeated vaginal and rectal use. A single intravaginal application of 1.0% C31G provided partial protection from acquiring cervical chlamydial infection.
 
Despite the scale-up of prevention of mother-to-child transmission (PMTCT) programs worldwide, the translation from research studies into public health policy has been slow. This report details the experiences of a city-driven PMTCT program in China using existing health resources. The PMTCT program was devised to hospital based and city-wide. It achieves full use of available resources: the local Centers for Disease Control and Prevention, the Infectious Disease Hospital, Maternal and Child Health Hospitals, and all qualified comprehensive hospitals. From 2000 to 2010, 1,843,122 pregnant women attended prenatal care or labor and delivery services. Overall, 97.4% received pretest HIV counseling, and 96.2% were tested for HIV. Among the 81.1% (1,495,122) of women who attended prenatal clinics, 97.2% (1,452,753) received pretest counseling and 95.7% (1,430,799) were tested for HIV. Among the 18.9% (348,000) of women with an undocumented HIV status at labor and delivery, 98.6% (343,038) received pretest counseling, and 98.1% (341,371) were tested for HIV. In total, 229 women were determined HIV positive for a prevalence of 1.3 per 10,000 pregnant women. Among the 107 HIV-infected women who carried to delivery, 87.9% received antiretroviral prophylaxis for themselves and their infants. Among the 58 women who were identified HIV positive at labor, 10.3% of mothers and 72.4% of infants received antiretroviral prophylaxis. The estimated mother-to-child transmission rate was 5.3% (95% confidence interval, 2.2%-10.7%). With appropriate integration, existing health care resources are adequate for a comprehensive city-driven PMTCT program in an area with a low HIV prevalence.
 
The most important risk factor for cervical neoplasia is genital infection with certain types of human papillomavirus (HPV). Genital warts (GW) are an easily recognizable condition caused by HPV. Although only a fraction of HPV infections are clinical, a history of ever having had GW could serve as a marker for exposure to HPV. To study the risk factors for ever having had GW. The association of GW with abnormal Papanicolaou (Pap) smear and relation to cervical neoplasia is also discussed. A case-control study among 10,838 women aged 20 to 29 years and reporting at least one lifetime sexual partner. The women were participants in a prospective cohort study on the relationship between HPV and cervical neoplasia in Copenhagen, Denmark. Data were obtained by means of personal interviews using structured questionnaires. In all, 1,820 women (17%) reported ever having had GW. The most important risk factor was the number of lifetime of sexual partners (adjusted odds ratio 5.2; 95% confidence interval: 3.4-8.0) for at least 40 partners vs. 1 to 2 partners). The number of regular partners, sexually active years, a history of chlamydial infection, and smoking were also associated with the risk of ever having had GW. Women who had had GW were 1.9 times more likely than other women to report an abnormal Pap smear. The study confirms the sexual transmission of the infection. There is also good concordance between risk factors for ever having had GW and cervical neoplasia. A close relationship between having had GW and an abnormal Pap smear was observed.
 
The mechanism of inhibition of Neisseria gonorrhoeae by pyocin 103 was examined. Pyocin 103 decreases the viability of N. gonorrhoeae immediately after its addition to logarithmically growing cells by single-hit kinetics. This inhibition was paralleled by an immediate cessation of protein synthesis, RNA synthesis, and active transport. From the data presented, it is likely that pyocin kills N. gonorrhoeae in the same manner that it kills Pseudomonas aeruginosa, i.e., by interfering with energy metabolism.
 
The national seroprevalence of the nononcogenic human papillomavirus (HPV) type 11, one of the types targeted by the quadrivalent HPV vaccine, has not been evaluated in the United States. The objectives of this study were to estimate the national seroprevalence and evaluate predictors of HPV-11 seropositivity. We tested serum samples for HPV-11 antibodies and analyzed questionnaire data from the second phase of the National Health and Nutrition Examination Survey III, 1991--1994. Seroprevalence estimates were weighted to represent the US population. : Overall seroprevalence of HPV-11 infection was 4.7%. Seroprevalence was significantly higher among females (5.7%) than among males (3.6%). Independent predictors of HPV-11 seropositivity included sex, race/ethnicity, lifetime number of sex partners, education, and HPV-16 seropositivity. This study represents the most comprehensive picture of HPV-11 infection in the United States to date, and provides baseline data on the prevalence of HPV-11 before availability of the quadrivalent HPV vaccine.
 
Natural history data on human papillomavirus (HPV) incidence and its risk factors have not been reported on from young women in Norway. We report on incidence and predictors of HPV-6, 11, 16, and 18; 6 or 11; 16 or 18; or all 4. A 48-month prospective study enrolled 898 women aged 16 to 24 between 1998 and 2000. HPV DNA polymerase chain reaction testing of genital tract specimens was performed and risk data collected every 6 months and HPV serology and genital Chlamydia trachomatis testing performed every 12 months. Cumulative incidence was estimated using the Kaplan-Meier method and covariates evaluated in Cox models. Among the women who were HPV DNA- and serology-negative at entry, 48-month cumulative incidences (95% confidence interval) were as follows: HPV-6: 20.0% (17.1-23.4), HPV-11: 2.2% (1.3-3.5), HPV-16: 25.0% (21.7-28.8), HPV-18: 13.6% (11.3-16.4), HPV-6 or -11: 21.5% (18.5-25.0), HPV-16 or -18: 30.4% (26.7-34.5), and HPV-6, -11, -16, or -18: 37.8% (33.6-42.3). Younger age at first intercourse, being single, having no regular partner, reporting new partners, and genital C. trachomatis infection were independent risk factors of incident HPV. Proxies measuring new partnerships and genital C. trachomatis infection predicted incident HPV-6, -11, -16, or -18. Incidence of HPV-6, -11, -16, or -18 in young Norwegian women is high, with more than one-third becoming infected over 48 months.
 
A possible reason for the failure to detect human papillomavirus (HPV) DNA in asymptomatic men who are likely to be infected is the sensitivity of the detection methods. The goal of this study was to identify a method for sampling the anogenital skin of men that was simple and well tolerated and that would permit the detection of asymptomatic or subclinical HPV infection, which is thought to occur commonly in sexually active men. Swabs of genital skin and urine from men at high and low risk of infection with types 6 and 11 were tested for HPV by polymerase chain reaction. These specimens had a low sensitivity for HPV detection, often because inadequate material was collected on the swab. Noninvasive sampling of genital skin to identify individuals with subclinical HPV infection remains a challenge. Future studies should involve the use of more abrasive sampling devices (such as cytobrushes), perhaps combined with some type of soap to dislodge more epithelial cells.
 
A vaccine to prevent human papillomavirus (HPV) 6, HPV 11, HPV 16, or HPV 18 and associated diseases is licensed for females, and it may be licensed for men in the future. There are limited data on HPV 6/11, 16, and/or 18 seroprevalence in men. A total of 490 men aged 18 to 40 years were enrolled in a study of HPV in men in Tucson, AZ, and Tampa, FL. Enrolled men completed a self-administered questionnaire, and HPV serology was performed using HPV 6/11, 16, and 18 VLP assays. Overall, seroprevalence to HPV 16 was 12.1%, HPV 6/11 was 9.7%, and to HPV 18 was 5.4%. Seroprevalence to HPV 6/11, 16, and/or 18 was 21% and was highest among 35 to 40 year olds (48%); prevalence in this age group was significantly higher compared to the 18 to 24 year olds (adjusted odds ratio (aOR) 6.8, 95% confidence interval (CI) 3.7, 12.8). Independent predictors of seropositivity to HPV 6/11, 16, and/or 18 were older age, greater number of female sex partners in the past 3 months, and current smoking. HPV vaccine-type seroprevalence was highest in 35 to 40 year old men. These data on the epidemiology of HPV seroprevalence in men are useful for discussions regarding recommendations for HPV vaccine if licensed for use in men.
 
HIV infection and associated immunodeficiency are known to alter the course of human papillomavirus (HPV) infections and of associated diseases. This study investigated the association between HIV and HPV and genital warts. HPV testing and physical examinations were performed in two large prospective studies: the Women's Interagency HIV Study (WIHS) and the HIV Epidemiology Research Study (HERS). Statistical methods incorporating dependencies of longitudinal data were used to examine the relationship between HIV and HPV and genital warts. A total of 1008 HIV-seronegative and 2930 HIV-seropositive women were enrolled in the two studies. The prevalence of HPV 6 or 11 was 5.6 times higher in HIV-seropositive women in the WIHS and 3.6 times higher in the HERS. Genital wart prevalence increased by a factor of 3.2 in the WIHS and 2.7 in the HERS in HIV-seropositive women. In the WIHS, infection with HPV type 6 or 11, in comparison with no HPV infection, was associated with odds of genital wart prevalence of 5.1 (95% CI: 2.9-8.8), 8.8 (95% CI: 6.1-12.8), and 12.8 (95% CI: 8.8-18.8) in HIV-seronegative women, HIV-seropositive women with > or =201 CD4 cells/microl, and HIV-seropositive women with < or =200 CD4 cells/microl, respectively. In the HERS, infection with HPV type 6 or 11 was associated with odds of 2.7 (95% CI: 1.6-4.6), 4.9 (95% CI: 3.2-7.7), and 5.3 (95% CI: 3.3-8.5) in these same groups. Other HPV types showed a similar dose-response relation, but of substantially lower magnitude and statistical significance. HIV infection and immunodeficiency synergistically modified the relation between HPV 6 or 11 infection and genital wart prevalence.
 
Human papillomavirus (HPV) is considered a necessary cause of cervical cancer. The aim of the current study was to determine the burden of HPV infection among randomly sampled Danish women before the vaccine against HPV is implemented. Further we assessed the risk factor profile for prevalent high risk (HR) HPV infection and infection with multiple HR HPV types. In the present cross-sectional study, we used baseline data from a population-based cohort study where participants were interviewed and had a gynecological examination. Cervical samples were analyzed for HR HPV using Hybrid capture 2 in 10,544 women aged 20-29 years and 1443 women aged 40-50 years. Genotyping was performed using LiPA. The prevalence of HR HPV was 17.9% and 4.4% in women aged 20-29 years and 40-50 years, respectively. HPV16 was the most common HR type overall and among women with abnormal cytology. Multiple HPV types were highly prevalent, notably in the younger cohort. Lifetime number of sexual partners was the main risk factor for HR HPV infection (adj. OR = 2.8 and OR = 3.4 for > or =15 partners vs. < or =4 in respectively younger and older women), whereas number of recent sexual partners was only associated with risk in younger women. Number of partners, oral contraceptive use and self-reported chlamydia infection increased the risk of having multiple HR HPV types (compared to having a single HR HPV type). HR HPV infection was common among younger women, with HPV16 as the predominant type. We confirmed the importance of sexual activity for the risk of HR HPV infection. In addition, we found that sexual behavior also play an important role for the risk of having multiple HR HPV types.
 
The World Health Organization has established a worldwide program for gonococcal antimicrobial surveillance, but so far no data on gonococcal susceptibility in Central Asia are available. The need for biological data on the susceptibility of Neisseria gonorrhoeae in Kyrghyzstan, to enable adaptation of the national treatment protocol for gonococcal infections, led Médecins Sans Frontières and Epicentre to conduct a survey in collaboration with the Alfred Fournier Institute in Paris and the health authorities in Bishkek. In vitro susceptibility of N gonorrhoeae strains was determined with use of the reference agar-plate dilution technique. Results for 11 antibiotics tested on 120 strains of gonococci showed a low proportion (11.7%) of penicillinase-producing N gonorrhoeae and high proportions of intermediate or resistant strains to the majority of the antibiotics tested, including fluoroquinolones (>or=25% of strains resistant). All the strains were susceptible to spectinomycin, and only two strains had decreased susceptibility to cefixime. The therapeutic choices available in Kyrghyzstan appear to be limited to cephalosporins and spectinomycin.
 
The concentration of the protein CA-125 in serum was determined in women with a normal pelvis visualized at laparoscopy (control group, n = 15) and compared with serum levels of this protein in women with pelvic inflammatory disease (PID) (n = 14). Mean serum concentrations of CA-125 were similar in the two groups: 17.4 +/- 2.3 (SE) units/ml for the control group vs. 17.0 +/- 4.3 units/ml for those with PID (P greater than 0.05). In addition, women with chlamydial cervicitis, histologically confirmed endometritis, and laparoscopically documented salpingitis had CA-125 levels that were not significantly different from those of controls. We conclude that serum levels of CA-125 will not be useful in the diagnosis of PID.
 
One hundred twenty-eight patients who had been treated for late latent syphilis were followed. Benzathine penicillin G (2.4 X 10(6) units given intramuscularly once a week for two weeks) was administered to 123 patients, and five patients were given tetracycline (500 mg orally four times daily for 12 days). Of these patients, 56 (44%) became seronegative within five years, and 72 (56%) had persistently positive reagin tests.
 
A retrospective study of 2498 patients who made multiple visits to a sexually transmitted disease clinic over a 13-year period analyzed risk factors, default patterns, and repeated infections associated with gonococcal urethritis. An analysis of visitation patterns found that being young, black, and male and having a history of gonococcal urethritis before visiting the clinic was positively related to the total time a patient remained involved with the clinic. Default rates for all patients increased with successive clinic visits. A focused analysis was carried out on the records of 146 patients who returned to the clinic within 12 months with a second diagnosis of gonococcal urethritis. It was found that this group of "repeaters," who comprised 15% of the total population with gonococcal urethritis, accounted for approximately 29% of all diagnoses of this infection over the 13-year study period. Repeaters were found to be more frequently male, black, single, and to be less likely to return for a test-of-cure culture. Longitudinal analysis found that the median time repeaters remained involved with the clinic was approximately 130 days. The relatively brief clinic "half-life" and rapid rates of removal of repeaters are discussed in terms of the development of strain-specific immunity to Neisseria gonorrhoeae in a closed population of patients.
 
This study aimed to investigate the prevalence of penicillinase-producing Neisseria gonorrhoeae (PPNG) and their blaTEM-135 gene variant in 2007 and 2012 in Nanjing, China. In addition, molecular epidemiological typing of all isolates was performed to elucidate the genetic relationships of the PPNG strains. A total of 199 and 77 N. gonorrhoeae isolates were collected at the National Center for STD Control in 2007 and 2012, respectively. Nitrocefin tests were performed to identify PPNG. Mismatch amplification mutation assay was used to identify blaTEM-135. All isolates were genotyped using N. gonorrhoeae multiantigen sequence typing (NG-MAST), and additionally, porB-based phylogenetic analysis was performed for the PPNG isolates. The total prevalence of PPNG isolates was 41% (114/276) and 58% (66/114) of these PPNG isolates possessed blaTEM-135. In 2007, 45% (90/199) produced β-lactamase, and of those PPNG, 58% (52/90) possessed blaTEM-135. In 2012, 31% (24/77) were PPNG, and 58% (14/24) of those isolates contained blaTEM-135. There were 162 NG-MAST STs among the 276 isolates, and 89 of those were novel STs. A strong association between specific NG-MAST STs and blaTEM-135 was found, and the porB-based phylogenetic analysis showed a distant evolutionary relationship between isolates in 2007 and isolates in 2012. A high prevalence of PPNG and blaTEM-135 was found in Nanjing, China. blaTEM-135 might be a precursor in the evolution into an extended-spectrum β-lactamase that can degrade ceftriaxone, which stresses the need to continuously monitor PPNG, blaTEM-135, and additional evolving blaTEM gene variants.
 
We report the first population-based assessment of national trends in chlamydia prevalence in the United States. We investigated trends in chlamydia prevalence in representative samples of the U.S. 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. 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. 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.
 
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. 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. 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). 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.
 
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. 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. 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. 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.
 
Evaluation of sexual behaviors is essential to better understand the epidemiology of sexually transmitted infections and their sequelae. The National Health and Nutrition Examination Surveys (NHANES) is an ongoing probability sample survey of the US population. Using NHANES sexual behavior data from 1999 to 2012, we performed the following: (1) trend analyses among adults aged 25 to 59 years by 10-year birth cohorts and (2) descriptive analyses among participants aged 14 to 24 years. Sex was defined as vaginal, anal, or oral sex. Among adults aged 25 to 59 years, median age at sexual initiation decreased between the 1940-1949 and 1980-1989 cohorts from 17.9 to 16.2 among females (Ptrend < 0.001) and from 17.1 to 16.1 among males (Ptrend < 0.001). Median lifetime partners increased between the 1940-1949 and 1970-1979 cohorts, from 2.6 to 5.3 among females (Ptrend < 0.001) and from 6.7 to 8.8 among males (Ptrend < 0.001). The percentage of females reporting ever having a same-sex partner increased from 5.2% to 9.3% between the 1940-1949 and 1970-1979 cohorts (Ptrend < 0.001). Among participants aged 14 to 24 years, the percentage having had sex increased with age, from 12.5% among females and 13.1% among males at age 14 years to more than 75% at age 19 years for both sexes. Among sexually experienced 14- to 19-year-olds, 45.2% of females and 55.0% of males had at least 3 lifetime partners; 39.4% of females and 48.6% of males had at least 2 partners in the past year. The proportion of females aged 20 to 24 years who reported ever having a same-sex partner was 14.9%. The proportion of participants aged 14-19 or 20-24 years reporting ever having sex did not differ by survey year from 1999 to 2012 for either males or females. Sexual behaviors changed with successive birth cohorts, with more pronounced changes among females. A substantial proportion of adolescents are sexually active and have multiple partners. These data reinforce existing recommendations for sexual health education and sexually transmitted infection prevention targeting adolescents before sexual debut.
 
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. 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. 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. 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.
 
Resurgence of syphilis in Canada and worldwide requires laboratories to update their methods for molecular epidemiology investigation and surveillance. This study utilizes polymerase chain reaction diagnostic tests for syphilis, identifies macrolide resistance, and uses a molecular typing system to characterize Treponema pallidum clinical strains causing syphilis in Alberta and Northwest Territories, Canada. In total 449 specimens including genital swabs, whole blood, sera, and cerebrospinal fluid were obtained from 374 patients with suspect syphilis in Alberta and Northwest Territories. Molecular subtyping was based on genetic characterization of treponemal repeat genes, arp and tpr. Detection of macrolide resistance was accomplished by identification of the 23S rRNA gene mutation associated with the resistance pattern. Forty-nine specimens obtained from 43 patients were found to be positive for T. pallidum DNA using bmp, tpp47 and polA polymerase chain reaction assays. Four molecular subtypes were identified, with one type, 14d, accounting for 70% of all cases and 83% of typeable strains. Seven patients (16%) were found to be infected by macrolide-resistant strains, of which 6 were men who have sex with men and 1 whose infection was acquired in China. A single molecular type of T. pallidum, characterized as 14d, caused the majority of the syphilis cases identified in this study. A more discriminatory typing method would be required to determine if these strains are clonal. Treatment of infectious syphilis with macrolide antibiotics should be restricted to patient populations where resistance is rare and clinical and serological follow up of patients is possible.
 
To compare the prevalence of condom use with clients and regular sex partners between female sex workers (FSWs) who were or were not injecting drug users (IDUs). Behavioral surveillance data (2002-2004) conducted in Sichuan, China were analyzed. Mapping exercises were done. About 250 to 400 FSWs were anonymously interviewed from selected establishments in 19 surveillance sites. Of all 15,379 FSWs studied, 3.2% were IDUs. This group, when compared with the non-IDU group, was less likely to have used condoms with clients (last episode: 71.1% vs. 81.2%, OR = 0.6, P < 0.01; consistent use in the last month: 26.7% vs. 40.4%, OR = 0.5, P < 0.01) or to possess a condom (68.7% vs. 77.8%, OR = 0.6, P < 0.01). The between-group difference in last month's consistent condom use with clients remained significant in the multivariate analyses, after adjusting for other significant factors [age, education level, age at first sex, having a regular sex partner, HIV-related knowledge and perceptions, HIV antibody testing (OR = 1.1-2.9, P < 0.05); STD symptoms, type of sex workers, longer duration of sex work, larger number of clients per week, and not having received HIV-related information (OR = 0.4-0.9)]. Comparable results were obtained for condom use with the last client. Such between-group differences were, however, not observed for condom use with regular sex partners (P > 0.05). Exposure to HIV-related services was associated with condom use with clients (OR = 1.3-2.8, P < 0.05). Higher sexual risk behaviors were found among FSWs who were also IDUs, when compared with those who were non-IUDs. A double-risk bridging population for HIV transmission thereby exists.
 
Analysis of Combined Effects* 
The objective of this article is to study the effect of PC-815, a novel combination microbicide containing carrageenan and the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150, in blocking HIV-1 and HIV-2 infections in vitro as compared with Carraguard alone. The goal of this study was to develop a combination microbicide that is more efficacious than Carraguard against HIV-1 and HIV-2. The microtiter syncytial assay was used to evaluate: 1) the antiviral and virucidal activity of MIV-150 against HIV-1MN; 2) the additive effect of MIV-150 when combined with carrageenan; and 3) a possible interference of seminal fluid in the antiviral activity of these compounds. MIV-150 effectively inactivated free virus. Combination of MIV-150 and Carraguard demonstrated an additive antiviral effect. Seminal fluid had no effect on the antiviral activity of MIV-150 or Carraguard. The average concentration that blocks 50% of infection (EC50) for PC-815 was approximately 10 times stronger than Carraguard for the different clinical isolates used in the study. Theoretically, PC-815 is likely to be a more efficacious microbicide than Carraguard.
 
The Renaissance artist Benvenuto Cellini admitted in his autobiography to the contraction of a sexually transmitted disease. Passages of Cellini's autobiography discussing symptoms are reviewed, and his own statements form the basis for concluding that he suffered from Reiter's disease.
 
HPV16 Seroprevalence and Seroincidence by Age-Group
Human papillomavirus 16 (HPV16) has been causally associated with approximately 70% of anal cancers. This cancer is markedly increasing among homosexual men. There is limited knowledge of the epidemiology and natural history of anal HPV infection in homosexual men. Behavioral data and sera for antibodies to HPV16 L1 were collected annually for 1427 HIV-negative and 245 HIV-positive Australian homosexual men. Seroprevalence, seroincidence, and risk factors were calculated. Among HIV-negative men, 25.4% were HPV16 seropositive at baseline compared with 44.3% of HIV-positive men. HPV16 seroincidence was 3.1/100 person-years among HIV-negative men and 1.3/100 person-years among HIV-positive men. Seroincidence among HIV-negative men remained >3% per year until 45 years of age, before declining. In multivariate analyses of data from HIV-negative men, seroprevalent HPV16 was associated with sexual risk behaviors and seropositivity for several viral sexually transmissible infections. Seroincident HPV16 was associated with younger age and unprotected anal intercourse with HIV-positive partners. Among men who predominantly practiced insertive anal intercourse, circumcision was associated with a 57% reduction in seroincident HPV16 (hazard ratio = 0.43, 95% confidence interval: 0.21-0.88, P = 0.021). HPV16 seroincidence remained common in men until their mid 40s suggesting that vaccination may be protective in sexually active young gay men. Both HPV16 seroprevalence and seroincidence correlated well with markers of higher risk sexual activity, particularly receptive anal sexual practices. An association between circumcision and decreased HPV16 seroconversion in HIV-negative men who preferred the insertive position in anal sex was observed.
 
Sexual behaviors have been linked to seropositivity for human papillomavirus (HPV) but not with the magnitude of the seroreactivity. The objective of this analysis was to examine the association of sexual behavior, cervical HPV 16 DNA positivity at enrollment (past) and at diagnosis (current), and other potential determinants with the likelihood and magnitude of HPV 16 seropositivity at diagnosis. With use of stored specimens from an incidence case-control study at Kaiser Permanente (Portland, OR), women were tested for seroreactivity to HPV 16 by enzyme-linked immunosorbent assay with virus-like particles at diagnosis and were tested for past and concurrent cervical HPV 16 DNA positivity with MY09/MY11 L1 consensus primer PCR. Questionnaire data were used to ascertain past sexual behavior. Increased lifetime number of sex partners (P(Trend) < 0.001), past HPV 16 DNA positivity (odds ratio = 6.9; 95% confidence interval = 1.5-31), and a current cytologic diagnosis (P(Trend) < 0.03) were independently associated with HPV 16 seropositivity. Among the seropositive, only lifetime number of sex partners (P(Trend) < 0.001) and past HPV 16 DNA positivity (P = 0.003) were independently associated with mean signal strength (optical density) in an age-adjusted analysis. Women negative for past and concurrent HPV 16 DNA had a significant trend of increasing optical densities associated with greater numbers of lifetime partners (P(Trend) < 0.001). Conversely, the mean signal strength for those women who were ever HPV 16 DNA-positive during the study did not depend on lifetime numbers of sex partners (P(Trend) = 0.36). HPV 16 seropositivity is a surrogate for past HPV 16 infection. Circulating levels of antibodies to HPV 16 may reflect recent HPV 16 infection or the frequency of past HPV 16 infection.
 
The aim of this study was to investigate whether HIV infection is a main risk factor for human papillomavirus (HPV)-16 and HPV-18 seropositivity in men who have sex with men (MSM), and what other risk factors are associated with HPV-16 and HPV-18 seropositivity in this population. Men who have sex with men visiting a sexually transmitted infection (STI) clinic in Amsterdam in 2008 to 2009 answered questions concerning demographics and sexual behavior. Sera were tested for HPV antibodies to the major HPV capsid protein L1 by Luminex-based multiplex serology. As it is known that site of exposure is associated with seropositivity, this analysis was restricted to MSM who reported receptive anal sex during the preceding 6 months. Using multivariable logistic regression, we examined whether HIV was associated with HPV serostatus. Included in the study were 415 HIV-negative and 205 HIV-positive MSM reporting receptive anal sex. Median age of the study population was 39 years (interquartile range, 31-44). Human papillomavirus seroprevalence differed significantly between HIV-negative and HIV-positive MSM: 31% versus 65% (P < 0.001) for HPV-16 and 28% versus 51% (P < 0.001) for HPV-18. After adjusting for important risk factors HPV-16 (adjusted odds ratio, 2.80; 95% confidence interval, 1.75-4.49) and HPV-18 (adjusted odds ratio, 1.78; 95% confidence interval, 1.11-2.85), seropositivity was significantly more common in HIV-positive than in HIV-negative MSM. We could not identify other consistent risk factors for HPV-16 and HPV-18 seropositivity. HIV infection is an important risk factor for HPV-16 and HPV-18 seropositivity among MSM reporting receptive anal sex in the preceding 6 months.
 
The objective of this study was to estimate Chlamydia trachomatis (CT) screening rates by using reported sexually transmitted disease (STD) tests for sexually active women aged 16 to 25 years in the U.S. general population. We analyzed data from the 2002 National Survey of Family Growth. Women were classified as sexually active if they reported having at least one male sex partner in the 12 months before the interview date. Women were classified as tested if they reported being tested for STDs by a healthcare provider in the preceding 12 months. Of 2,563 sampled women aged 16 to 25 years, 75% were estimated to be sexually active. Of sexually active women, 42% reported they had been tested for STDs and 73% reported they had received Pap smears or pelvic examinations in the preceding 12 months. Even if all women tested for STDs were screened for CT, only 42% of sexually active women aged 16 to 25 years would have been screened for CT. CT screening rates could be significantly increased if CT tests were performed when women had Pap smears or pelvic examinations, because most sexually active women have routine Pap smears or pelvic examinations.
 
Samples from 61 amniotic fluids (33 discolored and 28 clear) collected by amniocentesis between 16 and 20 weeks gestation were cultured for microorganisms. Two of the discolored fluids were positive for Mycoplasma hominis, and two were positive for Ureaplasma urealyticum. Neither organism was isolated from samples of clear amniotic fluids. No other bacteria, viruses, or chlamydiae were isolated from fluids of any patient. The results prove that both M. hominis and U. urealyticum can infect the amnionic sac early in gestation without rupture of the fetal membranes. U. urealyticum was shown to cause a clinically silent, chronic (up to two months) intrauterine infection characterized by an intense inflammatory response. Complications in three of the four patients from whom mycoplasmas were isolated suggest, but do not prove, that mycoplasmal infection of amniotic fluid may have an adverse effect on outcome of pregnancy. Further studies are necessary to substantiate this implication and to determine the relationship between infection and discoloration of amniotic fluid.
 
Individuals with human papillomavirus (HPV) infections can develop IgG antibodies to HPV proteins including the L1 capsid and E6 and E7 oncoproteins. Evidence on whether L1 antibodies reduce the risk of cervical HPV infection is mixed, but this has not been explored for oral HPV infections. Antibodies to HPV16's E6 oncoprotein have been detected in some oropharyngeal cancer cases years before cancer diagnosis, but it is unknown if these antibodies are associated with oral HPV16 DNA. Enzyme-linked immunosorbent assays tested for serum antibodies to HPV16's L1 capsid in 463 HIV-infected and 293 HIV-uninfected adults, and for antibodies to recombinantly expressed E6 and E7 oncoproteins to HPV16 in 195 HIV-infected and 69 HIV-uninfected cancer-free participants at baseline. Oral rinse samples were collected semiannually for up to 3 years and tested for HPV DNA using PGMY 09/11 primers. Adjusted Poisson, logistic, and Wei-Lin-Weissfeld regression models were used. Human papillomavirus 16 L1 seroreactivity did not reduce the subsequent risk of incident oral HPV16 infection in unadjusted (hazard ratio, 1.4; 95% confidence interval, 0.59-3.3) or adjusted (adjusted hazard ratio = 1.1; 95% confidence interval, 0.41-3.0) analysis. Antibodies to HPV16 E6 and E7 oncoproteins were detected in 7.6% and 3.4% of participants, respectively, but they were not associated with baseline oral HPV16 DNA prevalence or oral HPV16 persistence (each P > 0.40). Naturally acquired HPV16 L1 antibodies did not reduce the risk of subsequent oral HPV16 infection. Human papillomavirus 16 E6 and E7 seropositivity was not a marker for oral HPV16 infection in this population without HPV-related cancer.
 
The elevated risk for incident head and neck cancer among human papillomavirus (HPV)-16-seropositive individuals has substantiated a role for HPV in the etiology of head and neck cancers. The relationship between HPV seroreactivity and prevalent oral HPV infection in men and women without cancer has yet to be investigated. The goal of this study was to evaluate a possible association between oral HPV infection and HPV seroreactivity after adjustment for gender, sexual behaviors, and sexually transmitted disease. A cross-sectional study of factors associated with HPV-16, -18, and -33 seroreactivity was performed in a population of 586 men and women with and without HIV infection. Antibodies in sera were measured by use of a virus-like protein (VLP)-based enzyme-linked immunosorbent assay. Exfoliated cells from the tonsillar and oral mucosa were analyzed for the presence of 38 mucosal HPV types by polymerase chain reaction. Women had significantly greater seroreactivity for all HPV types investigated when compared with men (odds ratio, 4.3; 95% confidence interval, 3.0-6.0). Seroprevalence was greatest in men and women aged 35 to 45 years. Tonsillar HPV infection, oral sex with men, and HIV infection were independently associated with HPV seroreactivity in men after adjustment for age and number of sexual partners. In women, HSV-2 seropositivity and a history of sexually transmitted diseases were similarly important. Oral and tonsillar HPV infection were not associated with HPV seroreactivity in women. HPV seropositivity is associated with sexually transmitted diseases among women and possibly mucosal HPV exposures in men. Tonsillar HPV infection could impact seroprevalence, particularly in men.
 
Serological indicators of human papillomavirus (HPV) infection are being used to differentiate HPV-naïve from previously infected women in vaccine and epidemiologic/clinical studies. We investigated HPV16 and 18 seroepidemiology among young, unvaccinated women aged between 18 and 25. We conducted a cross-sectional evaluation of the enrollment visit in the ongoing community-based HPV16/18 Costa Rica Vaccine Trial. Prevaccination serum immunoglobulin G (IgG) antibodies were measured against HPV16 and HPV18 by enzyme-linked immunosorbent assay; cervical samples were tested for HPV DNA using Hybrid Capture 2 and SPF10/LiPA25. Seroprevalence and its correlates were evaluated using unconditional logistic regression. Among 5871 nonvirginal women, HPV16 and 18 seroprevalences were 30.8% and 28.1%, HPV16 and HPV18 DNA prevalences were 8.3% and 3.2%, respectively. About 37% of HPV16 DNA-positives and 42% of HPV18 DNA-positives were seronegative. Seroprevalence increased with time since sexual debut, whereas DNA prevalence did not. The correlates of HPV16 and/or 18 seropositivity were related to sexual behaviors, particularly higher number of lifetime sexual partners. There was no evidence of assay cross-reactivity as HPV16 seroprevalence was similar (approximately 34%) among women singly infected with genetically and nongenetically related species (α9 and non-α9); likewise, seropositivity to HPV18 was similar (approximately 30%) among women singly infected with α7 and non-α7 species. The increasing seroprevalence observed with time since first sex suggests that HPV serology is a cumulative marker of HPV exposure. However, many DNA infected women were seronegative; thus, serology is an imperfect measure of past exposure to cervical HPV, at best. Additionally, we found no evidence of assay cross-reactivity.
 
Syphilis rates in Connecticut increased four-fold between 1986 and 1988. During this time there were also signs of a large increase in cocaine use in the state. We studied links between these parallel trends in drug use and syphilis by examining two sources of data: information collected during syphilis case interviews and information from the syphilis screening program at the state's prison for women. As syphilis rates rose, there were large increases in the percentage of women with syphilis who reported prostitution or illicit drug use. In 1988, 41% of women with syphilis reported cocaine use, and 19% reported prostitution; 21% of male heterosexuals with syphilis reported cocaine use, and 31% reported sexual contact with prostitutes. Among incarcerated women, syphilis infection was frequent: of 113 women incarcerated for possession of illicit drugs in 1987-88, 7% were found to be infected with Treponema pallidum, and of 187 women incarcerated for prostitution in these years, 14% were infected. In both groups of incarcerated women studied, cocaine users had the highest syphilis rates, and those who administered drugs nonintravenously had rates similar to those who administered drugs intravenously. We concluded that the syphilis epidemic in Connecticut is related to the increase in use of illicit drugs (primarily cocaine) and that female drug users are at very high risk of syphilis regardless of whether they administer drugs intravenously or nonintravenously. We recommend that syphilis control efforts focus on wider serologic screening and early treatment of drug users, prostitutes, and their sex partners.
 
In 1763 Jan Fryderyk Knolle, a Polish physician, wrote his doctoral thesis on osseous syphilis, De Ossium Carie Venerea, at the University of Leipzig, Saxony (now East Germany). Knolle described the pathology, clinical picture, and treatment of syphilis of the bones and emphasized the severity and destructiveness of bony lesions, which could occur even in the early stage of the disease. An interesting and detailed drawing showing osteomyelitis of the femur, which appears to be of syphilitic origin, was included in Knolle's dissertation. This illustration is an example of 18th century syphilologic iconography. A comparison of the clinical picture of syphilis as described by Knolle with that of the present day suggests that syphilis has become a milder disease.
 
The mechanisms underlying the process of Treponema pallidum clearance from the central nervous system have not yet been established. Considering that neurosyphilis is associated with mild cerebrospinal fluid (CSF) pleocytosis with a lymphocytic predominance, it has been suggested that cells involved in the adaptive immune response may play a role in this process. In the current study, we assessed the cytokine production profile of T-helper cells in the serum and CSF of patients with early syphilis, with and without CSF abnormalities. Cerebrospinal fluid and blood samples were collected from 33 patients with secondary and early latent syphilis. Five patients (15%) had a reactive CSF Venereal Disease Research Laboratory test without any accompanying neurological symptoms. According to the Centers of Disease Control and Prevention classification, they were diagnosed with asymptomatic neurosyphilis. Serum and CSF levels of interferon-γ (IFN-γ; Th1-type cytokine), interleukin-4 (IL-4; Th2-type cytokine), and interleukin-17A (IL-17A; Th17-type cytokine) were determined by enzyme-linked immunosorbent assay. Patients with asymptomatic neurosyphilis had significantly higher levels of IL-17A (8-fold) and IFN-γ (7.8-fold) in the CSF compared with patients in the no-neurosyphilis group. Six individuals had CSF pleocytosis but a negative CSF Venereal Disease Research Laboratory test result (presumptive neurosyphilis group). In this group, CSF IFN-γ and CSF IL-17A levels were also significantly elevated when compared with no-neurosyphilis group. There was no correlation between serum and CSF concentrations of IL-17A. However, CSF pleocytosis correlated positively with both CSF IL-17A (r = 0.4, P = 0.01) and IFN-γ (r = 0.42, P = 0.01). Increased CSF levels of IFN-γ and IL-17A in syphilitic patients with CSF abnormalities suggest that cells of adaptive immunity (probably T-helper cells producing IFN-γ and IL-17) may contribute to the inflammatory response associated with neurosyphilis. In addition, the lack of correlation between serum and CSF IL-17A levels suggests intrathecal production of this cytokine. Further studies are needed to establish the exact nature of the immune response accompanying neurosyphilis and its clinical significance.
 
Oral human papillomavirus (HPV) infection is a cause of oropharyngeal squamous cell carcinoma, yet little is known about the epidemiology and natural history of infection. At a baseline and 3-month follow-up visit, 1000 young adults aged 18 to 30 years provided an oral rinse sample and completed a survey assessing demographic and behavioral risk factors. The oral rinse sample was analyzed for 37 types of HPV by use of a multiplex polymerase chain reaction assay. Factors associated with oral HPV detection were analyzed using univariate and bivariate logistic regression. The prevalence of oral HPV infection was 2.4% (95% CI: 1.4-3.4). Ever having consumed alcohol (OR, 0.2; 95% CI: 0.1-0.8), 5 or more lifetime open-mouth kissing (OR, 4.0; 95% CI: 1.1-14.8) or lifetime oral sex (OR, 4.0; 95% CI: 1.3-11.9) partners were associated with infection, controlling for lifetime vaginal sex partners. The incidence rate for oral HPV infection was 5.67 (95% CI: 3.12-8.16) per 1000 person-months. Incident infection was associated in univariate analysis with black race (OR, 4.7; 95% CI: 1.7-13.5) and having open-mouth kissed a new partner in the previous 3 months (OR, 2.6; 95% CI: 1.0-6.4). This study provides further evidence that oral sexual contact in the form of both oral-oral and oral-genital contact could play a role in the transmission of oral HPV.
 
Top-cited authors
Edward W Hook
  • University of Alabama at Birmingham
Sevgi Okten Aral
  • Centers for Disease Control and Prevention
Sharon L Hillier
  • University of Pittsburgh
Jonathan M Zenilman
  • Johns Hopkins Medicine
Jeffrey Klausner